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

Systematic review of reverse vaccinology and immunoinformatics data for non-viral sexually transmitted infections

Abstract Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million new cases of curable STIs yearly. Global efforts to control their spread have been insufficient in fulfilling their objective. As there is no vaccine for many of these infections, these efforts are focused on education and condom distribution. The development of vaccines for STIs is vital for successfully halting their spread. The field of immunoinformatics is a powerful new tool for vaccine development, allowing for the identification of vaccine candidates within a bacterium’s genome and allowing for the design of new genome-based vaccine peptides. The goal of this review was to evaluate the usage of immunoinformatics in research focused on non-viral STIs, identifying fields where research efforts are concentrated. Here we describe gaps in applying these techniques, as in the case of Treponema pallidum and Trichomonas vaginalis

What 'outliers' tell us about missed opportunities for tuberculosis control: a cross-sectional study of patients in Mumbai, India

BACKGROUND: India's Revised National Tuberculosis Control Programme (RNTCP) is deemed highly successful in terms of detection and cure rates. However, some patients experience delays in accessing diagnosis and treatment. Patients falling between the 96th and 100th percentiles for these access indicators are often ignored as atypical 'outliers' when assessing programme performance. They may, however, provide clues to understanding why some patients never reach the programme. This paper examines the underlying vulnerabilities of patients with extreme values for delays in accessing the RNTCP in Mumbai city, India. METHODS: We conducted a cross-sectional study with 266 new sputum positive patients registered with the RNTCP in Mumbai. Patients were classified as 'outliers' if patient, provider and system delays were beyond the 95th percentile for the respective variable. Case profiles of 'outliers' for patient, provider and system delays were examined and compared with the rest of the sample to identify key factors responsible for delays. RESULTS: Forty-two patients were 'outliers' on one or more of the delay variables. All 'outliers' had a significantly lower per capita income than the remaining sample. The lack of economic resources was compounded by social, structural and environmental vulnerabilities. Longer patient delays were related to patients' perception of symptoms as non-serious. Provider delays were incurred as a result of private providers' failure to respond to tuberculosis in a timely manner. Diagnostic and treatment delays were minimal, however, analysis of the 'outliers' revealed the importance of social support in enabling access to the programme. CONCLUSION: A proxy for those who fail to reach the programme, these case profiles highlight unique vulnerabilities that need innovative approaches by the RNTCP. The focus on 'outliers' provides a less resource- and time-intensive alternative to community-based studies for understanding the barriers to reaching public health programmes

The OpenMolcas Web: A Community-Driven Approach to Advancing Computational Chemistry

The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

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

Effect of environmental deprivation on anxiety in rats

853-857<span style="font-size: 15.0pt;mso-bidi-font-size:8.0pt;font-family:" times="" new="" roman","serif";="" color:black"="">Environmental deprivation (ED) induced a significant increase in open-field ambulation, rears, self-groomings, faecal pellets and decrease in activity in centre in Charles Foster albino rats of 30, 45 and 60 days age groups. In elevated plus maze, significant attenuation of open arm time I <span style="font-size:15.0pt;mso-bidi-font-size: 8.0pt;font-family:" times="" new="" roman","serif";color:black"="">entries and augmentation of enclosed arm time <span style="font-size:15.5pt; mso-bidi-font-size:8.5pt;font-family:" arial","sans-serif";color:black"="">I entries were noted in ED rats of all the three age groups. Similarly ED rats also showed significant decrease in time spent on open arms, entries, head dips and stretched attend postures in comparison to age matched rats reared under normal environmental conditions. The results indicate that imposition of environmental deprivation in rats' life consistently resulted in significant anxiogenic behaviour on all the tests. However, the anxiogenic effect of ED was less marked when i<span style="font-size:14.0pt; mso-bidi-font-size:7.0pt;font-family:" arial","sans-serif";color:black"="">t was imposed at 60<span style="font-size:12.5pt; mso-bidi-font-size:5.5pt;font-family:" times="" new="" roman","serif";color:black"="">th <span style="font-size:15.0pt;mso-bidi-font-size:8.0pt; font-family:" times="" new="" roman","serif";color:black"="">day of life in rats. </span

Effect of prenatal alprazolam exposure on anxiety patterns in rat offspring

35-39<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:black;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">Prenatal alprazolam (APZ) treatment in 0.1 and 0.2 mg/kg/day doses during 13-20 days of gestation induced significant increase in open-field ambulation, rearings, self-grooming and faecal pellets in rat offspring. Prenatal APZ treated rats displayed significantly increased anxiogenic behaviour on elevated plus maze (spent less time on open arms, more time on enclosed arms and made less number of entries on open arms) and increased anxiogenecity on elevated zero maze (APZ treated rats spent less time on open arms and made less number of head dips and stretched attend postures in comparison to control rat offspring). The results indicate persistent behavioural alterations in the rat offspring after prenatal exposure to APZ.</span

Hyperglycaemia in pregnancy: Effects on the offspring behaviour with special reference to anxiety paradigms

231-236Maternal hyperglycemic effect was studied on the offspring behaviour. Offspring were obtained from diabetic rats by mating a normal father with a diabetic mother (NFDM), diabetic father with normal mother (DFNM) and diabetic father with diabetic mother (DFDM). Rats were rendered diabetic by injecting streptozotocin (STZ, 50 mg/kg IP) in citrate buffer. Offspring were subjected to various anxiety parameters including open field exploratory behaviour, elevated plus maze and zero maze behaviours, and the social interaction tests at the age of 8 weeks. The results indicate that offspring of NFDM and DFDM showed anxiogenic activity on the elevated plus maze zero maze and the social interaction test. Offspring of NFDM and DFDM exhibited hyper and emotional activity in the open field behaviour test. The behavioural alterations observed in the offspring were comparable to the behavioural alterations noted in STZ diabetic rat as reported earlier. Further offspring of NFDM and DFDM exhibited mild hyperglycaemia. No significant behavioural alterations in the offspring of DFNM were observed. It may be concluded, that exposure of offspring to diabetic environment in their foetal life can lead to anxiogenic/emotional behaviours in adult life