bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel algorithm to accurately classify metagenomic sequences
Authors: Saha Subrata , Wang Zigeng , Rajasekaran Sanguthevar 
Published: October 2020

AbstractWidespread availability of next-generation sequencing (NGS) technologies has prompted a recent surge in interest in the microbiome. As a consequence, metagenomics is a fast growing field in bioinformatics and computational biology. An important problem in analyzing metagenomic sequenced data is to identify the microbes present in the sample and figure out their relative abundances. In this article we propose a highly efficient algorithm dubbed as “Hybrid Metagenomic Sequence Classifier” (HMSC) to accurately detect microbes and their relative abundances in a metagenomic sample. The algorithmic approach is fundamentally different from other state-of-the-art algorithms currently existing in this domain. HMSC judiciously exploits both alignment-free and alignment-based approaches to accurately characterize metagenomic sequenced data. To demonstrate the effectiveness of HMSC we used 8 metagenomic sequencing datasets (2mockand 6in silicobacterial communities) produced by 3 different sequencing technologies (e.g., HiSeq, MiSeq, and NovaSeq) with realistic error models and abundance distribution. Rigorous experimental evaluations show that HMSC is indeed an effective, scalable, and efficient algorithm compared to the other state-of-the-art methods in terms of accuracy, memory, and runtime.Availability of data and materialsThe implementations and the datasets we used are freely available for non-commercial purposes. They can be downloaded from:https://drive.google.com/drive/folders/132k5E5xqpkw7olFjzYwjWNjyHFrqJITe?usp=sharing
Individual small in-stream barriers contribute little to strong local population genetic structure five strictly aquatic macroinvertebrate taxa
Authors: Weiss Martina , Weigand Hannah , Leese Florian 
Published: October 2020

AbstractWater flow in river networks is frequently regulated by man-made in-stream barriers. These obstacles can hinder dispersal of aquatic organisms and isolate populations leading to the loss of genetic diversity. Although millions of small in-stream barriers exist worldwide, such as weirs below 2 m or tunnels and pipes, their impact on the dispersal of macroinvertebrates with strictly aquatic life cycles is unclear. We therefore assessed the effects of such barriers on the population structure and effective dispersal of five macroinvertebrate species with strictly aquatic life cycles: the amphipod crustacean Gammarus fossarum (clade 11), three snail species of the Ancylus fluviatilis species complex and the flatworm Dugesia gonocephala. We studied populations at nine weirs and eight culverts (3 pipes, 5 tunnels), built 33-109 years ago, in the heavily fragmented catchment of the river Ruhr (Sauerland, Germany). To assess fragmentation and barrier effects, we generated genome-wide SNP data using ddRAD sequencing and evaluated clustering, differentiation between populations up- and downstream of each barrier and effective migration rates among sites and across barriers. Additionally, we applied population genomic simulations to assess expected differentiation patterns under different gene flow scenarios. Our data show that populations of all species are highly isolated at regional and local scales within few kilometres. While the regional population structure likely results from historical processes, the strong local differentiation suggests that contemporary dispersal barriers exist. However, we identified significant barrier effects only for pipes (for A. fluviatilis II and III) and few larger weirs (>1.3 m; for D. gonocephala). Therefore our data suggest that most small in-stream barriers can probably be overcome by all studied taxa frequently enough to prevent fragmentation. Thus, the barriers leading to population isolation after few kilometres still need to be identified. Specifically, it remains to be tested if the strong local differentiation is a result of a cumulative effect of small barriers, or if e.g. larger in-stream barriers, land use, chemical pollution, urbanisation, or a combination of these factors impede gene flow.
Highly responsive single-fluorophore indicator to explore lactate dynamics in high calcium environments
Authors: Galaz A. , Sandoval PY. , Soto-Ojeda I. , Hertenstein H. , Schweizer J. , Schirmeier S. , Barros L.F , San Martín A. 
Published: October 2020

ABSTRACTLactate is an energy substrate and intercellular signaling molecule with multiple bodily functions. Lactate has physiological roles in neurogenesis, axon integrity, memory consolidation, immune response, exercise, adipose tissue lipolysis, etc, and is involved in inflammation, cancer and neurodegeneration. The FRET lactate indicator Laconic has been instrumental in the discovery of mechanisms involved in neurometabolic coupling, and has advanced the understanding of lactate transport, glycolysis and mitochondrial physiology. However, the low fluorescent response and the complex saturation kinetics of Laconic limit its use for high-throughput screening and quantitation. Using the bacterial periplasmic binding protein TTHA0766 fromThermus thermophilus, we have now developed the first single-fluorophore indicator for lactate. The sensor exhibited an intensiometric fluorescence increase of ΔF/F03.0 and a single binding site with a KDof 293 μM. The fluorescence is not affected by other monocarboxylates or pH. However, it is sensitive to Ca2+in the nanomolar range. Targeting of the sensor to the endoplasmic reticulum revealed that this organelle presents a high permeability for lactate. The functionality of the sensor in living tissue is demonstrated in the brain ofDrosophila melanogasterlarvae. This indicator, which we have termed CanlonicSF, is well suited to explore lactate dynamics in environments with micromolar Ca2+or higher, such as the endoplasmic reticulum and the extracellular space.
Establishment of a new sex-determining allele driven by sexually antagonistic selection
Authors: Sakamoto T. , Innan H. 
Published: October 2020

ABSTRACTSome species undergo frequent turnovers of sex-determining locus, rather than having stable diverged sex chromosomes. In such species, how often turnover occurs is a fundamental evolutionary question. We model the process with considering a linked locus under sexually antagonistic selection. The entire process of a turnover may be divided into two phases, which are referred to as the stochastic and deterministic phases. The stochastic phase is when a new sex-determining allele just arises and is still rare and random genetic drift plays an important role. In the deterministic phase, the new allele further increases in frequency by positive selection. The theoretical results currently available are for the deterministic phase, which demonstrated that a turnover of a newly arisen sex determining locus could benefit from selection at a linked locus under sexually antagonistic selection, by assuming that sexually antagonistic selection works in a form of balancing selection. In this work, we provide a comprehensive theoretical description of the entire process from the stochastic phase to the deterministic phase. In addition to balancing selection, we explore several other modes of selection on the linked locus. Our theory allows us make a quantitative argument on the rate of turnover and the effect of the mode of selection at the linked locus. We also performed simulations to explore the pattern of polymorphism around the new sex determining locus. We find that the pattern of polymorphism is informative to infer how selection worked through the turnover process.
Spatial fingerprinting: horizontal fusion of multi-dimensional bio-tracers as solution to global food provenance problems
Authors: Cazelles Kevin , Zemlak Tyler , Gutgesell Marie , Myles-Gonzalez Emelia , Hanner Robert , McCann Kevin S. 
Published: October 2020

AbstractBuilding the capacity of efficiently determining the provenance of food products represents a crucial step towards the sustainability of the global food system. Whether it is for enforcing existing egislation or providing reliable information to consumers, technologies to verify geographical origin of food are being actively developed. Biological tracers (bio-tracers) such as DNA and stable isotopes have recently demonstrated their potential for determining provenance. Here we show that the data fusion of bio-tracers is a very powerful technique for geographical provenance discrimination. Based on 90 individuals of Sockeye salmon that originate from 3 different areas for which we measured 17 bio-tracers, we demonstrate that increasing the combined bio-tracers results in stronger the discriminatory power. The generality of our results are mathematically demonstrated under simplifying assumptions and numerically confirmed in our case study using three commonly used supervised learning techniques.
Morphine alleviates pain after heart cryoinjury in zebrafish without impeding regeneration
Authors: Lelek Sara , Simões Mariana Guedes , Hu Bo , Alameldeen Ahmed M.A. , Czajkowski Maciej T. , Meyer Alexander M. , Ferrara Fabienne , Junker Jan Philipp , Panáková Daniela 
Published: October 2020

SummaryNociceptive response belongs to a basic animal behavior facilitating adaptability and survival upon external or internal stimuli. Fish, similarly to higher vertebrates, also possess nociceptive machinery. Current protocols involving procedures performed on adult zebrafish including heart cryoinjury do not, however, take into account the adverse effects including pain that may potentially arise from these methodologies. Here, we assess the effect of two analgesics, lidocaine and morphine, followed after heart cryoinjury in zebrafish. Monitoring swimming behavior together with histology and gene expression analysis at the single cell level using scRNA sequencing and RNAscope fluorescentin situhybridization technology, we show morphine, but not lidocaine, significantly improves animal welfare 6 hours post-cryoinjury, without impairing the heart regeneration process. Altogether, we propose morphine to be considered as the analgesic of choice to reduce post-surgical pain in adult zebrafish.HighlightsCryoinury could be considered as a potential noxious stimulus in adult zebrafish.Morphine but not lidocaine treatment effectively alleviates noxious effects post-cryoinjury.Lidocaine treatment delays heart repair and regeneration.6 hours Morphine treatment after cryoinjury does not impede heart regeneration.
Dwarf open reading frame (DWORF) peptide is a direct activator of the sarcoplasmic reticulum calcium pump SERCA
Authors: Fisher M’Lynn E. , Bovo Elisa , Cho Ellen E. , Pribadi Marsha P. , Dalton Michael P. , Lemieux M. Joanne , Rathod Nishadh , Aguayo-Ortiz Rodrigo , Espinoza-Fonseca L. Michel , Robia Seth L. , Zima Aleksey V. , Young Howard S. 
Published: October 2020

ABSTRACTThe cardiac sarcoplasmic reticulum calcium pump, SERCA, sequesters calcium in the sarco-endoplasmic reticulum (SR/ER) and plays a critical role in the contraction-relaxation cycle of the heart. A well-known regulator of SERCA in cardiac muscle is phospholamban (PLN), which interacts with the pump and reduces its apparent calcium affinity. A newly discovered SERCA regulatory subunit in cardiac muscle, dwarf open reading frame (DWORF), has added a new level of SERCA regulation. In this report, we modeled the structure of DWORF and evaluated it using molecular dynamics simulations. DWORF structure was modeled as a discontinuous helix with an unwound region at Pro15. This model orients an N-terminal amphipathic helix along the membrane surface and leaves a relatively short C-terminal transmembrane helix. We determined the functional regulation of SERCA by DWORF using a membrane reconstitution system. Surprisingly, we observed that DWORF directly activated SERCA by increasing its turnover rate. Furthermore, in-cell imaging of calcium dynamics demonstrated that DWORF increased SERCA-dependent ER calcium load, calcium reuptake rate, and spontaneous calcium release. Together, these functional assays suggest opposing effects of DWORF and PLN on SERCA function. The results agree with fluorescence resonance energy transfer experiments, which revealed changes in the affinity of DWORF for SERCA at low versus high cytosolic calcium concentrations. We found that DWORF has a higher affinity for SERCA in the presence of calcium, while PLN had the opposite behavior, a higher affinity for SERCA in low calcium. We propose a new mechanism for DWORF regulation of cardiac calcium handling in which DWORF directly enhances SERCA turnover by stabilizing the conformations of SERCA that predominate during elevated cytosolic calcium.
Identification of Influential Variants in Significant Aggregate Rare Variant Tests
Authors: Blumhagen Rachel Z. , Schwartz David A. , Langefeld Carl D. , Fingerlin Tasha E. 
Published: October 2020

AbstractIntroductionStudies that examine the role of rare variants in both simple and complex disease are increasingly common. Though the usual approach of testing rare variants in aggregate sets is more powerful than testing individual variants, it is of interest to identify the variants that are plausible drivers of the association. We present a novel method for prioritization of rare variants after a significant aggregate test by quantifying the influence of the variant on the aggregate test of association.MethodsIn addition to providing a measure used to rank variants, we use outlier detection methods to present the computationally efficientRare Variant InfluentialFilteringTool (RIFT) to identify a subset of variants that influence the disease association. We evaluated several outlier detection methods that vary based on the underlying variance measure: interquartile range (Tukey fences), median absolute deviation and standard deviation. We performed 1000 simulations for 50 regions of size 3kb and compared the true and false positive rates. We compared RIFT using the Inner Tukey to two existing methods: adaptive combination of p-values (ADA) and a Bayesian hierarchical model (BeviMed). Finally, we applied this method to data from our targeted resequencing study in idiopathic pulmonary fibrosis (IPF).ResultsAll outlier detection methods observed higher sensitivity to detect uncommon variants (0.001 < MAF > 0.03) compared to very rare variants (MAF < 0.001). For uncommon variants, RIFT had a lower median false positive rate compared to the ADA. ADA and RIFT had significantly higher true positive rates than that observed for BeviMed. When applied to two regions found previously associated with IPF including 100 rare variants, we identified six polymorphisms with the greatest evidence for influencing the association with IPF.DiscussionIn summary, RIFT has a high true positive rate while maintaining a low false positive rate for identifying polymorphisms influencing rare variant association tests. This work provides an approach to obtain greater resolution of the rare variant signals within significant aggregate sets; this information can provide an objective measure to prioritize variants for follow-up experimental studies and insight into the biological pathways involved.
Emerging strains of watermelon mosaic virus in Southeastern France: model-based estimation of the dates and places of introduction
Authors: Roques L , Desbiez C , Berthier K , Soubeyrand S , Walker E , Klein E K , Garnier J , Moury B , Papaïx J 
Published: October 2020

ABSTRACTWhere and when alien organisms are successfully introduced are central questions to elucidate biotic and abiotic conditions favorable to the introduction, establishment and spread of invasive species. We propose a modelling framework to analyze multiple introductions by several invasive genotypes or genetic variants, in competition with a resident population, when observations provide knowledge on the relative proportions of each variant at some dates and places. This framework is based on a mechanistic-statistical model coupling a reaction-diffusion model with a probabilistic observation model. We apply it to a spatio-temporal dataset reporting the relative proportions of five genetic variants of watermelon mosaic virus (WMV, genusPotyvirus, familyPotyviridae) in infections of commercial cucurbit fields. Despite the parsimonious nature of the model, it succeeds in fitting the data well and provides an estimation of the dates and places of successful introduction of each emerging variant as well as a reconstruction of the dynamics of each variant since its introduction.
Environmental DNA Metabarcoding for Simultaneous Monitoring and Ecological Assessment of Many Harmful Algae
Authors: Jacobs-Palmer Emily , Gallego Ramón , Cribari Kelly , Keller Abigail , Kelly Ryan P. 
Published: October 2020

AbstractHarmful algae can have profound economic, environmental, and social consequences. As the timing, frequency, and severity of harmful algal blooms (HABs) change alongside global climate, efficient tools to monitor and understand the current ecological context of these taxa are increasingly important. Here we employ environmental DNA metabarcoding to identify patterns in a wide variety of harmful algae and associated ecological communities in the Hood Canal of Puget Sound in Washington State, USA. We track trends of presence and abundance in a series of water samples across nearly two years. We find putative harmful algal sequences in a majority of samples, suggesting that these groups are routinely present in local waters. We report patterns in variants of the economically important genusPseudo-nitzschia(family Bacillariaceae), as well as multiple harmful algal taxa previously unknown or poorly documented in the region, including a cold-water variant from the saxitoxin-producing genusAlexandrium(family Gonyaulacaceae), two variants from the karlotoxin-producing genusKarlodinium(family Kareniaceae), and one variant from the parasitic genusHematodinium(family Syndiniaceae). We then use data on environmental variables and the biological community surrounding each algal taxon to illustrate the ecological context in which these species are commonly found. Environmental DNA metabarcoding thus simultaneously (1) alerts us to potential new or cryptic occurrences of harmful algae, (2) expands our knowledge of the co-occurring conditions and species associated with the growth of these organisms in changing marine environments, and (3) provides a tool for monitoring and management moving forward.
Rational Tuning of CAR Tonic Signaling Yields Superior T-Cell Therapy for Cancer
Authors: Chen Ximin , Khericha Mobina , Lakhani Aliya , Meng Xiangzhi , Salvestrini Emma , Chen Laurence C. , Shafer Amanda , Alag Anya , Ding Yunfeng , Nicolaou Demetri , Park Junyoung O. , Chen Yvonne Y. 
Published: October 2020

SUMMARYChimeric antigen receptors (CARs) are modular proteins capable of redirecting immune cells toward a wide variety of disease-associated antigens. Here, we explore the effects of CAR protein sequence and structure on CAR-T cell function. Based on the empirical observation that CD20 CARs with similar sequences exhibit divergent tonic-signaling and anti-tumor activities, we devised engineering strategies that aimed to improve CAR-T cell function by tuning the intensity of tonic signaling. We found that CARs designed to exhibit low but non-zero levels of tonic signaling show robust effector function upon antigen stimulation while avoiding premature functional exhaustion by CAR-T cells. Through alterations of the CAR’s ligand-binding domain and overall protein conformation, we generated CD20 CAR variants that outperform the CD19 CAR in mouse models of human lymphoma. We further demonstrate that rational modification of protein confirmation can be generalized to improve GD2 CAR-T cell efficacy against neuroblastoma. These findings point to tonic signaling and basal T-cell activation as informative parameters to guide the rational design of next-generation CARs for cancer therapy.
Seroprevalence of SARS-COV-2 Antibodies in Scottish Healthcare Workers
Authors: Abo-Leyah Hani , Gallant Stephanie , Cassidy Diane , Giam Yan Hui , Killick Justin , Marshall Beth , Hay Gordon , Pembridge Thomas , Strachan Rachel , Gallant Natalie , Parcell Benjamin J , George Jacob , Furrie Elizabeth , Chalmers James D 
Published: October 2020

AbstractIntroductionHealthcare workers are believed to be at increased risk of SARS-CoV-2 infection. The extent of that increased risk compared to the general population and the groups most at risk have not been extensively studied.MethodsA prospective observational study of health and social care workers in NHS Tayside (Scotland, UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Patients provided clinical information including demographics and workplace information. Controls, matched for age and sex to the general Tayside population, were studied for comparison.ResultsA total of 2062 health and social care workers were recruited for this study. The participants were predominantly female (81.7%) and 95.2% were white. 299 healthcare workers had a positive antibody test (14.5%). 11 out of 231 control sera tested positive (4.8%). Healthcare workers therefore had an increased likelihood of a positive test (odds ratio 3.4 95% CI 1.85-6.16, p<0.0001). Dentists, healthcare assistants and porters were the job roles most likely to test positive. Those working in front-line roles with COVID-19 patients were more likely to test positive (17.4% vs. 13.4%, p=0.02). 97.1% of patients who had previously tested positive for SARS-CoV-2 by RT-PCR had positive antibodies, compared to 11.8% of individuals with a symptomatic illness who had tested negative. Anosmia was the symptom most associated with the presence of detectable antibodies.ConclusionIn this study, healthcare workers were three times more likely to test positive for SARS-CoV-2 than the general population. The seroprevalence data in different populations identified in this study will be useful to protect healthcare staff during future waves of the pandemic.
Single Cell Analysis of Regions of Interest (SCARI) using a novel photoswitchable tag
Authors: van der Leun Anne M. , Hoekstra Mirjam E. , Reinalda Luuk , Scheele Colinda L.G.J. , Toebes Mireille , van de Graaff Michel J. , Li Hanjie , Bercovich Akhiad , Lubling Yaniv , David Eyal , Thommen Daniela S. , Tanay Amos , van Rheenen Jacco , Amit Ido , van Kasteren Sander I. , Schumacher Ton N. 
Published: October 2020

AbstractThe functional activity and differentiation potential of cells is determined by their interaction with surrounding cells. Approaches that allow the unbiased characterization of cell states while at the same time providing spatial information are of major value to assess this environmental influence. However, most current techniques are hampered by a trade-off between spatial resolution and cell profiling depth. Here, we developed a photoswitch-based technology that allows the isolation and in-depth analysis of live cells from regions of interest in complexex vivosystems, including human tissues. The use of a highly sensitive 4-nitrophenyl(benzofuran)-cage coupled to nanobodies allowed photoswitching of cells in areas of interest with low-intensity violet light and without detectable phototoxicity. Single cell RNA sequencing of spatially defined CD8+T cells was used to exemplify the feasibility of identifying location-dependent cell states at the single cell level. Finally, we demonstrate the efficient labeling and photoswitching of cells in live primary human tumor tissue. The technology described here provides a valuable tool for the analysis of spatially defined cells in diverse biological systems, including clinical samples.