36 research outputs found
MODELING EXCHANGE RATE VOLATILITIES IN CROATIA
Modeling and forecasting exchange rate volatility has important implications in a range of areas in macroeconomics and finance. A number of models have been developed in empirical finance literature to investigate this volatility across different regions and countries. Well known and frequently applied models to estimate exchange rate volatility are the autoregressive conditional heteroscedastic (ARCH) model advanced by Engle (1982) and the generalized (GARCH) model developed independently by Bollerslev (1986) and Taylor (1986). This paper examines the performance of several ARCH models for the EUR and USD against the HRK on daily data sets within the time period from 1997 to 2015. Evaluating the models through standard information criteria showed that the GARCH (2,1) is the best fitted model for the EUR/HRK and the GARCH (1,1) for the USD/HRK daily return volatility. In accordance to the estimated models there is no empirical evidence that negative and positive shocks imply a different next period volatility of the daily EUR/HRK as well as the USD/HRK exchange rate return.</p
Real-world experience of teriflunomide in relapsing multiple sclerosis: paramagnetic rim lesions may play a role
ObjectivesThe aims of this study were to report the effectiveness and safety of teriflunomide in Chinese patients with relapsingâremitting multiple sclerosis (RRMS) and to explore the association of paramagnetic rim lesion (PRL) burden with patient outcome in the context of teriflunomide treatment and the impact of teriflunomide on PRL burden.MethodsThis is a prospective observational study. A total of 100 RRMS patients treated with teriflunomide â„3 months were included in analyzing drug persistence and safety. Among them, 96 patients treated â„6 months were included in assessing drug effectiveness in aspects of no evidence of disease activity (NEDA) 3. The number and total volume of PRL were calculated in 76 patients with baseline susceptibility-weighted imaging (SWI), and their association with NEDA3 failure during teriflunomide treatment was investigated.ResultsOver a treatment period of 19.7 (3.1â51.7) months, teriflunomide reduced annualized relapse rate (ARR) from 1.1 ± 0.8 to 0.3 ± 0.5, and Expanded Disability Status Scale (EDSS) scores remained stable. At month 24, the NEDA3% and drug persistence rate were 43.8% and 65.1%, respectively. In patients with a baseline SWI, 81.6% had at least 1 PRL, and 42.1% had â„4 PRLs. The total volume of PRL per patient was 0.3 (0.0â11.5) mL, accounting for 2.3% (0.0%â49.0%) of the total T2 lesion volume. Baseline PRL number â„ 4 (OR = 4.24, p = 0.009), younger onset age (OR = 0.94, p = 0.039), and frequent relapses in initial 2 years of disease (OR = 13.40, p = 0.026) were associated with NEDA3 failure. The PRL number and volume were not reduced (p = 0.343 and 0.051) after teriflunomide treatment for more than 24 months. No new safety concerns were identified in this study.ConclusionTeriflunomide is effective in reducing ARR in Chinese patients with RRMS. Patients with less PRL burden, less frequent relapses, and relatively older age are likely to benefit more from teriflunomide, indicating that PRL might be a valuable measurement to inform clinical treatment decision
Role of Alpha-Synuclein Protein Levels in Mitochondrial Morphology and Cell Survival in Cell Lines
α-Synuclein is highly associated with some neurodegeneration and malignancies. Overexpressing wild-type or mutant α-synuclein promotes neuronal death by mitochondrial dysfunction, the underlying mechanisms of which remain poorly defined. It was recently reported that α-synuclein expression could directly lead to mitochondrial fragmentation in vitro and in vivo, which may be due to α-synuclein localization on mitochondria. Here, we applied a double staining method to demonstrate mitochondrial morphogenetic changes in cells overexpressed with α-synuclein. We show that mitochondrial localization of α-synuclein was increased following its overexpression in three distinct cell lines, including HeLa, SH-SY5Y, and PC12 cells, but no alteration in mitochondrial morphology was detected. However, α-synuclein knockdown prevents MPP+-induced mitochondrial fragmentation in SH-SY5Y and PC12 cells. These data suggest that α-synuclein protein levels hardly affect mitochondrial morphology in normal cell lines, but may have some influence on that under certain environmental conditions
α-Synuclein overexpression increases its localization on mitochondria without causing mitochondrial fragmentation in PC12 cells.
<p><b>A.</b> Representative double-staining images of α-synuclein (Green) and mitochondria (Red) in PC12 cells transfected with <i>SNCA</i> or an empty vector for 48 h. Amplified images clearly demonstrate that no perceptible alteration in mitochondrial morphology between these two groups. Cytofluorogram analysis shows that PC coefficient of that α-synuclein overexpressed cell (PCâ=â0.574982, CC Mxâ=â0.972038, CC Myâ=â0.98707) is much higher than Vector group (PCâ=â0.316512, CC Mxâ=â0.962559, CC Myâ=â0.439231). Scale bars for 10 ”m. B. Quantitative analysis shows that PC coefficients in <i>SNCA</i> group are remarkably elevated compared with Vector group. C. Immunoblotting assay shows that α-synuclein expression levels in PC12 cell lysates and mitochondrial lysates are both significantly increased after <i>SNCA</i> transfection for 48 h (nâ=â4). <b>D.</b> Quantitative analysis of changes in mitochondrial length shows no significant statistic difference between <i>SNCA</i> group and Vector group. Images of 20 cells from each group were processed for cytofluorogram (B) and mitochondrial morphology analysis (D), and the experiment was repeated three times. *P<0.05, **P<0.01.</p
Cell Fixation Does not Alter Mitochondrial Morphology Probed by Staining with MitoTracker-Red CMXRos.
<p><b>A.</b> Representative images of mitochondria in the same SH-SY5Y cells stained with MitoTracker-Red CMXRos were taken immediately before and 30 min after fixation with 4% paraformaldehyde on live cell imaging system. Mitochondrial morphology in SH-SY5Y cells remains almost the same after fixation for 30 min. Scale bars for 10 ”m. <b>B.</b> Quantitative analysis of changes in mitochondrial length of the same SH-SY5Y cells in images taken immediately before and 30 min after fixation. The experiment was carried out five times, and no perceptible difference in mitochondrial length is detected in SH-SY5Y cells after fixation.</p
α-Synuclein knockdown prevents MPP<sup>+</sup>-induced cell apoptosis and mitochondrial fragmentation in SH-SY5Y cells.
<p><b>A.</b> Immunoblotting assay demonstrates that α-synuclein expression is remarkably suppressed in SH-SY5Y cells transfected with <i>SNCA</i> siRNA (RNAi group) for 2â5 d, yet it is hardly affected in cells transfected with a negative control sequence (Neg group) (nâ=â5). <b>B.</b> Quantitative analysis of changes in mitochondrial length shows that MPP<sup>+</sup> (1 mM) decreases mitochondrial length in Neg group, however, it has little effect on the index in RNAi group. Images of 20 cells from each group were processed for mitochondrial morphology analysis, and the experiment was repeated three times. <b>C.</b> Flow cytometric analysis of cell apoptosis shows that MPP<sup>+</sup> leads to severe cell injury in Neg group, while it slightly harms SH-SY5Y cells in RNAi group (nâ=â4). *P<0.05, **P<0.01, ***P<0.001 Neg versus RNAi; #P<0.05, ##P<0.01, ###P<0.001 compared with Neg control.</p
The effects of α-synuclein suppression on mitochondrial morphology in SH-SY5Y cells.
<p>Representative images taken by live cell imaging system show no obvious alteration in mitochondrial morphology between Neg group (A) and RNAi group (D). MPP<sup>+</sup> (1 mM) induces severe mitochondrial fragmentation in Neg group (B and C) but has little effect on mitochondrial morphology in RNAi group (E and F). Scale bar for 10 ”m.</p
α-Synuclein overexpression in Hela cells promotes its co-localization with mitochondria without affecting mitochondrial morphology.
<p><b>A.</b> Representative double-staining images of α-synuclein (Green) and mitochondria (Red) in Hela cells transfected with <i>SNCA</i> or an empty vector for 48 h. Further amplified images show that no obvious change in mitochondrial morphology between these two groups. Cytofluorogram analysis demonstrates that PC coefficient in that α-synuclein overexpressed cell is remarkably elevated (PCâ=â0.374221, CC Mxâ=â0.998574, CC Myâ=â0.845116) compared with Vector group (PCâ=ââ0.0338751, CC Mxâ=â0.905173, CC Myâ=â0.796768). Scale bars for 10 ”m. B. Quantitative analysis demonstrates that PC coefficients in <i>SNCA</i> group are much higher than Vector group. C. Immunoblotting assay demonstrates that α-synuclein expression levels in Hela cell lysates and mitochondrial lysates are both remarkably increased after <i>SNCA</i> transfection for 48 h (nâ=â4). <b>D.</b> Quantitative analysis of changes in mitochondrial length shows no significant statistic difference between <i>SNCA</i> group and Vector group. Images of 20 cells from each group were processed for cytofluorogram (B) and mitochondrial morphology analysis (D), and the experiment was repeated three times. *P<0.05, **P<0.01.</p
α-Synuclein Distribution Patterns and Mitochondrial Morphology in Three Cell Lines.
<p><b>A.</b> Representative double-staining images show the patterns of α-synuclein distribution (green) and mitochondrial morphology (red) in SH-SY5Y, PC12 and Hela cells. Low levels of α-synuclein were expressed in all three cell lines, and it distributes in a small dotted fashion. α-Synuclein is relatively highly expressed in the nucleus in SH-SY5Y and Hela cells other than in PC12 cells. Amplified images further demonstrate that only a small part of cytoplasmic immunofluorescent staining of α-synuclein co-localizes with mitochondria in SH-SY5Y and Hela cells, while most of cytoplasmic α-synuclein reside in mitochondria in PC12 cells. Scale bars for 10 ”m. <b>B.</b> Cytofluorogram analysis of the double-staining images above shows that Pearson's Correlation (PC) coefficient is much higher in PC12 cells than those in SH-SY5Y and Hela cells. CC, colocalization coefficient.</p
An analysis of typical and atypical MRI findings of brain lesions in multiple sclerosis: a 82 cases report
Objective To analyse the typical and atypical magnetic resonance imaging (MRI) findings of brain multiple sclerosis (MS) lesions in Chinese MS patients. Methods MRI findings of 82 Chinese MS patients who fulfilled McDonald criteria were reviewed retrospectively. The analysis items included the distribution, size, number, shape, intensity and enhancement of all lesions on head MRI. Results The typical MRI findings of these patients were as follow: 1) most lesions were located at periventricle area (62 cases, 75.61%) and the deep part of supratentorial white matter (55 cases, 67.07%); 2) there were over 10 lesions in 62 cases (75.61%); 3) the lesions were predominantly †1 cm (62 cases, 75.61%), and the next were > 5 cm (23 cases, 28.05%); 4) intensity and enhancement features presented T1WI iso â or hypo â intensity, T2WI hyperintensity, and proton density weighted image (PDWI) lesions intensity higher than water in the ventricle; the black hole appeared in various size and mostly with round or patchy shape; nodular enhancement was more often seen in lesions smaller than 1 cm and ringâlike in middle size lesions; peripheral or irregular enhancement was popular for big lesions and arc â like for subcortical lesions. In the atypical MRI findings: 1) lesions were large [maximum diameter > 5 cm (23 cases, 28.05%)]; 2) lesion enhancement was remarkable and last longer; 3) brain stem lesions were more common (61 cases, 74.39%). Conclusion Multiple and small lesions at periventricle area or deep white matter are the typical MRI findings for MS. Deformation due to MS lesions, microâ black hole at convex or lineâshape black hole at periventricle, arc â like enhancement for juxtacortical lesions or enhancement beside the temporal horn are improtant in the diagnosis of MS. Big lesions with remarkable enhancement and prevalent in brain stem are the findings in Chinese MS patients which are different from American or European MS cases.
DOIïŒ10.3969/j.issn.1672-6731.2011.03.01