1. |
- Bode, Felix J., et al.
(author)
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Increased numbers of motor activity peaks during light cycle are associated with reductions in adrenergic alpha(2)-receptor levels in a transgenic Huntington's disease rat model
- 2009
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In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 205:1, s. 175-182
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Journal article (peer-reviewed)abstract
- Huntington's disease (HID) is a neurodegenerative disorder caused by a CAG repeat expansion in the HD gene. Besides psychiatric, motor and cognitive symptoms, HD patients suffer from sleep disturbances. In order to screen a rat model transgenic for HD (tgHD rats) for sleep-wake cycle dysregulation, we monitored their circadian activity peaks in the present study. TgHD rats of both sexes showed hyperactivity during the dark cycle and more frequent light cycle activity peaks indicative for a disturbed sleep-wake cycle. Focusing on males at the age of 4 and 14 months, analyses of receptor levels in the hypothalamus and the basal forebrain revealed that 5-HT2A- and adrenergic alpha(2)-receptor densities in these regions were significantly altered in tgHD rats compared to their wild-type littermates. Adrenergic receptor densities correlated negatively with the light cycle hyperactivity peaks at later stages of the disease in male tgHD rats. Furthermore, reduced leptin levels, a feature associated with circadian misalignment, were present. Our study demonstrates that the male tgHD rat is a suitable model to investigate HD associated sleep alterations. Further studies are warranted to elucidate the role of adrenergic- and 5-HT2A- receptors as therapeutic targets for dysregulation of the circadian activity in HD. (C) 2009 Elsevier B.V. All rights reserved.
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2. |
- Bode, Felix J., et al.
(author)
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Sex differences in a transgenic rat model of Huntington's disease: decreased 17 beta-estradiol levels correlate with reduced numbers of DARPP32(+) neurons in males
- 2008
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 17:17, s. 2595-2609
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Journal article (peer-reviewed)abstract
- Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed by experimental studies documenting the protective role of female sex hormones both in vitro and in vivo, although these studies did not specifically focus on Huntington's disease (HD). We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) morphological markers (numbers and characteristics of striatal DARPP32(+) medium-sized spiny neurons (MSNs) and dopamine receptor autoradiography) and (iii) peripheral sex hormone levels as well as striatal estrogen receptor expression. Independent of their sex, tgHD rats exhibited increased levels of food intake, elevated home-cage activity scores and anxiolytic-like behavior, whereas only males showed an impairment of motor function. In line with the latter finding, loss and atrophy of DARPP32(+) MSNs were apparent only in male tgHD rats. This result was associated with a decreased striatal dopamine D1 receptor density and lower plasma levels of 17 beta-estradiol at the age of 14 months. As DARPP32(+) MSNs expressed both alpha-and beta-estrogen receptors and showed a correlation between cell numbers and 17 beta-estradiol levels, our findings suggest sex-related differences in the HD phenotype pointing to a substantial neuroprotective effect of sex hormones and opening new perspectives on the therapy of HD.
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3. |
- Pivarcsi, Andor, et al.
(author)
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Tumor immune escape by the loss of homeostatic chemokine expression.
- 2007
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:48, s. 19055-60
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Journal article (peer-reviewed)abstract
- The novel keratinocyte-specific chemokine CCL27 plays a critical role in the organization of skin-associated immune responses by regulating T cell homing under homeostatic and inflammatory conditions. Here we demonstrate that human keratinocyte-derived skin tumors may evade T cell-mediated antitumor immune responses by down-regulating the expression of CCL27 through the activation of epidermal growth factor receptor (EGFR)-Ras-MAPK-signaling pathways. Compared with healthy skin, CCL27 mRNA and protein expression was progressively lost in transformed keratinocytes of actinic keratoses and basal and squamous cell carcinomas. In vivo, precancerous skin lesions as well as cutaneous carcinomas showed significantly elevated levels of phosphorylated ERK compared with normal skin, suggesting the activation of EGFR-Ras signaling pathways in keratinocyte-derived malignancies. In vitro, exogenous stimulation of the EGFR-Ras signaling pathway through EGF or transfection of the dominant-active form of the Ras oncogene (H-RasV12) suppressed whereas an EGFR tyrosine kinase inhibitor increased CCL27 mRNA and protein production in keratinocytes. In mice, neutralization of CCL27 led to decreased leukocyte recruitment to cutaneous tumor sites and significantly enhanced primary tumor growth. Collectively, our data identify a mechanism of skin tumors to evade host antitumor immune responses.
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4. |
- Baczko, Tadeusz, et al.
(author)
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Location Conditions in East Germany and in Poland from the Point of View of the Companies
- 2008
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In: DIW: Weekly Report. - : German Institute for Economic Research. - 1860-3343. ; 4:3, s. 14-20
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Journal article (peer-reviewed)abstract
- A joint research project at the European University Viadrina, DIW Berlin and the Polish Academy of Science has investigated how companies assess their locational conditions and whether there is a relationship between location attributes and the company performance. In both countries the majority of companies assessed the same location attributes as being important or unimportant for the company's performance. Some remarkable differences were found in the evaluation of locational quality. In both countries, the supply of skilled employees is deemed to be the most important quality criterion of a location, and the current situation regarding this location factor is assessed as satisfactory. The companies in Poland more often evaluate the supply of training and qualification facilities as important compared to companies in East Germany, and the availability is assessed as good in both regions. Less important are traffic conditions. This is-not unexpectedly-assessed worse by Polish companies compared to the East German ones. The support by chambers of commerce is more often important for the Polish companies compared to East German ones. This potentially reflects the different importance of commercial authorities in both countries. Local administration is on average rated worse by the East German companies compared to Polish counterparts.
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5. |
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6. |
- Badunenko, Oleg, et al.
(author)
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Allocative Efficiency Measurement Revisited : Do We Really Need Input Prices?
- 2008
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In: Economic Modelling. - : Elsevier. - 0264-9993 .- 1873-6122. ; 25:5, s. 1093-1109
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Journal article (peer-reviewed)abstract
- The traditional approach to measuring allocative efficiency exploits input prices, which are rarely known at the firm level. This paper proves allocative efficiency can be measured as a profit-oriented distance to the frontier in a profit-technical efficiency space. This new approach does not require information on input prices. To validate the new approach, we perform a Monte-Carlo experiment providing evidence that the estimates of allocative efficiency employing the new and the traditional approach are highly correlated. Finally, as an illustration, we apply the new approach to a sample of about 900 enterprises from the chemical manufacturing industry in Germany.
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7. |
- Badunenko, Oleg, et al.
(author)
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What Drives the Productive Efficiency of a Firm? : the importance of industry, location, R&D, and size
- 2008
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Reports (other academic/artistic)abstract
- This paper investigates the factors that explain the level and dynamics of manufacturing firm productive efficiency. In our empirical analysis, we use a unique sample of about 39,000 firms in 256 industries from the German Cost Structure Census over the years 1992-2005. We estimate the efficiencies of the firms and relate them to firm-specific and environmental factors. We find that (1) about half the model’s explanatory power is due to industry effects, (2) firm size accounts for another 20 percent, and (3) location of headquarters explains approximately 15 percent. Interestingly, most other firm characteristics, such as R&D intensity, outsourcing activities, or the number of owners, have extremely little explanatory power. Surprisingly, our findings suggest that higher R&D intensity is associated with being less efficient, though higher R&D spending increases a firm’s efficiency over time.
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8. |
- Barasinska, Nataliya, et al.
(author)
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Financial Risk Aversion and Household Asset Diversification
- 2008
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Reports (other academic/artistic)abstract
- This paper explores the relationship between risk attitude and asset diversification in household portfolios. We first examine the impact of manifested risk aversion on the total number of distinct assets held in a portfolio (naive diversification). The second part of the paper focuses on a more sophisticated strategy of diversification and asks whether financial theory is compatible with observed diversification patterns. Based on the German Socioeconomic Panel which provides unique measures of individual propensity for taking risk, the results of the regression analysis show that, along with some socioeconomic characteristics, the propensity for taking investment risk is an important predictor of a household's diversification strategy. However, some of our findings are strongly at odds with what the concept of mean-variance utility suggests.
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9. |
- Barasinska, Nataliya, et al.
(author)
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Hohe Risikoaversion privater Haushalte bei Geldanlagen
- 2008
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In: Wochenbericht. - Berlin : DIW Berlin. - 0012-1304. ; 75:45, s. 704-710
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Journal article (peer-reviewed)abstract
- Eine möglichst breite Streuung der Geldanlagengilt als eine wichtige Strategie der Risikominimierungbei Investitionsentscheidungen. Die Mehrzahlder Haushalte in Deutschland streut auch ihrGeldvermögen über mehrere Anlageformen. IhrAnlageverhalten stimmt jedoch nur bedingt mitder von Haushaltsvorständen bekundeten Risikobereitschaftüberein. Dies zeigt eine aktuelle empirischeStudie auf Basis des Sozio-oekonomischenPanels (SOEP). So steigt zwar die Wahrscheinlichkeit,seine Anlagen zu streuen tendenziell mit derRisikoaversion an, allerdings nur solange es sichnicht um einen „vollständig gestreuten Anlagekorb“handelt. Die Neigung, ein Portfolio mit allenAnlageformen zu halten, nimmt mit wachsenderScheu vor dem Risiko ab. Offenbar entscheidenHaushaltsvorstände nach dem bereits von Keynespropagierten Prinzip: Sicherheit und Liquiditätkommen zuerst. Die Bereitschaft in riskantere Anlagenzu investieren, steigt mit der Anzahl bereitsbestehender sicherer Anlagen im Portfolio.
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10. |
- Barasinska, Nataliya, et al.
(author)
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Private Households Display Strong Aversion to Investment Risk
- 2009
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In: DIW Berlin Weekly Report. - : German Institute for Economic Research. - 1860-3343. ; 5:2, s. 13-18
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Journal article (peer-reviewed)abstract
- The broadest possible diversification of investments is considered an important strategy for minimizing investment risk. Most households in Germany do distribute their financial assets over several types of investment. However, investment behavior is only partially consistent with the overall readiness for risk-taking reported by heads of households. This is demonstrated by a current empirical study based on data from the Socio-Economic Panel Study (SOEP). The probability of diversification does tend to rise according to the degree of risk aversion, yet not when it comes to a ""fully diversified investment basket."" With a higher fear of risk, the tendency to fill a portfolio with every kind of investment falls. Clearly, households make decisions in keeping with a principle propagated by Keynes: security and liquidity come first. The readiness to invest in riskier assets rises with the number of secure investments already in place in the portfolio.
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