Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Turnip mosaic virus : potential for crop losses in the grain belt of New South Wales, Australia

The potential of Turnip mosaic virus (TuMV) to infect and damage cool season crops in the grain belt of New South Wales, Australia, was investigated by serological tests on 24,689 dicot weed, grain, and forage specimens from 1999 to 2007 and infectivity/pathogenicity tests with six isolates. Natural infection by TuMV was common in Brassicaceae weeds. Infected grain crops included mustard (Brassica juncea), field pea (Pisum sativum), chickpea (Cicer arietinum), and coriander (Coriandrum sativum). Forage (turnip, Brassica rapa) was also infected. None of 9,816 canola (Brassica napus, at least 19 cultivars) or 1,967 faba bean (Vicia faba, three cultivars) plants were infected. Six isolates from weeds, mustard, and chickpea were inoculated on a range of weed and crop species including four B. napus pathotype differential lines. Inoculated Brassicaceae weeds, mustard, field pea cv. ‘Cressy Blue’, coriander, Chinese cabbage (B. rapa), and forage turnip (B. rapa) were usually infected. Field pea cv. Dundale and radishes (Raphanus sativus) were infected infrequently. Symptoms were severe in mustard, forage turnip, chickpea, and field pea. The reportedly susceptible canola cv. ‘Outback’ displayed only variable infectivity and mild symptoms for five isolates and no infectivity for one isolate. Faba bean, field pea cv. ‘Excell’, and two B. napus differentials appeared to be non-hosts. The results suggest that TuMV strains naturalised in Brassicaceae weeds in NSW in 1999–2007 could damage mustard, field pea, and forage turnip, but not canola or faba bean. These NSW strains appeared to be distinct from strains that damage canola in Europe, North America, and Asia

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC