10 research outputs found

    The Changing Amazon Hydrological Cycle—Inferences From Over 200 Years of Tree‐Ring Oxygen Isotope Data

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    Changes to the Amazon hydrological cycle have important consequences for world's largest tropical forest, and the biodiversity it contains. However, a scarcity of long-term climate data in the region makes it hard to contextualize recent observed changes in Amazon hydrology. Here, we explore to what extent tree-ring oxygen isotope (δ18OTR) chronologies can inform us about hydrological changes in the Amazon over the past two centuries. Two δ18OTR records from northern Bolivia and the Ecuadorian Andes are presented. The Ecuador record spans 1799–2012 (n = 16 trees) and the Bolivia record spans 1860–2014 (n = 32 trees), making them the longest δ18OTR records from the Amazon, and among the most highly-replicated δ18OTR records from the tropics to date. The two chronologies correlate well at interannual and decadal timescales, despite coming from sites more than 1,500 km apart. Both δ18OTR records are strongly related to interannual variation in Amazon River discharge measured at Óbidos, and accumulated upwind precipitation, suggesting a common climatic driver. In both records a strong increase in δ18OTR was observed up until approximately 1950, consistent with positive trends in the few other existing δ18O proxy records from across the Amazon. Considering all possible drivers of this long-term increase, a reduction in rainout fraction over the basin driven by rising sea surface temperatures in the North Atlantic is suggested as the most likely cause. The upward trend in δ18OTR reverses over the past 1–2 decades, consistent with the observed strengthening of the Amazon hydrological cycle since approximately 1990

    Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

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    Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

    Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

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    Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    An assessment of land-atmosphere interactions over South America using satellites, reanalysis and two global climate models

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    In South America, land-atmosphere interactions have an important impact on climate, particularly the regional hydrological cycle, but detailed evaluation of these processes in global climate models has been limited. Focussing on the satellite-era period of 2003–2014, we assess land-atmosphere interactions on annual to seasonal timescales over South America in satellite products, a novel reanalysis (ERA5-Land) and two global climate models: the Brazilian Global Atmospheric Model version 1.2 (BAM-1.2) and the UK Hadley Centre Global Environment Model version 3 (HadGEM3). We identify key features of South American land-atmosphere interactions represented in satellite and model datasets, including seasonal variation in coupling strength, large-scale spatial variation in the sensitivity of evapotranspiration to surface moisture, and a dipole in evaporative regime across the continent. Differences between products are also identified, with ERA5-Land, HadGEM3 and BAM-1.2 showing opposite interactions to satellites over parts of the Amazon and the Cerrado, and stronger land-atmosphere coupling along the North Atlantic coast. Where models and satellites disagree on the strength and direction of land-atmosphere interactions, precipitation biases and misrepresentation of processes controlling surface soil moisture are implicated as likely drivers. These results show where improvement of model processes could reduce uncertainty in the modelled climate response to land-use change, and highlight where model biases could unrealistically amplify drying or wetting trends in future climate projections. Finally, HadGEM3 and BAM-1.2 are consistent with the median response of an ensemble of nine CMIP6 models, showing they are broadly representative of the latest generation of climate models

    Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

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    10.1038/s41467-021-23143-7Nature Communications121329

    Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

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    Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between Mar

    Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

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    The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation

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