Dynamical diffraction effects on the geometric phase of inhomogeneous strain fields.

In specimens with an inhomogeneous displacement field in electron beam direction dynamical diffraction effects lead to complex non-linear properties of the diffracted electron wave. Consequently, the diffracted beam's phase contains information about the inhomogeneous displacement field. These phases are experimentally and theoretically investigated under different excitation errors and specimen thicknesses as well as for different depths of the displacement field. An inclined InGaAs layer with a larger lattice constant than the surrounding GaAs matrix serves as controlled displacement field, which is inhomogeneous in electron beam direction with a continuously changing depth. The phase and amplitude of the diffracted beam are measured by dark-field electron holography. The measurements agree with calculations performed by numerical propagation of the electron wave using the Darwin-Howie-Whelan equations. A strong dependency on the excitation conditions is found showing that the interplay between dynamical effects and the strain field must be considered in the interpretation of the geometric phase.

Subcellular expression and neuroprotective effects of SK channels in human dopaminergic neurons.

Small-conductance Ca(2+)-activated K(+) channel activation is an emerging therapeutic approach for treatment of neurological diseases, including stroke, amyotrophic lateral sclerosis and schizophrenia. Our previous studies showed that activation of SK channels exerted neuroprotective effects through inhibition of NMDAR-mediated excitotoxicity. In this study, we tested the therapeutic potential of SK channel activation of NS309 (25 µM) in cultured human postmitotic dopaminergic neurons in vitro conditionally immortalized and differentiated from human fetal mesencephalic cells. Quantitative RT-PCR and western blotting analysis showed that differentiated dopaminergic neurons expressed low levels of SK2 channels and high levels of SK1 and SK3 channels. Further, protein analysis of subcellular fractions revealed expression of SK2 channel subtype in mitochondrial-enriched fraction. Mitochondrial complex I inhibitor rotenone (0.5 µM) disrupted the dendritic network of human dopaminergic neurons and induced neuronal death. SK channel activation reduced mitochondrial membrane potential, while it preserved the dendritic network, cell viability and ATP levels after rotenone challenge. Mitochondrial dysfunction and delayed dopaminergic cell death were prevented by increasing and/or stabilizing SK channel activity. Overall, our findings show that activation of SK channels provides protective effects in human dopaminergic neurons, likely via activation of both membrane and mitochondrial SK channels. Thus, SK channels are promising therapeutic targets for neurodegenerative disorders such as Parkinson's disease, where dopaminergic cell loss is associated with progression of the disease.

The independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein profiles in women.

We performed this study to clarify the independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein levels in women with hyperandrogenaemia (HA) and anovulation which we designated as the polycystic ovary syndrome (PCO). We examined fasting lipid, lipoprotein, sex hormone and insulin levels in 38 women (21 obese (ob), 17 non-obese (nob] with HA and anovulation (PCO) and 38 normal ovulatory women (21 obese, 17 non-obese), matched for age and weight. The women with PCO had significantly increased androgen levels compared to the normal women. However, total oestradiol levels were similar in the PCO and normal women. Mean fasting insulin levels and 2-h glucose levels (both P less than 0.001) were significantly higher in ob PCO women. There were significant decreases (P less than or equal to 0.01) in high-density lipoprotein (HDL) levels in both the obese groups (ob PCO and ob normal) compared to the non-obese (nob PCO and nob normal) groups. Otherwise, mean lipid and lipoprotein levels did not differ in the ob or the nob PCO women compared to the control groups. The correlations between sex hormone, lipid and lipoprotein levels differed in the four groups of women. After statistical adjustment for potential hormonal interactions, nob PCO women had significant positive correlations between testosterone and LDL levels (R = 0.51, P less than 0.05) and insulin and TTG levels (R = 0.61, P less than 0.01). Ob normal women had a significant positive correlation between oestrone and TTG levels (R = 0.44, P less than or equal to 0.05). We conclude that (1) PCO women are in a low to risk for CVD primarily because of the increased prevalence of obesity rather than the reproductive hormone abnormalities associated with this disorder. However, by their lipid profiles, the PCO women were still in a low to intermediate risk group for CVD.

Beta-amyloid precursor detected in human cerebral cortex.

1. Amyloid deposition is one of the pathologic hallmarks of Alzheimer's disease. Since the isolation of the beta-amyloid gene, which revealed that the amyloid forming 4 kD protein is part of a larger precursor, interest has focused on the process by which amyloid is generated and deposited. 2. The authors have developed an immunologic means of detecting amyloid precursor proteins in human brain. 3. The method involves the expression of human beta-amyloid precursor cDNA in a recombinant vaccinia virus, so that antibodies are produced against the precursor proteins in their native forms. 4. By using this expression system, the amyloid precursor immunogens incorporate post-translational modifications that normally occur in vivo; this cannot be achieved with small synthetic peptides. 5. Using antibodies to the 695 residue amyloid precursor, we have detected using Western blot analysis a protein of approximately 120 kD in samples of cerebral cortex from three subjects with Alzheimer's disease and one control subject. 6. Additional antibodies to other amyloid-related proteins have been developed. These are being used to assess the differential expression of the various amyloid precursors and subdomains in additional cases.

Antigenic profile of plaques and neurofibrillary tangles in the amygdala in Down's syndrome: a comparison with Alzheimer's disease.

Most patients with Down's syndrome (DS) undergo a premature cognitive decline with aging, and eventually develop the neuropathologic changes of Alzheimer's disease (AD), including amyloid-containing neuritic plaques, and the formation of neurofibrillary tangles. The amygdala is a focus of marked neuropathologic change in older patients with DS and in AD. We examined the amygdala with immunocytochemical and histochemical methods in 6 cases with DS, ages 19, 20, 27, 29, 56 and 64 years and compared them to 4 cases with AD, ages 54, 76, 77 and 80 years. An antiserum to the A4 amyloid peptide demonstrated amyloid deposition in plaques in all 10 cases. Plaques were also revealed in all cases by the Alcian blue stain for glycosaminoglycans and by the Bielschowsky and Bodian silver stains. An antiserum to alpha-1-antichymotrypsin (ACT) showed plaques in the AD cases and in the 19, 56 and 64 year old DS cases. Neurofibrillary tangles were observed with silver stains only in the older DS and in the AD cases, and not in the 19, 20, 27 and 29 year old DS cases. Likewise, antisera to paired helical filament, to microtubule associated proteins tau and microtubule associated protein-2 (MAP-2), and to ubiquitin, all of which are components of neurofibrillary tangles, reacted with tangles and abnormal neurites only in the older DS and the AD cases. An antiserum to neurofilament epitopes labeled NFTs in the older DS cases and the AD cases, but not in the younger DS cases, except for two intraneuronal NFTs in the 27 year old case.(ABSTRACT TRUNCATED AT 250 WORDS)