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Various GPCRs display constitutive ligand-independent activity, but it remains unclear whether ligand-dependent and -independent conformations differ. Here the authors demonstrate the recognition and blocking of G protein recruitment of either the ligand-bound active, or the constitutively active apo-conformation of the viral GPCR US28 by different nanobodies that target similar intracellular loops of the receptor.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Geiger and colleagues use SILAC and mass spectrometry to study protein turnover in human T cells and examine how naive T cells maintain their quiescence and transition to activated cells.

Constitutive Btk signaling drives several B-cell cancers. Here the authors demonstrate key allosteric intramolecular interactions between the SH2 domain and the kinase domain of Btk, and propose an alternative approach for inhibition of both wild-type and tyrosine kinase inhibitor-resistant Btk.

Phagocytes drive formation & resolution of neuroinflammatory lesions. The authors use in vivo imaging to track expression of proinflammatory & resolution enzymes & follow temporal changes in individual phagocytes polarization states in inflamed CNS.

Expression of the exercise-induced myokine irisin (FNDC5) is lower in patients with AD. Whereas knockdown of FNDC5/irisin is sufficient to induce learning and memory deficits, restoration of its expression can ameliorate these phenotypes in rodent models.

Dynamic supramolecular systems can be designed to adapt phases in a pre-programmable way. Here the transient nature of a gel system is exploited, in combination with the application of mechanical stimuli, to obtain soft materials with aligned fibres in a controllable way.

Genome-wide analysis and genetic manipulation at loci regulated by p53, E2F4 and RFX7 show that convergent promoters with similar epigenetic features can be co-regulated and simultaneously expressed in the same direction.

Bulk or pooled epigenomic profiling in the heterogenous brain obscures cell-type-specificity and individual subject variability in gene regulation. Here the authors optimized a hybrid protocol, ICuRuS, to profile epigenetic features in neuronal subtypes from a single mouse.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

Targeting peptides from unmutated cancer drivers that are expressed in tumours but not in normal tissues using peptide-centric chimeric antigen receptors shows potential as treatment for cancer.

Antibody responses are critical for protection from developing severe COVID-19 following SARS-CoV-2 infection. Here the authors show that antibody responses against SARS-CoV-2 spike protein correlate with neutralizing capacity and protection, are not affected by heterologous boosting of influenza or common cold immunity, and can last up to 8 months.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

A regulatory mechanism that limits the number of complete protein molecules that can be synthesized from a single mRNA molecule of the human AMD1 gene encoding adenosylmethionine decarboxylase 1.

Lipid nanoparticles (LNPs) are potential platforms for RNA-based therapeutics, but the fate of LNP-RNAs upon internalization into the cell is unclear. Here, the authors show that LNP-mRNAs and ionizable lipids escape the endosomes and are re-released via extracellular vesicles which could deliver the functional mRNA to other cells.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Long-term stability of ecological communities is vital for maintaining ecosystem functioning. Here, Blüthgen et al. show that greater land-use intensity in grasslands and forests can have negative impacts on the stability of plant and animal communities, driven primarily by variation in asynchrony between species.

Little sulfur from the 2022 Hunga submarine eruption reached the atmosphere due to seawater–magma interactions, indicating that the climate impact of this type of eruption may be underestimated, according to analysis of ash collected throughout the event.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Ultra-high-capacity Li–air batteries have low Coulombic efficiency and degrade during re-charging, resulting in a poor cycle life. Redox mediators enable improvements but only at undesirably high potentials. The origin of this high potential and the impact of purported reactive intermediates has now been elucidated by resolving the charging mechanism using Marcus theory.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Antibody optimization is crucial for proper data interpretation, such as determining accurate protein localization. Here, this is performed for NR2F1, a transcription factors associated with a rare neurodevelopmental disorder and cancer.

Retron-Sen2 of Salmonella Typhimurium encodes a toxin and a reverse transcriptase, which, together with the Sen2 multi-copy single-stranded DNA synthesized by the reverse transcriptase make up a tripartite toxin–antitoxin system that functions in anti-phage defence.

Merz and colleagues perform single-cell multiomic analysis of mononuclear cells isolated from individuals receiving BCMA-directed CAR T cell therapy for myeloma and show that nonresponders are characterized by an immune-suppressive microenvironment.

The authors introduce PharmacoSTORM single-molecule imaging that uses fluorescent ligands and immunolabeling for cellular and subcellular nanoscale molecular pharmacology. They demonstrate its capabilities by visualizing cariprazine binding to D3 dopamine receptors on Islands of Calleja granule cell axons.

The subsurface biosphere across a convergent margin may reflect tectonic processes and reduce carbon transfer to the mantle, according to bacterial and geochemical correlations from hot springs across the Costa Rican margin.

Autophagy regulates multiple pathways including YAP/TAZ of the Hippo pathway, but precise mechanisms are unclear as autophagy may either activate or inhibit YAP/TAZ. Here, the authors show that autophagy can either activate or regulate YAP/TAZ via dynamic negative feedback loops involving alpha-catenin.

Life- and healthspan of organisms can be modulated by dietary, genetic, or pharmacological interventions, which often affect metabolic pathways. Here the authors report that Grainyhead 1 is an evolutionarily conserved, drug-inducible transcription factor that promotes longevity in C. elegans, and thus a potential target for the development of geroprotective drugs.

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 tumour microenvironment counteracts immune therapy in Glioblastomas. Authors show here, using spatially resolved and single cell transcriptomics, that dysfunctional T cells are induced by a myeloid cell subset via Interleukin-10 signalling, and inhibition of the downstream JAK/STAT pathway might restore glioblastoma immune therapy responsiveness.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

The genetically encoded GABA sensor iGABASnFR allows visualizing GABA signaling in vivo. Its application is demonstrated in mouse slices, in the awake mouse and in behaving zebrafish.

Satellite-borne radar systems are promising tools to obtain spatial habitat data with complete geographic coverage. Here the authors show that freely available Sentinel-1 radar data perform as well as standard airborne laser scanning data for mapping biodiversity of 12 taxa across temperate forests in Germany.

The development of the all solid-state battery requires the formation of stable solid/solid interfaces between different battery components. Here the authors tailor the composition to form both electrolyte and anode from the same novel family of perovskites with shared crystal chemistry.

An online approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups has been developed to help to improve current diagnostic standards.

The muscle-secreted, exercise-induced peptide hormone apelin decreases with aging and sarcopenia, and its repletion in aged mice with recombinant protein improves muscle mass and function.

During cellular senescence in human and mouse cells, L1 transposons become transcriptionally derepressed and trigger a type-1 interferon response, which contributes to age-associated inflammation and age-related phenotypes.

Semiconducting polymer nanoparticles can act as light-sensitive interfaces with retinal neurons, and on microinjection in the eye, rescue vision in retinas affected by photoreceptor degeneration, offering a potential new treatment option for inherited retinal dystrophies and late-stage age-related macular degeneration.

Analysis of genomic data from 25 distantly related plant species shows signatures of selection on the same gene families and functions that repeatedly contributed to local adaptation to climate.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Studies focussing on pharmacological manipulation of the kinase GSK3 have provided contradictory roles on the involvement of GSK3 in axon regeneration. Here Gobrecht et al., study transgenic mice with altered GSK3 signalling and show that in contrast to previous reports, GSK3 enhances axon regeneration.

The phytohormone auxin is sensed by SCF^TIR1-AUX/IAA receptors leading to AUX/IAA repressor ubiquitylation and turnover. Here the authors show that IAA6 and IAA19 differ in their ubiquitylation and turnover dynamics, differentially contributing to auxin sensing and enabling discrimination of auxin concentrations.

FDNC4 is a poorly characterized homologue of FNDC5/irisin, a myokine induced by exercise. Here the authors show that FDNC4 increases macrophage survival in growth factor deprivation, inhibits phagocytosis and transcriptional responses to M1 and M2 polarizing stimuli, and protects mice from DSS-induced colitis.