Amyloid B-peptide 1-40 increases neuronal membrane fluidity: role of cholesterol and brain region

There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid ß-peptide may play an important role in this interaction. Aß destabilizes brain membranes and this action of Aß may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Aß1-40 on the annular fluidity (i.e., lipid environment adjacent to proteins) and bulk fluidity of rat synaptic plasma membranes (SPM) of the cerebral cortex, cerebellum, and hippocampus using the fluorescent probe pyrene and energy transfer. Amounts of cholesterol and phospholipid of SPM from each brain region were determined. SPM of the cerebellum were significantly more fluid as compared with SPM of the cerebral cortex and hippocampus. Aß significantly increased (P 0.01) annular and bulk fluidity in SPM of cerebral cortex and hippocampus. In contrast, Aß had no effect on annular fluidity and bulk fluidity of SPM of cerebellum. The amounts of cholesterol in SPM of cerebral cortex and hippocampus were significantly higher (P 0.05) than amount of cholesterol in SPM of cerebellum. There was significantly less (P 0.05) total phospholipid in cerebellar SPM as compared with SPM of cerebral cortex. Neuronal membranes enriched in cholesterol may promote accumulation of Aß by hydrophobic interaction, and such an interpretation is consistent with recent studies showing that soluble Aß can act as a seed for fibrillogenesis in the presence of cholesterol.

Polymorphims in the Interferon-y/Interleukin 26 Gene Region Contribute to Sex Bias in Susceptibility to Rheumatoid Arthritis

Objective:

To determine whether polymorphisms in the interferon-? (IFN?)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA).

Methods:

Four microsatellite markers, located in a 118-kb interval that contains both the IFN? and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction–based fragment analysis.

Results:

Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [Pcorr] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32–0.78; P = 0.002, Pcorr = 0.03) but not in men with RA.

Conclusion:

Our results demonstrate that common polymorphisms in the IFN?/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.

Characterization of the 5' upstream regulatory region of the human myostatin gene: regulation of myostatin gene transcription by dexamethasone in vitro

We cloned and characterized a 3.3-kb fragment containing the 5'-regulatory region of the human myostatin gene. The promoter sequence contains putative muscle growth response elements for glucocorticoid, androgen, thyroid hormone, myogenic differentiation factor 1, myocyte enhancer factor 2, peroxisome proliferator-activated receptor, and nuclear factor-kappaB. To identify sites important for myostatin's gene transcription and regulation, eight deletion constructs were placed in C(2)C(12) and L6 skeletal muscle cells. Transcriptional activity of the constructs was found to be significantly higher in myotubes compared with that of myoblasts. To investigate whether glucocorticoids regulate myostatin gene expression, we incubated both cell lines with dexamethasone. On both occasions, dexamethasone dose dependently increased both the promoter's transcriptional activity and the endogenous myostatin expression. The effects of dexamethasone were blocked when the cells were coincubated with the glucocorticoid receptor antagonist RU-486. These findings suggest that glucocorticoids upregulate myostatin expression by inducing gene transcription, possibly through a glucocorticoid receptor-mediated pathway. We speculate that glucocorticoid-associated muscle atrophy might be due in part to the upregulation of myostatin expression.

Optimisation of source/drain extension region profile for suppression of short channel effects in sub-50 nm DG SOI MOSFETs with high- k gate dielectrics

Novel technology dependent scaling parameters i.e. spacer to gradient ratio and effective channel length (Leff) are proposed for source/drain engineered DG MOSFET, and their significance in minimizing short channel effects (SCES) in high-k gate dielectrics is discussed in detail. Results show that a high-k dielectric should be associated with a higher spacer to gradient ratio to minimise SCEs The analytical model agrees with simulated data over the entire range of spacer widths, doping gradients, high-k gate dielectrics and effective channel lengths.

Fe XIII emission lines in active region spectra obtained with the Solar Extreme-Ultraviolet Research Telescope and Spectrograph

Recent fully relativistic calculations of radiative rates and electron impact excitation cross-sections for FeXIII are used to generate emission-line ratios involving 3s23p2-3s3p3 and 3s23p2-3s23p3d transitions in the 170-225 and 235-450 Å wavelength ranges covered by the Solar Extreme-Ultraviolet Research Telescope and Spectrograph (SERTS). A comparison of these line ratios with SERTS active region observations from rocket flights in 1989 and 1995 reveals generally very good agreement between theory and experiment. Several new FeXIII emission features are identified, at wavelengths of 203.79, 259.94, 288.56 and 290.81 Å. However, major discrepancies between theory and observation remain for several FeXIII transitions, as previously found by Landi and others, which cannot be explained by blending. Errors in the adopted atomic data appear to be the most likely explanation, in particular for transitions which have 3s23p3d1D2 as their upper level. The most useful FeXIII electron-density diagnostics in the SERTS spectral regions are assessed, in terms of the line pairs involved being (i) apparently free of atomic physics problems and blends, (ii) close in wavelength to reduce the effects of possible errors in the instrumental intensity calibration, and (iii) very sensitive to changes in Ne over the range 108-1011cm-3. It is concluded that the ratios which best satisfy these conditions are 200.03/202.04 and 203.17/202.04 for the 170-225 Å wavelength region, and 348.18/320.80, 348.18/368.16, 359.64/348.18 and 359.83/368.16 for 235-450 Å.

High-resolution spectroscopic observations of B-type stars from the Edinburgh-Cape Survey - III. Completion of a magnitude range limited survey

High spectral resolution (R similar to 40 000) and signal-to- noise ratio observations of five high Galactic latitude early- type stars taken from the Edinburgh-Cape (EC) Faint Blue Object Survey are presented. These were required to complete a magnitude range-limited survey of young B-type objects with 11 <V <15. Of the five stars, four were rejected on the grounds that they are either subluminous (subdwarf or horizontal branch), were part of a binary system or possessed colours later than the (U - B) = -0.5 cut-off employed. The remaining star in the data set, EC 19596-5356, is found to exhibit normal young B-type stellar properties. A kinematic analysis reveals that an origin in the Galactic disc appears likely for all the stars in the sample. Some statistics are drawn about the number density of young stars in the Galactic halo.

High-resolution spectroscopic observations of post-asymptotic giant branch candidates from the Edinburgh-Cape Survey

High spectral resolution ( R similar to 40 000) and signal-to-noise optical spectra, obtained at the Very Large Telescope ( VLT), are presented for three post-asymptotic giant branch ( AGB) candidates selected from the Edinburgh-Cape ( EC) Faint Blue Object Survey. The stellar atmospheric parameters and chemical compositions, derived using sophisticated non-local thermodynamic equilibrium calculations, reveal that EC 14102-1337 and EC 20068-7324 are both in an evolved post-horizontal branch ( HB) evolutionary state. However, EC 11507-2253 is most likely a post-AGB star.