Insulin-Degrading Enzyme Efficiently Degrades polyQ Peptides but not Expanded polyQ Huntingtin Fragments.

Background: Huntington's disease is an inheritable autosomal dominant disorder caused by an expanded CAG trinucleotide repeat within the Huntingtin gene, leading to a polyglutamine (polyQ) expansion in the mutant protein. Objective: A potential therapeutic approach for delaying or preventing the onset of the disease involves enhancing the degradation of the aggregation-prone polyQ-expanded N-terminal mutant huntingtin (mHTT) exon1 fragment. A few proteases and peptidases have been identified that are able to cleave polyQ fragments with low efficiency. This study aims to identify a potent polyQ-degrading endopeptidase. Methods: Here we used quenched polyQ peptides to identify a polyQ-degrading endopeptidase. Next we investigated its role on HTT turnover, using purified polyQ-expanded HTT fragments and striatal cells expressing mHTT exon1 peptides. Results: We identified insulin-degrading enzyme (IDE) as a novel endopeptidase for degrading polyQ peptides. IDE was, however, ineffective in reducing purified polyQ-expanded HTT fragments. Similarly, in striatal cells expressing mHTT exon1 peptides, IDE did not enhance mHTT turnover. Conclusions: This study shows that despite IDE's efficiency in degrading polyQ peptides, it does not contribute to the direct degradation of polyQ-expanded mHTT fragments.

Evidence for coseismic subsidence events in a southern California coastal saltmarsh.

Paleoenvironmental records from a southern California coastal saltmarsh reveal evidence for repeated late Holocene coseismic subsidence events. Field analysis of sediment gouge cores established discrete lithostratigraphic units extend across the wetland. Detailed sediment analyses reveal abrupt changes in lithology, percent total organic matter, grain size, and magnetic susceptibility. Microfossil analyses indicate that predominantly freshwater deposits bury relic intertidal deposits at three distinct depths. Radiocarbon dating indicates that the three burial events occurred in the last 2000 calendar years. Two of the three events are contemporaneous with large-magnitude paleoearthquakes along the Newport-Inglewood/Rose Canyon fault system. From these data, we infer that during large magnitude earthquakes a step-over along the fault zone results in the vertical displacement of an approximately 5-km2 area that is consistent with the footprint of an estuary identified in pre-development maps. These findings provide insight on the evolution of the saltmarsh, coseismic deformation and earthquake recurrence in a wide area of southern California, and sensitive habitat already threatened by eustatic sea level rise.

Simple and sensitive determination of five quinolones in food by liquid chromatography with fluorescence detection.

A simple and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the determination of five different quinolones: enrofloxacin, ciprofloxacin, sarafloxacin, oxolinic acid and flumequine in pork and salmon muscle. The method includes one extraction and clean-up step for the five quinolones together which are detected in two separated HPLC runs by means of their fluorescence. The proposed analytical method involves homogenizing of the tissue sample with 0.05 M phosphate buffer, pH 7.4 and clean-up by Discovery DS-18 cartridges. For chromatographic separation a Symmetry C(18) column is used in two different runs: (1) ciprofloxacin, enrofloxacin and sarafloxacin with acetonitrile-0.02 M phosphate buffer pH 3.0 (18:82) as mobile phase and the detector at excitation wavelength: 280 nm and emission wavelength 450 nm; and (2) oxolinic acid and flumequine with acetonitrile-0.02 M phosphate buffer pH 3.0 (34:66) as mobile phase and excitation wavelength: 312 nm and emission wavelength: 366 nm. Detection limit was as low as 5 ng g(-1), except for sarafloxacin which had a limit of 10 ng g(-1). Standard curves using blank muscle tissues spiked at different levels showed a good linear correlation coefficient, r(2) higher than 0.999 for all quinolones.

Prueba de integridad funcional de la membrana espermatica: valor en el estudio del hombre infertil / Functional integrity test for the sperm membrane: the value in the study of interfile men

Se analiza el valor diagnóstico de la PIFME en 51 pacientes infértiles según la técnica descrita por Jeyedran (1984) clasificándolos en tres grupos: A) normozoospérmicos, B) oligozooespérmicos, C) astenozoospérmicos. Al comparar los valores medios del % de PIFME en cada grupo se encontraron diferencias significativas entre A y B entre B y C, pero no así entre A y C. De acuerdo a la movilidad, Ct/ml y morfología basal, los pacientes se agruparon atendiendo al criterio de normalidad de la OMS, hallándose diferencia estadísticamente significativa (p<0,02) entre los subgrupos de cada indicar. El índice de correlación encontrado entre el % de PIFME vs movilidad, Ct/ml y morfología en la muestra total fue de 0,33, 0,52 y 0,50 respectivamente. En el grupo de los normozooespérmicos no se encontró correlación significativa alguna, mientras que en los oligozoospérmicos se halló solamente con la movilidad (r = 0,61) ambos casos positiva y significativa. Se concluye que la PIFME debe ser considerada como un indicador más del análisis seminal sistemático, ya que su realización no es compleja, no eleva el costo de la investigación y permite precisar otra posible causa de disminución de la capacidad fecundante del espermatozoide