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SMARCB1 is frequently lost in solid cancer and reported to support tumourigenesis through STAT3 activation. Here, the authors show in several preclinical models that targeting IL6/JAK/STAT3 molecular pathway is a potential therapeutic approach for SMARCB1-deficient bladder cancer.

Here the authors show inducible genes and enhancers are regulated mainly by transcriptional burst frequency and that this is coordinated in single cells and individual alleles. Cohesin, which is important for inducible gene expression, is largely dispensable for regulating enhancer burst frequencies; however, it is required for coupling burst frequencies of inducible enhancers and promoters.

Global public expectations for carbon removal governance are: engagement beyond acceptance research; regulating industry beyond incentivizing innovation; systemic coordination; and prioritizing underlying and interrelated causes of unsustainability.

How normal cells proliferate without CDK4 and CDK6, two cancer-driving kinases, remains unclear. Here, the authors show that without CDK4/6 activity, cells start the cell cycle with a different signaling order and commitment point, revealing unexpected flexibility in cell-cycle entry mechanisms.

Virological, clinical and immunological characterization of a dengue virus 3 human challenge model could help with identifying vaccine and drug candidates.

In a mouse model of progeria, an adenine base editor delivered with adeno-associated virus corrects the pathogenic mutation in LMNA, rescues vascular pathology and markedly extends the lifespan of the mice.

The prognosis of cancer patients with lymph node (LN) metastasis is worse than those without. Here, the authors report that while histone deacetylase 11 (HDAC11) inhibition suppresses tumor growth within the LN, it also promotes cancer cell migration out of the LN to form distant metastasis, and therefore suggest caution with HDAC inhibitors.

Lipo-chitooligosaccharides (LCOs) are signaling molecules produced by certain bacteria and fungi that establish symbiotic relationships with plants. Here, the authors show that LCOs are produced also by many other, non-symbiotic fungi, and regulate fungal growth and development.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

Analysis of H3K27ac genome-wide maps across 387 brain, heart, muscle and lung samples, along with eQTL and genome-wide association studies (GWAS) data integration, identifies tissue-specific genetically influenced active regulatory regions and target genes that potentially mediate disease etiology.

The role of interferon-γ (IFNγ) in anti-viral immunity has been unclear. Here the authors show that bacterial-induced or intranasally administered IFNγ effectively restricts SARS-CoV-2 infection in mice through effects on non-hematopoietic cells.

Combinatorial Optimization problems can be solved by investigating the ground states of particular Ising models. Here, the authors developed a neuromorphic architecture to ensure asymptotic convergence to the ground state of an Ising problem and to consistently produce high-quality solutions.

Therapeutic options for non-small cell lung cancer patients with brain metastases are limited. Here the authors design B7-H3 targeting CAR-T cells engineered to express the chemokine receptor CCR2b, and show improved accumulation in the brain and enhanced anti-tumor activity in preclinical models of lung cancer brain metastases.

Transcription factor COUP-TFII is elevated in the hearts of non-ischaemic cardiomyopathy patients, but the nature of this correlation is unknown. Here the authors show that forced cardiac expression of COUP-TFII in mice causes dilated cardiomyopathy because of altered mitochondrial function and impaired metabolic remodelling.

A strategy for assessing blood microcirculation and tissue hydration relies on monitoring the temperature and thermal conductivity of skin, respectively. It is now shown that arrays of micrometre-sized sensors and heaters can be integrated on stretchable substrates that conformably adhere to the skin; these devices allow spatially resolved heating and real-time temperature mapping in patients without limiting their motion.

On the 75th anniversary of quantum electrodynamics, Chad Orzel reflects on the parallel work that led to the synthesis of the theory.

Amalio Telenti, Craig Venter and colleagues report common, low-frequency and rare variants associated with blood metabolite levels using whole-genome sequencing and comprehensive metabolite profiling in 1,960 individuals. They identify 246 metabolites whose levels are associated with genetic variation at 101 loci.

Biomphalaria glabrata is a fresh water snail that acts as a host for trematode Schistosoma mansoni that causes intestinal infection in human. This work describes the genome and transcriptome analyses from 12 different tissues of B glabrata, and identify genes for snail behavior and evolution.

The alternative sigma factor RpoS of Borrelia burgdorferi regulates a pathway implicated in tick transmission, mammalian infectivity and persistent infection. Here, the authors characterise the role of the RpoS negative regulator bbd18 and show that RpoS also controls induction of endogenous prophage.

Bacteriophage repressor proteins downregulate viral lytic gene expression. Herein, the authors present the X-ray crystal structure of a monomeric repressor that binds an asymmetric DNA sequence using two independent domains.

Mass-spectrometry-based profiling can be used to stratify tumours into molecular subtypes. Here, by classifying over 500 tumours, the authors show that this approach reveals proteomic subgroups which cut across tumour types.

Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction Here, the authors present a genome-wide association study of SCAD, finding an association at 1q21.2 which potentially affects expression of ADAMTSL4.

The liver possesses the ability to regenerate following sudden injury. Here, the authors use single-cell RNA-sequencing and in situ transcriptional analyses to identify a new phase of liver regeneration in mice aimed at maintaining essential functions throughout the regenerative process.

A large proportion of wetland extent is not mapped in currently available national datasets. Incorporating newly revealed wetlands into soil carbon mapping methods increases estimates of wetland soil carbon stock by 482%.

Fibromuscular dysplasia is a cardiovascular disease affecting mostly women with a mostly unknown genetic basis. Here the authors have performed a genome-wide association meta-analysis of Fibromuscular dysplasia to identify genetic loci, some of which are shared with common cardiovascular disease and traits.

Reading requires accurate and rapid distinction between similar visual stimuli. Thesen and colleagues use human intracranial electrophysiology and brain imaging to show that letter-selective responses, in an area of the brain immediately posterior to the visual word-form area, occur before word selection.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Efforts to produce aromatic monomers through catalytic lignin depolymerization were focused on aryl–ether bond cleavage, while the carbon–carbon bonds of a large fraction of aromatic monomers in lignin are difficult to cleave. Here, the authors report a catalytic autoxidation method using manganese and zirconium salts as catalysts to cleave the C–C bonds in lignin-derived dimers and oligomers from pine and poplar.

Murray et al. identified and characterized a small-molecule inhibitor of human COQ8A, which belongs to the UbiB protein family and is essential for coenzyme Q biosynthesis.

The relevance of non-coding somatic mutations in cancer remains elusive. Here, the combination of mass spectrometry-based proteomics and whole genome sequencing data across multiple cancer types helps to assess the effects of somatic structural variant breakpoint patterns on protein expression of nearby genes.

Estimated glomerular filtration rate (eGFR) is a measure of kidney function and used to characterize chronic kidney disease. Here, Graham et al. identify 53 novel loci for eGFR in a GWAS meta-analysis, a subset of which are associated with other common diseases, such as diabetes and hypertension, based on PheWAS.

Non-small cell lung cancer (NSCLC) is often associated with metastasis to the lungs. Here, the authors perform independent screens and identify NuRD as a co-repressor of ZEB1, and demonstrate TBC1D2b as a downstream target of ZEB1/NuRD complex regulating NSCLC metastasis.

Camacho et al. show that emotion concepts are represented throughout the brain, giving insight to how the brain perceives real-world emotions. These patterns are present before children enter school and become more standardized across adolescence.

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

The global impact of somatic structural variants (SSVs) on gene expression in childhood cancers is unclear. Here, the authors analyse cancer genome and RNA sequencing data of 854 pediatric brain tumours and report a landscape of genes deregulated by SSVs.

Meaningful public engagement is key to sustainable governance of carbon removal and solar radiation modification. A study across 22 countries emphasizes tailored approaches sensitive to local contexts, technological nuances, power dynamics and trust.

A functional interfacial material has been developed for soft integration of bioelectronic devices with biological tissues. This has been applied in battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy as well as wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays.

Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

PI3K inhibitors have limited efficacy in triple negative breast cancer (TNBC). Here, the authors show that MAPK4 activates AKT independent of PI3K and thus promotes tumour growth in a subset of TNBC and that MAPK4 inhibition sensitizes to PI3K blockade in these tumours.’

Enterotoxigenic Escherichia coli infections have been linked to non-diarrheal sequelae however, the reasons for this are unclear. Here, the authors present an additional role of heat-labile toxin in disrupting the structure and function of intestinal epithelial cells.

Two programs, GRAPE and GARLIC, work together to first predict biosynthetic gene clusters responsible for the production of polyketides and nonribosomal peptides, then link sequenced gene clusters to known and unknown natural products.

Lipid synthesis increases during the cell cycle to ensure sufficient membrane mass. Here, authors identify a lipid checkpoint in G1 phase that prevents cells from starting the cell cycle if lipid synthesis is low, thereby preventing mitotic defects.

Although continuous monitoring of tissue oxygenation is critically important after tissue/organ graft procedures, current technologies have key limitations. Here, the authors develop a miniaturized, minimally invasive, self-anchoring optical probe and demonstrate continuous monitoring of oxygenation in porcine flap and organ models.

Epigenetic information is transmitted from mother to daughter cells through mitosis. Here, the authors isolate native chromosomes from metaphase-arrested cells and perform LC-MS/MS to identify chromosome-bound proteins in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.