bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockout of ykcB, a putative glycosyltransferase, leads to vancomycin resistance in Bacillus subtilis
Authors: Ishikawa Kazuya , Shirakawa Riko , Takano Daiki , Kosaki Tomoki , Furuta Kazuyuki , Kaito Chikara 
Published: September 2022

ABSTRACTVancomycin resistance of gram-positive bacteria poses a serious health concern around the world. In this study, we searched for vancomycin-resistant mutants from a gene deletion library of a model gram-positive bacterium, Bacillus subtilis, to elucidate the mechanism of vancomycin resistance. We found that knockout of ykcB, a glycosyltransferase that is expected to utilize C55-P-glucose to glycosylate cell surface components, caused vancomycin resistance in B. subtilis. Knockout of ykcB altered the susceptibility to multiple antibiotics, including sensitization to β-lactams, and increased the pathogenicity to silkworms. Furthermore, the ykcB-knockout mutant had: i) an increased content of diglucosyl diacylglycerol, a glycolipid that shares a precursor with C55-P-glucose, ii) a decreased amount of lipoteichoic acid, and iii) decreased biofilm formation ability. These phenotypes and vancomycin resistance were abolished by knockout of ykcC, a ykcB-operon partner involved in C55-P-glucose synthesis. Overexpression of ykcC enhanced vancomycin resistance in both wild-type B. subtilis and the ykcB-knockout mutant. These findings suggest that ykcB deficiency induces structural changes of cell surface molecules depending on the ykcC function, leading to resistance to vancomycin, decreased biofilm formation ability, and increased pathogenicity to silkworms.IMPORTANCEAlthough vancomycin is effective against gram-positive bacteria, vancomycin-resistant bacteria is a major public health concern. While the vancomycin resistance mechanisms of clinically important bacteria such as Staphylococcus aureus, Enterococcus faecium, and Streptococcus pneumoniae are well-studied, they remain unclear in other gram-positive bacteria. In the present study, we searched for vancomycin-resistant mutants from a gene deletion library of a model gram-positive bacterium, Bacillus subtilis, and found that knockout of a putative glycosyltransferase, ykcB, caused vancomycin resistance in B. subtilis. Notably, unlike the previously reported vancomycin-resistant bacterial strains, ykcB-deficient B. subtilis exhibited increased virulence while maintaining its growth rate. Our results broaden the fundamental understanding of vancomycin-resistance mechanisms in gram-positive bacteria.
Impact of reinfection with SARS-CoV-2 Omicron variants in previously infected hamsters
Authors: Shiwa-Sudo Nozomi , Sakai Yusuke , Iwata-Yoshikawa Naoko , Watanabe Shinji , Yamada Souichi , Kuroda Yudai , Yamamoto Tsukasa , Shirakura Masayuki , Fujisaki Seiichiro , Miyazaki Kaya , Miura Hideka , Nagata Shiho , Fukushi Shuetsu , Maeda Ken , Hasegawa Hideki , Suzuki Tadaki , Nagata Noriyo 
Published: September 2022

ABSTRACTThe diversity of SARS-CoV-2 mutations raises the possibility of reinfection of individuals previously infected with earlier variants, and this risk is further increased by the emergence of the B.1.1.529 Omicron variant. In this study, we used anin vivo, hamster infection model to assess the potential for individuals previously infected with SARS-CoV-2 to be reinfected with Omicron variant and we also investigated the pathology associated with such infections. Initially, Syrian hamsters were inoculated with a lineage A, B.1.1.7, B.1.351, B.1.617.2 or a subvariant of Omicron, BA.1 strain and then reinfected with the BA.1 strain 5 weeks later. Subsequently, the impact of reinfection with Omicron subvariants (BA.1 and BA.2) in individuals previously infected with the BA.1 strain was examined. Although viral infection and replication were suppressed in both the upper and lower airways, following reinfection, virus-associated RNA was detected in the airways of most hamsters. Viral replication was more strongly suppressed in the lower respiratory tract than in the upper respiratory tract. Consistent amino acid substitutions were observed in the upper respiratory tract of infected hamsters after primary infection with variant BA.1, whereas diverse mutations appeared in hamsters reinfected with the same variant. Histopathology showed no acute pneumonia or disease enhancement in any of the reinfection groups and, in addition, the expression of inflammatory cytokines and chemokines in the airways of reinfected animals was only mildly elevated. These findings are important for understanding the risk of reinfection with new variants of SARS-CoV-2.IMPORTANCEThe emergence of SARS-CoV-2 variants and the widespread use of COVID-19 vaccines has resulted in individual differences in immune status against SARS-CoV-2. A decay in immunity over time and the emergence of variants that partially evade the immune response can also lead to reinfection. In this study, we demonstrated that, in hamsters, immunity acquired following primary infection with previous SARS-CoV-2 variants was effective in preventing the onset of pneumonia after reinfection with the Omicron variant. However, viral infection and multiplication in the upper respiratory tract were still observed after reinfection. We also showed that more diverse nonsynonymous mutations appeared in the upper respiratory tract of reinfected hamsters that had acquired immunity from primary infection. This hamster model reveals the within-host evolution of SARS-CoV-2 and its pathology after reinfection, and provides important information for countermeasures against diversifying SARS-CoV-2 variants.
Adapting UK Biobank imaging for use in a routine memory clinic setting: the Oxford Brain Health Clinic
Authors: Griffanti Ludovica , Gillis Grace , O’Donoghue M. Clare , Blane Jasmine , Pretorius Pieter M. , Mitchell Robert , Aikin Nicola , Lindsay Karen , Campbell Jon , Semple Juliet , Alfaro-Almagro Fidel , Smith Stephen M. , Miller Karla L. , Martos Lola , Raymont Vanessa , Mackay Clare E. 
Published: September 2022

AbstractThe Oxford Brain Health Clinic (BHC) is a joint clinical-research service that provides memory clinic patients and clinicians access to high-quality assessments not routinely available, including brain MRI aligned with the UK Biobank imaging study (UKB).In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) compared measures from BHC patients to the largest brain MRI study in the world (ultimately 100,000 participants).Adaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences (i.e., additional imaging modalities) to improve patients’ tolerance for the MRI assessment. We adapted the UKB structural MRI analysis pipeline to take into account the characteristics of a memory clinic population (e.g., high amount of white matter hyperintensities and hippocampal atrophy). We then compared the imaging derived phenotypes (IDPs) extracted from the structural scans to visual ratings from radiology reports, non-imaging factors (age, cognition) and to reference distributions derived from UKB data.Of the first 108 BHC attendees (August 2020-November 2021), 92.5% completed the clinical scans, 88.0% consented to use of data for research, and 48.1% completed at least one additional research sequence, demonstrating that the protocol is well tolerated. The high rates of consent to research makes this a unique real-world quality research dataset routinely captured in a clinical service. Modified tissue-type segmentation with lesion masking greatly improved grey matter volume estimation. CSF-masking marginally improved hippocampal segmentation. The IDPs were in line with radiology reports and showed significant associations with age and cognitive performance, in line with the literature. Due to the age difference between memory clinic patients of the BHC (age range 65-101 years, average 78.3 years) and UKB participants (44-82 years, average 64 years), additional scans on elderly healthy controls are needed to improve reference distributions. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.
Investigating the genotoxicity of occupational pesticide exposures in Arab countries: Protocol of a systematic review and meta-analysis
Authors: Sherif Moustafa , Makame Khadija Ramadhan , Östlundh Linda , Paulo Marilia Silva , Nemmar Abderrahim , Ali Bassam R. , Rifai Rami Al , Nagy Károly , Ádám Balázs 
Published: September 2022

AbstractBackgroundTens of millions of agricultural workers are directly exposed to pesticides through handling pesticide products, mostly in developing countries. Systematic data synthesis on the genotoxic consequences of such occupational exposures and their human health risks in agricultural settings is required in Arab countries. We aim to conduct a systematic review and, if possible, a meta-analysis to review published literature about the genotoxicity of occupational pesticide exposures in Arab countries, with the objectives of characterising the (1) prevalence rates of genotoxic pesticide exposures, (2) extent of genotoxic insults, (3) attributed risk factors, and (4) preventive measures against pesticide-induced genotoxic effects detectable by biomonitoring.MethodsThe research will follow the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. A comprehensive search will be conducted in November 2022 in the electronic databases PubMed (NLM), EMBASE (Elsevier), Web of Science (Clarivate), Scopus (Elsevier), and Agricola in addition to WHO Index Medicus for the Eastern Mediterranean (IMEMR). The search will be performed without any restrictions for publication years. A filter for English and Arabic language will be applied.The systematic search will include agricultural workers over the age of 18 years, located in Arabic speaking countries of the Middle East and North Africa (MENA) region, occupationally exposed to pesticides inducing genotoxic insult detectable by biomonitoring.Records identified in the search will be imported into the systematic review tool Covidence for blinded screening and selection by two reviewers independently. The reviewers will then extract data and conduct risk of bias assessment using the Navigation Guide RoB tool and the RoB-SPEO tool. The results will be synthetized narratively in summary tables, and, if findings allow, meta-analysis, including subgroup and sensitivity analysis, will be conducted on the prevalence of genotoxic pesticide exposures, and on the effect size of risk factors. The systematic review methodology does not require ethics approval.DiscussionThe systematic review will consider various types of pesticide exposures and genotoxicity biomarker assays to determine prevalence and extent of such occupational genotoxic insults, the correlation between genetic damage and various risk factors, e.g. work conditions, types of pesticides, environmental exposure routes, and the applied preventive measures. The review will provide gap-filling information about genotoxic pesticide exposures of agricultural workers in the local context, as well as it will contribute to our general knowledge on pesticide genotoxicity.Systematic review registrationPROSPERO registration number: CRD42022314453.
Depressive symptoms anticipate behavioral and emotional factors among older adults: A prospective cross-lagged panel design
Authors: Kazan Joseph , Gerlach Andrew R. , Mizuno Akiko , Andreescu Carmen , Aizenstein Howard J. , Ward Scott , Buente Kara J. , Stahl Sarah T. 
Published: September 2022

ABSTRACTThis study examined the temporal relationship among depression, anxiety, insomnia, perceived stress, and physical activity in adults aged 60+ years with a history of major depressive disorder. We conducted a longitudinal study with 12 weeks of follow-up. Assessments consisted of phone or video interviews and included questionnaires evaluating depression, anxiety, insomnia, perceived stress, and physical activity. Our analytic approach consisted of a depression-focused cross-lagged panel model (CLPM) to examine week-to-week correlations among the five measures. The depression-focused CLPM identified statistically significant week-to-week self-predictive effects for each of the five measures. Higher depressive symptom burden was a strong predictor of increased stress, greater insomnia, and less physical activity the following week. No other cross-measure predictions were statistically significant. Our analytical approach clarifies the directional relationship among variables that typically co-occur with depression showing that higher depression symptom burden predisposes older adults to poor sleep, a reduced level of daytime activity, and a greater sense of stress. These findings support the need for longitudinal assessments and targeted interventions for reducing symptoms of depression in older adults.
Family planning uptake and its associated factors among women of reproductive age in Uganda: an insight from the Uganda Demographic and Health Survey 2016
Authors: Ochen Anthony Mark , Chi Primus Che 
Published: September 2022

AbstractDespite the government efforts to reduce the high fertility levels and increase uptake of family planning services in Uganda, family planning use was still low at 30% which is the lowest in the East African region. This study was undertaken to determine the prevalence and factors associated with the uptake of family planning methods among women of reproductive age in Uganda. This is a community-based cross-sectional study that utilized secondary data from the Uganda Demographic and Health Survey (UDHS) of 2016. The survey data was downloaded from the Measure Demographic Health Survey website after data use permission was granted. Data was collected from a representative sample of women of the reproductive age group (15-49 years) from all the 15 regions in Uganda. A total of 19,088 eligible women were interviewed but interviews were completed with 18,506 women. Data analysis was performed using SPSS statistical software version 32.0 where univariable, bivariable, and multivariable analyses were conducted. The prevalence of family planning use was found to be 29.3% and that of modern contraceptive use was found to be 26.6%. Multivariable analysis showed higher odds of current family planning use among older women (40-44 years) (aOR=2.09, 95% CI: 1.40-3.12); women who had attained the secondary level of education (aOR=1.91, 95% CI: 1.32-2.76); those living in households with the highest wealth index (aOR=1.87, 95% CI: 1.29-2.72); and awareness of the availability of family planning methods (aOR=1.41, 95% CI: 1.17-1.72). In conclusion, the study found a low prevalence of current family planning use among women of reproductive age and this calls for more efforts toward the advancement of women’s education, awareness creation, designing policies to popularize use of FP among adolescents and young women, and socio-economic empowerment of women.
Norepinephrine regulates Ca2+ signals and fate of oligodendrocyte progenitor cells in the cortex
Authors: Fiore Frederic , Dereddi Ram R. , Alhalaseh Khaleel , Coban Ilknur , Harb Ali , Agarwal Amit 
Published: September 2022

AbstractOligodendrocyte precursor cells (OPCs) represent the most abundant group of proliferating cells in the adult central nervous system. OPCs serve as progenitors for oligodendrocyte (OLs) throughout the life, and contribute to developmental and adaptive myelination, and myelin repair during diseased state. OPCs make synaptic and extra-synaptic contacts with axons, and detect and respond to neuronal activity. How OPCs translate the information relayed by the neuronal activity into Ca2+ signals, which in turn influence their fate and survival, is less understood. We developed novel transgenic mouse lines expressing a cytosolic and membrane anchored variants of genetically encoded Ca2+ sensors (GCaMP6f or mGCaMP6s) in OPCs, performed 2-photon microscopy in the somatosensory cortex of the awake behaving mice, and simultaneously monitored intracellular Ca2+ signals and their cell-fate progression. We found Ca2+ signals in OPCs mainly occur within processes and confine to micrometer-size segments called Ca2+ microdomains. Microdomain Ca2+ signals enhanced in OPCs when mice engage in exploratory behavior. OPCs exhibit distinct Ca2+ signals while they proliferate to maintain their precursor pool or differentiate to generate new OL. When mice engaged in exploratory behavior, the cortical projections of noradrenergic neurons in locus coeruleus showed increased firing rate and norepinephrine release. Norepinephrine activated all three subtypes of alpha1 adrenergic receptor expressed by OPCs and evoked intracellular Ca2+ increase in OPCs. A chemogenetic activation of noradrenergic neurons, promoted differentiation of cortical OPCs into OL, and at the same time suppressed OPC proliferation rate. Hence, we uncovered that various cell types of oligodendrocyte lineage exhibits unique signatures of Ca2+ activity, which these cells might integrate for making their fate decisions, and norepinephrine signaling can be a potent regulator of OPC fate.
Interaction with C21ORF2 controls the cellular functioning of the NEK1 kinase
Authors: Gregorczyk Mateusz , Pastore Graziana , Lis Pawel , Lange Sven , Lamoliatte Frederic , Macartney Thomas , Toth Rachel , Brown Fiona , Hastie James , Durocher Daniel , Rouse John 
Published: September 2022

AbstractNEK1 is a pleiotropic protein kinase implicated in mitosis, ciliogenesis and DNA repair but little is known about its regulation or targets. Its relevance for human health is underscored by the association of NEK1 mutations with human diseases including axial spondylometaphyseal dyplasia (SMD) and amyotrophic lateral sclerosis (ALS). Mutations in the C21ORF2 gene are associated with a similar pattern of human diseases, suggesting close functional links with NEK1. Here we report that in unperturbed, untransformed cells, endogenous NEK1 and C21ORF2 form a tight complex that does not appear to contain other proteins. A small acidic domain “CID: C21ORF2 interaction domain” at the C-terminus of NEK1 is necessary and sufficient to interact with C21ORF2, and pathogenic mutations in this region disrupt the complex. AlphaFold modelling predicts with high confidence an extended binding interface between a leucine-rich repeat (LRR) domain in the N-terminal half of C21ORF2 and a stretch of the NEK1-CID; mutating residues mediating electrostatic interactions within this interface disrupts the NEK1-C21ORF2 interaction. This model also explains why pathogenic mutations disrupt the complex. We go on to show that the kinase activity of NEK1 and its interaction with C21ORF2 is critical for NEK1 function in cells. These data reveal C21ORF2 as a regulatory subunit of NEK1, illuminating our understanding of how this kinase is regulated and NEK1-C21ORF2-associated diseases.
Intestinal stem cell aging at single-cell resolution: functional perturbations alter cell developmental trajectory reversed by gerotherapeutics
Authors: Choi Jiahn , Houston Michele , Wang Ruixuan , Ye Kenny , Li Wenge , Zhang Xusheng , Huffman Derek M. , Augenlicht Leonard H. 
Published: September 2022

AbstractThe intestinal epithelium is consists of cells derived from continuously cycling Lgr5hi intestinal stem cells (Lgr5hi ISCs) that mature developmentally in an order fashion as the cells progress along the crypt-luminal axis. Perturbed function of Lgr5hi ISCs with aging is well documented but the consequent impact on overall mucosal homeostasis has not been defined. Using single-cell RNA sequencing, the progressive maturation of progeny was dissected in mouse intestine, which revealed that transcriptional reprogramming with aging in Lgr5hi ISCs retarded cell maturation in their progression along the crypt-luminal axis. Importantly, treatment with metformin or rapamycin at a late stage of mouse lifespan reversed the effects of aging on function of Lgr5hi ISCs and subsequent maturation of progenitors. The effects of metformin and rapamycin overlapped in reversing changes of transcriptional profiles, but were also complementary, with metformin more efficient than rapamycin in correcting the developmental trajectory. Therefore, our data identify novel effects of aging on stem cells and the maturation of their daughter cells contributing to the decline of functional Lgr5hi ISCs and the correction by geroprotectors.
Excel-SBOL Converter: Creating SBOL from Excel Templates and Vice Versa
Authors: Mante Jeanet , Abam Julian , Samineni Sai P. , Pötzsch Isabel M. , Singh Prubhtej , Beal Jacob , Myers Chris J. 
Published: September 2022

AbstractStandards support synthetic biology research by enabling the exchange of component information. However, using formal representations, such as the Synthetic Biology Open Language (SBOL), typically requires either a thorough understanding of these standards or a suite of tools developed in concurrence with the ontologies. Since these tools may be a barrier for use by many practitioners, the Excel-SBOL Converter was developed to allow easier use of SBOL and integration into existing workflows. The converter consists of two Python libraries: one that converts Excel templates to SBOL, and another that converts SBOL to an Excel workbook. Both libraries can be used either directly or via a SynBioHub plugin. We illustrate the operation of the Excel-SBOL Converter with two case studies: uploading experimental data with the study’s metadata linked to the measurements and downloading the Cello part repository.Graphical TOC Entry
Methanotrophs are vigorous H2S oxidizers using a sulfide:quinone oxidoreductase and a ba3-type terminal oxidase
Authors: Schmitz Rob A. , Peeters Stijn H. , Mohammadi Sepehr S. , Berben Tom , van Erven Timo , Iosif Carmen A. , van Alen Theo , Versantvoort Wouter , Jetten Mike S.M. , Op den Camp Huub J.M. , Pol Arjan 
Published: September 2022

ABSTRACTHydrogen sulfide (H2S) is produced in a wide range of anoxic environments where sulfate (SO42−) reduction is coupled to decomposition of organic matter. In the same environments, methane (CH4) is the end product of an anaerobic food chain and both H2S and CH4 diffuse upwards into oxic zones where aerobic microorganisms can utilize these gases. Methane-oxidizing bacteria are known to oxidize a major part of the produced CH4 in these ecosystems, mitigating the emissions of this potent greenhouse gas to the atmosphere. However, how methanotrophy is affected by toxic H2S is largely unexplored. Here, we show that a single microorganism can oxidize CH4 and H2S simultaneously. By oxidizing H2S, the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV can alleviate the inhibitory effects on CH4 oxidation. In response to H2S, strain SolV upregulated a type III sulfide:quinone oxidoreductase (SQR) and a sulfide-insensitive ba3-type terminal oxidase to dissipate the reducing equivalents derived from H2S oxidation. Through extensive chemostat cultivation of M. fumariolicum SolV we demonstrate that it converts high loads of H2S to elemental sulfur (S0). Moreover, we show chemolithoautotrophy by tracing 13CO2 fixation into new biomass by using H2S as sole energy source. Molecular surveys revealed several putative SQR sequences in a range of proteobacterial methanotrophs from various environments, suggesting that H2S detoxification is much more widespread in methanotrophs than previously assumed, enabling them to connect carbon and sulfur cycles in new ways.