Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Estimating dispersal among numerous sites using capture-recapture data

International audienc

Combination of marine and artificial freshwater habitats provides wintering Black-tailed Godwits with landscape supplementation

International audienceMigratory shorebirds, which have an energy-expensive lifestyle, must replenish their body reserves during winter to ensure their survival. Hence, birds have to select wintering habitats that provide the best net energy gain per unit of time while also considering possible disturbances such as predation risk, competition and resource depletion. Different foraging strategies can therefore emerge between species or individuals, such as focusing on one high-quality foraging habitat or making use of multiple habitats, resulting in contrasting distributions and movements patterns. By analysing the movements of 10 wintering Black-tailed Godwits Limosa limosa islandica through GPS-telemetry, our study aimed to understand and describe their spatiotemporal use of wetlands. Our results show that Black-tailed Godwits are flexible in terms of habitat use. All tracked godwits used more than one site during the survey period, with site shifts at both small and large spatial scales, and used multiple habitat types within sites. Indeed, although a dominant use of intertidal areas was observed, birds showed seasonal and daily habitat shifts by visiting inland marshes, saltpans and hunting ponds, with a habitat-specific activity rhythm. Finally, our results support the importance of the protected areas and the management of artificial wetland habitats to ensure the preservation of high-quality wintering areas for godwits