Variable-Temperature NMR Spectroscopy, Conformational Analysis, and Thermodynamic Parameters of Cyclic Adenosine 5'-Diphosphate Ribose Agonists and Antagonists.

Cyclic adenosine 5'-diphosphate ribose (cADPR) is a ubiquitous Ca2+-releasing second messenger. Knowledge of its conformational landscape is an essential tool for unraveling the structure-activity relationship (SAR) in cADPR. Variable-temperature 1H NMR spectroscopy, in conjunction with PSEUROT and population analyses, allowed us to determine the conformations and thermodynamic parameters of the furanose rings, γ-bonds (C4'-C5'), and ß-bonds (C5'-O5') in the cADPR analogues 2'-deoxy-cADPR, 7-deaza-cADPR, and 8-bromo-cADPR. A significant finding was that, although the analogues are similar to each other and to cADPR itself in terms of overall conformation and population (ΔG°), there were subtle yet important differences in some of thermodynamic properties (ΔH°, ΔS°) associated with each of the conformational equilibria. These differences prompted us to propose a model for cADPR in which the interactions between the A2'-N3, A5″-N3, and H2-R5' atoms serve to fine-tune the N-glycosidic torsion angles (χ).

A combined variable temperature 600 MHz NMR/MD study of the calcium release agent cyclic adenosine diphosphate ribose (cADPR): Structure, conformational analysis, and thermodynamics of the conformational equilibria.

A combined variable temperature 600 MHz NMR/molecular dynamics study of the Ca2+-release agent cyclic adenosine 5'-diphosphate ribose (cADPR) was conducted. In addition to elucidating the major and minor orientations of the conformationally flexible furanose rings, γ- (C4'-C5'), and ß- (C5'-O5') bonds, the thermodynamics (ΔHo, ΔSo) associated with each of these conformational equilibria were determined. Both furanose rings were biased towards a south conformation (64-74%) and both ß-bonds heavily favored trans conformations. The R-ring γ-bond was found to exist almost exclusively as the γ+ conformer, whereas the A-ring γ-bond was a mixture of the γ+ and γt conformers, with the trans conformer being slightly favored. Enthalpic factors accounted for most of the observed conformational preferences, although the R-ring furanose exists as its major conformation based solely on entropic factors. There was excellent agreement between the NMR and MD results, particularly with regard to the conformer identities, but the MD showed a bias towards γ+ conformers. The MD results showed that both N-glycosidic χ-bonds are exclusively syn. Collectively the data allowed for the construction of a model for cADPR in which many of the conformationally flexible units in fact effectively adopt single orientations and where most of the conformational diversity resides in its A-ring furanose and γ-bond.

Ways of giving benefits in marriage: norm use, relationship satisfaction, and attachment-related variability.

Couples reported on bases for giving support and on relationship satisfaction just prior to and approximately 2 years into marriage. Overall, a need-based, noncontingent (communal) norm was seen as ideal and was followed, and greater use of this norm was linked to higher relationship satisfaction. An exchange norm was seen as not ideal and was followed significantly less frequently than was a communal norm; by 2 years into marriage, greater use of an exchange norm was linked with lower satisfaction. Insecure attachment predicted greater adherence to an exchange norm. Idealization of and adherence to a communal norm dropped slightly across time. As idealization of a communal norm and own use and partner use of a communal norm decreased, people high in avoidance increased their use of an exchange norm, whereas people low in avoidance decreased their use of an exchange norm. Anxious individuals evidenced tighter links between norm use and marital satisfaction relative to nonanxious individuals. Overall, a picture of people valuing a communal norm and striving toward adherence to a communal norm emerged, with secure individuals doing so with more success and equanimity across time than insecure individuals.

Motivating change in relationships: can prayer increase forgiveness?

The objective of the current studies was to test whether praying for a relationship partner would increase willingness to forgive that partner. In Study 1 (N = 52), participants assigned to pray for their romantic partner reported greater willingness to forgive that partner than those who described their partner to an imagined parent. In Study 2 (N = 67), participants were assigned to pray for a friend, pray about any topic, or think positive thoughts about a friend every day for 4 weeks. Those who prayed for their friend reported greater forgiveness for their friend than did those in the other two conditions, even when we controlled for baseline forgiveness scores. Participants who prayed for their friend also increased in selfless concern during the 4 weeks, and this variable mediated the relationship between experimental condition and increased forgiveness. Together, these studies provide an enhanced understanding of the relationship benefits of praying for a partner and begin to identify potential mediators of the effect.

Benefits of expressing gratitude: expressing gratitude to a partner changes one's view of the relationship.

This research was conducted to examine the hypothesis that expressing gratitude to a relationship partner enhances one's perception of the relationship's communal strength. In Study 1 (N = 137), a cross-sectional survey, expressing gratitude to a relationship partner was positively associated with the expresser's perception of the communal strength of the relationship. In Study 2 (N = 218), expressing gratitude predicted increases in the expresser's perceptions of the communal strength of the relationship across time. In Study 3 (N = 75), participants were randomly assigned to an experimental condition, in which they expressed gratitude to a friend, or to one of three control conditions, in which they thought grateful thoughts about a friend, thought about daily activities, or had positive interactions with a friend. At the end of the study, perceived communal strength was higher among participants in the expression-of-gratitude condition than among those in all three control conditions. We discuss the theoretical and applied implications of these findings and suggest directions for future research.

Design, synthesis and determination of antifungal activity of 5(6)-substituted benzotriazoles.

In an effort to find inhibitors that are effective against both Candida and Aspergillus spp., a series of 5(6)-(un)substituted benzotriazole analogs, represented by compounds 3a-3h and 3b'-3f', were prepared using a crystalline oxirane intermediate 1 previously synthesized in our laboratory. All the compounds were evaluated for inhibitory activity against various species of Candida and Aspergillus. Compounds 3b' (5,6-dimethylbenzotriazol-2-yl derivative), 3d (5-chlorobenzotriazol-1-yl derivative) and 3e' (6-methylbenzotriazol-1-yl derivative) exhibited potent antifungal activity, with the MICs for Candida spp. and Aspergillus niger, ranging from 1.6 microg/mL to 25 microg/mL and 12.5 microg/mL to 25 microg/mL, respectively. The present work describes the design, synthesis, regioisomer characterization (through COSY and NOESY 2D-NMR spectroscopy and single molecule X-ray crystallography), antifungal evaluation, molecular docking, and structure-activity relationships of the various 5(6)-(un)substituted benzotriazole analogs.

A prototype analysis of gratitude: varieties of gratitude experiences.

The present research tested the hypothesis that concepts of gratitude are prototypically organized and explored whether lay concepts of gratitude are broader than researchers' concepts of gratitude. In five studies, evidence was found that concepts of gratitude are indeed prototypically organized. In Study 1, participants listed features of gratitude. In Study 2, participants reliably rated the centrality of these features. In Studies 3a and 3b, participants perceived that a hypothetical other was experiencing more gratitude when they read a narrative containing central as opposed to peripheral features. In Study 4, participants remembered more central than peripheral features in gratitude narratives. In Study 5a, participants generated more central than peripheral features when they wrote narratives about a gratitude incident, and in Studies 5a and 5b, participants generated both more specific and more generalized types of gratitude in similar narratives. Throughout, evidence showed that lay conceptions of gratitude are broader than current research definitions.

The positives of negative emotions: willingness to express negative emotions promotes relationships.

Four studies support the hypothesis that expressing negative emotion is associated with positive relationship outcomes, including elicitation of support, building of new close relationships, and heightening of intimacy in the closest of those relationships. In Study 1, participants read vignettes in which another person was experiencing a negative emotion. Participants reported they would provide more help when the person chose to express the negative emotion. In Study 2, participants watched a confederate preparing for a speech. Participants provided more help to her when she expressed nervousness. In Study 3, self-reports of willingness to express negative emotions predicted having more friends, controlling for demographic variables and extraversion. In Study 4, self-reports of willingness to express negative emotion measured prior to arrival at college predicted formation of more relationships, greater intimacy in the closest of those relationships, and greater received support from roommates across participants' first semester of college.

Self-esteem and organization of valenced information about others: the "Jekyll and Hyde"-ing of relationship partners.

The authors theorize that individuals with high self-esteem functionally integrate positive and negative partner information in memory, whereas those low in self-esteem segregate such information. The authors obtained support for this view in 7 studies. In a first set, participants judged whether positive and negative traits presented in an alternating or nonalternating order applied to a partner. Low but not high self-esteem individuals were slowed by the alternating order when judging relationship partners (but not inanimate objects). In a 2nd set, participants answered questions tapping integrated thinking, self-esteem, and other attributes. Higher self-esteem was associated with more integrated thinking when other attributes were controlled. In a final study, anxiously attached individuals were more labile in rating their spouse over a 5-day period.

cADPR analogues: effect of an adenosine 2'- or 3'-methoxy group on conformation.

[structure: see text] The 2'-OMe-A (2) and 3'-OMe-A (3) analogues of the calcium release agent cADPR (1) were prepared and their solution structures studied by NMR spectroscopy. Compared to 1, 2 shows a shift in its A ring conformation and changes in its R ring N:S and gammat:gamma+ ratios, while 3 displays a significant change in the conformation of its A ring gamma-bond.