Search bioRxiv⌕ Search

Biology subjects

Garcia-Lopez, R.

Publications and source records attributed to Garcia-Lopez, R..

3 recordsLinked to original sources

ATG4D loss leads to late-onset cardiomyopathy and stress-induced heart failure in mice, and its repression marks maladaptive cardiac remodeling in humans

In the last years, autophagy has emerged as an essential pathway for most cellular functions. Basal autophagy plays a protective role as a quality control mechanism by which damaged or noxious cellular components are degraded and cellular organelles are periodically renewed. Moreover, autophagic activity can be increased in situations of cellular stress, including nutrient or growth factor deprivation, hypoxia, reactive oxygen species, DNA damage, or the presence of intracellular pathogens. Normally, induction of autophagy is protective, although in some circumstances, such as conditions of hemodynamic stress, autophagosome accumulation upon autophagy induction can be a maladaptive process. The deficiency of the autophagic protease ATG4D in mice leads to the accumulation of cellular autophagosomes in most tissues, including the heart. Here, we show that the increased autophagosome content of atg4d-/- mice is linked to the development of late-onset cardiomyopathy and to increased susceptibility to heart failure induced by transverse aortic constriction. Furthermore, we report the existence of human ATG4D variants associated with cardiovascular pathologies and also that ATG4D expression is reduced in human obstructive hypertrophic cardiomyopathy and dilated cardiomyopathy, which highlights a conserved cardio-protective role of the ATG4D protease.

pathology↗

Regional epidemic dynamics and Delta variant diversity resulted in varying rates of spread of Omicron-BA.1 in Mexico

The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In Mexico, this subvariant began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in the country. Unlike previous SARS-CoV-2 variants, BA.1 did not acquire local substitutions nor exhibited a geographically distinct circulation pattern in Mexico. However, a regional difference in the speed of the replacement of the Delta variant was observed, as some northern states showed persistence of Delta lineages well into February 2022. Mexican states were divided into four regions (North, Central North, Central South, and Southeast) based on the lineage circulation before the dominance of BA.1 to study possible causes for this difference. For each region, the time to fixation of BA.1, the diversity of Delta sublineages in the weeks preceding BA.1 entry, the population density, and the level of virus circulation during the inter-wave interval were determined. An association between a faster Omicron spread and lower Delta diversity, as well as fewer COVID-19 cases during the Delta-BA.1.x inter-wave period, was observed. For example, the North region exhibited the slowest spread but had the highest diversity of Delta sublineages and the greatest number of inter-wave cases relative to the maximum amount of the virus circulating in the region, whereas the Southeast region showed the opposite. Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics. Nonetheless, if there is a significant difference in the fitness of the variants or the time allowed for the competition is sufficient, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico. Impact statementThe surveillance of lineage circulation of SARS-CoV-2 has helped identify variants that have a transmission advantage and are of concern to public health and to track the virus dispersion accurately. However, many factors contributing to differences in lineage spread dynamics beyond the acquisition of specific mutations remain poorly understood. In this work, a description of BA.1 entry and dispersion within Mexico is presented, and which factors potentially affected the spread rates of the Omicron variant BA.1 among geographical regions in the country are analyzed, underlining the importance of population density, the proportion of active cases, and viral lineage diversity and identity before the entry of BA.1. Data summaryThis work was carried out using data shared through the GISAID initiative. All sequences and metadate are available through GISAID with the accession EPI_SET_220927gw, accession numbers and metadata are also reported in the supplemental material of this article. Epidemiological data was obtained though the Secretaria de Salud website (https://www.gob.mx/salud/documentos/datos-abiertos-152127),

microbiology↗

Gut Microbiome Analysis In Adult Tropical Gars (Atractosteus tropicus)

Tropical gar (Atractosteus tropicus), is freshwater and estuarine fish that has inhabited the Earth since the Mesozoic era, undergoing limited physiological variation ever since. This omnivorous fish is endemic to southern Mexico and part of Central America. Besides its recognized cultural and scientific relevance, the species has seen remarkable growth in its economic impact due to pisciculture. Previous studies have highlighted the role of microbial communities in fish, particularly those in the gut microbiome, in maintaining their host homeostasis or disease. In this study, we present the first report of the whole taxonomic composition of microbial communities in gut contents of adults A. tropicus, by sex (female/male) and origin (wild/cultivated). Using culture-independent techniques, we extracted metagenomic DNA that was used for high throughput 16S rDNA profiling by amplifying the V4 - V5 hypervariable regions of the bacterial gene. A total of 364,735 total paired-end reads were obtained on an Illumina MiSeq sequencing platform, belonging to 508 identified genera, with the most and least abundant are Cetobacterium, Edwardsiella, Serratia, Clostridium sensu stricto, Paludibacter and Campylobacter, Snodgrassella, Albirhodobacter, Lentilitoribacter, respectively. We detected that, by sex and origin, Proteobacteria, Fusobacteria, Firmicutes and Bacteroidetes phyla are the core gut microbiome of the adults A. tropicus. We discover the Deinococcus-Thermus phylum sequence, wildtype males only, with extremophile capacity in another freshwater fish. We also identified the species Lactococcus lactis strains CAU929 and CAU6600, Cp6 and CAU9951, Cetobacterium strain H69, Aeromonas hydrophila strains P5 and WR-5-3-2, Aeromonas sobria strain CP DC28 and Aeromonas hydrophila with probiotic potential in aquaculture within the three dominant phyla, especially in wild-type organisms.

microbiology↗