5-Aminoisoquinolinone reduces renal injury and dysfunction caused by experimental ischemia/reperfusion

Background. Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the development of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of a water-soluble and potent PARP inhibitor, 5-aminoisoquinolinone (5-AIQ), on the renal injury and dysfunction caused by oxidative stress of the rat kidney in vitro and in vivo. Methods. Primary cultures of rat renal proximal tubular cells, subjected to oxidative stress caused by hydrogen peroxide (H2O2), were incubated with increasing concentrations of 5-AIQ (0.01 to 1 mmol/L) after which PARP activation, cellular injury, and cell death were measured. In in vivo experiments, anesthetized male Wistar rats were subjected to renal bilateral ischemia (45 minutes) followed by reperfusion (6 hours) in the absence or presence of 5-AIQ (0.3 mg/kg) after which renal dysfunction, injury and PARP activation were assessed. Results. Incubation of proximal tubular cells with H2O2 caused a substantial increase in PARP activity, cellular injury, and cell death, which were all significantly reduced in a concentration-dependent by 5-AIQ [inhibitory concentration 50 (IC50) similar to 0.03 mmol/L]. In vivo, renal I/R resulted in renal dysfunction, injury, and PARP activation, primarily in the proximal tubules of the kidney. Administration of 5-AIQ significantly reduced the biochemical and histologic signs of renal dysfunction and injury and markedly reduced PARP activation caused by I/R. Conclusion. This study demonstrates that 5-AIQ is a potent, water soluble inhibitor of PARP activity, which can significantly reduce (1) cellular injury and death caused to primary cultures of rat proximal tubular cells by oxidative stress in vitro, and (2) renal injury and dysfunction caused by I/R of the kidney of the rat in vivo

5-Aminoisoquinolinone reduces renal injury and dysfunction caused by experimental ischemia/reperfusion

Background. Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the development of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of a water-soluble and potent PARP inhibitor, 5-aminoisoquinolinone (5-AIQ), on the renal injury and dysfunction caused by oxidative stress of the rat kidney in vitro and in vivo. Methods. Primary cultures of rat renal proximal tubular cells, subjected to oxidative stress caused by hydrogen peroxide (H2O2), were incubated with increasing concentrations of 5-AIQ (0.01 to 1 mmol/L) after which PARP activation, cellular injury, and cell death were measured. In in vivo experiments, anesthetized male Wistar rats were subjected to renal bilateral ischemia (45 minutes) followed by reperfusion (6 hours) in the absence or presence of 5-AIQ (0.3 mg/kg) after which renal dysfunction, injury and PARP activation were assessed. Results. Incubation of proximal tubular cells with H2O2 caused a substantial increase in PARP activity, cellular injury, and cell death, which were all significantly reduced in a concentration-dependent by 5-AIQ [inhibitory concentration 50 (IC50) similar to 0.03 mmol/L]. In vivo, renal I/R resulted in renal dysfunction, injury, and PARP activation, primarily in the proximal tubules of the kidney. Administration of 5-AIQ significantly reduced the biochemical and histologic signs of renal dysfunction and injury and markedly reduced PARP activation caused by I/R. Conclusion. This study demonstrates that 5-AIQ is a potent, water soluble inhibitor of PARP activity, which can significantly reduce (1) cellular injury and death caused to primary cultures of rat proximal tubular cells by oxidative stress in vitro, and (2) renal injury and dysfunction caused by I/R of the kidney of the rat in vivo

Compactación inducida por el tránsito vehicular sobre un suelo en producción hortícola Induced compaction by the vehicular traffic in a soil for horticultural crop production

Se realizaron ensayos en campo con el objeto de caracterizar el estado de compactación de un suelo en producción hortícola inducida por el tránsito, luego del desarrollo del ciclo de un cultivo de repollo (Brassica oleracea L. grupo capitata ) y su incidencia sobre el rendimiento. Se efectuaron determinaciones de resistencia a la penetración, densidad aparente y humedad gravimétrica sobre el suelo y biomasa aérea al finalizar el ciclo del cultivo en los sectores de mayor y menor número de pasajes de vehículos. Los valores de resistencia a la penetración fueron de 1,7 y 1,3 MPa, significativamente mayores para el tratamiento de más de 7 y 3 pasadas respectivamente en el rango de profundidad de 0-100 mm . No se manifestaron diferencias en el parámetro densidad aparente en la totalidad del perfil. Se encontraron diferencias estadísticamente significativas en biomasa aérea, para el tratamiento de 3 pasadas (1902.6 g planta-1), en relación al de mas de 7 pasadas (1447,9 g planta-1). El pasaje repetido sobre los surcos originan incrementos en la resistencia a la penetración a nivel superficial. El peso fresco y la materia seca del cultivo son afectados por el número de pasadas de los tractores y máquinas agrícolas.<br>Field test were carried out with the objective of characterizing the state of compaction in horticultural soil induced by traffic, after the development of a cabbage crop (Brassica oleracea L. group capitata) cycle, and its incidence on yield. Measurements of penetration resistance, bulk density, and moisture content in soil were made and aeread biomass at the end of the cycle crop in sectors with larger and smaller number of vehicles passes. Values of penetration resistance of 1.7 and 1.3 MPa were found for treatment with more than 7 passes and 3 passes respectively in the depth range of 0-100 mm. No significant differences were found in bulk density parameter in the entire soil profile. Statistically significant differences were found for aereal biomass values of 3 passes treatment (1902.6 g plant-1), in relation to more than 7 passes (1447.9 g plant-1). Repeated passes on rows resulted in increments of penetration resistance at shallow depths. The number of the tractor and agricultural machinery passes influenced the fresh and dry weight of crop

R2d2 Drives Selfish Sweeps in the House Mouse

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolutio