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Chemotherapy induces bone loss that compromises skeletal health in cancer patients. Here, the authors show that chemotherapy-induced senescence in bone marrow adipo-lineage cells leads to bone loss and demonstrate that senolytic targeting of senescent cells preserves skeletal health during chemotherapy, providing a potential strategy to protect the skeleton in cancer therapy.

Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous disease associations.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

A machine-learning-based computational approach to probe pathway coessentiality reveals that complex II of the electron transport chain regulates de novo purine synthesis, and can be targeted to treat acute myeloid leukaemia.

ATP synthase powers cells by converting proton translocation into energy. Here, authors reveal distinct structural features of the P. aeruginosa ATP synthase that regulate activity and may serve as targets for new antimicrobial therapies.

Sequencing analysis of tamoxifen-associated uterine cancers and further in vivo analyses suggest that the drug tamoxifen can activate the PI3K pathway in the absence of oncogenic mutations.

Allogenic mesenchymal stem cells are engineered with three mRNAs to bind to multiple myeloma B cells while activating T cells for cancer therapy.

The HKU25 clade MERS-related coronaviruses with broad distribution are shown to use ACE2 as a functional receptor, revealing unexpected receptor plasticity and offering new insights into coronavirus evolution, host range and potential zoonotic risk.

John et al. show that upon classical activation, macrophages undergo nitric oxide-driven reprogramming of nucleotide metabolism, which affects immune functions and responses.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.

Carnitine uptake by OCTN2 supports fatty acid metabolism. Here, authors report cryo-EM structures of human OCTN2, revealing the mechanism of sodium ion-dependent carnitine transport and providing insight into disease-associated variants.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

DNA double strand break repair pathways ensure genome stability and prevent disease. Here the authors show that the actin nucleating factor DIAPH1 and γ-actin promote homologous recombination (HR)-dependent repair. Inherited mutations in DIAPH1 or ACTG1 give rise to clinical deficits similar to those associated with defective HR.

Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.

Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.

A mix-and-go system enables the rapid prototyping of antibody formulations, allowing control of their orientation on the surface of LNPs for specific cell targeting, significantly improving the ex vivo and in vivo deliveries of mRNA.

Mantle cell lymphoma (MCL) is a form of B-cell non-Hodgkin lymphoma with a high degree of genetic and clinical heterogeneity. Here, using a multi-omics approach, the authors investigate genetic alterations in association with the tumour microenvironment to identify potential therapeutic vulnerabilities.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

The SMC5/6 complex is critical for genome stability. Here, the authors identify mutations in SLF2 and SMC5 as cause of Atelís Syndrome characterized by microcephaly, short stature, anemia, segmented chromosomes and mosaic variegated hyperploidy.

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.

The molecular mechanisms of cell entry for the recently identified highly pathogenic feline coronavirus FCoV-23 are characterized in detail.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Zaman, Yang and Huang et al. demonstrate MDK’s suppressive effect on amyloid-β and its impact on amyloid burden and microglial activation in Alzheimer disease mice, highlighting its protective role in pathogenesis.

A newly developed monoclonal antibody, MARV16, broadly neutralizes all Marburg virus isolates and provides effective protection in guinea pigs with Marburg virus disease.

Dural-associated lymphoid tissues are lymphoid structures around vascular hubs in the dura mater that sample antigens and rapidly support humoral immune responses after local pathogen challenge.

Enterololin is a narrow-spectrum antibiotic that selectively kills Enterobacteriaceae in vitro and in a mouse model of adherent-invasive Escherichia coli gut infection. AI-guided mechanism-of-action studies identified LolCDE as its molecular target.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

Here the authors identify upstream open reading frames (uORFs), uORF1 and uORF2 in the Asian/American lineage and African uORF in the African lineage of Zika viruses, and show that uORF1 affects vimentin filaments and that the identified uORFs affect virus replication in neural cells.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Protein phosphorylation plays critical roles in myriad cell processes. In this work, the authors apply new mass spectrometer technology to detect and quantify tens of thousands of protein phosphorylation sites within one hour or less of analysis. This technology has potential to greatly accelerate biological discovery.

A high-throughput chemical screen identifies the salt-inducible kinase inhibitor HG-9-91-01 as a driver of β cell proliferation, acting through an ATF6-dependent unfolded protein response.

The replicative helicase CMG is targeted for removal or proteolysis by the E3 ubiquitin ligase TRAIP. This study describes how the de-ubiquitylating enzyme USP37 protects genome stability by preventing premature TRAIP-dependent CMG unloading when replication stress impedes timely termination.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The efficacy of immunotherapies in lung cancer is often restricted by formation of dense and aligned collagen fibers within the tumor microenvironment. Here the authors develop an inhalable lipid nanotherapeutic agent to disrupt collagen fiber alignment and alleviate immunosuppression in lung tumors.

Yong et al. highlight how sampling conditions affect metabolic profile in renal cancer, showing that prolonged ischemic exposure disrupts tissue metabolome stability and masks important phenotypes, such as suppressed gluconeogenesis.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Kim et al. show that NAD⁺ kinase 2 serves as a source of mitochondrial NADPH to support mitochondrial fatty acid synthesis, protein lipoylation and mitochondrial oxidative metabolism.

The emergence of acquired resistance to standard platinum-etoposide chemotherapy in small cell lung cancer (SCLC) is a common event. Here, the authors using paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models reveal a mechanism of drug resistance in SCLC mediated by Notch and nitric oxide activation of soluble guanylate cyclase signalling.

Aberrant crosstalk between cancer stem cells and their microenvironment triggers angiogenesis and TGFβ signalling, creating conditions that are conducive for hijacking leptin and leptin receptor signalling, which in turn launches downstream PI3K–AKT–mTOR signalling during the benign-to-malignant transition.

ABD957 is a potent and selective inhibitor of the ABHD17 family of depalmitoylases that disrupts N-Ras signaling in human acute myeloid leukemia cells and can synergize with MEK inhibition.

Retinoic acid is known to be effective against bone marrow metastatic neuroblastoma cells, but not primary tumors. Here, authors discover that bone morphogenetic protein signaling is responsible for determining neuroblastoma cell fate and sensitivity to retinoic acid.

UDP-glucuronic acid is a component of the extracellular matrix. Here, the authors report biallelic variants in the gene encoding UDP-Glucose 6-Dehydrogenase (UGDH) in individuals affected by developmental epileptic encephalopathies that impair UGDH stability, oligomerization, or enzymatic activity in vitro.