Search

Ubiquitin chains direct post-ER membrane proteins toward different degradation routes. Here, the authors show that K63 chains promote lysosomal sorting, whereas K48 chains trigger “CUTUP”, a protein shearing pathway mediated by two ubiquitin-dependent proteases, Ddi1 and Rbd2, and the proteasome.

Here the authors report NiGa₂O_4–x(OH)_y for light-driven CO₂ hydrogenation to methanol. The surface Lewis acid–base pairs and -OH groups act as conduits for H^- /H⁺ transport to active sites, enhancing photocatalytic methanol production.

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.

Taniuchi and colleagues show that differential phosphorylation of the terminal Y residue in Runx proteins connect MHC restriction with the helper versus cytotoxic T cell lineage choice.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

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.

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.

It remains unclear whether rRNA modifications can be naturally altered in response to antibiotics in bacteria. Here, the authors analyzed direct RNA nanopore sequencing data with an analytical pipeline Nanoconsensus, to investigate whether bacterial rRNA modifications are modulated upon exposure to various antibiotics.

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.

Here they show that the adhesion GPCR Gpr126/Adgrg6 regulates trabeculation during heart development. Its N-terminal fragment is required for maintaining cell adhesion and compact wall integrity while its C-terminal fragment is essential to provide trabecular identity.

Jacquemyn et al. identify key lipid determinants controlling ectosome shedding from neurons. They find that ectosomes are a major route for the intercellular transport of misfolded α-synuclein, with relevance to Parkinson’s disease pathology.

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.

Efficient nuclear delivery of DNA remains a major challenge in non-viral gene therapy. Here the authors present an improved workflow for generating DNA oligonucleotide-peptide conjugates which are ligated to linear DNA and achieve nuclear localization.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

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.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

Symmetry breaking is key to tissue formation. Now it is shown that symmetry breaking of epithelial spheroids is controlled by an interplay of collective migration with curvature and matrix remodelling.

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.

The authors show that increased Xist RNA levels can induce de novo silencing of genes that normally escape X inactivation. SPEN depletion prevents the silencing of escape genes upon Xist RNA overexpression in neural progenitors.

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.

Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

Polymerization-inducing chimeras are a novel bifunctional modality that uses protein symmetry to sequester targets by forming insoluble supramolecular assemblies. This approach overcomes reliance on accessory proteins and differs functionally from conventional inhibitors.

Elyaman and colleagues performed comparative single-cell transcriptomic and TCR repertoire analyses on T cells obtained from human cadaver brain and leptomeningeal tissues from individuals diagnosed with neurodegenerative disease.

An approach to discover reactive diazo-based metabolites by capture based on their reactivity coupled to mass spectrometry revealed two previously unknown diazo-containing compounds produced by the human lung pathogen Nocardia ninae using novel biosynthetic chemistry.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

A combination of genome-wide functional screening, imaging and chromatin profiling identifies a new class of highly prevalent genomic elements that help retain extrachromosomal DNA copies in dividing cells and persist across generations.

Selecting for varieties of commercial crops with enhanced nutritional quality is important in agriculture. Here, the authors identify alleles of a gene in tomatoes that give rise to increased levels of vitamin E and find that the promoter of the gene is differentially methylated.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

Here, the authors identify distinct, autism-specific diet microbiome interactions, showing how unhealthy diets and synthetic emulsifiers drive dysbiosis. The findings pave the way for microbiome-aware dietary strategies for autism.

Cardiac fibrosis arises from persistent myofibroblast activity. This study reveals how chromatin factors control scar-forming cells in the heart and shows that inhibiting KAT5 can reduce harmful cardiac fibrosis.

A computational method designs receptors called T-SenSERs, which have predictable signalling responses to tumour microenvironment soluble factors and can be co-expressed with conventional CARs in T cells to enhance their therapeutic activity.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

IL-17A, a cytokine important for tissue repair, can impair healing when increased, contributing to keratinocyte dysfunction in type 2 diabetic wounds. Here, the authors show that IL-17A drives this dysfunction via JMJD3-mediated epigenetic changes, and that blocking this pathway improves wound healing.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

Releasing only males remains a major hurdle for mosquito genetic control. Here, authors develop a mosquito strain using CRISPR and a synthetic sex chromosome, producing dark males and yellow females that develop slower and lay desiccation-sensitive eggs, enabling easy separation and safe releases.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

Kidney organoids derived from human pluripotent stem cells are infused in a normothermic machine perfusion system to condition explanted porcine kidneys, and the feasibility and viability of their in vivo engraftment are demonstrated.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

PSC can be differentiated into blood cells in vitro. In this report, Sun and Motazedian et al describe a differentiation method that generates blood-forming endothelial cells that push newly emerging blood cells to become lymphocytes.

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.

The authors present Gemini, their bifunctional replicon platform capable of functioning as either self-amplifying RNA (saRNA) or self-amplifying DNA (saDNA).

Haptotaxis was traditionally seen as migration up protein gradients. It is now shown that cells can also oscillate or migrate down the gradient.

Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells.

One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

Bromley and colleagues show that IL-4 decreases the responsiveness of CD8⁺ T cells to TGFβ, resulting in impaired formation of CD8⁺ T_RM cells.