bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for IgG antibody detection in severe and mild COVID-19 cases using a Luminex bead-based assay
Authors: Mariën Joachim , Michiels Johan , Heyndrickx Leo , Kerkhof Karen , Foque Nikki , Widdowson Marc-Alain , Desombere Isabelle , Jansens Hilde , Van Esbroeck Marjan , Ariën Kevin K. 
Published: July 2020

AbstractLarge-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS- CoV-2) will only be possible if serological tests are sufficiently reliable, rapid and inexpensive. Current assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or expensive with suboptimal specificity (e.g. commercial ELISAs). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies of other pathogens. Here, we compare the performance of four antigens for the detection of SARS-CoV-2 specific IgG antibodies in a panel of sera that includes both severe (n=40) and mild (n=52) cases, using a neutralization and a Luminex bead-based assay. While we show that neutralising antibody levels are significantly lower in mild than in severe cases, we demonstrate that a combination of recombinant nucleocapsid protein (NP), receptor- binding domain (RBD) and the whole spike protein (S1S2) results in a highly sensitive (96%) and specific (99%) bead-based assay that can detect IgG antibodies in both groups. Although S1-specific IgG levels correlate most strongly with neutralizing antibody levels, they fall below the detection threshold in 10% of the cases in our Luminex assay. In conclusion, our data supports the use of RBD, NP and S1S2 for the development of SARS-CoV-2 serological bead- based assays. Finally, we argue that low antibody levels in mild/asymptomatic cases might complicate the epidemiological assessment of large-scale surveillance studies.
Assessing the quality of nontraditional N95 filtering face-piece respirators available during the COVID-19 pandemic
Authors: Plana Deborah , Tian Enze , Cramer Avilash K. , Yang Helen , Carmack Mary M. , Sinha Michael S. , Bourgeois Florence T. , Yu Sherry H. , Masse Peter , Boyer Jon , Kim Minjune , Mo Jinhan , LeBoeuf Nicole R. , Li Ju , Sorger Peter K. 
Published: July 2020

ABSTRACTBackgroundDuring the current COVID-19 pandemic, supply chains for Personal Protective Equipment (PPE) have been severely disrupted and many products, particularly surgical N95 filtering facepiece respirators (FFRs; “masks”) are in short supply. As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union.MethodsWe conducted a survey of mask in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer. We then assembled a simple apparatus for performing a necessary (but not sufficient) test of filtration performance and tested masks from the inventory; an accompanying website shows how to build and use the testing apparatus.ResultsOur survey showed that, seven months after the start of the COVID-19 pandemic, over 100 different makes and models of N95-type masks are in the inventory of local hospitals as opposed to 2-5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many did not perform to accepted standards and are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers in the FDA EUA and confusing or inconsistent labeling of KN95 masks, it is difficult to distinguish legitimate and counterfeit products.ConclusionsMany of the FFR masks available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations for end users to assist in acquiring legitimate products. In particular, institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for U.S and Chinese regulatory agencies with regard to labeling and public disclosure aimed at increase pandemic resilience.
Enabling out-of-clinic human immunity studies via single-cell profiling of capillary blood
Authors: Dobreva Tatyana , Brown David , Park Jong Hwee , Thomson Matt 
Published: July 2020

AbstractAn individual’s immune system is driven by both genetic and environmental factors that vary over time. To better understand the temporal and inter-individual variability of gene expression within distinct immune cell types, we developed a platform that leverages multiplexed single-cell sequencing and out-of-clinic capillary blood extraction to enable simplified, cost-effective profiling of the human immune system across people and time at single-cell resolution. Using the platform, we detect widespread differences in cell type-specific gene expression between subjects that are stable over multiple days.SummaryIncreasing evidence implicates the immune system in an overwhelming number of diseases, and distinct cell types play specific roles in their pathogenesis.1,2Studies of peripheral blood have uncovered a wealth of associations between gene expression, environmental factors, disease risk, and therapeutic efficacy.4For example, in rheumatoid arthritis, multiple mechanistic paths have been found that lead to disease, and gene expression of specific immune cell types can be used as a predictor of therapeutic non-response.12Furthermore, vaccines, drugs, and chemotherapy have been shown to yield different efficacy based on time of administration, and such findings have been linked to the time-dependence of gene expression in downstream pathways.21,22,23However, human immune studies of gene expression between individuals and across time remain limited to a few cell types or time points per subject, constraining our understanding of how networks of heterogeneous cells making up each individual’s immune system respond to adverse events and change over time.
Exploring Efficient Linear Mixed Models to Detect Quantitative Trait Locus-by-Environment Interactions
Authors: Yamamoto Eiji , Matsunaga Hiroshi 
Published: July 2020

ABSTRACTGenotype-by-environment interactions (G×E) are important for understanding genotype–phenotype relationships. To date, various statistical models have been proposed to account for G×E effects, especially in genomic selection (GS) studies. Generally, GS does not focus on the detection of each quantitative trait locus (QTL), while the genome-wide association study (GWAS) was designed for QTL detection. G×E modeling methods in GS can be included as covariates in GWAS using unified linear mixed models (LMMs). However, the efficacy of G×E modeling methods in GS studies has not been evaluated for GWAS. In this study, we performed a comprehensive comparison of LMMs that integrate the G×E modeling methods to detect both QTL and QTL-by-environment interaction (Q×E) effects. Model efficacy was evaluated using simulation experiments. For the fixed effect terms representing Q×E effects, simultaneous scoring of specific and non-specific environmental effects was recommended because of the higher recall and improved genomic inflation factor value. For random effects, it was necessary to account for both G×E and genotype-by-trial (G×T) effects to control genomic inflation factor value. Thus, the recommended LMM includes fixed QTL effect terms that simultaneously score specific and non-specific environmental effects and random effects accounting for both G×E and G×T. The LMM was applied to real tomato phenotype data obtained from two different cropping seasons. We detected not only QTLs with persistent effects across the cropping seasons but also QTLs with Q×E effects. The optimal LMM identified in this study successfully detected more QTLs with Q×E effects.
Spatially guided distractor suppression during visual search
Authors: Feldmann-Wüstefeld Tobias , Weinberger Marina , Awh Edward 
Published: July 2020

AbstractPast work has demonstrated that active suppression of salient distractors is a critical part of visual selection. Evidence for goal-driven suppression includes below-baseline visual encoding at the position of salient distractors (Gaspelin and Luck, 2015) and neural signals such as the Pd that track the position and number of distractors in the visual field (Feldmann-Wustefeld and Vogel, 2019). One basic question regarding distractor suppression is whether it is inherently spatial or nonspatial in character. Indeed, past work has shown that distractors evoke both spatial (Theeuwes, 1992) and nonspatial forms of interference (Folk and Remington, 1998), motivating a direct examination of whether space is integral to goal-driven distractor suppression. Here, we provide clear evidence for a spatial gradient of suppression surrounding salient singleton distractors. Replicating past work, both reaction time and neural indices of target selection improved monotonically as the distance between target and distractor increased. Importantly, these target selection effects were paralleled by a monotonic decline in the amplitude of the Pd, an electrophysiological index of distractor suppression. Moreover, multivariate analyses revealed spatially selective activity in the theta band that tracked the position of the target and – critically – revealed suppressed activity at spatial channels centered on distractor positions. Thus, goal-driven selection of relevant over irrelevant information benefits from a spatial gradient of suppression surrounding salient distractors.
Neuroanatomical underpinning of diffusion kurtosis measurements in the cerebral cortex of healthy macaque brains
Authors: Zhu Tianjia , Peng Qinmu , Ouyang Austin , Huang Hao 
Published: July 2020

AbstractPurposeTo investigate the neuroanatomical underpinning of healthy macaque brain cortical microstructure measured by diffusion kurtosis imaging (DKI) which characterizes non-Gaussian water diffusion.MethodsHigh-resolution DKI was acquired from 6 postmortem macaque brains. Neurofilament density (ND) was quantified based on structure tensor from neurofilament histological images of a different macaque brain sample. After alignment of DKI-derived mean kurtosis (MK) maps to the histological images, MK and histology-based ND were measured at corresponding regions of interests characterized by distinguished cortical MK values in the prefrontal/precentral-postcentral and temporal cortices. Pearson correlation was performed to test significant correlation between these cortical MK and ND measurements.ResultsHeterogeneity of cortical MK across different cortical regions was revealed, with significantly and consistently higher MK measurements in the prefrontal/precentral-postcentral cortex compared to those in the temporal cortex across all 6 scanned macaque brains. Corresponding higher ND measurements in the prefrontal/precentral-postcentral cortex than in the temporal cortex were also found. The heterogeneity of cortical MK is associated with heterogeneity of histology-based ND measurements, with significant correlation between cortical MK and corresponding ND measurements (P <0.005).ConclusionThese findings suggested that DKI-derived MK can potentially be an effective noninvasive biomarker quantifying underlying neuroanatomical complexity inside the cerebral cortical mantle for clinical and neuroscientific research.
AggreCount: An unbiased image analysis tool for identifying and quantifying cellular aggregates in a spatial manner
Authors: Klickstein Jacob Aaron , Mukkavalli Sirisha , Raman Malavika 
Published: July 2020

AbstractProtein quality control is maintained by a number of integrated cellular pathways that monitor the folding and functionality of the cellular proteome. Defects in these pathways lead to the accumulation of misfolded or faulty proteins that may become insoluble and aggregate over time. Protein aggregates significantly contribute to the development of a number of human diseases such as Amyotrophic lateral sclerosis, Huntington’s and Alzheimer’s Disease.In vitro, imaging-based, cellular studies have defined key components that recognize and clear aggregates; however, no unifying method is available to quantify cellular aggregates. Here we describe an ImageJ macro called AggreCount to identify and measure protein aggregates in cells. AggreCount is designed to be intuitive, easy to use and customizable for different types of aggregates observed in cells. Minimal experience in coding is required to utilize the script. Based on a user defined image, AggreCount will report a number of metrics: (i) total number of cellular aggregates, (ii) percent cells with aggregates, (iii) aggregates per cell, (iv) area of aggregates and (v) localization of aggregates (cytosol, perinuclear or nuclear). A data table of aggregate information on a per cell basis as well as a summary table is provided for further data analysis. We demonstrate the versatility of AggreCount by analyzing a number of different cellular aggregates including aggresomes, stress granules and inclusion bodies caused by Huntingtin polyQ expansion.
Arabidopsis thalianainteraction withEnsifer melilotican support plant growth under N-deficiency
Authors: Armijo Grace , Kraiser Tatiana , Medina María P. , Gras Diana E. , Zúñiga Ana , González Bernardo , Gutiérrez Rodrigo A. 
Published: July 2020

ABSTRACTNitrogen (N) is an essential macronutrient for plants. Some plant species obtain this nutrient by interacting with N-fixing bacteria. These beneficial interactions are well described in legumes but have also been observed in non-legume plant species that are unable to form root nodules. We studied the expanding role of beneficial plant-bacteria interactions for N-nutrition in the widely used model plantArabidopsis thaliana. We found that the bacteriaEnsifer melilotienhancedA. thalianagrowth under severe N-deficiency conditions, allowing plants to complete their life cycle. Our results showed that bacteria colonize the rhizosphere associated with the epidermis of the plant root. We also demonstrated thatA. thalianapossesses genes that are critical for this beneficial interaction and are required for plant-growth promotion byE. melilotiunder N-deficiency.This work shows association betweenA. thalianaandE. melilotifor plant nutrition under severe N-deficiency, and suggests that plants have conserved-molecular mechanisms to interact with N-fixing bacteria to procure N and escape adverse conditions. Under these circumstances, the supply of N via N-fixation is critical for survival, allowing the plant to complete its life cycle. Our findings provide a new framework and an experimental model system that expand our understanding of plant-rhizobia interactions for plant N-nutrition.
A 3-D Constitutive Model for Finite Element Analyses of Agarose with a Range of Gel Concentrations
Authors: Wang Xiaogang , June Ronald K. , Pierce David M. 
Published: July 2020

AbstractHydrogels have seen widespread application across biomedical sciences and there is considerable interest in using hydrogels, including agarose, for creatingin vitrothree-dimensional environments to grow cells and study mechanobiology and mechanotransduction. Recent advances in the preparation of agarose gels enable successful encapsulation of viable cells at gel concentrations as high as 5%. Agarose with a range of gel concentrations can thus serve as an experimental model mimicking changes in the 3-D microenvironment of cells during disease progression and can facilitate experiments aimed at probing the corresponding mechanobiology, e.g. the evolving mechanobiology of chondrocytes during the progression of osteoarthritis. Importantly, whether stresses (forces) or strains (displacement) drive mechanobiology and mechanotransduction is currently unknown. We can use experiments to quantify mechanical properties of hydrogels, and imaging to estimate microstructure and even strains; however, only computational models can estimate intra-gel stresses in cell-seeded agarose constructs because the requiredin vitroexperiments are currently impossible. Finite element modeling is well-established for (computational) mechanical analyses, but accurate constitutive models for modeling the 3-D mechanical environments of cells within high-stiffness agarose are currently unavailable. In this study we aimed to establish a 3-D constitutive model of high-stiffness agarose with a range of gel concentrations. We applied a multi-step, physics-based optimization approach to separately fit subsets of model parameters and help achieve robust convergence. Our constitutive model, fitted to experimental data on progressive stress-relaxations, was able to predict reaction forces determined from independent experiments on cyclical loading. Our model has broad applications in finite element modeling aimed at interpreting mechanical experiments on agarose specimens seeded with cells, particularly in predicting distributions of intra-gel stresses. Our model and fitted parameters enable more accurate finite element simulations of high-stiffness agarose constructs, and thus better understanding of experiments aimed at mechanobiology, mechanotransduction, or other applications in tissue engineering.
Full genome characterization of Laem Singh virus (LSNV) in shrimpPenaeus monodon
Authors: Taengchaiyaphum Suparat , Srisala Jiraporn , Sanguanrut Piyachat , Ongvarrasopone Chalermporn , Flegel Timothy W. , Sritunyalucksana Kallaya 
Published: July 2020

ABSTRACTLaem Singh virus (LSNV) was discovered in 2006 and proposed as a necessary but insufficient cause of retarded growth in the giant tiger shrimpPenaeus monodon.Its closest relatives were plant viruses including an unassignedSobemovirusand viruses in the familyLuteoviridae. During succeeding years, attempts to obtain the full LSNV genome sequence by genome walking failed. However, recent publication of the full sequence of Wenzhou shrimp virus 9 (WZSV 9) at GenBank revealed that LSNV sequences in our database shared 99% sequence identity with it. Thus, we hypothesized that LSNV and WZSV 9 were different isolates of the same virus species. Here we confirm that hypothesis by cloning and sequencing of the full genome of LSNV fromP. monodonand by showing that it consists of two fragments each with 99% identity to the matching fragments of WZSV.
Differential activation of JAK-STAT signaling in blood cell progenitors reveals functional compartmentalization of theDrosophilalymph gland
Authors: Rodrigues Diana , Renaud Yoan , VijayRaghavan K. , Waltzer Lucas , Inamdar Maneesha S. 
Published: July 2020

AbstractBlood cells arise from diverse pools of stem and progenitor cells. Understanding progenitor heterogeneity is a major challenge. TheDrosophilalarval lymph gland is a well-studied model to understand blood progenitor maintenance and recapitulates several aspects of vertebrate hematopoiesis. However in-depth analysis has focused on progenitors located in lymph gland anterior lobes (AP), ignoring the progenitors from the posterior lobes (PP). Usingin situexpression mapping and transcriptome analysis we reveal PP heterogeneity and identify molecular-genetic tools to study this abundant progenitor population. Functional analysis shows that PP resist differentiation upon immune challenge, in a JAK-STAT-dependent manner. Upon wasp parasitism, AP downregulate JAK-STAT signaling and form lamellocytes. In contrast, we show that PP activate STAT92E and remain undifferentiated.Stat92Eknockdown in PP or genetically reducing JAK-STAT signaling permits PP lamellocyte differentiation. We discuss how heterogeneity and compartmentalization allow functional segregation in response to systemic cues and could be widely applicable.HighlightsWe provide anin situand transcriptome map of larval blood progenitors Posterior lymph gland progenitors are refractory to immune challenge STAT activation after wasp parasitism maintains posterior progenitors
The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State
Authors: Mansbach Rachael A. , Chakraborty Srirupa , Nguyen Kien , Montefiori David C. , Korber Bette , Gnanakaran S. 
Published: July 2020

SummaryThe COVID-19 pandemic underwent a rapid transition with the emergence of a SARS-CoV-2 variant that carried the amino acid substitution D614G in the Spike protein that became globally prevalent. The G-form is both more infectiousin vitroand associated with increased viral loads in infected people. To gain insight into the mechanism underlying these distinctive characteristics, we employed multiple replicas of microsecond all-atom simulations to probe the molecular-level impact of this substitution on Spike’s closed and open states. The open state enables Spike interactions with its human cellular receptor, ACE2. Here we show that changes in the inter-protomer energetics due to the D614G substitution favor a higher population of infection-capable (open) states. The inter-protomer interactions between S1 and S2 subunits in the open state of the D-form are asymmetric. This asymmetry is resolved in the G-form due to the release of tensile hydrogen bonds resulting in an increased population of open conformations. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive due to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies.
Regulated distribution of mitochondria in touch receptor neurons ofC. elegansinfluences touch response
Authors: Awasthi Anjali , Modi Souvik , Hegde Sneha , Chatterjee Anusheela , Mondal Sudip , Romero Eva , Sure Guruprasad R. , Koushika Sandhya P. 
Published: July 2020

AbstractDensity of mitochondria and their localization at specific sub-cellular regions of the neurons is regulated by molecular motors, their adaptors and the cytoskeleton. However, the regulation of the mitochondrial density, the positioning of mitochondria along the neuronal process and the role of axonal mitochondria in neuronal function remain poorly understood. This study shows that the density of mitochondria inC. eleganstouch receptor neuron processes remains constant through development. Simulations show that mitochondrial positioning along parts of the neuronal process that are devoid of synapses is regulated. Additionally, we also demonstrate that axonal mitochondria are necessary for maintaining touch responsiveness.