Aedes aegypti lachesin protein binds to the domain III of envelop protein of Dengue virus-2 and inhibits viral replication.

Dengue virus (DENV) comprises of four serotypes (DENV-1 to -4) and is medically one of the most important arboviruses (arthropod-borne virus). DENV infection is a major human health burden and is transmitted between humans by the insect vector, Aedes aegypti. Ae. aegypti ingests DENV while feeding on infected humans, which traverses through its gut, haemolymph and salivary glands of the mosquito before being injected into a healthy human. During this process of transmission, DENV must interact with many proteins of the insect vector, which are important for its successful transmission. Our study focused on the identification and characterisation of interacting protein partners in Ae. aegypti to DENV. Since domain III (DIII) of envelope protein (E) is exposed on the virion surface and is involved in virus entry into various cells, we performed phage display library screening against domain III of the envelope protein (EDIII) of DENV-2. A peptide sequence showing similarity to lachesin protein was found interacting with EDIII. The lachesin protein was cloned, heterologously expressed, purified and used for in vitro interaction studies. Lachesin protein interacted with EDIII and also with DENV. Further, lachesin protein was localised in neuronal cells of different organs of Ae. aegypti by confocal microscopy. Blocking of lachesin protein in Ae. aegypti with anti-lachesin antibody resulted in a significant reduction in DENV replication

Productivity, nitrogen balance and economics of winter maize (Zea mays) as influenced by QPM cultivars and nitrogen levels

The experimental findings suggests that SEEDTEC 2324 proved superior over other cultivars for increasing yield of winter maize and application of 240 kg N/ha was found most suitable for achieving higher yield and profitability of winter maize in eastern Uttar Pradesh conditions. Further investigations are required to bring yields of QPM cultivars at par with the best normal endosperm cultivars

Draft genome sequence of Sclerospora graminicola, the pearl millet downy mildew pathogen:Genome sequence of pearl millet downy mildew pathogen

Sclerospora graminicola pathogen is one of the most important biotic production constraints of pearl millet worldwide. We report a de novo whole genome assembly and analysis of pathotype 1. The draft genome assembly contained 299,901,251 bp with 65,404 genes. Pearl millet [Pennisetum glaucum (L.) R. Br.], is an important crop of the semi-arid and arid regions of the world. It is capable of growing in harsh and marginal environments with highest degree of tolerance to drought and heat among cereals (1). Downy mildew is the most devastating disease of pearl millet caused by Sclerospora graminicola (sacc. Schroet), particularly on genetically uniform hybrids. Estimated annual grain yield loss due to downy mildew is approximately 10?80 % (2-7). Pathotype 1 has been reported to be the highly virulent pathotype of Sclerospora graminicola in India (8). We report a de novo whole genome assembly and analysis of Sclerospora graminicola pathotype 1 from India. A susceptible pearl millet genotype Tift 23D2B1P1-P5 was used for obtaining single-zoospore isolates from the original oosporic sample. The library for whole genome sequencing was prepared according to the instructions by NEB ultra DNA library kit for Illumina (New England Biolabs, USA). The libraries were normalised, pooled and sequenced on Illumina HiSeq 2500 (Illumina Inc., San Diego, CA, USA) platform at 2 x100 bp length. Mate pair (MP) libraries were prepared using the Nextera mate pair library preparation kit (Illumina Inc., USA). 1 ?g of Genomic DNA was subject to tagmentation and was followed by strand displacement. Size selection tagmented/strand displaced DNA was carried out using AmpureXP beads. The libraries were validated using an Agilent Bioanalyser using DNA HS chip. The libraries were normalised, pooled and sequenced on Illumina MiSeq (Illumina Inc., USA) platform at 2 x300 bp length. The whole genome sequencing was performed by sequencing of 7.38 Gb with 73,889,924 paired end reads from paired end library, and 1.15 Gb with 3,851,788 reads from mate pair library generated from Illumina HiSeq2500 and Illumina MiSeq, respectively. The sequences were assembled using various assemblers like ABySS, MaSuRCA, Velvet, SOAPdenovo2, and ALLPATHS-LG. The assembly generated by MaSuRCA (9) algorithm was observed superior over other algorithms and hence used for scaffolding using SSPACE. Assembled draft genome sequence of S. graminicola pathotype 1 was 299,901,251 bp long, with a 47.2 % GC content consisting of 26,786 scaffolds with N50 of 17,909 bp with longest scaffold size of 238,843 bp. The overall coverage was 40X. The draft genome sequence was used for gene prediction using AUGUSTUS. The completeness of the assembly was investigated using CEGMA and revealed 92.74% proteins completely present and 95.56% proteins partially present, while BUSCO fungal dataset indicated 64.9% complete, 12.4% fragmented, 22.7% missing out of 290 BUSCO groups. A total of 52,285 predicted genes were annotated using BLASTX and 38,120 genes were observed with significant BLASTX match. Repetitive element analysis in the assembly revealed 8,196 simple repeats, 1,058 low complexity repeats and 5,562 dinucleotide to hexanucleotide microsatellite repeats.publishersversionPeer reviewe

Multi-environment field testing to identify stable sources of resistance to charcoal rot (Macrophomina phaseolina) disease in tropical maize germplasm

The charcoal rot caused by Macrophomina phaseolina is the devastating component of post flowering stalk rot (PFSR) complex which may cause 25 to 32 % yield loss in maize. Therefore for the first time, the study was carried out with multi-environments screening of 137 inbreds at three and 48 maize hybrids at six environments under artificially created epiphytotics at hot-spot locations to identify stable sources of charcoal rot resistance in Indian maize germplasm. Analysis of variance revealed strong effect of genotype by environment interaction on disease response and therefore indicated its complex nature. The mean disease score was ranging from 2.37 to 7.20 in inbreds, and 3.63 to 6.08 in hybrids. Additive main effects and multiplicative Interactions (AMMI) analysis could identifed, DQL1020, DML339, DML1, DQL1019, CM117-1-1 in inbreds and A-7501, CMH08-287, CMH08-292, BIO-562, and CMH08-350 in hybrids as stable sources of charcoal rot resistance. Each testing site viz., Ludhiana, Hyderabad and Delhi was identified as a separate test environment for screening against charcoal rot disease in India. In this study, AMMI model offers a good tool to assess the stability of genotypes and GGE biplot found an efficient tool to identify the mega environments in multi-environment testing. The identified sources of resistance in inbreds can be used in resistant breeding and hybrids can be recommended for cultivation in charcoal rot disease prone area

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation