35 research outputs found
Insecticide resistance mechanisms in Aedes aegypti
No full textDengue is the most rapidly spreading vector borne disease. In Thailand, the number of dengue cases increased from 46,829 in 2006 to 76,059 by September 2008 (WHO, 2008). Insecticides play a vital role in controlling this disease but the success of control programmes is continually threatened by the emergence and spread of insecticide resistance in the vector population.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Insecticide resistance mechanisms in Aedes aegypti
No full textDengue is the most rapidly spreading vector borne disease. In Thailand, the number of dengue cases increased from 46,829 in 2006 to 76,059 by September 2008 (WHO, 2008). Insecticides play a vital role in controlling this disease but the success of control programmes is continually threatened by the emergence and spread of insecticide resistance in the vector population
NIHR Global Health Research Group on Establishing Regional Hubs for Genomic Surveillance in West Africa
No full textOur goal is to expand capacity for genomic surveillance of malaria parasites and mosquito vectors in West Africa, and to generate essential information required for National Malaria Control Programmes (NMCPs) to plan sustainable interventions. Leveraging previous achievements in capacity building in The Gambia and Ghana, we aim to establish regional sequencing hubs that will provide NMCPs with timely, actionable genomic surveillance data
Mosquito age and susceptibility to insecticides
No full textInsecticides play a crucial role in controlling the transmission of mosquito-borne diseases and the development and spread of insecticide resistance is a major threat to sustainable control. Guidelines developed by the WHO to monitor for insecticide resistance recommend using 1-3 day old, non blood fed female mosquitoes. This standardisation facilitates comparison between different tests, which is important when monitoring for spatial or longitudinal variations in resistance in the field. However, mosquitoes of this age cannot transmit human pathogens. In order to transmit disease, the mosquito must live long enough to pick up the pathogen via a blood meal, survive the extrinsic incubation period and then pass on the pathogen during a subsequent blood meal. Previous studies have reported declines in insecticide resistance with mosquito age. If widely applicable this would have important implications for predictions of the impact of resistance that are based on results from WHO bioassays. This study investigated the impact of senescence and blood feeding on insecticide induced mortality in six different mosquito populations and found higher mortality after insecticide exposure in older mosquitoes in three populations of Aedes aegypti and two Anopheles gambiae populations. Age dependent changes in the expression of a known insecticide detoxification gene, GSTe2, and in the frequency of a target site mutation (kdr 1014F) were investigated in an attempt to explain the results.</p
Detection of three closely located single nucleotide polymorphisms in the EAAT2 promoter:Comparison of single-strand conformational polymorphism (SSCP), pyrosequencing and Sanger sequencing
No full textBackground: Single-strand conformational polymorphism (SSCP) is still a frequently used genotyping method across different fields for the detection of single nucleotide polymorphisms (SNPs) due to its simplicity, requirement for basic equipment accessible in most laboratories and low cost. This technique was previously used to detect rs4354668:A > C (g.-181A > C) SNP in the promoter of astroglial glutamate transporter (EAAT2) and the same approach was initially used here to investigate this promoter region in a cohort of newborns.Results: Unexpectedly, four distinct DNA migration patterns were identified by SSCP. Sanger sequencing revealed two additional SNPs: g.-200C > A and g.-168C > T giving a rise to a total of ten EAAT2 promoter variants. SSCP failed to distinguish these variants reliably and thus pyrosequencing assays were developed. g.-168C > T was found in heterozygous form in one infant only with minor allele frequency (MAF) of 0.0023. In contrast, g.-200C > A and -181A > C were more common (with MAF of 0.46 and 0.49, respectively) and showed string evidence of linkage disequilibrium (LD). In a systematic comparison, 16% of samples were miss-classified by SSCP with 25-31% errors in the identification of the wild-type and homozygote mutant genotypes compared to pyrosequencing or Sanger sequencing. In contrast, SSCP and pyrosequencing of an unrelated single SNP (rs1835740:C > T), showed 94% concordance.Conclusion: Our data suggest that SSCP cannot always detect reliably several closely located SNPs. Furthermore, caution is needed in the interpretation of the association studies linking only one of the co-inherited SNPs in the EAAT2 promoter to human diseases. © 2014 Rajatileka et al.; licensee BioMed Central Ltd.</p
Pyrethroid Resistance in Aedes aegypti from Grand Cayman
No full textThe Grand Cayman population of Aedes aegypti is highly resistant to DDT and pyrethroid insecticides. Glutathione transferase, cytochrome P450, and esterase levels were increased in the Grand Cayman population relative to a susceptible laboratory strain, but synergist studies did not implicate elevated insecticide detoxification as a major cause of resistance. The role of target site resistance was therefore investigated. Two substitutions in the voltage-gated sodium channel were identified, V1016I in domain II, segment 6 (IIS6) (allele frequency = 0.79) and F1534C in IIIS6 (allele frequency = 0.68). The role of the F1534C mutation in conferring resistance to insecticides has not been previously established and so a tetraplex polymerase chain reaction assay was designed and used to genotype mosquitoes that had been exposed to insecticides. The F1534C mutation was strongly correlated with resistance to DDT and permethrin.</p
Association between neonatal resuscitation and a single nucleotide polymorphism rs1835740
No full textAim: The aim of this work is to test if three single nucleotide polymorphisms (SNPs) implicated in glutamate homeostasis or signalling and cellular survival are associated with birth condition. Methods: This study is drawn from the Avon Longitudinal Study of Parents and Children. 7611 term infants were genotyped and patient outcome data retrieved from routine medical records. Exposure measures were the presence of one or more minor alleles in one of 3 SNPs (rs2284411, rs2498804, rs1835740). The primary outcome was the need for resuscitation at birth. Results: For SNP rs1835740, infants homozygous for the minor allele compared to wild-type were more likely to need resuscitation (9.2% vs. 7.0%, p=0.041) while the odds ratio for resuscitation was associated with each increasing minor allele (OR 1.17 (1.01 to 1.35)). Population attributable risk fraction was 6.5%. There was no evidence that the other two SNPs investigated were associated with birth condition. Conclusions: We have tested three candidate SNPs to measure any association with birth condition. The study revealed that the rs1835740 was associated with the need for resuscitation and Apgar scores, with a substantial population impact. This article is protected by copyright. All rights reserved
The oncogenic transcription factor ERG represses the transcription of the tumour suppressor gene PTEN in prostate cancer cells
No full text© 2017, Spandidos Publications. All rights reserved. The oncogene ETS-related gene (ERG) encodes a transcription factor with roles in the regulation of haematopoiesis, angiogenesis, vasculogenesis, inflammation, migration and invasion. The ERG oncogene is activated in >50% of prostate cancer cases, generally through a gene fusion with the androgen-responsive promoter of transmembrane protease serine 2. Phosphatase and tensin homologue (PTEN) is an important tumour suppressor gene that is often inactivated in cancer. ERG overexpression combined with PTEN inactivation or loss is often associated with aggressive prostate cancer. The present study aimed to determine whether or not ERG regulates PTEN transcription directly. ERG was demonstrated to bind to the PTEN promoter and repress its transcription. ERG overexpression reduced endogenous PTEN expression, whereas ERG knockdown increased PTEN expression. The ability of ERG to repress PTEN may contribute to a more cancer-permissive environment
Molecular Mechanism of Myosin Va Recruitment to Dense Core Secretory Granules
No full textThe brain-spliced isoform of Myosin Va (BR-MyoVa) plays an important role in the transport of dense core secretory granules (SGs) to the plasma membrane in hormone and neuropeptide-producing cells. The molecular composition of the protein complex that recruits BR-MyoVa to SGs and regulates its function has not been identified to date. We have identified interaction between SG-associated proteins granuphilin-a/b (Gran-a/b), BR-MyoVa and Rab27a, a member of the Rab family of GTPases. Gran-a/bBR-MyoVa interaction is direct, involves regions downstream of the Rab27-binding domain, and the C-terminal part of Gran-a determines exon specificity. MyoVa and Gran-a/b are partially colocalised on SGs and disruption of Gran-a/bBR-MyoVa binding results in a perinuclear accumulation of SGs which augments nutrient-stimulated hormone secretion in pancreatic beta-cells. These results indicate the existence of at least another binding partner of BR-MyoVa that was identified as rabphilin-3A (Rph-3A). BR-MyoVaRph-3A interaction is also direct and enhanced when secretion is activated. The BR-MyoVaRph-3A and BR-MyoVaGran-a/b complexes are linked to a different subset of SGs, and simultaneous inhibition of these complexes nearly completely blocks stimulated hormone release. This study demonstrates that multiple binding partners of BR-MyoVa regulate SG transport, and this molecular mechanism is universally used by neuronal, endocrine and neuroendocrine cells.</p
