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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.

T cells can recognise lipid antigen in the context of CD1d molecules. Here, the authors show that γδ T cell activation in response to CD1d differs from that of αβ T cells and determine the structure of a γδ T cell receptor that binds to CD1d independently of the presented lipid.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Researchers use a chimeric approach to reveal the first near-atomic resolution structures the yellow fever virion, showing key differences between vaccine and virulent strains that affect how antibodies recognise and neutralise the virus.

Brown adipose tissue is a heat-generating organ and promising therapeutic target for treating obesity and metabolic diseases. Its presence in adults supports metabolic health, whereas its decline with age and weight gain might promote chronic disease. Efforts to understand its fascinating biology and translational potential continue to gain momentum.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

TANK-binding kinase-1 (TBK1) and its homologue IκB kinase-ε (IKKε) are critical in the induction of the interferon response and the response to infection by pathogens. Here the authors show that pharmacological targeting of TBK1 AND IKKε reduces the immunopathology seen in a murine model of SARS-COV-2 infection.

The authors present a multicenter database to investigate the neural correlates of dreaming, including physiological, behavioral and experiential data. This database could boost the research on the mechanisms of dreaming in humans and the signatures of consciousness.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Using HDX-MS, X-ray crystallography, cryo-EM, and MD simulations, the authors examined the conformational dynamics of GAD65 in its apo- and holo- states and its interaction with the autoimmune polyendocrine syndrome type 2-associated autoantibody b96.11.

Mobilizing haematopoietic stem cells to the peripheral blood has largely replaced bone marrow transplants as a strategy in the clinic. Here, Cao et al. report the use of an α₉β₁/α₄β₁integrin antagonist to induce rapid mobilization of blood stem cells from the bone marrow in a humanized mouse model.

The microbiome can affect susceptibility to developing asthma. Marsland and colleagues show that changes in the microbial population lead to enrichment of an l-tyrosine metabolite, p-cresol sulfate, which can protect mice against allergic inflammation.

A temporal version of Young’s double-slit experiment shows characteristic interference in the frequency domain when light interacts with time slits produced by ultrafast changes in the refractive index of an epsilon-near-zero material.

The optimal timing between first and second mRNA COVID-19 vaccine doses has not been established. Here, the authors use electronic health record data from Georgia, USA in a target trial emulation study to estimate vaccine effectiveness against infection for different dose intervals.

Astrocytes have important roles in disease. However, modulation of their reactive state is challenging. Here the authors present a phenotypic in vitro screening platform they can leverage to identify chemical compounds able to modulate astrocyte reactivity in vitro and in vivo.

Outer membrane vesicles from Neisseria gonorrhoeae and other Gram-negative pathogens can kill macrophages via induction of mitochondrial apoptosis and activation of the pro-apoptotic BCL-2 family member BAK, and activate the NLRP3 inflammasome.

Aged hematopoietic stem cells (HSC) are characterised by reduced regenerative potential and a loss of quiescence. Here, the authors show nicotinamide riboside treatment shrinks the age-enlarged stem cell pool and shifts aged HSC functionally, metabolically and molecularly towards the young state.

Certain specific antigens have been shown to activate T cells in an MHC independent manner. Here the authors show a phycoerythrin reactive mouse TCR which recognises native protein and characterise the molecular nature of this interaction and that this specific TCR can be selected in the thymus.

The electronic correlation-driven Mott metal-insulator transition has been predicted in a 2D metal-organic framework with a kagome structure. Here the authors synthesize such a system in experiment and demonstrate an electrostatically controlled Mott transition.

An increasing prevalence of Gram-negative bacteria increases the interest in nanotherapies to treat antibiotic resistance. Here, the authors examine the antimicrobial activity of polymyxin-loaded cubosomes and explore a polytherapy treatment of pathogens with cubosomes in combination with polymyxin.

Biochemical and biophysical analyses of eye lenses from mouse strains that develop cataract due to mutations in α-, β-, or γ-crystallin proteins reveal that the mutant protein levels are largely reduced, but other crystallin proteins, including α-crystallins, precipitate.

An alternative model for the homeostasis of adult epidermis posits posits only one type of stem cell undergoes both symmetric and asymmetric divisions to ensure epidermal homeostasis. A genetic approach of marking single cells in the adult mouse tail epidermis shows that the clones of labelled cells that arise from their inducible labelling approach are most likely to come from a single compartment of proliferating cells, which may undergo an unlimited number of divisions.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

A study describes the split integrated stress response, a cellular stress response mechanism characterized by reduced eIF2B activity without eIF2α phosphorylation, which activates the eIF4E–ATF4–PCK2 axis, enabling metabolic reprogramming.

Precise and reliable gene delivery remains technically challenging. Here, the authors show that rationally designed frameshifting splicing can be used to express genes only in targeted cell types, with the potential to enhance the specificity AAV gene delivery.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The authors find subtype-specific influenza cross-reactivity patterns, including rapid declines for A(H3N2) within 6 years, sustained responses for A(H1N1)pdm09 and increased cross-reactive responses in humans after repeated A(H3N2) exposure.

This study reveals how the pathogen Staphylococcus aureus adapts to the lung microenvironment, rich in host metabolites fumarate and itaconate, by using a key enzyme, FumC, to support its metabolic fitness, survival, and persistence.

Differentiation therapy induces the maturation and clearance of acute myeloid leukemia cells. Here, using a mouse model, the authors show that a specific lineage of mature leukemia-derived cells persists during remission and is responsible for disease relapse.

The trihydrogen cation (H3+) plays a key role in the interstellar chemistry. Here the authors, using state of the art experiments and computation, identify factors that govern H3+ formation from doubly ionized small organic molecules, offering guidelines for examining alternative sources of H3+ in the universe.

Within-sibship genome-wide association analyses using data from 178,076 siblings illustrate differences between population-based and within-sibship GWAS estimates for phenotypes influenced by demographic and indirect genetic effects.

Observations from the JWST of the second brightest GRB ever detected, GRB 230307A, indicate that it belongs to the class of long-duration GRBs resulting from compact object mergers, with the decay of lanthanides powering the longlasting optical and infrared emission.

A20, encoded by TNFAIP3, is a negative-feedback inhibitor of NF-κB. Grey and colleagues identify natural human variants of TNFAIP3, which lower A20 activity and increase autoinflammatory responses. These alleles were inherited by descendants of Denisovans who crossed the Wallace Line to inhabit Oceania.

Michael Talkowski, David FitzPatrick, Erica Davis and colleagues report rare inherited or de novo missense variants in SMCHD1 in arhinia patients. Some of the same mutations in SMCHD1 are known to cause a phenotypically distinct muscular dystrophy disorder, FSHD2, and the distinct clinical features of the two disorders suggests that additional genes interact with SMCHD1 to cause arhinia.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Natural killer T (NKT) cells include type I that express semi-invariant T cell receptor (TCR), and type II that cover a broader repertoire. Here the authors describe the crystal structure of a type II NKT TCR complexed with CD1d/antigen to propose that type II NKT TCRs may adapt multiple CD1d docking modes to maximise antigen recognition efficacy.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

Cryogenic electron microscopy determines the structure of a fully assembled, MR1-reactive, human Vγ8Vδ3 TCR–CD3δγε₂ζ₂ complex bound by anti-CD3ε antibody Fab fragments.

The cytokine IL-6 controls the survival, proliferation and effector functions of lymphocytes. Jones and colleagues show that activation of CD4⁺ T cells leads to suppression of STAT1 activation by tyrosine phosphatases and changes the effector characteristics of memory CD4⁺ T cells in response to IL-6.