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)     

A meta-analysis of work–family conflict and various outcomes with a special emphasis on cross-domain versus matching-domain relations.

A literature review of studies analyzing work–family conflict and its consequences was conducted, and 427 effect sizes were analyzed meta-analytically. Work–family conflict was analyzed bidirectionally in terms of work interference with family (WIF) and family interference with work (FIW). We assessed 3 categories of potential outcomes: work-related outcomes, family-related outcomes, and domain-unspecific outcomes. Results show that WIF and FIW are consistently related to all 3 types of outcomes. Both types of interrole conflict showed stronger relationships to same-domain outcomes than to cross-domain outcomes. Thus, WIF was more strongly associated with work-related than with family-related outcomes, and FIW was more strongly associated with family-related than with work-related outcomes. In moderator analyses, parenthood could not explain variability in effect sizes. However, time spent at work did moderate the relationships between WIF and family-related outcomes, as well as FIW and domain-unspecific outcomes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Dietary Fat in Relation to Erythrocyte Fatty Acid Composition in Men

Erythrocyte membrane fatty acid (EMFA) composition is used in the validation of food frequency questionnaires (FFQ) and the evaluation of dietary fat quality. In this cross-sectional study we aimed to investigate associations of diet with EMFA. Altogether, 1,033 randomly selected Finnish men, aged from 47 to 75 years filled in a FFQ and their EMFA composition was analyzed. Marine polyunsaturated fatty acid (PUFA) intake correlated positively with erythrocyte eicosapentaenoic and docosahexaenoic acids (r _s = 0.415 and r _s = 0.340, respectively, P < 0.001) and inversely with all n-6 PUFA analyzed (P < 0.001). PUFA intake from spreads and cooking fats correlated positively with alpha-linolenic (ALA), linoleic (LNA) and nervonic acids (r _s = 0.229, r _s = 0.160 and r _s = 0.143, respectively, P < 0.001). Milk fat intake was associated with myristic and behenic acids (r _s = 0.186 and r _s = 0.132, respectively P < 0.001). Butter users had lower ALA and LNA proportions (mol%) than non-users (0.16 ± 0.04 vs. 0.19 ± 0.05, P < 0.001 and 7.77 ± 1.02 vs. 8.12 ± 1.11, P = 0.001). Higher PUFA intake from meat was related to decreased long-chain n-3 (P < 0.001) and increased n-6 PUFA (P < 0.001) proportions. In conclusion, EMFA composition reflects particularly well the intakes of n-3 PUFA, whereas other associations remained lower. Yet, all main sources of dietary fat were related with EMFA. The dietary effect on the nervonic acid proportion was confirmed.