Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo

Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokine but not lipid mediator release during non-infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody-induced arthritis and dermatitis in mice. Neutrophil-specific deletion of CARD9 is sufficient to induce that phenotype. Card9(-/-) neutrophils show defective immune complex-induced gene expression changes and pro-inflammatory chemokine/cytokine release but normal LTB4 production and other short-term responses. In vivo deletion of CARD9 reduces tissue levels of pro-inflammatory chemokines and cytokines but not LTB4. The CARD9-mediated signalling pathway involves Src-family kinases, Syk, PLCγ2, Bcl10/Malt1 and NFκB. Collectively, CARD9-mediated gene expression changes within neutrophils play important roles during non-infectious inflammation in vivo and CARD9 acts as a divergence point between chemokine/cytokine and lipid mediator release

Distribution and diversity of the vectors of Rift Valley fever along the livestock movement routes in the northeastern and coastal regions of Kenya

BACKGROUND : Knowledge of vector ecology is important in understanding the transmission dynamics of vector borne disease. In this study, we determined the distribution and diversity of mosquitoes along the major nomadic livestock movement routes (LMR) in the traditional pastoral ecozone of northeastern Kenya. We focused on the vectors of Rift Valley fever virus (RVFv) with the aim of understanding their ecology and how they can potentially influence the circulation of RVFv. METHODS : Mosquito surveys were conducted during the short and long rainy seasons from November 2012 to August 2014 using CO2-baited CDC light traps at seven sites selected for their proximity to stopover points that provide pasture, water and night bomas (where animals spend nights). We compared mosquito abundance and diversity across the sites, which were located in three ecological zones (IV, V and VI), based on the classification system of agro-ecological zones in Kenya. RESULTS : Over 31,000 mosquitoes were trapped comprising 21 species belonging to 6 genera. Overall mosquito abundance varied significantly by ecological zones and sites. Mansonia species (Ma. uniformis and Ma. africana) were predominant (n = 12,181, 38.3 %). This was followed by the primary RVF vectors, Ae. ochraceus and Ae. mcintoshi comprising 17.9 and 14.98 %, respectively, of the total captures and represented across all sites and ecological zones. The Shannon diversity index ranged from 0.8 to 2.4 with significant zone, site and seasonal variations. There was also significant species richness of RVF vector across ecological zones. CONCLUSION : Our findings highlight differential occurrence of RVFv vectors across ecological zones and sampling sites, which may be important in determining areas at risk of emergence and circulation of RVFv. Moreover, the vector distribution map along LMR generated in this study will guide potential interventions for control of the disease, including strategic vaccination for livestock.International Development Research Centre’s (IDRC) funding to icipe under the Eco-health program.http://www.parasitesandvectors.comhb201

Plant resting site preferences and parity rates among the vectors of Rift Valley Fever in northeastern Kenya

Background Mosquito lifespan can influence the circulation of disease causing pathogens because it affects the time available for infection and transmission. The life-cycle of mosquitoes is determined by intrinsic and environmental factors, which can include the availability of hosts and suitable resting environments that shelter mosquitoes from extreme temperature and desiccating conditions. This study determined the parity rates (an indirect measure of survival) and plant resting preference of vectors of Rift Valley fever (RVF) in northeastern Kenya. Methods Resting mosquitoes were trapped during the rainy and the dry season using a Prokopack aspirator from vegetation, whereas general adult populations were trapped using CDC light traps. At each site, sampling was conducted within a 1 km2 area, subdivided into 500 × 500 m quadrants and four 250 × 250 m sub-quadrants from which two were randomly selected as sampling units. In each sampling unit, plants were randomly selected for aspiration of mosquitoes. Only Aedes mcintoshi and Ae. ochraceus were dissected to determine parity rates while all mosquito species were used to assess plant resting preference. Results Overall, 1124 (79 %, 95 % CI = 76.8–81.1 %) mosquitoes were parous. There was no significant difference in the number of parous Ae. mcintoshi and Ae. ochraceus. Parity was higher in the rainy season than in the dry season. Daily survival rate was estimated to be 0.93 and 0.92 among Ae. ochraceus and Ae. mcintoshi, respectively. Duosperma kilimandscharicum was the most preferred plant species with the highest average capture of primary (3.64) and secondary (5.83) vectors per plant, while Gisekia africana was least preferred. Conclusion Survival rate of each of the two primary vectors of RVF reported in this study may provide an indication that these mosquitoes can potentially play important roles in the circulation of diseases in northern Kenya. Resting preference of the mosquitoes in vegetation may influence their physiology and enhance longevity. Thus, areas with such vegetation may be associated with an increased risk of transmission of arboviruses to livestock and humans

Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya

Background Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence. With each successive outbreak, RVF has been found to expand its geographic distribution to new areas, possibly driven by available vectors. The aim of the present study was to determine if RVF virus (RVFV) transmission risk in two different ecological zones in Kenya could be assessed by looking at the species composition, abundance and distribution of key primary and secondary vector species and the level of virus activity. Methodology Mosquitoes were trapped during short and long rainy seasons in 2014 and 2015 using CO2 baited CDC light traps in two counties which differ in RVF epidemic risk levels(high risk Tana-River and low risk Isiolo),cryo-preserved in liquid nitrogen, transported to the laboratory, and identified to species. Mosquito pools were analyzed for virus infection using cell culture screening and molecular analysis. Findings Over 69,000 mosquitoes were sampled and identified as 40 different species belonging to 6 genera (Aedes, Anopheles, Mansonia, Culex, Aedeomyia, Coquillettidia). The presence and abundance of Aedes mcintoshi and Aedes ochraceus, the primary mosquito vectors associated with RVFV transmission in outbreaks, varied significantly between Tana-River and Isiolo. Ae. mcintoshi was abundant in Tana-River and Isiolo but notably, Aedes ochraceus found in relatively high numbers in Tana-River (n = 1,290), was totally absent in all Isiolo sites. Fourteen virus isolates including Sindbis, Bunyamwera, and West Nile fever viruses were isolated mostly from Ae. mcintoshi sampled in Tana-River. RVFV was not detected in any of the mosquitoes. Conclusion This study presents the geographic distribution and abundance of arbovirus vectors in two Kenyan counties, which may assist with risk assessment for mosquito borne diseases

A New Model and Method for Understanding Wolbachia-Induced Cytoplasmic Incompatibility

Wolbachia are intracellular bacteria transmitted almost exclusively vertically through eggs. In response to this mode of transmission, Wolbachia strategically manipulate their insect hosts' reproduction. In the most common manipulation type, cytoplasmic incompatibility, infected males can only mate with infected females, but infected females can mate with all males. The mechanism of cytoplasmic incompatibility is unknown; theoretical and empirical findings need to converge to broaden our understanding of this phenomenon. For this purpose, two prominent models have been proposed: the mistiming-model and the lock-key-model. The former states that Wolbachia manipulate sperm of infected males to induce a fatal delay of the male pronucleus during the first embryonic division, but that the bacteria can compensate the delay by slowing down mitosis in fertilized eggs. The latter states that Wolbachia deposit damaging “locks” on sperm DNA of infected males, but can also provide matching “keys” in infected eggs to undo the damage. The lock-key-model, however, needs to assume a large number of locks and keys to explain all existing incompatibility patterns. The mistiming-model requires fewer assumptions but has been contradicted by empirical results. We therefore expand the mistiming-model by one quantitative dimension to create the new, so-called goalkeeper-model. Using a method based on formal logic, we show that both lock-key- and goalkeeper-model are consistent with existing data. Compared to the lock-key-model, however, the goalkeeper-model assumes only two factors and provides an idea of the evolutionary emergence of cytoplasmic incompatibility. Available cytological evidence suggests that the hypothesized second factor of the goalkeeper-model may indeed exist. Finally, we suggest empirical tests that would allow to distinguish between the models. Generalizing our results might prove interesting for the study of the mechanism and evolution of other host-parasite interactions

Smallholder Farmers’ Perspectives on Climatic Variability and Adaptation Strategies in East Africa: The Case of Mount Kilimanjaro in Tanzania, Taita and Machakos Hills in Kenya

Climate change is expected to have serious economic and social impacts in East Africa, particularly on rural farmers whose livelihoods largely depend on rain-fed agriculture, hence adaptation is required to offset projected drawbacks of climate change on crop productivity. This paper examines farmers' perceptions and understanding of climatic variability, coping strategies adopted and factors that influence the choice of a particular adaptation. The study uses cross section data collected from 510 farmers in three mountain gradients sites, namely; Mount Kilimanjaro of Tanzania, Taita and Machakos Hills of Kenya. Farmers’ perceptions were compared to actual trend in meteorological records over the last thirty years (1981-2010). The result revealed that farmers in East Africa were partly aware of climate variability, mainly in temperature and rainfall patterns. Many respondents reported that conditions are drier and rainfall timing is becoming less predictable. The perception of farmers on temperature and rainfall were in line with recorded meteorological data, but contrary with that of recorded rainfall in Machakos which was perceived to be decreasing by the farmers. Farmers perceived changes in rainfall and temperature to have negative effects on the production and management of crops. The common adaptation strategies used by farmers include water harvesting, soil conservation techniques and shifting of planting periods. The most important variables affecting farmers choices in regards to adaptation option were, lack of access to credit, farming experience and household size. As a conclusion, there is a need for these factors to be taken into account in the development and implementation of smallholder farmers’ adaptation strategies to climate variability in East Africa. Additionally, dedicated capacity building and extensive outreach initiatives on adaptation through governments, researchers, policy-makers and the farmers groups themselves are needed to achieve large scale success

New Insights into the Evolution of Wolbachia Infections in Filarial Nematodes Inferred from a Large Range of Screened Species

Wolbachia are intriguing symbiotic endobacteria with a peculiar host range that includes arthropods and a single nematode family, the Onchocercidae encompassing agents of filariases. This raises the question of the origin of infection in filariae. Wolbachia infect the female germline and the hypodermis. Some evidences lead to the theory that Wolbachia act as mutualist and coevolved with filariae from one infection event: their removal sterilizes female filariae; all the specimens of a positive species are infected; Wolbachia are vertically inherited; a few species lost the symbiont. However, most data on Wolbachia and filaria relationships derive from studies on few species of Onchocercinae and Dirofilariinae, from mammals.We investigated the Wolbachia distribution testing 35 filarial species, including 28 species and 7 genera and/or subgenera newly screened, using PCR, immunohistochemical staining, whole mount fluorescent analysis, and cocladogenesis analysis. (i) Among the newly screened Onchocercinae from mammals eight species harbour Wolbachia but for some of them, bacteria are absent in the hypodermis, or in variable density. (ii) Wolbachia are not detected in the pathological model Monanema martini and in 8, upon 9, species of Cercopithifilaria. (iii) Supergroup F Wolbachia is identified in two newly screened Mansonella species and in Cercopithifilaria japonica. (iv) Type F Wolbachia infect the intestinal cells and somatic female genital tract. (v) Among Oswaldofilariinae, Waltonellinae and Splendidofilariinae, from saurian, anuran and bird respectively, Wolbachia are not detected.The absence of Wolbachia in 63% of onchocercids, notably in the ancestral Oswaldofilariinae estimated 140 mya old, the diverse tissues or specimens distribution, and a recent lateral transfer in supergroup F Wolbachia, modify the current view on the role and evolution of the endosymbiont and their hosts. Further genomic analyses on some of the newly sampled species are welcomed to decipher the open questions

Labor Market Segmentation and Efficient Bargaining in a Macroeconomic Model

Claas O. Labor Market Segmentation and Efficient Bargaining in a Macroeconomic Model. Center for Mathematical Economics Working Papers. Vol 600. Bielefeld: Center for Mathematical Economics; 2018.This paper studies the implications of a segmented labor market with efficient wage– employment bargaining on the internal labor market and a competitive external labor market on the temporary equilibrium of a closed monetary macroeconomy of the AS– AD type with government activity, fiat money, and expectations. Workers have identical preferences, those on the internal labor market are represented by a labor union. There is no mobility between the labor markets. Union power measured by the share of the production surplus allotted to the union and union density measured by the fraction of workers who are union members impact the functional income distribution, but neither affect the individual employment levels nor the aggregate employment level and the aggregate supply function. The wage on the internal labor market is above the wage on the external labor market if and only if the profit share of total revenue is smaller than under a fully competitive labor market. Unique temporary equilibria exist for all combinations of union power and union density. The paper provides a complete comparative-statics analysis showing in particular a negative price effect of union power and a positive price effect of union density. In general, the effects of union power and union density on any equilibrium value are usually of opposite signs. Single-labor-market models with a fully competitive or a fully unionized labor market are special or limiting cases of the segmented-labor-market model

PPARγ Controls Dectin-1 Expression Required for Host Antifungal Defense against Candida albicans

We recently showed that IL-13 or peroxisome proliferator activated receptor γ (PPARγ) ligands attenuate Candida albicans colonization of the gastrointestinal tract. Here, using a macrophage-specific Dectin-1 deficient mice model, we demonstrate that Dectin-1 is essential to control fungal gastrointestinal infection by PPARγ ligands. We also show that the phagocytosis of yeast and the release of reactive oxygen intermediates in response to Candida albicans challenge are impaired in macrophages from Dectin-1 deficient mice treated with PPARγ ligands or IL-13. Although the Mannose Receptor is not sufficient to trigger antifungal functions during the alternative activation of macrophages, our data establish the involvement of the Mannose Receptor in the initial recognition of non-opsonized Candida albicans by macrophages. We also demonstrate for the first time that the modulation of Dectin-1 expression by IL-13 involves the PPARγ signaling pathway. These findings are consistent with a crucial role for PPARγ in the alternative activation of macrophages by Th2 cytokines. Altogether these data suggest that PPARγ ligands may be of therapeutic value in esophageal and gastrointestinal candidiasis in patients severely immunocompromised or with metabolic diseases in whom the prevalence of candidiasis is considerable