The Role of MeCP2 in Brain Development and Neurodevelopmental Disorders

Methyl CpG binding protein-2 (MeCP2) is an essential epigenetic regulator in human brain development. Rett syndrome, the primary disorder caused by mutations in the X-linked MECP2 gene, is characterized by a period of cognitive decline and development of hand stereotypies and seizures following an apparently normal early infancy. In addition, MECP2 mutations and duplications are observed in a spectrum of neurodevelopmental disorders, including severe neonatal encephalopathy, X-linked mental retardation, and autism, implicating MeCP2 as an essential regulator of postnatal brain development. In this review, we compare the mutation types and inheritance patterns of the human disorders associated with MECP2. In addition, we summarize the current understanding of MeCP2 as a central epigenetic regulator of activity-dependent synaptic maturation. As MeCP2 occupies a central role in the pathogenesis of multiple neurodevelopmental disorders, continued investigation into MeCP2 function and regulatory pathways may show promise for developing broad-spectrum therapies

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021

Background Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings In 2021, the global prevalence of anaemia across all ages was 24·3% (95% uncertainty interval [UI] 23·9–24·7), corresponding to 1·92 billion (1·89–1·95) prevalent cases, compared with a prevalence of 28·2% (27·8–28·5) and 1·50 billion (1·48–1·52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52·0 million (35·1–75·1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422·4 [95% UI 286·1–612·9]), haemoglobinopathies and haemolytic anaemias (89·0 [58·2–123·7]), and other neglected tropical diseases (36·3 [24·4–52·8]), collectively accounting for 84·7% (84·1–85·2) of anaemia YLDs. Interpretation Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding Bill & Melinda Gates Foundation

Rainfall and crop modeling-based water stress assessment for rainfed maize cultivation in peninsular India

Water stress due to uneven rainfall distribution causes a significant impact on the agricultural production of monsoon-dependent peninsular India. In the present study, water stress assessment for rainfed maize crop is carried out for kharif (June-October) and rabi (October-February) cropping seasons which coincide with two major Indian monsoons. Rainfall analysis (1976-2010) shows that the kharif season receives sufficient weekly rainfall (28 +/- 32 mm) during 26th-39th standard meteorological weeks (SMWs) from southwest monsoon, whereas the rabi season experiences a major portion of its weekly rainfall due to northeast monsoon between the 42nd and 51st SMW (31 +/- 42 mm). The later weeks experience minimal rainfall (5.5 +/- 15 mm) and thus expose the late sown maize crops to a severe water stress during its maturity stage. Wet and dry spell analyses reveal a substantial increase in the rainfall intensity over the last few decades. However, the distribution of rainfall shows a striking decrease in the number of wet spells, with prolonged dry spells in both seasons. Weekly rainfall classification shows that the flowering and maturity stages of kharif maize (33rd-39th SMWs) can suffer around 30-40% of the total water stress. In the case of rabi maize, the analysis reveals that a shift in the sowing time from the existing 42nd SMW (16-22 October) to the 40th SMW (1-7 October) can avoid terminal water stress. Further, AquaCrop modeling results show that one or two minimal irrigations during the flowering and maturity stages (33rd-39th SMWs) of kharif maize positively avoid the mild water stress exposure. Similarly, rabi maize requires an additional two or three lifesaving irrigations during its flowering and maturity stages (48th-53rd SMWs) to improve productivity. Effective crop planning with appropriate sowing time, short duration crop, and high yielding drought-resistant varieties will allow for better utilization of the monsoon rain, thus reducing water stress with an increase in rainfed maize productivity