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Garcia-Ruiz, A.

Publications and source records attributed to Garcia-Ruiz, A..

2 recordsLinked to original sources

Orsay virus infection is associated with reduced locomotion and alters cue-dependent food choice in Caenorhabditis elegans

Behavioral responses are an important component of host defense; however, most evidence in Caenorhabditis elegans comes from bacterial pathogens. Here, we tested whether infection with Orsay virus (OrV) alters host dispersal and food choice and whether these responses involve the RNA-processing factor EOL-1. When measuring distance travelled over a certain period of time in control and infected wild-type animals, we observed that OrV infection was associated with lower locomotion. Moreover, when presenting infected and control animals with food choices, we observed that infected animals preferred OrV infected food sources only when the alternative was a pure food source, preferring a non-inoculated food source when both control and viral food sources contained a C. elegans filtrate. Moreover, loss of EOL-1 altered baseline locomotion and attenuated the infection-associated reduction detected in the earlier motility assay, while also modifying the food choice response, suggesting that eol-1 contributes to the motility and behavioral changes induced by OrV infection. Collectively, these results support an overall association between OrV infection and reduced host dispersal, whereas its effect on food choice depends on the sensory context. These findings extend infection-associated behavioral responses to a natural viral pathogen and identify eol-1 as a modulator of their expression.

microbiology↗

Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4x10-9 per nt, we report that sun exposure creates pervasive mutations at sites with [~]100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3x10-5 per nt. Clonal expansion by neutral drift or passenger formation was nil. Tumor suppressor gene hotspots reached variant allele frequency 0.1-10% via 30-3,000 fold clonal expansion, in occasional biopsies. CPD hyperhotspots reached those frequencies in every biopsy, with modest clonal expansion. In vitro, tumor hotspot mutations arose occasionally over weeks of chronic low-dose exposure, whereas CPD hyperhotspot mutations arose in days at 1000-fold higher frequencies, growing exponentially. UV targeted mini-drivers in every skin cell.

genomics↗