PubMed Health⌕ Search

Biomedical subjects

Janet Hemingway

Publications and source records attributed to Janet Hemingway.

30 records · Page 2Linked to original sources
PubMed2003

Malaria parasite and vector genomes: partners in crime.

The publication of the genome sequences of the malaria parasite Plasmodium falciparum and the insect vector Anopheles gambiae paves the way for scientists to study these organisms by using technologies developed to observe global changes in transcription and translation, as well as computational tools. Researchers are now able to investigate complex changes involved in development, growth and reaction to external factors. Given the medical importance of these organisms, much of this work is targeted on drug or insecticide discovery (including mechanisms of resistance to existing treatments), but the genome information also provides the opportunity to develop novel therapies.

Animals↗
PubMed2003

KDR mutation, a genetic marker to assess events of introgression between the molecular M and S forms of Anopheles gambiae (Diptera: Culicidae) in the tropical savannah area of West Africa.

A sodium channel 'kdr'-type mutation was identified in the M form of Anopheles gambiae from Burkina Faso in the tropical savannah area belt. The molecular M form of An. gambiae is found at high frequencies in the flooded rice cultivation area of Kou Valley, where the insecticide selection pressure is limited. The spread of the mutation in the M population is an ongoing process, as it increased from a frequency of 0.006 in 1999 to 0.02 in 2000. The S molecular form occurs in sympatry in our study village, with the M form at a relatively low frequency. The common 'kdr' mutation was previously detected in this area in the S form, and has probably invaded the M population through genetic introgression. This impacts on the question of actual levels of gene flow between the two molecular forms in tropical savannah areas. A hybrid M/S individual was identified during the course of this study, which was homozygous for the 'kdr' mutation. Pyrethroid resistant An. gambiae were caught in October and November, which is the time of year that the molecular S form migrates into this area as rain-fed breeding sites in the cotton fields dry out.

Africa, Western↗
PubMed2002

Evolution of supergene families associated with insecticide resistance.

The emergence of insecticide resistance in the mosquito poses a serious threat to the efficacy of many malaria control programs. We have searched the Anopheles gambiae genome for members of the three major enzyme families- the carboxylesterases, glutathione transferases, and cytochrome P450s-that are primarily responsible for metabolic resistance to insecticides. A comparative genomic analysis with Drosophila melanogaster reveals that a considerable expansion of these supergene families has occurred in the mosquito. Low gene orthology and little chromosomal synteny paradoxically contrast the easily identified orthologous groups of genes presumably seeded by common ancestors. In A. gambiae, the independent expansion of paralogous genes is mainly a consequence of the formation of clusters among locally duplicated genes. These expansions may reflect the functional diversification of supergene families consistent with major differences in the life history and ecology of these organisms. These data provide a basis for identifying the resistance-associated enzymes within these families. This will enable the resistance status of mosquitoes, flies, and possibly other holometabolous insects to be monitored. The analyses also provide the means for identifying previously unknown molecules involved in fundamental biological processes such as development.

Animals↗
PubMed2002

An overview of insecticide resistance.

Insecticide resistance poses a serious threat to current malaria control efforts. The Anopheles gambiae genome will enable identification of new resistance genes and will provide new molecular targets for the design of more effective insecticides.

Africa South of the Sahara↗
PubMed2002

Purification, molecular cloning and heterologous expression of a glutathione S-transferase involved in insecticide resistance from the rice brown planthopper, Nilaparvata lugens.

A novel glutathione S-transferase (GST)-based pyrethroid resistance mechanism was recently identified in Nilaparvata lugens [Vontas, Small and Hemingway (2001) Biochem. J. 357, 65-72]. To determine the nature of GSTs involved in conferring this resistance, the GSTs from resistant and susceptible strains of N. lugens were partially purified by anion exchange and affinity chromatography. The majority of peroxidase activity, previously correlated with resistance, was confined to the fraction that bound to the affinity column, which was considerably elevated in the resistant insects. A cDNA clone encoding a GST (nlgst1-1) - the first reported GST sequence from Hemiptera with up to 54% deduced amino-acid identity with other insect class I GSTs - was isolated from a pyrethroid-resistant strain. Northern analysis showed that nlgst1-1 was overexpressed in resistant insects. nlgst1-1 was expressed in Escherichia coli, purified and characterized. The ability of the recombinant protein to bind to the S-hexylglutathione affinity matrix, its substrate specificities and its immunological properties confirmed that this GST was one from the elevated subset of N. lugens GSTs. Peroxidase activity of the recombinant nlgst1-1 indicated that it had a role in resistance, through detoxification of lipid peroxidation products induced by pyrethroids. Southern analysis of genomic DNA from the resistant and susceptible strains indicated that GST-based insecticide resistance may be associated with gene amplification in N. lugens.

Amino Acid Sequence↗
PubMed2002

Analysis of the promoters for the beta-esterase genes associated with insecticide resistance in the mosquito Culex quinquefasciatus.

Resistance to organophosphorus (OP) insecticides in the mosquito Culex quinquefasciatus is primarily due to the amplification and over-expression of non-specific esterases. Co-amplification of two esterase genes, estalpha2(1) and estbeta2(1), is the most common resistance genotype. In both resistant and susceptible mosquitoes the alpha- and beta-esterase genes are oriented in a head-to-head arrangement, the intergenic sequences containing promoter elements for the divergent transcription of both esterases. Transient transfection of luciferase reporter gene constructs into a C. quinquefasciatus cell line was used to study these promoters. A control vector was constructed with the strong Drosophila actin 5c promoter driving expression of beta-galactosidase. The beta-esterase promoters from both insecticide resistant and -susceptible insects were highly active in directing luciferase expression. Transfections with panels of deletions revealed several regions where binding sites for positive and negative regulatory elements are located, and candidate transcription factor sites have been identified. Gel shift assays have identified one DNA-protein interaction that is stronger with the resistant than with the equivalent but slightly altered susceptible sequence. The arthropod initiator site TCAGT 135bp upstream of the ATG in both beta-esterase promoters is essential for transcription initiation, but a putative TATA box is not involved.

Animals↗
PubMed2002

Molecular characterization of the amplified aldehyde oxidase from insecticide resistant Culex quinquefasciatus.

Primary structural information including the complete nucleotide sequence of the first insect aldehyde oxidase (AO) was obtained from the common house mosquito Culex quinquefasciatus (Say) through cloning and sequencing of both genomic DNA and cDNA. The deduced amino-acid sequence encodes a 150-kDa protein of 1266 amino-acid residues, which is consistent with the expected monomeric subunit size of AO. The Culex AO sequence contains a molybdopterin cofactor binding domain and two iron-sulfur centres. A comparison of the partial sequences of AO from insecticide resistant and susceptible strains of C. quinquefasciatus shows two distinct alleles of this enzyme, one of which is amplified in the insecticide resistant strain on a 30-kb DNA amplicon alongside two resistance-associated esterases. The amplified AO gene results in elevated AO activity in all life stages, but activity is highest in 3rd instar larvae. The elevated enzyme can be seen as a separate band on polyacrylamide gel electrophoresis. The role of AO in xenobiotic oxidation in mammals and the partial inhibition of elevated AO activity by a range of insecticides in Culex, suggest that this AO may play a role in insecticide resistance.

3' Untranslated Regions↗
PubMed2002

The role of agricultural use of insecticides in resistance to pyrethroids in Anopheles gambiae s.l. in Burkina Faso.

Agricultural use of insecticides is involved in the selection of resistance to these compounds in field populations of mosquitoes in Burkina Faso. Anopheles gambiae s.l. was resistant to permethrin and DDT in cotton-growing and urban areas, but susceptible in areas with limited insecticide selection pressure (rice fields and control areas). Nevertheless, resistance to these insecticides was observed in a village on the outskirts of the rice fields at the end of the rainy season, suggesting that the latter population of mosquitoes had migrated from the surrounding cotton villages into the rice fields. A seasonal variation of resistance observed in the cotton-growing area is related to the distribution of the molecular M and S forms of An. gambiae, since resistance to pyrethroids has so far only been reported in the S form. Pyrethroid resistance in west African An. gambiae was conferred by target site insensitivity through a knockdown resistance (kdr)-like mutation, which was present at high frequencies in mosquitoes in the cotton-growing and urban areas.

Animals↗
PubMedDate not supplied

Acceptability and perceived side effects of insecticide indoor residual spraying under different resistance management strategies.

OBJECTIVE: To assess household acceptability and perceived side effects of residual indoor pyrethroid (PYR), carbamate and organophosphate insecticides sprayed by annual rotation (ROT), spatial mosaic (MOS), and a single insecticide (DDT or PYR) in communities of the coastal plain of Chiapas, Mexico. MATERIAL AND METHODS: A questionnaire to assess the acceptability and perceived side effects of indoor insecticides was administered to one member of 30% of the families in eight villages of Chiapas. The association of different insecticide treatments with their responses was evaluated (Chi-square). The intensity of side effects indicated under different treatments was compared in an ordered logistic model, using a severity index as the response variable. RESULTS: Insecticide spraying as a probable cause of symptoms was identified by 2.1% of interviewees. A significantly high percentage of persons with blurred vision, dizziness, sneezing, coughing, numbness, watery eyes, and itching lived in villages under MOS and ROT and a high severity index was significantly associated with ROT treatment. Reduction of mosquito bites and cockroaches were the perceived main benefits, and most villagers that perceived no benefits lived in DDT treated villages. Most of the interviewees welcomed spraying (83.7%), but the smell and having to remove furniture from houses were the main arguments against it. CONCLUSIONS: Acceptability correlated with insecticide spray coverage, although the most frequent suggestion for improvement was to increase the understanding of the objectives of spraying in the communities. The frequency of side effects was low, but higher in localities where a combination of insecticides was applied. This is a limitation for the use of this type of resistance management strategy in public health.

Adolescent↗
PubMedDate not supplied

Knowledge and beliefs about malaria transmission and practices for vector control in southern Mexico.

OBJECTIVE: To investigate the knowledge and beliefs about malaria transmission and practices for vector control in eight villages on the coastal plain of Chiapas, Mexico. MATERIAL AND METHODS: A cross-sectional survey was conducted during May and June 1995 in Chiapas, Mexico. A questionnaire to investigate family structure, knowledge on malaria transmission, preventive measures and attitudes towards seeking treatment was applied to both family heads of a sample of households. Associations were analyzed by estimating odds ratios with confidence intervals and p values, using bivariate and multivariate logistic regression methods. RESULTS: Malaria knowledge was poor and only 48% associated malaria with mosquito bites. The perceived benefit of indoor residual spraying was associated to a reduction of mosquitoes, a reduction in the numbers of cockroaches and rats, but only 3% associated it directly with the prevention of malaria transmission. Most villagers (97.6%) agreed with the indoor residual spraying of insecticides. Ninety nine percent of villagers had mosquito bednets, 75.7% used them all year round. Other measures used by villagers to prevent mosquito bites were smoke and mosquito coils. Above 40% of villagers self-medicated when any member of the family had a fever episode, but 51% attended proper health services (community dispensary, private physician, health worker). About 61% used pesticides for agricultural or livestock purposes and 55% applied themselves. Women had a greater participation as family health promoters, with 70% of the housewives being in charge of the application of self-protection preventive measures. CONCLUSIONS: Educational programs aimed at increasing awareness on the participation of mosquitoes on malaria transmission could promote community participation in malaria control in the region. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

Animals↗