Browsing by Author "Martinez, Alexis"

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    Genomics of Re-Emergent Aeromonas salmonicida in Atlantic Salmon Outbreaks
    (2024) Godoy, Marcos; Montes de Oca, Marco; Suarez, Rudy; Martinez, Alexis; Pontigo, Juan Pablo; Caro, Diego; Kusch, Karina; Coca, Yoandy; Bohle, Harry; Bayliss, Sion; Kibenge, Molly; Kibenge, Frederick
    Furunculosis, caused by Aeromonas salmonicida, poses a significant threat to both salmonid and non-salmonid fish in diverse aquatic environments. This study explores the genomic intricacies of re-emergent A. salmonicida outbreaks in Atlantic salmon (Salmo salar). Previous clinical cases have exhibited pathological characteristics, such as periorbital hemorrhages and gastrointestinal abnormalities. Genomic sequencing of three Chilean isolates (ASA04, ASA05, and CIBA_5017) and 25 previously described genomes determined the pan-genome, phylogenomics, insertion sequences, and restriction-modification systems. Unique gene families have contributed to an improved understanding of the psychrophilic and mesophilic clades, while phylogenomic analysis has been used to identify mesophilic and psychrophilic strains, thereby further differentiating between typical and atypical psychrophilic isolates. Diverse insertion sequences and restriction-modification patterns have highlighted genomic structural differences, and virulence factor predictions can emphasize exotoxin disparities, especially between psychrophilic and mesophilic strains. Thus, a novel plasmid was characterized which emphasized the role of plasmids in virulence and antibiotic resistance. The analysis of antibiotic resistance factors revealed resistance against various drug classes in Chilean strains. Overall, this study elucidates the genomic dynamics of re-emergent A. salmonicida and provides novel insights into their virulence, antibiotic resistance, and population structure.
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    New Insights into the Spontaneous Human Alzheimer's Disease-Like Model Octodon degus : Unraveling Amyloid-beta Peptide Aggregation and Age-Related Amyloid Pathology
    (2018) Cisternas, Pedro; Zolezzi, Juan M.; Lindsay, Carolina; Rivera, Daniela S.; Martinez, Alexis; Bozinovic Kuscevic, Francisco; Inestrosa Cantín, Nibaldo
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    The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease
    (2020) Onate, Maritza; Catenaccio, Alejandra; Salvadores, Natalia; Saquel, Cristian; Martinez, Alexis; Moreno-Gonzalez, Ines; Gamez, Nazaret; Soto, Paulina; Soto, Claudio; Hetz, Claudio; Court, Felipe A.
    Parkinson's disease (PD) is the second most common neurodegenerative condition, characterized by motor impairment due to the progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine release in the striatum. Accumulating evidence suggest that degeneration of axons is an early event in the disease, involving destruction programs that are independent of the survival of the cell soma. Necroptosis, a programmed cell death process, is emerging as a mediator of neuronal loss in models of neurodegenerative diseases. Here, we demonstrate activation of necroptosis in postmortem brain tissue from PD patients and in a toxin-based mouse model of the disease. Inhibition of key components of the necroptotic pathway resulted in a significant delay of 6-hydroxydopamine-dependent axonal degeneration of dopaminergic and cortical neurons in vitro. Genetic ablation of necroptosis mediators MLKL and RIPK3, as well as pharmacological inhibition of RIPK1 in preclinical models of PD, decreased dopaminergic neuron degeneration, improving motor performance. Together, these findings suggest that axonal degeneration in PD is mediated by the necroptosis machinery, a process here referred to as necroaxoptosis, a druggable pathway to target dopaminergic neuronal loss.