bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatic analysis of B and T cell epitopes from SARS-CoV-2 Spike, Membrane and Nucleocapsid proteins as a strategy to assess possible cross-reactivity between emerging variants, including Omicron, and other human coronaviruses
Authors: Pacheco-Olvera Diana Laura , Remy-Hernández Stephanie Saint , García-Valeriano María Guadalupe , Rivera-Hernández Tania , López-Macías Constantino 
Published: February 2022

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 produced a global health emergency since December 2019, that up to the end of January 2022 had caused the death of more than 5.6 million people worldwide. Despite emergence of new variants of concern, vaccination remains one of the most important tools to control the pandemic. All approved vaccines and most of the vaccine candidates use the spike protein of the virus as a target antigen to induce protective immune responses. Several variants of the virus present key mutations in this protein which render the virus, at different rates, to evade the neutralizing antibody response. Although experimental evidence suggests that cross-reactive responses between coronaviruses are present in the population, it is unknown which potential antigens shared between different coronaviruses could be responsible for these responses. This study provides predictions of new potential B and T cell epitopes within SARS-CoV-2 Spike (S), Membrane (M) and Nucleocapsid (N) proteins together with a review of the reported B epitopes of these proteins. We also analyse amino acid changes present in the epitopes of variants of concern (VOC) and variants being monitored (VBM), and how these might affect the immune response, as these changes may alter the peptides’ immunogenicity index and the antigen presentation by related HLA alleles. Finally, given these observations, we performed an identity analysis between the repertoire of potential epitopes of SARS-CoV-2 and other human coronaviruses to identify which are conserved among them.The results shown here together with the published experimental evidence, allow us to support the hypothesis that antibody and T cell cross-reactive responses to common coronaviruses epitopes, could contribute to broaden the protective response to SARS-CoV-2 and its variants. This evidence could help not only to understand cross-reactive responses among coronaviruses but also contribute to elucidate their role in immunity to SARS-CoV-2 induced by infection and/or vaccination. Finally, these findings could promote targeted analysis of antigen-specific immune responses and might orient and drive the rational development of new SARS-CoV-2 vaccines including candidates that ideally provide “universal” protection against other coronaviruses relevant to human health.
Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells
Authors: Gerdes Patricia , Lim Sue Mei , Ewing Adam D. , Larcombe Michael R. , Chan Dorothy , Sanchez-Luque Francisco J. , Walker Lucinda , Carleton Alexander L. , James Cini , Knaupp Anja S. , Carreira Patricia E. , Nefzger Christian M. , Lister Ryan , Richardson Sandra R. , Polo Jose M. , Faulkner Geoffrey J. 
Published: February 2022

AbstractInduced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements (TEs) and prevent TE-mediated mutagenesis. Here we applied short-read or Oxford Nanopore Technologies (ONT) long-read genome sequencing to 38 bulk miPSC lines reprogrammed from 10 parental cell types, and 18 single-cell miPSC clones. While single nucleotide variants and structural variants restricted to miPSCs were rare, we found 83de novoTE insertions, including examples intronic toBrca1andDmd. LINE-1 (L1) retrotransposons were profoundly hypomethylated in miPSCs, beyond other TEs and the genome overall, and harbored alternative protein-coding gene promoters. Treatment with the L1 inhibitor lamivudine did not hinder reprogramming and efficiently blocked endogenous retrotransposition, as detected by ONT sequencing. These experiments reveal the complete spectrum and potential significance of mutations acquired by miPSCs.
The acute lag effects of elevated ambient air pollution on stillbirth risk in Ulaanbaatar, Mongolia
Authors: Enebish Temuulen , Warburton David , Habre Rima , Breton Carrie , Tuvshindorj Nomindelger , Tumur Gantuya , Munkhuu Bayalag , Franklin Meredith 
Published: February 2022

AbstractUlaanbaatar city (UB), the capital and the home to half of Mongolia’s total population, has experienced extreme seasonal air pollution in the past two decades with levels of fine particulate matter with an aerodynamic diameter less than 2.5 micrometers (PM2.5) exceeding 500 μg/m3 during winter. Based on monitoring data, (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) exposures were estimated for residential areas across UB using Random Forest models. We collected individual-level data on 1093 stillbirths from UB hospital records (2010-2013) and a surveillance database (2014-2018). Using a time-stratified case-crossover design, we investigated whether short-term increases in daily ambient air pollutants with different exposure lags (2 to 6 days) before delivery were associated with stillbirth. We estimated associations using conditional logistic regression and examined individual-level characteristics for effect modification. During the cold season (Oct-Mar) we observed significantly elevated relative odds of stillbirth per interquartile range increase in mean concentrations of PM2.5 (odds ratio [OR]=1.35, 95% confidence interval [CI]=1.07-1.71), SO2 (OR=1.71, 95% CI=1.06-2.77), NO2 (OR=1.30, 95% CI=0.99-1.72), and CO (OR=1.44, 95% CI=1.17-1.77) 6 days before delivery after adjusting for apparent temperature with a natural cubic spline. The associations of pollutant concentrations with stillbirth were significantly stronger among those younger than 25, nulliparous, and without comorbidities or pregnancy complications during stratified analyses. There was a clear pattern of increased risk for women living in areas of lower socioeconomic status. We conclude that acute exposure to ambient air pollution before delivery may trigger stillbirth, and this risk is higher for certain subsets of women.
A systematic review of previous MRI studies demonstrating the relationship between season and brain volume
Authors: Majrashi Naif A. , Alyami Ali S. 
Published: February 2022

AbstractIntroductionSpecific diseases such as Alzheimer’s, schizophrenia and multiple sclerosis have been associated with environmental changes, including changes in season. The relationship between changes in season or photoperiod and brain volume has been widely studied in animals. However, the relationship between changes in season and brain volume in humans is not yet well established. Here, we aim to provide a comprehensive and systematic review of magnetic resonance imaging (MRI) studies examining the effects of changes in season or photoperiod on brain volume.MethodsWe used a systematic review approach to study reports on the relationship between changes in season or photoperiod and brain volume using MRI. PubMed database and Google Scholar search engines were used to locate appropriate. PRISMA was used in selection of appropriate studies on season or photoperiod and brain volume using MRI.ResultsFive studies were included in the current review: three examined the relationship between changes in photoperiod and brain volumes while two studies examined the relationship between changes in season and brain volume.ConclusionWhen studying other variables like changes in temperature and humidity on how they affect brain volume, no effect was observed. It was, however, observed from studies that hydration status changed brain volumes when measured using MRI. Overall, we found evidence demonstrating differences in human brain volumes across different seasons. We suggest future longitudinal research to prove changes in brain volume across different seasons.
Brain regional identity and cell type specificity landscape of human cortical organoid models
Authors: Magni M. , Bossi B. , Conforti P. , Galimberti M. , Dezi F. , Lischetti T , He X. , Barker R.A. , Zuccato C. , Espuny-Camacho I. , Cattaneo E. 
Published: February 2022

ABSTRACTIn vitro models of corticogenesis using mouse and human pluripotent stem cells (PSC) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex.Here, we tested three cortical organoid protocols for brain regional identity, cell type-specificity and neuronal maturation. Overall all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. We showed that three months old cortical organoids showed a pattern of gene expression that resembled late human embryonic cortex. Comparatively, directed differentiation methods without WNT activation gave rise to the highest degree of cortical regional identity in brain organoids. Whereas, default “intrinsic” brain organoid differentiation produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage derived microglia cells of the brain. These results suggest that cortical organoid models produce diverse outcomes in terms of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.
Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3
Authors: Cupo Ryan R. , Rizo Alexandrea N. , Braun Gabriel A. , Tse Eric , Chuang Edward , Southworth Daniel R. , Shorter James 
Published: February 2022

SummaryThe AAA+ protein, Skd3 (human CLPB), solubilizes proteins in the mitochondrial intermembrane space, which is critical for human health. Skd3 variants with impaired protein-disaggregase activity cause severe congenital neutropenia (SCN) and 3-methylglutaconic aciduria type 7 (MGCA7). Yet how Skd3 disaggregates proteins remains poorly understood. Here, we report a high-resolution structure of a Skd3-substrate complex. Skd3 adopts a spiral hexameric arrangement that engages substrate via pore-loop interactions in the nucleotide-binding domain (NBD). Unexpectedly, substrate-bound Skd3 hexamers stack head-to-head via unique, adaptable ankyrin-repeat domain (ANK)-mediated interactions to form dodecamers. Deleting the ANK-linker region reduces dodecamerization and disaggregase activity. We elucidate apomorphic features of the Skd3 NBD and C-terminal domain that regulate disaggregase activity. We also define how Skd3 subunits collaborate to disaggregate proteins. Importantly, SCN-linked subunits sharply inhibit disaggregase activity, whereas MGCA7-linked subunits do not. Our findings illuminate Skd3 structure and mechanism, explain SCN and MGCA7 inheritance patterns, and suggest therapeutic strategies.
Mitochondrial genomes in Perkinsus decode conserved frameshifts in all genes
Authors: Gornik Sebastian G. , Flores Victor , Reinhardt Franziska , Erber Lieselotte , Douvropoulou Olga , Lassadi Imen , Einarsson Elin , Mörl Mario , Git Anna , Stadler Peter F. , Pain Arnab , Waller Ross F. 
Published: February 2022

ABSTRACTMitochondrial genomes of apicomplexans, dino-flagellates and chrompodellids, that collectively make up the Myzozoa, are uncommonly reduced in coding capacity and display divergent gene configuration and expression mechanisms. They encode only three proteins — COB, COX1, COX3 — contain rRNAs fragmented to ∼100-200 base pair elements, and employ extensive recombination, RNA trans-splicing, and RNA-editing for genome maintenance and expression. The early-diverging Perkinsozoa is the final major myzozoan lineage whose mitochondrial genomes remain poorly characterized. Previous reports of Perkinsus cox1 and cob partial gene sequences have indicated independent acquisition of non-canonical features, namely the occurrence of multiple frameshifts in both genes. To determine ancestral myzozoan mitochondrial genome features, as well as any novel ones in Perkinsozoa, we sequenced and assembled four Perkinsus species mitochondrial genomes. These data show a simple ancestral genome with the common reduced coding capacity, but one already prone to rearrangement. Moreover, we identified 75 frameshifts across the four species that are present in all genes, that are highly conserved in gene location, and that occur as four distinct types. A decoding mechanism apparently employs unused codons at the frameshift sites that advance translation either +1 or +2 frames to the next used codon. The locations of the frameshifts are seemingly positioned to regulate protein folding of the nascent protein as it emerges from the ribosome. COX3 is distinct in containing only one frameshift and showing strong selection against residues that are otherwise frequently encoded at the frameshift positions in COX3 and COB. All genes also lack cysteine codons implying a further constraint on these genomes with reduction to only 19 different amino acids. Furthermore, mitochondrion-encoded rRNA fragment complements are incomplete in Perkinsus spp. but some are found in the nuclear DNA, suggesting these may be imported into the organelle as for tRNAs. Perkinsus demonstrates additional remarkable trajectories of organelle genome evolution including pervasive integration of frameshift translation into genome expression.
Substrate Temperature and Seed Scarification on Germination Parameters of Butterfly Pea (Clitoria ternatea)
Authors: Campbell Sean M. , Pearson Brian J. , Marble S. Christopher 
Published: February 2022

AbstractRecent interest in the cultivation and use of butterfly pea (Clitoria ternatea) has increased demand for its commercial production. Successful germination of seed is a critical first step to its production; however, few studies have documented factors influential to germination success. To help support commercial production efforts, the influence of substrate temperature and seed scarification technique on germination parameters were evaluated. Two scarification (nicked and nicked and soaked) and three substrate temperature treatments (21, 24, and 27 °C) were imposed on C. ternatea seed. Following treatments, six germination parameters were recorded. Data showed seeds maintained at a substrate temperature of 21 °C reached maximal germination (54.8%) at the longest mean germination time (2.61 d) and slowest mean germination rate (0.39 d-1). Mechanical scarification by nicking the seed coat with a razor blade prior to soaking the seed for 24 hours reached maximal germination (80.95%) at the lowest mean germination time (2.06 d) and fastest mean germination rate (0.51 d-1). Optimal germination was attained when seed was scarified and soaked and then germinated in rockwool substrate maintained at a temperature (To) of 21 °C. Results provide commercial growers with production technique information helpful to fast and efficient germination of C. ternatea seed.
Spatiotemporal analysis of axonal autophagosome-lysosome dynamics reveals limited fusion events trigger two-step maturation
Authors: Cason Sydney E. , Mogre Saurabh S. , Holzbaur Erika L.F. , Koslover Elena F. 
Published: February 2022

AbstractMacroautophagy is a homeostatic process required to clear cellular waste including aggregated proteins and dysfunctional organelles. Neuronal autophagosomes form constitutively in the distal tip of the axon and are actively transported toward the soma, with cargo degradation initiated en route. Cargo turnover requires autophagosomes to fuse with lysosomes to acquire degradative enzymes; however, the timing and number of these fusion events in the axon have proven difficult to detect using microscopy alone. Here we use a quantitative model, parameterized and validated using data from live and fixed imaging of primary hippocampal neurons, to explore the autophagosome maturation process on a cellular scale. We demonstrate that retrograde autophagosome motility is independent from lysosomal fusion, and that most autophagosomes fuse with only a few lysosomes by the time they reach the soma. Furthermore, our imaging and model results highlight the two-step maturation of the autophagosome: fusion with a lysosome or late endosome is followed by the slow degradation of the autophagosomal inner membrane before actual cargo degradation can occur. Together, rigorous quantitative measurements and mathematical modeling elucidate the dynamics of autophagosome-lysosome interaction and autophagosomal maturation in the axon.
Sex differences in the immediate extinction deficit and renewal of extinguished fear in rats
Authors: Binette Annalise N. , Totty Michael S. , Maren Stephen 
Published: February 2022

AbstractExtinction learning is central to exposure-based behavioral therapies for reducing fear and anxiety in humans. However, patients with fear and anxiety disorders are often resistant to extinction. Moreover, trauma and stress-related disorders are highly prone to relapse and are twice as likely to occur in females compared to males, suggesting that females may be more susceptible to extinction deficits and fear relapse phenomena. In this report, we tested this hypothesis by examining sex differences in a stress-induced extinction learning impairment, the immediate extinction deficit (IED), and renewal, a common form of fear relapse. In contrast to our hypothesis, there were no sex differences in the magnitude of the immediate extinction deficit in two different rat strains (Long-Evans and Wistar). However, we did observe a sex difference in the renewal of fear when the extinguished conditioned stimulus was presented outside the extinction context. Male Wistar rats exhibited significantly greater renewal than female rats, a sex difference that has previously been reported after appetitive extinction. Collectively, these data reveal that stress-induced extinction impairments are similar in male and female rats, though the context-dependence of extinction is more pronounced in males.
Mitochondrial membrane potential acts as a retrograde signal to regulate cell cycle progression
Authors: Gorospe Choco Michael , Curbelo Alicia Herrera , Carvalho Gustavo , Marchhart Lisa , Niedźwiecka Katarzyna , Wanrooij Paulina H. 
Published: February 2022

AbstractMitochondria are central to numerous anabolic and catabolic pathways whereby mitochondrial dysfunction has a profound impact on metabolism and can manifest in disease. The consequences of mitochondrial dysfunction can be ameliorated by adaptive responses that rely on mito-cellular crosstalk to communicate mitochondrial distress to the rest of the cell. Such mito-cellular signaling slows cell cycle progression in mitochondrial-DNA deficient (ρ0) Saccharomyces cerevisiae cells, but the initial trigger and the pathway mediating the response has remained unknown. Here, we show that decreased mitochondrial membrane potential (ΔΨm) acts as the initial signal of mitochondrial stress that delays G1-to-S phase transition in both ρ0 and control cells. Accordingly, experimentally increasing ΔΨm was sufficient to restore timely cell cycle progression in ρ0 cells. Neither the RTG retrograde pathway nor central DNA damage checkpoint kinases were involved in mediating this form of mito-cellular communication. The identification of ΔΨm as a novel regulator of cell cycle progression may have implications for disease states involving mitochondrial dysfunction.
Abscisic Acid modulates neighbor proximity-induced leaf hyponasty in Arabidopsis
Authors: Michaud Olivier , Krahmer Johanna , Galbier Florian , Lagier Maud , Galvão Vinicius Costa , Ince Yetkin Çaka , Trevisan Martine , Knerova Jana , Dickinson Patrick , Hibberd Julian M. , Zeeman Samuel C. , Fankhauser Christian 
Published: February 2022

AbstractLeaves of shade avoiding plants like Arabidopsis thaliana change their growth pattern and position in response to a low red to far-red ratio (LRFR) that is encountered in dense plant communities. In LRFR, transcription factors of the phytochrome interacting family (PIFs) are de-repressed. PIFs induce auxin production, which is required to promote leaf hyponasty thereby favoring access to unfiltered sunlight. Abscisic acid (ABA) has also been implicated in the control of leaf hyponasty. In addition, gene expression patterns suggest that LRFR regulates the ABA response. Here we show that, in leaves, LRFR leads to a rapid increase in ABA levels. Changes in ABA levels depend on PIFs, which regulate the expression of genes encoding isoforms of the enzyme catalyzing a rate-limiting step in ABA biosynthesis. Interestingly, ABA biosynthesis and signaling mutants have more erect leaves in white light but respond less to LRFR. Consistent with this, ABA application decreases the leaf angle in white light but this response is inhibited in LRFR. Tissue-specific interference with ABA signaling indicates that an ABA response is required in different cell types for LRFR-induced hyponasty. Collectively, our data indicate LRFR triggers rapid PIF-mediated ABA production. ABA plays a different role in controlling hyponasty in white light compared to LRFR. Moreover, ABA exerts its activity in multiple cell types to control leaf position.One sentence summaryAbscisic acid biosynthesis and signaling are required to promote leaf hyponasty in response to a drop in the red to far-red ratio.
Bridging the rural digital divide: avoiding the user churn of rural public digital cultural services
Authors: Wang Meng , Hua Yuwen , Sun Honglei Lia , Chen Ya 
Published: February 2022

PurposeThe user churn (UC) of rural public digital cultural services (RPDCS) indicates that rural users no longer use RPDCS or have switched to other services. The purpose of this study is to investigate the factors influencing RPDCS's UC and to contribute toward bridging the rural digital divide.Design/methodology/approachBased on the stimulus-organism-response theory, this study proposes a theoretical framework to investigate the factors influencing RPDCS's user churn. A total of 120 RPDCS users were initially recruited and 90 representative participants were chosen. Data were collected from the 90 respondents and 20 follow-up interviews. To examine the proposed framework and validate the correlations between these factors and UC, an analysis of variance (ANOVA) and multiple regression analysis were used. In addition, recommendations are made to avoid the UC of RPDCS to bridge the rural digital divide.FindingsThe results indicate that the UC of RPDCS was stimulated by both physical and ability divides and RPDCS ineffectiveness, resulting in increased churn rates and an exacerbated digital divide. Thus, avoiding the UC of RPDCS is an important way to bridge the rural digital divide, which includes both the physical and ability divides.Originality/valueThis study adds new knowledge about RPDCS and distinguishes it from previous research on public digital cultural services. In addition, the authors discuss how to avoid the UC of RPDCS, to bridge the rural digital divide.