Science Translational Medicine

Journal: Science Translational Medicine

Abbreviation

Sci Transl Med

Publisher

AAAS

ISSN

1946-6234, 1946-6242

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Publications 1 - 10 of 47

Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data
Nadeau, Sarah Ann; Vaughan, Timothy G.; Beckmann, Christiane; et al. (2023)
Science Translational Medicine
Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020 - the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland’s border closures de-coupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86–98% reduction in introductions during Switzerland’s strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred, using a phylodynamic model. We found that transmission slowed 35–63% upon outbreak detection in summer 2020, but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics.
Epidemiological and antigenic inferences from serological cross-reactivity among arboviruses
O'Driscoll, Megan; Hozé, Nathanaël; Lefrancq, Noémie; et al. (2025)
Science Translational Medicine
Multiplex immunoassays can facilitate the parallel measurement of antibody responses against multiple antigenically related pathogens, generating a wealth of high-dimensional data that depict complex antibody-antigen relationships. In this study, we developed a generalizable analytical framework to maximize inferences from multipathogen serological studies. We fit the model to measurements of immunoglobulin antibody binding against 10 arboviral pathogens from a cross-sectional study in northwest Bangladesh with 1453 participants. We used our framework to jointly infer the prevalence of each pathogen by location and age as well as between-pathogen antibody cross-reactivity. Reconstructing immunological profiles, we found evidence of endemic transmission of Japanese encephalitis virus and recent outbreaks of dengue and chikungunya viruses in this district. Our estimates of antibody cross-reactivity were highly correlated with phylogenetic distances inferred from genetic data [correlation coefficient (r) = 0.94], demonstrating how antigenic landscapes can be inferred from population-level serological studies. Furthermore, we showed how our framework could be used to identify the presence of antigenically related pathogens that were not directly tested for, representing a potential opportunity for the detection of emerging pathogens. The presented analytical framework offers a tool that can be applied to a growing number of multipathogen studies and will help support the integration of serological testing into disease surveillance platforms.
Restoring Natural Sensory Feedback in Real-Time Bidirectional Hand Prostheses
Raspopovic, Stanisa; Capogrosso, Marco; Petrini, Francesco M.; et al. (2014)
Science Translational Medicine
Adoptive cell therapy with macrophage-drug conjugates facilitates cytotoxic drug transfer and immune activation in glioblastoma models
Sun, Miaomiao; Bialasek, Maciej; Mayoux, Maud; et al. (2025)
Science Translational Medicine
The treatment of solid tumors faces substantial hurdles because of inadequate drug delivery and the immunosuppressive tumor microenvironment. To address these challenges, we developed a therapeutic platform using macrophages loaded with ferritin-drug conjugates, referred to as macrophage-drug conjugates (MDC), and applied it to glioblastoma, an immunologically cold solid tumor. MDC loaded with ferritin-conjugated monomethyl auristatin E enabled efficient, cell contact-dependent transfer of the payload by a mechanism involving transfer of iron-binding proteins, from either mouse or human macrophages preferentially into glioma cells. This targeted delivery and therapeutic efficacy was demonstrated across in vitro coculture systems, ex vivo assays using dissociated glioblastoma patient tumor samples, and in vivo using orthotopic glioblastoma mouse models, all while maintaining a favorable preclinical safety profile evidenced by minimal systemic toxicity and localized drug biodistribution. Beyond direct tumor cell killing leading to significant tumor regression and prolonged survival in these models, MDC therapy reprogrammed the immunosuppressive tumor microenvironment. Immune profiling by spectral flow cytometry revealed enhanced infiltration and activation of cytotoxic T lymphocytes and B lymphocytes while reducing immunosuppressive regulatory T cells. This culminated in a robust, durable, T cell-dependent antitumor immune response, the necessity of which was confirmed through studies in immunodeficient mouse models and by lymphocyte depletion, and which conferred protection against tumor rechallenge. The combined cytotoxic and immunomodulatory effects highlight the potential of MDC therapy as a promising strategy for glioblastoma treatment and support its further clinical development.
Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis
Schukur, Lina; Geering, Barbara; Charpin-El Hamri, Ghislaine; et al. (2015)
Science Translational Medicine
Load-induced regulation of tendon homeostasis by SPARC, a genetic predisposition factor for tendon and ligament injuries
Wang, Tao; Passini, Fabian S.; Snedeker, Jess Gerrit; et al. (2021)
Science Translational Medicine
Tendons and tendon interfaces have a very limited regenerative capacity, rendering their injuries clinically challenging to resolve. Tendons sense muscle-mediated load; however, our knowledge on how loading affects tendon structure and functional adaption remains fragmentary. Here, we provide evidence that the matricellular protein secreted protein acidic and rich in cysteine (SPARC) is critically involved in the mechanobiology of tendons and is required for tissue maturation, homeostasis, and enthesis development. We show that tendon loading at the early postnatal stage leads to tissue hypotrophy and impaired maturation of Achilles tendon enthesis in Sparc−/− mice. Treadmill training revealed a higher prevalence of spontaneous tendon ruptures and a net catabolic adaptation in Sparc−/− mice. Tendon hypoplasia was attenuated in Sparc−/− mice in response to muscle unloading with botulinum toxin A. In vitro culture of Sparc−/− three-dimensional tendon constructs showed load-dependent impairment of ribosomal S6 kinase activation, resulting in reduced type I collagen synthesis. Further, functional calcium imaging revealed that lower stresses were required to trigger mechanically induced responses in Sparc−/− tendon fascicles. To underscore the clinical relevance of the findings, we further demonstrate that a missense mutation (p.Cys130Gln) in the follistatin-like domain of SPARC, which causes impaired protein secretion and type I collagen fibrillogenesis, is associated with tendon and ligament injuries in patients. Together, our results demonstrate that SPARC is a key extracellular matrix protein essential for load-induced tendon tissue maturation and homeostasis.
Dynamic Microenvironments: The Fourth Dimension
Tibbitt, Mark W.; Anseth, Kristi S. (2012)
Science Translational Medicine
Reproducible quantification of cancer-associated proteins in body fluids using targeted proteomics
Hüttenhain, Ruth; Soste, Martin; Selevsek, Nathalie; et al. (2012)
Science Translational Medicine
Tissue-resident CD8+ T cells drive compartmentalized and chronic autoimmune damage against CNS neurons
Frieser, David; Pignata, Aurora; Khajavi, Leila; et al. (2022)
Science Translational Medicine
The mechanisms underlying the chronicity of autoimmune diseases of the central nervous system (CNS) are largely unknown. In particular, it is unclear whether tissue-resident memory T cells (TRM) contribute to lesion pathogenesis during chronic CNS autoimmunity. Here, we observed that a high frequency of brain-infiltrating CD8+ T cells exhibit a TRM-like phenotype in human autoimmune encephalitis. Using mouse models of neuronal autoimmunity and a combination of T single-cell transcriptomics, high-dimensional flow cytometry, and histopathology, we found that pathogenic CD8+ T cells behind the blood-brain barrier adopt a characteristic TRM differentiation program, and we revealed their phenotypic and functional heterogeneity. In the diseased CNS, autoreactive tissue-resident CD8+ T cells sustained focal neuroinflammation and progressive loss of neurons, independently of recirculating CD8+ T cells. Consistently, a large fraction of autoreactive tissue-resident CD8+ T cells exhibited proliferative potential as well as proinflammatory and cytotoxic properties. Persistence of tissue-resident CD8+ T cells in the CNS and their functional output, but not their initial differentiation, were crucially dependent on CD4+ T cells. Collectively, our results point to tissue-resident CD8+ T cells as essential drivers of chronic CNS autoimmunity and suggest that therapies targeting this compartmentalized autoreactive T cell subset might be effective for treating CNS autoimmune diseases.
Enhancing functional abilities and cognitive integration of the lower limb prosthesis
Petrini, Francesco M.; Valle, Giacomo; Bumbasirevic, Marko; et al. (2019)
Science Translational Medicine

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