Limited genomic divergence between intraspecific forms of Culex pipiens under different ecological pressures

Abstract Background: Divergent selection can be a major driver of ecological speciation. In insects of medical importance, understanding the speciation process is both of academic interest and public health importance. In the West Nile virus vector Culex pipiens, intraspecific pipiens and molestus forms vary in ecological and physiological traits. Populations of each form appear to share recent common ancestry but patterns of genetic differentiation across the genome remain unknown. Here, we undertook an AFLP genome scan on samples collected from both sympatric and allopatric populations from Europe and the USA to quantify the extent of genomic differentiation between the two forms. Results: The forms were clearly differentiated but each exhibited major population sub-structuring between continents. Divergence between pipiens and molestus forms from USA was higher than in both inter- and intra-continental comparisons with European samples. The proportion of outlier loci between pipiens and molestus (≈3 %) was low but consistent in both continents, and similar to those observed between sibling species of other mosquito species which exhibit contemporary gene flow. Only two of the outlier loci were shared between inter-form comparisons made within Europe and USA. Conclusion: This study supports the molestus and pipiens status as distinct evolutionary entities with low genomic divergence. The low number of shared divergent loci between continents suggests a relatively limited number of genomic regions determining key typological traits likely to be driving incipient speciation and/or adaptation of molestus to anthropogenic habitats

Assessment of non-invasive ICP during CSF infusion test: an approach with transcranial Doppler.

BACKGROUND: This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP. METHOD: Cerebral blood flow velocity (FV), ICP and non-invasive arterial blood pressure (ABP) were recorded in 53 patients diagnosed for hydrocephalus. Non-invasive ICP methods were based on: (1) interaction between FV and ABP using black-box model (nICP_BB); (2) diastolic FV (nICP_FVd); (3) critical closing pressure (nICP_CrCP); (4) transcranial Doppler-derived pulsatility index (nICP_PI). Correlation between rise in ICP (∆ICP) and ∆nICP and averaged correlations for changes in time between ICP and nICP during infusion test were investigated. RESULTS: From baseline to plateau, all nICP estimators increased significantly. Correlations between ∆ICP and ∆nICP were better represented by nICP_PI and nICP_BB: 0.45 and 0.30 (p < 0.05). nICP_FVd and nICP_CrCP presented non-significant correlations: -0.17 (p = 0.21), 0.21 (p = 0.13). For changes in ICP during individual infusion test nICP_PI, nICP_BB and nICP_FVd presented similar correlations with ICP: 0.39 ± 0.40, 0.39 ± 0.43 and 0.35 ± 0.41 respectively. However, nICP_CrCP presented a weaker correlation (R = 0.29 ± 0.24). CONCLUSIONS: Out of the four methods, nICP_PI was the one with best performance for predicting changes in ∆ICP during infusion test, followed by nICP_BB. Unreliable correlations were shown by nICP_FVd and nICP_CrCP. Changes of ICP observed during the test were expressed by nICP values with only moderate correlations.DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Trust Scholarship. BCTC is supported by CNPQ (Research Project 203792/2014-9). DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s00701-015-2661-

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

How do MNC R&amp;D laboratory roles affect employee international assignments?

Research and development (R&#38;D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&#38;D laboratories in which these employees work on the international assignments they undertake. We categorise R&#38;D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&#38;D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&#38;D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

Impact of urban agriculture on malaria vectors in Accra, Ghana

To investigate the impact of urban agriculture on malaria transmission risk in urban Accra larval and adult stage mosquito surveys, were performed. Local transmission was implicated as Anopheles spp. were found breeding and infected Anopheles mosquitoes were found resting in houses in the study sites. The predominant Anopheles species was Anopheles gambiae s.s.. The relative proportion of molecular forms within a subset of specimens was 86% S-form and 14% M-form. Anopheles spp. and Culex quinquefasciatus outdoor biting rates were respectively three and four times higher in areas around agricultural sites (UA) than in areas far from agriculture (U). The annual Entomological Inoculation Rate (EIR), the number of infectious bites received per individual per year, was 19.2 and 6.6 in UA and U sites, respectively. Breeding sites were highly transitory in nature, which poses a challenge for larval control in this setting. The data also suggest that the epidemiological importance of urban agricultural areas may be the provision of resting sites for adults rather than an increased number of larval habitats. Host-seeking activity peaked between 2–3 am, indicating that insecticide-treated bednets should be an effective control method

Population structure of the malaria vector Anopheles moucheti in the equatorial forest region of Africa

<p>Abstract</p> <p>Background</p> <p><it>Anopheles moucheti </it>is a major malaria vector in forested areas of Africa. However, despite its important epidemiological role, it remains poorly known and insufficiently studied. Here, levels of genetic differentiation were estimated between different <it>A. moucheti </it>populations sampled throughout its distribution range in Central Africa.</p> <p>Methods</p> <p>Polymorphism at ten microsatellite markers was compared in mosquitoes sampled in Cameroon, the Democratic Republic of Congo and an island on Lake Victoria in Uganda. Microsatellite data were used to estimate genetic diversity within populations, their relative long-term effective population size, and the level of genetic differentiation between them.</p> <p>Results</p> <p>All specimens collected in Tsakalakuku (Democratic Republic of Congo) were identified as <it>A. m. bervoetsi </it>while other samples consisted of <it>A. m. moucheti</it>. Successful amplification was obtained at all microsatellite loci within all <it>A. m. moucheti </it>samples while only six loci amplified in <it>A. m. bervoetsi</it>. Allelic richness and heterozygosity were high for all populations except the island population of Uganda and <it>A. m. bervoetsi</it>. High levels of genetic differentiation were recorded between <it>A. m. bervoetsi </it>and each <it>A. m. moucheti </it>sample as well as between the island population of <it>A. m. moucheti </it>and mainland populations. Significant isolation by distance was evidenced between mainland populations.</p> <p>Conclusion</p> <p>High levels of genetic differentiation supports complete speciation of <it>A. m. bervoetsi </it>which should henceforth be recognized as a full species and named <it>A. bervoetsi</it>. Isolation by distance is the main force driving differentiation between mainland populations of <it>A. m. moucheti</it>. Genetically and geographically isolated populations exist on Lake Victoria islands, which might serve as relevant field sites for evaluation of innovative vector control strategies.</p

Extensive permethrin and DDT resistance in Anopheles arabiensis from eastern and central Sudan

<p>Abstract</p> <p>Background</p> <p>The distribution of insecticide treated nets (ITN) has been dramatically scaled up in eastern and central Sudan. Resistance to insecticides has already been reported in this region and there is an urgent need to develop appropriate resistance management strategies, which requires detailed information on the extent and causes of resistance. This study assessed resistance to permethrin and DDT in seven populations of <it>Anopheles arabiensis </it>from Sudan.</p> <p>Results</p> <p>Three out of the seven populations were defined as resistant to permethrin and five of six populations resistant to DDT according to WHO criteria. The 1014F kdr allele was present in all six populations tested and the presence of this allele was significantly correlated with resistance to permethrin (<it>P </it>= 0.0460). While homozygous 1014F individuals were statistically not more likely to survive (53.7%) permethrin than to be killed (38.6%) by the diagnostic dose, there was no difference in the likelihood of permethrin survival in heterozygotes (<it>P </it>= 0.7973). The susceptible genotypes were more likely to be killed by permethrin exposure than to survive (<it>P </it>= 0.0460). The 1014F allele failed to confer a survival advantage to the WHO diagnostic dose of DDT in either the homozygous or heterozygous state. The 1014S allele was not detected in any of the populations tested.</p> <p>Conclusion</p> <p>The kdr allele is certainly contributing to the extensive resistance to permethrin and DDT in Sudan but the high number of DDT (43%) and permethrin (16.7%) survivors that did not contain either kdr alleles suggests that other resistance mechanisms are also present in these populations. The high frequency of permethrin resistance throughout central and eastern Sudan is a cause of great concern for malaria control activities.</p

Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases

BACKGROUND: The negative binomial distribution is used commonly throughout biology as a model for overdispersed count data, with attention focused on the negative binomial dispersion parameter, k. A substantial literature exists on the estimation of k, but most attention has focused on datasets that are not highly overdispersed (i.e., those with k≥1), and the accuracy of confidence intervals estimated for k is typically not explored. METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. CONCLUSIONS: Results show that maximum likelihood estimates of k can be biased upward by small sample size or under-reporting of zero-class events, but are not biased downward by any of the factors considered. Confidence intervals estimated from the asymptotic sampling variance tend to exhibit coverage below the nominal level, with overestimates of k comprising the great majority of coverage errors. Estimation from outbreak datasets does not increase the bias of k estimates, but can add significant upward bias to estimates of the mean. Because k varies inversely with the degree of overdispersion, these findings show that overestimation of the degree of overdispersion is very rare for these datasets

The impact of the expansion of urban vegetable farming on malaria transmission in major cities of Benin

BACKGROUND: Urban agricultural practices are expanding in several cities of the Republic of Benin. This study aims to assess the impact of such practices on transmission of the malaria parasite in major cities of Benin. METHOD: A cross sectional entomological study was carried out from January to December 2009 in two vegetable farming sites in southern Benin (Houeyiho and Acron) and one in the northern area (Azèrèkè). The study was based on sampling of mosquitoes by Human Landing Catches (HLC) in households close to the vegetable farms and in others located far from the farms. RESULTS: During the year of study, 71,678 female mosquitoes were caught by HLC of which 25% (17,920/71,678) were Anopheles species. In the areas surveyed, the main malaria parasite, Plasmodium falciparum was transmitted in the south by Anopheles gambiae s.s. Transmission was high during the two rainy seasons (April to July and October to November) but declined in the two dry seasons (December to March and August to September). In the north, transmission occurred from June to October during the rainy season and was vehicled by two members of the An. gambiae complex: Anopheles gambiae s.s. (98%) and Anopheles arabiensis (2%).At Houeyiho, Acron and Azèrèkè, the Entomological Inoculation Rates (EIRs) and the Human Biting Rates (HBRs) were significantly higher during the dry season in Households Close to Vegetable Farms (HCVF) than in those located far from the vegetable areas (HFVF) (p 0.05).The knock-down resistance (kdr) mutation was the main resistance mechanism detected at high frequency (0.86 to 0.91) in An. gambiae s.l. at all sites. The ace-1R mutation was also found but at a very low frequency (< 0.1). CONCLUSION: These findings showed that communities living close to vegetable farms are permanently exposed to malaria throughout the year, whereas the risk in those living far from such agricultural practices is limited and only critical during the rainy seasons. Measures must be taken by African governments to create awareness among farmers and ultimately decentralize farming activities from urban to rural areas where human-vector contact is limited

The Microcephalin Ancestral Allele in a Neanderthal Individual

Background: The high frequency (around 0.70 worlwide) and the relatively young age (between 14,000 and 62,000 years) of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1) locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans.1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal. Methodology/Principal Findings: Here we report the first PCR amplification and high- throughput sequencing of nuclear DNA at the microcephalin (MCPH1) locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy). We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH