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The distribution and organisation of matrix molecules in the tumour stroma help shape solid tumour progression. Here they perform temporal proteomic profiling of the matrisome during breast cancer progression and show that collagen XII secreted from CAFs provides a pro-invasive microenvironment.

Phage satellites are bacterial genetic elements that co-opt phage machinery for their own dissemination. Here, Barcia-Cruz et al. identify a family of satellites, named PICMIs, that are characterized by reduced gene content and are broadly distributed in marine bacteria of the family Vibrionaceae.

The influence of stress relaxation of the extracellular matrix on the formation of intestinal organoids was investigated. It was shown that a stress-relaxing synthetic matrix promotes crypt budding through increased symmetry breaking and niche cell formation.

The expression of oncogenic MYC paralogs in small cell lung cancer is mutually exclusive. In this study, the authors show that MYC, but not MYCN or MYCL, represses BCL2, resulting in cells that are uniquely sensitive to apoptosis, and find that CHK1 and AURKA inhibitors may be useful for treating these cancers.

Kim et al. used directed evolution methods to identify a high-fidelity SpCas9 variant, Sniper2L, which exhibits high general activity but maintains high specificity at a large number of target sites.

Innate lymphoid cells (ILCs) play critical immunological roles including immune surveillance at mucosal sites. Here the authors show that during nasal inflammation pathogen-induced cytokine production guides the differentiation of ILCs.

Live-cell imaging shows that interactions within topologically associating domains are transient and frequent throughout the cell cycle. Convergent CTCF sites regulate the frequency and duration of interactions, which last a few minutes on average.

The authors report that mitophagy is impaired in Alzheimer’s disease. Stimulation of mitophagy reverses cognitive deficits in nematode and mouse models of Alzheimer’s disease, suggesting a potential therapeutic intervention.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

Colorectal cancer can lead to the development of peritoneal metastases, which are associated with worse disease outcome. Here, the authors characterize peritoneal metastases from 52 patients using RNA-seq and mutational sequencing and show a distinct molecular subtype.

The role of non-coding somatic mutations in ovarian cancer is unclear. Here, the authors integrate genomic and epigenomic data from patient samples to show that these mutations frequently converge on the PAX8 transcriptional network.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

The molecular steps that lead to the disaggregation of amyloid fibrils are shown to involve the synergistic action of HSP70 and its co-chaperones DNAJB1 and HSP110.

Conventional type 1 dendritic cells perform antigen processing and priming of CD4⁺ and CD8⁺ T cells against tumour antigens, orchestrating their cross-talk to effect anti-tumour immunity.

Defining cis-regulatory elements is an important goal in understanding how gene expression is regulated. Here the authors show blood cell-specific gene expression is controlled by the action of thousands of differentiation stage-specific sets of cis-elements that respond to cytokine signals terminating at signaling responsive transcription factors.

Integrative genomic and transcriptomic analyses reveal molecular events defining Richter transformation from CLL, and highlight the potential of cell-free DNA for early detection.

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .

This protocol describes in vitro procedures for generation of synthetic single-domain antibodies called ‘sybodies’. Sybodies can be engineered to target specific protein conformations, labile membrane proteins or protein complexes.

Leigh syndrome (LS) is a severe neurometabolic disorder which lacks effective models. Here, the authors developed human neuronal models of LS carrying mutations in SURF1 which show impaired neuronal morphogenesis due to metabolic deficiencies.

It is unclear how far the impact of deforestation can spread. Here the authors analyse freshwater eDNA data along two rivers in the Amazon forest, and find that low levels of deforestation are linked to substantial reductions of fish and mammalian diversity downstream.

There are many open questions about biogeochemical function in peatlands. Here, the authors investigate the nitrogen cycle of tropical peatlands, finding that a surprisingly high fraction of nitrous oxide production is abiotic and that denitrification is a coupled abiotic-biotic process.

Glycogen metabolism is tightly regulated. Here the authors describe the 3D structure of the PP1/PTG protein complex, which plays a prominent role in the activation of glycogen synthesis and in the pathogenesis of Lafora disease, the most severe form of pediatric progressive epilepsy.

The Ycf48 accessory factor is important for the assembly and repair of the photosystem II (PSII) complex of oxygenic photosynthesis. Here, the authors show that Ycf48 occupies the binding site of the oxygen evolving Mn cluster early in PSII biogenesis.

Latitudinal ecosystem boundaries in the global upper ocean may be driven by many factors. Here the authors investigate pole-to-pole eukaryotic phytoplankton metatranscriptomes, gene co-expression networks, and beta diversity, finding that geographic patterns are best explained by temperature gradients.

The emergence of acquired resistance to standard platinum-etoposide chemotherapy in small cell lung cancer (SCLC) is a common event. Here, the authors using paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models reveal a mechanism of drug resistance in SCLC mediated by Notch and nitric oxide activation of soluble guanylate cyclase signalling.

Geologic formations could be used for hydrogen storage and conversion to methane, yet technical feasibility is unclear as field-scale data are lacking. Here the authors perform field tests demonstrating that hydrogen can be stored and microbially converted to methane in a depleted underground hydrocarbon reservoir.

A new high-throughput assay applied to 1,000 enhancers and 1,000 promoters in human cells reveals how different classes of enhancers and promoters control RNA expression.

Barrett’s esophagus is a pro-oncogenic lesion in the proximal gastrointestinal tract, but with a distal colon-like morphology. Here the authors report that the distal HOX gene HOXA13 is expressed in Barrett’s esophagus and in single cells of the physiological esophagus, and may underlie the phenotypic aspects of metaplasia and increase proliferation.

The structure of the human NALCN channelosome and a model of the gating mechanism are determined.

Obesity and aging increase Alzheimer’s disease (AD) risk. Here, using an AD mouse model and high-fat diet, we suggest that immune exhaustion links the two risk factors, and identify a metabolite that can hasten immune dysfunction and memory deficit.

Improved Cas12a variants and sgRNA design rules enhance genome-wide screens.

The SARS-CoV-2 PANGO lineage C.1.2 has been under monitoring by global health authorities as it has spread worldwide. Here, Bhiman and colleagues characterise the emergence of the lineage, and its neutralisation sensitivity using data from vaccinees and previously infected individuals.

A genetic mouse model is used to reveal a two-pronged mechanism of fructose-induced de novo lipogenesis in the liver, in which fructose catabolism in hepatocytes provides a signal to promote lipogenesis, whereas fructose metabolism by the gut microbiota provides acetate as a substrate to feed lipogenesis.

Development of a safe and efficacious vaccine for respiratory syncytial virus (RSV) has been challenging. Here the authors generate a live-attenuated RSV vaccine that shows increased thermostability and immunogenicity, and protects cotton rats from RSV challenge.

Murine norovirus protects intestinal epithelial cells (IECs) from chemical injury by inducing a type I interferon (IFN-I) response in the colon via the viral non-structural protein NS1/2. IFN-I signalling in IECs, in turn, stimulates the production and signalling of the cytoprotective cytokine interleukin-22.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

Roquin-1 is a posttranscriptional regulator that controls the expression of many immune-related genes such as ICOS and TNFA. Here, the authors report a homozygous R688* loss of function mutation in Roquin-1 in a patient with syndromic uncontrolled hyperinflammation associated with immune cell activation and hypercytokinemia.

Here the authors visualize the workings of ELOF1 in transcription-coupled DNA repair, showing that ELOF1 repositions repair factors on the surface of DNA damage-stalled RNA polymerase II to facilitate its ubiquitylation by the CRL4^CSA E3 ligase and inactivation by UVSSA.

Loss of canonical Notch signaling in vascular endothelial cells induces spontaneous formation of proto-typical tertiary lymphoid structures in mouse kidney, liver and lungs, which form around central arteries that acquire a high endothelial cell signature

Analysis of a large set of marine vibrios and their phages identifies mechanisms of phage–host coevolution.

A current challenge in genome editing is delivering Cas9 and sgRNA into target cells. Here the authors engineer a delivery system based on murine leukemia virus-like particles loaded with Cas9-sgRNA ribonucleoproteins to induce efficient genome editing in both cell culture and in vivo in mouse.

Antimitotic compounds, such as paclitaxel, induce cell death in cycling cancer cells only. Here, the authors show that paclitaxel-targeted breast cancer cells prime neighboring cells to apoptosis through a STING-mediated paracrine signaling pathway.

Pneumococci can alternate between harmless and highly virulent forms. Here the authors show that such variation may be due to random rearrangements in a genetic locus encoding a restriction-modification system, resulting in epigenetic changes that affect expression of many genes.

Long-range cis-regulatory elements play important roles in regulating agronomic traits, but they are largely uncharacterized in crops. This study provides genetic, epigenomic and functional molecular evidence to support their widespread existence in the maize genome.

Investigating the evolutionary origins of montane biodiversity by sampling the entire biota from a single mountain, Mount Kinabalu in Borneo, allows for a better understanding not only of the origins of endemism, but also of this biota’s forecasted response to environmental change.

The authors provide mechanistic insights into the crosstalk between signalling components of pattern-triggered immunity and effector-triggered immunity and their molecular linkers.

The molecular mechanisms of mitochondrial dysfunction in the premature ageing Werner syndrome were elusive. Here the authors show that NAD⁺ depletion-induced impaired mitophagy contributes to this phenomenon, shedding light on potential therapeutics.