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Intuitive control of bionic arms has greatly improved over the past years, however, it is still not possible to restore natural sensory feedback. Here, the authors create a biological communication interface for both controlling a prosthesis and supplying sensations associated with the missing limb in rats.

The seasonal vertical migration of copepods in polar oceans can be considered as a dispersal throughout the water column rather than a translocation to depth, according to field sampling of copepods that overwinter in the Central Arctic Ocean.

Circular RNAs are widely expressed in eukaryotic cells but their functions and mechanisms of action are still being elucidated. Here the authors show that circANRILmodulates rRNA maturation and confers protection again atherosclerosis.

In fast proliferating embryonic stem cells (ESC) the DNA damage response is activated by mechanisms that are as yet elusive. Here, Ahuja et al.link the DNA damage response to replication stress in mouse ESCs, caused by a short G1 phase, and propose fork remodelling as maintaining genome stability in embryos.

Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated tumours and lacked information about the phosphoproteome. Here, the authors present a comprehensive HCC proteogenomics and phosphoproteomics study in patient samples from multiple etiologies and stages.

Mitochondrial dysfunction is a contributing factor in Parkinson’s disease. Here the authors carry out a multilayered omics analysis of Parkinson’s disease patient-derived neuronal cells, which reveals a reversible hypometabolism mediated by α-ketoglutarate dehydrogenase deficiency, which is correlated with disease progression in the donating patients.

Despite the described immunostimulatory properties of irradiation, the clinical benefit of radiotherapy-immunotherapy combinations has been modest so far. Here, in murine models of metastatic disease, the authors show that concomitant draining lymph node irradiation (DLN IR) abrogates the beneficial effect of combining radiotherapy with immune checkpoint inhibitors, while adjuvant DLN IR improves regional and distant disease control.

High-resolution spatial proteomics were used to map molecular events during hepatocyte stress in pseudotime across all fibrosis stages, recapitulating known disease progression markers and revealing early peroxisomal activation and late-stage proteotoxic phenotypes.

Analysis of monoclonal antibody responses to the Ebola virus vaccine rVSV-ZEBOV in human volunteers.

Bone marrow-derived cells can rapidly enter the systemic circulation, but how this is achieved is unclear. Grüneboom et al. identify tiny capillaries, termed trans-cortical vessels (TCVs), that connect the bone marrow cavity to the systemic vasculature, and show that the majority of blood in long bones passes through TCVs.

Using genetic approaches and transcriptional profiling, Kallies and colleagues reveal a common program of effector CD8⁺ T cell differentiation that is regulated by the cooperation of IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet.

Obesity is commonly accompanied by inflammatory responses in white adipose tissues. Chavakis and colleagues identify a vicious cycle involving α₄ integrins and the adhesion molecule VCAM-1 that promotes inflammatory macrophage–adipocyte interactions and suppresses beige adipogenesis.

Histone deacetylases (HDACs) are crucial regulators of cell identity. Ellmeier and colleagues show that HDAC1 and HDAC2 maintain CD4⁺ T cell lineage integrity by repressing Runx-CBFβ complexes in T_H1 cells but not in T_H2 cells.

Regulatory B (Breg) cells suppress excessive inflammation primary via the production of interleukin 10 (IL-10). Here the authors show that the function and homeostasis of mouse and human IL-10⁺ Breg cells are negatively regulated by the cell surface receptor, SLAMF5, to impact experimental autoimmunity, thereby hinting SLAMF5 as a potential target for immunotherapy.

Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

Working with cancer genomes from multiple projects can increase investigative power, but quality of sequences can vary. Here, the authors present a framework for comparing whole genome sequencing quality to help researchers guide downstream analyses and exclude poor quality samples.

Metabolic processes may be different in immune cells between neonates and adults. Here the authors measure metabolic changes in human monocytes from different aged donors and find enhanced oxidative phosphorylation fueling myeloid differentiation in neonates which contrasts glycolytic responses in early childhood and more effective inflammatory response.

Oncogene induced senescence protects cells from unrestricted growth and cancer. Here, the authors show that PAK4 overrides this senescence in breast cancer cells through phosphorylation of RELB, thereby inhibiting transcription of the senescence regulator C/EBPβ.

Findings from the TUXEDO-1 trial demonstrate efficacy of the antibody–drug conjugate trastuzumab deruxtecan for treatment of brain metastases in patients with HER2-positive breast cancer.

The adhesion receptor CD2 plays an important role in the full activation of T cells. Dustin and colleagues show that CD2 occupies a region in the periphery of the immunological synapse where it amplifies cognate antigen signals, whereas the presence of PD-1 disrupts this effect.

The X-ray crystal structure of the potassium channel TASK-1 reveals the presence of an X-gate, which traps small-molecule inhibitors in the intramembrane vestibule and explains their low washout rates from the channel.

T cell responses start with antigen-induced rapid cell divisions, and end by division cessation after pathogen clearance. Here, the authors use single-cell fate mapping and nucleoside analogue labelling to show that T central memory precursors proliferate slower than effector subsets and rely on antigenic rather than inflammatory stimuli to maintain their cell cycle speed.

Obesity is associated with altered N-acylethanolamine levels (NAE). Here the authors show that deletion of the gene encoding N-acylphosphatidylethanolamine phospholipase D, a key enzyme for NAE synthesis, in intestinal cells of mice leads to the development of obesity and hepatic steatosis via a mechanism involving the gut-brain axis.

Analyses of primary and relapse samples of embryonal tumours with multilayered rosettes provide insights into the molecular mechanisms that underlie the development and opportunities for the treatment of this deadly disease.

Recurrent glioblastomas (rGBM) have dismal outcomes, but long-term survival has been observed in subsets of patients after immunotherapy. Here the authors report a positive association between low tumor mutation burden, inflammatory gene signatures, and survival after immunotherapy in rGBM patients.

Here, the authors characterize the antibody response from vaccinated (Pfizer BNT-162b2), infected and uninfected individuals against emerging variants of concern of SARS-CoV-2, finding reduced neutralization of a South African isolate. High IgG titers in the saliva of vaccinees suggest that transmission may be reduced.

Serology is an important way to monitor SARS-CoV-2 infection in the population and support vaccine development. Here the authors develop a multiplex immunoassay including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses with high specificity and sensitivity.

Matthias Mann describes a 1992 paper by Donald Hunt and colleagues that revolutionized the use of mass spectrometry in molecular biology.

The authors perform parallel transcriptome sequencing, tRNA qPCR array, ribosome profiling and mass spectrometry across five stages of mouse neocortex development to model the dynamic transcriptome-to-proteome transition, discovering a critical prenatal window during which translational control is predominant.

Here, the authors show that IFNγ binding to heparan sulfate is a mechanism to restrain IFNγ at the site of production, thereby preventing high systemic levels of this cytokine and associated immunopathology.

Medin promotes the formation of vascular aggregates with amyloid-β in mouse models and in human patients with Alzheimer’s disease, and is associated with vascular defects and cognitive decline.

Perez-Shibayama et al. report that BMP4 signaling is downregulated in autoimmune myocarditis. Restoring BMP4 levels with antibodies that neutralize the BMP inhibitors gremlin-1 and gremlin-2 can ameliorate cardiac inflammation and improve function in mouse models.

Fanconi anemia proteins are required for repair of DNA interstrand crosslinks. Here, the authors show that these proteins are also recruited to DNA double-strand breaks to promote repair by homologous recombination.

Remotely sensed NDVI data and contemporary field data from 84 grasslands on 6 continents show increasing divergence in aboveground plant biomass between sites in different bioclimatic regions.

Methods to study anti-cancer drugs cytotoxicity are often low throughput and rely on population average. Here the authors present an automated image-based cytometry method to quantify multiple cytotoxicity parameters in single cells, and use it to study the effect of PARP inhibitors in cancer cells.

It has been increasingly recognised that tumours are not made up of a homogeneous population of cells. Here, the authors show heterogeneous expression of five protein markers in renal cell cancer and demonstrate that the progression of the tumour does not influence the degree of heterogeneity in the tumour.

Stable epigenetic changes indicate the existence of an obesogenic memory in mouse adipocytes that primes cells for pathological responses in an obesogenic environment and potentially contributes to the problematic ‘yo-yo’ effect often seen with dieting.

A microwell chip facilitates the single-cell characterization of the differentiation of aggregates of human induced pluripotent stem cells into pancreatic duct-like organoids and the discovery of secreted markers of pancreatic carcinogenesis.

Water availability is a major control of vegetation dynamics and terrestrial carbon cycling. Here, the authors show that vegetation sensitivity to soil moisture has been increasing in the last 36 years, especially in (semi)arid areas, and that state-of-the-art land surface models fail to capture this trend.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

The nasal commensal bacterium Staphylococcus lugdunensis produces a novel cyclic peptide antibiotic, lugdunin, that inhibits colonization by S. aureus in animal models and is associated with a significantly reduced S. aureus carriage rate in humans, suggesting that human commensal bacteria could be a valuable resource for the discovery of new antibiotics.

Blocking alternative activation of p38 in tumor-infiltrating CD4⁺ T cells reduces proinflammatory cytokine production and inhibits pancreatic cancer growth in mice.

Type 2 diabetes (T2D) is characterized by hyperglycemia caused by insufficient insulin release from pancreatic islets, often in combination with insulin resistance. Here the authors present an epigenetic case-control study in human pancreatic islets revealing changes that contribute to type 2 diabetes development, e.g., epigenetic downregulation of RHOT1.

The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation is located near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here the authors assessed M305L actin in vivo, in vitro, and in silico to characterize emergent pathological properties and define the mechanistic basis of disease.

Using a composite bioinformatics approach, the DNA:DNA:RNA triplex-forming lncRNAs HIF1α-AS1 was identified in human endothelial cells which recruits an epigenetic silencing complex to limit expression of triplex target genes.

This study describes sensing of circulating cell-free DNA after stroke as the mechanism leading to recurrent ischemic events.