Publications by authors named "Leonardo D Garma"

Article Synopsis
  • Epigenetic clocks estimate biological age based on DNA methylation, but older models may not work well with new technology like the EPICv2 array, which could render them obsolete.
  • In this study, researchers evaluated four existing epigenetic clocks against the new EPICv2 array and created a more effective model that works on multiple platforms, validated with thousands of samples.
  • The new model showed significant improvements, providing accurate age predictions and effectively detecting changes in epigenetic age related to cancer treatments and interventions, highlighting the need to update older models for better compatibility.
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The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson's disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD).

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Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangling the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq and spatial transcriptomics of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their inherent transcriptional structure in the human dorsal striatum. We propose a comprehensive taxonomy of striatal interneurons with eight main classes and fourteen subclasses, providing their full transcriptomic identity and spatial expression profile as well as additional quantitative FISH validation for specific populations.

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Article Synopsis
  • Dimensionality reduction techniques help scientists analyze big biological data, like COVID-19 info, using methods that can be tricky for students without math skills.
  • The study used easy examples and a 4-hour hands-on session with 15 students to teach these concepts using Python and Jupyter notebooks.
  • Most students found this method helpful, with many feeling more interested in Python and gaining useful research skills, showing that these teaching tools could help others learn better too.
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COVID-19 is associated with an increased risk of thrombotic events. However, the pathogenesis of these complications is unclear and reports on platelet infection and activation by the virus are conflicting. Here, we integrated single-cell transcriptomic data to elucidate whether platelet activation is a specific response to SARS-CoV-2 infection or a consequence of a generalized inflammatory state.

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3D vertical nanostructures have become one of the most significant methods for interfacing cells and the nanoscale and for accessing significant intracellular functionalities such as membrane potential. As this intracellular access can be induced by means of diverse cellular membrane poration mechanisms, it is important to investigate in detail the cell condition after membrane rupture for assessing the real effects of the poration techniques on the biological environment. Indeed, differences of the membrane dynamics and reshaping have not been observed yet when the membrane-nanostructure system is locally perturbed by, for instance, diverse membrane breakage events.

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Multi-electrode arrays (MEAs) have become a key element in the study of cellular phenomena in vitro. Common modern MEAs are still based on costly microfabrication techniques, making them expensive tools that researchers are pushed to reuse, compromising the reproducibility and the quality of the acquired data. There is a need to develop novel fabrication strategies, able to produce disposable devices that incorporate advanced technologies beyond the standard metal electrodes on rigid substrates.

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In vitro multi-electrode array (MEA) technology is nowadays involved in a wide range of applications beyond neuroscience, such as cardiac electrophysiology and bio-interface studies. However, the cost of commercially available acquisition systems severely limits its adoption outside specialized laboratories with high budget capabilities. Thus, the availability of low-cost methods to acquire signals from MEAs is important to allow research labs worldwide to exploit this technology for an ever-expanding pool of experiments independently from their economic possibilities.

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A total of six different structural alignment tools (TM-Align, TriangleMatch, CLICK, ProBis, SiteEngine and GA-SI) were assessed for their ability to perform two particular tasks: (i) discriminating FAD (flavin adenine dinucleotide) from non-FAD binding sites, and (ii) performing an all-to-all comparison on a set of 883 FAD binding sites for the purpose of classifying them. For the first task, the consistency of each alignment method was evaluated, showing that every method is able to distinguish FAD and non-FAD binding sites with a high Matthews correlation coefficient. Additionally, GA-SI was found to provide alignments different from those of the other approaches.

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A methodology for performing sequence-free comparison of functional sites in protein structures is introduced. The method is based on a new notion of similarity among superimposed groups of amino acid residues that evaluates both geometry and physico-chemical properties. The method is specifically designed to handle disconnected and sparsely distributed sets of residues.

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