A third way of evolution?

_{News
June 2, 2014

Evolution, News

1}_{Categories
Evolution
News}

Share: Facebook; Twitter/X; LinkedIn; Flipboard; Print; Email

That’s the new buzz here:

The vast majority of people believe that there are only two alternative ways to explain the origins of biological diversity. One way is Creationism that depends upon supernatural intervention by a divine Creator. The other way is Neo-Darwinism, which has elevated Natural Selection into a unique creative force that solves all the difficult evolutionary problems. Both views are inconsistent with significant bodies of empirical evidence and have evolved into hard-line ideologies. There is a need for a more open “third way” of discussing evolutionary change based on empirical observations.

Supporters include Shapiro, Noble, Koonin, Neuman, Jablonka—non-Darwin lobby researchers into evolution. Interested in understanding nature, not getting a judge to agree to enshrine their beliefs in a tax-funded, union-infested school system.

Sounds interesting. Stuff to get started.

Follow UD News at Twitter!

Comments

Schizosaccharomyces pombe centromere protein Mis19 links Mis16 and Mis18 to recruit CENP-A through interacting with NMD factors and the SWI/SNF complex
CENP-A is a centromere-specific variant of histone H3 that is required for accurate chromosome segregation. The fission yeast Schizosaccharomyces pombe and mammalian Mis16 and Mis18 form a complex essential for CENP-A recruitment to centromeres. It is unclear, however, how the Mis16-Mis18 complex achieves this function. Here, we identified, by mass spectrometry, novel fission yeast centromere proteins Mis19 and Mis20 that directly interact with Mis16 and Mis18. Like Mis18, Mis19 and Mis20 are localized at the centromeres during interphase, but not in mitosis. Inactivation of Mis19 in a newly isolated temperature-sensitive mutant resulted in CENP-A delocalization and massive chromosome missegregation, whereas Mis20 was dispensable for proper chromosome segregation. Mis19 might be a bridge component for Mis16 and Mis18. We isolated extragenic suppressor mutants for temperature-sensitive mis18 and mis19 mutants and used whole-genome sequencing to determine the mutated sites. We identified two groups of loss-of-function suppressor mutations in non-sense-mediated mRNA decay factors (upf2 and ebs1), and in SWI/SNF chromatin-remodeling components (snf5, snf22 and sol1). Our results suggest that the Mis16-Mis18-Mis19-Mis20 CENP-A-recruiting complex, which is functional in the G1-S phase, may be counteracted by the SWI/SNF chromatin-remodeling complex and non-sense-mediated mRNA decay, which may prevent CENP-A deposition at the centromere. Hayashi, T., Ebe, M., Nagao, K., Kokubu, A., Sajiki, K. and Yanagida, M. (2014), Schizosaccharomyces pombe centromere protein Mis19 links Mis16 and Mis18 to recruit CENP-A through interacting with NMD factors and the SWI/SNF complex. Genes to Cells, 19: 541–554. doi: 10.1111/gtc.12152
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
09:30 PM
9
09
30
PM
PDT}

interface between centriole and peri-centriolar material
The increase in centrosome size in mitosis was described over a century ago, and yet it is poorly understood how centrioles, which lie at the core of centrosomes, organize the pericentriolar material (PCM) in this process. Now, structured illumination microscopy reveals in Drosophila that, before clouds of PCM appear, its proteins are closely associated with interphase centrioles in two tube-like layers: an inner layer occupied by centriolar microtubules, Sas-4, Spd-2 and Polo kinase; and an outer layer comprising Pericentrin-like protein (Dplp), Asterless (Asl) and Plk4 kinase. Centrosomin (Cnn) and ?-tubulin associate with this outer tube in G2 cells and, upon mitotic entry, Polo activity is required to recruit them together with Spd-2 into PCM clouds. Cnn is required for Spd-2 to expand into the PCM during this maturation process but can itself contribute to PCM independently of Spd-2. By contrast, the centrioles of spermatocytes elongate from a pre-existing proximal unit during the G2 preceding meiosis. Sas-4 is restricted to the microtubule-associated, inner cylinder and Dplp and Cnn to the outer cylinder of this proximal part. ?-Tubulin and Asl associate with the outer cylinder and Spd-2 with the inner cylinder throughout the entire G2 centriole. Although they occupy different spatial compartments on the G2 centriole, Cnn, Spd-2 and ?-tubulin become diminished at the centriole upon entry into meiosis to become part of PCM clouds. doi: 10.1098/rsob.120104 http://rsob.royalsocietypublishing.org/content/2/8/120104.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
05:40 PM
5
05
40
PM
PDT}

Microtubule plus-ends within a mitotic cell are ‘moving platforms’ with anchoring, signalling and force-coupling roles
The microtubule polymer grows and shrinks predominantly from one of its ends called the ‘plus-end’. Plus-end regulation during interphase is well understood. However, mitotic regulation of plus-ends is only beginning to be understood in mammalian cells. During mitosis, the plus-ends are tethered to specialized microtubule capture sites. At these sites, plus-end-binding proteins are loaded and unloaded in a regulated fashion. Proper tethering of plus-ends to specialized sites is important so that the microtubule is able to translate its growth and shrinkage into pushing and pulling forces that move bulky subcellular structures. We discuss recent advances on how mitotic plus-ends are tethered to distinct subcellular sites and how plus-end-bound proteins can modulate the forces that move subcellular structures. Using end binding 1 (EB1) as a prototype plus-end-binding protein, we highlight the complex network of plus-end-binding proteins and their regulation through phosphorylation. Finally, we develop a speculative ‘moving platform’ model that illustrates the plus-end's role in distinguishing correct versus incorrect microtubule interactions. doi: 10.1098/rsob.120132 http://rsob.royalsocietypublishing.org/content/2/11/120132.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
05:37 PM
5
05
37
PM
PDT}

Exotic mitotic mechanisms
The emergence of eukaryotes around two billion years ago provided new challenges for the chromosome segregation machineries: the physical separation of multiple large and linear chromosomes from the microtubule-organizing centres by the nuclear envelope. In this review, we set out the diverse solutions that eukaryotic cells use to solve this problem, and show how stepping away from ‘mainstream’ mitosis can teach us much about the mechanisms and mechanics that can drive chromosome segregation. We discuss the evidence for a close functional and physical relationship between membranes, nuclear pores and kinetochores in generating the forces necessary for chromosome segregation during mitosis. doi: 10.1098/rsob.120140 http://rsob.royalsocietypublishing.org/content/2/12/120140.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
05:28 PM
5
05
28
PM
PDT}

Dual mechanisms prevent premature chromosome segregation during meiosis
In meiosis I, homologous chromosomes pair and then attach to the spindle so that the homologs can be pulled apart at anaphase I. The segregation of homologs before pairing would be catastrophic. We describe two mechanisms that prevent this. First, in early meiosis, Ipl1, the budding yeast homolog of the mammalian Aurora B kinase, triggers shedding of a kinetochore protein, preventing microtubule attachment. Second, Ipl1 localizes to the spindle pole bodies (SPBs), where it blocks spindle assembly. These processes are reversed upon expression of Ndt80. Previous studies have shown that Ndt80 is expressed when homologs have successfully partnered, and this triggers a rise in the levels of cyclin-dependent kinase (CDK). We found that CDK phosphorylates Ipl1, delocalizing it from SPBs, triggering spindle assembly. At the same time, kinetochores reassemble. Thus, dual mechanisms controlled by Ipl1 and Ntd80 coordinate chromosome and spindle behaviors to prevent the attachment of unpartnered chromosomes to the meiotic spindle. doi: 10.1101/gad.227454.113 Genes & Dev. 2013. 27: 2139-2146 © 2013 Kim et al.; Published by Cold Spring Harbor Laboratory Press
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
05:13 PM
5
05
13
PM
PDT}

Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle
The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules. doi: 10.1098/rsob.120185 http://rsob.royalsocietypublishing.org/content/3/3/120185.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
05:10 PM
5
05
10
PM
PDT}

chromosome segregation: insights from trypanosomes
Faithful transmission of genetic material is essential for the survival of all organisms. Eukaryotic chromosome segregation is driven by the kinetochore that assembles onto centromeric DNA to capture spindle microtubules and govern the movement of chromosomes. Its molecular mechanism has been actively studied in conventional model eukaryotes, such as yeasts, worms, flies and human. However, these organisms are closely related in the evolutionary time scale and it therefore remains unclear whether all eukaryotes use a similar mechanism. The evolutionary origins of the segregation apparatus also remain enigmatic. To gain insights into these questions, it is critical to perform comparative studies. Here, we review our current understanding of the mitotic mechanism in Trypanosoma brucei, an experimentally tractable kinetoplastid parasite that branched early in eukaryotic history. No canonical kinetochore component has been identified, and the design principle of kinetochores might be fundamentally different in kinetoplastids. Furthermore, these organisms do not appear to possess a functional spindle checkpoint that monitors kinetochore–microtubule attachments. With these unique features and the long evolutionary distance from other eukaryotes, understanding the mechanism of chromosome segregation in T. brucei should reveal fundamental requirements for the eukaryotic segregation machinery, and may also provide hints about the origin and evolution of the segregation apparatus. doi: 10.1098/rsob.130023 http://rsob.royalsocietypublishing.org/content/3/5/130023.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
04:57 PM
4
04
57
PM
PDT}

Check this out
Left–right asymmetry: cilia stir up new surprises in the node Cilia are microtubule-based hair-like organelles that project from the surface of most eukaryotic cells. They play critical roles in cellular motility, fluid transport and a variety of signal transduction pathways. While we have a good appreciation of the mechanisms of ciliary biogenesis and the details of their structure, many of their functions demand a more lucid understanding. One such function, which remains as intriguing as the time when it was first discovered, is how beating cilia in the node drive the establishment of left–right asymmetry in the vertebrate embryo. The bone of contention has been the two schools of thought that have been put forth to explain this phenomenon. While the ‘morphogen hypothesis’ believes that ciliary motility is responsible for the transport of a morphogen preferentially to the left side, the ‘two-cilia model’ posits that the motile cilia generate a leftward-directed fluid flow that is somehow sensed by the immotile sensory cilia on the periphery of the node. Recent studies with the mouse embryo argue in favour of the latter scenario. Yet this principle may not be generally conserved in other vertebrates that use nodal flow to specify their left–right axis. Work with the teleost fish medaka raises the tantalizing possibility that motility as well as sensory functions of the nodal cilia could be residing within the same organelle. In the end, how ciliary signalling is transmitted to institute asymmetric gene expression that ultimately induces asymmetric organogenesis remains unresolved. doi: 10.1098/rsob.130052 http://rsob.royalsocietypublishing.org/content/3/5/130052.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
04:53 PM
4
04
53
PM
PDT}

Interesting research
Microtubule dynamics in neuronal morphogenesis Microtubules (MTs) are essential for neuronal morphogenesis in the developing brain. The MT cytoskeleton provides physical support to shape the fine structure of neuronal processes. MT-based motors play important roles in nucleokinesis, process formation and retraction. Regulation of MT stability downstream of extracellular cues is proposed to be critical for axonogenesis. Axons and dendrites exhibit different patterns of MT organization, underlying the divergent functions of these processes. Centrosomal positioning has drawn the attention of researchers because it is a major clue to understanding neuronal MT organization. In this review, we focus on how recent advances in live imaging have revealed the dynamics of MT organization and centrosome positioning during neural development. doi: 10.1098/rsob.130061 http://rsob.royalsocietypublishing.org/content/3/7/130061.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
04:48 PM
4
04
48
PM
PDT}

Interesting research:
Coordinating cell polarity and cell cycle progression Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression. doi: 10.1098/rsob.130083 http://rsob.royalsocietypublishing.org/content/3/8/130083.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
04:45 PM
4
04
45
PM
PDT}

Interesting research
A CENP-S/X complex assembles at the centromere in S and G2 phases of the human cell cycle The functional identity of centromeres arises from a set of specific nucleoprotein particle subunits of the centromeric chromatin fibre. These include CENP-A and histone H3 nucleosomes and a novel nucleosome-like complex of CENPs -T, -W, -S and -X. Fluorescence cross-correlation spectroscopy and Förster resonance energy transfer (FRET) revealed that human CENP-S and -X exist principally in complex in soluble form and retain proximity when assembled at centromeres. Conditional labelling experiments show that they both assemble de novo during S phase and G2, increasing approximately three- to fourfold in abundance at centromeres. Fluorescence recovery after photobleaching (FRAP) measurements documented steady-state exchange between soluble and assembled pools, with CENP-X exchanging approximately 10 times faster than CENP-S (t1/2 ? 10 min versus 120 min). CENP-S binding to sites of DNA damage was quite distinct, with a FRAP half-time of approximately 160 s. Fluorescent two-hybrid analysis identified CENP-T as a uniquely strong CENP-S binding protein and this association was confirmed by FRET, revealing a centromere-bound complex containing CENP-S, CENP-X and CENP-T in proximity to histone H3 but not CENP-A. We propose that deposition of the CENP-T/W/S/X particle reveals a kinetochore-specific chromatin assembly pathway that functions to switch centromeric chromatin to a mitosis-competent state after DNA replication. Centromeres shuttle between CENP-A-rich, replication-competent and H3-CENP-T/W/S/X-rich mitosis-competent compositions in the cell cycle. doi: 10.1098/rsob.130229 http://rsob.royalsocietypublishing.org/content/4/2/130229.abstract?sid=fa03888e-fc4a-4255-bffc-cb615f0ead5d
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
04:39 PM
4
04
39
PM
PDT}

Interesting research
spermatozoal mRNA repertoires It is now well established that mature mammalian spermatozoa carry a population of mRNA molecules, at least some of which are transferred to the oocyte at fertilization, however, their function remains largely unclear. To shed light on the evolutionary conservation of this feature of sperm biology, we analysed highly purified populations of mature sperm from the fruitfly, Drosophila melanogaster. As with mammalian sperm, we found a consistently enriched population of mRNA molecules that are unlikely to be derived from contaminating somatic cells or immature sperm. Using tagged transcripts for three of the spermatozoal mRNAs, we demonstrate that they are transferred to the oocyte at fertilization and can be detected before, and at least until, the onset of zygotic gene expression. We find a remarkable conservation in the functional annotations associated with fly and human spermatozoal mRNAs, in particular, a highly significant enrichment for transcripts encoding ribosomal proteins (RPs). The substantial functional coherence of spermatozoal transcripts in humans and the fly opens the possibility of using the power of Drosophila genetics to address the function of this enigmatic class of molecules in sperm and in the oocyte following fertilization. doi: 10.1098/rspb.2012.0153
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
01:34 PM
1
01
34
PM
PDT}

Interesting research to keep an eye on:
We are interested in the molecular mechanisms governing asymmetric stem cell divisions, with emphasis on the role of the mitotic spindle orientation in determining daughter cells’ fate. The proper execution of asymmetric divisions is crucial in generating tissue diversity during development, as well as for tissue homeostasis and regeneration in adult organisms. An increasing body of literature supports the notion that certain human cancers arise from abnormalities in adult stem cells asymmetric divisions, able to alter cell fate and leading to over-proliferation (the so called cancer stem cell hypothesis). Indeed failures in asymmetric divisions occur when pathways controlling the position of the cytokinesis plane are compromised. They cause incorrect fate specification and abnormal proliferation during mammalian neurogenesis and skin development, and correlated with cancer progression. To make a cell division asymmetric, the position of the mitotic spindle has to be tightly coordinated to the cortical polarity, so that daughter cells will be properly positioned within the tissue, inherit unequal sets of fate determinants and follow differential fates. This observation sets the stage for our studies, aimed at gaining insight into the structural and functional organization of the molecular machines responsible for spindle coupling to polarity cues during stem cells asymmetric divisions. To address this biological problem, we use a combination of high-resolution X-ray crystallography, biochemical analyses on reconstituted protein complexes and stem cell biology. Using the detailed molecular information delivered by our structural studies, we formulate precise models of how intrinsic properties of individual protein relate to the behavior of the mitotic spindle during asymmetric cell divisions, that we challenge in living cells. An emerging concept in the cancer field is that cancer stem cells may be responsible for relapse and resistance to anticancer therapies. In this view, a clear molecular description of processes underlying asymmetric cell divisions will be instrumental in identifying new stem-cell specific drug targets for therapeutic intervention. https://www.ieo.it/it/RESEARCH/Basic-research/Department-of-Experimental-Oncology11/Molecular-basis-of-asymmetric-cell-division-Unit/
Dionisio_{July 6, 2014
July
07
Jul
6
06
2014
01:18 PM
1
01
18
PM
PDT}

Interesting mechanisms.
Architectural Niche Organization by LHX2 Is Linked to Hair Follicle Stem Cell Function Highlights •Ablation of LHX2 in skin impairs HF-SC maintenance, leading to baldness •LHX2 functions primarily as a transcriptional activator in hair follicle stem cells •LHX2 regulates the architectural organization of the stem cell niche •Without LHX2, the hair follicle stem cell niche transforms into a sebaceous gland Summary In adult skin, self-renewing, undifferentiated hair follicle stem cells (HF-SCs) reside within a specialized niche, where they spend prolonged times as a single layer of polarized, quiescent epithelial cells. When sufficient activating signals accumulate, HF-SCs become mobilized to fuel tissue regeneration and hair growth. Here, we show that architectural organization of the HF-SC niche by transcription factor LHX2 plays a critical role in HF-SC behavior. Using genome-wide chromatin and transcriptional profiling of HF-SCs in vivo, we show that LHX2 directly transactivates genes that orchestrate cytoskeletal dynamics and adhesion. Conditional ablation of LHX2 results in gross cellular disorganization and HF-SC polarization within the niche. LHX2 loss leads to a failure to maintain HF-SC quiescence and hair anchoring, as well as progressive transformation of the niche into a sebaceous gland. These findings suggest that niche organization underlies the requirement for LHX2 in hair follicle structure and function. DOI: http://dx.doi.org/10.1016/j.stem.2013.06.018
Dionisio_{July 4, 2014
July
07
Jul
4
04
2014
07:23 PM
7
07
23
PM
PDT}

Interesting, isn't it?
Immune Modulation of Stem Cells and Regeneration The immune system, best known as the first line of defense against invading pathogens, is integral to tissue development, homeostasis, and wound repair. In recent years, there has been a growing appreciation that cellular and humoral components of the immune system also contribute to regeneration of damaged tissues, including limbs, skeletal muscle, heart, and the nervous system. Here, we discuss key findings that implicate inflammatory cells and their secreted factors in tissue replacement after injury via stem cells and other reparative mechanisms. We highlight clinical conditions that are amenable to immune-mediated regeneration and suggest immune targeting strategies for tissue regeneration. DOI: http://dx.doi.org/10.1016/j.stem.2014.06.009
Dionisio_{July 4, 2014
July
07
Jul
4
04
2014
06:39 PM
6
06
39
PM
PDT}

There are many complex mechanisms in the plants too. More work for the 3rd way in their OOL research.
Rice actin-binding protein RMD is a key link in the auxin–actin regulatory loop that controls cell growth The plant hormone auxin plays a central role in plant growth and development. Auxin transport and signaling depend on actin organization. Despite its functional importance, the mechanistic link between actin filaments (F-actin) and auxin intracellular signaling remains unclear. Here, we report that the actin-organizing protein Rice Morphology Determinant (RMD), a type II formin from rice (Oryza sativa), provides a key link. Mutants lacking RMD display abnormal cell growth and altered configuration of F-actin array direction. The rmd mutants also exhibit an inhibition of auxin-mediated cell elongation, decreased polar auxin transport, altered auxin distribution gradients in root tips, and suppression of plasma membrane localization of auxin transporters O. sativa PIN-FORMED 1b (OsPIN1b) and OsPIN2 in root cells. We demonstrate that RMD is required for endocytosis, exocytosis, and auxin-mediated OsPIN2 recycling to the plasma membrane. Moreover, RMD expression is directly regulated by heterodimerized O. sativa auxin response factor 23 (OsARF23) and OsARF24, providing evidence that auxin modulates the orientation of F-actin arrays through RMD. In support of this regulatory loop, osarf23 and lines with reduced expression of both OsARF23 and OsARF24 display reduced RMD expression, disrupted F-actin organization and cell growth, less sensitivity to auxin response, and altered auxin distribution and OsPIN localization. Our findings establish RMD as a crucial component of the auxin–actin self-organizing regulatory loop from the nucleus to cytoplasm that controls rice cell growth and morphogenesis. The positive feedback loop between the auxin pathway and actin cytoskeleton is essential for auxin self-organizing responsive signaling during plant development; however, its underlying mechanism remains largely unknown. Here, we showed that an actin-binding protein, rice morphology determinant (RMD), acts as a key component mediating the auxin–actin loop pathway, affecting cell growth and morphogenesis. Auxin directly promotes RMD expression via binding of Oryza sativa auxin response factor 23 (OsARF23) and OsARF24 heterodimers on the RMD promoter, triggering changes in F-actin organization. In turn, RMD-dependent F-actin arrays affect auxin intracellular signaling, including polar auxin transport, localization and recycling of auxin efflux carriers, and auxin distribution in root cells. Our work identifies RMD as a key link in the auxin–actin self-organizing regulatory loop that is required for auxin-mediated cell growth. doi: 10.1073/pnas.1401680111
Dionisio_{July 2, 2014
July
07
Jul
2
02
2014
06:17 PM
6
06
17
PM
PDT}

Something else for the 3rd way to consider in their OOL research.
Keap1-Nrf2 system regulates cell fate determination of hematopoietic stem cells Nrf2 is a major transcriptional activator of cytoprotective genes against oxidative/electrophilic stress, and Keap1 negatively regulates Nrf2. Emerging works have also suggested a role for Nrf2 as a regulator of differentiation in various cells, but the contribution of Nrf2 to the differentiation of hematopoietic stem cells (HSCs) remains elusive. Clarifying this point is important to understand Nrf2 functions in the development and/or resolution of inflammation. Here, we established two transgenic reporter mouse lines that allowed us to examine Nrf2 expression precisely in HSCs. Nrf2 was abundantly transcribed in HSCs, but its activity was maintained at low levels due to the Keap1-mediated degradation of Nrf2 protein. When we characterized Keap1-deficient mice, their bone marrow cells showed enhanced granulocyte-monocyte differentiation at the expense of erythroid and lymphoid differentiation. Importantly, Keap1-null HSCs showed lower expression of erythroid and lymphoid genes than did control HSCs, suggesting granulocyte-monocyte lineage priming in Keap1-null HSCs. This abnormal lineage commitment was restored by a concomitant deletion of Nrf2, demonstrating the Nrf2-dependency of the skewing. Analysis of Nrf2-deficient mice revealed that the physiological level of Nrf2 is sufficient to contribute to the lineage commitment. This study unequivocally shows that the Keap1-Nrf2 system regulates the cell fate determination of HSCs. DOI: 10.1111/gtc.12126 © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd
Dionisio_{July 2, 2014
July
07
Jul
2
02
2014
01:26 PM
1
01
26
PM
PDT}

Here's a hint for the 3rd way. Maybe this can help them to figure out the origin of all this stuff?
Evolution of the ribosome at atomic resolution The origins and evolution of the ribosome, 3–4 billion years ago, remain imprinted in the biochemistry of extant life and in the structure of the ribosome. Processes of ribosomal RNA (rRNA) expansion can be “observed” by comparing 3D rRNA structures of bacteria (small), yeast (medium), and metazoans (large). rRNA size correlates well with species complexity. Differences in ribosomes across species reveal that rRNA expansion segments have been added to rRNAs without perturbing the preexisting core. Here we show that rRNA growth occurs by a limited number of processes that include inserting a branch helix onto a preexisting trunk helix and elongation of a helix. rRNA expansions can leave distinctive atomic resolution fingerprints, which we call “insertion fingerprints.” Observation of insertion fingerprints in the ribosomal common core allows identification of probable ancestral expansion segments. Conceptually reversing these expansions allows extrapolation backward in time to generate models of primordial ribosomes. The approach presented here provides insight to the structure of pre-last universal common ancestor rRNAs and the subsequent expansions that shaped the peptidyl transferase center and the conserved core. We infer distinct phases of ribosomal evolution through which ribosomal particles evolve, acquiring coding and translocation, and extending and elaborating the exit tunnel. Ribosomes exist in every cell and are responsible for translation from mRNA to protein. The structure of the ribosomal common core is highly conserved in all living species, while the outer regions of the ribosome are variable. Ribosomal RNA of eukaryotes contains expansion segments accreted onto the surface of the core, which is nearly identical in structure to that in prokaryotic ribosomes. Comparing eukaryotic and prokaryotic ribosomes allows us to identify 3D insertion fingerprints of the expansion segments. Similar fingerprints allow us to analyze the common core and detect ancestral expansion segments within it. We construct a molecular model of ribosomal evolution starting from primordial biological systems near the dawn of life, culminating with relatively recent changes specific to metazoans. doi: 10.1073/pnas.1407205111
There are many questions to ask about this paper. Let's deal with this later.Dionisio_{July 2, 2014
July
07
Jul
2
02
2014
04:46 AM
4
04
46
AM
PDT}

More stuff for the 3rd way to figure out in their ool investigation
Spatial and temporal mechanisms of cell fate determination in the developing CNS The generation of neural cell diversity in the developing central nervous system relies on mechanisms that provide spatial and temporal information to neural progenitor cells. The deployment of morphogen gradients is an important strategy to impart spatial information to the field of responding cells. In this process, cells translate different concentrations of signal into the expression of distinct sets of cell fate-determining transcription factors, which determine cell fate as progenitors leave the cell cycle and differentiate into neurons. However, the mechanisms by which time regulates cell fate determination are poorly understood. http://publications.ki.se/xmlui/handle/10616/40704?locale-attribute=en
Dionisio_{July 2, 2014
July
07
Jul
2
02
2014
04:24 AM
4
04
24
AM
PDT}

how are different cell types generated at specific times and domains throughout embryonic life?
Patterning and cell fate in the inner ear: a case for Notch in the chicken embryo. The development of the inner ear provides a beautiful example of one basic problem in development, that is, to understand how different cell types are generated at specific times and domains throughout embryonic life. The functional unit of the inner ear consists of hair cells, supporting cells and neurons, all deriving from progenitor cells located in the neurosensory competent domain of the otic placode. Throughout development, the otic placode resolves into the complex inner ear labyrinth, which holds the auditory and vestibular sensory organs that are innervated in a highly specific manner. How does the early competent domain of the otic placode give rise to the diverse specialized cell types of the different sensory organs of the inner ear? We review here our current understanding on the role of Notch signaling in coupling patterning and cell fate determination during inner ear development, with a particular emphasis on contributions from the chicken embryo as a model organism. We discuss further the question of how these two processes rely on two modes of operation of the Notch signaling pathway named lateral induction and lateral inhibition. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists. Dev Growth Differ. 2013 Jan;55(1):96-112. doi: 10.1111/dgd.12016. Epub 2012 Dec 17. PMID: 23252974 [PubMed - indexed for MEDLINE]
Dionisio_{July 2, 2014
July
07
Jul
2
02
2014
04:17 AM
4
04
17
AM
PDT}

Lots of things must be right in order for the whole thing to be right. Very easy to mess things up. Very difficult for the whole thing to work well. How many interrelated functions can we detect in these mechanisms?
The candidate splicing factor Sfswap regulates growth and patterning of inner ear sensory organs. The Notch signaling pathway is thought to regulate multiple stages of inner ear development. Mutations in the Notch signaling pathway cause disruptions in the number and arrangement of hair cells and supporting cells in sensory regions of the ear. In this study we identify an insertional mutation in the mouse Sfswap gene, a putative splicing factor, that results in [...] vestibular and cochlear defects that are consistent with disrupted Notch signaling. Homozygous Sfswap mutants display hyperactivity and circling behavior consistent with vestibular defects, and significantly impaired hearing. The cochlea of newborn Sfswap mutant mice shows a significant reduction in outer hair cells and supporting cells and ectopic inner hair cells. This phenotype most closely resembles that seen in hypomorphic alleles of the Notch ligand Jagged1 (Jag1). We show that Jag1; Sfswap compound mutants have inner ear defects that are more severe than expected from simple additive effects of the single mutants, indicating a genetic interaction between Sfswap and Jag1. In addition, expression of genes involved in Notch signaling in the inner ear are reduced in Sfswap mutants. There is increased interest in how splicing affects inner ear development and function. Our work is one of the first studies to suggest that a putative splicing factor has specific effects on Notch signaling pathway members and inner ear development. PLoS Genet. 2014 Jan;10(1):e1004055. doi: 10.1371/journal.pgen.1004055. Epub 2014 Jan 2. PMID: 24391519 [PubMed - indexed for MEDLINE] PMCID: PMC3879212
Dionisio_{July 2, 2014
July
07
Jul
2
02
2014
04:11 AM
4
04
11
AM
PDT}

More stuff for the 3rd way to figure out in their ool investigation
Notch signaling during cell fate determination in the inner ear. In the inner ear, Notch signaling has been proposed to specify the sensory regions, as well as regulate the differentiation of hair cells and supporting cell within those regions. In addition, Notch plays an important role in otic neurogenesis, by determining which cells differentiate as neurons, sensory cells and non-sensory cells. Here, I review the evidence for the complex and myriad roles Notch participates in during inner ear development. A particular challenge for those studying ear development and Notch is to decipher how activation of a single pathway can lead to different outcomes within the ear, which may include changes in the intrinsic properties of the cell, Notch modulation, and potential non-canonical pathways. Copyright © 2013 Elsevier Ltd. All rights reserved. Semin Cell Dev Biol. 2013 May;24(5):470-9. doi: 10.1016/j.semcdb.2013.04.002. Epub 2013 Apr 8. PMID: 23578865 [PubMed - indexed for MEDLINE] PMCID: PMC3725958
Dionisio_{July 2, 2014
July
07
Jul
2
02
2014
04:00 AM
4
04
00
AM
PDT}

maybe the 3rd way can demonstrate how this so called 'evolutionarily conserved' mechanism originated? in the meantime, scientists will continue to investigate how this whole thing functions
The centriole is an evolutionarily conserved organelle involved in microtubule organization. Pairs of centrioles form the centrosome, which is the major microtubule-organizing center in interphase and the mitotic cells of higher animals. Centriole number is subjected to tight regulation, and aberrant centriole numbers cause genome instability and cell proliferation defects, leading to tumorigenesis and other diseases. The centriole also forms the basal body of the cilium, a microtubule-based tail-like membrane protrusion. Epithelial cells, such as those seen lining the trachea, contain many cilia on their apical surface. How are the hundreds of centrioles required for multiciliogenesis created? Zhao et al. examined multicilia formation in mouse tissues and cell lines using super-resolution three-dimensional structured illumination microscopy. Multiple centrioles were produced in ring-shaped deuterosome structures. Two related genes, Cep63 and Deup1, were important for the generation of centrioles, with Deup67 being essential for assembling the deuterosome structures required to create multiple centrioles de novo. Cep63, on the other hand, was more important for mother-centriole–based centriole duplication. Nat. Cell Biol. 15, 1434 (2013). Science 20 December 2013: Vol. 342 no. 6165 p. 1418 DOI: 10.1126/science.342.6165.1418-b Cell Biology Centriole Central Stella M. Hurtley From http://www.sciencemag.org/content/342/6165/1418.2.full
Dionisio_{June 28, 2014
June
06
Jun
28
28
2014
06:53 AM
6
06
53
AM
PDT}

More stuff for the 3rd way to figure out in their ool investigation
Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes Cytoplasmic dynein is a molecular motor that transports a large variety of cargoes (e.g., organelles, mRNAs, and viruses) along microtubules over long intracellular distances. The dynactin protein complex is important for dynein activity in vivo, but its precise role has been unclear. Here, we found that purified mammalian dynein did not move processively on microtubules in vitro. However, when dynein formed a complex with dynactin and one of four different cargo-specific adapter proteins, the motor became ultra-processive, moving for distances similar to those of native cargoes in living cells. Thus, we propose that dynein is largely inactive in the cytoplasm and that a variety of adapter proteins activate processive motility by linking dynactin to dynein only when the motor is bound to its proper cargo. Science DOI: 10.1126/science.1254198
Dionisio_{June 28, 2014
June
06
Jun
28
28
2014
01:54 AM
1
01
54
AM
PDT}

Quite a bit of info to chew and digest here:
Centrosomes Coordinate Cancer Invasion The centrosome is the main microtubule-organizing center in animal cells. In dividing cells, the centrosome mediates chromosome segregation and cytokinesis; in nondividing cells, the centrosome functions as a site for microtubule polymerization. Rac1 is a guanosine triphosphatase (GTPase) that is stimulated by microtubule polymerization and contributes to cytoskeletal reorganization associated with cellular motility. Centrosome amplification can be lethal to cells, yet, in many cancers, it is associated with progression, recurrence, and poor patient survival. [...] found that centrosome amplification was associated with Rac1 signaling–mediated invasive activity in breast epithelial cells. Inducible expression of pololike kinase 4 (PLK4) or addition of dihydrocytochalasin B triggered centrosome amplification (indicated by a green fluorescent protein–tagged centrin) in the non-transformed breast epithelial cell line MCF10A. MCF10A cells cultured in a three-dimensional (3D) matrix under either condition exhibited increased formation of protrusions compared with control cells or cells induced to overexpress a truncated PLK4 mutant that retained kinase activity. Live-cell imaging showed that the protrusions were dynamic structures that initiated tracts along which multiple cells migrated out of acini (grapelike clusters of cells). Although centrosome amplification is associated with aneuploidy, cilia formation, increased p53 abundance, and altered centrosome polarization, none of these, nor changes associated with the epithelial-mesenchymal transition were involved in this invasive phenotype triggered by induction of PLK4. However, the PLK4-overexpressing cells exhibited enhanced cell scattering and defective formation of adherens junctions on a micropatterned fibronectin substrate, indicating loss of epithelial cell-cell adhesion. GTP loading of Rac1 was increased in MCF10A cells with induced overexpression of PLK4 and centrosome amplification. Inhibitors of either Rac1 or one of its targets, the Arp2/3 actin polymerization complex, prevented adherens junction defects in the micropatterned substrate assay and protrusion formation from PLK4-overexpressing MCF10A acini in 3D culture. Adding paclitaxel, a microtubule-stabilizing agent, to 3D cultures of PLK4-overexpressing MCF10A cells decreased Rac1 activation, as did knockdown of CEP192, which promotes microtubule nucleation, which suggested that the increase in microtubule polymerization due to centrosome amplification may be triggering the increase in Rac1 activity. CEP192 knockdown also enabled proper adherens junction formation and prevented invasive acini formation in 3D cultures of PLK4-overexpressing MCF10A cells, without affecting cell viability or centrosome number. The findings indicate that centrosome amplification may be another mechanism that promotes the invasive progression of tumors. Sci. Signal., 10 June 2014 Vol. 7, Issue 329, p. ec156 [DOI: 10.1126/scisignal.2005581] Science Signaling, AAAS, Washington, DC 20005, USA
Dionisio_{June 28, 2014
June
06
Jun
28
28
2014
01:44 AM
1
01
44
AM
PDT}

The 3rd. way may want to include this case in their pursue of the ultimate 'ool' explanation, while scientists continue to investigate how this develops and functions.
Genomic basis for the convergent evolution of electric organs Little is known about the genetic basis of convergent traits that originate repeatedly over broad taxonomic scales. The myogenic electric organ has evolved six times in fishes to produce electric fields used in communication, navigation, predation, or defense. We have examined the genomic basis of the convergent anatomical and physiological origins of these organs by assembling the genome of the electric eel (Electrophorus electricus) and sequencing electric organ and skeletal muscle transcriptomes from three lineages that have independently evolved electric organs. Our results indicate that, despite millions of years of evolution and large differences in the morphology of electric organ cells, independent lineages have leveraged similar transcription factors and developmental and cellular pathways in the evolution of electric organs. Science 27 June 2014: Vol. 344 no. 6191 pp. 1522-1525 DOI: 10.1126/science.1254432 •Report
Dionisio_{June 28, 2014
June
06
Jun
28
28
2014
01:09 AM
1
01
09
AM
PDT}

Lipid landscapes and pipelines in membrane homeostasis The lipid composition of cellular organelles is tailored to suit their specialized tasks. A fundamental transition in the lipid landscape divides the secretory pathway in early and late membrane territories, allowing an adaptation from biogenic to barrier functions. Defending the contrasting features of these territories against erosion by vesicular traffic poses a major logistical problem. To this end, cells evolved a network of lipid composition sensors and pipelines along which lipids are moved by non-vesicular mechanisms. We review recent insights into the molecular basis of this regulatory network and consider examples in which malfunction of its components leads to system failure and disease. Nature 510, 48–57 (05 June 2014) doi:10.1038/nature13474 Published online 04 June 2014
Evolved? How?Dionisio_{June 26, 2014
June
06
Jun
26
26
2014
11:17 PM
11
11
17
PM
PDT}

Transcriptional regulation in development http://www.cell-symposia-transcriptional-regulation.com/conference-program/
Dionisio_{June 24, 2014
June
06
Jun
24
24
2014
05:38 PM
5
05
38
PM
PDT}

Stem cell energetics
Growing evidence shows that cellular metabolism underlies stem cell fate, including pluripotency, differentiation and reprogramming. In addition to generating ATP, through oxidative phosphorylation, mitochondrial metabolism provides the building blocks to support biomass, such as amino acid and lipids, and is involved in cell signaling in determining stem cell fate. Altered stem cell metabolism has been implicated in aging and diseases, such as cancer, and serves as a potential target for therapeutic intervention. http://www.cell-symposia-stem-cell-energetics.com/
Dionisio_{June 24, 2014
June
06
Jun
24
24
2014
05:34 PM
5
05
34
PM
PDT}

A CULLINary ride across the secretory pathway: more than just secretion Mulitmeric cullin-RING ubiquitin ligases (CRLs) represent the largest class of ubiquitin ligases in eukaryotes. However, most CRL ubiquitylation pathways remain uncharacterized. CRLs control a myriad of functions by catalyzing mono- or poly-ubiquitylation of target proteins. Recently, novel CRLs have been identified along the secretory pathway where they modify substrates involved in diverse cellular processes such as vesicle coat assembly and cell cycle progression. This review discusses our current understanding of CRL ubiquitylation within the secretory pathway, with special emphasis on the emerging role of the Golgi as a ubiquitylation platform. CRLs are also implicated in endosome function, where their specific roles are less well understood. DOI: http://dx.doi.org/10.1016/j.tcb.2014.02.001
Dionisio_{June 24, 2014
June
06
Jun
24
24
2014
05:25 PM
5
05
25
PM
PDT}

Prev 1 … 37 38 39 40 41 … 43 Next

You must be logged in to post a comment.

Leave a Reply