Relationships between anopheline mosquitoes and topography in West Timor and Java, Indonesia

<p>Abstract</p> <p>Background</p> <p>Malaria is a serious health issue in Indonesia. Mosquito control is one aspect of an integrated malaria management programme. To focus resources on priority areas, information is needed about the vectors and their habitats. This research aimed to identify the relationship between anopheline mosquitoes and topography in West Timor and Java.</p> <p>Methods</p> <p>Study areas were selected in three topographic types in West Timor and Java. These were: coastal plain, hilly (rice field) and highland. Adult mosquitoes were captured landing on humans identified to species level and counted.</p> <p>Results</p> <p>Eleven species were recorded, four of which were significant for malaria transmission: <it>Anopheles aconitus, Anopheles barbirostris, Anopheles subpictus </it>and <it>Anopheles sundaicus</it>. Each species occupied different topographies, but only five were significantly associated: <it>Anopheles annularis, Anopheles vagus </it>and <it>Anopheles subpictus </it>(Java only) with hilly rice fields; <it>Anopheles barbirostris, Anopheles maculatus </it>and <it>Anopheles subpictus </it>(West Timor only) with coastal areas.</p> <p>Conclusion</p> <p>Information on significant malaria vectors associated with specific topography is useful for planning the mosquito control aspect of malaria management.</p

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

YOU’VE GOT NEWS: A PERMISSION-MARKETING MODEL USING ELECTRONIC

A model is proposed for ISP customers to receive sponsored electronic newsletters in exchange for a discount on the Internet fee. In the model, both online newspapers and ISPs receive fees from the advertisers while the end consumer pays less for the Internet connection. Advertisers gain by sending better-targeted messages through an accepted medium. In addition to collecting part of the advertising fees, the ISPs increase their customer base by offering an incentive as well as value-added services. Adherence to the model appeared to vary with gender, age, and attitude toward e-mail marketing