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Osteoclastic bone destruction is mediated by factors such as RANKL elaborated by tissue-destructive fibroblasts. Takayanagi and colleagues identify the transcription factor Ets1 as a major regulator of these pathogenic cells.

AAVs show potential for kidney gene therapy, however, kidney gene transfer remains challenging. Here, the authors show that differing viral capsids exhibit distinct delivery to tubules and podocytes which is also dependent on injection routes, disease state and species.

DPANN is a widespread and diverse group of archaeal obligate ectosymbionts that depend on their host for proliferation. Here, authors use cryo-ET and proteomics to reveal intercellular proteinaceous nanotubes to facilitate DPANN-host interactions.

Identification of biomarkers to stratify patients who might benefit from treatment is needed to optimize targeted therapies. Here, based on an analysis of the RANGE trial (NCT02426125), the authors report potentially predictive biomarkers for survival benefit in patients with platinum-refractory advanced urothelial carcinoma treated with the anti-VEGFR2 monoclonal antibody ramucirumab.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Atomic distribution in high-pressure water ice are directly observed, via neutron powder structure analysis, found hydrogen bonds become symmetric at pressures about 80 GPa, marking the transition from ice VII to ice X.

Low total energy expenditure (TEE) has been a hypothesized risk factor for weight gain, but longitudinal repeatability of TEE is incompletely understood. Here the authors report that TEE is repeatable for adults, but not for children, and increases in TEE (adjusted for fat-free mass, fat mass, age and sex) are not associated with body composition changes in short-term longitudinal analyses.

JN.1 lineage is a globally dominant variant of SARS-CoV-2. Here, the authors examine structural insights into the BA.2.86 and JN.1 spike dynamics to help understand the mechanisms underlying SARS-CoV-2 infection and its neutralizing-antibody evasion.

The secreted ligand Angiopoietin-1 is essential for embryonic blood vessel development and adult vascular homeostasis. Here the authors show, using conditional knockout mice, that myocardium-derived Angiopoietin-1 is required for the formation of coronary veins, but not arteries.

Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.

Carbohydrate binding modules (CBMs) are non-catalytic domains found within multi-modular carbohydrate-active enzymes like glycoside hydrolases. Here, the authors show the crystal structures of two CBM family 92 members, which use three different surface binding sites to bind to β-glucans.

Recent Omicron SARS-CoV-2 subvariants independently acquire 5 key Spike mutations. Here, the authors evaluate the evolutionary importance of the 5 mutations and characterize the virological properties of variant BQ.1.1 harboring all 5 mutations.

SrCu₂(BO₃)₂ realizes the Shastry-Sutherland model (SSM), a 2D frustrated dimer model. Here, via high-magnetic-field inelastic neutron scattering measurements and matrix-product-state calculations, Fogh et al. find evidence for Bose-Einstein condensation of S = 2 two-triplon bound states, which is a spin-nematic phase.

It is unclear whether microbes can efficiently degrade biodegradable plastics in the extreme environmental conditions of the seafloor. Here, Omura et al. show that biodegradable plastics can be degraded by the action of microorganisms on the deep-sea floor, although with much less efficiency than in coastal settings.

This study identifies TTTCA- and TTTTA-repeat expansions in benign adult familial myoclonic epilepsy. Cortical neurons from affected people exhibit RNA foci containing these expanded repeats, suggesting RNA toxicity as the mechanism underlying disease pathogenesis.

Isolation and characterization of an archaeon that is most closely related to eukaryotes reveals insights into how eukaryotes may have evolved from prokaryotes.

Tenuazonic acid is a mycotoxin produced by various plant pathogenic fungi but its biosynthetic gene is unknown to date. Here, the authors identify the tenuazonic acid biosynthetic gene encoding a protein with a unique KS domain that conducts cyclization step for tenuazonic acid release in Magnaporthe oryzae.

Active and passive demethylation pathways have been implicated in the genome-wide erasure of 5mC accompanying mammalian preimplantation development. Here the authors reveal a recently evolved, mammalian-specific pathway in which global hypomethylation is achieved by the coupling of active and passive demethylation.

Observations of a luminous quasar from the high-resolution spectrometer Resolve aboard XRISM revealed highly inhomogeneous wind structure outflowing from a supermassive black hole, which probably consists of up to a million clumps.

The P681R mutation in the spike protein renders the Delta variant more pathogenic than prototypic SARS-CoV-2 in infected hamsters, and facilitates spike protein cleavage and enhances viral fusogenicity.

F₁F_o ATP synthase works using a rotary catalysis mechanism. Here, the authors report cryo-EM structures of Bacillus PS3 F₁-ATPase encompassing the complete set of six states taken up during the catalytic cycle, including the binding- and catalytic-dwell states.

A series of Toll-like receptor 7 (TLR7)-specific antagonists and extensive structural analysis reveal the open conformation of the receptor and the structural basis of TLR7 antagonism. One of the compounds shows efficacy in treating mouse model of systemic lupus erythematosus.

Diabetes is known to increase the risk of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Here, the authors show in a mice model that insulin action in the gut may play a protective role in the development of NASH and HCC in diabetes.

A newly developed PET tracer allows visualization of AMPA receptors in the living human brain, providing a new tool to study their potential involvement in neurological or psychiatric disorders.

Sekine et al. show that macrophages utilize different pathways to sense acute and chronic hypoxia, the latter relying preferentially on PNPO–PLP rather than hypoxia-inducible factors.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

Deciphering charge dynamics is imperative to realize efficient oxysulfide photocatalysts. Herein, with experiments and modelling, the authors report the dominant mechanisms behind decay, estimate material parameters, and formulate design principles.

Compton scattering provides information on the Fermi surface (FS) hence very useful to understand the electronic structure of high temperature superconductors. Here, Yamase et al. perform Compton scattering measurements on La_2−xSr_xCuO₄ samples and observe deformed FS in CuO₂ plane due to nematicity but recovering fourfold symmetry in bulk FS.

Although not photosynthetic, some archaea possess RuBisCO, one of the enzymes characteristic of the photosynthetic Calvin-Benson cycle, but apparently lack another one, phosphoribulokinase (PRK). Here the authors describe a carbon metabolic pathway in methanogenic archaea, involving RuBisCO and PRK.

The UFM1 system, a ubiquitin-like conjugation system is crucial for endoplasmic reticulum (ER) homeostasis. Here, authors found that CYB5R3 is covalently conjugated with UFM1, which becomes a signal for ER-phagy, a selective autophagy of ER.

Class 1 CRISPR systems are not as developed for genome editing as Class 2 systems are. Here the authors show that Cas3 can be used to generate functional knockouts and knock-ins, as well as Cas3-mediated exon-skipping in DMD cells.

Spike and wave discharge (SWD) activity is seen during absence seizures and is thought to be thalamocortical in origin. Here, the authors show that SWDs are initiated through the impaired corticostriatal excitatory transmissions onto striatal fast spiking interneurons.

Here, the authors identify six risk SNPs for systemic sclerosis by performing GWAS on Japanese patients and meta-analyzing Japanese and European GWAS datasets. Downstream analyses indicate that B cells contribute to pathogenesis.