Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
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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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Comments

Cell shape and the microenvironment regulate nuclear translocation of NF??B [...] DOI 10.15252/msb.20145644 We speculate that shape?mediated differences in NF??B shuttling could therefore have profound effects on how healthy, wounded, and pathological tissues respond to cytokines. While some models of oscillation have been proposed which take morphology into account, more work is needed to determine how cell shape impacts NF??B cycling. Further high?content studies that incorporate live cell GFP?p65 and shape measurements will overcome the acyclic nature of Bayesian networks and elucidate whether a feedback exists from NF??B to cell shape and provide insight into these mechanisms. http://msb.embopress.org/content/11/3/790
Dionisio_{May 2, 2015
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What occurs to me is that it would not be unreasonable to use analogy to predict the amount of information and complexity required to control the described organogenesis. One could map out the control systems and the mechanisms employed to activate, monitor, and deactivate these processes. Anticipating this information is already being done of course, but the volume of interdependent information might be able to fine-tune investigation. This is an excellent example of the utility of the ID paradigm in my opinion, and it once again falsifies the incrementalism required for the theory of evolution. There's also the design behind organ. Specifically regarding cochlear operation, in addition to sensitivity to a frequency band and logarithmic amplitude, it's my understanding that it also acts as a comb filter, which provides additional spatial feedback. Genius! -QQuerius_{May 2, 2015
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Tissue stiffness dictates development, homeostasis, and disease progression. Tissue development is orchestrated by the coordinated activities of both chemical and physical regulators. While much attention has been given to the role that chemical regulators play in driving development, researchers have recently begun to elucidate the important role that the mechanical properties of the extracellular environment play. For instance, the stiffness of the extracellular environment has a role in orienting cell division, maintaining tissue boundaries, directing cell migration, and driving differentiation. http://www.atgcchecker.com/pubmed/25915734
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DOI: 10.1002/dvdy.24257 Organogenesis, the process of organ formation and homeostasis, relies on a symphony of interactions between different cells and tissues that collectively operate to maintain bodily function. Despite incredibly diverse architecture, size, shape, and tissue composition, the formation of distinct organs is remarkably similar. While it has long been appreciated that development is directed by information contained within the genome, and influenced by the maternal environment and epigenome, it is less well understood how variations in the fetal and maternal genome and epigenome interact with environmental factors and how this affects organogenesis. [...] organogenesis is a tremendously robust process that integrates many diverse cellular and molecular processes. The end result of this precise coordination is highly complex functional organ systems that carry out essential functions, act in concert to maintain to homeostasis, and continually adapt to ever challenging external environments. http://onlinelibrary.wiley.com/doi/10.1002/dvdy.24257/full
Fascinating!Dionisio_{May 2, 2015
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Adrenocortical zonation, renewal, and remodeling doi: 10.3389/fendo.2015.00027 The mechanisms involved in adrenocortical remodeling are complex and redundant so as to fulfill the offsetting goals of organ homeostasis and stress adaptation. The regulation of adrenocortical development and homeostasis has been the subject of intensive investigation over the past decade The continual remodeling of the zones of the adrenal cortex requires the precise control of cell growth and differentiation. The pathways involved are complex and redundant so as to fulfill the offsetting goals of organ homeostasis and stress adaptation. Disruption of these pathways can lead to neoplasia. Although much has been learned about the regulation of adrenocortical homeostasis and regeneration, there are still many unanswered questions. It has proven difficult to isolate and characterize adrenocortical stem cell populations, and we do not know how these populations vary with age. Nor do we understand the relative contributions of the hedgehog, DLK1, FGF, and WNT/?-catenin signaling pathways to adrenocortical differentiation, or how these pathways interface with classic endocrine signaling systems, such as the RAAS and the HPA axis. The positional cues that mediate differentiation during centripetal (or centrifugal) migration also remain enigmatic. To date, there has been little progress in the development of in vitro models to study adrenocortical differentiation. Hopefully, such techniques will emerge in the coming years and help drive the field forward. http://journal.frontiersin.org/article/10.3389/fendo.2015.00027/full
Let’s look forward, with much anticipation, to reading future research reports shedding more light on this important subject.Dionisio_{May 2, 2015
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The physiology of mechanoelectrical transduction channels in hearing. doi: 10.1152/physrev.00038.2013. Much is known about the mechanotransducer (MT) channels mediating transduction in hair cells of the vertrbrate inner ear. However, the MT channel protein is still not firmly identified, nor is it known whether the channel is activated by force delivered through accessory proteins or by deformation of the lipid bilayer. http://www.ncbi.nlm.nih.gov/pubmed/24987009
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Subunit determination of the conductance of hair-cell mechanotransducer channels doi: 10.1073/pnas.1420906112 Cochlear hair cells are sensory receptors of the inner ear that detect sound via opening of mechanically sensitive transduction channels at the tips of the eponymous hairs. The conductance of the channel increases two-fold along the cochlea, but neither its molecular structure nor mechanism of tonotopic variation is known. The molecular identity of this ion channel is still unclear, [...] Our present hypothesis is that the reverse-polarity current represents the pore-forming subunit of the native channel, but a number of important questions remain with regard to this current. What connects these disparate processes and what might be the common signal to induce the channel response? [...]the location of the underlying channels is not precisely known,[...] More experiments are needed to address the significance and localization of these channels. http://www.pnas.org/content/112/5/1589.full
Almost there...Dionisio_{May 1, 2015
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Querius @341 You have made very important observations and raised interesting questions. Thank you.Dionisio_{May 1, 2015
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A Balance of Form and Function: Planar Polarity and Development of the Vestibular Macular doi: 10.1016/j.semcdb.2013.03. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690145/ An outstanding question is the identity of this motor protein because its identification may show how subcellular planar polarity is coupled to PCP and tissue polarity. Although this does not rule out a function for Fat/Dachsous signaling in HC development, it strongly suggests that the core PCP proteins have a more significant role in HCs. [...] the significance of bundle rotation has not been established for development of tissue polarity in the maculae. Remarkably the abrupt change in stereociliary bundle orientation that occurs at the LPR does not require corresponding changes in the subcellular distribution of core PCP proteins. An interesting possibility is that... An alternative possibility is that... Despite these possibilities, mechanisms regulating tissue polarity and patterning the LPR in conjunction with the core PCP proteins have not been identified. Several lines of evidence, including [...] support a hypothesis that [...] However the cellular events enacting this coordination and whether these events are genetically encoded or activity dependent have not been determined. It is also important to understand how planar polarity is coordinated with other tissue-specific aspects of organ development. For example within the maculae, what prevents afferent neurons from contacting multiple HCs located on opposite sides of the LPR? And how is planar polarity influenced by the rapid and dynamic processes of inner ear morphogenesis? [...] this problem should be resolved in the near future through the study of conditional mutants and the application of Cre/LoxP technologies. When this limitation is removed, many of these outstanding questions of planar polarity will be addressed, and studying the vestibular maculae is likely to advance our understanding of planar polarity mechanisms in the auditory system and other developmental processes.
It seems like there are more new questions after they answered some outstanding ones? Apparently it ain't easy to figure all that out. Is it? Let's stay tuned... more to come.Dionisio_{May 1, 2015
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Dionisio @ 325, I watched the complete lecture. First off, the complexity is truly astounding. Naming the processes facilitates categorization, but it also makes them sound ordinary, even inevitable, which is of course not the case. Yes, the professor did imply that the 3D structural instructions were sequential rather than located in a comprehensive "master plan" (which of course doesn't obviate a master plan), and she indicated that she didn't have *enough time* to explore this further. But she just couldn't bring herself to say that researchers are utterly clueless on how the cells are made to respond in order to assemble themselves in an organ by a method other than simply forming sheets by preferential adhesion. The film showing a cell moving was amazing! How can students just sit there? How can they learn without asking questions? -QQuerius_{April 30, 2015
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The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlear doi: 10.1242/?bio.20149753 Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles [...] an intriguing possibility remains that Cdc42 is an effector of nectins in hair cells, similar as shown in other types of epithelial cells [...] This may indicate functional compensation between the two Rho GTPases, a possibility that would explain why defects were not manifested in all recombined OHCs in the Cdc42 mutant[...] Our results suggest that Cdc42 is involved in OHC stereociliogenesis early postnatally, likely through the regulation of actin dynamics [...] http://bio.biologists.org/content/4/4/516.full
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Segment-Specific Adhesion as a Driver of Convergent Extension •DOI: 10.1371/journal.pcbi.1004092 Convergent extension, the simultaneous extension and narrowing of tissues, is a crucial event in the formation of the main body axis during embryonic development. It involves processes on multiple scales: the sub-cellular, cellular and tissue level, which interact via explicit or intrinsic feedback mechanisms. Computational modelling studies play an important role in unravelling the multiscale feedbacks underlying convergent extension. Convergent extension usually operates in tissue which has been patterned or is currently being patterned into distinct domains of gene expression. How such tissue patterns are maintained during the large scale tissue movements of convergent extension has thus far not been investigated [...] in future work we aim to investigate the dynamic interplay between sequential segmentation and convergent extension. Considering such bidirectional feedback between patterning and morphogenesis may bring to light important principles of coordinating growth and patterning. http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004092
Work in progress...Dionisio_{April 30, 2015
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Morphogenesis on the Multicellular Level: Patterns of Mechanical Stresses and Main Modes of Collective Cell Behavior DOI10.1007/978-3-319-13990-6_3 Regular patterns of mechanical stresses are perfectly expressed on the macromorphological level in the embryos of all taxonomic groups studied in this respect. Stress patterns are characterized by the topological invariability retained during prolonged time periods and drastically changing in between. After explanting small pieces of embryonic tissues, they are restored within several dozens minutes. Disturbance of stress patterns in developing embryos irreversibly breaks the long-range order of subsequent development. Morphogenetically important stress patterns are established by three geometrically different modes of cell alignment: parallel, perpendicular, and oblique. The first of them creates prolonged files of actively elongated cells. The second is responsible for segregation of an epithelial layer to the domains of columnar and flattened cells. The model of this process, demonstrating its scaling capacities, is described. The third mode which follows the previous one is responsible for making the curvatures. It is associated with formation of “cell fans,” the universal devices for shapes formation due to slow relaxation of the stored elastic energy. http://link.springer.com/chapter/10.1007/978-3-319-13990-6_3

Morphomechanical Feedbacks DOI10.1007/978-3-319-13990-6_4 An attempt is made to reconstruct the natural successions of the developmental events on the basis of a common mechanically based trend. It is formulated in terms of a hyper-restoration (HR) hypothesis claiming that embryonic tissue responds to any external deforming force by generating its own one, directed toward the restoration of the initial stress value, but as a rule overshooting it in the opposite side. We give a mathematical formulation of this model, present a number of supporting evidences, and describe several HR-driven feedbacks which may drive forth morphogenesis. We use this approach for reconstructing in greater detail the gastrulation of the embryos from different taxonomic groups. Also, we discuss the application of this model to cytotomy, ooplasmic segregation, and shape complication of tubular rudiments (taking hydroid polyps as examples). In addition, we review the perspectives for applying morphomechanical approach to the problem of cell differentiation. http://link.springer.com/chapter/10.1007/978-3-319-13990-6_4
There yet? :)Dionisio_{April 30, 2015
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Morphomechanics: transforming tubes into organs doi:10.1016/j.gde.2014.03.004 After decades focusing on the molecular and genetic aspects of organogenesis, researchers are showing renewed interest in the physical mechanisms that create organs. This review deals with the mechanical processes involved in constructing the heart and brain, concentrating primarily on cardiac looping, shaping of the primitive brain tube, and folding of the cerebral cortex. Recent studies suggest that differential growth drives large-scale shape changes in all three problems, causing the heart and brain tubes to bend and the cerebral cortex to buckle. Relatively local changes in form involve other mechanisms such as differential contraction. Understanding the mechanics of organogenesis is central to determining the link between genetics and the biophysical creation of form and structure. http://www.sciencedirect.com/science/article/pii/S0959437X14000100
Glad to see more interest in that important aspect of development.Dionisio_{April 29, 2015
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Identification of the optic recess region as a morphogenetic entity in the zebrafish forebrain The 3D reconstruction and segmentation of the secondary prosencephalon in zebrafish revealed the unexpected complexity of the ventricular morphology, in particular that of the optic recess. The morphogenetic organization of the secondary prosencephalon is thus very difficult to interpret without 3D analysis of the data at cellular resolution. Its spatial organization directly derives from the ventricle-to-mantle orientation of the proliferation and differentiation stages of neural progenitors over time. A systematic application of these procedures will allow building a 3D atlas of the zebrafish forebrain at different time points during development, providing a powerful and comprehensive tool to analyze in detail morphogenesis, neurogenesis, and regionalization in the zebrafish brain, in a comparative perspective. http://www.nature.com/srep/2015/150304/srep08738/full/srep08738.html
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Alternative mRNA transcription, processing, and translation: insights from RNA sequencing DOI: http://dx.doi.org/10.1016/j.tig.2015.01.001 .RNA sequencing uncovers mechanisms regulating gene expression. •Use of alternative TSSs, PASs, and exons is the rule. •Alternative translation initiation at 5?-UTRs and downstream codons is widespread. •Transcription, RNA processing, and translation are often interdependent processes. The human transcriptome comprises >80?000 protein-coding transcripts and the estimated number of proteins synthesized from these transcripts is in the range of 250?000 to 1 million. These transcripts and proteins are encoded by less than 20?000 genes, suggesting extensive regulation at the transcriptional, post-transcriptional, and translational level. Here we review how RNA sequencing (RNA-seq) technologies have increased our understanding of the mechanisms that give rise to alternative transcripts and their alternative translation. We highlight four different regulatory processes: alternative transcription initiation, alternative splicing, alternative polyadenylation, and alternative translation initiation. We discuss their transcriptome-wide distribution, their impact on protein expression, their biological relevance, and the possible molecular mechanisms 0leading to their alternative regulation. We conclude with a discussion of the coordination and the interdependence of these four regulatory layers. http://www.rna-seqblog.com/wp-content/uploads/2015/02/alternative.jpg http://www.cell.com/trends/genetics/abstract/S0168-9525(15)00002-5?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0168952515000025%3Fshowall%3Dtrue
This is exciting news. Let’s look forward, with much anticipation, to reading future research reports shedding more light on this important subject.Dionisio_{April 29, 2015
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Comparative RNA-Seq analysis reveals pervasive tissue-specific alternative polyadenylation doi:10.1186/s12915-015-0116-6 Tissue-specific RNA plasticity broadly impacts the development, tissue identity and adaptability of all organisms, but changes in composition, expression levels and its impact on gene regulation in different somatic tissues are largely unknown. We have identified thousands of novel genes and isoforms differentially expressed between these three tissues. Active promoter regions in all three tissues reveal both known and novel enriched tissue-specific elements, along with putative transcription factors, suggesting novel tissue-specific modes of transcription initiation For the first time, PAT-Seq allowed us to directly study tissue specific gene expression changes in an in vivo setting and compare these changes between three somatic tissues from the same organism at single-base resolution within the same experiment. We pinpoint precise tissue-specific transcriptome rearrangements and for the first time link tissue-specific alternative polyadenylation to miRNA regulation, suggesting novel and unexplored tissue-specific post-transcriptional regulatory networks in somatic cells. http://www.biomedcentral.com/1741-7007/13/4
This is exciting news. Let’s look forward, with much anticipation, to reading future research reports shedding more light on this important subject.Dionisio_{April 29, 2015
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Poly(A)-tail profiling reveals an embryonic switch in translational control doi: 10.1038/nature13007 Poly(A) tails enhance the stability and translation of most eukaryotic mRNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other ‘housekeeping’ proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization. http://www.nature.com/nature/journal/v508/n7494/full/nature13007.html
Dionisio_{April 29, 2015
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Engineering design quality assurance procedures for testing different possible scenarios before the product is implemented or released to final customers have been known for many years. Also, some organizations test products available in the market, in order to check how they function and publish reports for potential consumers. Those tests may try to cover as many situations as possible. Now, is that what they call "evolutionary approach" in this recent paper? http://rnajournal.cshlp.org/content/21/2/202.full Also, regarding the actual objects being tested, are they showing anything besides elaborate built-in adaptation mechanisms in action? Did I get this wrong? Please correct me. Thanks.Dionisio_{April 27, 2015
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Translational reprogramming in cellular stress response DOI: 10.1002/wrna.1212 Cell survival in changing environments requires appropriate regulation of gene expression, including translational control. Multiple stress signaling pathways converge on several key translation factors, such as eIF4F and eIF2, and rapidly modulate messenger RNA (mRNA) translation at both the initiation and the elongation stages. Repression of global protein synthesis is often accompanied with selective translation of mRNAs encoding proteins that are vital for cell survival and stress recovery. The past decade has seen significant progress in our understanding of translational reprogramming in part due to the development of technologies that allow the dissection of the interplay between mRNA elements and corresponding binding proteins. Recent genome?wide studies using ribosome profiling have revealed unprecedented proteome complexity and flexibility through alternative translation, raising intriguing questions about stress?induced translational reprogramming. Many surprises emerged from these studies, including wide?spread alternative translation initiation, ribosome pausing during elongation, and reversible modification of mRNAs. Elucidation of the regulatory mechanisms underlying translational reprogramming will ultimately lead to the development of novel therapeutic strategies for human diseases. http://wires.wiley.com/WileyCDA/WiresArticle/wisId-WRNA1212.html
Significant progress! We like that, don't we? The sooner science will fill the outstanding gaps in biological understanding, the greater possibilities to get better medicines and health maintenance treatments for all. Also, every new discovery sheds more light on the elaborate cellular and molecular choreographies orchestrated within the biological systems. And doubtless many of us -specially those with information technology background- enjoy that kind of stuff, right? Best regards to all.Dionisio_{April 27, 2015
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Assessing the translational landscape of myogenic differentiation by ribosome profiling doi: 10.1093/nar/gkv281 The formation of skeletal muscles is associated with drastic changes in protein requirements known to be safeguarded by tight control of gene transcription and mRNA processing. The contribution of regulation of mRNA translation during myogenesis has not been studied so far. This study demonstrates that differential mRNA translation controls protein expression of specific subsets of genes during myogenesis. Ribosome footprints derived from coding and non-coding genes ...a relative high proportion of reads mapped to long intergenic non-coding RNAs (lincRNAs) (between 5 and 10% in average) and small RNAs (between 10 and 20% in average). Subsets of mRNAs primarily regulated at translational level during myoblasts differentiation In addition to the nature of the transcribed protein, the efficiency of translation seems to be tightly controlled. ...translation initiation represent a layer of regulation of protein expression in myogenesis for specific subsets of functionally correlated genes. Cellular processes controlled by selective mRNA translation in myogenesis ...a percentage of footprints derived from non-coding transcripts. Whether they lead to active translation is still debated,... These changes are highly reproducible between replicates, they are cell specific and tightly controlled during differentiation and therefore they likely represent a regulatory mechanism with relevance for muscle differentiation. The mechanisms regulating alternative TISs usage in myogenesis remain to be investigated. Previous studies have shown that proteins involved in the translation machinery are autoregulated and their synthesis is mainly controlled at the level of translation. Due to the many regulatory potential of uORFs, a full understanding of the translational control of these genes may be relevant for clinical purposes. The contribution of mRNA translation in myogenesis ...we also observed a dampening effect of translational regulation. The causes of this dampening effect remain to be elucidated. Translation can be regulated by many different mechanisms. ...the transcription of genes from distinct promoters, and the translation initiation from distinct start codons, seem to be two complementary mechanisms to control gene and protein expression in myogenesis. Our analysis might therefore underestimate the number of alternative TSSs which are in very close proximity and therefore overestimate the number of switches in TIS usage exclusively dependent on the translational control. It remains to be investigated to which extent this phenomenon may alter our results. ...suggesting a likely stronger regulatory potential. http://nar.oxfordjournals.org/content/early/2015/04/14/nar.gkv281.full
Let’s look forward, with much anticipation, to reading future research reports shedding more light on this important subject.Dionisio_{April 27, 2015
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The Extreme Anterior Domain Is an Essential Craniofacial Organizer Acting through Kinin-Kallikrein Signaling DOI: http://dx.doi.org/10.1016/j.celrep.2014.06.026 http://www.cell.com/cell-reports/fulltext/S2211-1247(14)00495-1 the mechanisms that direct the cranial NC into the face primordium, and the identity of localized guidance signals that facilitate this migration are not known. ...the embryonic pathway in Xenopus functions through a signaling sequence similar to that described for the adult mammalian pathway, and conservation is present in zebrafish. ...nitric oxide (NO) production is an outcome of the pathway and is necessary for mouth and neural crest (NC) development. ...the extreme anterior domain (EAD) functions as a craniofacial organizer and facilitates migration of first arch cranial NC into the face via Kinin-Kallikrein signaling. These findings add insight into localized signaling essential for craniofacial development. ...suggesting that different downstream receptors or alternate forms of peptide processing may be available to the NC. The demonstration that the EAD is necessary for migration of the first arch NC into the facial region addresses the long-standing question of what region might guide the migratory cranial NC into the face. ...but identify cpn locally expressed in the EAD as required for NC ingress, possibly through processing of Kng-derived peptides. ...highlighting complex spatiotemporal requirements for Kinin-Kallikrein signaling during NC development. ...suggesting that the Kinin-Kallikrein pathway may indirectly regulate mouth opening through the NC. ...raising the question of whether activity of this pathway during craniofacial development is conserved. It is also possible that redundant genes or another pathway such as endothelin signaling work together with Kinin-Kallikrein signaling. ...important future directions, including mechanistic studies addressing a putative NC guidance function for xBdk and other EAD-derived activities, and the relationship between NC migration and mouth formation. http://www.cell.com/cell-reports/fulltext/S2211-1247(14)00495-1
Let’s look forward, with much anticipation, to reading future research reports shedding more light on this important subject.Dionisio_{April 27, 2015
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Embryonic blood-cerebrospinal fluid barrier formation and function doi: 10.3389/fnins.2014.00343 Just as most civilizations develop along riverbanks and seashores, using the fluid medium that is immediately available to them to promote cohesion and transport, and to enhance the chances of survival of the people who live at the edge of the liquid medium, so the brain is also organized, from its embryonic beginnings and throughout adult life, around an extraordinarily dynamic, and complex fluid: the CSF. Continuing this simile, as civilizations build harbors from which to ship goods and control transport that becomes ever more complex as they develop, so the brain has evolved barrier mechanisms, which start to form very early in brain development and change their morphology and physiology in accordance with the changing developmental stages. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211391/
Really? How?Dionisio_{April 26, 2015
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Totally Tubular: The Mystery behind Function and Origin of the Brain Ventricular System doi: 10.1002/bies.200800207 Laura Anne Lowery and Hazel Siva A unique feature of the vertebrate brain is the brain ventricular system, a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. While CSF is critical for both adult brain function and embryonic brain development, neither development nor function of the brain ventricular system is fully understood. In this review, we discuss the mystery of why vertebrate brains have ventricles, and whence they originate. Neither development nor function of the vertebrate brain ventricular system is fully understood in any animal system, and a long list of unanswered questions remains. One significant future challenge is to understand the molecular connection between brain patterning and brain morphogenesis, including ventricle shaping. The precise role of epithelial junctional complexes and the ECM during brain morphogenesis and ventricle formation remain unclear. The connection between cell proliferation and brain morphogenesis is also not understood. The extent to which eCSF governs neuroepithelial fate remains an area of key interest. What is the role of eCSF flow and pressure? What are the roles of the many factors in the eCSF? Does the eCSF primarily govern cell division/proliferation in the brain, or is its primary role to direct formation of specific neuronal or glial subtypes? http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003255/
We want those questions answered ASAP, don't we? Perhaps some of them are already answered by NW, since the paper is kind of old (2009?). Sorry, no time left for OOL discussions. :)Dionisio_{April 26, 2015
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Co-regulation of translation in protein complexes Marlena Siwiak and Piotr Zielenkiewicz doi:10.1186/s13062-015-0048-7 Co-regulation of gene expression has been known for many years, and studied widely both globally and for individual genes. Nevertheless, most analyses concerned transcriptional control, which in case of physically interacting proteins and protein complex subunits may be of secondary importance. In case of translational co-regulation, however, there is still much to be discovered. This research is the first quantitative analysis that provides global-scale evidence for translation co-regulation among associated proteins. [...]the phenomenon of translational co-regulation applies to the variety of living organisms and concerns many complex constituents. [...]translational regulation of a protein should always be studied with respect to the expression of its primary interacting partners. Apparently the main purpose of translational co-regulation is to prevent waste of resources during synthesis of building blocks of stoichiometric complexes and guarantee their on time production http://www.biologydirect.com/content/10/1/18
Let’s look forward, with much anticipation, to reading future research reports shedding more light on this important subject.Dionisio_{April 26, 2015
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Outstanding development questions? This was said 4 years ago in official lectures at a very prestigious educational institution by a scientific authority in the given subject. This is serious stuff. However, maybe by now some (or all) of those raised questions have been answered? Research is advancing fast these days, hence recent discoveries could have resolved the issues presented in these two video lectures? Please, note that the below indicated time marks may not be exact, therefore start a little earlier and keep listening until the professor changes the subject and moves on to the next topic. You may just listen to the marked comments. Each takes just a couple of minutes or less. Enjoy it! Development 1:
@23:00 @23:21 beginning of life? @23:31 magically get together? @23:51 zygote - magical single cell? @24:00 two dying cells…? @43:00 how this works is not well understood, it's complex? https://www.youtube.com/embed/BK1afo-GMag
Development 2:
@21:11 still not known how the kidney gets built? There’s no organ where we can say “these are all the steps to build it. it's incredibly complex? @24:20 this is an engineering problem? @25:01 it's really amazing? @30:15 a student asked how do cells know where to go? The lecturer's answer is interesting. She mentions possible plans, instructions, somehow somewhere they unfold as organs are built, but she concludes it's really a fascinating question? https://www.youtube.com/embed/080BGpawP3I
Dionisio_{April 26, 2015
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Amazing orchestration: “Embryonic development has its own tempo—from the thumping rock beat of early cell division to something more like modern minimalism, where you have cells working together while still doing their own thing, making the music more melodious and complex. Finally, as nerves start working and sending impulses, it moves to something more syncopated and rhythmic.” Professor Hazel Sive, MIT. http://ocw.mit.edu/faculty/hazel-sive/
Dionisio_{April 25, 2015
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Toll-like receptor activation in immunity vs. tolerance doi: 10.3389/fimmu.2015.00146 After the discovery of Toll-like receptors (TLR) in the late 1990s, initial investigations were focused on understanding their role, stimulating immune responses against infectious agents. The mechanisms that underlie the immune regulatory properties of TLRs are not well understood. http://journal.frontiersin.org/article/10.3389/fimmu.2015.00146/full
Let's look forward, with much anticipation, to reading future research reports shedding more light on this important subject.Dionisio_{April 25, 2015
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Toll-like receptor mediated regulation of cancer: a case of mixed blessings doi: 10.3389/fimmu.2014.00224 Discovery of the role of TLRs in cancer biology have paved the way for development of new therapies targeting TLRs. There is a lot of interest to study the relation between inflammation and cancer as it has been termed as the seventh hallmark of cancer. TLRs play an important role in inflammation mediated cancers as well as cancer related inflammation. Activation of TLRs for therapy may be an exciting proposition, but one has to be careful as over activation of TLRs can also lead to development of tumors (Figure 1). Thus, regulatory mechanisms should also be taken into account before using TLRs for cancer therapy. Furthermore, molecular and genetic analysis of breast cancer sub-types should be considered before deciding the course of therapy with TLRs. There are some reports on the role of genetic polymorphisms in TLRs in the outcome of breast cancer therapy. More studies need to be conducted to determine whether the loss or gain of function polymorphisms in TLRs is an indicator of disease outcome or therapy. http://journal.frontiersin.org/article/10.3389/fimmu.2014.00224/full
Dionisio_{April 25, 2015
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Transcriptional and epigenetic networks of helper T and innate lymphoid cells DOI: 10.1111/imr.12208 The discovery of the specification of CD4+ helper T cells to discrete effector ‘lineages’ represented a watershed event in conceptualizing mechanisms of host defense and immunoregulation. However, our appreciation for the actual complexity of helper T-cell subsets continues unabated. Just as the Sami language of Scandinavia has 1000 different words for reindeer, immunologists recognize the range of fates available for a CD4+ T cell is numerous and may be underestimated. Added to the crowded scene for helper T-cell subsets is the continuously growing family of innate lymphoid cells (ILCs), endowed with common effector responses and the previously defined ‘master regulators’ for CD4+ helper T-cell subsets are also shared by ILC subsets. Within the context of this extraordinary complexity are concomitant advances in the understanding of transcriptomes and epigenomes. So what do terms like ‘lineage commitment’ and helper T-cell ‘specification’ mean in the early 21st century? How do we put all of this together in a coherent conceptual framework? It would be arrogant to assume that we have a sophisticated enough understanding to seriously answer these questions. Instead, we review the current status of the flexibility of helper T-cell responses in relation to their genetic regulatory networks and epigenetic landscapes. Recent data have provided major surprises as to what master regulators can or cannot do, how they interact with other transcription factors and impact global genome-wide changes, and how all these factors come together to influence helper cell function. http://onlinelibrary.wiley.com/doi/10.1111/imr.12208/abstract
Dionisio_{April 24, 2015
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