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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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Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein Stephan Heermann, Lucas Schütz, Steffen Lemke, Kerstin Krieglstein, Joachim Wittbrodt DOI: http://dx.doi.org/10.7554/eLife.05216 eLife 2015;4:e05216 http://elifesciences.org/content/4/e05216.full
The hemispheric, bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations. This cannot be explained by the classical view of eye development. Strikingly, and in contrast to the former model [...] This new perspective on optic cup formation raises the question of how [...] [...] forces established outside the neuroretina are likely to drive the flow [...] We speculate that this tissue contributes to the flow by changing its shape from a columnar to a flat epithelium, massively enlarging its surface. This remains an interesting point, in particular given that epithelial flow is maintained even if cell proliferation is inhibited in both neuroretina and RPE.
As outstanding questions get answered, new questions are raised. Complexity gets more complex. :) Unending Revelation of the Ultimate Reality.Dionisio
July 28, 2015
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Cell cycle gene expression networks discovered using systems biology: Significance in carcinogenesis Robert E. Scott, Prachi N. Ghule, Janet L. Stein and Gary S. Stein DOI: 10.1002/jcp.24990 http://onlinelibrary.wiley.com/doi/10.1002/jcp.24990/abstract Journal of Cellular Physiology Volume 230, Issue 10, pages 2533–2542, October 2015Dionisio
July 27, 2015
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The human genome of almost three billion nucleotides contains the complete instruction for generating over 100 billion neurons and 150 trillion synapses [...] Despite tremendous cellular heterogeneity and functional complexity, our genome encompasses only approximately 20,000 protein-coding genes [...] However, alternative splicing and use of alternate promoters can produce unique gene expression patterns associated with fate determination and cell-type specific functions [...] Furthermore, the non-protein-coding genomic DNA [the so-called “junk DNA”] is increasingly being recognized as an important “regulator” of the coding information.
http://www.sciencedirect.com/science/article/pii/S1350946215000063 Vision from next generation sequencing: Multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease Hyun-Jin Yang, Rinki Ratnapriya, Tiziana Cogliati, Jung-Woong Kim, Anand Swaroop Progress in Retinal and Eye Research Volume 46, May 2015, Pages 1–30
Fascinating...Dionisio
July 27, 2015
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The vertebrate retina is composed of six major neuronal cell types that are organized in three cellular layers forming exquisite neuronal circuits for detection of visual information. Light is captured by photoreceptors; visual signals then undergo enhancement, integration and processing through bipolar, horizontal and amacrine cells and by varied usage of parallel synaptic circuits, before eventually being transmitted via ganglion cells to the brain.
http://www.sciencedirect.com/science/article/pii/S1350946215000063 Vision from next generation sequencing: Multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease Hyun-Jin Yang, Rinki Ratnapriya, Tiziana Cogliati, Jung-Woong Kim, Anand Swaroop Progress in Retinal and Eye Research Volume 46, May 2015, Pages 1–30
remarkable complexityDionisio
July 27, 2015
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Genomics and genetics have invaded all aspects of biology and medicine, opening uncharted territory for scientific exploration. The definition of “gene” itself has become ambiguous, and the central dogma is continuously being revised and expanded.
http://www.sciencedirect.com/science/article/pii/S1350946215000063 Vision from next generation sequencing: Multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease Hyun-Jin Yang, Rinki Ratnapriya, Tiziana Cogliati, Jung-Woong Kim, Anand Swaroop Progress in Retinal and Eye Research Volume 46, May 2015, Pages 1–30
Oh, well, what else is new?Dionisio
July 26, 2015
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The overall complexity is getting more complex with some new discoveries. This is really exciting. :)Dionisio
July 26, 2015
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Early divergence of central and peripheral neural retina precursors during vertebrate eye development Sara J. Venters Takashi Mikawa, Jeanette Hyer DOI: 10.1002/dvdy.24218 http://onlinelibrary.wiley.com/doi/10.1002/dvdy.24218/full Developmental Dynamics Special Issue: Organogenesis Volume 244, Issue 3, pages 266–276, March 2015
Although these studies hint at some segregation of cells that incorporate into specific optic vesicle positions, a more comprehensive study is needed to determine differences in central and peripheral retina derivation at such early stages. As yet, it is not clear if this difference marks an inherent difference in potentiality or a restriction/gain of potential with maturation of the two precursor populations. Potentiality and lineage studies in the eye-forming regions of the blastoderm give some insight that such differences may arise early in development, but further experimentation with newer molecular tools is needed to resolve when the different progenitors are established. The mature eye comprises several tissues that progressively resolve with development. Little information is available regarding lineage relationships between mature optic cup tissues and the mechanisms that couple fate commitment to eye morphogenesis. A combination of molecular and direct lineage analyses highlight differences between how we demark tissue precursor populations of the eye and mechanistic models of normal eye morphogenesis. Refinement of our understanding of eye development and how it underlies domain-specific eye diseases and developmental disorders requires amalgamation of knowledge mined with such complimentary tools.
Outstanding questions answered, new questions raised.Dionisio
July 25, 2015
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Seeing the Unseen: Cell Strain and Mechanosensing Michael P. Duffy, Christopher R. Jacobs DOI: http://dx.doi.org/10.1016/j.bpj.2015.03.008 Volume 108, Issue 7, p1583–1584, 7 April 2015 http://www.cell.com/biophysj/abstract/S0006-3495(15)00239-8
Maintenance of healthy bone is a result of a complex and not fully understood process; mechanical loading is a critical signal in bone metabolism, but a clear understanding of its influence remains elusive, particularly because visualizing cells in their native environment during loading is challenging.
Outstanding questions answered, new questions raised.Dionisio
July 25, 2015
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A guide to mechanobiology: Where biology and physics meet Karin A. Jansen, Dominique M. Donato, Hayri E. Balcioglu, Thomas Schmidt, Erik H.J. Danen, Gijsje H. Koenderinka Biochimica et Biophysica Acta (BBA) - Molecular Cell Research doi:10.1016/j.bbamcr.2015.05.007 http://www.sciencedirect.com/science/article/pii/S0167488915001536
Cells actively sense and process mechanical information that is provided by the extracellular environment to make decisions about growth, motility and differentiation.
"sense and process information to make decisions"? What criteria are those decisions based on?Dionisio
July 25, 2015
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LTR retrotransposons, handy hitchhikers of plant regulation and stress response Marie-Angèle Grandbastien Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms Volume 1849, Issue 4, April 2015, Pages 403–416 doi:10.1016/j.bbagrm.2014.07.017 http://www.sciencedirect.com/science/article/pii/S1874939914002053
LTR retrotransposons are major components of plant genomes. They are regulated by a diverse array of external stresses and tissue culture conditions, displaying finely tuned responses to these stimuli, mostly in the form of upregulation. [...] complex and highly coordinated responses to external challenges.
Dionisio
July 25, 2015
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Retrotransposons in pluripotent cells: Impact and new roles in cellular plasticity Angela Macia, Eva Blanco-Jimenez, José L. García-Pérez Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms Volume 1849, Issue 4, April 2015, Pages 417–426 doi:10.1016/j.bbagrm.2014.07.007 http://www.sciencedirect.com/science/article/pii/S1874939914001953
[...] recent findings suggest that the main proportion of fixed non-mobile transposable elements might also have emerging roles in cellular plasticity.
Dionisio
July 25, 2015
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Stress induces cell dedifferentiation in plants Gideon Grafi, Simon Barak Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms Volume 1849, Issue 4, April 2015, Pages 378–384 doi:10.1016/j.bbagrm.2014.07.015 http://www.sciencedirect.com/science/article/pii/S187493991400203X
It appears that stress is perceived as a signal that directs plant cells to undergo reprogramming (dedifferentiation) as a means for adaptation and in preparation for a stimulus-based acquisition of a new cell fate.
Cool! Isn't it?Dionisio
July 25, 2015
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Stress as a fundamental theme in cell plasticity Ofer Shoshani, Dov Zipori Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms Volume 1849, Issue 4, April 2015, Pages 371–377 doi:10.1016/j.bbagrm.2014.07.006 http://www.sciencedirect.com/science/article/pii/S1874939914001941
It is proposed that cell stress, mechanistically sensed by isolation from neighboring cells, leads* to dedifferentiation, in an attempt to build a new stem cell reservoir for subsequent regeneration of the damaged tissue.
(*) why? how? attempt to build... for... ? Does the above quoted text imply some kind of intention, purpose?Dionisio
July 25, 2015
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Epigenetic regulation of smooth muscle cell plasticity ? Renjing Liua, b, Kristen L. Lesliec, Kathleen A. Martin doi:10.1016/j.bbagrm.2014.06.004 http://www.sciencedirect.com/science/article/pii/S1874939914001564m
Smooth muscle cells (SMC) are the major cell type in blood vessels. While there have been major advances in our understanding of SMC plasticity through the identification of growth factors and signals that can influence the SMC phenotype, how these regulate SMC plasticity remains unknown.
Dionisio
July 24, 2015
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Identification of rare variants in Alzheimer’s disease Front. Genet., http://dx.doi.org/10.3389/fgene.2014.00369 Jenny Lord1, Alexander J. Lu1 and Carlos Cruchaga1,2* http://journal.frontiersin.org/article/10.3389/fgene.2014.00369/full [...] a large proportion of the genetic component of the disorder remains unexplained. Recent evidence from the AD field, as with other complex diseases, suggests a large proportion of this “missing heritability” may be due to rare variants of moderate to large effect size, but the methodologies to detect such variants are still in their infancy. [...] with our current limited knowledge of the etiology of the disease, the appropriate targets and interventions remain unclear.
Dionisio
July 24, 2015
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Epigenetic regulation of cardiac myocyte differentiation† Front. Genet., http://dx.doi.org/10.3389/fgene.2014.00375 Kyohei Oyama, Danny El-Nachef, Yiqiang Zhang, Patima Sdek and W. Robb MacLellan http://journal.frontiersin.org/article/10.3389/fgene.2014.00375/full
Commitment to a particular lineage requires both the repression of unnecessary genes while simultaneously up-regulating lineage-specific genes. Although increasing evidence suggests crucial roles of epigenetic modifying proteins and epigenetic marks, their specific function in cardiac lineage commitment and differentiation as well as their orchestrating mechanisms still remain to be elucidated.
Dionisio
July 22, 2015
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Neuroprotective Effects of Protocatechuic Aldehyde against Neurotoxin-Induced Cellular and Animal Models of Parkinson’s Disease Xin Zhao, Shenyu Zhai, Ming-Sheng An, Yue-Hua Wang, Ying-Fan Yang, Hui-Qi Ge, Jin-Hao Liu, Xiao-Ping Pu PLOS •DOI: 10.1371/journal.pone.0078220 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078220
At present, PD drug treatment strategies are still not satisfactory. Therefore, there is still an urgent need for new drugs for PD therapy, and particularly for drugs with neuroprotective effects. Protocatechuic aldehyde (PAL). PAL is also an important compound in pharmaceutical preparations containing the roots of Salvia miltiorrhiza. [...] further studies are needed to investigate the detailed molecular mechanisms underlying the neuroprotective effects of PAL.
Interesting report.Dionisio
July 21, 2015
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Interactions between MSCs and Immune Cells: Implications for Bone Healing Tracy K. Kovach, Abhijit S. Dighe, Peter I. Lobo, and Quanjun Cui Journal of Immunology Research Volume 2015 (2015), Article ID 752510, 17 pages http://dx.doi.org/10.1155/2015/752510 http://www.hindawi.com/journals/jir/2015/752510/
The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. [...] it appears that a well-controlled, delicate balance of inflammatory factors is necessary for proper fracture repair. The role of various immune cells and their subtypes in bone healing is complex and not completely understood. Therefore, thorough understanding of the immune cells control of fracture healing and precise ways to control the immune cells will be necessary when modulating the inflammatory response as potential new therapy for bone tissue engineering. MSCs can be effectively used for this purpose since they possess abilities to modulate immune cells differentiation and functions in specific microenvironments.
Very promising research.Dionisio
July 21, 2015
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Low?dose TNF augments fracture healing in normal and osteoporotic bone by up?regulating the innate immune response James K Chan, Graeme E Glass, Adel Ersek, Andrew Freidin, Garry A Williams, Kate Gowers, Ana I Espirito Santo, Rosemary Jeffery, William R Otto, Richard Poulsom, Marc Feldmann, Sara M Rankin, Nicole J Horwood, Jagdeep Nanchahal DOI 10.15252/emmm.201404487 | Published online 14.03.2015 EMBO Molecular Medicine (2015) 7, 547-561 http://embomolmed.embopress.org/content/7/5/547
The mechanism by which trauma initiates healing remains unclear. The ideal biological therapy for accelerating fracture healing would entail local administration of pro?osteogenic factor(s) at the time of surgical treatment. Therefore, it is critical to understand how the early inflammatory response initiates and orchestrates fracture repair, an area that remains poorly understood. Therefore, there is a critical balance to ensure an optimal healing environment. It is currently unknown how early inflammation initiates the process of fracture healing. Studies of early fracture hematoma by other groups have shown that the inflammatory phase following fracture is critical to recruit cells and orchestrate the events necessary for fracture healing. Fracture repair involves a complex cascade of events involving numerous cell types and the spatially and temporally coordinated release of multiple factors. While these studies support the importance of the early inflammatory events in determining the final outcome of fracture healing, the precise cells and cytokines involved remain unclear. While neutrophils have traditionally been regarded as professional phagocytes which clear debris and bacterial pathogens and delay healing, evidence is emerging to support a much wider role in orchestrating downstream events. [...] the role of neutrophils in bone healing is currently poorly understood. [...] the role of early neutrophil?derived TNF in the inflammatory response is unknown. [...] how the prevailing cytokine environment affects the osteogenic activity of “osteomacs” remains to be elucidated. This study has a number of limitations. By systematically unraveling the initial events in the fracture?healing pathway, we have identified the potential of enhancing the early innate immune response following fracture to augment fracture repair.
Very encouraging discoveries.Dionisio
July 21, 2015
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Outstanding questions
How is the differential expression of an mRNA species regulated in neuronal subtypes and brain regions? While our understanding of localization elements and their interaction with RBPs and motors describes how distinct mRNAs have contrasting localization, it is unexplained how the same mRNA exhibits divergent localization patterns depending on its context. What is the minimal cis-acting RNA sequence that determines RNA transport into dendrites and/or axons? Methodical identification of the targeting and minimal targeting elements of neuronal genes will certainly reveal conserved sequences and axioms that target mRNAs into dendrites and axons. Many questions remain regarding the molecular composition of mRNPs and which proteins play roles in regulating the unique localization of individual mRNAs. These include: What are the adaptor proteins that recruit motor proteins to mRNP complexes in neurons? How specific are RBPs to one type of mRNA? Are there neuron-specific RBPs or proteins that generate unique mRNA behavior in neurons such as docking at synapses or long-distance trans-port? Enhancing our understanding of mRNP identity and function will lead to understanding how localization is determined. How are mRNPs recognized and captured at the activated dendritic regions or synapses? Identification of synaptic tags that lead to the capture of mRNAs and proteins following synaptic activity and to consolidation and memory formation will be transformative for our understanding of how local translation is directed to stimulated synapses or regions. While dendritic mRNAs may dock at spines, how do mRNAs behave in axons? Although mRNAs have long been established to localize to dendrites as well as the axons of certain types of neurons, information regarding the latter compartment has been subject to scrutiny due to claims of non-axonal mRNA contamination obfuscating legitimate axonally localized mRNAs. Notwithstanding this, there remains a great deal of opportunity to observe how mRNAs behave in axons using single-molecule technologies. Optical techniques such as single-molecule FISH and live tracking may reveal that mRNAs that have been previously characterized in dendrites behave in a different manner in axons. The unipolar microtubule orientation in axons may inhibit retrograde mRNA movements, which will be evident on live observations of the same mRNA species in both types of neuronal process. How do the transport kinetics of different mRNAs with different functions compare with those of well-characterized mRNAs such as b-actin and Arc? Although thousands of mRNAs are known to be transported into neuronal dendrites, very little is known about how and why different mRNAs respond differently to the same stimuli and why different mRNAs are regulated either at the level of their transcriptional or translational activity or in their positioning in the neuron. Live imaging and tracking of diverse mRNAs will demonstrate the unique and convergent transport mechanisms of mRNAs and perhaps expose regulatory mechanisms of transport that conform to the unique function of the mRNA being observed.
Single-molecule insights into mRNA dynamics in neurons Adina R. Buxbaum, Young J. Yoon, Robert H. Singer, Hye Yoon Park doi:10.1016/j.tcb.2015.05.005 http://www.sciencedirect.com/science/article/pii/S0962892415000951 http://www.einstein.yu.edu/uploadedfiles/labs/robert-singer-lab/SL150A.pdf
A few outstanding questions remain unanswered. Work in progress... stay tuned.Dionisio
July 20, 2015
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Single-molecule insights into mRNA dynamics in neurons Adina R. Buxbaum, Young J. Yoon, Robert H. Singer, Hye Yoon Park doi:10.1016/j.tcb.2015.05.005 http://www.sciencedirect.com/science/article/pii/S0962892415000951 www.einstein.yu.edu/uploadedfiles/labs/robert-singer-lab/SL150A.pdf
Dionisio
July 20, 2015
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[...] much like learning, new ideas and challenges to old conceptions can reinvigorate and improve the educational experience for teachers and students. Princeton enhances its brand as an institution that values "teaching as scholarship and the use of evidence-based science teaching methods,"
Summer institute encourages university educators to engage students in science Courtesy of Princeton University Office of Communications | By Morgan Kelly http://molbio.princeton.edu/news/other/908-summer-institute-encourages-university-educators-to-engage-students-in-science
Dionisio
July 20, 2015
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A time space translation hypothesis for vertebrate axial patterning A.J. Durston, K. Zhu doi:10.1016/j.semcdb.2015.06.001 How vertebrates generate their anterior–posterior axis is a >90-year-old unsolved problem. [...] a time space translation mechanism underlies initial axial patterning in the trunk part of the axis. [...] a timer in the gastrula's non organiser mesoderm (NOM) undergoes sequential timed interactions with the Spemann organiser (SO) during gastrulation to generate the spatial axial pattern. [...] this mechanism works via Hox collinearity and [...] it requires Hox functionality. The NOM timer is putatively Hox temporal collinearity. This generates a spatially collinear axial Hox pattern in the emerging dorsal central nervous system and dorsal paraxial mesoderm. The interactions with the organiser are mediated by a BMP–anti BMP dependent mechanism. Strengths and weaknesses, questions, uncertainties and holes in the evidence are identified. Future directions are indicated.
Work in progress... stay tuned.Dionisio
July 19, 2015
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Time, space and the vertebrate body axis A.J. Durston doi:10.1016/j.semcdb.2015.05.005 Anterior–posterior (A–P) patterning of the vertebrate main body axis regulated by timing. [and what regulates the timing?] Anterior structures are specified early, posterior late. (1) Timing involves timed decision points [...] It also involves complex timers, where large parts of the axis are patterned sequentially by a common upstream mechanism [...] http://www.sciencedirect.com/science/article/pii/S1084952115001020
A few issues remain unresolved. Timing involves timed decision points ? What criteria are those "timed" decisions based on? How exactly is that done? Outstanding questions answered, new questions raised. Work in progress... stay tuned.Dionisio
July 19, 2015
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Spatial and temporal aspects of Wnt signaling and planar cell polarity during vertebrate embryonic development Sergei Y. Sokol doi:10.1016/j.semcdb.2015.05.002 Wnt signaling pathways act at multiple locations and developmental stages to specify cell fate and polarity in vertebrate embryos. A long-standing question is how the same molecular machinery can be reused to produce different outcomes. The canonical Wnt/?-catenin branch modulates target gene transcription to specify cell fates along the dorsoventral and anteroposterior embryonic axes. By contrast, the Wnt/planar cell polarity (PCP) branch is responsible for cell polarization along main body axes, which coordinates morphogenetic cell behaviors during gastrulation and neurulation. Whereas both cell fate and cell polarity are modulated by spatially- and temporally-restricted Wnt activity, the downstream signaling mechanisms are very diverse. http://www.sciencedirect.com/science/article/pii/S1084952115000993
Dionisio
July 19, 2015
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Planar polarization of Vangl2 in the vertebrate neural plate is controlled by Wnt and Myosin II signaling Olga Ossipova, Kyeongmi Kim and Sergei Y. Sokol* doi: 10.1242/?bio.201511676 June 15, 2015 Biology Open 4, 722-730. The vertebrate neural tube forms as a result of complex morphogenetic movements, which require the functions of several core planar cell polarity (PCP) proteins, including Vangl2 and Prickle. Despite the importance of these proteins for neurulation, their subcellular localization and the mode of action have remained largely unknown. http://bio.biologists.org/content/4/6/722.full The mechanistic connection between AP-PCP and neural tube closure remains to be established. Additional studies are warranted to evaluate the molecular composition and the interactions between the anteroposterior and the mediolateral PCP systems. [...] the effects of ROCK or Myosin II modulation on the localization of core PCP proteins have not been assessed. Future studies are needed to determine whether AP-PCP reflects the conservation of Wnt signaling activity along the anteroposterior body axis in different models.
Work in progress... stay tuned.Dionisio
July 18, 2015
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Genetic, Epigenetic, and Environmental Contributions to Neural Tube Closure Annual Review of Genetics Vol. 48: 583-611 DOI: 10.1146/annurev-genet-120213-092208 The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and adhere to close the neural tube. The neural ectoderm and surrounding tissues also coordinate proliferation, differentiation, and patterning. This highly orchestrated process is susceptible to disruption, leading to neural tube defects (NTDs), a common birth defect. http://www.annualreviews.org/doi/abs/10.1146/annurev-genet-120213-092208
Dionisio
July 18, 2015
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Sox2 transcription network acts as a molecular switch to regulate properties of neural stem cells Koji Shimozaki. World J Stem Cells. 6(4): 485-490. doi: 10.4252/wjsc.v6.i4.485. Neural stem cells (NSCs) contribute to ontogeny by producing neurons at the appropriate time and location. Neurogenesis from NSCs is also involved in various biological functions in adults. Thus, NSCs continue to exert their effects throughout the lifespan of the organism. The mechanism regulating the core functional properties of NSCs is governed by intra- and extracellular signals. Among the transcription factors that serve as molecular switches, Sox2 is considered a key factor in NSCs. Sox2 forms a core network with partner factors, thereby functioning as a molecular switch. [...] many questions remain unanswered regarding the Sox2-based self-renewal mechanism and the regulatory mechanism underlying multipotency. Further research [...] is needed to explore functions of Sox2, its partner factors, and chromatin-regulating factors that interact with Sox2 and its partner factors as well as to identify the entire panel of Sox2 target genes. http://www.wjgnet.com/1948-0210/full/v6/i4/485.htm
Snapshot of a small part of an amazing system. A few questions remain unanswered. Work in progress... stay tuned.Dionisio
July 18, 2015
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Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices Nikolce Gjorevski, Alexandra S. Piotrowski, Victor D. Varner & Celeste M. Nelson Scientific Reports 5, Article number: 11458 doi:10.1038/srep11458 http://www.nature.com/srep/2015/150713/srep11458/full/srep11458.html Collective cell migration drives tissue remodeling during development, wound repair, and metastatic invasion. The physical mechanisms by which cells move cohesively through dense three-dimensional (3D) extracellular matrix (ECM) remain incompletely understood. Despite evidence showing that Rho-mediated contractions are required for collagen remodeling, it is unclear how matrix alignment is restricted to the leading edge of a globally contracting tissue. Comprehensive understanding of the differences between collective cell movement during morphogenesis and cancer progression will require dynamic spatiotemporal mapping of the force fields and matrix remodeling associated with the two types of processes in vivo.
Work in progress... stay tuned. As new discoveries shed more light on the elaborate molecular and cellular choreographies orchestrated within the biological systems, outstanding questions get answered, new questions are raised, the complexity turns more complex.Dionisio
July 16, 2015
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Gap geometry dictates epithelial closure efficiency Andrea Ravasio, Ibrahim Cheddadi, Tianchi Chen, Telmo Pereira, Hui Ting Ong, Cristina Bertocchi, Agusti Brugues, Antonio Jacinto, Alexandre J. Kabla, Yusuke Toyama, Xavier Trepat, Nir Gov, Luís Neves de Almeida & Benoit Ladoux Nature Communications 6, Article number: 7683 doi:10.1038/ncomms8683 http://www.nature.com/ncomms/2015/150709/ncomms8683/full/ncomms8683.html To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. [...] actin structures at the base of lamellipodia crawling and purse-string constriction seem to be antagonistic through a mechanism controlled by Rho and Rac. However, in our experiments, we observe the coexistence of such structures, suggesting for a regulatory mechanism, which unfortunately remains elusive at this point.
Some outstanding questions answered, new questions are raised.Dionisio
July 15, 2015
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