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The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

A protein biomarker, the NOTCH3 extracellular domain, identifies individuals with idiopathic pulmonary hypertension, correlates with disease progression, improves mortality risk prediction and provides a readily implementable, noninvasive blood test for this disease.

Proxy records from Lake Baikal show that rapid cooling coincided with Northern Hemisphere ice sheet expansion 2.7 million years ago, a change accompanied by a transition to open steppe ecosystems.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Mouse models demonstrate that vagal sensory neurons transmit signals from lung adenocarcinoma to the brain, increasing sympathetic efferent activity in the tumour microenvironment and thereby creating a immunologically permissive environment for tumour growth.

How leptin signalling produces anti‑obesity effects is incompletely understood. Here, the authors demonstrate that FAK and PYK2 are required for STAT3 activation, normal leptin responses, and HDAC6 inhibitor‑mediated weight loss, with their loss causing hyperphagic obesity.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as obesity, caloric restriction and changes to meal timing, alter hepatic protein secretion.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

A clinical cohort-based biomarker study in patients with metastatic renal cell carcinoma demonstrates that blood levels of soluble mucosal addressin cell adhesion molecule-1 are prognostic for survival in patients treated with tyrosine kinase inhibitors and immune checkpoint inhibitors and may serve as a surrogate marker for gut dysbiosis based on integrated data from three clinical trials.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Gapless modes emerging from non-equilibrium phase transitions are predicted to diffuse rather than propagate as sound waves. Now, the diffusion of these modes and their suppression under symmetry breaking are confirmed in a polariton condensate.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Integrated single-cell and spatial data analysis, combined with bidirectional CRISPR screens, identify the transcription factor GLIS3 as a key driver of chronic inflammation and fibrosis and a potential marker of disease severity in patients with ulcerative colitis.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

New methods for targeted covalent protein modification at low reactivity aspartates and glutamates are of high interest. Here, the authors report a technique inspired by the HaloTag technology, which employs a covalent conjugation reaction between ligands with a reactive chloroalkane linker and a specific aspartic acid, and use it to covalently modify lipoprotein chaperone PDEδ at a binding site glutamic acid.

Glucose deprivation triggers the secretion of the cytokine LIF, which promotes angiogenesis and immune suppression in lung cancer models.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Viral ribonucleoprotein–viral protein networks form pre-replication centres that nucleate viral factories and drive respiratory syncytial virus replication.

Down syndrome (DS) increases gene dosage that disrupts neurodevelopment and cognition. Using human-derived isogenic neurons, this study reveals altered network activity, synaptic dysfunction, and ion channel defects underlying DS neural impairment.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Wakita et al. systematically compare the efficacy of 21 senolytics and identify a subpopulation of senolytic-resistant cells. They demonstrate a mitochondrial basis of senolytic resistance and show that metabolic interventions enhance senescent cell clearance in vivo.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

WIN332 is an HIV-1 Env protein designed to elicit a new class of Asn332-glycan-independent antibodies (type II) to the V3-glycan site of Env. WIN332 immunization rapidly induces type-II V3-glycan antibodies with low inhibitory activity indicative of a neutralization activity in macaques.

Diatoms are critical for carbon fixation and have strong biotechnology potential. Here, the authors optimized DNA and protein delivery methods for the model diatom Phaeodactylum tricornutum, also showing that DNA pieces can be stitched together directly in algal cells.

The contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

The authors developed an LXR inverse agonist, TLC-2716, and show it is effective in reducing triglycerides and cholesterol in dysmetabolic preclinical models. Additionally, a phase 1 trial in healthy participants shows that TLC-2716 is well tolerated and reduces plasma triglycerides and postprandial remnant cholesterol, highlighting its potential for managing cardiovascular risk.

During development of eutherian females, one of the X-chromosomes is silenced. Here, authors show that alleles on the inactive X-chromosome are dynamically expressed along neural differentiation enhancing resilience of female neural tissue.

The Akt-mTOR axis influences cell activation, differentiation and metabolism. Jordan and colleagues show that thymic and inducible T_H17 cells exhibit different requirements for mTORC1 and mTORC2 as well as Akt isoforms.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Here they demonstrate a mechanism that converts analog stress stimuli into digital JNK activation, allowing organisms to make binary cell-fate decisions that avoid harmful reactions to mild stress while enabling robust responses to strong stress.

PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

There are similarities in airway inflammatory endotype between eosinophilic granulomatosis with polyangiitis (EGPA) and type 2 eosinophilic asthma. Here, the authors perform single-cell transcriptomics to compare EGPA with severe eosinophilic asthma and find differences in the innate immune cell populations and use mouse models to characterise the function and phenotype of these cells.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

METTL3 promotes healthy placenta function by regulating m⁶A methylation and histone epigenetics. Deficiency in METTL3 leads to premature senescence, inflammation activation of trophoblasts, contributing to pregnancy complications like preeclampsia.

Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) is important for invasion of reticulocytes and PvRBP2b antibodies correlate with protection. Here, Chan et al. isolate and characterize anti-PvRBP2b human monoclonal antibodies and describe mechanisms by which these antibodies inhibit invasion.

CRISPR activators are powerful tools for controlling gene expression, but they suffer from inconsistent efficacy and high toxicity. Here, authors develop a high-throughput method to test thousands of CRISPR activators, revealing distinct principles of activator biology and delivering improved tools.