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Biology subjects

Gonzalez-Freire, M.

Publications and source records attributed to Gonzalez-Freire, M..

3 recordsLinked to original sources

GDF15 and ACE2 stratify COVID19 patients according to severity while ACE2 mutations increase infection susceptibility.

Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and healthy control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility.

molecular biology↗

Aging skeletal muscle proteomics finds changes in spliceosome, immune factors, proteostasis and mitochondria

A progressive decline of skeletal muscle strength with aging is a primary cause of mobility loss and frailty in older persons, but the molecular mechanisms of such decline are not fully understood. Here, using quantitative discovery proteomic data from skeletal muscle specimens collected from 58 healthy persons aged 20 to 87 years show that ribosomal proteins and proteins related to energetic metabolism, including those related to the TCA cycle, mitochondria respiration, and glycolysis were underrepresented in older persons. Proteins with important roles in innate and adaptive immunity, involved in proteostasis and regulation of alternative splicing were all overrepresented in muscle from older persons. Changes with aging of alternative splicing were confirmed by RNA-seq. Overall, older muscle has a profound deficit of energetic metabolism, a pro-inflammatory environment and increased proteostasis. Upregulation of the splicing machinery maybe an attempt to compensate for these changes and this could be tested in future studies.

physiology↗

Automated methods for 3D Segmentation of Focused Ion Beam-Scanning Electron Microscopic Images

Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) is an imaging approach that enables analysis of the 3D architecture of cells and tissues at resolutions that are 1-2 orders of magnitude higher than that possible with light microscopy. The slow speeds of data collection and analysis are two critical problems that limit more extensive use of FIB-SEM technology. Here, we present a robust method that enables rapid, large-scale acquisition of data from tissue specimens, combined with an approach for automated data segmentation using machine learning, which dramatically increases the speed of image analysis. We demonstrate the feasibility of these methods through the 3D analysis of human muscle tissue by showing that our process results in an improvement in speed of up to three orders of magnitude as compared to manual approaches for data segmentation. All programs and scripts we use are open source and are immediately available for use by others.\n\nImpact StatementThe high-throughput, easy-to-use and versatile segmentation pipeline described in our manuscript will enable rapid, large-scale statistical analysis of sub-cellular structures in tissues.

cell biology↗