Alzheimer's disease-like alterations in peripheral cells from presenilin-1 transgenic mice

Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Expression of PS1 mutations in cell culture systems and in primary neurons from transgenic mice increases their vulnerability to cell death. Interestingly, enhanced vulnerability to cell death has also been demonstrated for peripheral lymphocytes from AD patients. We now report that lymphocytes from PS1 mutant transgenic mice show a similar hypersensitivity to cell death as do peripheral cells from AD patients and several cell culture systems expressing PS1 mutations. The cell death-enhancing action of mutant PS1 was associated with increased production of reactive oxygen species and altered calcium regulation, but not with changes of mitochondrial cytochrome c. Our study further emphasizes the pathogenic role of mutant PS1 and may provide the fundamental basis for new efforts to close the gap between studies using neuronal cell lines transfected with mutant PS1, neurons from transgenic animals, and peripheral cells from AD patients. Copyright 2001 Academic Press

Reduced antioxidant enzyme activity in brains of mice transgenic for human presenilin-1 with single or multiple mutations

Alzheimer's disease-related mutations in the presenilin-1 gene (PS1) are leading to an elevated production of neurotoxic beta-amyloid 1-42 and may additionally enhance oxidative stress. Here, we provide in vivo evidence indicating that brains of transgenic mice expressing different human Alzheimer-linked PS1 mutations exhibit a reduced activity of two antioxidant enzymes. For this purpose, mice transgenic for human PS1 and for single and multiple PS1 mutations were generated. Mice with multiple PS1 mutations showed a significantly decreased activity of the antioxidant enzymes Cu/Zn superoxide dismutase and glutathione reductase already at an age of 3-4 months. As expected, this effect was less pronounced for the mice with a single PS1 mutation. By contrast, animals bearing normal human PS1 showed significantly elevated enzyme activities relative to non-transgenic littermate controls

Symmetries and Triplet Dispersion in a Modified Shastry-Sutherland Model for SrCu_2(BO_3)_2

We investigate the one-triplet dispersion in a modified Shastry-Sutherland Model for SrCu_2(BO_3)_2 by means of a series expansion about the limit of strong dimerization. Our perturbative method is based on a continuous unitary transformation that maps the original Hamiltonian to an effective, energy quanta conserving block diagonal Hamiltonian H_{eff}. The dispersion splits into two branches which are nearly degenerated. We analyse the symmetries of the model and show that space group operations are necessary to explain the degeneracy of the dispersion at k=0 and at the border of the magnetic Brillouin zone. Moreover, we investigate the behaviour of the dispersion for small |k| and compare our results to INS data.Comment: 9 pages, 8 figures accepted by J. Phys.: Condens. Matte

Comorbidities Associated with Large Abdominal Aortic Aneurysms

BACKGROUND: Abdominal aortic aneurysm has become increasingly important owing to demographic changes. Some other diseases, for example, cholecystolithiasis, chronic obstructive pulmonary disease, and hernias, seem to co-occur with abdominal aortic aneurysm. The aim of this retrospective analysis was to identify new comorbidities associated with abdominal aortic aneurysm. METHODS: We compared 100 patients with abdominal aortic aneurysms and 100 control patients. Their preoperative computed tomographic scans were examined by two investigators independently, for the presence of hernias, diverticulosis, and cholecystolithiasis. Medical records were also reviewed. Statistical analysis was performed using univariate analysis and multiple logistic regression analysis. RESULTS: The aneurysm group had a higher frequency of diverticulosis (p = 0.008). There was no significant difference in the occurrence of hernia (p = 0.073) or cholecystolithiasis (p = 1.00). Aneurysm patients had a significantly higher American Society of Anesthesiology score (2.84 vs. 2.63; p = 0.015) and were more likely to have coronary artery disease (p < 0.001), congestive heart failure (p < 0.001), or chronic obstructive pulmonary disease (p < 0.001). Aneurysm patients were more likely to be former (p = 0.034) or current (p = 0.006) smokers and had a significantly higher number of pack years (p < 0.001). Aneurysm patients also had a significantly poorer lung function. In multivariate analysis, the following factors were associated with aneurysms: chronic obstructive pulmonary disease (odds ratio, OR = 12.24; p = 0.002), current smoking (OR = 4.14; p = 0.002), and coronary artery disease (OR = 2.60; p = 0.020). CONCLUSIONS: Our comprehensive analysis identified several comorbidities associated with abdominal aortic aneurysms. These results could help to recognize aneurysms earlier by targeting individuals with these comorbidities for screening

Ribonucleoparticle-independent transport of proteins into mammalian microsomes

There are at least two different mechanisms for the transport of secretory proteins into the mammalian endoplasmic reticulum. Both mechanisms depend on the presence of a signal peptide on the respective precursor protein and involve a signal peptide receptor on the cis-side and signal peptidase on the trans-side of the membrane. Furthermore, both mechanisms involve a membrane component with a cytoplasmically exposed sulfhydryl. The decisive feature of the precursor protein with respect to which of the two mechanisms is used is the chain length of the polypeptide. The critical size seems to be around 70 amino acid residues (including the signal peptide). The one mechanism is used by precursor proteins larger than about 70 amino acid residues and involves two cytosolic ribonucleoparticles and their receptors on the microsomal surface. The other one is used by small precursor proteins and relies on the mature part within the precursor molecule and a cytosolic ATPase

Скрытая масса и взрывная эволюция галактик

Быстрая эволюция числа массивных галактик при красном смещении z =6, обнаруженная в последние годы при анализе сверхглубокого поля Хаббла и Субару, может быть объяснена взрывным характером процесса слияния галактик.Швидка еволюція числа масивних галактик при червоному зміщенні z =6, яка була виявлена в останні роки з аналізу надглибокого поля Хаббла і Субару, може бути пояснена вибуховим характером процесу злиття галактик.The fast evolution of number of massive galaxies at the redshift z=6, which recent was found in analyses of the ultra deep Habble field and the same of Subaru, may be explained by the explosive character of galaxy mergings

Nucleosynthesis and the variation of fundamental couplings

We determine the influence of a variation of the fundamental ``constants'' on the predicted helium abundance in Big Bang Nucleosynthesis. The analytic estimate is performed in two parts: the first step determines the dependence of the helium abundance on the nuclear physics parameters, while the second step relates those parameters to the fundamental couplings of particle physics. This procedure can incorporate in a flexible way the time variation of several couplings within a grand unified theory while keeping the nuclear physics computation separate from any model-dependent assumptions.Comment: 8 pages, no figure