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Shock wave lithotripsy (SWL) represents the only noninvasive surgical treatment for urinary tract stones. Drawing on their considerable experience, Lingeman and colleagues outline the current utility and limitations of SWL, and highlight the technological advances that hold promise for improving the safety and efficacy of this treatment modality in the future.

Despite large numbers of patients being affected by stones, a surprising lack of knowledge exists on the relevance of stone compositions and pathological features to the outcomes of patients with stones. Here authors describe the potential of new technologies such as high-resolution endoscopes, and micro-CT imaging to address this lack of knowledge.

The most common predisposing factor for the formation of idiopathic calcium stones is hypercalciuria. Here, the authors discuss the mechanisms of idiopathic calcium stone formation and hypercalciuria as well as potential therapeutic strategies to reduce the risk of stone formation.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Adaptive optical vision Fourier transformer (AOViFT) is a machine learning-based framework for accurately inferring aberrations and restoring diffraction-limited performance in diverse biological specimens.

In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

Integrated data, including 100 human genomes from the Mesolithic, Neolithic and Early Bronze Age periods show that two major population turnovers occurred over just 1,000 years in Neolithic Denmark, resulting in dramatic changes in the genes, diet and physical appearance of the local people, as well as the landscape in which they lived.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

Evan Eichler and colleagues use single-molecule molecular-inversion probes to sequence the coding and splicing regions of 208 candidate genes in more than 11,730 individuals with neurodevelopmental disorders. They report 91 genes with an excess of de novo or private disruptive mutations, identify 25 genes showing a bias for autism versus intellectual disability, and highlight a network associated with high-functioning autism.

Nursing homes are high-risk settings for transmission of infections, but risks associated with specific activities are not well understood. Here, the authors investigate transmission dynamics of multi-resistant organisms in nursing homes in the United States with a focus on out-of-room, interactive visits.

Liquid–liquid phase separation plays an important role in creating cellular compartments and protocells, but designing small-molecule models remains difficult. A peptide-based synthon for liquid–liquid phase separation consisting of two stickers and a flexible, polar spacer has now been presented. Condensates formed by these synthons can concentrate biomolecules and catalyse anabolic reactions.

Using DNA from a finger bone, the genome of an archaic hominin from southern Siberia has been sequenced to about 1.9-fold coverage. The group to which this individual belonged shares a common origin with Neanderthals, and although it was not involved in the putative gene flow from Neanderthals into Eurasians, it contributed 4–6% of its genetic material to the genomes of present-day Melanesians. A tooth whose mitochondrial genome is very similar to that of the finger bone further suggests that these hominins are evolutionarily distinct from Neanderthals and modern humans.

Evan Eichler and colleagues present a detailed characterization of the chromosome 15q13.3 microdeletion region. They identify complex structural polymorphisms and find that the rearrangement breakpoints cluster in palindromic GOLGA8 core duplicons, providing evidence that this repeat and its palindromic architecture underlie the evolutionary and disease-related instability of this region.

Evan Eichler and colleagues analyze the relative impact of de novo and rare, inherited variants on autism risk. They show a statistically independent role for rare, inherited mutations and implicate several new candidate genes likely contributing to autism risk.

An analysis of human chromosome 15 — which is altered in Prader-Willi and Angelman syndromes — reveals that it resembles a hall of mirrors, as it contains a number of sequence duplications throughout its length. The evolutionary events that may have led to the high number of duplications was also reconstructed.

This study provides insights into unifying mechanisms that explain the impact of engineered nanomaterials across species and identifies those that underlie differing sensitivities.

Population mobility is associated with SARS-CoV-2 transmission but its impacts on other respiratory viruses are not well understood. Here, the authors investigate associations between mobile phone-derived mobility metrics and the dynamics of 18 respiratory viruses in Seattle, Washington from 2018 to 2022.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

The Human BioMolecular Atlas Program (HuBMAP) presents its production phase: the generation of spatial maps of functional tissue units across organs from diverse populations and the creation of tools and infrastructure to advance biomedical research.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

Segmental duplications in the genome are regions with the potential for the evolution of phenotypic novelties, but their cataloguing has been technically difficult. Here, the evolution and function of human duplications is characterized.

Analysis of whole-genome sequence data from 3,474 families finds an excess of private, likely gene-disrupting variants in individuals with autism. These variants are under purifying selection and suggest candidate genes not previously associated with autism.

Analysis of ~10,000 cases of developmental delay and autism identifies 253 candidate neurodevelopmental disease genes. Network analysis highlights cell-specific enrichments of disease-related genes in the D1⁺ and D2⁺ spiny neurons of the striatum.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

Autism spectrum disorders (ASD) are characterized by social impairments, communication deficits and repetitive stereotyped behaviours. Here, the authors show that de novo missense mutations, but not inherited missense mutations, in TBR1disrupt the protein function and contribute to ASD aetiology.

Family-based exome sequencing in a large autism study has identified 27 high-confidence gene targets and accurately estimates the contribution of both de novo gene-disrupting and missense mutations to the incidence of simplex autism, with target genes in affected females overlapping those in males of lower but not higher IQ; targets also overlap known targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes.

The genome of the grey short-tailed opossum Monodelphis domestica has been sequenced and analyzed, giving a first peek at a marsupial's genetic code. Of particular interest are the genetics of the immune system, which has been studied as a model for humans, and of the X chromosome for historical reasons.

This study characterizes the properties of disease-causing mutations that produce sporadic amino acid replacements in proteins of people with autism and developmental delay. The mutations tend to cluster and reoccur at specific regions important to protein function, highlighting for future follow-up ∼200 candidate genes, many involved in neuronal signaling.

Until now, fully sequenced human genomes of the indigenous hunter-gatherer peoples of southern Africa have been limited to recently diverged populations. The complete genome sequences of an indigenous hunter-gatherer from the Kalahari Desert and of a Bantu from southern Africa are now presented. The extent of whole-genome and exome diversity is characterized; the observed genomic differences may help to pinpoint genetic adaptations to an agricultural lifestyle.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

The recent surge in sequencing output has uncovered a wealth of genetic variation, but interpretation of these data remains a challenge. This Review discusses computational and experimental methods for estimating the deleteriousness and functional significance of genetic variants to better identify those that are potentially causal for disease.

Exome sequencing on a large cohort of parent–child trios with sporadic autism spectrum disorders shows that de novo point mutations are mainly paternal in origin and positively correlate with paternal age, and identifies a highly interconnected network formed from the products of the most severe mutations.

The merger of chemical and biocatalysis can offer powerful new options to synthetic chemists. Here a combination of a nickel-catalyzed Suzuki-Miyaura reaction and an enzymatic stereoselective reduction provides enantiomerically-enriched alcohols from amides in a single reaction vessel, in water.