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How the tropical mixed layer of the ocean reacts to near-inertial waves has rarely been observed directly. Here, the authors present new data that shows strongly elevated vertical diffusive heat flux in the presence of near-inertial waves, causing a cooling of the mixed layer that is particularly strong in summer.

Figge-Schlensok et al. show that leptin-sensitive neurons in the lateral hypothalamus encode anxiogenic stimuli and facilitate adaptive strategies to enable an animal to overcome anxiety in threatening situations.

Hepatitis B virus (HBV) capsid assembly modulators (CAM) represent a recent class of anti-HBV antivirals. Structural approaches provide limited conformational information on the CAM-induced off-path assemblies. Here, authors use solid-state NMR to establish a structural view on assembly modulation of the HBV capsid.

Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. Here the authors obtain crystal structures and NMR data to show the recognition of diaromatic peptide motifs on a noncanonical surface of the PEX13 SH3 domain, revealing a dynamic network which modulates peroxisomal matrix import.

Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Variably methylated intracisternal A particle (VM-IAP) retrotransposons are stable across the murine lifespan. VM-IAP retrotransposons are unaffected by maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation.

Protein phosphatase 1 (PP1) is regulated by intrinsically disordered proteins like inhibitor-3, I3. The authors show that I3 does not inhibit PP1 by forming a rigid complex but instead by binding dynamically with its active site metals, showing how flexibility is used in biology.

Legesse et al. present structural studies of a human GABAA receptor in complex with positive and negative modulator neurosteroids, uncovering mechanisms of potentiation and inhibition.

Maternal thyroid hormone is important for fetal development. Here, the authors show that hyperthyroidism during pregnancy can program the offsprings’ glucose sensitivity and response to cold via activation of maternal thyroid hormone receptor β in a sex dependent manner

Arctic marine ecosystems have experienced significant change through the Holocene. Here, the authors used sedaDNA from Northern Greenland to reconstruct marine mammal occurrence, demonstrating the impact of air temperature and sea ice cover over the past 12000 years.

The protein corona formed on nanoparticles can impact bioactivity. Here the authors show that the protein corona on lipid nanoparticles alters their function and reduces transfection efficiency, showing the importance of considering the protein corona in designing lipid nanoparticle-based therapeutics.

During refinement of inhibitory inputs to the lateral superior olive (LSO), terminals in the medial nucleus of the trapezoid body express VGLUT3 and co-release glutamate with glycine or GABA. Using mice lacking VGLUT3, the authors show impaired refinement of inhibitory inputs to the LSO and degraded tonotopic precision.

The authors optimize an in vitro human epiblast model, which they utilize to show that early TGFβ family inhibition prevents epithelial identity, whereas it is dispensable after epithelium formation. These phenomena are conserved in mice.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

Cryo-EM analysis of the human apelin receptor activated by either the endogenous peptide ligand or a potent synthetic small-molecule agonist reveals a mixture of homodimer and monomer organizations shedding light on a versatile regulation mechanism.

Though ubiquitin is known to broadly influence endosomal trafficking, few ubiquitin-utilizing enzymes targeting endosomal regulators are known. Here, the authors find that the deubiquitylating enzyme (DUB) USP32 influences endosomal membrane dynamics by deubiquitinating Rab7.

Fractional flow reserve (FFR) is the current gold standard method to quantify coronary blood flow (CBF) changes in coronary artery disease. In a large comparative study on 203 diseased arteries, Aubiniere-Robb et al. analyzed the degree of concordance between fractional and absolute CBF reduction and identified the FFR areas with high discordance. Patients with those FFR values may benefit from the additional absolute CBF measures.

Palmitoylation at C64 in stimulator of interferon genes (STING) is reported and, along with engagement of C91, is involved in dynamic cross talk with C148 to alter STING oligomer states and ultimately control STING activation.

Cancer cells often acquire molecular patterns of fast-growing embryonic tissues to enable propagation and invasion, which distinguish tumour tissues from their healthy adult counterpart. Here authors develop antibody fragments which specifically target oncofetal chondroitin sulphate on the cancer cell surface and in the tumour stroma, with the antibodies achieving therapeutic effect in multiple mouse models in antibody drug conjugate and bispecific immune cell engager formats.

During tissue injury blood cells in the microvasculature and tissue resident cells have differing phenotypes. Here the authors use single cell transcriptomics in mice models to assess the differences in phenotype of immune cells in multiple organs and the tissue resident cells before, after and during acute kidney infection.

Barbosa, Stein et al. show that rather than operating independently, PFC persistent activity and ‘activity-silent’ mechanisms interact dynamically to produce serial effects in working memory, consistent with attractor models with synaptic plasticity.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelin repair in adult mice, but is defective with aging.

In live-cell microscopy, motion blur limits resolution and contrast. Here the authors use 100 Hz super-resolving Rotating Coherent Scattering (ROCS) microscopy on various dynamic biological systems, and time-window analysis to understand biological effects.

The authors describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. They identify five mAbs that potently neutralized the majority of H5 clades and protected against lethal 2.3.4.4b H5N1 infection in mice.

The authors identify a single main-chain hydrogen bond required to keep GABA_A receptors closed in the absence of neurotransmitter. Electrophysiology and molecular dynamics simulations suggest disruption of this bond is a key component of channel opening during inhibitory synaptic signaling in the brain.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Most genomics research cohorts are made up of participants of European ancestry, which limits the reach of precision medicine. Here, the authors describe the genetic diversity in the All of Us research program, which is enriched in underrepresented ancestries.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

A new multilevel clustering approach applied retrospectively to 13,000 transcriptomes of different tumors reveals a new diagnostic classification of childhood cancers, in some cases allowing a better prediction of disease outcomes.

Roy et al. describe a generalized method for computationally designing miniproteins selective for a single integrin heterodimer and conformational state. The designed αvβ6 inhibitor remains monomeric and maintains biological activity following aerosolization and shows excellent efficacy in bleomycin induced lung fibrosis.

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.

Mucins on the surface of healthy T cells limit their phagocytic uptake by macrophages. Here the authors show that upon apoptosis induction in T cells, surface mucins are cleaved and released by ADAM10 to promote efferocytosis of the apoptotic cells.

This study shows how including different ancestry groups in a genome-wide association study for prostate-specific antigen levels can improve prostate cancer risk prediction, with implications for population screening.

Despite the progression of Actinium-225 (225Ac) radiopharmaceuticals, there is still a limited understanding of Ac coordination chemistry due to its radioactivity, poor availability, and lack of stable isotopes. Here, the authors demonstrate a platform to characterize the solution and solid-state behavior of the longest-lived Ac isotope, 227Ac.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The Global Flourishing Study provides a comprehensive view of the distribution and determinants of well-being by assessing domains such as health, happiness, meaning, character, relationships and financial security. Initial findings reveal significant variations in flourishing across countries and demographic groups, with factors such as age, marital status and religious service attendance showing strong associations with well-being.

The α7 nicotinic acetylcholine receptor plays important roles in the human nervous system. Here, authors use molecular simulations to develop a gating model and reveal cholesterol effects, offering insights applicable to drug design.

The number of contrail ice crystals can be tuned by adjusting the fuel’s sulfur content, as shown by in-flight measurements of emissions and contrails from an Airbus A350-900 burning different fuels.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Initial reports suggest unique radiation tolerance of perovskite solar cells. Here, the authors expose both n-i-p and p-i-n devices to low- and high-energy protons, providing a direct proof of radiation-induced efficiency recovery via tuning radiation-matter interactions in the devices.

Heterozygous de novo gain-of-function mutations in KCNK3, which encodes the two-pore-domain K⁺ channel TASK-1, cause a channelopathy characterized by developmental delay with sleep apnea.

Rebecca Fitzgerald and colleagues report the whole-genome sequences of 129 esophageal adenocarcinomas, showing frequent copy number alterations and prevalent mutations in receptor tyrosine kinases concomitant with mitogenic activation. They further characterize mutation signatures and find three distinct molecular subtypes with potential for application to clinical diagnosis and treatment.

In the final report of a phase 1 trial evaluating intracerebroventricular B7-H3-targeting CAR T cells in children and young adults with diffuse intrinsic pontine glioma, repeated intracranial infusions were feasible and well tolerated with a median overall survival of 19.8 months and 3 patients surviving over 40 months from diagnosis.

COVID-19 vaccines protect against infection, hospitalization and death in older adults, but their effectiveness is lower in this age group compared to young adults. Here, Palacios-Pedrero et al. show that age-dependent signs of immunosenescence in B and T cells in older adults correlate with poor immunological outcomes after mRNA COVID-19 vaccination but not after natural SARS-CoV-2 infection.

The association of telomere length with age and mortality across racially diverse pulmonary fibrosis populations is unknown. Here, the authors show that leukocyte telomere length associates with chronologic age and is predictive of mortality in pulmonary fibrosis across racial groups.