Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid

Pelargonidin (PEL), a common anthocyanidin with estrogenic activity, was tested in HL-60 cells for its genotoxicity and possible antigenotoxic effects against 4-nitroquinoline 1-oxide (NQO), a potent mutagen and carcinogen which induces oxidative stress. To take into account potential interactions between phytochemicals within normal human nutrition, we evaluated a combination of PEL with the nonestrogenic phytochemical chlorogenic acid (CLA), one of the most abundant polyphenols in the human diet. PEL (< or = 2 microM) and CLA (< or = 800 microM) were nongenotoxic in the micronucleus test. We observed significant antigenotoxic effects against NQO with both compounds, but no additive interaction of PEL and CLA. Comet assay results showed a nonsignificant reduction in NQO-induced DNA damage with both compounds and their combination. Flow cytometric analysis of oxidative stress revealed significant protection against NQO-induced oxidative stress by PEL, CLA, and their combination. Furthermore, PEL and CLA prevented the NQO-induced reduction in GSH level. This could be a mechanism for the observed reduction in genotoxicity. In conclusion, the phytoestrogen PEL revealed antioxidative and antigenotoxic properties in HL-60 cells, but no significant additive interaction with the abundant nutritional polyphenol CLA under the tested conditions.     

Metabolic profiling of glucuronides in human urine by LC-MS/MS and partial least-squares discriminant analysis for classification and prediction of gender

Mass spectrometry (MS) is increasingly being used for metabolic profiling, but detection modes such as constant neutral loss or multiple reaction monitoring have not often been reported. These modes allow focusing on structurally related compounds, which could be advantageous for situations in which the trait under investigation is associated with a particular class of metabolites. In this study, we analyzed endogenous glucuronides excreted in human urine by monitoring characteristic transitions of putative steroid glucuronides by LC-MS/MS for discrimination of females from males. Two methods for data extraction were used: (i) a manual procedure based on visual inspection of the chromatograms and selection of 23 peaks and (ii) a software-supported method (MarkerView) set to extract 100 peaks. Data from 10 female and 10 male students were analyzed by principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) using software SIMCA. With PCA, only the manual peak selection resulted in clustering males and females. With PLS-DA, the manual method provided full separation on the basis of one single discriminant; the software-supported approach required a two-component model for complete separation. Loading plots were analyzed for their ability to reveal peaks with high discriminating power, that is, potential biomarkers. The PLS-DA models were validated with urine samples collected from five new females and five new males. Gender was correctly assigned for all. Our results indicate that inclusion of biological criteria for variable selection coupled to class-specific MS analysis and data extraction by appropriate software may constitute a valuable addition to the methods available for metabolomics.     

Analysis and optimization of a cogeneration system based on biomass combustion

The paper deals with analysis and optimization of the performance of the combustion process in a biomass furnace at a biomass cogeneration plant. For the purpose a thermodynamic model for the biomass burning process in a grate furnace was developed. The mathematical model describes both, the thermal decomposition of the fuel on the grate as well as gas phase combustion in the secondary zone. The presented approach is based on energy equations for each individual step of the biomass combustion process.Measurement results from a biomass-fired cogeneration plant were used to validate the model. Comparison between simulation and measurement results shows good agreement. The model predicts accurately the temperature profiles in the combustion chamber.The presented approach is suitable for model based analysis and optimization of control strategies. The developed model was used to optimize the performance of the recirculation system of the combustion appliance. The simulation based analysis showed, that the flow rate of the recirculated exhaust fumes can be significantly reduced which results in energy savings of 17% of the auxiliary electrical power demand.     

Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal Psi

The interaction of the nucleocapsid NCp7 of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein with the RNA packaging signal Psi ensures specific encapsidation of the dimeric full length viral genome into nascent virus particles. Being an essential step in the HIV-1 replication cycle, specific genome encapsidation represents a promising target for therapeutic intervention. We previously selected peptides binding to HIV-1 Psi-RNA or stem loops (SL) thereof by phage display. Herein, we describe synthesis of peptide variants of the consensus HWWPWW motif on membrane supports to optimize Psi-RNA binding. The optimized peptide, psi-pepB, was characterized in detail with respect to its conformation and binding properties for the SL3 of the Psi packaging signal by NMR and tryptophan fluorescence quenching. Functional analysis revealed that psi-pepB caused a strong reduction of virus release by infected cells as monitored by reduced transduction efficiencies, capsid p24 antigen levels, and electron microscopy. Thus, this peptide shows antiviral activity and could serve as a lead compound to develop new drugs targeting HIV-1.     

Excited state dynamics with quantum trajectories

Nuclear quantum dynamics beyond the Born-Oppenheimer approximation is performed using quantum trajectories. Withintheadiabaticrepresentationoftheelectronicstates, NABDY(NonAdiabaticBohmianDYnamics) is used in combination with DFT and LR-TDDFT to perform on-the-fly nonadiabatic quantum dynamics. Simple numerical test systems and current limitations of the method are discussed.     

Modeling the field distribution in deep brain stimulation: the influence of anisotropy of brain tissue

The neurosurgical method of deep brain stimulation (DBS) is used to treat symptoms of movement disorders like Parkinson's disease by implanting stimulation electrodes in deep brain areas. The aim of this study was to examine the field distribution in DBS and the role of heterogeneous and anisotropic material properties in the brain areas where stimulation is applied. Finite element models of the human brain were developed comprising tissue heterogeneity and anisotropy. The tissue data were derived from averaged magnetic resonance imaging and diffusion tensor imaging datasets. Unilateral stimulation of the subthalamic nucleus (STN) was computed using an accurate model of an electrode used in clinical treatment of DBS extended with an encapsulation layer around the electrode body. Computations of anisotropic and isotropic brain models, which consider resistive tissue properties for unipolar and bipolar electrode configurations, were carried out. Electrode position was varied within an area around the stimulation center. Results have shown a deviation of 2% between anisotropic and isotropic field distributions in the vicinity of the STN. The sensitivity of this deviation referring to the electrode position remained small, but increased when the electrode position approached areas of high anisotropy.     

Assessing the way people look to judge their intentions.

[Correction Notice: An erratum for this article was reported in Vol 11(4) of Emotion (see record 2011-13790-001). Figure 1 should have been printed in color.] [Correction Notice: An erratum for this article was reported in Emotion July 4 2011 (see record 2011-13790-001). Figure 1, which should have been printed in color, was inadvertently printed in black and white. The online version has been corrected.] Faces of unknown persons are processed to infer the intentions of these persons not only when they depict full-blown emotions, but also at rest, or when these faces do not signal any strong feelings. We explored the brain processes involved in these inferences to test whether they are similar to those found when judging full-blown emotions. We recorded the event-related brain potentials (ERPs) elicited by faces of unknown persons who, when they were photographed, were not asked to adopt any particular expression. During the ERP recording, participants had to decide whether each face appeared to be that of a positively, negatively, ambiguously, or neutrally intentioned person. The early posterior negativity, the EPN, was found smaller for neutrally categorized faces than for the other faces, suggesting that the automatic processes it indexes are similar to those evoked by full-blown expressions and thus that these processes might be involved in the decoding of intentions. In contrast, in the same 200–400 ms time window, ERPs were not more negative at anterior sites for neutrally intentioned faces. Second, the peaks of the late positive potentials (LPPs) maximal at parietal sites around 700 ms postonset were not significantly smaller for neutrally intentioned faces. Third, the slow positive waves that followed the LPP were larger for faces that took more time to categorize, that is, for ambiguously intentioned faces. These three series of unexpected results may indicate processes similar to those triggered by full-blown emotions studies, but they question the characteristics of these processes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)