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Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.

Achieving the Paris Agreement’s climate goals depends on safeguarding and monitoring the permanence of forest carbon stocks, as delays in addressing their vulnerability to disturbances drastically increase mitigation costs and efforts.

Here, the authors show that bromodomain-containing protein 4 is recruited to the MYC enhancer by Mediator and activates transcription through elongation factors independently of bromodomains. This mechanism contributes to bromodomain and extraterminal domain inhibitor resistance in estrogen receptor-positive breast cancer.

T-bet and GATA3 regulate differentiation of T cells into Th1 or Th2 cell fates, but little is known about their functional interaction outside of the IFNγ and Il4 /Il5/Il13 loci. Kanhere et al. map these factors across the genome in human T cells, revealing unappreciated breadth of function and interplay between them.

Understanding the cellular target of hit compounds from phenotypic screens presents a major challenge yet is essential in the development of chemical probes. Here, the authors reveal the target of Hedgehog Pathway Inhibitor-1, by converting it to a bifunctional degrader, to be BET bromodomains.

Bromodomain and extraterminal proteins (BET) are reported as targets for anticancer therapy. Here, the authors report the final results of a phase I clinical trial of the BET inhibitor trotabresib in patients with solid tumours and diffuse large B-cell lymphoma.

Mycobacterium tuberculosis produces linoleic acid, which is released from macrophages during infection and upregulates regulatory T cell activity, to suppress macrophage control of intracellular bacteria in mice.

Different mutations found in endometrial and prostate tumors affecting the substrate-recognition domain of SPOP, a component of the E3 ubiquitin ligase complex, result in opposing degradation activity of BET proteins and response to BET inhibitors. This work, along with findings by Zhang et al. and Dai et al., highlights the divergent effects of recurrent mutations affecting different residues within the same functional domain of SPOP and provides scientific rationale to guide the administration of BET inhibitors in endometrial and prostate cancer patients harboring SPOP mutations.

Vertical transmission is thought to favour beneficial host–microbe interactions, but these may also be context dependent. Here Bruijning et al. show with a model that variable environments can select for bet-hedging by hosts via imperfect vertical transmission of microbes.

Activated B cells can tailor their ensuing antibody responses by isotype switching. McHeyzer-Williams and colleagues demonstrate B cell–intrinsic requirements for the transcription factors T-bet and RORα in maintaining IgG2a⁺ and IgA⁺ memory cells, respectively.

CD8⁺ T cells primed in the absence of CD4⁺ T cell help fail to develop a robust memory cell response. Zloza et al. now report that these CD4-unhelped CD8⁺ T cells can be rescued by activating their cell surface receptor NKG2D, which restores CD8⁺ T cell expansion and cytolytic activity during a recall response and protection in a mouse model of influenza infection.

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

Confidence could act as an implicit learning signal when explicit feedback is unavailable. The authors show confidence can also provide a distinct value signal in the presence of explicit feedback, both of which are integrated to drive perceptual learning via basal ganglia circuits.

Targeting the acetyllysine ‘reader’ activity of BET family transcriptional coactivators has emerged as an anticancer modality. A new class of dimeric JQ1 derivatives displays enhanced potency for bivalent targeting of tandem bromodomains in BET proteins.

BET inhibitors that target bromodomain chromatin readers such as BRD4 are being explored as potential therapeutics in cancer; here, in a MLL–AF9 mouse leukaemia model, resistance to BET inhibitors is shown to emerge from leukaemia stem cells, and be partly due to increased Wnt/β-catenin signalling.

Regulatory T cells expressing the transcription factor T-bet selectively suppress T_H1 and CD8 T cells, but not T_H2 or T_H17 activation and associated autoimmunity.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

BET inhibitors that target bromodomain chromatin readers such as BRD4 are being explored as potential therapeutics in cancer; here triple-negative breast cancer cell lines are shown to respond to BET inhibitors and resistance seems to be associated with transcriptional changes rather than drug efflux and mutations, opening potential avenues to improve clinical responses to BET inhibitors.

A Bayesian framework based on partially observable Markov decision processes (POMDPs) not only predicts subjects’ confidence in a perceptual decision making task but also explains well-known discrepancies between confidence and choice accuracy as arising from incomplete knowledge of the environment.

This study demonstrates 3D printing of hierarchically ordered, porous transition metal oxides and nitrides directed by block copolymer self-assembly, with record surface areas and nanoconfinement-induced critical fields in the nitride superconductors

Dendritic cells are supplied antigens by other cells such as lymphatic endothelial cells (LEC) at late time points after immunization. Here the authors show antigen archiving is defined by a transcriptional program that can predict antigen archiving depending on the priming pathogen, and that boosting of immune responses increases the archiving.

Aerogels made from metal–sulfur networks show high absorption of conjugated organic molecules and mercury ions and can easily separate H₂ from CO₂. Compared with the conventional sulfided Co-Mo/Al₂O₃ catalyst, these spongy, random porous networks are twice as active towards the hydrodesulfurization of thiophene.

There are currently no licensed vaccines to prevent Group A Streptococcus (GAS) infections. In this study, the authors evaluate the immune response and preclinical efficacy of a multicomponent mRNA lipid-nanoparticle vaccine against GAS.

Hypoxia induces d-serine production by Mycobacterium tuberculosis which inhibits mTORC1 and T-bet expression to restrict downstream CD8⁺ T cell immune responses and macrophage activation, and inhibit control of tuberculosis in mice.

Here the authors show that CD4⁺ effector T cells prevent or reverse CD8⁺ T cell dysfunction by licensing Kupffer cells to trigger IL-27 production, defining a liver-specific immune circuit and a potential target for chronic HBV therapeutics.

Here, the authors show that there is a pretumorigenic T_H17 subset in the intestines that can convert to being tumorigenic under the control of KLF6 and that this process can be prevented by TGFβ1 production from intestinal epithelial cells.

Accomplishing multiple synthetic tasks in parallel including substrate capture, separation, and reaction, all in one system, has remained a long-standing challenge in synthetic chemistry. Here, the authors report a sorting polymerization strategy that harnesses the multifunctional nature of a bichannel metal-organic framework.

Erlich et al. show that soluble LTα and membrane-bound LTα1β2 lymphotoxins expressed by B cells play distinct roles to attenuate the pathology observed in ileitis.

BET proteins regulate a reversible transcriptional switch that governs fibroblast activation in heart disease through the transcription factor MEOX1.

Metal–sulfur motifs are commonly found in enzymatic active sites and heterogeneous catalysis, but they remain underexplored in porous solids. Now, sulfur-based ligands have been incorporated into metal–organic frameworks through post-synthetic modifications. The resulting sulfide MOFs exhibit enhanced catalytic performance in the selective hydrogenation of nitroarenes compared with their parent MOFs containing terminal or bridging chloride and hydroxyl groups.

Arabzade, Shirnekhi, Varadharajan, Ippagunta and colleagues show that the zinc finger translocation-associated (ZFTA) fusion oncoproteins gain intrinsically disordered regions, inducing nuclear condensate formation and oncogenic activation.

Implicit biases are influenced by social contexts which, in cities, are shaped by the constraints of urban infrastructure networks. Here the authors show that more populous, more diverse, and less segregated cities are less biased and that this is predicted by a complex systems model.