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Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

In the SURMOUNT-3 trial, once-weekly treatment with tirzepatide was demonstrated to result in clinically meaningful additional weight loss in adults with overweight or obesity following initial successful weight loss of at least 5% body weight with intensive lifestyle intervention.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Mutations in the NRF2-KEAP1 pathway is found to be related with therapeutic resistance and poor outcomes of non-small cell lung cancer (NSCLC). Here this group reports that cystine/glutamate antiporter system xc−, controlled by NRF2, can be non-invasively imaged by positron emission tomography thereby providing a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

This study presents results from a SARS-CoV-2 genomic surveillance study at a university campus in which ~2,000 samples were sequenced over five months. The authors document the replacement of Delta with Omicron as the dominant variant, and describe clinical characteristics and transmission dynamics.

How the brain extracts and reproduces temporal regularities from incoming sensory information is poorly understood. Here, the authors discover the ability of neural populations in the primary visual cortex of behaving monkeys to extract precise temporal structure from unsupervised repetitive external stimulation.

Using several orthogonal loss-of-function approaches, Huang et al. provide a detailed assessment of the quantitative contribution of δ cell paracrine signalling to the glycaemic set point in mice.

Some autistic individuals experience aversion to social touch. Authors use Neuropixels probes and demonstrate that unlike wild type mice, Fmr1 knockout mice find social and non-social interactions equally aversive, and their cortical and striatal neurons are less able to discriminate social valence.

miR-132 was shown to drive pathological cardiac remodeling, a hallmark of heart failure. Here, the authors show that an antisense inhibitor of miR-132 has favourable pharmacokinetics, safety-tolerability and preclinical efficacy in mouse and porcine models of heart failure.

Although normal γδ T cell development depends on the E protein antagonist, Id3, Id3 deficiency produces different phenotypes in distinct γδ T cell subsets. Here, the authors demonstrate that Id3 deficiency impairs the development of Vγ3⁺ T cells, while promoting that of NKγδT cells expressing the invariant Vγ1Vδ6.3 TCR.

Neural networks must balance associative plasticity with rapid compensatory processes to maintain stable activity patterns. Andrei et al. provide in vivo evidence of a rapid homeostatic process that decreases network connectivity when excitatory neurons are synchronously activated.

Simon and colleagues show that liver cancer cells undergo cell cycle arrest and senescence upon deprivation of methionine and identify GSK3 inhibitors as a senolytic to selectively deplete MAT2A inhibited senescent liver cancer cells.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

The dynamics of SARS-CoV-2 transmission in the Middle East have been relatively under-studied. Here, the authors integrate genomic and travel data and show that introductions to the region were initially driven by intercontinental air travel, after which regional land travel became a more important driver.

An alternative HIV vaccine design facilitates generation of HIV-1-antibodies, with promising neutralization breadth in rodents and nonhuman primates.

The transmission of unrepaired DNA lesions through mitosis needs tight control. Here, the authors uncover a damaged chromatin marking mechanism driving the segregation of UV damage through mitosis with potential consequences on daughter cell fate.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Ajmera et al. use brain imaging and machine learning to dissociate young adults with loudness hyperacusis from matched controls. There are intrinsic functional connectivity differences related to emotion and cognitive processing between the two groups, but fewer differences with respect to auditory processing.

This Case Study describes a 55-year-old man with a history of coronary artery disease who was diagnosed with pheochromocytoma of the left adrenal gland. The authors discuss the diagnosis of this patient and his treatment with alpha-blockade therapy combined with phenoxybenzamine before open adrenalectomy.

Temporalis muscle thickness is a promising marker of lean muscle mass but has had limited utility due to its unknown normal growth trajectory and lack of standardized measurement. Here, the authors develop an automated deep learning pipeline to accurately measure temporalis muscle thickness from routine brain magnetic resonance imaging.

Prostate stromal cells can contribute to prostate tumorigenesis. Here the authors show that the loss of androgen receptor signalling in Gli1-lineage stromal cells diminishes prostate epithelial oncogenic transformation and tumor growth in mouse models and this is due to insulin-like growth factor binding protein 3-mediated inhibiting IGF1 and Wnt/β-catenin signalling activation.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

US president’s first budget proposal emphasizes applied research and public health, and aims to tackle climate change and racial injustice.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

A general tuning strategy is introduced for improving the utility of rhodamines for biological imaging applications. The strategy yielded bright, versatile and bioavailable far-red and near-infrared ‘Janelia Fluor’ dyes.

This study uncovers a new mechanism linking oxidative stress to telomere-driven senescence. A common oxidative lesion at telomeres causes rapid premature cellular aging by inducing telomere fragility, rather than telomere shortening.

The genomes of two fern species, Azolla filiculoides and Salvinia cucullata, are reported and provide insights into fern-specific whole-genome duplications, fern-specific insect-resistant gene evolution and fern–cyanobacterial symbiosis.

A retracted paper highlights chemistry’s history of trying to avoid the expensive, toxic — but necessary — catalyst.

The combination of optogenetic manipulation with standard chamber-based electrophysiological recordings in awake nonhuman primates enables the manipulation of short- and long-range feedforward and feedback circuits

Steroid-sensitive nephrotic syndrome (SRNS) can cause CKD and necessitate kidney transplant. Here the authors identify FAT1 mutations by homozygosity mapping and whole-exome sequencing in families with SRNS and provide functional mouse and zebrafish evidence that FAT1 is required for normal glomerular and tubular function and that FAT1 mutations can cause SRNS.

Variants of the genetically encoded sensor iGluSnFR extend the range of conditions under which glutamate neurotransmission can be visualized. In addition, chromatic variants of iGluSnFR improve compatibility with various illumination schemes.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.