Wing morphology covaries with migration distance in a highly aerial insectivorous songbird

According to classical prediction of aerodynamic theory, birds and other powered fliers that migrate over long distances should have longer and more pointed wings than those that migrate less. However, the association between wing morphology and migratory behavior can be masked by contrasting selective pressures related to foraging behavior, habitat selection and predator avoidance, possibly at the cost of lower flight energetic efficiency. We studied the handwing morphology of Eurasian barn swallows Hirundo rustica from four populations representing a migration distance gradient. This species is an aerial insectivore, so it flies extensively while foraging, and may migrate during the day using a ‘fly-and-forage’ migration strategy. Prolonged foraging flights may reinforce the effects of migration distance on flight morphology. We found that two wings’ aerodynamic properties—isometric handwing length and pointedness, both favoring energetically efficient flight, were more pronounced in barn swallows from populations undertaking longer seasonal migrations compared to less migratory populations. Our result contrast with two recent interspecific comparative studies that either reported no relationship or reported a negative relationship between pointedness and the degree of migratory behavior in hirundines. Our results may thus contribute to confirming the universality of the rule that longer migrations are associated with more pointed wings.Junta de Andalucía P12-RNM-2144National Science Centre DEC-2013/09/B/NZ8/03321European Union 106

Comprehensive analysis of R-spondin fusions and RNF43 mutations implicate novel therapeutic options in colorectal cancer.

PURPOSE Gene fusions involving R-spondin (RSPOfp) and RNF43 mutations have been shown to drive Wnt-dependent tumor initiation in colorectal cancer (CRC). Herein, we aimed to characterize the molecular features of RSPOfp/RNF43 mutated (mut) compared to wildtype CRCs to gain insights into potential rationales for therapeutic strategies. EXPERIMENTAL DESIGN A discovery cohort was classified for RSPOfp/RNF43 status using DNA/RNA sequencing and immunohistochemistry. An independent cohort was used to validate our findings. RESULTS The discovery cohort consisted of 7,245 CRC samples. RSPOfp and RNF43 mutations were detected in 1.3% (n=94) and 6.1% (n=443) of cases. We found 5 RSPO fusion events that had not previously been reported (e.g. IFNGR1-RSPO3). RNF43-mut tumors were associated with right-sided primary tumors. No RSPOfp tumors had RNF43 mutations. In comparison to wildtype CRCs, RSPOfp tumors were characterized by a higher frequency of BRAF, BMPR1A and SMAD4 mutations. APC mutations were observed in only a minority of RSPOfp-positive compared to wildtype cases (4.4 vs. 81.4%). Regarding RNF43 mutations, a higher rate of KMT2D and BRAF mutations were detectable compared to wildtype samples. While RNF43 mutations were associated with a microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) phenotype (64.3%), and a TMB {greater than or equal to}10 mt/Mb (65.8%), RSPOfp was not associated with MSI-H/dMMR. The validation cohort replicated our genetic findings. CONCLUSIONS This is the largest series of RSPOfp/RNF43-mut CRCs reported to date. Comprehensive molecular analyses asserted the unique molecular landscape associated with RSPO/RNF43 and suggested potential alternative strategies to overcome the low clinical impact of Wnt-targeted agents and immunotherapy

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes