Search

Exercise promotes recovery after stroke, but the underlying mechanisms are unclear. Here, the authors show that regulatory T cells enable exercise-induced repair by reducing neuronal hyperexcitability via interleukin-10, linking immunity to functional regeneration.

Here the authors provide a comprehensive transcriptomic dataset of human primary microglia for Alzheimer’s disease and healthy aging. They identify dysregulation of immune-related microglial functions as a hallmark of disease.

Understanding the regenerative capacity of the adult mammalian heart and the cell types involved is essential for developing therapies for cardiac repair.

Advances in the application of microfluidics technology to biological assays using the model organism Caenorhabditis elegans help to automate otherwise time-consuming experiments.

Genomic surveillance has been important for tracking the evolution and spread of SARS-CoV-2. Here, the authors analyse ~300,000 SARS-CoV-2 genomes from two years of sequencing in the Latin America and Caribbean regions and describe the emergence and spread of different lineages over time.

New insights into the actions of the hormone glucagon are provided by a recent study in rodents, which shows that glucagon can suppress hepatic glucose production by acting through the mediobasal hypothalamic region of the brain. This central regulatory mechanism is impaired in rats fed a high-fat diet, suggesting that hypothalamic glucagon resistance may be relevant to the hyperglycemia observed in obesity, diabetes or both (pages 766–772).

An antisense RNA may contribute to Alzheimer's disease by upregulating β-secretase (pages 723–730).

Three studies implicate Kindlin-3, a molecule that mediates signaling through integrins, in a rare disorder characterized by spontaneous bleeding and susceptibility to infection (pages 300–305, 306–312 and 313–318).

New findings show that a subpopulation of mucosal RORγt⁺ cells expresses natural killer cell receptors and produces interleukin 22. These innate immune cells may be pivotal in maintaining mucosal homeostasis.

MISO (MultI-modal Spatial Omics) integrates two or more spatial omics modalities, despite differences in data quality and spatial resolution for improved feature extraction and clustering to reveal biologically meaningful tissue organization.

The role of the transcription factor c-Maf varies in different CD4⁺ T cell subsets and can be associated with either pro-inflammatory activity or anti-inflammatory activity, depending on the cell context.

Autoimmunity develops when one's own immune cells and pathogenic antibodies react against the body, causing inflammation, degeneration, tissue destruction and even organ failure. But autoimmunity mediators can also evoke other pathological side effects, and individual factors can worsen the morbidity of the people suffering from autoimmune disorders, adding another level of complexity to these diseases. In 'Bedside to Bench', Mark Anderson and Michael Waterfield peruse a potential link between immunodeficiency and autoimmunity. Autoantibodies against cytokines involved in tackling Candida albicans infection may underlie the trait of increased susceptibility to yeast observed in people with such autoantibodies. In 'Bench to Bedside', Daniel Cua and Jonathan Sherlock discuss how the immune response induced by gut microbiota may be responsible for autoimmune attacks at distant sites, such as the joints.

A new study presents a protocol to differentiate human induced pluripotent stem cells (iPSCs) into microglia that closely resemble their in vivo counterparts. These cells offer an exciting new tool for learning more about the role of microglia in disease.

A remote, downstream event in the pathology of muscular dystrophy may have a key role in the disease (pages 325–330). It seems that induction of nitric oxide synthase causes calcium to leak inside the cell through ryanodine receptors. The findings provide new options for therapeutic interventions.

Combined population activity is usually used to control neural prosthetics. A recent study in Nature finds that a single primary motor cortex neuron can control the artificial stimulation of paralyzed wrist muscles to move a computer cursor.

The biology of RNA interference has greatly facilitated analysis of loss-of-function phenotypes, but correlating these phenotypes with small-molecule inhibition profiles is not always straightforward. We examine the rationale of comparing RNA interference to pharmacological intervention in chemical biology.

Collapsing glomerulopathy, the classic kidney lesion in HIV-associated nephropathy, is characterized by the closure of glomerular capillary loops and epithelial cell proliferation. A new study shows that upregulation of TERT, the reverse transcriptase component of telomerase, in podocytes, the key filtration cells in the kidney, plays a major part in the development of this condition by activating Wnt signaling (pages 111–119).

γ-secretase inhibitors inhibit Notch, a transmembrane receptor that drives many cases of T cell acute lymphoblastic leukemia—but there are safety concerns with such drugs. Combining these inhibitors with glucocorticoids could provide a more effective and safer approach (pages 50–58).

In the inherited anemia β-thalassemia, diseased red blood cell precursors release a blood-borne signal that promotes excessive intestinal iron absorption, predisposing affected individuals to multiorgan damage (pages 1096–1101).

Noise-induced hearing loss is caused primarily by damage to auditory hair cells; however, humans are unable to regenerate damaged hair cells, necessitating the development of new therapeutic strategies to protect auditory hair cells. A new study suggests that the use of phosphodiesterase 5 (PDE5) inhibitors may provide a protective therapeutic route for hearing loss (pages 252–259).

Women with pre-eclampsia, a potentially deadly complication of pregnancy, produce agonistic autoantibodies against angiotensin receptor-1, a transmembrane protein that regulates blood pressure. Findings in mice suggest how these antibodies might help trigger the condition (pages 855–862).

Pancreatic acinar cells have been reprogrammed in vivo into insulin-expressing cells by adenoviral delivery of three transcription factors.

Fibrosis is omnipresent and contributes to a substantial proportion of all natural deaths. A recent study (pages 1262–1270) provides evidence that the mysterious perivascular cell, also known as the pericyte, is the cell type responsible for fibrotic disease in skin and skeletal muscle.

A new study identifies recurrent somatic duplications of a NOTCH1-driven enhancer of MYC in human T cell leukemia. This enhancer is required for both normal and malignant T cell development.

Two studies describe progress in designing nanopores capable of detecting single protein molecules.

Naive T cells can spend hours 'sampling' dendritic cells before making a stable conjugate with a single dendritic cell. It is the antigen 'dose' that determines how long this process takes.

A relatively obscure immune cell, the eosinophil, has a dramatic way of defending against pathogens. It rapidly ejects mitochondrial DNA, ensnaring bacteria and hastening their demise (pages 949–953).

The mechanisms underlying adaptive response to the stress elicited by radiotherapy in glioma cells remains unclear. Here, the authors show that therapeutic ionizing radiation induces rapid genome-wide chromatin reorganization to facilitate P-TEFb-mediated nascent transcriptional induction, which could be targeted to sensitize radiotherapy response in glioma.

A key regulator of the balance of signals that activate effector mechanisms versus those that restrain them, β-arrestin 2 mediates the inhibition of natural killer cell cytotoxicity.

The blood-brain barrier constitutes a major obstacle to effective treatment of diseases affecting the central nervous system. A new strategy to target specifically the endothelium of diseased brain may allow the development of more effective gene-based therapies (pages 1215–1218).

The intrinsic stability of mRNA is important in the regulation of gene expression. New data show that the intrinsic stability of tumor necrosis factor–induced mRNA transcripts strongly influences the coordinated expression of genes that promote distinct phases of the inflammatory response.

The quest to improve influenza vaccines is aided by research into the immune response that they generate. Two recent studies have focused their attention on the specificities of antibodies induced after vaccination with conventional inactivated influenza vaccines.

A mouse model of Joubert syndrome helps identify a crucial role for Wnt signaling in early cerebellar proliferation and midline fusion (pages 726–731). Reduced activity of this pathway causes cerebellar hypoplasia reminiscent of the cerebellar malformation observed in humans with Joubert syndrome.

Two receptors have now been identified for the virus behind severe hand, foot and mouth disease (pages 794–797 and 798–801).

A molecular pathway requiring vitamin B3 increases the production of neutrophils (pages 151–158). These findings could lead to new ways to treat neutropenias, diseases involving low neutrophil counts.

Leaders gathered at the US National Institutes of Health in November 2014 to discuss recent advances and emerging research areas in aspects of maternal-fetal immunity that may affect fetal development and pregnancy success.

Contemporary M1 strains of Streptococcus pyogenes have acquired a DNase gene that improves the virulence of the bacterium, but its expression is repressed by the CovRS regulatory system. Walker et al. report that the bacteria are under selective pressure to mutate the covRS locus to maintain DNase expression for invasive infection (pages 982–986).

IFN-γ is a cytokine that is critical for defense against intracellular bacterial pathogens. New work provides evidence that the recognition of bacterial flagellin by the NLRC4 inflammasome in splenic dendritic cells triggers rapid release of IL-18, which leads to IFN-γ production by memory CD8⁺ T cells.

Analyses of population-level variation in gene and enhancer expression in the human brain characterize the gene–enhancer regulome and the regulatory mechanisms of transcribed enhancers in neuropsychiatric diseases.

Ten significantly active new (R)-transaminases, still very rare enzymes, were found among 21 designed variants obtained from nothing more than existing transaminase structures and alignment of pertinent fingerprints of annotated sequences.

The S6K1 kinase lies downstream of a signaling network crucial for muscle hypertrophy. It now seems that S6K1 also interacts with another kinase—AMPK—to integrate muscle-cell growth with metabolic regulation.

The medial entorhinal cortex contains spatially selective grid cells, whose lattice-like firing patterns are proposed to support path-integration-based navigation. However, direct behavioral evidence has been lacking. Gil et al. disrupt grid cells in a targeted manner, establishing a clear link between grid cell codes and navigation.

The sensing of viable pathogens by the receptor TLR8 on human monocytes provides key signals that initiate the differentiation of naive CD4⁺ T cells into follicular helper T cells. Targeting TLR8 might represent a novel approach for improving immunity following vaccination.

Neutralization breadth is thought to be an important feature of an effective vaccine against HIV-1. A study in one individual has now identified the specific viral variant that engaged the necessary antibody precursor, as well as the viral immunotypes that drove neutralization breadth, improving understanding of how to mimic this process with a vaccine.

Polygenic risk scores are nearing a level of differentiation required for their clinical utility in risk prediction in populations with high-risk rare pathogenic genetic variants.

How does the brain evaluate whether the benefits of a decision outweigh the costs? A study now reveals that neurons in the anterior cingulate cortex encode costs and benefits, and altering brain activity here biases choices away from negative outcomes. These results link anterior cingulate cortex with the regulation of emotional states.

Decisions between two alternatives have been extensively studied and modeled. A study now reports that during choices among several options, the responses of neurons in the lateral intraparietal area are still well described by the integration-to-bound model, supporting the general applicability of this computational framework.