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Systematic analysis of the zebrafish synapse proteome has been lacking. Here the authors characterize the ultrastructure of zebrafish synapse and compare the proteomes of postsynaptic density in zebrafish and mice, offering a resource for future studies using zebrafish to model diseases.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Initiation is the rate limiting step of protein translation. Here the authors show that recycling of the free ribosomal 40 S subunit is regulated by the deubiquitinase OTUD6. OTUD6 deubiquitinates monoubiquitinated RPS7/eS7 to promote 40 S recycling into the preinitiation complex.

Control of movements can be understood in terms of the interplay between a controller, a simulator and an estimator. Egger et. al. show that cortical neurons establish the same building blocks to control cognitive states in the absence of movement.

Analogues of α-ketoglutarate are used in many cellular studies but assumptions are made about cellular uptake. Here, the authors show that esterified analogues rapidly hydrolyse in aqueous medium resulting in an analogue which can be quickly taken up by many cell lines, contrary to prevailing assumptions.

The function of macrophages in myeloid leukaemia can be difficult to assess because of lack of differentiation between transformed and non-transformed cells. Here the authors use a chimeric mouse model to characterise the effect of myeloid leukaemia on bystander macrophages noting altered functional properties of these cells.

The protein composition of excitatory synapses differs in the areas of the human neocortex controlling language, emotion and other behaviors. This neocortical postsynaptic proteome data resource can be used to link genetics to brain imaging and behavior.

Kimmelman and colleagues show that inhibition of glutamine (Gln) metabolism using a Gln antagonist decreases pancreatic cancer tumor growth, but is compensated by upregulation of extracellular signal-regulated kinase signaling, which can be co-targeted.

Cryo-EM is used to visualize the SARS-CoV-2 RTC bound to each of the natural NTPs as well as remdesivir triphosphate (RDV-TP) in states poised for incorporation, explaining the interactions required for NTP recognition and RDV-TP selectivity.

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.

Avoiding catastrophic climate change requires that we avoid losing key natural carbon reserves. This study maps such irrecoverable carbon globally and finds a third of the remaining managed by Indigenous peoples and local communities and nearly a quarter in protected areas.

Understanding of the mycobacterial transcription system is useful to the development of therapeutics against tuberculosis infection. Here the authors present the crystal structure of a completeM. smegmatisRNA polymerase open promoter complex that reveals unique features of the mycobacterial polymerase.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

An analysis of longitudinal cohort data across diverse populations suggests that the incidence of wasting between birth and 24 months is higher than previously thought, and highlights the role of seasonal factors that affect child growth.

Cancer cells have altered lipid metabolism. Here the authors show that DAXX promotes lipogenesis and tumorigenesis through interaction with SREBP1/2.

Using JWST, more than 40 individual stars have been detected in a distant galaxy, dating back to when the Universe was only half of its current age. The stars appear to be red (super)giants that are magnified by factors of hundreds.

The online game Foldit invites players to solve problems involving protein structure prediction. Now Foldit players have been recruited to work on a modeling problem and ultimately solve the crystal structure of a retroviral protease that had resisted previous determination.

The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant transcription.

This preclinical study demonstrates the potential of a drug repurposing strategy using the coadministration of tamsulosin, metoprolol, and bromocriptine to provide a mutation-agnostic therapy for inherited retinal degeneration.

The seeding of native species is critical to the success of dryland restoration efforts. Here the authors evaluate success of seeding establishment at 174 sites on six continents, finding that some sites had nearly 100% of species successfully recruit, while 17% of sites had zero seedling success.

An allosteric inhibitor of acetyl-CoA carboxylase reveals a metabolic liability of non-small-cell lung cancer and slows tumor growth alone and in combination with chemotherapy in mouse models.

Baker and colleagues have already shown that protein folding can be turned into an online game played by nonscientists. Now, Foldit players tackle the problem of increasing an enzyme's catalytic activity—with promising results.

A pooled analysis of longitudinal studies in low- and middle-income countries identifies the typical age of onset of linear growth faltering and investigates recurrent faltering in early life.

An RNA aptamer that selectively binds FAD over FADH₂ shifted the reduction potential of the bound cofactor, similar to flavoproteins, and was shown through structural characterization to use π–π and donor–π interactions to drive the shift.

Experiments in mouse and hamster models show that monoclonal antibody combinations, using antibodies that correspond to products in clinical development, largely retain their efficacy in protecting against currently prevailing variant strains of SARS-CoV-2.

Programmable triangular DNA blocks self-assemble into distinct icosahedral shells with specific geometry and apertures that can encapsulate viruses and decrease viral infection.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

A crystal structure of the RNA-binding domain of Tetrahymena telomerase reverse transcriptase (TERT) with its template RNA (TER) reveals interactions that establish the template boundary element and direct the addition of telomeric DNA repeats.

A super-Förster energy-transfer regime, where coherent and incoherent energy transport processes enhance the diffusion of excitons, is observed at room temperature by tuning the distance between the chromophores’ binding sites in a virus scaffold.

Inhibition of the autophagy–lysosome system upregulates surface expression of MHC class I proteins and enhances antigen presentation, and evokes a potent anti-tumour immune response that is mediated by CD8⁺ T cells.

E2F transcription factors are regulators of cell division and cell fate decisions. Here the authors show that E2F4 is important for proliferation and survival of mouse ESCs, independent of the RB family, and that E2F4 interacts with chromatin regulators associated with gene activation.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in neurofibromin and associated with disruptions in physiology and behavior. Here the authors show that neurofibromin regulates metabolic homeostasis via a discrete brain circuit in a Drosophila model of NF1.

Reported COVID-19 mortality rates have been relatively low in Syria, but there has been concern about overwhelmed health systems. Here, the authors use community mortality indicators and estimate that <3% of COVID-19 deaths in Damascus were reported as of 2 September 2020.

The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression.

In this disease mapping study, the authors estimate disability-adjusted life year rates for three of the major causes of mortality for children under five 43 countries in sub-Saharan Africa. They identify significant heterogeneity at the subnational level, highlighting the need for a targeted intervention approach.

Through its association with Cdk–cyclin complexes, Cks has been implicated in the multisite phosphorylation of numerous cell cycle–regulatory proteins. A structural analysis of Cks1 bound to a target phosphopeptide, combined with binding-specificity studies, now reveals a Cks-binding consensus sequence and how Cks1 confers phosphodependent substrate specificity to Cdk1.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Glypican-1 identifies cancer exosomes and serves as a biomarker for detection of early pancreatic cancer in patients and mouse models of the disease; the findings may enable early and non-invasive identification, and prevention of malignant cancer.

A new study from the WHO African Region identifies features of countries that predict timing of the first case and the per capita mortality rate for the first and second waves of the COVID-19 epidemics.

Upon DNA binding cyclic GMP-AMP synthase (cGAS) produces a cyclic dinucleotide, which leads to the upregulation of inflammatory genes. Here the authors develop small molecule cGAS inhibitors, functionally characterize them and present the inhibitor and DNA bound cGAS crystal structures, which will facilitate drug development.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

Resistance to rifamycin antibiotics, which target bacterial RNA polymerases, is a growing problem. Here, the authors identify gene clusters from soil metagenomes encoding production of rifamycin analogues that are active against rifampicin-resistant bacteria through a distinct mechanism.

This Perspective reviews tools developed over the past five years in the macromolecular modeling, docking and design software Rosetta.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

SPAK kinase is a master regulator of cation-Cl⁻ cotransporters. Here the authors describe a new SPAK inhibitor with robust protective effects in rodent hydrocephalous and ischemic stroke models.