bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impulsivity and risk-seeking as Bayesian inference under dopaminergic control
Authors: Mikhael John G. , Gershman Samuel J. 
Published: October 2020

AbstractBayesian models successfully account for several of dopamine (DA)’s effects on contextual calibration in interval timing and reward estimation. In these models, tonic levels of DA control the precision of stimulus encoding, which is weighed against contextual information when making decisions. When DA levels are high, the animal relies more heavily on the (highly precise) stimulus encoding, whereas when DA levels are low, the context affects decisions more strongly. Here, we extend this idea to intertemporal choice and probability discounting tasks. In intertemporal choice tasks, agents must choose between a small reward delivered soon and a large reward delivered later, whereas in probability discounting tasks, agents must choose between a small reward that is always delivered and a large reward that may be omitted with some probability. Beginning with the principle that animals will seek to maximize their reward rates, we show that the Bayesian model predicts a number of curious empirical findings in both tasks. First, the model predicts that higher DA levels should normally promote selection of the larger/later option, which is often taken to imply that DA decreases ‘impulsivity,’ and promote selection of the large/risky option, often taken to imply that DA increases ‘risk-seeking.’ However, if the temporal precision is sufficiently decreased, higher DA levels should have the opposite effect—promoting selection of the smaller/sooner option (higher impulsivity) and the small/safe option (lower risk-seeking). Second, high enough levels of DA can result in preference reversals. Third, selectively decreasing the temporal precision, without manipulating DA, should promote selection of the larger/later and large/risky options. Fourth, when a different post-reward delay is associated with each option, animals will not learn the option-delay contingencies, but this learning can be salvaged when the post-reward delays are made more salient. Finally, the Bayesian model predicts correlations among behavioral phenotypes: Animals that are better timers will also appear less impulsive.
LEA 3: Factor models in population genetics and ecological genomics with R
Authors: Gain Cléement , François Olivier 
Published: October 2020

AbstractA major objective of evolutionary biology is to understand the processes by which organisms have adapted to various environments, and to predict the response of organisms to new or future conditions. The availability of large genomic and environmental data sets provides an opportunity to address those questions, and the R package LEA has been introduced to facilitate population and ecological genomic analyses in this context. By using latent factor models, the program computes ancestry coefficients from population genetic data, and performs genotype-environment association analyses with correction for unobserved confounding variables. In this study, we present new functionalities of LEA, which include imputation of missing genotypes, fast algorithms for latent factor mixed models using multivariate predictors for genotype-environment association studies, population differentiation tests for admixed or continuous populations, and estimation of genetic offset based on climate models. The new functionalities are implemented in version 3.0 and higher releases of the package. Using simulated and real data sets, our study provides evaluations and examples of applications, outlining important practical considerations when analyzing ecological genomic data in R.
Phase-locking of resting-state brain networks with the gastric basal electrical rhythm
Authors: Choe Ann S. , Tang Bohao , Smith Kimberly R. , Honari Hamed , Lindquist Martin A. , Caffo Brian S. , Pekar James J. 
Published: October 2020

ABSTRACTA network of myenteric interstitial cells of Cajal in the corpus of the stomach serves as its “pacemaker”, continuously generating aca.0.05 Hz electrical slow wave, which is transmitted to the brain chiefly by vagal afferents. A recent study combining resting-state functional MRI (rsfMRI) with concurrent surface electrogastrography (EGG), with cutaneous electrodes placed on the epigastrium, found 12 brain regions with activity that was significantly phase-locked with this gastric basal electrical rhythm. Therefore, we asked whether fluctuations in brain resting state networks (RSNs), estimated using a spatial independent component analysis (ICA) approach, might be synchronized with the stomach. In the present study, in order to determine whether any RSNs are phase-locked with the gastric rhythm, an individual participant underwent 22 scanning sessions; in each, two 15-minute runs of concurrent EGG and rsfMRI data were acquired. EGG data from three sessions had weak gastric signals and were excluded; the other 19 sessions yielded a total of 9.5 hours of data. The rsfMRI data were analyzed using group ICA; RSN time courses were estimated using dual regression; for each run, the phase-locking value (PLV) was computed between each RSN and the gastric signal. To assess statistical significance, PLVs from all pairs of “mismatched” data (EGG and rsfMRI data acquired on different days) were used as surrogate data to generate a null distribution for each RSN. Of a total of 18 RSNs, three were found to be significantly phase-locked with the basal gastric rhythm, namely, a cerebellar network, a dorsal somatosensory-motor network, and a default mode network. Disruptions to the gut-brain axis, which sustains interoceptive feedback between the central nervous system and the viscera, are thought to be involved in various disorders; manifestation of the infra-slow rhythm of the stomach in brain rsfMRI data could be useful for studies in clinical populations.
The role of concentration on drop formation and breakup of collagen, fibrinogen, and thrombin solutions during inkjet bioprinting
Authors: Gudapati Hemanth , Ozbolat Ibrahim T. 
Published: October 2020

AbstractThe influence of protein concentration on drop formation and breakup of aqueous solutions of fibrous proteins collagen, fibrinogen, and globular protein thrombin in different concentration regimes is investigated during drop-on-demand (DOD) inkjet bioprinting. The capillary-driven thinning and breakup of dilute (c/c* < 1, wherecis the concentration andc* is the overlap concentration) collagen, fibrinogen, and thrombin solutions is predominantly resisted by inertial force on the initial onset of necking. The minimum diameter (Dfmin(t)) of the necked fluid up to the critical pinch-off time (tc) scales with time asDfmin(t) ∼ (tc−t)2/3, a characteristic of potential flows. Although the capillary-driven thinning and breakup of semidilute unentangled collagen (1 ≤c/c* ≤ 4) and fibrinogen (1 ≤c/c* ≤ 1.3) solutions is predominantly resisted by inertial force on the initial onset of necking, the breakup of droplets is delayed beyondtc, where the minimum diameter of the necked fluid decreases exponentially with time because of the resistance of elastic force. The resistance of viscous force to the necking of both the dilute and semidilute untangled protein solutions is negligible. Aggregates or subvisible particles (between 1 and 100 μm) constantly disrupt the formation of droplets for the semidilute unentangled protein solutions, even when their inverse Ohnesorge number (Z) is within the printability range of 4 ≤Z≤ 14. Although aggregates are present in the dilute protein solutions, they do not disrupt the formation of droplets.
Ancestry inference and grouping from principal component analysis of genetic data
Authors: Privé Florian 
Published: October 2020

AbstractHere we propose a simple, robust and effective method for global ancestry inference and grouping from Principal Component Analysis (PCA) of genetic data. The proposed approach is particularly useful for methods that need to be applied in homogeneous samples. First, we show that Euclidean distances in the PCA space are proportional toFSTbetween populations. Then, we show how to use this PCA-based distance to infer ancestry in the UK Biobank and the POPRES datasets. We propose two solutions, either relying on projection of PCs to reference populations such as from the 1000 Genomes Project, or by directly using the internal data. Finally, we conclude that our method and the community would benefit from having an easy access to a reference dataset with an even better coverage of the worldwide genetic diversity than the 1000 Genomes Project.
Natural variation of the cardiac transcriptome in humans
Authors: Domitrovic Tatiana , Moreira Mariana H. , Carneiro Rodolfo L. , Ribeiro-Alves Marcelo , Palhano Fernando L. 
Published: October 2020

ABSTRACTWe investigated the gene-expression variation among humans by analyzing previously published mRNA-seq and ribosome footprint profiling (RP) of heart left-ventricles from healthy donors. We ranked the genes according to their coefficient of variation values and found that the top 5% most variable genes had special features compared to the rest of the genome, such as lower mRNA levels and shorter half-lives coupled to increased translation efficiency. We observed that these genes are mostly involved with immune response and have a pleiotropic effect on disease phenotypes, indicating that asymptomatic conditions contribute to the gene expression diversity of healthy individuals.
F-Seq2: improving the feature density based peak caller with dynamic statistics
Authors: Zhao Nanxiang , Boyle Alan P. 
Published: October 2020

ABSTRACTGenomic and epigenomic features are captured at a genome-wide level by using high-throughput sequencing technologies. Peak calling is one of the first essential steps in analyzing these features by delineating regions such as open chromatin regions and transcription factor binding sites. Our original peak calling software, F-Seq, has been widely used and shown to be the most sensitive and accurate peak caller for DNase I hypersensitive sites sequencing (DNase-seq) data. However, F-Seq lacks support for user-input control dataset nor reporting test statistics, limiting its ability to capture systematic and experimental biases and accurately estimate background distributions. Here we present an improved version, F-Seq2, which combined the power of kernel density estimation and a dynamic “continuous” Poisson distribution to robustly account for local biases and solve ties when ranking candidate peaks. In F-score and motif distance analysis, we demonstrated the superior performance of F-Seq2 than other competing peak callers used by the ENCODE Consortium on simulated and real ATAC-seq and ChIP-seq datasets. The output of F-Seq2 is suitable for irreproducible discovery rate (IDR) analysis as the test statistics calculated for individual candidate summit and ties are robustly solved.
Phylogeographic analysis of shrubby beardtongues reveals range expansions during the Last Glacial Maximum and implicates the Klamath Mountains as a hotspot for hybridization
Authors: Stone Benjamin W. , Wolfe Andrea D. 
Published: October 2020

AbstractQuaternary glacial cycles often altered species’ geographic distributions, which in turn altered the geographic structure of a species’ genetic diversity. In many cases, glacial expansion forced species in temperate climates to contract their ranges and reside in small pockets of suitable habitat (refugia), where they were likely to interact closely with other species, setting the stage for potential gene exchange. These introgression events, in turn, would have degraded species boundaries, making the inference of phylogenetic relationships challenging. Using high-throughput sequence data, we employ a combination of species distribution models, models of demographic history, and hybridization tests to assess the effect of glaciation on the geographic distributions, phylogenetic relationships, and patterns of gene flow of five species ofPenstemonsubgenusDasanthera, long-lived shrubby angiosperms distributed throughout the Pacific Northwest of North America. Surprisingly, we find that rather than reducing their ranges to small refugia, mostPenstemonsubgenusDasantheraspecies experienced increases in suitable habitat during the Last Glacial Maximum. We also find substantial evidence for gene exchange between species, with the bulk of introgression events occurring in or near the Klamath Mountains of southwestern Oregon and northwestern California. Subsequently, our phylogenetic inference reveals blurred taxonomic boundaries in the Klamath Mountains, where introgression is most prevalent. Our results question the classical paradigm of temperate species’ responses to glaciation, and highlight the importance of contextualizing phylogenetic inference with the demographic histories of the species of interest.
Altered Dynamics of Cortical Beta-Oscillations during Motor Learning in Cerebellar Ataxia
Authors: Klimpke Jana , Henkel Dorothea , Heinze Hans-Jochen , Stenner Max-Philipp 
Published: October 2020

AbstractCerebellar ataxia is associated with an implicit motor learning dysfunction, specifically, a miscalibration of internal models relating motor commands to state changes of the body. Explicit cognitive strategies could compensate for deficits in implicit calibration. Surprisingly, however, patients with cerebellar ataxia use insufficient strategies compared to healthy controls. We report a candidate physiological phenomenon of disrupted strategy use in cerebellar ataxia, reflected in an interaction of implicit and explicit learning effects on cortical beta oscillations. We recorded electroencephalography in patients with cerebellar ataxia (n=18), age-matched healthy controls (n=19), and young, healthy individuals (n=34) during a visuomotor rotation paradigm in which an aiming strategy was either explicitly instructed, or had to be discovered through learning. In young, healthy individuals, learning a strategy, but not implicit learning from sensory prediction error alone, decreased the post-movement beta rebound. Disrupted learning from sensory prediction error in patients, on the other hand, unmasked effects of explicit and implicit control that are normally balanced. Specifically, the post-movement beta rebound increased during strategy use when implicit learning was disrupted, i.e., in patients, but not controls. We conclude that a network disturbance due to cerebellar degeneration surfaces in imbalanced cortical beta oscillations normally involved in strategy learning.
Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia
Authors: Janssens Derek H. , Meers Michael P. , Wu Steven J. , Babaeva Ekaterina , Meshinchi Soheil , Sarthy Jay F. , Ahmad Kami , Henikoff Steven 
Published: October 2020

AbstractAcute myeloid and lymphoid leukemias often harbor chromosomal translocations involving theMixed Lineage Leukemia-1gene, encoding the KMT2A lysine methyltransferase. The most common translocations produce in-frame fusions of KMT2A to other chromatin regulatory proteins. Here we develop a strategy to map the genome-wide occupancy of oncogenic KMT2A fusion proteins in primary patient samples regardless of fusion partner. By modifying the versatile CUT&Tag method for full automation we identify common and tumor-specific patterns of aberrant chromatin regulation induced by different KMT2A fusion proteins. Integration of automated and single-cell CUT&Tag uncovers epigenomic heterogeneity within patient samples and predicts sensitivity to therapeutic agents.
A pair of effectors encoded on a conditionally dispensable chromosome ofFusarium oxysporumsuppress host-specific immunity
Authors: Ayukawa Yu , Asai Shuta , Gan Pamela , Tsushima Ayako , Ichihashi Yasunori , Shibata Arisa , Komatsu Ken , Houterman Petra M. , Rep Martijn , Shirasu Ken , Arie Tsutomu 
Published: October 2020

AbstractMany plant pathogenic fungi contain conditionally dispensable (CD) chromosomes that are associated with virulence, but not growthin vitro. Virulence-associated CD chromosomes carry genes encoding effectors and/or host-specific toxin biosynthesis enzymes that may contribute significantly to determining host specificity.Fusarium oxysporumcauses devastating diseases of more than 100 plant species. Among a large number of host-specific forms,F. oxysporumf. sp.conglutinans(Focn) can infect Brassicaceae plants including Arabidopsis and cabbage. Here we show thatFocnhas multiple CD chromosomes involved in virulence but also in vegetative growth, which is an atypical feature of CD chromosomes. We identified specific CD chromosomes that are required for virulence on Arabidopsis, cabbage, or both, and describe a pair of effectors encoded on one of the CD chromosomes that is required for suppression of Arabidopsis-specific phytoalexin-based immunity. The effector pair is highly conserved inF. oxysporumisolates capable of infecting Arabidopsis, but not of other plants. This study provides insight into how host specificity ofF. oxysporummay be determined by a pair of effector genes on a transmissible CD chromosome.
Western-style diet impedes colonization and clearance of gut bacterial pathogens
Authors: Gewirtz Andrew T. , Zou jun , ZHAO XU , Noriega Juan 
Published: October 2020

Western-style diet (WSD), which is high in fat and low in fiber, lacks nutrients to support gut microbiota. Consequently, WSD promotes microbiota encroachment and reduces microbiota density, potentially influencing colonization resistance, immune system readiness, and, consequently host defense against pathogenic bacteria. Additionally, the low-nutrient colonic environment resulting from WSD might impact bacterial pathogens. Hence, we examined the impact of WSD on infection and colitis in response to gut bacterial pathogens. Mice fed grain-based chow (GBC), WSD, or various versions thereof, were orally infected with Citrobacter rodentium or C. difficile. Colonization and its consequences, including inflammation and death were monitored. We observed that WSD delayed Citrobacter growth, reduced its virulence gene expression and ameliorated inflammation. However, while GBC-fed mice uniformly cleared Citrobacter and were impervious to subsequent Citrobacter challenges, most WSD-fed mice remained chronically infected with Citrobacter while those that cleared it were highly prone to re-infection. Such persistent proneness to Citrobacter infection did not reflect reduced immune responsiveness but rather reflected reduced colonization resistance likely from the low microbiota density resulting from WSD feeding. While persistent Citrobacter infection did not cause overt inflammation, it was associated with low-grade inflammation in colon and adipose tissue that was associated with insulin resistance. An analogous pattern was seen in response to C. difficile with WSD resulting in delayed colonization and mortality while enriching WSD with fiber hastened colonization but afforded clearance and survival. Thus, altering microbiota via diet can profoundly impact the course and consequence of infection following exposure to gut bacterial pathogens.
Quantitation analysis by flow cytometry shows thatWt1is required for development of the proepicardium and epicardium
Authors: Biben Christine , Borobokas Bette , Menon Mary Kamala , Hartley Lynne , Harvey Richard Paul , Taoudi Samir , Prall Owen William John 
Published: October 2020

ABSTRACTThe epicardium is a cell layer found on the external surface of the heart. During development it has an epithelial identity and contains progenitor cells for coronary smooth muscle and cardiac fibroblasts. The epicardium has been suggested to have therapeutic potential in cardiac repair. Study of epicardial development has been difficult because it is dynamic and morphologically complex. We developed a flow cytometry-based method to quantify cardiac development including the epicardial lineage. This provided accurate and sensitive analysis of (1) the emergence of epicardial progenitors within the proepicardium (2) their transfer to the heart to form the epicardium, and (3) their epithelial-to-mesenchymal transition (EMT) to create the subepicardium. Platelet-derived growth factor alpha (Pdgfra) and Wilms tumor protein (Wt1) have both been reported to be pro-mesenchymal during epicardial EMT. Quantitative analysis with flow cytometry confirmed a pro-mesenchymal role for Pdgfra but not for Wt1. Analysis ofWt1null embryos showed that they had (1) poor formation of proepicardial villi, (2) reduced transfer of proepicardial cells to the heart, (3) a discontinuous epicardium with poor epithelial identity, and (4) a proportionally excessive number of mesenchymal-like cells. This data shows that Wt1 is essential for epicardial formation and maintenance rather than being pro-mesenchymal.
Genetic requirements for cell division in a genomically minimal cell
Authors: Pelletier James F. , Sun Lijie , Wise Kim S. , Assad-Garcia Nacyra , Karas Bogumil J. , Deerinck Thomas J. , Ellisman Mark H. , Mershin Andreas , Gershenfeld Neil , Chuang Ray-Yuan , Glass John I. , Strychalski Elizabeth A. 
Published: October 2020

AbstractGenomically minimal cells, such as JCVI-syn3.0, offer a platform to clarify genes underlying core physiological processes. While this minimal cell includes genes essential for population growth, the physiology of its single cells remained uncharacterized. To investigate striking morphological variation in JCVI-syn3.0 cells, we present an approach to characterize cell propagation and determine genes affecting cell morphology. Microfluidic chemostats allowed observation of intrinsic cell dynamics resulting in irregular morphologies. The addition of 19 genes not retained in JCVI-syn3.0 generated JCVI-syn3A, which presents significantly less morphological variation than JCVI-syn3.0. We further identified seven of these 19 genes, including two known cell division genesftsZandsepFand five genes of unknown function, required together to restore cell morphology and division similar to JCVI-syn1.0. This surprising result emphasizes the polygenic nature of cell morphology, as well as the importance of a Z-ring and membrane properties in the physiology of genomically minimal cells.