Odorant-Binding Proteins of the Malaria Mosquito Anopheles funestus sensu stricto

Background The mosquito Anopheles funestus is one of the major malaria vector species in sub-Saharan Africa. Olfaction is essential in guiding mosquito behaviors. Odorant-binding proteins (OBPs) are highly expressed in insect olfactory tissues and involved in the first step of odorant reception. An improved understanding of the function of malaria mosquito OBPs may contribute to identifying new attractants/repellents and assist in the development of more efficient and environmentally friendly mosquito controlling strategies. Methodology In this study, a large screening of over 50 ecologically significant odorant compounds led to the identification of 12 ligands that elicit significant electroantennographic (EAG) responses from An. funestus female antennae. To compare the absolute efficiency/potency of these chemicals, corrections were made for differences in volatility by determining the exact amount in a stimulus puff. Fourteen AfunOBP genes were cloned and their expression patterns were analyzed. AfunOBP1, 3, 7, 20 and 66 showed olfactory tissue specificity by reverse transcriptase PCR (RT-PCR). Quantitative real-time PCR (qRT-PCR) analysis showed that among olfactory-specific OBPs, AfunOBP1 and 3 are the most enriched OBPs in female antennae. Binding assay experiments showed that at pH 7, AfunOBP1 significantly binds to 2-undecanone, nonyl acetate, octyl acetate and 1-octen-3-ol but AfunOBP3, which shares 68% identify with AfunOBP1 at amino acid level, showed nearly no binding activity to the selected 12 EAG-active odorant compounds. Conclusion This work presents for the first time a study on the odorants and OBPs of the malaria vector mosquito An. funestus, which may provide insight into the An. funestus olfactory research, assist in a comparative study between major malaria mosquitoes An. gambiae and An. funestus olfactory system, and help developing new mosquito control strategies to reduce malaria transmission

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

Hemodynamic changes, plasma catecholamine responses, and echocardiographically detected contractile reserve during two different dobutamine-infusion protocols

We studied hemodynamic changes, catecholamine responses, and the occurrence of improved wall thickening by echocardiography during two different dobutamine-infusion protocols. Forty-three patients were studied by using a stepwise incremental dobutamine dose-infusion protocol (10-40 μg/kg/min, 3-min intervals); a subgroup of 11 patients also underwent a continuous dobutamine-infusion protocol (10 μg/kg/min for 12 min) in random order. No patient used β-blockers. At 3-min intervals, blood pressure, heart rate, and plasma concentrations of dobutamine, epinephrine, and norepinephrine were measured. The echocardiographic improvement of wall thickening was analyzed only in paired protocols by visual assessment in left ventricular regions with normal wall motion at rest. The mean heart rate increased in the continuous and stepwise protocols from 73 to 99 and 74 to 132 beats/min. There was no significant change in blood pressure response between the two protocols. The mean plasma dobutamine concentrations during the continuous and stepwise protocols at 0, 3, 6, 9, and 12 min were 0/0; 31/38; 80/203; 106/448; and 120/692 ng/ml, respectively. In each patient, a response curve was constructed for the plasma dobutamine concentration versus heart rate. The heart rate increment and dobutamine concentration at which wall thickening was detected were similar with both protocols (14 ± 5 vs. 12 ± 7 beats/min) and (8) ± 40 vs. 92 ± 48 ng/ml; mean ± SD). Wall thickening was noted in two of 11 patients b

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Polynitroxyl functionalized dendrimers as paramagnetic relaxation enhancers : effects of structure on relaxivity

The 1H NMR relaxivity of ortho and para dinitroxide substituted phthalate esters and a series of nitroxyl functionalized poly(propylene imine) dendrimers has been measured in acetonitrile and methanol. Studies of dinitroxide relaxivity indicate that electron exchange rate has only a small effect on relaxivity. In studies on dendritic polynitroxides, the per-nitroxide based relaxivity nearly doubles for the generation 5 nitroxyl functionalized dendrimer as compared to a mononitroxide model. This relaxivity enhancement may be due to crowding of dendrimer surface groups in higher generation dendrimers. Dendritic polynitroxides exhibit high relaxivities, making them exciting candidates for magnetic resonance imaging applications. [on SciFinder (R)

Relaxivity studies on dinitroxide and polynitroxyl functionalized dendrimers: effect of electron exchange and structure on paramagnetic relaxation enhancement

The 1H NMR relaxivity of o- and p-dinitroxide-substituted phthalate esters and a series of nitroxyl-functionalized poly(propyleneimine) dendrimers was measured in acetonitrile and methanol. Studies of dinitroxide relaxivity indicate that the electron exchange rate has only a small effect on relaxivity. Outer-sphere relaxivity was measured using benzene as a probe mol. In studies on dendritic polynitroxides, the per-nitroxide-based outer-sphere relaxivity nearly doubles for the generation 5 nitroxyl-functionalized dendrimer as compared to a mononitroxide model. This relaxivity enhancement may be due to crowding of dendrimer surface groups in higher generation dendrimers. Water relaxivity was measured for these polynitroxides as well, and a significant inner-sphere contribution to relaxivity is found. Dendritic polynitroxides exhibit higher per-nitroxide-based water relaxivity as compared to a mononitroxide model. This relaxivity enhancement is attributed to an increase in rotational correlation time (tc) for the dendritic polynitroxides. [on SciFinder (R)

Relaxivity studies on dinitroxide and polynitroxyl functionalized dendrimers: effect of electron exchange and structure on paramagnetic relaxation enhancement

The 1H NMR relaxivity of o- and p-dinitroxide-substituted phthalate esters and a series of nitroxyl-functionalized poly(propyleneimine) dendrimers was measured in acetonitrile and methanol. Studies of dinitroxide relaxivity indicate that the electron exchange rate has only a small effect on relaxivity. Outer-sphere relaxivity was measured using benzene as a probe mol. In studies on dendritic polynitroxides, the per-nitroxide-based outer-sphere relaxivity nearly doubles for the generation 5 nitroxyl-functionalized dendrimer as compared to a mononitroxide model. This relaxivity enhancement may be due to crowding of dendrimer surface groups in higher generation dendrimers. Water relaxivity was measured for these polynitroxides as well, and a significant inner-sphere contribution to relaxivity is found. Dendritic polynitroxides exhibit higher per-nitroxide-based water relaxivity as compared to a mononitroxide model. This relaxivity enhancement is attributed to an increase in rotational correlation time (tc) for the dendritic polynitroxides. [on SciFinder (R)

Breder screenen op hemoglobinopathie: niet alleen na de geboorte testen op HbP, maar ook daarvóór.

Vrijwel overal ter wereld wordt dragerschapsscreening op hemoglobinopathie aanbevolen tijdens of voorafgaand aan de zwangerschap met het oog op reproductieve keuzes. In Nederland wordt sinds 2007 sikkelcelziekte neonataal opgespoord ter preventie van complicaties bij het kind (hielprik). Ook dragerschap kan aan het licht komen bij neonatale screening, maar artsen weten onvoldoende hoe hiermee om te gaan. Dragerschapstesten zijn verder in Nederland alleen bij anemie of positieve familieanamnese beschikbaar. Dragerschapsscreening voor en tijdens de zwangerschap zou op indicatie ‘niet-westerse voorouders’ en kinderwens beschikbaar moeten zijn in de eerste lijn. (aut. ref.

A description and morphometric comparison of eggs of species of the Anopheles gambiae complex

Egges of the 6 named species of the #Anopheles gambiae complex are described from scanning electron micrographs of specimens obtained from laboratory colonies or wild-caught females. Morphometric measurements of eggs from 5 sources of #Anopheles arabiensis, 2 of #Anopheles gambiae, one of #Anopheles quadriannulatus, 2 of #Anopheles bwambae$, 2 of Anopheles merus$, and one of #Anopheles gambiae are compared, and relationships are analyzed by multivariate statistics. No morphologic characters were species-diagnostic, although tendencies of the saltwater species #An. merus and #An. melas to have wider decks and shorter floats were confirmed. Species and populations overlapped considerably in principal components and discriminant function analyses based on 10 attributes of eggs. Nevertheless, discriminant functions revealed similarities in eggs of species believed to be most closely related, namely, #An. gambiae and #An. arabiensis, #An. merus and #An. melas, and #An. quadriannulatus and #An. bwambae$. (Résumé d'auteur