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Protein AMPylation is a post-translational modification whose implications in cellular physiology are not fully understood. Here the authors develop a cell-permeable AMPylation probe and use it to identify new AMP modified proteins and investigate the role of FICD in neuronal differentiation using cerebral organoids.

In a proof-of-concept randomized trial in schoolchildren from Northern Senegal, artesunate–mefloquine at antimalarial dosage was noninferior to standard-care praziquantel for the treatment of schistosomiasis.

Whole-genome sequence data for 108 individuals representing 28 language groups across Australia and five language groups for Papua New Guinea suggests that Aboriginal Australians and Papuans diverged from Eurasian populations approximately 60–100 thousand years ago, following a single out-of-Africa dispersal and subsequent admixture with archaic populations.

Targeted inhibition of the ERK-MAPK pathway is challenged by the development of resistance and toxicity. Here, the authors show that SHOC2 genetic inhibition impairs lung tumour development and improves MEK inhibitor efficacy in RAS- and EGFR-mutant cells.

Europe hosts isolated remnants of the steppe belt that once covered much of Eurasia. Here the authors combine genomic data and ecological niche modelling on three plant and three insect species to show evolution independent of the zonal steppe and high conservation value of these extrazonal steppes.

The neuronal diversity of the Drosophila optic lobe is described throughout pupal development by single-cell sequencing, leading to the discovery of transient extrinsic neurons and a dorsoventral asymmetry of the visual circuits.

The epithelial protein Coxsackievirus Adenovirus Receptor (CAR) is a virus receptor but may have other functions. Here the authors show that deletion of CAR in mice leads to reduced house dust mite-induced lung inflammation, reduced neutrophil accumulation and alterations in airway remodelling.

Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

A longitudinal analysis of immune responses in patients with moderate or severe COVID-19 identifies a maladapted immune response profile linked to severe disease.

Developing inhibitors that target specific protein-protein interactions (PPIs) is challenging. Here, the authors show that target selectivity and PPI blocking can be achieved simultaneously with PPI inhibitors that contain two functional modules, and create a paralog-selective PSD-95 inhibitor as proof-of-concept.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Despite growing interest in the role of autophagy in neurons, it remains unclear how this process is regulated, in particular, how autophagy is spatially restricted in subcellular compartments in neurons. In this study, the authors use an unbiased proteomic approach to show that the autophagy initiating kinase UNC-51/ULK and autophagosome formation are inhibited by the ubiquitin ligase RPM-1, and demonstrate that this interaction is within specific axonal compartments.

Glucose-dependent insulinotropic polypeptide (GIP) is a gut incretin hormone released in response to nutrients. Here, the authors report an anti-inflammatory and antiobesogenic mechanism of GIP by showing that loss of GIP receptor signalling in myeloid cells promotes pro-inflammatory S100A8/A9 release in adipose tissue.

Short term systemic expression of the reprogramming factors Oct-3/4, Sox2, Klf4, c-Myc (OSKM) rejuvenates aging cells and promotes tissue regeneration. Here the authors show that myofiber-specific expression of OSKM accelerates muscle regeneration by reducing secretion of muscle stem cell quiescence promoting Wnt4.

Basal progenitors are enriched in gyrencephalic species like humans contributing to neuronal expansion. Here the authors show that LGALS3BP de novo variants are related to reduced cortical complexity and area in humans and that LGALS3BP regulates neural progenitor position in organoids, human fetal tissue and mice.

Tuberculosis is a major cause of mortality, and the rise of drug-resistant strains of Mycobacterium tuberculosis requires the urgent development of safe and effective treatments. In this work, the authors develop a compound against lysyl-tRNA synthetase, demonstrating on-target mechanism of action and efficacy in vivo.

Using an atomic gas aggregation process in the laboratory to simulate the conditions in the inner regions of a carbon-rich evolved star, Martínez, Santoro, Merino and colleagues. show that aromatic species and fullerenes form surprisingly inefficiently, and that amorphous carbon nanograins and aliphatic clusters dominate.

Previous studies have shown that the CD40L-CD40 signaling axis plays a role in atherosclerosis. Here the authors investigate the cell-specific functions of the most relevant CD40L-expressing cell types in atherosclerosis. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization while platelet-derived CD40L ameliorates atherothrombosis.

Multiple sclerosis (MS) lesions are initiated by the infiltration of T cells to the CNS. Here, Kendirli et al. use a genome-wide CRISPR screen in an MS model to define the molecules that regulate T cell entry to the CNS.

Enzyme engineering is opening up new chemistries. Here, the authors report enzymes engineered to contain two biological active sites — also showing that one site can be converted to a metal-complex catalyst — and demonstrate the utility of such dual sites in a range of catalytic processes.

Bernards and colleagues identify cFLIP as a common dependency of cancer cells by conferring protection from senolytic-induced cell death. They nominate combination of DR5 activation and cFLIP suppression for enhanced killing of senescent cancer cells.

Across 46 proglacial landscapes worldwide, environmental properties and biodiversity have shown complex patterns of change since glaciers retreated.

SARS-CoV-2 is shown to infect and replicate in human pancreatic tissue, including in β-cells, which is associated with morphological, transcriptomic and functional changes.

The atmosphere has dried across most regions of Europe in recent decades, a trend that can be attributed primarily to human impacts, according to tree ring records spanning 400 years and Earth system model simulations.

A complex regulatory network of temporally expressed transcription factors in Drosophila optic lobe stem cells regulates the generation of all neuronal diversity.

Hydrocarbons are challenging to functionalize. Here, the authors present an electrochemical oxo-functionalization of cyclic alkanes and alkenes to ketones and dicarboxylic acids via mediating nitrate-based supporting electrolyte and molecular oxygen.

Individuals with long COVID show marked biological changes in cortisol and immune factors relative to convalescent populations.

RAD51 is a well known player of DNA repair and homologous recombination. Here the authors reveal a function for RAD51 in protecting under-replicated DNA in mitotic human cells, promoting mitotic DNA synthesis (MiDAS) and successful chromosome segregation.

van Lengerich et al. developed a human TREM2 antibody with a transport vehicle (ATV) that improves brain exposure and biodistribution in mouse models. ATV:TREM2 promotes microglial energetic capacity and metabolism via mitochondrial pathways.

Restoring mitochondrial function has emerged as a promising therapeutic strategy for diabetic retinopathy. Here, the authors show that mitochondrial hyperfusion blunts mitophagy during the disease process, and that rescuing this process pharmacologically confers retinal neuroprotection independent of an improved glycaemic status in type-1 diabetic mice.

Adipose tissue (AT) inflammation is strongly associated with obesity and constitutes an obesogenic memory upon weight loss. Here, the authors show that intermittent fasting leads to an adipocyte p53-signaling dependent emergence of lipid-associated macrophages in visceral AT of obese mice which limits the systemic fasting response.

The contribution of chromosomal rearrangements to fitness remains to be directly quantified. By constructing rearrangements in fission yeast, the authors show that the resulting defects in meiosis may be compensated for by a strong growth advantage in mitosis.

Adhesion of the human pathogen Mycoplasma pneumoniae to pulmonary epithelial cells is mediated by a transmembrane complex composed of proteins P1 and P40/P90. Here, the authors present the structures of M. pneumoniae P1 and P40/P90, show that P40/P90 binds sialylated oligosaccharides and have also determined the crystal structures of P40/P90 complexes with 3’-Sialyllactose and 6’-Sialyllactose, which provide insights into the mechanisms of adhesion and gliding on host cell surfaces.

The authors report that genetic disruption of the connectivity of CCK⁺ basket cells during development reveals a critical role for these interneurons in the regulation of theta oscillatory activity and in the coding of spatial information in the adult mouse hippocampus.

New delivery platforms are needed to allow broader application of biotherapeutics for CNS diseases. Here, the authors show enhanced CNS delivery with a transport vehicle engineered to bind CD98hc, a highly expressed target at the blood-brain barrier.

Identification of safe and effective broad-spectrum antivirals based on modified chitosan sulfate derivatives.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Chemical structures are typically published as nonmachine-readable images in scientific literature. Here, the authors present DECIMER.ai, an open platform for translating chemical structures in publications into machine-readable representations.

Ryanodine receptor type 1 (RyR1) are involved in skeletal muscle contraction. Here, the authors show that a transient calcium leak in response to exercise-induced post translational modifications of RyR1 causes mitochondrial remodeling to improve respiration.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

Meta-analyses of genome-wide association studies for endometriosis identify 49 distinct association signals. Fine-mapping of causal variants explores functional effects across various tissues. Genetic correlations between endometriosis and other pain conditions are also highlighted.

Single-cell RNA-seq and ATAC-seq, combined with spatial transcriptomics, identify age- and location-related cellular dynamics of diffuse midline gliomas, such as variable oligodendrocyte precursor-like tumor stem cell populations and increased mesenchymal states with age.

Dielectric metasurfaces have different Q-factor and light localisation requirements for sensing and imaging. Here, the authors present a dielectric metasurface, supporting two optical modes with sharp Fano resonances for high Q-factors and strong spatial confinement, allowing both sensing and imaging.

Age-related macular degeneration (AMD) is a leading cause of vision loss, and there is no approved treatment for AMD with geographic atrophy. Here, the authors used transcriptomic and proteomic analyses of patient induced pluripotent stem cell-derived retinal pigment epithelium to better understand disease mechanisms.

The precise lineage relationship between innate lymphoid cells and lymphoid tissue–inducer cells is poorly understood. Using single-cell transcriptional analysis and cultures of fetal liver precursor cells, Bendelac and colleagues define the divergence of these cells.

The expression of the nucleolar protein nucleophosmin (NPM) decreases during the differentiation of various cell types. Here, the authors show that the collaboration between the RNA-binding proteins, HuR and KSRP, reduces the stability of NPM mRNA in myoblasts, thereby allowing myogenesis.

A study demonstrates that plasticity in the head direction system in Drosophila is modulated by dopamine, which increases learning when reorienting movements are bringing in new spatial information.

Population-based surveys are the gold standard for estimating seroprevalence but are expensive and often only capture a small geographic area or window of time. This study describes a new platform, SCALE-IT, for serosurveillance based on algorithmic sampling of electronic health records, and uses it to estimate the seroprevalence of SARS-CoV-2 in San Francisco.