Determining how genetic polymorphisms enable certain fungi to persist in mammalian hosts can improve understanding of opportunistic fungal pathogenesis, a source of substantial human morbidity and mortality. We examined the genetic basis of fungal persistence in mice using a cross between a clinical isolate and the lab reference strain of the budding yeast Saccharomyces cerevisiae. Employing chromosomally-encoded DNA barcodes, we tracked the relative abundances of 822 genotyped, haploid segregants in multiple organs over time and performed linkage mapping of their persistence in hosts. Detected loci showed a mix of general and antagonistically pleiotropic effects across organs. General loci showed similar effects across all organs, while antagonistically pleiotropic loci showed contrasting effects in the brain versus the kidneys, liver, and spleen. Persistence in an organ required both generally beneficial alleles and organ-appropriate pleiotropic alleles. This genetic architecture resulted in many segregants persisting in the brain or in non-brain organs, but few segregants persisting in all organs. These results show complex combinations of genetic polymorphisms collectively cause and constrain fungal persistence in different parts of the mammalian body.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration.

Determining how genetic polymorphisms enable certain fungi to persist in mammalian hosts can improve understanding of opportunistic fungal pathogenesis, a source of substantial human morbidity and mortality. We examined the genetic basis of fungal persistence in mice using a cross between a clinical isolate and the lab reference strain of the budding yeast Saccharomyces cerevisiae. Employing chromosomally-encoded barcodes, we tracked the relative abundances of 822 genotyped, haploid segregants in multiple organs over time and performed linkage mapping of their persistence in hosts. Detected loci showed a mix of general and antagonistically pleiotropic effects across organs. General loci showed similar effects across all organs, while antagonistically pleiotropic loci showed contrasting effects in the brain and the kidneys, liver, and spleen. Persistence in an organ required both generally beneficial alleles and organ-appropriate pleiotropic alleles. This genetic architecture resulted in many segregants persisting in the brain or in non-brain organs, but few segregants persisting in all organs. These results show complex combinations of genetic polymorphisms collectively cause and constrain fungal persistence in different parts of the mammalian body.

Evaluación fenotípica y molecular de alelos de los genes Ppd-1 en una población biparental de trigo pan Lombardo, L. A., Nisi, M. M., Ghione, C. E., Fisore, G. D. y Helguera, M.resumen El constante incremento de las temperaturas -como consecuencia del cambio climático-en las regiones donde se cultiva trigo, exige ajustar el ciclo del cultivo a períodos más cortos para evitar o disminuir los estreses causados por las altas temperaturas. En este sentido, el descubrimiento de fuentes genéticas innovadoras de modulación de la espigazón, así como también el desarrollo de herramientas moleculares que permitan capitalizarlas, tienen un rol central en el mejoramiento de este cultivo. En el presente estudio se evalúa, bajo condiciones controladas, el efecto de los genes Ppd-1 sobre la espigazón en una población biparental de trigo pan. Para tal fin, se desarrollaron marcadores moleculares inéditos para los genes Ppd-A1 y Ppd-B1. Los resultados obtenidos muestran un efecto desigual de los loci Ppd-1 (Ppd-A1, Ppd-B1 y Ppd-D1) sobre la respuesta al fotoperíodo. Ppd-D1 fue el locus con mayor efecto sobre la respuesta al fotoperíodo, mientras que Ppd-B1 y Ppd-A1 presentaron un efecto menor y nulo, respectivamente. Se concluye de este estudio, que la estimulación en condiciones de días largos no es un proceso esencial para que se produzca la espigazón en el trigo. The constant increase in temperatures, as a consequence of climate change, affects the regions where wheat is grown and thus demands an adjustment of crop cycle to shorter periods with the purpose of decreasing the high temperature stress. Therefore, the discovery of new genetic sources of flowering modulation and the development of molecular tools that enable their use, take a main role in wheat breeding. In this study, the effect of Ppd-1 on flowering time was evaluated in a bread wheat biparental population, under controlled conditions. Novel molecular markers for Ppd-A1 and Ppd-B1 genes were developed. The results showed an unequal effect of Ppd-1 loci (Ppd-A1, Ppd-B1 and Ppd-D1) on photoperiod response. Ppd-D1 was the locus with the Fecha de recepción: 23/03/2017; fecha de aceptación: 13/11/2017. AGRISCIENTIA, 2017, VOL. 34 (II): 45-57 46 AGRISCIENTIA greatest effect on photoperiod response, while Ppd-B1 and Ppd-A1 presented minor and null effects, respectively. It could be concluded that long day stimulation is not essential to wheat flowering.