bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serological testing in addition to PCR screening for the re-opening of American colleges and universities: potential for cost-savings without compromising pandemic mitigation
Authors: Jo Youngji , Singh Ruby , Rao Gabriella , Galea Sandro , Nichols Brooke 
Published: October 2020

AbstractImportanceThe addition of a serological testing could reduce the overall testing costs of a PCR-based SARS-CoV-2 testing reopening plan for colleges/universities in the United States, without compromising the efficacy of the testing plan.ObjectivesTo determine whether a college/university reopening SARS-CoV-2 testing plan that includes serological testing can be cost-saving compared to a PCR-only testing.Design, Setting, and ParticipantsWe assessed costs of serological testing in addition to PCR testing under various scenarios of university sizes (2000, 10,000, and 40,000) and epidemic conditions (initial antibody prevalence 2.5-15%; cumulative SARS-CoV-2 incidence during the school year 5-30%) of SARS-CoV-2 in the United States. We estimated total testing costs and relative percentage of cost-savings of different screening (i.e. targeted/ universal) and testing (i.e. in-sourcing/out-sourcing) scenarios between September 2020-May 2021.Main Outcomes and MeasuresTesting costs of serological testing and PCR testing, Relative percentage of cost saving by including serology testing in addition to PCR testing.ResultsIncluding baseline serology testing alongside routine regular PCR testing can reduce total test volumes and related costs throughout the school year. While the total testing cost is likely much lower if regular PCR testing is insourced compared to outsourced ($5 million vs $34 million for university size 10,000), including serologic testing could achieve the up to 20% cost-savings relative to PCR testing alone. The insourcing of serological testing when PCR testing is insourced can achieve greater cost-savings under high initial antibody prevalence (>5%) and cumulative incidence throughout the school year (>10%) at medium and large sized universities. If PCR testing is outsourced, however, the inclusion of serological testing becomes always preferred in most university sizes and epidemic conditions.Conclusions and RelevanceWhile regular PCR testing alone is the preferred strategy for containing epidemics, including serology testing may help achieve cost-savings if outbreaks are anticipated, or if baseline seropositivity is high.Key Points (96/100)QuestionCan the addition of a serological testing reduce the overall testing costs of a PCR-based SARS-CoV-2 testing reopening plan for universities in the United States?FindingsThis costing study suggested that inclusion of serological testing in addition to outsourced PCR testing as part of a university re-opening strategy could achieve cost savings of up to 20%. The amount of savings, or additional costs, is dependent on insourcing or outsourcing of testing, epidemic conditions and university size.MeaningThe relative cost-savings depend strongly on whether PCR and/or serology are being insourced or outsourced, university sizes and cumulative incidence.
Reconstructing the diet, trophic level, and migration pattern of Mysticete whales based on baleen isotopic composition
Authors: Riekenberg Philip M. , Camalich Jaime , Svensson Elisabeth , IJsseldijk Lonneke L. , Brasseur Sophie M.J.M. , Witbaard Rob , Leopold Mardik F. , Rebolledo Elisa Bravo , Middelburg Jack J. , van der Meer Marcel T.J. , Damsté Jaap S. Sinninghe , Schouten Stefan 
Published: October 2020

AbstractBaleen from mysticete whales is a well-preserved proteinaceous material that can be used to identify migrations and feeding habits for species whose migration pathways are unknown. Analysis of δ13C and δ15N from bulk baleen has been used to infer migration patterns for individuals. However, this approach has fallen short of identifying migrations between regions as it is difficult to determine variations in isotopic shifts without temporal sampling of prey items. Here we apply analysis of δ15N values of amino acids to five baleen plates belonging to three species, revealing novel insights on trophic position, metabolic state, and migration between regions. Humpback and minke whales had higher reconstructed trophic levels than fin whales (3.4-3.5 versus 2.7-2.9, respectively) as expected due to different feeding specialization. Isotopic niche areas between baleen minima and maxima were well separated, indicating regional resource use for individuals during migration that aligned with isotopic gradients in Atlantic Ocean particulate organic matter. δ15N values from phenylalanine confirmed regional separation between the niche areas for two fin whales as migrations occurred and elevated glycine and threonine δ15N values revealed physiological changes due to fasting. Simultaneous resolution of trophic level and physiological changes allow for identification of regional migrations in mysticetes.
Force-dependent remodeling of cytoplasmic ZO-1 condensates contributes to robust cell-cell adhesion
Authors: Kinoshita Noriyuki , Yamamoto Takamasa S. , Yasue Naoko , Takagi Chiyo , Fujimori Toshihiko , Ueno Naoto 
Published: October 2020

SummaryAlthough the physiological importance of biomolecular condensates is widely recognized, how it is controlled in time and space during development is largely unknown. Here we show that a tight junction protein ZO-1 forms cytoplasmic condensates in the trophectoderm (TE) of the mouse embryo before E4.0. These disappear via dissolution, and ZO-1 accumulates at the cell junction as the blastocyst cavity grows and internal pressure on TE cells increases. In contrast, this dissolution was less evident in TE cells attached to the inner cell mass, as they receive weaker tensile forces. Furthermore, analyses using MDCK cells have demonstrated that the ZO-1 condensates are generated and maintained by liquid-liquid phase separation. Our study also highlights that the dynamics of these condensates depends on the physical environment via an interaction between ZO-1 and F-actin. We propose that the force-dependent regulation of ZO-1 condensation contributes to establishing robust cell-cell adhesion during early development.
Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals
Authors: Lutz Pierre-Eric , Almeida Daniel , Filliol Dominique , Jollant Fabrice , Kieffer Brigitte L. , Turecki Gustavo 
Published: October 2020

AbstractThe mu opioid receptor (MOR) is a G protein-coupled receptor that plays an essential role in reward and hedonic processes, and that has been implicated in disorders such as depression and addiction. Over the last decade, several brain imaging studies in depressed patients have consistently found that dysregulation of MOR function occurs in particular in the anterior insular cortex, an important brain site for the perception of internal states and emotional regulation. To investigate molecular mechanisms that may underlie these effects, here we assessed genetic polymorphisms, expression, and functional G-protein coupling of MOR in a large post-mortem cohort (N=95) composed of depressed individuals who died by suicide, and healthy controls. Results indicated that depression, but not comorbid substance use disorder or acute opiate consumption, was associated with increased MOR activity. This effect was partly explained by a specific increase in expression of the inhibitory alpha G-protein subunit GNAI2. Consistent with previous neuroimaging studies, our findings support the notion that enhanced endogenous opioidergic tone in the anterior insula may buffer negative affective states in depressed individuals, a mechanism that could potentially contribute to the antidepressant efficacy of emerging opioid-based medications.
Protlego: A Python package for the analysis and design of chimeric proteins
Authors: Ferruz Noelia , Noske Jakob , Höcker Birte 
Published: October 2020

AbstractMotivationGene duplication and recombination of protein fragments have led to the highly diverse protein space that we observe today. By mimicking this natural process, the design of protein chimeras via fragment recombination has proven experimentally successful and has opened a new era for the design of customizable proteins. Thein-silicobuilding of structural models for these chimeric proteins, however, remains a manual task that requires a considerable degree of expertise and is not amenable for high-throughput studies. Energetic and structural analysis of the designed proteins often require the use of several tools, each with their unique technical difficulties and available in different programming languages or web servers.ResultsWe have implemented a Python package that enables automated, high-throughput design of chimeras and their structural analysis. First, it is possible to fetch evolutionarily conserved fragments from a built-in database (also available at fuzzle.uni-bayreuth.de). These relationships can then be represented via networks or further selected for chimera construction via recombination. Designed chimeras or natural proteins are then scored and minimised with the Charmm and Amber forcefields and their diverse structural features can be analysed at ease. Here, we showcase Protlego’s pipeline by exploring the relationships between the P-loop and Rossmann superfolds and building and characterising their offspring chimeras. We believe that Protlego provides a powerful new tool for the protein design community.Availability and implementationProtlego is freely available at (https://hoecker-lab.github.io/protlego/) with tutorials and documentation.
High-throughput generation and phenotypic characterization of zebrafish CRISPR mutants of DNA repair genes
Authors: Shin Unbeom , Nakhro Khriezhanuo , Oh Chang-Kyu , Carrington Blake , Song Hayne , Varshney Gaurav , Kim Youngjae , Song Hyemin , Jeon Sangeun , Robbins Gabrielle , Kim Sangin , Yoon Suhyeon , Choi Yongjun , Park Suhyung , Kim Yoo Jung , Burgess Shawn , Kang Sukhyun , Sood Raman , Lee Yoonsung , Myung Kyungjae 
Published: October 2020

ABSTRACTA systematic knowledge of the roles of DNA repair genes at the level of the organism has been limited due to the lack of appropriate experimental techniques. Here, we generated zebrafish loss-of-function mutants for 32 DNA repair and replication genes through multiplexed CRISPR/Cas9-mediated mutagenesis. High-throughput phenotypic characterization of our mutant collection revealed that three genes (atad5a,ddb1, pcna) are essential for proper embryonic development and hematopoiesis; seven genes (apex1,atrip,ino80,mre11a,shfm1,telo2,wrn) are required for growth and development during juvenile stage and six genes (blm,brca2,fanci, rad51,rad54l,rtel1) play critical roles in sex development. Furthermore, mutation in six genes (atad5a,brca2,polk,rad51,shfm1,xrcc1) displayed hypersensitivity to DNA damage agents. Further characterization ofatad5a−/−mutants demonstrate that Atad5a is required for normal brain development and hematopoiesis. Our zebrafish mutant collection provides a unique resource for understanding of the roles of DNA repair genes at the organismal level.
Biogeographical and ecological factors associated with kill rates of an apex predator
Authors: Cristescu Bogdan , Elbroch L. Mark , Dellinger Justin A. , Binder Wesley , Wilmers Christopher C. , Wittmer Heiko U. 
Published: October 2020

AbstractKill rates and functional responses are fundamental to the study of predator ecology and the understanding of predatory-prey dynamics. As the most widely distributed apex predator in the western hemisphere pumas (Puma concolor) have been widely studied yet a biogeographical synthesis of their kill rates is currently lacking. We reviewed the literature and compiled data on sex- and age-specific kill rate estimates of pumas on ungulates, and conducted analyses aimed at understanding ecological factors explaining the observed variation across their range. Kill rate studies on pumas, while numerous, were primarily conducted in Temperate Conifer Forests (< 10% of puma range), revealing a dearth of knowledge across much of their range, especially from tropical and subtropical habitats. Across studies, kill rates in ungulates/week were highest for adult females with kitten(s) (1.24 ± 0.41 ungulates/week) but did not vary significantly between adult males (0.84 ± 0.18) and solitary adult females (0.99 ± 0.26). Kill rates in kg/day did not differ significantly among reproductive classes. Kill rates of adult pumas increased with ungulate density. Ungulate species richness had a weak negative association with adult male kill rates. Neither scavenger richness, the proportion of non-ungulate prey in the diet, nor regional human population density had a significant effect on ungulate kill rates. Our results had a strong temperate-ecosystem bias highlighting the need for further research across the diverse biomes pumas occupy in order to make species level inferences. Data from more populations would also allow for multivariate analyses providing deeper inference into the ecological and behavioural factors driving kill rates and functional responses of pumas, and apex predators in general.
Whole Genome Sequencing identifies novel structural variant in a large Indian family affected with X - linked agammaglobulinemia
Authors: Jain Abhinav , Govindaraj Geeta Madathil , Edavazhippurath Athulya , Faisal Nabeel , Bhoyar Rahul C , Gupta Vishu , Uppuluri Ramya , Manakkad Shiny Padinjare , Kashyap Atul , Kumar Anoop , Divakar Mohit Kumar , Imran Mohamed , Sawant Sneha , Dalvi Aparna , Chakyar Krishnan , Madkaikar Manisha , Raj Revathi , Sivasubbu Sridhar , Scaria Vinod 
Published: October 2020

AbstractBackgroundX - linked agammaglobulinemia (XLA, OMIM #300755) is a primary immunodeficiency disorder caused by pathogenic variations in theBTKgene, characterized by failure of development and maturation of B lymphocytes. The estimated prevalence worldwide is 1 in 190,000 male births. Recently, genome sequencing has been widely used in difficult to diagnose and familial cases. We report a large Indian family suffering from XLA with five affected individuals.MethodsWe performed complete blood count, immunoglobulin assay, and lymphocyte subset analysis for all patients and analyzed Btk expression for one patient and his mother. Whole exome sequencing (WES) for four patients, and whole genome sequencing (WGS) for two patients have been performed. Carrier screening was done for 17 family members using Multiplex Ligation-dependent Probe Amplification (MLPA) and haplotype ancestry mapping using fineSTRUCTURE was performed.ResultsAll patients had hypogammaglobulinemia and low CD19+ B cells. One patient who underwent Btk estimation had low expression and his mother showed a mosaic pattern. On structural variant analysis of WGS data, we found a novel large deletion of 5,296 bp at loci chrX:100,624,323-100,629,619 encompassing exons 3-5 of theBTKgene. Family screening revealed seven carriers for the deletion. Two patients had a successful HSCT. Haplotype mapping revealed mainly South Asian ancestry.ConclusionWhole genome sequencing led to identification of the accurate genetic mutation which could help in early diagnosis leading to improved outcomes, prevention of permanent organ damage and improved quality of life, as well as enabling prenatal diagnosis.
Development of a customised data management system for a COVID-19-adapted colorectal cancer pathway
Authors: Gunn Frances , Miller Janice , Dunlop Malcolm G , Din Farhat V N , Maeda Yasuko 
Published: October 2020

AbstractPurposeThe COVID-19 pandemic posed an unprecedented challenge to healthcare systems around the world. To mitigate the risks of those referred with possible colorectal cancer during the pandemic we implemented a clinical pathway which required a customised data management system for robust operation. Here, we describe the principal concepts and evaluation of the performance of a spreadsheet-based data management system.MethodsA system was developed using Microsoft Excel® 2007 aiming to retain the spreadsheets inherent intuitiveness of direct data entry. Data was itemised limiting entry errors. Visual Basic for Applications (VBA) was used to construct a user-friendly interface to enhance efficiency of data entry and segregate the data required for operational tasks. This was done with built-in loop-back data entry. Finally data derivation and analysis was performed to facilitate pathway monitoring.ResultsFor a pathway which required rapid implementation and development of a customised data management system, the use of a spreadsheet was advantageous due to its user-friendly direct data entry capability. Its function was enhanced by UserForm and large data handling by data segregation using VBA macros. Data validation and conditional formatting minimised data entry errors. Computation by the COUNT function facilitated live data monitoring on a dashboard. During the three months the pathway ran for, the system processed 36 nodal data points for each of the included 837 patients. Data monitoring confirmed its accuracy.ConclusionLarge volume data management using a spreadsheet system is possible with appropriate data definition and VBA programmed data segregation. Clinicians’ regular input and optimisation made the system adaptable for rapid implementation.
Comprehensive characterization of migration profiles of murine cerebral cortical neurons during development using FlashTag labeling
Authors: Yoshinaga Satoshi , Shin Minkyung , Kitazawa Ayako , Ishii Kazuhiro , Tanuma Masato , Kasai Atsushi , Hashimoto Hitoshi , Kubo Ken-ichiro , Nakajima Kazunori 
Published: October 2020

SummaryIn mammalian cerebral neocortex, different regions have different cytoarchitecture, neuronal birthdates and functions. In most regions, neuronal migratory profiles have been speculated similar to each other based on observations using thymidine analogues. Few reports investigated regional migratory differences from mitosis at the ventricular surface. Here, in mice, we applied FlashTag technology, in which dyes are injected intraventricularly, to describe migratory profiles. We revealed a mediolateral regional difference in migratory profiles of neurons that is dependent on the developmental stages, e.g., neurons labeled at E12.5-15.5 reached their destination earlier dorsomedially than dorsolaterally even where there were underlying ventricular surfaces, reflecting sojourning below the subplate. This difference was hardly recapitulated by thymidine analogues, which visualize neurogenic gradient, suggesting biological significance different from neurogenic gradient. These observations advance understanding of cortical development, portraying strength of FlashTag in studying migration, and are thus a resource for studies of normal and abnormal neurodevelopment.
A framework for comparing microbial networks reveals core associations
Authors: Röttjers Lisa , Vandeputte Doris , Raes Jeroen , Faust Karoline 
Published: October 2020

AbstractMicrobial network construction and analysis is an important tool in microbial ecology. As microbial interactions are challenging to infer experimentally, such networks are often constructed from statistically inferred associations and may not represent ecological interactions. Hence, microbial association networks contain a large number of errors and their derived properties do not necessarily reflect true community structure. Such errors can be identified with the use of appropriate null models. We have developed anuran, a toolbox for investigation of noisy networks with null models, for identification of non-random patterns in groups of association networks. This toolbox compares multiple networks to identify conserved subsets (core association networks, CANs) and other network properties that are shared across all networks. Such groups of networks can be generated from a collection of time series data or from cross-sectional sample sets. We use data from the Global Sponge Project to demonstrate that different orders of sponges have a larger CAN than expected at random.
Multiplexing Mutation Rate Assessment: Determining Pathogenicity of Msh2 Variants inS. cerevisiae
Authors: Ollodart Anja R. , Yeh Chiann-Ling C. , Miller Aaron W. , Shirts Brian H. , Gordon Adam S. , Dunham Maitreya J. 
Published: October 2020

AbstractDespite the fundamental importance of mutation rate as a driving force in evolution and disease risk, common methods to assay mutation rate are time consuming and tedious. Established methods such as fluctuation tests and mutation accumulation experiments are low-throughput and often require significant optimization to ensure accuracy. We established a new method to determine the mutation rate of many strains simultaneously by tracking mutation events in a chemostat continuous culture device and applying deep sequencing to link mutations to alleles of a DNA-repair gene. We applied this method to assay the mutation rate of hundreds ofSaccharomyces cerevisiaestrains carrying mutations in the gene encoding Msh2, a DNA repair enzyme in the mismatch repair pathway (MMR). Loss-of-function (LOF) mutations inMSH2are associated with hereditary non-polyposis colorectal cancer (HNPCC), an inherited disorder that increases risk for many different cancers. However, the vast majority ofMSH2variants found in human populations have insufficient evidence to be classified as either pathogenic or benign. We first benchmarked our method against Luria-Delbrück fluctuation tests using a collection of publishedMSH2variants. Our pooled screen successfully identified previously-characterized non-functional alleles as high mutators. We then created an additional 185 human variants in the yeast ortholog, including both characterized and uncharacterized alleles curated from ClinVar and other clinical testing data. In a set of alleles of known pathogenicity, our assay recapitulated ClinVar’s classification; we then estimated pathogenicity for 157 variants classified as uncertain or conflicting reports of significance. This method is capable of studying the mutation rate of many microbial species and can be applied to problems ranging from the generation of high-fidelity polymerases to measuring the rate of antibiotic resistance emergence.
Trans-generational inheritance of centromere identity requires the CENP-A N-terminal tail in theC. elegansmaternal germ line
Authors: Prosée Reinier F. , Wenda Joanna M. , Gabus Caroline , Delaney Kamila , Schwager Francoise , Gotta Monica , Steiner Florian A. 
Published: October 2020

AbstractCentromere protein A (CENP-A) is a histone H3 variant that defines centromeric chromatin and is essential for centromere function. In most eukaryotes CENP-A-containing chromatin is epigenetically maintained, and centromere identity is inherited from one cell cycle to the next. In the germ line of the holocentric nematodeCaenorhabditis elegans, this inheritance cycle is disrupted. CENP-A is removed at the mitosis-to-meiosis transition and is establishedde novoon chromatin during diplotene of meiosis I. Here we show that the N-terminal tail of CENP-A is required for thede novoestablishment of centromeres, but dispensable for centromere maintenance during embryogenesis. Worms homozygous for a CENP-A tail deletion maintain a functional centromere during development, but give rise to inviable offspring because they fail to re-establish centromeres in the maternal germ line. We identify the N-terminal tail of CENP-A as a critical domain for the interaction with the conserved kinetochore protein KNL-2, and argue that this interaction plays an important role in setting centromere identity in the germ line. We conclude that centromere establishment and maintenance are functionally distinct inC. elegans.