Biology subjects

Castro, E.

Publications and source records attributed to Castro, E..

22 records · Page 2Linked to original sources

bioRxiv2021

Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge

Early events in the host response to SARS-CoV-2 are thought to play a major role in determining disease severity. During pulmonary infection, the virus encounters both myeloid and epithelioid lineage cells that can either support or restrict pathogen replication as well as respond with host protective versus detrimental mediators. In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guerin (BCG) has been reported to confer non-specific resistance to unrelated pulmonary pathogens, a phenomenon attributed to the induction of long-lasting alterations within the myeloid cell compartment. Here we demonstrate that prior intravenous, but not subcutaneous, administration of BCG protects human-ACE2 transgenic mice against lethal challenge with SARS-CoV-2 and results in reduced viral loads in non-transgenic animals infected with an alpha variant. The observed increase in host resistance was associated with reductions in SARS-CoV-2-induced tissue pathology, inflammatory cell recruitment and cytokine production that multivariate analysis revealed to be only partially related to diminished viral load. We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and the ensuing immunopathology.

immunology↗

bioRxiv2021

Eosinophils are an integral component of the pulmonary granulocyte response in Tuberculosis and promote host resistance in mice

Host resistance to Mycobacterium tuberculosis infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. Influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, employing complementary genetic models of eosinophil deficiency, we demonstrate that, in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.

immunology↗

bioRxiv2021

MVD-Fuse: Detection of White Matter Degeneration via Multi-View Learning of Diffusion Microstructure

Detecting neuro-degenerative disorders in early-stage and asymptomatic patients is challenging. Diffusion MRI (dMRI) has shown great success in generating biomarkers for cellular organization at the microscale level using complex biophysical models, but there has never been a consensus on a clinically usable standard model. Here, we propose a new framework (MVD-Fuse) to integrate measures of diverse diffusion models to detect alterations of white matter microstructure. The spatial maps generated by each measure are considered as a different diffusion representation (view), the fusion of these views being used to detect differences between clinically distinct groups. We investigate three different strategies for performing intermediate fusion: neural networks (NN), multiple kernel learning (MKL) and multi-view boosting (MVB). As a proof of concept, we applied MVD-Fuse to a classification of premanifest Huntingtons disease (pre-HD) individuals and healthy controls in the TRACK-ON cohort. Our results indicate that the MVD-Fuse boosts predictive power, especially with MKL (0.90 AUC vs 0.85 with the best single diffusion measure). Overall, our results suggest that an improved characterization of pathological brain microstructure can be obtained by combining various measures from multiple diffusion models.

neuroscience↗

bioRxiv2020

Shark movements in the Revillagigedo Archipelago and connectivity with the Eastern Tropical Pacific

Long-distance movements of sharks within and between islands pose substantial challenges for resource managers working with highly migratory species. When no-take zones do not cover the critical areas that sharks use as part of their lifecycle, exposure to fishing activities can be significant. Shark movements between the Marine Protected Areas (MPAs) of the Eastern Tropical Pacific (ETP) have been studied for several years, however little is known about the strength of connectivity between these islands. We analyzed the extensive MigraMar ultrasonic telemetry dataset to assess how Galapagos sharks (Carcharhinus galapagensis) and silky sharks (Carcharhinus falciformis) use different islands as stepping-stones during their migrations within the Revillagigedo National Park and other ETP islands. Of the 66 sharks monitored, 63.5% moved within the same island, 25.4% between two islands or more and only 10.1% across different MPAs. A C. falciformis tagged in Roca Partida Island, Revillagigedo, travelled to Clipperton Atoll and another one tagged in Darwin Island travelled to the atoll on two different years. The largest movement of C. galapagensis was accomplished by a shark tagged at Socorro Island, Revillagigedo, later detected at Clipperton and finally recorded in Darwin Island, Galapagos. This last path was in fact, one of the longest movements ever recorded for the species. Although long-distance dispersion was not common, our results highlight the need for co-operation between different countries to ensure adequate protection for sharks in the form of swimways and other conservation tools in the ETP.

ecology↗