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One of the main topics of cardiovascular research is the study of calcium (Ca2+) handling, as even small changes in Ca2+ concentration can alter cell functionality (Bers, Annu Rev Physiol, 2014, 76, 107-127). Ionic calcium (Ca2+) plays the role of a second messenger in eukaryotic cells, associated with cellular functions such as cell cycle regulation, transport, motility, gene expression, and regulation. The use of fluorometric techniques in isolated cells loaded with Ca2+-sensitive fluorescent probes allows quantitative measurement of dynamic events occurring in living, functioning cells. The Cardiomyocytes Images Analyzer Python (CardIAP) application addresses the need to analyze and retrieve information from confocal microscopy images systematically, accurately, and rapidly. Here we present CardIAP, an open-source tool developed entirely in Python, freely available and useable in an interactive web application. In addition, CardIAP can be used as a standalone Python library and freely installed via PIP, making it easy to integrate into biomedical imaging pipelines. The images that can be generated in the study of the heart have the particularity of requiring both spatial and temporal analysis. CardIAP aims to open the field of cardiomyocytes and intact hearts image processing. The improvement in the extraction of information from the images will allow optimizing the usage of resources and animals. With CardIAP, users can run the analysis to both, the complete image, and portions of it in an easy way, and replicate it on a series of images. This analysis provides users with information on the spatial and temporal changes in calcium releases and characterizes them. The web application also allows users to extract calcium dynamics data in downloadable tables, simplifying the calculation of alternation and discordance indices and their classification. CardIAP aims to provide a tool that could assist biomedical researchers in studying the underlying mechanisms of anomalous calcium release phenomena.

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Background: SARS-CoV-2 infection is associated with a wide range of clinical manifestations and severity. Pediatric cases represent <10% of total cases, with a mortality rate below 1%. Data of correlation between SARS-CoV-2 viral load in respiratory samples and severity of disease in pediatric patients is scarce. The cycle threshold (CT) value for the detection of SARS-CoV-2 could be used as an indirect indicator of viral load in analyzed respiratory samples. Objective: The aim of this study was to describe CT values and their correlation with clinical manifestations, epidemiology and laboratory parameters in pediatric patients with confirmed COVID-19. Methods: In this observational, retrospective, analytic and single-center study we included patients under 15 years with confirmed COVID-19 by RT-PCR SARS-CoV-2 admitted to the Isidoro Iriarte Hospital (Argentina) between March 1st 2020 and April 30th 2021. Results: 485 patients were included, the distribution according to disease severity was: 84% (408 patients) presented mild disease, 12% (59 patients) moderate disease and 4% (18 patients) severe disease. Patients with moderate and severe illness had an increased hospitalization rate, prolonged hospitalization, higher frequency of comorbidities and oxygen and antibiotics use. CT values, that could be used as an indirect measure of viral load, was associated with severity of clinical manifestations and age under 12 months. No patient required admission to PICU nor mechanical ventilation. No deaths were registered. Conclusions: In this study, the viral load of SARS-CoV-2 in respiratory samples, determined by the cycle threshold, was significantly correlated with moderate to severe cases and with age.

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Promiscuous activities have been related to the capacity to catalyze reactions different from those a protein has evolved to sustain. In this work, we rethought the serum albumin's promiscuous behavior using evolutionary and structural analysis. We found that the cross aldol condensation of acetone and p-formylbenzonitrile is a promiscuous reaction conserved in humans serum albumin and in closely related albumins from other mammals. Evolutionary analysis indicates that the residues involved in this promiscuous reaction are evolving under positive selection, an evolutionary pattern indicating a putative functional adaptation. Also, key residues are located in an evolutionary conserved cavity connected with the protein surface with an also conserved tunnel and mutations involving these residues are described in human diseases. Overall, our results suggest that albumin could have evolved to sustain a still unknown biological function among the many others it maintains. Our results could contribute to better characterize the serum albumin family and raise questions about the evolution of protein promiscuity and function.

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Promiscuous behaviour in proteins and enzymes remains a challenging feature to understand the structure-function relationship. Here we present ProtMiscuity, a manually curated online database of proteins showing catalytic promiscuity. ProtMiscuity contains information about canonical and promiscuous activities comprising 88 different reactions in 57 proteins from 40 different organisms. It can be searched or browsed by protein names, organisms and descriptions of canonical and promiscuous reactions. Entries provide information on reaction substrates, products and kinetic parameters, mapping of active sites to sequence and structure and links to external resources with biological and functional annotations. ProtMiscuity could assist in studying the underlying mechanisms of promiscuous reactions by offering a unique and curated collection of experimentally derived data that is otherwise hard to find, retrieve and validate from literature.

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