bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity
Authors: Padoan Andrea , Bonfante Francesco , Pagliari Matteo , Bortolami Alessio , Negrini Davide , Zuin Silvia , Bozzato Dania , Cosma Chiara , Sciacovelli Laura , Plebani Mario 
Published: August 2020

AbstractBackgroundReliable high-throughput serological assays for SARS-CoV-2 antibodies (Abs) are urgently needed for the effective containment of the COVID-19 pandemic, as it is of crucial importance to understand the strength and duration of immunity after infection, and to make informed decisions concerning the activation or discontinuation of physical distancing restrictions.MethodsIn 184 serum samples from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT).FindingsPrecision results ranged from 0.9% to 11.8% for all assays. Elecsys anti-SARS-CoV-2 demonstrated linearity of results at concentrations within the cut-off value. Overall, sensitivity ranged from 78.5 to 87.8%, and specificity, from 97.6 to 100%. On limiting the analysis to samples collected 12 days after onset of symptoms, the sensitivity of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. The strongest PRNT50 correlation with antibody levels was obtained with ENZY-Well SARS-CoV-2 IgG (rho = 0.541, p < 0.001).InterpretationThe results confirmed that all immunoassays had an excellent specificity, whereas sensitivity varied across immunoassays, depending strongly on the time interval between symptoms onset and sample collection. Further studies should be conducted to achieve a stronger correlation between antibody measurement and PRNT50 in order to obtain useful information for providing effective passive antibody therapy, and developing a vaccine against the SARS-CoV-2 virus.
Monitoring migratory birds in stopover habitat: assessing the value of extended duration audio recording
Authors: Roark Ellie , Gaul Willson 
Published: August 2020

ABSTRACTBecause birds are frequently detected by sound, autonomous audio recorders (called automated recording units or ARUs) are now an established tool in addition to in-person observations for monitoring the status and trends of bird populations. ARUs have been evaluated and applied during breeding seasons, and to monitor the nocturnal flight calls of migrating birds. However, birds behave differently during migration stopover than during the breeding season. Here we present a method for using ARUs to monitor land birds in migration stopover habitat.We conducted in-person point counts next to continuously recording ARUs, and compared estimates of the number of species detected and focal species relative abundance from point counts and ARUs. We used a desk-based audio bird survey method for processing audio recordings, which does not require automated species identification algorithms. We tested two methods of using extended duration ARU recording: surveying consecutive minutes, and surveying randomly selected minutes.Desk-based surveys using randomly selected minutes from extended duration ARU recordings performed similarly to point counts, and better than desk-based surveys using consecutive minutes from ARU recordings. Surveying randomly selected minutes from ARUs provided estimates of relative abundance that were strongly correlated with estimates from point counts, and successfully showed the increase in abundance associated with migration timing. Randomly selected minutes also provided estimates of the number of species present that were comparable to estimates from point counts.ARUs are an effective way to track migration timing and intensity in remote or seasonally inaccessible migration stopover habitats. We recommend that desk-based surveys use randomly sampled minutes from extended duration ARU recordings, rather than using consecutive minutes from recordings. Our methods can be immediately applied by researchers with the skills to conduct point counts, with no additional expertise necessary in automated species identification algorithms.
Evaluating the Immunological cross-reactivity of Indian polyvalent antivenoms towards the venom ofHypnale hypnale(hump-nosed pit viper) from the Western Ghats
Authors: Vanuopadath Muralidharan , Raveendran Dileepkumar , Gopalakrishnan Nair Bipin , Sadasivan Nair Sudarslal 
Published: August 2020

AbstractHypnale hypnale(hump-nosed pit viper) is a venomous pit viper species found in the Western Ghats of India and Sri Lanka. Due to the severe life-threatening envenomation effects induced by its venom components,Hypnale hypnalehas been classified under ‘category 1’ of medically important snake species by the World Health Organization. Since there are no specific antivenoms available to combat its envenomation in India, the only option available is to administer Indian polyvalent antivenoms. However, the cross-neutralization potential of the commercially available polyvalent antivenoms on IndianHypnale hypnalevenom has not been explored so far. In the current study, in vitro immunological cross-reactivity ofHypnale hypnalevenom towards various Indian polyvalent antivenoms were assessed using end point titration ELISA and Western blotting. A three to four-fold increase in EC50values were obtained forHypnale hypnalevenom towards all the antivenoms tested. Observation of minimal binding specificities towards low and high molecular mass venom proteins are suggestive of the fact that commercially available polyvalent antivenoms failed to detect and bind to the antigenic epitopes of considerable number of proteins present inHypnale hypnalevenom. This highlights the importance of includingHypnale hypnalevenom in the immunization mixture while raising antivenoms.
Predictive visual motion extrapolation emerges spontaneously and without supervision at each layer of a hierarchical neural network with spike-timing-dependent plasticity
Authors: Burkitt Anthony N. , Hogendoorn Hinze 
Published: August 2020

AbstractThe fact that the transmission and processing of visual information in the brain takes time presents a problem for the accurate real-time localisation of a moving object. One way this problem might be solved is extrapolation: using an object’s past trajectory to predict its location in the present moment. Here, we investigate how a simulatedin silicolayered neural network might implement such extrapolation mechanisms, and how the necessary neural circuits might develop. We allowed an unsupervised hierarchical network of velocity-tuned neurons to learn its connectivity through spike-timing dependent plasticity. We show that the temporal contingencies between the different neural populations that are activated by an object as it moves causes the receptive fields of higher-level neurons to shift in the direction opposite to their preferred direction of motion. The result is that neural populations spontaneously start to represent moving objects as being further along their trajectory than where they were physically detected. Due to the inherent delays of neural transmission, this effectively compensates for (part of) those delays by bringing the represented position of a moving object closer to its instantaneous position in the world. Finally, we show that this model accurately predicts the pattern of perceptual mislocalisation that arises when human observers are required to localise a moving object relative to a flashed static object (the flash-lag effect).Significance StatementOur ability to track and respond to rapidly changing visual stimuli, such as a fast moving tennis ball, indicates that the brain is capable of extrapolating the trajectory of a moving object in order to predict its current position, despite the delays that result from neural transmission. Here we show how the neural circuits underlying this ability can be learned through spike-timing dependent synaptic plasticity, and that these circuits emerge spontaneously and without supervision. This demonstrates how the neural transmission delays can, in part, be compensated to implement the extrapolation mechanisms required to predict where a moving object is at the present moment.
Schizophrenia-associated differential DNA methylation in the superior temporal gyrus is distributed to many sites across the genome and annotated by the risk gene MAD1L1
Authors: McKinney Brandon C. , Hensler Christopher M. , Wei Yue , Lewis David A. , Wang Jiebiao , Ding Ying , Sweet Robert A. 
Published: August 2020

ABSTRACTBackgroundMany genetic variants and multiple environmental factors increase risk for schizophrenia (SZ). SZ-associated genetic variants and environmental risk factors have been associated with altered DNA methylation (DNAm), the addition of a methyl group to a cytosine in DNA. DNAm changes, acting through effects on gene expression, represent one potential mechanism by which genetic and environmental factors confer risk for SZ and alter neurobiology.MethodsWe investigated the hypothesis that DNAm in superior temporal gyrus (STG) is altered in SZ. We measured genome-wide DNAm in postmortem STG from 44 SZ subjects and 44 non-psychiatric comparison (NPC) subjects using Illumina Infinium MethylationEPIC BeadChip microarrays. We applied tensor composition analysis to extract cell type-specific DNAm signals.ResultsWe found that DNAm levels differed between SZ and NPC subjects at 242 sites, and 44 regions comprised of two or more sites, with a false discovery rate cutoff of q=0.1. We determined differential methylation at nine of the individual sites were driven by neuron-specific DNAm alterations. Glia-specific DNAm alterations drove the differences at two sites. Notably, we identied SZ-associated differential methylation within within mitotic arrest deficient 1-like 1 (MAD1L1), a gene strongly associated with SZ through genome-wide association studies.ConclusionsThis study adds to a growing number of studies that implicate DNAm, and epigenetic pathways more generally, in SZ. Our findings suggest differential methylation may contribute to STG dysfunction in SZ. Future studies to identify the mechanisms by which altered DNAm, especially within MAD1L1, contributes to SZ neurobiology are warranted.
Neutralizing antibody against SARS-CoV-2 spike in COVID-19 patients, health care workers and convalescent plasma donors: a cohort study using a rapid and sensitive high-throughput neutralization assay
Authors: Zeng Cong , Evans John P. , Pearson Rebecca , Qu Panke , Zheng Yi-Min , Robinson Richard T. , Hall-Stoodley Luanne , Yount Jacob , Pannu Sonal , Mallampalli Rama K. , Saif Linda , Oltz Eugene , Lozanski Gerard , Liu Shan-Lu 
Published: August 2020

ABSTRACTRapid and specific antibody testing is crucial for improved understanding, control, and treatment of COVID-19 pathogenesis. Herein, we describe and apply a rapid, sensitive, and accurate virus neutralization assay for SARS-CoV-2 antibodies. The new assay is based on an HIV-1 lentiviral vector that contains a secreted intron Gaussia luciferase or secreted Nano-luciferase reporter cassette, pseudotyped with the SARS-CoV-2 spike (S) glycoprotein, and is validated with a plaque reduction assay using an authentic, infectious SARS-CoV-2 strain. The new assay was used to evaluate SARS-CoV-2 antibodies in serum from individuals with a broad range of COVID-19 symptoms, including intensive care unit (ICU) patients, health care workers (HCWs), and convalescent plasma donors. The highest neutralizing antibody titers were observed among ICU patients, followed by general hospitalized patients, HCWs and convalescent plasma donors. Our study highlights a wide phenotypic variation in human antibody responses against SARS-CoV-2, and demonstrates the efficacy of a novel lentivirus pseudotype assay for high-throughput serological surveys of neutralizing antibody titers in large cohorts.
Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells
Authors: Zhou Lanlan , Huntington Kelsey , Zhang Shengliang , Carlsen Lindsey , So Eui-Young , Parker Cassandra , Sahin Ilyas , Safran Howard , Kamle Suchitra , Lee Chang-Min , Lee Chun Geun , Elias Jack A. , Campbell Kerry S. , Naik Mandar T. , Atwood Walter J. , Youssef Emile , Pachter Jonathan A. , Navaraj Arunasalam , Seyhan Attila A. , Liang Olin , El-Deiry Wafik S. 
Published: August 2020

AbstractCOVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. In serum-deprived and stimulated cells treated with remdesivir and MEKi we observed correlations between pRB, pERK, and ACE2 expression further supporting role of proliferative state and MAPK pathway in ACE2 regulation. We show elevated cytokines in COVID-19-(+) patient plasma (N=9) versus control (N=11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1α, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed MEKi stimulation of NK-cell killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope infected human bronchial epithelial cells, small airway epithelial cells, or lung cancer cells and MEKi suppressed infectivity of the pseudovirus. We show a drug class-effect with MEKi to stimulate NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection to allow immune responses and antiviral agents to control disease progression.
Permutation tests for hypothesis testing with animal social network data: problems and potential solutions
Authors: Farine Damien R. , Carter Gerald G. 
Published: August 2020

ABSTRACTPermutation tests are widely used to test null hypotheses with animal social network data, but suffer from high rates of type I and II error when the permutations do not properly simulate the intended null hypothesis.Two common types of permutations each have limitations. Pre-network (or datastream) permutations can be used to control “nuisance effects” like spatial, temporal, or sampling biases, but only when the null hypothesis assumes random social structure. Node (or node-label) permutation tests can test null hypotheses that include nonrandom social structure, but only when nuisance effects do not shape the observed network.We demonstrate one possible solution addressing these limitations: using pre-network permutations to adjust the values for each node or edge before conducting a node permutation test. We conduct a range of simulations to estimate error rates caused by confounding effects of social or non-social structure in the raw data.Regressions on simulated datasets suggest that this “double permutation” approach is less likely to produce elevated error rates relative to using only node permutations, pre-network permutations, or node permutations with simple covariates, which all exhibit elevated type I errors under at least one set of simulated conditions. For example, in scenarios where type I error rates from pre-network permutation tests exceed 30%, the error rates from double permutation remain at 5%.The double permutation procedure provides one potential solution to issues arising from elevated type I and type II error rates when testing null hypotheses with social network data. We also discuss alternative approaches that can provide robust inference, including fitting mixed effects models, restricted node permutations, testing multiple null hypotheses, and splitting large datasets to generate replicated networks. Finally, we highlight ways that uncertainty can be explicitly considered and carried through the analysis.
Src activates retrograde membrane traffic through phosphorylation of GBF1
Authors: Chia Joanne , Wang Shyi-Chyi , Wee Sheena , Gill David James , Tay Felicia , Kannan Srinivasaraghavan , Verma Chandra S , Gunaratne Jayantha , Bard Frederic A. 
Published: August 2020

AbstractThe Src tyrosine kinase controls cancer-critical protein glycosylation through Golgi to ER relocation of GALNTs enzymes. How Src induces this trafficking event is unknown. Golgi to ER transport depends on the GTP Exchange factor (GEF) GBF1 and small GTPase Arf1. Here we show that Src induces the formation of tubular transport carriers containing GALNTs through promotion of a GBF1-Arf1 complex. The complex is initiated by phosphorylation on GBF1 on 10 tyrosine residues; two of them, Y876 and Y898 are located near the C-terminus of the Sec7 GEF domain. Their phosphorylation promotes partial melting of the Sec7 domain, favoring binding to the GTPase. Perturbation of these rearrangements prevent GALNTs relocation. In sum, Src promotes GALNTs relocation by favoring binding of GBF1 to Arf1. Regulation of a GEF-Arf axis by tyrosine phosphorylation appears to be a highly conserved and wide-spread mechanism.
BioCRNpyler: Compiling Chemical Reaction Networks from Biomolecular Parts in Diverse Contexts
Authors: Poole William , Pandey Ayush , Shur Andrey , Tuza Zoltan A. , Murray Richard M. 
Published: August 2020

AbstractBiochemical interactions in systems and synthetic biology are often modeled with chemical reaction networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in Python, that compiles high-level design specifications represented using a modular library of biochemical parts, mechanisms, and contexts to CRN implementations. This compilation process offers four advantages. First, the building of the actual CRN representation is automatic and outputs Systems Biology Markup Language (SBML) models compatible with numerous simulators. Second, a library of modular biochemical components allows for different architectures and implementations of biochemical circuits to be represented succinctly with design choices propagated throughout the underlying CRN automatically. This prevents the often occurring mismatch between high-level designs and model dynamics. Third, high-level design specification can be embedded into diverse biomolecular environments, such as cell-free extracts andin vivomilieus. Finally, our software toolbox has a parameter database, which allows users to rapidly prototype large models using very few parameters which can be customized later. By using BioCRNpyler, users ranging from expert modelers to novice script-writers can easily build, manage, and explore sophisticated biochemical models using diverse biochemical implementations, environments, and modeling assumptions.Author summaryThis paper describes a new software package BioCRNpyler (pronounced “Biocompiler”) designed to support rapid development and exploration of mathematical models of biochemical networks and circuits by computational biologists, systems biologists, and synthetic biologists. BioCRNpyler allows its users to generate large complex models using very few lines of code in a way that is modular. To do this, BioCRNpyler uses a powerful new representation of biochemical circuits which defines their parts, underlying biochemical mechanisms, and chemical context independently. BioCRNpyler was developed as a Python scripting language designed to be accessible to beginning users as well as easily extendable and customizable for advanced users. Ultimately, we see Biocrnpyler being used to accelerate computer automated design of biochemical circuits and model driven hypothesis generation in biology.
Cross-neutralization of a SARS-CoV-2 antibody to a functionally conserved site is mediated by avidity
Authors: Liu Hejun , Wu Nicholas C. , Yuan Meng , Bangaru Sandhya , Torres Jonathan L. , Caniels Tom G. , Schooten Jelle van , Zhu Xueyong , Lee Chang-Chun D. , Brouwer Philip J.M. , Gils Marit J. van , Sanders Rogier W. , Ward Andrew B. , Wilson Ian A. 
Published: August 2020

ABSTRACTMost antibodies isolated from COVID-19 patients are specific to SARS-CoV-2. COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here we determined a crystal structure of COVA1-16 Fab with the SARS-CoV-2 RBD, and a negative-stain EM reconstruction with the spike glycoprotein trimer, to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long CDR H3, and competes with ACE2 binding due to steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with structural and functional rationale for the epitope conservation, provide a blueprint for development of more universal SARS-like coronavirus vaccines and therapies.
Proteomic analysis of SUMO1-SUMOylome changes during defense elicitation inArabidopsis
Authors: Ingole Kishor D. , Dahale Shraddha K. , Bhattacharjee Saikat 
Published: August 2020

AbstractRapid adaptation of plants to developmental or physiological cues is facilitated by specific receptors that transduce the signals mostly via post-translational modification (PTM) cascades of downstream partners. Reversible covalent attachment of SMALL UBIQUITIN-LIKE MODIFIER (SUMO), a process termed as SUMOylation, influence growth, development and adaptation of plants to various stresses. Strong regulatory mechanisms maintain the steady-state SUMOylome and mutants with SUMOylation disturbances display mis-primed immunity often with growth consequences. Identity of the SUMO-substrates undergoing SUMOylation changes during defences however remain largely unknown. Here we exploit either the auto-immune property of an Arabidopsis mutant or defense responses induced in wild-type plants againstPseudomonas syringaepvtomato(PstDC3000) to enrich and identify SUMO1-substrates. Our results demonstrate massive enhancement of SUMO1-conjugates due to increased SUMOylation efficiencies during defense responses. Of the 261 proteins we identify, 29 have been previously implicated in immune-associated processes. Role of others expand to diverse cellular roles indicating massive readjustments the SUMOylome alterations may cause during induction of immunity. Overall, our study highlights the complexities of a plant immune network and identifies multiple SUMO-substrates that may orchestrate the signalling.
TractoFlow-ABS (Atlas-Based Segmentation)
Authors: Theaud Guillaume , Houde Jean-Christophe , Boré Arnaud , Rheault François , Morency Felix , Descoteaux Maxime 
Published: August 2020

AbstractIn Diffusion MRI (dMRI), pathological brains are a challenge for tractography processing, where most pipelines are not are not robust to white matter lesions. Intensity of white matter lesions on T1 images can have similar contrasts to gray matter tissue, which leads to misclassifications or “holes” in the white matter mask. These holes produce premature stop for tracking algorithms. To handle these issues, we developedTractoFlow-ABS(Atlas-BasedSegmentation).TractoFlow-ABSuses theFreesurferatlas to compute tissue masks instead ofFSL fastin standardTractoFlow.TractoFlow-ABSis therefore a derived version ofTractoFlowthat is robust to white matter anomalies such as hyperintensities and lesions.