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This study characterizes the interaction between the clinical candidate anle138b and Aβ₄₀ fibrils in a lipid environment. The compound reduced fibril formation by approximately 75%, providing insights relevant to Alzheimer’s drug development.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Caroline Fox and colleagues report results of a large genome-wide association meta-analysis and replication study for indices of renal function. Their work identifies 13 new loci associated with renal function and 7 loci associated with creatinine production and secretion.

Femtosecond laser spectroscopy has contributed to our understanding of structure and function of matter. Here, the authors explore the applicability of superfluid helium nanodroplets as a sample preparation method that allows investigation of previously inaccessible classes of tailor-made or fragile molecular systems.

Arrays of quantum dots can exhibit a variety of quantum properties, being sensitive to their spacing. Here, the authors fine tune interdot coupling using hexagonal molecular networks in which the dots are separated by single or double haloaromatic compounds, structurally identical but for a single atom.

The molecular landscape of chromothriptic medulloblastoma remains to be characterised. Here, spatial transcriptomics analysis of 13 chromothriptic and non-chromothriptic medulloblastomas identifies distinct spatial composition patterns and cell communication networks in these tumours.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Chromothripsis (CT) is a type of genome instability which is prevalent in medulloblastoma with germline TP53 mutations (Li-Fraumeni syndrome, LFS). Here the authors combine single-cell genomic and transcriptomic analyses to reveal the clonal heterogeneity and functional consequences of CT in LFS medulloblastoma.

Tc toxins are a major class of bacterial toxin translocation systems that inject toxic enzymes into target cells. Here the authors present functional and structural data showing that the toxic enzyme can be replaced by other small proteins and identify prerequisites required for successful translocation, which could facilitate the development of functional Tc-based protein injection devices.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Ultra-low-temperature-actuated adsorption-driven chillers that rely on water as the cooling agent are desirable for energy-efficient and environmentally benign cooling devices. Here the authors show that the metal–organic framework of composition [Al(OH)(C₆H₂O₄S)] displays high water uptake capacity, high stability, and driving temperatures as low as 60 °C.

Joshua Bis, Christopher O'Donnell and colleagues report a meta-analysis of genome-wide association studies from the CHARGE Consortium that identifies loci associated with carotid intima media thickness and plaque. These are established measures of subclinical atherosclerosis that predict future cardiovascular disease events.

Cristen Willer and colleagues report genome-wide association analyses for blood lipid levels in 188,578 individuals. They identify 62 loci newly associated with blood lipid levels, refine the association signals at 12 loci and examine associations with cardiovascular and metabolic traits.

Forest dynamics are monitored at large scales with remote sensing, but individual tree data are necessary for ground-truthing and mechanistic insights. This study on high temporal resolution dendrometer data across Europe reveals that the 2018 heatwave affected tree physiology and growth in unexpected way.

The molecular genetic landscape of leiomyosarcoma (LMS) is largely unknown. Here, the authors identify frequent DNA copy number alterations, whole-genome duplication, TP53 and RB1 inactivation, alternative telomere lengthening, and genomic imprints of defective DNA repair via homologous recombination as a potential therapeutic target in LMS patients.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

Nona Sotoodehnia and colleagues report a meta-analysis of 14 genome-wide association studies for QRS interval, an electrocardiogram measurement of cardiac ventricular conduction. They identify 22 loci associated with QRS duration.

Nicholas Luscombe, Cameron Osborne and colleagues report the use of Capture Hi-C (CHi-C) to detect the long-range interactions of almost 22,000 promoters in 2 human cell types. They found that transcriptionally inactive genes interact with previously uncharacterized elements that may act as long-range silencers.

Nicole Soranzo and colleagues report a meta-analysis of genome-wide association datasets identifying 22 associations to 8 clinically relevant hematological traits. They also identify a long-range haplotype at 12q24 that includes variants associated with platelet counts as well as coronary artery disease and shows evidence of a selective sweep in Europeans.

The mechanisms regulating the balance between proliferation and differentiation in medulloblastomas with extensive nodularity (MBEN) remain poorly understood. Here, single cell multi-omics and spatial analysis characterises the spatial tissue organisation of MBEN in the context of the developmental trajectory.

Christopher Newton-Cheh and colleagues report genome-wide association analyses for QT interval, an electrocardiographic measure reflecting myocardial repolarization, in 100,000 individuals. They identify 35 loci associated with QT interval and highlight a role for calcium regulation in myocardial repolarization.

Papillary thyroid cancer (PTC) is one of the most common type of endocrine malignancy. Here, the authors use proteogenomic approaches to analyse the primary tumour and lymph node metastases from a PTC patient and report an oncogenic RET fusion, and potential druggable targets from the ubiquitin signaling machinery for treating human PTCs.

The shattering of chromosomes is a dramatic early event in tumourigenesis and is termed chromothripsis. Here, the authors examine chromothripsis across 28 tumour types and show that 49% of cancers exhibit features of chromothripsis.

Isabel Ernst et al. use single-molecule FRET measurements and in silico analyses to show the conformational changes of bacterial SecA. They show that the Preprotein Binding Domain is highly dynamic in the absence of ATP and moves toward the Helical Wing Domain when ATP is bound into the “wide open” position.

Analysis of 82 indictors of ecosystem functioning at the Jena grassland biodiversity experiment shows that multifunctionality increases strongly with diversity, but depends on the number and identity of the functions considered.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

During infection, the Legionella effector Lem3 removes a phosphocholine moiety from the human protein Rab1. Here, the authors present the crystal structure of the stabilised Lem3:Rab1b complex, revealing the catalytic mechanism and substrate recognition of PPM phosphatases shaped Lem3.

A single-cell screening approach identifies targets for CAR-T cells in acute myeloid leukemia.

A meta-analysis of genome-wide association studies in more than 66,000 individuals identifies 68 new genomic loci that reliably associate with platelet count and volume, and reveals new gene functions.

Anna Köttgen and colleagues report genome-wide association studies for serum urate in over 140,000 individuals from the Global Urate Genetics Consortium (GUGC). They identify 18 loci newly associated with serum urate concentrations and confirm 10 known loci, characterize their associations with gout and include a network analysis suggesting a role for inhibins-activins pathways in regulating urate homeostasis.

The effects of biodiversity on ecosystem function are usually studied within trophic levels. These authors conduct a large experiment across trophic levels to show how manipulations of plant diversity affect function in different groups. The effects are consistent across groups, but are stronger at adjacent trophic levels and in above-ground rather than below-ground groups.

Ceria-based oxides are used in diverse energy-related applications, with functionalities arising from a defective structure due to the formation of mobile oxygen vacancies. Here authors reveal sub-Ångström details of oxygen dynamics during the reversible phase transition of Gd-doped ceria (CGO).

We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

Chemical genomic approaches offer an alternative to traditional high-throughput screening for drug discovery and provide an emerging approach to probing cellular biology. The 58^th Ernst Schering Foundation Workshop on “Chemical Genomics: Small Molecule Probes to Study Cellular Function,” held April 6–8, 2005, in Berlin, Germany, captured recent chemical genomics advances and highlighted the power of a tight integration of chemistry and biology.

Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer.