Browsing by Author "Rojas-Herrera, Marcelo"

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    Fecal Microbiome Characteristics and the Resistome Associated With Acquisition of Multidrug-Resistant Organisms Among Elderly Subjects
    (Frontiers Media S.A., 2019-09) Araos, Rafael; Battaglia, Thomas; Ugalde, Juan; Rojas-Herrera, Marcelo; Blaser, Martin; D'Agata, Erika
    Infections caused by multidrug-resistant organisms (MDRO) lead to considerable morbidity and mortality. The elderly population residing in nursing homes are a major reservoir of MDRO. Our objective was to characterize the fecal microbiome of 82 elderly subjects from 23 nursing homes and compare their resistome to that of healthy young persons. Comparisons of microbiome composition and the resistome between subjects who acquired MDRO or not were analyzed to characterize specific microbiome disruption indices (MDI) associated with MDRO acquisition. An approach based on both 16S rRNA amplicon and whole metagenome shotgun (WMS) sequencing data was used. The microbiome of the study cohort was substantially perturbed, with Bacteroides, Firmicutes, and Proteobacteria predominating. Compared to healthy persons, the cohort of elderly persons had an increased number, abundance, and diversity of antimicrobial resistance genes. High proportions of study subjects harbored genes for multidrug-efflux pumps (96%) and linezolid resistance (52%). Among the 302 antimicrobial resistance gene families identified in any subject, 60% were exclusively detected within the study cohort, including Class D beta-lactamase genes. Subjects who acquired MDRO or not had significant differences in bacterial taxa; Odoribacter laneus, and Akkermansia muciniphila were significantly greater among subjects who did not acquire MDRO whereas Blautia hydrogenotrophica predominated among subjects who acquired MDRO. These findings suggest that specific MDI may identify persons at high risk of acquiring MDRO.
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    Identification and characterization of miRNAs and lncRNAs of coho salmon (Oncorhynchus kisutch) in normal immune organs
    (Elsevier Inc, 2020) Leiva, Francisco; Rojas-Herrera, Marcelo; Reyes, Daniela; Bravo, Scarleth; García, Killen; Moya, Javier; Vidal, Rodrigo
    MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two relevant non-coding RNAs (ncRNAs) class. Oncorhynchus kisutch (coho salmon) is an important aquaculture pacific salmon species without report of miRNAs and a very limited register of lncRNAs. To gain knowledge about the interaction and discovery of miRNAs and lncRNAs in coho salmon we used high-throughput sequencing technology to sequence small and transcriptome libraries from three immune organs. A total of 163 mature miRNAs and 4,975 lncRNAs were discovered. The profiles of expression of both ncRNAs indicated that liver and head-kidney share relatively similar expression patterns. We identified 814 and 181 putative target sequences for 1048 lncRNAs and 47 miRNAs, respectively. The results obtained provide new information and enlarge our understanding of the diversities of ncRNAs in coho salmon.
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    Identification of genetic modifiers of murine hepatic β-glucocerebrosidase activity
    (2021) Durán, Anyelo; Rebolledo-Jaramillo, Boris; Olguin, Valeria; Rojas-Herrera, Marcelo; Las Heras, Macarena; Calderón, Juan F.; Zanlungo, Silvana; Priestman, David A.; Platt, Frances M.; Klein, Andrés
    The acid β-glucocerebrosidase (GCase) enzyme cleaves glucosylceramide into glucose and ceramide. Loss of function variants in the gene encoding for GCase can lead to Gaucher disease and Parkinson’s disease. Therapeutic strategies aimed at increasing GCase activity by targeting a modulating factor are attractive and poorly explored. To identify genetic modifiers, we measured hepatic GCase activity in 27 inbred mouse strains. A genome-wide association study (GWAS) using GCase activity as a trait identified several candidate modifier genes, including Dmrtc2 and Arhgef1 (p=2.1x10− 7 ), and Grik5 (p=2.1x10− 7 ). Bayesian integration of the gene mapping with transcriptomics was used to build integrative networks. The analysis uncovered additional candidate GCase regulators, highlighting modules of the acute phase response (p=1.01x10− 8 ), acute inflammatory response (p=1.01x10− 8 ), fatty acid beta-oxidation (p=7.43x10− 5 ), among others. Our study revealed previously unknown candidate modulators of GCase activity, which may facilitate the design of therapies for diseases with GCase dysfunction.

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