13 research outputs found
Elucidating mechanisms of carbamate resistance and carbamate/pyrethroid cross resistance in An. funestus in Africa
No full textMalaria remains one of the most debilitating tropical diseases with more than 90% of cases in Africa among children under five and pregnant women. Resistance observed against the main insecticides used in public health sector in major vectors such as Anopheles funestus is threatening the success of vector control interventions. To improve the design of suitable resistance management strategies, it is crucial to elucidate the underlining molecular basis of resistance or cross-resistance between insecticides and also establish patterns of gene flow between populations to predict the speed and direction of spread of resistance genes. To address these questions, this study has investigated the molecular basis of resistance to carbamates and cross/resistance to carbamates/pyrethroids in a population of An. funestus from Malawi. This study has revealed that metabolic resistance is the main mechanism driving carbamate resistance through the over-expression of Cytochrome P450 genes. Genome-wide microarray-based transcription analyses consistently revealed that the duplicated P450 genes CYP6P9a and CYP6P9b were among the most up-regulated genes (>2-fold;
In-Building DAS for High Data Rate Indoor Mobile Communication
No full textAs well known, providing high data rate wireless mobile services is difficult in indoor environments, particularly in multi-floor buildings. One way to achieve high data rate wireless transmissions is to reduce the radio transmission distance between the transmitter and the receiver by using distributed antenna systems (DASs) employing frequency reuse. However, frequency reuse causes co-channel interference, which is detrimental to system performance. In this paper, the impact of cochannel interference on the achievable uplink spectral efficiency of an in-building wireless communication system employing DAS is examined. In the system, remote antenna units (RAUs) are deployed on each floor throughout the building and connected to a central unit (CU) where received signals are processed. System performance is investigated by using a propagation channel model derived from multi-floor, in-building measurement results. The proposed scheme exploits the penetration loss of the signal through the floors, resulting in frequency reuse in spatially separated floors, which increases system spectral efficiency and also reduces co-channel interference. Location based RAU selection and deployment options are investigated. System performance is evaluated in terms of location-specific spectral efficiency for a range of potential mobile terminal (MT) locations and various in-building propagation characteristics
Considerações Morfológicas Sobre a Veia Facial de Humanos
No full textO Conhecimento do trajeto da veia facial é de grande importância por ser o principal vaso de drenagem da face e apresentar anastomoses com veias intracranianas, o que pode contribuir na disseminação de infecções. Diversos são os trabalhos relacionados à variação anatômica apresentado por esta veia, o que motivou-nos a realizar este trabalho de revisão de literatura. Através do mesmo verificamos que a maior variação, quanto ao trajeto, foi encontrado ao nível de glândula submandibular e de sua desenbocadura
The P450 CYP6Z1 confers carbamate/pyrethroid cross-resistance in a major African malaria vector beside a novel carbamate-insensitive N485I acetylcholinesterase-1 mutation
No full textCarbamates are increasingly used for vector control notably in areas with pyrethroid resistance. However, a cross-resistance between these insecticides in major malaria vectors such as Anopheles funestus could severely limit available resistance management options. Unfortunately, the molecular basis of such cross-resistance remains uncharacterized in An. funestus, preventing effective resistance management.Here, using a genome-wide transcription profiling, we revealed that metabolic resistance through up-regulation of cytochrome P450 genes is driving carbamate resistance. The P450s CYP6P9a, CYP6P9b and CYP6Z1 were the most up-regulated detoxification genes in the multiple resistant mosquitoes. However, in silico docking simulations predicted CYP6Z1 to metabolise both pyrethroids and carbamates, whereas CYP6P9a and CYP6P9b were predicted to metabolise only the pyrethroids. Using recombinant enzyme metabolism and inhibition assays we demonstrated that CYP6Z1 metabolizes bendiocarb and pyrethroids, whereas CYP6P9a and CYP6P9b metabolise only the pyrethroids. Other up-regulated gene families in resistant mosquitoes included several cuticular protein genes suggesting a possible reduced penetration resistance mechanism. Investigation of the target-site resistance in acetylcholinesterase 1 (ace-1) gene detected and established the association between the new N485I mutation and bendiocarb resistance (Odds ratio 7.3; P<0.0001). The detection of multiple haplotypes in single mosquitoes after cloning suggested the duplication of ace-1. A TaqMan genotyping of the N485I in nine countries revealed that the mutation is located only in Southern Africa with frequency of 10-15% suggesting its recent occurrence.These findings will help in monitoring the spread and evolution of carbamate resistance and improve the design of effective resistance management strategies to control this malaria vector.</p
Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control.
No full textInsecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the 'resistance curve' and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistance-associated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised
Directionally selected cytochrome P450 alleles are driving the spread of pyrethroid resistance in the major malaria vector Anopheles funestus
No full textPyrethroid insecticides are critical for malaria control in Africa. However, resistance to this insecticide class in the malaria vector Anopheles funestus is spreading rapidly across Africa, threatening the success of ongoing and future malaria control programs. The underlying resistance mechanisms driving the spread of this resistance in wild populations remain largely unknown. Here, we show that increased expression of two tandemly duplicated P450 genes, CYP6P9a and CYP6P9b, is themain mechanism driving pyrethroid resistance in Malawi and Mozambique, two southern African countries where this insecticide class forms the mainstay of malaria control. Genome-wide transcription analysis using microarray and quantitative RT-PCR consistently revealed that CYP6P9a and CYP6P9b are the two genes most highly overexpressed (>50-fold; q < 0.01) in permethrin-resistant mosquitoes. Transgenic expression of CYP6P9a and CYP6P9b in Drosophila melanogaster demonstrated that elevated expression of either of these genes confers resistance to both type I (permethrin) and type II (deltamethrin) pyrethroids. Functional characterization of recombinant CYP6P9b confirmed that this protein metabolized both type I (permethrin andbifenthrin) and type II (deltamethrin and Lambda-cyhalothrin) pyrethroids but not DDT. Variability analysis identified that a single allele of each of these genes is predominantly associated with pyrethroid resistance in field populations from both countries, which is suggestive of a single origin of this resistance that has since spread across the region. Urgent resistance management strategies should be implemented in this region to limit a further spread of this resistance and minimize its impact on the success of ongoing malaria control programs.</p
UTILIZAÇÃO DE EXTRATO DE CALÊNDULA EM CREME EM FERIDA LACERANTE DE EQUINO: RELATO DE CASO
No full text<p>Lesões com feridas e grandes lacerações ocorrem com bastante fequência na rotina clínica de cavalos. O tratamento de feridas com segunda intenção é o mais comum na clínica equine, que consiste, para além do desbridamento cirúrgico a utilização de tratamento alopático ou fitoterapêutica. Neste sentido, diversos fitoterápicos são empregados na medicina popular, e têm obtido excelêntes resultados na espécie equina, especialmente a calêndula (<em>Calendula officinalis L</em>.), indicada pelo comitê científico alemão como antisséptica e cicatrizante. O objetivo deste estudo será avaliar a eficácia do creme não iónico de <em>Calendula officinalis</em> na concentração de 2% em ferida lacerante extensa de um equídeo fêmea da raça quarto de milha tratada no Hospital Veterinário da Universidade Federal Rural do Rio de Janeiro (UFRRJ). O trabalho objetiva a demonstração de contribuição positiva para a utilização de terapias alternativas emlesões abertas, como fitoterápicos em questão, uma vez que se revelou viável, além de furta-se da utilização de alopáticos, com custos e associações de custo mais elevado e que não impacte no ambiente em sua produção e utilização, e ainda no surgimento de possível resistência bacteriana.</p>
The selective sweep at <i>rp1</i> in southern Africa coincides with the scale-up in pyrethroid use in malaria control.
No full textA) Gene diversity at microsatellites on chromosome 2R in mosquitoes collected before widespread pyrethroid-based intervention in Malawi, 2002 (purple) and Mozambique, 2002 (red), and ‘post-intervention’ in Malawi, 2010 (green) and Mozambique, 2009 (yellow). B) Fine-scale nucleotide sequence analysis of the 120kb rp1 locus in Cameroon (orange) or pre-intervention samples (Malawi (CKW2002) = brown and Mozambique (MOZ2009) = pink) compared to Post intervention samples from Chikwawa (green), Salima (light blue), Nkhotakota (blue) Malawi, Chokwe (purple) Mozambique, and Kaoma (dark blue) Zambia. C) TCS haplotype network at ‘BAC25’. Haplotypes including sequences from more than one location are denoted by an H and include the frequency, haplotypes from one location Malawi (blue) and Mozambique (yellow) are only present in pre-intervention samples. D) Change in average pairwise diversity (Pi) in the CYP6P9a gene pre- vs. post-intervention in Malawi and Mozambique. E) Phylogeny of CYP6P9a sequences including both Malawi (Ckw) and Mozambique (Moz) shows that post-intervention samples (red) are almost completely homogenous while pre-intervention samples (black) are diverse.</p
Genome-wide analysis of selection on the <i>An</i>. <i>funestus</i> genome.
No full textA) Sites with a significantly different allele frequency between 2002 and 2014 per genomic scaffold plotted against scaffold length identifies scaffold KB669169 as an outlier in which significantly skewed sites are over-represented. B) Plot of P-values of the difference in allele frequency for sites on scaffold KB669169. Grey dotted lines indicate the 120kb region represented by a sequenced BAC clone containing the rp1 locus. C) Mean frequency of non-reference alleles (for 101 adjacent variant sites) on scaffold KB669169. D) Allele frequencies as in C, showing a magnified region spanning the rp1 locus. E) Mean frequency of non-reference alleles (for 51 adjacent variant sites) on the BAC clone containing the rp1 locus. Positions of genes in the P450 cluster are indicated and CYP6P9a and CYP6P9b are labelled.</p
Africa-wide analysis of genetic diversity across the <i>rp1</i> pyrethroid resistance locus.
No full textA) Genetic diversity (pi) across the 120kb rp1 in Cameroon (orange), Malawi (blue), and Mozambique (green). B) Phylogeny of the ‘BAC25’ fragment (located 25kb along the BAC sequence and 9kb upstream of the CYP6P9a gene), which shows the most extreme difference in diversity between Cameroon (orange) and southern populations Malawi (blue) and Mozambique (green), which form a single clade. C) Phylogeny of the CYP6P9a gene sampled from throughout Africa, showing clear geographical divergence between southern Africa (Malawi and Mozambique; 100% bootstrap support), East Africa (Uganda; 87% bootstrap support) and West/Central Africa (Ghana, Benin, Cameroon; 78% bootstrap support). D) Haplotype network for Non-synonymous nucleotide variants in CYP6P9a. Light blue = haplotype shared between Malawi and Mozambique (MAL/MOZ); pink = haplotype shared between Benin, Cameroon and Ghana (BN/CAM/GH); teal = Benin (BN); red = Ghana (GH); orange = Cameroon (CAM); green = Mozambique (MOZ); blue = Malawi (MAL); purple = Uganda (UG). The size of the shapes is proportional to the frequency of the haplotype and numbers on each branch show the mutational steps separating haplotypes.</p
