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Viruses such as coxsackievirus B (CVB) have been associated with type I diabetes (T1D) and islet destruction. Here the authors show that Yes-associated protein (YAP) is upregulated in the whole pancreas in T1D and at-risk autoantibody (AAb + ) organ donors and that YAP over-expression enhances CVB replication, islet inflammation and β-cell apoptosis and suggest exocrine-islet-immune interactions as targeted interventions for T1D.

Synthetic receptors are a powerful approach for engineering cell-based therapies that can sense and respond to their environment. Here cytokine receptor domains have been repurposed to develop engineered T cells that can sense and respond to cues associated with cancer or immune dysfunction.

Post-acute sequelae of SARS-CoV-2 infection affecting the cardiovascular system have been reported, but evidence in young people is limited. Here, the authors quantify the incidence of a range of outcomes in children and adolescents using electronic health records from the United States.

Controlling nanoscale colloidal crystallization is not straightforward. Such control is now achieved by leveraging a metastable liquid phase of charged nanocrystals.

Immune checkpoint blockade activates T cell immunity by reprogramming the STAT3 and STAT5 transcriptional pathways in dendritic cells, and STAT3 degradation is effective for treating tumours of multiple cancer types in mouse models.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

Mosaic copy number gains arising from an extra parentally derived chromosome 1q allele are found in brain tissue from five individuals with focal epilepsy. These copy number gains are strongly enriched in astrocytes, indicating somatic rescue in other tissues during development.

Post-acute sequelae of SARS-CoV-2 infection (PASC) have been shown to vary by race/ethnicity, but evidence is limited for children and adolescents. Here, the authors investigate variations in PASC by race/ethnicity in those aged under 21 years using electronic health record data from the United States.

The COVID-19 pandemic has raised concerns about increased neuropsychiatric conditions in children and youths, with potential links to SARS-CoV-2 infection. Here, the authors analyze EHR data from 25 institutions, showing that COVID-19 positive children and youths have a modestly increased risk of developing neuropsychiatric conditions, such as anxiety, depression, and ADHD, compared to those who tested negative.

Mucosal melanoma (MM) is a cancer with poor prognosis derived from mucosal melanocytes. Here, the authors implement a combination of genetic changes that occur in MM patients in a zebrafish model, revealing the potential MM cell of origin and showing that patient and zebrafish MMs share a gene signature that is more metastatic and immune-evasive.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

Characterising the response to SARS-CoV-2 post vaccination is critical in the appraisement of the induced immune response, performance and protective potential. Here the authors present data from a phase 4 clinical trial in autoimmune rheumatic disease patients 6 months post second dose of Sinovac-CoronaVac inactivated vaccine that show a marked reduction in antibody particularly in males or those under treatment with immune targeting therapies but saw no rise in COVID-19 disease.

Here, the authors report the development of a genetic platform for mRNA-LNP vaccines that encodes the two major influenza virus glycoprotein genes into a single mRNA molecule. They show that this approach is generalizable to diverse influenza virus strains and is immunogenic and protective in mouse and ferret models of influenza disease.

Here they show that ATF7IP/SETDB1-mediated epigenetic programming governs T lymphoid progenitor trafficking and differentiation, providing important insights into the pathogenesis of human T lymphoid diseases.

Although vaccination drops COVID-19 mortality in older adults, post-vaccine fatal COVID-19 in nursing home outbreaks was linked to Delta, Gamma and Mu variants, persistently detected in aerosols. Mortality was predicted by IFNB1 or age, ORF7a and ACE2 mRNAs.

CRISPR-CasRx effectively reduces ALS- and FTD-causing C9orf72 sense and antisense repeat derived RNAs and proteins in cell lines, patient iPSC-neurons and two independent mouse models of C9orf72 repeat expansion.

Understanding gene expression involves studying the transcriptional effects of perturbations. Here, the authors monitor RNA transcripts after applying 83 epigenetic compounds, identifying responsive genes enriched with chromatin marks and regulators in line with their mechanisms of action.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

We can often ‘fill in’ missing or occluded sounds from a speech signal—an effect known as phoneme restoration. Leonard et al. found a real-time restoration of the missing sounds in the superior temporal auditory cortex in humans. Interestingly, neural activity in frontal regions prior to the stimulus can predict the word that the participant would later hear.

Here the authors present cyclic peptide-based AND-gated nanosensors to detect concomitant protease activity. These nanosensors improve detection specificity during immune checkpoint blockade therapy compared with off-tumour anti-viral immunity in a mouse model.

Key cardiac transcription factors require precise regulation for heart development and function. Here, the authors show that the miR-200 family controls cardiomyocyte differentiation and maturation, with its loss causing structural heart defects.

Biologics can be specifically delivered to T cells by genetically engineering cells to secrete extracellular vesicles that actively load protein cargo and that display high-affinity T-cell-targeting domains and fusogenic glycoproteins.

Bhattacharya and colleagues assess the impact of antigenic imprinting using samples from mRNA vaccinated or unvaccinated individuals primarily infected with the SARS-CoV-2 variants Delta and Omicron BA.1.

Precise control of charge and spin states in quantum dots is often challenging. Here, the authors show systematic manipulation of the electron occupation in graphene nanoribbons laying on MgO.

Here, we report the mutation rate of SARS-CoV-2, the virus responsible for COVID-19. We find that the secondary structure of the RNA-encoded viral genome is crucial to modulating the mutation rate and evolves under strong selective constraints.

In a post-approval study including more than 17,000 patients on the safety of pulsed field ablation, a new method for treatment of atrial fibrillation, the procedure was found to have a low rate of adverse events but was associated with some unexpected rare complications that will need further study.

Understanding principles that govern protein association with extracellular vesicles should expand their potential as a therapeutic modality. Here, the authors show that by localizing proteins to the plasma membrane and lipid rafts, a variety of proteins can be preferentially loaded into extracellular vesicles.

Macrophage activation is tightly regulated to maintain immune homeostasis, yet activation is also heterogeneous. Here, the authors show that macrophages coordinate activation by partitioning into two phenotypes that can nonlinearly amplify collective inflammatory cytokine production as a function of cell density.

Recent studies show that targeting CXCL12 can improve the effect of radiotherapy (RT) in preclinical models of glioblastoma (GBM). Here, the authors report the safety and preliminary efficacy of a phase I/II clinical trial investigating an L-RNA aptamer-based CXCL12 inhibitor (NOX-A12) in combination with RT in patients with newly-diagnosed GBM.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

In this study, the authors report the small molecule inhibitor EDP-235 as a potent inhibitor of SARS-CoV-2 and show that it is effective against a range of variants and other coronaviruses and that it suppresses virus replication, reduces lung damage, and prevents transmission in small animal models.

Lazarevic and colleagues show that the transcription factor EGR2 controls a transcriptional program specific to pathogenic T_H17 cells in the CNS.

The targeted development of proteome-wide selective covalent probes remains a challenge. Here, the authors show the exploration of the natural product Sulphostin as a starting point for dipeptidyl peptidase 8 and 9 inhibitor development.