A mitochondrial membrane-bridging machinery mediates signal transduction of intramitochondrial oxidation

Mitochondria are the main site for generating reactive oxygen species, which are key players in diverse biological processes. However, the molecular pathways of redox signal transduction from the matrix to the cytosol are poorly defined. Here we report an inside-out redox signal of mitochondria. Cysteine oxidation of MIC60, an inner mitochondrial membrane protein, triggers the formation of disulfide bonds and the physical association of MIC60 with Miro, an outer mitochondrial membrane protein. The oxidative structural change of this membrane-crossing complex ultimately elicits cellular responses that delay mitophagy, impair cellular respiration and cause oxidative stress. Blocking the MIC60–Miro interaction or reducing either protein, genetically or pharmacologically, extends lifespan and health-span of healthy fruit flies, and benefits multiple models of Parkinson’s disease and Friedreich’s ataxia. Our discovery provides a molecular basis for common treatment strategies against oxidative stress

Strokectomy for malignant middle cerebral artery infarction: experience and meta-analysis of current evidence

Strokectomy means surgical excision of infarcted brain tissue post-stroke with preservation of skull integrity, distinguishing it from decompressive hemicraniectomy. Both can mitigate malignant middle cerebral artery (MCA) syndrome but evidence regarding strokectomy is sparse. Here, we report our data and meta-analysis of strokectomy compared to hemicraniectomy for malignant MCA infarction. All malignant MCA stroke cases requiring surgical intervention in a large tertiary centre (January 2012–December 2017, N = 24) were analysed for craniotomy diameter, complications, length of follow-up and outcome measured using the modified Rankin score (mRS). Good outcome was defined as mRS 0–3 at 12 months. In a meta-analysis, outcome from strokectomy (pooled from our cohort and published strokectomy studies) was compared with hemicraniectomy (our cohort pooled with published DECIMAL, DESTINY and HAMLET clinical trial data). In our series (N = 24, 12/12 F/M; mean age: 45.83 ± 8.91, range 29–63 years), 4 patients underwent strokectomy (SC) and 20 hemicraniectomy (HC). Among SC patients, craniotomy diameter was smaller, relative to HC patients (86 ± 13.10 mm, 120 ± 4.10 mm, respectively; p = 0.003), complications were less common (25%, 55%) and poor outcomes were less common (25%, 70%). In the pooled data (N = 41 SC, 71 HC), strokectomy tended towards good outcome more than hemicraniectomy (OR 2.2, 95% CI 0.99–4.7; p = 0.051). In conclusion, strokectomy may be non-inferior, lower risk and cost saving relative to hemicraniectomy sufficiently to be worthy of further investigation and maybe a randomised trial

Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the Global Burden of Disease Study 2021

BACKGROUND: Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. METHODS: We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures-borrowing strength from predictive covariates and across age, time, and geography-and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). FINDINGS: Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1-16·5), to 515 000 (425 000-614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3-44·9), from 5·46 million (4·62-6·45) in 2000 to 7·74 million (6·51-9·2) in 2021. We estimated 34 400 (25 000-45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000-467 000). In children younger than 5 years, there were 81 100 (58 800-108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. INTERPRETATION: Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease. FUNDING: Bill & Melinda Gates Foundation

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Not AvailabletFarmers in peri-urban areas of developing countries depend on wastewaters for their livelihood but withgrave health and environmental risks. An 8-year field experiment compared food grain (FGPS), agro-forestry (AFS), fodder (FPS) and vegetable (VPS) production systems and quantified responses to fertilizers(NP 25–100%) when irrigated with sewage (SW; EC 1.3 ± 0.3 dS m−1BOD 82 ± 11, NO3–N 3.2 ± 0.4, NH4–N9.6 ± 0.5, P 1.8 ± 0.3, K 6.4 ± 0.4 mg L−1) vis-à-vis groundwater (GW). Productivity improved with SW by14–28% while trends were negative with sub-optimal NP under GW. Partial factor productivity (PFP)averaged 18.0, 11.1, 157 and 149 kg kg−1NP with GW in FGPS, AFS, FPS and VPS, respectively. Counterfigures were 13.8, 8.8, 96 and 56 kg kg−1NP with SW. Paddy-wheat equivalent yields were 5.5, 1.8 and19.9 fold under AFS, FPS and VPS with SW. About 40, 33, 75 and 20% of fertilizer NP with SW was sufficientfor similar production as with recommended NP and GW in FGPS, AFS, FPS and VPS, respectively. Qualityof produce improved in terms of crude protein and the micronutrients in edible parts with SW while toxicmetals were within the permissible limits. However, the keeping quality of vegetables was lowered due tofaster decay with pathogens contamination (Aerobic bacterial plate counts 5 × 105–4.2 × 108cfu g−1andEscherichia coli <2 × 102–7 × 105). Thus, the sewage proved as a vital resource in improving productivity,sustainability and saving fertiliser costs but this may pose health risks because of pathogenic infestationthat need to be regulated.Not Availabl

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Not AvailableFarmers in developing countries irrigate crops using raw urban and industrial effluents with consequent risks from metal contamination. Therefore, soils, crops and groundwater from an effluent irrigation use site were assessed for Cd, Cr, Ni and Pb. Total and available contents of metals in soil followed the order Pb Ni Cr Cd. Crops accumulated more Pb, followed by Cd, Ni and Cr. Pb exceeded the permissible limit with wastewater irrigation only, but Cd exceeded the limit even with combined irrigations of wastewater and groundwater. Among crops, sugar beet assimilated highest Cd (3.14 lg g - 1) and Pb (6.42 lg g - 1) concentrations. Legumes accumulated more metals than cereals. Long - term use of wastewater and its conjunctive use with groundwater led to toxic accumulations of Cd, Pb, Ni and Cr. Cd with higher availability and mobility indices and lower toxicity limit, posed the maximum risk of food - chain contamination.Not Availabl

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Not AvailableLarge areas in arid and semi-arid regions remain barren due to lack of irrigation. The underground aquifers in these regions are either saline or sodic. Groundwater surveys indicate that poor-quality water is used to irrigate arable crops in 25–84 %of the total groundwater development areas in north-western states of India. The present long-term study assessed the performance of low-water-requiring, salt-tolerant fruit-based (Carissa carandas, Emblica officinalis, Aegle marmelos) agroforestry systems with saline irrigation under sem-iarid conditions. The companion crops such as Hordeum vulgare for malt, Brassica juncea, a seed oil (winter), and Cyamopsis tetragonoloba for gum and Pennisetum typhoides, a coarse grain/fodder (summer), were grown in inter-row spaces. The fruit trees were successfully established in the sill of furrows using low (EC 4–5 dS m-1) salinity water. Subsequently, all the systems were irrigated with water of low and high (8.5–10.0 dS m-1) salinity and their alternate use as per treatments. Fruit yields under alternate and high saline irrigation reduced by 18–27.5 % in Carissa, 41.6 % in Emblica and 31.7–54.8 % in Aegle, respectively. There was no significant reduction in grain yields of Pennisetum and Hordeum. However, in subsequent years, the seed yields of Cyamopsis and Brassica reduced with saline water and more so when intercropped with Aegle. Carissa with Pennisetum and Hordeum performed best with saline water. The study shows that saline water (ECiw up to 10 dS m-1) could be used sustainably for these fruit-based agroforestry systems without significant salinity build-up in sandy loam calcareous soils. Thus, such fruit-based agroforestry systems could be a viable option for the areas with only saline groundwater available for irrigation.Not Availabl

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Not AvailableMungbean is a relatively drought tolerant leguminous crop with a short life cycle. Using leaf water loss (LWL) as a screen for drought tolerance, two mungbean genotypes exhibiting more than two–fold variation in leaf water loss were explored for the genetic variation in their physiological and molecular responses to drought. Efficient stomatal regulation together with better photosynthetic capacity constituted an important trait combination for drought adaptation in water saving low LWL genotype. The stomatal closure under drought was accompanied with a concomitant down-regulation of farnesyl transferase gene. However, cooler canopy temperature, a well branched root system coupled with a relatively higher proline accumulation in water spending high LWL genotype constituted another set of adaptive traits operating when exposed to deficit soil moisture conditions. We report drought induced down-regulation of proline dehydrogenase and the presence of 118 base pair intron in this gene. The high seed yield of low LWL genotype despite a hotter canopy might be attributed to higher net assimilation and quantum yield recorded under drought in this genotype. Thus, these interlinked features contribute to adaptive mechanisms of mungbeans which is widely grown in harsh environments exposed to drought and high temperatures.Not Availabl