Biology subjects

Suresh, J.

Publications and source records attributed to Suresh, J..

3 recordsLinked to original sources

bioRxiv2019

Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modeling study of three potential use cases

BackgroundWhile bednets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides are therefore generating much interest. Here we explore the conditions under which long-lasting systemic insecticides would have a substantial impact on transmission and burden.\n\nMethodsHypothetical long-lasting systemic insecticides with effective durations ranging from 14 days to 90 days are simulated using an individual-based mathematical model of malaria transmission. The impact of systemic insecticides when used to complement existing vector control and drug campaigns is evaluated in three settings - a highly seasonal high-transmission setting, a near-elimination setting with seasonal travel to a high-risk area, and a near-elimination setting in southern Africa.\n\nResultsAt 60% coverage, a single round of long-lasting systemic insecticide with effective duration of at least 60 days, distributed at the start of the season alongside a seasonal malaria chemoprevention campaign in a high-transmission setting, results in further burden reduction of 30-90% depending on the sub-populations targeted. In a near-elimination setting where transmission is sustained by seasonal travel to a high-risk area, targeting high-risk travelers with systemic insecticide with effective duration of at least 30 days can result in likely elimination even if intervention coverage is as low as 50%. In near-elimination settings with robust vector control, the addition of a 14-day systemic insecticide alongside an antimalarial in mass drug administration (MDA) campaigns can decrease the necessary MDA coverage from about 85% to the more easily achievable 65%.\n\nConclusionsWhile further research into the safety profile of systemic insecticides is necessary before deployment, we find that long-lasting systemic insecticides can play a critical role in reducing burden or eliminating malaria in a range of contexts with different target populations, existing malaria control methods, and transmission intensities.

epidemiology↗

bioRxiv2017

An Embryonic System To Assess Wnt Transcriptional Targets

During animal development, complex signals determine and organize a vast number of tissues using a very small number of signal transduction pathways. These developmental signaling pathways determine cell fates through a coordinated transcriptional response that remains poorly understood. The Wnt pathway is involved in a variety of these cellular functions, and its signals are transmitted in part through a {beta}-catenin/TCF transcriptional complex. Here we report an in vivo Drosophila assay that can be used to distinguish between activation, de-repression and repression of transcriptional responses, separating upstream and downstream pathway activation and canonical/non-canonical Wnt signals in embryos. We find specific sets of genes downstream of both {beta}-catenin and TCF with an additional group of genes regulated by Wnt, while the non-canonical Wnt4 regulates a separate cohort of genes. We correlate transcriptional changes with phenotypic outcomes of cell differentiation and embryo size, showing our model can be used to characterize developmental signaling compartmentalization in vivo.

developmental biology↗

bioRxiv2017

TGH: Trans-Generational Hormesis And The Inheritance Of Aging Resistance

Animals respond to dietary changes by adapting their metabolism to available nutrients through insulin and insulin-like growth factor signalling. Restricting calorie intake generally extends life and health span, but Drosophila fed non-ideal sugars such as galactose are stressed and have shorter life spans. Here, we report that although these flies have shorter life spans, their offspring show significant life extension if switched to a normal sugar (glucose) diet. We define this as TGH or trans-generational hormesis, a beneficial effect that comes from a mild stress. We trace the effects to changes in stress responses in parents, ROS production, effects on lipid metabolism, and changes in chromatin and gene expression. We find that this mechanism is similar to what happens to the long lived Indy mutants on normal food, but surprisingly find that Indy is required for life span extension for galactose fed flies. Indy mutant flies grown on galactose do not live longer as do their siblings grown on glucose, rather overexpression of Indy rescues lifespan for galactose reared flies. We define a process where sugar metabolism can generate epigenetic changes that are inherited by offspring, providing a mechanism for how transgenerational nutrient sensitivities are passed on.

biochemistry↗