bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCAIM controls effector T cell generation by preventing Mitochondria-Endoplasmic Reticulum Contact Site-initiated Cholesterol Biosynthesis
Authors: Iwert Christina , Stein Julia , Appelt Christine , Vogt Katrin , Rainer Roman Josef , Tummler Katja , Mühle Kerstin , Stanko Katarina , Schumann Julia , Uebe Doreen , Jürchott Karsten , Lisec Jan , Janek Katharina , Gille Christoph , Textoris-Taube Kathrin , Sai Somesh , Petersen Ansgar , Kühl Anja A. , Klipp Edda , Meisel Christian , Sawitzki Birgit 
Published: April 2021

AbstractT cells need to adapt their cellular metabolism for effector cell differentiation. This relies on alterations in mitochondrial physiology. Which signals and molecules regulate those alterations remains unclear. We recently reported, that the mitochondrial protein TCAIM inhibits activation-induced changes in mitochondrial morphology and function and thus, CD4+effector T cell formation. Using conditional TCAIM knock-in (KI) and knockout (KO) mice, we now show that it also applies to CD8+T cells and more importantly, delineate the molecular processes in mitochondria by which TCAIM controls effector cell differentiation. TCAIM KI resulted in reduced activation-induced HIF1α protein expression. Metabolomics and transcriptional data in combination with mathematical flux modeling revealed an impaired induction of anabolic pathways, especially of the mevalonate pathway and cholesterol biosynthesis in TCAIM KI CD8+T cells. Addition of cholesterol completely rescued HIF1α protein expression, activation and proliferation of TCAIM KI CD8+T cells. At the molecular level, TCAIM delayed activation-induced mitochondria-ER contact (MERC) formation by binding to MERC promoting proteins such as RMD3 and VDAC2. In summary, we demonstrate that TCAIM suppresses effector cell differentiation by inhibiting MERC formation, which induce HIF1α-mediated increase in cellular metabolism and cholesterol biosynthesis.
SENSV: Detecting Structural Variations with Precise Breakpoints using Low-Depth WGS Data from a Single Oxford Nanopore MinION Flowcell
Authors: Leung Henry CM , Yu Huijing , Zhang Yifan , Leung Wing Sze , Lo Ivan FM , Luk Ho Ming , Law Wai-Chun , Ma Ka Kui , Wong Chak Lim , Wong Yat Sing , Luo Ruibang , Lam Tak-Wah 
Published: April 2021

AbstractStructural variation (SV) is a major cause of genetic disorders. In this paper, we show that low-depth (specifically, 4x) whole-genome sequencing using a single Oxford Nanopore MinION flow cell suffices to support sensitive detection of SV, in particular, pathogenic SV for supporting clinical diagnosis. Existing SV calling software, when using 4x ONT WGS data, often fails to detect pathogenic SV especially in the form of long deletion, terminal deletion, duplication, and unbalanced translocation. Our new SV calling software SENSV is able to achieve high sensitivity for all types of SV and a breakpoint precision typically ±100 bp, both features are important for clinical concerns. The improvement achieved by SENSV stems from several new algorithms. We evaluated SENSV and other software using both real and simulated data. The former was based on 24 patient samples, each diagnosed with a genetic disorder. SENSV found the pathogenic SV in 22 out of 24 cases (all heterozygous, size from hundreds of Kbp to a few Mbp), reporting breakpoints within 100 bp of the true answers. No existing software can detect the pathogenic SV in more than 10 out of 24 cases, even when the breakpoint requirement is relaxed to ±2,000 bp.
Host EPAC1 modulates rickettsial adhesion to vascular endothelial cells via regulation of ANXA2 Y23 phosphorylation
Authors: Su Zhengchen , Shelite Thomas , Qiu Yuan , Chang Qing , Wakamiya Maki , Bei Jiani , He Xi , Zhou Changcheng , Liu Yakun , Gaitas Angelo , Saito Tais , Gong Bin 
Published: April 2021

AbstractRecently we have identified that endothelial surface annexin A2 (ANAX2) functions as a receptor for spotted fever group rickettsial adhesin outer membrane protein B (OmpB), which binds to the endothelial cell (EC) surface. Moreover, we reported that intracellular cAMP receptor EPAC1 modulates ANXA2 tyrosine (Y) 23 phosphorylation, and inactivation of EPAC1 suppresses ANXA2 expression on the EC luminal surface by downregulating Y23 phosphorylation. Since we reported that EPAC1 plays a critical role in the initial step to successfully establish rickettsial infection of ECs, this work aims to answer the following: (a) What is the mechanism underlying the regulatory role of EPAC1 in ECs during the initial step of bacterial infection? (b) Is the EPAC1-ANXA2 signaling pathway involved in the regulation of rickettsial adhesion to ECs?In the present study, an established system that is anatomically-based and quantifies bacterial adhesion to ECsin vivowas combined with novel fluidic force microscopy (FluidFM) to dissect the functional role of the EPAC1-ANXA2 signaling pathway in rickettsiae–EC adhesion. We reveal that the deletion of theEPAC1gene impedes rickettsial binding to endotheliumin vivo. In addition, single living brain microvascular EC study that employs FluidFM and site-directed mutagenesis provides evidence that supports our finding that EPAC1 governs rickettsial adhesion to EC surfaces via regulation of ANXA2 Y23 phosphorylation.
Rapid and Efficient Inactivation of SARS-CoV-2 from Surfaces using UVC Light Emitting Diode Device
Authors: Dwivedi Varun , Park Jun-Gyu , Grenon Stephen , Medendorp Nicholas , Hallam Cory , Torrelles Jordi B. , Martinez-Sobrido Luis , Kulkarni Viraj 
Published: April 2021

AbstractEfforts are underway to develop countermeasures to prevent the environmental spread of COVID-19 pandemic caused by SARS-CoV-2. Physical decontamination methods like Ultraviolet radiation has shown to be promising. Here, we describe a novel device emitting ultraviolet C radiation (UVC), called NuvaWave, to rapidly and efficiently inactivate SARS-CoV-2. SARS-CoV-2 was dried on a chambered glass slides and introduced in a NuvaWave robotic testing unit. The robot simulated waving NuvaWave over the virus at a pre-determined UVC radiation dose of 1, 2, 4 and 8 seconds. Post-UVC exposure, virus was recovered and titered by plaque assay in Vero E6 cells. We observed that relative control (no UVC exposure), exposure of the virus to UVC for one or two seconds resulted in a >2.9 and 3.8 log10reduction in viral titers, respectively. Exposure of the virus to UVC for four or eight seconds resulted in a reduction of greater than 4.7-log10reduction in viral titers. The NuvaWave device inactivates SARS-CoV-2 on surfaces to below the limit of detection within one to four seconds of UVC irradiation. This device can be deployed to rapidly disinfect surfaces from SARS-CoV-2, and to assist in mitigating its spread in a variety of settings.
Integrative analysis of the hydroxypyruvate reductases revealing their distinct roles in photorespiration of Chlamydomonas
Authors: Shi Menglin , Zhao Lei , Wang Yong 
Published: April 2021

AbstractPhotorespiration plays an important role in maintaining normal physiological metabolism in higher plants and other oxygenic organisms such as algae. The unicellular eukaryotic organismChlamydomonasis reported to have a different photorespiration system from that in higher plants, and only two out of nine genes encoding photorespiratory enzymes have been experimentally characterized. Hydroxypyruvate reductase (HPR), which is responsible for the conversion of hydroxypyruvate into glycerate, is poorly understood and not yet explored in Chlamydomonas. To identify the candidate genes encoding hydroxypyruvate reductase in Chlamydomonas (CrHPR) and uncover their elusive functions, we performed sequence comparison, enzyme activity measurement, subcellular localization, and analysis of knockout/knockdown strains. Together we identify five proteins to be good candidates as CrHPRs, all of which are detected with the activity of hydroxypyruvate reductase. CrHPR1, a NADH-dependent enzyme in mitochondria, may function as the major component of photorespiration, and deletion ofCrHPR1causes severe photorespiratory defects. CrHPR2 takes parts in the cytosolic bypass of photorespiration as the compensatory pathway of CrHPR1 for the reduction of hydroxypyruvate. CrHPR4, with NADH as the cofactor, may participate in photorespiration by acting as the chloroplastidial glyoxylate reductase in glycolate-quinone oxidoreductase system. Therefore, our results reveal that the CrHPRs are far more complex than previously recognized, and provide a greatly expanded knowledge base for studies to understand how CrHPRs perform their functions in photorespiration. These will facilitate the genetic engineering for crop improvement by synthetic biology.Brief summaryIdentification and characterization of genes encoding hydroxypyruvate reductases in Chlamydomonas, demonstrating difference in the enzymatic activity, subcellular location, as well as function in photorespiration.
The Autophagy Receptor TAX1BP1 (T6BP) is a novel player in antigen presentation by MHC-II molecules
Authors: Pereira Mathias , Richetta Clémence , Sarango Gabriela , Kumari Anita , Ghosh Michael , Bertrand Lisa , Pionneau Cédric , Gall Morgane Le , Grégoire Sylvie , Jeger-Madiot Raphaël , Rosoy Elina , Subra Frédéric , Delelis Olivier , Faure Mathias , Esclatine Audrey , Graff-Dubois Stéphanie , Stevanović Stefan , Manoury Bénédicte , Ramirez Bertha Cecilia , Moris Arnaud 
Published: April 2021

AbstractCD4+T lymphocytes play a major role in the establishment and maintenance of immunity. They are activated by antigenic peptides derived from extracellular or newly synthesized (endogenous) proteins presented on the surface of antigen presenting cells (APCs) by the MHC-II molecules. The pathways leading to endogenous MHC-II presentation remain poorly characterized. We demonstrate here that the autophagy receptor, T6BP, influences both autophagy-dependent and -independent endogenous presentation of HIV- and HCMV-derived peptides. By studying the immunopeptidome of MHC-II molecules, we show that T6BP affects both the quantity and quality of peptides presented. T6BP silencing induces the mislocalization of the MHC-II-loading compartments and a rapid degradation of the invariant chain (CD74) without altering the expression and internalization kinetics of MHC-II molecules. We determined the interactome of T6BP, identified calnexin as a T6BP partner and show that CANX cytosolic tail is required for this interaction. Remarkably, calnexin silencing replicates the functional consequences of T6BP silencing: decreased CD4+T cell activation and exacerbated CD74 degradation. Altogether, we unravel T6BP as a key player of the MHC-II-restricted endogenous presentation pathway and we propose one potential mechanism of action.
Viscous shear is a key force inDrosophilaventral furrow morphogenesis
Authors: Goldner Amanda Nicole , Cheikh Mohamad Ibrahim , Osterfield Miriam , Doubrovinski Konstantin 
Published: April 2021

ABSTRACTVentral furrow (VF) formation inDrosophila melanogasteris an important model of epithelial folding. Previous models of VF formation require cell volume conservation to convert apically localized constriction forces into lateral cell elongation and tissue folding. Here, we investigated embryonic morphogenesis in anillin knockdown (scraRNAi) embryos, where basal cell membranes fail to form and therefore cells can lose cytoplasmic volume through their basal side. Surprisingly, the mesoderm elongation and subsequent folding that comprise VF formation occurred essentially normally. We hypothesized that the effects of viscous shear may be sufficient to drive membrane elongation, providing effective volume conservation, and thus driving tissue folding. Since this hypothesis may not be possible to test experimentally, we turned to a computational approach. A minimal model of VF formation accounting for fluid dynamics indicated that shear forces can indeed explain our experimental observation. However, this conclusion depended on specific values of the model parameters. To test whether viscous shear is a dominant force for morphogenesisin vivo, we developed a highly realistic computational model incorporating both accurate cell and tissue geometry and experimentally measured material parameters. Results from this model demonstrate that viscous shear generates sufficient force to drive cell elongation and tissue foldingin vivo.
Genomic diversification of dehydrin gene family in vascular plants: three distinctive orthologue groups and a novel KS-dehydrin conserved protein motif
Authors: Melgar Alejandra E. , Zelada Alicia M. 
Published: April 2021

AbstractDehydrins (DHNs) are a family of plant proteins that play important roles on abiotic stress tolerance and seed development. They are classified into five structural subgroups: K-, SK-, YK-, YSK-, and KS-DHNs, according to the presence of conserved motifs named K-, Y- and S-segments.We carried out a comparative structural and phylogenetic analysis of these proteins, focusing on the less-studied KS-type DHNs. A search for conserved motifs in DHNs from 56 plant genomes revealed that KS-DHNs possess a unique and highly conserved N-terminal, 15-residue amino acid motif not previously described. This novel motif, that we named H-segment, is present in DHNs of angiosperms, gymnosperms and lycophytes, suggesting that HKS-DHNs were present in the first vascular plants. Phylogenetic and microsynteny analyses indicate that the five structural subgroups of angiosperm DHNs can be assigned to three groups of orthologue genes, characterized by the presence of the H-, F- or Y-segments. Importantly, the hydrophilin character of DHNs correlate with the phylogenetic origin of the DHNs rather than to the traditional structural subgroups. We propose that angiosperm DHNs can be ultimately subdivided into three orthologous groups, a phylogenetic framework that should help future studies on the evolution and function of this protein family.
Informed breeding dispersal following stochastic changes to patch quality in a pond‐breeding amphibian
Authors: Barrile Gabriel M. , Walters Annika , Webster Matthew , Chalfoun Anna D. 
Published: April 2021

Abstract

The unidirectional movement of animals between breeding patches (i.e. breeding dispersal) has profound implications for the ecological and evolutionary dynamics of spatially structured populations. In spatiotemporally variable environments, individuals are expected to adjust their dispersal decisions according to information gathered on the environmental and/or social cues that reflect the fitness prospects in a given breeding patch (i.e. informed dispersal).

A paucity of empirical work limited our understanding of the ability of animals to depart from low‐quality breeding patches and settle in high‐quality breeding patches. We examined the capacity of individuals to respond to stochastic changes in habitat quality via informed breeding dispersal in a pond‐breeding amphibian.

We conducted a 5‐year (2015–2019) capture–recapture study of boreal toads Anaxyrus boreas boreas (n = 1,100) that breed in beaver ponds in western Wyoming, USA. During early spring of 2017, an extreme flooding event destroyed several beaver dams and resulted in the loss of breeding habitat. We used multi‐state models to investigate how temporal changes in pond characteristics influenced breeding dispersal, and determine whether movement decisions were in accordance with prospects for reproductive fitness.

Boreal toads more often departed from low‐quality breeding ponds (without successful metamorphosis) and settled in high‐quality breeding ponds (with successful metamorphosis). Movement decisions were context‐dependent and associated with pond characteristics altered by beaver dam destruction. Individuals were more likely to depart from shallow ponds with high vegetation cover and settle in deep ponds with low vegetation cover. The probability of metamorphosis was related to the same environmental cues, suggesting that boreal toads assess the fitness prospects of a breeding patch and adjust movement decisions accordingly (i.e. informed breeding dispersal).

We demonstrated that stochastic variability in environmental conditions and habitat quality can underpin dispersal behaviour in amphibians. Our study highlighted the mechanistic linkages between habitat change, movement behaviour and prospects for reproductive performance, which is critical for understanding how wild animals respond to rapid environmental change.
An ethnocultural perspective on loneliness in young adulthood: A population‐based study in Israel
Authors: Achdut Netta , Refaeli Tehila 
Published: April 2021

AbstractYoung adults are a high‐risk group for experiencing loneliness. We examine (1) the prevalence of loneliness among young adults in three ethnocultural groups in Israel: native Jews, former Soviet Union immigrants and Arabs; (2) the associations between loneliness and ethnicity, perceived poverty, physical and mental health, perceived discrimination, social capital and online social capital; (3) the distinct sensitivity of the three ethnocultural groups to the determinants of loneliness. Cross‐sectional representative data for individuals aged 20–34 were taken from the 2016 to 2017 Israeli Social Surveys (N = 4253). Hierarchical logistic models were estimated to predict loneliness. Differences in the prevalence of loneliness were observed among the groups, with immigrants at higher risk. We found both common and distinct risk factors among the groups and only little evidence for moderation. Ethnic differences in loneliness between the native Jews and the Arabs can be ascribed to differences in their demographic characteristics and the prevalence of other risk factors. The risk for loneliness remained higher for immigrants after controlling for the entire set of risk factors. Eliminating the possibility that immigrants are more sensitive to any risk factor considered suggests the effect of ethnicity per se or rather that other factors affect loneliness in young immigrant adults.
Assessing the effect of facial disguises on forensic facial comparison by morphological analysis
Authors: Bacci Nicholas , Briers Nanette , Steyn Maryna 
Published: April 2021

AbstractDisguises are commonly used to mask a person's facial appearance in areas under closed‐circuit television (CCTV) surveillance. While many studies attempted to understand the effects of disguises, such as hats and glasses, on facial recognition, limited studies have looked at disguises in forensic facial comparison. The aim of this study was to compare the outcomes of forensic facial comparison by morphological analysis (MA) in a CCTV sample with sunglasses and brimmed caps. The sample was obtained from the Wits Face Database and organized into 81 face pools of one target facial image wearing a disguise (cap or sunglasses) and 10 potential matching images. MA was conducted across face pools, and confusion matrices were used to assess the outcomes. Surprisingly, sunglasses had limited effect on MA performance both in accuracy (90.4%) and in reliability (κ = 0.798), while caps markedly decreased both accuracy (68.1%) and reliability (κ = 0.639). Error rates were associated primarily with false negatives in both samples (caps: 42.4%; sunglasses: 16.1%) despite the sample distribution favoring false‐positive errors, which were very low (caps: 0.6%; sunglasses: 0%). Similarly to other studies, hats and caps were more harmful to correct identification when compared to sunglasses, which actually resulted in better accuracy than regular CCTV recordings. The effect of brimmed caps on accuracy was attributed to the overall loss of facial information caused. On training analysts, it may be helpful to instruct purposefully avoiding overreliance on easily disguised facial features, as other regions of the face also contain substantial feature information.
Combination therapy with plasma exchange and glucocorticoid may be effective for severe COVID‐19 infection: A retrospective observational study
Authors: Matsushita Yasushi , Kusaoi Makio , Hiki Makoto , Murayama Goh , Abe Yoshiyuki , Nozawa Kazuhisa , Takahashi Kazuhisa , Yamaji Ken , Tamura Naoto , Naito Toshio 
Published: April 2021

AbstractWe retrospectively analyzed the characteristics and outcomes of five patients with COVID‐19 who were received glucocorticoid (with or without pulse therapy) and therapeutic plasma exchange. The efficacy of the treatment was determined by whether the patient was able to be transferred from the COVID‐19 exclusive ICU to the general ward. In comparing patients who received prednisolone pulse therapy (three cases) with those who did not (two cases), 2/3 (66%) and 0/2 (0%) patients could be discharged from the COVID‐19 dedicated ICU, respectively. Among five patients who was performed plasma exchange, two elderly male patients who underwent plasma exchange as early as within 8 days of disease exacerbation survived and were able to be transferred to the general ward. This observational study indicates that plasma exchange in conjunction with methylprednisolone pulse therapy at the appropriate time may be an effective treatment for elderly patients with severe COVID‐19.
No evidence for enzootic plague within black‐tailed prairie dog (Cynomys ludovicianus) populations
Authors: COLMAN Rebecca E. , BRINKERHOFF R. Jory , BUSCH Joseph D. , RAY Chris , DOYLE Adina , SAHL Jason W. , KEIM Paul , COLLINGE Sharon K. , WAGNER David M. 
Published: April 2021

AbstractYersinia pestis, causative agent of plague, occurs throughout the western United States in rodent populations and periodically causes epizootics in susceptible species, including black‐tailed prairie dogs (Cynomys ludovicianus). How Y. pestis persists long‐term in the environment between these epizootics is poorly understood but multiple mechanisms have been proposed, including, among others, a separate enzootic transmission cycle that maintains Y. pestis without involvement of epizootic hosts and persistence of Y. pestis within epizootic host populations without causing high mortality within those populations. We live‐trapped and collected fleas from black‐tailed prairie dogs and other mammal species from sites with and without black‐tailed prairie dogs in 2004 and 2005 and tested all fleas for presence of Y. pestis. Y. pestis was not detected in 2126 fleas collected in 2004 but was detected in 294 fleas collected from multiple sites in 2005, before and during a widespread epizootic that drastically reduced black‐tailed prairie dog populations in the affected colonies. Temporal and spatial patterns of Y. pestis occurrence in fleas and genotyping of Y. pestis present in some infected fleas suggest Y. pestis was introduced multiple times from sources outside the study area and once introduced, was dispersed between several sites. We conclude Y. pestis likely was not present in these black‐tailed prairie dog colonies prior to epizootic activity in these colonies. Although we did not identify likely enzootic hosts, we found evidence that deer mice (Peromyscus maniculatus) may serve as bridging hosts for Y. pestis between unknown enzootic hosts and black‐tailed prairie dogs.