Deciphering the cause of evolutionary variance within intrinsically disordered regions in human proteins

<p>Why the intrinsically disordered regions evolve within human proteome has became an interesting question for a decade. Till date, it remains an unsolved yet an intriguing issue to investigate why some of the disordered regions evolve rapidly while the rest are highly conserved across mammalian species. Identifying the key biological factors, responsible for the variation in the conservation rate of different disordered regions within the human proteome, may revisit the above issue. We emphasized that among the other biological features (multifunctionality, gene essentiality, protein connectivity, number of unique domains, gene expression level and expression breadth) considered in our study, the number of unique protein domains acts as a strong determinant that negatively influences the conservation of disordered regions. In this context, we justified that proteins having a fewer types of domains preferably need to conserve their disordered regions to enhance their structural flexibility which in turn will facilitate their molecular interactions. In contrast, the selection pressure acting on the stretches of disordered regions is not so strong in the case of multi-domains proteins. Therefore, we reasoned that the presence of conserved disordered stretches may compensate the functions of multiple domains within a single domain protein. Interestingly, we noticed that the influence of the unique domain number and expression level acts differently on the evolution of disordered regions from that of well-structured ones.</p

Global emerging Omicron variant of SARS-CoV-2: Impacts, challenges and strategies

Newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuously posing high global public health concerns and panic resulting in waves of coronavirus disease 2019 (COVID-19) pandemic. Depending on the extent of genomic variations, mutations and adaptation, few of the variants gain the ability to spread quickly across many countries, acquire higher virulency and ability to cause severe disease, morbidity and mortality. These variants have been implicated in lessening the efficacy of the current COVID-19 vaccines and immunotherapies resulting in break-through viral infections in vaccinated individuals and recovered patients. Altogether, these could hinder the protective herd immunity to be achieved through the ongoing progressive COVID-19 vaccination. Currently, the only variant of interest of SARS-CoV-2 is Omicron that was first identified in South Africa. In this review, we present the overview on the emerging SARS-CoV-2 variants with a special focus on the Omicron variant, its lineages and hybrid variants. We discuss the hypotheses of the origin, genetic change and underlying molecular mechanism behind higher transmissibility and immune escape of Omicron variant. Major concerns related to Omicron including the efficacy of the current available immunotherapeutics and vaccines, transmissibility, disease severity, and mortality are discussed. In the last part, challenges and strategies to counter Omicron variant, its lineages and hybrid variants amid the ongoing COVID-19 pandemic are presented

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 202

The global, regional, and national burden of cancer, 1990–2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023

The global, regional, and national burden of cancer, 1990–2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023</p

Global, regional, and national burden of chronic respiratory diseases and impact of the COVID-19 pandemic, 1990–2023: a Global Burden of Disease study

Global, regional, and national burden of chronic respiratory diseases and impact of the COVID-19 pandemic, 1990–2023: a Global Burden of Disease stud

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 202

Global, regional, and national burden of breast cancer among females, 1990–2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023

Global, regional, and national burden of breast cancer among females, 1990–2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 202

Global, regional, and national burden of stroke and its risk factors, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Global, regional, and national burden of stroke and its risk factors, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021</p

Global, regional, and national age-sex-specific burden of diarrhoeal diseases, their risk factors, and aetiologies, 1990–2021, for 204 countries and territories: a systematic analysis for the Global Burden of Disease Study 2021

Background: Diarrhoeal diseases claim more than 1 million lives annually and are a leading cause of death in children younger than 5 years. Comprehensive global estimates of the diarrhoeal disease burden for specific age groups of children younger than 5 years are scarce, and the burden in children older than 5 years and in adults is also understudied. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to assess the burden of, and trends in, diarrhoeal diseases overall and attributable to 13 pathogens, as well as the contributions of associated risk factors, in children and adults in 204 countries and territories from 1990 to 2021. Methods: We used the Cause of Death Ensemble modelling strategy to analyse vital registration data, verbal autopsy data, mortality surveillance data, and minimally invasive tissue sampling data. We used DisMod-MR (version 2.1), a Bayesian meta-regression tool, to analyse incidence and prevalence data identified via systematic reviews, population-based surveys, and claims and inpatient data. We calculated diarrhoeal disability-adjusted life-years (DALYs) as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for each location, year, and age–sex group. For aetiology estimation, we used a counterfactual approach to quantify population-attributable fractions (PAFs). Additionally, we estimated the diarrhoeal disease burden attributable to the independent effects of risk factors using the comparative risk assessment framework. Findings: In 2021, diarrhoeal diseases caused an estimated 1·17 million (95% uncertainty interval 0·793–1·62) deaths globally, representing a 60·3% (50·6–69·0) decrease since 1990 (2·93 million [2·31–3·73] deaths). The most pronounced decline was in children younger than 5 years, with a 79·2% (72·4–84·6) decrease in diarrhoeal deaths. Global YLLs also decreased substantially, from 186 million (147–221) in 1990 to 51·4 million (39·9–65·9) in 2021. In 2021, an estimated 59·0 million (47·2–73·2) DALYs were attributable to diarrhoeal diseases globally, with 30·9 million (23·1–42·0) of these affecting children younger than 5 years. Leading risk factors for diarrhoeal DALYs included low birthweight and short gestation in the neonatal age groups, child growth failure in children aged between 1–5 months and 2–4 years, and unsafe water and poor sanitation in older children and adults. We estimated that the removal of all evaluated diarrhoeal risk factors would reduce global DALYs from 59·0 million (47·2–73·2) to 4·99 million (1·99–10·0) among all ages combined. Globally in 2021, rotavirus was the predominant cause of diarrhoeal deaths across all ages, with a PAF of 15·2% (11·4–20·1), followed by norovirus at 10·6% (2·3–17·0) and Cryptosporidium spp at 10·2% (7·03–14·3). In children younger than 5 years, the fatal PAF of rotavirus was 35·2% (28·7–43·0), followed by Shigella spp at 24·0% (15·2–37·9) and adenovirus at 23·8% (14·8–36·3). Other pathogens with a fatal PAF greater than 10% in children younger than 5 years included Cryptosporidium spp, typical enteropathogenic Escherichia coli, and enterotoxigenic E coli producing heat-stable toxin. Interpretation: The substantial decline in the global burden of diarrhoeal diseases since 1990, particularly in children younger than 5 years, supports the effectiveness of health interventions such as oral rehydration therapy, enhanced water, sanitation, and hygiene (WASH) infrastructure, and the introduction and scale-up of rotavirus vaccination. Targeted interventions and preventive measures against key risk factors and pathogens could further reduce this burden. Continued investment in the development and distribution of vaccines for leading pathogens remains crucial. Funding: Bill & Melinda Gates Foundation.</p

Global, regional, and national burden of stroke and its risk factors, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990–2021. Methods: We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, and metabolic risks) at the global and regional levels (21 GBD regions and Socio-demographic Index [SDI] quintiles), using the standard GBD methodology. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In 2021, stroke was the third most common GBD level 3 cause of death (7·3 million [95% UI 6·6–7·8] deaths; 10·7% [9·8–11·3] of all deaths) after ischaemic heart disease and COVID-19, and the fourth most common cause of DALYs (160·5 million [147·8–171·6] DALYs; 5·6% [5·0–6·1] of all DALYs). In 2021, there were 93·8 million (89·0–99·3) prevalent and 11·9 million (10·7–13·2) incident strokes. We found disparities in stroke burden and risk factors by GBD region, country or territory, and SDI, as well as a stagnation in the reduction of incidence from 2015 onwards, and even some increases in the stroke incidence, death, prevalence, and DALY rates in southeast Asia, east Asia, and Oceania, countries with lower SDI, and people younger than 70 years. Globally, ischaemic stroke constituted 65·3% (62·4–67·7), intracerebral haemorrhage constituted 28·8% (28·3–28·8), and subarachnoid haemorrhage constituted 5·8% (5·7–6·0) of incident strokes. There were substantial increases in DALYs attributable to high BMI (88·2% [53·4–117·7]), high ambient temperature (72·4% [51·1 to 179·5]), high fasting plasma glucose (32·1% [26·7–38·1]), diet high in sugar-sweetened beverages (23·4% [12·7–35·7]), low physical activity (11·3% [1·8–34·9]), high systolic blood pressure (6·7% [2·5–11·6]), lead exposure (6·5% [4·5–11·2]), and diet low in omega-6 polyunsaturated fatty acids (5·3% [0·5–10·5]). Interpretation: Stroke burden has increased from 1990 to 2021, and the contribution of several risk factors has also increased. Effective, accessible, and affordable measures to improve stroke surveillance, prevention (with the emphasis on blood pressure, lifestyle, and environmental factors), acute care, and rehabilitation need to be urgently implemented across all countries to reduce stroke burden. Funding: Bill & Melinda Gates Foundation