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The role of mosquito saliva proteins in viral infection remains incompletely understood. Here, the authors show that sialokinin facilitates viral dissemination while suppressing immune response and inflammation in chikungunya virus-infected mice.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Zhang et al. show that in mice, an adipocyte population with high expression of the transcription factor JunB in the brown adipose tissue shows reduced thermogenic capacity. Depletion of JunB increases the fraction of adipocytes with high thermogenic capacity and ameliorates diet-induced insulin resistance.

TMEM127 is a tumor suppressor protein, loss of which predisposes to catecholamine-secreting tumors. Here the authors show that TMEM127 expression is modulated by nutritional status and that it has a role in regulating organismal insulin sensitivity.

Hruska et al. suggest an architectural basis for NMDAR-dependent spine plasticity mediated by addition of unitary pre- and postsynaptic nanomodules that function as building blocks of synaptic organization and enable structural plasticity.

The mechanisms that determine whether fibrosis occurs during chronic skin inflammation are poorly understood. Here, the authors show that chronic inflammatory skin diseases characterized by skin fibrosis share activation of EGFR-STAT1 signaling in pathologic fibroblasts as a disease defining signaling mechanism.

Hartley et al. report the bidirectional remodeling of a basolateral amygdala-to-central amygdala neural circuit, where input onto corticotropin-releasing factor (CRF)-expressing and CRF-negative neurons is shaped by the acquisition and extinction of fear memory.

A microfluidics- and electron-microscopy-based method enables the characterization of polyclonal antibody responses to infection and vaccination.

The processes regulating cardiomyocyte (CM) maturation are unclear. Here, the authors show that serum response factor regulates CM maturation only in neonatal CMs through stage-specific chromatin occupancy that affects cell size, sarcomere and transverse-tubule organization, and mitochondria

The cessation of nephrogenesis determines nephron endowments in mammals. Here the authors show that differential translation of Wnt antagonists versus agonists determines the tipping point from self-renewal to differentiation of nephron progenitors during nephrogenesis, using mutant mice with elevated nephron numbers.

Why joints are highly responsive to systemic inflammation is unknown. Hasegawa et al. sought to address this question, developing a whole-mount imaging system of the entire synovium to profile the vascular, neuronal and immune components.

The relevance of mitochondrial cysteine metabolism to ferroptosis is unknown. Here, Ward et al. show that mitochondrial Fe-S cluster synthesis persists under cysteine limitation via the catabolism of glutathione and at the expense of cell viability.

Profiling transcriptional crosstalk between promoters and cell-type-specific enhancers allows large gene cargo delivery.

Most genetic association studies have been done on single nucleotide polymorphisms and small indels, while other types of variants have been less studied. Here, the authors use whole genome sequencing in a diverse population to identify and provide experimental evidence for associations between structural variants and blood-cell traits.

Minogue et al. show that glutarate, a metabolite derived from tryptophan catabolism, has the ability to shape anti-tumour T cell responses by modulating pyruvate handling and alpha-ketoglutarate-dependent dioxygenases.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

A bedside-to-bench analysis identifies single-chain variable fragment linker length as an important component of chimeric antigen receptor (CAR) structure and suggests that, in contrast to CD28-based CAR T cells, tonic signaling can be beneficial for 4-1BB-based CAR T cell function.

DNA hydroxymethylation (5hmC) is typically altered in age-related diseases. Here, the authors show that 5hmC accumulates in gene bodies, partially due to prolonged quiescence, and restricts the magnitude of transcriptional changes with age.

A genome-wide association study of Mycobacterium tuberculosis clinical isolates finds mutations in prpR that alter propionate metabolism and mediate multidrug tolerance.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Here the authors apply synNotch receptors to spatially control differentiation of endothelial and skeletal muscle cells in a multicellular construct on assorted biomaterials.

Cytotoxic response is mediated by delivery of lytic molecules at the effector cell/target cell junction site, termed the immunological synapse. Here the authors find, using single cell biophysical measurements, that the during this process the αLβ2 integrin, LFA-1, helps focus lytic granule release via talin-dependent, pulling force-mediated spatial guidance.

Senescent cells can exert detrimental effects, yet beneficial roles of p16 highly expressing cells have been reported in contexts such as wound healing. Enhancing our understanding of the heterogeneity of senescence in vivo, Gasek et al. identify a distinct and detrimental p21 highly expressing cell population induced upon wound healing.

CELESTA identifies cell types in multiplexed imaging datasets based on the expression profiles of cells and their spatial information.

The structures of both human and yeast mitochondrial ribosomal small subunits undergoing assembly are uncovered.

Host-parasite interactions during the exoerythrocytic stage of Plasmodium infection remains poorly understood. Using dual RNA-Seq, the authors show that human mucosal immunity protein mucin-13 is upregulated during Plasmodium hepatic-stage infection and marks infected cells independent of tested Plasmodium species.

Breathing is controlled automatically but is also conditionally integrated with behavior and emotion in awake animals. Here, authors identify brainstem neurons that are important for controlling awake-state-dependent breathing patterns in mice.

This study reports that nuclear speckle constituents have two expression states in cancer correlating with patient survival and HIF-2α functional programs. HIF-2α mediates nuclear speckle association of key genes activated in renal cancer.

This protocol describes the isolation from brain tissue of extracellular vesicle subpopulations, including microvesicles, exosomes and mitochondria-derived mitovesicles, using a high-resolution (iodixanol) density step gradient. Extracellular vesicle characterization and analysis are also presented.

The alternative splicing regulator MBNL1 is overexpressed in MLL-rearranged leukaemia. Here, the authors show that MBNL1-mediated alternative splicing leads to a specific splicing profile in MLL-rearranged leukaemia and loss or inhibition of MBNL1 impairs leukaemia development in vitro and in vivo.

Epidemiological studies of cardiovascular disease generally, and coronary heart disease specifically, have provided the basis for clinical trials that document the efficacy of risk-factor interventions, and are the basis of preventive cardiology. In this Review, Nathan Wong discusses the evolution of CHD epidemiology from the 1940s to the present, and examines the contributions of large population studies to the field.

Integration of single-cell RNA sequencing with genome-wide association data implicates specific brain cell types in schizophrenia. Gene sets previously associated with schizophrenia implicate the same cell types, which include pyramidal cells and medium spiny neurons.

The authors discovered that proinflammatory senescent myeloid cells may recruit peripheral immune cells in the aged mouse brain. Their findings implicate senescent cell clearance as a strategy to counter aged brain inflammation and cognitive decline.

The functional organization rules of retinal orientation are not fully understood. Here the authors show that orientation detection, a crucial task for visual perception, is organized in the mouse retina along concentric axes, and that this organization develops even in the absence of visual experience or patterned spontaneous activity.

Li et al. identify dynorphin as an endogenous ligand for orphan receptor GPR139 introducing it as a non-canonical member of the opioid receptor family that triggers excitatory signaling to balance the inhibitory effects of opioids.

Accurate cell-type identification is vital for single-cell analysis. Here, the authors develop a computational pipeline called “LungMAP CellRef” for efficient, automated cell-type annotation of normal and disease human and mouse lung single-cell datasets.

Coordinated neuronal activity may mediate memory in hippocampal CA1. Here, the authors use an array of machine-learning classifiers to reveal how higher-order population dynamics and learning-induced spine plasticity are disrupted in amnestic mice.

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

Caloric restriction improves Alzheimer’s Disease outcomes in mice, but this diet not only reduces calories, but imposes a prolonged fast between meals. Here, the authors show this fast is essential to improve Alzheimer’s pathology and cognition.

Mouse models of severe congenital neutropenia using patient-derived mutations in the GFI1 locus are used to determine the mechanisms by which the disease progresses.

The prelimbic region of the prefrontal cortex is involved in goal-directed action. Here the authors investigate the function of the prelimbic pathways projecting along the anterior posterior striatal axis in value based decision making in male mice.

The ATR inhibitor ceralasertib has shown clinical activity in combination with immune-checkpoint inhibitors in several cancer types. Here the authors report the anti-tumor activity and the immunomodulatory changes, dependent on up-regulation of type I interferon pathway, following intermittent ATR inhibition in preclinical cancer models.

The dynamics of antigenic variation in extravascular parasite populations using VSG-seq, a high-throughput sequencing approach for profiling variant surface glycoproteins expressed in populations of Trypanosoma brucei, are explored, showing the role of extravascular spaces in pathogen diversification.

Bacteria often express multiple adhesive proteins (adhesins) for biofilm formation, but it is often unclear whether adhesins have specialized or redundant roles. Here, the authors show that Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.