Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

Background Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease. Methods In this study, we have analyzed a mouse model containing the p.A216P mutation in Prpf31 gene. Results We found that mutant Prpf31 protein produces cytoplasmic aggregates in the retinal pigment epithelium and decreasing the protein levels of this splicing factor in the nucleus. Additionally, normal protein was recruited in insoluble aggregates when the mutant protein was overexpressed in vitro. In response to protein aggregation, Hspa4l is overexpressed. This member of the HSP70 family of chaperones might contribute to the correct folding and solubilization of the mutant protein, allowing its translocation to the nucleus. Conclusions Our data suggests that a mechanism haploinsufficiency and dominant-negative is involved in retinal degeneration due to mutations in PRPF31. HSP70 over-expression might be a new therapeutic target for the treatment of retinal degeneration due to PRPF31 mutations.This project has been financed through a) The ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071. b) The European Union’s Horizon 2020 research and innovation program, under grant agreement No 634479. c) Regional Ministry of Economy, Innovation and Science of the Junta de Andalucía, No P09-CTS-04967.info:eu-repo/semantics/publishedVersio

Multiwavelength Photometric and Spectropolarimetric Analysis of the FSRQ 3C 279

In this paper, we present light curves for 3C 279 over a time period of six years; from 2008 to 2014. Our multiwavelength data comprise 1 mm to gamma-rays, with additional optical polarimetry. Based on the behaviour of the gamma-ray light curve with respect to other bands, we identified three different activity periods. One of the activity periods shows anomalous behaviour with no gamma-ray counterpart associated with optical and NIR flares. Another anomalous activity period shows a flare in gamma-rays, 1 mm and polarization degree, however, it does not have counterparts in the UV continuum, optical and NIR bands. We find a significant overall correlation of the UV continuum emission, the optical and NIR bands. This correlation suggests that the NIR to UV continuum is co-spatial. We also find a correlation between the UV continuum and the 1 mm data, which implies that the dominant process in producing the UV continuum is synchrotron emission. The gamma-ray spectral index shows statistically significant variability and an anti-correlation with the gamma-ray luminosity. We demonstrate that the dominant gamma-ray emission mechanism in 3C 279 changes over time. Alternatively, the location of the gamma-ray emission zone itself may change depending on the activity state of the central engine.Comment: 32 pages, 19 figures, Accepted for publication in MNRA

Tunable ferromagnetic resonance in coupled trilayers with crossed in-plane and perpendicular magnetic anisotropies

An original approach to tune the ferromagnetic resonance frequency of a soft magnetic Ni80Fe20 (Permalloy = Py) film with in-plane magnetic anisotropy (IMA) based on the controlled coupling to a hard magnetic NdCox film with perpendicular magnetic anisotropy (PMA) through a nonmagnetic Al spacer is studied. Using the transverse magneto-optical Kerr effect (T-MOKE), alternating gradient magnetometry (AGM), and vector network analyzer ferromagnetic resonance (VNA-FMR) spectroscopy, the influence of both the Co concentration and the Al spacer thickness on the static and dynamic magnetic properties of the coupled IMA/PMA system is investigated. Compared to a single Py film, two striking effects of the coupling between IMA and PMA layers can be observed in their FMR spectra. First, there is a significant increase in the zero-field resonance frequency from 2.0 GHz up to 6.4 GHz, and second, an additional frequency hysteresis occurs at low magnetic fields applied along the hard axis. The maximum frequency difference between the frequency branches for increasing and decreasing magnetic fields is as high as 1 GHz, corresponding to a tunability of about 20% at external fields of typically less than ±70 mT. The origin of the observed features in the FMR spectra is discussed by means of magnetization reversal curves

La universidad y la promoción del cambio social

Aunque pensar en la universidad no es cosa nueva, y mucho menos pensar en el cambio social, sí resulta actual y necesaria la revisión de los esfuerzos universitarios modernos, traducidos en hechos concretos, porque forman parte de la dinámica de transformación social que se desarrolla en su entorno; cuestión que, en ocasiones, se desenvuelve frente a nosotros aún sin que podamos simplemente reconocerla. Para superar este estado de puro reconocimiento, múltiples universidades en el país han desarrollado modalidades diversas de participación en los grandes y pequeños procesos de cambio social intencionado. Ello ha cuestionado, en cierta medida, el ser y el quehacer de la propia universidad.ITESO, A.C.Fundación Friedrich NaumannPraxi

Biotreatments Using Microbial Mixed Cultures with Crude Glycerol and Waste Pinewood as Carbon Sources: Influence of Application on the Durability of Recycled Concrete

[EN] Two eco-friendly healing bioproducts generated from microbial mixed cultures (MMC) for the production of polyhydroxyalkanoates (PHA) were used as surface treatments, with two resid- ual materials used as the substrates, namely crude glycerol and pinewood bio-oil. Their ability to im- prove the durability of concrete samples containing recycled aggregates was assessed. To determine this protective capacity, 180 samples were analyzed using different tests, such as water penetration under pressure, capillary absorption, freeze–thaw and water droplet absorption test. Three types of conditions were used: outdoor–indoor exposure, re-application of biopolymers and application in vertical exposure conditions. The results showed reductions of up to 50% in the water penetration test and a delay in the water droplet absorption test of up to 150 times relative to the reference. The surface application of these bioproducts significantly reduced the degree of water penetration in recycled concrete, increasing its useful lifespan and proving to be a promising treatment for protecting concrete surfaces

Biotreatments Using Microbial Mixed Cultures with Crude Glycerol and Waste Pinewood as Carbon Sources: Influence of Application on the Durability of Recycled Concrete

BIA2017-83526-R LA/P/0140/2020 LAQV-UIDB/50006/2020Two eco-friendly healing bioproducts generated from microbial mixed cultures (MMC) for the production of polyhydroxyalkanoates (PHA) were used as surface treatments, with two residual materials used as the substrates, namely crude glycerol and pinewood bio-oil. Their ability to improve the durability of concrete samples containing recycled aggregates was assessed. To determine this protective capacity, 180 samples were analyzed using different tests, such as water penetration under pressure, capillary absorption, freeze–thaw and water droplet absorption test. Three types of conditions were used: outdoor–indoor exposure, re-application of biopolymers and application in vertical exposure conditions. The results showed reductions of up to 50% in the water penetration test and a delay in the water droplet absorption test of up to 150 times relative to the reference. The surface application of these bioproducts significantly reduced the degree of water penetration in recycled concrete, increasing its useful lifespan and proving to be a promising treatment for protecting concrete surfaces.publishersversionpublishe

Stable nitrogen isotope studies of the pelagic food web on the Atlantic shelf of the Iberian Peninsula

Publicado

Caracterización de PRPF31

Motivación: La retinitis pigmentosa es un grupo heterogéneo de distrofias retinales caracterizada por una progresiva degeneración de los fotorreceptores, que acaba produciendo deficiencia visual o ceguera. PRPF31 es uno de los genes cuya mutación causa este tipo de distrofia. Aunque la proteína Prpf31 es un factor de splicing presente en todo el organismo, su mutación sólo produce distrofia retinal. Actualmente no se conoce el mecanismo implicado en la enfermadad, por lo que intentaremos discernirlo con ayuda de este proyecto.Métodos: Utilizando la secuencia del gen PRPF31, planteamos clonarla en el vector p3XFLAG y transfectar con la construcción células de mamífero. La fusión con FLAG facilitará los estudios de localización subcelular y de las interacciones por inmunoprecipitación. Transfectaremos con la construcción las líneas celulare RPE1, derivada de epitelio pigmentario de la retina (RPE) humana y 293, para estudiar la localización y las interacciones de Prpf31 con otras proteínas, con el objetivo de estudiar la base molecular de la enfermedad y poder desarrollar terapias génicas, farmacológicas y/o celulares. Resultados: La clonación de la secuencia de PRPF31 aún está en proceso ya que no hemos obtenido la construcción diseñada a pesar de probar diversos métodos. Se han empezado a poner a punto las condiciones de transfección usando otra construcción similar, tanto con la línea 293 como con RPE1. Se ha estudiado la distribución de Prpf31 en retina y RPE de ratón por western blot, mostrando una mayor abundancia en RPE, lo que no es común a otros factores de splicing como el PRPF3 y PRPF8, con los que se ha comparado. Conclusiones: PRPF31 debe tener alguna función específica en RPE, aún por definir, por lo que la degeneración de los fotorreceptores será secundaria a una disfunción del RPE. Hay otros casos en los que un gen presenta una función específicamente diferente en la retina, como en el caso de ATR, que causa síndrome de Seckel. ATR es un controlador de la división celular, pero en la retina este gen es crítico para el desarrollo postnatal de los fotorreceptores, por lo que su mutación causa degeneraciónen la retina

Root Structure and Growth in Diverse Soils

Unlike most biofuel species, Jatropha curcas has promise for use in marginal lands, but it may serve an additional role by stabilizing soils. We evaluated the growth and structural responsiveness of young J. curcas plants to diverse soil conditions. Soils included a sand, a sandy-loam, and a clay-loam from eastern Mexico. Growth and structural parameters were analyzed for shoots and roots, although the focus was the plasticity of the primary root system architecture (the taproot and four lateral roots). The sandy soil reduced the growth of both shoot and root systems significantly more than sandy-loam or clay-loam soils; there was particularly high plasticity in root and shoot thickness, as well as shoot length. However, the architecture of the primary root system did not vary with soil type; the departure of the primary root system from an index of perfect symmetry was 14 ± 5% (mean ± standard deviation). Although J. curcas developed more extensively in the sandy-loam and clay-loam soils than in sandy soil, it maintained a consistent root to shoot ratio and root system architecture across all types of soil. This strong genetic determination would make the species useful for soil stabilization purposes, even while being cultivated primarily for seed oil