This parody of evo devo makes it sound a lot like ID

2351 typo correction evo devo Dionisio

The whole eve devo enchilada: https://www.ncbi.nlm.nih.gov/pubmed?term=%22Evodevo%22[jour] :) Dionisio

Evolutionary biosemiotics and multilevel construction networks Alexei A. Sharon Biosemiotics. 9(3): 399–416. doi: 10.1007/s12304-016-9269-0 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283393/pdf/nihms810857.pdf Dionisio

Principles of constructivism are used here to explore how organisms develop tools, subagents, scaffolds, signs, and adaptations. Here I discuss reasons why organisms have composite nature and include diverse subagents that interact in partially cooperating and partially conflicting ways. Such modularity is necessary for efficient and robust functionality, including mutual construction and adaptability at various time scales. Subagents interact via material and semiotic relations, some of which force or prescribe actions of partners. Other interactions, which I call "guiding", do not have immediate effects and do not disrupt the evolution and learning capacity of partner agents. However, they modify the extent of learning and evolutionary possibilities of partners via establishment of scaffolds and constraints. As a result, subagents construct reciprocal scaffolding for each other to rebalance their communal evolution and learning. As an example, I discuss guiding interactions between the body and mind of animals, where the pain system adjusts mind-based learning to the physical and physiological constraints of the body. Reciprocal effects of mind and behaviors on the development and evolution of the body includes the effects of Lamarck and Baldwin. Composite Agency: Semiotics of Modularity and Guiding Interactions. Sharov AA1. Biosemiotics. 2017 Jul;10(2):157-178. doi: 10.1007/s12304-017-9301-z. Dionisio

Evolution of natural agents: preservation, advance, and emergence of functional information Alexei A. Sharov Biosemiotics. 9(1): 103–129. doi: 10.1007/s12304-015-9250-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978442/pdf/nihms773099.pdf Dionisio

Analysis of gene function in complex organisms relies extensively on tools to detect the cellular and subcellular localization of gene products, especially proteins. Typically, immunostaining with antibodies provides these data. However, due to cost, time, and labor limitations, generating specific antibodies against all proteins of a complex organism is not feasible. Furthermore, antibodies do not enable live imaging studies of protein dynamics. Hence, tagging genes with standardized immunoepitopes or fluorescent tags that permit live imaging has become popular. Importantly, tagging genes present in large genomic clones or at their endogenous locus often reports proper expression, subcellular localization, and dynamics of the encoded protein. Moreover, these tagging approaches allow the generation of elegant protein removal strategies, standardization of visualization protocols, and permit protein interaction studies using mass spectrometry. Here, we summarize available genomic resources and techniques to tag genes and discuss relevant applications that are rarely, if at all, possible with antibodies. Gene Tagging Strategies To Assess Protein Expression, Localization, and Function in Drosophila. Kanca O1,2, Bellen HJ3,2,4,5,6, Schnorrer F7. Genetics. 2017 Oct;207(2):389-412. doi: 10.1534/genetics.117.199968. Dionisio

The role of protein localization along the apical-basal axis of polarized cells is difficult to investigate in vivo, partially due to lack of suitable tools. Despite of its importance, the role of protein localization and the effects of forced protein mislocalization have not been studied extensively and hence remain in many cases not well understood. A nanobody-based toolset to investigate the role of protein localization and dispersal in Drosophila Stefan Harmansa,1,† Ilaria Alborelli,1,† Dimitri Bieli,1 Emmanuel Caussinus,1,2 and Markus Affolter eLife. 2017; 6: e22549. doi: 10.7554/eLife.22549 Dionisio

Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS). Most of REs hosting TFBS were highly diverged repeats, and for the evolutionary young (0–8% diverged) elements we identified only ~7% of all RE-linked TFBS. The gene-specific distributions of RE-linked TFBS generally correlated with the distributions for all TFBS. However, several groups of molecular processes were highly enriched in the RE-linked TFBS regulation. They were strongly connected with the immunity and response to pathogens, with the negative regulation of gene transcription, ubiquitination, and protein degradation, extracellular matrix organization, regulation of STAT signaling, fatty acids metabolism, regulation of GTPase activity, protein targeting to Golgi, regulation of cell division and differentiation, development and functioning of perception organs and reproductive system. By contrast, the processes most weakly affected by the REs were linked with the conservative aspects of embryo development. We also identified differences in the regulation features by the younger and older fractions of the REs. The regulation by the older fraction of the REs was linked mainly with the immunity, cell adhesion, cAMP, IGF1R, Notch, Wnt, and integrin signaling, neuronal development, chondroitin sulfate and heparin metabolism, and endocytosis. The younger REs regulate other aspects of immunity, cell cycle progression and apoptosis, PDGF, TGF beta, EGFR, and p38 signaling, transcriptional repression, structure of nuclear lumen, catabolism of phospholipids, and heterocyclic molecules, insulin and AMPK signaling, retrograde Golgi-ER transport, and estrogen signaling. The immunity-linked pathways were highly represented in both categories, but their functional roles were different and did not overlap. Our results point to the most quickly evolving molecular pathways in the recent and ancient evolution of human genome. (2018). Profiling of Human Molecular Pathways Affected by Retrotransposons at the Level of Regulation by Transcription Factor Proteins. Frontiers in Immunology. 9. . 10.3389/fimmu.2018.00030. Dionisio

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases. Djerbal, Linda & Lortat-Jacob, Hugues & Kwok, JCF. (2017). Chondroitin sulfates and their binding molecules in the central nervous system. Glycoconjugate Journal. 34. . 10.1007/s10719-017-9761-z. Dionisio

Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans are abundant on the cell surface and in the extracellular matrix and have important functions in matrix structure, cell-matrix interaction and signaling. The DS epimerases 1 and 2, encoded by Dse and Dsel, respectively, convert CS to a CS/DS hybrid chain, which is structurally and conformationally richer than CS, favouring interaction with matrix proteins and growth factors. We recently showed that Xenopus Dse is essential for the migration of neural crest cells by allowing cell surface CS/DS proteoglycans to adhere to fibronectin. Here we investigate the expression of Dse and Dsel in Xenopus embryos. We show that both genes are maternally expressed and exhibit partially overlapping activity in the eyes, brain, trigeminal ganglia, neural crest, adenohypophysis, sclerotome, and dorsal endoderm. Dse is specifically expressed in the epidermis, anterior surface ectoderm, spinal nerves, notochord and dermatome, whereas Dsel mRNA alone is transcribed in the spinal cord, epibranchial ganglia, prechordal mesendoderm and myotome. The expression of the two genes coincides with sites of cell differentiation in the epidermis and neural tissue. Several expression domains can be linked to previously reported phenotypes of knockout mice and clinical manifestations, such as the Musculocontractural Ehlers-Danlos syndrome and psychiatric disorders. Gouignard, Nadege & Schön, Tanja & Holmgren, Christian & Strate, Ina & Ta?öz, Emirhan & Wetzel, Franziska & Maccarana, Marco & Pera, Edgar. (2018). Gene expression of the two developmentally regulated dermatan sulfate epimerases in the Xenopus embryo. PLOS ONE. 13. e0191751. 10.1371/journal.pone.0191751. Dionisio

Presomitic mesoderm (PSM) cells are the precursors of the somites, which flank both sides of the neural tube and give rise to the musculo-skeletal system shaping the vertebrate body. WNT and FGF signaling control the formation of both the PSM and the somites and show a graded distribution with highest levels in the posterior PSM. The ability to generate PSM cells of either posterior or anterior PSM identity with high efficiency in vitro will promote the investigation of the gene regulatory networks controlling the formation of nascent PSM cells and their switch to differentiating/somitic paraxial mesoderm. Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States of WNT-Induced Presomitic Mesoderm. Sudheer S1,2, Liu J1, Marks M1, Koch F1, Anurin A1,3, Scholze M1, Senft AD1,4, Wittler L1, Macura K1, Grote P1,5, Herrmann BG1 Stem Cells. 2016 Jul;34(7):1790-800. doi: 10.1002/stem.2371. Epub 2016 Apr 18. Dionisio

How metabolism is rewired during embryonic development is still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Combined, our approach identifies a gradient of glycolytic activity across the PSM, and we provide evidence that these spatiotemporal metabolic changes are intrinsically linked to PSM development and differentiation. [...] very little is known about the metabolic state in the context of mammalian embryonic development, particularly in organogenesis-stage mammalian embryos. The ability to reveal metabolite levels and potentially metabolic transitions with spatiotemporal resolution will be critical in future studies that will address how metabolic and signaling gradients are mechanistically and functionally linked within the context of embryonic development. Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development. Bulusu V1, Prior N2, Snaebjornsson MT2, Kuehne A3, Sonnen KF2, Kress J2, Stein F4, Schultz C4, Sauer U3, Aulehla A5. Dev Cell. 2017 Feb 27;40(4):331-341.e4. doi: 10.1016/j.devcel.2017.01.015. Dionisio

KF @338, Good comment. Thanks. Dionisio

DNA nanostructures represent the confluence of materials science, computer science, biology, and engineering. As functional assemblies, they are capable of performing mechanical and chemical work. In this study, we demonstrate global twisting of DNA nanorails made from two DNA origami six-helix bundles. Twisting was controlled using ethidium bromide or SYBR Green I as model intercalators. Our findings demonstrate that DNA nanorails: (i) twist when subjected to intercalators and the amount of twisting is concentration dependent, and (ii) twisting saturates at elevated concentrations. This study provides insight into how complex DNA structures undergo conformational changes when exposed to intercalators and may be of relevance when exploring how intercalating drugs interact with condensed biological structures such as chromatin and chromosomes, as well as chromatin analogous gene expression devices. Zadegan, Reza & G. Lindau, Elias & P. Klein, William & Green, Christopher & Graugnard, Elton & Yurke, Bernard & Kuang, Wan & L. Hughes, William. (2017). Twisting of DNA Origami from Intercalators. Scientific Reports. 7. . 10.1038/s41598-017-07796-3. Dionisio

DiEb, 311: Several times, you have raised the issue of search. I have pointed out that at base, it is tantamount to sampling from a configuration space. In the sense, blind search, by chance and/or mechanical necessity without intelligent direction or control or guidance or influence generally. This is directly relevant to the challenge of "finding" -- strictly, happening upon the shorelines of -- deeply isolated islands of function in config spaces of 500 - 1,000 bits or more of complexity. In these cases,

a: the atomic resources of the sol system or observed cosmos [10^57 to 10^80 atoms, more or less] b: treated as observers each sampling at fast chemical reaction rates [~10^14 samples or observations/sec] c: for 10^17 s (order of time since the typical projection to the singularity) will be __________________________________ d: utterly overwhelmed by the scope of search to plausibly sample enough of the space to credibly hit one or more shorelines of function.

This does not require any detailed probability assessment, but indicates that by many orders of magnitude the challenge overwhelms the search resources. As a direct result, blind search is not a plausible means of discovering zones exhibiting functionally specific complex organisation and/or associated information [FSCO/I] in sufficiently complex configuration spaces. Where, per search samples the space, it is a subset, so the set of possible searches is comparable to the power set. If the direct set is of magnitude n, the set of searches is comparable in magnitude to 2^n. Thus, search for a golden search is plausibly exponentially harder than direct search. Of course, typical discussions of fitness landscapes are about incremental hill-climbing within islands of function. They thus beg the question of arriving at shorelines of function. Where also, deep isolation is a direct result of FSCO/I requiring multiple, well matched components properly arranged and coupled to produce relevant results. And as a consequence of OOL requiring credibly 100k - 1,000 k bases and body plans 10 - 100 millions, we are well beyond the FSCO/I threshold in these cases. So, it is not plausible that the FSCO/I seen in life forms at origin or at basic body plan level, originated by blind search. Pausing, it is worth noting that the proposal that ability to reproduce leading to descent with incremental modification solves the problem typically overlooks that at OOL, there is need to account for the FSCO/I of the von Neumann kinematic self-replicator found in the living cell. Likewise, that for body plan origins, many co-ordinated changes (often, involving reproduction) will have to be accounted for. Natural selection of reproducing entities does not evade the origin of FSCO/I challenge. What, per Newton's vera causa principle, has right to be regarded as an observed effective cause of FSCO/I? Intelligently directed configuration, aka design. Indeed, we are well within our inductive logic, epistemic rights, to hold that FSCO/I is a well tested, highly reliable sign of design as materially relevant cause. On a trillion member observation base. KF kairosfocus

Most DNA processes are governed by molecular interactions that take place in a sequence-specific manner. Determining the sequence selectivity of DNA ligands is still a challenge, particularly for small drugs where labeling or sequencing methods do not perform well. Here, we present a fast and accurate method based on parallelized single molecule magnetic tweezers to detect the sequence selectivity and characterize the thermodynamics and kinetics of binding in a single assay. Mechanical manipulation of DNA hairpins with an engineered sequence is used to detect ligand binding as blocking events during DNA unzipping, allowing determination of ligand selectivity both for small drugs and large proteins with nearly base-pair resolution in an unbiased fashion. The assay allows investigation of subtle details such as the effect of flanking sequences or binding cooperativity. Unzipping assays on hairpin substrates with an optimized flat free energy landscape containing all binding motifs allows determination of the ligand mechanical footprint, recognition site, and binding orientation. Manosas, Maria & Camunas-Soler, Joan & Croquette, Vincent & Ritort, Felix. (2017). Single molecule high-throughput footprinting of small and large DNA ligands. Nature Communications. 8. . 10.1038/s41467-017-00379-w. Dionisio

Single-molecule approaches present a powerful way to obtain detailed kinetic information at the molecular level. However, the identification of small rate changes is often hindered by the considerable noise present in such single-molecule kinetic data. We present a general method to detect such kinetic change points in trajectories of motion of processive single molecules having Gaussian noise, with a minimum number of parameters and without the need of an assumed kinetic model beyond piece-wise linearity of motion. Kinetic change points are detected using a likelihood ratio test in which the probability of no change is compared to the probability of a change occurring, given the experimental noise. A predetermined confidence interval minimizes the occurrence of false detections. Applying the method recursively to all sub-regions of a single molecule trajectory ensures that all kinetic change points are located. The algorithm presented allows rigorous and quantitative determination of kinetic change points in noisy single molecule observations without the need for filtering or binning, which reduce temporal resolution and obscure dynamics. The statistical framework for the approach and implementation details are discussed. The detection power of the algorithm is assessed using simulations with both single kinetic changes and multiple kinetic changes that typically arise in observations of single-molecule DNA-replication reactions. Implementations of the algorithm are provided in ImageJ plugin format written in Java and in the Julia language for numeric computing, with accompanying Jupyter Notebooks to allow reproduction of the analysis presented here. R. Hill, Flynn & van Oijen, Antoine & Duderstadt, Karl. (2018). Detection of kinetic change points in piece-wise linear single molecule motion. The Journal of Chemical Physics. 148. 123317. 10.1063/1.5009387. Dionisio

The astonishing efficiency and accuracy of DNA replication has long suggested that refined rules enforce a single highly reproducible sequence of molecular events during the process. This view was solidified by early demonstrations that DNA unwinding and synthesis are coupled within a stable molecular factory, known as the replisome, which consists of conserved components that each play unique and complementary roles. However, recent single-molecule observations of replisome dynamics have begun to challenge this view, revealing that replication may not be defined by a uniform sequence of events. Instead, multiple exchange pathways, pauses, and DNA loop types appear to dominate replisome function. These observations suggest we must rethink our fundamental assumptions and acknowledge that each replication cycle may involve sampling of alternative, sometimes parallel, pathways. Here, we review our current mechanistic understanding of DNA replication while highlighting findings that exemplify multi-pathway aspects of replisome function and considering the broader implications. J. Scherr, Matthias & Safaric, Barbara & Duderstadt, Karl. (2017). Noise in the Machine: Alternative Pathway Sampling is the Rule During DNA Replication. BioEssays. 40. 1700159. 10.1002/bies.201700159. Dionisio

The replisome, the multiprotein system responsible for genome duplication, is a highly dynamic complex displaying a large number of different enzyme activities. Recently, the Saccharomyces cerevisiae minimal replication reaction has been successfully reconstituted in vitro. This provided an opportunity to uncover the enzymatic activities of many of the components in a eukaryotic system. Their dynamic behavior and interactions in the context of the replisome, however, remain unclear. We use a tethered-bead assay to provide real-time visualization of leading-strand synthesis by the S. cerevisiae replisome at the single-molecule level. The minimal reconstituted leading-strand replisome requires 24 proteins, forming the CMG helicase, the Pol ? DNA polymerase, the RFC clamp loader, the PCNA sliding clamp, and the RPA single-stranded DNA binding protein. We observe rates and product lengths similar to those obtained from ensemble biochemical experiments. At the single-molecule level, we probe the behavior of two components of the replication progression complex and characterize their interaction with active leading-strand replisomes. The Minichromosome maintenance protein 10 (Mcm10), an important player in CMG activation, increases the number of productive replication events in our assay. Furthermore, we show that the fork protection complex Mrc1-Tof1-Csm3 (MTC) enhances the rate of the leading-strand replisome threefold. The introduction of periods of fast replication by MTC leads to an average rate enhancement of a factor of 2, similar to observations in cellular studies. We observe that the MTC complex acts in a dynamic fashion with the moving replisome, leading to alternating phases of slow and fast replication. S. Lewis, Jacob & Spenkelink, Lisanne & D. Schauer, Grant & R. Hill, Flynn & E. Georgescu, Roxanna & E. O’Donnell, Michael & van Oijen, Antoine. (2017). Single-molecule visualization of Saccharomyces cerevisiae leading-strand synthesis reveals dynamic interaction between MTC and the replisome. Proceedings of the National Academy of Sciences. 114. 201711291. 10.1073/pnas.1711291114. Dionisio

Genetic recombination occurs in all organisms and is vital for genome stability. Indeed, in humans, aberrant recombination can lead to diseases such as cancer. Our understanding of homologous recombination is built upon more than a century of scientific inquiry, but achieving a more complete picture using ensemble biochemical and genetic approaches is hampered by population heterogeneity and transient recombination intermediates. Recent advances in single-molecule and super-resolution microscopy methods help to overcome these limitations and have led to new and refined insights into recombination mechanisms, including a detailed understanding of DNA helicase function and synaptonemal complex structure. The ability to view cellular processes at single-molecule resolution promises to transform our understanding of recombination and related processes. Kaniecki, Kyle & De Tullio, Luisina & C. Greene, Eric. (2017). A change of view: homologous recombination at single-molecule resolution. Nature Reviews Genetics. . 10.1038/nrg.2017.92. Dionisio

Single molecule microscopy techniques allow to visualize the translocation of single transport receptors and cargo molecules or particles through nuclear pore complexes. These data indicate that cargo molecule import into the nucleus takes less than 10 milliseconds and nuclear export of messenger RNA (mRNA) particles takes 50 to 350 milliseconds, up to several seconds for extremely bulky particles. This review summarizes and discusses experimental results on transport of nuclear transport factor 2 (NTF2), importin ? and mRNA particles. Putative regulatory functions of importin ? for the NPC transport mechanism and the RNA helicase Dbp5 for mRNA export kinetics are discussed. Kubitscheck, Ulrich & Siebrasse, Jan. (2017). Kinetics of transport through the nuclear pore complex. Seminars in Cell & Developmental Biology. . 10.1016/j.semcdb.2017.06.016. Dionisio

Force sensing and generation at the tissular and cellular scale is central to many biological events. There is a growing interest in modern cell biology for methods enabling force measurements in vivo Optical trapping allows non-invasive probing of pico-Newton forces and thus emerged as a promising mean for assessing biomechanics in vivo Nevertheless, the main obstacles rely in the accurate determination of the trap stiffness in heterogeneous living organisms, at any position where the trap is used. A proper calibration of the trap stiffness is thus required for performing accurate and reliable force measurements in vivo Here, we introduce a method that overcomes these difficulties by accurately measuring hemodynamic profiles in order to calibrate the trap stiffness. Doing so, and using numerical methods to assess the accuracy of the experimental data, we measured flow profiles and drag forces imposed to trapped red blood cells of living zebrafish embryos. Using treatments enabling blood flow tuning, we demonstrated that such method is powerful in measuring hemodynamic forces in vivo with accuracy and confidence. Altogether, this study demonstrates the power of optical tweezing in measuring low range hemodynamic forces in vivo and offers an unprecedented tool in both cell and developmental biology. Harlepp, Sebastien & Thalmann, Fabrice & Follain, Gautier & Goetz, Jacky. (2017). Hemodynamic forces can be accurately measured in vivo with optical tweezers. Molecular Biology of the Cell. 28. mbc.E17-06. 10.1091/mbc.E17-06-0382. Dionisio

Identifying the key structural and dynamical determinants that drive the association of biomolecules, whether in solution, or perhaps more importantly in a membrane environment, has critical implications for our understanding of cellular dynamics, processes, and signaling. With recent advances in high-resolution imaging techniques, from the development of new molecular labels to technical advances in imaging methodologies and platforms, researchers are now reaping the benefits of being able to directly characterize and quantify local dynamics, structures, and conformations in live cells and tissues. These capabilities are providing unique insights into association stoichiometries, interactions, and structures on sub-micron length scales. We previously examined the role of lipid headgroup chemistry and phase state in guiding the formation of pseudoisocyanine (PIC) dye J-aggregates on supported planar bilayers [Langmuir, 25, 10,719]. We describe here how these same J-aggregates can report on the in situ formation of organellar membrane domains in live cells. Live cell hyperspectral confocal microscopy using GFP-conjugated GTPase markers of early (Rab5) and late (Rab7) endosomes revealed that the PIC J-aggregates were confined to domains on either the limiting membrane or intralumenal vesicles (ILV) of late endosomes, known to be enriched in the anionic lipid bis(monoacylglycero)phosphate (BMP). Correlated confocal fluorescence - atomic force microscopy performed on endosomal membrane-mimetic supported planar lipid bilayers confirmed BMP-specific templating of the PIC J-aggregates. These data provide strong evidence for the formation of BMP-rich lipid domains during multivesicular body formation and portend the application of structured dye aggregates as markers of cellular membrane domain structure, size, and formation. C.H. Mo, Gary & M. Yip, Christopher. (2017). Structural Templating of J-aggregates: Visualizing Bis(monoacylglycero)phosphate domains in live cells. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1865. . 10.1016/j.bbapap.2017.07.019. Dionisio

With new approaches in imaging—from new tools or reagents to processing algorithms—come unique opportunities and challenges to our understanding of biological processes, structures, and dynamics. Although innovations in super-resolution imaging are affording novel perspectives into how molecules structurally associate and localize in response to, or in order to initiate, specific signaling events in the cell, questions arise as to how to interpret these observations in the context of biological function. Just as each neighborhood in a city has its own unique vibe, culture, and indeed density, recent work has shown that membrane receptor behavior and action is governed by their localization and association state. There is tremendous potential in developing strategies for tracking how the populations of these molecular neighborhoods change dynamically. Oreopoulos, John & D. Gray-Owen, Scott & Yip, Christopher. (2017). High Density or Urban Sprawl: What Works Best in Biology?. ACS Nano. 11. . 10.1021/acsnano.7b00061. Dionisio

Single-molecule manipulation and imaging techniques have become important elements of the biologist's toolkit to gain mechanistic insights into cellular processes. By removing ensemble averaging, single-molecule methods provide unique access to the dynamic behavior of biomolecules. Recently, the use of these approaches has expanded to the study of complex multiprotein systems and has enabled detailed characterization of the behavior of individual molecules inside living cells. In this review, we provide an overview of the various force- and fluorescence-based single-molecule methods with applications both in vitro and in vivo, highlighting these advances by describing their applications in studies on cytoskeletal motors and DNA replication. We also discuss how single-molecule approaches have increased our understanding of the dynamic behavior of complex multiprotein systems. These methods have shown that the behavior of multicomponent protein complexes is highly stochastic and less linear and deterministic than previously thought. Further development of single-molecule tools will help to elucidate the molecular dynamics of these complex systems both inside the cell and in solutions with purified components. Monachino, Enrico & Spenkelink, Lisanne & van Oijen, Antoine. (2016). Watching cellular machinery in action, one molecule at a time. The Journal of cell biology. 216. . 10.1083/jcb.201610025. Dionisio

Kinesin motors play central roles in establishing and maintaining the mitotic spindle during cell division. Unlike most other kinesins, Cin8, a kinesin-5 motor in Saccharomyces cerevisiae, can move bidirectionally along microtubules, switching directionality according to biochemical conditions, a behavior that remains largely unexplained. To this end, we used biochemical rate and equilibrium constant measurements as well as cryo-electron microscopy methodologies to investigate the microtubule interactions of the Cin8 motor domain. These experiments unexpectedly revealed that, while Cin8 ATPase kinetics fell within measured ranges for kinesins (especially kinesin-5 proteins), approximately four motors can unexpectedly bind each ab-tubulin dimer within the microtubule lattice. This result contrasted with those observations on other known kinesins, which can bind only a single "canonical" site per ab-tubulin dimer. Competition assays with human kinesin-5 (Eg5) only partially abrogated this behavior, indicating that Cin8 binds microtubules not only at the canonical site, but also one or more separate ("noncanonical") sites. Moreover, we found that deleting the large, class-specific insert in the microtubule-binding loop 8 reverts Cin8 to one motor per tubulin in the microtubule. The novel microtubule-binding mode of Cin8 identified here provides a potential explanation for Cin8 clustering along microtubules and potentially may contribute to the mechanism for direction reversal. M Bell, Kayla & Cha, Hyo Keun & Sindelar, Charles & C Cochran, Jared. (2017). The yeast kinesin-5 Cin8 interacts with the microtubule in a noncanonical manner. Journal of Biological Chemistry. 292. jbc.M117.797662. 10.1074/jbc.M117.797662 Dionisio

The bipolar kinesin-5 motors perform essential functions in mitotic spindle dynamics. We previously demonstrated that phosphorylation of at least one of the Cdk1 sites in the catalytic domain of the Saccharomyces cerevisiae kinesin-5 Cin8 (S277, T285, S493) regulates its localization to the anaphase spindle. The contribution of these three sites to phospho-regulation of Cin8, as well as the timing of such contributions, remains unknown. Here, we examined the function and spindle localization of phospho-deficient (serine/threonine to alanine) and phospho-mimic (serine/threonine to aspartic acid) Cin8 mutants. In vitro, the three Cdk1 sites undergo phosphorylation by Clb2-Cdk1. In cells, phosphorylation of Cin8 affects two aspects of its localization to the anaphase spindle, translocation from the spindle-pole bodies (SPBs) region to spindle microtubules (MTs) and the midzone, and detachment from the mitotic spindle. We found that phosphorylation of S277 is essential for the translocation of Cin8 from SPBs to spindle MTs and the subsequent detachment from the spindle. Phosphorylation of T285 mainly affects the detachment of Cin8 from spindle MTs during anaphase, while phosphorylation at S493 affects both the translocation of Cin8 from SPBs to the spindle and detachment from the spindle. Only S493 phosphorylation affected the anaphase spindle elongation rate. We conclude that each phosphorylation site plays a unique role in regulating Cin8 functions and postulate a model in which the timing and extent of phosphorylation of the three sites orchestrates the anaphase function of Cin8. Goldstein, Alina & Siegler, Nurit & Goldman, Darya & Judah, Haim & Valk, Ervin & Kõivomägi, Mardo & Loog, Mart & Gheber, Larisa. (2017). Three Cdk1 sites in the kinesin-5 Cin8 catalytic domain coordinate motor localization and activity during anaphase. Cellular and Molecular Life Sciences. 74. . 10.1007/s00018-017-2523-z. Dionisio

Lazo, Pedro. (2017). Is Centrosomal Protein 70, a Centrosomal Protein with New Roles in Breast Cancer Dissemination and Metastasis, a Facilitator of Epithelial-Mesenchymal Transition?. The American Journal of Pathology. 187. . 10.1016/j.ajpath.2016.12.008. This commentary highlights the article by Shi et al that identified centrosomal protein 70 as a key mediator of breast cancer growth and metastasis. Dionisio

Chromosome stability is ensured by precisely fine-tuned dynamics of mitotic spindles, which are controlled by a network of various microtubule-associated and interacting proteins including the kinesin-13 family. The best characterized member of this family is the mitotic centromere-associated kinesin (MCAK). By efficiently depolymerizing microtubules, MCAK influences various key events during mitosis. MCAK itself is regulated by its interaction partners, its intrinsic conformation switch and the phosphorylation of mitotic kinases like Aurora A/B, cyclin-dependent kinase 1 and Polo-like kinase 1. Perturbing its regulation alters MCAK’s conformation, catalytic activity, subcellular localization and stability, leading further to mitotic defects in spindle formation and chromosome movement. Indeed, MCAK is aberrantly regulated in various cancer types, which is linked to increased invasiveness, metastasis and drug resistance. In the current review, we summarize recently published data concerning MCAK, correlate its conformation changes with its depolymerization activity and function, propose a model of its regulation by multiple mitotic kinases and highlight its potential involvement in oncogenesis and drug resistance. Ritter, Andreas & Kreis, Nina-Naomi & Louwen, Frank & Wordeman, Linda & Yuan, Juping. (2016). Molecular insight into the regulation and function of MCAK. Critical Reviews in Biochemistry and Molecular Biology. 51. 1-18. 10.1080/10409238.2016.1178705. Dionisio

Polo-like kinase 1 (Plk1) has been established as one of the most promising targets for molecular anticancer intervention. In fact, various Plk1 inhibitors have been identified and characterized. While the data derived from the bench are prospective, the clinical outcomes are less encouraging by showing modest efficacy. One of the explanations for this discrepancy could be unintendedly targeting of non-malignant cells by Plk1 inhibitors. In this work, we have addressed the effect of Plk1 inhibition in adipose tissue-derived mesenchymal stem cells (ASCs). We show that both visceral and subcutaneous ASCs display monopolar spindles, reduced viability and strong apoptosis induction upon treatment with BI 2536 and BI 6727, the Plk1 kinase domain inhibitors, and with Poloxin, the regulatory Polo-box domain inhibitor. While Poloxin triggers quickly apoptosis, BI 2536 and BI 6727 result in mitotic arrest in ASCs. Importantly, survived ASCs exhibit DNA damage and a pronounced senescent phenotype. In addition, Plk1 inhibition impairs ASCs' motility and homing ability. These results show that Plk1 inhibitors target slowly proliferating ASCs, an important population of anti-inflammation and immune modulation. The toxic effects on primary cells like ASCs could be partially responsible for the reported moderate antitumor activity in patients treated with Plk1 inhibitors. Ritter, Andreas & Friemel, Alexandra & Kreis, Nina-Naomi & Louwen, Frank & Yuan, Juping. (2016). Impact of Polo-like kinase 1 inhibitors on human adipose tissue-derived mesenchymal stem cells. Oncotarget. 7. . 10.18632/oncotarget.12482 Dionisio

Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression. © 2015 by The Rockefeller University Press. Platani, Melpomeni & Trinkle-Mulcahy, Laura & Porter, Michael & Arulanandam, Dr. Arockia Jeyaprakash & Earnshaw, William. (2015). Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes. The Journal of Cell Biology. 210. 45-62. 10.1083/jcb.201410001 Dionisio

Spindle orientation determines the axis of division and is crucial for cell fate, tissue morphogenesis, and the development of an organism. In animal cells, spindle orientation is regulated by the conserved G?i–LGN–NuMA complex, which targets the force generator dynein–dynactin to the cortex. In this study, we show that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it acts independently of G?i, the kinase Aurora A, and the phosphatase PP2A. Our data show that in anaphase, when the spindle elongates, PP1/Repo-Man promotes the accumulation of NuMA at the cortex. In metaphase, p37 negatively regulates this function of PP1, resulting in lower cortical NuMA levels and correct spindle orientation. Lee, Byung Ho & Schwager, Françoise & Meraldi, Patrick & Gotta, Monica. (2017). p37/UBXN2B regulates spindle orientation by limiting cortical NuMA recruitment via PP1/Repo-Man. The Journal of Cell Biology. jcb.201707050. 10.1083/jcb.201707050. Dionisio

Accurate spindle positioning is essential for error-free cell division. The one-cell Caenorhabditis elegans embryo has proven instrumental for dissecting mechanisms governing spindle positioning. Despite important progress, how the cortical forces that act on astral microtubules to properly position the spindle are modulated is incompletely understood. [...] Aurora A kinases and PP6 phosphatases have an ancient function in modulating spindle positioning, thus contributing to faithful cell division. Aurora A kinase regulates proper spindle positioning in C. elegans and in human cells. Kotak S1, Afshar K1, Busso C1, Gönczy P2. J Cell Sci. 129(15):3015-25. doi: 10.1242/jcs.184416. Dionisio

Chromatin-remodelling factors change nucleosome positioning and facilitate DNA transcription, replication, and repair. The conserved remodelling factor chromodomain-helicase-DNA binding protein 1(Chd1) can shift nucleosomes and induce regular nucleosome spacing. Chd1 is required for the passage of RNA polymerase IIthrough nucleosomes and for cellular pluripotency. Chd1 contains the DNA-binding domains SANT and SLIDE, a bilobal motor domain that hydrolyses ATP, and a regulatory double chromodomain. Here we report the cryo-electron microscopy structure of Chd1 from the yeast Saccharomyces cerevisiae bound to a nucleosome at a resolution of 4.8 Å. Chd1 detaches two turns of DNA from the histone octamer and binds between the two DNA gyres in a state poised for catalysis. The SANT and SLIDE domains contact detached DNA around superhelical location (SHL) -7 of the first DNA gyre. The ATPase motor binds the second DNA gyre at SHL +2 and is anchored to the N-terminal tail of histone H4, as seen in a recent nucleosome-Snf2 ATPase structure. Comparisons with published results reveal that the double chromodomain swings towards nucleosomal DNA at SHL +1, resulting in ATPase closure. The ATPase can then promote translocation of DNA towards the nucleosome dyad, thereby loosening the first DNA gyre and remodelling the nucleosome. Translocation may involve ratcheting of the two lobes of the ATPase, which is trapped in a pre- or post-translocation state in the absence or presence, respectively, of transition state-mimicking compounds. Farnung, Lucas & Vos, Seychelle & Wigge, Christoph & Cramer, Patrick. (2017). Nucleosome–Chd1 structure and implications for chromatin remodelling. Nature. 550. . 10.1038/nature24046. Dionisio

The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint. The past few years have witnessed significant progress in understanding the quantitative mechanisms underlying these varied APC/C functions. This review integrates the overall functions and properties of the APC/C with mechanistic insights gained from recent cryo-electron microscopy (cryo-EM) studies of reconstituted human APC/C complexes. Alfieri, Claudio & Zhang, Suyang & Barford, David. (2017). Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C). Open Biology. 7. 170204. 10.1098/rsob.170204. Dionisio

During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis. Mangal, Sriyash & Sacher, Jennifer & Kim, Taekyung & Osorio, Daniel & Motegi, Fumio & Xavier Carvalho, Ana & Oegema, Karen & Zanin, Esther. (2018). TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis. The Journal of Cell Biology. jcb.201706021. 10.1083/jcb.lkm. Dionisio

Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans are abundant on the cell surface and in the extracellular matrix and have important functions in matrix structure, cell-matrix interaction and signaling. The DS epimerases 1 and 2, encoded by Dse and Dsel, respectively, convert CS to a CS/DS hybrid chain, which is structurally and conformationally richer than CS, favouring interaction with matrix proteins and growth factors. We recently showed that Xenopus Dse is essential for the migration of neural crest cells by allowing cell surface CS/DS proteoglycans to adhere to fibronectin. Here we investigate the expression of Dse and Dsel in Xenopus embryos. We show that both genes are maternally expressed and exhibit partially overlapping activity in the eyes, brain, trigeminal ganglia, neural crest, adenohypophysis, sclerotome, and dorsal endoderm. Dse is specifically expressed in the epidermis, anterior surface ectoderm, spinal nerves, notochord and dermatome, whereas Dsel mRNA alone is transcribed in the spinal cord, epibranchial ganglia, prechordal mesendoderm and myotome. The expression of the two genes coincides with sites of cell differentiation in the epidermis and neural tissue. Several expression domains can be linked to previously reported phenotypes of knockout mice and clinical manifestations, such as the Musculocontractural Ehlers-Danlos syndrome and psychiatric disorders. Gouignard, Nadege & Schön, Tanja & Holmgren, Christian & Strate, Ina & Ta?öz, Emirhan & Wetzel, Franziska & Maccarana, Marco & Pera, Edgar. (2018). Gene expression of the two developmentally regulated dermatan sulfate epimerases in the Xenopus embryo. PLOS ONE. 13. e0191751. 10.1371/journal.pone.0191751. Dionisio

The range of biological outcomes generated by many signalling proteins in development and homeostasis is increased by their interactions with glycosaminoglycans, particularly heparan sulfate (HS). This interaction controls the localization and movement of these signalling proteins, but whether such control depends on the specificity of the interactions is not known. We used five fibroblast growth factors with an N-terminal HaloTag (Halo-FGFs) for fluorescent labelling, with well-characterized and distinct HS-binding properties, and measured their binding and diffusion in pericellular matrix of fixed rat mammary 27 fibroblasts. Halo-FGF1, Halo-FGF2 and Halo-FGF6 bound to HS, whereas Halo-FGF10 also interacted with chondroitin sulfate/dermatan sulfate, and FGF20 did not bind detectably. The distribution of bound FGFs in the pericellular matrix was not homogeneous, and for FGF10 exhibited striking clusters. Fluorescence recovery after photobleaching showed that FGF2 and FGF6 diffused faster, whereas FGF1 diffused more slowly, and FGF10 was immobile. The results demonstrate that the specificity of the interactions of proteins with glycosaminoglycans controls their binding and diffusion. Moreover, cells regulate the spatial distribution of different protein-binding sites in glycosaminoglycans independently of each other, implying that the extracellular matrix has long-range structure. Sun, Changye & Marcello, Marco & Li, Yong & Mason, David & Lévy, Raphaël & G. Fernig, David. (2016). Selectivity in glycosaminoglycan binding dictates the distribution and diffusion of fibroblast growth factors in the pericellular matrix. Open Biology. 6. 150277. 10.1098/rsob.150277. Dionisio

Developmental biology research would benefit greatly from tools that enable protein function to be regulated, both systematically and in a precise spatial and temporal manner, in vivo In recent years, functionalized protein binders have emerged as versatile tools that can be used to target and manipulate proteins. Such protein binders can be based on various scaffolds, such as nanobodies, designed ankyrin repeat proteins (DARPins) and monobodies, and can be used to block or perturb protein function in living cells. In this Primer, we provide an overview of the protein binders that are currently available and highlight recent progress made in applying protein binder-based tools in developmental and synthetic biology. Harmansa, Stefan & Affolter, Markus. (2018). Protein binders and their applications in developmental biology. Development. 145. dev148874. 10.1242/dev.148874. Dionisio

The role of protein localization along the apical-basal axis of polarized cells is difficult to investigate in vivo, partially due to lack of suitable tools. Here, we present the GrabFP system, a collection of four nanobody-based GFP-traps that localize to defined positions along the apical-basal axis. We show that the localization preference of the GrabFP traps can impose a novel localization on GFP-tagged target proteins and results in their controlled mislocalization. These new tools were used to mislocalize transmembrane and cytoplasmic GFP fusion proteins in the Drosophila wing disc epithelium and to investigate the effect of protein mislocalization. Furthermore, we used the GrabFP system as a tool to study the extracellular dispersal of the Decapentaplegic (Dpp) protein and show that the Dpp gradient forming in the lateral plane of the Drosophila wing disc epithelium is essential for patterning of the wing imaginal disc. Harmansa, Stefan & Alborelli, Ilaria & Bieli, Dimi & Caussinus, Emmanuel & Affolter, Markus. (2017). A nanobody-based toolset to investigate the role of protein localization and dispersal in Drosophila. eLife Sciences. 6. . 10.7554/eLife.22549. Dionisio

According to morphogen gradient theory, extracellular ligands produced from a localized source convey positional information to receiving cells by signaling in a concentration-dependent manner. How do morphogens create concentration gradients to establish positional information in developing tissues? Surprisingly, the answer to this central question remains largely unknown. Morphogen transport: theoretical and experimental controversies Takuya Akiyama, Matthew C. Gibson Wiley Interdiscip Rev Dev Biol. 4(2):99-112. doi: 10.1002/wdev.167 Interesting, the same year this paper was published, a distinguished professor claimed to know exactly the answer to that question. Dionisio

Search is a central term in the work of Dr. Dr. William Dembski jr, Dr. Winston Ewert, and Dr. Robert Marks II (DEM): it appears in the title of a couple of papers written by at least two of the authors, and it is mentioned hundreds of times in their textbook “Introduction to Evolutionary Informatics“. Strangely – and in difference from the other central term information, it is not defined in this textbook, and neither is search problem or search algorithm. Luckily, dozens of examples of searches are given. I took a closer look to find out what DEM see as the search problem in the “Introduction to Evolutionary Informatics” and how their model differs from those used by other mathematicians and scientists. http://theskepticalzone.com/wp/the-search-problem-of-william-dembski-winston-ewert-and-robert-marks/ DiEb

Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which allows Cdc20 to activate the APC/C. Both APC/C activation and inhibition depend on Cdc20 fluxing through the same binding site at kinetochores. The microtubule attachment status of kinetochores therefore optimizes mitotic duration by controlling the balance between opposing Cdc20 fates. Kim, Taekyung & Lara-Gonzalez, Pablo & Prevo, Bram & Meitinger, Franz & Cheerambathur, Dhanya & Oegema, Karen & Desai, Arshad. (2017). Kinetochores accelerate or delay APC/C activation by directing Cdc20 to opposing fates. Genes & Development. 31. . 10.1101/gad.302067.117. Dionisio

@307: "pushing rather than pulling"??? Oops!!! sorry... :) Dionisio

@300-307: There yet? :) Dionisio

Oops! it was the opposite!!! :)

Previously, it had been thought that centering during metaphase was due to dynein-dependent cortical pulling forces; however, several mechanical, genetic and theoretical arguments all point to centering by pushing rather than pulling.

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning. Howard J1, Garzon-Coral C2. Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700122. PMID: 28960439 PMCID: PMC5698852 [Available on 2018-11-01] http://onlinelibrary.wiley.com/doi/10.1002/bies.201700122/full Dionisio

@305 "are likely"???!?? Dionisio

“are likely”? not sure yet? :)

[...] pushing forces, generated by microtubule polymerization and using energy derived from the GTPase activity of tubulin, are likely responsible for maintaining the C. elegans mitotic spindle at the cell center during metaphase. [...] cortical pushing and cytoplasmic pulling are likely the principle mechanisms for centering mitotic spindles, while cortical pulling forces are used is move or rotate the spindle away from the cell center.

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning. Howard J1, Garzon-Coral C2. Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700122. PMID: 28960439 PMCID: PMC5698852 [Available on 2018-11-01] http://onlinelibrary.wiley.com/doi/10.1002/bies.201700122/full Dionisio

[...] the conservation of molecular machineries suggests that related mechanisms are likely operating. Microtubules play a key role in spindle positioning. [...] spindle positioning depends both on microtubule dynamics, which is powered by the GTPase activity of tubulin, and on motor proteins, which are powered by ATP hydrolysis. This does not preclude other molecular mechanisms, such as the actin cytoskeleton, also playing a role.

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning. Howard J1, Garzon-Coral C2. Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700122. PMID: 28960439 PMCID: PMC5698852 [Available on 2018-11-01] http://onlinelibrary.wiley.com/doi/10.1002/bies.201700122/full Dionisio

One of the stunning features of cell division is the accuracy and precision with which the mitotic spindle is centered In symmetric cell division the spindle is centered so that when the mother cell is bisected the daughters have equal size. In asymmetric cell division the spindle is often displaced from the center prior to division so that the daughters have unequal sizes and often different fates.[23, 30] Regardless of whether the division is symmetric or asymmetric, the orientation of the spindle is critical for positioning the two daughters within the growing tissue.[21] A key question is to understand the molecular mechanisms underlying spindle positioning and its precision.

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning. Howard J1, Garzon-Coral C2. Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700122. PMID: 28960439 PMCID: PMC5698852 [Available on 2018-11-01] http://onlinelibrary.wiley.com/doi/10.1002/bies.201700122/full Dionisio

The shaping and patterning of living organisms is remarkable in its intricacy yet reproducibility The precision of chemical patterning is limited by fluctuations in the concentrations of morphogens. [...] directed cell movements lead to stratification[18] or elongation of tissues along a specified axis[19]; [...] what are the molecular mechanisms and physical limits that set the precision by which the spindle is positioned and orientated during mitosis [?]

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning. Howard J1, Garzon-Coral C2. Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700122. PMID: 28960439 PMCID: PMC5698852 [Available on 2018-11-01] http://onlinelibrary.wiley.com/doi/10.1002/bies.201700122/full Dionisio

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against- the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning. Howard J1, Garzon-Coral C2. Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700122. PMID: 28960439 PMCID: PMC5698852 [Available on 2018-11-01] http://onlinelibrary.wiley.com/doi/10.1002/bies.201700122/full Dionisio

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces Jonathon Howard, Carlos Garzon-Coral Bioessays. Author manuscript; available in PMC 2018 Nov 1. Published in final edited form as: Bioessays. 2017 Nov; 39(11): 10.1002/bies.201700122. Published online 2017 Sep 28. doi: 10.1002/bies.201700122 PMCID: PMC5698852 Related Manuscript ID: NIHMS918054 Reason: This article has a delayed release (embargo) and will be available in PMC on November 1, 2018. An abstract of the article is available in PubMed, which may also have a link to the full text at the journal site. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698852/ http://onlinelibrary.wiley.com/doi/10.1002/bies.201700122/full Dionisio

Epithelial–mesenchymal transition (EMT) plays key roles during embryonic development, wound healing and cancer metastasis. Cells in a partial EMT or hybrid epithelial/mesenchymal (E/M) phenotype exhibit collective cell migration, forming clusters of circulating tumour cells—the primary drivers of metastasis. Activation of cell–cell signalling pathways such as Notch fosters a partial or complete EMT, yet the mechanisms enabling cluster formation remain poorly understood. [...] future modelling efforts will benefit from integrating the different signalling aspects of Numb and Numbl with population-level models of stem cell division. [...] quantitative differences in effect of Numb versus Numbl, and that in individual versus combined inhibition remain elusive. Numb prevents a complete epithelial–mesenchymal transition by modulating Notch signalling Federico Bocci,1,2,† Mohit K. Jolly,1,† Satyendra C. Tripathi,6,† Mitzi Aguilar,6 Samir M. Hanash,6 Herbert Levine,1,3,4,5 and José N. Onuchic1,2,4,5 J R Soc Interface. 2017 Nov; 14(136): 20170512. doi: 10.1098/rsif.2017.0512 PMCID: PMC5721160 Dionisio

Cell division is commonly thought to involve the equal distribution of cellular components into the two daughter cells. During many cell divisions, however, proteins, membrane compartments, organelles, or even DNA are asymmetrically distributed between the two daughter cells. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer Ralph A. Neumüller and Juergen A. Knoblich Genes Dev. 2009 Dec 1; 23(23): 2675–2699. doi: 10.1101/gad.1850809 PMCID: PMC2788323 Old paper Dionisio

Motor neurons located in the spinal cord and innervating muscle cells throughout the body are responsible for virtually all motor functions, from locomotion to respiration or speech. They arise from differentiation of progenitor cells within the neural tube under spatiotemporally well-defined morphogen concentration profiles, and extend axons into the peripheral nervous system following a precisely orchestrated sequence of events involving secreted chemo-attractants and repellents and dynamic expression of the corresponding ligand receptors. Finally, they form neuromuscular junctions, the synapses that transmit electrical signals to the muscle effectors. Failure for these motor neurons to develop or function properly, caused by developmental or neurodegenerative genetic disorders, or as a result of traumatic injuries, lead to highly incapacitating or even lethal malformation and conditions. Microfabricated platforms and optogenetic technologies have proven to be valuable tools to control the microenvironment, biochemical cues and the stimulation applied to neuronal tissues. Precise control of the geometry of microfluidic devices together with their ability to host 3D cell culture has enhanced the physiological relevance of such neuronal tissues relative to traditional 2D culture assays. And the ability to selectively excite neuronal cells with light has opened tremendous opportunities in the field of neuroscience. In this thesis, we combine these two technologies to stimulate and subject cells to chemical and physical microenvironments that emulate their in vivo counterpart. First, we present a microfluidic platform that generates orthogonal concentration gradients and emulates the confined appearance of motor neurons within the developing spinal cord. Then, we introduce a new device capable of forming a 3D compartmentalized neuron-muscle coculture and demonstrate remote stimulation of the myofibers by the motor neurons resulting in muscle contraction. By targeting the stem cells from which the motor neurons are derived with the light sensitive ion channel Channelrhodopsin, we form, in this microfluidic device, the first in vitro light-activatable neuromuscular junction. Keywords: microfluidics, optogenetics, morphogenesis, cell migration, neuromuscular junctions. G. M Uzel, Sébastien. (2015). Microfluidic and optogenetic technologies to model spinal cord development and neuromuscular junction formation and function. . Dionisio

In response to the commentaries, we have refined our suggested model and discussed ways in which the model could be further expanded. In this context, we have elaborated on the role of specific continuous magnitudes. We have also found it important to devote a section to evidence considered the “smoking gun” of the approximate number system theory, including cross-modal studies, animal studies, and so forth. Lastly, we suggested some ways in which the scientific community can promote more transparent and collaborative research by using an open science approach, sharing both raw data and stimuli. We thank the contributors for their enlightening comments and look forward to future developments in the field. Leibovich-Raveh, Tali & Katzin, Naama & Salti, Moti & Henik, Avishai. (2017). Toward an integrative approach to numerical cognition. Behavioral and Brain Sciences. 40. . 10.1017/S0140525X17000619,. Dionisio

Innovations are generally unexpected, often spectacular changes in phenotypes and ecological functions. The contributions to this theme issue are the latest conceptual, theoretical and experimental developments, addressing how ecology, environment, ontogeny and evolution are central to understanding the complexity of the processes underlying innovations. Here, we set the stage by introducing and defining key terms relating to innovation and discuss their relevance to biological, cultural and technological change. Discovering how the generation and transmission of novel biological information, environmental interactions and selective evolutionary processes contribute to innovation as an ecosystem will shed light on how the dominant features across life come to be, generalize to social, cultural and technological evolution, and have applications in the health sciences and sustainability. This article is part of the theme issue ‘Process and pattern in innovations from cells to societies’. © 2017 The Author(s) Published by the Royal Society. All rights reserved. Hochberg, Michael & A. Marquet, Pablo & Boyd, Robert & Wagner, Andreas. (2017). Innovation: An emerging focus from cells to societies. Philosophical Transactions of the Royal Society B: Biological Sciences. 372. 20160414. 10.1098/rstb.2016.0414. Dionisio

Evolutionary transitions in individuality (ETIs) occur when formerly autonomous organisms evolve to become parts of a new, ‘higher-level’ organism. One of the first major hurdles that must be overcome during an ETI is the emergence of Darwinian evolvability in the higher-level entity (e.g. a multicellular group), and the loss of Darwinian autonomy in the lower-level units (e.g. individual cells). Here, we examine how simple higher-level life cycles are a key innovation during an ETI, allowing this transfer of fitness to occur ‘for free’. Specifically, we show how novel life cycles can arise and lead to the origin of higher-level individuals by (i) mitigating conflicts between levels of selection, (ii) engendering the expression of heritable higher-level traits and (iii) allowing selection to efficiently act on these emergent higher-level traits. Further, we compute how canonical early life cycles vary in their ability to fix beneficial mutations via mathematical modelling. Life cycles that lack a persistent lower-level stage and develop clonally are far more likely to fix ‘ratcheting’ mutations that limit evolutionary reversion to the pre-ETI state. By stabilizing the fragile first steps of an evolutionary transition in individuality, nascent higher-level life cycles may play a crucial role in the origin of complex life. This article is part of the themed issue ‘Process and pattern in innovations from cells to societies’. © 2017 The Author(s) Published by the Royal Society. All rights reserved. Ratcliff, William & Herron, Matthew & Conlin, Peter & Libby, Eric. (2017). Nascent life cycles and the emergence of higher-level individuality. Philosophical Transactions of the Royal Society B: Biological Sciences. 372. 20160420. 10.1098/rstb.2016.0420. Dionisio

The origin of evolutionary innovations is a central problem in evolutionary biology. To what extent such innovations have adaptive or non-adaptive origins is hard to assess in real organisms. This limitation, however, can be overcome using digital organisms, i.e. self-replicating computer programs that mutate, evolve and coevolve within a user-defined computational environment. Here, we quantify the role of the non-adaptive origins of host resistance traits in determining the evolution of ecological interactions among host and parasite digital organisms. We find that host resistance traits arising spontaneously as exaptations increase the complexity of antagonistic host–parasite networks. Specifically, they lead to higher host phenotypic diversification, a larger number of ecological interactions and higher heterogeneity in interaction strengths. Given the potential of network architecture to affect network dynamics, such exaptationsmay increase the persistence of entire communities. Our in silico approach, therefore, may complement current theoretical advances aimed at disentangling the ecological and evolutionary mechanisms shaping species interaction networks. This article is part of the themed issue ‘Process and pattern in innovations from cells to societies’. © 2017 The Author(s) Published by the Royal Society. All rights reserved. A. Fortuna, Miguel & Zaman, Luis & Wagner, Andreas & Bascompte, Jordi. (2017). Non-adaptive origins of evolutionary innovations increase network complexity in interacting digital organisms. Philosophical Transactions of the Royal Society B: Biological Sciences. 372. 20160431. 10.1098/rstb.2016.0431. Dionisio

Sewall Wright's fitness landscape introduced the concept of evolutionary spaces in 1932. George Gaylord Simpson modified this to an adaptive, phenotypic landscape in 1944 and since then evolutionary spaces have played an important role in evolutionary theory through fitness and adaptive landscapes, phenotypic and functional trait spaces, morphospaces and related concepts. Although the topology of such spaces is highly variable, from locally Euclidean to pre-topological, evolutionary change has often been interpreted as a search through a pre-existing space of possibilities, with novelty arising by accessing previously inaccessible or difficult to reach regions of a space. Here I discuss the nature of evolutionary novelty and innovation within the context of evolutionary spaces, and argue that the primacy of search as a conceptual metaphor ignores the generation of new spaces as well as other changes that have played important evolutionary roles. This article is part of the themed issue ‘Process and pattern in innovations from cells to societies’. Erwin, Douglas. (2017). The topology of evolutionary novelty and innovation in macroevolution. Philosophical Transactions of the Royal Society B: Biological Sciences. 372. 20160422. 10.1098/rstb.2016.0422. Dionisio

The history of life as documented by the fossil record encompasses evolutionary diversifications at scales ranging from the Ediacaran-Cambrian explosion of animal life and the invasion of land by vascular plants, insects and vertebrates to the diversification of flowering plants over the past 100 million years and the radiation of horses. Morphological novelty and innovation has been a recurrent theme. The architects of the modern synthesis of evolutionary theory made three claims about evolutionary novelty and innovation: first, that all diversifications in the history of life represent adaptive radiations; second, that adaptive radiations are driven principally by ecological opportunity rather than by the supply of new morphological novelties, thus the primary questions about novelty and innovation focus on their ecological and evolutionary success; and third, that the rate of morphological divergence between taxa was more rapid early in the history of a clade but slowed over time as ecological opportunities declined. These claims have strongly influenced subsequent generations of evolutionary biologists, yet over the past two decades each has been challenged by data from the fossil record, by the results of comparative phylogenetic analyses and through insights from evolutionary developmental biology. Consequently a broader view of novelty and innovation is required. An outstanding issue for future work is identifying the circumstances associated with different styles of diversification and whether their frequency has changed through the history of life. Erwin, Douglas. (2015). Novelty and Innovation in the History of Life. Current Biology. 25. R930-R940. 10.1016/j.cub.2015.08.019. Dionisio

Since the last major theoretical integration in evolutionary biology—the modern synthesis (MS) of the 1940s—the biosciences have made significant advances. The rise of molecular biology and evolutionary developmental biology, the recognition of ecological development, niche construction and multiple inheritance systems, the ‘-omics’ revolution and the science of systems biology, among other developments, have provided a wealth of new knowledge about the factors responsible for evolutionary change. Some of these results are in agreement with the standard theory and others reveal different properties of the evolutionary process. A renewed and extended theoretical synthesis, advocated by several authors in this issue, aims to unite pertinent concepts that emerge from the novel fields with elements of the standard theory. The resulting theoretical framework differs from the latter in its core logic and predictive capacities. Whereas the MS theory and its various amendments concentrate on genetic and adaptive variation in populations, the extended framework emphasizes the role of constructive processes, ecological interactions and systems dynamics in the evolution of organismal complexity as well as its social and cultural conditions. Single-level and unilinear causation is replaced by multilevel and reciprocal causation. Among other consequences, the extended framework overcomes many of the limitations of traditional gene-centric explanation and entails a revised understanding of the role of natural selection in the evolutionary process. All these features stimulate research into new areas of evolutionary biology. Müller, Gerd. (2017). Why an extended evolutionary synthesis is necessary. Interface Focus. 7. 20170015. 10.1098/rsfs.2017.0015. Dionisio

The encounter in the 1960s between molecular biology and evolutionary biology had short- and long-term consequences. Comparison of protein sequences suggested that evolution proceeded at a regular pace, obeying a molecular clock. It rapidly led evolutionary biologists to give neutral variations a larger role in their models. The development of genetic engineering technologies opened the door to progressive replacement of the abstract notions of gene and gene mutation hitherto used by evolutionary biologists by precise molecular descriptions. The precise structural and functional characterization of mutations assumed an increasing role and supported the introduction of a hierarchy between genes and between gene mutations that is clearly visible in evolutionary developmental biology. I will examine how far the accumulation of molecular data has challenged the Modern Synthesis established in the 1940s. In particular, different molecular mechanisms have been successively proposed to support a Lamarckian form of evolution. My conclusion will be that molecularization of evolutionary biology is still in its infancy, and that the Modern Synthesis will be replaced by a functional synthesis in which models of evolutionary biology and a description of molecular mechanisms will be intimately dovetailed. Morange, Michel. (2017). Molecularizing Evolutionary Biology. 271-288. 10.1007/978-3-319-69123-7_12. Dionisio

In this paper, We study an one--dimensional morphogenesis model considered by C. Stinner et al. in (Math. Meth. Appl. Sci. 2012,35 (445-465). Under homogeneous boundary conditions, we prove the existence of nonconstant positive steady states through local bifurcation theories. We also rigorously study the stability of the nonconstant solutions when the sensitivity function are chosen to be linear and logarithmic function respectively. Finally, we present numerical solutions to illustrate the formation of stable spatially inhomogeneous patterns. Our numerical simulations suggests that this model can develop very complicated and interesting structures even over one--dimensional finite domains. Chen, Haohao & Tong, Bo & Wang, Qi. (2014). Existence and stability of nonconstant positive steady states of morphogenesis models. Mathematical Methods in the Applied Sciences. 38. . 10.1002/mma.3321. Dionisio

Morphogen transport is a biological process, occurring in the tissue of living organisms, which is a determining step in cell differentiation. We present rigorous analysis of a simple model of this process, which is a system coupling parabolic PDE with ODE. We prove existence and uniqueness of solutions for both stationary and evolution problems. Moreover we show that the solution converges exponentially to the equilibrium in $C^1times C^0$ topology. We prove all results for arbitrary dimension of the domain. Our results improve significantly previously known results for the same model in the case of one dimensional domain. Ma?ogrosz, Marcin. (2011). Well-posedness and asymptotic behavior a multidimensional model of morphogen transport. Journal of Evolution Equations. 12. . 10.1007/s00028-012-0135-5. Dionisio

We analyse a one dimensional version of a model of morphogen transport, a biological process governing cell differentiation. The model was proposed by Hufnagel et al. to describe the forming of morphogen gradient in the wing imaginal disc of the fruit fly. In mathematical terms the model is a system of reaction-diffusion equations which consists of two parabolic PDE's and three ODE's. The source of ligands is modelled by a Dirac Delta. Using semigroup approach and $L_1$ techniques we prove that the system is well-posed and possesses a unique steady state. All results are proved without imposing any artificial restrictions on the range of parameters. Ma?ogrosz, Marcin. (2012). A model of morphogen transport in the presence of glypicans I. Nonlinear Analysis: Theory, Methods & Applications. 83. . 10.1016/j.na.2012.10.012. Dionisio

A model of morphogen transport consisting of two evolutionary PDEs of reaction-diffusion type and three ODEs posed on a rectangular domain is analysed. We prove that the problem is globally well-posed and that the corresponding solutions converge, as the width of the rectangle tends to zero, to the unique solution of the one dimensional system which was analyzed in the first paper of the series. Main difficulties in the analysis stem from the presence of a singular source term - a Dirac Delta combined with no smoothing effect in the ODE part of the system. Ma?ogrosz, Marcin. (2014). A model of morphogen transport in the presence of glypicans II. . . . 10.1016/j.jmaa.2015.07.053. Dionisio

We analyse a stationary problem for the two dimensional model of morphogen transport introduced by Hufnagel et al. The model consists of one linear elliptic PDE posed on a rectangle which is coupled via a nonlinear boundary condition with a second order semilinear ODE posed on the side of the domain. The main result of the article is the existence of the unique steady state for all ranges of parameters present in the system. Moreover, we consider the problem of the dimension reduction. After introducing an appropriate scaling in the model we prove that the stationary solution converges to the unique steady state of the one-dimensional simplification of the model which was analysed in the first part of the series of papers. The main difficulty in obtaining appropriate estimates stems from the presence of a measure source term in the boundary condition. Ma?ogrosz, Marcin. (2015). A model of morphogen transport in the presence of glypicans III. Nonlinear Analysis: Real World Applications. 31. . 10.1016/j.nonrwa.2016.01.007. Dionisio

Morphogens are diffusive molecules produced by cells, sending signals to neighboring cells in tissues for communication. As a result, tissues develop cellular patterns that depend on the concentration levels of the morphogens. The formation of morphogen gradients is among the most fundamental biological processes during development, regeneration, and disease. During the past two decades, sophisticated mathematical models have been utilized to decipher the complex biological mechanisms that regulate the spatial and temporal dynamics of morphogens. Here, we review the model formulations for morphogen systems and present the mathematical questions and challenges that arise from the model analysis, with an emphasis on Drosophila. We discuss several important aspects of modeling frameworks: robustness, stochastic dynamics, growth control, and mechanics of morphogen-mediated patterning. Lei, Jinzhi & Lo, Wing Cheong & Nie, Qing. (2016). Mathematical models of morphogen dynamics and growth control. Annals of Mathematical Sciences and Applications. 1. 427-471. 10.4310/AMSA.2016.v1.n2.a6. Dionisio

Very old paper: In the development of a biological entity, ligands (such as Decapentaplegic (Dpp) along the anterior-posterior axis of the Drosophila wing imaginal disc) are synthesized at a localized source and transported away from the source for binding with cell surface receptors to form concentration gradients of ligand-receptor complexes for cell signaling. Generally speaking, activities such as diffusion and reversible binding with degradable receptors also take place in the region of ligand production. The effects of such morphogen activities in the region of localized distributed ligand source on the ligand-receptor concentration gradient in the entire biological entity have been modeled and analyzed as System F in [1]. In this paper, we deduce from System F, a related end source model (System A) in which the effects of the distributed ligand source is replaced by an idealized point stimulus at the border between the (posterior) chamber and the ligand production region that simulates the average effects of the ligand activities in the production zone. This aggregated end source model is shown to adequately reproduce the significant implications of System F and to contain the corresponding ad hoc point source model, System R of [2], as a special case. Because of its simpler mathematical structure and the absence of any limitation on the ligand synthesis rate for the existence of steady-state gradients, System A type models are expected to be used widely. An example of such application is the recent study of the inhibiting effects of the formation of nonsignaling ligand-nonreceptor complexes [3]. Lander, AD & Nie, Q & Vargas, B & Y M Wan, F. (2005). Aggregation of a Distributed Source in Morphogen Gradient Formation. SIAM journal on applied dynamical systems. 114. 343-374. 10.1111/j.0022-2526.2005.01556.x. Dionisio

Influenza A virus (IAV) consists of eight viral RNA (vRNA) segments that are replicated in the host cell nucleus and transported to the plasma membrane for packaging into progeny virions. We have previously proposed a model where subcomplexes of vRNA are exported from the nucleus and assembled en route to the plasma membrane. However, the role of host cytoskeletal proteins in the cytoplasmic assembly of IAV vRNA segments remains unknown. Previous studies have suggested that IAV vRNA segments are transported via Rab11A-containing recycling endosomes (RE) and use both microtubules (MT) and actin. Rab11A RE transport primarily along MT; therefore, investigation of the role of MT in vRNA assembly is warranted. We explored the role of MT in vRNA assembly and replication by using multiple IAV strains in various cell types, including primary human airway epithelial cells. We observed that Rab11A localization was altered in the presence of MTdepolymerizing drugs, but growth of IAV in all of the cell types tested was unchanged. Fluorescent in situ hybridization was performed to determine the role of MT in the assembly of multiple vRNA segments. Unexpectedly, we found that vRNAvRNA association in cytoplasmic foci was independent of MT. Given the disparity of localization between Rab11A and vRNA segments in the absence of intact MT filaments, we analyzed the three-dimensional spatial relationship between Rab11A and vRNA in the cytoplasm of infected cells. We found that Rab11A and vRNA colocalization is dependent upon dynamic MT filaments. Taken together, our data suggest that cytoplasmic transport of influenza vRNA may include a Rab11A RE-independent mechanism.

Nturibi, Eric & R. Bhagwat, Amar & Coburn, Stefanie & M. Myerburg, Mike & Lakdawala, Seema. (2017). Intracellular Colocalization of Influenza Viral RNA and Rab11A Is Dependent upon Microtubule Filaments. Journal of Virology. 91. JVI.01179-17. 10.1128/JVI.01179-17.

Dionisio

Cell division-cytokinesis-involves large-scale rearrangements of the entire cell. Primarily driven by cytoskeletal proteins, cytokinesis also depends on topological rearrangements of the plasma membrane, which are coordinated with nuclear division in both space and time. Despite the fundamental nature of the process, different types of eukaryotic cells show variations in both the structural mechanisms of cytokinesis and the regulatory controls. In animal cells and fungi, a contractile actomyosin-based structure plays a central, albeit flexible, role. Here, the underlying molecular mechanisms are summarized and integrated and common themes are highlighted.

Glotzer, Michael. (2016). Cytokinesis in Metazoa and Fungi. Cold Spring Harbor perspectives in biology. 9. . 10.1101/cshperspect.a022343.

Dionisio

@278 addendum

After reading recent reviews on cytokinesis (D’Avino et al., 2015; Willet et al., 2015b; Cheffings et al., 2016; Glotzer, 2016; Meitinger and Palani, 2016; Bhavsar-Jog and Bi, 2017), a new research assistant in a friend’s laboratory asked, “Because so much is known about cytokinesis, why is research on cytokinesis still important?” Although much has been learned in the past 40 yr since cell biologists reported in the Journal of Cell Biology the first molecules contributing to cytokinesis, actin filaments (Schroeder, 1972), and myosin-II (Fujiwara and Pollard, 1976; Mabuchi and Okuno, 1977), the process is so complicated that many fundamental questions remain. Nine questions, most posed 40 to 50 yr ago, remain unanswered or incompletely understood (Fig. 1).

Nine unanswered questions about cytokinesis Thomas D. Pollard J Cell Biol Aug 2017, jcb.201612068; DOI: 10.1083/jcb.201612068 http://jcb.rupress.org/content/early/2017/08/11/jcb.201612068

No comments. Dionisio

Experiments on model systems have revealed that cytokinesis in cells with contractile rings (amoebas, fungi, and animals) depends on shared molecular mechanisms in spite of some differences that emerged during a billion years of divergent evolution. Understanding these fundamental mechanisms depends on identifying the participating proteins and characterizing the mechanisms that position the furrow, assemble the contractile ring, anchor the ring to the plasma membrane, trigger ring constriction, produce force to form a furrow, disassemble the ring, expand the plasma membrane in the furrow, and separate the daughter cell membranes. This review reveals that fascinating questions remain about each step. D. Pollard, Thomas. (2017). Nine unanswered questions about cytokinesis. The Journal of Cell Biology. 216. jcb.201612068. 10.1083/jcb.201612068. http://jcb.rupress.org/content/early/2017/08/11/jcb.201612068.full-text.pdf Dionisio

Fluorescent nanodiamonds are promising probes for nanoscale magnetic resonance measurements. Their physical properties predict them to have particularly useful applications in intracellular analysis. Before using them in intracellular experiments however, it should be clear whether diamond particles influence cell biology. While cytotoxicity has already been ruled out in previous studies, we consider the non-fatal influence of fluorescent nanodiamonds on the formation of reactive oxygen species (an important stress indicator and potential target for intracellular sensing) for the first time. We investigated the influence of different sizes, shapes and concentrations of nanodiamonds on the genetic and protein level involved in oxidative stress-related pathways of the HeLa cell, an important model cell line in research. The changes in viability of the cells and the difference in intracellular levels of free radicals, after diamond uptake, are surprisingly small. At lower diamond concentrations, the cellular metabolism cannot be distinguished from that of untreated cells. This research supports the claims of non-toxicity and includes less obvious non-fatal responses. Finally, we give a handhold concerning the diamond concentration and size to use for non-toxic, intracellular measurements in favour of (cancer) research in HeLa cells. Hemelaar, Simon & Saspaanithy, Babujhi & R. M. L’Hommelet, Severin & P. Perona Martinez, Felipe & J. van der Laan, Kiran & Schirhagl, R. (2018). The Response of HeLa Cells to Fluorescent NanoDiamond Uptake. Sensors. 18. 355. 10.3390/s18020355. Dionisio

Cytokinesis cleaves a cell into two daughters at the end of mitosis, and must be spatially coordinated with chromosome segregation to prevent aneuploidy. The dogma is that the mitotic spindle governs the assembly and constriction of an actomyosin ring. Here, we reveal a function for active Ran in spatially restricting the ring. Our model is that during anaphase, 'free' importins, whose gradient inversely correlates with active Ran and chromatin position, function as a molecular ruler for the recruitment and localization of anillin, a contractile protein and crucial regulator of cytokinesis. We found that decreasing Ran-GTP levels, or tethering active Ran to the equatorial membrane affects anillin's localization and causes cytokinesis phenotypes. Anillin contains a conserved Nuclear Localization Signal (NLS) in its C-terminus that binds to importin-?, and is required for cortical polarity and cytokinesis. Mutating the NLS decreases anillin's cortical affinity, causing it to be more dominantly regulated by microtubules. Anillin contains a RhoA-GTP binding domain, which autoinhibits the NLS and neighbouring microtubule-binding domain, and RhoA-GTP binding may relieve this inhibition during mitosis. Retention of the C-terminal NLS in anillin homologues suggests that this is a conserved mechanism to control anillin function. Beaudet, Daniel & Akhshi, Tara & Phillipp, Julia & Law, Christopher & Piekny, Alisa. (2017). Active Ran regulates anillin function during cytokinesis. Molecular Biology of the Cell. 28. mbc.E17-04. 10.1091/mbc.E17-04-0253. Dionisio

@274 & @276 Very interesting Dionisio

During cytokinesis, a contractile ring generates the constricting force to divide a cell into two daughters. This ring is composed of filamentous actin and the motor protein myosin, along with additional structural and regulatory proteins, including anillin. Anillin is a required scaffold protein that links the actomyosin ring to membrane and its organizer, RhoA. However, the molecular basis for timely action of anillin at cytokinesis remains obscure. Here, we find that phosphorylation regulates efficient recruitment of human anillin to the equatorial membrane. Anillin is highly phosphorylated in mitosis, and is a substrate for mitotic kinases. We surveyed function of 46 residues on anillin previously found to be phosphorylated in human cells to identify those required for cytokinesis. Among these sites, we identified S635 as a key site mediating cytokinesis. Preventing S635 phosphorylation adjacent to the AH domain disrupts anillin concentration at the equatorial cortex at anaphase, whereas a phosphomimetic mutant, S635D, partially restores this localization. Time-lapse videomicroscopy reveals impaired recruitment of S635A anillin to equatorial membrane and a transient unstable furrow followed by ultimate failure in cytokinesis. A phosphospecific antibody confirms phosphorylation at S635 in late cytokinesis, although it does not detect phosphorylation in early cytokinesis, possibly due to adjacent Y634 phosphorylation. Together, these findings reveal that anillin recruitment to the equatorial cortex at anaphase onset is enhanced by phosphorylation and promotes successful cytokinesis. Kim, Hyunjung & M. Johnson, James & Lera, Robert & Brahma, Sarang & E. Burkard, Mark. (2017). Anillin Phosphorylation Controls Timely Membrane Association and Successful Cytokinesis. PLOS Genetics. 13. e1006511. 10.1371/journal.pgen.1006511. Dionisio

The processing of amyloid precursor protein (APP) to the neurotoxic pro-aggregatory A? peptide is controlled by the mechanisms that govern the trafficking and localisation of APP. We hypothesised that genes involved in endosomal protein sorting could play an important role in regulating APP processing and, therefore, analysed ~ 40 novel endosome-to-Golgi retrieval genes previously identified in a genome-wide siRNA screen. We report that phospholipase D3 (PLD3), a type II membrane protein, functions in endosomal protein sorting and plays an important role in regulating APP processing. PLD3 co-localises with APP in endosomes and loss of PLD3 function results in reduced endosomal tubules, impaired trafficking of several membrane proteins and reduced association of sortilin-like 1 with APP. S. Mukadam, Aamir & Y. Breusegem, Sophia & Seaman, Matthew. (2018). Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing. Cellular and Molecular Life Sciences. . 10.1007/s00018-018-2752-9. Dionisio

Necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis. Here, we show that the ?-herpesvirus Epstein–Barr virus (EBV) blocks necroptosis in EBV-infected human nasopharyngeal epithelial cells and nasopharyngeal carcinoma cells. Our findings indicate that EBV-encoded latent membrane protein 1 (LMP1), which lacks an RIP homotypic interaction motif (RHIM) domain, has mechanisms distinct from RHIM signaling competition to inhibit this necroptotic pathway. Intriguingly, LMP1 interacts directly with both RIPK1 and RIPK3 through its C-terminal activation region. More importantly, LMP1 can modulate the post-translational modification of the two receptor-interacting proteins. We then show that LMP1-mediated promotion of K63-polyubiquitinated RIPK1, suppression of RIPK1 protein expression and inhibition of K63-polyubiquitinated RIPK3 induced a switch in cell fate from necroptotic death to survival. These findings provide direct evidence for the suppression of necroptosis by EBV and define a mechanism of LMP1 to interrupt the initiation process of necroptosis before necrosome formation. Liu, Xiaolan & Li, Yueshuo & Peng, Songling & yu, Xinfang & Li, Wei & Shi, Feng & Luo, Xiangjian & Tang, Min & Tan, Zheqiong & Bode, Ann & Cao, Ya. (2018). Epstein-Barr virus encoded latent membrane protein 1 suppresses necroptosis through targeting RIPK1/3 ubiquitination. Cell Death & Disease. 9. 53. 10.1038/s41419-017-0081-9. Dionisio

Acute respiratory distress syndrome (ARDS) is the leading cause of death in critical care medicine. The syndrome is typified by an exaggerated inflammatory response within the lungs. ARDS has been reported in many species, including dogs. We have previously reported a fatal familial juvenile respiratory disease accompanied by occasional unilateral renal aplasia and hydrocephalus, in Dalmatian dogs. The condition with a suggested recessive mode of inheritance resembles acute exacerbation of usual interstitial pneumonia in man. We combined SNP-based homozygosity mapping of two ARDS-affected Dalmatian dogs and whole genome sequencing of one affected dog to identify a case-specific homozygous nonsense variant, c.31C>T; p.R11* in the ANLN gene. Subsequent analysis of the variant in a total cohort of 188 Dalmatians, including seven cases, indicated complete segregation of the variant with the disease and confirmed an autosomal recessive mode of inheritance. Low carrier frequency of 1.7% was observed in a population cohort. The early nonsense variant results in a nearly complete truncation of the ANLN protein and immunohistochemical analysis of the affected lung tissue demonstrated the lack of the membranous and cytoplasmic staining of ANLN protein in the metaplastic bronchial epithelium. The ANLN gene encodes an anillin actin binding protein with a suggested regulatory role in the integrity of intercellular junctions. Our study suggests that defective ANLN results in abnormal cellular organization of the bronchiolar epithelium, which in turn predisposes to acute respiratory distress. ANLN has been previously linked to a dominant focal segmental glomerulosclerosis in human without pulmonary defects. However, the lack of similar renal manifestations in the affected Dalmatians suggest a novel ANLN-related pulmonary function and disease association. Holopainen, Saila & Hytönen, Marjo & Syrja, Pernilla & Arumilli, Meharji & Järvinen, Anna-Kaisa & Rajamäki, Minna & Lohi, Hannes. (2017). ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs. PLoS genetics. 13. e1006625. 10.1371/journal.pgen.1006625. Dionisio

The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the C. elegans one-cell embryo, the astral microtubule dependent pathway requires anillin, NOP-1 and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the G?-dependent force-generating complex that positions the spindle during asymmetric division. However, whether LET-99's role in cytokinesis is specific to asymmetric division, and whether it acts through G? to promote furrowing is unclear. Here we show that LET-99 localizes to the equator in the symmetrically dividing AB cell where it is required for astral microtubule dependent furrowing, but G? is not needed. LET-99 acts in a pathway parallel to anillin and is required for myosin enrichment into the contractile ring. These and other results suggest a feedback model in which LET-99 localizes to the presumptive cleavage furrow in response to the spindle and myosin. Once positioned there, LET-99 enhances myosin accumulation to promote furrowing in both symmetrically and asymmetrically dividing cells. L. Price, Kari & S. Rose, Lesilee. (2017). LET-99 functions in the astral furrowing pathway where it is required for myosin enrichment in the contractile ring. Molecular Biology of the Cell. 28. mbc.E16-12. 10.1091/mbc.E16-12-0874. Dionisio

During female meiosis, haploid eggs are generated from diploid oocytes. This reduction in chromosome number occurs through two highly asymmetric cell divisions resulting in one large egg and two small polar bodies. Unlike mitosis, where an actomyosin contractile ring forms between the sets of segregating chromosomes, the meiotic contractile ring forms on the cortex adjacent to one spindle pole, then ingresses down the length of the spindle to position itself at the exact midpoint between the two sets of segregating chromosomes. Depletion of casein kinase 1 gamma (CSNK-1) in C. elegans led to the formation of large polar bodies that contain all maternal DNA because the contractile ring ingressed past the spindle midpoint. Depletion of CSNK-1 also resulted in the formation of deep membrane invaginations during meiosis, suggesting an effect on cortical myosin. Both myosin and anillin assemble into dynamic rho-dependent cortical patches that rapidly disassemble in wild-type embryos. CSNK-1 was required for disassembly of both myosin patches and anillin patches. Disassembly of anillin patches was myosin independent suggesting that CSNK-1 prevents expulsion of the entire meiotic spindle into a polar body by negatively regulating the rho pathway rather than through direct inhibition of myosin. Flynn, Jonathan & J. McNally, Francis. (2017). A Casein Kinase 1 Prevents Expulsion of the Oocyte Meiotic Spindle into a Polar Body by Regulating Cortical Contractility. Molecular Biology of the Cell. 28. mbc.E17-01. 10.1091/mbc.E17-01-0056. Dionisio

@267 addendum Van Arsdale, Adam. (2017). Human Evolution as a Theoretical Model for an Extended Evolutionary Synthesis. 105-130. 10.1007/978-3-319-69123-7_6. Dionisio

Humans have occupied a paradoxical position within the history of evolutionary studies. On one end, humans have been central to both the academic motivation of the field and the public tensions surrounding evolution. Simultaneously, humans have been cast aside as a poor model organism for understanding the processes that underlie evolutionary theory. As a result, anthropologists who work within an evolutionary context, often chided as being two decades behind mainstream biology, have come to occupy a unique position with respect to the understanding of how evolution operates on humans. Incorporating theoretical developments from a diverse set of related evolutionary fields, biological anthropologists have begun to gather empirical data on the unique evolutionary processes that have shaped our own evolutionary path. Some of the important components that have emerged in human evolutionary studies—biocultural feedback systems, culturally mediated niche construction, and technological ratchet effects—have shed new light not only on how human evolution has proceeded but also on the range of capabilities of evolution more broadly. While not rejecting traditional neo-Darwinian theory and the importance of genetic inheritance, these new developments have highlighted the tremendous complexity afforded by the cumulative action of both selective and neutral evolutionary forces across a range of inheritance modes. Rather than a poor evolutionary model, many of these evolutionary processes are best, or perhaps only, observable in humans. The traits which have structured critical transitions in our hominin past—encephalization, expanded childhood development, and generative language—open up new windows into thinking about an Extended Evolutionary Synthesis. Where's the beef? Dionisio

Zinc is a metal ion that is an essential cell signaling molecule. Highlighting this, zinc is an insulin mimetic, activating cellular pathways that regulate cellular homeostasis and physiological responses. Previous studies have linked dysfunctional zinc signaling with several disease states including cancer, obesity, cardiovascular disease and type 2 diabetes. The present study evaluated the insulin-like effects of zinc on cell signaling molecules including tyrosine, PRSA40, Akt, ERK1/2, SHP-2, GSK-3? and p38, and glucose oxidation in human and mouse skeletal muscle cells. Insulin and zinc independently led to the phosphorylation of these proteins over a 60-minute time course in both mouse and human skeletal muscle cells. Similarly, utilizing a protein array we identified that zinc could active the phosphorylation of p38, ERK1/2 and GSK-3B in human and ERK1/2 and GSK-3B in mouse skeletal muscle cells. Glucose oxidation assays were performed on skeletal muscle cells treated with insulin, zinc, or a combination of both and resulted in a significant induction of glucose consumption in mouse (p<0.01) and human (p<0.05) skeletal muscle cells when treated with zinc alone. Insulin, as expected, increased glucose oxidation in mouse (p<0.001) and human (0.001) skeletal muscle cells, however the combination of zinc and insulin did not augment glucose consumption in these cells. Zinc acts as an insulin mimetic, activating key molecules implicated in cell signaling to maintain glucose homeostasis in mouse and human skeletal muscle cells. Zinc is an important metal ion implicated in several biological processes. The role of zinc as an insulin memetic in activating key signaling molecules involved in glucose homeostasis could provide opportunities to utilize this ion therapeutically in treating disorders associated with dysfunctional zinc signaling. (2018). Zinc stimulates glucose oxidation and glycemic control by modulating the insulin signaling pathway in human and mouse skeletal muscle cell lines. PLOS ONE. 13. e0191727. 10.1371/journal.pone.0191727. Dionisio

@264: More questions than answers? What else is new? Dionisio

Human cardiac muscle cells are the most physically energetic cells in the body, and according to various researchers they contain two nuclei in 25–40%. In humans, the heart during prenatal development consists mainly of cardiomyocytes with one nucleus. Just before birth, binucleation begins and can extend into early neonatal life. The physiological importance of binucleation is still poorly understood. In this critical review, we provide a summary of the latest research on binucleation of cardiac muscle cells, with special emphasis on the potential application of such knowledge to the fields of regenerative medicine. We summed up and discussed about ten possible biological arguments why binucleation may be beneficial for cardiac muscle cells as well as for the whole myocardium. These arguments include increase of gene expression, purposeful cell shaping, increase of metabolic activity, energy-saving growth and function, need for organ growth despite of telomere depletion, adaptation to stress (tissue regeneration), prevention of overgrowth – organ shaping, prevention of aneuploidy, terminally differentiated state (cardiomyocytes exit the cell cycle, end of proliferation activity); or, we hypothesize, binucleation is just an unwanted side product. Miko, Michal & Kyselovic, Jan & Danišovi?, ?uboš & Barczi, Tomas & Polak, Stefan & Varga, Ivan. (2017). Two nuclei inside a single cardiac muscle cell. More questions than answers about the binucleation of cardiomyocytes. Biologia. 72. . 10.1515/biolog-2017-0107. Dionisio

Stable cytoplasmic bridges arise from failed cytokinesis, the last step of cell division, and are a key feature of syncytial architectures in the germ line of most metazoans. Whereas the C. elegans germ line is syncytial, its formation remains poorly understood. We found that the germline precursor blastomere, P4, fails cytokinesis, leaving a stable cytoplasmic bridge between the two daughter cells, Z2 and Z3 Depletion of several regulators of actomyosin contractility resulted in a regression of the membrane partition between Z2 and Z3, indicating that they are required to stabilize the cytoplasmic bridge. Epistatic analysis revealed a pathway in which Rho regulators promote accumulation of the non-cannonical anillin ANI-2 at the stable cytoplasmic bridge, which in turns promotes the accumulation of the non-muscle myosin II NMY-2 and the midbody component CYK-7 at the bridge, in part by limiting the accumulation of canonical anillin ANI-1. Our results uncover key steps in C. elegans germline formation and define a set of conserved regulators that are enriched at the primordial germ cell cytoplasmic bridge to ensure its stability during embryonic development. Goupil, Eugénie & Amini, Rana & H. Hall, David & Labbé, Jean-Claude. (2017). Actomyosin contractility regulators stabilize the cytoplasmic bridge between the two primordial germ cells during C. elegans embryogenesis. Molecular Biology of the Cell. 28. mbc.E17-08. 10.1091/mbc.E17-08-0502. Dionisio

The anaphase-promoting complex/cyclosome (APC/C) is a large multisubunit ubiquitin ligase that triggers the metaphase-to-anaphase transition in the cell cycle by targeting the substrates cyclin B and securin for destruction. APC/C activity toward these two key substrates requires the coactivator Cdc20. To ensure that cells enter mitosis and partition their duplicated genome with high accuracy, APC/C(Cdc20) activity must be tightly controlled. Here, we discuss the mechanisms that regulate APC/C(Cdc20) activity both before and during mitosis. We focus our discussion primarily on the chromosomal pathways that both accelerate and delay APC/C activation by targeting Cdc20 to opposing fates. The findings discussed provide an overview of how cells control the activation of this major cell cycle regulator to ensure both accurate and timely cell division. Lara-Gonzalez, Pablo & Kim, Taekyung & Desai, Arshad. (2017). Taming the Beast: Control of APC/C Cdc20 -Dependent Destruction. Cold Spring Harbor Symposia on Quantitative Biology. 033712. 10.1101/sqb.2017.82.033712. Dionisio

Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the APC/C. Here, we show that flux of Cdc20 through kinetochores also accelerates mitotic exit by promoting its dephosphorylation by kinetochore-localized protein phosphatase 1, which allows Cdc20 to activate the APC/C. Both APC/C activation and inhibition depend on Cdc20 fluxing through the same binding site at kinetochores. The microtubule attachment status of kinetochores therefore optimizes mitotic duration by controlling the balance between opposing Cdc20 fates. Kim, Taekyung & Lara-Gonzalez, Pablo & Prevo, Bram & Meitinger, Franz & Cheerambathur, Dhanya & Oegema, Karen & Desai, Arshad. (2017). Kinetochores accelerate or delay APC/C activation by directing Cdc20 to opposing fates. Genes & Development. 31. . 10.1101/gad.302067.117. Dionisio

Blebs are involved in various biological processes such as cell migration, cytokinesis, and apoptosis. While the expansion of blebs is largely an intracellular pressure-driven process, the retraction of blebs is believed to be driven by RhoA activation that leads to the reassembly of the actomyosin cortex at the bleb membrane. However, it is still poorly understood how RhoA is activated at the bleb membrane. Here, we provide evidence demonstrating that nonmuscle myosin II-interacting guanine nucleotide exchange factor (MYOGEF) is implicated in bleb retraction via stimulating RhoA activation and the reassembly of an actomyosin network at the bleb membrane during bleb retraction. Interactions of MYOGEF with ezrin, a well-known regulator of bleb retraction, are required for MYOGEF localization to retracting blebs. Notably, knockout of MYOGEF or ezrin not only disrupts RhoA activation at the bleb membrane, but also interferes with nonmuscle myosin II localization and activation as well as actin polymerization in retracting blebs. Importantly, MYOGEF knockout slows down bleb retraction. We propose that ezrin interacts with MYOGEF and recruits it to retracting blebs, where MYOGEF activates RhoA and promotes the reassembly of the cortical actomyosin network at the bleb membrane, thus contributing to the regulation of bleb retraction. Jiao, Mona & Wu, Di & Wei, Qize. (2018). Myosin II-interacting guanine nucleotide exchange factor (MYOGEF) promotes bleb retraction via stimulating cortex reassembly at the bleb membrane. Molecular Biology of the Cell. mbc.E17-10. 10.1091/mbc.E17-10-0579. Dionisio

During cytokinesis, a signal from the central spindle that forms between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis. TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis Sriyash Mangal, Jennifer Sacher, Taekyung Kim, Daniel Sampaio Osório, Fumio Motegi, Ana Xavier Carvalho, Karen Oegema, Esther Zanin J Cell Biol Jan 2018, jcb.201706021; DOI: 10.1083/jcb.201706021 Dionisio

The position of the spindle determines the position of the cleavage plane, and is thus crucial for cell division. Although spindle positioning has been extensively studied, the underlying forces ultimately responsible for moving the spindle remain poorly understood. A recent pioneering study by Garzon-Coral et al. uses magnetic tweezers to perform the first direct measurements of the forces involved in positioning the mitotic spindle. Combining this with molecular perturbations and geometrical effects, they use their data to argue that the forces that keep the spindle in its proper position for cell division arise from astral microtubules growing and pushing against the cell's cortex. Here, we review these ground-breaking experiments, the various biomechanical models for spindle positioning that they seek to differentiate, and discuss new questions raised by these measurements. Forces positioning the mitotic spindle: Theories, and now experiments. Wu HY1,2, Nazockdast E3, Shelley MJ3,4, Needleman DJ2,5 Bioessays. 2017 Feb;39(2). doi: 10.1002/bies.201600212. Epub 2016 Dec 27. Dionisio

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against- the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells. Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning. Howard J1, Garzon-Coral C2 Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700122. Epub 2017 Sep 28. Dionisio

During cell division, the correct positioning and orientation of the mitotic spindle are important for the developmental fate of the daughter cells. [...] the centering of the mitotic spindle in the one-cell C. elegans embryo is highly precise and stable. [...] the accuracy, precision, and stability of spindle positioning, during metaphase of mitosis of the one-cell embryo of C. elegans, is very high. The Mitotic Spindle in the One-Cell C. elegans Embryo Is Positioned with High Precision and Stability. Pécréaux J1, Redemann S2, Alayan Z3, Mercat B3, Pastezeur S3, Garzon-Coral C4, Hyman AA5, Howard J Biophys J. 2016 Oct 18;111(8):1773-1784. doi: 10.1016/j.bpj.2016.09.007. Dionisio

Precise positioning of the mitotic spindle is important for specifying the plane of cell division, which in turn determines how the cytoplasmic contents of the mother cell are partitioned into the daughter cells, and how the daughters are positioned within the tissue. [...] the large number of microtubules in the asters provides a highly precise mechanism for positioning the spindle during metaphase while assembly is completed before the onset of anaphase. The Mitotic Spindle in the One-Cell C. elegans Embryo Is Positioned with High Precision and Stability. Pécréaux J1, Redemann S2, Alayan Z3, Mercat B3, Pastezeur S3, Garzon-Coral C4, Hyman AA5, Howard J Biophys J. 2016 Oct 18;111(8):1773-1784. doi: 10.1016/j.bpj.2016.09.007. Dionisio

DiEb, Thanks for the tip. Dionisio

DiEB- Over on TSZ the are actually using an easily refutable article from talk origins as some authority on nested hierarchies. Yet Theobald chokes his way through it. Then they can't seem to understand that Darwinian evolution is undirected. You will never see a piece on TSZ about the evolution of any vision system evolving by means of blind and mindless processes. You will never see them trying to support the claims of their position. Here ID has been supported over and over again. Here people get banned for acting like imbeciles and not supporting their claims. Their people get banned for exposing them as imbeciles who cannot support their claims. ET

@Dionisio: maybe this is of interest for you: UD and TSZ in 2017 BTW: instead of

98 DiEb writes to gpuccio https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649257

you could use the following syntax

<a href="#comment-649257">98: DiEb to gpuccio<a>

and get:

98: DiEb to gpuccio

DiEb

Cell polarity in one-cell C. elegans embryos guides an asymmetric cell division that starts the resulting cells along different developmental paths. Cell polarization starts in response to a signal from the centrosomes, triggering a cell-wide reorganization of the cortex. Functionally, the most notable change is the establishment of two mutually exclusive, antagonistic cortical domains, each composed of distinct PAR proteins. PAR proteins are a diverse but generally conserved group of polarity regulators that exert their polarizing effects through different downstream components. In one-cell C. elegans embryos, PAR polarity dictates the asymmetric segregation of fate determinants in the cytoplasm and controls the position of the cleavage furrow, allowing for unequal cell division. C. elegans embryos have been informative in identifying cell polarity factors, largely because embryo development is invariant and thus deviations from normal are easy to detect. It is becoming increasingly apparent that the invariance of C. elegans polarization results from parallel pathways and backup mechanisms that ensure robustness when components vary or the system is compromised. Recent work now points to a significant role of protein homeostasis in the accuracy and precision of polarity establishment in C. elegans, raising questions about the regulatory circuits that underlie this robustness. Mikl M., Cowan C.R. (2015) Cell Polarity in One-Cell C. elegans Embryos: Ensuring an Accurate and Precise Spatial Axis During Development. In: Ebnet K. (eds) Cell Polarity 2. Springer, Champ DOI 10.1007/978-3-319-14466-5_1 Dionisio

Collective cell migration is a highly regulated process involved in wound healing, cancer metastasis and morphogenesis. Mechanical interactions among cells provide an important regulatory mechanism to coordinate such collective motion. Using a Self-Propelled Voronoi (SPV) model that links cell mechanics to cell shape and cell motility, we formulate a generalized mechanical inference method to obtain the spatio-temporal distribution of cellular stresses from measured traction forces in motile tissues and show that such traction-based stresses match those calculated from instantaneous cell shapes. We additionally use stress information to characterize the rheological properties of the tissue. We identify a motility-induced swim stress that adds to the interaction stress to determine the global contractility or extensibility of epithelia. We further show that the temporal correlation of the interaction shear stress determines an effective viscosity of the tissue that diverges at the liquid-solid transition, suggesting the possibility of extracting rheological information directly from traction data. Yang, Xingbo & Bi, Dapeng & Czajkowski, Michael & Merkel, Matthias & Manning, M. Lisa & Marchetti, M Cristina. (2017). Correlating Cell Shape and Cellular Stress in Motile Confluent Tissues. Proceedings of the National Academy of Sciences. 114. . 10.1073/pnas.1705921114. Dionisio

Host plants possibly represent the strongest selection pressure for the evolution of reproductive traits in phytophagous insects. In a first part of this chapter, we review how plant quality affects both female and male life history traits and their respective reproductive success, and how the production and transfer to females of male sperm and associated nongametic substances (spermatophores as nuptial gifts) also depend on the host plant choice. At first glance, it seems that reproductive traits in phytophagous insects should be selected to maximize the success of this short-term interaction between host plant and phytophagous insects. This, however, ignores the fact that variation in reproductive success is detrimental to long-term fitness, which may explain that reproductive traits depart from their short-term expectation in unpredictable environments. Bet-hedging strategies – as exemplified by spatial or temporal dispersal (e.g., prolonged diapause) – can therefore evolve in such environments, as described in the second part of this chapter. The knowledge reviewed in this chapter is also integrated in the broader applied perspective of insect pest population management. Moreau, Jérôme & Desouhant, Emmanuel & Louâpre, Philippe & Goubault, Marlène & Rajon, Etienne & Jarrige, Alicia & Menu, F & Thiery, Denis. (2017). How Host Plant and Fluctuating Environments Affect Insect Reproductive Strategies?. Advances in Botanical Research. 259-288. 10.1016/bs.abr.2016.09.008. Dionisio

Many life-history traits are important determinants of the generation time. For instance, semelparous species whose adults reproduce only once have shorter generation times than iteroparous species that reproduce on several occasions, assuming equal development duration. A shorter generation time ensures a higher growth rate in stable environments where resources are in excess and is therefore a positively selected feature in this situation. In a stable and limiting environment, all combinations of traits that produce the same number of viable offspring are selectively equivalent. Here we study the neutral evolution of life-history strategies with different generation times and show that the slowest strategy represents the most likely evolutionary outcome when mutation is considered. Indeed, strategies with longer generation times generate fewer mutants per time unit, which makes them less likely to be replaced within a given time period. This turnover bias favors the evolution of strategies with long generation times. Its real impact, however, depends on both the population size and the nature of selection on life-history strategies. The latter is primarily impacted by the relationships between life-history traits whose estimation will be crucial to understanding the evolution of life-history strategies. Verin, Mélissa & Bourg, Salomé & Menu, Frédéric & Rajon, Etienne. (2017). The Biased Evolution of Generation Time. The American Naturalist. 190. E000-E000. 10.1086/692324. Dionisio

In the era of explosion in biological data, machine learning techniques are becoming more popular in life sciences, including biology and medicine. This research note examines the rise and fall of the most commonly used machine learning techniques in life sciences over the past three decades. Koohy, Hashem. (2018). The rise and fall of machine learning methods in biomedical research. F1000Research. 6. 2012. 10.12688/f1000research.13016.2. Dionisio

This book describes the latest advances in systems biology in four plant-based marine ecosystems: seaweeds, seagrasses, microalgae, and corals. Marine organisms that inhabit the oceanic environment experience a diverse range of environmental fluctuations, anthropogenic stress, and threats from invasive species and pathogens. Systems biology integrates physiology, genomics, transcriptomics, proteomics, and metabolomics into numerical models and is emerging as an important approach to elucidate the functional adaptations of marine organisms to adverse environmental conditions. This book focuses on how ecophysiology, omics platforms, their integration (a systems biology perspective), and next generation sequencing tools are being used to address the stress response of marine seaweeds, seagrasses, corals, marine microbe diversity, and micro-and macroalgae/corals-bacterial interactions to global climate change and anthropogenic activities. The contents of the book are of special interest to graduate and postgraduate marine biology students and marine biology researchers, particularly those interested in marine ecology, stress physiology of marine macrophytes/corals/phytoplankton, and environmental microbiology. This book would also be of interest to marine engineers engaged in the management and conservation of our valuable marine resources.. Kumar, Manoj & Ralph, Peter. (2017). Systems Biology of Marine Ecosystems. 10.1007/978-3-319-62094-7. This book describes the latest advances in systems biology in four plant-based marine ecosystems: seaweeds, seagrasses, microalgae, and corals. Marine organisms that inhabit the oceanic environment experience a diverse range of environmental fluctuations, anthropogenic stress, and threats from invasive species and pathogens. Systems biology integrates physiology, genomics, transcriptomics, proteomics, and metabolomics into numerical models and is emerging as an important approach to elucidate the functional adaptations of marine organisms to adverse environmental conditions. This book focuses on how ecophysiology, omics platforms, their integration (a systems biology perspective), and next generation sequencing tools are being used to address the stress response of marine seaweeds, seagrasses, corals, marine microbe diversity, and micro-and macroalgae/corals-bacterial interactions to global climate change and anthropogenic activities. The contents of the book are of special interest to graduate and postgraduate marine biology students and marine biology researchers, particularly those interested in marine ecology, stress physiology of marine macrophytes/corals/phytoplankton, and environmental microbiology. This book would also be of interest to marine engineers engaged in the management and conservation of our valuable marine resources. Systems Biology of Marine Ecosystems Book · January 2017 DOI 10.1007/978-3-319-62094-7 ISBN 978-3-319-62092-3 Springer International Publishing AG 2017 119 M. Kumar, P. Ralph (eds.), Systems Biology of Marine Ecosystems, DOI 10.1007/978-3-319-62094-7_6 Dionisio

This paper presents a brief history of Systems Theory, progresses to Systems Biology, and its relation to the more traditional investigative method of reductionism. The emergence of Systems Medicine represents the application of Systems Biology to disease and clinical issues. The challenges faced by this transition from Systems Biology to Systems Medicine are explained; the requirements of physicians at the bedside, caring for patients, as well as the place of human-human interaction and the needs of the patients are addressed. An organ-focused transition to Systems Medicine, rather than a genomic-, molecular-, or cell-based effort is emphasized. Organ focus represents a middle-out approach to ease this transition and to maximize the benefits of scientific discovery and clinical application. This method manages the perceptions of time and space, the massive amounts of human- and patient-related data, and the ensuing complexity of information. Berlin, Richard & Gruen, Russell & Best, James. (2017). Systems Medicine—Complexity Within, Simplicity Without. Journal of Healthcare Informatics Research. 1. 1-19. 10.1007/s41666-017-0002-9. Dionisio

The emergence of systems biology raises many fascinating questions: What does it mean to take a systems approach to problems in biology? To what extent is the use of mathematical and computational modelling changing the life sciences? How does the availability of big data influence research practices? What are the major challenges for biomedical research in the years to come? This book addresses such questions of relevance not only to philosophers and biologists but also to readers interested in the broader implications of systems biology for science and society. The book features reflections and original work by experts from across the disciplines including systems biologists, philosophers, and interdisciplinary scholars investigating the social and educational aspects of systems biology. In response to the same set of questions, the experts develop and defend their personal perspectives on the distinctive character of systems biology and the challenges that lie ahead. Readers are invited to engage with different views on the questions addressed, and may explore numerous themes relating to the philosophy of systems biology. This edited work will appeal to scholars and all levels, from undergraduates to researchers, and to those interested in a variety of scholarly approaches such as systems biology, mathematical and computational modelling, cell and molecular biology, genomics, systems theory, and of course, philosophy of biology. Philosophy of Systems Biology: Perspectives from Scientists and Philosophers | Request PDF. Available from: https://www.researchgate.net/publication/321540063_Philosophy_of_Systems_Biology_Perspectives_from_Scientists_and_Philosophers [accessed Jan 25 2018]. Philosophy of Systems Biology: Perspectives from Scientists and Philosophers Sara Green Book · January 2017?with?3 Reads DOI 10.1007/978-3-319-47000-9 ISSN 2211-1948 ISBN 978-3-319-46999-7 Dionisio

The infraorder Systellognatha is the most species-rich clade in the insect order Plecoptera and includes six families in two superfamilies: Pteronarcyoidea (Pteronarcyidae, Peltoperlidae, and Styloperlidae) and Perloidea (Perlidae, Perlodidae, and Chloroperlidae). To resolve the debatable phylogeny of Systellognatha, we carried out the first mitochondrial phylogenetic analysis covering all the six families, including three newly sequenced mitogenomes from two families (Perlodidae and Peltoperlidae) and 15 published mitogenomes. The three newly reported mitogenomes share conserved mitogenomic features with other sequenced stoneflies. For phylogenetic analyses, we assembled five datasets with two inference methods to assess their influence on topology and nodal support within Systellognatha. The results indicated that inclusion of the third codon positions of PCGs, exclusion of rRNA genes, the use of nucleotide datasets and Bayesian inference could improve the phylogenetic reconstruction of Systellognatha. The monophyly of Perloidea was supported in the mitochondrial phylogeny, but Pteronarcyoidea was recovered as paraphyletic and remained controversial. In this mitochondrial phylogenetic study, the relationships within Systellognatha were recovered as (((Perlidae + (Perlodidae + Chloroperlidae)) + (Pteronarcyidae + Styloperlidae)) + Peltoperlidae). Chen, Zhi-Teng & Zhao, Meng-Yuan & Xu, Cheng & Du, Yu-Zhou. (2018). Molecular phylogeny of Systellognatha (Plecoptera: Arctoperlaria) inferred from mitochondrial genome sequences. International Journal of Biological Macromolecules. 111. . 10.1016/j.ijbiomac.2018.01.065. Dionisio

Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental biophysical stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Torday, J.S. & Miller, William. (2017). Terminal addition in a cellular world. Progress in Biophysics and Molecular Biology. . 10.1016/j.pbiomolbio.2017.12.003. Dionisio

The knowledge that has being built on transcriptome, proteome and, specially, the metabolome (Ryan and Robards, 2006) has showed that the higher levels of organization contribute to regulate the lower levels in a downward causation chain (Figure 1), indicating that there is no a privileged level of causation in the organization of biological systems (Noble, 2012). do Amaral, Marcelo & Souza, Gustavo. (2017). The Challenge to Translate OMICS Data to Whole Plant Physiology: The Context Matters. Frontiers in Plant Science. 8. . 10.3389/fpls.2017.02146 Dionisio

[...] starting from the Galilean scientific revolution (sixteenth century) until the end of twenty and beginning of twenty-first centuries, occidental science was successful to uncover the layers of complexity underlying to the biological organisms, opening the OMICS era with the genome. But the “whole picture” was not clear yet. do Amaral, Marcelo & Souza, Gustavo. (2017). The Challenge to Translate OMICS Data to Whole Plant Physiology: The Context Matters. Frontiers in Plant Science. 8. . 10.3389/fpls.2017.02146 Dionisio

The exponential development of high-throughput technologies in the last decades, supporting and improving the OMICS science, has allowed uncovering successfully the complexity of the organizational network patterns in the cell’s metabolism to the plant phenome, founding the science of system biology (Mochida and Shinozaki, 2011). Further, the huge data sets and growing computational power have stimulated scientists to glimpse about how plants respond to the environmental changes, and how such knowledge could engender new technologies, for instance, to increase crop yields (Edwards and Batley, 2004; Tardieu et al., 2017). Through these technologies, researchers are describing deeply the different hierarchical levels of plant organization, improving the possibility to predict the behavior of whole plant (phenome). Based on extensive analyses of gene expression (genome and transcriptome) and/or metabolic networks (metabolome), it has been possible to monitor and control cellular responses to genetic perturbations or environmental changes (Fukushima et al., 2009). do Amaral, Marcelo & Souza, Gustavo. (2017). The Challenge to Translate OMICS Data to Whole Plant Physiology: The Context Matters. Frontiers in Plant Science. 8. . 10.3389/fpls.2017.02146. Dionisio

With the recent developments in the field of multi-omics integration, the interest in factors such as data preprocessing, choice of the integration method and the number of different omics considered had increased. In this work, the impact of these factors is explored when solving the problem of sample classification, by comparing the performances of five unsupervised algorithms: Multiple Canonical Correlation Analysis, Multiple Co-Inertia Analysis, Multiple Factor Analysis, Joint and Individual Variation Explained and Similarity Network Fusion. These methods were applied to three real data sets taken from literature and several ad hoc simulated scenarios to discuss classification performance in different conditions of noise and signal strength across the data types. The impact of experimental design, feature selection and parameter training has been also evaluated to unravel important conditions that can affect the accuracy of the result. Tini, Giulia & Marchetti, Luca & Priami, Corrado & Scott-Boyer, Marie-Pier. (2017). Multi-omics integration-a comparison of unsupervised clustering methodologies. Briefings in bioinformatics. . 10.1093/bib/bbx167. Dionisio

Data obtained by studying mammalian cells in absence of gravity strongly support the notion that cell fate specification cannot be understood according to the current molecular model. A paradigmatic case in point is provided by studying cell populations growing in absence of gravity. When the physical constraint (gravity) is 'experimentally removed', cells spontaneously allocate into two morphologically different phenotypes. Such phenomenon is likely enacted by the intrinsic stochasticity, which, in turn, is successively 'canalized' by a specific gene regulatory network. Both phenotypes are thermodynamically and functionally 'compatibles' with the new, modified environment. However, when the two cell subsets are reseeded into the 1g gravity field the two phenotypes collapse into one. Gravity constraints the system in adopting only one phenotype, not by selecting a pre-existing configuration, but more precisely shaping it de-novo through the modification of the cytoskeleton three-dimensional structure. Overall, those findings highlight how macro-scale features are irreducible to lower-scale explanations. The identification of macroscale control parameters - as those depending on the field (gravity, electromagnetic fields) or emerging from the cooperativity among the field's components (tissue stiffness, cell-to-cell connectivity) - are mandatory for assessing boundary conditions for models at lower scales, thus providing a concrete instantiation of top-down effects. Masiello, Maria & Verna, Roberto & Cucina, Alessandra & Bizzarri, Mariano. (2018). Physical constraints in cell fate specification. A case in point: Microgravity and phenotypes differentiation. Progress in Biophysics and Molecular Biology. . 10.1016/j.pbiomolbio.2018.01.001. Dionisio

The question whether evolution is blind is usually presented as a choice between no goals at all (‘the blind watchmaker’) and long-term goals which would be external to the organism, for example in the form of special creation or intelligent design. The arguments either way do not address the question whether there are short-term goals within rather than external to organisms. Organisms and their interacting populations have evolved mechanisms by which they can harness blind stochasticity and so generate rapid functional responses to environmental challenges. They can achieve this by re-organising their genomes and/or their regulatory networks. Epigenetic as well as DNA changes are involved. Evolution may have no foresight, but it is at least partially directed by organisms themselves and by the populations of which they form part. Similar arguments support partial direction in the evolution of behavior. Noble, Ray & Noble, Denis. (2017). Was the Watchmaker Blind? Or Was She One-Eyed?. Biology. 6. 47. 10.3390/biology6040047. Dionisio

To test whether growth limitation induces mutations, Cairns and Foster constructed an E. coli strain whose mutant lac allele provides 1-2% of normal ability to use lactose. This strain cannot grow on lactose, but produces about 50 Lac+ revertant colonies per 108 plated cells over 5 days. About 80% of revertants carry a stable lac+ mutation made by the error-prone DinB polymerase, which may be induced during growth limitation. Ten percent of Lac+ revertants are stable but form without DinB. The remaining 10% grow by amplifying their mutant lac allele and are unstably Lac+ Induced DinB mutagenesis has been explained in two ways: 1) Up-regulation of dinB expression in non-growing cells (stress-induced mutagenesis) or 2) Selected local over-replication of the lac and dinB+ genes on lactose medium (selected amplification) in cells that are not dividing. Up-regulation of dinB transcription is necessary but not sufficient for mutagenesis. Evidence is presented that DinB enhances reversion only when encoded somewhere on the F'lac plasmid that carries the mutant lac gene. A new model will propose that rare pre-existing cells (1 in a 1000) have about 10 copies of the F'lac plasmid, providing them with enough energy to divide, mate and over-replicate their F'lac plasmid under selective conditions. In these clones, repeated replication of F'lac in non-dividing cells directs opportunities for lac reversion and increases the copy number of the dinB+ gene. Amplification of dinB+ increases the error-rate of replication and increases the number of lac+ revertants. Thus, reversion is enhanced in non-dividing cells not by stress-induced mutagenesis, but by selected co-amplification of the dinB and lac genes, both of which happen to lie on the F'lac plasmid. Yamayoshi, Itsugo & Maisnier-Patin, Sophie & Roth, John. (2018). Selection-Enhanced Mutagenesis of lac Genes Is Due to Their Co-amplification with dinB Encoding an Error-Prone DNA Polymerase. Genetics. genetics.300409.2017. 10.1534/genetics.117.300409. Dionisio

The very small fraction of putative binding sites (BSs) that are occupied by transcription factors (TFs) in vivo can be highly variable across different cell types. This observation has been partly attributed to changes in chromatin accessibility and histone modification (HM) patterns surrounding BSs. Previous studies focusing on BSs within DNA regulatory regions found correlations between HM patterns and TF binding specificities. However, a mechanistic understanding of TF-DNA binding specificity determinants is still not available. The ability to predict in vivo TF binding on a genome-wide scale requires the identification of features that determine TF binding based on evolutionary relationships of DNA binding proteins. To reveal protein family-dependent mechanisms of TF binding, we conducted comprehensive comparisons of HM patterns surrounding BSs and non-BSs with exactly-matched core motifs for TFs in three cell lines: 33 TFs in GM12878, 37 TFs in K562, and 18 TFs in H1-hESC. These TFs displayed protein family-specific preferences for HM patterns surrounding BSs, with high agreement among cell lines. Moreover, compared to models based on DNA sequence and shape at flanking regions of BSs, HM-augmented quantitative machine-learning methods resulted in increased performance in a TF family-specific manner. Analysis of the relative importance of features in these models indicated that TFs, displaying larger HM pattern differences between BSs and non-BSs, bound DNA in an HM-specific manner on a protein family-specific basis. We propose that TF family-specific HM preferences reveal distinct mechanisms that assist in guiding TFs to their cognate BSs by altering chromatin structure and accessibility. Xin, Beibei & Rohs, Remo. (2018). Relationship between histone modifications and transcription factor binding is protein family specific. Genome Research. gr.220079.116. 10.1101/gr.220079.116. Dionisio

Among the diverse transcription factors that are necessary to elicit changes in cell fate, both in embryonic development and in cellular reprogramming, a subset of factors are capable of binding to their target sequences on nucleosomal DNA and initiating regulatory events in silent chromatin. Such 'pioneer transcription factors' initiate cooperative interactions with other regulatory proteins to elicit changes in local chromatin structure. As a consequence of pioneer factor binding, the local chromatin can either become open and competent for activation, closed and repressed, or transcriptionally active. Understanding how pioneer factors initiate chromatin dynamics and how such can be blocked at heterochromatic sites provides insights into controlling cell fate transitions at will. S Zaret, Kenneth & Mango, Susan. (2016). Pioneer Transcription Factors, Chromatin Dynamics, and Cell Fate Control. Current Opinion in Genetics & Development. 37. 76-81. 10.1016/j.gde.2015.12.003. Dionisio

Esophageal cancer (EC) was one of the most lethal malignancies worldwide with intricate mechanisms. Here we reported that Forkhead box C1 (FoxC1), a member of the forkhead family transcription factors, was up-regulated in EC tissues and cell lines in comparison with controls. FoxC1 levels were negatively correlated with tumor stage, lymph node metastasis and survival status of EC patients. Knockdown of FoxC1 inhibited the proliferation, colony formation and epithelial-mesenchymal transition (EMT) of EC cells, while overexpression of FoxC1 promoted these biological behaviors. Mechanically, serial deletion and chromatin immunoprecipitation assays showed that ZEB2, a well-reported transcriptional suppressor of E-cadherin, was a direct transcriptional target of FoxC1. Moreover, FoxC1 was recruited to the ZEB2 promoter by its interaction with the pioneer transcription factor pre-B-cell leukemia homeobox 1 (PBX1). Importantly, significant correlation between levels of FoxC1 and ZEB2 was observed in EC tissues and the two proteins could be used as prognostic biomarkers together. Hence, our results revealed a critical role of FoxC1 in the EMT process of EC and uncovered a novel mechanism for the regulation of ZEB2-E-cadherin axis in EC. Zhu, Xiaoming & Wei, Li & Bai, Yangqiu & Wu, Sen & Han, Shuangyin. (2017). FoxC1 promotes epithelial-mesenchymal transition through PBX1 dependent transactivation of ZEB2 in esophageal cancer. American journal of cancer research. 7. 1642-1653. Dionisio

Pioneer factors are proteins that can recognize their target sites in barely accessible chromatin and initiate a cascade of events that allows for later transcriptional activation of the respective genes. Pioneer factors are therefore particularly well-suited to initiate cell fate changes. To date, only a small number of pioneer factors have been identified and studied in depth, such as FOXD3/FOXA1, OCT4, or SOX2. Interestingly, several recent studies reported that the PBC transcription factor PBX1 can access transcriptionally inactive genomic loci. Here, we summarize the evidence linking PBX1 with transcriptional pioneer functions, suggest potential mechanisms involved and discuss open questions to be resolved. Grebbin, Moyo & Schulte, Dorothea. (2017). PBX1 as pioneer factor: A case still open. Frontiers in Cell and Developmental Biology. 5. . 10.3389/fcell.2017.00009. Dionisio

Zinc (Zn) is one of the essential mineral elements for both plants and humans. Zn deficiency in human is one of the major causes of hidden hunger, a serious health problem observed in many developing countries. Therefore, increasing Zn concentration in edible part is an important issue for improving human Zn nutrition. Here, we found that an Australian wild rice O. meridionalis showed higher grain Zn concentrations compared with cultivated and other wild rice species. The quantitative trait loci (QTL) analysis was then performed to identify the genomic regions controlling grain Zn levels using backcross recombinant inbred lines derived from O. sativa ‘Nipponbare’ and O. meridionalis W1627. Four QTLs responsible for high grain Zn were detected on chromosomes 2, 9, and 10. The QTL on the chromosome 9 (named qGZn9), which showed the largest effect on grain Zn concentration was confirmed with the introgression line, which had a W1627 chromosomal segment covering the qGZn9 region in the genetic background of O. sativa ‘Nipponbare’. Fine mapping of this QTL resulted in identification of two tightly linked loci, qGZn9a and qGZn9b. The candidate regions of qGZn9a and qGZn9b were estimated to be 190 and 950 kb, respectively. Furthermore, we also found that plants having a wild chromosomal segment covering qGZn9a, but not qGZn9b, is associated with fertility reduction. qGZn9b, therefore, provides a valuable allele for breeding rice with high Zn in the grains. Ishikawa, Ryo & Iwata, Masahide & Taniko, Kenta & Monden, Gotaro & Miyazaki, Naoya & Orn, Chhourn & Tsujimura, Yuki & Yoshida, Shusaku & Feng Ma, Jian & Ishii, Takashige. (2017). Detection of quantitative trait loci controlling grain zinc concentration using Australian wild rice, Oryza meridionalis, a potential genetic resource for biofortification of rice. PLOS ONE. 12. e0187224. 10.1371/journal.pone.0187224. Dionisio

Mineral elements taken up by the roots will be delivered to different organs and tissues depending on their requirements. In Poaceae, this selective distribution is mainly mediated in the nodes, which have highly developed and fully organized vascular systems. Inter-vascular transfer of mineral elements from enlarged vascular bundles to diffuse vascular bundles is required for their preferential distribution to developing tissues and reproductive organs. A number of transporters involved in this inter-vascular transfer processes have been identified mainly in rice. They are localized at the different cell layers and form an efficient machinery within the node. Furthermore, some these transporters show rapid response to the environmental changes of mineral elements at the protein level. In addition to the node-based transporters, distinct nodal structures including enlarged xylem area, folded plasma membrane of xylem transfer cells and presence of an apoplastic barrier are also required for the efficient inter-vascular transfer. Manipulation of node-based transporters will provide a novel breeding target to improve nutrient use efficiency, productivity, nutritional value and safety in cereal crops. Yamaji, Naoki & Feng, Jian. (2017). Node-controlled allocation of mineral elements in Poaceae. Current Opinion in Plant Biology. 39. . 10.1016/j.pbi.2017.05.002. Dionisio

Monocot stems lack the vascular cambium and instead have characteristic structures in which intercalary meristems generate internodes and veins remain separate and scattered. Developmental processes of these unique structures, however, have been poorly described. BELL1-like Homeobox (BLH) transcription factors (TFs) are known to heterodimerize with KNOTTED1-like Homeobox (KNOX) TFs to play crucial roles in shoot meristem maintenance, but their functions are elusive in monocots. We found that maize BLH12 and BLH14 have redundant but important roles in stem development. BLH12/14 interact with KNOTTED1 (KN1) in vivo, and accumulate in overlapping domains in shoot meristems, young stems and provascular bundles. Similar to kn1 loss-of-function mutants, blh12 blh14 (blh12/14) double mutants fail to maintain axillary meristems. Unique to blh12/14 is an abnormal tassel branching and precocious internode differentiation that results in dwarfism and reduced veins in stems. Micro-computed tomography (CT) observation of vascular networks revealed that blh12/14 double mutants had reduced vein number due to fewer intermediate veins in leaves and precocious anastomosis in young stems. Based on these results, we propose two functions of BLH12/14 during stem development: (1) maintaining intercalary meristems that accumulate KN1 and prevent precocious internode differentiation, (2) preventing precocious anastomosis of provascular bundles in young stems to ensure the production of sufficient independent veins. Tsuda, Katsutoshi & Abraham, Jazmin & Maeno, Akiteru & Dong, Zhaobin & Aromdee, Dale & Meeley, Robert & Shiroishi, Toshihiko & Nonomura, Kenichi & Hake, Sarah. (2017). KNOTTED1 cofactors, BLH12 and BLH14, regulate internode patterning and vein anastomosis in maize. The Plant cell. 29. . 10.1105/tpc.16.00967. Dionisio

In addition to protein-coding genes, RNA polymerase II (pol II) transcribes numerous genes for non-coding RNAs, including the small-nuclear (sn)RNA genes. snRNAs are an important class of non-coding RNAs, several of which are involved in pre-mRNA splicing. The molecular mechanisms underlying expression of human pol II-transcribed snRNA genes are less well characterized than for protein-coding genes and there are important differences in expression of these two gene types. Here, we review the DNA features and proteins required for efficient transcription of snRNA genes and co-transcriptional 3? end formation of the transcripts. Guiro, Joana & Murphy, Shona. (2017). Regulation of expression of human RNA polymerase II-Transcribed snRNA genes. Open Biology. 7. 170073. 10.1098/rsob.170073. Dionisio

Transcription factors (TFs) are gene expression regulators that bind to DNA in a sequence-specific manner and determine the functional characteristics of the gene. It is worthwhile to study the unique characteristics of such specific TF-binding pattern in DNA. Sox2 recognizes a 6- to 7-base pair consensus DNA sequence; the central four bases of the binding site are highly conserved, whereas the two to three flanking bases are variable. Here, we attempted to analyze the binding affinity and specificity of the Sox2 protein for distinct DNA sequence patterns via steered molecular dynamics, in which a pulling force is employed to dissociate Sox2 from Sox2-DNA during simulation to study the behavior of a complex under nonequilibrium conditions. The simulation results revealed that the first two stacking bases of the binding pattern have an exclusive impact on the binding affinity, with the corresponding mutant complexes showing greater binding and longer dissociation time than the experimental complexes do. In contrast, mutation of the conserved bases tends to reduce the affinity, and mutation of the complete conserved region disrupts the binding. It might pave the way to identify the most likely binding pattern recognized by Sox2 based on the affinity of each configuration. The ?2-helix of Sox2 was found to be the key player in the Sox2-DNA association. The characterization of Sox2's binding patterns for the target genes in the genome helps in understanding of its regulatory functions. Yesudhas, Dhanusha & Anwar, Muhammad Ayaz & Panneerselvam, Suresh & Kim, Han-Kyul & Choi, Sangdun. (2017). Evaluation of Sox2 binding affinities for distinct DNA patterns using steered molecular dynamics simulation. FEBS Open Bio. 7. . 10.1002/2211-5463.12316. Dionisio

Proteins in the form of transcription factors (TFs) bind to specific DNA sites that regulate cell growth, differentiation, and cell development. The interactions between proteins and DNA are important toward maintaining and expressing genetic information. Without knowing TFs structures and DNA-binding properties, it is difficult to completely understand the mechanisms by which genetic information is transferred between DNA and proteins. The increasing availability of structural data on protein-DNA complexes and recognition mechanisms provides deeper insights into the nature of protein-DNA interactions and therefore, allows their manipulation. TFs utilize different mechanisms to recognize their cognate DNA (direct and indirect readouts). In this review, we focus on these recognition mechanisms as well as on the analysis of the DNA-binding domains of stem cell TFs, discussing the relative role of various amino acids toward facilitating such interactions. Unveiling such mechanisms will improve our understanding of the molecular pathways through which TFs are involved in repressing and activating gene expression. Yesudhas, Dhanusha & Batool, Maria & Anwar, Muhammad Ayaz & Panneerselvam, Suresh & Choi, Sangdun. (2017). Proteins Recognizing DNA: Structural Uniqueness and Versatility of DNA-Binding Domains in Stem Cell Transcription Factors. Genes. 8. . 10.3390/genes8080192. Dionisio

Objectives Homeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis. Materials and methods An electronic search was undertaken using combination of keywords e.g. Homeobox genes, tooth development, dental diseases, stem cells, induced pluripotent stem cells, gene control region was used as search terms in PubMed and Web of Science and relevant full text articles and abstract were retrieved that were written in English. A manual hand search in text books were also carried out. Articles related to homeobox genes in dentistry and tissue engineering and regenerative medicine of odontogenesis were selected. Results The possible perspective of stem cells technology in odontogenesis and subsequent analysis of gene correction pertaining to dental disorders through the possibility of induced pluripotent stem cells technology is also inferred. Conclusions We demonstrate the promising role of tissue engineering and regenerative medicine on odontogenesis, which can generate a new ray of hope in the field of dental science. Ramanathan, Anand & Srijaya, Thekkeparambil & Sukumaran, Prema & Zain, Rosnah & Noor Hayaty, Abu Kasim. (2017). Homeobox genes and tooth development: Understanding the biological pathways and applications in regenerative dental science. Archives of Oral Biology. 85. . 10.1016/j.archoralbio.2017.09.033. Dionisio

We report and discuss the results of a quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven three amino acid loop extension (TALE) homeobox genes (four KNOTTED-like homeobox (KNOX) and three BEL1-like homeobox (BELL) genes) identified after next generation sequencing (NGS) and assembly of the sporophyte and gametophyte transcriptomes of the endangered fern species Vandenboschia speciosa. Among the four KNOX genes, two belonged to the KNOX1 class and the other two belonged to the KNOX2 class. Analysis of the deduced amino acid sequences supported the typical domain structure of both types of TALE proteins, and the homology to TALE proteins of mosses, lycophytes, and seed plant species. The expression analyses demonstrate that these homeodomain proteins appear to have a key role in the establishment and development of the gametophyte and sporophyte phases of V. speciosa lifecycle, as well as in the control of the transition between both phases. Vandenboschia speciosa VsKNAT3 (a KNOX2 class protein) as well as VsBELL4 and VsBELL10 proteins have higher expression levels during the sporophyte program. On the contrary, one V. speciosa KNOX1 protein (VsKNAT6) and one KNOX2 protein (VsKNAT4) seem important during the development of the gametophyte phase. TALE homeobox genes might be among the key regulators in the gametophyte-to-sporophyte developmental transition in regular populations that show alternation of generations, since some of the genes analyzed here (VsKNAT3, VsKNAT6, VsBELL4, and VsBELL6) are upregulated in a non-alternating population in which only independent gametophytes are found (they grow by vegetative reproduction outside of the range of sporophyte distribution). Thus, these four genes might trigger the vegetative propagation of the gametophyte and the repression of the sexual development in populations composed of independent gametophytes. This study represents a comprehensive identification and characterization of TALE homeobox genes in V. speciosa, and gives novel insights about the role of these genes in fern development. Ruiz-Estévez, Mercedes & Bakkali, Mohammed & Martín-Blázquez, Rubén & Garrido-Ramos, Manuel. (2017). Identification and Characterization of TALE Homeobox Genes in the Endangered Fern Vandenboschia speciosa. Genes. 8. 275. 10.3390/genes8100275. Dionisio

Background Hox gene clusters with at least 13 paralog group (PG) members are common in vertebrate genomes and in that of amphioxus. Ascidians, which belong to the subphylum Tunicata (Urochordata), are phylogenetically positioned between vertebrates and amphioxus, and traditionally divided into two groups: the Pleurogona and the Enterogona. An enterogonan ascidian, Ciona intestinalis (Ci), possesses nine Hox genes localized on two chromosomes; thus, the Hox gene cluster is disintegrated. We investigated the Hox gene cluster of a pleurogonan ascidian, Halocynthia roretzi (Hr) to investigate whether Hox gene cluster disintegration is common among ascidians, and if so, how such disintegration occurred during ascidian or tunicate evolution. Results Our phylogenetic analysis reveals that the Hr Hox gene complement comprises nine members, including one with a relatively divergent Hox homeodomain sequence. Eight of nine Hr Hox genes were orthologous to Ci-Hox1, 2, 3, 4, 5, 10, 12 and 13. Following the phylogenetic classification into 13 PGs, we designated Hr Hox genes as Hox1, 2, 3, 4, 5, 10, 11/12/13.a, 11/12/13.b and HoxX. To address the chromosomal arrangement of the nine Hox genes, we performed two-color chromosomal fluorescent in situ hybridization, which revealed that the nine Hox genes are localized on a single chromosome in Hr, distinct from their arrangement in Ci. We further examined the order of the nine Hox genes on the chromosome by chromosome/scaffold walking. This analysis suggested a gene order of Hox1, 11/12/13.b, 11/12/13.a, 10, 5, X, followed by either Hox4, 3, 2 or Hox2, 3, 4 on the chromosome. Based on the present results and those previously reported in Ci, we discuss the establishment of the Hox gene complement and disintegration of Hox gene clusters during the course of ascidian or tunicate evolution. Conclusions The Hox gene cluster and the genome must have experienced extensive reorganization during the course of evolution from the ancestral tunicate to Hr and Ci. Nevertheless, some features are shared in Hox gene components and gene arrangement on the chromosomes, suggesting that Hox gene cluster disintegration in ascidians involved early events common to tunicates as well as later ascidian lineage-specific events. Electronic supplementary material The online version of this article (10.1186/s40851-017-0078-3) contains supplementary material, which is available to authorized users. Sekigami, Yuka & Kobayashi, Takuya & Omi, Ai & Nishitsuji, Koki & Ikuta, Tetsuro & Fujiyama, Asao & Satoh, Noriyuki & Saiga, Hidetoshi. (2017). Hox gene cluster of the ascidian, Halocynthia roretzi, reveals multiple ancient steps of cluster disintegration during ascidian evolution. Zoological Letters. 3. . 10.1186/s40851-017-0078-3. Dionisio

Like many transcription factors, the yeast protein MATalpha2 (?2) undergoes rapid proteolysis via the ubiquitin-proteasome system (UPS). At least two ubiquitylation pathways regulate ?2 degradation: one pathway utilizes the ubiquitin ligase (E3) Doa10 and the other the heterodimeric E3 Slx5/Slx8. Doa10 is a transmembrane protein of the endoplasmic reticulum/inner nuclear membrane, whereas Slx5/Slx8 localizes to the nucleus and binds DNA nonspecifically. While a single protein can often be ubiquitylated by multiple pathways, the reasons for this 'division of labor' are not well understood. Here we show that ?2 mutants with impaired DNA binding become inaccessible to the Slx5/Slx8 pathway but are still rapidly degraded through efficient shunting to the Doa10 pathway. These results are consistent with the distinct localization of these E3s. We also characterized a novel class of DNA binding-defective ?2 variants whose degradation is strongly impaired. Our genetic data suggest this is due to a gain-of-function interaction that limits their access to Doa10. Together, these results suggest multiple ubiquitin-ligation mechanisms may have evolved to promote rapid destruction of a transcription factor that resides in distinct cellular subcompartments under different conditions. Moreover, gain-of-function mutations, which also occur with oncogenic forms of human transcription factors such as p53, may derail this fail-safe system. M. Hickey, Christopher & Xie, Yang & Hochstrasser, Mark. (2018). DNA Binding by the MAT?2 Transcription Factor Controls its Access to Alternative Ubiquitin-modification Pathways. Molecular Biology of the Cell. mbc.E17-10. 10.1091/mbc.E17-10-0589. Dionisio

Here, we provide an update of our review on homeobox genes that we wrote together with Walter Gehring in 1994. Since then, comprehensive surveys of homeobox genes have become possible due to genome sequencing projects. Using the 103 Drosophila homeobox genes as example, we present an updated classification. In animals, there are 16 major classes, ANTP, PRD, PRD-LIKE, POU, HNF, CUT (with four subclasses: ONECUT, CUX, SATB, and CMP), LIM, ZF, CERS, PROS, SIX/SO, plus the TALE superclass with the classes IRO, MKX, TGIF, PBC, and MEIS. In plants, there are 11 major classes, i.e., HD-ZIP (with four subclasses: I to IV), WOX, NDX, PHD, PLINC, LD, DDT, SAWADEE, PINTOX, and the two TALE classes KNOX and BEL. Most of these classes encode additional domains apart from the homeodomain. Numerous insights have been obtained in the last two decades into how homeodomain proteins bind to DNA and increase their specificity by interacting with other proteins to regulate cell- and tissue-specific gene expression. Not only protein-DNA base pair contacts are important for proper target selection; recent experiments also reveal that the shape of the DNA plays a role in specificity. Using selected examples, we highlight different mechanisms of homeodomain protein-DNA interaction. The PRD class of homeobox genes was of special interest to Walter Gehring in the last two decades. The PRD class comprises six families in Bilateria, and tinkers with four different motifs, i.e., the PAIRED domain, the Groucho-interacting motif EH1 (aka Octapeptide or TN), the homeodomain, and the OAR motif. Homologs of the co-repressor protein Groucho are also present in plants (TOPLESS), where they have been shown to interact with small amphipathic motives (EAR), and in yeast (TUP1), where we find an EH1-like motif in MAT?2. Electronic supplementary material The online version of this article (doi:10.1007/s00412-015-0543-8) contains supplementary material, which is available to authorized users. R Bürglin, Thomas & Affolter, Markus. (2015). Homeodomain proteins: an update. Chromosoma. 125. . 10.1007/s00412-015-0543-8. Dionisio

This Special Issue of Journal of Developmental Biology (JDB) covers an indeed very “special” (at least to me) family of highly evolutionarily conserved genes, the Hox genes. Despite over three decades having passed since the discovery of the homeobox, the excellent level and the wide range of topics of the articles and reviews published in this Special Issue testify the long-standing and ongoing interest in the functions of this unique gene family. The studies gathered in this issue of JDB cover subjects ranging from the use of Hox genes as a paradigm for the development of computational methods of protein family classification, to the role of Hox genes in the development and evolution of appendices, and the mechanisms underlying the expression of specific Hox proteins. Zappavigna, Vincenzo. (2017). Special Issue on HOX Genes in Development. Journal of Developmental Biology. 5. 5. 10.3390/jdb5020005. Dionisio

Genitalia are among the most studied phenotypes because they exhibit high anatomical diversity, experience fast evolutionary rates and may be shaped by several evolutionary mechanisms. A key element to uncover the mechanisms behind such impressive diversity is their copulatory function. This topic has been overlooked, especially concerning structures not directly involved in sperm transfer and reception. Here, we conduct a hypothesis-driven experimental study to elucidate the operation of various external genital parts in five species of stink bugs with differing levels of phylogenetic relatedness. These insects are unique because their male and female genitalia are externally well developed, rigid and composed of multiple components. In contrast with their anatomical complexity and diversity, we show that genital structures work jointly to perform a single function of mechanical stabilization during copula. However, distinct lineages have evolved alternative strategies to clasp different parts of the opposite sex. In spite of a high functional correspondence between male and female traits, the overall pattern of our data does not clearly support an intersexual coevolutionary scenario. We propose that the extraordinary male genital diversity in the family is probably a result of a process of natural selection enhancing morphological accommodation, but we consider alternative mechanisms. Genevcius, Bruno. (2017). Strong functional integration among multiple parts of the complex male and female genitalia of stink bugs. Biological Journal of the Linnean Society. 1-13. 10.1093/biolinnean/blx095. Dionisio

The copulatory process in animals is preceded by a series of integrated communication processes which are often under selection to guarantee species-specific courtship and copula. However, individuals of species supposedly in reproductive isolation frequently copulate in nature, which has sparked the attention of evolutionary biologists for decades. While studies on this topic have strongly focused on recently diverged species or populations, few instances of heterospecific copula between distantly related species are known. Here we report an intriguing case of interspecific copula between two distantly related species of stink bugs in nature. We replicated this observation in laboratory conditions and revealed an asymmetric relation: males of Chinavia obstinata copulated with females of C. erythrocnemis but the reverse combination did not occur. We propose a series of hypotheses to explain our observations in the light of the current knowledge on mate recognition and reproductive isolation in stink bugs, considering the potential pre- and postcopulatory barriers involved. Once these two species have probably evolved in allopatry and contacted secondarily, the absence of directional selection against mating signals differentiation is a probable process. We argue that similarities in genital shape and size, most likely a result of convergent evolution, may have played a fundamental role in guaranteeing that these species achieved proper coupling. Bianchi, Filipe & Genevcius, Bruno & da S. Vicentini, Barbara. (2017). Heterospecific mating between distantly related species of stink bugs and its evolutionary implications. Journal of Natural History. 51. 1-9. 10.1080/00222933.2017.1395095. Dionisio

Despite claims that genitalia are among the fastest evolving phenotypes, few studies have tested this trend in a quantitative and phylogenetic framework. In systems where male and female genitalia coevolve, there is a growing effort to explore qualitative patterns of evolution and their underlying mechanisms, but the temporal aspect remains overlooked. An intriguing question is how fast male and female genitalia may change in a coevolutionary scenario. Here we apply a series of comparative phylogenetic analyses to reveal a scenario of correlated evolution and to investigate how fast male and female external, non-homologous and functionally integrated genitalia change in a group of stink bugs. We report three findings: the female gonocoxite 8 and the male pygophore showed a clear pattern of correlated evolution, both genitalia were estimated to evolve much faster than non-genital traits, and rates of evolution of the male genitalia were twice as fast as the female genitalia. Our results corroborate the widely held view that male genitalia evolve fast and add to the scarce evidence for rapidly evolving female genitalia. Different rates of evolution exhibited by males and females suggest either distinct forms or strengths of selection, despite their tight functional integration and coevolution. The morphological characteristic of this coevolutionary trend are more consistent with a cooperative adjustment of the genitalia, suggesting a scenario of female choice, morphological accommodation, lock-and-key or some combination of the three This article is protected by copyright. All rights reserved. Genevcius, Bruno & Caetano, Daniel & Schwertner, Cristiano. (2016). Rapid differentiation and asynchronous coevolution of male and female genitalia in stink bugs. Journal of evolutionary biology. 30. . 10.1111/jeb.13026. Dionisio

RNF20/Bre1 mediated H2B ubiquitination (H2Bub) has various physiological functions. Recently, we found that H2Bub participates in meiotic recombination by promoting chromatin relaxation during meiosis. We then analyzed the phylogenetic relationships among the E3 ligase for H2Bub, its E2 Rad6 and their partner WW domain-containing adapter with a coiled-coil (WAC) or Lge1, and found that the molecular mechanism underlying H2Bub is evolutionarily conserved from yeast to mammals. However, RNF20 has diverse physiological functions in different organisms, which might be caused by the evolutionary divergency of their domain/motif architectures. In the current extra view, we not only elucidate the evolutionarily conserved molecular mechanism underlying H2Bub, but also discuss the diverse physiological functions of RNF20 during meiosis. Wang, Liying & Cao, Cunwei & Wang, Fang & Zhao, Jianguo & Li, Wei. (2017). H2B ubiquitination: Conserved molecular mechanism, diverse physiologic functions of the E3 ligase during meiosis. Nucleus. 8. 00-00. 10.1080/19491034.2017.1330237. Dionisio

Gene transcription requires the complex association of several factors, such as histone-modifying complexes, transcription factors, and chromatin remodeling factors. Among them, histone marks coordinate with each other extensively to modulate transcription. These marks can crosstalk with adjacent marks in cis or with marks present on other histones in trans to promote transcriptional activation or repression. In this chapter, we describe various crosstalk mechanisms potentiated by different histone marks, mainly histone lysine methylation, acetylation, monoubiquitination, phosphorylation, and arginine methylation. We also explain the role of chromatin-associated complexes that contain subunits with different functions and their coordination to modulate a single transcriptional response. These crosstalk mechanisms overall function as a cascade of events to help in the activation or repression of gene expression. Deregulation of these mechanisms result in pathological conditions like cancers, and understanding these pathways may greatly help in the development of specific therapeutic targets to cure diseases. Nagarajan, Sankari & Johnsen, Steven. (2016). Crosstalk Between Histone Modifications Integrates Various Signaling Inputs to Fine-Tune Transcriptional Output. Chromatin Signaling and Diseases. 217-239. 10.1016/B978-0-12-802389-1.00012-5. Dionisio

Background Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. Results Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-“suppressed” genes is associated with enhancer activation via FOXL2. Conclusion Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications. Xie, Wanhua & Nagarajan, Sankari & J. Baumgart, Simon & Kosinsky, Robyn Laura & Najafova, Zeynab & Kari, Vijayalakshmi & Hennion, Magali & Indenbirken, Daniela & Bonn, Stefan & Grundhoff, Adam & Wegwitz, Florian & Mansouri, Ahmed & Johnsen, Steven. (2017). RNF40 regulates gene expression in an epigenetic context-dependent manner. Genome Biology. 18. . 10.1186/s13059-017-1159-5. Dionisio

Usually I may not pay much attention to details and my reading comprehension is poor, but I 'cheaply' justify myself saying that I'm not a scientist, specially a mathematician. Here I've been disappointed by an alleged mathematician's apparent poor attention to accuracy, coherence, comprehension: 42 DiEb critical comment on Dionisio’s post @22 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648751 43 Dionisio responds to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648760 49 DiEb responds to Dionisio https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648890 50 Dionisio responds to DiEb 51 DiEb responds to Dionisio 52 Dionisio writes a related commentary https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648896 53 Dionisio writes a related commentary 55 DiEb comments on Dionisio @52 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648909 58 Dionisio responds to DiEb @49 in reference to 43 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648958 59 Dionisio responds to DiEb @55 60 DiEb responds 62 Dionisio responds to DiEb @55 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648985 63 DiEb responds 70 gpuccio writes to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649057 87 gpuccio writes to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649126 98 DiEb writes to gpuccio https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649257 103 gpuccio writes to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649277 122 gpuccio writes insightful comment https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649412 123 gpuccio writes insightful comment https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649414 152 Dionisio notes absence of DiEb’s response to gpuccio @103 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649598 186 Dionisio writes about the referenced papers 187 DiEb refers to gpuccio @186 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649680 188 DiEb comments 189 DiEb comments 190 DiEb comments 192 gpuccio writes to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649700 196 DiEb responds to gpuccio https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649714 202 gpuccio responds to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649723 Dionisio

@210 addendum (between 60 and 70) 62 Dionisio responds to DiEb @55 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648985 63 DiEb responds Dionisio

@209 addendum (what preceded 70?) 42 DiEb comments on Dionisio's post @22 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648751 43 Dionisio responds to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648760 49 DiEb responds to Dionisio https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648890 50 Dionisio responds to DiEb 51 DiEb responds to Dionisio 52 Dionisio writes a related commentary https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648896 53 Dionisio writes a related commentary 55 DiEb comments on Dionisio @52 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648909 58 Dionisio responds to DiEb @49 in reference to 43 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-648958 59 Dionisio responds to DiEb @55 60 DiEb responds Dionisio

@208 addendum (what preceded 103?) 70 gpuccio writes to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649057 87 gpuccio writes to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649126 98 DiEb writes to gpuccio https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649257 Dionisio

Mathematician's attention to details? 103 gpuccio writes to DiEb https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649277 122 gpuccio writes insightful comment https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649412 123 gpuccio writes insightful comment https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649414 152 Dionisio notes absence of DiEb's response to gpuccio @103 https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649598 186 Dionisio writes about the referenced papers 187 DiEb refers to gpucchio @186 Dionisio

@204 addendum Off topic quote:

Due to the lapse in government funding, the information on this web site may not be up to date, transactions submitted via the web site may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. Updates regarding government operating status and resumption of normal operations can be found at opm.gov.

just thought it’s an interesting example of the effects of sociopolitical situations on science. Dionisio

ET @198, Thanks for reminding us not to take some objectors seriously. They lack what is required for engaging in serious discussions. They are usually experts in making noise. No substance. Poor things. BTW, there's hope. I've been there, done that too. For many years. A piece of wood or a rock were more serious discussants than I was. Really shameful. Simply embarrassing. Dionisio

KF @201,

[...] many really important domains defy precising definition. For instance, define biological life.

You've touched a highly sensitive point indeed. Thanks for that important reminder. [emphasis added] Dionisio

KF, Off topic quote:

PubMed is open, however it is being maintained with minimal staffing due to the lapse in government funding. Information will be updated to the extent possible, and the agency will attempt to respond to urgent operational inquiries. Updates regarding government operating status and resumption of normal operations can be found at opm.gov.

just thought it's an interesting example of the effects of sociopolitical events on science. Dionisio

ET, I am positively trembling with fear of how my utter lack of intelligence, knowledge and ability to add up 2 and 3 have been exposed before the watching penumbra of animus sites. KF kairosfocus

DiEb: "gpucchio: what a pity – it seems that our areas of expertise do not overlap very much. I will follow your discussions with interest, but I doubt that I will contribute very much!" No problems! I appreciate your interest just the same. :) gpuccio

Dionisio, many really important domains defy precising definition. For instance, define biological life. We need not go beyond that to the soul. In many cases we are left to making a family resemblance case by case comparison between examples and counter-examples, an extended ostensive definition that guides conception that we have yet to be able to reduce to an exact statement of necessary and sufficient conditions or else genus and difference. Where Math comes in, we may be able to come up with models and structure relationships so that logic of structure and quantity applies. Sometimes we don't get that far. And in this case we are using ideas long familiar from statistical thermodynamics. And beyond: searching for a needle in a haystack is proverbial. KF kairosfocus

DiEb, FYI -since apparently you haven't noticed it yet- gpuccio's name does not have any letter 'h'. No idea where you got that from, but you wrote it incorrectly more than once. Please, show that you are indeed a mathematician and pay attention to details. At least to the important ones. A person's name is very important. Dionisio

KF @193:

definitionitis is an old complaint and too often a disease of the hyperskeptic that makes a mountain out of a mole-hill.

Very interesting description of an old problem. Perhaps this also applies to the still unsettled issues with terms like "evolution", "macroevolution", "microevolution"? Dionisio

DiEB:

KF, you obviously have no idea how modern mathematics work.

kairosfocus must be devastated by such a cunning and indepth argument. You really showed him, DiEB. :roll: ET

DiEb, really. There is a subject of interest that happens to be connected to the way statistical thermodynamics works. In that context, we can explore cut-down phase spaces (configuration spaces) and see what search challenge implies. The implication is plain, and it shows a good reason why inferring intelligently directed configuration on observing FSCO/I is reasonable. KF PS: Here are Davies and Walker, in a very similar vein:

In physics, particularly in statistical mechanics, we base many of our calculations on the assumption of metric transitivity, which asserts that a system’s trajectory will eventually [--> given "enough time and search resources"] explore the entirety of its state space – thus everything that is phys-ically possible will eventually happen. It should then be trivially true that one could choose an arbitrary “final state” (e.g., a living organism) and “explain” it by evolving the system backwards in time choosing an appropriate state at some ’start’ time t_0 (fine-tuning the initial state). In the case of a chaotic system the initial state must be specified to arbitrarily high precision. But this account amounts to no more than saying that the world is as it is because it was as it was, and our current narrative therefore scarcely constitutes an explanation in the true scientific sense. We are left in a bit of a conundrum with respect to the problem of specifying the initial conditions necessary to explain our world. A key point is that if we require specialness in our initial state (such that we observe the current state of the world and not any other state) metric transitivity cannot hold true, as it blurs any dependency on initial conditions – that is, it makes little sense for us to single out any particular state as special by calling it the ’initial’ state. If we instead relax the assumption of metric transitivity (which seems more realistic for many real world physical systems – including life), then our phase space will consist of isolated pocket regions and it is not necessarily possible to get to any other physically possible state (see e.g. Fig. 1 for a cellular automata example).

[--> or, there may not be "enough" time and/or resources for the relevant exploration, i.e. we see the 500 - 1,000 bit complexity threshold at work vs 10^57 - 10^80 atoms with fast rxn rates at about 10^-13 to 10^-15 s leading to inability to explore more than a vanishingly small fraction on the gamut of Sol system or observed cosmos . . . the only actually, credibly observed cosmos]

Thus the initial state must be tuned to be in the region of phase space in which we find ourselves [--> notice, fine tuning], and there are regions of the configuration space our physical universe would be excluded from accessing, even if those states may be equally consistent and permissible under the microscopic laws of physics (starting from a different initial state). Thus according to the standard picture, we require special initial conditions to explain the complexity of the world, but also have a sense that we should not be on a particularly special trajectory to get here (or anywhere else) as it would be a sign of fine–tuning of the initial conditions. [ --> notice, the "loading"] Stated most simply, a potential problem with the way we currently formulate physics is that you can’t necessarily get everywhere from anywhere (see Walker [31] for discussion). ["The “Hard Problem” of Life," June 23, 2016, a discussion by Sara Imari Walker and Paul C.W. Davies at Arxiv.]

kairosfocus

gpucchio: what a pity - it seems that our areas of expertise do not overlap very much. I will follow your discussions with interest, but I doubt that I will contribute very much! DiEb

KF, you obviously have no idea how modern mathematics work. DiEb

gpuccio @192:

"I am more than satisfied to demonstrate the empirical truth of the statement, in a specific context (biological systems)." "The concept of functional information greatly simplifies the approach to biological systems, and does not require a general theory of information or specification. It is a simple and powerful tool, perfectly appropriate for empirical design inference." "Empirical ID is, IMO, a very strong tool to demonstrate beyond any doubt the essential role of consciousness in generating complex functional information, and therefore the essential role of consciousness in reality."

I'm not a mathematician either, hence I like empirical evidences -specially in biology. The topic of complex functionally specified information associated with proteins and the interesting quantification approach you have described so extensively in several threads, are clear illustrations of the power of empirical demonstrations in biology. Dionisio

DiEb, definitionitis is an old complaint and too often a disease of the hyperskeptic that makes a mountain out of a mole-hill. In the context, we have dealt with configuration spaces, which can be regarded as phase spaces in which momentum issues are not material. In such spaces, we can see complexity through combinatorial explosion, e.g. for text strings. Since such strings can be used to describe a 3-d entity or a process etc, discussion on strings is WLOG. Now, certain clusters of configs in the space of possibilities w [for omega the traditional symbol in stat thermo-d] may be observably and identifiably distinct e.g. by providing some structurally based function, such as the correctly assembled parts of a 6500 c3 fishing reel, my favourite case. Thus we have a cluster of states that are functional in some way and a vastly larger number of clumped or scattered states that will not function in any relevant way. Of course the issue that relevant systems are self replicating is trotted out. the problem is we are looking at a cell-scale von Neuman kinematic self replicator, which is a further example of functionally specific complex orgtanisation and associated information that needs to be explained before it is allowed to drive all sorts of conclusions. Yes, OOL must be solved first. We then can ask ourselves, how do we get to such a cluster or island of function, a case e from a zone E within w. If by blind chance and/or mechanical necessity, any reasonable assignment of probabilities of accessing cases c for a complex case such that c is in E, will be rapidly negligibly different from zero. Exponential explosion of possibilities as n bits have 2^n possible configs. More complex cases can be reduced to bits. This of course runs into challenges of numerically or algebraically defining probabilities and defining functional targets. There is an answer: search challenge. Long since put here at UD and elsewhere. Once the space w is for at least 500 - 1,000 bits, we are looking at 3.27*10^150 - 1.07*10^301 possibilities. The atomic resources and atomic interaction rates for the 10^57 atoms of the sol system for the low end and the 10^80 for the observed cosmos at the high end, are such that the fraction of selected possibilities c from w is negligibly different from 0. So, it is maximally implausible to reach any reasonably isolated island of function in the space by blind search. Plausibility fail, backed up by utter want of empirical observation. And, search then is implied as sampling of subsets in config spaces relevant to our studies. Here, as default, blindly by chance and mechanical necessity. Try AA sequence space and codon space that targets it. We could try random bit strings for AUTOCAD, hoping to come up with a design for a reel, or we can try random ASCII text to get text from the corpus of literature in English or the like. All these cases give the same result, for rather obvious reasons. Likewise, we can then say oh we have some circumstance that searches are very effective as natural selection is held to be. Of course that is within islands of function, when we need to find the islands as the first problem, not incremental hill climbing within the island. In any case as searches are effectively subsets, they come from the power set of the space and so are exponentially harder, space of size w has power set of size 2^w. Search for golden search is far worse than direct search per whatever atomic level interactions occur in sol system or observed cosmos. Such cases of functionally specific complex organisation and associated information have just one well known causal source: intelligently directed configuration. But the whole point is, after years and years you and others of like ilk still want to sweep that inconvenient fact off the board and so repeatedly rhetorically pretend we have not provided a serious answer. It has been there, for decades. KF kairosfocus

DiEb: "I could agree with such a definition" I suppose that's enough form me. :) "BTW: my definition of a search is quite straight-forward: find the alpha in a space Omega where a given function f: Omega -> R takes its optimum. (R should be suitable…) This definition seems to work for all examples in DEM’s textbook…." I am not a mathematician, but your definition seems fine, as far as I can say. I can certainly agree with you on one point: it is very important to have explicit and clear definitions of the things we debate. That's why I have started my OPs here, some time ago, by giving my personal and explicit definitions of design and of complex functional information: https://uncommondescent.com/intelligent-design/defining-design/ https://uncommondescent.com/intelligent-design/functional-information-defined/ I cannot really follow the theoretical and mathematical problems that arise in the specific tasks that Dembski and Marks are pursuing. I am not a mathematician. I understand that they are trying to prove mathematically that complex specified information cannot arise in any possible system. I believe that they are right, essentially, but I cannot judge if they have succeeded in demonstrating that point rigorously. I am more than satisfied to demonstrate the empirical truth of the statement, in a specific context (biological systems). For example, I must confess that I have always had problems with Dembski's paper about specification: https://billdembski.com/documents/2005.06.Specification.pdf Many times, in the discussions here, I have been invited to defend it, but I cannot do that, because I certainly don't understand it, so usually I suspend any judgement about it. For my reasonings, I have always used, very simply, the concept of functional specification, which can be objectively defined and applied: https://uncommondescent.com/intelligent-design/functional-information-defined/ The concept of functional information greatly simplifies the approach to biological systems, and does not require a general theory of information or specification. It is a simple and powerful tool, perfectly approrpiate for empirical design inference. I am not really sure that specification can be universally defined without making any reference to conscious agents, because it arises in consciousness, and it requires consciousness to be defined and detected. Using a conscious agent to define "any possible function", as I do in my definition of functional information, does not make the functional specification in any way subjective. It reamins a very objective property, which can be objectively assessed in real systems. I am very intrigued by the concept of conservation of information. Intuitively, I believe that it is true. But probably it is very difficult to define it mathematically. So, I hope that Dembski and Marks may have the greatest success in their research, but I am not the best person to judge it in detail. Empirical ID is, IMO, a very strong tool to demonstrate beyond any doubt the essential role of consiousness in generating complex functional information, and therefore the essential roole of consciousness in reality. gpuccio

Private debate? Your email would just ask what they meant by the word "search". And if they don't respond then just use the standard dictionary definitions. The context would determine which definition is being used. ET

Has DiEB ever just bothered to ask Dembski, Marks or Ewert what the meant or if they are using the word differently than standardly defined?

There is no forum for such questions - even when Dr. Dembski was on the helm of this blog, he didn't engage his critics were often. The authors often ignore emails: Dr. Marks once said that he would not engage in private debate with those who are publicly critical to his position... IIRC, the last time critics had an opportunity to ask questions of one of the authors of "Introduction to Evolutionary Informatics" was in 2015 on UD: Dr. Ewert Answers. Unfortunately, Dr. Ewert did not accept any follow-up questions, so the whole exercise was somewhat futile... DiEb

Evolution by means of blind and mindless processes isn't a search. It isn't a creative force, either. Has DiEB ever just bothered to ask Dembski, Marks or Ewert what the meant or if they are using the word differently than standardly defined? ET

BTW: my definition of a search is quite straight-forward: find the alpha in a space Omega where a given function f: Omega -> R takes its optimum. (R should be suitable...) This definition seems to work for all examples in DEM's textbook.... DiEb

gpucchio @186:

Can you agree with this kind of definition of “search” (or any other way we can agree to call it)?

I could agree with such a definition, but I'm afraid that Dembski, Marks, and Ewert could not. For their ideas in "A Search for a Search" (S4S) and subsequent papers, they need a definition which allows to identify a search with a probability measure (S4S) or at least to be represented by a p.m. (as in their article "A General Theory of Information Cost Incurred by Successful Search" in "Biological Information - New Perspectives") I found both of these definitions troubling: in S4S, the space on which they defined their measure (the set of all queries of a certain length) wasn't a measurable space in any sensible way, while the other definition implied that all complete searches work on average only as well as a single random guess. In "Introduction to Evolutionary Informatics", they use the term search quite a lot, but without defining it properly - at least I haven't found the definition yet, perhaps another reader can show it to me? They just state that

We note, however, the choice of an algorithm along with its parameters and initialization imposes a probability distribution over the search space. (p. 173)

That's a bold statement - and as far as I can see, it is just wrong. DiEb

Lots of “where’s the beef?” questions for the referenced papers. Lots of "parole, parole, parole" in the referenced papers. Dionisio

F-box proteins are substrate adaptors used by the SKP1-CUL1-F-box protein (SCF) complex, a type of E3 ubiquitin ligase complex in the ubiquitin proteasome system (UPS). SCF-mediated ubiquitylation regulates proteolysis of hundreds of cellular proteins involved in key signaling and disease systems. However, our knowledge of the evolution of the F-box gene family in Euarchontoglires is limited. In the present study, 559 F-box genes and nine related pseudogenes were identified in eight genomes. Lineage-specific gene gain and loss events occurred during the evolution of Euarchontoglires, resulting in varying F-box gene numbers ranging from 66 to 81 among the eight species. Both tandem duplication and retrotransposition were found to have contributed to the increase of F-box gene number, whereas mutation in the F-box domain was the main mechanism responsible for reduction in the number of F-box genes, resulting in a balance of expansion and contraction in the F-box gene family. Thus, the Euarchontoglire F-box gene family evolved under a birth-and-death model. Signatures of positive selection were detected in substrate-recognizing domains of multiple F-box proteins, and adaptive changes played a role in evolution of the Euarchontoglire F-box gene family. In addition, single nucleotide polymorphism (SNP) distributions were found to be highly non-random among different regions of F-box genes in 1092 human individuals, with domain regions having a significantly lower number of non-synonymous SNPs. Wang, Ailan & Fu, Mingchuan & Jiang, Xiaoqian & Y.H., Mao & Li, Xiangchen & Tao, Shiheng. (2014). Evolution of the F-Box Gene Family in Euarchontoglires: Gene Number Variation and Selection Patterns. PloS one. 9. e94899. 10.1371/journal.pone.0094899. Dionisio

Thermodynamic stability, as expressed by the Second Law, generally constitutes the driving force for chemical assembly processes. Yet, somehow, within the living world most self-organisation processes appear to challenge this fundamental rule. Even though the Second Law remains an inescapable constraint, under energy-fuelled, far-from-equilibrium conditions, populations of chemical systems capable of exponential growth can manifest another kind of stability, dynamic kinetic stability (DKS). It is this stability kind based on time/persistence, rather than on free energy, that offers a basis for understanding the evolutionary process. Furthermore, a threshold distance from equilibrium, leading to irreversibility in the reproduction cycle, is needed to switch the directive for evolution from thermodynamic to DKS. The present report develops these lines of thought and argues against the validity of a thermodynamic approach in which the maximisation of the rate of energy dissipation/entropy production is considered to direct the evolutionary process. More generally, our analysis reaffirms the predominant role of kinetics in the self-organisation of life, which, in turn, allows an assessment of semi-quantitative constraints on systems and environments from which life could evolve. Pross, Addy & Pascal, Robert. (2017). How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution. Beilstein Journal of Organic Chemistry. 13. 665-674. 10.3762/bjoc.13.66. http://www.beilstein-journals.org/bjoc/content/supplementary/1860-5397-13-66-S1.pdf Dionisio

Mateus, Marcos. (2017). Milking spherical cows—Yet another facet of model complexity. Ecological Modelling. 354. . 10.1016/j.ecolmodel.2017.03.001. download here: https://authors.elsevier.com/a/1Us-X15DJ~pjN7 Dionisio

A significant number of synthetic systems capable of replicating themselves or entities that are complementary to themselves have appeared in the last 30 years. Building on an understanding of the operation of synthetic replicators in isolation, this field has progressed to examples where catalytic relationships between replicators within the same network and the extant reaction conditions play a role in driving phenomena at the level of the whole system. Systems chemistry has played a pivotal role in the attempts to understand the origin of biological complexity by exploiting the power of synthetic chemistry, in conjunction with the molecular recognition toolkit pioneered by the field of supramolecular chemistry, thereby permitting the bottom-up engineering of increasingly complex reaction networks from simple building blocks. This review describes the advances facilitated by the systems chemistry approach in relating the expression of complex and emergent behaviour in networks of replicators with the connectivity and catalytic relationships inherent within them. These systems, examined within well-stirred batch reactors, represent conceptual and practical frameworks that can then be translated to conditions that permit replicating systems to overcome the fundamental limits imposed on selection processes in networks operating under closed conditions. This shift away from traditional spatially homogeneous reactors towards dynamic and non-equilibrium conditions, such as those provided by reaction–diffusion reaction formats, constitutes a key change that mimics environments within cellular systems, which possess obvious compartmentalisation and inhomogeneity. Kosikova, Tamara & Philp, Douglas. (2017). Exploring the emergence of complexity using synthetic replicators. Chemical Society Reviews. 46. . 10.1039/C7CS00123A. Dionisio

Lots of "where's the beef?" questions for the referenced papers. Dionisio

The creation of reaction networks capable of exhibiting responses that are properties of entire systems represents a significant challenge for the chemical sciences. The system-level behavior of a reaction network is linked intrinsically to its topology and the functional connections between its nodes. A simple network of chemical reactions constructed from four reagents, in which each reagent reacts with exactly two others, can exhibit upregulation of two products even when only a single chemical reaction is addressed catalytically. We implement a system with this topology using two maleimides and two nitrones of different sizes—either short or long and each bearing complementary recognition sites—that react pairwise through 1,3-dipolar cycloaddition reactions to create a network of four length-segregated replicating templates. Comprehensive 1H NMR spectroscopy experiments unravel the network topology, confirming that, in isolation, three out of four templates self-replicate, with the shortest template exhibiting the highest efficiency. The strongest template effects within the network are the mutually crosscatalytic relationships between the two templates of intermediate size. The network topology is such that the addition of different preformed templates as instructions to a mixture of all starting materials elicits system-level behavior. Instruction with a single template up-regulates the formation of two templates in a predictable manner. These results demonstrate that the rules governing system-level behavior can be unraveled through the application of wholly synthetic networks with well-defined chemistries and interactions. Sadownik, Jan & Kosikova, Tamara & Philp, Douglas. (2017). Generating System-Level Responses from a Network of Simple Synthetic Replicators. Journal of the American Chemical Society. 139. . 10.1021/jacs.7b09735. Dionisio

As a step towards understanding pre-evolutionary organization in non-genetic systems, we develop a model to investigate the emergence and dynamics of proto-autopoietic networks in an interacting population of simple information processing entities (automata). These findings may be relevant to understanding how inanimate systems such as chemically communicating protocells can initiate the transition to living matter prior to the onset of contemporary evolutionary and genetic mechanisms. Emergence and dynamics of self-producing information niches as a step towards pre-evolutionary organization Richard J. Carter, Karoline Wiesner, Stephen Mann DOI: 10.1098/rsif.2017.0807 Journal of the Royal Society Interface http://rsif.royalsocietypublishing.org/content/15/138/20170807 Dionisio

Large facilities and the evolving ribosome, the cellular machine for genetic-code translation Ada Yonath DOI: 10.1098/rsif.2009.0167.focus Journal of the Royal Society Interface Dionisio

R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters http://www.sciencedirect.com/science/article/pii/S1097276517307578 Dionisio

gooshy, If I got your joke right, the mainstream media can turn anyone into a celebrity if they want to. Celebrities are objects they promote for profitable sale. What made you write in this thread? I'm just curious. Thanks. Dionisio

Dionisio @159, yes it was. Just a little levity. gooshy

Genitalia are among the most studied phenotypes because they exhibit high anatomical diversity, experience fast evolutionary rates and may be shaped by several evolutionary mechanisms. A key element to uncover the mechanisms behind such impressive diversity is their copulatory function. This topic has been overlooked, especially concerning structures not directly involved in sperm transfer and reception. Here, we conduct a hypothesis-driven experimental study to elucidate the operation of various external genital parts in five species of stink bugs with differing levels of phylogenetic relatedness. These insects are unique because their male and female genitalia are externally well developed, rigid and composed of multiple components. In contrast with their anatomical complexity and diversity, we show that genital structures work jointly to perform a single function of mechanical stabilization during copula. However, distinct lineages have evolved alternative strategies to clasp different parts of the opposite sex. In spite of a high functional correspondence between male and female traits, the overall pattern of our data does not clearly support an intersexual coevolutionary scenario. We propose that the extraordinary male genital diversity in the family is probably a result of a process of natural selection enhancing morphological accommodation, but we consider alternative mechanisms. Genevcius, Bruno. (2017). Strong functional integration among multiple parts of the complex male and female genitalia of stink bugs. Biological Journal of the Linnean Society. 1-13. 10.1093/biolinnean/blx095. https://www.researchgate.net/profile/Bruno_Genevcius/publication/320615982_Strong_functional_integration_among_multiple_parts_of_the_complex_male_and_female_genitalia_of_stink_bugs/links/59f09dbfaca272cdc7cde80c/Strong-functional-integration-among-multiple-parts-of-the-complex-male-and-female-genitalia-of-stink-bugs.pdf Dionisio

Despite claims that genitalia are among the fastest evolving phenotypes, few studies have tested this trend in a quantitative and phylogenetic framework. In systems where male and female genitalia coevolve, there is a growing effort to explore qualitative patterns of evolution and their underlying mechanisms, but the temporal aspect remains overlooked. An intriguing question is how fast male and female genitalia may change in a coevolutionary scenario. Here we apply a series of comparative phylogenetic analyses to reveal a scenario of correlated evolution and to investigate how fast male and female external, non-homologous and functionally integrated genitalia change in a group of stink bugs. We report three findings: the female gonocoxite 8 and the male pygophore showed a clear pattern of correlated evolution, both genitalia were estimated to evolve much faster than non-genital traits, and rates of evolution of the male genitalia were twice as fast as the female genitalia. Our results corroborate the widely held view that male genitalia evolve fast and add to the scarce evidence for rapidly evolving female genitalia. Different rates of evolution exhibited by males and females suggest either distinct forms or strengths of selection, despite their tight functional integration and coevolution. The morphological characteristic of this coevolutionary trend are more consistent with a cooperative adjustment of the genitalia, suggesting a scenario of female choice, morphological accommodation, lock-and-key or some combination of the three This article is protected by copyright. All rights reserved. Genevcius, Bruno & Caetano, Daniel & Schwertner, Cristiano. (2016). Rapid differentiation and asynchronous coevolution of male and female genitalia in stink bugs. Journal of evolutionary biology. 30. . 10.1111/jeb.13026. https://www.researchgate.net/profile/Bruno_Genevcius/publication/311704430_Rapid_differentiation_and_asynchronous_coevolution_of_male_and_female_genitalia_in_stink_bugs/links/58bf013a92851cd83aa1253b/Rapid-differentiation-and-asynchronous-coevolution-of-male-and-female-genitalia-in-stink-bugs.pdf Dionisio

Systematists and geneticists study biological diversity, but they use different approaches that rarely intersect. A very common pattern that is of interest for both researchers is the rapid evolution of genitalia, a trait of significant taxonomic utility in several sexually reproducing animal clades. The idea that both male and female genitalia are species-specific and play a role in reproductive isolation has long been controversial but has recently gained a renewed interest by speciation and developmental geneticists. Here, I highlight six unresolved questions in genitalia coevolution and I argue that systematists, with their well training in comparative morphology, usage of large and geographically diverse collections, and ability to apply molecular genetics techniques, can make important contributions. Such an extension of systematics into the speciation and developmental genetics realms is a promising opportunity to expand “integrative taxonomy” comparisons between DNA and morphology into more explanatory relationships between the two sources of taxonomic data. Yassin, Amir. (2016). Unresolved questions in genitalia coevolution: bridging taxonomy, speciation, and developmental genetics. Organisms Diversity & Evolution. 16. . 10.1007/s13127-016-0286-2. Dionisio

Recently a new species of bombyliid fly, Marleyimyia xylocopae, was described by Marshall & Evenhuis (2015) based on two photographs taken during fieldwork in the Republic of South Africa. This species has no preserved holotype. The paper generated some buzz, especially among dipterists, because in most cases photographs taken in the field provide insufficient information for properly diagnosing and documenting species of Diptera. Amorim, Dalton & Santos, Charles & Krell, Frank-Thorsten & Dubois, Alain & Nihei, Silvio & Oliveira, Otto & Pont, Adrian & SONG, HOJUN & Verdade, Vanessa & Fachin, Diego & Klassa, Bruna & Lamas, Carlos & Oliveira, Sarah & De Carvalho, Claudio & Mello-Patiu, Cátia & Hajdu, Eduardo & S. COURI, MÁRCIA & Silva, Vera & Capellari, Renato & Grimaldi, David. (2016). Timeless standards for species delimitation. Zootaxa. 4137. 121. 10.11646/zootaxa.4137.1.9. https://www.researchgate.net/profile/Antonio_Marques8/publication/305039414_Timeless_standards_for_species_delimitation/links/577fa7bf08ae9485a439a574/Timeless-standards-for-species-delimitation.pdf Dionisio

Evolutionary developmental biology (evo-devo) suggests a distinction between modular and systemic variation. In the case of modular change, the conservation of the overall structure helps recognizing affinities, while a single, fast evolving module is likely to produce a bonanza for the taxonomist, while systemic changes produce strongly deviating morphologies that cause problems in tracing homologies. Similarly, changes affecting the whole life cycle are more challenging than those limited to one stage. Developmental modularity is a precondition for heterochrony. Analyzing a matrix of morphological data for paedomorphic taxa requires special care. It is, however, possible to extract phylogenetic signal from heterochronic patterns. The taxonomist should pay attention to the intricacies of the genotype-->. phenotype map. When using genetic data to infer phylogeny, a comparison of gene sequences is just a first step. To bridge the gap between genes and morphology we should consider the spatial and temporal patterns of gene expression, and their regulation. Minor genetic change can have major phenotypic effects, sometimes suggesting saltational evolution. Evo-devo is also relevant in respect to speciation: changes in developmental schedules are often implicated in the divergence between sympatric morphs, and a developmental modulation of 'temporal phenotypes' appears to be responsible for many cases of speciation. Minelli, Alessandro. (2015). Biological Systematics in the Evo-Devo era. European Journal of Taxonomy. 0. . 10.5852/ejt.2015.125. https://www.researchgate.net/profile/Alessandro_Minelli/publication/279250861_Biological_Systematics_in_the_Evo-Devo_era/links/55ddd06e08ae45e825d39045/Biological-Systematics-in-the-Evo-Devo-era.pdf Dionisio

The chordates are usually characterized as bilaterians showing deuterostomy, i.e. the mouth developing as a new opening between the archenteron and the ectoderm, serial gill pores/slits, and the complex of chorda and neural tube. Both numerous molecular studies and studies of morphology and embryology demonstrate that the neural tube must be considered homologous to the ventral nerve cord(s) of the protostomes, but the origin of the 'new' mouth of the deuterostomes has remained enigmatic. However, deuterostomy is known to occur in several protostomian groups, such as the chaetognaths and representatives of annelids, molluscs, arthropods and priapulans. This raises the question whether the deuterostomian mouth is in fact homologous with that of the protostomes, viz. the anterior opening of the ancestral blastopore divided through lateral blastopore fusion, i.e. amphistomy. A few studies of gene expression show identical expression patterns around mouth and anus in protostomes and deuterostomes. Closer studies of the embryology of ascidians and vertebrates show that the mouth/stomodaeum differentiates from the anterior edge of the neural plate. Together this indicates that the chordate mouth has moved to the anterior edge of the blastopore, so that the anterior loop of the ancestral circumblastoporal nerve cord, which is narrow in the protostomes, has become indistinguishable. In the vertebrates, the mouth has moved further around the anterior pole to the 'ventral' side. The conclusion must be that the chordate mouth (and that of the deuterostomes in general) is homologous to the protostomian mouth and that the latest common ancestor of protostomes and deuterostomes developed through amphistomy, as suggested by the trochaea theory. Nielsen, Claus. (2015). Evolution of deuterostomy - and origin of the chordates. Biological reviews of the Cambridge Philosophical Society. 92. . 10.1111/brv.12229. Dionisio

Hox proteins are one of the best studied sets of transcription factors in developmental biology. They are major determinants for establishing morphological differences along the anterior-posterior axis of animals and are generally regarded as highly conserved in function. This view is based on experiments comparing a few (anterior) Hox proteins, however, the extent to which central or abdominal Hox proteins share sequence features or functions remains largely unexplored. To shed light on the origin and functional divergence of the central Hox proteins, we combine a powerful bioinformatics tool (CLANS) with a large-scale phylogeny of species. CLANS is used to differentiate between the various types of central Hox protein sequences, while the phylogeny provides an evolutionary context to the analysis. The combination of both enables us to infer the relative timepoint at which a given central Hox protein type arose. We identify seven distinct central Hox protein sequence types, only one of which is common to all protostome and deuterostome clades (Antp/Hox7). Together, these results lead us to suggest reevaluating the usefulness of the increasingly depicted synteny-based classification scheme that assumes a one-to-one orthology between protostome and deuterostome central Hox proteins. Instead, we propose that the use of sequence-based classification schemes able to resolve the central and posterior Hox proteins provides a more promising and biologically meaningful alternative to resolving these groups. This analysis, which provides a unique overview of the Hox protein sequence types present across protostomes and deuterostomes as well as a relative dating for the emergence of the central Hox protein types, provides a crucial clue to illuminate how and when the distinct developmental blueprints for organisms evolved within the evolutionarily immensely successful bilaterian lineage. Hueber, Stefanie & Rauch, Jens & Djordjevic, Michael & Gunter, Helen & Weiller, Georg & Frickey, Tancred. (2013). Analysis of central Hox protein types across bilaterian clades: On the diversification of central Hox proteins from an Antennapedia/Hox7-like protein. Developmental biology. 383. . 10.1016/j.ydbio.2013.09.009. Dionisio

Hox genes encode a family of transcriptional regulators that elicit distinct developmental programmes along the head-to-tail axis of animals. The specific regional functions of individual Hox genes largely reflect their restricted expression patterns, the disruption of which can lead to developmental defects and disease. Here, we examine the spectrum of molecular mechanisms controlling Hox gene expression in model vertebrates and invertebrates and find that a diverse range of mechanisms, including nuclear dynamics, RNA processing, microRNA and translational regulation, all concur to control Hox gene outputs. We propose that this complex multi-tiered regulation might contribute to the robustness of Hox expression during development. The regulation of Hox gene expression during animal development Moisés Mallo, Claudio R. Alonso Development 2013 140: 3951-3963; doi: 10.1242/dev.068346 http://dev.biologists.org/content/140/19/3951.full.pdf Dionisio

This Special Issue of Journal of Developmental Biology (JDB) covers an indeed very “special” (at least to me) family of highly evolutionarily conserved genes, the Hox genes. Despite over three decades having passed since the discovery of the homeobox, the excellent level and the wide range of topics of the articles and reviews published in this Special Issue testify the long-standing and ongoing interest in the functions of this unique gene family. The studies gathered in this issue of JDB cover subjects ranging from the use of Hox genes as a paradigm for the development of computational methods of protein family classification, to the role of Hox genes in the development and evolution of appendices, and the mechanisms underlying the expression of specific Hox proteins Zappavigna, Vincenzo. (2017). Special Issue on HOX Genes in Development. Journal of Developmental Biology. 5. 5. 10.3390/jdb5020005. http://www.mdpi.com/2221-3759/5/2/5/pdf Dionisio

Phylogenetic methods are key to providing models for how a given protein family evolved. However, these methods run into difficulties when sequence divergence is either too low or too high. Here, we provide a case study of Hox and ParaHox proteins so that additional insights can be gained using a new computational approach to help solve old classification problems. For two (Gsx and Cdx) out of three ParaHox proteins the assignments differ between the currently most established view and four alternative scenarios. We use a non-phylogenetic, pairwise-sequence-similarity-based method to assess which of the previous predictions, if any, are best supported by the sequence-similarity relationships between Hox and ParaHox proteins. The overall sequence-similarities show Gsx to be most similar to Hox2–3, and Cdx to be most similar to Hox4–8. The results indicate that a purely pairwise-sequence-similarity-based approach can provide additional information not only when phylogenetic inference methods have insufficient information to provide reliable classifications (as was shown previously for central Hox proteins), but also when the sequence variation is so high that the resulting phylogenetic reconstructions are likely plagued by long-branch-attraction artifacts. Hueber, Stefanie & Frickey, Tancred. (2016). Solving Classification Problems for Large Sets of Protein Sequences with the Example of Hox and ParaHox Proteins. Journal of Developmental Biology. 4. 8. 10.3390/jdb4010008. http://www.mdpi.com/2221-3759/4/1/8/pdf Dionisio

Here, we provide an update of our review on homeobox genes that we wrote together with Walter Gehring in 1994. Since then, comprehensive surveys of homeobox genes have become possible due to genome sequencing projects. Using the 103 Drosophila homeobox genes as example, we present an updated classification. In animals, there are 16 major classes, ANTP, PRD, PRD-LIKE, POU, HNF, CUT (with four subclasses: ONECUT, CUX, SATB, and CMP), LIM, ZF, CERS, PROS, SIX/SO, plus the TALE superclass with the classes IRO, MKX, TGIF, PBC, and MEIS. In plants, there are 11 major classes, i.e., HD-ZIP (with four subclasses: I to IV), WOX, NDX, PHD, PLINC, LD, DDT, SAWADEE, PINTOX, and the two TALE classes KNOX and BEL. Most of these classes encode additional domains apart from the homeodomain. Numerous insights have been obtained in the last two decades into how homeodomain proteins bind to DNA and increase their specificity by interacting with other proteins to regulate cell- and tissue-specific gene expression. Not only protein-DNA base pair contacts are important for proper target selection; recent experiments also reveal that the shape of the DNA plays a role in specificity. Using selected examples, we highlight different mechanisms of homeodomain protein-DNA interaction. The PRD class of homeobox genes was of special interest to Walter Gehring in the last two decades. The PRD class comprises six families in Bilateria, and tinkers with four different motifs, i.e., the PAIRED domain, the Groucho-interacting motif EH1 (aka Octapeptide or TN), the homeodomain, and the OAR motif. Homologs of the co-repressor protein Groucho are also present in plants (TOPLESS), where they have been shown to interact with small amphipathic motives (EAR), and in yeast (TUP1), where we find an EH1-like motif in MAT?2. Electronic supplementary material The online version of this article (doi:10.1007/s00412-015-0543-8) contains supplementary material, which is available to authorized users. R Bürglin, Thomas & Affolter, Markus. (2015). Homeodomain proteins: an update. Chromosoma. 125. . 10.1007/s00412-015-0543-8. http://link.springer.com/content/pdf/10.1007%2Fs00412-015-0543-8.pdf Dionisio

We report the complete sequence analysis of the entire complement of eight typical homeobox (Hox) genes (Lab, Pb, Dfd, Scr, Antp, Ubx, Abd-A, and Abd-B) and two other genes (Hox3 and Ftz) in a 324.6-kb region in the water flea Daphnia magna. In the water flea D. magna Hox genes, we found one long interspersed nuclear element (LINE)/R2-NeSL between Ubx and Abd-A, but it was not present in Daphnia pulex Hox genes. In basal expression of Hox genes on different developmental stages, biothorax complex genes (Ubx, Abd-A, and Abd-B) and some of antennapedia complex genes (Lab, Scr, Antp) were moderately expressed but Hox3 gene was barely expressed, while three homeobox genes (Antp, Ubx, Abd-A) were highly expressed in 6-7 days after releasing from brood chamber and/or adult stage. The structural array and transcribed orientation of Dm-Hox genes were identical to the sister species D. pulex (~340 kb), indicating that the Hox gene structure in daphnids is highly conserved. However, the structural array and transcribed orientation of Dm- and Dp-Hox3, -deformed (Dfd), -fushi tarazu (Ftz) genes varied from orthologous genes in pancrustacean species. Kim, Duck-Hyun & Lee, Bo-Young & Kim, Hui-Su & Jeong, Chang-Bum & Hwang, Dae-sik & Kim, Il-Chan & Lee, Jae-Seong. (2018). Identification and characterization of homeobox (Hox) genes and conservation of the single Hox cluster (324.6 kb) in the water flea Daphnia magna. Journal of Experimental Zoology Part B Molecular and Developmental Evolution. 0. 0. https://www.researchgate.net/profile/Jae-Seong_Lee/publication/320798695_Identification_and_characterization_of_homeobox_Hox_genes_and_conservation_of_the_single_Hox_cluster_3246_kb_in_the_water_flea_Daphnia_magna/links/5a62bd95aca272a15819a8c2/Identification-and-characterization-of-homeobox-Hox-genes-and-conservation-of-the-single-Hox-cluster-3246-kb-in-the-water-flea-Daphnia-magna.pdf Dionisio

The discovery of the broad conservation of embryonic regulatory genes across animal phyla, launched by the cloning of homeotic genes in the 1980s, was a founding event in the field of evolutionary developmental biology (evo-devo). While it had long been known that fundamental cellular processes, commonly referred to as housekeeping functions, are shared by animals and plants across the planet-processes such as the storage of information in genomic DNA, transcription, translation and the machinery for these processes, universal codon usage, and metabolic enzymes-Hox genes were different: mutations in these genes caused "bizarre" homeotic transformations of insect body parts that were certainly interesting but were expected to be idiosyncratic. The isolation of the genes responsible for these bizarre phenotypes turned out to be highly conserved Hox genes that play roles in embryonic patterning throughout Metazoa. How Hox genes have changed to promote the development of diverse body plans remains a central issue of the field of evo-devo today. For this Memorial article series, I review events around the discovery of the broad evolutionary conservation of Hox genes and the impact of this discovery on the field of developmental biology. I highlight studies carried out in Walter Gehring's lab and by former lab members that have continued to push the field forward, raising new questions and forging new approaches to understand the evolution of developmental mechanisms. Pick, Leslie. (2015). Hox genes, evo-devo, and the case of the ftz gene. Chromosoma. 125. . 10.1007/s00412-015-0553-6. https://www.researchgate.net/profile/Leslie_Pick/publication/284562965_Hox_genes_evo-devo_and_the_case_of_the_ftz_gene/links/5811fa0108ae8b130d0bceac/Hox-genes-evo-devo-and-the-case-of-the-ftz-gene.pdf There yet? :) Dionisio

The role of allometry in producing the variation in autopodial morphology observed among the lizards is not well understood. Allometry of metapodial and digit lengths in the manus and pes of the primitively padless gekkotan (Eublepharis macularius) is explored using maximum-likelihood repeated-measures ANCOVAs with body length as the covariate. Estimated variance–covariance matrices differed significantly within and between autopodia, and integration was stronger among the metapodials than the digits. The first metapodial and the first digit of each autopodium exhibit the strongest covariances with each of the remaining components in each variance–covariance matrix, suggesting that the lengths of the first rays are important for allometric integration of both manus and pes. Metapodials scale isometrically and digits negatively allometrically; both display allometric heterogeneity among themselves in both autopodia. Both autopodia exhibit changes in proportion over the ontogenetic size range, attributable to variation in scaling among the components of the rays. Allometric coefficients do not vary among pedal digits, despite differences in phalanx number, although phalanx number is associated with differences in slope in the manual digits. This is suggestive of heterogeneity in allometry among the manual phalanges, which thus may be associated with variation in phalanx length within gekkotan digits. Powell, G & J. Osgood, Geoffrey & P. Russell, Anthony. (2017). Ontogenetic allometry of the digital rays of the leopard gecko (Gekkota: Eublepharidae; Eublepharis macularius). Acta Zoologica. . 10.1111/azo.12215. Dionisio

Chameleon species have recently been adopted as models for evo-devo and macroevolutionary processes. However, most anatomical and developmental studies of chameleons focus on the skeleton , and information about their soft tissues is scarce. Here, we provide a detailed morphological description based on contrast enhanced micro-CT scans and dissections of the adult phenotype of all the forelimb and hindlimb muscles of the Veiled Chameleon (Chamaeleo calyptratus) and compare these muscles with those of other chameleons and lizards. We found the appendicular muscle anatomy of chameleons to be surprisingly conservative considering the remarkable structural and functional modifications of the limb skeleton, particularly the distal limb regions. For instance, the zygodactyl autopodia of chameleons are unique among tetrapods, and the carpals and tarsals are highly modified in shape and number. However, most of the muscles usually present in the manus and pes of other lizards are present in the same configuration in chameleons. The most obvious muscular features related to the peculiar opposable autopodia of chameleons are: (1) presence of broad, V-shaped plantar and palmar aponeuroses, and absence of intermetacarpales and intermeta-tarsales, between the digits separated by the cleft in each autopod; (2) oblique orientation of the superficial short flexors originating from these aponeuroses, which may allow these muscles to act as powerful adductors of the " super-digits " ; and (3) well-developed abductor digiti minimi muscles and abductor pollicis/hallucis brevis muscles, which may act as powerful abductors of the " super-digits. Molnar, Julia & Diaz, Raul & Skorka, Tautis & , Grant & Diogo, Rui. (2017). Comparative musculoskeletal anatomy of chameleon limbs, with implications for the evolution of arboreal locomotion in lizards and for teratology. Journal of morphology. 278. . 10.1002/jmor.20708. Dionisio

gooshy @157, Is your comment related to the comment @5? https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-645907 I haven't had the opportunity to listen to the named Canadian singer, but have heard dolphins. Dionisio

Since the rise of evo-devo (evolutionary developmental biology) in the 1980s, few authors have attempted to combine the increasing knowledge obtained from the study of model organisms and human medicine with data from comparative anatomy and evolutionary biology in order to investigate the links between development, pathology, and macroevolution. Fortunately, this situation is slowly changing, with a renewed interest in evolutionary developmental pathology (evo-devo-path) in the past decades, as evidenced by the idea to publish this special, and very timely, issue on “Developmental Evolution in Biomedical Research.” As all of us have recently been involved, independently, in works related in some way or another with evolution and developmental anomalies, we decided to join our different perspectives and backgrounds in the present contribution for this special issue. Specifically, we provide a brief historical account on the study of the links between evolution, development, and pathologies, followed by a review of the recent work done by each of us, and then by a general discussion on the broader developmental and macroevolutionary implications of our studies and works recently done by other authors. Our primary aims are to highlight the strength of studying developmental anomalies within an evolutionary framework to understand morphological diversity and disease by connecting the recent work done by us and others with the research done and broader ideas proposed by authors such as Étienne Geoffroy Saint-Hilaire, Waddington, Goldschmidt, Gould, and Per Alberch, among many others to pave the way for further and much needed work regarding abnormal development and macroevolution. Diogo, Rui & Guinard, Geoffrey & Diaz, Raul. (2016). Dinosaurs, Chameleons, Humans, and Evo?Devo Path: Linking Étienne Geoffroy's Teratology, Waddington's Homeorhesis, Alberch's Logic of “Monsters,” and Goldschmidt Hopeful “Monsters”. Journal of Experimental Zoology Part B Molecular and Developmental Evolution. 328. . 10.1002/jez.b.22709. Dionisio

Sorry if somebody told this already, but in re canadian pop stars: What's the difference between Justin Bieber and a dolphin? One makes really annoying high-pitched squeaks. The other is a large marine mammal. gooshy

It's worth reminding all about these two insightful comments by gpuccio @122 & @123: https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649412 Dionisio

This paper describes and summarizes approaches for visualization and statistical analysis using data from Ralstonia solanacearum infection experiments based on methods and concepts that are broadly applicable. Members of the R. solanacearum species complex cause bacterial wilt disease. Bacterial wilt is a lethal plant disease and has been studied for over 100 years. During this time various methods to quantify disease and different ways to analyze the generated data have been employed. Here, I aim to provide a general background on three distinct and commonly used measures of disease: the area under the disease progression curve, longitudinal recordings of disease severity and host survival. I will discuss how one can proceed with visualization, statistical analysis, and interpretation using different datasets while revisiting the general concepts of statistical analysis. Datasets and R code to perform all analyses discussed here are included in the supplement. Schandry, Niklas. (2017). A Practical Guide to Visualization and Statistical Analysis of R. solanacearum Infection Data Using R. Frontiers in Plant Science. 8. . 10.3389/fpls.2017.00623. https://www.researchgate.net/profile/Niklas_Schandry/publication/316459410_A_Practical_Guide_to_Visualization_and_Statistical_Analysis_of_R_solanacearum_Infection_Data_Using_R/links/59082b43a6fdccd580dd0ce1/A-Practical-Guide-to-Visualization-and-Statistical-Analysis-of-R-solanacearum-Infection-Data-Using-R.pdf Dionisio

Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA)-responsive genes NtPR1a/c, NtPR2 and NtCHN50, JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26. Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum. Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection. Tang, Yuanman & Liu, Qiuping & Liu, Ying & Zhang, Linli & Ding, Wei. (2017). Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum. Frontiers in Plant Science. 08. 1963. 10.3389/fpls.2017.01963. https://www.researchgate.net/publication/321100396_Overexpression_of_NtPR-Q_Up-Regulates_Multiple_Defense-Related_Genes_in_Nicotiana_tabacum_and_Enhances_Plant_Resistance_to_Ralstonia_solanacearum/fulltext/5a0d8e6d0f7e9b9e33ab51dd/321100396_Overexpression_of_NtPR-Q_Up-Regulates_Multiple_Defense-Related_Genes_in_Nicotiana_tabacum_and_Enhances_Plant_Resistance_to_Ralstonia_solanacearum.pdf Dionisio

F-box proteins are substrate adaptors used by the SKP1-CUL1-F-box protein (SCF) complex, a type of E3 ubiquitin ligase complex in the ubiquitin proteasome system (UPS). SCF-mediated ubiquitylation regulates proteolysis of hundreds of cellular proteins involved in key signaling and disease systems. However, our knowledge of the evolution of the F-box gene family in Euarchontoglires is limited. In the present study, 559 F-box genes and nine related pseudogenes were identified in eight genomes. Lineage-specific gene gain and loss events occurred during the evolution of Euarchontoglires, resulting in varying F-box gene numbers ranging from 66 to 81 among the eight species. Both tandem duplication and retrotransposition were found to have contributed to the increase of F-box gene number, whereas mutation in the F-box domain was the main mechanism responsible for reduction in the number of F-box genes, resulting in a balance of expansion and contraction in the F-box gene family. Thus, the Euarchontoglire F-box gene family evolved under a birth-and-death model. Signatures of positive selection were detected in substrate-recognizing domains of multiple F-box proteins, and adaptive changes played a role in evolution of the Euarchontoglire F-box gene family. In addition, single nucleotide polymorphism (SNP) distributions were found to be highly non-random among different regions of F-box genes in 1092 human individuals, with domain regions having a significantly lower number of non-synonymous SNPs. Wang, Ailan & Fu, Mingchuan & Jiang, Xiaoqian & Y.H., Mao & Li, Xiangchen & Tao, Shiheng. (2014). Evolution of the F-Box Gene Family in Euarchontoglires: Gene Number Variation and Selection Patterns. PloS one. 9. e94899. 10.1371/journal.pone.0094899. https://www.researchgate.net/profile/Mingchuan_Fu/publication/261608607_Evolution_of_the_F-Box_Gene_Family_in_Euarchontoglires_Gene_Number_Variation_and_Selection_Patterns/links/5506a0430cf231de077824c8/Evolution-of-the-F-Box-Gene-Family-in-Euarchontoglires-Gene-Number-Variation-and-Selection-Patterns.pdf Dionisio

I don't recall seeing DiEb's response to gpuccio's nice invitation to present his math-based ideas. gpuccio's nice invitation was posted @103 here: https://uncommondescent.com/evolution/this-parody-of-evo-devo-makes-it-sound-a-lot-like-id/#comment-649277 Did I miss the response? Was it posted in another website? Can someone point to the response for me? Thanks. Dionisio

Added website names in the list. Please, note that no web info service is 100% reliable. Also note that the numbers keep fluctuating. However, the different reports confirm that UD is comfortably within 1% of the currently active websites. KF's OP title was very cautious, but still provoked some objectors to bark up the wrong trees. That's unavoidable in a free forum like this. https://www.alexa.com/siteinfo/uncommondescent.com MIT.edu___________481 Nature.com________860 Harvard.edu_________873 Biblegateway.com_______1,001 mtgsalvation.com______10,201 Desiringgod.org_______10,908 Answersingenesis.org_____28,882 Ligonier.org__________40,278 Truthforlife.org______42,349 Gty.org_______45,516 Samaritanspurse.org_____51,000 freethoughtblogs.com_____76,655 Icr.org_______77,874 sermonsearch.com______81,317 Religionnews.com_____96,212 Royalsociety.org_____102,052 keepbelieving.com______144,829 sermonnotebook.org_____146,899 Rzim.org_______148,154 Evolutionnews.org_____168,380 gospelinlife.com______231,645 Kodugamelab.com______311,217 Reasons.org___________346,070 fpcjackson.org_______358,074 asa3.org_____________428,374 Jamesmacdonald.com_____460,457 discovery.org__________542,905 Uncommondescent.com_____644,999 Pandasthumb.org__________906,313 intelligentdesign.org_____932,239 ideacenter.org___________1,655,821 arn.org__________________1,956,610 theskepticalzone.com______5,147,609 biologicinstitute.org_____6,450,899 Evoinfo.org_______________10,309,075 * Active websites (10%): 132M to 173M UD 0.4% – 0.5% PT. 0.5% – 0.7% TSZ 3% – 4% All websites UD 0.04% – 0.05% (*) mentioned @25 Dionisio

The Red Queen Hypothesis proposes that perpetual co-evolution among organisms can result from purely biotic drivers. After more than four decades, there is no satisfactory understanding as to which mechanisms trigger Red Queen dynamics or their implications for ecosystem features such as biodiversity. One reason for such a knowledge gap is that typical models are complicated theories where limit cycles represent an idealized Red Queen, and therefore cannot be used to devise experimental setups. Here, we bridge this gap by introducing a simple model for microbial systems able to show Red Queen dynamics. We explore diverse biotic sources that can drive the emergence of the Red Queen and that have the potential to be found in nature or to be replicated in the laboratory. Our model enables an analytical understanding of how Red Queen dynamics emerge in our setup, and the translation of model terms and phenomenology into general underlying mechanisms. We observe, for example, that in our system the Red Queen offers opportunities for the increase of biodiversity by facilitating challenging conditions for intraspecific dominance, whereas stasis tends to homogenize the system. Our results can be used to design and engineer experimental microbial systems showing Red Queen dynamics. Bonachela, Juan & Wortel, Meike & Chr. Stenseth, Nils. (2017). Eco-evolutionary Red Queen dynamics regulate biodiversity in a metabolite-driven microbial system. Scientific Reports. 7. . 10.1038/s41598-017-17774-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732168/pdf/ Dionisio

In antagonistic symbioses, such as host-parasite interactions, one population's success is the other's loss. In mutualistic symbioses, such as division of labor, both parties can gain, but they might have different preferences over the possible mutualistic arrangements. The rates of evolution of the two populations in a symbiosis are important determinants of which population will be more successful: Faster evolution is thought to be favored in antagonistic symbioses (the "Red Queen effect"), but disfavored in certain mutualistic symbioses (the "Red King effect"). However, it remains unclear which biological parameters drive these effects. Here, we analyze the effects of the various determinants of evolutionary rate: generation time, mutation rate, population size, and the intensity of natural selection. Our main results hold for the case where mutation is infrequent. Slower evolution causes a long-term advantage in an important class of mutualistic interactions. Surprisingly, less intense selection is the strongest driver of this Red King effect, whereas relative mutation rates and generation times have little effect. In antagonistic interactions, faster evolution by any means is beneficial. Our results provide insight into the demographic evolution of symbionts. Veller, Carl & K Hayward, Laura & Hilbe, Christian & Nowak, Martin. (2017). The Red Queen and King in finite populations. Proceedings of the National Academy of Sciences of the United States of America. 114. . 10.1073/pnas.1702020114. Dionisio

Host plants possibly represent the strongest selection pressure for the evolution of reproductive traits in phytophagous insects. In a first part of this chapter, we review how plant quality affects both female and male life history traits and their respective reproductive success, and how the production and transfer to females of male sperm and associated nongametic substances (spermatophores as nuptial gifts) also depend on the host plant choice. At first glance, it seems that reproductive traits in phytophagous insects should be selected to maximize the success of this short-term interaction between host plant and phytophagous insects. This, however, ignores the fact that variation in reproductive success is detrimental to long-term fitness, which may explain that reproductive traits depart from their short-term expectation in unpredictable environments. Bet-hedging strategies – as exemplified by spatial or temporal dispersal (e.g., prolonged diapause) – can therefore evolve in such environments, as described in the second part of this chapter. The knowledge reviewed in this chapter is also integrated in the broader applied perspective of insect pest population management. Moreau, Jérôme & Desouhant, Emmanuel & Louâpre, Philippe & Goubault, Marlène & Rajon, Etienne & Jarrige, Alicia & Menu, F & Thiery, Denis. (2017). How Host Plant and Fluctuating Environments Affect Insect Reproductive Strategies?. Advances in Botanical Research. 259-288. 10.1016/bs.abr.2016.09.008. https://www.researchgate.net/profile/Marlene_Goubault/publication/309280375_How_Host_Plant_and_Fluctuating_Environments_Affect_Insect_Reproductive_Strategies/links/59db7221a6fdcc0ffd1aa093/How-Host-Plant-and-Fluctuating-Environments-Affect-Insect-Reproductive-Strategies.pdf Dionisio

evo devo despacito? Many life-history traits are important determinants of the generation time. For instance, semelparous species whose adults reproduce only once have shorter generation times than iteroparous species that reproduce on several occasions, assuming equal development duration. A shorter generation time ensures a higher growth rate in stable environments where resources are in excess and is therefore a positively selected feature in this situation. In a stable and limiting environment, all combinations of traits that produce the same number of viable offspring are selectively equivalent. Here we study the neutral evolution of life-history strategies with different generation times and show that the slowest strategy represents the most likely evolutionary outcome when mutation is considered. Indeed, strategies with longer generation times generate fewer mutants per time unit, which makes them less likely to be replaced within a given time period. This turnover bias favors the evolution of strategies with long generation times. Its real impact, however, depends on both the population size and the nature of selection on life-history strategies. The latter is primarily impacted by the relationships between life-history traits whose estimation will be crucial to understanding the evolution of life-history strategies. Verin, Mélissa & Bourg, Salomé & Menu, Frédéric & Rajon, Etienne. (2017). The Biased Evolution of Generation Time. The American Naturalist. 190. E000-E000. 10.1086/692324. Dionisio

Project Mutation, Randomness and Evolution (book) Arlin Stoltzfus Goal: The randomness doctrine appears to refer to a property of mutation, but when examined more closely, it emerges as one facet of a broad and deep commitment to the unequal marriage of variation and selection proposed by Darwin, in which selection is a governing principle, while variation is relegated to the provision of raw material--- clay to be shaped by the potter---, supplying substance only, not initiative, direction, or creativity. This book uses a dissection of the randomness doctrine to re-think the role of variation in evolution, providing (1) a fresh and useful explanation of how mutation works, and why it is not "random" in any precise sense, (2) how there are different domains of population genetics, only some of which correspond to the neo-Darwinian verbal theories of causation used by nearly all evolutionary biologists, (3) how a commitment to the Darwinian view of roles continues to shape evolutionary thinking, and (4) new analyses showing how mutation operates importantly as a source of initiative and direction, violating the role assigned to it in neo-Darwinism. https://www.researchgate.net/project/Mutation-Randomness-and-Evolution-book Dionisio

In 2011, the serial of the European Group on Biological Invasions Neobiota was relaunched as an international, open access journal by Pensoft Publishers. In the editorial of the first issue, a large group of co-editors claimed for openness in covering a broad range of issues in invasion science, including the intersections with applied and social sciences, and referring to different groups of taxa and geographical regions. What happened since then? We here shortly reflect how the new NeoBiota journal has developed in the first years of its infancy – based on some data on the published papers, the addressed topics and the geographical background of our contributing authors. Kühn, Ingolf & Pyšek, Petr & Kowarik, Ingo. (2017). Seven years of NeoBiota – the times, were they a changin’?. NeoBiota. 36. 57-69. 10.3897/neobiota.36.21926. https://neobiota.pensoft.net/article/21926/download/pdf/ Dionisio

We identified emerging scientific, technological, and sociopolitical issues likely to affect how biological invasions are studied and managed over the next two decades. Issues were ranked according to their probability of emergence, pervasiveness, potential impact, and novelty. Top-ranked issues include the application of genomic modification tools to control invasions, effects of Arctic globalization on invasion risk in the Northern Hemisphere, commercial use of microbes to facilitate crop production, the emergence of invasive microbial pathogens, and the fate of intercontinental trade agreements. These diverse issues suggest an expanding interdisciplinary role for invasion science in biosecurity and ecosystem management, burgeoning applications of biotechnology in alien species detection and control, and new frontiers in the microbial ecology of invasions. Ricciardi, Anthony & Blackburn, Tim & Carlton, James & Dick, Jaimie & E. Hulme, Philip & Iacarella, Josephine & M. Jeschke, Jonathan & Liebhold, Andrew & L. Lockwood, Julie & MacIsaac, Hugh & Pyšek, Petr & Richardson, David & Ruiz, Gregory & Simberloff, Daniel & Sutherland, William & Wardle, David & Aldridge, David. (2017). Invasion Science: A Horizon Scan of Emerging Challenges and Opportunities. Trends in Ecology & Evolution. 32. . 10.1016/j.tree.2017.03.007. https://www.researchgate.net/profile/Josephine_Iacarella/publication/315948056_Invasion_Science_A_Horizon_Scan_of_Emerging_Challenges_and_Opportunities/links/58ee541faca2724f0a28a0bf/Invasion-Science-A-Horizon-Scan-of-Emerging-Challenges-and-Opportunities.pdf Dionisio

Bottlenecks in population size can reduce fitness and evolutionary potential, yet introduced species often become invasive. This poses a dilemma referred to as the genetic paradox of invasion. Three characteristics must hold true for an introduced population to be considered paradoxical in this sense. First, it must pass through a bottleneck that reduces genetic variation. Second, despite the bottleneck, the introduced population must not succumb to the many problems associated with low genetic variation. Third, it must adapt to the novel environment. Some introduced populations are not paradoxical as they do not combine these conditions. In some cases, an apparent paradox is spurious, as seen in introduced populations with low diversity in neutral markers that maintain high genetic variation in ecologically relevant traits. Even when the genetic paradox is genuine, unique aspects of a species’ biology can allow a population to thrive. We propose research directions into remaining paradoxical aspects of invasion genetics. Estoup, Arnaud. (2016). IS THERE A GENETIC PARADOX OF BIOLOGICAL INVASION?. Annual Review of Ecology and Systematics. . 10.1146/annurev-ecolsys-121415–032116. Dionisio

evo devo despacito? :) https://uncommondescent.com/intelligent-design/how-embryonic-development-bears-on-evolution/ https://uncommondescent.com/intelligent-design/allmon-and-ross-demolish-evolution/ Dionisio

evo devo despacito? :) In neo-Darwinian theory, adaptation results from a response to selection on relatively slowly accumulating genetic variation. However, more rapid adaptive responses are possible if selectable or plastic phenotypic variation is produced by epigenetic differences in gene expression. This rapid path to adaptation may prove particularly important when genetic variation is lacking, such as in small, bottlenecked, or asexual populations. To examine the potential for an epigenetic contribution to adaptive variation, we examined morphological divergence and epigenetic variation in genetically impoverished asexual populations of a freshwater snail, Potamopyrgus antipodarum, from distinct habitats (two lakes versus two rivers). These populations exhibit habitat specific differences in shell shape, and these differences are consistent with adaptation to water current speed. Between these same habitats, we also found significant genome wide DNA methylation differences. The differences between habitats were an order of magnitude greater than the differences between replicate sites of the same habitat. These observations suggest one possible mechanism for the expression of adaptive shell shape differences between habitats involves environmentally induced epigenetic differences. This provides a potential explanation for the capacity of this asexual snail to spread by adaptive evolution or plasticity to different environments. L.M. Thorson, Jennifer & Smithson, Mark & Beck, Daniel & Sadler-Riggleman, Ingrid & Nilsson, Eric & Dybdahl, Mark & K. Skinner, Michael. (2017). Epigenetics and adaptive phenotypic variation between habitats in an asexual snail. Scientific Reports. 7. . 10.1038/s41598-017-14673-6. https://www.researchgate.net/publication/320630309_Epigenetics_and_adaptive_phenotypic_variation_between_habitats_in_an_asexual_snail/fulltext/59f37f580f7e9b553eba71a0/320630309_Epigenetics_and_adaptive_phenotypic_variation_between_habitats_in_an_asexual_snail.pdf Dionisio

evo devo despacito? :) In the last 15 years considerable attempts have been undertaken to develop the obligately parthenogenetic marbled crayfish Procambarus virginalis as a new model in biology. Its main advantage is the production of large numbers of offspring that are genetically identical to the mother, making this crustacean particularly suitable for research in epigenetics. Now, a draft genome, transcriptome and genome-wide methylome are available opening new windows for research. In this article, I summarize the biological advantages and genomic and epigenetic features of marbled crayfish and, based on first promising data, discuss what this new model could contribute to answering of "big" biological questions. Genome mining is expected to reveal new insights into the genetic specificities of decapod crustaceans, the genetic basis of arthropod reproduction, moulting and immunity, and more general topics such as the genetic underpinning of adaptation to fresh water, omnivory, biomineralization, sexual system change, behavioural variation, clonal genome evolution, and resistance to cancer. Epigenetic investigations with the marbled crayfish can help clarifying the role of epigenetic mechanisms in gene regulation, tissue specification, adult stem cell regulation, cell ageing, organ regeneration and disease susceptibility. Marbled crayfish is further suitable to elucidate the relationship between genetic and epigenetic variation, the transgenerational inheritance of epigenetic signatures and the contribution of epigenetic phenotype variation to the establishment of social hierarchies, environmental adaptation and speciation. These issues can be tackled by experiments with highly standardized laboratory lineages, comparison of differently adapted wild populations and the generation of genetically and epigenetically edited strains. Vogt, Günter. (2017). Investigating the genetic and epigenetic basis of big biological questions with the new crayfish model Procambarus virginalis. . Dionisio

evo devo despacito? :) There is increasing evidence, particularly from plants, that epigenetic mechanisms can contribute to environmental adaptation and evolution. The present article provides an overview on this topic for animals and highlights the special suitability of clonal, invasive, hybrid, polyploid, and domesticated species for environmental and evolutionary epigenetics. Laboratory and field studies with asexually reproducing animals have shown that epigenetically diverse phenotypes can be produced from the same genome either by developmental stochasticity or environmental induction. The analysis of invasions revealed that epigenetic phenotype variation may help to overcome genetic barriers typically associated with invasions such as bottlenecks and inbreeding. Research with hybrids and polyploids established that epigenetic mechanisms are involved in consolidation of speciation by contributing to reproductive isolation and restructuring of the genome in the neo-species. Epigenetic mechanisms may even have the potential to trigger speciation but evidence is still meager. The comparison of domesticated animals and their wild ancestors demonstrated heritability and selectability of phenotype modulating DNA methylation patterns. Hypotheses, model predictions, and empirical results are presented to explain how epigenetic phenotype variation could facilitate adaptation and speciation. Clonal laboratory lineages, monoclonal invaders, and adaptive radiations of different evolutionary age seem particularly suitable to empirically test the proposed ideas. A respective research agenda is presented. Vogt, Günter. (2017). Facilitation of environmental adaptation and evolution by epigenetic phenotype variation: insights from clonal, invasive, polyploid, and domesticated animals. Environmental Epigenetics. 3. . 10.1093/eep/dvx002. http://academic.oup.com/eep/article-pdf/3/1/dvx002/11124301/dvx002.pdf Dionisio

evo devo despacito? :) What role does non-genetic inheritance play in evolution? In recent work we have independently and collectively argued that the existence and scope of non-genetic inheritance systems, including epigenetic inheritance, niche construction/ecological inheritance, and cultural inheritance—alongside certain other theory revi-sions—necessitates an extension to the neo-Darwinian Modern Synthesis (MS) in the form of an Extended Evo-lutionary Synthesis (EES). However, this argument has been challenged on the grounds that non-genetic inheri-tance systems are exclusively proximate mechanisms that serve the ultimate function of calibrating organisms to stochastic environments. In this paper we defend our claims, pointing out that critics of the EES (1) conflate non-genetic inheritance with early 20th-century notions of soft inheritance; (2) misunderstand the nature of the EES in relation to the MS; (3) confuse individual phenotypic plasticity with trans-generational non-genetic inheritance; (4) fail to address the extensive theoretical and empirical literature which shows that non-genetic inheritance can generate novel targets for selection, create new genetic equilibria that would not exist in the absence of non-genetic inheritance, and generate phenotypic variation that is independent of genetic variation; (5) artificially limit ultimate explanations for traits to gene-based selection, which is unsatisfactory for phenotypic traits that originate and spread via non-genetic inheritance systems; and (6) fail to provide an explanation for biological organization. Mesoudi, Alex & Blanchet, Simon & Charmantier, Anne & Danchin, Etienne & Fogarty, Laurel & Jablonka, Eva & Laland, Kevin & Morgan, Thomas & Müller, Gerd & Odling-Smee, John & Pujol, Benoit. (2013). Is Non-genetic Inheritance Just a Proximate Mechanism? A Corroboration of the Extended Evolutionary Synthesis. Biological Theory. . . 10.1007/s13752-013-0091-5. https://www.researchgate.net/profile/Anne_Charmantier/publication/236873985_Is_Non-genetic_Inheritance_Just_a_Proximate_Mechanism_A_Corroboration_of_the_Extended_Evolutionary_Synthesis/links/59c20c23a6fdcc69b92fb603/Is-Non-genetic-Inheritance-Just-a-Proximate-Mechanism-A-Corroboration-of-the-Extended-Evolutionary-Synthesis.pdf Dionisio

evo devo despacito? :) A central challenge in evolutionary biology concerns the mechanisms by which complex adaptations arise. Such adaptations depend on the fixation of multiple, highly specific mutations, where intermediate stages of evolution seemingly provide little or no benefit. It is generally assumed that the establishment of complex adaptations is very slow in nature, as evolution of such traits demands special population genetic or environmental circumstances. However, blueprints of complex adaptations in molecular systems are pervasive, indicating that they can readily evolve. We discuss the prospects and limitations of non-adaptive scenarios, which assume numerous neutral or deleterious steps in the evolution of complex adaptations. Next, we examine how complex adaptations can evolve by natural selection in a changing environment. Finally, we argue that molecular ‘springboards’ such as phenotypic heterogeneity and promiscuous interactions facilitate this process by providing access to new adaptive paths. The evolution of complex adaptations poses conceptual challenges. Here, the authors discuss adaptive and non-adaptive scenarios in the evolution of complex adaptations and propose molecular mechanisms that provide access to new adaptive paths. Pál, Csaba & Papp, Balázs. (2017). Evolution of complex adaptations in molecular systems. Nature Ecology & Evolution. 1. 1084-1092. 10.1038/s41559-017-0228-1. Dionisio

evo devo despacito? :) Darwinism is one of several research traditions in evolutionary biology. I identify it, both before and after its unification with genetics, with Darwin’s theory of descent by natural selection from a common ancestor. Other traditions include saltationism/mutationism, Lamarckism, and evolutionary developmentalism (“evo-devo”). I argue that Darwinism’s continued dominance in evolutionary science reflects its proven ability to interact productively with these other traditions, an ability impressed on it by its founder’s example. Evolution by sudden leaps (saltations) is alien to the spirit of Darwinism, but Darwinism advanced its own agenda by incorporating and subverting saltationist themes. Similarly, Lamarckism’s belief in the heritability of acquired characteristics has been discredited, but some of the facts to which it seems congenial reappear in genetic Darwinism as phenotypic plasticity and niche construction. These examples help assess challenges to Darwinism’s hegemony currently arising from the role of regulatory genes and epigenetic factors in development. Rather than executing already entrenched genetic programs and relying on chance mutation to initiate evolutionary change, the developmental process appears to generate heritable variations that ab initio respond to environmental factors in an adaptive way. Depew, David. (2017). Darwinism in the Twentieth Century: Productive Encounters with Saltation, Acquired Characteristics, and Development. 61-88. 10.1007/978-3-319-69123-7_4. Dionisio

evo devo despacito? :) Project Genes, Environments, and the Creativity of Natural Selection in the Modern Evolutionary Synthesis and Beyond It (In Preparation) Bruce Weber Goal: (rest of title) Evolutionary Synthesis -- and Beyond David Depew and Bruce Weber (in press) Dionisio

evo devo despacito? :) The neo-Darwinian paradigm, focusing on natural selection of genes responsible for differential adaption, provides the foundation for explaining evolutionary processes. The modern synthesis is broader, however, focusing on organisms rather than on gene transmissions per se. Yet, strands of current biology argue for further supplementation of Darwinian theory, pointing to nonbiotic drivers of evolutionary development, for example, self-organization of physical structures, and the interaction between individual organisms, groups of organisms, and their nonbiotic environments. According to niche construction theory, when organisms and groups develop, they not only adapt to their environments but modify their environments, creating new habitats for later generations. Insofar as ecological niches persist beyond the lifecycle of individual organisms, an ecological inheritance system exists alongside genetic inheritance. Such ecological structures may even facilitate the development of a cultural inheritance system, as we see in humans. The article discusses theological perspectives of such new developments within holistic biology. Henrik Gregersen, Niels. (2017). THE EXPLORATION OF ECOSPACE: EXTENDING OR SUPPLEMENTING THE NEO-DARWINIAN PARADIGM?: with Fraser Watts and Michael J. Reiss, “Holistic Biology: What It Is and Why It Matters”; Michael Ruse, “The Christian's Dilemma: Organicism or Mecha. Zygon(r). 52. 561-586. 10.1111/zygo.12344. Dionisio

evo devo despacito? :) Recent developments toward a more holistic biology do not eliminate reductionism and determinism, but they do suggest more complex forms of them, in which there are multiple, interacting influences, as there are in complex or chaotic systems. Though there is a place in biology for both systemic and atomistic modes of explanation, for those with a theological perspective the shift to complex explanations in biology is often welcome. It suggests a more subtle view of divine action in which God's purposes are affected through engagement with the complex systems of creation rather than by discrete interventions. It also invites us to connect the biological interdependence with the interdependence in the nature and purposes of God, and it is consonant with a mystical vision of the unity of all things. Watts, Fraser & Reiss, Michael. (2017). HOLISTIC BIOLOGY: WHAT IT IS AND WHY IT MATTERS. Zygon(r). 52. 419-441. 10.1111/zygo.12339. Dionisio

evo devo despacito? :) Using the evolution of the stickleback family of subarctic fish as a touchstone, we explore the effect of new discoveries about regulatory genetics, developmental plasticity, and epigenetic inheritance on the conceptual foundations of the Modern Evolutionary Synthesis. Identifying the creativity of natural selection as the hallmark of the Modern Synthesis, we show that since its inception its adherents have pursued a variety of research projects that at first seemed to conflict with its principles, but were accommodated. We situate challenges coming from developmental biology in a dialectic between innovation and tradition, suggesting on the basis of past episodes that even if developmental plasticity and epigenetic inheritance are aligned with its principles the Modern Synthesis (and its image in the public reception of evolution) will be significantly affected. Depew, David & Weber, Bruce. (2017). DEVELOPMENTAL BIOLOGY, NATURAL SELECTION, AND THE CONCEPTUAL BOUNDARIES OF THE MODERN EVOLUTIONARY SYNTHESIS: with Fraser Watts and Michael J. Reiss, “Holistic Biology: What It Is and Why It Matters”; Michael Ruse, “The Christian's Dilemma: Organicism or Mecha. Zygon(r). 52. 468-490. 10.1111/zygo.12332. Dionisio

evo devo despacito? :) Smulders, Tom. (2017). Evolution Driven by Organismal Behaviour – a Unifying View of Life, Function, Form, Mismatches, and Trends By Rui Diogo, 252 pages. Springer International Publishing AG, Cham, Switzerland, 2017. ISBN: 978?3?319?47580?6.. Journal of Anatomy. . 10.1111/joa.12750. Dionisio

evo devo despacito? :) Bateson, Patrick & Cartwright, Nancy & Dupré, John & Laland, Kevin & Noble, Denis. (2017). New trends in evolutionary biology: Biological, philosophical and social science perspectives. Interface Focus. 7. 20170051. 10.1098/rsfs.2017.0051. https://www.researchgate.net/profile/John_Dupre/publication/319191327_New_trends_in_evolutionary_biology_Biological_philosophical_and_social_science_perspectives/links/599fee394585151e3c73d877/New-trends-in-evolutionary-biology-Biological-philosophical-and-social-science-perspectives.pdf Dionisio

Since nobody answered the quiz, let's try to encourage more enthusiastic participation in next quiz. Maybe we could offer a nice prize to the winner of the quiz? What could we offer? Here's an idea: A dinner for two at the best restaurant by the littoral in Palermo. This was originally the prize for whoever could explain evolution, but since we have realized that it won't happen, then the funds can be used for the evo devo despacito quiz prize. Would that motivate more enthusiastic participation in the evo devo despacito quiz next time? :) Dionisio

evo devo despacito quiz: What does MESS stand for? Modern Evolutionary Shaky Synthesis which is based on Messy Evolutionary Shaky Standards IOW, MESS on top of MESS :) Dionisio

gpuccio @123:

all this stuff about biased mutations being an important factor in explaining biological function is completely unwarranted. Biological variation is both random and unrelated to function. It can explain nothing.

Clear point. Thanks. Dionisio

gpuccio @123:

the “bias” towards certain mutations cannot in any way explain how the code for a complex functional protein arises.

That's clear. Thanks. Dionisio

gpuccio @123:

the laws that determine the different probabilities of outcomes of random variation (for example, the different probabilities of specific nucleotide mutations) have no connection at all with the laws that determine the meaning of nucleotide sequences (as coded by the genetic code) and the biochemical functions of protein sequences (which depend on extremely complex biochemical laws, including those which cause folding).

Very valid point. Thanks. Dionisio

gpuccio @122, That's a valid point. Thanks. Is the author of the paper you referenced @122 another example of someone trying to butter their bread on both sides? :) Dionisio

Dionisio: d) But there is another important sense in which biological variation can be considered "random", even if random is not the correct word here. Let's say that biological variation, if unguided, is unrelated to function. IOWs, there is no reason why we should expect any statistically significant relationship between random (in the sense discussed at points b) and c) ) biological variation and biological function. Why? Because the laws that determine the different probabilities of outcomes of random variation (for example, the different probabilities of specific nucleotide mutations) have no connection at all with the laws that determine the meaning of nucleotide sequences (as coded by the genetic code) and the biochemical functions of protein sequences (which depend on extremely complex biochemical laws, including those which cause folding). IOWs, the "bias" towards certain mutations cannot in any way explain how the code for a complex functional protein arises. So, all this stuff about biased mutations being an important factor in explaining biological function is completely unwarranted. Biological variation is both random and unrelated to function. It can explain nothing. We can easily see the difference with the concept of NS. NS, even with all its extreme limitations, which I have discussed here: https://uncommondescent.com/intelligent-design/what-are-the-limits-of-natural-selection-an-interesting-open-discussion-with-gordon-davisson/ is, at least, related in some way to function. That's why the traditional algorithm of RV + NS remains the only weapon for neo-darwinism and, in general, for all non design "explanations". We know how weak that weapon is, but it's all they have... :) gpuccio

Dionisio: Having partially read some of the references you give, I would like to offer a couple of thought about the random nature of biological variation: a) If we exclude the scenario of design, and therefore of guided variation, we can certainly say that biological variation is random, in two important senses that I will try to clarify. b) The first sens is that biological variation is random because we cannot predict it according to necessity laws. In that sense, it is as random as tossing a coin. Both biological variation and coin tossing are completely deterministic (driven by the laws of physics and chemistry), but both systems cannot be described by a necessity system and are better described by a probabilistic system. c) It is absolutely true that biological variation is not an example of uniform distribution of probability. For example, nucleotide mutations are certainly not uniformly distributed, as we can see in this interesting paper by one of the authors you quote: https://academic.oup.com/jhered/article/100/5/637/782212 But I believe that the author is wrong in saying that this means that those mutations are "non random". They are random, because they can be described only by a probabilistic system, but of course the probabilities of the different events are different. That happens in most random systems, For example, in rolling two dice, the probability of the outcomes are very different. So, biological variation is truly random, but certainly different outcomes have different probabilities. More in next post. gpuccio

Whoever reads the posted paper references in this thread should figure out how to respond the easy evo devo despacito quiz. Dionisio

Ok, here's the answer to the evo devo despacito quiz: MESS is the acronym for... Dionisio

Hey, no one dares to respond the evo devo despacito quiz yet? Dionisio

evo devo despacito quiz: What does MESS stand for? Dionisio

evo devo despacito? Laland, Kevin & Uller, Tobias & Feldman, Marcus & Sterelny, Kim & Müller, Gerd & Moczek, Armin & Jablonka, Eva & Odling-Smee, John. (2014). Does evolutionary theory need a rethink? - POINT Yes, urgently. Nature. 514. 161-164. https://www.researchgate.net/profile/Gerd_Mueller/publication/278258986_Does_evolutionary_theory_need_a_rethink_-_POINT_Yes_urgently/links/55cd2f8708aebd6b88e05e5f/Does-evolutionary-theory-need-a-rethink-POINT-Yes-urgently.pdf Dionisio

evo devo despacito? :) Many readers of this journal have been schooled in both Darwinian evolution and Skinnerian psychology, which have in common the vision of powerful control of their subjects by their sequalae. Individuals of species that generate more successful offspring come to dominate their habitat; responses of those individuals that generate more reinforcers come to dominate the repertoire of the individual in that context. This is unarguable. What is questionable is how large a role these forces of selection play in the larger landscape of existing organisms and the repertoires of their individuals. Here it is argued that non-Darwinian and non-Skinnerian selection play much larger roles in both than the reader may appreciate. The argument is based on the history of, and recent advances in, microbiology. Lessons from that history re-illuminate the three putative domains of selection by consequences: The evolution of species, response repertoires, and cultures. It is argued that before, beneath, and after the cosmically brief but crucial epoch of Darwinian evolution that shaped creatures such as ourselves, non-Darwinian forces pervade all three domains. Killeen, Peter. (2017). The non-Darwinian evolution of behavers and behaviors. Behavioural Processes. . 10.1016/j.beproc.2017.12.024. https://www.researchgate.net/profile/Peter_Killeen2/publication/322143232_The_non-Darwinian_evolution_of_behavers_and_behaviors/links/5a5eeb54a6fdcc68fa993749/The-non-Darwinian-evolution-of-behavers-and-behaviors.pdf Dionisio

evo devo despacito? :) Noble, Denis & Jablonka, Eva & J. Joyner, Michael & Müller, Gerd & W. Omholt, Stig. (2014). Evolution evolves: Physiology returns to centre stage. The Journal of Physiology. 592. . 10.1113/jphysiol.2014.273151. Dionisio

evo devo despacito? :) Project Mutation, Randomness and Evolution (book) Arlin Stoltzfus Goal: The randomness doctrine appears to refer to a property of mutation, but when examined more closely, it emerges as one facet of a broad and deep commitment to the unequal marriage of variation and selection proposed by Darwin, in which selection is a governing principle, while variation is relegated to the provision of raw material--- clay to be shaped by the potter---, supplying substance only, not initiative, direction, or creativity. This book uses a dissection of the randomness doctrine to re-think the role of variation in evolution, providing (1) a fresh and useful explanation of how mutation works, and why it is not "random" in any precise sense, (2) how there are different domains of population genetics, only some of which correspond to the neo-Darwinian verbal theories of causation used by nearly all evolutionary biologists, (3) how a commitment to the Darwinian view of roles continues to shape evolutionary thinking, and (4) new analyses showing how mutation operates importantly as a source of initiative and direction, violating the role assigned to it in neo-Darwinism. Dionisio

evo devo despacito? :) The Functional Constructivism (FC) paradigm is an alternative to behaviorism and considers behavior as being generated every time anew, based on an individual's capacities, environmental resources and demands. Walter Freeman's work provided us with evidence supporting the FC principles. In this paper we make parallels between gradual construction processes leading to the formation of individual behavior and habits, and evolutionary processes leading to the establishment of biological systems. Referencing evolutionary theory, several formal descriptors of such processes are proposed. These FC descriptors refer to the most universal aspects for constructing consistent structures: expansion of degrees of freedom, integration processes based on internal and external compatibility between systems and maintenance processes, all given in four different classes of systems: (a) Zone of Proximate Development (poorly defined) systems; (b) peer systems with emerging reproduction of multiple siblings; (c) systems with internalized integration of behavioral elements ("cruise controls"); and (d) systems capable of handling low-probability, not yet present events. The recursive dynamics within this set of descriptors acting on (traditional) downward, upward and horizontal directions of evolution, is conceptualized as diagonal evolution, or di-evolution. Two examples applying these FC descriptors to taxonomy are given: classification of the functionality of neuro-transmitters and temperament traits; classification of mental disorders. The paper is an early step towards finding a formal language describing universal tendencies in highly diverse, complex and multi-level transient systems known in ecology and biology as "contingency cycles". Trofimova, Irina. (2017). Functional constructivism: In search of formal descriptors. Nonlinear Dynamics, Psychology, and Life Sciences. 21. 441-474. https://www.researchgate.net/profile/Irina_Trofimova2/publication/320418805_Functional_constructivism_In_search_of_formal_descriptors/links/59f89bd00f7e9b553ec0b8da/Functional-constructivism-In-search-of-formal-descriptors.pdf Dionisio

evo devo despacito? :) Trypanosoma brucei is transmitted between mammalian hosts by the tsetse fly. In the mammal, they are exclusively extracellular, continuously replicating within the bloodstream. During this stage, the mitochondrion lacks a functional electron transport chain (ETC). Successful transition to the fly, requires activation of the ETC and ATP synthesis via oxidative phosphorylation. This life cycle leads to a major problem: in the bloodstream, the mitochondrial genes are not under selection and are subject to genetic drift that endangers their integrity. Exacerbating this, T. brucei undergoes repeated population bottlenecks as they evade the host immune system that would create additional forces of genetic drift. These parasites possess several unique genetic features, including RNA editing of mitochondrial transcripts. RNA editing creates open reading frames by the guided insertion and deletion of U-residues within the mRNA. A major question in the field has been why this metabolically expensive system of RNA editing would evolve and persist. Here, we show that many of the edited mRNAs can alter the choice of start codon and the open reading frame by alternative editing of the 5’ end. Analyses of mutational bias indicate that six of the mitochondrial genes may be dual-coding and that RNA editing allows access to both reading frames. We hypothesize that dual-coding genes can protect genetic information by essentially hiding a non-selected gene within one that remains under selection. Thus, the complex RNA editing system found in the mitochondria of trypanosomes provides a unique molecular strategy to combat genetic drift in non-selective conditions. E. Kirby, Laura & Koslowsky, Donna. (2017). Mitochondrial dual-coding genes in Trypanosome brucei. PLOS Neglected Tropical Diseases. 11. e0005989. 10.1371/journal.pntd.0005989. http://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0005989&type=printable Dionisio

evo devo despacito? :) Ehsani, Sepehr. (2017). Relativism as a means to alleviate biology from genomic reductionism: But is the remedy effective?: Denis Noble: Dance to the Tune of Life: Biological Relativity. Cambridge University Press, December 2016, 302pp, £17.99 HB. Metascience. . 10.1007/s11016-017-0255-1. https://link.springer.com/content/pdf/10.1007/s11016-017-0255-1.pdf Dionisio

evo devo despacito? :) Over the last several hundred years of scientific progress, we have arrived at a deep understanding of the non-living world. We have not yet achieved an analogous, deep understanding of the living world. The origins of life is our best chance at discovering scientific laws governing life, because it marks the point of departure from the predictable physical and chemical world to the novel, history-dependent living world. This theme issue aims to explore ways to build a deeper understanding of the nature of biology, by modelling the origins of life on a sufficiently abstract level, starting from prebiotic conditions on Earth and possibly on other planets and bridging quantitative frameworks approaching universal aspects of life. The aim of the editors is to stimulate new directions for solving the origins of life. The present introduction represents the point of view of the editors on some of the most promising future directions. This article is part of the themed issue 'Reconceptualizing the origins of life'. © 2017 The Author(s) Published by the Royal Society. All rights reserved. Walker, Sara & Packard, N & D. Cody, G. (2017). Re-conceptualizing the origins of life. Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences. 375. 20160337. 10.1098/rsta.2016.0337. Dionisio

evo devo despacito? :) This paper briefly describes process metaphysics, and argues that it is better suited for describing life than the more standard thing, or substance, metaphysics. It then explores the implications of process metaphysics for conceptualising evolution. After explaining what it is for an organism to be a process, the paper takes up the Hull/Ghiselin thesis of species as individuals and explores the conditions under which a species or lineage could constitute an individual process. It is argued that only sexual species satisfy these conditions, and that within sexual species the degree of organisation varies. This, in turn, has important implications for the species’ evolvability. One important moral is that evolution will work differently in different biological domains. Dupré, John. (2017). The Metaphysics of Evolution. Interface focus: a theme supplement of Journal of the Royal Society interface. 7. . 10.1098/rsfs.2016.0148. https://www.researchgate.net/profile/John_Dupre/publication/317956232_The_Metaphysics_of_Evolution/links/5996babba6fdcc35c6c84cff/The-Metaphysics-of-Evolution.pdf Dionisio

evo devo despacito? :) Stochasticity is harnessed by organisms to generate functionality. Randomness does not, therefore, necessarily imply lack of function or 'blind chance' at higher levels. In this respect, biology must resemble physics in generating order from disorder. This fact is contrary to Schrödinger's idea of biology generating phenotypic order from molecular-level order, which inspired the central dogma of molecular biology. The order originates at higher levels, which constrain the components at lower levels. We now know that this includes the genome, which is controlled by patterns of transcription factors and various epigenetic and reorganization mechanisms. These processes can occur in response to environmental stress, so that the genome becomes 'a highly sensitive organ of the cell' (McClintock). Organisms have evolved to be able to cope with many variations at the molecular level. Organisms also make use of physical processes in evolution and development when it is possible to arrive at functional development without the necessity to store all information in DNA sequences. This view of development and evolution differs radically from that of neo-Darwinism with its emphasis on blind chance as the origin of variation. Blind chance is necessary, but the origin of functional variation is not at the molecular level. These observations derive from and reinforce the principle of biological relativity, which holds that there is no privileged level of causation. They also have important implications for medical science. Noble, Denis. (2017). Evolution viewed from physics, physiology and medicine. Interface Focus. 7. 20160159. 10.1098/rsfs.2016.0159. Dionisio

evo devo despacito? The question whether evolution is blind is usually presented as a choice between no goals at all (‘the blind watchmaker’) and long-term goals which would be external to the organism, for example in the form of special creation or intelligent design. The arguments either way do not address the question whether there are short-term goals within rather than external to organisms. Organisms and their interacting populations have evolved mechanisms by which they can harness blind stochasticity and so generate rapid functional responses to environmental challenges. They can achieve this by re-organising their genomes and/or their regulatory networks. Epigenetic as well as DNA changes are involved. Evolution may have no foresight, but it is at least partially directed by organisms themselves and by the populations of which they form part. Similar arguments support partial direction in the evolution of behavior. Noble, Ray & Noble, Denis. (2017). Was the Watchmaker Blind? Or Was She One-Eyed?. Biology. 6. 47. 10.3390/biology6040047. http://www.mdpi.com/2079-7737/6/4/47/pdf Dionisio

gpuccio @103: Interesting comment. Thanks. Dionisio

evo devo despacito? :) High-level debates in evolutionary biology often treat the Modern Synthesis as a framework of population genetics, or as an intellectual lineage with a changing distribution of beliefs. Unfortunately, these flexible notions, used to negotiate decades of innovations, are now thoroughly detached from their historical roots in the original Modern Synthesis (OMS), a falsifiable scientific theory. The OMS held that evolution can be adequately understood as a process of smooth adaptive change by shifting the frequencies of small-effect alleles at many loci simultaneously, without the direct involvement of new mutations. This shifting gene frequencies theory was designed to support a Darwinian view in which the course of evolution is governed by selection, and to exclude a mutation-driven view in which the timing and character of evolutionary change may reflect the timing and character of events of mutation. The OMS is not the foundation of current thinking, but a special case of a broader conception that includes (among other things) a mutation-driven view introduced by biochemists in the 1960s, and now widely invoked. This innovation is evident in mathematical models relating the rate of evolution directly to the rate of mutation, which emerged in 1969, and now represent a major branch of theory with many applications. In evo-devo, mutationist thinking is reflected by a concern for the "arrival of the fittest". Though evolutionary biology is not governed by any master theory, and incorporates views excluded from the OMS, the recognition of these changes has been hindered by woolly conceptions of theories, and by historical accounts, common in the evolutionary literature, that misrepresent the disputes that defined the OMS. Reviewers: This article was reviewed by W. Ford Doolittle, Eugene Koonin and J. Peter Gogarten. Stoltzfus, Arlin. (2017). Why we don’t want another “Synthesis”. Biology Direct. 12. 23. 10.1186/s13062-017-0194-1. https://www.researchgate.net/publication/320178983_Why_we_don%27t_want_another_Synthesis/fulltext/59d303780f7e9b4fd7fca0ca/320178983_Why_we_don%27t_want_another_Synthesis.pdf Dionisio

evo devo despacito? :) Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology. Fábregas-Tejeda, Alejandro & Vergara-Silva, Francisco. (2017). Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts. Evolutionary Biology. 1-13. 10.1007/s11692-017-9438-3. Dionisio

DiEb at #98: Thank you for your comments. I have read your linked post at TSZ, and I have of course no objections to it: I have not really tried the R simulation, but I am sure that your numbers are correct. OK, as you say, is it a big deal? I would say not, but any error deserves correction. I am more interested in your "pet-peeve" about the definition of search. I can agree that the word can be confusing. Speaking from my "empirical" perspective, I think we can definitely avoid it at all. For my purposes, the only important concept is to define some system where probabilistic events happen (in our case, some biological system on our planet, where RV happens in already existing organisms), and where, in a specified time window, some new specific configuration arises in the existing genomes. Of course, the new configuration has some level of functional information in itself, which can be measured (usually indirectly) in reference to some well defined function (usually the function biologically observed). In this context, we can say that a "search" in the probabilistic system "generated" that amount of functional information. Of course, it is not really a search, just some sequence of random events that brings about, in something that could be well described as a random walk, the observed result. In this sense, we can try to evaluate: a) The set of all possible configurations that can arise in the system (the search space). b) The subset of the specific configurations that can implement the observed function (the target space). c) The functional information linked to the observed function (-log2 (b/a)) d) The probabilistic resources of the system (the total number of different configurations that can be reached in the system in the defined time span). e) Comparing c) and d) we can derive the probability of the observed event in the system by RV alone. Of course, many of these steps require approximations, as in all empirical science. Can you agree with this kind of definition of "search" (or any other way we can agree to call it)? By the way, this is more or less what I have tried to do in my OP about the limits of RV: https://uncommondescent.com/intelligent-design/what-are-the-limits-of-random-variation-a-simple-evaluation-of-the-probabilistic-resources-of-our-biological-world/ And, of course, I have tried to factor in the possible role of NS in this other OP: https://uncommondescent.com/intelligent-design/what-are-the-limits-of-natural-selection-an-interesting-open-discussion-with-gordon-davisson/ gpuccio

ET @99, Interesting. ET, we know the final score of this game, even before it's over. Please, let's be magnanimous in victory. Let's show compassion to the defeated side. Dionisio

ET @97, Spot on! Again. Dionisio

ET @96, Spot on! Thanks. Dionisio

DiEB @ 55:

Now, you seem to be ignorant about Jeffrey Shallit.

I have had some discussions with Jeffrey and he seems to be ignorant. Jeff said that it is foolish to say that information requires a mind because computer programs can produce information and they don't have minds. I stepped in and told him that the mind is that of the programmer. He refused to understand cuz he says that if that programmer is dead then my point is moot. :roll: ET

@gpucchio: Thank you for your comments!

I think that the discussion about ID has shifted mainly to biological and empirical problems.

I suppose that this is the best think what can happen for ID: the maths was always quite problematic. I wanted to present a pet-peeve of mine - the definition of "search". I looked through the textbook "Introduction to Evolutionary Informatics", but I could find no place where this frequently used term was actually defined. Then I got side-tracked - here is the result: Prof. Marks gets lucky at Cracker Barrel I will revisit my initial project soon... DiEb

And in typical denialist ignorance biologist John Harshman says::

Pretty standard explanation of evo-devo. Is there supposed to be some comfort for creationists in it?

The fact that your position has nothing that can account for it gives every anti-blind watchmaker evolutionist comfort. The fact that only intelligent agencies can produce codes and regulatory networks gives us comfort. ET

One thing is clear- evolutionists don't have a coherent, scientific explanation for developmental biology. It goes against everything we know to say that blind and mindless processes can produce what is observed in developmental biology. ET

evo devo meeting http://www.evodevopanam.org/uploads/4/0/3/2/40325263/2017panamsedbprogramshort_updated_8.19.17b.pdf http://www.evodevopanam.org/uploads/4/0/3/2/40325263/2017panamsedbprogramabstracts_updated_8.18.17b.pdf http://www.evodevopanam.org/2nd-biennial-meeting.html Dionisio

According to the fundamental evo-devo formulation given @93, most papers referenced in this thread fail to answer this important question: where's the beef? :) Dionisio

Is this the fundamental evo-devo formulation? Dev(d) = Dev(a)+ Delta(a,d) Dev(a) is the entire* spatiotemporal development of a biological system 'a' that is ancestor to a given biological system 'd'. Dev(d) is the entire* spatiotemporal development of a biological system 'd' that is descendent from a given biological system 'a'. Delta(a,d) is the entire* set of all the spatiotemporal changes required in Dev(a) in order to get Dev(d) (*) the whole enchilada :) PS. Please, correct any errors you may notice. Thanks. Dionisio

evo devo despacito? Integration of anatomy ontologies and Evo-Devo using structured Markov chains suggests a new framework for modeling discrete phenotypic traits Sergei Tarasov doi: https://doi.org/10.1101/188672 Modeling discrete phenotypic traits for either ancestral character state reconstruction or morphology-based phylogenetic inference suffers from ambiguities of character coding, homology assessment, dependencies, and selection of adequate models. These drawbacks occur because trait evolution is driven by the two key processes - hierarchical and hidden - which are not accommodated simultaneously by the available phylogenetic methods. The hierarchical process refers to the dependencies between anatomical body parts, while the hidden process refers to the evolution of gene regulatory networks (GRNs) underlying trait development. Herein, I demonstrate that these processes can be efficiently modeled using structured Markov chains equipped with hidden states, which resolves the majority of the problems associated with discrete traits. Integration of structured Markov chains with anatomy ontologies adequately incorporates the hierarchical dependencies, while use of the hidden states accommodates hidden GRN evolution and mutation rate heterogeneity. This model is insensitive to alternative coding approaches which is shown by solving the Maddison's tail color problem. Additionally, this model provides new insight into character concept and homology assessment. The practical considerations for implementing this model in phylogenetic inference and comparative methods are discussed. Dionisio

Heuristic, based on known alternative causes for aspects of an entity, system or process. Calibrated against reliable signs. An algorithm. Aspect is a very carefully chosen term, different aspects may have different explanations as to credible cause. Any significant aspect by design is decisive. First default, natural mechanical necessity per low contingency, reliably repeatable outcome under similar circumstances. Failing such, second being chance, for high contingency. With in addition high functional specificity, design per inference on reliable sign. KF kairosfocus

Dionisio. "Does “good reasoning” include “open mindedness” / “unbiased thinking” too?" I would definitely say so. And love for truth, which is a quality of the heart. gpuccio

Here's a recent article that fails the most fundamental question: Where's the beef? What evolutionary developmental biology (evo devo) brings to evolutionary biology by professor Armin P Moczek http://extendedevolutionarysynthesis.com/what-evo-devo-brings-to-evolutionary-biology/ Dionisio

gpuccio @87: "Design is not the logic alternative to contingency and necessity. It is an empirical explanation of observed facts, based on other observed facts and good reasoning." Agree. No logical theorem. Empirical. Does "good reasoning" include "open mindedness" / "unbiased thinking" too? :) Dionisio

DiEB and Dionisio: Just to be more clear, one of the points where my approach is somewhat different from what is (probably) Dembski's approach is in the intepretation of the explanatory filter. I apologize in advance if I understand badly Dembski's thought (which is certainly possible). However, in the discussions here, I have many times found the statement (from both sides) that the explanatory filter should be considered as a logical theorem. IOWs, to put it simply, if some objective configuration of matter cannot be explained by contingency, and it cannot be explained by necessity laws, then it follows by logic that it is designed. I have never interpreted the explanatory filter that way. My approach is completely empirical. IOWs, my apporach is: a) If some objective configuration of matter cannot be explained by contingency (because the bits linked to some well defined function are beyond any reasonable threshold of what contingency can empirically find) and b) At the same time if cannot be explained by any known necessity laws then c) We say that it exhibits complex functionally specified information. This part is an empirical definition. Then: d) We observe that complex functionally specified information is never found in the observable world, except for human artifacts and biological objects. e) In particular, human artifacts are products of design (the configuration of matter originates, directly or indirectly, in conscious representations). That is the only reasonable explanation of the ability of humans to generate something that is never observed otherwise (with the exception of biological objects, whose origin is the thing we are discussing) f) Therefore, the most reasonable explanation for FSCI in biological objects is design (the functional configurations originated in conscious representations). g) Of course, we have the duty to verify if the only non design explanation which has ever been proposed (RV+NS) is an empirical exception to these observations. h) Any realistic analysis of what RV + NS can do will easily falsify the idea that it is a reasonable explanation for what we observe. See here: https://uncommondescent.com/intelligent-design/what-are-the-limits-of-natural-selection-an-interesting-open-discussion-with-gordon-davisson/ and here: https://uncommondescent.com/intelligent-design/what-are-the-limits-of-random-variation-a-simple-evaluation-of-the-probabilistic-resources-of-our-biological-world/ I apologize for the brevity of this summary (and for any possible imprecision). I am available to discuss each single point, as I have done in the past. My point here is very simple: my reasoning is not a mathematical theorem. Design is not the logic alternative to contingency and necessity. It is an empirical explanation of observed facts, based on other observed facts and good reasoning. gpuccio

evo devo despacito? Svensson, Erik. (2017). On Reciprocal Causation in the Evolutionary Process. Evolutionary Biology. . 10.1007/s11692-017-9431-x. Recent calls for a revision of standard evolutionary theory (SET) are based partly on arguments about the reciprocal causation. Reciprocal causation means that cause–effect relationships are bi-directional, as a cause could later become an effect and vice versa. Such dynamic cause-effect relationships raise questions about the distinction between proximate and ultimate causes, as originally formulated by Ernst Mayr. They have also motivated some biologists and philosophers to argue for an Extended Evolutionary Synthesis (EES). The EES will supposedly expand the scope of the Modern Synthesis (MS) and SET, which has been characterized as gene-centred, relying primarily on natural selection and largely neglecting reciprocal causation. Here, I critically examine these claims, with a special focus on the last conjecture. I conclude that reciprocal causation has long been recognized as important by naturalists, ecologists and evolutionary biologists working in the in the MS tradition, although it it could be explored even further. Numerous empirical examples of reciprocal causation in the form of positive and negative feedback are now well known from both natural and laboratory systems. Reciprocal causation have also been explicitly incorporated in mathematical models of coevolutionary arms races, frequency-dependent selection, eco-evolutionary dynamics and sexual selection. Such dynamic feedback were already recognized by Richard Levins and Richard Lewontin in their bok The Dialectical Biologist. Reciprocal causation and dynamic feedback might also be one of the few contributions of dialectical thinking and Marxist philosophy in evolutionary theory. I discuss some promising empirical and analytical tools to study reciprocal causation and the implications for the EES. Finally, I briefly discuss how quantitative genetics can be adapated to studies of reciprocal causation, constructive inheritance and phenotypic plasticity and suggest that the flexibility of this approach might have been underestimated by critics of contemporary evolutionary biology. https://www.researchgate.net/publication/319912624_On_Reciprocal_Causation_in_the_Evolutionary_Process/fulltext/59c14f3ba6fdcc69b92bbf19/319912624_On_Reciprocal_Causation_in_the_Evolutionary_Process.pdf Dionisio

evo devo despacito? Charlesworth, Deborah & H. Barton, Nicholas & Charlesworth, Brian. (2017). The sources of adaptive variation. Proceedings of the Royal Society B: Biological Sciences. 284. 20162864. 10.1098/rspb.2016.2864. The role of natural selection in the evolution of adaptive phenotypes has undergone constant probing by evolutionary biologists, employing both theoretical and empirical approaches. As Darwin noted, natural selection can act together with other processes, including random changes in the frequencies of phenotypic differences that are not under strong selection, and changes in the environment, which may reflect evolutionary changes in the organisms themselves. As understanding of genetics developed after 1900, the new genetic discoveries were incorporated into evolutionary biology. The resulting general principles were summarized by Julian Huxley in his 1942 book Evolution: the modern synthesis. Here, we examine how recent advances in genetics, developmental biology and molecular biology, including epigenetics, relate to today’s understanding of the evolution of adaptations. We illustrate how careful genetic studies have repeatedly shown that apparently puzzling results in a wide diversity of organisms involve processes that are consistent with neo-Darwinism. They do not support important roles in adaptation for processes such as directed mutation or the inheritance of acquired characters, and therefore no radical revision of our understanding of the mechanism of adaptive evolution is needed. © 2017 The Author(s) Published by the Royal Society. All rights reserved. Really? Where's the beef ? :) https://www.researchgate.net/profile/Deborah_Charlesworth/publication/317266422_The_sources_of_adaptive_variation/links/5a118bf3aca27287ce299f57/The-sources-of-adaptive-variation.pdf Dionisio

evo devo despacito? Domestication as a model system for the extended evolutionary synthesis. Zeder, Melinda. (2017). Interface Focus. 7. 20160133. 10.1098/rsfs.2016.0133. One of the challenges in evaluating arguments for extending the conceptual framework of evolutionary biology involves the identification of a tractable model system that allows for an assessment of the core assumptions of the extended evolutionary synthesis (EES). The domestication of plants and animals by humans provides one such case study opportunity. Here, I consider domestication as a model system for exploring major tenets of the EES. First I discuss the novel insights that niche construction theory (NCT, one of the pillars of the EES) provides into the domestication processes, particularly as they relate to five key areas: coevolution, evolvability, ecological inheritance, cooperation and the pace of evolutionary change. This discussion is next used to frame testable predictions about initial domestication of plants and animals that contrast with those grounded in standard evolutionary theory, demonstrating how these predictions might be tested in multiple regions where initial domestication took place. I then turn to a broader consideration of how domestication provides a model case study consideration of the different ways in which the core assumptions of the EES strengthen and expand our understanding of evolution, including reciprocal causation, developmental processes as drivers of evolutionary change, inclusive inheritance, and the tempo and rate of evolutionary change. https://www.researchgate.net/profile/Melinda_Zeder/publication/319190747_Domestication_as_a_model_system_for_the_extended_evolutionary_synthesis/links/599b101445851574f4ac5ce8/Domestication-as-a-model-system-for-the-extended-evolutionary-synthesis.pdf Dionisio

evo devo despacito? J. Futuyma, Douglas. (2017). Evolutionary biology today and the call for an extended synthesis. Interface Focus. 7. 20160145. 10.1098/rsfs.2016.0145. Evolutionary theory has been extended almost continually since the evolutionary synthesis (ES), but except for the much greater importance afforded genetic drift, the principal tenets of the ES have been strongly supported. Adaptations are attributable to the sorting of genetic variation by natural selection, which remains the only known cause of increase in fitness. Mutations are not adaptively directed, but as principal authors of the ES recognized, the material (structural) bases of biochemistry and development affect the variety of phenotypic variations that arise by mutation and recombination. Against this historical background, I analyse major propositions in the movement for an 'extended evolutionary synthesis'. 'Niche construction' is a new label for a wide variety of well-known phenomena, many of which have been extensively studied, but (as with every topic in evolutionary biology) some aspects may have been understudied. There is no reason to consider it a neglected 'process' of evolution. The proposition that phenotypic plasticity may engender new adaptive phenotypes that are later genetically assimilated or accommodated is theoretically plausible; it may be most likely when the new phenotype is not truly novel, but is instead a slight extension of a reaction norm already shaped by natural selection in similar environments. However, evolution in new environments often compensates for maladaptive plastic phenotypic responses. The union of population genetic theory with mechanistic understanding of developmental processes enables more complete understanding by joining ultimate and proximate causation; but the latter does not replace or invalidate the former. Newly discovered molecular phenomena have been easily accommodated in the past by elaborating orthodox evolutionary theory, and it appears that the same holds today for phenomena such as epigenetic inheritance. In several of these areas, empirical evidence is needed to evaluate enthusiastic speculation. Evolutionary theory will continue to be extended, but there is no sign that it requires emendation. [really?] Dionisio

Evolution Driven by Organismal Behaviour – a Unifying View of Life, Function, Form, Mismatches, and Trends By Rui Diogo, 252 pages. Springer International Publishing AG, Cham, Switzerland, 2017. ISBN: 978?3?319?47580?6. Art Tom V. Smulders DOI: 10.1111/joa.12750 Smulders, Tom. (2017). Evolution Driven by Organismal Behaviour – a Unifying View of Life, Function, Form, Mismatches, and Trends By Rui Diogo, 252 pages. Springer International Publishing AG, Cham, Switzerland, 2017. ISBN: 978?3?319?47580?6.. Journal of Anatomy. . 10.1111/joa.12750. Dionisio

evo devo despacito? Project A Process Ontology for Contemporary Biology John Dupré Goal: This ERC funded project aims to rethink central issues in the philosophy of biology by elaborating an ontology for biology that takes full account of the processual nature of living systems. It explores the possibility of seeing living things - genes, cells, organisms, etc. - as fundamentally processes, maintained in relatively stable conditions by yet further processes. Three postdoctoral researchers work on the project: Stephan Guttinger, Anne Sophie Meincke, and Daniel J. Nicholson Dionisio

evo devo despacito? :) New trends in evolutionary biology: Biological, philosophical and social science perspectives DOI: 10.1098/rsfs.2017.0051 Introduction to New Trends in Evolutionary Biology: biological, philosophical and social science perspectives Patrick Bateson, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ ppgb@cam.ac.uk. Nancy Cartwright, Department of Philosophy Durham University 50 Old Elvet Durham DH13HN nancy.cartwright@durham.ac.uk John Dupré, Egenis, The Centre for the Study of Life Sciences Byrne House, St German’s Road University of Exeter, Exeter, EX4 4PJ J.a.dupre@exeter.ac.uk Kevin Laland, Centre for Biodiversity School of Biology University of St Andrews Harold Mitchell Building St Andrews Fife KY16 9TH, UK, e-mail: knl1@st-andrews.ac.uk Denis Noble Department of Physiology, Anatomy & Genetics University of Oxford Parks Road, OX1 3PT Denis.noble@dpag.ox.ac.uk https://www.researchgate.net/profile/John_Dupre/publication/319191327_New_trends_in_evolutionary_biology_Biological_philosophical_and_social_science_perspectives/links/599fee394585151e3c73d877/New-trends-in-evolutionary-biology-Biological-philosophical-and-social-science-perspectives.pdf Dionisio

evo devo despacito? Project: [let's try to come up with a reasonable explanation ASAP] :) The Extended Life Cycle Nayely Velez-Cruz, Manfred Laubichler Goal: We aim to devise a robust mathematical and multiresolution data analytic framework for a mechanistic explanation of phenotypic evolution that is conceptually rooted in a developmental evolutionary biology. This is motivated by the lack of evolutionary models that integrate the biological reality of multiple simultaneously-occurring mechanisms of inheritance with developmental biology to explain the origins of evolutionary novelty. We introduce The Extended Life Cycle, a conceptual framework for theory integration in the biological sciences, and its mathematical realization via the Phenotype-Genotype-Phenotype (PGP) Map. Dionisio

evo devo despacito? Austin, Christopher. (2017). Recent Work in The Philosophy of Biology. Analysis. DOI: 10.1093/analys/anx032 The biological sciences have always proven a fertile ground for philosophical analysis, one from which has grown a rich tradition stemming from Aristotle and flowering with Darwin. And although contemporary philosophy is increasingly becoming conceptually entwined with the study of the empirical sciences with the data of the latter now being regularly utilised in the establishment and defence of the frameworks of the former, a practice especially prominent in the philosophy of physics, the development of that tradition hasn't received the wider attention it so thoroughly deserves. This review will briefly introduce some recent significant topics of debate within the philosophy of biology, focusing on those whose metaphysical themes (in everything from composition to causation) are likely to be of wide-reaching, cross-disciplinary interest. Dionisio

evo-devo despacito? Why an extended evolutionary synthesis is necessary Gerd B. Müller DOI: 10.1098/rsfs.2017.0015 Since the last major theoretical integration in evolutionary biology—the modern synthesis (MS) of the 1940s—the biosciences have made significant advances. The rise of molecular biology and evolutionary developmental biology, the recognition of ecological development, niche construction and multiple inheritance systems, the ‘-omics’ revolution and the science of systems biology, among other developments, have provided a wealth of new knowledge about the factors responsible for evolutionary change. Some of these results are in agreement with the standard theory and others reveal different properties of the evolutionary process. A renewed and extended theoretical synthesis, advocated by several authors in this issue, aims to unite pertinent concepts that emerge from the novel fields with elements of the standard theory. The resulting theoretical framework differs from the latter in its core logic and predictive capacities. Whereas the MS theory and its various amendments concentrate on genetic and adaptive variation in populations, the extended framework emphasizes the role of constructive processes, ecological interactions and systems dynamics in the evolution of organismal complexity as well as its social and cultural conditions. Single-level and unilinear causation is replaced by multilevel and reciprocal causation. Among other consequences, the extended framework overcomes many of the limitations of traditional gene-centric explanation and entails a revised understanding of the role of natural selection in the evolutionary process. All these features stimulate research into new areas of evolutionary biology. http://rsfs.royalsocietypublishing.org/content/7/5/20170015.full.pdf Dionisio

evo-devo despacito? Organisms as Persisters Subrena E. Smith DOI: 10.3998/ptb.6959004.0009.014 https://philarchive.org/archive/ESMOAP Philos Theor Pract Biol (2017) 9:14 https://www.ptpbio.org/ Dionisio

DiEb & GP: You may find this RW case driven discussion of the design inference explanatory filter relevant: https://uncommondescent.com/design-inference/alien-megastructure-is-not-the-cause-of-the-dimming-of-tabbys-star-design-inference-filter-in-action-sci-fi-fans-disappointed/ It is the context for my previous linked. KF kairosfocus

DiEb, You may want to seriously heed KF's suggestion @71. Dionisio

DiEb, Please, read very carefully gpuccio's comment @70, which is addressed to you. Please, pay special attention to the last paragraph. Now gpuccio has graciously provided to you with a nice opportunity to present a strong mathematical support for your constant criticism of ID. If you miss this rare opportunity, you will confirm that your void rants are just what the beautiful Italian singer Mina said in a popular song she sang so well: "Parole, parole, parole". This is your moment to shine. Don't miss it! Dionisio

gpuccio @70: "empirical formulation of biological ID" I like that! Biological ID (BID) Empirical Formulation of Biological ID (EFOBID) Biological ID Empirical Formulation (BIDEF) A title for a future article? Dionisio

GP & DiEb note this current thread: https://uncommondescent.com/selective-hyperskepticism/tabbys-star-on-the-extraordinary-evidence-claim/ KF kairosfocus

DiEb: "While virtually every single branch, every mathematical idea has internet fora on which it is discussed vigorously, there is no such forum left for the maths of Intelligent Design. I’m afraid that this is mainly due to lack of general interest – and due to a lack of new ideas in this field." I think that the discussion about ID has shifted mainly to biological and empirical problems. IMO, the mathematical basis for ID is simple enough, and if correctly applied to an empirical framework about biology, it is more than enough to infer design with overwhelming scientific strength. For me, Dembski's explanatory filter is enough, provided that we interpret it as an empirical tool, and not as a logical theorem. I have tried to do exactly that in my discussions here. I would be interested to know what are your main arguments against ID from a mathematical point of view, to understand if those arguments really apply to an empirical formulation of biological ID. Could you please point to some place where I can find your interventions, or just simply express the main points briefly here? gpuccio

Evo-devo despacito? [almost a decade old?] Are they getting a little nervous? Evolutionary Developmental Biology Offers a Significant Challenge to the Neo?Darwinian Paradigm DOI: 10.1002/9781444314922.ch11 In book: Contemporary Debates in Philosophy of Biology, pp.199 - 212 Manfred Laubichler 38.29 Arizona State University Abstract In this paper, I note that in evaluating present-day evo-devo the question for us is not only whether evo-devo is revolutionary in some sense, but also whether sometimes a "revolutionary" position in science can actually resemble more a "counter-revolution." I argue that the relationship between evo-devo and the neo-Darwinian paradigm can be interpreted exactly like that, and that the revolutionary nature of evo-devo lies precisely in its return to a more inclusive conception of phenotypic evolution, one that more closely resembles the conceptual framework of Darwin and the first few generations of evolutionists than the more narrowly focused interpretation of the Modern Synthesis. However, I also argue that evo-devo is by no means "reactionary" as it approaches these more traditional conceptual problems with all the methodological, technological, and empirical advances of the last six decades of biological research. https://www.researchgate.net/profile/Manfred_Laubichler/publication/228028772_Evolutionary_Developmental_Biology_Offers_a_Significant_Challenge_to_the_Neo-Darwinian_Paradigm/links/5a157fb7a6fdccd697bc2a89/Evolutionary-Developmental-Biology-Offers-a-Significant-Challenge-to-the-Neo-Darwinian-Paradigm.PDF Dionisio

ET @67, Those folks make it quite easier to do so. Their fumbling seems constant. It's the typical attitude of the losers. However, always I must remind myself to be gracious toward others, as God has been gracious to me, despite the fact that I'm not better that others. I make many mistakes too. It's part of our human imperfections. Had we remained in Eden, none of this would have been an issue. Dionisio

I just love turning the tables ET

ET @61, Valid questions. Dionisio

DiEb @63: Huh? Dionisio

DiEb @60: Huh? Dionisio

@Dionisio: word-games about "surprise" - quelle surprise DiEb

DiEb @55:

I was surprised that you seemingly were not acquainted with the website evoinfo.org

I had not opened that website before reading your comment about being surprised. :) In the list of websites @56, these are the ones I enjoy visiting: Biblegateway.com_________1,001 Desiringgod.org_________10,908 Truthforlife.org________42,349 Gty.org__________45,516 Apparently -looking at their rankings- other people like them too. :) I've also downloaded some video material from mit.edu and as you well know I've been in this UD website "a few times" too. :) Ah, I've also been quite a bit in Kodugamelab.com______311,217 because it's related to one of the projects I'm working on lately. The last time I was surprised it was by grace. Don't recall being surprised by much since then. Dionisio

DiEB:

I always wondered how IDst and creationists got this reputation of enjoying word-games over discussing content…

LoL- when have evos ever discussed content? When have they ever discussed science? ET

@Dionisio: I always wondered how IDst and creationists got this reputation of enjoying word-games over discussing content... DiEb

DiEb @55:

I was surprised that you seemingly was not acquainted with the website evoinfo.org

I think you've mentioned that English is not your first language? If that's the case, then join the club!!! I can use any help coming my way in the form of grammar corrections. Unfortunately some English-speaking folks don't like to correct my language errors. I miss that.

I was surprised that you seemingly were not acquainted with the website evoinfo.org

[Emphasis added] Dionisio

DiEb @49, In the text that you quoted from my comment @43, there are some typo errors that I should correct:

A couple of years ago a distinguished biochemistry professor at a Canadian university stopped an incipient discussion we tried to have. He ran for the door after mistakenly answering a very simple biology-related question. Apparently he couldn’t stand the heat. I don’t know what happened him that day. Perhaps he had a brief mental lapse? He just said that he won’t discuss with me because I don’t ask honest questions. The simple question he failed was: "Do you know exactly how the morphogen gradients form?" He answered ‘Yes’. Unbelievable! He later complained about the ‘tricky’ word ‘exactly’ embedded in the question. Some folks suggested that I should have highlighted the ‘tricky’ word ‘exactly’ in bold characters, so that it could be easily noticeable. Oh well, my fault. I’ll try better next time. :)

His mistake was very significant by any standard and quite embarrassing in the context it occurred. He knew very well that it wasn't known exactly how those signaling profiles are constructed. There are still fundamental issues awaiting resolution. Important outstanding questions remain unanswered. Details about what happened that day here are publicly available. They are all recorded here in this website. Anyone can search them very easily. No one knows what made such a distinguished biochemistry professor write that embarrassing 'Yes'. But I believe I know why it happened. I quoted the explanation at the end of my comment @43. But many people won't understand what that text means. Dionisio

Interesting proteins: DNA-binding proteins SATB1 and SATB2 July 14, 2017 Posted by gpuccio 305 Comments Visited 2,181 times https://uncommondescent.com/intelligent-design/interesting-proteins-dna-binding-proteins-satb1-and-satb2 Dionisio

Please, note that no web info service is 100% reliable. Also note that the numbers keep fluctuating. However, the different reports confirm that UD is comfortably within 1% of the currently active websites. https://www.alexa.com/siteinfo/uncommondescent.com MIT.edu___________481 Nature.com________860 Harvard.edu_________873 Biblegateway.com_______1,001 mtgsalvation.com______10,201 Desiringgod.org_______10,908 Answersingenesis.org_____28,882 Truthforlife.org______42,349 Gty.org_______45,516 Samaritanspurse.org_____51,000 freethoughtblogs.com_____76,655 Icr.org_______77,874 sermonsearch.com______81,317 Religionnews.com_____96,212 Royalsociety.org_____102,052 keepbelieving.com______144,829 sermonnotebook.org_____146,899 Rzim.org_______148,154 Evolutionnews.org_____168,380 gospelinlife.com______231,645 Kodugamelab.com______311,217 Reasons.org___________346,070 fpcjackson.org_______358,074 asa3.org_____________428,374 Jamesmacdonald.com_____460,457 discovery.org__________542,905 Uncommondescent.com_____644,999 Pandasthumb.org__________906,313 intelligentdesign.org_____932,239 ideacenter.org___________1,655,821 arn.org__________________1,956,610 theskepticalzone.com______5,147,609 biologicinstitute.org_____6,450,899 Evoinfo.org_______________10,309,075 * Active websites (10%): 132M to 173M UD 0.4% – 0.5% PT. 0.5% – 0.7% TSZ 3% – 4% All websites UD 0.04% – 0.05% (*) mentioned @25 Dionisio

Dionisio @52: I was surprised that you seemingly was not acquainted with the website evoinfo.org - you seem to be amused by the fact that its ranking is virtually unmeasurable in the 10,000,000... Now, you seem to be ignorant about Jeffrey Shallit. Perhaps you should read up on W. Dembski's and R. Marks's oeuvre, and have a look at the main critics. Perhaps you do know that this blog was started by W. Dembski - a philosopher and mathematician. It is no surprise that some mathematically inclined people have lost interest in Uncommon Descent as the last time that there happened something like a discussion between mathematicians on a technical subject was in 2015. Articles like this one are just painful to read for mathematicians, and they may not be interested in the endless discussions on philosophy and theology. While virtually every single branch, every mathematical idea has internet fora on which it is discussed vigorously, there is no such forum left for the maths of Intelligent Design. I'm afraid that this is mainly due to lack of general interest - and due to a lack of new ideas in this field. DiEb

Please, note that no web info service is 100% reliable. Also note that the numbers keep fluctuating. However, the different reports confirm that ID is within 1% of the currently active websites. https://www.alexa.com/siteinfo/uncommondescent.com MIT.edu___________481 Nature.com________860 Harvard.edu_________873 Biblegateway.com_______1,001 Desiringgod.org_______10,908 Answersingenesis.org_____28,882 Truthforlife.org______42,349 Gty.org_______45,516 Samaritanspurse.org_____51,000 freethoughtblogs.com_____76,655 Icr.org_______77,874 Religionnews.com_____96,212 Royalsociety.org_____102,052 Rzim.org_______148,154 Evolutionnews.org_____168,380 Kodugamelab.com______311,217 Reasons.org___________346,070 asa3.org_____________428,374 Jamesmacdonald.com_____460,457 discovery.org__________542,905 Uncommondescent.com_____644,999 Pandasthumb.org__________906,313 intelligentdesign.org_____932,239 ideacenter.org___________1,655,821 arn.org__________________1,956,610 theskepticalzone.com______5,147,609 biologicinstitute.org_____6,450,899 Evoinfo.org_______________10,309,075 * Active websites (10%): 132M to 173M UD 0.4% – 0.5% PT. 0.5% – 0.7% TSZ 3% – 4% All websites UD 0.04% – 0.05% (*) mentioned @25 Dionisio

@52 addendum An interesting detail is that a blogger within a relatively more popular website seems to keep an eye on what they write here in UD (a relatively less popular website), or at least got the tip from someone else? Dionisio

Sometimes one could find very good restaurants just from spotting nonsense written online by whiners*: “they are rude, the waiter said ‘hi’ instead of ‘hello'” (*) a.k.a. “tontos útiles” in Spanish. Someone I know provided this information: Here's a relatively popular website (much higher than UD in the Alexa ranking), apparently a hub of approximately 40 blogs (this may partially explain the hub website popularity): https://www.alexa.com/siteinfo/freethoughtblogs.com freethoughtblogs.com 76,655 Last April 17, in the blog named 'recursivity' within the mentioned hub, the blogger posted an article against UD (what else is new?). In the follow up discussion, someone else commented not being aware that UD was still active:

heddle says April 18, 2017 at 5:46 am I didn’t even know Uncommon Descent was still active.

https://freethoughtblogs.com/recursivity/2017/04/17/uncommon-descent-lies-again/#comment-376 That means that the 'whining' post about UD let someone know that UD is still up and running. Perhaps other readers (apparently they have many) heard of UD also for the first time in that article. BTW, I realize that perhaps some readers of this comment here had never heard of the mentioned hub website before. Maybe I've just returned the PR? :) Dionisio

Sorry, I'm not Russian. DiEb

DiEb, Ty umnitsa! Prosto molodyets! ;) Dionisio

Dionisio @43:

A couple of years ago a distinguished biochemistry professor at a Canadian university stopped an incipient discussion we tried to have. He ran for the door after mistakenly answering a very simple biology-related question. Apparently he couldn’t stand the heat. I don’t know what happened him that day. Perhaps he had a brief mental lapse? He just said that he won’t discuss with me because it don’t ask honest questions. The simple question he failed was: Do you know exactly how the morphogen gradients form? He answered ‘Yes’. Unbelievable! He later complained about the ‘tricky’ word ‘exactly’ embedded in the question. Some folks suggested that I should have highlighted the ‘tricky’ word ‘exactly’ in bold characters, smother it could be easily noticeable. Oh well, my fault. I’ll try better next time.

Perhaps he assumed (correctly) that you were the type of guy who would crow about a simply correctable mistake for years to come... DiEb

Evo-devo despacito?

It has been argued here that the discontent is better understood as stemming from a few inescapable properties of living things, which lead to disappointment with evolutionary biology, and a nagging feeling that reform must be overdue. Evolutionary biology, like history, but unlike other natural sciences, raises issues of purpose and agency, alongside those of complexity and generality [...] It is remarkable, for example, that much of the funding for challenging current practice in evolutionary biology comes from The John Templeton Foundation (Pennisi 2016), which is committed to using science to reveal underlying purpose, and rejecting what Nagel (2012) calls “the Materialist Neo-Darwinian Conception of Nature”. [...] claims that evolutionary biology is misguided or importantly incomplete are not harmless, but actively hinder progress in the field. [...] a field that urgently needs reform is a field “in crisis” (Mazur 2010), and when it fails to reform, this lends credibility to claims that scientists are, at best, hidebound and foolish, and at worst, guilty of ideologically-motivated deception (Mazur 2010; Teresi 2011).

What’s wrong with evolutionary biology? John J. Welch Biology & Philosophy March 2017, Volume 32, Issue 2, pp 263–279

Dionisio

Evo-devo despacito?

The characteristics of life also guarantee that the explanatory frameworks of evolutionary biology will be disappointing to some. Disappointment is caused partly by the sheer complexity of life’s dynamical processes. This means that our predictive power will always be weak in certain ways, and that our descriptions of evolution will always be enormous simplifications.

What’s wrong with evolutionary biology? John J. Welch Biology & Philosophy March 2017, Volume 32, Issue 2, pp 263–279

Dionisio

Evo-devo despacito?

Some problems for evolutionary biology are caused by the basic characteristics of life. Some banal practical problems are caused by the sheer scope of evolutionary biology. [...] new data appear at a very rapid rate, particularly, in recent years, from molecular biology.

What’s wrong with evolutionary biology? John J. Welch Biology & Philosophy March 2017, Volume 32, Issue 2, pp 263–279

Dionisio

Usually, evolutionary economists equate evolutionary theory with modern Darwinism. However, the rise of evolutionary developmental biology (Evo-Devo) puts into question the monopoly of Darwinism in evolutionary biology. The major divergences between the two paradigms in evolutionary biology are drawn in the analysis of three trade-offs: population vs. typological thinking, creative role of natural selection vs. internal (inherent) change, and microevolution vs. macroevolution. It is argued here that the Evo-Devo breakthrough helps us to understand better the limits to Darwinism in the social realm and outline the contours of an alternative paradigm in evolutionary economics that favors structural macroevolution and what Schumpeter called “change from within”.

The challenge of Evo-Devo: implications for evolutionary economists George Liagouras https://doi.org/10.1007/s00191-017-0525-5 Journal of Evolutionary Economics September 2017, Volume 27, Issue 4, pp 795–823

Dionisio

. Dionisio

DiEb, I'm glad you've posted your question here in this thread, which is not mine, but it's associated with a funny video about the evo-devo stuff that most people have no clue about and probably don't care much either. Thanks. Now we can chat, if you will. :) It seems like you've done a very thorough investigation on the website that I mentioned @22 and found that it's not active since a number of years ago. I appreciate you've caught that and warned us about it. Perhaps you've noticed that I've looked at other sources of that kind of information after you mentioned that problem. Actually, the discussion that followed your comments about the validity of the numbers made me look into internet-related stats that I wasn't aware of before. Actually, I don't recall ever thinking about how many websites are in the internet. Much less about the number of active websites at any given moment. Reading a little about this subject was interesting. As you can see, your warning comments had some side benefits too. :) Now let me answer the question you've been so anxiously asking. I'm going to say things that are off topic for the thread where you posted your question first. In my family education is a topic of conversation sometimes. My wife has an engineering degree and a master in business administration degree from a different university. She's been associated with business-oriented software development. I have an engineering degree in control systems and have worked on an engineering design software development project before switching career to different projects partially associated with biology research and education. That may explain why I look at some biology-related research papers, which sometimes I share in this website too. There's a cool software named Zotero that helps with that kind of information gathering. Perhaps you've used it too. One of my children got a master degree in finance from a known university and later got a CPA license from another. But the rest of my children pursued careers somehow associated with biology. One of them got a master degree in microbiology, others became medical doctors. Some of them graduated from the same university, but obviously few years apart (we don't have twins). They're all on their own. Don't depend on my wife and me anymore. However, sometimes we still talk about education among other things. Also we have relatives and friends who studied or work at universities in various countries, or whose children are going to the university soon. Now my wife and I enjoy having wonderful grandchildren God has graciously given to us. Education is an important subject when we think about our grandkids too. One topic I bring up to discussion with them sometimes is the worldwide ranking of universities. Sometimes I search for that information online. Usually the search tool I use most is Bing. But I use Google tools sometimes too. The website ranking.com just popped up in one of those searches. I played with it for a moment, then thought to post that comparative list just for fun, continuing the tone set by the funny musical video in the OP of this thread. Now you know the rest of the story. As you can see, there's no conspiracy theory whatsoever. Please, let me know if my answer satisfies your curiosity. If you have more questions, please ask them here in this funny evo-devo* thread. And please, do it 'despacito'. :) Have a good day. (*) if you want to discuss the current state of affairs in evo-devo or thoroughly analyze its fundamental formulation: Dev(d) = Dev(a) + Delta(a,d) and its implications for this growing field in biology, you're very welcome anytime! PS. As I stated in the 'ranking' discussion thread, the discussions I'm interested in are biology-related, like the excellent discussions gpuccio has with the a distinguished biology professor at the University of Kentucky, As you can see, their interesting discussion is on pause while gpuccio waits for the professor to come back and present a valid counterargument that could make a shallow dent or at least a minor scratch on gpuccio's presented case. I don't think that will happen, but we better wait and see. That's the kind of discussions where the ID folks (I don't count myself among them, though) can make a difference. Because every day in research is bringing bad news for the moribund neo-Darwinian ideas. The ranking stuff is for side entertainment, but it doesn't mean much in serious terms. It's just to take a break from the real stuff. A couple of years ago a distinguished biochemistry professor at a Canadian university stopped an incipient discussion we tried to have. He ran for the door after mistakenly answering a very simple biology-related question. Apparently he couldn't stand the heat. I don't know what happened him that day. Perhaps he had a brief mental lapse? He just said that he won't discuss with me because it don't ask honest questions. The simple question he failed was: Do you know exactly how the morphogen gradients form? He answered 'Yes'. Unbelievable! He later complained about the 'tricky' word 'exactly' embedded in the question. Some folks suggested that I should have highlighted the 'tricky' word 'exactly' in bold characters, smother it could be easily noticeable. Oh well, my fault. I'll try better next time. As you can see, a nobody like me asked a simple question that made a distinguished scientist run for the door. Do you know why? Because it was really not me whom the distinguished scientist was running away from. Not at all. The explanation is in the below quoted text, which many people can't or don't want to understand:

Christ the Wisdom and Power of God 18 For the word of the cross is folly to those who are perishing, but to us who are being saved it is the power of God. 19 For it is written, “I will destroy the wisdom of the wise, and the discernment of the discerning I will thwart.” 20 Where is the one who is wise? Where is the scribe? Where is the debater of this age? Has not God made foolish the wisdom of the world? 21 For since, in the wisdom of God, the world did not know God through wisdom, it pleased God through the folly of what we preach[b] to save those who believe. 22 For Jews demand signs and Greeks seek wisdom, 23 but we preach Christ crucified, a stumbling block to Jews and folly to Gentiles, 24 but to those who are called, both Jews and Greeks, Christ the power of God and the wisdom of God. 25 For the foolishness of God is wiser than men, and the weakness of God is stronger than men. 26 For consider your calling, brothers: not many of you were wise according to worldly standards,[c] not many were powerful, not many were of noble birth. 27 But God chose what is foolish in the world to shame the wise; God chose what is weak in the world to shame the strong; 28 God chose what is low and despised in the world, even things that are not, to bring to nothing things that are, 29 so that no human being[d] might boast in the presence of God. 30 And because of him[e] you are in Christ Jesus, who became to us wisdom from God, righteousness and sanctification and redemption, 31 so that, as it is written, “Let the one who boasts, boast in the Lord.” Footnotes: a.1 Corinthians 1:10 Or brothers and sisters. In New Testament usage, depending on the context, the plural Greek word adelphoi (translated “brothers”) may refer either to brothers or to brothers and sisters; also verses 11, 26 b.1 Corinthians 1:21 Or the folly of preaching c.1 Corinthians 1:26 Greek according to the flesh d.1 Corinthians 1:29 Greek no flesh e.1 Corinthians 1:30 Greek And from him

Dionisio

Dionisio @22: You are using a web-ranking by a site called "ranking.com", to which you link in your comment. Though this website seems to be up-to-date on a first glance, KF has shown that the data is at least five years out of date. Indeed, some deeper digging shows that ranking.com is affiliated with 7Search.com and 7MetaSearch.com and was using an application called 7FaSSt - advertised as "BrowserAccelerator" - to gather their data. In 2008, 7FaSSt was classified as malware or spyware by McAffee and other security providers. It seems that 7FaSSt was not spread on a larger scale at the end of the first decade of this century any longer. Today, the only left over purpose of the site "ranking.com" seems to be to fish for contact addresses. Therefore my question: How did you come up with “ranking.com”? Some possibilities: Your were mislead, or you did stumble over it innocently – then you should spare others this experience. Or perhaps you are linked to 7MetaSearch.com in some capacity – then you could explain to us why this out-of-date site should still be visited. DiEb

Total number of Websites 1,318,086,225 10% = 131,808,622 or 132M Websites online right now http://www.internetlivestats.com/total-number-of-websites/ January 2017 Web Server Survey In the January 2017 survey we received responses from 1,800,047,111 sites and 6,328,006 computers, reflecting a gain of 61 million sites and 159,000 computers. https://news.netcraft.com/archives/2017/01/12/january-2017-web-server-survey.html December 2017 Web Server Survey In the December 2017 survey we received responses from 1,734,290,608 sites across 212,870,632 unique domain names and 7,014,428 web-facing computers. This reflects a gain of 5.34 million domains and 121,000 computers. https://news.netcraft.com/archives/2017/12/26/december-2017-web-server-survey.html Search Web by Domain Explore 1,094,729 web sites visited by users of the Netcraft Toolbar https://searchdns.netcraft.com/?restriction=site+contains&host=uncommondescent.com&lookup=wait..&position=limited Dionisio

https://www.alexa.com/siteinfo/uncommondescent.com MIT.edu........................481 Nature.com.....................860 Harvard.edu....................873 Biblegateway.com.............1,001 Desiringgod.org.............10,908 Answersingenesis.org........28,882 Truthforlife.org............42,349 Gty.org.....................45,516 Samaritanspurse.org.........51,200 Icr.org.....................77,874 Religionnews.com............96,212 Royalsociety.org...........102,052 Rzim.org...................148,154 Evolutionnews.org..........168,380 Kodugamelab.com............311,217 Jamesmacdonald.com.........460,457 Uncommondescent.com........644,999 Pandasthumb.org............906,313 theskepticalzone.com.....5,147,609 Dionisio

Some Biology-related threads by gpuccio in 2017: The spliceosome: a molecular machine that defies any non-design explanation. December 21, 2017 Posted by gpuccio under Intelligent Design 347 Comments Visited 2,569 times https://uncommondescent.com/intelligent-design/the-spliceosome-a-molecular-machine-that-defies-any-non-design-explanation/ What are the limits of Random Variation? A simple evaluation of the probabilistic resources of our biological world October 31, 2017 Posted by gpuccio under Intelligent Design 273 Comments Visited 2,877 times https://uncommondescent.com/intelligent-design/what-are-the-limits-of-random-variation-a-simple-evaluation-of-the-probabilistic-resources-of-our-biological-world/ What are the limits of Natural Selection? An interesting open discussion with Gordon Davisson October 5, 2017 Posted by gpuccio under Intelligent Design 349 Comments Visited 2,898 times https://uncommondescent.com/intelligent-design/what-are-the-limits-of-natural-selection-an-interesting-open-discussion-with-gordon-davisson/ Dionisio

Some biology-related threads in 2017: 1. Evolutionary Biology’s Wrong Turn November 29, 2017 Posted by johnnyb under Darwinism, Intelligent Design 30 Comments Most people mistakenly think that Intelligent Design is anti-evolution. That is not correct. To understand Intelligent Design’s criticism of evolution, it is important to pinpoint specifically where we believe evolutionary biology made a wrong turn and why it matters. 2. Good question: What is an individual organism in biology? November 27, 2017 Posted by News under Evolution, Intelligent Design, Origin Of Life, speciation 1 Comment It ranks right up there with “What is a species?” From Derek J. Skillings at Aeon: Evolution itself is meant to tell us which entities count as individuals. Because natural selection is the engine of evolution, Hull said, we need to account for individuality in terms of what is required for selection. At their most […] 3. Rethinking biology: What role does physical structure play in the development of cells? November 10, 2017 Posted by News under Cell biology, Evolution, Intelligent Design 290 Comments That’s structuralism, in part. Further to Evelyn Fox Keller’s comment that the landscape of biological thought is being “radically reconfigured,” a cancer geneticist writes to say that a tumor’s physical environment fuels its growth and causes treatment resistance: The forces of cancer In vitro experiments showing that cancer cells actively migrate in response to fluid […] 4. Microbiology needs more math to help sort out the concept of “species”? Oh but wait… October 20, 2017 Posted by News under Cell biology, Genomics, Intelligent Design, speciation 4 Comments From Mikhail Tikhonov at The Scientist: More profoundly, microbial ecosystems are a strange world where many familiar concepts start to break down, including “species,” “fitness,” and maybe even “organism.” In our everyday experience, we are rarely in doubt whether a given creature is a fox or a rabbit. Further, it seems very easy to delineate […] 5. From Biology Direct: Darwinism, now thoroughly detached from its historical roots as a falsifiable theory, “must be abandoned” October 12, 2017 Posted by News under Culture, Darwinism, Evolution, Intelligent Design 8 Comments Evolutionary biology, we are told, does not need a master theory. Researchers should think in terms of “contemporary mainstream thinking.” From Arlin Stoltzfus at Biology Direct: Why we don’t want another “Synthesis” Abstract:High-level debates in evolutionary biology often treat the Modern Synthesis as a framework of population genetics, or as an intellectual lineage with a […] 6. Darwinian philosopher asks: Do we need purpose in biology? October 9, 2017 Posted by News under Darwinism, Evolution, Intelligent Design, Naturalism, Philosophy 4 Comments J. Scott Turner’s recent Purpose and Desire:What Makes Something “Alive” and Why Modern Darwinism Has Failed to Explain It makes the case that life is not comprehensible without the concept of purpose and that Darwinism’s failure to explain is an “impending crisis.” Michael Ruse, author of many books on the triumph of Darwinism, tells us […] 7. Biology prof Bret Weinstein’s persecutors face sanctions from Evergreen State College October 3, 2017 Posted by News under academic freedom, Culture, Intelligent Design, News No Comments You know, that non-PC nerd who was warned that it wasn’t safe for him to go back to teach and eventually settled for $500k. From Eric Owens at Daily Caller: School officials at the 4,000-student school received approximately 120 incident reports involving 180 students during the days-long series of protests, reports The Olympian, the main […] 8. Astrobiology: Water can be corrosive to life forms so what about alternatives? October 1, 2017 Posted by News under Fine tuning, Intelligent Design, Origin Of Life 3 Comments From Astrobiology: Life on early Earth seems to have begun with a paradox: while life needs water as a solvent, the essential chemical backbones of early life-forming molecules fall apart in water. Our universal solvent, it turns out, can be extremely corrosive. … In recent years the solvent often put forward as the eligible alternative […] 9. This just in: Evergreen U settles with biology prof over threat of harm due to non-PC stance September 17, 2017 Posted by News under academic freedom, Biology, Culture, science education 8 Comments From Ian Miles Cheong at Daily Caller: Evergreen State College has settled a tort claim with professor Bret Weinstein and his wife Heather Heying for $500,000 in connection to the 2017 “Day of Absence” protests, which saw anarchy spread throughout the campus earlier this year. “Through a series of decisions made at the highest levels, […] 10. Special issue of Biology: Evolution Beyond Selection will be open access September 10, 2017 Posted by News under Biology, Darwinism, Evolution, Intelligent Design 7 Comments Here: The conventional NeoDarwinian appraisal of evolution is based on corresponding pillars of random genetic variation and selection via differential fitness. In the 21st century, a salient question arises. Is this a sufficient evolutionary narrative? This Special Issue will offer several differing perspectives on evolutionary development and phylogeny that extend beyond Darwinian selection. The role […] 11. Are there really few thought experiments in biology? September 8, 2017 Posted by News under Darwinism, Evolutionary biology, Intelligent Design 2 Comments A friend writes to draw our attention to an interesting 2014 paper Thought Experiments in Biology, by Guillaume Schlaepfer and Marcel Weber: Unlike in physics, the category of thought experiment is not very common in biology. At least there are no classic examples that are as important and as well-known as the most famous thought […] 12. Philosopher of biology: Darwinian natural selection is a poor predictor of evolutionary success August 28, 2017 Posted by News under Darwinism, Evolution, Intelligent Design No Comments From Bengt Autzen at the British Journal for the Philosophy of Science: Musing on Means: Fitness, Expectation and the Principles of Natural Selection How to measure fitness in the theory of natural selection? A fitness measure that has been proposed in both the biological and the philosophical literature is the expected relative reproductive success. The […] 13. Philosopher of science: Are there laws in biology, as in physics? August 19, 2017 Posted by News under Intelligent Design, Philosophy, Science 2 Comments From Massimo Pigliucci at Footnotes to Plato: Theoretical biology’ is a surprisingly heterogeneous field, partly because it encompasses ‘‘doing theory’’ across disciplines as diverse as molecular biology, systematics, ecology, and evolutionary biology. Moreover, it is done in a stunning variety of different ways, using anything from formal analytical models to computer simulations, from graphic representations […] 14. A note on that fired Google engineer (a biology major)… August 9, 2017 Posted by News under Culture, Evolutionary psychology, Intellectual freedom, Intelligent Design, Naturalism 8 Comments The one who got drowned in diversicrat social media politics. The story provides good illustration of the way in which traditional media today are not up to the job of newsgathering in a non-gatekeeper digital age and should not be trusted. From Bre Davis at the Federalist: Here Are All The Media Outlets Blatantly Lying […] 15. rom Philip Cunningham: Darwinian Materialism vs Quantum Biology July 31, 2017 Posted by News under Cell biology, Intelligent Design 5 Comments Sources here. See also: Ribosome precisely structured for cell growth 16. Evergreen biology prof Bret Weinstein’s shocking testimony at You Tube: July 27, 2017 Posted by News under academic freedom, Education, Intelligent Design, Science 16 Comments Here is his report. If his testimony is accurate (and we expect it is), American taxpayers are funding the equivalent of a prison riot: No wonder Weinstein is suing. So where are the science organizations that should be supporting him? Communing with their shoes? Added: Note: Crash course for sci nerds: How political correctness morphed […] 17. Alan Sokal, buy yourself a latte: “Star Wars” biology paper accepted July 27, 2017 Posted by News under Biology, Intelligent Design, Peer review, Science No Comments Physicist Sokal perpetrated the first hoax paper over two decades ago, to prove a point. From Stephanie Pappas at LiveScience: Mitochondria: totally real cell organelles that convert sugars, fats and oxygen into usable energy for cells. Midi-chlorians: completely made-up and widely derided microscopic life-forms that give Jedi warriors their ability to use the Force in […] 18. From the Atlantic: Montana Trailer Park guy upends biology July 25, 2017 Posted by News under Cell biology, Evolution, Intelligent Design, Symbiosis 1 Comment Ed Yong tells us at the Atlantic: In the 150 years since Schwendener, biologists have tried in vain to grow lichens in laboratories. Whenever they artificially united the fungus and the alga, the two partners would never fully recreate their natural structures. It was as if something was missing—and Spribille might have discovered it. He […] 19. Cell atlases reveal extreme complexity at biology’s frontiers July 24, 2017 Posted by News under Cell biology, Intelligent Design 3 Comments From Jordana Cepelewicz at Quanta: For over a century, distinctions between types of cells relied on how they appeared under a microscope: their shapes, sizes, locations and their uptake of staining dyes. Recent decades, however, witnessed a shift to molecular methods that use fluorescently labeled antibodies to target protein markers on the cell’s surface. Although […] 20. Chalkman!! comes to biology prof’s rescue June 6, 2017 Posted by News under academic freedom, Science 5 Comments From William Hicks on Evergreen at Heat Street: The campus erupted in protest a two weeks ago when biology professor Bret Weinstein emailed a student criticizing their plans for the “Day of Absence.” Usually the event is conducted by students of color leaving the campus for the day, but this year they wanted to coerce […] 21. Konrad Lorenz Institute: Following through on non-Darwinian biology May 16, 2017 Posted by News under Culture, Darwinism, Epigenetics, Evolutionary biology, News 7 Comments Does anyone remember the Altenberg 16, a group of dissenting evolution theorists who met so nervously at the Konrad Lorenz institute in Austria that they locked a journalist out of the meeting?* They seem to be continuing to write papers, according to Massimo Pigliucci, I have just spent three delightful days at the Konrad Lorenz […] 22. Biology program without the Darwin worship April 10, 2017 Posted by News under Biology, science education 2 Comments Aimed, one guesses, at people who already have a religion or don’t think they need one. From a group of instructors at Wake Forest University: BioBook Basic Edition and its linked resources are available free to everyone. Click on the Table of Contents tab to browse topics. Registered users must log in here or in […] 23. Doug Axe: The culture of engineering vs. the culture of biology, and what Hidden Figures can tell us about that March 3, 2017 Posted by News under Biology, Culture, Darwinism, Engineering, Intelligent Design 2 Comments From Douglas Axe, author of Undeniable, at The Stream: Hidden Figures — the true story of three brilliant African-American women who proved themselves in a 1960s NASA culture dominated by white men — is sure to inspire. The film is filled with emotive lessons, most powerfully a vindication of the hope that those who persevere […] 24. AM-Nat Biology Abstracts Posted February 22, 2017 Posted by johnnyb under Biology, Naturalism, Philosophy 1 Comment Just wanted to let everyone know that we have posted the abstracts for this weekend’s Alternatives to Methodological Naturalism in Biology conference online. 25. Online Biology Conference This Weekend February 20, 2017 Posted by johnnyb under Biology, Intelligent Design, Naturalism, Philosophy, Science No Comments The Alternatives to Methodological Naturalism in Biology conference is this Saturday February 25th. Since the conference is online, you can attend from anywhere in the world as long as you have an Internet connection. 26. Sign Up for the AM-Nat Biology Online Conference February 14, 2017 Posted by johnnyb under Biology, Naturalism, Philosophy 5 Comments The second Alternatives to Methodological Naturalism online conference is right around the corner! On February 25th, we will convene AM-Nat Biology, focusing on biological applications for alternatives to methodological naturalism. 27. Deadline Today for Abstracts for AM-Nat Biology January 31, 2017 Posted by johnnyb under Biology, Intelligent Design, Naturalism No Comments For those of you interested in the Alternatives to Methodological Naturalism series of online conferences, I thought I’d let you know that today is the last day you can submit an abstract for the conference. 28. Darwinism: The steam engine of modern biology January 20, 2017 Posted by News under Evolution, Evolutionary biology, Intelligent Design, theistic evolution No Comments In response to our Steampunk Darwin, David Klinghoffer observes, at Evolution News & Views, a classic example of the way in which mediocrities know they are right: Because they can attract a consensus of, mainly, themselves to end discussions of problematic new information: Shutting Down the Evolution Debate, the “Mainstream Science” Way We noted the other […] 29. Alternatives to Methodological Naturalism in Biology Submissions Starting to Come In January 12, 2017 Posted by johnnyb under Biology, Intelligent Design, Naturalism 10 Comments We are excited to report that we have received a steady stream of submissions to AM-Nat Biology over the last few weeks. If you haven’t submitted your abstract, please do so soon. 30. Atheist Biology Professor Asks if There is a Role for Intelligence in Evolution January 4, 2017 Posted by Barry Arrington under Intelligent Design 8 Comments His answer is “Yes!”* _________ *so long as by “intelligence” you mean something other than “intelligence,” and by “evolution” you mean something other than “evolution.” In this article, atheist Kevin N. Laland, Professor of Behavioral and Evolutionary Biology at the University of St Andrews, argues that human culture affects evolution of the human genome. Here […] 31. Submission Deadline Approaching for AM-Nat Biology Conference January 2, 2017 Posted by johnnyb under Biology, Naturalism 7 Comments If you are interested in submitting a paper for the Alternatives to Methodological Naturalism in Biology online conference, the deadline is fast approaching! Dionisio

Netcraft estimates that there are 172 million active sites (those that get regular changes). The number of active sites has fallen slightly from 177 million in 2015. Despite the huge growth in websites only around 10% contribute fresh information to the Internet. http://tekeye.uk/computing/how-many-websites-are-there Dionisio

http://www.internetlivestats.com/total-number-of-websites/ http://tekeye.uk/computing/how-many-websites-are-there Dionisio

https://www.bing.com/search?q=how+many+active+websites+are+in+the+internet%3F&qs=n&form=QBLH&sp=-1&pq=how+many+active+websites+are+in+the+internet&sc=2-44&sk=&cvid=72D5F10B1A9B4DF3A4A1B67D4F8E14F2 Dionisio

@26 addendum We look at the data, mit.edu has 890 rank in the world wide web. The Google page rank of this website is 9/10. Website ping to the server is timed at 181 ms. https://www.pagevisr.com/www/mit.edu We look at the data, biblegateway.com has 1266 rank in the world wide web. The Google page rank of this website is 7/10. Website ping to the server is timed at 580 ms. https://www.pagevisr.com/www/biblegateway.com We look at the data, desiringgod.org has 17002 rank in the world wide web. The Google page rank of this website is 6/10. Website ping to the server is timed at 578 ms. https://www.pagevisr.com/www/desiringgod.org We look at the data, truthforlife.org has 0 rank in the world wide web. The Google page rank of this website is 4/10. Website ping to the server is timed at 499 ms. https://www.pagevisr.com/www/truthforlife.org We look at the data, uncommondescent.com has 256260 rank in the world wide web. The Google page rank of this website is 5/10. Website ping to the server is timed at 1291 ms. https://www.pagevisr.com/www/uncommondescent.com We look at the data, pandasthumb.org has 378043 rank in the world wide web. The Google page rank of this website is 7/10. Website ping to the server is timed at 187 ms. https://www.pagevisr.com/www/pandasthumb.org Dionisio

Quantcast.com https://www.quantcast.com/uncommondescent.com?qcLocale=en_US Dionisio

Another one: https://www.similarweb.com/website/uncommondescent.com Global Rank Traffic rank of site, as compared to all other sites in the world Worldwide 338,765 Country Rank Traffic rank of site, as compared to all other sites in its leading country United States 86,770 United States 45.65% +11.09% Canada 12.57% +8.12% Spain 7.48% +138.7% Netherlands 4.76% -2.60% United Kingdom 4.06% -44.92% Dionisio

This is interesting too: http://www.webometrics.info/en/world Dionisio

To see websites that link to this: Google link:www.uncommondescent.com Dionisio

UD is publicly presented as an ID website, hence ID topics should be discussed. And these days I think the main ID topic is biology research, where real complex functionally specified informational complexity is increasingly being revealed by dedicated scientists using more sophisticated technologies that allow the wet lab researchers to peek deeper within the biological systems “in vivo”, dumping an avalanche of data on the cloud servers for many dry lab researchers to process it using better computer systems and algorithms. Multilayered controls within marvelously designed biological systems are leaving researchers speechless. Multidisciplinary research teams are working hard in many scientific institutions trying to understand all that functional complexity. As outstanding questions get answered, new ones are raised. It’s beyond fantastic. But we ain’t seen nothing yet. The most fascinating discoveries are still ahead. The noise we’re hearing is just the cacophony produced by the orchestra musicians tuning their individual instruments separately. That’s why we read so many times expressions like “surprisingly” and “unexpectedly” in the research papers. That’s the result of their narrow-minded reductionist bottom-up research approach. But that’s most of the information available to us today, so we have to use it in our studies. We haven’t heard the orchestra playing the most wonderful symphony yet. The curtains are not quite open. The beautiful biological ballet choreography hasn’t been displayed with all its splendor. All that is still ahead. We should encourage more young students who like science to consider pursuing biology-related research careers. Then they’ll enjoy seeing true wonders beyond anything they ever imagined. Dionisio

GP’s biology-related article, posted last December 21, about 21 days ago, has received over 2,000 anonymous visits so far. Over 100 anonymous visits daily? Not bad for such a highly technical topic, reserved for a reduced audience. Several people (DATCG, Eric Anderson, ET, PaV, Mung, and others) have commented in this discussion. Actually DATCG and other commenters provided very interesting information that made GP write a few additional comments for the benefit of his readers. A distinguished biology professor at the University of Kentucky, well respected in academic scientific circles, who has co-authored a substantial number of peer-reviewed papers, posted a comment @25 that started a serious discussion with GP. So far nobody has been able to make a dent in GP’s strong ID presentation. But we expected the professor, who kindly started the discussion, to present a valid counterargument to GP’s OP and follow up comments. Here’s a quick summary: Discussion between AH and GP Index of posted comments: AH @25 …….……. GP @28 AH @50 AH @51 …….……. GP @54 AH @56 * …….……. GP @60 …….……. GP @69 …….……. GP @75 …….……. GP @86 …….……. GP @98 …….……. GP @106 …….……. GP @118 ** …….……. GP @119 ** …….……. GP @127 …….……. GP @129 AH @130 …….……. GP @136 …….……. GP @138 …….……. GP @146 …….……. GP @162 AH @164 …….……. GP @167 …….……. GP @176 …….……. GP @182 …….……. GP @198 …….……. GP @200 …….……. GP @201 …….……. GP @210 …….……. GP @211 …….……. GP @212 …….……. GP @231 …….……. GP @242 …….……. GP @253 ** …….……. GP @254 ** …….……. GP @263 …….……. GP @268 …….……. GP @294 …….……. GP @295 …….……. GP @296 …….……. GP @297 …….……. GP @313 ** …….……. GP @317 ** …….……. GP @319 ** …….……. GP @330 ** AH is the distinguished biology professor Arthur Hunt at the University of Kentucky GP is the author of the excellent OP that started this discussion thread (*) first publicly admitted mistake @56 (**) related to the main discussion, but not addressed to professor A. Hunt directly (to be continued…) https://uncommondescent.com/intelligent-design/the-spliceosome-a-molecular-machine-that-defies-any-non-design-explanation/ the distinguished biology professor apparently tried to punch a hole in a very revealing ID case presented by gpuccio. The fact that their serious discussion hasn’t finished yet, but so far the distinguished visitor hasn’t ben able to make even a shallow dent on the presented ID case seems very indicative of the situation in biology today. That’s why former neo-Darwinian very respected scientists are jumping out of that anachronistic train and starting their own ‘third way’ attempt to keep their ball rolling. But as gpuccio has stated before, there’s only one game in town in the biology science arena: ID facts vs. the modern synthesis / neo-Darwinian pseudoscientific ‘just-so’ fairytales. a distinguished biology profesor at the University of Kentucky found an OP gpuccio posted last December 21 here: https://uncommondescent.com/intelligent-design/the-spliceosome-a-molecular-machine-that-defies-any-non-design-explanation/#comment-647600 The visiting professor posted his first comment here: https://uncommondescent.com/intelligent-design/the-spliceosome-a-molecular-machine-that-defies-any-non-design-explanation/#comment-646028 I don’t know when exactly gpuccio posted his OP that day, but the first comment was posted by mike1962 that same day December 21, 2017 at 10:44 am. The visiting professor posted his first comment @25 that same day December 21, 2017 at 8:08 pm. Assuming that all the time stamps are related to the same server in Denver, CO. then the visiting professor knew about the posting of GP’s OP the same day, less than 10 hours after the first comment had been posted. Is it only me or also you see something interesting in this case? To me that was pretty fast, no matter how we look at it. Unless someone tell me that this professor has commented here before and had an account in this site, where perhaps he could have some ways of getting notified when a particular topic is being posted. Could that be the explanation? Otherwise, this is kind of interesting to me. Perhaps the best way is to ask him directly. He shouldn’t mind telling us how he heard about the OP, right? At least I wouldn’t if I were in that case. That tells more than many stats provided by some companies in some obscure ways. Maybe I’m making a big deal out of something that isn’t? Maybe… PS. Here’s a piece of information obtained from Google search, where someone in this site commented about a 2007 article the given professor posted in another website: On the non-evolution of Irreducible Complexity – How Arthur Hunt … https://uncommondescent.com/…/on-the-non-evolution-of-irreducible-complexity-ho… Feb 24, 2011 – Recently, someone referred me to two articles (one, two) on the Panda’s Thumb website (from back in 2007), by Arthur Hunt (professor in Department of Plant and Soil Sciences at the …… Regarding Tierra, I suggest you re-read PaV’s original comment at https://uncommondescent.com…..ent-366926 Never mind. It’s much simpler than I thought. The U-KY biology professor posted comments in this site long before I came here: https://uncommondescent.com/intelligent-design/another-day-another-bad-day-for-darwinism/#comment-357595 Dionisio

Google "uncommondescent.com" About 50,500 results 23 pages In order to show you the most relevant results, we have omitted some entries very similar to the 230 already displayed. If you like, you can repeat the search with the omitted results included. "pandasthumb.org" About 8,540 results 15 pages In order to show you the most relevant results, we have omitted some entries very similar to the 150 already displayed. If you like, you can repeat the search with the omitted results included. "theskepticalzone.com" About 6,300 results 8 pages In order to show you the most relevant results, we have omitted some entries very similar to the 78 already displayed. If you like, you can repeat the search with the omitted results included. Dionisio

We look at the data, uncommondescent.com has 256260 rank in the world wide web. The website server is using IP address 216.70.69.190 and is hosted in United States. The Google page rank of this website is 5/10. Website ping to the server is timed at 1291 ms. . https://www.pagevisr.com/www/uncommondescent.com Dionisio

https://www.alexa.com/siteinfo/evolutionnews.org Global Rank 169,652 ?up by 12,028 Rank in United States 51,389 https://www.alexa.com/siteinfo/uncommondescent.com Global rank 648,783 ?down by 92,426 Rank in United States 227,899 Dionisio

KF, Thank you for the clarifying information. I was glad to see that the second to the last in the list is much lower than UD. Also glad to see the ones I like so far above too. The universities, the journal, the Royal Society, and MSFT kodu are inserted for comparison. Dionisio

Dionisio, there are over 10^9 web sites, perhaps 1/4 of these active. So the top 1 percent would run out to the 2.5 millionth or thereabouts. All of the above are in the top 1% of global web sites that are active. KF kairosfocus

http://www.ranking.com/ Web Rank Biblegateway.com 168 MIT.edu 7,280 HARVARD.edu 7,246 Nature.com 7,449 Desiringgod.org 10,105 Answersingenesis.org 11,865 Gty.org 15,018 Icr.org 19,037 Religionnews.com 22,188 Rzim.org 35,858 Samaritanspurse.org 40,274 Truthforlife.org 49,862 Royalsociety.org 53,686 Evolutionnews.org 58,755 Jamesmacdonald.com 60,164 Reasons.org 65,259 Uncommondescent.com 80,763 Pandasthumb.org 106,377 Kodugamelab.com 668,032 Dionisio

Central pattern generators (CPGs) are neural circuits that produce the patterns of neural activity that underlie rhythmic motor behaviours such as walking, swimming and feeding [...]

Evolution of central pattern generators and rhythmic behaviours. Katz PS1. Philos Trans R Soc Lond B Biol Sci. 2016 Jan 5;371(1685):20150057. doi: 10.1098/rstb.2015.0057. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685589/pdf/rstb20150057.pdf

where's the beef? Dionisio

Was this the state of evo-devo over 6 years ago?

The connections between patterns at the macroevolutionary level and microevolutionary processes observed within populations on an experimental time scale remain essentially unmade [12]. The next quarter of a century will clearly reveal more of how the genotype to phenotype map works for the whole functional phenotype, and will demonstrate the extent to which the evolution of form is special with its own largely private mechanisms and machinery. The association between evolution in form and the timing of modification of development in ontogeny remains unclear, especially with respect to evolutionary novelties. Associations of this type will also prove fascinating to unravel for behavioural traits. Hopefully, future work will unravel more effectively the genetical from the developmental properties The extent to which natural selection is all-powerful in different organisms remains unclear whether one is considering morphological, behavioural or life-history traits (e.g. [12,49,53]). An integration of experimental work on key traits using model species with a more comparative phylogenetic approach across species in eco- and trait-space is needed to progress further. How exactly this machinery has been recruited and co-opted at the origin of some novel structure, and then elaborated upon in subsequent adaptive radiations in morphospace facilitated by the structure remains an exciting challenge for the future [19].

Evo-devo and accounting for Darwin's endless forms Paul M. Brakefield Philosophical Transactions of the Royal Society B Biological Sciences Published 20 June 2011. DOI: 10.1098/rstb.2011.0007

Dionisio

@18 False alarm. Dionisio

Apparently the above lyrics posted in genius.com is missing parts. I’ll try to review this later. Dionisio

interface? files? subprograms? switches, circuit boards and boot code? Huh? Say what? Dionisio

TWSYF, That’s amazing, isn’t it? :) Dionisio

Dionisio @ 14: Absolutely! Cells are great coders and planners. Very smart little buggers. Truth Will Set You Free

"How our cells encode this architectural plan" Huh? Did somebody say 'encode'? Did somebody say 'plan'? Dionisio

"We Are built of modules combined in a planned out way Each new piece must be told where to go" "told where to go"? Huh? By whom? How is that 'telling' ? Dionisio

"We Are built of modules combined in a planned out way" "planned out way"? Did somebody say "planned"? Huh? By whom? Dionisio

"See One cell divide and decide on a thousand fates Did you ever figure how they know?" Do cells know anything? Do they have knowledge? Dionisio

"One cell divide and decide on a thousand fates" Did somebody say "decide"? Huh? Do cells make decisions? :) Dionisio

This reminds me of the last decade of the Cold War, when the soviets, after trying a few party leaders consecutively, finally got a guy who trying to revitalize their weakening system, slightly opening a window to let some fresh air get into their tightly closed society. Glasnost and perestroika were tried as their magic solution in vain. Eventually the whole structure collapsed. Dionisio

This reminds me of a Cold War joke: The soviets sent a spaceship to the moon. The cosmonauts painted the whole moon red. On earth people watching the moon turned red wondered what's that? When the soviets returned, the Americans sent their spaceship to the moon, the astronauts unloaded white paint and wrote on the red surface: Drink Coca-Cola Let them popularize evo-devo as much as possible. Perhaps many people will ask the 'why' and 'how' questions. Then we'll bring the white paint. :) Dionisio

Here's from the website Genius.com Evo-Devo (Despacito Biology Parody) A Capella Science Lyrics

EVO-DEVO Huxley B. Mac Oh Carroll, Carroll Gould, Stephen Jay yeah D-D-D-D-Davidson and Peter See One cell divide and decide on a thousand fates Did you ever figure how they know? B. Mac We Are built of modules combined in a planned out way Each new piece must be told where to go Oh Now there's a science helping us to understand How our cells encode this architectural plan Signalling each other with genetic tools oh Oh yeah Wow Phenotype the interface for mouse and man Genotype the files and the subprograms What then are the switches, circuit boards and boot code? Evo-Devo Looking at the logic in the ways that we grow Every gene directed by a signal key code Proteins that can activate, enhance or veto Evo-Devo Signals are controlled by other genes that signal Calculating in a network labyrinthal Where the heart and liver and the hands and feet go Signal mapping tells each region what it ought to be yo With circuits so deeply built upon They're older than the Paleo The Paleozoic Era baby In a crucial pathway changes tend to get torpedoed Where they go calamity goes As this cyclopic sheep knows.. See down they cascade like a domino Like you and I drosophila The path that makes us optical Was laid a long long time ago Back before we blew up the cambrian like a bomb bomb Now my eye protein can make you see out of your bom bom And Hedgehog and its relatives like Indian and Sonic Set up set up in a gradient on segments embryonic Split forebrains and asymmetric parts depend upon it Flipping on genetic switches and logic From devo to evo Adult and embryo Mostly don't evolve in the genes of the genome Safer the mutation aimed at regulation Keep the building blocks and swap their activation From devo to evo Parts have alter egos Homologs evolved from repeats in the schema Switch a couple bases in the proper places You'll be watching flies grow legs out of their faces oh yeah Evo-Devo Stick around for Modern Synthesis the sequel Only by combining can a new theory grow Evolution and development amigos Evo-Devo Signals trigger patterns of complexity so Switching up the switches of a signalling node Gives a modular and simple way to evolve Look at how our spinal segments generate a neat row Built on a molecular clock One cycle, one vertebra One vertebra one vertebra baby Speeding up its rate is snakes' developmental cheat code That and where a lizard's feet grow They turn off distal aminos Evo-Devo This is how we go from single cells to people Every generation and in life primeval Life in variations endless and beautiful Badaboom From devo to evo Larva to mosquito Patterns are resolved as the signals proceed yo Map out a gene with a glow tag Kill it with a morpholino Short oligo morpholino baby From devo to evo Voyage of the Beagle Body plans evolve when proteins steer the genome In this manner life's beauty grows Aesthetica in vivo Evo-Devo

https://genius.com/Tim-blais-evo-devo-despacito-biology-parody-a-capella-science-lyrics

Tim Blais, AKA A Capella Science, uses Despacito to teach us evolutionary developmental biology, or evo-devo. It’s a new science showing how genes can be controlled by other genes, and how that can explain how evolution works when most mutations just seem to mess up organisms.

Dionisio

Evo-Devo (Despacito Biology Parody) A Capella Science Tim Blais https://genius.com/Tim-blais-evo-devo-despacito-biology-parody-a-capella-science-lyrics Dionisio

Perhaps the popular Canadian singer Justin Bieber should contact "A Cappella Science" Tim Blais and learn the English language version of the popular song, so that next time he doesn't have to dodge water bottles hurled at him by upset fans after refusing to sing the original lyrics in Spanish. That could make evo-devo even more popular among younger generations. That would be nice for the ID folks. :) Dionisio

According to the Merriam-Webster dictionary, the term "reggaeton" refers to a popular music of Puerto Rican origin that combines rap with Caribbean rhythms like reggae. Dionisio

The fundamental formulation of evo-devo is: Dev(d) = Dev(a) + Delta(a,d) Where: Dev(a) is the entire* developmental process of a given ancestor Dev(d) is the entire* developmental process of a given descendant Delta(a,d) is the complete* set of spatiotemporal changes required in Dev(a) in order to get Dev(d). (*) the whole enchilada Dionisio

Let them popularize evo-devo, the most complex task in the neo-Darwinian paradigm. They're doing -unknowingly- the work for the ID folks. Just be thankful for that. It'll pay dividends. They ain't seen nothin' yet. The most fascinating discoveries are still ahead. All they're hearing is like the cacophony produced by the orchestra musicians tuning their individual instruments. The curtains are still closed. The scenario is hidden behind. The ballet choreography hasn't been shown in all its splendor yet. Dionisio

My favorite lines: Switch a couple bases From their proper places And you'll be watching flies Grow legs from their faces Barry Arrington