bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent assessment of gait kinematics using marker-based and markerless motion capture
Authors: Kanko Robert , Laende Elise K. , Davis Elysia M. , Selbie W. Scott , Deluzio Kevin J. 
Published: December 2020

AbstractKinematic analysis is a useful and widespread tool used in research and clinical biomechanics for the estimation of human pose and the quantification of human movement. Common marker-based optical motion capture systems are expensive, time intensive, and require highly trained operators to obtain kinematic data. Markerless motion capture systems offer an alternative method for the measurement of kinematic data with several practical benefits. This work compared the kinematics of human gait measured using a deep learning algorithm-based markerless motion capture system to those of a common marker-based motion capture system. Thirty healthy adult participants walked on a treadmill while data were simultaneously recorded using eight video cameras (markerless) and seven infrared optical motion capture cameras (marker-based). Video data were processed using markerless motion capture software, marker-based data were processed using marker-based capture software, and both sets of data were compared. The average root mean square distance (RMSD) between corresponding joints was less than 2.5 cm for all joints except the hip, which was 3.6 cm. Lower limb segment angles indicated pose estimates from both systems were very similar, with RMSD of less than 5.5° for all segment angles except those that represent rotations about the long axis of the segment. Lower limb joint angles captured similar patterns for flexion/extension at all joints, ab/adduction at the knee and hip, and toe-in/toe-out at the ankle. These findings demonstrate markerless motion capture can measure similar 3D kinematics to those from marker-based systems.
Single-trial neural dynamics influence auditory category learning
Authors: Mankel Kelsey , Pavlik Philip I. , Bidelman Gavin M. 
Published: December 2020

AbstractPercepts are naturally grouped into meaningful categories to process continuous stimulus variations in the environment. Theories of category acquisition have existed for decades, but how they arise in the brain due to learning is not well understood. Here, advanced computational modeling techniques borrowed from educational data mining and cognitive psychology were used to trace the development of auditory categories within a short-term training session. Nonmusicians were rapidly trained for 20 min on musical interval identification (i.e., minor and major 3rdinterval dyads) while their brain activity was recorded via EEG. Categorization performance and neural responses were then assessed for the trained (3rds) and novel untrained (major/minor 6ths) continua. Computational modeling was used to predict behavioral identification responses and whether the inclusion of single-trial features of the neural data could predict successful learning performance. Model results revealed meaningful brain-behavior relationships in auditory category learning detectible on the single-trial level; smaller P2 amplitudes were associated with a greater probability of correct interval categorization after learning. These findings highlight the nuanced dynamics of brain-behavior coupling that help explain the temporal emergence of auditory categorical learning in the brain.
Molecular evolutionary trends and biosynthesis pathways in the Oribatida revealed by the genome ofArchegozetes longisetosus
Authors: Brückner Adrian , Barnett Austen A. , Antoshechkin Igor A. , Kitchen Sheila A. 
Published: December 2020

AbstractOribatid mites are a specious order of microarthropods within the subphylum Chelicerata, compromising about 11,000 described species. They are ubiquitously distributed across different microhabitats in all terrestrial ecosystems around the world and were among the first animals colonizing terrestrial habitats as decomposers and scavengers. Despite their species richness and ecological importance genomic resources are lacking for oribatids. Here, we present a 190-Mb genome assembly of the clonal, all-female oribatid mite speciesArchegozetes longisetosusAoki, a model species used by numerous laboratories for the past 30 years. Comparative genomic and transcriptional analyses revealed patterns of reduced body segmentation and loss of segmental identity geneabd-Awithin Acariformes, and unexpected expression of key eye development genes in these eyeless mites across developmental stages. Consistent with their soil dwelling lifestyle, investigation of the sensory genes revealed a species-specific expansion of gustatory receptors, the largest chemoreceptor family in the genome used in olfaction, and evidence of horizontally transferred enzymes used in cell wall degradation of plant and fungal matter, both components of theA. longisetosusdiet. Oribatid mites are also noted for their biosynthesis capacities and biochemical diversity. Using biochemical and genomic data, we were able to delineate the backbone biosynthesis of monoterpenes, an important class of compounds found in the major exocrine gland system of Oribatida – the oil glands. Given the mite’s strength as an experimental model, the new high-quality resources provided here will serve as the foundation for molecular research in Oribatida and will enable a broader understanding of chelicerate evolution.
Genetic Fine-mapping with Dense Linkage Disequilibrium Blocks: genetics of nicotine dependence
Authors: Mo Chen , Ye Zhenyao , Hatch Kathryn , Zhang Yuan , Wu Qiong , Liu Song , Kochunov Peter , Hong L. Elliot , Ma Tianzhou , Chen Shuo 
Published: December 2020

AbstractFine-mapping is an analytical step to perform causal prioritization of the polymorphic variants on a trait-associated genomic region observed from genome-wide association studies (GWAS). The prioritization of causal variants can be challenging due to the linkage disequilibrium (LD) patterns among hundreds to thousands of polymorphisms associated with a trait. We propose a novelℓ0graph norm shrinkage algorithm to select causal variants from dense LD blocks consisting of highly correlated SNPs that may not be proximal or contiguous. We extract dense LD blocks and perform regression shrinkage to calculate a prioritization score to select a parsimonious set of causal variants. Our approach is computationally efficient and allows performing fine-mapping on thousands of polymorphisms. We demonstrate its application using a large UK Biobank (UKBB) sample related to nicotine addiction. Our results suggest that polymorphic variances in both neighboring and distant variants can be consolidated into dense blocks of highly correlated loci. Simulations were used to evaluate and compare the performance of our method and existing fine-mapping algorithms. The results demonstrated that our method outperformed comparable fine-mapping methods with increased sensitivity and reduced false-positive error rate regarding causal variant selection. The application of this method to smoking severity trait in UKBB sample replicated previously reported loci and suggested the causal prioritization of genetic effects on nicotine dependency.Author summaryDisentangling the complex linkage disequilibrium (LD) pattern and selecting the underlying causal variants have been a long-term challenge for genetic fine-mapping. We find that the LD pattern within GWAS loci is intrinsically organized in delicate graph topological structures, which can be effectively learned by our novelℓ0graph norm shrinkage algorithm. The extracted LD graph structure is critical for causal variant selection. Moreover, our method is less constrained by the width of GWAS loci and thus can fine-map a massive number of correlated SNPs.
Integrative genomics identifies lncRNA regulatory networks across 1,044 pediatric leukemias and extra-cranial solid tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Gerhard Daniela S. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J. 
Published: December 2020

AbstractLong non-coding RNAs (lncRNAs) play an important role in gene regulation and contribute to tumorigenesis. While pan-cancer studies of lncRNA expression have been performed for adult malignancies, the lncRNA landscape across pediatric cancers remains largely uncharted. Here, we curate RNA sequencing data for 1,044 pediatric leukemia and solid tumors and integrate paired tumor whole genome sequencing and epigenetic data in relevant cell line models to explore lncRNA expression, regulation, and association with cancer. We report a total of 2,657 robustly expressed lncRNAs across six pediatric cancers, including 1,142 exhibiting histotype-specific expression. DNA copy number alterations contributed to lncRNA dysregulation at a proportion comparable to protein coding genes. Application of a multi-dimensional framework to identify and prioritize lncRNAs impacting gene networks revealed that lncRNAs dysregulated in pediatric cancer are associated with proliferation, metabolism, and DNA damage hallmarks. Analysis of upstream regulation via cell-type specific transcription factors further implicated distinct histotype-specific and developmental lncRNAs. We integrated our analyses to prioritize lncRNAs for experimental validation and showed that silencing ofTBX2-AS1, our top-prioritized neuroblastoma-specific lncRNA, resulted in significant growth inhibition of neuroblastoma cells, confirming our computational predictions. Taken together, these data provide a comprehensive characterization of lncRNA regulation and function in pediatric cancers and pave the way for future mechanistic studies.
Bacterial adaptation by a transposition burst of an invading IS element
Authors: Miller Scott R. , Abresch Heidi E. , Ulrich Nikea J. , Sano Emiko B. , Demaree Andrew H. , Garber Arkadiy I. 
Published: December 2020

AbstractThe impact of transposable elements on host fitness range from highly deleterious to beneficial, but their general importance for adaptive evolution remains debated. Here, we investigated whether IS elements are a major source of beneficial mutations during 400 generations of laboratory evolution of the cyanobacteriumAcaryochloris marinastrain CCMEE 5410, which has experienced a recent or on-going IS element expansion. The dynamics of adaptive evolution were highly repeatable among eight independent experimental populations and included beneficial mutations related to exopolysaccharide production and inorganic carbon concentrating mechanisms for photosynthetic carbon fixation. Most detected mutations were IS transposition events, but, surprisingly, the majority of these involved the copy-and-paste activity of only a single copy of an unclassified element (ISAm1) that has recently invaded the genome ofA. marinastrain CCMEE 5410. Our study reveals that the activity of a single transposase can fuel adaptation for at least several hundred generations.Impact statementA single transposable element can fuel adaptation to a novel environment for hundreds of generations without an apparent accumulation of a deleterious mutational load.
ORMDL1 is upregulated and associated with favorable outcome in colorectal cancer
Authors: Wang Qian , Liu Wanjun , Chen Si , Luo Qianxin , Li Yichen , Peng Shaoyong , Wang Huaiming , Liu Xiaoxia , Chen Daici 
Published: December 2020

AbstractBackgroundORMDL1 gene encodes a transmembrane protein for endoplasmic reticulum and is known as crucial negative regulator for sphingolipid biogenesis. However, it has been rarely studied in tumor-related context. Therefore, its prognostic value and functional significance in colorectal cancer (CRC) remain to be explored.MethodsTCGA CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the ORMDL1 expression level. The association between ORMDL1 expression and various clinical characteristics were analyzed by Chi-square tests. CRC patients’ overall survival (OS) was analyzed by Kaplan-Meier analysis.In vitroandin vivocell-based assays were performed to explore the role of ORMDL1 in cell proliferation, invasion and migration. Transcriptional changes of cells either with ORMDL1 knockdowned or overexpressed were compared and analyzed.ResultsORMDL1 was upregulated in CRC tissues either in TCGA cohort or in our cohort. Interestingly, its expression was significantly lower in patients with metastasis compared to patients without metastasis, and high expression group had longer OS than low expression group. Knockdown of ORMDL1 expression can promote proliferation, colony formation and invasion, while attenuate migration in CRC cell lines. In opposite, forced overexpression of ORMDL1 reduced cell proliferation, colony formation and invasion, while enhanced cell migration. Epithelial-to-mesenchymal transition (EMT) related genes were enriched among differentially expressed genes when ORMDL1 was knockdowned in cells, which was consistent with morphologic change by microscopy observation. Finally, stable knockdown of ORMDL1 can promote cancer cell proliferationin vivoto some extent.ConclusionORMDL1 is upregulated and may serve as biomarker to predict favourable outcome in colorectal cancer.
Oblique transmission, conformity, and preference in the evolution of altruism
Authors: Denton Kaleda K. , Ram Yoav , Feldman Marcus W. 
Published: December 2020

AbstractThe evolution of altruism is frequently studied using models of non-random assortment, including kin selection. In genetic kin selection models, under certain assumptions including additive costs and benefits, the criterion for altruism to invade a population is Hamilton’s rule. Deviations from Hamilton’s rule occur when vertical transmission has cultural and genetic components, or when costs and benefits are combined multiplicatively. Here, we include oblique and vertical cultural transmission and genetic transmission in four models—two forms of parent-to-offspring altruism, sibling-to-sibling altruism, and altruism between offspring that meet assortatively—under additive or multiplicative assumptions. Oblique transmission may be conformist (anti-conformist), where the probability that an individual acquires a more common cultural variant is greater (less) than its frequency. Inclusion of conformist or anti-conformist oblique transmission may reduce or increase the threshold for invasion by altruism relative to Hamilton’s rule. Thresholds for invasion by altruism are lower with anti-conformity than with conformity, and lower or the same with additive rather than multiplicative fitness components. Invasion by an allele that increases the preference for altruism does not depend on oblique phenotypic transmission, and with sibling-to-sibling altruism, this allele’s invasion threshold can be higher with additive rather than multiplicative fitnesses.
First Glimpse of Gut Microbiota of Quarantine Insects in China
Authors: Yu Yanxue , Wang Qi , Zhou Ping , Lv Na , Li Wei , Zhao Fangqing , Zhu Shuifang , Liu Di 
Published: December 2020

AbstractQuarantine insects are economically important pests that frequently invade new habitats. A rapid and accurate monitoring method to trace the geographical source of invaders is therefore needed for prevention, detection, and eradication. Current methods based on insect genetics are often too slow. We developed a novel tracing method based on insect gut microbiota. The source location of microbiota of insects can be used to rapidly determine the insects’ geographic origin. We analyzed 179 gut microbiota samples belonging to 591 individuals of 22 quarantine insect species collected from 36 regions in China and abroad. The gut microbiotas of these insects mainly included Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, Proteobacteria, and Tenericutes. The diversity of the insect gut microbiota was closely related to geographic and environmental factors. Different insect species could be distinguished at the phylum level of microbiota. Populations of individual insect species from different regions could be distinguished at the genus level of microbiota. A method for determining the geographical origin of invasive insect species was tentatively established, but its practical applicability requires further study.
TiMEG: an integrative approach for partially missing multi-omics data with an application to tuberous sclerosis
Authors: Das Sarmistha , Mukhopadhyay Indranil 
Published: December 2020

1AbstractMulti-omics data integration is widely used to understand the genetic architecture of disease. In multi-omics association analysis, data collected on multiple omics for the same set of individuals are immensely important for biomarker identification. But when the sample size of such data is limited, the presence of partially missing individual-level observations poses a major challenge in data integration. More often, genotype data are available for all individuals under study but gene expression and/or methylation information are missing for different subsets of those individuals. Here, we develop a statistical model TiMEG, for the identification of disease-associated biomarkers in a case-control paradigm by integrating the above-mentioned data types, especially, in presence of missing omics data. Based on a likelihood approach, TiMEG exploits the inter-relationship among multiple omics data to capture weaker signals, that remain unidentified in single-omics analyses. Its application on a real tuberous sclerosis dataset identified functionally relevant genes in the disease pathway.
Evaluation of seasonal dynamics of fungal DNA assemblages in a flow-regulated stream in a restored forest using eDNA metabarcoding
Authors: Matsuoka Shunsuke , Sugiyama Yoriko , Shimono Yoshito , Ushio Masayuki , Doi Hideyuki 
Published: December 2020

AbstractInvestigation of seasonal variation in fungal communities is essential for understanding biodiversity and ecosystem functions. However, the conventional sampling method, with substrate removal and high spatial heterogeneity of community composition, makes surveying the seasonality of fungal communities challenging. Recently, water environmental DNA (eDNA) analysis has been explored for its utility in biodiversity surveys. In this study, we assessed whether the seasonality of fungal communities can be detected by monitoring eDNA in a forest stream. We conducted monthly water sampling in a forest stream over two years and used DNA metabarcoding to identify fungal eDNA. The stream water contained DNA from functionally diverse aquatic and terrestrial fungi, such as plant decomposers, parasites, and mutualists. The variation in the fungal assemblage showed a regular annual periodicity, meaning that the assemblages in a given season were similar, irrespective of the year or sampling. Furthermore, the strength of the annual periodicity varied among functional groups. Our results suggest that forest streams may act as a “trap” for terrestrial fungal DNA derived from different habitats, allowing the analysis of fungal DNA in stream water to provide information about the temporal variation in fungal communities in both the aquatic and the surrounding terrestrial ecosystems.
Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis
Authors: Ng Benjamin , Widjaja Anissa A. , Viswanathan Sivakumar , Dong Jinrui , Chothani Sonia P. , Lim Stella , Shekeran Shamini G. , Tan Jessie , Schafer Sebastian , Cook Stuart A. 
Published: December 2020

AbstractGenetic loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and craniosynostosis. The impact of genetic LOF in IL11 has not been characterized. We generated IL11-knockout (Il11-/-) mice, which are born in normal Mendelian ratios, have normal hematological profiles and are protected from bleomycin-induced lung fibro-inflammation. Noticeably, baseline IL6 levels in the lungs of Il11-/- mice are lower than those of wild-type mice and are not induced by bleomycin damage, placing IL11 upstream of IL6. Lung fibroblasts from Il11-/- mice are resistant to pro-fibrotic stimulation and show evidence of reduced autocrine IL11 activity. Il11-/- female mice are infertile. Unlike Il11ra1-/- mice, Il11-/- mice do not have a craniosynostosis-like phenotype and exhibit mildly reduced body weights. These data highlight similarities and differences between LOF in IL11 or IL11RA while establishing further the role of IL11 signaling in fibrosis and stromal inflammation.
Cell type-specific biogenesis of novel vesicles containing viral products in human cytomegalovirus infection
Authors: Momtaz Samina , Molina Belen , Mlera Luwanika , Goodrum Felicia , Wilson Jean M. 
Published: December 2020

AbstractHuman cytomegalovirus (HCMV), while highly restricted for the human species, infects an unlimited array of cell types in the host. Patterns of infection are dictated by the cell type infected, but cell type-specific factors and how they impact tropism for specific cell types is poorly understood. Previous studies in primary endothelial cells showed that HCMV infection induces large multivesicular-like bodies that incorporate viral products including dense bodies and virions. Here we define the nature of these large vesicles using a recombinant virus where UL32, encoding the pp150 tegument protein, is fused in frame with green fluorescent protein (GFP, TB40/E-UL32-GFP). Cells were fixed and labeled with antibodies against subcellular compartment markers and imaged using confocal and super-resolution microscopy. In fibroblasts, UL32-GFP-positive vesicles were marked with classical markers of MVBs, including CD63 and lysobisphosphatidic acid (LBPA), both classical MVB markers, as well as the clathrin and LAMP1. Unexpectedly, UL32-GFP-positive vesicles in endothelial cells were not labeled by CD63, and LBPA was completely lost from infected cells. We defined these UL32-positive vesicles in endothelial cells using markers for the cis-Golgi (GM130), lysosome (LAMP1), and autophagy (LC3B). These findings suggest that virus-containing MVBs in fibroblasts are derived from the canonical endocytic pathway and takeover classical exosomal release pathway. Virus containing MVBs in HMVECs are derived from the early biosynthetic pathway and exploit a less characterized early Golgi-LAMP1-associated non-canonical secretory autophagy pathway. These results reveal striking cell-type specific membrane trafficking differences in host pathways that are exploited by HCMV.ImportanceHuman cytomegalovirus (HCMV) is a herpesvirus that, like all herpesvirus, that establishes a life long infection. HCMV remains a significant cause of morbidity and mortality in the immunocompromised and HCMV seropositivity is associated with increased risk vascular disease. HCMV infects many cells in the human and the biology underlying the different patterns of infection in different cell types is poorly understood. Endothelial cells are important target of infection that contribute to hematogenous spread of the virus to tissues. Here we define striking differences in the biogenesis of large vesicles that incorporate virions in fibroblasts and endothelial cells. In fibroblasts, HCMV is incorporated into canonical MVBs derived from an endocytic pathway, whereas HCMV matures through vesicles derived from the biosynthetic pathway in endothelial cells. This work defines basic biological differences between these cell types that may impact the outcome of infection.