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Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Mathematical tools can be used to help identify pathological features from images of diseased lungs. Here, the authors used mathematical tools combined with high resolution multiplex imaging mass cytometry to show an association between immature neutrophils, CD8 T cells and proliferating alveolar epithelial cells in areas of maximal alveolar damage in COVID-19 lungs.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Acute stress can help individuals to respond to challenging events, although chronic stress leads to maladaptive changes. Here, the authors present a multi omic analysis profiling acute stress-induced changes in the mouse hippocampus, providing a resource for the scientific community.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

There is increasing evidence that epigenetic mechanisms contribute to therapeutic resistance in cancer. Here the authors study AML patient samples and a mouse model of non-genetic resistance and find that transcriptional plasticity drives stable epigenetic resistance, and identify regulators of enhancer function as important modulators of resistance.

Which contralesional circuits adapt after traumatic brain injury (TBI) is unclear. Here the authors used in vivo imaging, retrograde labeling, rabies tracing, clearing and functional imaging to demonstrate that callosal neurons selectively adapt after TBI in mice.

It is unclear whether fallopian tube epithelium or ovarian surface epithelium is the cell-of-origin of high grade serous ovarian carcinoma (HGSOC). Here the authors report a dualistic origin for HGSOC using genetically engineered mouse models and observe differential chemotherapy sensitivity depending on the cell-of-origin.

The application of all-perovskite tandem photovoltaics is limited by the poor operational stability of the solar cell. Here, the authors report a solar-assisted water-splitting system using an electrochemical flow cell and a tandem solar cell and achieve a solar-to-hydrogen efficiency of 17.8%.

The study demonstrates that the C2 domain-containing protein CaLB1 interacts with and induces phase separation of the ESCRT protein ALIX on autophagosomes. This modulates autophagosome maturation, particularly in response to salt stress, in Arabidopsis.

SpCas9 off-targets are a safety concern. Here the authors report a cleavage rule that governs the on-target and off-target cleavage of increased(/high)-fidelity SpCas9 variants: the variants have differences in fidelity small enough to comprise an optimal variant for each target, irrespective of its cleavability ranking.

The angiopoietins regulate vascular maturation, angiogenesis and lymphangiogenesis via their Tie receptors that were long believed to be endothelium-specific. Here the authors show that angiopoietins activate and control pericyte function through pericyte-expressed Tie2 triggering of Calpain, Akt and FOXO3A signalling cascades.

Filamentous cable bacteria conduct electrical currents over centimeter distances through fibers embedded in their cell envelope. Here, Boschker et al. show that the fibers consist of a conductive core containing nickel proteins that is surrounded by an insulating protein shell.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

CB₂ receptor agonists are developed as potential analgesics or immune-modulatory compounds. Here, the authors characterize the pharmacological properties of widely used CB₂ receptor agonists and antagonists, recommending three that appear most suitable for in vitro and in vivostudies.

Implantation of lung tissue into humanized mice enables in vivo study of the human immune response to pathogens.

LIF is a pleiotropic cytokine that promotes an immunosuppressive microenvironment and has critical functions in embryonic development. Here, the authors show that LIF regulates CD8⁺ T cell tumor infiltration in cancer by repressing CXCL19 and promoting the presence of protumoral macrophages and thatLIF inhibition, via neutralizing antibodies, promotes T cell infiltration and synergizes with immune checkpoint inhbitors resulting in tumor regression and immunological memory.

Ruminococcus gnavus is a mucus-associated gut commensal that can release the sialic acid, 2,7-anhydro-Neu5Ac. Here, the authors identify the pathway for its transportation and metabolism in R. gnavus, and show that this pathway is essential for its spatial localization in vivo.

Mechanotransduction of cells is of interest for a number of reasons but model in vitro systems remain a challenge. Here, the authors report on a hydrogel which changes properties upon near infrared irradiation to create cyclic forces and demonstrate the application of these gels to study mechanotransduction.

Here the authors show that the patterning signals WNT, BMP, and FGF control chromosome segregation fidelity during early lineage specification and neurogenesis, which could provide a rationale for the spatio-temporal distribution of genomic mosaicism during human development.

Increased-fidelity SpCas9 variants have been developed, but often show proportionally reduced activity. Here the authors characterise the on-target activity and off-target propensity of SuperFi-Cas9 in mammalian cells and also see strongly reduced activity but with high fidelity features.

Synthetic nanocages that can adapt the size and shape of their cavity in response to a given guest have potential applications in various areas, including chemical purification. Now a flexible, pseudo-cubic metal–organic cage has been developed that is able to dynamically expand its cavity from 46% to 154% of its initial volume by flipping its cage faces.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

To eliminate transport emissions by 2050, low carbon fuels must rapidly replace fossil fuels. The authors model these technological transitions for each transport mode and evaluate economy-wide tradeoffs of varied levels of transport decarbonization.

How the histone variant H2A.Z controls cell fate remains unclear. Here, the authors reveal that the H2A.Z interacting partner HMG20A plays a key role in regulating transcription during early head and heart development.

Retinal pigment epithelial cells are identified as a local source of insulin in the retina, which is stimulated by phagocytosis of photoreceptor outer segments and starvation and has the potential to influence retinal physiology and disease.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

Thomas, Egan et al. report that hexokinase 2 localizes to the nucleus of leukaemic and normal haematopoietic cells to maintain stemness by interacting with nuclear proteins and modulating chromatin accessibility independently of its kinase activity.

Gangwar et al. describe the cumulative effect of the potentiating CNIH2 and inhibitory γ5 auxiliary subunits on GluA2 AMPA receptor activation and desensitization gating, polyamine block and noncompetitive inhibition by antiepileptic drug perampanel.

Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Here, the authors show that Cdk5 and GSK3β are negative regulators of fast Endophilin-mediated endocytosis (FEME).

PU.1 is a master regulator of myeloid development but its role in disease-relevant neutrophils is not well known. Here, the authors look at primary neutrophils from a human population and find that genetic variants affecting binding of PU.1 are associated with cell count and disease susceptibility.

N-terminal protein acetylation is required for plant viability. Here the authors show that reducing N-terminal acetylation by NatA leads to an increase in global protein turnover that is facilitated by absent masking of a novel N-degron

GPR84 is an important GPCR regulating macrophage function. Here, the authors show the pro-phagocytic function of the GPR84-Gi signaling axis in native macrophages and determine a cryo-EM structure of the GPR84-Gi complex with a synthetic agonist.

A candidate vaccine against SARS-CoV-2 that uses the yellow fever 17D live-virus vector is highly efficacious and displays a favourable safety profile in Syrian hamster, mouse and cynomolgus macaque models.

An inhibitor of NAPE-PLD involved in lipid biosynthesis lowers levels of the endocannabinoid anandamide and other N-acylethanolamines in cells and mouse brain and activates the hypothalamus–pituitary–adrenal axis and impaired fear extinction.

Cytokine therapies have been used to treat cancer but are susceptible to adverse effects owing to the activation of systemic inflammatory pathways. Here the authors avoid this toxicity by developing CD45-targeted IL-12 and IL-15 immunocytokines that are effective in treating tumors in mice when dosed intratumorally.

Lassé et al. show that genes involved in kidney organoid proteomic response to TNFα segregate a subset of individuals with poor outcomes in proteinuric kidney disease, demonstrating the relevance of kidney organoid modeling to human kidney disease.

The functions of specific lipids in autophagosome biogenesis are not entirely clear. Here, the authors show that the ER protein GRAMD1C, a cholesterol transport protein, suppresses autophagy initiation and has roles in mitochondrial cholesterol homeostasis and respiration.

Methods for direct covalent ligation of microorganism surfaces are scarce. Here, the authors developed a rapid electrochemical process for the direct covalent ligation and labelling of the surfaces of virus, bacteria and cells using N-methylluminol, a fully tyrosine-selective protein anchoring group.

B cell malignancies resistant to conventional treatments are potentially sensitive to CAR-T cell immune therapy, but its clinical applicability is limited by immune related adverse effects. Here authors show in a humanized mouse model that blocking IFNγ with the monoclonal antibody emapalumab mitigates the adverse effects of CAR.CD19-T cells without compromising their anti-lymphoma efficacy.

Recreating the structural complexity of meat has been a major challenge in developing alternative proteins. Here, the authors present two injectable metamaterials that mimic the multi-scale properties of fat and muscle, enabling a cost-effective process for injection molding of whole cuts.