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Inhibition of fatty acid biosynthesis re-sensitizes colistin-resistant clinically relevant bacteria in vivo by inducing stress responses and altering membrane composition.

There is concern that ocean acidification will negatively affect the sensory abilities and behaviour of marine fishes. This study shows that negative impacts of elevated CO₂ on fish behaviour are not diminished by transgenerational acclimation.

The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking Aβ fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.

The pathways available for self-assembly are affected by the shape anisotropy of the building blocks, but the details are still unclear. Here, Hsiao et al. show that colloidal discoids self-assemble into metastable states with orientational order when kinetic trapping is incorporated as a design principle.

Rett syndrome (RTT) is caused by mutations in MeCP2. This study describes a new line of knock-in mutant mice that mimics a MeCP2 mutation found in individuals with RTT and recapitulates RTT-like phenotypes, including motor and cognitive impairments. These MeCP2 knock-in mice also have age-dependent abnormalities in audiogenic event-related neuronal information processing.

Turbidity currents are driven by surge dynamics within their frontal cell, with fast surges from behind providing momentum, sustaining flow fronts for <1,000 km, as revealed by ocean-bottom seismometer data documenting their internal speed and structure.

Metastatic prostate cancer can be difficult to biopsy and characterise. Here, the authors use cell-free DNA methylation analysis to illustrate changes in hypermethylation in metastatic disease.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Genetic associations with particular patterns of brain folding may provide insight into brain development and function. Here, the authors identify and replicate 388 genetic associations with brain sulcal morphology across 40,169 UK Biobank MRI scans, revealing insights into the processes guiding cortical development and genetic correlations with neuropsychiatric phenotypes.

Medulloblastomas lacking p53 do not express surface class I major histocompatibility complex (MHC-I) and are resistant to immune rejection. Tumor necrosis factor rescues MHC-I expression and synergizes with immune checkpoint inhibitors to promote rejection.

Analysing the regulatory consequences of mutations and splice variants at large scale in cancer requires efficient computational tools. Here, the authors develop RegTools, a software package that can identify splice-associated variants from large-scale genomics and transcriptomics data with efficiency and flexibility.

Glioma stem cells (GSCs) retain the ability to partially differentiate, but it is unclear how the brain microenvironment may influence this response. Here the authors show that glioblastoma cells infiltrating into the white matter acquire pre-oligodendrocyte-like fate in a process that mimics myelin repair and results in tumour suppression

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Pemphigoid diseases involve autoimmune mediated blistering and immunopathology of the upper dermis. Here, the authors implicate granzyme B in the immunopathology in multiple in vivo models of pemphigoid diseases and utilise a topical granzyme B inhibitor that attenuates disease phenotypes in vivo.

Amyloid-like proteins are central to age-related diseases, such as Alzheimer’s and Parkinson’s. Here, the authors show that transcription errors can produce mutant proteins with enhanced amyloid- and prion-like properties in human cells.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

ACVR1 and H3.1K27M mutations co-occur in diffuse intrinsic pontine glioma. Here, the authors generate a mouse model that recapitulates these genetic lesions and show, using genetic and pharmacological approaches, that the bone morphogenetic protein pathway may be a therapeutic target in these tumours.

Little is known about the genetic landscape of people living in the Nile region prior to the Islamic migrations of the late 1st millennium CE. Here, the authors report genome-wide data for 66 ancient individuals to investigate the genetic ancestry of a Christian Period group from Kulubnarti.

Torpor is a state of reduced metabolism and body temperature that conserves energy when food is scarce. Here the authors show that estrogen-sensitive neurons in the hypothalamus regulate torpor in mice, maintaining torpor in both sexes but initiating torpor and regulating core temperature differentially across sex.

Bathymetric surveys of the submarine Congo Canyon show damming by canyon-flank landslides led to the temporary storage of substantial masses of sediment and organic carbon, interrupting their transport to the deep sea.

Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca²⁺ transport and AMPAR currents.”

Here, the authors describe the global distribution of crAssphage, its presence in Old-World and New-World primates, and its association with gut bacterial communities and dietary factors, providing insights into the origin, evolution and epidemiology of human gut crAssphage.

This report finds that dietary restriction, the most extensively studied anti-aging intervention, can be mimicked by blocking food odour signaling and identifies a neural network of food perception that functions through serotonin and dopamine.

The AAA protein spastin is needed for cell division and organelle transport. Testing spastin constructs with engineered mutations resulted in the identification of a chemical probe to analyze spastin-specific functions in cells.

A study reports the distribution, replication and persistence of SARS-CoV-2 throughout the human body including in the brain at autopsy from acute infection to more than seven months following symptom onset.

Evaluations of the UK’s contact tracing programme have shown that it has had limited impact on COVID-19 control. Here, the authors show that with high levels of reporting and adherence, contact tracing could reduce transmission, but it should not be used as the sole control measure.

Jovanovic et al. show that a gel-based diet can be used as a minimally invasive alternative system for the delivery of small molecules for microglia depletion and inducible Cre recombination in mice.

The European X-ray free-electron laser (EuXFEL) in Hamburg is the first XFEL with a megahertz repetition rate. Here the authors present the 2.9 Å structure of the large membrane protein complex Photosystem I from T. elongatus that was determined at the EuXFEL.

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.

Morphogenesis of tissue sheets is well studied, but mechanisms that shape bulk tissues are unclear. Here, the authors show that mesenchymal cells intercalate in 3D to shape the mouse branchial arch, with cortical forces driving intercalations in a Wnt5a-, Yap/Taz- and Piezo1-dependent manner.

Drug combinations consisting of two cell death-targeting drugs are enriched for antagonism and ‘single-agent dominance’, where the faster-acting drug suppresses the slower-acting drug due to inhibitory crosstalk between cell death pathways.

MCL-1 is an anti-apoptotic BCL-2 family member and is frequently upregulated in cancer, but the mechanism by which it promotes cell survival has been elusive. Opferman and colleagues provide insight into this process by showing that MCL-1 exists in different forms with discrete localizations and functions. MCL-1 variants targeted to the outer mitochondrial membrane antagonize BAX and BAK activation, whereas an N-terminally truncated isoform localizes to the mitochondrial matrix and regulates mitochondrial metabolism.

Variation around colour pattern genes is highly modular in Heliconius butterflies. This modular architecture explains the diversity of colour patterns and provides a flexible mechanism for rapid morphological diversification.

Small-molecule drugs and biologics that alter the microbiome or its interaction with host tissues are poised to change the face of microbiome therapeutics.

A small-molecule enhancer of Toxoplasma gondii invasion inhibits a previously uncharacterized parasite palmitoyl thioesterase, TgPPT1.

Nathan Pankratz, Santhi Ganesh and colleagues use exome chip data to identify rare and common variants influencing blood cell traits. They report associations at several loci, including a rare missense variant in S1PR4 associated with circulating neutrophil counts, and present functional studies supporting a role for S1PR4 in neutrophil recruitment and resolution in response to tissue injury.

Stuart Macregor, Tien Wong and colleagues report meta-analyses that identify 16 new loci associated with central corneal thickness. They also identify two loci associated with risk of developing keratoconus, a common corneal ectasia.

Fatty acid amide hydrolase (FAAH) is a key regulator of endocannabinoid signalling. Here, the authors develop a knock-in mouse that recapitulates a common human mutation in the FAAH gene and demonstrate parallel neural and behavioural alterations across species, suggesting a gain-of-function in fear regulation.

Studies of the hepatitis C virus internal ribosome entry site (IRES) mechanism have focused on how IRES assembles an 80S ribosome at the start codon. Structural and functional analyses demonstrate that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause conformational changes and that the mutated domain decreases IRES activity by inhibiting ribosome translocation and, thereby, translation elongation.

Novak, Lin et al. use AI computational drug prediction and CRISPR-enabled in vivo disease modeling to identify therapeutic strategies for the treatment of Rett syndrome. Findings reveal the therapeutic efficacy of vorinostat in a mouse model of Rett syndrome.