bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testcrosses are an efficient strategy for identifyingcisregulatory variation: Bayesian analysis of allele specific expression (BASE)
Authors: Miller Brecca , Morse Alison , Borgert Jacqueline E. , Liu Zihao , Sinclair Kelsey , Gamble Gavin , Zou Fei , Newman Jeremy , León-Novelo Luis , Marroni Fabio , McIntyre Lauren M. 
Published: October 2020

ABSTRACTAllelic imbalance (AI) occurs when alleles in a diploid individual are differentially expressed and indicatescisacting regulatory variation. What is the distribution of allelic effects in a natural population? Are all alleles the same? Are all alleles distinct? Tests of allelic effect are performed by crossing individuals and comparing expression between alleles directly in the F1. However, a crossing scheme that compares alleles pairwise is a prohibitive cost for more than a handful of alleles as the number of crosses is at least (n2-n)/2wherenis the number of alleles. We show here that a testcross design followed by a hypothesis test of AI between testcrosses can be used to infer differences between non-tester alleles, allowingnalleles to be compared withncrosses. Using a mouse dataset where both testcrosses and direct comparisons have been performed, we show that ∼75% of the predicted differences between non-tester alleles are validated in a background of ∼10% differences in AI. The testing for AI involves several complex bioinformatics steps. BASE is a complete bioinformatics pipeline that incorporates state-of-the-art error reduction techniques and a flexible Bayesian approach to estimating AI and formally comparing levels of AI between conditions. The modular structure of BASE has been packaged in Galaxy, made available in Nextflow and sbatch. (https://github.com/McIntyre-Lab/BASE_2020). In the mouse data, the direct test identifies moreciseffects than the testcross.Cis-by-transinteractions withtrans-acting factors on the X contributing to observedciseffects in autosomal genes in the direct cross remains a possible explanation for the discrepancy.
Widespread agrochemicals differentially affect zooplankton biomass and community structure
Authors: Hébert Marie-Pier , Fugère Vincent , Beisner Beatrix E. , da Costa Naíla Barbosa , Barrett Rowan D. H. , Bell Graham , Shapiro B. Jesse , Yargeau Viviane , Gonzalez Andrew , Fussmann Gregor F. 
Published: October 2020

AbstractAnthropogenic environmental change is causing habitat deterioration at unprecedented rates in freshwater ecosystems. Despite increasing more rapidly than other agents of global change, synthetic chemical pollution –including agrochemicals such as pesticides– has received relatively little attention in freshwater biotic assessments. Determining the effects of multiple agrochemicals on complex community and ecosystem properties remains a major challenge, requiring a cross-field integration of ecology and ecotoxicology. Using a large-scale array of experimental ponds, we investigated the response of zooplankton community properties (biomass, composition, diversity metrics) to the individual and joint presence of three widespread agrochemicals: the herbicide glyphosate, the neonicotinoid insecticide imidacloprid, and fertilisers. We tracked temporal variation in community biomass and structure (i.e., composition, diversity metrics) along single and combined pesticide gradients (each spanning eight levels), under low (mesotrophic) and high (eutrophic) nutrient-enriched conditions, and quantified (i) agrochemical interactions, (ii) response threshold concentrations, and (iii) community resistance and recovery. We found that major zooplankton groups differed in their sensitivity to pesticides: ≥3 µg/L imidacloprid impaired copepods, rotifers collapsed at glyphosate levels ≥0.3 mg/L, whereas some cladocerans were highly tolerant to pesticide contamination. Glyphosate was the most influential driver of community properties, with biomass and community structure responding rapidly but recovering unequally over time. Zooplankton biomass showed little resistance when first exposed to glyphosate, but rapidly recovered and even increased with glyphosate concentration; in contrast, richness declined in more contaminated ponds but failed to recover. Our results show that the biomass of tolerant taxa compensated for the loss of sensitive species, conferring greater resistance upon subsequent exposure; a rare example of pollution-induced community tolerance in freshwater metazoans. Overall, zooplankton biomass appears to be more resilient to agrochemical pollution than community structure, yet all community properties measured in this study were affected at glyphosate levels below common water quality guidelines in North America.
The economics of organellar gene loss and endosymbiotic gene transfer
Authors: Kelly Steven 
Published: October 2020

AbstractThe endosymbiosis of the bacterial progenitors of mitochondrion and the chloroplast are landmark events in the evolution of life on earth. While both organelles have retained substantial proteomic and biochemical complexity, this complexity is not reflected in the content of their genomes. Instead, the organellar genomes encode fewer than 5% of genes found in living relatives of their ancestors. While many of the 95% of missing organellar genes have been discarded, others have been transferred to the host nuclear genome through a process known as endosymbiotic gene transfer. Here we demonstrate that the difference in the per-cell copy number of the organellar and nuclear genomes presents an energetic incentive to the cell to either delete genes or transfer them to the nuclear genome. We show that, for the majority transferred genes, the energy saved by nuclear-transfer exceeds the costs incurred from importing the encoded protein into the organelle where it can provide its function. Finally, we show that the net energy saved by endosymbiotic gene transfer can constitute an appreciable proportion of total cellular energy budgets, and is therefore sufficient to impart a selectable advantage to the cell. Thus, reduced cellular cost and improved energy efficiency likely played a role in the reductive evolution of mitochondrial and chloroplast genomes and the transfer of organellar genes to the nuclear genome.Significance statementThe endosymbioses of the mitochondrion and the chloroplast were each followed by substantial gene loss and transfer of organellar genes to the nuclear genome. Here we show that the high per-cell copy number of these organellar genomes creates an energetic incentive for the cell to discard genes or transfer them to the nuclear genome. Thus, organellar gene loss and endosymbiotic gene transfer can be intrinsically advantageous to the cell.
ThePhaeodactylum tricornutumDiaminopimelate Decarboxylase was Acquired via Horizontal Gene Transfer from Bacteria and Displays Substrate Promiscuity
Authors: Bielinski Vincent A. , Brunson John K. , Ghosh Agnidipta , Moosburner Mark A. , Garza Erin A. , Fussy Zoltan , Bai Jing , McKinnie Shaun M.K. , Moore Bradley S. , Allen Andrew E. , Almo Steven C. , Dupont Christopher L. 
Published: October 2020

ABSTRACTDiatoms are predicted to synthesize certain amino acids within the chloroplast, including L-lysine via a diaminopimelate-dependent pathway. Herein, we report that the model diatom,Phaeodactylum tricornutum, possesses a chimeric lysine biosynthetic pathway, which coalesces bacterial and plant genes, and is terminated by a chloroplast-localized diaminopimelate decarboxylase (DAPDC,PtLYSA). We show that while RNAi ablation ofPtLYSAis either synthetically lethal or concomitant with a slower growth rate, Cas9-mediated mutagenesis ofPtLYSAresults in recovery of heterozygous cells lines, suggesting thatPtLYSAis an essential gene. Previously characterized DAPDCs are unique within the PLP-dependent decarboxylases where catalysis occurs at the D-stereocenter of the substrate and display a strict stereochemical preference for a (D,L)- ormeso-substrate and not the D,D- or L,L-isomers of diaminopimelate (DAP) to synthesize L-lysine. Using decarboxylation assays and differential scanning calorimetry analyses, we validate thatPtLYSA is abona fideDAPDC and uncover its unexpected stereopromiscuous behavior in substrate specificity. The crystal structure ofPtLYSA confirms the enzyme is an obligate homodimer in which both protomers reciprocally participate in the active site. The structure underscores features unique to thePtLYSA clan of DAPDC and provides structural insight into the determinants responsible for the substrate-promiscuity observed inPtLYSA.
Improved Wound Closure Rates and Mechanical Properties Resembling Native Skin in Murine Diabetic Wounds Treated with a Tropoelastin and Collagen Wound Healing Device
Authors: Kellar Robert S. , Diller Robert B. , Tabor Aaron J. , Dominguez Dominic D. , Audet Robert G. , Bardsley Tatum A. , Talbert Alyssa J. , Cruz Nathan , Ingraldi Alison , Ensley Burt D. 
Published: October 2020

AbstractChronic wounds in patients suffering from type II diabetes mellitus (DMII) where wounds remain open with a complicated pathophysiology, healing, and recovery process is a public health concern. Normal wound healing plays a critical role in wound closure, restoration of mechanical properties, and the biochemical characteristics of the remodeled tissue. Biological scaffolds provide a tissue substitute to help facilitate wound healing by mimicking the extracellular matrix (ECM) of the dermis. In the current study an electrospun biomimetic scaffold, wound healing device (WHD), containing tropoelastin (TE) and collagen was synthesized to mimic the biochemical and mechanical characteristics of healthy human skin. The WHD was compared to a commercially available porcine small intestinal submucosa (SIS) matrix that has been used in both partial and full-thickness wounds, Oasis®Wound Matrix. Wound closure rates, histochemistry, qPCR, and mechanical testing of treated wound sites were evaluated. The WHD in a splinted, full-thickness, diabetic murine wound healing model demonstrated an enhanced rate of wound closure, decreased tissue inflammation, skin organ regeneration, and a stronger and more durable remodeled tissue that more closely mimics native unwounded skin compared to the control device.
Late cortical potentials are not a reliable marker of somatosensory awareness
Authors: Schröder Pia , Nierhaus Till , Blankenburg Felix 
Published: October 2020

AbstractTwo types of scalp-recorded event-related potentials have been proposed as neural correlates of perceptual awareness in humans: an early, modality-specific negativity and a late, modality-independent positivity. However, whether these potentials genuinely reflect perception or result from task demands remains controversial. To address this question, we compared results from a classical somatosensory detection task (direct report task) to a somatosensory-visual matching task, in which overt reports were decorrelated from target detection, equated the behavioural relevance of detected and undetected stimuli, and mitigated the influence of attentional processes. By means of Bayesian model selection, we show that the early N140 component was the first to reflect target detection in both tasks, whereas the late P300 component was task dependent, with strong detection effects in the direct report task that were absent in the matching task. We conclude that the P300 is not a genuine correlate of somatosensory awareness but reflects postperceptual processing.
The branching code: a model of actin-driven dendrite arborisation
Authors: Stürner Tomke , Castro André Ferreira , Philipps Maren , Cuntz Hermann , Tavosanis Gaia 
Published: October 2020

SummaryDendrites display a striking variety of neuronal type-specific morphologies, but the mechanisms and principles underlying such diversity remain elusive. A major player in defining the morphology of dendrites is the neuronal cytoskeleton, including evolutionarily conserved actin-modulatory proteins (AMPs). Still, we lack a clear understanding of how AMPs might support developmental phenomena such as neuron-type specific dendrite dynamics. To address precisely this level ofin vivospecificity, we concentrated on a defined neuronal type, the class III dendritic arborisation (c3da) neuron ofDrosophilalarvae, displaying actin-enriched short terminal branchlets (STBs). Computational modelling reveals that the main branches of c3da neurons follow a general growth model based on optimal wiring, but the STBs do not. Instead, model STBs are defined by a short reach and a high affinity to grow towards the main branches. We thus concentrated on c3da STBs and developed new methods to quantitatively describe dendrite morphology and dynamics based onin vivotime-lapse imaging of mutants lacking individual AMPs. In this way, we extrapolated the role of these AMPs in defining STB properties. We propose that dendrite diversity is supported by the combination of a common step, refined by a neuron type-specific second level. For c3da neurons, we present a molecular model of how the combined action of multiple AMPsin vivodefine the properties of these second level specialisations, the STBs.In briefA quantitative morphological dissection of the concerted actin-modulatory protein actions provides a model of dendrite branchlet outgrowth.HighlightsActin organisation in small terminal branchlets ofDrosophilaclass III dendritic arborisation neuronsSix actin-modulatory proteins individually control the characteristic morphology and dynamics of branchletsQuantitative tools for dendrite morphology and branch dynamics enable a comparative analysisA two-step computational growth model reproduces c3da dendrite morphology
Discovering Key Transcriptomic Regulators in Pancreatic Ductal Adenocarcinoma using Dirichlet Process Gaussian Mixture Model
Authors: Mosaddek Hossain Sk Md , Halsana Aanzil Akram , Khatun Lutfunnesa , Ray Sumanta , Mukhopadhyay Anirban 
Published: October 2020

ABSTRACTPancreatic Ductal Adenocarcinoma (PDAC) is the most lethal type of pancreatic cancer (PC), late detection of which leads to its therapeutic failure. This study aims to find out key regulatory genes and their impact on the progression of the disease helping the etiology of the disease which is still largely unknown. We leverage the landmark advantages of time-series gene expression data of this disease, and thereby the identified key regulators capture the characteristics of gene activity patterns in the progression of the cancer. We have identified the key modules and predicted gene functions of top genes from the compiled gene association network (GAN). Here, we have used the natural cubic spline regression model (splineTimeR) to identify differentially expressed genes (DEG) from the PDAC microarray time-series data downloaded from gene expression omnibus (GEO). First, we have identified key transcriptomic regulators (TR) and DNA binding transcription factors (DbTF). Subsequently, the Dirichlet process and Gaussian process (DPGP) mixture model is utilized to identify the key gene modules. A variation of the partial correlation method is utilized to analyze GAN, which is followed by a process of gene function prediction from the network. Finally, a panel of key genes related to PDAC is highlighted from each of the analyses performed.Please note: Abbreviations should be introduced at the first mention in the main text – no abbreviations lists. Suggested structure of main text (not enforced) is provided below.
A likelihood-based deconvolution of bulk gene expression data using single-cell references
Authors: Erdmann-Pham Dan D. , Fischer Jonathan , Hong Justin , Song Yun S. 
Published: October 2020

AbstractDirect comparison of bulk gene expression profiles is complicated by distinct cell type mixtures in each sample which obscure whether observed differences are actually due to changes in expression levels themselves or simply due to differing cell type compositions. Single-cell technology has made it possible to measure gene expression in individual cells, achieving higher resolution at the expense of increased noise. If carefully incorporated, such single-cell data can be used to deconvolve bulk samples to yield accurate estimates of the true cell type proportions, thus enabling one to disentangle the effects of differential expression and cell type mixtures. Here, we propose a generative model and a likelihood-based inference method that uses asymptotic statistical theory and a novel optimization procedure to perform deconvolution of bulk RNA-seq data to produce accurate cell type proportion estimates. We demonstrate the effectiveness of our method, called RNA-Sieve, across a diverse array of scenarios involving real data and discuss extensions made uniquely possible by our probabilistic framework, including a demonstration of well-calibrated confidence intervals.
Intestinal epithelium-derived high density lipoprotein restrains liver injury via the portal vein
Authors: Han Yong-Hyun , Onufer Emily J. , Huang Li-Hao , Czepielewski Rafael S. , Warner Brad W. , Randolph Gwendalyn J. 
Published: October 2020

SummaryAssembly of high density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most HDL in blood, HDL synthesis also occurs in the small intestine. However, distinct functions for intestinal HDL are unknown. Here we show that HDL in the portal vein, which connects intestine to liver, derivesd mainly from intestine and potently neutralizes lipopolysaccharide (LPS). In a mouse model of short bowel syndrome where liver inflammation and fibrosis was driven by the LPS receptor TLR4, loss of intestine-derived HDL worsened liver injury, whereas liver status was improved by therapeutics that elevated and depended upon intestinal HDL production. Thus, protection of the liver from injury in response to gut-derived signals like LPS is a major function of intestinally synthesized HDL.
A hybrid mesh and voxel based Monte Carlo algorithm for accurate and efficient photon transport modeling in complex bio-tissues
Authors: Yan Shijie , Fang Qianqian 
Published: October 2020

AbstractOver the past decade, an increasing body of evidence has suggested that threedimensional (3-D) Monte Carlo (MC) light transport simulations are affected by the inherent limitations and errors of voxel-based domain boundaries. In this work, we specifically address this challenge using a hybrid MC algorithm, namely split-voxel MC or SVMC, that combines both mesh and voxel domain information to greatly improve MC simulation accuracy while remaining highly flexible and efficient in parallel hardware, such as graphics processing units (GPU). We achieve this by applying a marching-cubes algorithm to a pre-segmented domain to extract and encode sub-voxel information of curved surfaces, which is then used to inform ray-tracing computation within boundary voxels. This preservation of curved boundaries in a voxel data structure demonstrates significantly improved accuracy in several benchmarks, including a human brain atlas. The accuracy of the SVMC algorithm is comparable to that of mesh-based MC (MMC), but runs 2x-6x faster and requires only a lightweight preprocessing step. The proposed algorithm has been implemented in our open-source software and is freely available athttp://mcx.space.
Standard and Non-Standard Measurements of Acidity and the Bacterial Ecology of Northern Temperate Mineral Soils
Authors: Braus Michael J. , Whitman Thea 
Published: October 2020

AbstractDatabases of soil pH values today guide the decisions of land managers and the experimental designs of microbiologists and biogeochemists. Soil acidity underpins fundamental properties and functions in the soil, such as the solubilities of exchangeable ions and nutrients, or bacterial use of gradients of internal and external acidity to generate ATP and turn flagellar motors. Therefore, it is perhaps unsurprising that soil pH has emerged as the strongest predictor of soil bacterial community composition. However, the measurement of these particular values today does not address whether soil pH accurately represents the in situ acidity of soil microhabitats where microorganisms survive and reproduce. This study analyzes and compares soils of a large-scale natural soil pH gradient and a long-term experimental soil pH gradient for the purposes of testing new methods of measuring and interpreting soil acidity when applied to soil ecology. We extracted and prepared soil solutions using laboratory simulation of levels of carbon dioxide and soil moisture more typical of soil conditions while also miniaturizing extraction methods using a centrifuge for extractions. The simulation of in situ soil conditions resulted in significantly different estimates of soil pH. Furthermore, for soils from the long-term experimental soil pH gradient trial, the simulated soil pH values substantially improved predictions of bacterial community composition (from R2 = 0.09 to R2 = 0.16). We offer suggestions and cautions for researchers considering how to better represent soil pH as it exists in situ.
Development of a species diagnostic molecular tool for an invasive pest,Mythimna loreyiusing LAMP
Authors: Nam Hwa Yeun , Kwon Min , Kim Hyun Ju , Kim Juil 
Published: October 2020

AbstractTheMythimna loreyi(Duponchel) is one of the well-known a noctuid pest in Africa, Australia, and many Asian countries. This species has recently emerged as an invasive pest of some cereal crops in Korea. However, it is extremely difficult to identify the morphologically similar species,Mythimna separate, which occur at the cornfield in the larvae stage. Therefore, it is hard to accurately investigate invasive pests. In this study, the LAMP assay was developed for rapid, simple, effective species identification. By analyzing the mt genome, the species-specific sequence was found at the coding region of the NADH dehydrogenase subunit 5 gene. Based on this unique sequence, four LAMP primers and two loop primers were designed. The F3 and B3 primers were able to diagnose species-specific in general and multiplex PCR, and specifically reacted within the inner primers in LAMP assay. The optimal incubation condition of the LAMP assay was 61 □ for 60 minutes with four LAMP primers, though additional loop primer, BF and LF, did not significantly shorten the amplification time. The broad range of DNA concentration was workable in LAMP assay, in which the minimum detectable DNA concentration was 100 pg. Here, DNA releasing method was applied which took five minutes of incubation at 95 □ without the DNA extraction process, and only some pieces of tissue from larvae and adult samples were needed. The incidence of invasive pests is gradually diversifying, therefore, this simple and accurate LAMP assay possibly applied in the intensive field monitoring for the invasive pests and integrated management ofMythimna loreyi.