Exome and transcriptome sequencing of Aedes aegypti identifies a locus that confers resistance to Brugia malayi and alters the immune response.

Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.This work was funded by a Cambridge- KAUST Academic Excellence Alliance (AEA2) project grant to AP and CVA was supported by a Cambridge Overseas Trust Studentship. JA was supported by a Darwin Trust of Edinburgh. WJP was supported by a Medical Research Council. FMJ was supported by Royal Society Research. EASIH is supported by Cambridge NIHR-BRC. The Wellcome Trust Centre for Human Genetics is funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC hub grant G0900747 91070. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.his is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100476

Alternative patterns of sex chromosome differentiation in Aedes aegypti (L).

BACKGROUND: Some populations of West African Aedes aegypti, the dengue and zika vector, are reproductively incompatible; our earlier study showed that divergence and rearrangements of genes on chromosome 1, which bears the sex locus (M), may be involved. We also previously described a proposed cryptic subspecies SenAae (PK10, Senegal) that had many more high inter-sex FST genes on chromosome 1 than did Ae.aegypti aegypti (Aaa, Pai Lom, Thailand). The current work more thoroughly explores the significance of those findings. RESULTS: Intersex standardized variance (FST) of single nucleotide polymorphisms (SNPs) was characterized from genomic exome capture libraries of both sexes in representative natural populations of Aaa and SenAae. Our goal was to identify SNPs that varied in frequency between males and females, and most were expected to occur on chromosome 1. Use of the assembled AaegL4 reference alleviated the previous problem of unmapped genes. Because the M locus gene nix was not captured and not present in AaegL4, the male-determining locus, per se, was not explored. Sex-associated genes were those with FST values ≥ 0.100 and/or with increased expected heterozygosity (H exp , one-sided T-test, p < 0.05) in males. There were 85 genes common to both collections with high inter-sex FST values; all genes but one were located on chromosome 1. Aaa showed the expected cluster of high inter-sex FST genes proximal to the M locus, whereas SenAae had inter-sex FST genes along the length of chromosome 1. In addition, the Aaa M-locus proximal region showed increased H exp levels in males, whereas SenAae did not. In SenAae, chromosomal rearrangements and subsequent suppressed recombination may have accelerated X-Y differentiation. CONCLUSIONS: The evidence presented here is consistent with differential evolution of proto-Y chromosomes in Aaa and SenAae

Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

Purpose: Neurofibromatosis type 1 (NF1) is characterized by a highly variable clinical presentation, but almost all NF1-affected adults present with cutaneous and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild phenotype without any externally visible tumors. Methods: A total of 135 individuals from 103 unrelated families, all carrying the constitutional NF1 p.Met992del pathogenic variant and clinically assessed using the same standardized phenotypic checklist form, were included in this study. Results: None of the individuals had externally visible plexiform or histopathologically confirmed cutaneous or subcutaneous neurofibromas. We did not identify any complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors, mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning disabilities. In an individual with the NF1 constitutional c.2970_2972del and three astrocytomas, we provided proof that all were NF1-associated tumors given loss of heterozygosity at three intragenic NF1 microsatellite markers and c.2970_297

Gestational diabetes mellitus – The modern Indian perspective

Gestational diabetes mellitus (GDM) is a serious and most frequent health complication during pregnancy which is associated with a significant increase in the risk of maternal and neonatal outcomes. GDM is usually the result of β-cell dysfunction along with chronic insulin resistance during pregnancy. Seshiah et al. pioneer work led to the adoption of Diabetes in Pregnancy Study Group in India criteria as the norm to diagnose GDM, especially in the community setting. In 2014, the Maternal Health Division of the Ministry of Health and Family Welfare, Government of India, updated guidelines and stressed upon the proper use of guidelines such as using a glucometer for self-monitoring and the use of oral hypoglycaemic agents. The 2018 Government of India guidelines stress the importance of counselling about lifestyle modifications, weight control, exercise, and family planning

Efficacy and safety of an <i style="">Ayurvedic</i> regimen in <i style="">Medoroga</i>

379-386A study with an Ayurveda regimen consisting of Navaka guggulu, Sthaulyahara kashayam, a diet pattern and walk exercise for a treatment period of 3 mandalams (120 days) in medoroga was conducted to probe the efficacy and safety aspects of the regimen. 71 patients of medoroga were recruited for the study, and 34 patients formed the sample conforming to certain inclusion and exclusion criteria. Assessment of efficacy at the end of the 120-day treatment period vis-à-vis baseline was done using a self-designed proforma considering the symptoms in accordance with the Ayurvedic system and the physical parameters chest (uras) circumference, abdomen (udara) circumference and hip (sphik) circumference as enunciated in the classical texts. Certain hepatic and renal function tests were done to examine the safety profile of the treatment regimen. At the end of the treatment period, noteworthy symptomatic improvement was found in the patients; statistically significant (pAyurvedic treatment regimen when administered for a period of 120 days to patients of medoroga. The importance of doing exercise in addition to intake of the medicines and a diet pattern in medoroga is emphasized

Design and synthesis of novel anthracene derivatives as n-type emitters for electroluminescent devices: a combined experimental and DFT study

Six novel anthracene-oxadiazole derivatives, 4a (2-(4-(anthracen-9-yl)phenyl)-5-p-tolyl-1,3,4-oxadiazole), 4b (2-(4-(anthracen-9-yl)phenyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole), 4c (2-(4-(anthracen-9-yl)phenyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazole), 8a (2-(4-(anthracen-9-yl)phenyl)-5-m-tolyl-1,3,4-oxadiazole), 8b (2-(3-(anthracen-9-yl)phenyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole) and 8c (2-(3-(anthracen-9-yl)phenyl)-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole) have been synthesized and characterized for use as emitters in organic light emitting devices (OLEDs). They show good thermal stability (T-d, 297-364 degrees C) and glass transition temperatures (T-g) in the range of 82-98 degrees C, as seen from the thermo gravimetric analysis and differential scanning calorimetric studies. The solvatochromism phenomenon and electrochemical properties have been studied in detail using UV-Vis absorption, fluorescence spectroscopy and cyclic voltammetry. TD-DFT calculations have been carried out to understand the electrochemical and photophysical properties. The spatial structures of 4b and 8c are further confirmed by X-ray diffraction analysis. Un-optimized non-doped electroluminescent devices were fabricated using these anthracene derivatives as emitters with the following device configuration: ITO (120 nm)/alpha-NPD (30 nm)/4a-4c or 8a-8c (35 nm)/BCP (6 nm)/Alq(3) (28 nm)/LiF (1 nm)/Al (150 nm). Among all the six compounds, 8a displays the maximum brightness of 1728 cd m(-2) and current efficiency 0.89 cd A(-1). Furthermore, as an electron transporter, 8a exhibited superior performance (current efficiency is 11.7 cd A(-1)) than the device using standard Alq(3) (current efficiency is 8.69 cd A(-1)), demonstrating its high potential for employment in OLEDs. These results indicate that the new anthracene-oxadiazole derivatives could play an important role in the development of OLEDs

Surface modified ZnO nanoparticles: structure, photophysics, and its optoelectronic application

Nanostructured ZnO has been synthesized by wet chemical route. Poly(vinylpyrrolidone) is used for stabilization and surface passivation of synthesized nanoparticles, thus tailoring the growth of ZnO at nanoscale. Structural characterization using X-ray diffraction, scanning electron microscopy, high-resolution transmission electron micoroscopy and Fourier transformed infrared spectroscopy of the synthesized nanoparticles confirm the evolution of nanocrystalline ZnO prevailing in hexagonal wurtzite phase. UV-Vis and photoluminescence spectroscopy studies show blue shift phenomenon in the synthesized nanoparticle in contrast to the bulk ZnO furnishing evidence in support of quantumsize effect. The nanocomposites of ZnO and poly [9,9-dioctylfluorenyl-2,7-diyl] are prepared and characterized to investigate its luminescent and spectral emission effects. The nanocomposites are then incorporated in light-emitting diodes, and influence of ZnO on the device performance has been explored via electroluminescence, current density evaluation, and corresponding CIE coordinates calculation