Improved transient silencing of gene expression in the mosquito female Aedes aegypti

Gene silencing using RNA interference (RNAi) has become a widely used genetic technique to study gene function in many organisms. In insects, this technique is often applied through the delivery of dsRNA. In the adult female Aedes aegypti, a main vector of human-infecting arboviruses, efficiency of gene silencing following dsRNA injection varies greatly according to targeted genes. Difficult knockdowns using dsRNA can thus hamper gene function analysis. Here, by analysing silencing of three different genes in female Ae. aegypti (p400, ago2 and E75), we show that gene silencing can indeed be dsRNA sequence dependent but different efficiencies do not correlate with dsRNA length. Our findings suggest that silencing is likely also gene dependent, probably due to gene-specific tissue expression and/or feedback mechanisms. We demonstrate that use of high doses of dsRNA can improve knockdown efficiency, and injection of a transfection reagent along with dsRNA reduces the variability in efficiency between replicates. Finally, we show that gene silencing cannot be achieved using siRNA injection in Ae. aegypti adult females. Overall, this work should help future gene function analyses using RNAi in adult females Ae. aegypti, leading toward a better understanding of physiological and infectious processes.     

Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.     

Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases - SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly...     

Cutting Edge Issues in the Churg–Strauss Syndrome

Churg–Strauss syndrome (CSS) is a rare systemic small-vessel vasculitis that develops in the background of bronchial asthma, which is characterized by eosinophilia and eosinophilic infiltration of various tissues. It belongs to the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides. The triggering factors and pathogenesis of CSS are still unknown. The possible role of eotaxin-3 and CCR4-related chemokines in selective recruitment of eosinophils to the target tissues in CSS has been recently suggested, but the role of eosinophilic inflammation in the development of vasculitic lesions is not completely understood. From the clinical view, two distinct phenotypes of the disease are slowly emerging depending on the ANCA-positivity status. Glucocorticoids are still the mainstay of treatment; however, data are accumulating regarding the beneficial role of novel immunosuppressants and biologic compounds, especially in patients with poorer prognosis.