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cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Defective neurotransmission is a hallmark of spinal muscular atrophy (SMA). Here, the authors show that local presynaptic Munc13-1synthesis is defective in SMA and that modification of the Munc13-1 mRNA rescues presynaptic architecture and excitability.

Multi-omics profiling of monkeypox virus infected human primary cells was used to characterize the infection process and to prioritize potential antiviral drug targets.

SUMOylation is a key regulator of genome stability. Here, the authors show that SUMO chain modification of PCNA and Rad52 controls DNA repair pathway choice, preventing excessive recombination and maintaining centromere integrity under endogenous replication stress.

Peroxisomes contain detergent resistant core structures. Bäcker et al. show that these core structures contain diverse enzymes and serve to enable metabolic compartmentalization of the peroxisome lumen.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

Curved cell shapes are common among bacteria, but the underlying morphogenetic mechanisms are incompletely understood. Here, the authors identify an outer-membrane protein complex that promotes cell curvature in Rhodospirillum rubrum by forming helical ribbon structures that modulate the dynamics of cell wall biosynthesis, biasing cell growth towards the cell’s outer curve.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Lightning Pose is an efficient pose estimation approach that requires few labeled training data owing to its semi-supervised learning strategy and ensembling.

C-COMPASS is an open-source software designed to predict the spatial cellular distribution of proteins and lipids from cellular organelle profiling using a neural network-based regression model.

Solvent plays a critical role in electron-transfer reactions, but short-range solvation dynamics are challenging to observe. Now, femtosecond X-ray solution scattering has been used to directly monitor the reorganization of water upon ultrafast intramolecular electron transfer in a bimetallic complex. Coherent motions of the first-shell water molecules are observed, arising from changes in solute–solvent hydrogen bonding.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

Methods to assess organellar content are important. Here, Park et al develop a method for rapid isolation of early/sorting endosomes and demonstrate the application of the approach for analysis of endosomal proteomes and lipidomes, and for analysis of APP processing to Aβ via β and γ-Secretases.

Many studies assess epigenetic marks in white blood cells, but it is unclear how much immune factors affect the epigenome. Here, the authors show that fine-scale blood cell composition and cytomegalovirus infection affect the DNA methylome of adults.

This work investigates changes in regularity of crop failure, heatwave and wildfire exposure for different future climate scenarios. Major shifts in dominant periods are observed when moving from pre-industrial to current climate conditions.

The unpredictability of evolution makes it difficult to deal with drug resistance because over the course of a treatment there may be mutations that we cannot predict. The authors propose to use quantum methods to control the speed and distribution of potential evolutionary outcomes.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Multi-species occupancy modelling using camera-trap data from 725 sites across 20 North American cities shows how environmental and climate characteristics interact with species traits to influence the effects of urbanization on wildlife communities.

Monitoring the flux of gas from volcanoes is a fundamental component of volcano monitoring programs and is used as a basis for eruption forecasting. Here, the authors present a new method using video images of volcanic gas plumes to measure the speed of convective structures and to estimate volcanic fluxes.

Brazil has operated a conditional cash transfer program to support families living in precarious conditions since 2004. Here, the authors use linked administrative and health data to investigate the impacts of the program on HIV/AIDS-related outcomes, demonstrating strong positive associations.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Analysis of a deeply phenotyped, longitudinal cohort of 249 participants elucidates the network of concurrent molecular and macroscopic patterns related to insurgence and course of ME/CFS.

Watt, Dauber, Szkop and colleagues find that H3K4me3 remodels 5′UTR selection in hypoxia and that this process is independent of HIF-1 transcriptional mechanisms.

HER2-targeted therapy improves patient’s outcome in early breast cancer. Here, the authors present the efficacy and biomarker analysis of two HER2-targeted combinations (ado-trastuzumab emtansine plus pertuzumab and paclitaxel, trastuzumab and pertuzumab) in the context of the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence.

The challenge of accurate particle picking in cryo-EM analysis is addressed with Topaz, a neural-network-based algorithm that shows advantages over other tools, especially in picking unusually shaped particles.

Materials with a Kitaev spin liquid ground state are sought after as models of quantum phases but candidates so far form either zig-zag or incommensurate magnetic order. Ruiz et al. find a crossover between these states in β-Li₂IrO₃ under weak magnetic fields, indicating strongly frustrated spin interactions.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Cancer cells have altered lipid metabolism. Here the authors show that DAXX promotes lipogenesis and tumorigenesis through interaction with SREBP1/2.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Navigation involves perception, cognition, and movement. Here, the authors use computational modelling to show that different navigation behaviors, their errors, and variability arise from interactions of spatial uncertainties in optimal feedback control under uncertainty.

Using cryo-electron microscopy and integrative modeling, the authors defined the structure of vimentin intermediate filaments, revealing a helical tube built of five protofibrils that enclose a fiber of low-complexity N-terminal domains.

Cooperative species of extrachromosomal DNAs are coordinately inherited through mitotic co-segregation.

Passive immunisation for respiratory syncytial virus for infants is recommended by the World Health Organization but products currently available have limited duration of protection. Here, the authors investigate the age distribution of infant hospitalisation for respiratory syncytial virus to inform optimal timing of immunisation.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

The cryo-EM structure of the TssKFGE baseplate wedge complex of the type VI secretion system (T6SS) from enteroaggregative Escherichia coli helps to elucidate the molecular architecture of the whole T6SS baseplate, and its assembly and mode of action.

City-level analysis of data from the SALURBAL project shows vast heterogeneity in life expectancy across cities within the same country, in addition to substantive differences in causes of death among nine Latin American countries, revealing modifiable factors that could be leveraged by municipal-level policies aimed toward improving health in urban environments.

Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

In membranous nephropathy autoantibodies target podocytes of the kidney filter resulting in injury. Here the authors show that the ensuing proteostatic disturbances and proteinuria relate to aberrant interactions of non-functional UCH-L1 enzyme with the proteasome, curtailing its capacity.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Understanding the dynamics of the gut microbiota over the course of cancer treatment regimens and their associated adverse events can help identify microbial features that associate with response to immune checkpoint blockade.

Patient-derived xenografts (PDX) could contribute to understanding how colorectal cancer (CRC) responds to targeted therapies like cetuximab. Here, the authors characterise the response to cetuximab in 231 CRC PDXs using multiomics and develop an integrative ensemble classifier - CeSta - to predict sensitivity to cetuximab.

WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 complex traits and diseases.

European governments control resurging waves of COVID-19 using nonpharmaceutical interventions. Here, the authors estimate the effectiveness of 17 interventions in Europe’s second wave, and analyse differences to the first wave as well as implications for the future of the pandemic.