bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applied tutorial for the design and fabrication of biomicrofluidic devices by resin 3D printing
Authors: Musgrove Hannah B. , Catterton Megan A. , Pompano Rebecca R. 
Published: November 2021

AbstractStereolithographic (SL) 3D printing, especially digital light processing (DLP) printing, is a promising rapid fabrication method for bio-microfluidic applications such as clinical tests, lab-on-a-chip devices, and sensor integrated devices. The benefits of 3D printing lead many to believe this fabrication method will accelerate the use of microfluidics, but there are a number of potential obstacles to overcome for bioanalytical labs to fully utilize this technology. For commercially available printing materials, this includes challenges in producing prints with the print resolution and mechanical stability required for a particular design, along with cytotoxic components within many SL resins and low optical compatibility for imaging experiments. Potential solutions to these problems are scattered throughout the literature and rarely available in head-to-head comparisons. Therefore, we present here a concise guide to the principles of resin 3D printing most relevant for fabrication of bioanalytical microfluidic devices. Intended to quickly orient labs that are new to 3D printing, the tutorial includes the results of selected systematic tests to inform resin selection, strategies for design optimization, and improvement of biocompatibility of resin 3D printed bio-microfluidic devices.
LRRC15 is an inhibitory receptor blocking SARS-CoV-2 spike-mediated entry in trans
Authors: Song Jaewon , Chow Ryan D. , Pena-Hernandez Mario , Zhang Li , Loeb Skylar A. , So Eui-Young , Liang Olin D. , Wilen Craig B. , Lee Sanghyun 
Published: November 2021

ABSTRACTSARS-CoV-2 infection is mediated by the entry receptor ACE2. Although attachment factors and co-receptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory receptor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not co-expressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory receptor for SARS-CoV-2 regulating viral entry in trans.
The PAIR-R24M Dataset for Multi-animal 3D Pose Estimation
Authors: Marshall Jesse D. , Klibaite Ugne , Gellis Amanda , Aldarondo Diego E. , Ölveczky Bence P. , Dunn Timothy W. 
Published: November 2021

AbstractUnderstanding the biological basis of social and collective behaviors in animals is a key goal of the life sciences, and may yield important insights for engineering intelligent multi-agent systems. A critical step in interrogating the mechanisms underlying social behaviors is a precise readout of the 3D pose of interacting animals. While approaches for multi-animal pose estimation are beginning to emerge, they remain challenging to compare due to the lack of standardized training and benchmark datasets. Here we introduce the PAIR-R24M (Paired Acquisition of Interacting oRganisms - Rat) dataset for multi-animal 3D pose estimation, which contains 24.3 million frames of RGB video and 3D ground-truth motion capture of dyadic interactions in laboratory rats. PAIR-R24M contains data from 18 distinct pairs of rats and 24 different viewpoints. We annotated the data with 11 behavioral labels and 3 interaction categories to facilitate benchmarking in rare but challenging behaviors. To establish a baseline for markerless multi-animal 3D pose estimation, we developed a multi-animal extension of DANNCE, a recently published network for 3D pose estimation in freely behaving laboratory animals. As the first large multi-animal 3D pose estimation dataset, PAIR-R24M will help advance 3D animal tracking approaches and aid in elucidating the neural basis of social behaviors.
Genome-wide characterization of SARS-CoV-2 cytopathogenic proteins in the search of antiviral targets
Authors: Zhang Jiantao , Li Qi , Cruz Cosme Ruth S. , Gerzanich Volodymyr , Tang Qiyi , Simard J. Marc , Zhao Richard Y. 
Published: November 2021

AbstractTherapeutic inhibition of critical viral functions is important for curtailing coronavirus disease-2019 (COVID-19). We sought to identify antiviral targets through genome-wide characterization of SARS-CoV-2 proteins that are crucial for viral pathogenesis and that cause harmful cytopathic effects. All twenty-nine viral proteins were tested in a fission yeast cell-based system using inducible gene expression. Twelve proteins including eight non-structural proteins (NSP1, NSP3, NSP4, NSP5, NSP6, NSP13, NSP14 and NSP15) and four accessory proteins (ORF3a, ORF6, ORF7a and ORF7b) were identified that altered cellular proliferation and integrity, and induced cell death. Cell death correlated with the activation of cellular oxidative stress. Of the twelve proteins, ORF3a was chosen for further study in mammalian cells. In human pulmonary and kidney epithelial cells, ORF3a induced cellular oxidative stress associated with apoptosis and necrosis, and caused activation of pro-inflammatory response with production of the cytokines TNF-α, IL-6, and IFN-β1, possibly through the activation of NF-κB. To further characterize the mechanism, we tested a natural ORF3a Beta variant, Q57H, and a mutant with deletion of the highly conserved residue, ΔG188. Compared to wild type ORF3a, the ΔG188 variant yielded more robust activation of cellular oxidative stress, cell death, and innate immune response. Since cellular oxidative stress and inflammation contribute to cell death and tissue damage linked to the severity of COVID-19, our findings suggest that ORF3a is a promising, novel therapeutic target against COVID-19.SignificanceThe ongoing SARS-CoV-2 pandemic has claimed over 5 million lives with more than 250 million people infected world-wide. While vaccines are effective, the emergence of new viral variants could jeopardize vaccine protection. Antiviral drugs provide an alternative to battle against COVID-19. Our goal was to identify viral therapeutic targets that can be used in antiviral drug discovery. Utilizing a genome-wide functional analysis in a fission yeast cell-based system, we identified twelve viral candidates, including ORF3a, which cause cellular oxidative stress, inflammation and apoptosis and necrosis that contribute to COVID-19. Our findings indicate that antiviral agents targeting ORF3a could greatly impact COVID-19.
Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals
Authors: Andeweg Stijn P. , Vennema Harry , Veldhuijzen Irene , Smorenburg Naomi , Schmitz Dennis , Zwagemaker Florian ,   SeqNeth Molecular surveillance group,   RIVM COVID-19 Molecular epidemiology group, van Gageldonk-Lafeber Arianne B. , Hahné Susan J.M. , Reusken Chantal , Knol Mirjam J. , Eggink Dirk 
Published: November 2021

AbstractThe extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) break through infection- or vaccine-induced immunity is not well understood. Here, we analyze 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We find evidence for an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared to the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14-59 days after complete vaccination compared to 60 days and longer. In contrast to vaccine-induced immunity, no increased risk for reinfection with Beta, Gamma or Delta variants relative to Alpha variant was found in individuals with infection-induced immunity.
Microbial community analysis of biofilters reveals a dominance of either comammox Nitrospira or archaea as ammonia oxidizers in freshwater aquaria
Authors: McKnight Michelle M. , Neufeld Josh D. 
Published: November 2021

AbstractNitrification by aquarium biofilters transforms toxic ammonia waste (NH3/NH4+) to less toxic nitrate (NO3-) via nitrite (NO2-). Ammonia oxidation is mediated by ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA), and the recently discovered complete ammonia oxidizing (comammox) Nitrospira. Prior to the discovery of comammox Nitrospira, previous research revealed that AOA dominate among ammonia oxidizers in freshwater biofilters. Here, we characterized the composition of aquarium filter microbial communities and quantified the abundance of all three known groups of ammonia oxidizers. Aquarium biofilter and water samples were collected from representative freshwater and saltwater systems in Southwestern Ontario, Canada. Using extracted DNA, we performed 16S rRNA gene sequencing and quantitative PCR (qPCR) to assess community composition and quantify the abundance of amoA genes, respectively. Our results show that aquarium biofilter microbial communities were consistently represented by putative heterotrophs of the Proteobacteria and Bacteroides phyla, with distinct profiles associated with fresh versus saltwater biofilters. Among nitrifiers, comammox Nitrospira amoA genes were detected in all 38 freshwater aquarium biofilter samples and were the most abundant ammonia oxidizer in 30 of these samples, with the remaining biofilters dominated by AOA, based on amoA gene abundances. In saltwater biofilters, AOA or AOB were differentially abundant, with no comammox Nitrospira detected. These results demonstrate that comammox Nitrospira play an important role in biofilter nitrification that has been previously overlooked and such microcosms are useful for exploring the ecology of nitrification for future research.
Structural biases in disordered proteins are prevalent in the cell
Authors: Moses David , Guadalupe Karina , Yu Feng , Flores Eduardo , Perez Anthony , McAnelly Ralph , Shamoon Nora M. , Cuevas-Zepeda Estefania , Merg Andrea D. , Martin Erik W. , Holehouse Alex S. , Sukenik Shahar 
Published: November 2021

AbstractIntrinsically disordered proteins and protein regions (IDPs) are essential to cellular function in all proteomes. Unlike folded proteins, IDPs exist in an ensemble of rapidly interchanging conformations. IDP sequences encode interactions that create structural biases within the ensemble. Such structural biases determine the three-dimensional shape of IDP ensembles and can affect their activity. However, the plasticity and sensitivity of IDP ensembles means structural biases, often measured in vitro, may differ in the dynamic and heterogeneous intracellular environment. Here we reveal that structural biases found in vitro in well-studied IDPs persist inside human-derived cells. We further show that a subset of IDPs are able to sense changes in cellular physical-chemical composition and modulate their ensemble in response. We propose that IDP ensembles can evolve to sense and respond to intracellular physicochemical changes, or to resist them. This property can be leveraged for biological function, be the underlying cause of IDP-driven pathology, or be leveraged for the design of disorder-based biosensors and actuators.
Engineered ACE2-Fc counters murine lethal SARS-CoV-2 infection through direct neutralization and Fc-effector activities
Authors: Chen Yaozong , Sun Lulu , Ullah Irfan , Beaudoin-Bussières Guillaume , Anand Sai Priya , Hederman Andrew P. , Tolbert William D. , Sherburn Rebekah , Nguyen Dung N. , Marchitto Lorie , Ding Shilei , Wu Di , Luo Yuhong , Gottumukkala Suneetha , Moran Sean , Kumar Priti , Piszczek Grzegorz , Mothes Walther , Ackerman Margaret E. , Finzi Andrés , Uchil Pradeep D. , Gonzalez Frank J. , Pazgier Marzena 
Published: November 2021

ABSTRACTSoluble Angiotensin-Converting Enzyme 2 (ACE2) constitutes an attractive antiviral capable of targeting a wide range of coronaviruses utilizing ACE2 as their receptor. Here, using structure-guided approaches, we developed divalent ACE2 molecules by grafting the extracellular ACE2-domain onto a human IgG1 or IgG3 (ACE2-Fc). These ACE2-Fcs harbor structurally validated mutations that enhance spike (S) binding and remove angiotensin enzymatic activity. The lead variant bound tightly to S, mediated in vitro neutralization of SARS-CoV-2 variants of concern (VOCs) with sub-nanomolar IC50 and was capable of robust Fc-effector functions, including antibody-dependent-cellular cytotoxicity, phagocytosis and complement deposition. When tested in a stringent K18-hACE2 mouse model, it delayed death or effectively resolved lethal SARS-CoV-2 infection in a prophylactic or therapeutic setting utilizing the combined effect of neutralization and Fc-effector functions. These data confirm the utility of ACE2-Fcs as valuable agents in preventing and eliminating SARS-CoV-2 infection and demonstrate that ACE2-Fc therapeutic activity require Fc-effector functions.
Altered neurogenic pathways in experimental rat models of ischemic cerebral stroke: A transcriptome based meta-analysis
Authors: Roshan Syed Aasish , Elangovan Gayathri , Gunaseelan Dharani , K. Jayachandran Swaminathan , Kandasamy Mahesh , Anusuyadevi Muthuswamy 
Published: November 2021

1)AbstractObjectivesPromoting neurogenesis mediated recovery is one of the most sought after strategies in recovery after cerebral stroke. In this paper we elucidate how neurogenesis related genes are altered in the early stroke environment, to hint at potential pathways for therapeutic recovery.Materials and MethodsAround 97 microarray datasets derived from stroke affected rat brains were collected from NCBI-GEO. Datasets were normalized and subjected to meta-analysis in Network Analyst to identify differentially expressed genes. Gene enrichment analyses were carried out using GSEA, and WebGestalt, and results were visualized using Cytoscape Enrichment mapping.ResultsNearly 939 differentially expressing genes were identified in the cerebral stroke group. Among them 30 neurogenesis related genes were identified through enrichment mapping analysis, and 35 genes through Protein- Protein Interaction analysis. Highest upregulated neurogenesis genes were found to be TSPO, GFAP, VIM, and TGFB1. Highest Downregulated neurogenesis genes were found to be THY1, NR1D1, CDK5, STX1B, and NOG.ConclusionsThrough this study, we have identified that during the acute time frame after stroke, majority of the neurogenesis genes related to neural proliferation and neural differentiation are downregulated, while the majority of the genes related to neuronal migration were upregulated. Single or combined therapeutic approach against the identified dysregulated genes could greatly aid neural restoration and functional recovery during the postischemic stage.
Unravelling consensus genomic regions associated with quality traits in wheat (Triticum aestivum L.) using meta-analysis of quantitative trait loci
Authors: Gudi Santosh , Saini Dinesh K , Singh Gurjeet , Halladakeri Priyanka , Shamshad Mohammad , Tanin Mohammad Jafar , Kumar Pradeep , Sharma Achla 
Published: November 2021

AbstractA meta-analysis of quantitative trait loci (QTLs) associated with following six major quality traits (i) arabinoxylan, (ii) dough rheology properties, (iii) nutritional traits, (iv) polyphenol content, (v) processing quality traits, and (vi) sedimentation volume was conducted in wheat. For this purpose, as many as 2458 QTLs were collected from the 50 mapping studies published during 2013-20. Of the total QTLs, 1126 QTLs were projected on to the consensus map saturated with 2,50,077 markers resulting into the identification of 110 meta-QTLs (MQTLs) with average confidence interval (CI) of 5.6 cM. These MQTLs had 18.84 times reduced CI compared to CI of initial QTLs. Fifty-one (51) MQTLs were also verified with the marker-trait associations (MTAs) detected in earlier genome-wide association studies (GWAS). Physical region occupied by a single MQTL ranged from 0.12 to 749.71 Mb with an average of 130.25 Mb. Candidate gene mining allowed the identification of 2533 unique gene models from the MQTL regions. In-silico expression analysis discovered 439 differentially expressed gene models with >2 transcripts per million (TPM) expression in grains and related tissues which also included 44 high-confidence candidate genes known to be involved in the various cellular and biochemical processes related to quality traits. Further, nine functionally characterized wheat genes associated with grain protein content, high molecular weight glutenin and starch synthase enzymes were also found to be co-localized with some of the MQTLs. In addition, synteny analysis between wheat and rice MQTL regions identified 23 wheat MQTLs syntenic to 16 rice MQTLs. Furthermore, 64 wheat orthologues of 30 known rice genes were detected in 44 MQTL regions. These genes encoded proteins mainly belonging to the following families: starch synthase, glycosyl transferase, aldehyde dehydrogenase, SWEET sugar transporter, alpha amylase, glycoside hydrolase, glycogen debranching enzyme, protein kinase, peptidase, legumain and seed storage protein enzyme.Main ConclusionMeta-QTL analysis in wheat for major quality traits identified 110 MQTLs with reduced confidence interval. Candidate gene mining and expression analysis discovered differentially expressed genes involve in quality traits.
Pulse-Width Modulation-based TMS mimics effects of conventional TMS on human primary motor cortex
Authors: Memarian Sorkhabi Majid , Wendt Karen , O’Shea Jacinta , Denison Timothy 
Published: November 2021

AbstractObjectiveWe developed a novel transcranial magnetic stimulation (TMS) device to generate flexible stimuli and patterns. The system synthesizes digital equivalents of analog waveforms, relying on the filtering properties of the nervous system. Here, we test the hypothesis that the novel pulses can mimic the effect of conventional pulses on the cortex.ApproachA second-generation programmable TMS (pTMS2) stimulator with magnetic pulse shaping capabilities using pulse-width modulation (PWM) was tested. A computational and an in-human study on twelve healthy participants compared the neuronal effects of conventional and modulation-based stimuli.Main resultsBoth the computational modeling and the in-human stimulation showed that the PWM-based system can synthesize pulses to effectively stimulate the human brain, equivalent to conventional stimulators. The comparison includes motor threshold, MEP latency and input-output curve measurements.SignificancePWM stimuli can fundamentally imitate the effect of conventional magnetic stimuli while adding considerable flexibility to TMS systems, enabling the generation of highly configurable TMS protocols.HighlightsThe PWM method promises the implementation of flexible neurostimulationPWM magnetic pulses were well tolerated by the participants without adverse eventsRMTs and MEPs were compared for PWM and conventional stimuliPWM-equivalent of conventional pulses has relatively similar effects on the cortexThe use of digital synthesis techniques to create novel patterns is a promising method for future neuromodulation
Non-invasive real-time access to spatial attention information from 3T fMRI BOLD signals
Authors: Loriette C. , De Sousa C. , Clavagnier S. , Lamberton F. , Ibarolla D. , Ben Hamed S. 
Published: November 2021

AbstractAccess to higher cognitive functions in real-time remains very challenging, because these functions are internally driven and their assessment is based onto indirect measures. In addition, recent finding show that these functions are highly dynamic. Previous studies using intra-cortical recordings in monkeys, succeed to access the (x,y) position of covert spatial attention, in real-time, using classification methods applied to monkey prefrontal multi-unit activity and local field potentials. In contrast, the direct access to attention with non-invasive methods is limited to predicting the attention localisation based on a quadrant classification. Here, we demonstrate the feasibility to track covert spatial attention localization using non-invasive fMRI BOLD signals, with an unprecedented spatial resolution. We further show that the errors produced by the decoder are not randomly distributed but concentrate on the locations neighbouring the cued location and that behavioral errors correlate with weaker decoding performance. Last, we also show that the voxels contributing to the decoder precisely match the visual retinotopic organization of the occipital cortex and that single trial access to attention is limited by the intrinsic dynamics of spatial attention. Taken together, these results open the way to the development of remediation and enhancement neurofeedback protocols targeting the attentional function.