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Homo sapiens evolved hundreds of thousands of years ago in Africa, later spreading across the globe1, but the early evolutionary process is debated2–6. Here we present whole-genome sequencing data for 28 ancient southern African individuals, including six individuals with 25× to 7.2× genome coverage, dated to between 10,200 and 150 calibrated years before present (cal. bp). All ancient southern Africans dated to more than 1,400 cal. bp show a genetic make-up that is outside the range of genetic variation in modern-day humans (including southern African Khoe-San people, although some retain up to 80% ancient southern African ancestry), manifesting in a large fraction of Homo sapiens-specific variants that are unique to ancient southern Africans. Homo sapiens-specific variants at amino acid-altering sites fixed for all humans—which are likely to have evolved rapidly on the Homo sapiens branch—were enriched for genes associated with kidney function. Some Homo&nbsp

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Over the past several decades, the pharmaceutical industry has progressed from identifying small-molecule natural products with favourable pharmacological properties mediated by unknown molecular mechanisms, to deliberate engineering of chemical compounds and macro-molecules that alter the activities of prespecified targets in predefined ways. The past quarter century has seen the emergence of an entirely new drug category: multispecific molecular drugs that are prospectively designed to engage two or more entities to exert their pharmacological effect. This design elicits emergent properties that endow the drugs with capabilities that are inaccessible to monospecific therapies. Furthermore, these properties enable multispecific drugs to circumvent biological barriers to pharmacology, including rapid clearance, functional redundancy, on-target/off-tissue toxicity, and lack of druggable features. Here, I describe how a new wave of approved multispecific drugs is recalibrating expectatio

Here, the authors present the cryoEM structure of the sodium-translocating methyltransferase (Mtr) complex from Methanosarcina mazei. Along with providing catalytic insights, they identify MtrI, an un...

The long-term existence of diverse virulent phages within cultures of Escherichia coli and others challenges the virulent–temperate dichotomy and points to non-canonical phage lifestyles.

The long-term existence of diverse virulent phages within cultures of Escherichia coli and others challenges the virulent–temperate dichotomy and points to non-canonical phage lifestyles.

Long COVID is an infection-associated chronic condition that typically occurs within 3 months of acute COVID-19 infection in which symptoms are intermittently or continuously present for at least 3 months. Long COVID is estimated to affect between 80 and 400 million people globally, with an incidence of 5–20% in the community and up to 50% among hospitalized patients following acute SARS-CoV-2 infection. Common neuropsychiatric and mental health symptoms of long COVID include memory deficits, executive dysfunction, anxiety, depression, recurring headaches, sleep disturbances, neuropathies, problems with taste and smell, and dizziness that accompanies erratic heart rates and severe post-exertional malaise. Underlying pathophysiological mechanisms includes SARS-CoV-2 viral persistence, herpesvirus reactivation, microbiota dysbiosis, autoimmunity, clotting and endothelial abnormalities, and chronic immune activation. Owing to the variability in the clinical presentation, management must b

きのう、東京・奥多摩町の林道で、臓器の一部がない男性の遺体が見つかりました。動物に襲われた可能性もあるとみられます。 きのう午後2時前、奥多摩町日原の小川谷林道で、登山中の男性が男性の遺体を見つけ

Plasmids play significant roles in microbial adaptation to ecosystems, yet their dynamics remain poorly understood due to identification challenges. We present the Global Soil Plasmidome Resource (GSPR), a comprehensive dataset of 98,728 plasmid sequences amassed from 6860 terrestrial microbial communities and isolates. We explore this resource through various computational approaches, including phylogenetic diversity analysis, host prediction, and extensive functional annotation, to understand the contribution of plasmids to the genetic and functional diversity in soil, correlating these findings with sample type, as well as the soil habitat they were retrieved from. Our analysis reveals insights into plasmid-encoded functions such as effector modules, quorum sensing, and stress resistance, which may contribute to their persistence and microbial adaptation in soil. Furthermore, CRISPR analysis suggests a prevalent role of these elements related to intra-plasmid competition. By co

Lung development generates a complex tree-like architecture through proximal-distal patterning and branching morphogenesis. However, the gene regulatory programs governing embryonic lung development remain poorly understood. Here, we present a comprehensive single-cell multi-omics atlas of mouse embryonic lungs, integrating gene expression and chromatin accessibility profiles. Through systematic analysis, we identify 13 distinct cell types and map cis-regulatory elements, peak-to-gene linkages, and transcription factors underlying lung development. Leveraging this multi-modal dataset, we uncover lineage-determining transcription factors driving cell differentiation, including the Activated Protein-1 complex. We further delineate gene regulatory networks involving diverse transcription regulators, including CCCTC-binding factor (CTCF). Using the Ctcf conditional knockout mouse, coupled with histological and multi-omics analyses, we demonstrate that CTCF orchestrates lung progenitor main

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Diverse genomes of lytic phages are found in bacterial assemblies, challenging assumptions about the nature of the lytic lifestyle.