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Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Rapid diagnosis and implementation of treatments is crucial in many genetic conditions. Here the authors describe Genome-to-Treatment, a virtual disease management system that can achieve a rapid diagnosis by expedited whole genome sequencing in 13.5 hours and provide guidance to clinicians for possible therapies.

Many diseases are driven by the insufficient expression of critical genes, but few technologies are capable of rescuing these endogenous protein levels. Here, Cao et al. present an RNA-based technology that boosts protein production from endogenous mRNAs by upregulating their translation.

Physical realizations of qubits are often vulnerable to leakage errors, where the system ends up outside the basis used to store quantum information. A leakage removal protocol can suppress the impact of leakage on quantum error-correcting codes.

It is hoped that quantum computers may be faster than classical ones at solving optimization problems. Here the authors implement a quantum optimization algorithm over 23 qubits but find more limited performance when an optimization problem structure does not match the underlying hardware.

The authors developed a computational approach to probe the stability of amyloid fibrils and discover networks of hotspot interactions. Understanding the mechanisms of amyloid folding will help identify novel methods to treat protein (mis)folding diseases.

R-spondins are secreted factors that potentiate Wnt signalling by inhibiting the degradation of Wnt receptors by transmembrane E3 ubiquitin ligases. Zebisch et al.present a panel of crystal structures that reveal how this inhibition occurs.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

A large-scale meta-analysis across eight biobank datasets identifies common genetic variants associated with mosaic loss of the X chromosome in female participants.

This description of the Sphagnum (peat moss) genome includes a newly discovered sex chromosome. Interactions among sex, autosomes and environment show direct effects on Sphagnum growth which influences global carbon sequestration.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

In this alternative approach to quantum computation, the all-electrical operation of two qubits, each encoded in three physical solid-state spin qubits, realizes swap-based universal quantum logic in an extensible physical architecture.

Crystal structures of the σ₂ receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ₂-selective ligands and providing insight into the role of σ₂ in neuropathic pain.

DNA methylation profiles from 26 bat species accurately predicts chronological age, while longevity-related methylation patterns across the genome suggest that bat longevity results from augmented immune response and cancer suppression.

Vicinity of small bodies might be dangerous to the spacecrafts and to their instrumentation. Here the authors show the operational environment of asteroid Bennu, validate its photometric phase function and demonstrate the accelerating rotational rate due to YORP effect using the data acquired during the approach phase of OSIRIS-REx mission.

The SARS-CoV-2 papain-like protease (PLpro) is of interest as an antiviral drug target. Here, the authors synthesize and characterise naphthalene-based inhibitors for PLpro and present the crystal structures of PLpro in its apo state and with the bound inhibitors, which is of interest for further structure-based drug design efforts.

Temozolomide therapy seems to lead to mismatch repair deficiency and hypermutation in gliomas, but not to an increase in response to immunotherapy.

A closed-loop machine learning methodology of optimizing fast-charging protocols for lithium-ion batteries can identify high-lifetime charging protocols accurately and efficiently, considerably reducing the experimental time compared to simpler approaches.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

Foot-and-mouth disease virus (FMDV) capsids are often unstable, thus limiting their use as vaccines. A computational method was used to strengthen protein-protein interfaces and engineer stabilized FMDV capsids, which generated improved antibody responses in vaccinated calves and guinea pigs.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

A manufacturable platform for quantum computing with photons is introduced and a set of monolithically integrated silicon-photonics-based modules is benchmarked, demonstrating dual-rail photonic qubits with performance close to thresholds required for operation.

Adaptation policies can considerably influence the intensity and spatial patterns of sealevel rise-related migration, with managed retreat and setback zones leading to outmigration, while hard protection measures favor migration toward the coast.

Environmental variability is one potential driver of behavioural and cultural diversity in humans and other animals. Here, the authors show that chimpanzee behavioural diversity is higher in habitats that are more seasonal and historically unstable, and in savannah woodland relative to forested sites.

Myeloid cells modulate the immune response within the tumour microenvironment, but the underlying mechanisms remain largely unknown. Here, the authors show that Fcmr – the putative receptor for soluble IgM – is a potent negative regulator of anti-tumour immunity.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Bennu’s surface has experienced continuous changes, mostly induced by its accelerating spin rate, which could have resulted in a collapse of its interior in the past. This scenario is also supported by the heterogeneity of Bennu’s internal mass distribution.

Synaptic activity controls the extinction of conditioned fear. Here the authors discovered a new way that the brain controls memories of fear: a long noncoding RNA called Gas5 that coordinates the activity of RNA granules in the synaptic compartment.

Analysis of fossils of the oldest known caecilian provide insights into the origin and morphological and functional evolution of caecilians.

Stereocilia of the inner ear have graded heights that are thought to be regulated by the myosin-III family members MYO3A and MYO3B. Here the authors identify espin-1 and espin-like (ESPNL) as cargo that differentially influence the functions of both motors to regulate stereocilia length.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Experiments measuring light-evoked responses in postmortem mouse and human retinas are used to quantify decay of photoreceptors following death and optimise conditions for reviving trans-synaptic transmission.

A transcriptome-wide characterization of the molecular pathology of post-traumatic stress disorder (PTSD) postmortem brains provides a comprehensive resource for mechanistic insight and therapeutic development.

Sea-level rise threatens coastal mangroves, with global consequences for these important blue carbon sinks. Here the authors analyse four Holocene sediment cores from islands in Florida Bay and find that mangroves that comprised the South Florida coastline 4–3000 years ago rapidly transitioned to estuarine conditions, despite low rates of sea-level rise, and propose that their demise was driven by high climate variability.

Bennu’s surface presents evidence of a variety of particle sizes, from fine regolith to metre-sized boulders. Its moderate thermal inertia suggests that the boulders are very porous or blanketed by thin dust. Bennu’s boulders exhibit high albedo variations, indicating different origins and/or ages.

Antigen escape represents a potential drawback of chimeric antigen receptor T cell (CAR-T) therapy targeting a single tumor-associated antigen. To reduce the risk of antigen escape, here the authors report the design and characterization of a BAFF ligand CAR-T that can recognize three different receptors (BAFF-R, BCMA and TACI), demonstrating in vitro and in vivo cytotoxicity against multiple B cell cancer models.

Pappalardi and colleagues identify a potent noncovalent DNMT1-selective inhibitor with improved tolerability and efficacy in preclinical AML models compared with clinically validated covalent pan-DNMT inhibitors.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.