Patterns of Genetic Diversity in Highly Invasive Species: Cogongrass \u3ci\u3e(Imperata cylindrica)\u3c/i\u3e Expansion in the Invaded Range of the Southern United States (US)

The spatial expansions of invasive organisms in the novel range are generally expected to follow an isolation-by-distance relationship (IBD) if the invasion is biologically driven; however, many invasions are facilitated anthropogenically. This research focused on the extant expansion patterns of cogongrass (Imperata cylindrica). Cogongrass is a widespread invasive species throughout the southern United States (US). Patterns of infestation vary among US states. Cogongrass is pyrogenic, and its invasion threatens softwood (Pinus spp.) plantations, a substantial economic market for this US region. Over 600 individuals were sampled from seven invaded US states, using amplified fragment length polymorphisms (AFLPs) to assess genetic diversity and population structure. We suspected that differences in historical management efforts among US states influenced differences in genetic diversity and structure. We detected two genetic lineages at the highest level of analysis. One genetic lineage was locally restricted, whereas the other was found throughout the study region. Admixed individuals were found in all US states and consistently co-occurred with the dominant lineage, suggesting that secondary contact and hybridization may have facilitated expansion. The widespread prevalence of only one of the two detected genetic lineages suggests a primary genetic lineage responsible for on-going population expansion in the US

Phenotypic differentiation among native, expansive and introduced populations influences invasion success

Aim: Humans influence species distributions by modifying the environment and by dispersing species beyond their natural ranges. Populations of species that have established in disjunct regions of the world may exhibit trait differentiation from native populations due to founder effects and adaptations to selection pressures in each distributional region. We compared multiple native, expansive and introduced populations of a single species across the world, considering the influence of environmental stressors and transgenerational effects. Location: United States Gulf and Atlantic coasts, United States interior, European Atlantic and Mediterranean coasts, east coast of Australia. Taxon: Baccharis halimifolia L. (eastern baccharis). Methods: We monitored seed germination, seedling emergence, survival and early growth in a common garden experiment, conducted with over 18,200 seeds from 80 populations. We also evaluated the influence of environmental stress and maternal traits on progeny performance. Results: Introduced European Atlantic populations had faster germination and early growth than native populations. However, this was not the case for the more recently naturalized European Mediterranean populations. Introduced Australian populations grew faster than native populations in non-saline environments but had lower survival in saline conditions commonly encountered in the native range. Similarly, expansive inland US populations germinated faster than coastal native populations in non-saline environments but grew and germinated more slowly in saline environments. Maternal inflorescence and plant size were positively related with seed germination and seedling survival, whereas flower abundance was positively correlated with seedling early growth and survival. However, maternal traits explained a much lower fraction of the total variation in early demographic stages of B. halimifolia than did distributional range. Main conclusions: Phenotypic differentiation could allow B. halimifolia to adapt to different biotic and abiotic selection pressures found in each distributional range, potentially contributing to its success in introduced and expansive ranges

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING: For detailed information per study, see Acknowledgments.This work was supported by a grant from the US National Heart, Lung, and Blood Institute (N01-HL-25195; R01HL 093328 to RSV), a MAIFOR grant from the University Medical Center Mainz, Germany (to PSW), the Center for Translational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, and the Federal Ministry of Research and Education, Germany (BMBF 01EO1003 to PSW). This work was also supported by the research project Greifswald Approach to Individualized Medicine (GANI_MED). GANI_MED was funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania (contract 03IS2061A). We thank all study participants, and the colleagues and coworkers from all cohorts and sites who were involved in the generation of data or in the analysis. We especially thank Andrew Johnson (FHS) for generation of the gene annotation database used for analysis. We thank the German Center for Cardiovascular Research (DZHK e.V.) for supporting the analysis and publication of this project. RSV is a member of the Scientific Advisory Board of the DZHK. Data on CAD and MI were contributed by CARDIoGRAMplusC4D investigators. See Supplemental Acknowledgments for consortium details. PSW, JFF, AS, AT, TZ, RSV, and MD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

A global examination on the differential impacts of roadsides on native vs. exotic and weedy plant species

Roads cause multiple ecological impacts by altering biotic and abiotic conditions that affect ecosystem structure and functioning from local to regional scales. Roadside plant assemblages are driven by the interplay between propagule arrival and seedling establishment, which are highly influenced by roadside characteristics, landscape configuration and road management and maintenance practices. Multiple plant species with different growth forms use roadsides as temporary or permanent habitats and/or dispersal corridors. Over the past seven decades, numerous studies have documented how roadsides affect the distribution and dispersal of plant species; however, a comprehensive review of those is lacking in the literature. Here, we addressed this issue and found 1,098 studies that met all the study eligibility criteria. Over half of the studies reported the effects of roadsides on the distribution and dispersal of exotic/weed species only, of which all but one indicated a positive effect, and around three quarters of the studies that considered native species showed a positive effect of roadsides on such species. Only 10 studies corroborated the use of roadsides as linear corridors by some native species to expand their distributional ranges. Generally, roadsides had the most positive effects for native species in landscapes that are greatly impacted by intensive agriculture, urbanization and forest management, while negative effects were concentrated in areas that have not been highly altered by humans. Furthermore, studies regarding exotic/weed species were concentrated within a few regions of the world. We conclude that roadsides are key to maintain native biodiversity, especially in highly modified anthropogenic landscapes, but also serve as landscape corridors for exotic species. Keywords: Dispersal corridor, Exotic plant invasion, Landscape context, Native species, Roadside ecology, Roadside plant assemblag