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

Protein choreography? How are they put together for different functional situations?
Correlated motions are a fundamental property of ?-sheets Nature Communications 5, Article number: 4070 doi:10.1038/ncomms5070 Published 11 June 2014 Correlated motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery. The mechanisms that underlie these processes remain largely unknown due mainly to limitations in their direct detection. Here, based on a detailed analysis of protein structures deposited in the protein data bank, as well as on state-of-the art molecular simulations, we provide general evidence for the transfer of structural information by correlated backbone motions, mediated by hydrogen bonds, across ?-sheets. We also show that the observed local and long-range correlated motions are mediated by the collective motions of ?-sheets and investigate their role in large-scale conformational changes. Correlated motions represent a fundamental property of ?-sheets that contributes to protein function.
Dionisio_{June 12, 2014
June
06
Jun
12
12
2014
02:38 PM
2
02
38
PM
PDT}

protein choreography ? This is not about the physical and chemical properties of the individual proteins, not even about the physical or chemical properties that allow the interactions between proteins, because those properties are the same in all choreographies. The question is mainly about their specific coordinated arrangements in space and time, which are different for separate choreographies, so that all things work together to produce the observed specific effects. What steps would it take to put together each of those choreographies? As analogy, the same ballet dancers can appear in different scenes, and also in different ballet choreographies. The same orchestra, with the same musicians playing on the same instruments, and directed by the same conductor, can produce totally different ballet choreographies.
The team of scientists have discovered how the motions of various parts of proteins, although physically far apart, are correlated. “The same thing happens to proteins as happens to the choreography of ballet dancers, where the movements of the participants are interconnected in spite of being physically apart. If the first one lifts an arm, the last one lifts an arm too,” described the researcher. http://www.dddmag.com/news/2014/06/scientists’-findings-may-revolutionize-drug-discovery?et_cid=3992150&et_rid=653535995&type=cta
Dionisio_{June 12, 2014
June
06
Jun
12
12
2014
02:30 PM
2
02
30
PM
PDT}

Can the 3rd. way explain the origin of all these mechanisms, while scientists keep trying to understand what they do and how they function?
Cyclin B2 and p53 control proper timing of centrosome separation Nature Cell Biology 16, 538–549 (2014) doi:10.1038/ncb2952 Published online 28 April 2014 Cyclins B1 and B2 are frequently elevated in human cancers and are associated with tumour aggressiveness and poor clinical outcome; however, whether and how B-type cyclins drive tumorigenesis is unknown. Here we show that cyclin B1 and B2 transgenic mice are highly prone to tumours, including tumour types where B-type cyclins serve as prognosticators. Cyclins B1 and B2 both induce aneuploidy when overexpressed but through distinct mechanisms, with cyclin B1 inhibiting separase activation, leading to anaphase bridges, and cyclin B2 triggering aurora-A-mediated Plk1 hyperactivation, resulting in accelerated centrosome separation and lagging chromosomes. Complementary experiments revealed that cyclin B2 and p53 act antagonistically to control aurora-A-mediated centrosome splitting and accurate chromosome segregation in normal cells. These data demonstrate a causative link between B-type cyclin overexpression and tumour pathophysiology, and uncover previously unknown functions of cyclin B2 and p53 in centrosome separation that may be perturbed in many human cancers.
Dionisio_{June 12, 2014
June
06
Jun
12
12
2014
02:45 AM
2
02
45
AM
PDT}

The 3rd. way may want to explain the origin of this, while scientists try to understand it well:
The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival NEK2 is a serine/threonine kinase that promotes centrosome splitting and ensures correct chromosome segregation during the G2/M phase of the cell cycle, through phosphorylation of specific substrates. Aberrant expression and activity of NEK2 in cancer cells lead to dysregulation of the centrosome cycle and aneuploidy. Thus, a tight regulation of NEK2 function is needed during cell cycle progression. In this study, we found that NEK2 localizes in the nucleus of cancer cells derived from several tissues. In particular, NEK2 co-localizes in splicing speckles with SRSF1 and SRSF2. Moreover, NEK2 interacts with several splicing factors and phosphorylates some of them, including the oncogenic SRSF1 protein. Overexpression of NEK2 induces phosphorylation of endogenous SR proteins and affects the splicing activity of SRSF1 toward reporter minigenes and endogenous targets, independently of SRPK1. Conversely, knockdown of NEK2, like that of SRSF1, induces expression of pro-apoptotic variants from SRSF1-target genes and sensitizes cells to apoptosis. Our results identify NEK2 as a novel splicing factor kinase and suggest that part of its oncogenic activity may be ascribed to its ability to modulate alternative splicing, a key step in gene expression regulation that is frequently altered in cancer cells. http://nar.oxfordjournals.org/content/early/2013/12/24/nar.gkt1307.full
Dionisio_{June 10, 2014
June
06
Jun
10
10
2014
07:57 PM
7
07
57
PM
PDT}

Hey, they're getting close, almost there. Just a few more things and bingo! they'll have all the missing pieces in the biological puzzle. Then finally, the 3rd. way will have it very easy to explain how this all started. But let's take it easy, no rush, 'poco a poco'. In the meantime, let the scientists continue their research.
Neural Correlates of Feedback Processing in Toddlers External feedback provides essential information for successful learning. Feedback is especially important for learning in early childhood, as toddlers strongly rely on external signals to determine the consequences of their actions. In adults, many electrophysiological studies have elucidated feedback processes using a neural marker called the feedback-related negativity (FRN). The neural generator of the FRN is assumed to be the ACC, located in medial frontal cortex. As frontal brain regions are the latest to mature during brain development, it is unclear when in early childhood a functional feedback system develops. Is feedback differentiated on a neural level in toddlers and in how far is neural feedback processing related to children's behavioral adjustment? In an EEG experiment, we addressed these questions by measuring the brain activity and behavioral performance of 2.5-year-old toddlers while they played a feedback-guided game on a touchscreen. Electrophysiological results show differential brain activity for feedback with a more negative deflection for incorrect than correct outcomes, resembling the adult FRN. This provides the first neural evidence for feedback processing in toddlers. Notably, FRN amplitudes were predictive of adaptive behavior: the stronger the differential brain activity for feedback, the better the toddlers' adaptive performance during the game. Thus, already in early childhood toddlers' feedback-guided performance directly relates to the functionality of their neural feedback processing. Implications for early feedback-based learning as well as structural and functional brain development are discussed. Journal of Cognitive Neuroscience July 2014, Vol. 26, No. 7, Pages 1519-1527 Posted Online May 29, 2014. (doi:10.1162/jocn_a_00560) © 2014 Massachusetts Institute of Technology
Dionisio_{June 10, 2014
June
06
Jun
10
10
2014
06:15 PM
6
06
15
PM
PDT}

Another simple neuroscience case. Maybe the 3rd. way can explain the origin of this, while scientists continue to research the mechanisms behind the functionality of all this stuff?
Medial-lateral Organization of the Orbitofrontal Cortex Emerging evidence suggests that specific cognitive functions localize to different subregions of OFC, but the nature of these functional distinctions remains unclear. One prominent theory, derived from human neuroimaging, proposes that different stimulus valences are processed in separate orbital regions, with medial and lateral OFC processing positive and negative stimuli, respectively. Thus far, neurophysiology data have not supported this theory. We attempted to reconcile these accounts by recording neural activity from the full medial-lateral extent of the orbital surface in monkeys receiving rewards and punishments via gain or loss of secondary reinforcement. We found no convincing evidence for valence selectivity in any orbital region. Instead, we report differences between neurons in central OFC and those on the inferior-lateral orbital convexity, in that they encoded different sources of value information provided by the behavioral task. Neurons in inferior convexity encoded the value of external stimuli, whereas those in OFC encoded value information derived from the structure of the behavioral task. We interpret these results in light of recent theories of OFC function and propose that these distinctions, not valence selectivity, may shed light on a fundamental organizing principle for value processing in orbital cortex. Journal of Cognitive Neuroscience July 2014, Vol. 26, No. 7, Pages 1347-1362 Posted Online May 29, 2014. (doi:10.1162/jocn_a_00573) © 2014 Massachusetts Institute of Technology
Dionisio_{June 10, 2014
June
06
Jun
10
10
2014
02:52 PM
2
02
52
PM
PDT}

The 3rd. Way shouldn't run out of work, even if all they will do is try to explain the origin of the biological systems, while the scientists try to understand better how those systems function. Here's an easy one to start from:
Different Neural Networks Are Involved in Audiovisual Speech Perception Depending on the Context How are we able to easily and accurately recognize speech sounds despite the lack of acoustic invariance? One proposed solution is the existence of a neural representation of speech syllable perception that transcends its sensory properties. In the present fMRI study, we used two different audiovisual speech contexts both intended to identify brain areas whose levels of activation would be conditioned by the speech percept independent from its sensory source information. We exploited McGurk audiovisual fusion to obtain short oddball sequences of syllables that were either (a) acoustically different but perceived as similar or (b) acoustically identical but perceived as different. We reasoned that, if there is a single network of brain areas representing abstract speech perception, this network would show a reduction of activity when presented with syllables that are acoustically different but perceived as similar and an increase in activity when presented with syllables that are acoustically similar but perceived as distinct. Consistent with the long-standing idea that speech production areas may be involved in speech perception, we found that frontal areas were part of the neural network that showed reduced activity for sequences of perceptually similar syllables. Another network was revealed, however, when focusing on areas that exhibited increased activity for perceptually different but acoustically identical syllables. This alternative network included auditory areas but no left frontal activations. In addition, our findings point to the importance of subcortical structures much less often considered when addressing issues pertaining to perceptual representations. Journal of Cognitive Neuroscience July 2014, Vol. 26, No. 7, Pages 1572-1586 Posted Online May 29, 2014. (doi:10.1162/jocn_a_00565) © 2014 Massachusetts Institute of Technology
Dionisio_{June 10, 2014
June
06
Jun
10
10
2014
02:35 PM
2
02
35
PM
PDT}

To the 3rd. way: where did these mechanisms come from? How? To the researchers: how do these mechanisms work?
gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size Nature Communications 5, Article number: 3885 doi:10.1038/ncomms4885 Published 30 May 2014 Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly.
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
10:41 PM
10
10
41
PM
PDT}

While scientists try to understand this mystery, the 3rd. Way could try to explain the origin of the mysterious mechanisms.
Where Have All the Mitochondria Gone? It’s common knowledge that all organisms inherit their mitochondria—the cell’s “power plants”—from their mothers. But what happens to all the father’s mitochondria? Surprisingly, how—and why—paternal mitochondria are prevented from getting passed on to their offspring after fertilization is still shrouded in mystery; the only thing that’s certain is that there must be a compelling reason, seeing as this phenomenon has been conserved throughout evolution. Now, Dr. Eli Arama and a team in the Weizmann Institute’s Molecular Genetics Department have discovered special cellular vesicles that originate in the female fruit flies’ egg and which actively seek out and destroy the father’s mitochondria upon fertilization. http://www.biosciencetechnology.com/videos/2014/05/where-have-all-mitochondria-gone
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
10:01 PM
10
10
01
PM
PDT}

While scientists try to understand these complex mechanisms, the 3rd. way folks could try to explain the origin of those mechanisms.
Homeostatic control of polo-like kinase-1 engenders non-genetic heterogeneity in G2 checkpoint fidelity and timing Hongqing Liang, Nature Communications 5, Article number: 4048 doi:10.1038/ncomms5048 Published 04 June 2014 The G2 checkpoint monitors DNA damage, preventing mitotic entry until the damage can be resolved. The mechanisms controlling checkpoint recovery are unclear. Here, we identify non-genetic heterogeneity in the fidelity and timing of damage-induced G2 checkpoint enforcement in individual cells from the same population. Single-cell fluorescence imaging reveals that individual damaged cells experience varying durations of G2 arrest, and recover with varying levels of remaining checkpoint signal or DNA damage. A gating mechanism dependent on polo-like kinase-1 (PLK1) activity underlies this heterogeneity. PLK1 activity continually accumulates from initial levels in G2-arrested cells, at a rate inversely correlated to checkpoint activation, until it reaches a threshold allowing mitotic entry regardless of remaining checkpoint signal or DNA damage. Thus, homeostatic control of PLK1 by the dynamic opposition between checkpoint signalling and pro-mitotic activities heterogeneously enforces the G2 checkpoint in each individual cell, with implications for cancer pathogenesis and therapy.
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
09:23 PM
9
09
23
PM
PDT}

recent email to The 3rd. Way:
Sent: ?Thu, ?Jun? ?5?, ?2014 at ?5?:?53? ?AM To: mail@thethirdwayofevolution.com Subject: FYI- Your 3rd. Way is a discussion topic in the UD blog. Hello! Your initiative seems very interesting. FYI- Your 3rd. Way is a discussion topic in this blog: https://uncommondescent.com/evolution/a-third-way-of-evolution/#comment-502812 I want to share with you several comments I have posted in that particular discussion thread. However, the thread about your new blog does not seem like attracting as much attention (visitors) as other topics in the same blog. The majority of the comments in that thread have been mine. At this point I'm more interested in learning how certain biological systems work, not how they originated. But it's interesting to look at the origin discussion from the side, at least from time to time. Kind regards.
My enormous science-related ignorance compels me to respect the members of The Third Way and recognize their tremendous scientific knowledge and academic experience. Seriously would like to read their opinions within the ongoing 'origin' debate. However, I'm more interested in learning about the way certain biological systems function in their current state, not how they originated. I strongly believe science should focus in on trying to understand very well how biological systems work, so better medical treatments and preventive programs can be developed and implemented soon. Can the 'origin' discussion produce comparable benefits? Fortunately, most scientists are busy working on interesting research projects that should discover more details about the wonderful biological systems.Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
06:44 PM
6
06
44
PM
PDT}

Can the 3rd. Way explain the origin of the 'right' route(s) to bipolarity and the rest of these mechanisms? In the meantime, scientists could work on trying to understand how they work and what could mess them up.
Mitotic spindle multipolarity without centrosome amplification Nature Cell Biology 16, 386–394 (2014) doi:10.1038/ncb2958 Published online 02 May 2014 Mitotic spindle bipolarity is essential for faithful segregation of chromosomes during cell division. Multipolar spindles are often seen in human cancers and are usually associated with supernumerary centrosomes that result from centrosome over-duplication or cytokinesis failure. A less-understood path to multipolar spindle formation may arise due to loss of spindle pole integrity in response to spindle and/or chromosomal forces. Here we discuss the different routes leading to multipolar spindle formation, focusing on spindle multipolarity without centrosome amplification. We also present the distinct and common features between these pathways and discuss their therapeutic implications.
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
04:36 PM
4
04
36
PM
PDT}

Can the 3rd. Way figure out how to explain the origin of these mechanisms, while scientists try to understand their effect and how they work?
Cargo recognition and trafficking in selective autophagy Nature Cell Biology 16, 495–501 (2014) doi:10.1038/ncb2979 Published online 30 May 2014 Selective autophagy is a quality control pathway through which cellular components are sequestered into double-membrane vesicles and delivered to specific intracellular compartments. This process requires autophagy receptors that link cargo to growing autophagosomal membranes. Selective autophagy is also implicated in various membrane trafficking events. Here we discuss the current view on how cargo selection and transport are achieved during selective autophagy, and point out molecular mechanisms that are congruent between autophagy and vesicle trafficking pathways.
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
04:04 PM
4
04
04
PM
PDT}

Can the 3rd. Way explain the origin of these mechanisms? In the meantime, scientists can work hard on trying to understand how these mechanisms work.
The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification Nature Cell Biology 16, 516–528 (2014) doi:10.1038/ncb2965 Published online 25 May 2014 The precise relationship of embryonic stem cells (ESCs) to cells in the mouse embryo remains controversial. We present transcriptional and functional data to identify the embryonic counterpart of ESCs. Marker profiling shows that ESCs are distinct from early inner cell mass (ICM) and closely resemble pre-implantation epiblast. A characteristic feature of mouse ESCs is propagation without ERK signalling. Single-cell culture reveals that cell-autonomous capacity to thrive when the ERK pathway is inhibited arises late during blastocyst development and is lost after implantation. The frequency of deriving clonal ESC lines suggests that all E4.5 epiblast cells can become ESCs. We further show that ICM cells from early blastocysts can progress to ERK independence if provided with a specific laminin substrate. These findings suggest that formation of the epiblast coincides with competence for ERK-independent self-renewal in vitro and consequent propagation as ESC lines.
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
12:07 PM
12
12
07
PM
PDT}

The 3rd. Way may try to explain the origin of this, while scientists try to understand how this works. The latter is what may help for medical advance, hence research should focus in on that area.
A centrosomal route for cancer genome instability Nature Cell Biology 16, 504–506 (2014) doi:10.1038/ncb2978 Published online 30 May 2014 Despite the widespread occurrence of aneuploidy in cancer cells, the molecular causes for chromosomal instability are not well established. Cyclin B2 is now shown to control a pathway — involving the centrosomal kinases aurora A and Plk1 and the tumour suppressor p53 — the alteration of which causes defective centrosome separation, aneuploidy and tumour development.
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
03:44 AM
3
03
44
AM
PDT}

The 3rd. Way may try to explain the origin of this, while scientists try to understand how this works. Is the latter by far more important for medical advance? Is the former just to fuel the ongoing philosophical debates?
Somatic Guidance for the Oocyte DOI: http://dx.doi.org/10.1016/j.devcel.2013.12.006 The capacity of oocytes to support embryo development and a healthy pregnancy is dependent on complex and poorly understood interactions with the somatic cells that enclose it during its development.
Dionisio_{June 9, 2014
June
06
Jun
9
09
2014
03:28 AM
3
03
28
AM
PDT}

Can the 3rd. way explain the origin of this, while scientists try to understand how it works?
Synergy between Multiple Microtubule-Generating Pathways Confers Robustness to Centrosome-Driven Mitotic Spindle Formation DOI: http://dx.doi.org/10.1016/j.devcel.2013.12.001 •Chromosome-driven MT generation exists in embryos and is dependent on D-HURP •Centrosome disruption results in cytoplasmic aMTOCs, driving spindle formation •Augmin generates MTs from centrosomal, chromatin, and aMTOC MTs indiscriminately •Reducing one pathway synergistically increases MT growth of the remaining pathways The mitotic spindle is defined by its organized, bipolar mass of microtubules, which drive chromosome alignment and segregation. Although different cells have been shown to use different molecular pathways to generate the microtubules required for spindle formation, how these pathways are coordinated within a single cell is poorly understood. We have tested the limits within which the Drosophila embryonic spindle forms, disrupting the inherent temporal control that overlays mitotic microtubule generation, interfering with the molecular mechanism that generates new microtubules from preexisting ones, and disrupting the spatial relationship between microtubule nucleation and the usually dominant centrosome. Our work uncovers the possible routes to spindle formation in embryos and establishes the central role of Augmin in all microtubule-generating pathways. It also demonstrates that the contributions of each pathway to spindle formation are integrated, highlighting the remarkable flexibility with which cells can respond to perturbations that limit their capacity to generate microtubules.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
08:26 PM
8
08
26
PM
PDT}

Can the 3rd. way explain the origin of this, while scientists try to understand how it works? Piece of cake, isn't it?
APCCdc20 Suppresses Apoptosis through Targeting Bim for Ubiquitination and Destruction DOI: http://dx.doi.org/10.1016/j.devcel.2014.04.022 •Bim expression is repressed during M phase of cell cycle, when Cdc20 is most active •Cdc20 promotes Bim ubiquitination and destruction in a D-box-dependent manner •Hyperactivation of Cdc20 by paclitaxel confers chemoresistance via Bim destruction •Cdc20 knockdown sensitizes cancer cells to chemoradiation via Bim accumulation Anaphase-promoting complex Cdc20 (APCCdc20) plays pivotal roles in governing mitotic progression. By suppressing APCCdc20, antimitotic agents activate the spindle-assembly checkpoint and induce apoptosis after prolonged treatment, whereas depleting endogenous Cdc20 suppresses tumorigenesis in part by triggering mitotic arrest and subsequent apoptosis. However, the molecular mechanism(s) underlying apoptosis induced by Cdc20 abrogation remains poorly understood. Here, we report the BH3-only proapoptotic protein Bim as an APCCdc20 target, such that depletion of Cdc20 sensitizes cells to apoptotic stimuli. Strikingly, Cdc20 and multiple APC-core components were identified in a small interfering RNA screen that, upon knockdown, sensitizes otherwise resistant cancer cells to chemoradiation in a Bim-dependent manner. Consistently, human adult T cell leukemia cells that acquire elevated APCCdc20 activity via expressing the Tax viral oncoprotein exhibit reduced Bim levels and resistance to anticancer agents. These results reveal an important role for APCCdc20 in governing apoptosis, strengthening the rationale for developing specific Cdc20 inhibitors as effective anticancer agents.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
06:32 PM
6
06
32
PM
PDT}

Can the 3rd. way explain the origin of this?
Developmental Regulation of Microtubule Dynamics DOI: http://dx.doi.org/10.1016/j.devcel.2014.03.007 •MT dynamics can be followed throughout differentiation in situ •MT dynamics are regulated stepwise over the course of differentiation •Distinct MAPs are required for tissue biogenesis and tissue function •Selective MT dynamics are required in proliferative versus differentiated cells Microtubules (MTs) are cytoskeletal polymers that undergo dynamic instability, the stochastic transition between growth and shrinkage phases. MT dynamics are required for diverse cellular processes and, while intrinsic to tubulin, are highly regulated. However, little is known about how MT dynamics facilitate or are regulated by tissue biogenesis and differentiation. We imaged MT dynamics in a smooth muscle-like lineage in intact developing Caenorhabditis elegans. All aspects of MT dynamics change significantly as stem-like precursors exit mitosis and, secondarily, as they differentiate. We found that suppression, but not enhancement, of dynamics perturbs differentiated muscle function in vivo. Distinct ensembles of MT-associated proteins are specifically required for tissue biogenesis versus tissue function. A CLASP family MT stabilizer and the depolymerizing kinesin MCAK are differentially required for MT dynamics in the precursor or differentiated cells, respectively. All of these multidimensional phenotypic comparisons were facilitated by a data display method called the diamond graph.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
06:46 AM
6
06
46
AM
PDT}

Can the 3rd. Way explain the origin of this, while scientists try to understand how this actually works?
A Microtubule-Associated Zinc Finger Protein, BuGZ, Regulates Mitotic Chromosome Alignment by Ensuring Bub3 Stability and Kinetochore Targeting DOI: http://dx.doi.org/10.1016/j.devcel.2013.12.013 •BuGZ regulates kinetochore-microtubule interaction via Bub3 •BuGZ and Bub3 form a complex of equal stoichiometry •BuGZ uses its GLEBS motif to bind and stabilize Bub3 •The microtubule-binding domain of BuGZ facilitates Bub3 loading onto kinetochores Equal chromosome segregation requires proper assembly of many proteins, including Bub3, onto kinetochores to promote kinetochore-microtubule interactions. By screening for mitotic regulators in the spindle envelope and matrix (Spemix), we identify a conserved Bub3 interacting and GLE-2-binding sequence (GLEBS) containing ZNF207 (BuGZ) that associates with spindle microtubules and regulates chromosome alignment. Using its conserved GLEBS, BuGZ directly binds and stabilizes Bub3. BuGZ also uses its microtubule-binding domain to enhance the loading of Bub3 to kinetochores that have assumed initial interactions with microtubules in prometaphase. This enhanced Bub3 loading is required for proper chromosome alignment and metaphase to anaphase progression. Interestingly, we show that microtubules are required for the highest kinetochore loading of Bub3, BubR1, and CENP-E during prometaphase. These findings suggest that BuGZ not only serves as a molecular chaperone for Bub3 but also enhances its loading onto kinetochores during prometaphase in a microtubule-dependent manner to promote chromosome alignment.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
06:31 AM
6
06
31
AM
PDT}

Can the third way explain the origin of this?
BuGZ Is Required for Bub3 Stability, Bub1 Kinetochore Function, and Chromosome Alignment DOI: http://dx.doi.org/10.1016/j.devcel.2013.12.014 •BuGZ is a kinetochore protein that binds to and stabilizes Bub3 •BuGZ localizes to the kinetochore and binds to Bub3 through a conserved GLEBS domain •BuGZ depletion in transformed cells results in severe chromosome alignment defects •Inhibiting Bub3’s GLEBS domain interactions may be a therapeutic strategy for GBM Summary During mitosis, the spindle assembly checkpoint (SAC) monitors the attachment of kinetochores (KTs) to the plus ends of spindle microtubules (MTs) and prevents anaphase onset until chromosomes are aligned and KTs are under proper tension. Here, we identify a SAC component, BuGZ/ZNF207, from an RNAi viability screen in human glioblastoma multiforme (GBM) brain tumor stem cells. BuGZ binds to and stabilizes Bub3 during interphase and mitosis through a highly conserved GLE2p-binding sequence (GLEBS) domain. Inhibition of BuGZ results in loss of both Bub3 and its binding partner Bub1 from KTs, reduction of Bub1-dependent phosphorylation of centromeric histone H2A, attenuation of KT-based Aurora B kinase activity, and lethal chromosome congression defects in cancer cells. Phylogenetic analysis indicates that BuGZ orthologs are highly conserved among eukaryotes, but are conspicuously absent from budding and fission yeasts. These findings suggest that BuGZ has evolved to facilitate Bub3 activity and chromosome congression in higher eukaryotes.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
05:16 AM
5
05
16
AM
PDT}

Can the 3rd. way explain the origin of this?
A Protective Chaperone for the Kinetochore Adaptor Bub3 Zhejian Ji, Hongtao Yu DOI: http://dx.doi.org/10.1016/j.devcel.2014.01.024 two complementary studies by Jiang et al. (2014) and Toledo et al. (2014) identify BuGZ as an interacting protein of the kinetochore adaptor Bub3 and show that it promotes the stabilization and kinetochore loading of Bub3, chromosome alignment, and mitotic progression.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
05:11 AM
5
05
11
AM
PDT}

Can the 3rd. Way explain the origin of this? [although science is busy trying to understand just how this works]
Rab11 Endosomes Contribute to Mitotic Spindle Organization and Orientation Heidi Hehnly, Stephen Doxsey DOI: http://dx.doi.org/10.1016/j.devcel.2014.01.014 Highlights •Endosomes are not rendered inactive during mitosis as previously envisioned •Endosomes are MT-nucleating, MT-anchoring, and spindle pole material carriers •Rab11 regulates mitotic progression and spindle symmetry •Rab11 activity regulates astral microtubule organization Summary During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo. However, little is known about Rab11 endosomes in mitosis. Here, we show that Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at poles. We found that mitotic recycling endosomes bind ?-TuRC components and associate with tubulin in vitro. Rab11 depletion or dominant-negative Rab11 expression disrupts astral microtubules, delays mitosis, and redistributes spindle pole proteins. Reciprocally, constitutively active Rab11 increases astral microtubules, restores ?-tubulin spindle pole localization, and generates robust spindles. This suggests a role for Rab11 activity in spindle pole maturation during mitosis. Rab11 depletion causes misorientation of the mitotic spindle and the plane of cell division. These findings suggest a molecular mechanism for the organization of astral microtubules and the mitotic spindle through Rab11-dependent control of spindle pole assembly and function. We propose that Rab11 and its associated endosomes contribute to these processes through retrograde transport to poles by dynein.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
05:06 AM
5
05
06
AM
PDT}

Can the 3rd. Way explain the origin of this?
Spindlegate: The Biological Consequences of Disrupting Traffic Megan M. Gnazzo, Ahna R. Skop DOI: http://dx.doi.org/10.1016/j.devcel.2014.02.014 The function of membrane trafficking during mitosis has become the focus of increasing interest. In this issue of Developmental Cell, Hehnly and Doxsey (2014) provide new insight into the role that endosomes play during spindle assembly.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
04:55 AM
4
04
55
AM
PDT}

Can the 3rd. way folks explain the origin of this?
Asymmetric Friction of Nonmotor MAPs Can Lead to Their Directional Motion in Active Microtubule Networks Scott Forth, Kuo-Chiang Hsia, Yuta Shimamoto, Tarun M. Kapoor DOI: http://dx.doi.org/10.1016/j.cell.2014.02.018 Highlights •Motion along microtubules of non-motor proteins generates friction •Magnitudes of frictional force differ for three proteins needed for cell division •Frictional forces can be anisotropic with respect to filament polarity •Asymmetric friction can lead to motion of proteins in active microtubule networks Summary Diverse cellular processes require microtubules to be organized into distinct structures, such as asters or bundles. Within these dynamic motifs, microtubule-associated proteins (MAPs) are frequently under load, but how force modulates these proteins’ function is poorly understood. Here, we combine optical trapping with TIRF-based microscopy to measure the force dependence of microtubule interaction for three nonmotor MAPs (NuMA, PRC1, and EB1) required for cell division. We find that frictional forces increase nonlinearly with MAP velocity across microtubules and depend on filament polarity, with NuMA’s friction being lower when moving toward minus ends, EB1’s lower toward plus ends, and PRC1's exhibiting no directional preference. Mathematical models predict, and experiments confirm, that MAPs with asymmetric friction can move directionally within actively moving microtubule pairs they crosslink. Our findings reveal how non-motor MAPs can generate frictional resistance in dynamic cytoskeletal networks via micromechanical adaptations whose anisotropy may be optimized for MAP localization and function within cellular structures.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
04:30 AM
4
04
30
AM
PDT}

Maybe the 'third way' group can figure out the origin of this?
Friction on MAP Determines Its Traveling Direction on Microtubules Sadanori Watanabe, Gohta Goshima DOI: http://dx.doi.org/10.1016/j.devcel.2014.03.022 Microtubule networks generate various forces, and the forces are applied to microtubule-associated proteins (MAPs). Forth et al. (2014) show in a recent issue of Cell that asymmetric frictional force between MAPs and microtubules leads to directional movement of MAPs along microtubules, providing insight into the mechanism of microtubule network self-organization.
Dionisio_{June 8, 2014
June
06
Jun
8
08
2014
04:20 AM
4
04
20
AM
PDT}

Another task for the 3rd way: find the origin of this:
Exploring the Function of Cell Shape and Size during Mitosis Clotilde Cadart 3, Ewa Zlotek-Zlotkiewicz 3, Maël Le Berre, Matthieu Piel, Helen K. Matthews 3Co-first author DOI: http://dx.doi.org/10.1016/j.devcel.2014.04.009 Dividing cells almost always adopt a spherical shape. This is true of most eukaryotic cells lacking a rigid cell wall and is observed in tissue culture and single-celled organisms, as well as in cells dividing inside tissues. While the mechanisms underlying this shape change are now well described, the functional importance of the spherical mitotic cell for the success of cell division has been thus far scarcely addressed. Here we discuss how mitotic rounding contributes to spindle assembly and positioning, as well as the potential consequences of abnormal mitotic cell shape and size on chromosome segregation, tissue growth, and cancer.
Dionisio_{June 7, 2014
June
06
Jun
7
07
2014
09:35 PM
9
09
35
PM
PDT}

Another question for The Third Way: where did this come from?
Genome Stress Response in Early Development William F. Marzluff, Robert J. Duronio DOI: http://dx.doi.org/10.1016/j.devcel.2014.05.010 Cells with irreparable genomic damage pose a problem for development and must be eliminated to prevent disease. Reporting in this issue of Developmental Cell, Iampietro et al. (2014) describe a mechanism in Drosophila that removes damaged nuclei from syncytial blastoderm embryos via DNA damage checkpoint kinase-mediated retention of specific mRNAs within the nucleus.
Dionisio_{June 7, 2014
June
06
Jun
7
07
2014
08:18 PM
8
08
18
PM
PDT}

More questions for the 3rd. Way folks about origin: how did all this start?
Cell fate can be controlled through asymmetric division and segregation of protein determinants, but the regulation of this process in the hematopoietic system is poorly understood. Here we show that the dynein-binding protein Lis1 is critically required for hematopoietic stem cell function and leukemogenesis. Conditional deletion of Lis1 (also known as Pafah1b1) in the hematopoietic system led to a severe bloodless phenotype, depletion of the stem cell pool and embryonic lethality. Further, real-time imaging revealed that loss of Lis1 caused defects in spindle positioning and inheritance of cell fate determinants, triggering accelerated differentiation. Finally, deletion of Lis1 blocked the propagation of myeloid leukemia and led to a marked improvement in survival, suggesting that Lis1 is also required for oncogenic growth. These data identify a key role for Lis1 in hematopoietic stem cells and mark its directed control of asymmetric division as a critical regulator of normal and malignant hematopoietic development. From http://www.nature.com/ng/journal/v46/n3/full/ng.2889.html
Dionisio_{June 6, 2014
June
06
Jun
6
06
2014
08:34 PM
8
08
34
PM
PDT}

What's the origin of these mechanisms?
Structural basis for the inhibition of Polo-like kinase 1 Nature Structural & Molecular Biology 20, 1047–1053 (2013) doi:10.1038/nsmb.2623 Received 13 December 2012 Accepted 30 May 2013 Published online 28 July 2013 Polo-like kinase 1 (PLK1) is a master regulator of mitosis and is considered a potential drug target for cancer therapy. PLK1 is characterized by an N-terminal kinase domain (KD) and a C-terminal Polo-box domain (PBD). The KD and PBD are mutually inhibited, but the molecular mechanisms of the autoinhibition remain unclear. Here we report the 2.3-Å crystal structure of the complex of the Danio rerio KD and PBD together with a PBD-binding motif of Drosophila melanogaster microtubule-associated protein 205 (Map205PBM). The structure reveals that the PBD binds and rigidifies the hinge region of the KD in a distinct conformation from that of the phosphopeptide-bound PBD. This structure provides a framework for understanding the autoinhibitory mechanisms of PLK1 and also sheds light on the activation mechanisms of PLK1 by phosphorylation or phosphopeptide binding. http://www.nature.com/nsmb/journal/v20/n9/full/nsmb.2623.html
Dionisio_{June 5, 2014
June
06
Jun
5
05
2014
10:55 PM
10
10
55
PM
PDT}

Prev 1 … 40 41 42 43 Next

You must be logged in to post a comment.

Leave a Reply