bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast signaling and focal connectivity of PV+ interneurons ensure efficient pattern separation by lateral inhibition in a full-scale dentate gyrus network model
Authors: Guzman Segundo Jose , Schlögl Alois , Espinoza Claudia , Zhang Xiaomin , Suter Ben , Jonas Peter 
Published: May 2019

ABSTRACTPattern separation is a fundamental brain computation that converts small differences in synaptic input patterns into large differences in action potential (AP) output patterns. Pattern separation plays a key role in the dentate gyrus, enabling the efficient storage and recall of memories in downstream hippocampal CA3 networks. Several mechanisms for pattern separation have been proposed, including expansion of coding space, sparsification of neuronal activity, and simple thresholding mechanisms. Alternatively, a winner-takes-all mechanism, in which the most excited cells inhibit all less-excited cells by lateral inhibition, might be involved. Although such a mechanism is computationally powerful, it remains unclear whether it operates in biological networks. Here, we develop a full-scale network model of the dentate gyrus, comprised of granule cells (GCs) and parvalbumin+ (PV+) inhibitory interneurons, based on experimentally determined biophysical cellular properties and synaptic connectivity rules. Our results demonstrate that a biologically realistic principal neuron–interneuron (PN–IN) network model is a highly efficient pattern separator. Mechanistic dissection in the model revealed that a winner-takes-all mechanism by lateral inhibition plays a crucial role in pattern separation. Furthermore, both fast signaling properties of PV+ interneurons and focal GC–interneuron connectivity are essential for efficient pattern separation. Thus, PV+ interneurons are not only involved in basic microcircuit functions, but also contribute to higher-order computations in neuronal networks, such as pattern separation.
Systematics and geographical distribution ofGalbaspecies, a group of cryptic and worldwide freshwater snails
Authors: Alda Pilar , Lounnas Manon , Vázquez Antonio A. , Ayaqui Rolando , Calvopiña Manuel , Celi-Erazo Maritza , Dillon Robert T. , González Ramírez Luisa Carolina , Loker Eric S. , Muzzio-Aroca Jenny , Nárvaez Alberto Orlando , Noya Oscar , Pereira Andrés Esteban , Robles Luiggi Martini , Rodríguez-Hidalgo Richar , Uribe Nelson , David Patrice , Jarne Philippe , Pointier Jean-Pierre , Hurtrez-Boussès Sylvie 
Published: May 2019

AbstractCryptic species can present a significant challenge to the application of systematic and biogeographic principles, especially if they are invasive or transmit parasites or pathogens. Detecting cryptic species requires a pluralistic approach in which molecular markers facilitate the detection of coherent taxonomic units that can then be analyzed using various traits (e.g., internal morphology) and crosses. In asexual or self-fertilizing species, the latter criteria are of limited use. We studied a group of cryptic freshwater snails (genusGalba)from the family Lymnaeidae that have invaded almost all continents, reproducing mainly by self-fertilization and transmitting liver flukes to humans and livestock. We aim to clarify the systematics, distribution and phylogenetic relationships of these species with an integrative approach that includes morphology (shell and reproductive anatomy), molecular markers, wide-scale sampling across America, and data retrieved from GenBank (to include Old World samples). Our phylogenetic analysis suggests that the genusGalbaoriginated ca. 22 Myr ago and today comprises six clusters of species. Four of these clusters (G.truncatula,G.cubensis/viator,G.humilisandG.schirazensis) are morphologically cryptic and constitute species or species complexes with wide variation in their genetic diversity, geographic distribution and invasiveness. The other two clusters constitute a single species or a species complex (Galba cousini/meridensis) that demonstrate more geographically restricted distributions and exhibit an alternative morphology more phylogenetically derived than the cryptic one. Further genetic studies are required to clarify the status of bothG. cousini/meridensisandG.cubensis/viator. We emphasize that noGalbaspecies should be identified without molecular markers and that additional sampling is required, especially in North America, Eurasia and Africa to clarify remaining questions in systematics and biogeography. We also discuss several hypotheses that can explain crypsis inGalba, such as convergence and morphological stasis, and hypothesize a role for stabilizing selection in amphibious (rather than strictly freshwater) habitats.
Genesis and Gappa: Processing, Analyzing and Visualizing Phylogenetic (Placement) Data
Authors: Czech Lucas , Barbera Pierre , Stamatakis Alexandros 
Published: May 2019

SummaryWe present GENESIS, a library for working with phylogenetic data, and GAPPA, an accompanying command line tool for conducting typical analyses on such data. The tools target phylogenetic trees and phylogenetic placements, sequences, taxonomies, and other relevant data types, offer high-level simplicity as well as low-level customizability, and are computationally efficient, well-tested, and field-proven.Availability and ImplementationBoth GENESIS and GAPPA are written in modern C++11, and are freely available under GPLv3 at http://github.com/lczech/genesis and http://github.com/lczech/gappa.Contactlucas.czech@h-its.org and alexandros.stamatakis@h-its.org.
Structural imaging of native cryo-preserved secondary cell walls reveals presence of macrofibrils composed of cellulose, lignin and xylan
Authors: Lyczakowski Jan J. , Bourdon Matthieu , Terrett Oliver M. , Helariutta Ykä , Wightman Raymond , Dupree Paul 
Published: May 2019

AbstractThe woody secondary cell walls of plants are the largest repository of renewable carbon biopolymers on the planet. These walls are made principally from cellulose and hemicelluloses and are impregnated with lignin. Despite their importance as the main load bearing structure for plant growth, as well as their industrial importance as both a material and energy source, the precise arrangement of these constituents within the cell wall is not yet fully understood. We have adapted low temperature scanning electron microscopy (cryo-SEM) for imaging the nanoscale architecture of angiosperm and gymnosperm cell walls in their native hydrated state. Our work confirms that cell wall macrofibrils, cylindrical structures with a diameter exceeding 10 nm, are a common feature of the native hardwood and softwood samples. We have observed these same structures in Arabidopsis thaliana secondary cell walls, enabling macrofibrils to be compared between mutant lines that are perturbed in cellulose, hemicellulose and lignin formation. Our analysis indicates that the macrofibrils in Arabidopsis cell walls are composed, at least partially, of cellulose, xylan and lignin. This study is a useful additional approach for investigating the native nanoscale architecture and composition of hardwood and softwood secondary cell walls and demonstrates the applicability of Arabidopsis genetic resources to relate fibril structure with wall composition and biosynthesis.
Breaking down defenses: quantitative analysis of malaria infection dynamics reveals distinct immune defense strategies
Authors: Wale Nina , Jones Matthew J. , Sim Derek G. , Read Andrew F. , King Aaron A. 
Published: May 2019

ABSTRACTHosts defend themselves against pathogens by mounting an immune response. Fully understanding the immune response as a driver of host disease and pathogen evolution requires a quantitative account of its impact on parasite population dynamics. Here, we use a data-driven modeling approach to quantify the birth and death processes underlying the dynamics of infections of the rodent malaria parasite,Plasmodium chabaudi, and the red blood cells (RBCs) it targets. We decompose the immune response into three components, each with a distinct effect on parasite and RBC vital rates, and quantify the relative contribution of each component to host disease and parasite density. Our analysis suggests that these components are deployed in a coordinated fashion to realize distinct resource-directed defense strategies that complement the killing of parasitized cells. Early in the infection, the host deploys a strategy reminiscent of siege and scorched-earth tactics, in which it both restricts the supply of RBCs and destroys them. Late in the infection, a ‘juvenilization’ strategy, in which turnover of RBCs is accelerated, allows the host to recover from anemia while holding parasite proliferation at bay. By quantifying the impact of immunity on both parasite fitness and host disease, we reveal that phenomena often interpreted as immunopathology may in fact be beneficial to the host. Finally, we show that, across mice, the components of the host response are consistently related to each other, even when infections take qualitatively different trajectories. This suggests the existence of simple rules that govern the immune system’s deployment.
Shortened TDP43 isoforms upregulated by neuronal hyperactivity drive TDP43 pathology in ALS
Authors: Weskamp Kaitlin , Tank Elizabeth M. , Miguez Roberto , McBride Jonathon P. , Gómez Nicolás B. , White Matthew , Lin Ziqiang , Gonzalez Carmen Moreno , Serio Andrea , Sreedharan Jemeen , Barmada Sami J. 
Published: May 2019

AbstractCortical hyperexcitability and mislocalization of the RNA-binding protein TDP43 are highly-conserved features in amyotrophic lateral sclerosis (ALS). Nevertheless, the relationship between these phenomena remains poorly defined. Here, we showed that hyperexcitability recapitulates TDP43 pathology by upregulating shortened (s) TDP43 splice isoforms. These truncated isoforms accumulated in the cytoplasm and formed insoluble inclusions that sequestered full-length TDP43 via preserved N-terminal interactions. Consistent with these findings, sTDP43 overexpression was toxic to mammalian neurons, suggesting neurodegeneration arising from complementary gain- and loss-of-function mechanisms. In humans and mice, sTDP43 transcripts were enriched in vulnerable motor neurons, and we observed a striking accumulation of sTDP43 within neurons and glia of ALS patients. Collectively, these studies uncover a pathogenic role for alternative TDP43 isoforms in ALS, and implicate sTDP43 as a key contributor to the susceptibility of motor neurons in this disorder.
DNA damage response in peripheral mouse blood leukocytesin vivoafter variable, low-dose rate exposure
Authors: Wang Qi , Pujol Monica C. , Garty Guy , Taveras Maria , Perrier Jay , Bueno-Beti Carlos , Shuryak Igor , Brenner David J. , Turner Helen C. 
Published: May 2019

AbstractEnvironmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident and improvised nuclear device and highlights the need to develop biological assays for low dose rate, internal emitter radiation. To mimic low dose rates attributable to fallout, we have developed a VAriable Dose-rate External137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low dose rate irradiations in the range of 1.2 to 0.1 Gy/day, while circumventing the complexities of dealing with radioactively-contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate137Cs exposure. C57BL/6 mice were placed in the VADER over 7 days with total accumulated dose up to 2.7 Gy. Peripheral blood response including the leukocytes depletion, apoptosis signal protein p53 and DNA repair biomarker γ-H2AX were measured. The results illustrated that blood leukocyte count had significantly dropped by days 7. P53 levels peaked at day 2 (total dose=0.91Gy) and then declined whereas γ-H2AX yields generally increased with accumulated dose and peaked at day 5 (total dose=2.08Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX as a biomarker dosimetry in a protracted, environmental exposure scenario.
Balancing selection via life-history trade-offs maintains an inversion polymorphism in a seaweed fly
Authors: Mérot Claire , Llaurens Violaine , Normandeau Eric , Bernatchez Louis , Wellenreuther Maren 
Published: May 2019

AbstractHow genetic diversity is maintained in natural populations is an evolutionary puzzle. Over time, genetic variation within species can be eroded by drift and directional selection, leading to the fixation or elimination of alleles. However, some loci show persistent variants at intermediate frequencies for long evolutionary time-scales, implicating a role of balancing selection, but studies are seldom set up to uncover the underlying processes. Here, we identify and quantify the selective pressures involved in the widespread maintenance of an inversion polymorphism in the seaweed fly Coelopa frigida, using an experimental evolution approach to estimate fitness associated with different allelic combinations. By precisely evaluating reproductive success and survival rates separately, we show that the maintenance of the polymorphism is governed by a life-history trade-off, whereby each inverted haplotype has opposed pleiotropic effects on survival and reproduction. Using numerical simulations, we confirm that this uncovered antagonism between natural and sexual selection can maintain inversion variation in natural populations of C. frigida. Moreover, our experimental data highlights that inversion-associated fitness is affected differently by sex, dominance and environmental heterogeneity. The interaction between these factors promotes polymorphism maintenance through antagonistic pleiotropy. Taken together, our findings indicate that combinations of natural and sexual selective mechanisms enable the persistence of diverse trait in nature. The joint dynamics of life history trade-offs and antagonistic pleiotropy documented here is likely to apply to other species where large phenotypic variation is controlled by structural variants.Significance statementPersistence of chromosomal rearrangements is widespread in nature and often associated with divergent life-history traits. Understanding how contrasted life-history strategies are maintained in wild populations has implications for food production, health and biodiversity in a changing environment. Using the seaweed fly Coelopa frigida, we show that a polymorphic chromosomal inversion is maintained by a trade-off between survival and reproduction, and thus provide empirical support for a role of balancing selection via antagonistic pleiotropy. This mechanism has long been overlooked because it was thought to only apply to a narrow range of ecological scenarios. These findings empirically reinforce the recent theoretical predictions that co-interacting factors (dominance, environment and sex) can lead to polymorphism maintenance by antagonistic pleiotropy and favour life-history variation.
Algorithms for efficiently collapsing reads with Unique Molecular Identifiers
Authors: Liu Daniel 
Published: May 2019

AbstractBackgroundUnique Molecular Identifiers (UMI) are used in many experiments to find and remove PCR duplicates. Although there are many tools for solving the problem of deduplicating reads based on their finding reads with the same alignment coordinates and UMIs, many tools either cannot handle substitution errors, or require expensive pairwise UMI comparisons that do not efficiently scale to larger datasets.ResultsWe formulate the problem of deduplicating UMIs in a manner that enables optimizations to be made, and more efficient data structures to be used. We implement our data structures and optimizations in a tool called UMICollapse, which is able to deduplicate over one million unique UMIs of length 9 at a single alignment position in around 26 seconds.ConclusionsWe present a new formulation of the UMI deduplication problem, and show that it can be solved faster, with more sophisticated data structures.
Interpretable attention model in transcription factor binding site prediction with deep neural networks
Authors: Chen Chen , Hou Jie , Shi Xiaowen , Yang Hua , Birchler James A. , Cheng Jianlin 
Published: May 2019

AbstractDue to the complexity of the biological factors that may influence the binding of transcription factors to DNA sequences, prediction of the potential binding sites remains a difficult task in computational biology. The attention mechanism in deep learning has shown its capability to learn from input features with long-range dependencies. Until now, no study has applied this mechanism in deep neural network models with input data from massively parallel sequencing. In this study, we aim to build a model for binding site prediction with the combination of attention mechanism and traditional deep learning techniques, including convolutional neural networks and recurrent neural networks. The performance of our methods is evaluated on the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge datasets.The benchmark shows that our implementation with attention mechanism (called DeepGRN) improves the performance of the deep learning models. Our model achieves better performance in at least 9 of 13 targets than any of the methods participated in the DREAM challenge. Visualization of the attention weights extracted from the trained models reveals how those weights shift when binding signal peaks move along the genomic sequence, which can interpret how the predictions are made. Case studies show that the attention mechanism helps to extract useful features by focusing on regions that are critical to successful prediction while ignoring the irrelevant signals from the input.
Auditory binaural and spatial hearing impairments in a Fragile X Syndrome mouse model
Authors: McCullagh Elizabeth A. , Poleg Shani , Greene Nathaniel T. , Huntsman Molly M. , Tollin Daniel J. , Klug Achim 
Published: May 2019

AbstractThe auditory brainstem compares sound-evoked excitation and inhibition from both ears to compute sound source location. Although alterations to the anatomy and physiology of the auditory brainstem have been demonstrated in Fragile X Syndrome (FXS) it is not known whether these changes cause sound localization impairments in FXS. To test the hypothesis that FXS-related alterations to brainstem circuits impair spatial hearing abilities, a reflexive prepulse inhibition (PPI) task, with sound source location as the prepulse stimulus, was used to show that Fmr1 knockout mice have decreased inhibition of their startle responses. Specifically, Fmr1 mice show decreased PPI compared to wildtype during gap detection, changes in sound source location, and spatial release from masking with no alteration to their overall startle thresholds compared to wildtype. Lastly, Fmr1 mice have increased latency to respond in these tasks suggesting additional impairments in the pathway responsible for reacting to a startling sound.
Functional synapse types via characterization of short-term synaptic plasticity
Authors: Lee Jung Hoon , Campagnola Luke , Seeman Stephanie C. , Jarsky Tim , Mihalas Stefan 
Published: May 2019

AbstractThe strengths of synaptic connections dynamically change depending on the history of synaptic events, which is referred to as short-term plasticity (STP). While STP’s underlying mechanisms are well researched, its exact functions remain poorly understood. This is in part due to the diverse patterns of STP experimentally reported. Recently, the Allen Institute for Brain Science has launched the synaptic physiology pipeline to characterize the diverse properties of synapses. Since this pipeline generates a large-scale survey of synapses in mouse primary visual cortex using highly standardized experimental protocols, it provides a unique opportunity to study diverse patterns of STP. Here, we develop an end-to-end workflow that can characterize STP from the Allen Institute for Brain Science pipeline data and conduct network simulations to infer STP’s functions. Employing this workflow, we find 1) that diverse patterns of STP exist even in the same synapse classes and 2) that postsynaptic neurons’ responses have distinct characteristics depending on STP.
Frontal Midline Theta Reflects Cognitive Control During Planning
Authors: Domic-Siede Marcos , Irani Martín , Valdés Joaquín , Perrone-Bertolotti Marcela , Ossandón Tomás 
Published: May 2019

ABSTRACTNeural correlates of cognitive planning are not understood well at present. Behavioral paradigms targeting this function are a current challenge in cognitive neuroscience. We recorded EEG activity while subjects were performing a novel behavioral paradigm that evaluates cognitive planning function. Participants showed longer reaction times and decreased accuracy during the planning condition compared to the control condition, suggesting that the planning condition is more time consuming, therefore reflecting higher cognitive demand. Moreover, cognitive planning induced a frontal midline theta (FMθ) frequency band originating in prefrontal cortex (PFC) as shown in previous cognitive control studies. When subjects began planning, there was a progressive and sustained increase in FMθ starting after 500 milliseconds (ms) of planning. Hence, we characterized for first time, both spatial and temporal FMθ dynamics of cognitive planning as a marker of cognitive control function.
Comparison ofEscherichia colisurface attachment methods for single-cell,in vivomicroscopy
Authors: Wang Yao-Kuan , Krasnopeeva Ekaterina , Lin Ssu-Yuan , Bai Fan , Pilizota Teuta , Lo Chien-Jung 
Published: May 2019

ABSTRACTForin vivo, single-cell imaging bacterial cells are commonly immobilised via physical confinement or surface attachment. Different surface attachment methods have been used both for atomic force and optical microscopy (including super resolution), and some have been reported to affect bacterial physiology. However, a systematic comparison of the effects these attachment methods have on the bacterial physiology is lacking. Here we present such a comparison for bacteriumEscherichia coli, and assess the growth rate, size and intracellular pH of cells growing attached to different, commonly used, surfaces. We demonstrate thatE. coligrow at the same rate, length and internal pH on all the tested surfaces when in the same growth medium. The result suggests that tested attachment methods can be used interchangeably when studyingE. coliphysiology.