bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretable machine learning models for single-cell ChIP-seq imputation
Authors: Albrecht Steffen , Andreani Tommaso , Andrade-Navarro Miguel A. , Fontaine Jean-Fred 
Published: December 2019

AbstractMotivationSingle-cell ChIP-seq (scChIP-seq) analysis is challenging due to data sparsity. High degree of data sparsity in biological high-throughput single-cell data is generally handled with imputation methods that complete the data, but specific methods for scChIP-seq are lacking. We present SIMPA, a scChIP-seq data imputation method leveraging predictive information within bulk data from ENCODE to impute missing protein-DNA interacting regions of target histone marks or transcription factors.ResultsImputations using machine learning models trained for each single cell, each target, and each genomic region accurately preserve cell type clustering and improve pathway-related gene identification on real data. Results on simulated data show that 100 input genomic regions are already enough to train single-cell specific models for the imputation of thousands of undetected regions. Furthermore, SIMPA enables the interpretation of machine learning models by revealing interaction sites of a given single cell that are most important for the imputation model trained for a specific genomic region. The corresponding feature importance values derived from promoter-interaction profiles of H3K4me3, an activating histone mark, highly correlate with co-expression of genes that are present within the cell-type specific pathways. An imputation method that allows the interpretation of the underlying models facilitates users to gain an even deeper understanding of individual cells and, consequently, of sparse scChIP-seq datasets.Availability and implementationOur interpretable imputation algorithm was implemented in Python and is available athttps://github.com/salbrec/SIMPA
Determining insulin sensitivity from glucose tolerance tests in Iberian and Landrace pigs
Authors: Rodríguez-López JM , Lachica M , González-Valero L , Fernández-Fígares I 
Published: December 2019

ABSTRACTAs insulin sensitivity may help to explain divergences in growth and body composition between native and modern breeds, metabolic responses to glucose infusion were measured using an intra-arterial glucose tolerance test (IAGTT). Iberian (n = 4) and Landrace (n = 5) barrows (47.0 ± 1.2 kg BW), fitted with a permanent carotid artery catheter were injected with glucose (500 mg/kg BW) and blood samples collected at −10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120 and 180 min following glucose infusion. Plasma samples were analysed for insulin, glucose, lactate, triglycerides, cholesterol, creatinine, albumin and urea. Insulin sensitivity indices were calculated and analyed. Mean plasma glucose, creatinine and cholesterol concentrations were lower (P< 0.01) in Iberian (14, 68 and 22%, respectively) compared with Landrace pigs during the IAGTT. However, mean plasma insulin, lactate, triglycerides and urea concentrations were greater (P< 0.001) in Iberian (50, 35, 18 and 23%, respectively) than in Landrace pigs. Iberian pigs had larger area under the curve (AUC) of insulin (P< 0.05) and lactate (P< 0.1), and smaller (P< 0.05) AUC for glucose 0-60 min compared with Landrace pigs. Indices for estimating insulin sensitivity in fasting conditions indicated improved β-cell function in Iberian compared with Landrace pigs, but no difference (P> 0.10) in calculated insulin sensitivity index was found after IAGTT between breeds. A time response (P< 0.05) was obtained for insulin, glucose and lactate so that maximum concentration was achieved 10 and 15 min post-infusion for insulin (Iberian and Landrace pigs, respectively), immediately post-infusion for glucose, and 20 min post-infusion for lactate, decreasing thereafter until basal levels. There was no time effect for the rest of metabolites evaluated. In conclusion, growing Iberian pigs challenged with an IAGTT showed changes in biochemical parameters and insulin response that may indicate an early stage of insulin resistance.
Spatial Areas of Genotype Probability (SPAG): predicting the spatial distribution of adaptive genetic variants under future climatic conditions
Authors: Rochat Estelle , Joost Stéphane 
Published: December 2019

AbstractIn a context of rapid global change, one of the key components for the survival of species is their genetic adaptive potential. Many methods have been developed to identify adaptive genetic variants, but few tools were made available to integrate this knowledge into conservation management. We present here the SPatial Areas of Genotype probability (SPAG), using genotype-environment logistic associations to map the probability of finding beneficial variants in a study area. We define a univariate model predicting the spatial distribution of a single genotype, and three multivariate models allowing the integration of several genotypes, potentially associated with various environmental variables. We then integrate climate change projections to map the corresponding future distribution of genotypes. The analysis of the mismatch between current and future SPAGs makes it possible to identify a) populations that are better adapted to the future climate through the presence of genetic variants able to cope with future conditions, and b) vulnerable populations where genotype(s) of interest are not frequent enough for the individuals to adapt to the future climate. We validate the SPAG approach using simulations and we use it to study the potential adaptation of 161 Moroccan and 382 European goats to the bioclimatic conditions. In Morocco, using whole genome sequence data, we identify seven genomic regions strongly associated with the precipitation seasonality (WorldClim database). The predicted shift in SPAGs under a strong climate change scenario for 2070 highlights goat populations likely to be threatened by the expected increase in precipitation variation in the future. In Europe, we find genomic regions associated with low precipitation, the shift in SPAGs highlighting vulnerable populations not adapted to the very dry conditions expected in 2070. The SPAG methodology is successfully validated using cross-validations and provides an efficient tool to take the adaptive potential into account in general conservation frameworks.
Oligodendrocytes support axonal transport and maintenance via exosome secretion
Authors: Frühbeis Carsten , Kuo-Elsner Wen Ping , Müller Christina , Barth Kerstin , Peris Leticia , Tenzer Stefan , Möbius Wiebke , Werner Hauke B. , Nave Klaus-Armin , Fröhlich Dominik , Krämer-Albers Eva-Maria 
Published: December 2019

AbstractNeurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to underlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties of exosomes, which upon delivery to neurons improve neuronal viability in vitro. Here, we show that oligodendroglial exosome secretion is impaired in two mouse mutants exhibiting secondary axonal degeneration due to oligodendrocyte-specific gene defects. Wildtype oligodendroglial exosomes support neurons by improving the metabolic state and promoting axonal transport in nutrient deprived neurons. Mutant oligodendrocytes release less exosomes that share a common signature of underrepresented proteins. Notably, mutant exosomes lack the ability to support nutrient deprived neurons and to promote axonal transport. Together, these findings indicate that glia to neuron exosome transfer promotes neuronal long-term maintenance by facilitating axonal transport, providing a novel mechanistic link between myelin diseases and secondary loss of axonal integrity.
Stimulus-choice (mis)alignment in primate MT cortex
Authors: Zhao Yuan , Yates Jacob L. , Levi Aaron J. , Huk Alexander C. , Park Il Memming 
Published: December 2019

AbstractFor stimuli near perceptual threshold, the trial-by-trial activity of single neurons in many sensory areas is correlated with the animal’s perceptual report. This phenomenon has often been attributed to feedforward readout of the neural activity by the downstream decision-making circuits. The interpretation of choice-correlated activity is quite ambiguous, but its meaning can be better understood in the light of population-wide correlations among sensory neurons. Using a statistical nonlinear dimensionality reduction technique on single-trial ensemble recordings from the middle temporal area during perceptual-decision-making, we extracted low-dimensional neural tra jectories that captured the population-wide fluctuations. We dissected the particular contributions of sensory-driven versus choice-correlated activity in the low-dimensional population code. We found that the neural trajectories strongly encoded the direction of the stimulus in single dimension with a temporal signature similar to that of single MT neurons. If the downstream circuit were optimally utilizing this information, choice-correlated signals should be aligned with this stimulus encoding dimension. Surprisingly, we found that a large component of the choice information resides in the subspace orthogonal to the stimulus representation inconsistent with the optimal readout view. This misaligned choice information allows the feedforward sensory information to coexist with the decision-making process. The time course of these signals suggest that this misaligned contribution likely is feedback from the downstream areas. We hypothesize that this non-corrupting choice-correlated feedback might be related to learning or reinforcing sensory-motor relations in the sensory population.Author summaryIn sensorimotor decision-making, internal representation of sensory stimuli is utilized for the generation of appropriate behavior for the context. Therefore, the correlation between variability in sensory neurons and perceptual decisions is sometimes explained by a causal, feedforward role of sensory noise in behavior. However, this correlation could also originate via feedback from decision-making mechanisms downstream of the sensory representation. This cannot be resolved by analyzing single unit responses, but requires a population level analysis. Area MT contains both sensory and choice information and is known to be the key sensory area for visual motion perception. Thus the decision-making process may be corrupting the sensory representation. However, we find that the sensory stimuli and choice variables are separate at the population level,contradicting the previous interpretations based on single unit recordings. This new insight postulates how neural systems can maintain a mixed representation while allows learning and adaptation.
A four-step regulatory cascade controls bistable transfer competence development of the integrative and conjugative element ICEclcinPseudomonas
Authors: Carraro Nicolas , Richard Xavier , Sulser Sandra , Delavat François , Mazza Christian , van der Meer Jan Roelof 
Published: December 2019

AbstractGenetic bistability controls different phenotypic programs in defined subpopulations of genetically identical bacteria. Conjugative transfer of the integrative and conjugative element ICEclcinPseudomonasrequires development of a transfer competence state in stationary phase, but this state arises only in 3-5% of individual cells. The mechanisms controlling and underlying the bistable switch between non-active and transfer competence cells have long remained enigmatic. Using a variety of genetic tools combined with stochastic modeling, we characterize here the factors and overall network architecture controlling bistable ICEclcactivation of transfer competence. Two new key regulators (BisR and BisDC) were uncovered, that link the hierarchical cascade of ICEclctransfer competence activation to in total four regulatory nodes. The final activator complex named BisDC drives a positive feedback on its own transcription, and directly controls the “late” ICE promoters for excision and transfer. Stochastic mathematical modeling conceptually explained the arisal and maintenance of bistability by the feedback loop, and demonstrated its importance to guarantee consistent prolonged downstream output in activated cells. A minimized gene set allowing controllable bistable output in aPseudomonas putidain absence of the ICEclclargely confirmed model predictions. Phylogenetic analyses further showed that the two new ICEclcregulatory factors are widespread among putative ICEs found inGamma- andBeta- proteobacteria, highlighting the conceptual importance of our findings for the behaviour of this wide family of conjugative elements.Author summaryIntegrative and conjugative elements (ICEs) are mobile genetic elements present in virtually every bacterial species, which can confer adaptive functions to their host, such as antibiotic resistance or xenometabolic pathways. Integrated ICEs maintain by replication along with the genome of their bacterial host, but in order to transfer, the ICE excises and conjugates into a new recipient cell. Single-cell studies on a unique but widely representative ICE model fromPseudomonas(ICEclc) showed that transfer only occurs from a small dedicated subpopulation of cells that arises during stationary phase conditions. This bistable subpopulation differentiation is highly significant for ICE behaviour and fitness, but how it is regulated has remained largely unknown. The present work unveiled the architecture of the ICEclctransfer competence regulation, and showed its widespread occurrence among ICEs of the same family. Stochastic mathematical modeling explained how bistability is generated and maintained, prolonging the capacity of stationary phase cells to complete all stages of ICE activation.
PolyQ-independent toxicity associated with novel translational products from CAG repeat expansions
Authors: Rudich Paige D. , Watkins Simon , Lamitina Todd 
Published: December 2019

AbstractExpanded CAG nucleotide repeats are the underlying genetic cause of at least 14 incurable diseases, including Huntington’s disease (HD). The toxicity associated with many CAG repeat expansions is thought to be due to the translation of the CAG repeat to create a polyQ protein, which forms toxic oligomers and aggregates. However, recent studies show that HD CAG repeats undergo a non-canonical form of translation calledRepeat-associatednon-AUG dependent (RAN) translation. RAN translation of the CAG sense and CUG anti-sense RNAs produces six distinct repeat peptides: polyalanine (polyAla, from both CAG and CUG repeats), polyserine (polySer), polyleucine (polyLeu), polycysteine (polyCys), and polyglutamine (polyGln). The toxic potential of individual CAG-derived RAN polypeptides is not well understood. We developed pureC. elegansprotein models for each CAG RAN polypeptide using codon-varied expression constructs that preserve RAN protein sequence but eliminate repetitive CAG/CUG RNA. While all RAN polypeptides formed aggregates, only polyLeu was consistently toxic across multiple cell types. In GABAergic neurons, which exhibit significant neurodegeneration in HD patients, codon-varied (Leu)38, but not (Gln)38, caused substantial neurodegeneration and motility defects. Our studies provide the firstin vivoevaluation of CAG-derived RAN polypeptides and suggest that polyQ-independent mechanisms, such as RAN-translated polyLeu peptides, may have a significant pathological role in CAG repeat expansion disorders.
Effect of intensity of agronomic practices on the yield of two breeding types of winter oilseed rape cultivars
Authors: Wójtowicz Marek , Wójtowicz Andrzej , Jajor Ewa , Korbas Marek , Wielebski Franciszek 
Published: December 2019

AbstractThe effect of three fungicide treatment programmes and the level of spring nitrogen fertilisation on the seed yield of two types of cultivars ofBrassica napusL. sown at two different seeding rates was studied in a field experiment carried out in a split-split-plot design. The subject of the study was an open-pollinated cultivar (Casoar) and a restored hybrid cultivar (Visby). Three plant protection programmes, two levels of spring nitrogen fertilisation (160 and 220 kg N·ha-1), and two different seeding rates for each cultivar (Visby—50 and 70 seeds·m-2; Casoar—60 and 80 seeds·m-2) were included. The most intensive protection programme comprised three fungicide treatments: first in autumn at the six-leaves-unfolded stage—BBCH 16, second in spring at the stem elongation stage—BBCH 33, and third at the full flowering stage—BBCH 65. One of two less intensive programmes of plant protection included fungicide application in autumn at the six-leaves-unfolded stage—BBCH 16 and at the full flowering stage—BBCH 65, while the second included fungicide application in spring at the stem elongation stage—BBCH 33 and at the full flowering stage—BBCH 65.The effectiveness of the protection programmes and nitrogen fertilisation was influenced by the intensity of abiotic stress factors. However, the average yield from the plots protected against pathogens was significantly higher than that from the untreated plots. The increase of nitrogen fertilisation from 160 to 220 kg·ha-1also caused significant increase of average seed yield. The yield of cultivar Visby was higher and less dependent on the seeding rate compared to cultivar Casoar. Cultivars responded similarly to plant protection programmes and the rate of nitrogen fertilisation in spring. Higher yields of Visby cultivar can be attributed to the higher number of seeds per silique and the higher number of siliques per m2.
Bmal1 integrates mitochondrial metabolism and macrophage activation
Authors: Alexander Ryan K. , Liou Yae-Huei , Knudsen Nelson H. , Starost Kyle A. , Xu Chuanrui , Hyde Alexander L. , Liu Sihao , Jacobi David , Liao Nan-Shih , Lee Chih-Hao 
Published: December 2019

ABSTRACTMetabolic pathways and inflammatory processes are under circadian regulation. While rhythmic immune cell recruitment is known to impact infection outcomes, whether the circadian clock modulates immunometabolism remains unclear. We find the molecular clock Bmal1 is induced by inflammatory stimulants, including Ifn-γ/lipopolysaccharide (M1) and tumor conditioned medium, to maintain mitochondrial metabolism under these metabolically stressed conditions in mouse macrophages. Upon M1 stimulation, myeloid-specificBmal1knockout (M-BKO) renders macrophages unable to sustain mitochondrial function, enhancing succinate dehydrogenase (SDH)-mediated mitochondrial ROS production and Hif-1α-dependent metabolic reprogramming and inflammatory damage. In tumor-associated macrophages, the aberrant Hif-1α activation and metabolic dysregulation by M-BKO contribute to an immunosuppressive tumor microenvironment. Consequently, M-BKO increases melanoma tumor burden, while administrating an SDH inhibitor dimethyl malonate suppresses tumor growth. Therefore, Bmal1 functions as a metabolic checkpoint integrating macrophage mitochondrial metabolism, redox homeostasis and effector functions. This Bmal1-Hif-1α regulatory loop may provide therapeutic opportunities for inflammatory diseases and immunotherapy.
Epiphytic Microbiome of Grapes Berries Varies Between Phenological Timepoints, Growing Seasons and Regions
Authors: Hall Megan E. , O’Bryon Isabelle , Wilcox Wayne F. , Osier Michael V. , Cadle-Davidson Lance 
Published: December 2019

AbstractExtensive research into the microbial ecology of grapes near harvest, with a primary focus on yeasts, has improved our understanding of some components of variation that influence grapevine terroir. Metagenomic tools enable a broader exploration of the plant microbiome and components of variability due to such factors as year, location, management, and phenological stage. In 2014, to characterize the microbial changes of the grape surface over the course of the growing season in the Finger Lakes region of New York, we examined the epiphytic microbiome of grapes at five key phenological stages: pea-sized, bunch closure, Veraison, 15 Brix and harvest. This experiment was repeated in two subsequent years in the Finger Lakes, New York in 2015, and in Tasmania, Australia in 2016, to examine variability of regional terroir. We found significant shifts in taxa presence and relative taxa abundance between phenological timepoints, and determined that the epiphytic microbiome differed significantly not just between regions but also within a single region from one year to the next. These findings call into question the role of the phytobiome in the expression of terroir, as the phytobiome is dynamically responding to its environment, within and between years and locations. On the berry surface in particular, these dynamics are complicated by weather and management. Understanding that the grape surface microbiome is consistently changing may influence how we manage the berry epiphytic microbiome, potentially affecting disease management and vinification decisions.
MethylStar: A fast and robust pre-processing pipeline for bulk or single-cell whole-genome bisulfite sequencing data
Authors: Shahryary Yadollah , Hazarika Rashmi R. , Johannes Frank 
Published: December 2019

AbstractBackground:Whole-Genome Bisulfite Sequencing (WGBS) is a Next Generation Sequencing (NGS) technique for measuring DNA methylation at base resolution. Continuing drops in sequencing costs are beginning to enable high-throughput surveys of DNA methylation in large samples of individuals and/or single cells. These surveys can easily generate hundreds or even thousands of WGBS datasets in a single study. The efficient pre-processing of these large amounts of data poses major computational challenges and creates unnecessary bottlenecks for downstream analysis and biological interpretation.Results:To offer an efficient analysis solution, we present MethylStar, a fast, stable and flexible pre-processing pipeline for WGBS data. MethylStar integrates well-established tools for read trimming, alignment and methylation state calling in a highly parallelized environment, manages computational resources and performs automatic error detection. MethylStar offers easy installation through a dockerized container with all preloaded dependencies and also features a user-friendly interface designed for experts/non-experts. Application of MethylStar to WGBS from human, maize and Arabidopsis shows that it outperforms existing pre-processing pipelines in terms of speed and memory requirements.Conclusions:MethylStar is a fast, stable and flexible pipeline for high-throughput pre-processing of bulk or single-cell WGBS data. Its easy installation and user-friendly interface should make it a useful resource for the wider epigenomics community. MethylStar is distributed under GPL-3.0 license and source code is publicly available for download from githubhttps://github.com/jlab-code/MethylStar. Installation through a docker image is available fromhttp://jlabdata.org/methylstar.tar.gz