bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Phenome-wide Consequences of Anorexia Nervosa Genes
Authors: Johnson Jessica S. , Cote Alanna C. , Dobbyn Amanda , Sloofman Laura G. , Xu Jiayi , Cotter Liam , Charney Alexander W. ,   Eating Disorders Working Group of the Psychiatric Genomics Consortium, Jordan Jennifer , Kennedy Martin , Landén Mikael , Maguire Sarah L , Martin Nicholas G , Mortensen Preben Bo , Bulik Cynthia M. , Huckins Laura M. 
Published: February 2021

ABSTRACTAnorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional GWAS studies produce principal evidence for the association of genetic variants with disease, and provide a jumping-off point for downstream functional analyses. Transcriptomic imputation (TI) allows for the translation of SNPs into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a more broad setting through the use of phenome-wide association studies (PheWAS) in large and diverse clinical biobank populations with electronic health record (EHR) phenotypes. Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed PheWAS on over 2000 clinical outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of BMI on AN-GReX clinical associations.Our S-PrediXcan analysis identified 47 genes associated with AN, including what is, to our knowledge, the first genetic association of AN with the Major Histocompatibility Complex (MHC). AN-GReX was associated with autoimmune, anthropometric, metabolic, psychiatric and gastrointestinal diagnoses in our biobank cohort, as well as measures of anthropometry, substance use, and pain score. Our analyses reveal that AN-GReX associations with measures of weight and substance use are modified by BMI, and indicate potential avenues of functional mechanism to investigate further.
Optimal Allocation of COVID-19 Vaccines in the Philippines
Authors: Buhat Christian Alvin H. , Lutero Destiny SM. , Olave Yancee H. , Quindala Kemuel M. , Recreo Mary Grace P. , Talabis Dylan Antonio SJ. , Torres Monica C. , Tubay Jerrold M. , Rabajante Jomar F. 
Published: February 2021

AbstractVaccine allocation is a national concern especially for countries such as the Philippines that have limited resources in acquiring COVID-19 vaccines. As such, certain groups are suggested to be prioritized for vaccination to protect the most vulnerable before vaccinating others. Our model suggests an allocation of vaccines such that COVID-19 deaths are minimized while the prioritization framework is satisfied. Results of the model show that a vaccine coverage of at least 50 to 70% of the population can be enough for a community with limited supplies, and an increase in vaccine supply is beneficial if initial coverage is less than the specified target range. Also, among the vaccines considered in the study, the one with 89.9% effectiveness and has a 183 Philippine peso (Php) price per dose projected the least number of deaths. Compared to other model variations and common allocation approaches, the model has achieved both an optimal and equitable allocation. This will be helpful for policymakers in determining a vaccine distribution for a resource-constrained community.
Interplay between brassinosteroids and TORC signaling in Arabidopsis revealed by integrated multi-dimensional analysis
Authors: Montes Christian , Liao Ching-Yi , Nolan Trevor M , Song Gaoyuan , Clark Natalie M , Guo Hongqing , Bassham Diane C , Yin Yanhai , Walley Justin W 
Published: February 2021

AbstractBrassinosteroids (BR) and Target of Rapamycin Complex (TORC) are two major processes coordinating plant growth and stress responses. BRs function through a signaling pathway to extensively regulate gene expression and TORC is known to regulate translation and autophagy. Recent studies revealed that these two pathways crosstalk, but a system-wide view of their interplay is still missing. Thus, we performed transcriptome, proteome, and phosphoproteome profiling of Arabidopsis mutants with altered levels of either BIN2 or RAPTOR1B, two key players in BR and TORC signaling, respectively. We found that perturbation of BIN2 or RAPTOR1B levels affects a common set of gene-products involved in growth and stress responses. Additionally, we performed Multiplexed Assay for Kinase Specificity (MAKS), which provided a system-wide view of direct BIN2 substrates. Furthermore, phosphoproteomic data was used to reconstruct a kinase-signaling network and to identify novel proteins dependent on BR and/or TORC signaling pathways. Loss of function mutants of many of these proteins led to an altered BR response and/or modulated autophagy activity. Altogether, these results provide genome-wide evidence for crosstalk between BR and TORC signaling and established a kinase signaling network that defines the molecular mechanisms of BR and TORC interactions in the regulation of plant growth/stress balance.
Characterization of SARS-CoV-2 genetic structure and infection clusters in a large German city based on integrated genomic surveillance, outbreak analysis, and contact tracing
Authors: Walker Andreas , Houwaart Torsten , Finzer Patrick , Ehlkes Lutz , Tyshaieva Alona , Damagnez Maximilian , Strelow Daniel , Duplessis Ashley , Nicolai Jessica , Wienemann Tobias , Tamayo Teresa , Vasconcelos Malte Kohns , Hülse Lisanna , Hoffmann Katrin , Lübke Nadine , Hauka Sandra , Andree Marcel , Däumer Martin P. , Thielen Alexander , Kolbe-Busch Susanne , Göbels Klaus , Zotz Rainer , Pfeffer Klaus , Timm Jörg , Dilthey Alexander T. ,   German COVID-19 OMICS Initiative (DeCOI)
Published: February 2021

AbstractViral genome sequencing can address key questions about SARS-CoV-2 evolution and viral transmission. Here, we present an integrated system of genomic surveillance in the German city of Düsseldorf, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) analysis of hospital outbreaks, d) integration of public health authority contact tracing data, and e) a user-friendly dashboard application as a central data analysis platform. The generated surveillance sequencing data (n = 320 SARS-CoV-2 genomes) showed that the development of the local viral population structure from August to December 2020 was consistent with European trends, with the notable absence of SARS-CoV-2 variants 20I/501Y.V1/B.1.1.7 and B.1.351 until the end of the local sampling period. Against a background of local surveillance and other publicly available SARS-CoV-2 data, four putative SARS-CoV-2 outbreaks at Düsseldorf University Hospital between October and December 2020 (n = 44 viral genomes) were investigated and confirmed as clonal, contributing to the development of improved infection control and prevention measures. An analysis of the generated surveillance sequencing data with respect to infection clusters in the population based on a greedy clustering algorithm identified five candidate clusters, all of which were subsequently confirmed by the integration of public health authority contact tracing data and shown to be represent transmission settings of particular relevance (schools, care homes). A joint analysis of outbreak and surveillance data identified a potential transmission of an outbreak strain from the local population into the hospital and back; and an in-depth analysis of one population infection cluster combining genetic with contact tracing data enabled the identification of a previously unrecognized population transmission chain involving a martial arts gym. Based on these results and a real-time sequencing experiment in which we demonstrated the feasibility of achieving sample-to-turnaround times of <30 hours with the Oxford Nanopore technology, we discuss the potential benefits of routine ultra-fast sequencing of all detected infections for contact tracing, infection cluster detection, and, ultimately, improved management of the SARS-CoV-2 pandemic.
Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
Authors: Yuan Meng , Huang Deli , Lee Chang-Chun D. , Wu Nicholas C. , Jackson Abigail M. , Zhu Xueyong , Liu Hejun , Peng Linghang , van Gils Marit J. , Sanders Rogier W. , Burton Dennis R. , Reincke S. Momsen , Prüss Harald , Kreye Jakob , Nemazee David , Ward Andrew B. , Wilson Ian A. 
Published: February 2021

AbstractThe protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.
A tissue-aware machine learning framework enhances the mechanistic understanding and genetic diagnosis of Mendelian and rare diseases
Authors: Simonovsky Eyal , Sharon Moran , Ziv Maya , Mauer Omry , Hekselman Idan , Jubran Juman , Vinogradov Ekaterina , Argov Chanan M. , Basha Omer , Kerber Lior , Yogev Yuval , Segrè Ayellet V. , Im Hae Kyung ,   GTEx Consortium, Birk Ohad , Rokach Lior , Yeger-Lotem Esti 
Published: February 2021

ABSTRACTGenetic studies of Mendelian and rare diseases face the critical challenges of identifying pathogenic gene variants and their modes-of-action. Previous efforts rarely utilized the tissue-selective manifestation of these diseases for their elucidation. Here we introduce an interpretable machine learning (ML) platform that utilizes heterogeneous and large-scale tissue-aware datasets of human genes, and rigorously, concurrently and quantitatively assesses hundreds of candidate mechanisms per disease. The resulting tissue-aware ML platform is applicable in gene-specific, tissue-specific, or patient-specific modes. Application of the platform to selected Mendelian disease genes pinpointed mechanisms that lead to tissue-specific disease manifestation. When applied jointly to diseases that manifest in the same tissue, the models revealed common known and previously underappreciated factors that underlie tissue-selective disease manifestation. Lastly, we harnessed our ML platform toward genetic diagnosis of tissue-selective rare diseases. Patient-specific models of candidate disease-causing genes from 50 patients successfully prioritized the pathogenic gene in 86% of the cases, implying that the tissue-selectivity of rare diseases aids in filtering out unlikely candidate genes. Thus, interpretable tissue-aware ML models can boost mechanistic understanding and genetic diagnosis of tissue-selective heritable diseases. A webserver supporting gene prioritization is available at https://netbio.bgu.ac.il/trace/.
Role and patterns of butterflies and hawkmoths in plant-pollinator networks at different elevations and seasons in tropical rainforests of Mount Cameroon
Authors: Mertens Jan E.J. , Brisson Lucas , Janeček Štěpán , Klomberg Yannick , Maicher Vincent , Sáfián Szabolcs , Delabye Sylvain , Potocký Pavel , Kobe Ishmeal N. , Pyrcz Tomasz , Tropek Robert 
Published: February 2021

AbstractButterflies and moths are well-visible flower visitors. Nevertheless, almost no quantification of their role in plant-pollinator interactions exists at a community level, especially from tropical rainforests. Moreover, we have virtually no knowledge on environmental and other factors affecting lepidopteran flower visits.We focused on the role of butterflies and hawkmoths as flower visitors in tropical rainforests of Mount Cameroon, especially on its elevational and seasonal changes. We also analysed their preferences to selected floral traits, with a specific focus on pollination syndromes.We video-recorded flower visitors of 1,115 specimens of 212 plant species (>26,000 recording hrs) along the complete elevational gradient of rainforests in two main seasons, and compared frequencies of flower-visiting lepidopterans to other visitors. We compared characteristics of plant-lepidopteran networks among elevations and seasons, and analysed patterns of selected lepidopteran traits. Finally, we analysed inter-family differences in their floral preferences.Altogether, we recorded 734 flower visits by 80 butterflies and 27 hawkmoth species, representing only ~4% of all 18,439 flower visits. Although lepidopterans visited only a third species, they appeared key visitors of several plants. The most flower visits by lepidopterans were recorded in mid-elevations and dry season, mirroring the general patterns of lepidopteran diversity. The networks showed no apparent elevational or seasonal patterns, probably because of the surprisingly high specialisation of interactions in all networks. Significant non-linear changes of proboscis and forewing lengths were found along elevation, and long-proboscid hesperiid butterflies visited flowers with longer tubes or spurs. Substantial differences in floral preferences were found between sphingids, and papilionid, nymphalid and lycaenid butterflies, revealing importance of nectar production, floral size and shape for sphingids, and floral colour for butterflies.Butterflies and hawkmoths were confirmed as relatively minor visitors of tropical forest flowers, although they seemed crucial for pollination of some plant species. Moreover, the revealed floral preferences and trait-matchings confirmed a potential of some lepidopteran families to drive floral evolution in tropical ecosystems.
Optical Estimation of Absolute Membrane Potential Using One- and Two-Photon Fluorescence Lifetime Imaging Microscopy
Authors: Lazzari-Dean Julia R. , Miller Evan W. 
Published: February 2021

AbstractBackgroundMembrane potential (Vmem) exerts physiological influence across a wide range of time and space scales. To study Vmemin these diverse contexts, it is essential to accurately record absolute values of Vmem, rather than solely relative measurements.Materials & MethodsWe use fluorescence lifetime imaging of a small molecule voltage sensitive dye (VF2.1.Cl) to estimate mV values of absolute membrane potential.ResultsWe test the consistency of VF2.1.Cl lifetime measurements performed on different single photon counting instruments and find that they are in striking agreement (differences of <0.5 ps/mV in the slope and <50 ps in the y-intercept). We also demonstrate that VF2.1.Cl lifetime reports absolute Vmemunder two-photon (2P) illumination with better than 20 mV of Vmemresolution, a nearly 10-fold improvement over other lifetime-based methods.ConclusionsWe demonstrate that VF-FLIM is a robust and portable metric for Vmemacross imaging platforms and under both one-photon and two-photon illumination. This work is a critical foundation for application of VF-FLIM to record absolute membrane potential signals in thick tissue.
Sec17/Sec18 can support membrane fusion without help from completion of SNARE zippering
Authors: Song Hongki , Torng Thomas , Orr Amy , Brunger Axel T. , Wickner William 
Published: February 2021

AbstractMembrane fusion requires R-, Qa-, Qb-, and Qc-family SNAREs that zipper into RQaQbQc coiled coils, driven by the sequestration of apolar amino acids. Zippering has been thought to provide all the force driving fusion. Sec17/SNAP can form an oligomeric assembly with SNAREs with the Sec17 C-terminus bound to Sec18/NSF, the central region bound to SNAREs, and a crucial apolar loop near the N-terminus poised to insert into membranes. Though Sec17 aids zippering, we now report that Sec17 and Sec18 will drive robust fusion without requiring zippering completion. Zippering-driven fusion is blocked by deleting the C-terminal quarter of any Q-SNARE domain or by replacing the apolar amino acids of the Qa-SNARE which face the center of the 4-SNARE coiled coils with polar residues. These blocks to fusion, singly or combined, are bypassed by Sec17 and Sec18, and SNARE-dependent fusion is restored without help from completing zippering.
AirLift: A Fast and Comprehensive Technique for Remapping Alignments between Reference Genomes
Authors: Kim Jeremie S. , Firtina Can , Cavlak Meryem Banu , Cali Damla Senol , Hajinazar Nastaran , Alser Mohammed , Alkan Can , Mutlu Onur 
Published: February 2021

AirLift is the first read remapping tool that enables users to quickly and comprehensively map a read set, that had been previously mapped to one reference genome, to another similar reference. Users can then quickly run downstream analysis of read sets for each latest reference release. Compared to the state-of-the-art method for remapping reads (i.e., full mapping), AirLift reduces the overall execution time to remap read sets between two reference genome versions by up to 27.4×. We validate our remapping results with GATK and find that AirLift provides high accuracy in identifying ground truth SNP/INDEL variants.Code AvailabilityAirLift source code and readme describing how to reproduce our results are available athttps://github.com/CMU-SAFARI/AirLift.
Synthesizing VERDICT maps from standard DWI data using GANs
Authors: Chiou Eleni , Valindria Vanya , Giganti Francesco , Punwani Shonit , Kokkinos Iasonas , Panagiotaki Eleftheria 
Published: February 2021

AbstractVERDICT maps have shown promising results in clinical settings discriminating normal from malignant tissue and identifying specific Gleason grades non-invasively. However, the quantitative estimation of VERDICT maps requires a specific diffusion-weighed imaging (DWI) acquisition. In this study we investigate the feasibility of synthesizing VERDICT maps from standard DWI data from multi-parametric (mp)- MRI by employing conditional generative adversarial networks (GANs). We use data from 67 patients who underwent both standard DWI-MRI and VERDICT MRI and rely on correlation analysis and mean squared error to quantitatively evaluate the quality of the synthetic VERDICT maps. Quantitative results show that the mean values of tumour areas in the synthetic and the real VERDICT maps were strongly correlated while qualitative results indicate that our method can generate realistic VERDICT maps that could supplement mp-MRI assessment for better diagnosis.
Molecular effects of mannanase-hydrolyzed coprameal to intestinal immunity in the Pacific white shrimp(Litopenaeus vannamei)
Authors: Rungrassamee Wanilada , Arayamethakorn Sopacha , Karoonuthaisiri Nitsara , Chen Shih-Chu , Chang Eric , Chan Samu , Yoshida Yasuhiko , Maebuchi Motohiro , Ibuki Masahisa 
Published: February 2021

AbstractTo mitigate disease outbreak, an alternative approach through enhancing shrimp immunity was explored. Mannan oligosaccharides (MOS) have been previously reported to enhance shrimp immune system. Here, coprameal samples were digested with mannanase to yield MOS, namely, mannanase-hydrolyzed coprameal (MCM) and feasibility of MCM as shrimp immunostimulant in grow-out ponds was determined. Pacific white shrimp (Litopenaeus vannamei) were fed with the commercial diet containing 1% MCM as the MCM-supplemented group and compared to the non-MCM control diet. There was no significant difference in survival rates between the MCM-supplemented and the control groups throughout the 4-month-period of the trial (p> 0.05). Gene expression analysis in shrimp intestines revealed that the transcript levels of antimicrobial peptides (anti-lipopolysaccharide factor isoform 1(alf1),penaeidin (pen3a)andcrustin (crus))and lysozymes(lyz)were not significantly different in the MCM-supplemented group. Meanwhile,C-type lectinandtoll-like receptortranscript levels, whose gene products play roles as pattern recognition proteins, were significantly higher in a group fed with MCM for 2- and 4-month periods than those of the control group (p< 0.05). The increased transcript levels ofC-type lectinandtoll-like receptorprovide evidence for potential implementation of MCM as feed supplement to modulate shrimp immune system.
Shades of grey: Coat-colour dependent effect of urbanization on the bacterial microbiome of a wild mammal
Authors: Stothart Mason R. , Newman Amy E.M. 
Published: February 2021

AbstractBackgroundHost-associated microbiota can be fundamental to the ecology of their host and may even help wildlife species colonize novel niches or cope with rapid environmental change. Urbanization is a globally replicated form of severe environmental change which we can leverage to better understand wildlife microbiomes. Does the colonization of separate cities result in parallel changes in the intestinal microbiome of wildlife, and if so, does within-city habitat heterogeneity matter? Using 16S rRNA gene amplicon sequencing, we quantified the effect of urbanization on the microbiome of eastern grey squirrels (Sciurus carolinensis). Eastern grey squirrels are ubiquitous in both rural and urban environments throughout their native range, across which they display an apparent coat colour polymorphism (agouti, black, intermediate).ResultsGrey squirrel microbiomes differed between rural and city environments; however, comparable variation was explained by habitat heterogeneity within cities. Our analyses suggest that operational taxonomic unit (OTU) community structure was more strongly influenced by local environmental conditions (rural and city forests versus human built habitats) than urbanization of the broader landscape (city versus rural). Many of the bacterial genera identified as characterizing the microbiomes of built-environment squirrels are though to specialize on host-derived products and have been linked in previous research to low fibre diets. However, despite an effect of urbanization at fine spatial scales, phylogenetic patterns in the microbiome were coat colour phenotype dependent. City and built environment agouti squirrels displayed greater phylogenetic beta-dispersion than those in rural or forest environments, and null modelling results indicated that the phylogenetic structure of urban agouti squirrels did not differ greatly from stochastic phylogenetic expectations.ConclusionsHabitat heterogeneity at fine spatial scales affects host-associated microbiomes, however, we found little evidence that this pattern was the result of similar selective pressures acting on the microbiome within environments. Further, this result, those of phylogeny-independent analyses, and patterns of beta-dispersion lead us to suggest that microbiota dispersal and ecological drift are integral to shaping the inter-environmental differences we observed. These patterns were partly mediated by squirrel coat colour phenotype, and therefore putatively, host physiology. Given a well-known urban cline in squirrel coat colour melanism, grey squirrels provide an ideal free-living system with which to study how host genetics mediate environment x microbiome interactions.