bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous vaccination with a live attenuated Yersinia pseudotuberculosis plague vaccine
Authors: Derbise Anne , Guillas Chloé , Gerke Christiane , Carniel Elisabeth , Pizarro-Cerdà Javier , Demeure Christian E. 
Published: October 2019

AbstractA single oral inoculation to mice of the live attenuated Yersinia pseudotuberculosis VTnF1 strain producing an F1 pseudocapsule protects against bubonic and pneumonic plague. However oral vaccination can fail in humans exposed to frequent intestinal infections. We evaluated in mice the efficacy of subcutaneous vaccine injection as an alternative way to induce protective immunity, while reducing the dose and avoiding strain release in nature. A single subcutaneous dose of up to 108 CFU induced dose-dependent antibody production. At the dose of 107 CFU, i.e. 10 times less than via the oral route, it caused a modest skin reaction and protected 100% against bubonic and 80% against pneumonic plague, caused by high doses of Yersinia pestis. Bacteria migrating to lymph nodes and spleen, but not feces, were rapidly eliminated. Thus, subcutaneous injection of VTnF1 would represent a good alternative when dissemination in nature and human intestinal responsiveness are limitations.
Degradation of non-coding RNAs promotes recycling of termination factors at sites of transcription
Authors: Villa Tommaso , Barucco Mara , Martin-Niclos Maria-Jose , Jacquier Alain , Libri Domenico 
Published: October 2019

SUMMARYA large share of the non-coding transcriptome in yeast is controlled by the Nrd1-Nab3-Sen1 (NNS) complex, which promotes transcription termination of non-coding RNA (ncRNA) genes, and by the nuclear exosome, which limits the steady state levels of the transcripts produced. How unconstrained ncRNA levels impact RNA metabolism and gene expression are longstanding and important question. Here we show that degradation of ncRNAs by the exosome is required for freeing Nrd1 and Nab3 from the released transcript after termination. In exosome mutants, these factors are sequestered by ncRNAs and cannot be efficiently recycled to sites of transcription, inducing termination defects at NNS targets. ncRNA-dependent, genome-wide termination defects can be recapitulated by the expression of a degradation-resistant, circular RNA containing a natural NNS target in exosome proficient cells. Our results have important implications for the mechanism of termination, the general impact of ncRNAs abundance and the importance of nuclear ncRNA degradation.
A single nucleotide polymorphism of PLIN2 is associated with nonalcoholic steatohepatitis and causes phenotypic changes in hepatocyte lipid droplets
Authors: Faulkner Claire S , White Collin , Jophlin Loretta L 
Published: October 2019

ABSTRACTPerilipin 2 (PLIN2) is a lipid droplet-associated protein which regulates cellular lipid storage and is highly expressed in the liver. Previous studies of a missense single nucleotide polymorphism (SNP) in PLIN2, Ser251Pro, (i.e. rs3556875) have shown this SNP to cause decreased lipolysis and increased intracellular lipid accumulation. To explore if this SNP is associated with nonalcoholic steatohepatitis (NASH), we genotyped 116 adults with NASH and 67 age- and gender-matched controls. rs3556875 was significantly associated with NASH with an allelic odds ratio of 2.98 (95% confidence interval 1.12 - 7.31, p=0.02) and in a dominant inheritance model. In an in vitro model of hepatic steatosis, expression of the Pro251 variant protein led to phenotypic changes in intracellular lipid droplets, yielding smaller diameter and up to 7 fold more lipid droplets per cell when compared to wild type PLIN2. In conclusion, the Ser251Pro SNP of PLIN2 may convey risk for NASH and causes phenotypic changes in hepatocyte lipid droplets.
A functional spiking-neuron model of activity-silent working memory in humans based on calcium-mediated short-term synaptic plasticity
Authors: Pals Matthijs , Stewart Terrence C. , Akyürek Elkan G. , Borst Jelmer P. 
Published: October 2019

AbstractIn this paper, we present a functional spiking-neuron model of human working memory (WM). This model combines neural firing for encoding of information with activity-silent maintenance. While it used to be widely assumed that information in WM is maintained through persistent recurrent activity, recent studies have shown that information can be maintained without persistent firing; instead, information can be stored in activity-silent states. A candidate mechanism underlying this type of storage is short-term synaptic plasticity (STSP), by which the strength of connections between neurons rapidly changes to encode new information. To demonstrate that STSP can lead to functional behavior, we integrated STSP by means of calcium-mediated synaptic facilitation in a large-scale spiking-neuron model and added a decision mechanism. The model was used to simulate a recent study that measured behavior and EEG activity of participants in three delayed-response tasks. In these tasks, one or two visual gratings had to be maintained in WM, and compared to subsequent probes. The original study demonstrated that WM contents and its priority status could be decoded from neural activity elicited by a task-irrelevant stimulus displayed during the activity-silent maintenance period. In support of our model, we show that it can perform these tasks, and that both its behavior as well as its neural representations are in agreement with the human data. We conclude that information in WM can be effectively maintained in activity-silent states by means of calcium-mediated STSP.Author SummaryMentally maintaining information for short periods of time in working memory is crucial for human adaptive behavior. It was recently shown that the human brain does not only store information through neural firing – as was widely believed – but also maintains information in activity-silent states. Here, we present a detailed neural model of how this could happen in our brain through short-term synaptic plasticity: rapidly adapting the connection strengths between neurons in response to incoming information. By reactivating the adapted network, the stored information can be read out later. We show that our model can perform three working memory tasks as accurately as human participants can, while using similar mental representations. We conclude that our model is a plausible and effective neural implementation of human working memory.
Cation-chloride cotransporters and the polarity of GABA signaling in mouse hippocampal parvalbumin interneurons
Authors: Otsu Yo , Donneger Florian , Schwartz Eric J , Poncer Jean Christophe 
Published: October 2019

AbstractTransmembrane chloride gradients govern the efficacy and polarity of GABA signaling in neurons and are usually maintained by the activity of cation chloride cotransporters, such as KCC2 and NKCC1. Whereas their role is well established in cortical principal neurons, it remains poorly documented in GABAergic interneurons. We used complementary electrophysiological approaches to compare the effects of GABAAR activation in adult mouse hippocampal parvalbumin interneurons (PV INs) and pyramidal cells (PCs). Loose cell attached, tight-seal and gramicidin-perforated patch recordings all show GABAAR-mediated transmission is slightly depolarizing and yet inhibitory in both PV INs and PCs. Focal GABA uncaging in whole-cell recordings reveal that KCC2 and NKCC1 are functional in both PV INs and PCs but differentially contribute to transmembrane chloride gradients in their soma and dendrites. Blocking KCC2 function depolarizes the reversal potential of GABAAR-mediated currents in PV INs and PCs, often beyond firing threshold, showing KCC2 is essential to maintain the inhibitory effect of GABAARs. Finally, we show that repetitive 10 Hz activation of GABAARs in both PV INs and PCs leads to a progressive decline of the postsynaptic response independently of the ion flux direction or KCC2 function. This suggests intraneuronal chloride buildup may not predominantly contribute to activity-dependent plasticity of GABAergic synapses in this frequency range. Altogether our data demonstrate similar mechanisms of chloride regulation in mouse hippocampal PV INs and PCs and suggest KCC2 downregulation in the pathology may affect the valence of GABA signaling in both cell types.Key point summaryCation-chloride cotransporters (CCCs) play a critical role in controlling the efficacy and polarity of GABAA receptor (GABAAR)-mediated transmission in the brain, yet their expression and function in GABAergic interneurons has been overlooked.We compared the polarity of GABA signaling and the function of CCCs in mouse hippocampal pyramidal neurons and parvalbumin-expressing interneurons.Under resting conditions, GABAAR activation was mostly depolarizing and yet inhibitory in both cell types. KCC2 blockade further depolarized the reversal potential of GABAAR-mediated currents often above action potential threshold.However, during repetitive GABAAR activation, the postsynaptic response declined independently of the ion flux direction or KCC2 function, suggesting intracellular chloride buildup is not responsible for this form of plasticity.Our data demonstrate similar mechanisms of chloride regulation in mouse hippocampal pyramidal neurons and parvalbumin interneurons.
Cumulus: a cloud-based data analysis framework for large-scale single-cell and single-nucleus RNA-seq
Authors: Li Bo , Gould Joshua , Yang Yiming , Sarkizova Siranush , Tabaka Marcin , Ashenberg Orr , Rosen Yanay , Slyper Michal , Kowalczyk Monika S , Villani Alexandra-Chloé , Tickle Timothy , Hacohen Nir , Rozenblatt-Rosen Orit , Regev Aviv 
Published: October 2019

AbstractMassively parallel single-cell and single-nucleus RNA-seq (sc/snRNA-seq) have opened the way to systematic tissue atlases in health and disease, but as the scale of data generation is growing, so does the need for computational pipelines for scaled analysis. Here, we developed Cumulus, a cloud-based framework for analyzing large scale sc/snRNA-seq datasets. Cumulus combines the power of cloud computing with improvements in algorithm implementations to achieve high scalability, low cost, user-friendliness, and integrated support for a comprehensive set of features. We benchmark Cumulus on the Human Cell Atlas Census of Immune Cells dataset of bone marrow cells and show that it substantially improves efficiency over conventional frameworks, while maintaining or improving the quality of results, enabling large-scale studies.
Discovery of a prevalent picornavirus by visualizing zebrafish immune responses
Authors: Balla Keir M. , Rice Marlen C. , Gagnon James A. , Elde Nels C. 
Published: October 2019

AbstractThe discovery of new viruses currently outpaces our capacity for experimental examination of infection biology. To better couple virus discovery with immunology, we genetically modified zebrafish to visually report on virus infections. After generating a strain that expresses green fluorescent protein (GFP) under an interferon-stimulated gene promoter, we repeatedly observed transgenic larvae spontaneously expressing GFP days after hatching. RNA sequencing of GFP-positive zebrafish revealed a picornavirus distantly related to known viruses. We detected this virus in publicly available sequencing data from seemingly asymptomatic zebrafish in research institutes world-wide. These data revealed widespread tissue tropism and identified the clonal CG2 strain as notably vulnerable to picornavirus infection. Infection induces the expression of numerous antiviral immune defense genes in zebrafish, an effect also evident in public data. Our study describes a prevalent picornavirus that infects zebrafish, and provides new strategies for simultaneously discovering viruses and their impact on vertebrate hosts.
Comparative analysis of seed size, germination, and vegetative allocation in annual and herbaceous perennial crops and their wild relatives inLupinusandPhaseolus(Fabaceae)
Authors: Herron Sterling A. , Rubin Matthew J. , Ciotir Claudia , Crews Timothy E. , Van Tassel David L. , Miller Allison J. 
Published: October 2019

ABSTRACTHerbaceous perennial species are receiving increased attention for their potential to provide both edible products and ecosystem services in agricultural systems. Many legumes (Fabaceae Lindl.) are of special interest due to nitrogen fixation carried out by bacteria in their roots and their production of protein-rich, edible seeds. However, herbaceous perennial legumes have yet to enter widespread use as pulse crops, and the response of wild, herbaceous, perennial species to artificial selection for increased seed yield remains under investigation. Here we compare cultivated and wild accessions of congeneric annual and herbaceous perennial legume species to investigate associations of lifespan and cultivation with seed size, germination, and first year vegetative growth patterns, and to characterize covariation among traits. We use “cultivated” to describe accessions with a history of human planting and use, which encompasses a continuum of domestication. Analyses focused on three annual and eight perennialLupinusspecies, and three annual and four perennialPhaseolusspecies. We found a significant association of both lifespan and cultivation status with seed size (weight, area, length), germination proportion, node number, stem diameter, shoot dry mass, and root dry mass. Wild seed size was greater in annuals forLupinusand greater for perennials inPhaseolus. Germination was lower in wild perennials than wild annuals in both genera, and vegetative allocation was roughly equivalent across lifespans in wildPhaseolus. Relative to wild forms, both cultivated annual and cultivated perennial accessions exhibited greater seed size, lower germination proportion, and larger overall plant size. Seed size traits were positively correlated with vegetative growth traits, and all biomass traits examined here were positively correlated. This study highlights some basic similarities and differences between annual and herbaceous perennial legumes, and provides insights into how perennial legumes might respond to artificial selection compared to annual species.
Spondweni virus causes fetal harm in a mouse model of vertical transmission and is transmitted byAedes aegyptimosquitoes
Authors: Jaeger Anna S. , Weiler Andrea M. , Moriarty Ryan V. , Rybarczyk Sierra , O’Connor Shelby L. , O’Connor David H. , Seelig Davis M. , Fritsch Michael K. , Friedrich Thomas C. , Aliota Matthew T. 
Published: October 2019

AbstractSpondweni virus (SPONV) is the most closely related known flavivirus to Zika virus (ZIKV). Its pathogenic potential and vector specificity have not been well defined. SPONV has been found predominantly in Africa, but was recently detected in a pool ofCulex quinquefasciatusmosquitoes in Haiti. Here we show that SPONV can cause significant fetal harm, including demise, comparable to ZIKV, in a mouse model of vertical transmission. Following maternal inoculation, we detected infectious SPONV in placentas and fetuses, along with significant fetal and placental histopathology, together indicating vertical transmission. To test vector competence, we exposedAedes aegyptiandCulex quinquefasciatusmosquitoes to SPONV-infected bloodmeals.Aedes aegypticould efficiently transmit SPONV, whereasCulex quinquefasciatuscould not. Our results suggest that SPONV has the same features that made ZIKV a public health risk.
Full-length immunoglobulin high-throughput sequencing reveals specific novel mutational patterns in POEMS syndrome
Authors: Bender Sébastien , Javaugue Vincent , Saintamand Alexis , Ayala Maria Victoria , Alizadeh Mehdi , Filloux Matthieu , Pascal Virginie , Gachard Nathalie , Lavergne David , Auroy Fabienne , Cogne Michel , Bridoux Frank , Sirac Christophe , Jaccard Arnaud 
Published: October 2019

AbstractPOEMS syndrome is a rare multisystem disease due to an underlying plasma cell (PC) dyscrasia. The pathophysiology of the disease remains unclear but the role of the monoclonal immunoglobulin (Ig) light chain (LC) is strongly suspected, due to the highly restrictive usage of two λ variable (V) domains (IGLV1-40 and IGLV1-44) and the general improvement of clinical manifestations following PC clone-targeted treatment. However, the diagnostic value of Ig LC sequencing, especially in case of incomplete forms of the disease, remains to be determined. Using a sensitive high-throughput Ig repertoire sequencing on RNA (RACE-RepSeq), we detected a λ LC monoclonal expansion in the bone marrow (BM) of 85% of patients with POEMS syndrome, including some in whom bone marrow tests routinely performed to diagnose plasma cell dyscrasia failed to detect λ+monoclonal PCs. Twenty-four of the 30 LC clonal sequences found (80%) were derived from the IGLV1-40 and IGLV1-44 germline genes, two from the closely related IGLV1-36 gene, and all were associated with an IGLJ3*02 junction (J) gene, confirming the high restriction of VJ region usage in POEMS syndrome. RACE-RepSeq VJ full-length sequencing additionally revealed original mutational patterns, the strong specificity of which might crucially help establish or eliminate the diagnosis of POEMS syndrome in uncertain cases. Thus, RACE-RepSeq appears as a sensitive, rapid and specific tool to detect low-abundance PC clones in BM, and assign them to POEMS syndrome, with all the consequences for therapeutic options hereby.
Analysing the safe and just operating space of agriculture in the world: past, present and future
Authors: Roy Ajishnu , Pramanick Kousik 
Published: October 2019

AbstractAgriculture, along with industry and household sector are three major sectors of human consumption. Agriculture has proved to be a major contributor to exceeding planetary boundaries. Here, we have explored the impact of agriculture in the Earth system processes, through eight dimensions of planetary boundaries or safe operating spaces: climate change (10.73%), freshwater use (91.56%), arable land use (37.27%), nitrogen use (95.77%), phosphorus use (87.28%), ecological footprint (19.42%), atmospheric pollution (2.52% - 38.08%) and novel entities. In this work, we have also shown role of agriculture to the socio-economic development dimensions: gender equality, employment and economic growth. We have shown that the safe operating limits for agriculture are going to decline by almost 55% (climate change), 300% (freshwater use), 50-55% (arable land use), 180% (nitrogen use), 265% (phosphorus use) and 20% (ecological footprint) in 2050, if the most inefficient way of consumption is chosen and continued. To alleviate the role of agriculture in transgressing planetary boundaries, it is indispensable to comprehend how many roles of agriculture is playing and where which target should be set to framework the national agricultural policies in coherence with attaining sustainable development goals of UN by 2030.
Bayesian Neural Networks for Cellular Image Classification and Uncertainty Analysis
Authors: Deodato Giacomo , Ball Christopher , Zhang Xian 
Published: October 2019

AbstractOver the last decades, deep learning models have rapidly gained popularity for their ability to achieve state-of-the-art performances in different inference settings. Novel domains of application define a new set of requirements that transcend accurate predictions and depend on uncertainty measures. The aims of this study are to implement Bayesian neural networks and use the corresponding uncertainty estimates to improve predictions and perform dataset analysis. We identify two main advantages in modeling the predictive uncertainty of deep neural networks performing classification tasks. The first is the possibility to discard highly uncertain predictions to increase model accuracy. The second is the identification of unfamiliar patterns in the data that correspond to outliers in the model representation of the training data distribution. Such outliers can be further characterized as either corrupted observations or data belonging to different domains. Both advantages are well demonstrated on benchmark datasets. Furthermore we apply the Bayesian approach to a biomedical imaging dataset where cancer cells are treated with diverse drugs, and show how one can increase classification accuracy and identify noise in the ground truth labels with uncertainty analysis.
Leveraging multiple layers of data to predict Drosophila complex traits
Authors: Morgante Fabio , Huang Wen , Sørensen Peter , Maltecca Christian , Mackay Trudy F. C. 
Published: November 2019

AbstractAn important challenge in genetics is to be able to predict complex traits accurately. Despite recent advances, prediction accuracy for most complex traits remains low. Here, we used the Drosophila Genetic Reference Panel (DGRP), a collection of 200 lines with whole-genome sequences and deep RNA sequencing data, to evaluate the usefulness of using high-quality gene expression levels compared to relying on genotypes for predicting three complex traits. We found that expression levels provided higher accuracy than genotypes for starvation resistance, similar accuracy for chill coma recovery, and lower accuracy for startle response. Models including both genotype and expressions levels did not outperform the best single component model. However, accuracy increased considerably for all the three traits when we included another layer of information, i.e., gene ontology (GO). We found that a limited number of GO terms, some of which had a clear biological interpretation, were strongly predictive of the traits. In summary, this study shows that integrating different sources of information can improve prediction accuracy, especially when large samples are not available.
Integrative Multi-Omics Analysis of Barley Genotypes Shows Differential Salt-Induced Osmotic Barriers and Response Phases Among Rootzones
Authors: Wing Ho Ho William , Hill Camilla B. , Doblin Monika S. , Shelden Megan C. , van de Meene Allison , Rupasinghe Thusitha , Bacic Antony , Roessner Ute 
Published: October 2019

ABSTRACTThe mechanisms underlying rootzone-localised responses to salinity stress during early stage of barley development remains fragmentary and elusive. Here, we performed a comprehensive detection of the multi-root-omes (transcriptomes, metabolomes, lipidomes) of a domesticated barley cultivar (Clipper) and a landrace (Sahara) with seedling root growth maintained and restricted in response to salt stress, respectively. Novel generalized linear models were designed to determine differentially expressed genes (DEG) or abundant metabolites (DAM) specific to salt treatments, genotypes, or rootzones (meristematic Z1, elongation Z2, maturation Z3). Based on pathway over-representation of the DEG and DAM, phenylpropanoid biosynthesis is the most statistically over-represented biological pathways among all salinity responses observed. Together with the histological evidence, an intense salt-induced lignin impregnation was found only at the stelic cell wall of Clipper Z2, comparing to a unique elevation of suberin deposition across Sahara Z2. This suggests two differential salt-induced modulations of apoplastic flow between the genotypes. Based on global correlation network construction of the DEG and DAM, callose deposition that potentially adjusted the symplastic flow in roots was almost independent of salinity in rootzones of Clipper, but was markedly decreased in that of Sahara. Through closer examinations of molecular and hormonal clues, we further demonstrate that the salinity response in rootzones of Clipper were mostly at recovery phase, comparing to Sahara with rootzones retained at quiescence. Taken together, we propose that two distinctive salt tolerance mechanisms could exist in Clipper (growth-sustaining) and Sahara (salt-shielding), providing important clues for improving crop plasticity to cope with the deteriorating global salinization of soil.