RESUMEN
Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.
Asunto(s)
Proteína Ácida Fibrilar de la Glía/sangre , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/líquido cefalorraquídeo , Animales , Femenino , Humanos , Proteómica , Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , PorcinosRESUMEN
Trichomycete fungi are gut symbionts of arthropods living in aquatic habitats. The lack of a central platform with accessible collection records and associated ecological metadata has limited ecological investigations of trichomycetes. We present CIGAF (short for Collections of Insect Gut-Associated Fungi), a trichomycetes-focused digital database with interactive visualization functions enabled by the R Shiny web application. CIGAF curated 3120 collection records of trichomycetes across the globe, spanning from 1929 to 2022. CIGAF allows the exploration of nearly 100 years of field collection data through the web interface, including primary published data such as insect host information, collection site coordinates, descriptions and date of collection. When possible, specimen records are supplemented with climatic measures at collection sites. As a central platform of field collection records, multiple interactive tools allow users to analyze and plot data at various levels. CIGAF provides a comprehensive resource hub to the research community for further studies in mycology, entomology, symbiosis and biogeography.
Asunto(s)
Hongos , Insectos , Animales , Bases de Datos Factuales , Metadatos , Programas InformáticosRESUMEN
Calibrated simulations are used to study a dielectric modulated, electrically doped, dual metal gate, SiGe heterojunction, double gate TFET biosensor in this work. Use of lower bandgap SiGe at the source side helps in improving the ON current of the biosensor. Electric doping is preferred over physical doping to overcome the random dopant fluctuations and high thermal budget problems. Non-ideal situations having partially and non-uniformly filled cavity regions are analyzed in this work. Partially filled cavity has fill factor less than 100% and is studied by considering 50%, 20%, and 10% fill factors. Different positions of biomolecules inside a partially filled cavity are also studied through extensive simulations and are found to affect the sensitivity largely. Four different non-uniform profiles, decreasing, increasing, convex and concave, are created in the cavity region and their sensitivity values are compared for different dielectric constants (k) and charge densities ( Q Bio ). Among the different non-uniform profiles considered, maximum sensitivity is obtained for decreasing profile and it improves with an increase in dielectric constant and positive charge density while it decreases when negative charge density increases.