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Stojanov et al. updated and internally validated a prediction model for the occurrence of post-operative shoulder stiffness following primary arthroscopic rotator cuff repair in Switzerland. Their findings support the development of further prediction models for an evidence-based and individualized decision-making in orthopedics.

JAK inhibitors display very good clinical responses in patients with myeloproliferative neoplasms, irrespective of JAK2 mutational status. Here, the authors discover that JAK inhibitors exert their anti-tumorigenic effects by targeting the bone marrow stroma and non-malignant hematopoietic cells instead of the oncogenic signaling in myeloproliferative neoplasms.

Species-specific gamete recognition is needed to maintain species boundaries. Here, Müller et al. show that ARTUMES regulates pollen tube recognition between different Arabidopsisspecies, representing the first gene known to exclusively influence inter- but not intraspecific gamete interaction in plants.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but seems to be largely redundant physiologically.

varVAMP is open-source software for designing primers for tiled-amplicon sequencing and qPCR. It simplifies primer design for viral pathogens with high genomic variability by including sequence variations into primer sequences.

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.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Authors present both preclinical data in mice and clinical data from humans in support of the hypothesis that stress negatively affects bone growth and repair. These effects are mediated by neutrophil-derived catecholamines inhibiting cartilage-to-bone transition via β2-adrenoceptor signaling in chondrocytes.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

COVID-19, similarly to systemic autoimmune diseases, is characterised by the presence of autoantibodies. Authors show here that the abundance and network signature of autoantibodies targeting G protein-coupled receptors and RAS-related proteins are altered in COVID-19 patients, and the level of disruption marks clinical severity.

Elucidating specific effects of protein kinase Akt isoforms remains challenging. Here, the authors establish an Akt isoform-dependent cellular model system and use it, together with X-ray crystallography and structure-based ligand design, to develop isoform-selective covalent-allosteric Akt inhibitors

Biomedical image analysis challenges have increased in the last ten years, but common practices have not been established yet. Here the authors analyze 150 recent challenges and demonstrate that outcome varies based on the metrics used and that limited information reporting hampers reproducibility.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Pertussis toxin is used extensively for perturbing Gαi/o pathways in the study of physiology and disease, but an equivalent inhibitor of Gαq signalling is not currently available to the research community. Here the authors characterize FR900359 as a specific Gq inhibitor and demonstrate its utility to dissect GPCR signalling and its potential to inhibit melanoma cells.

Combining the kinase inhibitor sorafenib with allogeneic stem cell transplantation boosts immune responses against a subtype of acute myelogenous leukemia, suggesting potential clinical benefit.

In Alzheimer’s disease, neurons are considered the sole source of amyloid-β (Aβ) peptides that form plaques. Here the authors show that oligodendrocytes, the myelinating glial cells of the brain, also contribute to Aβ plaque burden alongside neurons.

Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.

Understanding degradation mechanisms in perovskite solar cells is key to their development. Now, Guo et al. show a greater degradation of the perovskite structure and morphology for devices operated under vacuum than under nitrogen.

This study reports the X-ray structure of the α_1B-adrenergic G protein-coupled receptor bound to an inverse agonist, and unveils key determinants of subtype-selective ligand binding that may help the design of aminergic drugs with fewer side-effects.

Nucleosomes form arrays with even spacing between them in virtually all eukaryotes; however, their biogenesis is incompletely understood. Here the authors show that nucleosome density and DNA sequence along with the Ino80 chromatin remodeling complex play a role in nucleosome array formation in yeast and that the transcriptional machinery disrupts evenly-spaced nucleosomes.

The insulin inhibitory receptor (inceptor) is identified as a negative regulator of insulin and IGF1 signalling that could be targeted for β-cell regeneration in treatments for diabetes.

Single-cell analysis reveals how anti-hypertensive drugs affect the risk of severe disease in patients with COVID-19 who have hypertension.

Frank Rosenbauer and colleagues show that alternative functional programs of hematopoietic stem cells are governed by gradual differences in the cellular DNA methylation level.

In a phase I/II dose-escalation clinical trial, the mRNA COVID-19 vaccine BNT162b1 elicits specific T cell and antibody responses that suggest it has protective potential.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4⁺ and CD8⁺ T-cell immunity.

Bacteria such as Neisseria gonorrhoeaeuse filamentous appendages known as pili to move on surfaces. Here, using a combined theoretical and experimental approach, the authors show that pili are coordinated through a tug-of-war mechanism that provides directional persistence.

It is unclear whether SARS-CoV-2 immunity decreases transmission through reduction in contagiousness of cases or susceptibility of contacts. Here, the authors use testing and contact data from Geneva, Switzerland and find that increased protection of contacts was the main driver of reduced transmission.

In a phase-I/II trial in healthy adults, the BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells against SARS-CoV-2 epitopes that are conserved in a wide range of currently circulating variants.

Metrics Reloaded is a comprehensive framework for guiding researchers in the problem-aware selection of metrics for common tasks in biomedical image analysis.

Inducible nitric oxide (NO) synthase (iNOS) is essential in the response to mycobacterial infection, yet NOS signalling can occur through NO-dependent or NO-independent pathways. Here the authors show macrophage Gch1 and tetrahydrobiopterin mediate NO-independent control of Mycobacterial infection.

Walle & Bajaj et al. assess the frequency of cytokine release syndrome upon COVID-19 vaccination in patients with cancer receiving immune-checkpoint inhibitors and find that while elevated cytokines levels are common, they do not manifest in detectable CRS.

Autoantibodies are implicated in autoimmunity, but may also be present in healthy individuals. Here the authors find that the autoantibody specificity signatures against various G protein-coupled receptors are associated with multiple parameters, including disease states, to imply a physiological function in maintaining immune homeostasis.

Kaminski et al. demonstrate that combined expression of the transcription factors Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells.

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.

The corvid songbird family comprises crows, jays, magpies and other close relatives. Veit and Nieder investigate neuronal processing underlying executive control in crows and identify single neurons that encode behavioural rules in an abstract fashion and that predict the crows’ decisions.