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Imaging live cells at nanometre resolution is challenging because radiation damage kills the cells during exposure. Here, the authors overcome this difficulty in a ‘diffraction before destruction’ experiment using an X-ray laser and record signal to 4 nm resolution on a free-flying cell.

Castro, Shindyapina et al. explore how aging promotes B cell lymphoma in mice, identifying a population of age-associated clonal B cells that expands through mutation, c-Myc activation and epigenetic alterations to drive age-associated malignancy.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

This study defined spatial gene expression in the human dorsolateral prefrontal cortex. It reveals layer-enriched expression of genes associated with schizophrenia and autism, highlighting the clinical relevance of spatially defined expression.

Intense, coherent X-ray pulses from a free-electron laser can be used to obtain high-resolution morphology of individual sub-micrometre particles in their native state, while at the same time their composition is analysed by mass spectrometry.

The SARS-CoV-2 main protease is an important target for the development of COVID-19 therapeutics. Here, the authors combine X-ray crystallography and mass spectrometry and performed a large scale fragment screening campaign, which yielded 96 liganded structures of this essential viral protein that are of interest for further drug development efforts.

Cancers of the same tissue type are characterized with different molecular features depending on anatomical location. Here, the authors show that proximal and distal colon stem cells have distinct transcriptional programs mediated by the transcription factor CDX2, with differential roles in colon cancers based on anatomical location.

A reconstruction of the distribution of cold traps on the Moon at spatial scales varying from 1 km to 1 cm shows that the smallest ones are also the most numerous, 10–20% of the total. The total surface area of the Moon that can efficiently trap water is revised substantially upward, to 40,000 km².

Researchers describe a mechanism capable of compressing fast and intense X-ray pulses through the rapid loss of crystalline periodicity. It is hoped that this concept, combined with X-ray free-electron laser technology, will allow scientists to obtain structural information at atomic resolutions.

Lipidic sponge phase crystallization yields membrane protein microcrystals that can be injected into an X-ray free electron laser beam, yielding diffraction patterns that can be processed to recover the crystal structure.

The dynamics of thin magnetic films revealed by ultrafast laser techniques cannot be explained by standard equilibrium descriptions. Diffraction experiments using an X-ray laser now allow the spin dynamics of the separate magnetic constituents of ferromagnetic GdFeCo alloys to be spatially resolved.

The surface topography of breast implants mediates the immune responses to them, and implants with an average roughness of 4 μm largely suppress foreign body response and fibrosis.

The advancement of upper tract urothelial carcinoma (UTUC) research is hampered by the lack of disease-specific models. Here, the authors report patient derived xenograft and cell line models of UTUC, and show that these models retain the genomic and biological heterogeneity of human disease.

70,000 diffraction patterns captured over twelve minutes at the Linac Coherent Light Source yield reconstructions of the smallest single biological objects imaged with an X-ray laser.

Screening of a library of bile acid metabolites revealed two derivatives of lithocholic acid that act as regulators of T helper cells that express IL-17a and regulatory T cells, thus influencing host immune responses.

In tumours aberrant epigenetic modifications can alter the transcriptional state. Here, the authors identify a common tumour-specific shift to transcriptional repression associated with DNA methylation and chromatin dysregulation at the transcription start site.

An important goal for neuroscience tool development is improving the performance of genetically encoded voltage sensors. Here, the authors report two mutants of Arch, ‘Archers’, with high baseline fluorescence and sensitivity and show proof of principle for detecting voltage changes in response to sensory stimulus in live C. elegans.

Laser-generated ion acceleration has received increasing attention due to recent progress in super-intense lasers. Here the authors demonstrate the role of the self-generated magnetic field on the ion acceleration and limitations on the energy scaling with laser intensity.

A draft map of the human proteome is presented here, accounting for over 80% of the annotated protein-coding genes in humans; some novel protein-coding regions, including translated pseudogenes, non-coding RNAs and upstream open reading frames, are identified.

Studying ageing at the single-cell level has provided insight into the changes that occur systemically and in tissues as we age. For example, we now have a greater appreciation of the heterogeneity and dynamic nature of immune cell ageing and of the impact of age-associated tissue remodelling on the immune system, together contributing to increased vulnerability to some diseases.

The microbiota of centenarians (aged 100 years and older) comprise gut microorganisms that are capable of generating unique secondary bile acids, including isoallolithocholic acid, a bile acid with potent antimicrobial effects against Gram-positive—but not Gram-negative—multidrug-resistant pathogens.

Intervertebral disc degeneration is a leading cause of chronic back pain and disability. Here the authors show that long term treatment with senolytic compounds Dasatinib and Quercetin reduces disc senescence burden and ameliorates age-dependent degeneration in mice.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

Identifying patients that will respond to a particular therapy remains a key challenge in precision oncology. Here, in gastric cancer, the authors show that circulating tumour DNA can predict recurrence, provided that the signal from white blood cells is filtered out.

A study of zebrafish identifies an innate mechanism of blood vessel formation through the transdifferentiation of lymphatic endothelial cells, and provides in vivo evidence for a link between cell ontogeny and functionality in endothelial cells.

A complex regulatory network of temporally expressed transcription factors in Drosophila optic lobe stem cells regulates the generation of all neuronal diversity.

Amino acid propensities at sites change over evolutionary time, due to epistatically interacting sites or environmental changes. Here, the authors develop an approach to distinguish between these, and model the fitness dynamics of each, then annotate indicative sites in vertebrate and insect genomes.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Rachael Stolzenberg-Solomon, Laufey Amundadottir and colleagues report a genome-wide association study of pancreatic cancer. They identify four new susceptibility loci.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

IWS1 regulates multiple steps in RNA metabolism, including RNA elongation and alternative RNA splicing. Here the authors show that AKT3 phosphorylates IWS1, which alters U2AF2 RNA splicing and promotes growth of lung adenocarcinomas via a Sororin/ERK-dependent pathway.

Analyses of genome and transcriptome data are unable to accurately predict protein levels and function in tumour samples. Here, the authors carry out a comprehensive protein analysis in 3,467 samples from the cancer genome atlas, providing a resource to study the prognostic and therapeutic potential of tumour proteins.

Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.

Pappalardi and colleagues identify a potent noncovalent DNMT1-selective inhibitor with improved tolerability and efficacy in preclinical AML models compared with clinically validated covalent pan-DNMT inhibitors.

The authors describe a two-cell-type CRISPR screen to identify tumour-intrinsic genes that regulate the sensitivity of cancer cells to effector T cell function.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

The RNA binding protein MUSASHI-2 (MSI2) is a potential therapeutic target for acute myeloid leukemia. Here the authors identify a small molecule inhibitor of MSI2 and characterize its effects in a murine leukemia model.

In severe autism, deleterious variants at conserved residues are enriched in patients arising from female-enriched multiplex families, enhancing the detection of key autism genes in modest numbers of cases.

Immunotherapy often fails as a single option treatment in cancer. Here, the authors show that targeting of DNA methyltransferases, such as DNMT1, can potentiate anti-tumor immunity and response to checkpoint inhibition by increasing MHC gene expression and the recruitment of CD8+ T cells.

The shock breakout (SBO) is the first electromagnetic signature of a supernova (SN) explosion. Förster et al. find that in nearly all type II SNe they survey that the SBO occurs on a timescale of days, indicating that the progenitors were surrounded by thick circumstellar matter when they exploded.

Matthew Meyerson, Ramaswamy Govindan and colleagues examine the exome sequences and copy number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumors. They identify novel significantly mutated genes and amplification peaks and find that around half of the tumors have at least five predicted neoepitopes.

Prostate cancer often develops resistance to androgen receptor (AR) targeting drugs. Here, the authors show that, under conditions of hypoxia, AR inhibition via enzalutamide increases the expression of the glycolytic enzyme phosphoglucose isomerase (GPI) promoting a metabolic rewiring that allows the cells to survive, and consistent GPI inhibition restores sensitivity to enzalutamide.

The pseudokinase JH2 domain of JAK2 is a negative regulator of JAK2 activity, but the mechanism for this is unclear. Now it is shown that JH2 is actually an active kinase that phosphorylates negative regulatory sites on JAK2, thus inhibiting JAK2 signaling.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.