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

How these different types of regulators interact in floral boundary formation is one of the important questions that remain to be well understood. [...] common genes or pathways likely play pivotal roles in the floral organ boundaries and the relationships of these regulators can form a comprehensive network that explains the molecular mechanism of floral organ boundary formation.
Molecular Mechanisms of Floral Boundary Formation in Arabidopsis. Yu H1,2, Huang T3. Int J Mol Sci. ;17(3):317. doi: 10.3390/ijms17030317.

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Boundary formation is a crucial developmental process in plant organogenesis. Boundaries separate cells with distinct identities and act as organizing centers to control the development of adjacent organs. Organ boundaries are groups of specialized cells with restricted growth that are crucial for the development of plants and animals. Boundaries delineate identities by separating distinct functional domains, such as the meristem and organ primordia or adjacent organs, and also function as organizing centers for the downstream signaling events to pattern the organs at later stages [...]
Molecular Mechanisms of Floral Boundary Formation in Arabidopsis. Yu H1,2, Huang T3. Int J Mol Sci. ;17(3):317. doi: 10.3390/ijms17030317.

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Thidiazuron (N-phenyl-N'-1,2,3-thiadiazol-5-ylurea; TDZ) is an artificial plant growth regulator that is widely used in plant tissue culture. Protocorm-like bodies (PLBs) induced by TDZ serve as an efficient and rapid in vitro regeneration system in Rosa species. Despite this, the mechanism of PLB induction remains relatively unclear.
Thidiazuron Triggers Morphogenesis in Rosa canina L. Protocorm-Like Bodies by Changing Incipient Cell Fate. Kou Y1, Yuan C2, Zhao Q1, Liu G1, Nie J1, Ma Z1, Cheng C1, Teixeira da Silva JA3, Zhao L1. Front Plant Sci. ;7:557. doi: 10.3389/fpls.2016.00557.

Another case where the effects of chemicals artificially administered to plants are not well understood?Dionisio_{August 7, 2016
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Addressing these questions will bring us closer to understanding how polar auxin transport is both a robust system in some contexts but highly dynamic and versatile in others. Integrating these different regulatory modules into one unifying model will also be a challenge for the coming years that will certainly require multidisciplinary approaches ranging from structural biology to quantitative biochemistry and cell imaging as well as mathematical modeling.
Regulation of polar auxin transport by protein and lipid kinases. Armengot L1, Marquès-Bueno MM1, Jaillais Y2. J Exp Bot. 67(14):4015-37. doi: 10.1093/jxb/erw216.

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Among the outstanding questions that remain unanswered are: How the differential phosphorylations of PIN proteins act either on their polarity or activity? How auxin and GOLVEN peptides are perceived to regulate PIN intracellular trafficking? What are the molecular steps, independent of transcription, between cytokinin perception and PIN polarity regulation? What are the proteins regulated by phosphoinositides that control PIN trafficking and polarity? How other environmental (e.g. halotropism (Galvan-Ampudia et al., 2013)) and developmental (e.g. GA signaling (Lofke et al., 2013; Willige et al., 2011)) regulatory cues coalesce in the regulation of PIN trafficking and activity?
Regulation of polar auxin transport by protein and lipid kinases. Armengot L1, Marquès-Bueno MM1, Jaillais Y2. J Exp Bot. 67(14):4015-37. doi: 10.1093/jxb/erw216.

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The directional transport of auxin, known as polar auxin transport, allows asymmetric distribution of this hormone in different cells and tissues. This system creates local auxin maxima, minima and gradients that are instrumental in both organ initiation and shape determination. [...] it is clear that much still need to be addressed to understand each pathway [...]
Regulation of polar auxin transport by protein and lipid kinases. Armengot L1, Marquès-Bueno MM1, Jaillais Y2. J Exp Bot. 67(14):4015-37. doi: 10.1093/jxb/erw216.

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[...] these proposals will likewise have to be re-evaluated in light of our findings. [...] this only pushes the patterning question back a level: how, then, are the patterns in perception or transport established? Another outstanding question is how low cytokinin signalling levels are maintained in the metaxylem position. [...] we cannot describe the factors which lead to one pole being favoured over the other in any given instance [...] A full understanding of this phenomenon is likely to require incorporating existing longitudinal and transverse auxin transport models into a three-dimensional model of the root.
Parsimonious Model of Vascular Patterning Links Transverse Hormone Fluxes to Lateral Root Initiation: Auxin Leads the Way, while Cytokinin Levels Out. el-Showk S1, Help-Rinta-Rahko H2, Blomster T2, Siligato R2, Marée AF3, Mähönen AP2, Grieneisen VA PLoS Comput Biol. 11(10):e1004450. doi: 10.1371/journal.pcbi.1004450.

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This finding is reinforced by spatial-temporal considerations of hormone diffusion within the context of this system: in order to be informative on the transverse scale of the Arabidopsis stele (around 50?m), a gradient would need to have a characteristic length of roughly the same order [...] [...] our analysis raises questions and challenges regarding the mechanics and dynamics of cytokinin transport which must be further addressed by experiments and more modelling alike. It is therefore important when constructing verbal or conceptual models to consider constraints which are introduced by conflicting requirements at different spatial scales. Quantitative considerations can lead to different qualitative mechanisms for how patterning occurs.
Parsimonious Model of Vascular Patterning Links Transverse Hormone Fluxes to Lateral Root Initiation: Auxin Leads the Way, while Cytokinin Levels Out. el-Showk S1, Help-Rinta-Rahko H2, Blomster T2, Siligato R2, Marée AF3, Mähönen AP2, Grieneisen VA PLoS Comput Biol. 11(10):e1004450. doi: 10.1371/journal.pcbi.1004450.

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[...] contrary phenotypes are observed in the root and leaf, suggesting that the picture may be more complex. [...] specific LAX genes may act in concert with AUX1 in different developmental contexts, amplifying and buffering the auxin pattern generated by the PIN transporters. [...] demonstrating the implausibility of an informative cytokinin gradient forming on this scale via diffusive processes (whether or not combined with apolar transport)[...]
Parsimonious Model of Vascular Patterning Links Transverse Hormone Fluxes to Lateral Root Initiation: Auxin Leads the Way, while Cytokinin Levels Out. el-Showk S1, Help-Rinta-Rahko H2, Blomster T2, Siligato R2, Marée AF3, Mähönen AP2, Grieneisen VA PLoS Comput Biol. 11(10):e1004450. doi: 10.1371/journal.pcbi.1004450.

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[...] emerging methodologies will provide new mechanistic insights into how the advance, retraction, and turning of the growth cone vehicle can be orchestrated during axon guidance, and how these behaviors are organized downstream of extracellular cues. [...] +TIPs have emerged as molecular tour guides that can inform and direct these axonal behaviors, by modulating their interactions with both actin and MT cytoskeletons in response to signaling cascades. It is evident, then, that future works that expand the breadth and depth of +TIP identification, function, and regulation will be instrumental to our understanding of axon guidance behaviors.
TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance. Bearce EA1, Erdogan B1, Lowery LA1. Front Cell Neurosci. ;9:241. doi: 10.3389/fncel.2015.00241.

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[...] we have described how numerous +TIPs are phosphorylated downstream of signaling molecules. However, it is clear that our current knowledge of these interactions is over-simplified. Determining how multiple signaling cascades and kinase activities can be integrated constructively to designate a +TIP’s localization and behavior may be considered an ultimate pursuit within the field.
TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance. Bearce EA1, Erdogan B1, Lowery LA1. Front Cell Neurosci. ;9:241. doi: 10.3389/fncel.2015.00241.

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[...] kinesin-5 and kinesin-12 families have also shown commanding involvement in growth cone turning [...], though whether an EB interaction is involved in their localization in this context is not known. [...] CLIP-115 and CLIP-190 have been investigated in many shared examinations with CLIP-170 [...], but their individual roles in the growth cone are less well-clarified, and may emerge with time. As new +TIPs are frequently being established in a number of systems, it will be necessary to begin to not only consider their individual interactions in axon guidance, but also to examine their interplay with one another.
TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance. Bearce EA1, Erdogan B1, Lowery LA1. Front Cell Neurosci. ;9:241. doi: 10.3389/fncel.2015.00241.

Emphasis mine.Dionisio_{August 6, 2016
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The growth cone is able to correctly maneuver through a myriad of extracellular cues, leading its axon accurately through the developing nervous system, turning in response to attractive or repulsive stimuli, and halting when it has arrived at the correct destination. The mechanisms by which this responsive cytoskeletal machine is able to detect and then translate numerous guidance signals are largely unknown.
TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance. Bearce EA1, Erdogan B1, Lowery LA1. Front Cell Neurosci. ;9:241. doi: 10.3389/fncel.2015.00241.

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The growth cone is a dynamic cytoskeletal vehicle, which drives the end of a developing axon. It serves to interpret and navigate through the complex landscape and guidance cues of the early nervous system. +TIPs accumulate at the dynamic ends of MTs, where they are well-positioned to encounter and respond to key signaling events downstream of guidance receptors, catalyzing immediate changes in microtubule stability and actin cross-talk, that facilitate both axonal outgrowth and turning events.
TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance. Bearce EA1, Erdogan B1, Lowery LA1. Front Cell Neurosci. ;9:241. doi: 10.3389/fncel.2015.00241.

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The connectome can be envisioned as the “wiring of the CNS” but the “wires” are highly dynamics and plastic elements whose structure and functions are continuously modified by the network activity itself.
Morphogenetic and Histogenetic Roles of the Temporal-Spatial Organization of Cell Proliferation in the Vertebrate Corticogenesis as Revealed by Inter-specific Analyses of the Optic Tectum Cortex Development Melina Rapacioli,1 Verónica Palma,2 and Vladimir Flores Front Cell Neurosci. 10: 67. doi: 10.3389/fncel.2016.00067

Complex complexity. :)Dionisio_{August 6, 2016
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A fashionable idea that has generated a great expectation in the fields of the psychology, cognitive neurology, sociology and so on, is that the overall human behavior, including the consciousness with its emotional and moral components will be explained, in the not too distant future, in terms of the networking of the highest cortical areas and their corresponding subcortical centers.
Morphogenetic and Histogenetic Roles of the Temporal-Spatial Organization of Cell Proliferation in the Vertebrate Corticogenesis as Revealed by Inter-specific Analyses of the Optic Tectum Cortex Development Melina Rapacioli,1 Verónica Palma,2 and Vladimir Flores Front Cell Neurosci. 10: 67. doi: 10.3389/fncel.2016.00067

The peer-review publications should stand firmly against the consumption of any hallucinogenic drugs by the authors before their papers get published. :) BTW, is psychology a science? :)Dionisio_{August 6, 2016
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It is presumed that the modern neurosciences will accumulate enough information as to describe the human mind in terms of the function of interconnecting cortical and subcortical neuronal circuit networks. While this could be a long-range goal, a less ambitious objective could be the description of the behaviors of lower species in terms of defined patterns of activity of the above mentioned neuronal circuits.
Morphogenetic and Histogenetic Roles of the Temporal-Spatial Organization of Cell Proliferation in the Vertebrate Corticogenesis as Revealed by Inter-specific Analyses of the Optic Tectum Cortex Development Melina Rapacioli,1 Verónica Palma,2 and Vladimir Flores Front Cell Neurosci. 10: 67. doi: 10.3389/fncel.2016.00067

There yet? :)Dionisio_{August 6, 2016
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The central nervous system areas displaying the highest structural and functional complexity correspond to the so called cortices, i.e., concentric alternating neuronal and fibrous layers. Corticogenesis, i.e., the development of the cortical organization, depends on the temporal-spatial organization of several developmental events:
(a) the duration of the proliferative phase of the neuroepithelium, (b) the relative duration of symmetric (expansive) versus asymmetric (neuronogenic) sub phases, ? (c) the spatial organization of each kind of cell division, (e) the time of determination and cell cycle exit and (f) the time of onset of the post-mitotic neuronal migration and (g) the time of onset of the neuronal structural and functional differentiation.
The first five events depend on molecular mechanisms that perform a fine tuning of the proliferative activity. Changes in any of them significantly influence the cortical size or volume (tangential expansion and radial thickness), morphology, architecture and also impact on neuritogenesis and synaptogenesis affecting the cortical wiring.
Morphogenetic and Histogenetic Roles of the Temporal-Spatial Organization of Cell Proliferation in the Vertebrate Corticogenesis as Revealed by Inter-specific Analyses of the Optic Tectum Cortex Development Melina Rapacioli,1 Verónica Palma,2 and Vladimir Flores Front Cell Neurosci. 10: 67. doi: 10.3389/fncel.2016.00067

Is there (d) between (c) and (e)? :)Dionisio_{August 6, 2016
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Is there exchange and conversion from one complex to the next? For example, following CORVET recruitment to early endosomes, does the core remain and the other subunits are turned over while new ones recruited to build HOPS? Likewise, does GARP reach the recycling endosome and is converted there into EARP? Alternatively, individual complex assembly may occur on membranes according to demand. What can we make of the moonlighting functions of tether components? The action of Vps39 as a tether in organellar contact sites is very intriguing and it is conceivable that the cell reuses successful units in different contexts.
Membrane Tethering Complexes in the Endosomal System Anne Spang* Front Cell Dev Biol. 4: 35. doi: 10.3389/fcell.2016.00035

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A lot of open questions remain; below are a few to consider. Do we know the identity of all tethers in the endosomal system? Likely not, In particular the function of the orphan CHEVI complex needs to be established and the missing interaction partners for both CHEVI and FERARI must be identified. Since it is likely that the individual subunits of the tethers are not forming very stable complexes in the cytoplasm, we may not be able to detect easily other complexes by biochemical means. Hence, we will also require help from genetics. The combination of both will be instrumental in elucidating the identity and function of additional tethers in the endosomal system and beyond.
Membrane Tethering Complexes in the Endosomal System Anne Spang* Front Cell Dev Biol. 4: 35. doi: 10.3389/fcell.2016.00035

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[...] there are other tethering functions in the endosomal system as there are multiple pathways through which proteins can be delivered from endosomes to either the TGN or the plasma membrane. Furthermore, proteins that may be part of novel tethering complexes have been recently identified. Thus, it is likely that more tethering factors exist.
Membrane Tethering Complexes in the Endosomal System Anne Spang* Front Cell Dev Biol. 4: 35. doi: 10.3389/fcell.2016.00035

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Here, we describe a new connexion between Nuf, an adaptor of Rab11-GTPase to the microtubule motor proteins in the recycling endosomes (RE) process, and aPKC, one of the main regulators of cell polarity. We demonstrate that aPKC phosphorylates Nuf, modifying Nuf subcellular distribution and, thus, RE delivery. We also show that aPKC’s apical recycling is maintained through Nuf-Rab11-RE. Thus, our results provide a novel link between cell polarity regulation and cellular traffic control.
Nuclear fallout provides a new link between aPKC and polarized cell trafficking. Calero-Cuenca FJ1, Espinosa-Vázquez JM1, Reina-Campos M2, Díaz-Meco MT2, Moscat J2, Sotillos S3. BMC Biol. ;14:32. doi: 10.1186/s12915-016-0253-6.

Complex complexity. :)Dionisio_{August 5, 2016
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Cells must be organized in different functional domains to maintain cell homeostasis and exert their functions. This is achieved through conserved proteins that polarize the cell or regulate directional trafficking of cellular vesicles. Both mechanisms must be coordinated but there is little information about their relationship.
Nuclear fallout provides a new link between aPKC and polarized cell trafficking. Calero-Cuenca FJ1, Espinosa-Vázquez JM1, Reina-Campos M2, Díaz-Meco MT2, Moscat J2, Sotillos S3. BMC Biol. ;14:32. doi: 10.1186/s12915-016-0253-6.

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Cell polarity, essential for cell physiology and tissue coherence, emerges as a consequence of asymmetric localization of protein complexes and directional trafficking of cellular components. Although molecules required in both processes are well known their relationship is still poorly understood.
Nuclear fallout provides a new link between aPKC and polarized cell trafficking. Calero-Cuenca FJ1, Espinosa-Vázquez JM1, Reina-Campos M2, Díaz-Meco MT2, Moscat J2, Sotillos S3. BMC Biol. ;14:32. doi: 10.1186/s12915-016-0253-6.

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Making correct cell fate decisions fundamentally contributes to both the developmental and homeostasis of complex tissue structures in multicellular organisms. The exact biological reason(s) for biased centrosome inheritance, and whether centrosome identity directly participates in the cell fate decision process, remains to be fully answered. Cell fate acquisition is determined by the unequal distribution of fate-determining protein complexes into daughter cells during mitosis. Coordinated links between cortical polarity and mitotic spindle orientation underlie the cell’s ability to generate asymmetric daughter fates. Continued efforts to define the molecular mechanisms of asymmetric cell division will further illuminate this fascinating biological process [...] Surely additional regulatory mechanisms remain to be discovered, including how cell polarity and spindle positioning are coordinated with the cell cycle.
Cell Fate Decision Making through Oriented Cell Division. Dewey EB1, Taylor DT1, Johnston CA1. J Dev Boil. 3(4):129-157 DOI: 10.3390/jdb3040129

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The ability to dictate cell fate decisions is critical during animal development. Moreover, faithful execution of this process ensures proper tissue homeostasis throughout adulthood [...] [...] protein complexes control cell fate decisions across diverse tissues. Maintaining proper daughter cell inheritance patterns of these determinants during mitosis is therefore a fundamental step of the cell fate decision-making process.
Cell Fate Decision Making through Oriented Cell Division. Dewey EB1, Taylor DT1, Johnston CA1. J Dev Boil. 3(4):129-157 DOI: 10.3390/jdb3040129

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[...] the modulation of the relative dynamics of SBD and NBD, observed by MD simulations on the ns scale and quantified by the centre of mass analysis, could effectively reflect the efficacy of the allosteric communication between the domains, as well as the modulation of the ATPase function of Hsp70.
An atomistic view of Hsp70 allosteric crosstalk: from the nucleotide to the substrate binding domain and back Federica Chiappori,1 Ivan Merelli,1 Luciano Milanesi,b,1 Giorgio Colombo,2 and Giulia Mora Sci Rep. 6: 23474. doi: 10.1038/srep23474

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The Hsp70 is an allosterically regulated family of molecular chaperones. They consist of two structural domains, NBD and SBD, connected by a flexible linker. ATP hydrolysis at the NBD modulates substrate recognition at the SBD, while peptide binding at the SBD enhances ATP hydrolysis.
An atomistic view of Hsp70 allosteric crosstalk: from the nucleotide to the substrate binding domain and back Federica Chiappori,1 Ivan Merelli,1 Luciano Milanesi,b,1 Giorgio Colombo,2 and Giulia Mora Sci Rep. 6: 23474. doi: 10.1038/srep23474

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[...] the details of the Hsp70-Hsp40 interaction remain elusive. [...] it is not clear how Hsp40s alone, or together with the substrate, influence allosteric signal transmission between the domains. It is not clear whether they alter, either alone or in cooperation with other cochaperones like nucleotide exchange factors, the interdomain communication in Hsp70s to facilitate transfer of the substrate to Hsp90 or to stabilize the Hsp70-substrate complex for timely release at the proteasome. [...] it is not known whether interdomain communication is subject to modulation by the post-translational modifications of Hsp70s that occur in eukaryotes
Insights into the molecular mechanism of allostery in Hsp70s. Mayer MP1, Kityk R1. Front Mol Biosci. ;2:58. doi: 10.3389/fmolb.2015.00058.

Merriam-Webster Dictionary Definition of allosteric: of, relating to, undergoing, or being a change in the shape and activity of a protein (as an enzyme) that results from combination with another substance at a point other than the chemically active siteDionisio_{August 4, 2016
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Hsp70s chaperone an amazing number and variety of cellular protein folding processes. Hsp70 is probably the most versatile of all chaperones, constituting a central hub of the cellular protein folding network. [...] the intricate mechanism of the Hsp70 machine itself makes it such a versatile tool. Recent years have brought about significant progress in understanding the underlying mechanisms of interdomain communication in Hsp70s. Despite these advances many questions are still not solved.
Insights into the molecular mechanism of allostery in Hsp70s. Mayer MP1, Kityk R1. Front Mol Biosci. ;2:58. doi: 10.3389/fmolb.2015.00058.

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