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Distinct signatures of the airway microbiota associate with acute respiratory distress syndrome, hospital-acquired pneumonia and prolonged mechanical ventilation, and may help to inform clinical outcomes in critically ill patients.

Astrocytes adopt diverse states in response to brain injuries. Here, the authors develop a platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO (tissue-digital microfluidic isolation of single cells for -Omics) to uncover the spatial boundaries of molecularly distinct reactive astrocyte populations in stroke.

An individual’s pattern of resting state brain connectivity, as measured with fMRI, has been shown to predict cognitive and behavioral traits. Here, the authors show that different traits are predicted by different time-scales of resting state activity (dynamic vs. static).

This study reveals an important chondrocytic progenitor population for maintenance of adult articular cartilage marked by Gremlin 1. Loss of these progenitors causes osteoarthritis and suggests methods to sustain them may be effective future targets for management of osteoarthritis.

In this Analysis, Liu et al. benchmark more than 200 pairwise statistics for functional brain connectivity in tasks such as hub mapping, distance relationships, structure–function coupling and behavior prediction, revealing varying effectiveness for specific neurophysiological applications.

Classical physics says it should be impossible to generate a string of truly random numbers using any process that isn't completely random. However, Gallego et al. show that using quantum non-locality it should be possible to amplify the indeterminism of an imperfectly random source to do exactly this.

Filaments of keratin — stable protein polymers best known for their function in hair and nails — provide a memory of cell polarity at a crucial stage in early mouse development.

Extinctions of megafauna can have cascading effects on their ecological communities. Here, Lim et al. investigate the relationships of historical and current mammalian frugivore body size with palm fruit size, then project how further mammal extinctions are likely to affect palm communities.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Iron homoeostasis is tightly orchestrated to avoid toxic iron overload. Here Lim and colleagues show that iron excess activates Nrf2 via mitochondrial reactive oxygen species, enhancing the expression of Bmp6 in liver sinusoidal endothelial cells, which in turn promotes hepcidin expression by hepatocytes, decreasing systemic iron levels.

Large-scale multivariate analyses across populations of European ancestry identify risk loci for the metabolic syndrome, improving polygenic prediction models and highlighting associations with diverse traits beyond cardiometabolic diseases.

Cassava mosaic disease is caused by geminiviruses and suppresses cassava yields throughout the tropics. Here, the authors show that mutations in MePOLD1, encoding DNA polymerase δ subunit 1, co-segregate with CMD2, the major source of genetic resistance for this disease.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Here, the authors identify a novel regulator of autophagy, skeletal muscle mass and integrity named MYTHO. Silencing MYTHO protects against muscle atrophy in a wide range of acute catabolic conditions, while prolonged silencing causes a severe myopathy.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

The Plk1 kinase is a major regulator of mitosis that is often overexpressed in human cancers. Studies on phosphopeptide inhibitors specific to the polo-box domain of Plk1 reveal the determinants for specificity and may provide insight into the development of new therapeutics targeting protein-protein interactions.

The authors show that leucine-rich repeat kinase 2 (Lrrk2) binds protein kinase A (PKA) regulatory subunit IIβ to decrease PKA activity in striatal projection neurons (SPNs). Lrrk2 regulation of PKA prevents its synaptic translocation, altering synaptogenesis and transmission in developing SPNs. A Parkinson's disease–associated mutant of Lrrk2 prevented its interaction with PKARIIβ.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Johannes Krause et al. synthesized seagrass carbon stock data from 2700+ soil cores to find that they vary by plant functional group and coastal setting, indicating where conservation efforts would most effectively avoid emissions from seagrass loss

The MAPK pathway is an important therapeutic target in pancreatic ductal adenocarcinoma (PDAC), but success is limited by pathway reactivation, which drives resistance. Here, the authors investigate the mechanism underlying HER2-reactivation post KRAS-MAPK inhibition, identifying combination of MAPK and HER2 inhibition as a therapeutic strategy.

A study of 36 massive galaxies at redshifts between 5 and 9 from the JWST FRESCO survey finds that galaxy formation of the most massive galaxies is 2–3 times higher than the most efficient galaxies at later epochs.

NADP(H) and NAD(H) are crucial energy molecules in plant metabolism. Here, via the use of circularly permutated fluorescent protein sensors, the authors demonstrate dynamic changes in NADPH and the NADH/NAD⁺ ratio during photosynthesis and photorespiration at the subcellular level in planta.

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

Pollen tube growth involves coordinated energy fluxes between plastids, the cytosol, and mitochondria. Here using ratiometric biosensors, the authors delineate energy flux in growing Arabidopsis pollen tubes by monitoring ATP, NADPH and the NADH/NAD + ratio at the subcellular level.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

The study of the pathophysiology and possible interventions for non-ST-segment elevation myocardial infarction is hindered by the lack of a reproducible pre-clinical model. Here, authors develop an ovine model to reproduce post-ischemic remodeling in non-ST myocardial infarction and reveal distinct complex sugar moieties in cellular membranes and extracellular matrix patterns in infarcted tissue.

Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.

Metal-fluoride-based lithium-ion battery cathodes are typically classified as conversion materials because reconstructive phase transitions are presumed to occur upon lithiation. Metal fluoride lithiation is now shown to be dominated instead by diffusion-controlled displacement mechanisms.

A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Here the authors use the evolutionary model EVcouplings to computationally design highly mutated variants of TEM-1 ß-lactamase, and characterise these designs experimentally.

Many mountain species are threatened by climate change and habitat loss. Here, the authors investigate population declines and range shifts of orchids in an alpine region in NE Italy over 28 years. For most species, population size decreased, while range shifts were idiosyncratic with over half of the species lagging behind climate change.

The Asian Working Group for Sarcopenia updates its consensus on sarcopenia, highlighting the need to extend diagnosis to middle-aged adults and use the World Health Organization’s Integrated Care for Older People to promote muscle health. Multimodal interventions involving exercise and nutrition are recommended to prevent age-related decline in Asian populations.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Glucagon is hormone that signals via a dedicated g-protein coupled receptor, but downstream signaling is poorly understood. Here, Wu et al. uncover liver glucagon signaling using phosphoproteomics and define a role for the vesicle trafficking protein SEC22B in distinct metabolic actions.

Cell morphology is one of the most described phenotypes in biology, yet systematic quantification and classification of morphology remains limited. Here, the authors present a computational approach for cell morphometry and multi-modal analysis based on concepts from metric geometry.