561975 research outputs found
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A transcriptomic and proteomic map of primary human cell types
No full textMolecular profiling of human primary cell types is essential for understanding human biology. We present a transcriptome and proteome map of 28 primary human cell types. Three major clusters of epithelial, endothelial, and mesenchymal cell types were observed in both the transcriptome and proteome levels along with the discovery of cell type enriched molecules including GRAP and C1orf116. The epithelial cell specific protein C1orf116 was further validated using immunohistochemistry across various human tissues. An exhaustive protein database search considering 39 post-translational modifications (PTMs) revealed novel insights into the PTM landscape including identification of understudied PTMs such as serine O-acetylation and histidine methylation. This also enabled comprehensive characterization of proteins with diverse PTMs. Interestingly, an unexpectedly higher frequency of dioxidation on tryptophan compared to methionine led to the identification of oxidative mitochondria complex subunit proteins. Further, a search strategy accounting for alternative translational start sites, splice junctions and translational readthrough refined genome annotation using proteomic evidence. For example, peptides from translational readthrough including extended sequence of LDHB and MDH1 were detected representing the first peptide-level evidence of these protein readthrough isoforms. Our comprehensive transcriptome and proteome data revealed cell type-specific molecular cues and heterogeneity, offering new insights into disease mechanisms often overlooked by tissue proteomics
Biomarker innovations in precision psychiatry diagnostics and treatment strategies
No full textPrecision psychiatry is an approach designed to improve diagnosis and treatment of mental disorders by leveraging biological insights and developing innovative, mechanism-based treatment strategies unconstrained by current diagnostic boundaries. At its core, precision psychiatry aims to pinpoint the underlying neurobiological mechanisms responsible for the emergence and persistence of symptoms of mental health conditions. This approach strives to create diagnostic tools and therapies targeting these mechanisms, potentially addressing previously resistant aspects of mental health conditions by providing more precise symptom management and possibly altering the disease trajectory. Although still in its nascent stages, the realization of precision psychiatry will result in a more refined and biology-informed diagnostic system for mental disorders, requiring significant adaptations for clinicians, industry, patients and regulators. Identifying, validating and applying both fluid and functional biomarkers are critical steps in the development, testing and application of new precision psychiatry diagnostics and treatments. As part of the 2025 Precision Psychiatry Roadmap initiative meeting in Frankfurt, experts came together to present and discuss the current status of biomarker identification and validation, patient subtyping, and targeted interventions for stratified patient groups. This report features lecture summaries, meeting outcomes, and recommendations from both online and in-person audiences. In general, the recommendations emphasize standardization, collaboration, clinical implementation, digital innovation, long-term planning, and, importantly, patient engagement, as key priorities for advancing precision psychiatry. Despite existing challenges, there is strong optimism for the future of precision psychiatry, with continuous efforts to refine diagnostic tools and treatment strategies. Copyright © 2026. Published by Elsevier B.V
Unlocking photochemical tunability in functionalised bridged-isoindigo molecular motors
No full textArtificial molecular machines enable precise control over motion on the molecular scale. Dual-rotor molecular motors offer unique opportunities for the development of responsive functional systems and molecular machines, yet remain considerably underexplored compared to single-rotor motors. Here, we report six new light-driven bridged-isoindigo-based dual motors, developed through strategic rotor substitution, to investigate the tunability of their rotational behaviour. While thermal processes were largely unaffected by rotor substitution, the photochemical properties were significantly influenced. All functionalised motors retained visible-light addressability, with substitution enabling additional modulation of their absorption wavelengths. Rotor functionalisation also impacted the photostationary state composition and the photochemical accessibility of specific intermediates. Notably, we made the unique observation of a photochemical generated double metastable state in light-driven molecular motors, highlighting the potential for advanced control over dual motor function. The synthetic versatility of the bridged-isoindigo scaffold was further demonstrated by the successful post-functionalisation and membrane incorporation of a representative motor, underscoring its promise for future applications in adaptive molecular systems
uPA-mediated remodeling of CCL21 gradients regulates lymphatic migration of dendritic cells
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Viral communities in Metania sp. sponge microbiomes with possible effects on CO2 fixation
No full textBackground Brazilian sponges of the genus Metania (phylum Porifera) are filter-feeding organisms from freshwater ecosystems. Here, we explored viral communities of Metania sp., their functional role in the sponge and how they differ from those in surrounding water.Results We identified 1163 viral operational taxonomic units (vOTUs) from sponge tissue and adjacent water, with 555 vOTUs shared across habitats. Viral diversity was higher in sponges than in water, and community composition differed significantly (PERMANOVA, p = 0.037). Sponge-associated vOTUs exhibited broad phylogenetic diversity, including deep-branching and unclassified clades, and several exclusively sponge-associated Caudoviricetes. Virus-host predictions revealed 173 interactions, largely with sponge-associated bacteria, supported by CRISPR spacer matches, variant formation in multiple vOTUs across sponge individuals, and a high prevalence of microbial defence systems, particularly restriction-modification, abortive infection, and CRISPR-Cas pathways. Functionally, viral communities carried diverse auxiliary viral genes, including those involved in amino acid and central carbon metabolism, carbohydrate degradation, fatty acid biosynthesis, stress responses (e.g., metacaspase-1), and sulphur cycling. Nine sponge-associated vOTUs encoded carbonic anhydrase (CA), and phylogenomic as well as structural analyses showed strong conservation of CA active sites between sponge viruses, bacterial symbionts, and the sponge host. Protein-level homology searches revealed broad biogeographic distribution of viral CA homologs across global ocean microbiomes, despite limited nucleotide similarity, highlighting deep functional conservation.Conclusions These findings reveal a phylogenetically diverse and functionally rich viral community associated with freshwater Metania sp., characterized by extensive host interactions, diverse defence mechanisms, and auxiliary metabolic capacities. The structural conservation and widespread distribution of viral carbonic anhydrase genes further suggest ecologically significant roles in carbon transformation within freshwater sponges and potentially across aquatic ecosystems
Emergence and evolution of protein-coding de novo genes
No full textDe novo genes generally refer to genes that arise from previously non-coding sequences. This evolutionary path - when randomly expressed sequences become folded and active proteins - challenges our understanding of genetic innovation and has prompted studies to address the evolutionary and mechanistic knowledge gaps. More specifically, prior work has illuminated the mechanisms underlying the origin of de novo genes, their potential functional roles in the cell and the evolutionary processes that lead to these functions. Recent advances in both experimental and computational approaches have contributed to insights into the emergence of de novo genes and the broader implications for our understanding of biological complexity. In this Review, we place particular emphasis on efforts to quantify the likelihood of de novo gene emergence in eukaryotes given genomic characteristics, as well as the mechanisms by which de novo protein structures that are not actively selected against become amenable to selection-driven changes
Neural replay is connected to latent cause inference and supports fast generalization
No full textGeneralizing from previous experience in value-based tasks requires discovering and exploiting hidden structure to draw inferences beyond direct observations, and thereby update information about the values of states. We combined behavior, functional magnetic resonance imaging, and computational modeling to test how latent cause inference guides neural replay, enabling fast generalization. Over two days, fifty-two participants performed a sequential decision task in which multiple visual sequences either shared a latent reward source or were associated with an independent reward. On day 1, participants learned this correlation structure and exploited it to achieve 1-shot value generalization after reversals. Multivariate decoding and sequentiality analyses revealed backward replay in visual cortex during rest intervals that was selective to unobserved reward-linked sequences, consistent with non-local value updating. In parallel, the representation of the abstract reward structure in medial temporal lobe (MTL) increased from early to late blocks on day 1. On day 2, we covertly changed which sequences shared rewards. Participants flexibly reorganized generalization, and replay patterns adapted, parallel to a reorganization of MTL representations. A LCI model captured the initial learning trajectory and adaptation upon changes in latent structure. The model captured individual differences in structure learning, and its value updating of unobserved states predicted trial-wise fluctuations in replay strength. These results provide a mechanistic account in which latent structure discovery and replay interact to propagate value and enable rapid, flexible generalization