bluuebunny/crossref_metadata_2025_split huggingface dataset:
GBA variants in REM sleep behavior disorder: a multicenter study
Authors: Krohn Lynne , Ruskey Jennifer A. , Rudakou Uladzislau , Leveille Etienne , Asayesh Farnaz , Hu Michele T.M. , Arnulf Isabelle , Dauvilliers Yves , Högl Birgit , Stefani Ambra , Monaca Christelle Charley , Beatriz Abril , Plazzi Giuseppe , Antelmi Elena , Ferini-Strambi Luigi , Heidbreder Anna , Boeve Bradley F. , Espay Alberto J. , De Cock Valérie Cochen , Mollenhauer Brit , Sixel-Döring Friederike , Trenkwalder Claudia , Sonka Karel , Kemlink David , Figorilli Michela , Puligheddu Monica , Dijkstra Femke , Viaene Mineke , Oertel Wolfgang , Toffoli Marco , Gigli Gian Luigi , Valente Mariarosaria , Gagnon Jean-François , Desautels Alex , Montplaisir Jacques Y. , Postuma Ronald B. , Rouleau Guy A. , Gan-Or Ziv 
Published: November 2019

AbstractObjectiveTo study the role of GBA variants in the risk for isolated rapid-eye-movement (REM)-sleep behavior disorder (iRBD) and conversion to overt neurodegeneration.MethodsA total of 4,147 individuals were included: 1,061 iRBD patients and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyzed the effects of GBA variants on the risk for iRBD, age at onset (AAO) and conversion rates.ResultsGBA variants were found in 9.5% of iRBD patients compared to 4.1% in controls (odds ratio [OR]=2.45, 95% CI=1.87–3.22, p=1×10−10). The estimated OR for mild p.N370S variant carriers was 3.69, 95% CI=1.90–7.14, p=3.5×10−5, while for severe variant carriers it was 17.55, 95% CI=2.11–145.9, p=0.0015. Carriers of severe GBA variants had an average AAO of 52.8 years, 7-8 years earlier than those with mild variants or non-carriers (p=0.029). Of the GBA variant carriers with available data, 52.5% had converted, compared to 35.6% in non-carriers (p=0.011), with a trend for faster conversion among severe GBA variant carriers. However, the results on AAO and conversion were based on small numbers and should be taken with caution.ConclusionsGBA variants robustly and differentially increase the risk of iRBD. The rate of conversion to neurodegeneration is also increased and may be faster among severe GBA variant carriers, although confirmation will be required in larger samples. Screening for RBD in healthy carriers of GBA variants should be studied as a potential way to identify GBA variant carriers who will develop a synucleinopathy in the future.
Eco-evolutionary dynamics of nested Darwinian populations and the emergence of community-level heredity
Authors: Doulcier Guilhem , Lambert Amaury , De Monte Silvia , Rainey Paul B. 
Published: November 2019

AbstractInteractions among microbial cells can generate new chemistries and functions, but exploitation requires establishment of communities that reliably recapitulate community-level phenotypes. Using mechanistic mathematical models, we show how simple manipulations to population structure can exogenously impose Darwinian-like properties on communities. Such scaffolding causes communities to participate directly in the process of evolution by natural selection and drives the evolution of cell-level interactions to the point where, despite underlying stochasticity, derived communities give rise to offspring communities that faithfully re-establish parental phenotype. The mechanism is akin to a developmental process (developmental correction) that arises from density dependent interactions among cells. Knowledge of ecological factors affecting evolution of developmental correction has implications for understanding the evolutionary origin of major egalitarian transitions, symbioses, and for top-down engineering of microbial communities.
Sample demultiplexing, multiplet detection, experiment planning and novel cell type verification in single cell sequencing
Authors: Xin Hongyi , Yan Qi , Jiang Yale , Lian Qiuyu , Luo Jiadi , Erb Carla , Duerr Richard , Chen Kong , Chen Wei 
Published: November 2019

AbstractIdentifying and removing multiplets from downstream analysis is essential to improve the scalability and reliability of single cell RNA sequencing (scRNA-seq). High multiplet rates create artificial cell types in the dataset. Sample barcoding, including the cell hashing technology and the MULTI-seq technology, enables analytical identification of a fraction of multiplets in a scRNA-seq dataset.We propose a Gaussian-mixture-model-based multiplet identification method, GMM-Demux. GMM-Demux accurately identifies and removes the sample-barcoding-detectable multiplets and estimates the percentage of sample-barcoding-undetectable multiplets in the remaining dataset. GMM-Demux describes the droplet formation process with an augmented binomial probabilistic model, and uses the model to authenticate cell types discovered from a scRNA-seq dataset.We conducted two cell-hashing experiments, collected a public cell-hashing dataset, and generated a simulated cellhashing dataset. We compared the classification result of GMM-Demux against a state-of-the-art heuristic-based classifier. We show that GMM-Demux is more accurate, more stable, reduces the error rate by up to 69×, and is capable of reliably recognizing 9 multiplet-induced fake cell types and 8 real cell types in a PBMC scRNA-seq dataset.
Unique allometry of group size and collective brain mass in humans and primates relative to other mammals
Authors: Hamilton Marcus J. , Walker Robert S. 
Published: November 2019

AbstractGroup living is common in mammals, particularly in primates and humans. Across species, groups are social networks where co-residing members exchange information and balance trade-offs between competition and cooperation for space, resources, and reproductive opportunities. From a macroecological perspective, species-specific group sizes are ultimately constrained by body size, population density, and the environmental supply rate of home ranges. Here, we derive an allometric null model for group size in mammals based on individual energy demands and ecological constraints. Using Bayesian phylogenetic mixed models we show that primates exhibit unique allometries relative to other mammals. Moreover, as large-bodied primates, human hunter-gatherers have among the largest social groups of any mammal. We then explore the consequences of this unique social allometry by considering how mammalian brain size scales up in social groups that differ in size across mammals. We show similarly unique allometries in what we term the collective brain mass of social groups in primates relative to all other mammals. These results show that for a given body size primates have both larger brains and larger social networks than other mammals. Consequently, proportionally larger primate brains interact in proportionally larger social networks with important consequences for group cognition. We suggest that the size, scale, and complexity of human social networks in the 21stcentury have deep evolutionary roots in primate ecology and mammalian brain allometry.
Cortical cell stiffness is independent of substrate mechanics
Authors: Rheinlaender Johannes , Dimitracopoulos Andrea , Wallmeyer Bernhard , Kronenberg Nils M. , Chalut Kevin J. , Gather Malte C. , Betz Timo , Charras Guillaume , Franze Kristian 
Published: November 2019

AbstractCortical stiffness is an important cellular property that changes during migration, adhesion, and growth. Previous atomic force microscopy (AFM) indentation measurements of cells cultured on deformable substrates suggested that cells adapt their stiffness to that of their surroundings. Here we show that the force applied by AFM onto cells results in a significant deformation of the underlying substrate if it is softer than the cells. This ‘soft substrate effect’ leads to an underestimation of a cell’s elastic modulus when analyzing data using a standard Hertz model, as confirmed by finite element modelling (FEM) and AFM measurements of calibrated polyacrylamide beads, microglial cells, and fibroblasts. To account for this substrate deformation, we developed the ‘composite cell-substrate model’ (CoCS model). Correcting for the substrate indentation revealed that cortical cell stiffness is largely independent of substrate mechanics, which has significant implications for our interpretation of many physiological and pathological processes.
Translationally relevant transcriptomic alterations in mouse ischemic cerebral microvessels
Authors: Callegari Keri , Dash Sabyasachi , Uchida Hiroki , Lee Yunkyoung , Ito Akira , Zhang Tuo , Xiang Jenny , Sanchez Teresa 
Published: November 2019

ABSTRACTIncreasing evidence implicates cerebral microvascular dysfunction in the pathophysiology of numerous central nervous system pathologies, including stroke. Understanding the molecular alterations in cerebral microvessels in these conditions will provide original opportunities for scientific investigation at the pre-clinical and clinical levels. In this study, we conducted a novel genome-wide transcriptomic analysis of microvessels in a mouse model of transient focal cerebral ischemia. Using a publicly available human ischemic stroke dataset, we identified shared alterations in our microvessel dataset with implications for human pathophysiology. From this unbiased analysis, we report predicted alterations in inter- and intra-cellular signaling, emphasizing perturbations in genes involved in blood brain barrier function, endothelial cell activation and metabolism. Furthermore, our study unveiled previously unreported gene expression changes associated with altered sphingolipid metabolism. Altogether, our results have identified microvessel-specific transcriptomic changes in a number of translationally relevant pathways that support the targeting of these pathways in preclinical studies. The data shared here provide a resource for future investigation of translationally relevant pathways in ischemic stroke.
Unraveling the complex story of intergenomic recombination in ABB allotriploid bananas
Authors: Alberto Cenci , Julie Sardos , Yann Hueber , Guillaume Martin , Catherine Breton , Nicolas Roux , Rony Swennen , Christian Carpentier Sebastien , Mathieu Rouard 
Published: November 2019

AbstractBackground and AimsBananas (Musa spp.) are a major staple food for hundreds of millions of people in developing countries. The cultivated varieties are seedless and parthenocarpic clones of which the ancestral origin remains to be clarified. The most important cultivars are triploids with an AAA, AAB, or ABB genome constitution, with A and B genomes provided by M. acuminata and M. balbisiana, respectively. Previous studies suggested that inter-genome recombinations were relatively common in banana cultivars and that triploids were more likely to have passed through an intermediate hybrid. In this study, we investigated the chromosome structure within the ABB group, composed of starchy cooking bananas that play an important role in food security.MethodsUsing SNP markers called from RAD-Seq data, we studied the chromosome structure of 36 ABB genotypes spanning defined taxonomic subgroups. To complement our understanding, we search for similar events within nine AB hybrid genotypes.Key ResultsRecurrent Homoeologous Exchanges (HEs), i.e. chromatin exchanges between A and B subgenomes were unraveled with at least 9 founding events at the origin of the ABB bananas prior to the clonal diversification. The discovery of this nine founding events allows discussing the possible routes that led to the creation of the different subgroups and formulate new hypotheses. Based on our observations, we suggest different routes that gave rise to the current diversity in the ABB cultivars. Routes involving primary AB hybrids, routes leading to shared HEs and routes leading to a B excess ratio. Genetic fluxes took place between M. acuminata and M. balbisiana, particularly in India, where these unbalanced AB hybrids and ABB allotriploid originated and where cultivated M. balbisiana are abundant.ConclusionsThe result of this study clarifies the classification of ABB cultivars and leading possibly to the revision of the classification of this subgroup. This is an important step to unravel the origin of polyploid bananas, and contributes to possible scenarios on the origin. ABB bananas are hypothesized to be more drought tolerant. Knowing the origin of our current cultivars and so their potential parents will help breeders to make the right choices for future crosses. The M. balbisiana genome is a good source to create new cultivars able to answer the numerous challenges of banana breeding.
Immediate activation of chemosensory neuron gene expression by bacterial metabolites is selectively induced by distinct cyclic GMP-dependent pathways inC. elegans
Authors: Park Jaeseok , Meisel Joshua D , Kim Dennis H 
Published: November 2019

AbstractDynamic gene expression in neurons shapes fundamental processes of the nervous systems of animals. But how different stimuli that activate the same neuron can lead to distinct transcriptional responses remains unclear. We have been studying how microbial metabolites modulate gene expression in chemosensory neurons ofCaenorhabditis elegans. Considering the diverse environmental stimuli that can activate chemosensory neurons ofC. elegans, we have sought to understand how specific transcriptional responses can be generated in these neurons in response to distinct cues. We have focused on the mechanism of rapid (<6 min) and selective transcriptional induction ofdaf-7, a gene encoding a TGF-β ligand that promotes bacterial lawn avoidance, in the ASJ chemosensory neurons in response to the pathogenic bacteriumPseudomonas aeruginosa. Here, we define the involvement of two distinct cyclic GMP (cGMP)-dependent pathways that are required fordaf-7expression in the ASJ neuron pair in response toP. aeruginosa. We show that a calcium-independent pathway dependent on the cGMP-dependent protein kinase G (PKG) EGL-4, and a canonical calcium-dependent signaling pathway dependent on the activity of a cyclic nucleotide-gated channel subunit CNG-2, function in parallel to activate rapid, selective transcription ofdaf-7in response toP. aeruginosametabolites. Our data suggest a requirement for PKG in promoting the fast, selective early transcription of neuronal genes in shaping responses to distinct microbial stimuli in a pair of chemosensory neurons ofC. elegans.Author SummaryThe nervous systems of animals carry out the crucial roles of sensing and interpreting the external environment. When the free-living microscopic roundwormC. elegansis exposed to the pathogenic bacteriaPseudomonas aeruginosa, sensory neurons detect metabolites produced by the pathogen and induce expression of the gene for a neuroendocrine ligand called DAF-7. In turn, activity of DAF-7 is required for the full avoidance response to theP. aeruginosa, allowing the animals to reduce bacterial load and survive longer. Here, we systematically dissect the molecular pathway between the sensation ofP. aeruginosametabolites and the expression ofdaf-7in a pair of C. elegans sensory neurons. We show that the intracellular signaling molecule cyclic GMP is a key signaling intermediate. In addition, we show that there are calcium-dependent and calcium-independent pathways that are both required to engagedaf-7expression, highlighting an organizational principle that allows neurons to distinguish between various stimuli.
Relationships between puroindoline-prolamin interactions and wheat grain hardness
Authors: Geneix Nathalie , Dalgalarrondo Michèle , Tassy Caroline , Nadaud Isabelle , Barret Pierre , Bakan Bénédicte , Elmorjani Khalil , Marion Didier 
Published: November 2019

AbstractGrain hardness is an important quality trait of cereal crops. In wheat, it is mainly determined by theHardnesslocus that harbors genes encoding puroindoline A (PINA) and puroindoline B (PINB). Any deletion or mutation of these genes leading to the absence of PINA or to single amino acid changes in PINB leads to hard endosperms. Although it is generally acknowledged that hardness is controlled by adhesion strength between the protein matrix and starch granules, the physicochemical mechanisms connecting puroindolines and the starch-protein interactions are unknown as of this time. To explore these mechanisms, we focused on PINA. The overexpression in a hard wheat cultivar (cv. Courtot with thePina-D1aandPinb-D1dalleles) decreased grain hardness in a dose-related effect, suggesting an interactive process. When PINA was added to gliadins in solution, large aggregates of up to 13 µm in diameter were formed. Turbidimetry measurements showed that the PINA-gliadin interaction displayed a high cooperativity that increased with a decrease in pH from neutral to acid (pH 4) media, mimicking the pH change during endosperm development. No turbidity was observed in the presence of isolated α– and γ-gliadins, but non-cooperative interactions of PINA with these proteins could be confirmed by surface plasmon resonance. A significant higher interaction of PINA with γ-gliadins than with α–gliadins was observed. Similar binding behavior was observed with a recombinant repeated polypeptide that mimics the repeat domain of gliadins, i.e., (Pro-Gln-Gln-Pro-Tyr)8. Taken together, these results suggest that the interaction of PINA with a monomeric gliadin creates a nucleation point leading to the aggregation of other gliadins, a phenomenon that could prevent further interaction of the storage prolamins with starch granules. Consequently, the role of puroindoline-prolamin interactions on grain hardness should be addressed on the basis of previous observations that highlight the similar subcellular routing of storage prolamins and puroindolines.
Robust, general purpose, digital power line hum filter which is free of deformations and which can be applied to large transients
Authors: de Lussanet de la Sablonière Marc H. E. 
Published: November 2019

AbstractPower line interference (“hum noise”) is a common source of noise in recorded biological data. It has a highly constant frequency with harmonics and little variation in amplitude and wave shape. In contrast to stochastic noise it is phasic, i.e., the phase relation remains constant across long intervals. In digital recordings, the measurement frequency is typically very close to a multiple of the hum frequency (50 or 60 Hz). Common filters introduce various kinds of distortions and errors. The here proposed subtraction method makes use of the specific properties of power line hum. For this, it computes a moving estimate of the hum noise by taking the periodic median of the high-pass filtered signal. The resulting periodic median subtraction (PMS) filter reliably removes hum of any harmonic composition, even if the ground frequency is lacking. The filter is completely free of border artifacts. It does not introduce distortions, even if around sharp transients such as in force plate recordings of jumping. The filter is validated on recorded and artificial data. The errors are quantified. The results also show that the errors of hum filters generally increase with the high-frequency content of the data. Thus, the removal of hum from a force plate recording generally gives better results than from an EMG recoding. Compared to other filters, the errors of the PMS filter are generally lower than the best hum filters currently known.
An integrated multiscale, multicellular skin model
Authors: Tasseff Ryan , Aguilar Boris , Kahan Simon , Kang Seunghwa , Bascom Charles C. , Isfort Robert J. 
Published: November 2019

ABSTRACTSkin is our primary barrier to the outside world, protecting us from physical, biological and chemical threats. Developing innovative products that preserve and improve skin barrier function requires a thorough understanding of the mechanisms underlying barrier response to topical applications. In many fields, computer simulations already facilitate understanding, thus accelerating innovation. Simulations of software models allow scientists to test hypothesized mechanisms by comparing predicted results to physical observations. They also enable virtual product optimization, without physical experiments, once mechanisms have been validated. The physical accessibility and abundant knowledge of skin structure makes it a prime candidate for computational modeling. In this article, we describe a computational multiscale multicellular skin model used to simulate growth and response of the epidermal barrier. The model integrates several modeling styles and mathematical frameworks including ordinary differential equations, partial differential equations, discrete agent-based modeling and discrete element methods. Specifically, to capture cell biology and physical transport, we combined four distinct sub-models from existing literature. We also implemented methods for elastic biomechanics. Our software implementation of the model is compatible with the high-performance computing simulation platform Biocellion. The integrated model recapitulates barrier formation, homeostasis and response to environmental, chemical and mechanical perturbation. This work exemplifies methodology for integrating models of vastly different styles. The methodology enables us to effectively build on existing knowledge and produce “whole-system” tissue models capable of displaying emergent properties. It also illustrates the inherent technical difficulties associated with the mounting complexity of describing biological systems at high fidelity. Among the challenges are validation of the science, the mathematical representations approximating the science and the software implementing these representations. Responsibility for a discrepancy observed between in silico and in vitro results may as easily lie at one of these three levels as at another, demanding that any sustainable modeling endeavor engage expertise from biology, mathematics and computing.
DCP2plays multiple roles duringDrosophiladevelopment – possible case of moonlighting?
Authors: Kunar Rohit , Roy Jagat K 
Published: November 2019

AbstractmRNA decapping proteins (DCPs) are components of the P-bodies in the cell which are hubs of mRNAs targeted for decay and they provide the cell with a reversible pool of mRNAs in response to cellular demands. TheDrosophilagenome codes for two decapping proteins, DCP1 and DCP2 out of which DCP2 is the cognate decapping enzyme. The present endeavour explores the endogenous promoter firing, transcript and protein expression ofDCP2inDrosophilawherein, besides a ubiquitous expression across development, we identify active expression paradigm during dorsal closure and a plausible moonlighting expression in the Corazonin neurons of the larval brain. We also demonstrate that the ablation ofDCP2leads to embryonic lethality and defects in vital morphogenetic processes whereas a knockdown ofDCP2in the Corazonin neurons reduces the sensitivity to ethanol in adults, thereby ascribing novel regulatory roles to DCP2. Our findings unravel novel putative roles for DCP2 and identify it as a candidate for studies on the regulated interplay of essential molecules during early development inDrosophila, nay the living world.