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Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

GestaltMatcher uses a deep convolutional neural network to improve recognition of rare disorders based on facial morphology. The framework detects similarities among patients with previously unseen syndromes, aiding discovery of new disease genes.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

Crude oil is a mixture of different hydrocarbons, and their separation remains challenging. Here this work shows a molecular sieve that allows for direct, selective and sustainable isolation of valuable components.

X-ray crystallography, solution NMR and biochemical and cell-based analyses reveal a model where catalytically repressed receptor tyrosine kinases accomplish activation loop (A-loop) tyrosine transphosphorylation.

Generation and analysis of high-quality, genome assemblies from Middle Eastern trios demonstrate the utility of ancestry-matched data and assembly-based variation analysis.

But challenges remain for United Nations meeting in run-up to a new 2015 emissions treaty.

Cross-neutralization assays of early variants and the 501Y.V2 variant of SARS-CoV-2 show that plasma from individuals infected with 501Y.V2 effectively neutralizes all variants, indicating that a vaccine that targets 501Y.V2 may also be effective against other SARS-CoV-2 variants.

The Omicron BA.2.86 subvariant differs from previous variants by over 30 spike mutations. Here, the authors report that BA.2.86 likely evolved in Southern Africa and that its immune escape is not larger than recently circulating SARS-CoV-2 strains. Neither its replication nor its pathogenicity are enhanced in vitro.

There is limited data on immune factors contributing to SARS-CoV-2 viral clearance in people living with HIV. Here, the authors show that re-emergence of the neutralizing antibody response may be key to clearing persistent SARS-CoV-2 infection in ART-mediated recovery from immunosuppression in advanced HIV disease.

Plasma from individuals vaccinated with BNT162b2 exhibits 22-fold less neutralization capacity against Omicron (B.1.1.529) than against an ancestral SARS-CoV-2 strain but residual neutralization is maintained in those with high levels of neutralization of ancestral virus.

A study quantifying the neutralization of severe acute respiratory syndrome coronavirus 2 variants in individuals infected with Omicron/BA.1 shows that vaccinated individuals previously infected with Omicron have enhanced protection against reinfection with current variants, \including Omicron/BA.2, while Omicron/BA.1 infected unvaccinated individuals have limited protection.

The evolution of the chemical and pharmaceutical industry requires effective and less energy intensive separation technologies but engineering materials at a large scale with tunable properties for molecular separation is challenging. Here, the authors report a thin film composite membranes prepared by the interfacial polymerization of porous organic cages.

This study reveals how Klotho and heparan sulfate glycosaminoglycan coreceptors enable FGF hormones to induce asymmetric 1:2 FGF–FGFR dimerization mandatory for FGFR kinase activation and hence signalling.

Crystal structures of free and ligand-bound β-klotho reveal that it acts as a primary receptor for FGF21, and demonstrate how a sugar-cutting enzyme has evolved to become a receptor for hormones that regulate metabolic processes.

Here the authors show that disordered polypeptide-RNA condensates exhibit rheological properties similar to that of a viscoelastic Maxwell fluid, and use simple polypeptide design rules to create microcondensates with tunable viscoelasticity.

Loss of the cadherin FAT1 has been associated with nephropathy and epithelial cell adhesion defects. Here, the authors report five families with a syndromic form of coloboma associated with homozygous frameshift variants in FAT1 and recapitulate the phenotype in mutant mice and zebrafish.

Engineering thin membranes for molecular separation with well tailored nanoporosity and which can withstand harsh conditions is still a big challenge. Here, the authors introduce a trianglamine macrocycle as a molecular building block for cross-linked membranes, prepared by facile interfacial polymerization, for high performance selective separations.

The central roles of members of the fibroblast growth factor (FGF) family in human developmental processes and disease have been well documented. In their Review, Beenken and Mohammadi discuss the more established applications of FGF-related therapies in the treatment of cancer and cardiovascular disease, emphasizing their potential to modulate aspects of the metabolic syndrome and hypophosphataemic diseases.

Structural data has provided insight into the molecular mechanisms that modulate fibroblast growth factor (FGF) signalling to generate distinct biological outputs in development, tissue homeostasis and metabolism. Mechanisms include alternative splicing of ligand and receptor, homodimerization and site-specific proteolytic cleavage of ligand, and interaction of ligand and receptor with heparan sulphate and Klotho co-receptors.

Acne vulgarisis a common, inflammatory skin disorder. Here the authors carry out a genome-wide association study and identify three genetic variants that associate with an increased risk of developing acne, which together suggest a mechanistic role for the TGFβ cell signalling pathway in acne development and progression.

Liquid ribonucleoprotein condensates typically involve a dense network of multiple proteins and RNAs. Here, the authors employ a minimal system composed of Prion-like polypeptides (PLP), Arg-rich polypeptides (RRP), and RNA to form biphasic condensates with diverse morphologies tunable via mixture stoichiometry and hierarchy of intermolecular interactions.

Acne vulgaris is a chronic inflammation of the skin, the genetic basis of which is incompletely understood. Here, Petridis et al. perform GWAS and meta-analysis for acne in 26,722 individuals and identify 12 novel risk loci that implicate structure and maintenance of the skin in severe acne risk.

High-quality draft genomes have been generated for the two commercially cultivated jute species, Corchorus olitorius and Corchorus capsularis. Transcriptome analyses revealed key regulatory and structural genes involved in fibre formation.

The fibroblast growth factor (FGF) family play critical regulatory roles in development, metabolism and tissue homeostasis and their therapeutic applications are being widely explored. This Review highlights recent advances in understanding of FGF signalling, discusses the current status of endocrine FGF-based drug development and assesses the emerging potential of harnessing paracrine FGFs in the treatment of metabolic diseases.

Rationing of scarce health-care resources is distressing. Clinicians therefore require clear guidance, which should be developed systematically and transparently through multi-stakeholder engagement. Rationing is seldom required in high-income settings but is often necessary in low-income settings. Global solidarity and health system strengthening are required to reduce the need for rationing.