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Mystery at the heart of life

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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Classic and novel stem cell niches in brain homeostasis and repair Ruihe Lin, Lorraine Iacovitti doi:10.1016/j.brainres.2015.04.029 the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury
Rewriting Dogma: evidence for new niches beyond the SVZ and SGZ In the past several decades, it has become dogma in the field that adult neurogenesis is limited to the two forebrain zones of the SVZ and SGZ. So entrenched is this concept in the literature that it has been difficult to move beyond the SVZ and SGZ, despite a growing arsenal of evidence of more widespread neurogenesis and gliogenesis throughout the neuroaxis
it was recently shown that metabolic factors arising from a high fat diet substantially enhance neurogenesis in the median eminence of the hypothalamus Whether CVO stem cells, like NSCs in classic niches, decline with age or increase with stimuli like exercise remains to be studied. our most recent studies further revealed the surprising* existence of additional novel niches along the walls of the third and fourth ventricles This is indeed an exciting and transitional period for stem cell research as exciting new evidence continues to show that stem cell niches are not limited to forebrain subventricular and subgranular zones as once believed but instead exist at multiple sites along the entire ventricular system, [...] Despite these promising findings, there is still much to learn about the new brain niche sites, including details of their cellular composition and cytoarchitecture, their relative contribution to homeostasis in the healthy brain and to repair in the injured or aged brain. Thus far, what is known is that changes as routine as modifications in diet and as severe as stroke can induce de novo neurogenesis in the adult brain. Continued work in this area will no doubt open new avenues of inquiry that may ultimately lead to the therapeutic targets of the future. http://www.sciencedirect.com/science/article/pii/S000689931500325X
(*) surprising? why? Rewriting Dogma? again?
So entrenched is this concept in the literature that it has been difficult to move beyond [...] despite a growing arsenal of evidence
Haven't we seen this before? what else is new? been there, done that.Dionisio
June 13, 2015
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Nanotechnologies for the study of the central nervous system doi:10.1016/j.pneurobio.2014.09.004 current gold-standard techniques used to study the CNS have limitations that pose unique challenges to furthering our understanding of functional CNS development. it remains unclear how gene function, synapse development, and circuit physiology effectively map onto patient symptomology at a clinical level Advancements in nanodiagnostic neuroimaging have shown significant potential to revolutionise how the brain is visualised. Further studies on biodistribution, pharmacokinetics, and local and systemic toxicity will need to be addressed, Over the next decade, nanotechnological approaches will continue to play a vital role in neuroscience, The recent announcements of the Human Brain Project and BRAIN Initiative in Europe and the USA respectively, point to an awareness of the need to refocus efforts on utilising such advancements in technology to help understand the fundamental processes underlying brain function There is little doubt that there are still several challenges that must be overcome to fulfil the promise of nanotechnological applications in neuroscience. http://www.sciencedirect.com/science/article/pii/S030100821400104X
Dionisio
June 13, 2015
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Active zone stability: insights from fly neuromuscular junction DOI: 10.4103/1673-5374.156942 Year : 2015 | Volume : 10 | Issue : 5 | Page : 677-678 Xiaolin Tian, Chunlai Wu Ph.D. The presynaptic active zone is a dynamic structure that orchestrates regulated release of neurotransmitters. Developmental and aging processes, and changes in neuronal network activity can all modulate the number, size and composition of active zone and thereby synaptic efficacy. However, very little is known about the mechanism that controls the structural stability of active zone. http://www.nrronline.org/article.asp?issn=1673-5374;year=2015;volume=10;issue=5;spage=677;epage=678;aulast=Tian
Not quite there yet, but making progress... :)Dionisio
June 13, 2015
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It's definitely very exciting to see how deeply researchers can penetrate the biological intricacies these days. New research papers shed more light on cellular and molecular details, thus helping to clarify the big picture of the marvelously designed biological systems. One discovery at a time, outstanding questions are being answered, while newer questions are raised. Sometimes this extensive exploration gives the impression of a never-ending story, doesn't it? After spending so many years working on very interesting and successful engineering design software development projects, the sight of these elaborate cellular and molecular choreographies orchestrated within the biological systems leaves me speechless. It’s simply beyond anything control engineers and computer scientists could have dreamed of. While trying to understand these fascinating interwoven signaling pathways and epigenetic regulatory networks, one can wonder…Dionisio
June 13, 2015
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Interplay of environmental signals and progenitor diversity on fate specification of cortical GABAergic neurons Juliana A. Brandão and Rodrigo N. Romcy-Pereira* Front. Cell. Neurosci., http://dx.doi.org/10.3389/fncel.2015.00149 Cortical GABAergic interneurons constitute an extremely diverse population of cells organized in a well-defined topology of precisely interconnected cells. [...] only recently, studies have revealed some of the mechanisms generating the heterogeneity of neuronal subtypes and their modes of integration in brain networks. [...] distributed network of neurons that coordinate the action [...] [...] precise spatio-temporal control of excitation and inhibition in local and long-range networks [...] Cell fate specification of cortical interneurons seems to require the interplay of both intrinsic and extrinsic molecular signals. However, the distinct aspects of such delicate control just began to be unveiled. Time of signaling, cell-type targeting, magnitude of phenotypic effects, and the particular molecular mechanisms involved are still unknown. Future experiments should bring some light on these open questions. http://journal.frontiersin.org/article/10.3389/fncel.2015.00149/full
Work in progress... a few questions remain unanswered. Stay tuned...Dionisio
June 12, 2015
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How do disordered regions achieve comparable functions to structured domains? Natasha S. Latysheva†,*, Tilman Flock, Robert J. Weatheritt, Sreenivas Chavali and M. Madan Babu†,* DOI: 10.1002/pro.2674 http://onlinelibrary.wiley.com/doi/10.1002/pro.2674/abstract The traditional structure to function paradigm conceives of a protein's function as emerging from its structure. In recent years, it has been established that unstructured, intrinsically disordered regions (IDRs) in proteins are equally crucial elements for protein function, regulation and homeostasis.
Dionisio
June 10, 2015
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SOCS1 mimetics and antagonists: a complementary approach to positive and negative regulation of immune function imageChulbul M. I. Ahmed, imageJoseph Larkin III and imageHoward M. Johnson* Front. Immunol., http://dx.doi.org/10.3389/fimmu.2015.00183 http://journal.frontiersin.org/article/10.3389/fimmu.2015.00183/full
Dionisio
June 10, 2015
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Rethinking gene regulatory networks in light of alternative splicing, intrinsically disordered protein domains, and post-translational modifications Karl J. Niklas1*, Sarah E. Bondos2, A. Keith Dunker3 and Stuart A. Newman4 Front. Cell Dev. Biol., http://dx.doi.org/10.3389/fcell.2015.00008 Just as genes per se have long been rejected as the exclusive or privileged level of determination of phenotype and evolutionary change, new understanding of the complexities of gene expression and the conditional identities of its protein products call into question a deterministic GRN-based reductionism in developmental and evolutionary biology. http://journal.frontiersin.org/article/10.3389/fcell.2015.00008/abstract
This whole paper is very juicy. Enjoy it!Dionisio
June 10, 2015
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RNA helicase DDX21 coordinates transcription and ribosomal RNA processing Eliezer Calo, Ryan A. Flynn, Lance Martin, Robert C. Spitale, Howard Y. Chang & Joanna Wysocka Nature 518, 249–253 doi:10.1038/nature13923 DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle1, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Our results uncover the multifaceted role of DDX21 in multiple steps of ribosome biogenesis, and provide evidence implicating a mammalian RNA helicase in RNA modification and Pol II elongation control. http://www.nature.com/nature/journal/v518/n7538/full/nature13923.html
Dionisio
June 10, 2015
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Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions Valentina Turinetto* and Claudia Giachino* Nucl. Acids Res. 43 (5): 2489-2498. doi: 10.1093/nar/gkv061 http://nar.oxfordjournals.org/content/43/5/2489.full DNA is structured into chromatin, an organization that is important for both resolving problems of spatial accommodation, and for functional utilization of the DNA and proper coordination of its metabolic activities To allow an efficient repair, chromatin decondenses near the DSBs, but the mechanism for this remodelling is unclear. The molecular basis and biological function of both sex body formation and meiotic sex chromosome inactivation (MSCI) have long remained unknown. A more recent work contributed to uncover the molecular mechanism underlying MSCI, focusing on MDC1. It is not yet known whether this SPO11-independent augmentation of the ?H2AX signal is due to further DSB formation, [...] The subsequent stability of the Xi is likely due to [...] It has become clear in the past few years that post-translational modifications of histones play critical roles in both structural and functional chromatin regulation during mitosis [...] a possible structural H2AX role in neural stem cell development remains to be determined and could be an interesting matter for future studies. Asymmetric sister chromosome segregation:
They speculate that ?H2AX could function as a mark that distinguishes sister chromatids with newer template strand from those having the older template strand and could transmit a signal interpreted by the mitotic spindle as ‘pick me’ or ‘do not pick me’
A deeper understanding of how these structures assemble and function will probably enrich insights into the mechanisms that link DNA damage, inflammation, and aging. Definition of these new functions in more details will surely deserve interesting scenarios.
Excellent paper!Dionisio
June 10, 2015
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The polarity protein Baz forms a platform for the centrosome orientation during asymmetric stem cell division in the Drosophila male germline Mayu Inaba, Zsolt G Venkei, Yukiko M Yamashita DOI: http://dx.doi.org/10.7554/eLife.04960 eLife 2015;4:e04960
Because precocious cell division before establishing cell polarity would lead to failure in ACD, these two processes must be tightly coupled; however, the underlying mechanism is poorly understood.
Intensive investigation has revealed the mechanisms that polarize cells and orient the division plane; however, less is known about how cells might respond to perturbation of cell polarity and whether/how cells might ensure that cell division occurs only after the establishment of correct polarity.
Despite the importance of asymmetric divisions in the development of multicellular organisms, the potential checkpoint mechanisms that ensure asymmetric cell divisions, similar to the SPOC in the budding yeast, are poorly defined.
The physical basis of correct centrosome orientation monitored by the COC remains a mystery In the operation of the COC, what is sensed as correct or incorrect centrosome orientation to inactivate or activate the COC remains unknown. [...] the association between Baz and the centrosome is the key event that is interpreted to indicate ‘correct centrosome orientation’ by GSCs. Our study provides a framework of the mechanism by which GSC sense correct cell polarity.
Although intensive investigations have revealed the mechanisms of cell polarity and asymmetrical cell division along the polarity axis, much less is known about how cells ensure the correct temporary order of cell polarization and cell division.
[...] the presence of checkpoint mechanisms to ensure asymmetric division has not been thoroughly investigated. [...] the COC may serve as a model system to study a new class of checkpoints that specialize in monitoring division orientation in multicellular organisms. [...] Baz is a critical player in centrosome orientation and its checkpoint in Drosophila male GSCs. [...] Baz-centrosome docking is the cellular event that is recognized by the COC as correct centrosome orientation. [...] Par-1-mediated phosphorylation of Baz is critical for spindle orientation, although the mechanistic details of phosphorylated Baz function are yet to be determined. [...] it is unclear how temporal regulation of Baz phosphorylation relates to steps of Baz-centrosome docking, mitotic entry, and spindle orientation [...] [...] it is puzzling that overexpression of Baz causes high frequency of spindle misorientation in wild type, whereas the overexpression of the same construct in Par-1 RNAi background lowers spindle misorientation.
Future investigation is required to understand how distinct isoforms of Baz (phosphorylated vs non-phosphorylated) participate in distinct aspects of centrosome/spindle orientation. In summary, our study reveals a cellular mechanism by which stem cells integrate information about cell polarity to regulate their cell cycle progression. We speculate that the orientation checkpoint may be present in many other multicellular organisms, and the understanding of the COC in Drosophila may provide a conceptual framework for understanding orientation checkpoint mechanisms in genera
Dionisio
June 10, 2015
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Mung @517 Yes, that's amazing indeed. Specially how would it do it.Dionisio
June 9, 2015
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The Choreography of Fertilization Oogenesis pp 289-306 Giovanni Coticchio B.Sc., M.Sc., M.Med.Sc., Ph.D., Fausta Brambillasca B.Sc., Ph.D [...] oocyte-sperm fusion creates a unique cellular machinery whose regulation in time and space influences the long term destiny of the ensuing embryo. http://link.springer.com/chapter/10.1007/978-0-85729-826-3_20
Dionisio
June 9, 2015
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Apoptosis is essential for development. Amazing that it would co-evolve along with embryogenesis.Mung
June 9, 2015
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The importance of being dead: cell death mechanisms assessment in anti-sarcoma therapy Front. Oncol., http://dx.doi.org/10.3389/fonc.2015.00082 http://journal.frontiersin.org/article/10.3389/fonc.2015.00082/full [...] have not been yet properly addressed [...] [...] in most cases the precise sequence of events remains poorly characterized. [...] scientific efforts in this discipline are historically undermined by the relative low investments and isolated work [...] The scientific landscape involving cell death mechanisms in sarcomas can be improved. Many studies about cell death in sarcomas just describe the occurrence of cell death without a proper characterization of the sequence-of-events leading to a particular form of death.
Dionisio
June 9, 2015
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Casein Kinase 1 and Phosphorylation of Cohesin Subunit Rec11 (SA3) Promote Meiotic Recombination through Linear Element Formation Naina Phadnis, Lubos Cipak, Silvia Polakova, Randy W. Hyppa, Ingrid Cipakova, Dorothea Anrather, Lucia Karvaiova, Karl Mechtler, Gerald R. Smith Juraj Gregan PLOS •DOI: 10.1371/journal.pgen.1005225 Although the outlines of these two events are known, how they are regulated and coordinated remains unclear. We were surprised* that the hhp1-as (M84G) ATP-analog-sensitive mutant had a dramatic, differential phenotype even in the absence of added analog [...] http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005225
(*) surprised? Why?Dionisio
June 9, 2015
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Hrr25/CK1?-directed release of Ltv1 from pre-40S ribosomes is necessary for ribosome assembly and cell growth Homa Ghalei,1 Franz X. Schaub,1,3 Joanne R. Doherty,1 Yoshihiko Noguchi,2 William R. Roush,2 John L. Cleveland,1,3 M. Elizabeth Stroupe,4,5 and Katrin Karbstein1 http://jcb.rupress.org/content/208/6/745.abstract JCB vol. 208 no. 6 745-759 The Rockefeller University Press, doi: 10.1083/jcb.201409056 © 2015 Ghalei et al. [...] the substrates of Hrr25 and CK1?/? that are necessary for cell growth and survival are unknown. These findings validate the ribosome assembly pathway as a novel target for the development of anticancer therapeutics.
Dionisio
June 9, 2015
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CK1? restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1?/ARNT complex formation Maria Kourtia, Georgia Ikonomoua, c, Nikolaos-Nikiforos Giakoumakisb, Maria Anna Rapsomanikib, Ulf Landegrenc, Symeon Siniossogloud, Zoi Lygeroub, George Simosa, , , Ilias Mylonisa, , doi:10.1016/j.cellsig.2015.02.017 These data reveal a novel role for CK1? in regulating lipid metabolism and, through it, cell adaptation to low oxygen conditions. Oxygen deprivation of cells and tissues (hypoxia) causes a dramatic alteration in gene expression and characterizes major pathological processes like ischemia and cancer. The response to hypoxia is mainly mediated by the hypoxia-inducible factors (HIFs) [...] These data lead to the conclusion that increased proliferation of cells under hypoxia requires HIF-1 and also, surprisingly*, a lipin-1-mediated function such as, possibly, up-regulation of lipid droplet formation. CK1? restricts this phenomenon and can limit cellular proliferation under hypoxia by modifying HIF-1? and impairing its association with ARNT and DNA As HIF-1 is associated with severe pathological conditions such as tissue ischemia and cancer, it is vital to identify in detail the mechanisms that affect its activity in order to develop novel therapeutic approaches. [...] inhibition of HIF-1-dependent lipin-1 expression by CK1?, appears to restrict cancer cell growth under hypoxia. The complex multi-layer control of CK1 and its ubiquitous nature create an obstacle in understanding the possible connection between CK1 regulation and the physiological response to hypoxia, which require additional extensive studies. Apart from cancer, where HIF-1 is associated with pathogenesis and poor patient outcome, HIF-1 has also an important and protective role in a wide range of disorders characterized by ischemia and inflammation. [both deleterious and beneficial effects?] http://www.sciencedirect.com/science/article/pii/S0898656815000637
(*) surprisingly? why?Dionisio
June 9, 2015
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Kinetochore-localized BUB-1/BUB-3 complex promotes anaphase onset in C. elegant JCB vol. 209 no. 4 507-517 The Rockefeller University Press, doi: 10.1083/jcb.201412035 © 2015 Kim et al. These results reveal an unexpected* role for the BUB-1/BUB-3 complex in promoting anaphase onset that is distinct from its well-studied functions in checkpoint signaling and chromosome alignment, and suggest a new mechanism contributing to the coordination of the metaphase-to-anaphase transition. http://jcb.rupress.org/content/209/4/507.abstract
(*) unexpected? why? what were they expecting?Dionisio
June 9, 2015
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Spatiotemporal regulation of the anaphase-promoting complex in meiosis Sushama Sivakumar & Gary J. Gorbsky Nature Reviews Molecular Cell Biology 16, 82–94 (2015) doi:10.1038/nrm3934 http://www.nature.com/nrm/journal/v16/n2/full/nrm3934.html The appropriate timing of events that lead to chromosome segregation during mitosis and cytokinesis is essential to prevent aneuploidy, and defects in these processes can contribute to tumorigenesis. Key mitotic regulators are controlled through ubiquitylation and proteasome-mediated degradation. The APC/C (anaphase-promoting complex; also known as the cyclosome) is an E3 ubiquitin ligase that has a crucial function in the regulation of the mitotic cell cycle, particularly at the onset of anaphase and during mitotic exit. Co-activator proteins, inhibitor proteins, protein kinases and phosphatases interact with the APC/C to temporally and spatially control its activity and thus ensure accurate timing of mitotic events.
This is really cool! isn't it? After spending so many years working on very interesting and successful engineering design software development projects, the sight of these elaborate cellular and molecular choreographies orchestrated within the biological systems leaves me speechless. It's simply beyond anything control engineers and computer scientists could have dreamed of. While trying to understand these fascinating interwoven signaling pathways and regulatory networks, one can wonder...Dionisio
June 9, 2015
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Signalling dynamics in the spindle checkpoint response Nitobe London & Sue Biggins Nature Reviews Molecular Cell Biology 15, 736–748 (2014) doi:10.1038/nrm3888 In contrast to the traditional view of a binary checkpoint response — either completely on or off — new findings indicate that the checkpoint response strength is variable. http://www.nature.com/nrm/journal/v15/n11/full/nrm3888.html
This is a repeat... it's very interesting, can't get enough of this exciting stuff.Dionisio
June 9, 2015
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Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint Gang Zhang, Tiziana Lischetti, Daniel G. Hayward & Jakob Nilsson Nature Communications 6, Article number: 7162 doi:10.1038/ncomms8162 Future work needs to address the role of Bub3 in localizing BubR1 and the regulation of the BubR1–Bub1 interaction. Is there then any role of kinetochore localized BubR1 in generating the SAC signal? [...] it is possible that these pools of BubR1 have distinct functions in the checkpoint. Ongoing efforts in the lab are focused on investigating these models. http://www.nature.com/ncomms/2015/150602/ncomms8162/full/ncomms8162.html
Work in progress... this is exciting, isn't it? Can't wait to reading the next reports on this ongoing research. :)Dionisio
June 9, 2015
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The current view for the silencing of the spindle assembly checkpoint DOI:10.4161/cc.29027 Yanchang Wang, Fengzhi Jin, Ryan Higgins & Kelly McKnight Cell Cycle Volume 13, Issue 11, 2014 pages 1694-1701 http://www.tandfonline.com/doi/abs/10.4161/cc.29027 A fundamental question in cell biology is how cells ensure that chromosome segregation only occurs after bipolar attachment. [...] is poorly understood. A long-standing debate is whether [...] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111715/ [...] , the SAC silencing process is much less clear. Although a reasonable speculation is that [...], [...] is still missing at the molecular level. [...] suggests additional mechanisms for SAC silencing. [...] no evidence indicates the direct link between [...] and [...]. It is likely that [...]. We speculate that either [...] or [...] could [...] One open question is how [...] Moreover, it is important to know [...] [...] the role of [...] remains controversial, [...] [...] additional mechanisms should also contribute [...] An unresolved debate is whether [...] It will be informative to analyze [...] [...] an important question regarding [...] Further studies are needed to verify whether [...] [...] one untested possibility is that [...] [...] more components remain to be identified. Much more work is needed to elucidate the molecular details for this signaling pathway.
Dionisio
June 8, 2015
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Design of cell niches for the regulation of stem cell fate in central nervous tissue regeneration doi:10.1016/j.matlet.2015.02.079 Cell therapy based on biomaterials and stem cells has made outstanding performance in central nervous tissue engineering. To stimulate stem cell behavior and obtain maximum functional recovery, researchers have paid great effort to elucidate the function of stem cell microenvironments. However, optimum scaffold conditions vary among biomaterials and cells. During the development in scaffolds, stem cells detect different aspects of scaffold signals and change their behavior accordingly, where as the synergism of scaffold biochemical and geometric properties are usually neglected by current reports. To provide a reference for scaffold designs based on specific types of biomaterials and stem cells, we performed this review to make discussion on the function of the geometric properties of scaffolds with reference to the corresponding biomaterials. http://www.sciencedirect.com/science/article/pii/S0167577X15002761
Dionisio
June 8, 2015
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Positive Feedback of NDT80 Expression Ensures Irreversible Meiotic Commitment in Budding Yeast •DOI: 10.1371/journal.pgen.1004398 There are two main types of cell division cycles, mitosis and meiosis. During mitosis, DNA is replicated and then chromosomes segregate, producing two daughter cells with the same ploidy as the progenitor cell. During meiosis, DNA is replicated and then chromosomes undergo two rounds of segregation, producing four gametes with half the ploidy of the progenitor cell.
The molecular mechanisms that define meiotic commitment are not well understood.
[...] the external signals that initiate the switch into meiosis in various organisms are quite diverse [...] An understanding of the regulatory mechanisms that drive cells through meiotic commitment points will provide insight into mechanisms that constrain cells to a developmental path. The commitment to meiosis has been conceptually defined as the point at which cells can no longer return to mitosis, even in the absence of the inducing environmental signal. However, the molecular mechanisms that regulate this transition are not well understood. In the future, it will be important to determine if nested feedback loops tune the response to the environmental factors that influence meiotic commitment in budding yeast. Comparisons of the network architectures that ensure the irreversibility of the transition through meiotic commitment in different organisms will provide insight into the general properties that govern meiotic commitment points. http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004398
Dionisio
June 8, 2015
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DNA Damage Checkpoint Ndd1 Turnover by SCFGrr1 Is Inhibited by the DNA Damage Checkpoint in Saccharomyces cerevisiae •DOI: 10.1371/journal.pgen.1005162 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005162 Ndd1 is the dedicated transcriptional activator of the mitotic gene cluster, which includes thirty-three genes that encode key mitotic regulators, making Ndd1 a hub for the control of mitosis. We propose a model in which Ndd1 is stabilized in damage, while its activity is independently inhibited. Our speculation is that accumulated Ndd1 can be quickly de-phosphorylated during recovery following the repair of DNA damage to allow for rapid activation of its transcriptional targets to promote mitosis. Unfortunately, it is difficult to experimentally test this model, due to the fact that CDK phosphorylations promote both activation of Ndd1 and its destruction.
Dionisio
June 8, 2015
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Cyclin-dependent kinases regulate lysosomal degradation of hypoxia-inducible factor 1? to promote cell-cycle progression PNAS vol. 111 no. 32 > Maimon E. Hubbi, E3325–E3334, doi: 10.1073/pnas.1412840111 http://www.pnas.org/content/111/32/E3325.full Oxygen availability is a critical and dynamic regulator of cell proliferation. Hypoxia elicits a variety of adaptive cellular and systemic responses, which include changes in angiogenesis, red blood cell production, metabolism, and autophagy [...] cells possess a mechanism to selectively degrade HIF-1? during S phase of the cell cycle. [...] a novel role for the lysosome as a regulator of cell-cycle progression under hypoxic conditions. The mechanism by which these cells maintain proliferation in the presence of elevated HIF-1? levels is unclear. lysosomal degradation of HIF-1? is an essential step for the maintenance of cell-cycle progression under hypoxic conditions. [is it sufficient?] Cdk-dependent regulation of HIF-1? lysosomal degradation is essential for DNA replication under hypoxic conditions. [is it sufficient?] Cdk1 and Cdk2 regulate lysosomal degradation of HIF-1?. Additional studies are required to determine if Cdk2 phosphorylates HIF-1? (on a residue other than Ser-688) to increase its lysosomal degradation. Progression through the cell cycle is a highly controlled process, dependent on cell-cycle phase-specific synthesis and degradation of multiple regulatory proteins.
Dionisio
June 8, 2015
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Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression DOI 10.1002/embj.201386877 The EMBO Journal 33, 1044-1060 http://emboj.embopress.org/content/33/9/1044 Although Cdk1 is known to be required for robust regulation of cell cycle?regulated gene expression, the mechanism by which it controls the TF network is not well understood. In the future, it will be of interest to determine whether this model applies to regulation by Cdk1 in other systems. In the future, it will be of great interest to test whether unrelated Cdk1 targets with different cellular functions exhibit similar, coordinate regulation. In addition, it will be important to determine whether these general principles of regulation by Cdk1 are conserved in other systems.
Dionisio
June 7, 2015
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A Micropeptide Encoded by a Putative Long Noncoding RNA Regulates Muscle Performance DOI: http://dx.doi.org/10.1016/j.cell.2015.01.009 Functional micropeptides can be concealed within RNAs that appear to be noncoding. These findings [...] highlight the possibility that additional micropeptides are encoded in the many RNAs currently annotated as noncoding. http://www.cell.com/cell/abstract/S0092-8674(15)00010-0
Dionisio
June 6, 2015
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Phosphoinositides: Lipids with informative heads and mastermind functions in cell division doi:10.1016/j.bbalip.2014.10.013 Phosphoinositides are low abundant but essential phospholipids in eukaryotic cells and refer to phosphatidylinositol and its seven polyphospho-derivatives. In this review, we summarize our current knowledge on phosphoinositides in multiple aspects of cell division in animal cells, including mitotic cell rounding, longitudinal cell elongation, cytokinesis furrow ingression, intercellular bridge abscission and post-cytokinesis events. We describe how the multiple functions of phosphoinositides in cell division reflect their distinct roles in local recruitment of protein complexes, membrane traffic and cytoskeleton remodeling. This article is part of a Special Issue entitled Phosphoinositides. http://www.sciencedirect.com/science/article/pii/S1388198114002224
informative heads and mastermind functions ? Wow! (whatever that means) :)Dionisio
June 6, 2015
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