bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simplified spiking model of grid-cell scale and intrinsic frequencies
Authors: Santos-Pata Diogo , Zucca Riccardo , López-Carral Héctor , Verschure Paul F. M. J. 
Published: February 2019

AbstractThe hexagonal tessellation pattern of grid cells scales up progressively along the dorsal-to-ventral axis of the medial entorhinal cortex (MEC) layer II. This scaling gradient has been hypothesized to originate either from inter population synaptic dynamics as postulated by attractor networks, from projected theta frequencies to different axis levels, as in oscillatory models, or from cellular dynamics dependent on hyperpolarization-activated cation currents. To test the hypothesis that intrinsic cellular properties account for the scale gradient as well as the different oscillatory frequencies observed along the dorsal-to-ventral axis, we have modeled and analyzed data from a population of grid cells simulated with spiking neurons interacting through low-dimensional attractor dynamics. To investigate the causal relationship between oscillatory frequencies and grid scale increase, we analyzed the dominant frequencies of the membrane potential for cells with distinct after-spike dynamics. We observed that intrinsic neuronal membrane properties of simulated cells could induce an increase of grid scale when modulated by after-spike reset values. Differences in the membrane potential oscillatory frequency were observed along the simulated dorsal-to-ventral axis, suggesting that, rather than driving to the increase of grid scale as proposed by interference models of grid cells, they are the result of intrinsic cellular properties of neurons at each axis level. Overall, our results suggest that the after-spike dynamics of cation currents may play a major role in determining the grid cells’ scale and that oscillatory frequencies are a consequence of intrinsic cellular properties that are specific to different levels of the dorsal-to-ventral axis in the MEC layer II.
Potential link between selection for high GC content and repair of double strand breaks in prokaryotic genomes
Authors: Weissman Jake L. , Fagan William F. , Johnson Philip L.F. 
Published: February 2019

AbstractGenomic GC content varies widely among microbes for reasons unknown. While mutation bias partially explains this variation, prokaryotes near-universally have a higher GC content than predicted solely by this bias. Debate surrounds the relative importance of the remaining explanations of selection versus biased gene conversion favoring GC alleles. Some environments (e.g. soils) are associated with a high genomic GC content of their inhabitants, which implies that this content may be a selective adaptation to particular habitats. Here, we report a novel association between the presence of the non-homologous end joining DNA doublestrand break repair pathway and GC content; this observation suggests that high GC content may be an adaptation to facilitate repair of double strand breaks when homologous recombination is not possible. We discuss potential mechanisms accounting for the observed association, and provide preliminary evidence that sites experiencing higher rates of doublestrand breaks are under selection for increased GC content relative to the genomic background.
Dot1L-dependent H3K79 methylation facilitates histone variant H2A.Z exchange at DNA double strand breaks and is required for high fidelity, homology-directed DNA repair
Authors: Alvarez Nehemiah S. , Brachova Pavla , Fields Timothy A. , Fields Patrick E. 
Published: February 2019

AbstractIn eukaryotic cells, the homology-directed repair (HDR) and non-homologous end joining (NHEJ) pathways are required for the repair of DNA double strand breaks (DSB). The high-fidelity HDR pathway is particularly important for maintenance of genomic stability. In mammals, histone post-translational modifications and histone variant exchange into nucleosomes at sites of DSB generate an open chromatin state necessary for repair to take place. However, the specific contributions of histone modifications to histone variant exchange at DSB sites and the influence of these changes on the DNA repair process and genome stability are incompletely understood. Here we show that Dot1L-catalyzed methylation of H3 histone on lysine 79 (H3K79) is required for efficient HDR of DSB. In cells with DNA DSB either lacking Dot1L or expressing a methylation-dead Dot1L, there is altered kinetics of DNA repair factor recruitment, markedly decreased H2A.Z incorporation at DSB sites, and a specific and profound reduction in HDR, which results in significant genomic instability. These findings demonstrate a new role for Dot1L, identifying it as a critical regulator of the DNA repair process and a steward of genomic integrity.
Assaying how the success of phagocytosis depends on the mechanics of a large viscoelastic target
Authors: Davis-Fields M. , Bakhtiari L. , Kovach K. , Gordon V. D. 
Published: February 2019

AbstractThe state of the art does not provide a method for determining how the success of phagocytosis depends on the mechanics of a target that is much larger than the phagocytosing cell. We have developed such a method. We vary the elastic moduli of millimeter-sized abiotic gels that contain fluorescent beads to act as tracers for phagocytosis. We isolate human neutrophils, expose them to gels for one hour, and then measure what percentage of neutrophils contain beads – this is our metric for successful phagocytosis. Both increased polymer concentration in agarose gels and increased crosslinking density in alginate gels are associated with decreased success of phagocytosis. When we plot the percentage of neutrophils containing beads as a function of the gel elastic modulus, we find that data from both alginate and agarose gels collapse onto the same curve. This demonstrates the utility of our method as a way of measuring how the viscoelastic mechanics of a large target impact the success of phagocytosis.
Compound-V formations in shorebird flocks
Authors: Corcoran Aaron J. , Hedrick Tyson L. 
Published: February 2019

AbstractAnimal groups have emergent properties that result from simple interactions among individuals. However, we know little about why animals adopt different interaction rules because of sparse sampling among species. Here, we identify an interaction rule that holds across single and mixed-species flocks of four migratory shorebird species spanning a seven-fold range of body masses. The rule, aligning with a 1-wingspan lateral distance to nearest neighbors in the same horizontal plane, scales linearly with wingspan but is independent of nearest neighbor distance and neighbor species. This rule propagates outward to create a global flock structure that we term the compound-V formation. We propose that this formation represents an intermediary between the cluster flocks of starlings and the simple-V formations of geese and other large migratory birds. Analysis of individual wingbeat frequencies and airspeeds indicates that the compound-V formation may be an adaptation for aerodynamic flocking.
Morphological deconvolution of beta-lactam polyspecificity inE. coli
Authors: Godinez William J. , Chan Helen , Hossain Imtiaz , Li Cindy , Ranjitkar Srijan , Rasper Dita , Simmons Robert L. , Zhang Xian , Feng Brian Y. 
Published: February 2019

AbstractBeta-lactam antibiotics comprise one of the earliest known classes of antibiotic therapies. These molsecules covalently inhibit enzymes from the family of penicillin-binding proteins, which are essential to the construction of the bacterial cell wall. As a result, beta-lactams have long been known to cause striking changes to cellular morphology. The exact nature of the changes tend to vary by the precise PBPs engaged in the cell since beta-lactams exhibit a range of PBP enzyme specificity. The traditional method for exploring beta-lactam polyspecificity is a gel-based binding assay which is low-throughput and typically runex situin cell extracts. Here, we describe a medium-throughput, image-based assay combined with machine learning methods to automatically profile the activity of beta-lactams inE. colicells. By testing for morphological change across a panel of strains with perturbations to individual PBP enzymes, our approach automatically and quantifiably relates different beta-lactam antibiotics according to their preferences for individual PBPs in cells. We show the potential of our approach for guiding the design of novel inhibitors towards different PBP-binding profiles by recapitulating the activity of two recently-reported PBP inhibitors.
pH controlled histone acetylation amplifies melanocyte differentiation program downstream of MITF
Authors: Raja Desingu Ayyappa , Gotherwal Vishvabandhu , Subramaniam Yogaspoorthi J , Sultan Farina , Vats Archana , Singh Archana , Sivasubbu Sridhar , Gokhale Rajesh S , Natarajan Vivek T 
Published: February 2019

AbstractTanning response and melanocyte differentiation are mediated by the central transcription factor MITF. Enigmatically, these involve rapid and selective induction of melanocyte maturation genes, while concomitantly maintaining the expression of other effectors. In this study using cell-based and zebrafish model systems, we elucidate a pH mediated feed-forward mechanism of epigenetic regulation that enables selective amplification of melanocyte maturation program. We demonstrate that MITF activation directly elevates the expression of Carbonic Anhydrase 14 (Ca14) enzyme. Nuclear localized Ca14 increases the intracellular pH, resulting in the activation of histone acetyl transferase activity of p300/CBP. In turn enhanced H3K27 histone acetylation marks of select differentiation genes facilitates their amplified expression by MITF. CRISPR-mediated targeted missense mutation of CA14 in zebrafish results in immature acidic melanocytes with decreased pigmentation, establishing the centrality of this mechanism in rapidly activating melanocyte differentiation. Thereby we reveal a novel epigenetic control through pH modulation that reinforces a deterministic cell fate by altering chromatin dynamics.
XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures
Authors: Ellwanger Kornelia , Arnold Christine , Briese Selina , Kienes Ioannis , Pfannstiel Jens , Kufer Thomas A. 
Published: February 2019

ABSTRACTThe receptor interacting serine/threonine kinase 2 (RIPK2) is essential for linking activation of the pattern recognition receptors NOD1 and NOD2 to cellular signaling events.Recently, it was shown that RIPK2 forms higher order molecular structuresin vitro, which were proposed to activate signaling. Here, we demonstrate that RIPK2 forms detergent insoluble complexes in the cytosol of host cells upon infection with invasive enteropathogenic bacteria. Formation of these structures occurred after NF-κB activation and depends on the CARD of NOD1 or NOD2. Complex formation upon activation was dependent on RIPK2 autophosphorylation at Y474 and influenced by phosphorylation at S176. Inhibition of activity of the cIAP protein XIAP induced spontaneous complex formation of RIPK2 but blocked NOD1-dependet NF-κB activation. Using immunoprecipitation, we identified 14-3-3 proteins as novel binding partners of non-activated RIPK2, whereas complexed RIPK2 was bound by the prohibitin proteins Erlin-1 and Erlin-2.Taken together, our work reveals novel roles of XIAP, 14-3-3 and Erlin proteins in the regulation of RIPK2 and expands our knowledge on the function of RIPK2 posttranslational modifications in NOD1/2 signaling.
Ionomycin Ameliorates Hypophosphatasia via Rescuing Alkaline Phosphatase Deficiency-mediated L-type Ca2+ Channel Internalization in Mesenchymal Stem Cells
Authors: Li Bei , He Xiaoning , Dong Zhiwei , Xuan Kun , Sun Wei , Gao Li , Liu Shiyu , Liu Wenjia , Hu Chenghu , Zhao Yimin , Shi Songtao , Jin Yan 
Published: February 2019

AbstractLoss-of-function mutations in ALPL result in hypophosphatasia (HPP), an inborn error of metabolism that causes skeletal mineralization defect. In adults, main clinical involvement includes early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, and fractures. However, guidelines for the treatment of adults with HPP are not available. Here, we show that ALPL deficiency caused reduction of intracellular Ca2+ influx resulting in osteoporotic phenotype due to downregulated osteogenic differentiation and upregulated adipogenic differentiation in both human and mouse BMSCs. To elevate intracellular level of calcium in bone marrow mesenchymal stem cells (BMSCs) by ionomycin treatment rescues the osteoporotic phenotype in alpl+/- mice and BMSC-specific (Prrx1-alpl-/-) conditional alpl knockout mice. Mechanistically, ALPL is required to maintain intracellular Ca2+ influx by regulating L-type Ca2+ channel trafficking via binding to the α2δ subunits, which regulates the internalization of L-type Ca2+ channel. Decreased Ca2+ flux inactivates Akt/GSK3β/β-catenin signaling pathway that regulates lineage differentiation of BMSCs. This study identifies a previous unknown role of ectoenzyme ALPL in maintenance of calcium channel trafficking to keep stem cell lineage differentiation and bone homeostasis. Accelerating Ca2+ flux through L-type Ca2+ channel by ionomycin treatment may be a promising therapeutic approach for adult HPP patients.One Sentence SummaryALP regulates internalization of L-Type Ca2+ Channel of BMSCs in Hypophosphatasia.
Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L
Authors: Chatzi Christina , Zhang Gina , Hendricks William , Chen Yang , Schnell Eric , Goodman Richard H. , Westbrook Gary L. 
Published: February 2019

AbstractExercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked mature hippocampal dentate granule cells that were specifically activated during exercise using conditional Fos-TRAP mice. Only a few dentate granule cells were active at baseline, but two hours of voluntary exercise markedly increased the number of activated neurons. Activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied gene in the adult brain. Overexpression of Mtss1L in neurons increased spine density, leading us to hypothesize that its I-BAR domain initiated membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.One Sentence SummarySingle episodes of voluntary exercise induced a functional increase in hippocampal synapses mediated by activity-dependent expression of the BAR protein Mtss1L, acting as a novel early effector of synapse formation.
Adult-born neurons inhibit developmentally-born neurons in the dentate gyrus
Authors: Cahill Shaina P. , Martinovic Angela , Cole John Darby , Snyder Jason S. 
Published: February 2019

AbstractDuring hippocampal-dependent memory formation, sensory signals from the neocortex converge in the dentate gyrus. It is generally believed that the dentate gyrus decorrelates inputs in order to minimize interference between codes for similar experiences, often referred to as pattern separation. Emerging evidence from mouse models suggests that adult-born neurons exert an inhibitory influence on the dentate gyrus, which may be important for maintaining the sparse code that is needed to form precise memories. However, since the dentate gyrus is composed of a heterogeneous population of cells that are born throughout life, it is unclear if newborn neurons inhibit all cells equally. We therefore investigated whether adult neurogenesis in rats modulates activity in dentate gyrus neurons that are born at the peak of early postnatal development. Adult neurogenesis was increased by subjecting rats to an alternating running and memantine treatment schedule, and it was decreased with a transgenic GFAP-TK rat model. Activity was measured by quantifying experience-induced Fos expression in BrdU+ cells. Consistent with an inhibitory role, enhancing neurogenesis blocked experience-dependent Fos expression in developmentally-born neurons and also in the broader granule cell population. In contrast, blocking neurogenesis did not significantly impact activity patterns. These results confirm previous work in mice and identify the developmentally-born population of neurons as a major target of neurogenesis-mediated inhibition. Treatments that target neurogenesis may therefore benefit disorders that are characterized by excitation-inhibition imbalance in the hippocampus, such as age-related memory impairments, fear and anxiety, and epilepsy.
A plant perspective on nitrogen cycling in the rhizosphere
Authors: Moreau Delphine , Bardgett Richard D. , Finlay Roger D. , Jones David L. , Philippot Laurent 
Published: February 2019

Abstract

Nitrogen is the major nutrient limiting plant growth in terrestrial ecosystems, and the transformation of inert nitrogen to forms that can be assimilated by plants is mediated by soil micro‐organisms.

The last decade has witnessed many significant advances in our understanding of plant–microbe interactions with evidence that plants have evolved multiple strategies to cope with nitrogen limitation by shaping and recruiting nitrogen‐cycling microbial communities. However, most studies have typically focused on the impact of plants on only one, or relatively few, processes within the nitrogen cycle.

This review synthesizes recent advances in our understanding of the various routes by which plants influence the availability of nitrogen via an array of interactions with different guilds of nitrogen‐cycling micro‐organisms. We also propose a plant trait‐based framework for linking plant nitrogen acquisition strategies to the activities of nitrogen‐cycling microbial guilds. In doing so, we provide a more comprehensive picture of the ecological relationships between plants and nitrogen‐cycling micro‐organisms in terrestrial ecosystems.

Finally, we identify previously overlooked processes within the nitrogen cycle that could be targeted in future research and be of interest for plant health or for improving plant nitrogen acquisition, while minimizing nitrogen inputs and losses in sustainable agricultural systems.

A plain language summary is available for this article.
Live fast, don't die young: Survival–reproduction trade‐offs in long‐lived income breeders
Authors: Culina Antica , Linton Danielle Marie , Pradel Roger , Bouwhuis Sandra , Macdonald David W. 
Published: February 2019

Abstract

Trade‐offs between survival and reproduction are at the core of life‐history theory, and essential to understanding the evolution of reproductive tactics as well as population dynamics and stability. Factors influencing these trade‐offs are multiple and often addressed in isolation. Further problems arise as reproductive states and survival in wild populations are estimated based on imperfect and potentially biased observation processes, which might lead to flawed conclusions.

In this study, we aimed at elucidating trade‐offs between current reproduction (both pregnancy and lactation), survival and future reproduction, including the specific costs of first reproduction, in long‐lived, income breeding small mammals, an under‐studied group.

We developed a novel statistical framework that encapsulates the breeding life cycle of females, and accounts for incomplete information on female pregnancy and lactation and imperfect and biased recapture rates. We applied this framework to longitudinal data on two sympatric, closely related bat species (Myotis daubentonii and M. nattereri).

We revealed the existence of several, to our knowledge previously unknown, trends in survival and breeding of these closely related, sympatric species and detected remarkable differences in their age and costs of first reproduction, as well as their survival–reproduction trade‐offs.

Our results indicate that species with this type of life history exhibit a mixture of patterns expected for long‐lived and short‐lived animals, and between income and capital breeders. Thus, we call for more studies to be conducted in similar study systems, increasing our ability to fully understand the evolutionary origin and fitness effects of trade‐offs and senescence.
Species asynchrony and response diversity determine multifunctional stability of natural grasslands
Authors: Sasaki Takehiro , Lu Xiaoming , Hirota Mitsuru , Bai Yongfei 
Published: February 2019

Abstract

A growing body of empirical evidence has suggested that biodiversity affects the simultaneous performance of multiple ecosystem functions (i.e. ecosystem multifunctionality). Given increasing environmental variability and uncertainty under global change, an emerging question is how biodiversity influences the stability of multiple functions (i.e. multifunctional stability). We currently know little, however, about the determinants and mechanisms of multifunctional stability, which is of practical importance for ensuring the sustainable provision of multiple functions.

Here, we examined mechanisms contributing to stability (quantified as the ratio of the mean to the standard deviation) of multiple functions related to ecosystem productivity and carbon sequestration, including plant above‐ground and below‐ground productivity, litter production, gross primary productivity and ecosystem respiration, in a large grassland biodiversity experiment in Inner Mongolia.

We found that community‐wide species asynchrony was a strong driver to stabilize multiple functions. Community‐wide asynchrony mediated the positive effects of species richness and response diversity (describing how species with similar effects on ecosystem function respond differently to environmental change) on multifunctional stability. However, species richness had a negative direct effect on multifunctional stability because, although it increased the averaged temporal mean of multiple functions, it strongly increased the averaged temporal standard deviation of multiple functions. The overall effects of species richness on multifunctional stability were thus negative, whereas those of response diversity were positive.

Synthesis. The studied ecosystem functions related to ecosystem productivity and carbon sequestration are important in natural grasslands across the world. We conclude that species asynchrony and response diversity, rather than species richness, are key to the ecosystem multifunctional stability. The loss of response diversity and compensatory mechanisms would likely reduce the long‐term sustainability of grasslands in the face of global change.