bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogeography and resistome of pneumococcal meningitis in West Africa before and after vaccine introduction
Authors: Senghore Madikay , Tientcheu Peggy-Estelle , Worwui Archibald Kwame , Jarju Sheikh , Okoi Catherine , Suso Sambou M. S. , Foster-Nyarko Ebenezer , Ebruke Chinelo , Sonko Mohamadou , Kourna Mamdou Hama , Agossou Joseph , Tsolenyanu Enyonam , Renner Lorna Awo , Ansong Daniel , Sanneh Bakary , Cisse Catherine Boni , Boula Angeline , Miwanda Berthe , Lo Stephanie W. , Gladstone Rebecca A. , Schwartz Stephanie , Hawkins Paulina , McGee Lesley , Klugman Keith P. , Breiman Robert F. , Bentley Stephen D. , Mwenda Jason M. , Kwambana-Adams Brenda Anna , Antonio Martin 
Published: July 2021

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of

Streptococcus pneumoniae

which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185

S

.

pneumoniae

isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.
Examining risk factors for weight change during midlife: A Mendelian randomization study
Authors: Power Grace M. , Tyrrell Jessica , Gkatzionis Apostolos , Fang Si , Heron Jon , Davey Smith George , Richardson Tom G. 
Published: July 2021

AbstractBackgroundMaintaining a healthy weight across adulthood reduces morbidity and mortality risk in later life. This study aimed to examine factors contributing to weight change over a one-year interval in midlife. While conventional epidemiological analyses have reported risk factors associated with weight change, biases such as confounding present challenges when inferring causality.MethodsConventional observational analyses were used in addition to a one-sample Mendelian randomization (MR) approach to estimate the genetically predicted effects of four exposures (alcohol consumption, smoking intensity, educational attainment and Alzheimer’s disease liability) on weight change (mean age: 56.9 years) using data from 329 531 participants in the UK Biobank.ResultsOne-sample MR indicated strong evidence that Alzheimer’s disease liability increased the odds of weight loss whilst conventional analyses reported little evidence of this. In MR and conventional epidemiological analyses, higher educational attainment was associated with maintaining a steady weight. In addition, higher alcohol consumption was associated with weight gain in conventional analyses only. Finally, whilst conventional analyses showed that smoking heaviness was associated with weight gain, the converse was supported by MR, which indicated strong evidence that smoking heaviness reduced the odds of weight gain.ConclusionsOur findings highlight important risk factors for weight change in midlife and emphasise the public health importance of evaluating the dynamic changes to body weight within a causal inference setting.
Assessing the Utility of Low Resolution Brain Imaging: Treatment of Infant Hydrocephalus
Authors: Harper Joshua R. , Cherukuri Venkateswararao , O’Reilly Tom , Yu Mingzhao , Mbabazi-Kabachelor Edith , Mulando Ronald , Sheth Kevin N. , Webb Andrew G. , Warf Benjamin C. , Kulkarni Abhaya V. , Monga Vishal , Schiff Steven J. 
Published: July 2021

AbstractAs low-field MRI technology is being disseminated into clinical settings around the world, it is important to assess the image quality required to properly diagnose and treat a given disease and evaluate the role of machine learning algorithms, such as deep learning, in the enhancement of lower quality images. In this post-hoc analysis of an ongoing randomized clinical trial, we assessed the diagnostic utility of reduced-quality and deep learning enhanced images for hydrocephalus treatment planning. CT images of post-infectious infant hydrocephalus were degraded in terms of spatial resolution, noise, and contrast between brain and CSF and enhanced using deep learning algorithms. Both degraded and enhanced images were presented to three experienced pediatric neurosurgeons accustomed to working in low- to middle-income countries (LMIC) for assessment of clinical utility in treatment planning for hydrocephalus. In addition, enhanced images were presented alongside their ground-truth CT counterparts in order to assess whether reconstruction errors caused by the deep learning enhancement routine were acceptable to the evaluators. Results indicate that image resolution and contrast-to-noise ratio between brain and CSF predict the likelihood of an image being characterized as useful for hydrocephalus treatment planning. Deep learning enhancement substantially increases contrast-to-noise ratio improving the apparent likelihood of the image being useful; however, deep learning enhancement introduces structural errors which create a substantial risk of misleading clinical interpretation. We find that images with lower quality than is customarily acceptable can be useful for hydrocephalus treatment planning. Moreover, low quality images may be preferable to images enhanced with deep learning, since they do not introduce the risk of misleading information which could misguide treatment decisions. These findings advocate for new standards in assessing acceptable image quality for clinical use.
regentrans: a framework and R package for using genomics to study regional pathogen transmission
Authors: Hoffman Sophie , Lapp Zena , Wang Joyce , Snitkin Evan S 
Published: July 2021

AbstractIncreasing evidence of regional pathogen transmission networks highlights the importance of investigating the dissemination of multidrug-resistant organisms (MDROs) across a region to identify where transmission is occurring and how pathogens move across regions. We developed a framework for investigating MDRO regional transmission dynamics using whole-genome sequencing data and created regentrans, an easy-to-use, open source R package that implements these methods (https://github.com/Snitkin-Lab-Umich/regentrans). Using a dataset of over 400 carbapenem-resistant Klebsiella pneumoniae isolates collected from patients in 21 long-term acute care hospitals over a one-year period, we demonstrate how to use our framework to gain insights into differences in inter- and intra-facility transmission across different facilities and over time. This framework and corresponding R package will allow investigators to better understand the origins and transmission patterns of MDROs, which is the first step in understanding how to stop transmission at the regional level.Impact statementIncreasing evidence suggests that pathogen transmission occurs across healthcare facilities. Genomic epidemiologic investigations into regional transmission shed light on potential drivers of regional prevalence and can inform coordinated interventions across healthcare facilities to reduce transmission. Here we present a framework for studying regional pathogen transmission using whole-genome sequencing data, and a corresponding open-source R package, regentrans, that implements these methods to streamline analyses and make them more accessible to other researchers and public health practitioners. We also discuss how these methods can be extended to study transmission in other settings.Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.The regentrans R package can be downloaded from GitHub: https://github.com/Snitkin-Lab-Umich/regentrans/The manuscript figures are generated from regentrans example data and can also be found on GitHub: https://github.com/Snitkin-Lab-Umich/regentrans/tree/master/vignettes/manuscript_figuresThe example data used in the package and manuscript is from BioProject accession no. PRJNA415194. The specific SRA accession numbers can be found in supplementary file S1. The metadata corresponding to these sequences can be found on the SRA Run Selector (isolate column) and as example data in the regentrans package.The KPNIH1 sequence was used as the reference genome (SRA accession number SRZ080789)
Genome-wide characterization of Salmonella Typhimurium genes required for the fitness under iron restriction
Authors: Karash Sardar , Jiang Tieshan , Kwon Young Min 
Published: July 2021

AbstractIron is a crucial element for bacterial survival and virulence. During Salmonella infection, the host utilizes a variety of mechanisms to starve the pathogen from iron. However, Salmonella activates distinctive defense mechanisms to acquire iron and survive in iron-restricted host environments. Yet, the comprehensive set of the conditionally essential genes that underpin Salmonella survival under iron-restricted niches have not been fully explored. Here, we employed transposon sequencing (Tn-seq) method for high-resolution elucidation of the genes in Salmonella Typhimurium (S. Typhimurium) 14028s strain required for the growth under the in vitro conditions with 4 different levels of iron restriction achieved by iron chelator 2,2′-Dipyridine (Dip): mild (100 and 250), moderate (250) and severe iron restriction (400 μM). We found that the fitness of the mutants reduced significantly for 28 genes, suggesting the importance of these genes for the growth under iron restriction. These genes include sufABCDSE, iron transport fepD, siderophore tonB, sigma factor E ropE, phosphate transport pstAB, and zinc exporter zntA. The siderophore gene tonB was required in mild and moderate iron-restricted conditions, but they became dispensable in severe iron-restricted conditions. Remarkably, rpoE was required in moderate and severe iron restrictions, leading to complete attenuation of the mutant under these conditions. We also identified 30 genes for which the deletion of the genes resulted in increased fitness under iron-restricted conditions. The findings broaden our knowledge of how S. Typhimurium survives in iron-deficient environments, which could be utilized for the development of new therapeutic strategies targeting the pathways vital for iron metabolism, trafficking, and scavenging.
Microbiome structure of a wildDrosophilacommunity along tropical elevational gradients and comparison to laboratory lines
Authors: Brown Joel J. , Jandová Anna , Jeffs Christopher T. , Higgie Megan , Nováková Eva , Lewis Owen T. , Hrček Jan 
Published: July 2021

AbstractVariation along environmental gradients in host-associated microbial communities is not well understood, compared to free-living microbial communities. Because elevational gradients may serve as natural proxies for climate change, understanding patterns along these gradients can inform our understanding of the threats hosts and their symbiotic microbes face in a warming world. In this study, we analysed bacterial microbiomes from pupae and adults of fourDrosophilaspecies native to Australian tropical rainforests. We sampled wild individuals at high and low elevation along two mountain gradients, to determine natural diversity patterns. Further, we sampled laboratory-reared individuals from isofemale lines established from the same localities, to see if any natural patterns are retained in the lab. In both environments, we controlled for diet to help elucidate other deterministic patterns of microbiome composition. We found small but significant differences inDrosophilabacterial community composition across elevation, with some notable taxonomic differences between differentDrosophilaspecies and sites. Further, we found that field-collected fly pupae had significantly richer microbiomes than laboratory-reared pupae. We also found similar microbiome composition in both types of provided diet, suggesting that the significant differences found amongDrosophilamicrobiomes are the product of surrounding environments with different bacterial species pools, possibly bound to elevational differences in temperature. Our results suggest that comparative studies between lab and field specimens help reveal the true variability in microbiome communities that can exist within a single species.ImportanceBacteria form microbial communities inside most higher-level organisms, but we know little about how the microbiome varies along environmental gradients and between natural host populations and laboratory colonies. To explore such effects on insect-associated microbiomes, we studied gut microbiome in fourDrosophilaspecies over two mountain gradients in tropical Australia. We also compared these data to individuals kept in the laboratory to understand how different settings changed microbiome communities. We found that field sampled individuals had significantly higher microbiome diversity than those from the lab. In wildDrosophilapopulations, elevation explains a small but significant amount of the variation in their microbial communities. Our study highlights the importance of environmental bacterial sources forDrosophilamicrobiome composition across elevational gradients, and shows how comparative studies help reveal the true flexibility in microbiome communities that can exist within a species.
Crocosphaeraas a major consumer of fixed nitrogen despite its capability of nitrogen fixation
Authors: Masuda Takako , Inomura Keisuke , Kodama Taketoshi , Shiozaki Takuhei , Kitajima Satoshi , Armin Gabrielle , Matsui Takato , Suzuki Koji , Takeda Shigenobu , Prášil Ondřej , Furuya Ken 
Published: July 2021

AbstractCrocosphaera watsonii(hereafterCrocosphaera) is a key nitrogen (N) fixer in the ocean, but its ability to consume combined N sources is still unclear. Usingin situmicrocosm incubations with an ecological model, we show thatCrocosphaerahas high competitive capability both under low and moderately high combined N concentrations. In field incubations,Crocosphaeraaccounted for the highest consumption of ammonium and nitrate, followed by pico-eukaryotes. The model analysis shows that cells have a high ammonium uptake rate (∼7 mol N (mol N)-1d-1at the maximum), which allows them to compete against pico-eukaryotes and non-diazotrophic cyanobacteria when combined N is sufficiently available. Even when combined N is depleted, their capability of nitrogen fixation allows higher growth rates compared to potential competitors. These results suggest the high fitness ofCrocosphaerain combined N limiting, oligotrophic oceans, and thus heightens its potential significance in its ecosystem and in biogeochemical cycling.
CDKs-mediated phosphorylation of PNKP is required for end-processing of single-strand DNA gaps on Okazaki Fragments and genome stability
Authors: Tsukada Kaima , Miyake Tomoko , Imamura Rikiya , Saikawa Kotaro , Saito Mizuki , Kase Naoya , Ishiai Masamichi , Matsumoto Yoshihisa , Shimada Mikio 
Published: July 2021

AbstractPolynucleotide kinase phosphatase (PNKP) has enzymatic activities as 3′ -phosphatase and 5′ - kinase of DNA ends to promote DNA ligation and repair. Here, we show that cyclin-dependent kinases (CDKs) regulate the phosphorylation of threonine 118 (T118) in PNKP. This phosphorylation allows recruitment to the gapped DNA structure found in single-strand DNA nicks and/or gaps between Okazaki fragments (OFs) during DNA replication. T118A (alanine)-substituted PNKP-expressing cells exhibited accumulation of single-strand DNA gaps in S phase and accelerated replication fork progression. Furthermore, PNKP is involved in poly (ADP-ribose) polymerase 1 (PARP1)-dependent replication gap filling as a backup pathway in the absence of OFs ligation. Altogether, our data suggest that CDK-mediated PNKP phosphorylation at T118 is important for its recruitment to single-strand DNA gaps to proceed with OFs ligation and its backup errors via the gap-filling pathway to maintain genome stability.
Sleep spindle dynamics suggest over-consolidation in post-traumatic stress disorder
Authors: van der Heijden A.C. , Hofman W.F. , de Boer M. , Nijdam M.J. , van Marle H. J. F. , Jongedijk R. A. , Olff M. , Talamini L.M. 
Published: July 2021

AbstractDevastating and persisting traumatic memories are a central symptom of post-traumatic stress disorder (PTSD). Sleep problems are highly co-occurrent with PTSD and intertwined with its etiology. Notably, sleep hosts memory consolidation processes, supported by sleep spindles (11-16 Hz). Here we assess the hypothesis that intrusive memory symptoms in PTSD may arise from excessive memory consolidation, reflected in exaggerated spindling. We use a newly developed spindle detection method, entailing minimal assumptions regarding spindle phenotype, to assess spindle activity in PTSD patients and traumatized controls (n=2×14, matched on gender). Our results show increased spindle activity in PTSD, which positively correlates with daytime intrusive memory symptoms. Together, these findings provide a putative mechanism through which profound sleep disturbance in PTSD may contribute to memory problems. Due to its uniform and unbiased approach, the new, minimal assumption spindle detection method seems a promising tool to detect aberrant spindling in psychiatric disorders.
Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing
Authors: Frey Nina , Tortola Luigi , Egli David , Janjuha Sharan , Marquart Kim Fabiano , Rothgangl Tanja , Ampenberger Franziska , Kopf Manfred , Schwank Gerald 
Published: July 2021

AbstractPancreatic ductal adenocarcinoma (PDA) is an inherently immune cell deprived tumor, characterized by desmoplastic stroma and suppressive immune cells. Here we systematically dissected PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening, and identified Rnf31 and Vps4b as essential factors required for escaping CD8+ T cell-killing. Using murine PDA cells and human PDA organoids, we demonstrate that Rnf31 protects from TNF-mediated caspase 8 cleavage and subsequent apoptosis induction. For Vps4b we found that inactivation impairs autophagy, resulting in increased accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis. Orthotopic transplantation of Rnf31− or Vps4b deficient pancreatic tumors, moreover, revealed increased CD8+ T cell infiltration and effector function, and markedly reduced tumor growth in mice. Our work uncovers vulnerabilities in PDA that might be exploited to render these tumors more susceptible to the immune system.
Dual Roles for Nuclear RNAi Argonautes in C. elegans Dosage Compensation
Authors: Davis Michael B. , Chawla Bahaar , Jash Eshna , Tushman Lillian E. , Haines Rebecca A. , Csankovszki Györgyi 
Published: July 2021

ABSTRACTDosage compensation involves chromosome-wide gene regulatory mechanisms which impact higher order chromatin structure and are crucial for organismal health. Using a genetic approach, we identified Argonaute genes which promote dosage compensation in C. elegans. Dosage compensation in C. elegans hermaphrodites is initiated by the silencing of xol-1 and subsequent activation of the Dosage Compensation Complex (DCC) which binds to both hermaphrodite X chromosomes and reduces transcriptional output by twofold. A hallmark phenotype of dosage compensation mutants is decondensation of the X chromosomes. We characterized this phenotype in Argonaute mutants using X chromosome paint probe and fluorescence microscopy. We found that while nuclear Argonaute mutants hrde-1 and nrde-3 exhibit de-repression of xol-1 transcripts, they also effect X chromosome condensation in a xol-1-independent manner. We also characterized the physiological contribution of Argonaute genes to dosage compensation using genetic assays and find that hrde-1 and nrde-3, together with the piRNA Argonaute prg-1, contribute to healthy dosage compensation both upstream and downstream of xol-1.