Pyrethroid Resistance Reduces the Efficacy of Space Sprays for Dengue Control on the Island of Martinique (Caribbean)

The mosquito Aedes aegypti is the major vector of the Dengue virus in human populations and is responsible of serious outbreaks worldwide. In most countries, vector control is implemented by the use of insecticides to reduce mosquito populations. During epidemics, insecticides of the pyrethroid family (blocking the voltage gated sodium channel protein in the nerve sheath) are used by space spraying with vehicle mounted thermal foggers to kill adult mosquitoes. Unfortunately some populations of Ae. aegypti have become resistant to these insecticides, leading to operational challenges for public health services. In Martinique (French West Indies), resistance to pyrethroids was detected in the 1990s. The present study assessed the impact of this resistance on the efficacy of vector control operations in 9 localities of Martinique. Here we showed that the resistance strongly reduces the efficacy of pyrethroid-based treatments, thus emphasizing the urgent need for alternative insecticides or tools to reduce dengue transmission

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs

STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the endoplasmic reticulum (ER) and regulate store-operated Ca2+ entry (SOCE). The function of STIMs in the brain is only beginning to be explored, and the relevance of SOCE in nerve cells is being debated. Here we identify STIM2 as a central organizer of excitatory synapses. STIM2, but not its paralogue STIM1, influences the formation of dendritic spines and shapes basal synaptic transmission in excitatory neurons. We further demonstrate that STIM2 is essential for cAMP/PKA-dependent phosphorylation of the AMPA receptor (AMPAR) subunit GluA1. cAMP triggers rapid migration of STIM2 to ER–plasma membrane (PM) contact sites, enhances recruitment of GluA1 to these ER-PM junctions, and promotes localization of STIM2 in dendritic spines. Both biochemical and imaging data suggest that STIM2 regulates GluA1 phosphorylation by coupling PKA to the AMPAR in a SOCE-independent manner. Consistent with a central role of STIM2 in regulating AMPAR phosphorylation, STIM2 promotes cAMP-dependent surface delivery of GluA1 through combined effects on exocytosis and endocytosis. Collectively our results point to a unique mechanism of synaptic plasticity driven by dynamic assembly of a STIM2 signaling complex at ER-PM contact sites

Novel Monte Carlo approach quantifies data assemblage utility and reveals power of integrating molecular and clinical information for cancer prognosis

WV is a SULSA Systems Biology Prize PhD Student; VAS is supported by the BBSRC Research Council [grant number BB/F001398/1] and Medical Research Scotland [grant number FRG353]. DJH is supported by CASyM Concerted Action [grant number EU HEALTH-F4-2012-305033] and the Chief Scientist Office of Scotland.Current clinical practice in cancer stratifies patients based on tumour histology to determine prognosis. Molecular profiling has been hailed as the path towards personalised care, but molecular data are still typically analysed independently of known clinical information. Conventional clinical and histopathological data, if used, are added only to improve a molecular prediction, placing a high burden upon molecular data to be informative in isolation. Here, we develop a novel Monte Carlo analysis to evaluate the usefulness of data assemblages. We applied our analysis to varying assemblages of clinical data and molecular data in an ovarian cancer dataset, evaluating their ability to discriminate one-year progression-free survival (PFS) and three-year overall survival (OS). We found that Cox proportional hazard regression models based on both data types together provided greater discriminative ability than either alone. In particular, we show that proteomics data assemblages that alone were uninformative (p = 0.245 for PFS, p = 0.526 for OS) became informative when combined with clinical information (p = 0.022 for PFS, p = 0.048 for OS). Thus, concurrent analysis of clinical and molecular data enables exploitation of prognosis-relevant information that may not be accessible from independent analysis of these data types.Publisher PDFPeer reviewe

Body composition-derived BMI cut-offs for overweight and obesity in Indians and Creoles of Mauritius: comparison with Caucasians

Global estimates of overweight and obesity prevalence are based on the World Health Organisation (WHO) body mass index (BMI) cut-off values of 25 and 30 kg m⁻², respectively. To validate these BMI cut-offs for adiposity in the island population of Mauritius, we assessed the relationship between BMI and measured body fat mass in this population according to gender and ethnicity.Methods: In 175 young adult Mauritians (age 20-42 years) belonging to the two main ethnic groups—Indians (South Asian descent) and Creoles (African/Malagasy descent), body weight, height and waist circumference (WC) were measured, total body fat assessed by deuterium oxide (D2O) dilution and trunk (abdominal) fat by segmental bioimpedance analysis.Results: Compared to body fat% predicted from BMI using Caucasian-based equations, body fat% assessed by D2O dilution in Mauritians was higher by 3–5 units in Indian men and women as well as in Creole women, but not in Creole men. This gender-specific ethnic difference in body composition between Indians and Creoles is reflected in their BMI–Fat% relationships, as well as in their WC–Trunk Fat% relationships. Overall, WHO BMI cut-offs of 25 and 30 kg m⁻² for overweight and obesity, respectively, seem valid only for Creole men (~24 and 29.5, respectively), but not for Creole women whose BMI cut-offs are 2–4 units lower (21–22 for overweight; 27–28 for obese) nor for Indian men and women whose BMI cut-offs are 3–4 units lower (21–22 for overweight; 26–27 for obese).Conclusions: The use of BMI cut-off points for classifying overweight and obesity need to take into account both ethnicity and gender to avoid gross adiposity status misclassification in this population known to be at high risk for type-2 diabetes and cardiovascular diseases. This is particularly of importance in obesity prevention strategies both in clinical medicine and public health