Predicted Functional Implications of Phosphorylation of Regulator of G Protein Signaling Protein in Plants

Heterotrimeric G proteins function in development, biotic, and abiotic stress responses, hormone signaling as well as sugar sensing. We previously proposed that discrimination of these various external signals in the G protein pathway is accomplished in plants by membrane-localized receptor-like kinases (RLKs) rather than G-protein-coupled receptors. Arabidopsis thaliana Regulator of G Signaling protein 1 (AtRGS1) modulates G protein activation and is phosphorylated by several RLKs and by WITH-NO-LYSINE kinases (WNKs). Here, a combination of in vitro kinase assays, mass spectrometry, and computational bioinformatics identified and functionally prioritized phosphorylation sites in AtRGS1. Phosphosites for two more RLKs (BRL3 and PEPR1) were identified and added to the AtRGS1 phosphorylation profile. Bioinformatics analyses revealed that RLKs and WNK kinases phosphorylate plant RGS proteins within regions that are conserved across eukaryotes and at a high frequency. Four phospho-sites among 14 identified are proximal to equivalent mammalian phosphosites that impact RGS function, including: pS437 and pT267 in GmRGS2, and pS339 and pS436 in AtRGS1. Based on these analyses, we propose that pS437 and pS436 regulate GmRGS2 and AtRGS1 protein interactions and/or localization, whereas pT267 is important for modulation of GmRGS2 GAP activity and localization. Moreover, pS339 most likely affects AtRGS1 activation

New genomic regions identified for resistance to spot blotch and terminal heat stress in an interspecific population of triticum aestivum and T. spelta

Wheat is one of the most widely grown and consumed food crops in the world. Spot blotch and terminal heat stress are the two significant constraints mainly in the Indo–Gangetic plains of South Asia. The study was undertaken using 185 recombinant lines (RILs) derived from the interspecific hybridization of ‘Triticum aestivum (HUW234) × T. spelta (H+26)’ to reveal genomic regions associated with tolerance to combined stress to spot blotch and terminal heat. Different physiological (NDVI, canopy temperature, leaf chlorophyll) and grain traits (TGW, grain size) were observed under stressed (spot blotch, terminal heat) and non-stressed environments. The mean maturity duration of RILs under combined stress was reduced by 12 days, whereas the normalized difference vegetation index (NDVI) was 46.03%. Similarly, the grain size was depleted under combined stress by 32.23% and thousand kernel weight (TKW) by 27.56% due to spot blotch and terminal heat stress, respectively. The genetic analysis using 6734 SNP markers identified 37 significant loci for the area under the disease progress curve (AUDPC) and NDVI. The genome-wide functional annotation of the SNP markers revealed gene functions such as plant chitinases, NB-ARC and NBS-LRR, and the peroxidase superfamily Cytochrome P450 have a positive role in the resistance through a hypersensitive response. Zinc finger domains, cysteine protease coding gene, F-box protein, ubiquitin, and associated proteins, play a substantial role in the combined stress of spot blotch and terminal heat in bread wheat, according to genomic domains ascribed to them. The study also highlights T. speltoides as a source of resistance to spot blotch and terminal heat tolerance

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Achieving cost efficiency through increased inventory leanness: Evidence from manufacturing industry

Inventory management’s fundamental problem starts with maintaining equilibrium among the operating efficiency, cost of investment, and other allied costs with extensive inventories to keep the actual conflicts at the minimum while optimizing the inventory holding levels. But, inventory management practices have not been well exploited in various manufacturing industries yet. In this study, inventory management tools, i.e., ABC and VED analysis, have been applied in the manufacturing industry, considering 146 items as raw material for an assembly. A total of 15 items under ‘AV’ class have been identified that consume 82.05 % of the total cost, and these items need strict control and frequent ordering. Sigma level of suppliers is also calculated, which comes out to be 2.36, and it must be improved to reduce the overall inventory cost

PROCESS VALIDATION OF LOPERAMIDE HCl TABLET

ABSTRACT To survive in competitive market and to be successful, it is necessary to achieve high level of product quality. Loperamide HCl [4-(P-chlorophenyl)-4-hydroxy-N,N-dimethyldiphenyl-1-piperidine butyramide hydrochloride), is an opiate agonist widely used as an effective drug for the control and relief of acute diarrhoea. Loperamide HCl tablets were prepared by wet granulation method. After process validation, it has been found that the prepared tablets showed good physical characteristics, drug content and all parameters were within the limits. Hence, it can be recommended that, the same parameters shall be considered as final for further commercial routine production batches of Loperamide HCl tablets

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Not AvailableXanthomonas campestris pv. campestris is a causative agent of black rot disease of cruciferous crops. A whole-genome sequence of any race of X. campestris pv. campestris has not been reported from India. The isolate Xcc-C7, race 4, of X. campestris pv. campestris was isolated from cabbage (Brassica oleracea var. capitata) from Bengaluru, in the southern parts of India. Whole-genome sequence data were generated by the next-generation sequencing-based single-molecule real-time sequencing (SMRT) techniques. This study will improve our knowledge of genomic diversity in X. campestris pv. campestris and pave the way for research on host–pathogen interactions (crucifer crops–X. campestris pv. campestris) to develop resistance in cultivated Brassicaceae crops.Not Availabl

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Not AvailableHalf of the global human population is dependent on rice as a staple food crop and more than 25% increase in rice productivity is required to feed the global population by 2030. With increase in irrigation, global warming and rising sea level, rising salinity has become one of the major challenges to enhance the rice productivity. Since the loss on this account is to the tune of US$12 billion per annum, it necessitates the global attention. In the era of technological advancement, substantial progress has been made on phenomics and genomics data generation but reaping benefit of this in rice salinity variety development in terms of cost, time and precision requires their harmonization. There is hardly any comprehensive holistic review for such combined approach. Present review describes classical salinity phenotyping approaches having morphological, physiological and biochemical components. It also gives a detailed account of invasive and non-invasive approaches of phenomic data generation and utilization. Classical work of rice salinity QLTs mapping in the form of chromosomal atlas has been updated. This review describes how QTLs can be further dissected into QTN by GWAS and transcriptomic approaches. Opportunities and progress made by transgenic, genome editing, metagenomics approaches in combating rice salinity problems are discussed. Major aim of this review is to provide a comprehensive over-view of hitherto progress made in rice salinity tolerance research which is required to understand bridging of phenotype based breeding with molecular breeding. This review is expected to assist rice breeders in their endeavours by fetching greater harmonization of technological advances in phenomics and genomics for better pragmatic approach having practical perspective.Not Availabl