Search

Proteolysis targeting chimeras (PROTACs) promote the degradation of targets by ensuring the proximity of the E3-ligase and the target, and understanding the structure of PROTACs at the atomic level is key to developing more efficient degraders. Here the authors determine the complete atomic-level structure of an amorphous Von Hippel-Lindau (VHL)-based SMARCA2 PROTAC (PROTAC 2).

Charge transport and extraction in polycrystalline perovskite films are often hindered by inefficient carrier transfer across grain domain boundaries (GDBs). Here, authors employ supramolecular assisted Rb+ delivery for in-situ GDB bridging, achieving efficiency of 26.02% for perovskite solar cells.

Accurate segmentation of ischemic stroke lesions from brain MRI is crucial for timely diagnosis and treatment planning. Here, the authors present DeepISLES, an AI ensemble for stroke MRI analysis that outperforms previous methods and matches expert radiologist performance in identifying stroke lesions.

The Integrated Food Security Phase Classification system is the global method for classifying food insecurity severity and allocating humanitarian aid. An evaluation of 10,000 Integrated Food Security Phase Classification subnational analyses from 2017 to 2023 indicates that food severity might have been undercounted.

Rifampicin-resistant tuberculosis (RR-TB) requires longer, more toxic therapy than rifampicin-sensitive disease and is associated with a higher occurrence of long-term sequelae. In this mathematical modeling study, the authors estimate that incident RR-TB in 2020 will be responsible for ~6.9 million disability-adjusted life years; 44% due to post-tuberculosis sequelae.

The atomic-level ensemble structure of an amorphous form of a drug is determined by combining NMR experiments with molecular dynamics simulations and machine-learned chemical shifts. The structure explains the stabilization of the amorphous form.

The defects at the perovskite/carrier transport layer interface pose significant challenges to the performance of perovskite solar cells. Here, the authors introduce a dual host-guest complexation strategy with Cs-crown-ether and ammonium salt, achieving a high PCE of 25.9% with superior stability.

Clean water is a fundamental resource, yet the economic impacts of pollution, drinking water availability, and greenhouse gas emissions from freshwaters are unknown. Here the authors combine models with economic assessments and find trillions of dollars in savings by mitigating lake methane emissions.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

In Alzheimer’s disease, the role of connectivity in facilitating pathology accumulation remains unclear. Using in-vivo neuroimaging, the authors show that tau and reactive microglia follow connectome gradients, underlying cognitive decline.

Determining the structure of amorphous solids is important for optimization of pharmaceutical formulations, but direct relation of molecular dynamics (MD) simulations and NMR to achieve this is challenging. Here, the authors use a machine learning model of chemical shifts to solve the atomic-level structure of the hydrated amorphous drug AZD5718 by combining dynamic nuclear polarization-enhanced solid-state NMR with predicted shifts for MD simulations of large systems.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

It remains a challenge to achieve a balance between performance and stability, as well as addressing the environmental impact of perovskite solar cells. Here, the authors propose a multimodal host-guest complexation strategy enabling these shortcomings to be addressed simultaneously.

The authors predict biodiversity loss under potential future agricultural change. Agricultural expansion threatens species richness and abundance worldwide (up to one-third in some areas), often with little overlap between protected areas and high-risk expansion areas.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

The Pharma Proteomics Project generates the largest open-access plasma proteomics dataset to date, offering insights into trans protein quantitative trait loci across multiple biological domains, and highlighting genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks.

Element doping has been proven a useful strategy to tune the properties of halide perovskites. Here Xiang et al. show that barium unexpectedly does not incorporate in perovskite lattice but induces phase segregation and bandgap reduction and inhibits non-radiative recombination.

Various approaches have been developed to push higher the efficiency of halide perovskite solar cells. Here Alharbi et al. show that ammonium salts treatment can reduce the defect density at the perovskite surface and understand the passivation mechanism with 2D-solid state NMR.

Incorporation of the pseudo-halide anion formate during the fabrication of α-FAPbI₃ perovskite films eliminates deleterious iodide vacancies, yielding solar cell devices with a certified power conversion efficiency of 25.21 per cent and long-term operational stability.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Gulli et al. record neurons in the monkey hippocampus during multiple tasks in a virtual reality environment and find that spatial coding is task-dependent. Their analyses reveal rich nonspatial sensory and mnemonic coding of task-related features.

Tropical deforestation rates are linked to large-scale land investments, according to georeferenced land deal records and remote sensing of forest loss over the past two decades.

Mammalian DNA replication relies on various helicases and nucleases to ensure accurate genetic duplication, but how these enzymes are properly directed is unclear. Here, the authors identify USP50 as a key protein for promoting ongoing replication, restarting stalled forks, maintaining telomeres, and ensuring cell survival.

Whole-exome sequencing analysis of 454,787 individuals in the UK Biobank is used to examine the association of protein-coding variants with nearly 4,000 health-related traits, identifying 564 distinct genes with significant trait associations.

The aggregation prone D76N beta-2 microglobulin mutant causes systemic amyloidosis. Here the authors combine crystallography, solid-state NMR, and computational studies and show that the D76N mutation increases protein dynamics and destabilizes the outer strands, which leads to an exposure of amyloidogenic parts explaining its aggregation propensity.

Cultivated areas have expanded at the expense of forests, including primary and protected forests, in Southeast Asian highlands, according to an analysis of satellite imagery of the region.

Circulating liver enzymes, like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are highly heritable and predictive of disease. Here, the authors perform a genome-wide association study on ALT and AST, revealing a rare variant in SLC30A10 associated with elevated ALT and AST.

Trans-ancestry genome-wide analyses identify multiple loci associated with ascending aortic diameter. A polygenic score constructed from these loci predicted prevalent risk of thoracic aortic aneurysm in independent populations.

Genome-wide meta-analysis of SARS-CoV-2 susceptibility and severity phenotypes in up to 756,646 samples identifies a rare protective variant proximal to ACE2. A 6-SNP genetic risk score provides additional predictive power when added to known risk factors.

A microtechnology involving force sensors embedded in elastomers for cell culture enables the high-throughput measurement of single-cell force generation from contractile cells in a scalable and highly parallelized manner.

Analysis of whole-exome sequencing data from over 200,000 individuals in the UK Biobank provides new insights into the contribution of rare variants to cardiometabolic diseases and traits.

Bone mineral density (BMD) is associated with fracture risk and many genetic loci with small effect sizes have been discovered by genome-wide association studies (GWAS). Here, the authors discover a large-effect rare loss-of-function genetic variant for BMD in the MEPE gene in the Norwegian HUNT study which replicates in the UK Biobank.

The world keeps urbanizing. This study finds that since 1985 global urban lands have expanded four times faster than previously recognized and faster than population is growing.

Solid-state NMR is useful to study the local structure, dynamics and dopant speciation in metal halide perovskites. This Perspective describes the practical aspects of the method that make it broadly applicable to optoelectronic materials.

The UK Biobank Exome Sequencing Consortium aims to sequence all the exomes of approximately 500,000 UK Biobank participants. This Perspective describes the results from approximately 200,000 exomes and discusses the lessons learned from this UK Biobank–biopharmaceutical company collaboration.

This Primer on solid-state nuclear magnetic resonance spectroscopy summarizes the most common experiments and data analysis approaches used to determine the structure and dynamics of solids and semi-solids as applied to biology, chemistry and materials sciences.