Wigginsfernandez7009

Funds allocated to biodiversity are associated with a reduction in the number of threatened species and the rate of biodiversity loss of about 1% per year. Each US$1 billion investment in biodiversity is associated with an annual reduction in the proportion of threatened to total species of about 0.57%. Population growth is associated with lower financial support for biodiversity and an increase in the proportion of threatened to total species in a country.The initiation and progression of cancers reflect the underlying process of somatic evolution, in which the diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination-a key diversification mechanism throughout all strata of life. On the basis of observations of spontaneous fusions involving cancer cells, the reported genetic instability of polypoid cells and the precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions between genetically distinct cancer cells could produce parasexual recombination. Using differentially labelled tumour cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer both in vitro and in vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modelling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumour cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape (relative to strictly asexual populations), which may substantially accelerate a tumour's ability to adapt to new selective pressures.As our planet emerges into a new epoch in which humans dominate the Earth system, it is imperative that societies initiate a new phase of responsible environmental stewardship. Here we argue that information from the past has a valuable role to play in enhancing the sustainability and resilience of our societies. We highlight the ways that past data can be mobilized for a variety of efforts, from supporting conservation to increasing agricultural sustainability and food security. At a practical level, solutions from the past often do not require fossil fuels, can be locally run and managed, and have been tested over the long term. Past failures reveal non-viable solutions and expose vulnerabilities. To more effectively leverage increasing knowledge about the past, we advocate greater cross-disciplinary collaboration, systematic engagement with stakeholders and policymakers, and approaches that bring together the best of the past with the cutting-edge technologies and solutions of tomorrow.Assessing extinction risk from climate drivers is a major goal of conservation science. Few studies, however, include a long-term perspective of climate change. Without explicit integration, such long-term temperature trends and their interactions with short-term climate change may be so dominant that they blur or even reverse the apparent direct relationship between climate change and extinction. Here we evaluate how observed genus-level extinctions of arthropods, bivalves, cnidarians, echinoderms, foraminifera, gastropods, mammals and reptiles in the geological past can be predicted from the interaction of long-term temperature trends with short-term climate change. We compare synergistic palaeoclimate interaction (a short-term change on top of a long-term trend in the same direction) to antagonistic palaeoclimate interaction such as long-term cooling followed by short-term warming. Synergistic palaeoclimate interaction increases extinction risk by up to 40%. The memory of palaeoclimate interaction including the climate history experienced by ancestral lineages can be up to 60 Myr long. The effect size of palaeoclimate interaction is similar to other key factors such as geographic range, abundance or clade membership. Insights arising from this previously unknown driver of extinction risk might attenuate recent predictions of climate-change-induced biodiversity loss.Admixed populations are routinely excluded from genomic studies due to concerns over population structure. Here, we present a statistical framework and software package, Tractor, to facilitate the inclusion of admixed individuals in association studies by leveraging local ancestry. We test Tractor with simulated and empirical two-way admixed African-European cohorts. Tractor generates accurate ancestry-specific effect-size estimates and P values, can boost genome-wide association study (GWAS) power and improves the resolution of association signals. Using a local ancestry-aware regression model, we replicate known hits for blood lipids, discover novel hits missed by standard GWAS and localize signals closer to putative causal variants.To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P  less then  5 × 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal P = 1.28 × 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10-10  less then  P  less then  5 × 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.Clinical laboratory tests are a critical component of the continuum of care. We evaluate the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank (n = 363,228 individuals). We identify 1,857 loci associated with at least one trait, containing 3,374 fine-mapped associations and additional sets of large-effect (>0.1 s.d.) protein-altering, human leukocyte antigen (HLA) and copy number variant (CNV) associations. Through Mendelian randomization (MR) analysis, we discover 51 causal relationships, including previously known agonistic effects of urate on gout and cystatin C on stroke. Finally, we develop polygenic risk scores (PRSs) for each biomarker and build 'multi-PRS' models for diseases using 35 PRSs simultaneously, which improved chronic kidney disease, type 2 diabetes, gout and alcoholic cirrhosis genetic risk stratification in an independent dataset (FinnGen; n = 135,500) relative to single-disease PRSs. Together, our results delineate the genetic basis of biomarkers and their causal influences on diseases and improve genetic risk stratification for common diseases.Despite the strong genetic basis of psychiatric disorders, the underlying molecular mechanisms are largely unmapped. RNA-binding proteins (RBPs) are responsible for most post-transcriptional regulation, from splicing to translation to localization. RBPs thus act as key gatekeepers of cellular homeostasis, especially in the brain. However, quantifying the pathogenic contribution of noncoding variants impacting RBP target sites is challenging. Here, we leverage a deep learning approach that can accurately predict the RBP target site dysregulation effects of mutations and discover that RBP dysregulation is a principal contributor to psychiatric disorder risk. RBP dysregulation explains a substantial amount of heritability not captured by large-scale molecular quantitative trait loci studies and has a stronger impact than common coding region variants. We share the genome-wide profiles of RBP dysregulation, which we use to identify DDHD2 as a candidate schizophrenia risk gene. This resource provides a new analytical framework to connect the full range of RNA regulation to complex disease.The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory1,2, neurologic3 and neoplastic diseases4. Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure remains uncertain5-11. Nevertheless, twin studies clearly suggest host genetics as a driver of microbiome composition11. In a genome-wide association analysis of 8,956 German individuals, we identified 38 genetic loci to be associated with single bacteria and overall microbiome composition. Further analyses confirm the identified associations of ABO histo-blood groups and FUT2 secretor status with Bacteroides and Faecalibacterium spp. Mendelian randomization analysis suggests causative and protective effects of gut microbes, with clade-specific effects on inflammatory bowel disease. This holistic investigative approach of the host, its genetics and its associated microbial communities as a 'metaorganism' broaden our understanding of disease etiology, and emphasize the potential for implementing microbiota in disease treatment and management.Cerebrovascular injuries can cause severe edema and inflammation that adversely affect human health. XL413 manufacturer Here, we observed that recanalization after successful endovascular thrombectomy for acute large vessel occlusion was associated with cerebral edema and poor clinical outcomes in patients who experienced hemorrhagic transformation. link2 To understand this process, we developed a cerebrovascular injury model using transcranial ultrasound that enabled spatiotemporal evaluation of resident and peripheral myeloid cells. We discovered that injurious and reparative responses diverged based on time and cellular origin. Resident microglia initially stabilized damaged vessels in a purinergic receptor-dependent manner, which was followed by an influx of myelomonocytic cells that caused severe edema. Prolonged blockade of myeloid cell recruitment with anti-adhesion molecule therapy prevented severe edema but also promoted neuronal destruction and fibrosis by interfering with vascular repair subsequently orchestrated by proinflammatory monocytes and proangiogenic repair-associated microglia (RAM). link3 These data demonstrate how temporally distinct myeloid cell responses can contain, exacerbate and ultimately repair a cerebrovascular injury.The recent introduction of Pseudogymnoascus destructans (the fungal pathogen that causes white-nose syndrome in bats) from Eurasia to North America has resulted in the collapse of North American bat populations and restructured species communities. The long evolutionary history between P. destructans and bats in Eurasia makes understanding host life history essential to uncovering the ecology of P. destructans. In this Review, we combine information on pathogen and host biology to understand the patterns of P. destructans spread, seasonal transmission ecology, the pathogenesis of white-nose syndrome and the cross-scale impact from individual hosts to ecosystems. Collectively, this research highlights how early pathogen detection and quantification of host impacts has accelerated the understanding of this newly emerging infectious disease.