Search

Most DNA-encoded library (DEL) syntheses are limited by the presence of sensitive DNA-based constructs. Here, the authors develop DOSEDO, a diverse 3.7 million compound DEL, generated through diversity-oriented synthesis that provides enhanced scaffold and exit vector diversity and gives validated binding hits for multiple protein targets.

An insertion of an Alu element into an intron of the TBXT gene is identified as a genetic mechanism of tail-loss evolution in humans and apes, with implications for human health today.

Adolescent drug use augments psychiatric risk. Here the authors show that abused drugs dysregulate adolescent Netrin-1/DCC signaling, triggering ectopic long-distance dopamine axon growth in males while Netrin1 compensatory events protect females.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Circular RNAs (circRNAs) are non-coding RNAs generated from pre-mRNAs of coding genes by the splicing machinery whose function in the heart is poorly understood. Here the authors show that AAV-mediated delivery of the circRNA circFndc3b prevents cardiomyocyte apoptosis, enhances angiogenesis, and attenuates LV dysfunction post-MI in mice by regulating FUS-VEGF-A signalling.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists’ forecasts were on average no more accurate than those of simple statistical models.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

Non-ribosomal peptide synthases are multimodular enzymes comprised of adenylation (A), condensation (C) and thiolation domains. Here, the authors show that non-ribosomal peptides can be generated solely by A domain substitutions, providing evidence that the postulated substrate specifying role of C-domains may be rare in nature.

Atherosclerotic plaques with macrocalcification are stable, whereas microcalcification is a key feature of rupture-prone plaques. Here the authors show that¹⁸F-NaF PET/CT imaging can distinguish between macro- and microcalcification providing a potential, non-invasive imaging technique to identify patients with high-risk atheroma.

Schuster et al. engaged researchers and public health professionals working in molecular HIV surveillance (MHS) to assess how they value strategies to improve its use. Participants indicate that the greatest emphasis should be placed on providing certainty of benefit, considering the range of ethical, legal, and social implications of MHS.

A large survey in 19 US states covering just over a decade shows that values regarding wildlife are shifting toward seeing it as one’s community, as opposed to a resource to use for human benefit.

Patient-derived xenografts recapitulate major genomic signatures and transcriptome profiles of their original tumours. Here, the authors, performing proteomic and phosphoproteomic analyses of 24 breast cancer PDX models, demonstrate that druggable candidates can be identified based on a comprehensive proteogenomic profiling.

The role of reciprocal tumour-stroma interactions in tumour invasion remains poorly characterised. Here, single-cell and spatial transcriptomics identifies the cell populations and their transcriptional reprogramming contributing to the spatial organization of the basal cell carcinoma invasive niche.

Drug-likeness is a key consideration when selecting compounds during the early stages of drug discovery, but its evaluation in absolute terms does not adequately reflect the spectrum of compound quality. Here, an intuitive and transparent quantitative measure of drug-likeness is proposed that attempts to capture the abstract notion of aesthetics in medicinal chemistry.

In his capacity as immediate past president of the Federation of Associations of Behavioral and Brain Sciences, Jeremy Wolfe interviews Mike Lauer about the new NIH clinical trials policy. Mike Lauer is NIH’s deputy director for extramural research, serving as the principal scientific leader and advisor to the NIH director on the extramural research programme.

The double-strand break sensor MRE11 is identified as a pivotal mediator of cGAS activation in response to multiple types of DNA damage.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease resulting in reduced mucus clearance and impaired lung function. Here, the authors show that mutations in PIH1D3 are responsible for an X-linked form of PCD, affecting assembly of a subset of inner arm dyneins.

The biophysical properties of cells can be used to predict the cellular age of humans with higher accuracy than conventional biomolecular markers.

Brain-inspired neuromorphic algorithms and systems have shown essential advance in efficiency and capabilities of AI applications. In this Perspective, the authors introduce NeuroBench, a benchmark framework for neuromorphic approaches, collaboratively designed by researchers across industry and academia.

Dorsal membrane ruffles in macrophages accompany pathogen contact and appear before macropinocytosis and phagocytosis. Here, the authors show that these structures are the sites of the accumulation of Toll-like receptor 4 complexes involved in the signalling cascade activated by bacterial lipopolysaccharide.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

Mathematical modelling of 15 years of data from South Africa reveals the spread and vaccine-driven changes in fitness and antimicrobial resistance of Streptococcus pneumoniae.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

A multi-omics survey of progressive compared to regressive carcinoma in situ lesions provides a molecular map of early lung cancer development.

Trump administration’s controversial science and environment policies could come under extra scrutiny as Democrats gain in Congress.

Meta-analysis of genome-wide association studies of 542,934 individuals identifies 336 novel loci associated with refractive error and implicates eye development, circadian rhythm and pigmentation pathways in controlling myopia.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

As part of the modENCODE initiative, which aims to characterize functional DNA elements in D. melanogaster and C. elegans, this study uses RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages of the fruitfly. Among the results are scores of new genes, coding and non-coding transcripts, as well as splicing and editing events.

Some of the best-performing semiconducting polymers for electronic devices show a surprising lack of long-range order to support their electrical conductivity. Here Zhang et al.find a common alignment of the structural backbones of these polymers, explaining their superior charge transport.

Imaging of neuronal activity across the whole zebrafish brain in combination with online analysis allows for manipulating neuronal activity according to function. This approach is used to ablate or activate neurons in fictively swimming zebrafish larvae.

Artificial evolution implements the rules of natural evolution in algorithms that aim to solve biological and computational problems. The authors propose a new discipline, computational evolution, that replaces the outdated principles of artificial evolution with a modern understanding of biology.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.