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Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

The metastable state with a complex ___domain structure in 1T-TaS₂ has been intensively studied. Using a multi-tip scanning tunnelling microscope, Mraz et al. reveal the microscopic dynamics of the current-pulse-induced metastable state and interpret it in terms of transport in a doped Wigner crystal lattice.

DiNardo et al. perform a phase 1b/2 clinical trial of telaglenastat (CB-839) in combination with azacytidine in persons with advanced myelodysplastic syndromes and report on the treatment safety and efficacy, including a definition of clinical responders.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The most efficient silicon solar cells use interdigitated back-contact silicon heterojunction architectures. Here, the authors fabricate this type of cell via a simpler process, using an interband silicon tunnel junction for the electron contact and reaching a certified efficiency higher than 22%.

The BTK inhibitor ibrutinib is used to treat chronic lymphocytic leukaemia, however some patients develop resistance to the drug. Here, the authors use genomic analyses to examine the clonal evolution of 5 patients that develop resistance to ibrutinib.

Front- and back-junction silicon photovoltaics dominate the market thanks to a lower manufacturing complexity compared with that of other device designs yet advances in efficiency remain elusive. Richter et al. now present an optimized design for the front and back junctions that leads to a 26.0%-efficient cell.

The Tyrolean Iceman is 5,300 years old and his mitochondrial genome has been previously sequenced. This study reports the full genome sequence of the Iceman and reveals that he probably had brown eyes, was at risk for coronary disease and may have been infected with the pathogen Lyme borreliosis.

High-throughput microscopy combined with gene silencing by RNA interference is a powerful method for studying gene function. Here, a genome-wide method is presented for phenotypic screening of each of the ∼21,000 human protein-coding genes, using two-day imaging of dividing cells with fluorescently labelled chromosomes. The method enabled the identification of hundreds of genes involved in biological functions such as cell division, migration and survival.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Weak topological insulators (WTI) remain difficult to be observed in experiments. Here, the authors discover a WTI state in RhBi₂, where the topological surface states with saddle points result in a van Hove singularity along the (100) direction near Fermi energy.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

Numerous tissues are derived from the lateral plate mesoderm (LPM) but how this is specified is unclear. Here, the authors identify a pan-LPM reporter activity found in the zebrafish draculin (drl) gene that also shows transgenic activity in LPM-corresponding territories of several chordates, including chicken, axolotl, lamprey, Ciona, and amphioxus.

Phosphatidylserine-exposing extracellular vesicles in body fluids can inhibit infection of viruses that use viral apoptotic mimicry for infection, but not viruses that use other entry mechanisms.

A genomic, transcriptomic and epigenomic analysis of chronic lymphocytic leukemia identifies genetic drivers and molecular subtypes associated with clinical outcomes.

The ancestry of the European bison (wisent) remains a mystery. Here, Cooper and colleagues examine ancient DNA from fossil remains of extinct bison, and reveal the wisent originated through the hybridization of the extinct Steppe bison and ancestors of modern cattle.

The mesothelium supports homeostasis and regeneration, yet its development origins remain unclear. Here, the authors uncovered the earliest mesothelium progenitor cells in zebrafish, linking Hand2 gene function to mesothelium formation and its re-activation to mesothelioma tumors.

Global spatial data for terrestrial vertebrate and vascular plant diversity, above- and below-ground biomass carbon, and potential clean freshwater volume are combined in a joint optimization study to identify potential synergies for conservation management.

IFITM proteins can inhibit several viruses, but effects on SARS-CoV-2 infection are not well understood. Here, the authors show that endogenous IFITMs support SARS-CoV-2 infection in different in vitro models by binding spike and enhancing virus entry.

In a subset of patients with chronic lymphocytic leukemia (CLL) treated with targeted agents, such as ibrutinib, drug resistant subclones emerge. Here, the authors report on transcriptional changes in CLL patients treated with ibrutinib and identify early clonal shifts associated with evolution of resistant clones.

In recent years, a number of novel agents have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). Herein, Jan A. Burger and Susan O’Brien outline the emerging paradigm of individualized therapy for patients with CLL aimed at exploiting the advantages of these novel agents but also integrating traditional therapies for selected patients.

Mitosis poses a challenge for transcriptional programs, as it is thought that several proteins lose binding on condensed chromosomes. Here, the authors analyze the chromatin-bound proteome through the cell cycle, revealing retention of most transcription factors and preservation of the regulatory landscape.

Idelalisib, the first PI3Kδ inhibitor in clinical use, has excellent activity in patients with chronic lymphocytic leukaemia and indolent B-cell lymphomas, heralding a new era of targeted therapy for these types of cancer. Idelalisib intercepts critical communications between B cells and the microenvironment, including B-cell receptor signalling and chemokine networks.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

Chronic lymphocytic leukaemia cells depend on glutathione to counteract their high reactive oxygen species (ROS) levels. However, their ability to synthesize this antioxidant is compromised by inefficient cystine uptake. Huang and colleagues now show that bone marrow stromal cells promote leukaemia cell survival by metabolizing cystine to cysteine and releasing it into the microenvironment to be taken up by leukaemia cells.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

This Resource describes genetic tools for microbial eukaryotes, providing a roadmap for developing genetically tractable organisms.

Late-differentiating second heart field progenitors contribute to atrium, ventricle, and outflow tract in the zebrafish heart but how remains unclear. Here, the authors image heart formation in transgenics based on the cardiopharyngeal gene tbx1 and show that progenitors are continuously added.

Dendritic cells are specialized antigen-presenting cells that are necessary for inducing immunity and regulating immune tolerance. Understanding how these cells regulate adaptive immune responses has aided the development of a number of novel immunotherapies. In this article, Comabella and colleagues provide an overview of dendritic cell function and evaluate the potential of these therapies to treat multiple sclerosis.

In this Review, Burger and Wiestner describe the latest insights into B cell receptor (BCR) signalling with respect to its contribution to B cell malignancies and discuss how inhibitors that target kinases downstream of the BCR are changing treatment outcomes for patients with B cell neoplasms.