Plant perfomance across latitude: the role of plasticity and local adaltation in aquatic plant

Geographic variation can lead to the evolution of different local varieties within a given species, therefore influencing its distribution and genetic structure. We investigated the contribution of plasticity and local adaptation to the performance of a common aquatic plant (Potamogeton pectinatus) in contrasting climates, using reciprocal transplants at three experimental sites across a latitudinal cline in Europe. Plants from 54 genets, originally collected from 14 populations situated within four climatic regions (sub- arctic, cold temperate, mild temperate, and mediterranean) were grown in three different localities within three of these regions (cold temperate, Nor way; mild temperate, The Netherlands; mediterranean, Spain). Tuber production was highest for the mild-temperate genets, irrespective of locality where the genets were grown. Selection coefficients indicated that populations at the European center of the species distribution perform better than all other populations, at all sites. However, marginal populations showed changes in life-histor y traits, such as compressed life cycles in the north and true perenniality in the south, that may allow them to perform better locally, at the limits of their distribution range. Our results thus suggest that local adaptation may overlap spatially with center–peripher y gra- dients in performance caused by genetic factors (such as genetic drift and inbreeding in range-marginal populations).Peer reviewe

Addition of nintedanib or placebo to neoadjuvant gemcitabine and cisplatin in locally advanced muscle-invasive bladder cancer (NEOBLADE) : a double-blind, randomised, phase 2 trial

Background Recurrence is common after neoadjuvant chemotherapy and radical treatment for muscle-invasive bladder cancer. We investigated the effect of adding nintedanib to neoadjuvant chemotherapy on response and survival in muscle-invasive bladder cancer. Methods NEOBLADE was a parallel-arm, double-blind, randomised, placebo-controlled, phase 2 trial of neoadjuvant gemcitabine and cisplatin chemotherapy with nintedanib or placebo in locally advanced muscle-invasive bladder cancer. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0–1, were recruited from 15 hospitals in the UK. Patients were randomly assigned (1:1) to nintedanib or placebo using permuted blocks with random block sizes of two or four, stratified by centre and glomerular filtration rate. Treatments were allocated using an interactive web-based system, and patients and investigators were masked to treatment allocation throughout the study. Patients received oral nintedanib (150 mg or 200 mg twice daily for 12 weeks) or placebo, in addition to usual neoadjuvant chemotherapy with intravenous gemcitabine 1000 mg/m2 on days 1 and 8 and intravenous cisplatin 70 mg/m2 on day 1 of a 3-weekly cycle. The primary endpoint was pathological complete response rate, assessed at cystectomy or at day 8 of cycle 3 (plus or minus 7 days) if cystectomy did not occur. Primary analyses were done in the intention-to-treat population. The trial is registered with EudraCT, 2012-004895-01, and ISRCTN, 56349930, and has completed planned recruitment. Findings Between Dec 4, 2014, and Sept 3, 2018, 120 patients were recruited and were randomly allocated to receive nintedanib (n=57) or placebo (n=63). The median follow-up for the study was 33·5 months (IQR 14·0–44·0). Pathological complete response in the intention-to-treat population was reached in 21 (37%) of 57 patients in the nintedanib group and 20 (32%) of 63 in the placebo group (odds ratio [OR] 1·25, 70% CI 0·84–1·87; p=0·28). Grade 3 or worse toxicities were observed in 53 (93%) of 57 participants who received nintedanib and 50 (79%) of 63 patients in the placebo group (OR 1·65, 95% CI 0·74–3·65; p=0·24). The most common grade 3 or worse adverse events were thromboembolic events (17 [30%] of 57 patients in the nintedanib group vs 13 [21%] of 63 patients in the placebo group [OR 1·63, 95% CI 0·71–3·76; p=0·29]) and decreased neutrophil count (22 [39%] in the nintedanib group vs seven [11%] in the placebo group [5·03, 1·95–13·00; p=0·0006]). 45 treatment-related serious adverse events occurred in the nintedanib group and 43 occurred in the placebo group. One treatment-related death occurred in the placebo group, which was due to myocardial infarction. Interpretation The addition of nintedanib to chemotherapy was safe but did not improve the rate of pathological complete response in muscle-invasive bladder cancer

TP53 polymorphisms and haplotypes in breast, cervical and ovarian cancer

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN032369 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Plant perfomance across latitude: the role of plasticity and local adaltation in aquatic plant

Geographic variation can lead to the evolution of different local varieties within a given species, therefore influencing its distribution and genetic structure. We investigated the contribution of plasticity and local adaptation to the performance of a common aquatic plant (Potamogeton pectinatus) in contrasting climates, using reciprocal transplants at three experimental sites across a latitudinal cline in Europe. Plants from 54 genets, originally collected from 14 populations situated within four climatic regions (sub- arctic, cold temperate, mild temperate, and mediterranean) were grown in three different localities within three of these regions (cold temperate, Nor way; mild temperate, The Netherlands; mediterranean, Spain). Tuber production was highest for the mild-temperate genets, irrespective of locality where the genets were grown. Selection coefficients indicated that populations at the European center of the species distribution perform better than all other populations, at all sites. However, marginal populations showed changes in life-histor y traits, such as compressed life cycles in the north and true perenniality in the south, that may allow them to perform better locally, at the limits of their distribution range. Our results thus suggest that local adaptation may overlap spatially with center–peripher y gra- dients in performance caused by genetic factors (such as genetic drift and inbreeding in range-marginal populations).Peer reviewe

Plant performance across latitude: the role of plasticity and local adaptation in a clonal aquatic plant

Geographic variation can lead to the evolution of different local varieties within a given species, therefore influencing its distribution and genetic structure. We investigated the contribution of plasticity and local adaptation to the performance of a common aquatic plant (Potamogeton pectinatus) in contrasting climates, using reciprocal transplants at three experimental sites across a latitudinal cline in Europe. Plants from 54 genets, originally collected from 14 populations situated within four climatic regions (subarctic, cold temperate, mild temperate, and mediterranean) were grown in three different localities within three of these regions (cold temperate, Norway; mild temperate, The Netherlands; mediterranean, Spain). Tuber production was highest for the mild-temperate genets, irrespective of locality where the genets were grown. Selection coefficients indicated that populations at the European center of the species distribution perform better than all other populations, at all sites. However, marginal populations showed changes in life-history traits, such as compressed life cycles in the north and true perenniality in the south, that may allow them to perform better locally, at the limits of their distribution range. Our results thus suggest that local adaptation may overlap spatially with center–periphery gradients in performance caused by genetic factors (such as genetic drift and inbreeding in range-marginal populations Key words:climate; clonal reproduction; distribution; latitude; [KEYWORDS: climate; clonal reproduction; distribution; latitude; local adaptation; plasticity; Potamogeton pectinatus; reciprocal transplant; shoot morphology; survival; vegetative growth]

Environment and biogeography drive aquatic plant and cladoceran species richness across Europe

1. The relative role of environmental and regional processes in determining patterns of biodiversity may vary across spatial scales. In inland aquatic communities, macrophytes and zooplankton have the potential to disperse over large spatial scales (hundreds of kilometres), but the role of environmental and regional processes in determining species richness (SR) at different spatial scales is poorly understood. 2. To assess the relative importance of environmental and regional processes acting on both regional (within-region) and continental (among-region) scales, we surveyed 139 waterbodies in five geographic regions (Spain, Italy, the Netherlands, Scotland and Norway) and in each region measured environmental variables, descriptors of connectivity and SR of two aquatic taxa, namely aquatic plants and cladocerans. 3. Analyses using boosted regression trees and generalised linear models, integrated with multiple imputation of missing data, indicated that both environmental and regional processes were related to local SR. 4. Total phosphorus was the main environmental correlate of SR, showing a unimodal relationship with both taxonomic groups. Conductivity and lake depth were also related to cladoceran SR, and Secchi depth was related to aquatic plant richness. 5. The SR of aquatic plants and cladocerans were significantly correlated, but this relationship was mainly indirect (i.e. determined by the effect of common environmental variables). 6. The limited role of connectivity and space (lack of spatial autocorrelation in model residuals) relative to environment suggests that dispersal limitation is not as important as the environment in explaining richness patterns for both groups within regions. However, region identity strongly influenced SR, which suggests an important effect of biogeographic factors (e.g. the level of endemicity; the number of unique species in each region) and/or dispersal limitation at the continental scale. 7. We conclude that environmental factors and biogeographic processes largely determine the patterns of local and regional SR in aquatic plants and zooplankton

Plant performance across latitude: the role of plasticity and local adaptation in an aquatic plant

Geographic variation can lead to the evolution of different local varieties within a given species, therefore influencing its distribution and genetic structure. We investigated the contribution of plasticity and local adaptation to the performance of a common aquatic plant (Potamogeton pectinatus) in contrasting climates, using reciprocal transplants at three experimental sites across a latitudinal cline in Europe. Plants from 54 genets, originally collected from 14 populations situated within four climatic regions (subarctic, cold temperate, mild temperate, and mediterranean) were grown in three different localities within three of these regions (cold temperate, Norway; mild temperate, The Netherlands; mediterranean, Spain). Tuber production was highest for the mild-temperate genets, irrespective of locality where the genets were grown. Selection coefficients indicated that populations at the European center of the species distribution perform better than all other populations, at all sites. However, marginal populations showed changes in life-history traits, such as compressed life cycles in the north and true perenniality in the south, that may allow them to perform better locally, at the limits of their distribution range. Our results thus suggest that local adaptation may overlap spatially with center–periphery gradients in performance caused by genetic factors (such as genetic drift and inbreeding in range-marginal populations)