Parkinson’s disease (PD) is caused by dopaminergic neuronal death in the substantia nigra, resulting in a reduced level of dopamine in the striatum. Oxidative stress and mitochondrial dysfunction are ...thought to be major causes of neurodegeneration in PD. Although genetic and environmental factors are thought to affect the onset of PD, precise mechanisms at the molecular level have not been elucidated. The DJ-1 gene is a causative gene for familial PD (park7) and also an oncogene. DJ-1 has various functions, including transcriptional regulation, antioxidative stress reaction, and chaperone, protease, and mitochondrial regulation, and its activity is regulated by its oxidative status, especially that of cysteine 106 (C106) of DJ-1. Excess oxidation of DJ-1, which renders DJ-1 inactive, has been observed in patients with sporadic PD and Alzheimer’s disease, suggesting that DJ-1 also participates in the onset and pathogenesis of sporadic PD as well as familial PD. DJ-1 is also a stress sensor and its expression is increased upon various stresses, including oxidative stress. In this review, we describe functions of DJ-1 against oxidative stress and possible roles of DJ-1 in the pathogenesis of PD.
DJ-1 is a novel oncogene and also a causative gene for familial Parkinson's disease (park7). DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone ...and mitochondrial regulation. Mitochondrial dysfunction is observed in DJ-1-knockout mice and fry, and mitochondrial DJ-1 is more protective against oxidative stress-induced cell death. Although translocation of DJ-1 into mitochondria is enhanced by oxidative stress that leads to oxidation of cysteine 106 (C106) of DJ-1, the characteristics of mitochondrial DJ-1 and the mechanism by which DJ-1 is translocated into mitochondria are poorly understood. In this study, immunostaining, co-immunoprecipitation, cell fractionation and pull-down experiments showed that mutants of glutamine 18 (E18) DJ-1 are localized in mitochondria and do not make homodimers. Likewise, DJ-1 with mutations of two cysteines located in the dimer interface, C46S and C53A, and pathogenic mutants, M26I and L166P DJ-1, were found to be localized in mitochondria and not to make homodimers. Mutant DJ-1 harboring both E18A and C106S, in which C106 is not oxidized, was also localized in mitochondria, indicating that oxidation of C106 is important but not essential for mitochondrial localization of DJ-1. It should be noted that E18A DJ-1 was translocated from mitochondria to the cytoplasm when mitochondrial membrane potential was reduced by treatment of cells with CCCP, an uncoupler of the oxidative phosphorylation system in mitochondria. Furthermore, deletion or substitution of the N-terminal 12 amino acids in DJ-1 resulted in re-localization of E18A, M26I and L166P DJ-1 from mitochondria into the cytoplasm. These findings suggest that a monomer and the N-terminal 12 amino acids are necessary for mitochondrial localization of DJ-1 mutants and that conformation change induced by C106 oxidation or by E18 mutation leads to translocation of DJ-1 into mitochondria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
In-situ measurements of soil water content provide important constraints on local/global hydrology. We demonstrate that the attenuation of the underground flux of cosmic-ray electromagnetic ...(EM) particles can be used to monitor the variation of soil water content after rainfalls. We developed a detection system that preferably selects EM particles by considering the coincidence of distant plastic scintillators. The calibration test beneath the water pool revealed that the count rate decreased by 0.6–0.7% with a 1 cm increase in the water level. The field measurement performed in the horizontal tunnel showed that the count rate dropped according to 48-h precipitation, after correcting the effects originating from atmospheric and water vapour pressures. These characteristics were confirmed using dedicated Monte Carlo simulations. This new method is called cosmic electromagnetic particle (CEMP) radiography.
Characterizing the size and settling velocity of pyroclastic fragments injected into the atmosphere during volcanic eruptions (i.e., tephra) is crucial to the forecasting of plume and cloud ...dispersal. Optical disdrometers have been integrated into volcano monitoring networks worldwide in order to best constrain these parameters in real time. Nonetheless, their accuracy during tephra fallout still needs to be assessed. A significant complication is the occurrence of particle aggregates that modify size and velocity distributions of falling tephra. We made the first use of the Thies Clima Laser Precipitation Monitor (LPM) for tephra-fallout detection at Sakurajima volcano (Japan), which is characterized by a lower size detection window with respect to more commonly used disdrometers (e.g., Parsivel
) and can more easily distinguish different falling objects. For the first time, individual particles have been distinguished from most aggregates based on disdrometer data, with the potential to provide useful grain-size information in real time. In case of negligible aggregation, LPM and collected sample-based estimates are in agreement for both grain-size and sedimentation rate. In case of significant aggregation, particle shape analyses and a dedicated drag equation are used to filter out aggregates from LPM data that also provide good agreement with collected tephra samples.
Deletion and point (L166P) mutations of DJ‐1 have recently been shown to be responsible for the onset of familial Parkinson's disease (PD, PARK7). The aim of this study was to determine the role of ...DJ‐1 in PD. We first found that DJ‐1 eliminated hydrogen peroxide in vitro by oxidizing itself. We then found that DJ‐1 knockdown by short interfering RNA rendered SH‐SY5Y neuroblastoma cells susceptible to hydrogen peroxide‐, MPP+‐ or 6‐hydroxydopamine‐induced cell death and that cells harbouring mutant forms of DJ‐1, including L166P, became susceptible to death in parallel with the loss of oxidized forms of DJ‐1. These results clearly showed that DJ‐1 has a role in the antioxidative stress reaction and that mutations of DJ‐1 lead to cell death, which is observed in PD.
Using a three-dimensional fluid dynamic model for eruption cloud dynamics, we present numerical simulations of the development of a volcanic eruption column and umbrella cloud formed during the 13 ...February 2014 eruptions of Mount Kelud, Indonesia. The model used in this study quantitatively reproduces the observed data and, in particular, the plume height and the horizontal expansion level and rate of the umbrella cloud. The simulation results suggest that on the basis of the plume height and structures and the horizontal expansion level of the umbrella cloud the mass eruption rate (MER) for the 2014 Kelud eruptions was 3×107 to 4×107kgs−1. On the basis of the horizontal expansion rate of the umbrella cloud, on the other hand, the estimated MER was 1×108kgs−1. The difference between these two estimates implies the strong diffusion in the umbrella cloud or the efficient entrainment of ambient air by eruption column.
•We performed 3D numerical simulations for the 2014 Kelud eruption.•Simulation results agree well with the various observations.•The mass eruption rate for this eruption is estimated to be 0.3–1.0×108kgs−1.
DJ-1 is a novel oncogene and also causative gene for familial Parkinson's disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and ...mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A hydrophobic sphere, freely released from a certain height, entering water makes a cavity behind it. This paper visually demonstrates underwater sound produced by the water entry with the use of a ...hydrophone synchronized with a high-speed camera. The acoustic signal of the underwater sound recorded can be found to include two predominant frequencies. A remarkable finding is the fact that the higher predominant frequency sound can be excited by the breathing mode of a residual bubble behind the sphere after the cavity pinching off. In addition, the lower frequency sound is predicted to be driven by the oscillation of the free surface caused by the impact of the sphere.
Graphical abstract
Seismic anisotropy, the directional dependence of wave speeds, may be caused by stress-oriented cracks or by strain-oriented minerals, yet few studies have quantitatively compared anisotropy to ...stress and strain over large regions. Here we compare crustal stress and strain rates on the Island of Kyushu, Japan, as measured from inversions of focal mechanisms, GPS and shear wave splitting. Over 85,000 shear wave splitting measurements from local and regional earthquakes are obtained from the NIED network between 2004 and 2012, and on Aso, Sakurajima, Kirishima and Unzen volcano networks. Strain rate measurements are made from the Japanese Geonet stations. JMA-determined S arrival times processed with the MFAST shear wave splitting code measure fast polarisations (Φ), related to the orientation of the anisotropic medium and time delays (dt), related to the path length and the percent anisotropy. We apply the TESSA 2-D delay time tomography and spatial averaging code to the highest quality events, which have nearly vertical incidence angles, separating the 3455 shallow (depth < 40 km) from the 4957 deep (>=40 km) earthquakes. Using square grids with 30 km sides for all the inversions, the best correlations are observed between splitting from shallow earthquakes and stress. Axes of maximum horizontal stress (SHmax) and Φ correlate with a coefficient c of 0.56, significant at the 99% confidence level. Their mean difference is 31.9°. Axes of maximum compressional strain rate and SHmax are also well aligned, with an average difference of 28°, but they do not correlate with each other, meaning that where they differ, the difference is not systematic. Anisotropy strength is negatively correlated with the stress ratio parameter determined from focal mechanism inversion (c=−0.64; significant at the 99% confidence level). The anisotropy and stress results are consistent with stress-aligned microcracks in the crust in a dominantly strike-slip regime. Eigenvalues of maximum horizontal strain rate correlate positively with stress ratio (c=0.43, significant at 99% confidence). All three orientations are E–W in central Kyushu, where the compressional strain rate is highest. Both splitting and stress suggest plate-boundary-parallel maximum principal stress just off the coast of Kyushu, where strain rate measurements are sparse. South western Kyushu has the largest difference between directions of strain rate and stress. Φ from shallow and deep earthquakes are not well aligned, suggesting that the deep earthquake waveforms are not simply split in the crust. Causes for the anisotropy may be olivine crystals aligned by drag of the subducting Philippine Sea plate in the mantle and stress-aligned microcracks in the crust.
•Shallow earthquake fast directions (ϕ) correlate well with maximum horizontal stress.•Delay times correlate with stress ratio R.•Stress-controlled cracks in strike-slip strain regime explain these observations.•Structure-controlled ϕ along shearing Median Tectonic Line.•ϕ from deep earthquakes may record mantle flow patterns.
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