bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated strain-level analytic pipeline utilizing longitudinal metagenomic data
Authors: Zhou Boyan , Wang Chan , Putzel Gregory , Hu Jiyuan , Liu Menghan , Wu Fen , Chen Yu , Pironti Alejandro , Li Huilin 
Published: February 2022

AbstractThe development of sequencing technology and analytic tools have advanced our insights into the complexity of microbiome. Since different strains within species may display great phenotypic variability, studying within-species variations enhances the understanding of microbial biological processes. However, most existing methods for strain-level analysis do not allow for the simultaneous interrogation of strain proportions and genome-wide variants in longitudinal metagenomic samples. In this study, we introduce LongStrain, an integrated pipeline for the analysis of metagenomic data from individuals with longitudinal or repeated samples. Our algorithm improves the efficiency and accuracy of strain identification by jointly modeling the strain proportion and genomic variants in combined multiple samples within individuals. With simulation studies of a microbial community and single species, we show that LongStrain is superior to three extensively used methods in variant calling and proportion estimation. Furthermore, we illustrate the potential applications of LongStrain in the real data analysis of The Environmental Determinants of Diabetes in the Young (TEDDY) study and a gastric intestinal metaplasia microbiome study. We investigate the association between the dynamic change of strain proportions and early life events, such as birth delivery mode, antibiotic treatment, and weaning. By joint analysis of phylogeny and strain transition, we also identify a subspecies clade of Bifidobacterium longum which is significantly correlated with breastfeeding.
DeepVelo: Single-cell Transcriptomic Deep Velocity Field Learning with Neural Ordinary Differential Equations
Authors: Chen Zhanlin , King William C. , Hwang Aheyon , Gerstein Mark , Zhang Jing 
Published: February 2022

AbstractRecent advances in single-cell RNA sequencing technology have provided unprecedented opportunities to simultaneously measure the gene expression profile and transcriptional velocity of individual cells, enabling us to sample gene regulatory network dynamics along developmental trajectories. However, traditional methods have faced challenges in modeling gene expression dynamics within individual cells due to sparse, non-linear (e.g., obligate heterodimer transcription factors), and high-dimensional measurements. Here, we present DeepVelo, a neural-network-based ordinary differential equation model that can learn non-linear, high-dimensional single-cell transcriptome dynamics and describe continuous gene expression changes within individual cells across time. We applied DeepVelo to multiple published datasets from different technical platforms and demonstrated its utility to 1) formulate transcriptome dynamics on different timescales, 2) measure the instability of cell states, and 3) identify developmental driver genes upstream of a signaling cascade. Benchmarking against state-of-the-art methods shows that DeepVelo can improve velocity field representation accuracy by at least 50% in out-of-sample cells. Further, perturbation studies revealed that single-cell dynamical systems may exhibit properties similar to those of chaotic systems. In summary, DeepVelo allows for the data-driven discovery of differential equations that delineate single-cell transcriptome dynamics.TeaserEmbedding neural networks into ordinary differential equations to model gene expression changes within single cells across time.
Hamiltonian Monte Carlo with strict convergence criteria reduces run-to-run variability in forensic DNA mixture deconvolution
Authors: Susik Mateusz , Schönborn Holger , Sbalzarini Ivo F. 
Published: February 2022

AbstractMotivationAnalysing mixed DNA profiles is a common task in forensic genetics. Due to the complexity of the data, such analysis is often performed using Markov Chain Monte Carlo (MCMC)-based genotyping algorithms. These trade off precision against execution time. When the default settings are used, as large as a 10-fold changes in inferred likelihood ratios (LR) are observed when the software is run twice on the same case. So far, this uncertainty has been attributed to the stochasticity of MCMC algorithms. Since LRs translate directly to strength of the evidence in a criminal trial, forensic laboratories desire LR with small run-to-run variability.ResultsWe present a Hamiltonian Monte Carlo (HMC) algorithm that reduces run-to-run variability in forensic DNA mixture deconvolution by around an order of magnitude without increased runtime. We achieve this by enforcing strict convergence criteria. We show that the choice of convergence metric strongly influences precision. We validate our method by reproducing previously published results for benchmark DNA mixtures (MIX05, MIX13, and ProvedIt). We also present a complete software implementation of our algorithm that is able to leverage GPU acceleration, accelerating the inference process. In the benchmark mixtures, on consumer-grade hardware, the runtime is less than 7 minutes for 3 contributors, less than 35 minutes for 4 contributors, and less than an hour for 5 contributors with one known contributor.
Secondary sexual dimorphism traits under abiotic stress in dioecious species: The case of Amaranthus palmeri
Authors: Korres Nicholas E. , Norsworthy Jason K. , FitzSimons Toby , Roberts Trenton L. , Oosterhuis Derrick M. , Govindjee Govindjee 
Published: February 2022

AbstractThe evolution of secondary sex-specific traits of dioecious species under abiotic stress conditions has received limited research, especially in the case of Amaranthus palmeri, a fast adapting and highly competing plant. Here, we have examined the interactive effects of abiotic stress on mineral accumulation, chlorophyll a and b content, and the operating capacity of Photosystem II (PSII) in both male and female A. palmeri plants grown under three different intensities (150, 450 and 1300 μmol photons m−2 s−1) of white light, and under N, K or P deficiency. Mineral profiling of the leaves and stems (with inflorescence) highlighted intra- and intersexual differences in their accumulation pattern and mineral associations. Chlorophyll a and b content was different between the male and the female plants, being lower in the latter, at high light intensity, especially as the flowering progressed, or when they were under K or P deficient condition. Further, the chlorophyll a/b ratio was lower at the higher light intensity in the female, over that in the male, plants. Chlorophyll fluorescence parameters, i.e., steady state (F’S) and maximum (F’M) fluorescence increased under high light intensity, whereas the PSII operating efficiency (ΦPSII) decreased in the female plants, indicating reduced PSII capacity. Sex-specific differences in A. palmeri showed a differential response to stressful conditions because of differences in their ontogeny and physiology, and possibly due to the cost of reproduction. We suggest that the breeding system of dioecious species has weaknesses that can be used for the ecological management of dioecious weed species.
Blood Concentrations of Per- and Polyfluoroalkyl Substances are Associated with Autoimmunity-like Effects in the American Alligator
Authors: Guillette T. C. , Jackson Thomas W. , Guillette Matthew P. , McCord James P. , Belcher Scott M. 
Published: February 2022

AbstractSurface and ground water of the Cape Fear River basin in central and coastal North Carolina is contaminated with high levels of per- and polyfluoroalkyl substances (PFAS). Elevated levels of PFAS have also been found in blood of fish and wildlife living in and around the Cape Fear River, and in the blood of human populations reliant on contaminated well or surface water from the Cape Fear River basin as a sources of drinking water. While the public and environmental health impacts of long-term PFAS exposures are poorly understood, elevated blood concentrations of some PFAS are linked with immunotoxicity and increased incidence of some chronic autoimmune diseases in human populations. The goal of this study was to evaluate PFAS exposure and biomarkers related to immune health in populations of American alligators (Alligator mississippiensis), a protected and predictive sentinel species of adverse effects caused by persistent toxic pollutants. We found that serum PFAS concentrations in a representative population of alligators from the Cape Fear River were increased compared to a reference population of alligators from the adjoining Lumber River basin. The elevated serum PFAS concentrations in the Cape Fear River alligators were associated with increased innate immune activities, and autoimmune-like phenotypes were observed in this population. In addition to evidence of significantly higher double stranded-DNA binding autoantibodies in adult Cape Fear River alligators, our qRT-PCR analysis found remarkably high induction of Interferon-α αsignature genes implicated in the pathology of human autoimmune disease. We interpret the association of increased PFAS exposure with disrupted immune functions to indicate that PFAS broadly alters immune activities resulting in autoimmune-like pathology in American alligators. This work substantiates and extends evidence from experimental models and human epidemiology studies showing that some PFAS are immune toxicants.HighlightsSerum PFAS concentration were elevated in alligator populations from the Cape Fear RiverHigher PFAS concentrations were associated with disrupted innate immune functionsInfa-responsive autoimmunity signature genes were induced in Cape Fear River alligatorsElevated PFAS levels were associated with autoimmune-like activity in alligators 26
Neocentromere formation through Robertsonian fusion and centromere repositioning during the evolution of zebras
Authors: Cappelletti Eleonora , Piras Francesca M. , Sola Lorenzo , Santagostino Marco , Abdelgadir Wasma A. , Raimondi Elena , Nergadze Solomon G. , Giulotto Elena 
Published: February 2022

ABSTRACTCentromeres are epigenetically specified by the histone H3 variant CENP-A and typically associated to highly repetitive satellite DNA. We previously discovered natural satellite-free neocentromeres inEquus caballusandE. asinus. Here, through ChIP-seq with an anti-CENP-A antibody, we found an extraordinarily high number of centromeres lacking satellite DNA in the zebrasE. burchelli(15 of 22) andE. grevyi(13 of 23), demonstrating that the absence of satellite DNA at the majority of centromeres is compatible with genome stability and species survival and challenging the role of satellite DNA in centromere function. Nine neocenstromeres are shared between the two species in agreement with their recent separation. Wede novoassembled all neocentromeric regions and improved the reference genome ofE. burchelli. Sequence analysis of the CENP-A binding domains revealed that they are LINE-1 and AT-rich with four of them showing DNA amplification. In the two zebras, satellite-free centromeres emerged from centromere repositioning or following Robertsonian fusion. In five chromosomes, the centromeric function arose near the fusion points, which are located within regions marked by traces of ancestral pericentromeric sequences. Therefore, besides centromere repositioning, Robertsonian fusions are an important source of satellite-free centromeres during evolution. Finally, in one case, a neocentromere was seeded on an inversion breakpoint. At eleven chromosomes, whose primary constrictions seemed to be associated to satellite repeats by cytogenetic analysis, neocentromeres were instead located near the ancestral inactivated satellite-based centromeres, therefore, the centromeric function has shifted away from a satellite repeat containing locus to a satellite-free new position.
Nuclear Receptor 5A2 Regulation of Agrp underlies Olanzapine-induced Hyperphagia
Authors: Zapata Rizaldy C. , Zhang Dinghong , Libster Avraham , Porcu Alessandra , Montilla-Perez Patricia , Zhang Zhi , Correa Stephanie M , Telese Francesca , Osborn Olivia 
Published: February 2022

Summary/AbstractAntipsychotic (AP) drugs are highly efficacious treatments for psychiatric disorders, but a serious side effect of their use is excessive weight gain and subsequent development of metabolic disease. Increased food intake is the underlying driver of AP-induced weight gain, although the underlying mechanisms remain unknown. In previous studies, we identified hypothalamic genes whose expression level was altered following APs-induced hyperphagia. Among these genes, the orexigenic peptide Agrp and the transcription factor nuclear receptor subfamily 5 group A member 2 (Nr5a2) were two of the most significantly upregulated genes by APs. NR5a2 is broadly expressed throughout the body, but little is known about its role in the brain. In this study, we investigated the role of hypothalamic NR5a2 in AP-induced hyperphagia and weight gain. In hypothalamic cell lines, OLZ treatment resulted in a dose-dependent increase in gene expression of NR5a2 and Agrp. In mice, administration of a specific Nr5a2 inhibitor decreased olanzapine-induced hyperphagia and weight gain, while knockdown of Nr5a2 in the arcuate nucleus (ARC) partially reversed olanzapine-induced hyperphagia. Chromatin-immunoprecipitation-PCR studies showed for the first time that NR5a2 directly binds to the Agrp promoter region. In addition, in situ hybridization studies confirm that NR5a2 and Agrp are co-localized in a subset of cells in the arcuate nucleus. In summary, we identify Nr5a2 as a key mechanistic driver of AP-induced food intake and these findings can be used to inform future clinical development of APs that do not activate hyperphagia and weight gain.
Seeing light from a different angle: the effects of diffuse light on the function, structure, and growth of tomato plants
Authors: Ellertson Kendra B. L. , Goldsmith Gregory R. , Berry Z. Carter 
Published: February 2022

AbstractWhile considerable attention has been paid to how plants respond to changes in the spectral distribution and quantity of light, less attention has been paid to how plants respond to changes in the angular qualities of light. Evidence from both leaf- and ecosystem-scale measurements indicate that plants vary in their response to diffuse compared to direct light growing environments. Because of the significant implications for agricultural production, we quantified how changes in light quality affect the structure, function, and growth of Roma tomatoes in an open-air greenhouse experiment with direct and diffuse light treatments. Diffuse light conditions (ca. 50-60% diffuse) were created with a glass coating to diffuse light without significantly reducing the quantity of light. We measured leaf physiology and structure, as well as whole plant physiology, morphology, and growth. Light-saturated photosynthetic rates were set by the growing light environment and were unchanged by short-term exposure to the opposite light environment. Thus, after two months, plants in the diffuse light treatment demonstrated lower photosynthesis and had thinner leaves with higher chlorophyll concentration. However, relative growth rates did not differ between treatments and plants grown in diffuse light had significantly higher biomass at the conclusion of the experiment. While there was no difference in leaf or whole-plant water-use efficiency, plants in the diffuse light treatment demonstrated significantly lower leaf temperatures, highlighting the potential for diffuse light coatings and/or materials to reduce greenhouse energy use. Our results highlight the need to advance our understanding of the effects of diffuse light conditions on agricultural crops growing on a changing planet.
Measuring drift by mean deviation: unequal breeding sex ratio revisited
Authors: Qin Ben 
Published: February 2022

AbstractWhen it comes to estimating the magnitude of genetic drift, there is hardly any indexes other than the effective population size. Starting from the binomial sampling distribution, this research proposed using mean deviation of allele frequency change as a direct measurement of drift, then tested it in a classical example concerning unequal breeding sex ratio. This study found that: (1) mean deviation offers a new dimension in measuring the magnitude of drift; (2) the measurement displays a “half-half” pattern; (3) allele frequency determines the efficacy of hitchhiking effect of rare alleles, and in what way that “half-half” pattern should be divided.
RAID: Regression Analysis based Inductive DNA microarray for Precise Read-Across
Authors: Amano Yuto , Yamane Masayuki , Honda Hiroshi 
Published: February 2022

AbstractChemical structure-based read-across represents a promising method for chemical toxicity evaluation without the need for animal testing; however, a chemical structure is not necessarily related to toxicity. Therefore, in vitro studies were often used for read-across reliability refinement; however, their external validity has been hindered by the gap between in vitro and in vivo conditions. Thus, we developed a virtual DNA microarray, Regression Analysis based Inductive DNA microarray (RAID), which quantitatively predicts in vivo gene expression profiles based on the chemical structure and/or in vitro transcriptome data. For each gene, elastic-net models were constructed using chemical descriptors and in vitro transcriptome data to predict in vivo data from in vitro data (in vitro to in vivo extrapolation; IVIVE). In feature selection, useful genes for assessing the quantitative structure activity relationship (QSAR) and IVIVE were identified. Predicted transcriptome data derived from the RAID system reflected the in vivo gene expression profiles of characteristic hepatotoxic substances. Moreover, gene ontology and pathway analyses indicated that xenobiotic response and metabolic activation via nuclear receptors are related to those gene expressions. The identified IVIVE-related genes were associated with fatty acid-, xenobiotic-, and drug metabolism, indicating that in vitro studies were effective in evaluating these key events. Furthermore, validation studies revealed that chemical substances associated with these key events could be detected as hepatotoxic biosimilar substances. These results indicate that the RAID system could represent an alternative screening test for repeated-dose toxicity test and toxicogenomic analyses. Our technology provides a critical solution to IVIVE-based read-across by considering the mode of action and chemical structures.
Niche differentiation following whole-genome duplication? The importance of considering the intricate evolutionary history of polyploids when assessing climatic niche evolution
Authors: Padilla-García Nélida , Šrámková Gabriela , Záveská Eliška , Šlenker Marek , Clo Josselin , Zeisek Vojtěch , Lučanová Magdalena , Rurane Ieva , Kolář Filip , Marhold Karol 
Published: February 2022

AimAlthough whole genome duplication (WGD) is an important speciation force, we still lack a consensus on the role of niche differentiation in polyploid evolution. In addition, the role of genome doubling per se vs. later divergence on polyploid’s niche evolution remains obscure. One reason for this might be that the intraspecific genetic structure of polyploid complexes and interploidy gene flow is often neglected in ecological studies. Here, we aim to investigate to which extent these evolutionary processes impact our inference on niche differentiation of autopolyploids.LocationEuropeTaxonArabidopsis arenosa (Brassicaceae)MethodsLeveraging a total of 352 cytotyped populations of diploid-autotetraploid A. arenosa, we examined differences among climatic niches of diploid and tetraploid lineages both globally, and independently for each tetraploid lineage with respect to the niche of its evolutionary closest relative. Then, we tested if there was an effect of additional interploidy introgression from other sympatric but more ancestral diploid lineages of A. arenosa on climatic niches of tetraploids.ResultsEcological niche shift of tetraploids is only detected when the assignment of populations to intraspecific genetic lineages is considered. We found different patterns of climatic niche evolution (i.e. niche conservatism, contraction or expansion) in each tetraploid lineage when compared to its evolutionary closest relatives. We observed an effect of interploidy gene flow in patterns of climatic niche evolution of tetraploid ruderal plants of A. arenosa.Main conclusionsThe niche shift of tetraploids in A. arenosa is not driven by WGD per se but rather reflects dynamic post-WGD evolution in the species, involving tetraploid migration out of their ancestral area and interploidy introgression with other diploid lineages. Our study supports that evolutionary processes following WGD - which usually remain undetected by studies neglecting evolutionary history of polyploids - may play a key role in the adaptation of polyploids to challenging environments.
The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance
Authors: Klein Anders B. , Nicolaisen Trine S. , Johann Kornelia , Fritzen Andreas M. , Mathiesen Cecilie V. , Gil Cláudia , Pilmark Nanna S. , Karstoft Kristian , Blond Martin B. , Quist Jonas S. , Seeley Randy J. , Færch Kristine , Lund Jens , Kleinert Maximilian , Clemmensen Christoffer 
Published: February 2022

SUMMARYMetformin is a blood glucose lowering medication with physiological effects that extend beyond its anti-diabetic indication. Recently, it was reported that metformin lowers body weight via induction of growth differentiation factor 15 (GDF15), which suppresses food intake by binding to the GDNF family receptor α-like (GFRAL) in the hindbrain. At the same time, we demonstrated that recombinant GDF15 suppresses voluntary exercise in a GFRAL-dependent fashion. Here, we corroborate that metformin increases circulating GDF15 in mice and humans, but that it does not reduce voluntary running activity in mice. Unexpectedly, we fail to confirm previous reports that the GDF15-GFRAL pathway is necessary for the weight-lowering effects of metformin. Instead, our studies in wild-type, GDF15 knockout and GFRAL knockout mice suggest that the GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. The data presented here question whether metformin is a sufficiently strong stimulator of GDF15 to drive anorexia and weight loss and emphasize that additional work is needed to untangle the relationship among metformin, GDF15 and energy balance.