The genetic basis of host preference and resting behavior in the major African malaria vector, Anopheles arabiensis

Malaria transmission is dependent on the propensity of Anopheles mosquitoes to bite humans (anthropophily) instead of other dead end hosts. Recent increases in the usage of Long Lasting Insecticide Treated Nets (LLINs) in Africa have been associated with reductions in highly anthropophilic and endophilic vectors such as Anopheles gambiae s.s., leaving species with a broader host range, such as Anopheles arabiensis, as the most prominent remaining source of transmission in many settings. An. arabiensis appears to be more of a generalist in terms of its host choice and resting behavior, which may be due to phenotypic plasticity and/or segregating allelic variation. To investigate the genetic basis of host choice and resting behavior in An. arabiensis we sequenced the genomes of 23 human-fed and 25 cattle-fed mosquitoes collected both in-doors and out-doors in the Kilombero Valley, Tanzania. We identified a total of 4,820,851 SNPs, which were used to conduct the first genome-wide estimates of “SNP heritability”for host choice and resting behavior in this species. A genetic component was detected for host choice (human vs cow fed; permuted P = 0.002), but there was no evidence of a genetic component for resting behavior (indoors versus outside; permuted P = 0.465). A principal component analysis (PCA) segregated individuals based on genomic variation into three groups which were characterized by differences at the 2Rb and/or 3Ra paracentromeric chromosome inversions. There was a non-random distribution of cattle-fed mosquitoes between the PCA clusters, suggesting that alleles linked to the 2Rb and/or 3Ra inversions may influence host choice. Using a novel inversion genotyping assay, we detected a significant enrichment of the standard arrangement (non-inverted) of 3Ra among cattle-fed mosquitoes (N = 129) versus all non-cattle-fed individuals. Thus, tracking the frequency of the 3Ra in An. arabiensis populations may be of use to infer selection on host choice behavior within these vector populations; possibly in response to vector control. Controlled host-choice assays are needed to discern whether the observed genetic component has a direct relationship with innate host preference. A better understanding of the genetic basis for host feeding behavior in An. arabiensis may also open avenues for novel vector control strategies based on driving genes for zoophily into wild mosquito populations

Effectiveness and cost of an incentive-based intervention on food safety and income in "dibiteries" in Dakar, Senegal

BACKGROUND: Rapid urbanisation in Sub-Saharan African cities such as Dakar, Senegal, leads to proliferation of informal braised meat restaurants known as "dibiteries". Dibiteries do not often comply with minimal hygiene and food safety standards. The primary objective of this study was to assess the effectiveness and cost of a good hygiene practice intervention, identify factors that incentivize hygiene improvement and how that impacts on dibiteries' income. METHODS: A randomized controlled trial was carried out in Dakar dibiteries. The 120 random samples of braised meat were collected in three phases: (i) one-month pre-intervention, (ii) 2 months post-intervention, (iii) 10 months post-intervention. The trial comprised four groups of 10 dibiteries each: (a) (control) received no intervention, (b) a standardized training module, (c) a hygiene kit, (d) a training module and hygiene kit. Laboratory analysis of samples determined the total aerobic mesophilic flora (TAMF), thermotolerant coliforms (TC) and Staphylococcus aureus (SA). A questionnaire-based survey and focus group discussion were used to identify pre-intervention hygiene practices, and socioeconomic determinants of hygiene management in dibiteries post-intervention, respectively. RESULTS: Samples were found to be contaminated with TAMF, TC and SA. In phase 1, 27 and 13% of the samples contained TC and SA, respectively. In phase 2, no significant improvement of contamination rates was seen. In phase 3, microbiological quality of samples was significantly improved, with only 11.5% showing contamination with any of the bacterial species analysed (p < 0.1). Compared to the control group, only samples from dibiteries in group (b) had significantly reduced bacterial load in phase 3. The cost of intervention and hygiene improvement was estimated at 67 FCFA ($0.12) and 41 FCFA ($ 0.07) / day respectively and did not significantly impact on dibiterie profitability. Incentives to sustainably implement good hygiene practices were mainly linked to access to secure long-term workspaces. CONCLUSION: This intervention may have worked, but globally the results are mixed and not quite significant. However, continuous training in good hygiene practice and access to secure and sustainable infrastructure for dibiterie restaurants are the incentives necessary to achieve sustainable investments and behavioural change. We recommend further intervention refinement and testing other factors for promoting the adoption of good hygiene practices in the dibiteries in relation to consumers health risk

An experimental hut study to quantify the effect of DDT and airborne pyrethroids on entomological parameters of malaria transmission

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Current malaria vector control programmes rely on insecticides with rapid contact toxicity. However, spatial repellents can also be applied to reduce man-vector contact, which might ultimately impact malaria transmission. The aim of this study was to quantify effects of airborne pyrethroids from coils and DDT used an indoor residual spray (IRS) on entomological parameters that influence malaria transmission.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The effect of Transfluthrin and Metofluthrin coils compared to DDT on house entry, exit and indoor feeding behaviour of Anopheles gambiae sensu lato were measured in experimental huts in the field and in the semi-field. Outcomes were deterrence - reduction in house entry of mosquitoes; irritancy or excito-repellency – induced premature exit of mosquitoes; blood feeding inhibition and effect on mosquito fecundity.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Transfluthrin coils, Metofluthrin coils and DDT reduced human vector contact through deterrence by 38%, 30% and 8%, respectively and induced half of the mosquitoes to leave huts before feeding (56%, 55% and 48%, respectively). Almost all mosquitoes inside huts with Metofluthrin and Transfluthrin coils and more than three quarters of mosquitoes in the DDT hut did not feed, almost none laid eggs and 67%, 72% and 70% of all mosquitoes collected from Transfluthrin, Metofluthrin and DDT huts, respectively had died after 24 hours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; This study highlights that airborne pyrethroids and DDT affect a range of anopheline mosquito behaviours that are important parameters in malaria transmission, namely deterrence, irritancy/excito-repellency and blood-feeding inhibition. These effects are in addition to significant toxicity and reduced mosquito fecundity that affect mosquito densities and, therefore, provide community protection against diseases for both users and non-users. Airborne insecticides and freshly applied DDT had similar effects on deterrence, irritancy and feeding inhibition. Therefore, it is suggested that airborne pyrethroids, if delivered in suitable formats, may complement existing mainstream vector control tools

Consumer perception on purchase decision factors and health indicators related to the quality and safety of meat sold in dibiteries in Dakar, Senegal

Accelerated socio-economic and demographic changes have led to the transformation of eating habits in sub-Saharan African cities including Dakar, Senegal. The result is the proliferation of informal fast-food establishments, such as the 'dibiteries' serving braised sheep meat. However, owing to poor hygiene practices, consumption of dibiterie meat poses a public health concern. It was unclear how the dibiterie meat quality and safety were perceived among customers who define their own purchasing social norms. A total of 165 meat consumers were randomly selected and interviewed, from 165 dibiteries sampled by convenience in the Dakar region using a structured questionnaire. Results showed that purchase decisions were guided by trust in the salesperson's expertise, the taste of the product, perceived risk of meat contamination, tenderness, price, the nutritional value, the smell and the colour and freshness of the meat. The perceived quality and safety of dibiterie meat was expressed by the 'organoleptic quality', 'environment and service' and 'price and trust of the product's safety' factors. The majority of consumers (61%) were 'less concerned' about the safety of dibiterie meat, and the acceptable price range of the product was between $5.08 and$7.62. As this food product is gaining popularity in Dakar and the majority of our participating consumers do not show high levels of concern, we suggest stricter standards

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications

Aggregation and Representation in the European Parliament Party Groups

While members of the European Parliament are elected in national constituencies, their votes are determined by the aggregation of MEPs in multinational party groups. The uncoordinated aggregation of national party programmes in multinational EP party groups challenges theories of representation based on national parties and parliaments. This article provides a theoretical means of understanding representation by linking the aggregation of dozens of national party programmes in different EP party groups to the aggregation of groups to produce the parliamentary majority needed to enact policies. Drawing on an original data source of national party programmes, the EU Profiler, the article shows that the EP majorities created by aggregating MEP votes in party groups are best explained by cartel theories. These give priority to strengthening the EP’s collective capacity to enact policies rather than voting in accord with the programmes they were nationally elected to represent

Elevated O-GlcNAc-dependent signaling through inducible mOGT expression selectively triggers apoptosis

O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAc addition to numerous cellular proteins including transcription and nuclear pore complexes and plays a key role in cellular signaling. One differentially spliced isoform of OGT is normally targeted to mitochondria (mOGT) but is quite cytotoxic when expressed in cells compared with the ncOGT isoform. To understand the basis of this selective cytotoxicity, we constructed a fully functional ecdysone-inducible GFP–OGT. Elevated GFP–OGT expression induced a dramatic increase in intracellular O-GlcNAcylated proteins. Furthermore, enhanced OGT expression efficiently triggered programmed cell death. Apoptosis was dependent upon the unique N-terminus of mOGT, and its catalytic activity. Induction of mOGT expression triggered programmed cell death in every cell type tested including INS-1, an insulin-secreting cell line. These studies suggest that deregulated activity of the mitochondrially targeted mOGT may play a role in triggering the programmed cell death observed with diseases such as diabetes mellitus and neurodegeneration

Human plague: An old scourge that needs new answers

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach

Chitosan Modification of Adenovirus to Modify Transfection Efficiency in Bovine Corneal Epithelial Cells

BACKGROUND: The purpose of this study is to modulate the transfection efficiency of adenovirus (Ad) on the cornea by the covalent attachment of chitosan on adenoviral capsids via a thioether linkage between chitosan modified with 2-iminothiolane and Ad cross-linked with N-[gamma-maleimidobutyryloxy]succinimide ester (GMBS). METHODOLOGY/PRINCIPAL FINDINGS: Modified Ad was obtained by reaction with the heterobifunctional crosslinking reagent, GMBS, producing maleimide-modified Ad (Ad-GMBS). Then, the chitosan-SH was conjugated to Ad-GMBS via a thioether bond at different ratios of Ad to GMBS to chitosan-SH. The sizes and zeta potentials of unmodified Ad and chitosan-modified Ads were measured, and the morphologies of the virus particles were observed under transmission electron microscope. Primary cultures of bovine corneal epithelial cells were transfected with Ads and chitosan-modified Ads in the absence or presence of anti-adenovirus antibodies. Chitosan modification did not significantly change the particle size of Ad, but the surface charge of Ad increased significantly from -24.3 mV to nearly neutral. Furthermore, primary cultures of bovine corneal epithelial cells were transfected with Ad or chitosan-modified Ad in the absence or presence of anti-Ad antibodies. The transfection efficiency was attenuated gradually with increasing amounts of GMBS. However, incorporation of chitosan partly restored transfection activity and rendered the modified antibody resistant to antibody neutralization. CONCLUSIONS/SIGNIFICANCE: Chitosan can provide a platform for chemical modification of Ad, which offers potential for further in vivo applications