Temozolomide increases heat shock proteins in extracellular vesicles released from glioblastoma cells

Molecular Biology Reports - Glioblastoma (GBM) is the most malignant and the fastest-progressing type of primary brain tumours. Temozolomide (TMZ) is a chemotherapeutic drug for the treatment of...     

Electron donor effect on nitrate reduction pathway and kinetics in a mixed methanogenic culture

The effect of different electron donors on the pathway and kinetics of nitrate reduction in a sulfide-acclimated mixed, mesophilic (35 degrees C) methanogenic culture was investigated. A mixture of dextrin and peptone, glucose, propionate, acetate, and H(2)/CO(2) were used as substrates at an initial chemical oxygen demand of 1,500 mg/L and the initial nitrate concentration ranged between 0 and 300 mg N/L. The fastest nitrate reduction was observed in the H(2)/CO(2) and acetate-fed cultures. In the case of propionate, nitrate reduction was the slowest followed by partial recovery of methanogenesis and accumulation of volatile fatty acids due to inhibition as a result of accumulation of denitrification intermediates. Similarly, accumulation of nitrite and nitric oxide and partial or complete inhibition of methanogenesis was observed in the H(2)/CO(2)-fed cultures. Methanogenesis completely recovered in the dextrin/peptone-, glucose-, and acetate-fed cultures at all nitrate levels. Denitrification was the dominant pathway of nitrate reduction in the propionate-, acetate-, and H(2)/CO(2)-fed cultures regardless of the COD/N value. However, both denitrification and dissimilatory nitrate reduction to ammonia (DNRA) were observed in the dextrin/peptone- and glucose-fed cultures and the degree of predominance of either of the two pathways was a function of the COD/N value. Therefore, the type of electron donor used affected both the nitrate reduction pathway and kinetics, as well as the recovery of fermentation and/or methanogenesis in the mixed methanogenic culture.     

Taxonomic study on the genus Eremopyrum (Ledeb.) Jaub. et Spach (Poaceae) in Turkey

In this study, we examined whether a satisfactory infrageneric grouping in Eremopyrum (Ledeb.) Jaub. & Spach can be achieved with the help of cluster analysis based on external vegetative and floral morphological characters of specimens either gathered from the field or borrowed from various herbaria. Twenty morphological characters were chosen and scored for 36 populations representing the genus. The data were subjected to numerical taxonomic analyses, and a phenogram was obtained by applying Gower general similarity index. The results of this study suggest that there are basically five species in Turkey, namely E. triticeum (Gaertner) Nevski, E. orientale (L.) Jaub. & Spach, E. distans (K. Koch) Nevski, E. bonaepartis (Sprengel) Nevski, and E. confusum Melderis. For the first time a new variety, E. bonaepartis (Sprengel) Nevski. var. aristatum Cabi & Do?an, is proposed along with two new combinations: E. bonaepartis (Sprengel) Nevski. var. sinaicum (Steudel) Cabi & Do?an and E. confusum Melderis var. sublanuginosum (Drob.) Cabi & Dogan. An account of Eremopyrum in Turkey is given, including a key to the species and varieties, and a general indication of their distribution.     

Beta1-Adrenoceptor Polymorphism Predicts Flecainide Action in Patients with Atrial Fibrillation

Background

Antiarrhythmic action of flecainide is based on sodium channel blockade. Beta₁-adrenoceptor (β₁AR) activation induces sodium channel inhibition, too. The aim of the present study was to evaluate the impact of different β₁AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation.

Methodology/Principal Findings

In 145 subjects, 87 with atrial fibrillation, genotyping was performed to identify the individual β₁AR Arg389Gly and Ser49Gly polymorphism. Resting heart rate during atrial fibrillation and success of flecainide-induced cardioversion were correlated with β₁AR genotype. The overall cardioversion rate with flecainide was 39%. The Arg389Arg genotype was associated with the highest cardioversion rate (55.5%; OR 3.30; 95% CI; 1.34–8.13; p = 0.003) compared to patients with Arg389Gly (29.5%; OR 0.44; 95% CI; 0.18–1.06; p = 0.066) and Gly389Gly (14%; OR 0.24; 95% CI 0.03–2.07; p = 0.17) variants. The single Ser49Gly polymorphism did not influence the conversion rate. In combination, patients with Arg389Gly-Ser49Gly genotype displayed the lowest conversion rate with 20.8% (OR 0.31; 95% CI; 0.10–0.93; p = 0.03). In patients with Arg389Arg variants the heart rate during atrial fibrillation was significantly higher (110±2.7 bpm; p = 0.03 vs. other variants) compared to Arg389Gly (104.8±2.4 bpm) and Gly389Gly (96.9±5.8 bpm) carriers. The Arg389Gly-Ser49Gly genotype was more common in patients with atrial fibrillation compared to patients without atrial fibrillation (27.6% vs. 5.2%; HR 6.98; 95% CI; 1.99–24.46; p<0.001).

Conclusions

The β₁AR Arg389Arg genotype is associated with increased flecainide potency and higher heart rate during atrial fibrillation. The Arg389Gly-Ser49Gly genotype might be of predictive value for atrial fibrillation.     

Functional dissection of the TBK1 molecular network

TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction. They are associated with three adaptor proteins called TANK, Sintbad (or TBKBP1) and NAP1 (or TBKBP2, AZI2) whose functional relationship to TBK1 and IKK-i is poorly understood. We performed a systematic affinity purification-mass spectrometry approach to derive a comprehensive TBK1/IKK-i molecular network. The most salient feature of the network is the mutual exclusive interaction of the adaptors with the kinases, suggesting distinct alternative complexes. Immunofluorescence data indicated that the individual adaptors reside in different subcellular locations. TANK, Sintbad and NAP1 competed for binding of TBK1. The binding site for all three adaptors was mapped to the C-terminal coiled-coil 2 region of TBK1. Point mutants that affect binding of individual adaptors were used to reconstitute TBK1/IKK-i-deficient cells and dissect the functional relevance of the individual kinase-adaptor edges within the network. Using a microarray-derived gene expression signature of TBK1 in response virus infection or poly(I∶C) stimulation, we found that TBK1 activation was strictly dependent on the integrity of the TBK1/TANK interaction.     

Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells

Molecular Biology Reports - High expression of heat shock proteins (Hsp) in breast cancer has been closely associated with tumor cell proliferation and thus a poor clinical outcome. Quercetin, a...