Experimental study of the mechanical transmission of rabbit hemorrhagic disease virus (RHDV2/b) by Aedes Albopictus (Diptera: Clicidae) and Phlebotomus papatasi (diptera: psychodidae); 34447999

Rabbit hemorrhagic disease (RHD) is caused by a lagovirus mainly affecting European rabbits (Oryctolagus cuniculus), although other European and North American lagomorph species are also susceptible to fatal infection by the new viral variant RHDV2/b. In the present work, direct mechanical transmission of the rabbit hemorrhagic disease virus (RHDV2/b variant) by the hematophagous Diptera Aedes albopictus (Skuse) (Diptera: Culicidae) and the sand fly Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) was tested. For each species, six and three laboratory rabbits were exposed to bites of dipterous females partially fed on RHDV2/b viral suspension 2 h and 24 h prior to exposure, respectively. The rabbits were then monitored for clinical changes and mortality for 35 d, and seroconversion was assessed by indirect ELISA. No rabbit died or showed clinical signs of disease, and seroconversion was recorded in two rabbits challenged with P. papatasi females fed the viral suspension 2 h prior to exposure. The number of RHDV2/b RNA copies/female was higher in Ae. albopictus than in P. papatasi but the decrease over time of RNA load in Ae. albopictus was greater than that in P. papatasi. The results of this study suggest the inability of Ae. albopictus to serve as a direct mechanical vector of RHDV2/b, but sand flies could play a role in the local transmission of RHD. © The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America

Education as Risk Factor of Mild Cognitive Impairment:The Link to the Gut Microbiome

Background: With differences apparent in the gut microbiome in mild cognitive impairment (MCI) and dementia, and risk factors of dementia linked to alterations of the gut microbiome, the question remains if gut microbiome characteristics may mediate associations of education with MCI. Objectives: We sought to examine potential mediation of the association of education and MCI by gut microbiome diversity or composition. Design: Cross-sectional study. Setting: Luxembourg, the Greater Region (surrounding areas in Belgium, France, Germany). Participants: Control participants of the Luxembourg Parkinson’s Study. Measurements: Gut microbiome composition, ascertained with 16S rRNA gene amplicon sequencing. Differential abundance, assessed across education groups (0–10, 11–16, 16+ years of education). Alpha diversity (Chao1, Shannon and inverse Simpson indices). Mediation analysis with effect decomposition was conducted with education as exposure, MCI as outcome and gut microbiome metrics as mediators. Results: After exclusion of participants below 50, or with missing data, n=258 participants (n=58 MCI) were included (M [SD] Age=64.6 [8.3] years). Higher education (16+ years) was associated with MCI (Odds ratio natural direct effect=0.35 [95% CI 0.15–0.81]. Streptococcus and Lachnospiraceae-UCG-001 genera were more abundant in higher education. Conclusions: Education is associated with gut microbiome composition and MCI risk without clear evidence for mediation. However, our results suggest signatures of the gut microbiome that have been identified previously in AD and MCI to be reflected in lower education and suggest education as important covariate in microbiome studies

The C5 variant of the butyrylcholinesterase tetramer includes a noncovalently bound 60 kDa lamellipodin fragment

© 2017 by the authors. Licensee MDPI. Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100% of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90% of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10% of adults with C5 BChE

Susceptibility of Aedes albopictus and Culex quinquefasciatus to Japanese encephalitis virus; 35710580

Background: Japanese encephalitis virus (JEV) is the principal cause of mosquito-borne encephalitis in human populations within Asia. If introduced into new geographic areas, it could have further implications for public and animal health. However, potential mosquito vectors for virus transmission have not been fully investigated. The Asian tiger mosquito, Aedes albopictus, has emerged in Europe and is now expanding its geographical range into more northerly latitudes. Culex quinquefasciatus, although absent from Europe, has been detected in Turkey, a country with territory in Europe, and could act as a vector for JEV in other regions. To assess the risk of these invasive species acting as vectors for JEV and therefore potentially contributing to its geographical expansion, we have investigated the vector competence of Ae. albopictus and Cx. quinquefasciatus. Methods: Two colonised lines of Ae. albopictus (Italy and Spain) and a line of Cx. quinquefasciatus (Tanzania) were compared for susceptibility to infection by oral feeding with JEV strain SA-14, genotype III at 106 PFU/ml and maintained at 25 °C. Specimens were processed at 7 and 14 days post-inoculation (dpi). Rates of infection, dissemination and transmission were assessed through detection of viral RNA by real-time polymerase chain reaction (RT-PCR) in mosquito body, legs and saliva, respectively, at each time point. Where possible, infection and dissemination were confirmed by immunohistochemical (IHC) detection of the JEV envelope protein. Results: Aedes albopictus from Italy showed no susceptibility to infection with JEV strain SA-14. Conversely, Ae. albopictus colonised in Spain was susceptible and 100% of infected mosquitoes that were subjected to saliva screening expressed viral RNA at 14 dpi. Culex quinquefasciatus was highly susceptible to infection as early as 7 dpi and 50% of infected mosquitoes that were subjected to saliva screening expressed viral RNA at 14 dpi. Infection and dissemination were confirmed in Cx. quinquefasciatus by IHC detection of JEV envelope protein in both the mid-gut and salivary glands. Conclusions: Aedes albopictus from two different locations in Europe range from being susceptible to JEV and capable of transmission through to being resistant. Culex quinquefasciatus also appears highly susceptible; therefore, both species could potentially act as vectors for JEV and facilitate the emergence of JEV into new regions. Graphical Abstract: Figure not available: see fulltext.] © 2022, The Author(s)

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Chlorpromazine reduces avoidance performance deficit in rats with dorsomedial thalamic lesions

Rats with bilateral lesions of the dorsomedial area of the thalamus were shown to have a significant performance deficit on the acquisition of a one-way active shock-avoidance task relative to sham-operated controls. Administration of chlorpromazine prior to testing was shown to reduce this deficit among the DMT-lesioned animals

Determinants of the current and future distribution of the West Nile virus mosquito vector Culex pipiens in Spain

Changes in environmental conditions, whether related or not to human activities, are continuously modifying the geographic distribution of vectors, which in turn affects the dynamics and distribution of vector-borne infectious diseases. Determining the main ecological drivers of vector distribution and how predicted changes in these drivers may alter their future distributions is therefore of major importance. However, the drivers of vector populations are largely specific to each vector species and region. Here, we identify the most important human-activity-related and bioclimatic predictors affecting the current distribution and habitat suitability of the mosquito Culex pipiens and potential future changes in its distribution in Spain. We determined the niche of occurrence (NOO) of the species, which considers only those areas lying within the range of suitable environmental conditions using presence data. Although almost ubiquitous, the distribution of Cx. pipiens is mostly explained by elevation and the degree of urbanization but also, to a lesser extent, by mean temperatures during the wettest season and temperature seasonality. The combination of these predictors highlights the existence of a heterogeneous pattern of habitat suitability, with most suitable areas located in the southern and northeastern coastal areas of Spain, and unsuitable areas located at higher altitude and in colder regions. Future climatic predictions indicate a net decrease in distribution of up to 29.55%, probably due to warming and greater temperature oscillations. Despite these predicted changes in vector distribution, their effects on the incidence of infectious diseases are, however, difficult to forecast since different processes such as local adaptation to temperature, vector-pathogen interactions, and human-derived changes in landscape may play important roles in shaping the future dynamics of pathogen transmission.info:eu-repo/semantics/acceptedVersio

Modelling the spatial risk of malaria through probability distribution of Anopheles maculipennis s.l. and imported cases

Malaria remains one of the most important infectious diseases globally due to its high incidence and mortality rates. The influx of infected cases from endemic to non-endemic malaria regions like Europe has resulted in a public health concern over sporadic local outbreaks. This is facilitated by the continued presence of competent Anopheles vectors in non-endemic countries. We modelled the potential distribution of the main malaria vector across Spain using the ensemble of eight modelling techniques based on environmental parameters and the Anopheles maculipennis s.l. presence/absence data collected from 2000 to 2020. We then combined this map with the number of imported malaria cases in each municipality to detect the geographic hot spots with a higher risk of local malaria transmission. The malaria vector occurred preferentially in irrigated lands characterized by warm climate conditions and moderate annual precipitation. Some areas surrounding irrigated lands in northern Spain (e.g. Zaragoza, Logroño), mainland areas (e.g. Madrid, Toledo) and in the South (e.g. Huelva), presented a significant likelihood of A. maculipennis s.l. occurrence, with a large overlap with the presence of imported cases of malaria. While the risk of malaria re-emergence in Spain is low, it is not evenly distributed throughout the country. The four recorded local cases of mosquito-borne transmission occurred in areas with a high overlap of imported cases and mosquito presence. Integrating mosquito distribution with human incidence cases provides an effective tool for the quantification of large-scale geographic variation in transmission risk and pinpointing priority areas for targeted surveillance and prevention

Polarized secretion of Leukemia Inhibitory Factor

<p>Abstract</p> <p>Background</p> <p>The direction of cytokine secretion from polarized cells determines the cytokine's cellular targets. Leukemia inhibitory factor (LIF) belongs to the interleukin-6 (IL-6) family of cytokines and signals through LIFR/gp130. Three factors which may regulate the direction of LIF secretion were studied: the site of stimulation, signal peptides, and expression levels. Stimulation with IL-1β is known to promote IL-6 secretion from the stimulated membrane (apical or basolateral) in the human intestinal epithelial cell line Caco-2. Since LIF is related to IL-6, LIF secretion was also tested in Caco-2 following IL-1β stimulation. Signal peptides may influence the trafficking of LIF. Two isoforms of murine LIF, LIF-M and LIF-D, encode different signal peptides which have been associated with different locations of the mature protein in fibroblasts. To determine the effect of the signal peptides on LIF secretion, secretion levels were compared in Madin-Darby canine kidney (MDCK) clones which expressed murine LIF-M or LIF-D or human LIF under the control of an inducible promoter. Low and high levels of LIF expression were also compared since saturation of the apical or basolateral route would reveal specific transporters for LIF.</p> <p>Results</p> <p>When Caco-2 was grown on permeable supports, LIF was secreted constitutively with around 40% secreted into the apical chamber. Stimulation with IL-1β increased LIF production. After treating the apical surface with IL-1β, the percentage secreted apically remained similar to the untreated, whereas, when the cells were stimulated at the basolateral surface only 20% was secreted apically. In MDCK cells, an endogenous LIF-like protein was detected entirely in the apical compartment. The two mLIF isoforms showed no difference in their secretion patterns in MDCK. Interestingly, about 70% of murine and human LIF was secreted apically from MDCK over a 400-fold range of expression levels within clones and a 200,000-fold range across clones.</p> <p>Conclusion</p> <p>The site of stimulation affected the polarity of LIF secretion, while, signal peptides and expression levels did not. Exogenous LIF is transported in MDCK without readily saturated steps.</p

Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins

Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.Funding Agencies|Swedish Research Council (Vetenskapsradet)|2008-3356|Swedish Foundation for Swedish Research|FFL4|Swedish Healthcare System (ALF)||Region Skane||</p