Generalized biomolecular modeling and design with RoseTTAFold All-Atom

Deep learning methods have revolutionized protein structure prediction and design but are currently limited to protein-only systems. We describe RoseTTAFold All-Atom (RFAA) which combines a residue-based representation of amino acids and DNA bases with an atomic representation of all other groups to model assemblies containing proteins, nucleic acids, small molecules, metals, and covalent modifications given their sequences and chemical structures. By fine tuning on denoising tasks we obtain RFdiffusionAA, which builds protein structures around small molecules. Starting from random distributions of amino acid residues surrounding target small molecules, we design and experimentally validate, through crystallography and binding measurements, proteins that bind the cardiac disease therapeutic digoxigenin, the enzymatic cofactor heme, and the light harvesting molecule bilin

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4 (62.3 (55.1�70.8) million) to 6.4 (58.3 (47.6�70.7) million), but is predicted to remain above the World Health Organization�s Global Nutrition Target of <5 in over half of LMICs by 2025. Prevalence of overweight increased from 5.2 (30 (22.8�38.5) million) in 2000 to 6.0 (55.5 (44.8�67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic. © 2020, The Author(s)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

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Not AvailableOrganic agriculture’s economic benefits and widespread adoption are well documented, but its impact on soil C dynamics in rainfed regions of semiarid tropics is less understood. The use of organic amendments in organic farming not only supply nutrients but also have the potential to contribute to soil carbon sequestration. Carbon storage and various soil organic pools are affected differently by various crops and production systems. A study was conducted with three crops (sunflower, pigeonpea, and greengram) under three production systems (control, organic and integrated) to assess the effect on soil C stocks, carbon sequestration potential, and crop yield. After seven years of experiment, pigeonpea (Cajanus cajan L.) cultivation improved soil bulk density, porosity and water holding capacity compared to greengram [Vigna radiata (L) Wilczek] and sunflower (Helianthus annuus L.). Furthermore, plots under pigeonpea cultivation being on par with greengram had 15.6% higher total C (113.52 Mg C ha−1), 14% higher easily oxidizable organic C (17.5 Mg C ha−1) and C sequestration rate of 1.22 Mg C ha−1 yr−1 compared to sunflower. Among the three production systems, plots under organic management had significantly lower bulk density and higher water holding capacity and porosity at all of the profile depths compared to integrated production system and control. Similarly, organic production system being on par with integrated production system improved the easily oxidizable, oxidizable and weakly oxidizable organic C fractions at different soil depths compared to control. The C sequestration rate ranged from 0.21 to 0.85 Mg C ha−1 yr−1 in organic production systems compared to negligible rate (0.01–0.04 Mg ha−1 yr−1) in the plots under control. On average, integrated production system being on par with organic management recorded significantly higher pigeonpea equivalent seed yield (886 kg ha−1) compared to control (792 kg ha−1). These results suggest the potential of organic production system in improving soil properties, C sequestration, and crop yields in semiarid rainfed areasNot Availabl