Der "Heidi-loves-you-shop" lag in der Bockenheimer ... : vom alten zum neuen Literaturhaus: ein Wegweiser für literarische Spaziergänge durch Frankfurt

Rezension zu: Maria Gazzetti (Hrsg.) : Frankfurt : Literarische Spaziergänge. S. Fischer Verlag, Frankfurt 2005, ISBN 3-596-16935-6, 207 Seiten, 9,95 Euro

Modulatory effects of levodopa on cerebellar connectivity in Parkinson’s disease

Levodopa has been the mainstay of symptomatic therapy for Parkinson’s disease (PD) for the last five decades. However, it is associated with the development of motor fluctuations and dyskinesia, in particular after several years of treatment. The aim of this study was to shed light on the acute brain functional reorganization in response to a single levodopa dose. Functional magnetic resonance imaging (fMRI) was performed after an overnight withdrawal of dopaminergic treatment and 1 h after a single dose of 250 mg levodopa in a group of 24 PD patients. Eigenvector centrality was calculated in both treatment states using resting-state fMRI. This offers a new data-driven and parameter-free approach, similar to Google’s PageRank algorithm, revealing brain connectivity alterations due to the effect of levodopa treatment. In all PD patients, levodopa treatment led to an improvement of clinical symptoms as measured with the Unified Parkinson’s Disease Rating Scale motor score (UPDRS-III). This therapeutic effect was accompanied with a major connectivity increase between cerebellar brain regions and subcortical areas of the motor system such as the thalamus, putamen, globus pallidus, and brainstem. The degree of interconnectedness of cerebellar regions correlated with the improvement of clinical symptoms due to the administration of levodopa. We observed significant functional cerebellar connectivity reorganization immediately after a single levodopa dose in PD patients. Enhanced general connectivity (eigenvector centrality) was associated with better motor performance as assessed by UPDRS-III score. This underlines the importance of considering cerebellar networks as therapeutic targets in PD

Putting the “We” Into Well‐being: Using Collectivism‐Themed Measures of Well‐Being Attenuates Well‐being's Association With Individualism

Studies repeatedly have documented that societal well‐being is associated with individualism. Most of these studies, however, have conceptualized/measured well‐being as individual life satisfaction—a type of well‐being that originates in Western research traditions. Drawing from the latest research on interdependent happiness and on family well‐being, we posit that people across cultures pursue different types of well‐being, and test whether more collectivism‐themed types of well‐being that originate in Confucian traditions also are associated with individualism. Based on data collected from 2,036 participants across 12 countries, we find support for the association between individual life satisfaction and individualism at the societal level, but show that well‐being's association with individualism is attenuated when some collectivism‐themed measures of well‐being are considered. Our article advances knowledge on the flourishing of societies by suggesting that individualism may not always be strongly linked with societal well‐being. Implications for public policies are signaled

Ultrahigh Piezoelectric Strains in PbZr1−xTixO3 single crystals with controlled Ti content close to the tricritical point

Intensive investigations of PbZr Ti O (PZT) materials with the ABO perovskite structure are connected with their extraordinary piezoelectric properties. Especially well known are PZT ceramics at the Morphotropic Phase Boundary (MPB), with x~0.48, whose applications are the most numerous among ferroelectrics. These piezoelectric properties are often obtained by doping with various ions at the B sites. Interestingly, we have found similar properties for undoped PZT single crystals with low Ti content, for which we have confirmed the existence of the tricritical point near x~0.06. For a PbZr Ti O crystal, we describe the ultrahigh strain, dielectric, optical and piezoelectric properties. We interpret the ultrahigh strain observed in the region of the antiferroelectric-ferroelectric transition as an inverse piezoelectric effect generated by the coexistence of domains of different symmetries. The complex domain coexistence was confirmed by determining optical indicatrix orientations in domains. The piezoelectric coefficient in this region reached an extremely high value of 5000 pm/V. We also verified that the properties of the PZT single crystals from the region near the tricritical point are incredibly susceptible to a slight deviation in the Ti content

Restoration of Podocyte Structure and Improvement of Chronic Renal Disease in Transgenic Mice Overexpressing Renin

Proteinuria is a major marker of the decline of renal function and an important risk factor of coronary heart disease. Elevated proteinuria is associated to the disruption of slit-diaphragm and loss of podocyte foot processes, structural alterations that are considered irreversible. The objective of the present study was to investigate whether proteinuria can be reversed and to identify the structural modifications and the gene/protein regulation associated to this reversal.We used a novel transgenic strain of mouse (RenTg) that overexpresses renin at a constant high level. At the age of 12-month, RenTg mice showed established lesions typical of chronic renal disease such as peri-vascular and periglomerular inflammation, glomerular ischemia, glomerulosclerosis, mesangial expansion and tubular dilation. Ultrastructural analysis indicated abnormal heterogeneity of basement membrane thickness and disappearance of podocyte foot processes. These structural alterations were accompanied by decreased expressions of proteins specific of podocyte (nephrin, podocin), or tubular epithelial cell (E-cadherin and megalin) integrity. In addition, since TGFbeta is considered the major pro-fibrotic agent in renal disease and since exogenous administration of BMP7 is reported to antagonize the TGFbeta-induced phenotype changes in kidney, we have screened the expressions of several genes belonging in the TGFbeta/BMP superfamily. We found that the endogenous inhibitors of BMPs such as noggin and Usag-1 were several-fold activated inhibiting the action of BMPs and thus reinforcing the deleterious action of TGFbeta.Treatment with an AT1 receptor antagonist, at dose that did not decrease arterial pressure, gradually reduced albuminuria. This decrease was accompanied by re-expression of podocin, nephrin, E-cadherin and megalin, and reappearance of podocyte foot processes. In addition, expressions of noggin and Usag-1 were markedly decreased, permitting thus activation of the beneficial action of BMPs.These findings show that proteinuria and alterations in the expression of proteins involved in the integrity and function of glomerular and renal epithelial phenotype are reversible events when the local action of angiotensin II is blocked, and provide hope that chronic renal disease can be efficiently treated

Keratinocyte Growth Factor Induces Gene Expression Signature Associated with Suppression of Malignant Phenotype of Cutaneous Squamous Carcinoma Cells

Keratinocyte growth factor (KGF, fibroblast growth factor-7) is a fibroblast-derived mitogen, which stimulates proliferation of epithelial cells. The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair. However, the role of KGF in cutaneous carcinogenesis and cancer progression is not known. We have examined the role of KGF in progression of squamous cell carcinoma (SCC) of the skin. The expression of KGF receptor (KGFR) mRNA was lower in cutaneous SCCs (n = 6) than in normal skin samples (n = 6). Expression of KGFR mRNA was detected in 6 out of 8 cutaneous SCC cell lines and the levels were downregulated by 24-h treatment with KGF. KGF did not stimulate SCC cell proliferation, but it reduced invasion of SCC cells through collagen. Gene expression profiling of three cutaneous SCC cell lines treated with KGF for 24 h revealed a specific gene expression signature characterized by upregulation of a set of genes specifically downregulated in SCC cells compared to normal epidermal keratinocytes, including genes with tumor suppressing properties (SPRY4, DUSP4, DUSP6, LRIG1, PHLDA1). KGF also induced downregulation of a set of genes specifically upregulated in SCC cells compared to normal keratinocytes, including genes associated with tumor progression (MMP13, MATN2, CXCL10, and IGFBP3). Downregulation of MMP-13 and KGFR expression in SCC cells and HaCaT cells was mediated via ERK1/2. Activation of ERK1/2 in HaCaT cells and tumorigenic Ha-ras-transformed HaCaT cells resulted in downregulation of MMP-13 and KGFR expression. These results provide evidence, that KGF does not promote progression of cutaneous SCC, but rather suppresses the malignant phenotype of cutaneous SCC cells by regulating the expression of several genes differentially expressed in SCC cells, as compared to normal keratinocytes