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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.

The APC/C ubiquitylates histones to regulate gene expression in pluripotent cells. Here, the authors pair cryo-EM and biochemical and biophysical assays to show that instead of modifying nucleosome-incorporated histones, the APC/C ubiquitylates extranucleosomal histone complexes through a mechanism that bypasses canonical substrate degrons.

CAR-T cells are engineered to express CBD-IL-12 upon STEAP1 recognition to enhance tumour-specific immune responses in mice.

Developmental and epileptic encephalopathies are devastating neurological disorders. Here, the authors establish a cohort of patients with variants in the gene DENND5A and use human stem cells to discover a disease mechanism involving altered cell division.

Transport measurements on the Kitaev quantum spin liquid candidate α-RuCl3 subjected to a magnetic field reveal oscillating behaviour in its thermal conductivity, reminiscent of Shubnikov de Haas oscillations in metals.

Certain RIFINs from Plasmodium falciparum can bind to both inhibitory (KIR2DL1) and activating (KIR2DS1) immune receptors on natural killer cells, demonstrating the potential role of activating killer immunoglobulin-like receptors in targeting pathogens and controlling malaria infection.

Coexistence of a spin-glass phase with antiferromagnetism in an intercalated crystal produces a large exchange bias effect. This is due to the interplay of disorder and frustration.

JADE is a subunit of human acetyltransferase complex HBO1 that is essential in transcriptional regulation. Gaurav et al. characterize the molecular mechanism by which JADE mediates genomic association and enzymatic and pathological activities of the HBO1 complex.

Germ-free mice were colonized with complex defined communities to show T cell recognition of commensals is focused on widely conserved, highly expressed cell-surface antigens, opening the door to new therapeutic strategies.

This study provides evidence of a long-term anomalous behavior of the geomagnetic field in the South Atlantic from paleodirectional data of Trindade Island. Furthermore, field models suggest the persistence of anomalous features for the past 10 Myr.

The diversity of ponerine ants varies widely across the globe. This study finds that the origin and early colonization in Gondwana’s tropical regions mainly shaped this distribution, while differences in diversification and dispersal have balanced regional diversity over time.

Hippocampal neurons adapt to experience through changes in gene expression and chromatin accessibility. Here, authors show that novel environment exposure induces region- and cell-type specific transcriptional changes coordinated by FOS/AP-1.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

A mass spectrometry–based approach is used to investigate the mechanisms by which different NUP98 fusion proteins cause leukemia, revealing that the fusion proteins share common interactors and alter the composition of nuclear condensates.

Metabolic rewiring during tachycardia promotes tissue hypoxia, elevated glucose utilization and the suppression of oxidative phosphorylation, driving contractile dysfunction.

Chronic antigen stimulation leads to CD8⁺ T cell exhaustion, which is mediated by persistent activation of the transcription factor NFAT in the absence of AP-1. Seo, González-Avalos and colleagues show that overexpressed BATF cooperates with IRF4 to counteract NFAT-induced exhaustion and promote better tumor control by CAR T cells in mouse models.

Lentiviral vectors that express a fluorescent reporter and a selectable marker in pluripotent cells improve and simplify isolation of induced pluripotent stem cell lines in mouse and human.

Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A₂, thereby enhancing the immune response against metastasis.

TCF1⁺ ‘stem-like’ CD4⁺ T cells have a capacity for self-renewal and effector differentiation when required. Here the authors show how these stem-like T cells mediate allograft rejection via the replenishment of their effector differentiation.

T cells undergo metabolic reprogramming after they are activated. Rathmell and colleagues show that inflammatory Toll-like receptor signals induce glycolysis and impair the suppression of regulatory T cells, but Foxp3 can promote a switch to oxidative phosphorylation and suppression.

Human acetyltransferases MOZ and MORF mediate development programs and are dysregulated in diseases. Here the authors identified two winged helix (WH) domains in MORF/MOZ and characterized their DNA binding functions, including targeting of CpG by WH1.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

“Although aberrant promoter DNA hypermethylation is a hallmark of cancer, it is not clear whether it is sufficient to drive transformation. Here, the authors use CRISPR-dCas9 to perform hit-and-run epigenetic editing, which prevents senescence entry in primary breast cells from healthy donors.”

PLXDC2 marks hematopoietic stem cells in mouse and human cord blood, enabling reliable identification with reporter mice and an antibody, and serving as a tool for imaging and transplantation studies.

Although epigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, previous studies have been limited in sample size and brain region used. Here, the authors combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differentially methylated loci across cortex.

Ferritin, the cellular iron storage complex, binds NCOA4 and is trafficked to the lysosome for degradation and iron release. Here, authors present the cryo-EM structure of the NCOA4-Ferritin complex with biophysical and cellular characterization.

A meta-analysis of the make-up and properties of transwell and microfluidic models of the human blood–brain barrier reveals the factors that are necessary for the recapitulation of the barrier’s healthy and diseased states.

Fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with long COVID.