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See detailMutation analysis of the neurofilament M gene in Parkinson's disease.
Krüger, Rejko UL; Fischer, Christian; Schulte, Thorsten et al

in Neuroscience letters (2003), 351(2), 125-9

Neurofilament M, a major component of Lewy bodies, represents an interesting candidate in the pathogenesis of Parkinson's disease (PD). We performed detailed mutation analyses of the NF-M gene in 322 ... [more ▼]

Neurofilament M, a major component of Lewy bodies, represents an interesting candidate in the pathogenesis of Parkinson's disease (PD). We performed detailed mutation analyses of the NF-M gene in 322 familial and sporadic PD patients. Two polymorphisms (Ala475Thr and Gly697Arg) occurred at similar frequencies in PD patients and controls. A Pro725Gln substitution and a deletion of valine in position 829 were identified in two PD patients. These substitutions affect residues of the NF-M protein that are highly conserved among different species. None of our patients carried the Gly336Ser substitution, which has been described in familial PD. Our results argue against a major role of NF-M in PD. However, rare variants of the NF-M gene may act as susceptibility factors for PD and functional analyses of the identified variations are warranted to decipher possible mechanisms in neurodegeneration. [less ▲]

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See detailPolymorphisms of the alpha-synuclein promoter: expression analyses and association studies in Parkinson's disease.
Holzmann, C.; Krüger, Rejko UL; Saecker, A. M. M. Vieira et al

in Journal of neural transmission (Vienna, Austria : 1996) (2003), 110(1), 67-76

Mutations of the alpha-synuclein gene have shown to be relevant in some rare families with autosomal dominant Parkinson's disease (PD). Furthermore, alpha-synuclein protein is a major component of the ... [more ▼]

Mutations of the alpha-synuclein gene have shown to be relevant in some rare families with autosomal dominant Parkinson's disease (PD). Furthermore, alpha-synuclein protein is a major component of the Lewy bodies also in sporadic PD patients. Increased levels of wildtype alpha-synuclein in the cell leads to increased intracellular hydrogen peroxide levels and causes death of dopaminergic neurons in rat primary culture. Subsequently, oxidative stress has been directly linked with alpha-synuclein aggregation in vitro. This raises the question whether increased alpha-synuclein expression might be linked to higher susceptibility to PD and whether alpha-synuclein promoter polymorphisms are associated with PD. Here, two polymorphisms (-116C>G and -668T>C) of the alpha-synuclein promoter defining four haplotypes have been characterized in 315 German PD patients. The influence of the four haplotypes on gene expression was studied by CAT reporter gene assays in neuronal SK-N-AS cells. The -668C/-116G haplotype revealed significant higher CAT expression than the -668T/-116G or the -668T/-116C haplotype, respectively. Although the -668C/-116G haplotype was more common in PD patients, this difference was not significant. [less ▲]

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See detailRational promoter selection for gene transfer into cardiac cells.
Maass, Alexander; Langer, Stephen J.; Oberdorf-Maass, Silke et al

in Journal of molecular and cellular cardiology (2003), 35(7), 823-31

Cardiomyocytes (CMCs) are extremely difficult to transfect with non-viral techniques, but they are efficiently infected by adenoviruses. The most commonly used promoters to drive protein expression in ... [more ▼]

Cardiomyocytes (CMCs) are extremely difficult to transfect with non-viral techniques, but they are efficiently infected by adenoviruses. The most commonly used promoters to drive protein expression in cardiac myocytes are of viral origin, since they are believed to be constitutively active and minimally regulated by physiological or pharmacological challenge of cells. In recombinant adenoviruses, we systematically compared three different promoters: the cytomegalovirus (CMV), the Rous sarcoma virus (RSV), and a synthetic promoter with three MEF2 transcription factor-binding sites upstream of the heat-shock protein 68 minimal promoter. We determined their basal activity in primary cardiac cells as well as their possible stimulation by commonly used agonists. The CMV promoter was activated up to 60-fold by the phorbol ester phorbol myristate acetate (PMA) and/or forskolin in neonatal rat CMCs and cardiac fibroblasts. Primary adult rat CMCs had higher basal expression from the CMV promoter that was not activated by PMA or forskolin. The RSV promoter was less affected by agonists and was more active in cardiac myocytes compared to cardiac fibroblasts. The MEF2-responsive promoter showed high basal expression in both myocytes and fibroblasts, and minimal induction by phorbol esters and forskolin. The relevance of reporter gene induction was confirmed with a contractile protein, troponin T (TnT). The CMV promoter driving TnT could be induced more than 15-fold with phenylephrine or forskolin to replace the endogenous protein almost to completion at a multiplicity of infection of 10. These results suggest the following use of the tested promoters: an inducible system (CMV), a myocyte-enriched system (RSV), or a stable control system (MEF2). [less ▲]

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See detailHaploinsufficiency at the alpha-synuclein gene underlies phenotypic severity in familial Parkinson's disease.
Kobayashi, Hirokazu; Krüger, Rejko UL; Markopoulou, Katerina et al

in Brain : a journal of neurology (2003), 126(Pt 1), 32-42

To date, two point mutations, G209A and G88C, have been reported in the coding region of the alpha-synuclein gene in autosomal dominant familial Parkinson's disease. When translated, these lead to the ... [more ▼]

To date, two point mutations, G209A and G88C, have been reported in the coding region of the alpha-synuclein gene in autosomal dominant familial Parkinson's disease. When translated, these lead to the missense mutations Ala53Thr and Ala30Pro, respectively. Reduced mRNA expression of the G209A allele was reported recently in a Greek-American family. Here, we show that alpha-synuclein mRNA is normally expressed in blood cells and report the results of an analysis of alpha-synuclein mRNA and protein expression in lymphoblastoid cell lines established from kindreds with the G209A and G88C mutations. mRNA expression was characterized using a TaqMan real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. We assessed five affected and three unaffected members of a German family with the G88C mutation and two affected members in different, unrelated Greek families with the G209A mutation. The ratio of wild-type to mutant alpha-synuclein allele expression ranged from 2.2 to 9.2 in the affected individuals with a severe clinical phenotype. The ratios of the expression levels of the wild-type to mutant alleles were only slightly decreased in mild cases and were less than 1.0 in two asymptomatic heterozygotes. Sequence analysis of the RT-PCR products showed only the presence of G in position 88 and G in position 209 in severely affected heterozygotes of the German and Greek families, respectively. High performance liquid chromatography/mass spectrometry demonstrated that, relative to wild-type alpha-synuclein, there is a reduction of Ala30Pro alpha-synuclein in lymphoblastoid cell lines originating from severely affected, but not mildly affected G88C/+ heterozygotes. Taken together, these data indicate that there is haploinsufficiency at the alpha-synuclein gene and that the ratio of expression of the wild-type to mutant alleles correlates with the severity of the clinical phenotype. Furthermore, these findings suggest that haploinsufficiency of alpha-synuclein mutations may contribute to disease progression in these forms of familial Parkinson's disease. [less ▲]

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See detailImprovement of endothelial dysfunction by selective estrogen receptor-alpha stimulation in ovariectomized SHR.
Widder, Julian; Pelzer, Theo; von Poser-Klein, Christine et al

in Hypertension (2003), 42(5), 991-6

Both known estrogen receptors, ERalpha and ERbeta, are expressed in blood vessels. To gain further insight into the role of ERalpha in a functional setting, we investigated the effect of the novel highly ... [more ▼]

Both known estrogen receptors, ERalpha and ERbeta, are expressed in blood vessels. To gain further insight into the role of ERalpha in a functional setting, we investigated the effect of the novel highly selective ERalpha agonist Cpd1471 on vascular reactivity in ovariectomized spontaneously hypertensive rats (SHR). After ovariectomy or sham operation, 12-week-old female SHR received either 17beta-estradiol (E2, 2 microg/kg body wt per day), the selective ERalpha agonist Cpd1471 (30 microg/kg body wt per day), or placebo. Acetylcholine-induced endothelium-dependent vasorelaxation was significantly blunted in aortas from ovariectomized rats (Rmax, 53%+/-3% versus sham, 79%+/-2%; P<0.001). Treatment with E2 or Cpd1471 significantly augmented acetylcholine-induced relaxation in ovariectomized rats (Rmax, 70%+/-2%; resp, 73%+/-2%). Endothelium-independent relaxation induced by sodium nitroprusside was not different among the four groups. The contractile response induced by the nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine, an index of basal NO formation, was significantly lower in ovariectomized rats compared with sham-operated animals (53+/-2% versus 77%+/-5%; P<0.01) and was normalized by both E2 (70%+/-2%) and Cpd1471 (70%+/-3%). Aortic endothelial NO synthase (eNOS) expression and phosphorylation of the vasodilator-stimulated phosphoprotein, an index of NO/cGMP-signaling, was reduced in ovariectomized SHR and normalized by E2 and Cpd1471. In SHR after ovariectomy, endothelium-dependent NO-mediated vasorelaxation and eNOS expression are attenuated. The novel selective ERalpha agonist Cpd1471 prevented these pathophysiological changes to a similar extent as E2. Thus, the pharmacological principle of selective ERalpha activation mediates positive vascular effects. [less ▲]

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See detailThe molecular basis of myocardial hypertrophy and heart failure.
Ritter, Oliver; Neyses, Ludwig UL

in Trends in molecular medicine (2003), 9(7), 313-21

Heart failure (HF) is the inability of the heart to cope with the metabolic demands of the periphery. It is the common end-stage of many frequent cardiac diseases and is characterized by relentless ... [more ▼]

Heart failure (HF) is the inability of the heart to cope with the metabolic demands of the periphery. It is the common end-stage of many frequent cardiac diseases and is characterized by relentless progression. Mechanisms of progression include renal sodium and water retention, neurohumoral activation and alterations of the protein composition (gene programme) of the heart itself. In this review, we explain the often confusing terminology in the subject, briefly touch upon the peripheral mechanisms of HF, and then focus on the changes in the gene programme of the failing heart and the molecular mechanisms leading to them. Understanding the basic processes underlying HF will help uninitiated readers to gain insight into recent novel approaches to its treatment. [less ▲]

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See detailLie-algebraic characterization of manifold structures
Poncin, Norbert UL

Scientific Conference (2003)

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See detailInteraction of the plasma membrane Ca2+ pump 4b/CI with the Ca2+/calmodulin-dependent membrane-associated kinase CASK.
Schuh, Kai; Uldrijan, Stjepan; Gambaryan, Stepan et al

in The Journal of biological chemistry (2003), 278(11), 9778-83

Spatial and temporal regulation of intracellular Ca(2+) is a key event in many signaling pathways. Plasma membrane Ca(2+)-ATPases (PMCAs) are major regulators of Ca(2+) homeostasis and bind to PDZ (PSD-95 ... [more ▼]

Spatial and temporal regulation of intracellular Ca(2+) is a key event in many signaling pathways. Plasma membrane Ca(2+)-ATPases (PMCAs) are major regulators of Ca(2+) homeostasis and bind to PDZ (PSD-95/Dlg/ZO-1) domains via their C termini. Various membrane-associated guanylate kinase family members have been identified as interaction partners of PMCAs. In particular, SAP90/PSD95, PSD93/chapsyn-110, SAP97, and SAP102 all bind to the C-terminal tails of PMCA "b" splice variants. Additionally, it has been demonstrated that PMCA4b interacts with neuronal nitric-oxide synthase and that isoform 2b interacts with Na(+)/H(+) exchanger regulatory factor 2, both via a PDZ domain. CASK (calcium/calmodulin-dependent serine protein kinase) contains a calmodulin-dependent protein kinase-like domain followed by PDZ, SH3, and guanylate kinase-like domains. In adult brain CASK is located at neuronal synapses and interacts with various proteins, e.g. neurexin and Veli/LIN-7. In kidney it is localized to renal epithelia. Surprisingly, interaction with the Tbr-1 transcription factor, nuclear transport, binding to DNA T-elements (in a complex with Tbr-1), and transcriptional competence has been shown. Here we show that the C terminus of PMCA4b binds to CASK and that both proteins co-precipitate from brain and kidney tissue lysates. Immunofluorescence staining revealed co-expression of PMCA, CASK, and calbindin-d-28K in distal tubuli of rat kidney sections. To test if physical interaction of both proteins results in functional consequences we constructed a T-element-dependent reporter vector and investigated luciferase activity in HEK293 lysates, previously co-transfected with PMCA4b expression and control vectors. Expression of wild-type PMCA resulted in an 80% decrease in T-element-dependent transcriptional activity, whereas co-expression of a point-mutated PMCA, with nearly eliminated Ca(2+) pumping activity, had only a small influence on regulation of transcriptional activity. These results provide evidence of a new direct Ca(2+)-dependent link from the plasma membrane to the nucleus. [less ▲]

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See detailAngular distribution of highly charged ions transmitted through metallic microcapillaries
Tokesi, K.; Wirtz, Ludger UL; Lemell, C. et al

in Journal of Electron Spectroscopy & Related Phenomena (2003), 129(2-3), 195-200

The angular distribution of Xe6+ ions with an energy of 800 eV/q transmitted through Ni microcapillaries is studied by a classical trajectory simulation. The results for clean and contaminated by layers ... [more ▼]

The angular distribution of Xe6+ ions with an energy of 800 eV/q transmitted through Ni microcapillaries is studied by a classical trajectory simulation. The results for clean and contaminated by layers of insulating materials of the internal surface of capillary are presented. We show that the angular distributions can be used to identify different phases of hollow ion formation for clean metal surface. We also show that the angular distribution changes dramatically for the case of contaminated surface, i.e. when the image acceleration is depressed. (C) 2003 Elsevier Science B.V. All rights reserved. [less ▲]

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See detailSchulischer Fremdsprachenunterricht und migrationsbedingte Mehrsprachigkeit.
Hu, Adelheid UL

Book published by Gunter Narr (2003)

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See detailLie algebras of differential operators
Poncin, Norbert UL

Scientific Conference (2003)

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See detailAT2 receptor activation regulates myocardial eNOS expression via the calcineurin-NF-AT pathway.
Ritter, Oliver; Schuh, Kai; Brede, Marc et al

in FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2003), 17(2), 283-5

The role of AT2-receptors has recently been subject of considerable debate. We investigated the influence of AT2-stimulation/inhibition on myocardial endothelial NO-synthase (eNOS, NOS-III) promoter ... [more ▼]

The role of AT2-receptors has recently been subject of considerable debate. We investigated the influence of AT2-stimulation/inhibition on myocardial endothelial NO-synthase (eNOS, NOS-III) promoter activity and eNOS protein expression. Stimulation of rat cardiomyocytes with angiotensin II (AngII) increased eNOS protein expression 3.3-fold. This was blocked by Cyclosporin A (CsA). Inhibition of the AT1-receptor did not reduce AngII-mediated eNOS protein expression, whereas AT2 stimulation increased it 2.4-fold and AT2 inhibition suppressed it. The modulatory effects of the AT2-receptor on eNOS expression was confirmed in mice with a genetic deletion of the AT2-receptor (AT2-KO). In gel shift assays two putative NF-AT sites in a 1.6 kb eNOS promoter fragment showed NF-AT binding and a supershift by NF-AT2(-c1)-specific antibodies. Stimulation of transfected cells with AngII or specific AT2-receptor agonists resulted in a significant increase in eNOS promoter activity, which was blocked by CsA, MCIP1, and mutation of an upstream NF-AT site. CONCLUSION: 1) AngII-stimulation of the myocardium, both in vivo and in vitro, is accompanied by increased expression of eNOS. 2) This effect is mediated by the calcineurin pathway and is induced by the AT2-receptor. 3) These results define a calcineurin/NF-AT/eNOS pathway as downstream effector of AT2-receptor activation in the myocardium. [less ▲]

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See detailRegulation of vascular tone in animals overexpressing the sarcolemmal calcium pump.
Schuh, Kai; Quaschning, Thomas; Knauer, Sebastian et al

in The Journal of biological chemistry (2003), 278(42), 41246-52

The mechanisms governing vascular smooth muscle tone are incompletely understood. In particular, the role of the sarcolemmal calcium pump PMCA (plasma membrane calmodulin-dependent calcium ATPase), which ... [more ▼]

The mechanisms governing vascular smooth muscle tone are incompletely understood. In particular, the role of the sarcolemmal calcium pump PMCA (plasma membrane calmodulin-dependent calcium ATPase), which extrudes Ca2+ from the cytosol, and its importance compared with the sodium/calcium exchanger remain speculative. To test whether the PMCA is a regulator of vascular tone, we generated transgenic mice overexpressing the human PMCA4b under control of the arterial smooth muscle-specific SM22alpha promoter. This resulted in an elevated systolic blood pressure compared with littermate controls. In PMCA-overexpressing mice, endothelium-dependent relaxation of norepinephrine-preconstricted aortic rings to acetylcholine did not differ from wild type controls (76 +/- 8% versus 79 +/- 8% of maximum relaxation; n = 12, n.s.). De-endothelialized aortas of transgenic mice exhibited stronger maximum contraction to KCl (100 mmol/liter) compared with controls (86 +/- 6% versus 68 +/- 7% of reference KCl contraction at the beginning of the experiment; p <0.05). Preincubation of de-endothelialized vessels with the nitric oxide synthase (NOS) inhibitor l-NAME (l-N(G)-nitroarginine methyl ester) (10-5 mol/liter) resulted in a stronger contraction to KCl (p <0.05 versus without l-NAME), thus unmasking vasodilatory effects of inherent NO production. Maximum contraction to KCl after preincubation with l-NAME did not differ between PMCA mice and controls. In analogy to the results in PMCA-overexpressing mice, contractions of de-endothelialized aortas of neuronal NOS-deficient mice to KCl were significantly increased compared with controls (151 +/- 5% versus 131 +/- 6% of reference KCl contraction; p <0.05). In conclusion, our data suggest a model in which the sarcolemmal Ca2+ pump down-regulates activity of the vascular smooth muscle Ca2+/calmodulin-dependent neuronal NOS by a functionally relevant interaction. Therefore, the PMCA represents a novel regulator of vascular tone. [less ▲]

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See detailModulation of disease risk according to a cathepsin D / apolipoprotein E genotype in Parkinson's disease.
Schulte, T.; Bohringer, S.; Schols, L. et al

in Journal of neural transmission (Vienna, Austria : 1996) (2003), 110(7), 749-55

Aspartyl protease Cathepsin D (CTSD) has been suggested to play a role in the pathogenesis of sporadic Alzheimer's disease (AD) due to interference with protein degradation mechanisms. A C224T (A38V ... [more ▼]

Aspartyl protease Cathepsin D (CTSD) has been suggested to play a role in the pathogenesis of sporadic Alzheimer's disease (AD) due to interference with protein degradation mechanisms. A C224T (A38V) polymorphism in exon 2 of the CTSD gene is reported to be associated with an increased risk for AD. The partially overlapping pathology between AD and Parkinson's disease (PD) led us to investigate the role of this polymorphism in PD. Using association studies in 457 German PD patients and 340 controls we found no evidence for direct association between the CTSD genotype and PD. However, stratification for the apolipoprotein E (APOE) epsilon4 allele suggests a protective effect of the CTSD T-allele in PD (OR = 0.24, p = 0.002). Our findings suggest interference of CTSD and APOE polymorphisms in the pathogenesis of PD, in the sense of modulating disease risk. [less ▲]

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See detailSeveral entries
Schlichenmaier, Martin UL

in Bagger, J.; Duplij, S.; Siegel, W. (Eds.) Concise Encyclopedia on supersymmetry and non-commutative structures in mathematics and physics (2003)

Detailed reference viewed: 26 (0 UL)
See detailseveral entries in the field algebra, algebraic topology, homological algebra, categories
Schlichenmaier, Martin UL

in Walz (Ed.) Lexikon der Mathematik (2003)

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See detailDifferent glassy states, as indicated by a violation of the generalized Cauchy relation.
Krüger, Jan-Kristian UL; Britz, Th; le Coutre, A. et al

in New Journal of Physics (2003), 5(80), 1-11

Using Brillouin spectroscopy as a probe for high-frequency clamped acoustic properties, a shear modulus can be measured in addition to the longitudinal modulus already well above the thermal glass ... [more ▼]

Using Brillouin spectroscopy as a probe for high-frequency clamped acoustic properties, a shear modulus can be measured in addition to the longitudinal modulus already well above the thermal glass transition. On slow cooling of the liquid through the thermal glass transition temperature Tg, both moduli show a kink-like behaviour and the function follows a generalized Cauchy relation (gCR) defined by the linear relation , which completely hides the glass transition. In this work we show experimentally that on fast cooling this linear transformation becomes violated within the glassy state, but that thermal ageing drives the elastic coefficients towards the gCR, i.e. towards a unique glassy state. [less ▲]

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See detailMehrsprachigkeitsforschung, Identität- und Kulturtheorie: Tendenzen der Konvergenz.
Hu, Adelheid UL

in De Florio Hansen, I.; Hu, Adelheid (Eds.) Plurilingualität und Identität. Zur Selbst- und Fremdwahrnehmung mehrsprachiger Menschen (2003)

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See detailPlurilingualität und Identität. Zur Selbst- und Fremdwahrnehmung mehrsprachiger Menschen
Hu, Adelheid UL; De Florio-Hansen, Inez Ed

Book published by Stauffenburg (2003)

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