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

Invaginations in the membranes of embryonic cells appear to orient cell division in sea squirts.
Cellular fingers take hold Yukiko M Yamashita eLife. 2016; 5: e19405. doi: 10.7554/eLife.19405

Dionisio_{October 1, 2016
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Development of the air sac primordium requires components of the PCP system Dpp and FGF signaling requires Prickle and Van Gogh The constitution of the ECM is dependent on prickle and Van Gogh Dpp signaling depends on dally but FGF signaling depends on dlp Cytonemes navigate in a stratified ECM Cytoneme-mediated signaling requires integrin function
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Huang H1, Kornberg TB Elife. ;5. pii: e18979. doi: 10.7554/eLife.18979.

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gpuccio: Glad to see your insightful comments here again! Thank you! What you stated @2054 is highly interesting indeed. That's a very good observation. Yes, agree with you that the referred paper definitely seems like a research jewel. Please, keep reviewing the references and let us know if you spot another 'juicy' paper here. Since professor L.M. of the U. of T. in Canada decided not to share his profound knowledge about how exactly morphogenesis occurs, I have no option but to search the available literature myself. :) But this is not easy for me at all. It would have been much nicer to have someone explain this complex complexity to the rest of us, right? But he said I don't ask honest questions, whatever that means. :) That's why I appreciate so much your very insightful comments on the referenced papers.Dionisio_{October 1, 2016
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[...] secreted signaling proteins and signaling protein receptors are not distributed in the extracellular environment and are not bound to the ECM, but rather that the cytonemes that mediate Dpp and FGF signaling contact the ECM directly in ways that involve both integrins and specific HSPG interactions.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Huang H1, Kornberg TB Elife. ;5. pii: e18979. doi: 10.7554/eLife.18979.

Complex complexity.Dionisio_{October 1, 2016
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[...] the extracellular space is organized and regulated [...] [...] the extracellular matrix is essential for developmental signaling. [...] it is not known whether the cells between the producing and receiving cells (henceforth called 'intermediate cells') also contribute to cytoneme-mediated signaling.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Huang H1, Kornberg TB Elife. ;5. pii: e18979. doi: 10.7554/eLife.18979.

Dionisio_{October 1, 2016
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The language of development has a small vocabulary of signaling proteins that consists in part of Fibroblast growth factor (FGF) and Bone morphogenic proteins such as Drosophila Decapentaplegic (Dpp). This language may be used in most or all metazoan organs.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Huang H1, Kornberg TB Elife. ;5. pii: e18979. doi: 10.7554/eLife.18979.

Did anybody say language ? Another language ? Wasn't the language in the genome? How many languages do the biological systems speak? Are they multilingual? Complex complexity. :) Emphasis mine.Dionisio_{October 1, 2016
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Dionisio: Thank you for your continuing work! You really point to important and very interesting papers from the literature. :) I was specially impressed by this one: "Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration" The idea that similar electro-biological levels of control could be responsible for both cellular development in metazoa and information processing in the brain is new and stimulating. And the idea that epigenetic information can be stored as some electrical pattern in cells and tissues is really promising. I repost here the abstract, in case someone else can be interested:
A key problem in evolutionary developmental biology is identifying the sources of instructive information that determine species-specific anatomical pattern. Understanding the inputs to large scale morphology is also crucial for efforts to manipulate pattern formation in regenerative medicine and synthetic bioengineering. Recent studies have revealed a physiological system of communication among cells that regulates pattern during embryogenesis and regeneration in vertebrate and invertebrate models. Somatic tissues form networks using the same ion channels, electrical synapses, and neurotransmitter mechanisms exploited by the brain for information processing. Experimental manipulation of these circuits was recently shown to override genome default patterning outcomes, resulting in head shapes resembling those of other species in planaria and Xenopus. The ability to drastically alter macroscopic anatomy to that of other extant species, despite a wild-type genomic sequence, suggests exciting new approaches to the understanding and control of patterning. Here, we review these results and discuss hypotheses regarding nongenomic systems of instructive information that determine biological growth and form.
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Future challenges include understanding how the layers of the extracellular matrix form and how information is encoded in these layers for the cytonemes to decipher as they navigate to their targets.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Huang H1, Kornberg TB Elife. ;5. pii: e18979. doi: 10.7554/eLife.18979.

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The embryos of animals develop in a controlled manner that ensures that their tissues and organs form properly and at the right time. These processes depend on molecules called morphogens that are distributed throughout the embryo in specific ways and that are dispersed via extensions that protrude from the surfaces of cells. These extensions, called cytonemes, transport the morphogens across the distances that separate cells and transfer these molecules to target cells via direct contact. However, it was not known how cytonemes navigate to their targets. [...] cytonemes interact directly and specifically with proteins in the stratified ECM.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. Huang H1, Kornberg TB Elife. ;5. pii: e18979. doi: 10.7554/eLife.18979.

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[...] why are the zones arranged as concentric spheres? One answer may be that this has the potential to maximize the likelihood of diffused products arriving at their targets.
Functional Zonation of the Adult Mammalian Adrenal Cortex Gavin P. Vinson Front Neurosci. 2016; 10: 238. doi: 10.3389/fnins.2016.00238

Wow! Nature is so smart! :)Dionisio_{September 30, 2016
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[...] it more and more appears that the functions of the gland should be viewed as an integrated whole, greater than the sum of its component parts. The nature and significance of the zonation of the mammalian adrenal cortex has attracted considerable interest during the fifteen decades following the first description of its three main zones, zona glomerulosa, zona fasciculata, and zona reticularis, by Arnold (1866). Like the human body itself, the function of the adrenal gland is an integrated whole, much greater than the sum of its parts. We should aim to think of it that way.
Functional Zonation of the Adult Mammalian Adrenal Cortex Gavin P. Vinson Front Neurosci. 2016; 10: 238. doi: 10.3389/fnins.2016.00238

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The standard model of adrenocortical zonation holds that the three main zones, glomerulosa, fasciculata, and reticularis each have a distinct function, producing mineralocorticoids (in fact just aldosterone), glucocorticoids, and androgens respectively. Recent progress in understanding the development of the gland and the distribution of steroidogenic enzymes, trophic hormone receptors, and other factors suggests that this model needs refinement.
Functional Zonation of the Adult Mammalian Adrenal Cortex Gavin P. Vinson Front Neurosci. 2016; 10: 238. doi: 10.3389/fnins.2016.00238

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Morphogens are long-range signals thought to induce different cell behaviors in a concentration-dependent manner, but how such graded signals can be established in the face of noise and how they specify sharp boundaries of target gene expression remain unclear. [...] RA gradient persists during gastrulation and establishment of rhombomeres. [...] the fluctuations in RA levels that we observed in embryos are clearly biological in origin. [...] cells actively control the magnitude of noise in a signaling molecule in a multicellular system in vivo. [...] it seems likely that cells possess mechanisms to limit this noise propagation.
Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain Julian Sosnik,1,2,3 Likun Zheng,2,4 Christopher V Rackauckas,2,4 Michelle Digman,1,2,5 Enrico Gratton,1,2,5 Qing Nie,1,2,4 and Thomas F Schilling eLife. 2016; 5: e14034. doi: 10.7554/eLife.14034

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Morphogen gradients induce sharply defined domains of gene expression in a concentration-dependent manner, yet how cells interpret these signals in the face of spatial and temporal noise remains unclear. Animal cells need to be able to communicate with each other so that they can work together in tissues and organs. To do so, cells release signaling molecules that can move around within a tissue and be detected by receptors on other cells. A future challenge will be to see if similar retinoic acid gradients and noise control occur in other tissues, and if the noise has any positive role to play in development.
Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain Julian Sosnik,1,2,3 Likun Zheng,2,4 Christopher V Rackauckas,2,4 Michelle Digman,1,2,5 Enrico Gratton,1,2,5 Qing Nie,1,2,4 and Thomas F Schilling eLife. 2016; 5: e14034. doi: 10.7554/eLife.14034

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[...] it is possible that factors produced by other species living within a host organism's body can serve as an additional input to the organism's pattern by editing or altering its endogenous bioelectrical circuits This adds a layer of complexity to the typical “evo-devo” story [...] The list of the molecular signals that propagate through physiological networks is likely to grow rapidly in the following years. However, several players (current, calcium, neurotransmitters) are already implicated. The molecular and algorithmic analogies between how somatic tissues and the brain utilize these same components are a fertile area for novel inquiry, and remain to be tested in specific contexts.
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration Kelly G. Sullivan,† Maya Emmons-Bell,† and Michael Levin Commun Integr Biol. 9(4): e1192733. doi: 10.1080/19420889.2016.1192733

Dionisio_{September 29, 2016
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[...] the DNA specifies the hardware (the complement of channels, neurotransmitters, and GJ proteins), while the resulting bioelectric activity of these circuits (with spontaneous symmetry-breaking, self-organization, and other complex dynamics) is the software.
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration Kelly G. Sullivan,† Maya Emmons-Bell,† and Michael Levin Commun Integr Biol. 9(4): e1192733. doi: 10.1080/19420889.2016.1192733

How did we get that software?Dionisio_{September 29, 2016
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[...] bioelectric networks facilitate robustness of physiological states and the patterning they regulate (via negative feedback loops and long-range state sensing). Morphogenetic functions guided by bioelectric circuits are also robust to mutation in channels and their transcriptional regulation. bioelectric states as control points tend to be powerful “master regulators”, allowing the initiation of self-limiting patterning modules as subroutines from a low information content input (trigger); this is due to the existence of positive feedback loops, which sustain and amplify bioelectric states once a threshold has been surpassed by a transient bioelectric stimulus (exploited also by action potentials in brain circuits).
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration Kelly G. Sullivan,† Maya Emmons-Bell,† and Michael Levin Commun Integr Biol. 9(4): e1192733. doi: 10.1080/19420889.2016.1192733

Dionisio_{September 29, 2016
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The functional signaling properties of physiological networks are determined by the electrical activity, not the mere presence or absence of specific molecules. This implies a departure from the standard molecular biological paradigm, where cell state is thought to be derivable by proteomic and transcriptomic profiling. Bioelectric information can only be read out in the living state (not in fixed, biochemically-analyzed tissue).
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration Kelly G. Sullivan,† Maya Emmons-Bell,† and Michael Levin Commun Integr Biol. 9(4): e1192733. doi: 10.1080/19420889.2016.1192733

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[...] bioelectric circuits have their own unique and complex dynamics that derive from the fact that ion channels and GJs determine cell voltage but are also themselves regulated by voltage gradients. These feedback loops and the resulting electric circuit state transitions over time are not predictable from the rules governing genetic sequence, transcriptional networks, or chromatin state53 because channels and GJs open and close post-translationally, implementing functional signaling that is invisible to profiling at transcriptional or translational levels.
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration Kelly G. Sullivan,† Maya Emmons-Bell,† and Michael Levin Commun Integr Biol. 9(4): e1192733. doi: 10.1080/19420889.2016.1192733

Dionisio_{September 29, 2016
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Biological patterning is at the nexus of most of the important problems facing basic biology and biomedicine. Understanding the instructive signals that ensure self-assembly and maintenance of complex 3-dimensional morphology is crucial for basic evolutionary and developmental biology. How do cells, all derived from the same fertilized egg (the original stem cell) and bearing the same DNA, become not only differentiated into distinct cell types, but arranged into stereotypical spatial patterns with no external guidance? This question is at the center of understanding evolutionary change because development is what links genetics (upon which mutation acts) with form and function (upon which selection operates).
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration Kelly G. Sullivan,† Maya Emmons-Bell,† and Michael Levin Commun Integr Biol. 9(4): e1192733. doi: 10.1080/19420889.2016.1192733

Dionisio_{September 28, 2016
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A key problem in evolutionary developmental biology is identifying the sources of instructive information that determine species-specific anatomical pattern. Understanding the inputs to large-scale morphology is also crucial for efforts to manipulate pattern formation in regenerative medicine and synthetic bioengineering. Recent studies have revealed a physiological system of communication among cells that regulates pattern during embryogenesis and regeneration in vertebrate and invertebrate models. Somatic tissues form networks using the same ion channels, electrical synapses, and neurotransmitter mechanisms exploited by the brain for information-processing. Experimental manipulation of these circuits was recently shown to override genome default patterning outcomes, resulting in head shapes resembling those of other species in planaria and Xenopus. The ability to drastically alter macroscopic anatomy to that of other extant species, despite a wild-type genomic sequence, suggests exciting new approaches to the understanding and control of patterning. Here, we review these results and discuss hypotheses regarding non-genomic systems of instructive information that determine biological growth and form.
Physiological inputs regulate species-specific anatomy during embryogenesis and regeneration Kelly G. Sullivan,† Maya Emmons-Bell,† and Michael Levin Commun Integr Biol. 9(4): e1192733. doi: 10.1080/19420889.2016.1192733

Dionisio_{September 28, 2016
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The temporal components of different sensory, motor, cognitive and learning tasks often require different levels of accuracy, precision, flexibility (e.g. the time it takes to ‘reset’ a clock between tasks) and complexity (e.g. simple intervals or complex patterns). Whether or not STP and intrinsic dynamics of recurrent circuits account for timing in the subsecond range remains an open question. [...] the mechanisms underlying the diverse forms of temporal processing the brain performs remain to be elucidated [...]
Timing as an intrinsic property of neural networks: evidence from in vivo and in vitro experiments Anubhuti Goel and Dean V. Buonomano Philos Trans R Soc Lond B Biol Sci. 369(1637): 20120460. doi: 10.1098/rstb.2012.0460

Dionisio_{September 27, 2016
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[...] the human brain is exquisitely capable of processing temporal information and generating temporal patterns. Indeed, the sophistication of temporal processing is well illustrated by the observation that humans can reduce communication to a purely temporal code, as occurs when people communicate using Morse code. Despite the obvious importance of temporal processing to communication, learning, cognition, and sensory and motor processing, even the most basic mechanisms of how animals discriminate simple intervals or generate timed responses remains unknown.
Timing as an intrinsic property of neural networks: evidence from in vivo and in vitro experiments Anubhuti Goel and Dean V. Buonomano Philos Trans R Soc Lond B Biol Sci. 369(1637): 20120460. doi: 10.1098/rstb.2012.0460

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The discrimination and production of temporal patterns on the scale of hundreds of milliseconds are critical to sensory and motor processing. Indeed, most complex behaviours, such as speech comprehension and production, would be impossible in the absence of sophisticated timing mechanisms. Despite the importance of timing to human learning and cognition, little is known about the underlying mechanisms, in particular whether timing relies on specialized dedicated circuits and mechanisms or on general and intrinsic properties of neurons and neural circuits.
Timing as an intrinsic property of neural networks: evidence from in vivo and in vitro experiments Anubhuti Goel and Dean V. Buonomano Philos Trans R Soc Lond B Biol Sci. 369(1637): 20120460. doi: 10.1098/rstb.2012.0460

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Eukaryotic genomes are organized into chromatin, a higher?order structure comprising histones and DNA. Dynamic assembly of nucleosomes is essential for the control of DNA?templated processes such as replication, DNA damage repair, and gene regulation [...] [...] oligomerization of isolated Nap1 and Nap1–histone complexes occurs under physiological conditions in vitro and in vivo [...] The physiological role of such oligomerization has remained unclear. Future studies need to experimentally demonstrate the role of the NLS and how defective oligomerization or histone loading interferes with the yNap1 functional cycle. The transport of histones into or out of the nucleus is an essential step in chromatin assembly and the masking and unmasking of NLS sequences, as a function of histone binding and oligomerization may be a mechanism for regulating subcellular localization of yNAP1 and histones.
Structural evidence for Nap1?dependent H2A–H2B deposition and nucleosome assembly Carmen Aguilar?Gurrieri, Amédé Larabi, Vinesh Vinayachandran, Nisha A Patel, Kuangyu Yen, Rohit Reja, Ima?O Ebong, Guy Schoehn, Carol V Robinson, B Franklin Pugh, ? View ORCID ProfileDaniel Panne DOI 10.15252/embj.201694105 The EMBO Journal 35, 1465-1482

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What determines whether a TF depends on the chromatin context of its target genes or whether it is able to initiate a remodeling process that will reshape the epigenetic landscape, making it permissive for gene expression? Is this the prerogative of a specific class of TFs, the “pioneer factors,” or can many TFs do this depending on expression level and interactions with other factors? How are chromatin-modifying enzymes, with PRC2 as a prime example, targeted to their genomic locations?
Chromatin Control of Developmental Dynamics and Plasticity Matteo Perino, Gert Jan C. Veenstra DOI: http://dx.doi.org/10.1016/j.devcel.2016.08.004 Volume 38, Issue 6, p610–620 Developmental Cell

Dionisio_{September 26, 2016
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How are the influences of signaling and germ layer specification integrated with the cell-autonomous influences of maternal factors and specific signals embedded within the DNA sequence of regulatory regions to direct chromatin state and the developmental program? With what temporal dynamics and mechanistic hierarchy does this happen, and how are cellular competence and potency balanced with the need for commitment and epigenetic stability of cell fate? What does cell-fate specification and determination mean at the level of chromatin state of genes involved in different developmental programs?
Chromatin Control of Developmental Dynamics and Plasticity Matteo Perino, Gert Jan C. Veenstra DOI: http://dx.doi.org/10.1016/j.devcel.2016.08.004 Volume 38, Issue 6, p610–620 Developmental Cell

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Multicellular animals owe their complexity to their capacity to produce and maintain a multitude of different cell types that share virtually the same genomic DNA. Such complexity requires tight regulation of gene expression to unambiguously specify and constrain the developmental paths taken by cells in the embryo. It will be important to address a number of remaining questions. Studies in recent years have made exciting inroads into these questions, and much progress is expected in addressing the outstanding questions in years to come. [...] integration of these powerful techniques, alongside synergistic approaches combining developmental and computational biology, will provide insight into the profound questions associated with the multiple levels of complexity of the developing embryo, from egg to organism.
Chromatin Control of Developmental Dynamics and Plasticity Matteo Perino, Gert Jan C. Veenstra DOI: http://dx.doi.org/10.1016/j.devcel.2016.08.004 Volume 38, Issue 6, p610–620 Developmental Cell

Dionisio_{September 26, 2016
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It would be interesting to know whether the non-BMP-activated HSCs in the FL are also controlled by Hh/VEGF signaling, and an appropriate culture system should be developed to test this. Whether the increase in AGM explant HSCs is due to the expansion and shift in BMP-activation status of existing HSCs, or the new generation of HSCs (non-BMP-activated), or both, remains unclear. It will be interesting in future studies to examine these cells and the early hematopoietic tissues in the context of BMP, as well as Hh signaling through fate-mapping approaches.
BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo Mihaela Crisan,1,2 Parham Solaimani Kartalaei,1,3 Alex Neagu,1 Sofia Karkanpouna,1 Tomoko Yamada-Inagawa,1 Caterina Purini,1 Chris S. Vink,1,3 Reinier van der Linden,1 Wilfred van Ijcken,4 Susana M. Chuva de Sousa Lopes,5 Rui Monteiro,6 Christine Mummery,5 and Elaine Dzierzak1, Stem Cell Reports. 6(3): 383–395. doi: 10.1016/j.stemcr.2016.01.016

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Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs.
BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo Mihaela Crisan,1,2 Parham Solaimani Kartalaei,1,3 Alex Neagu,1 Sofia Karkanpouna,1 Tomoko Yamada-Inagawa,1 Caterina Purini,1 Chris S. Vink,1,3 Reinier van der Linden,1 Wilfred van Ijcken,4 Susana M. Chuva de Sousa Lopes,5 Rui Monteiro,6 Christine Mummery,5 and Elaine Dzierzak1, Stem Cell Reports. 6(3): 383–395. doi: 10.1016/j.stemcr.2016.01.016

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