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Gothenborg, Sweden

Reiter W.,University of Vienna | Reiter W.,Christian Doppler Laboratory | Anrather D.,University of Vienna | Dohnal I.,Christian Doppler Laboratory | And 7 more authors.
Proteomics | Year: 2012

Global phosphoproteomic studies based on MS have generated qualitative and quantitative data describing protein phosphorylation events in various biological systems. Since high-throughput data for protein modifications are inherently incomplete, we developed a strategy to extend and validate such primary datasets. We selected interesting protein candidates from a global screen in yeast and employed a modified histidine biotin tag that allows tandem affinity purifications of our targets under denaturing conditions. Products in question can be digested directly from affinity resins and phosphopeptides can be further enriched via TiO2 before MS analysis. Our robust protocol can be amended for SILAC as well as iTRAQ quantifications or label-free approaches based on selective reaction monitoring, allowing completion of the phosphorylation pattern in a first step, followed by a detailed analysis of the phosphorylation kinetics. We exemplify the value of such a strategy by an in-depth analysis of Pan1, a highly phosphorylated factor involved in early steps of endocytosis. The study of Pan1 under osmotic stress conditions in different mutant backgrounds allowed us to differentiate between mitogen-activated protein kinase Hog1 driven and Hog1 independent stress responses. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Qian W.,Peking University | Shan X.,Peking University | Chen D.,University of Gothenborg | Zhu C.,Chinese Academy of Meteorological Sciences | Zhu Y.,Peking University
Climatic Change | Year: 2012

Historical annual dry-wet index for 1470-2003 combined with instrumental precipitation since 1951 were used to identify extremely dry years and events near the northern fringe of the East Asian summer monsoon in China-the Great Bend of the Yellow River (GBYR) region. In total, 49 drought years, of which 26 were severe, were identified. Composites of the dry-wet index under the drought years show an opposite wet pattern over the Southeast China. The longest drought event lasted for 6 years (1528-1533), the second longest one 4 years (1637-1640). The most severe 2-year-long drought occurred in 1928-1929, and the two driest single years were 1900 and 1965. These persistent and extreme drought events caused severe famines and huge losses of human lives. Wavelet transform applied to the dry-wet index indicates that the severe drought years are nested in several significant dry-wet variations across multiple timescales, i.e., the 65-85 year timescale during 1600- 1800, 40-55 year timescale before 1640 and 20-35 year timescale mainly from 1550 to 1640. These timescales of dry-wet variations are discussed in relation to those forcing such as cycles of solar radiation, oscillation in the thermohaline circulation and the Pacific Decadal Oscillation (PDO). Comparing 850 hPa winds in Asia in extremely dry and wet years, it was concluded that dry-wet variability in the GBYR region strongly depends upon whether the southerly monsoon flow can reach northern China. © 2011 Springer Science+Business Media B.V.

Frankr C.G.,Technical University of Denmark | Knudsen M.V.,Technical University of Denmark | Noren K.,Lund University | Nazarenko E.,University of Gothenborg | And 2 more authors.
Acta Crystallographica Section D: Biological Crystallography | Year: 2012

The crystal structures of three conformations, T6, T 3R3 and R6, of bovine insulin were solved at 1.40, 1.30 and 1.80 Å resolution, respectively. All conformations crystallized in space group R3. In contrast to the T6 and T3R3 structures, different conformations of the N-terminal B-chain residue PheB1 were observed in the R6 insulin structure, resulting in an eightfold doubling of the unit-cell volume upon cooling. The zinc coordination in each conformation was studied by X-ray absorption spectroscopy (XAS), including both EXAFS and XANES. Zinc adopts a tetrahedral coordination in all R3 sites and an octahedral coordination in T3 sites. The coordination distances were refined from XAS with a standard deviation of <0.01 Å. In contrast to the distances determined from the medium-resolution crystal structures, the XAS results were in good agreement with similar coordination geometries found in small molecules, as well as in other high-resolution insulin structures. As the radiation dose for XRD experiments is two orders of magnitude higher compared with that of XAS experiments, the single crystals were exposed to a higher degree of radiation damage that affected the zinc coordination in the T3 sites in particular. Furthermore, XANES spectra for the zinc sites in T6 and R6 insulin were successfully calculated using finite difference methods and the bond distances and angles were optimized from a quantitative XANES analysis. © 2012 International Union of Crystallography Printed in Singapore - All Rights Reserved.

Cetin S.,29 Mayis Hospital | Ozturk M.A.,Gazi University | Barindik N.,29 Mayis Hospital | Imren E.,29 Mayis Hospital | Peker Y.,University of Gothenborg
Bosnian Journal of Basic Medical Sciences | Year: 2014

The relationship between glycaemic control and coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) is controversial. In the current cross-sectional study, we addressed the relationship between Hemoglobin A1c (HbA1c) values and the need for revascularization among diabetic patients undergoing coronary angiography. A total of 301 consecutive patients with known T2DM (age 6i.8±io.1 years, 46.2 % women) requiring coronary angiography due to CAD symptoms were included. T2DM patients were categorized into two groups based on their HbAic values: 93 (30.9%) diabetics with good glycaemic control (HbA1c<7 %), and 208 (69.1%) diabetics with poor glycaemic control (HbA1c>7 %). A total of 123 patients (40.9%) required revascularization. The revascularization rate was 28.0% among T2DM patients with good glycaemic control and 46.6% among T2DM patients with poor glycaemic control, respectively (ρ=0.002). In a logistic regression analysis, the need for revascularization was predicted by poor glycaemic control (Odds Ratio [OR] 2.26, 95% Confidence Interval [CI] 1.32-3.82; ρ=0.003) adjusted for age, gender, Body-Mass-Index and diabetes duration. Moreover, there was a linear relationship between HbAic values and number of affected coronary arteries (r= 0.169; ρ=0.003). Our data suggest that there is a close association between poor glycaemic control and increased revascularization rate in T2DM, which should be considered in primary and secondary prevention models. © 2014 Association of Basic Medical Sciences of FB&H.

Arcopinto M.,IRCCS Policlinico San Donato Milanese | Salzano A.,University of Naples Federico II | Isgaard J.,The Interdisciplinary Center | Cittadini A.,University of Naples Federico II | Cittadini A.,University of Gothenborg
Current Opinion in Cardiology | Year: 2015

Purpose of review Despite major advances in medical treatments, survival rates of chronic heart failure (CHF) have not significantly changed in the past 50 years, making it imperative to search for novel pathophysiological mechanisms and therapeutic targets. In this article, we summarize the current knowledge regarding the possibility to treat such anabolic deficiencies with hormone replacement therapy (HRT). Recent findings Mounting evidence supports the concept that CHF is a disease characterized not only by excessive neurohormonal activation but also by a reduced anabolic drive that carries functional and prognostic significance. The recent demonstration of overall beneficial effects of HRT in CHF may pave the way to slow the disease progression in patients with coexisting CHF and hormone deficiencies. The hypothesis is to identify a considerable subset of CHF patients also affected with hormone deficiency and to treat them with HRT. Summary Single or multiple HRT may in theory be performed in CHF. Such a novel approach may improve left ventricular architecture, function, and physical capacity as well as quality of life. Larger randomized, controlled trials are needed to confirm this working hypothesis. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

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