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Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes.

Background: Alzheimer's disease (AD) may present retinal changes before brain pathology, suggesting the retina as an accessible biomarker of AD. The present work is a diachronic study using spectral domain optical coherence tomography (SD-OCT) to determine the total retinal thickness and retinal nerve fiber layer (RNFL) thickness in an APPNL−F/NL−F mouse model of AD at 6, 9, 12, 15, 17, and 20 months old compared to wild type (WT) animals. Methods: Total retinal thickness and RNFL thickness were determined. The mean total retinal thickness was analyzed following the Early Treatment Diabetic Retinopathy Study sectors. RNFL was measured in six sectors of axonal ring scans around the optic nerve. Results: In the APPNL−F/NL−F group compared to WT animals, the total retinal thickness changes observed were the following: (i) At 6-months-old, a significant thinning in the outer temporal sector was observed; (ii) at 15-months-old a significant thinning in the inner temporal and in the inner and outer inferior retinal sectors was noticed; (iii) at 17-months-old, a significant thickening in the inferior and nasal sectors was found in both inner and outer rings; and (iv) at 20-months-old, a significant thinning in the inner ring of nasal, temporal, and inferior retina and in the outer ring of superior and temporal retina was seen. In RNFL thickness, there was significant thinning in the global analysis and in nasal and inner-temporal sectors at 6 months old. Thinning was also found in the supero-temporal and nasal sectors and global value at 20 months old. Conclusions: In the APPNL−F/NL−F AD model, the retinal thickness showed thinning, possibly produced by neurodegeneration alternating with thickening caused by deposits and neuroinflammation in some areas of the retina. These changes over time are similar to those observed in the human retina and could be a biomarker for AD. The APPNL−F/NL−F AD model may help us better understand the different retinal changes during the progression of AD.

Se estudió el efecto del prebiótico inulina y ácido fúlvico, adicionados en el alimento, sobre el crecimiento, supervivencia, prevalencia de WSSV y sistema inmune de Litopenaeus vannamei. Para esto, se realizó un bioensayo, con tratamientos por triplicado, donde se probaron diferentes concentraciones de los aditivos. Se hizo un análisis de WSSV en organismos infectados con una carga viral relativamente alta utilizando la PCR sencilla y anidada. Al final del bioensayo se extrajo la hemolinfa y se estudió el sistema inmune en hemocitos a nivel bioquímico y genético (PCR cuantitativo). El peso final fue similar en todos los tratamientos y la supervivencia estuvo entre 66,7% y 93,3%. La prevalencia de WSSV disminuyó un 13% respecto al control. El número de hemocitos, la actividad de la fenoloxidasa y la concentración de anión superóxido fueron similares en todos los tratamientos. Los aditivos modularon la expresión de los genes transglutaminasa, superóxido dismutasa y profenoloxidasa, pero no la del receptor Toll. Los aditivos no afectan negativamente el crecimiento y protegen al camarón contra WSSV en organismos infectados con una carga viral relativamente alta. No se observó efecto de los aditivos en los efectores del sistema inmune estudiados a nivel bioquímico pero si modularon la expresión de algunos genes relacionados con el sistema inmune en L. vannamei. The effect of inulin and fulvic acid, added in the feed, on growth, survival, WSSV prevalence, and immune system was studied in Litopenaeus vannamei. To the above, a bioassay, with treatments in triplicate, was performed to test different additive concentrations. WSSV analysis was done in organisms infected with a relatively high viral load using single and nested PCR. At the end of the bioassay, hemolymph was extracted and the immune system was studied in hemocytes at biochemical and genetic level (quantitative PCR). The final growth was similar in all treatments and survival was between 66,7% and 93,3%. WSSV prevalence decreased 13% as compared to control. The number of hemocytes, phenoloxidase activity, and superoxide anion concentration were similar in all treatments. Inulin and fulvic acid modulated the expression of transglutaminase, superoxide dismutase, and prophenoloxidase genes, but not the Toll receptor. Additives do not negatively affect growth of white shrimp and they protect them against WSSV when infected with a relatively high viral load. Additives did not affect the immune system effectors studied at biochemical level but they modulated the expression of some immune-related genes in L. vannamei.

11p.-5 fig.-1 tab., The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well as its crucial role as a regulator of inflammation. Here, we have compared a cohort wild-type and AhR-null mice along aging to study the relationship between this receptor and age-associated inflammation, termed as "inflammaging," both at a systemic and the CNS level. Our results show that AhR deficiency is associated with a premature aged phenotype, characterized by early inflammaging, as shown by an increase in plasma cytokines levels. The absence of AhR also promotes the appearance of brain aging anatomic features, such as the loss of the white matter integrity. In addition, AhR-/- mice present an earlier spatial memory impairment and an enhanced astrogliosis in the hippocampus when compared with their age-matched AhR+/+ controls. Importantly, we have found that AhR protein levels decrease with age in this brain structure, strongly suggesting a link between AhR and aging.-Bravo-Ferrer, I., Cuartero, M. I., Medina, V., Ahedo-Quero, D., Peña-Martínez, C., Pérez-Ruíz, A., Fernández-Valle, M. E., Hernández-Sánchez, C., Fernández-Salguero, P. M., Lizasoain, I., Moro, M. A. Lack of the aryl hydrocarbon receptor accelerates aging in mice., This work was supported by the Spanish Ministry of Economy and Competitiveness (Grants SAF2015-68632-R and SAF2016-81716-REDC to M.A.M.), Instituto de Salud Carlos III,cofinanced by Fondo Europeo de Desarrollo Regional (FEDER) Una Manera de Hacer Europa (Grants PI17/01601 and RD16/0019/0009 to I.L.), and the Regional Madrid Government (Grant B2017/BMD-3688 to I.L.).

The effect of Echinacea purpurea and Uncaria tomentosa on growth performance, survival, WSSV prevalence, and immune response of Litopenaeus vannamei was evaluated under laboratory conditions. Powder of plants (PP) was sprayed onto feed (Nutrimentos Acuicolas Azteca S.A. de C.V.®, 35% protein) at 0, 0.5, 1.0, 2.0, and 4.0 g kg feed- 1. A bioassay, performed with treatments in triplicate, was conducted for 30 days. Feed supplemented with plants did not enhance growth and survival. However, PP decreased the prevalence of WSSV in shrimp treated (83.3, 50.0, 16.6, and 8.3%) as compared with the control group (100%). The PP significantly increased the activity of phenoloxidase in plasma in shrimp fed 4 g kg feed- 1. The results indicate that PP at concentrations of 2.0 and 4.0 g kg feed- 1 is a suitable feed additive against WSSV in shrimp with low viral load.

La incidencia de las enfermedades virósicas en plantas, normalmente son realizadas observando sintomatologías típicas; método por el cual no se tienen resultados certeros. El presente trabajo tuvo como propósito determinar la incidencia y distribución del Rayado fino del maíz, causado por el Maize rayado fino virus (MRFV), Moteado clorótico del maíz, causado por el Maize chlorotic mottle virus (MCMV) y el Mosaico de la grama china, causado por el Johnsongrass mosaic virus strain O (JGMV-0) (Maize dwarf mosaic virus strain - O) con la técnica serológica de NCM-ELISA (prueba inmunoenzimática en membrana de nitrocelulosa), la cual consiste en colectar al azar, muestras de hojas de maíz, en campos de cultivo de maíz amiláceo en estado de 100% de floración femenina; las zonas muestreadas fueron las principales zonas productoras de maíz amiláceo del Callejón de Huaylas: Ranrahirca, Pampac y Acopampa, ubicadas en la zona sierra del Departamento de Ancash. Se encontró que el cultivo de maíz amiláceo en el Callejón de Huaylas, el virus que tiene mayor incidencia es el Maize rayado fino virus, encontrado en una incidencia promedia de 70% y el Maize chlorotic mottle virus (MCMV) en una incidencia promedia de 39%, siendo éstos diferentes estadísticamente. No se encuentra la presencia del Johnsongrass mosaic virus strain O (JGMV-0) (Maize dwarf mosaic virus strain — O). Las infecciones por virus en las zonas en estudio no tienen diferencias estadísticas significativas.Palabras Claves: Maize rayado fino virus (MRFV), Maize chlorotic mottle virus (MCMV), Maize dwarf mosaic virus strain O (MDMV-0), Johnsongrass mosaic virus strain O (JGMV-0), incidencia de virus en maíz amiláceo, Callejón de Huaylas.

Se evaluó el efecto del prebiótico inulina y las plantas medicinales en polvo: Rhoeo discolor (Rd) y una mezcla de Echinacea purpurea y Uncaria tomentosa (EU), adicionadas al alimento, en el crecimiento, supervivencia, microbiota intestinal, sistema inmune y prevalencia de WSSV en Litopenaeus vannamei. Se realizaron tres bioensayos con tratamientos por triplicado. Bioensayo 1 (peso, 0.74±0.25 g): I) Control, alimento comercial (AC) + celulosa (4 g/kg); II) AC + Rd (0.5 g/kg); III) AC + Rd (1 g/kg); IV) AC + Rd (2 g/kg) y V) AC + Rd (4 g/kg). Bioensayo 2 (peso, 12.9±1.73 g): I) Control, AC + celulosa (6.5 g/kg); II) AC + mezcla EU (1 g/kg) + inulina (0.7 g/kg); III) AC + mezcla EU (2 g/kg) + inulina (1.25 g/kg) y IV) AC + mezcla EU (4 g/kg) + inulina (2.5 g/kg). Bioensayo 3 (peso, 3.38±0.97 g): I) Control, AC + celulosa (6.5 g/kg); II) AC + mezcla EU (4 g/kg) + inulina (2.5 g/kg) a diario; III) AC + mezcla EU (4 g/kg) + inulina (2.5 g/kg) cada 2 días y IV) AC + mezcla EU (4 g/kg) + inulina (2.5 g/kg) cada 3 días. Se realizó un análisis de WSSV con la PCR al inicio y final de los bioensayos, y se determinó la tasa de crecimiento específico (TCE) y la supervivencia de L. vannamei (Bioensayos 1, 2 y 3). Se cuantificó (qPCR) la expresión relativa de 4 genes del sistema inmune: proFO, TGasa, SOD y LvToll (Bioensayos 2 y 3). Al final del bioensayo 3 se hizo un conteo total de hemocitos (CTH), se determinó bioquímicamente la concentración de anión superóxido, la actividad de la fenoloxidasa y la concentración de proteína en plasma y sobrenadante lisado de hemocitos (SLH). Además, se determinó el número de UFC/g de intestino de vibrios, bacterias ácido lácticas (BAL) y bacilos. No hubo diferencias significativas entre tratamientos en el crecimiento y supervivencia de los organismos en los 3 bioensayos. La prevalencia de WSSV disminuyó 8.34% en el tratamiento V del bioensayo 1, en comparación con el control. En el bioensayo 2, la prevalencia de WSSV en el tratamiento IV disminuyó 15.4%, y en el bioensayo 3 un 33.33% (mezcla dada a diario y cada 3 días) y 22.23% (mezcla dada cada 2 días), respecto al control. La mezcla EU y la inulina aumentaron la expresión de los genes proFO, TGasa y SOD, así como la cantidad de anión superóxido y la concentración de proteína. Además, mejoran la microbiota intestinal, especialmente las BAL. La mezcla de plantas e inulina tienen efecto inmunoestimulante y protector en los camarones, particularmente cuando se administran en el alimento cada 2 y cada 3 días.

We characterized a mitochondrial DNA deletion in a patient with Kearns-Sayre syndrome. Southern blot hybridization showed that 86 to 93% of the mitochondrial genome harbored a 5.0 kb deletion. The percentage of affected genomes is higher than in previously described cases. Direct sequencing of the breakpoint region revealed that the deletion extended 5025 by from nt 10050 in the tRNA Gly gene to nt 15 076 in the cytochrome b gene, thus 30% of the total mitochondrial genome was lost by this deletion. A pair of extremely short mirror sequences flanking the mitochondrial DNA breakpoints were identified. These flanking sequences differ from previously published consensus ‘hot-spots’, known to give rise to deletions in human mitochondrial DNA.