A flavin-dependent monooxygenase produces nitrogenous tomato aroma volatiles using cysteine as a nitrogen source.

Tomato (Solanum lycopersicum) produces a wide range of volatile chemicals during fruit ripening, generating a distinct aroma and contributing to the overall flavor. Among these volatiles are several aromatic and aliphatic nitrogen-containing compounds for which the biosynthetic pathways are not known. While nitrogenous volatiles are abundant in tomato fruit, their content in fruits of the closely related species of the tomato clade is highly variable. For example, the green-fruited species Solanum pennellii are nearly devoid, while the red-fruited species S. lycopersicum and Solanum pimpinellifolium accumulate high amounts. Using an introgression population derived from S. pennellii, we identified a locus essential for the production of all the detectable nitrogenous volatiles in tomato fruit. Silencing of the underlying gene (SlTNH1;Solyc12g013690) in transgenic plants abolished production of aliphatic and aromatic nitrogenous volatiles in ripe fruit, and metabolomic analysis of these fruit revealed the accumulation of 2-isobutyl-tetrahydrothiazolidine-4-carboxylic acid, a known conjugate of cysteine and 3-methylbutanal. Biosynthetic incorporation of stable isotope-labeled precursors into 2-isobutylthiazole and 2-phenylacetonitrile confirmed that cysteine provides the nitrogen atom for all nitrogenous volatiles in tomato fruit. Nicotiana benthamiana plants expressing SlTNH1 readily transformed synthetic 2-substituted tetrahydrothiazolidine-4-carboxylic acid substrates into a mixture of the corresponding 2-substituted oxime, nitro, and nitrile volatiles. Distinct from other known flavin-dependent monooxygenase enzymes in plants, this tetrahydrothiazolidine-4-carboxylic acid N-hydroxylase catalyzes sequential hydroxylations. Elucidation of this pathway is a major step forward in understanding and ultimately improving tomato flavor quality.

How both partners' individual differences, stress, and behavior predict change in relationship satisfaction: Extending the VSA model.

We pooled data from 10 longitudinal studies of 1,104 married couples to test the Vulnerability-Stress-Adaptation (VSA) model of change in relationship satisfaction. Studies contained both spouses' self-reports of neuroticism, attachment anxiety, and attachment avoidance; observational measures of engagement and opposition during problem-solving discussions at baseline; and repeated reports of both spouses' stress and marital satisfaction over several years. Consistent with the VSA model, all three individual and partner qualities predicted changes in marital satisfaction that were mediated by observations of behavior and moderated by both partners' experiences with stress. In contrast to the VSA model, however, rather than accentuating the association between individual differences and behavior, both partners' stress moderated the strength, and even direction, of the association between behavior and changes in marital satisfaction over time. Taken together, these findings indicate that 1) qualities of both couple members shape their behavioral exchanges, 2) these behaviors explain how individuals and their partners' enduring qualities predict relationship satisfaction, and 3) stress experienced by both couple members strongly determines how enduring qualities and behavior predict changes in relationship satisfaction over time. The complex interplay among both partners' enduring qualities, stress, and behavior helps explain why studies may fail to document direct main effects of own and partner enduring qualities and behavior on changes in relationship satisfaction over time.

Rapid entry to phenanthroindolizidine alkaloids via an acid-catalysed acyliminium ion-electrocyclization cascade.

A rapid total synthesis of seco-phenanthroindolizidine alkaloids was achieved involving a one-pot acid catalyzed deprotection- condensation-electrocyclization strategy. This synthetic route provided a concise synthesis of (±)-seco-antofine and (±)-septicine in only 4 steps with an overall yield of 22% and 17%, respectively.

Evidence of a Bidirectional Association Between Daily Sexual and Relationship Satisfaction That Is Moderated by Daily Stress.

Prior research provides mixed evidence regarding the direction of the association between sexual and marital satisfaction. Whereas some studies suggest a bidirectional association, other studies fail to document one direction or the other. The current investigation used a 12-day diary study of 287 married individuals to clarify the nature of this association. Results from time-lagged mixed modeling revealed a significant positive bidirectional association. Both higher global sexual satisfaction one day and satisfaction with sex that occurred that day predicted higher marital satisfaction the next day; likewise, higher marital satisfaction one day significantly predicted higher global sexual satisfaction the next day and higher satisfaction with sex that occurred the next day. Both associations remained significant after controlling for participant's gender/sex, neuroticism, attachment insecurity, self-esteem, stress, perceived childhood unpredictability and harshness, age of first intercourse, construal level, age, and length of marriage. We also explored whether these covariates moderated either direction of the association. Daily stress was the most reliable moderator, with three of the four interactions tested remaining significant after Bonferroni corrections. The bidirectional association between global sexual and marital satisfaction and the positive association between satisfaction with sex that occurred that day and marital satisfaction the next day were significantly stronger when individuals experienced high versus low stress. Although the exploratory nature of all moderation analyses suggests they should be replicated before drawing strong conclusions, these findings highlight the importance of sexual satisfaction to marital satisfaction and vice versa and point to the power of stress in strengthening these associations.

Perceptions of Infectability to Disease Moderate the Association between Daily Concerns about Contracting COVID-19 and Satisfaction with Sex.

The behavioral immune system is an evolved adaptation comprised of automatic behavioral, cognitive, and affective reactions that has allowed humans throughout evolutionary history to avoid situations that risk infection by pathogens (e.g., physical proximity to sick people). Although behavioral immune system activation may be functional by helping people avoid such situations, experiencing these automatic reactions during sexual interactions may undermine people's evaluations of those interactions because sex requires close physical contact. We examined whether two sources of behavioral immune system activation (daily concern over contracting COVID-19 and individual differences in infection concern) undermined satisfaction with sex among 318 partnered adults in the U.S. during the COVID-19 pandemic. Participants reported individual differences in perceived infectability and then, every night for two weeks, reported their (a) daily concern about contracting COVID-19, (b) daily stress, (c) whether they had sex with their partner, and (d) their satisfaction with sex when it occurred. People's perceived infectability moderated the association between their daily concern about contracting COVID-19 and the extent to which they enjoyed sex when it occurred, such that people higher, but not lower, in perceived infectability enjoyed sex less on days that they were more worried about contracting COVID-19 than usual. This effect was not moderated by biological sex and remained significant when controlling for biological sex, age, relationship length, and frequency of sex. Results highlight the importance of the behavioral immune system to sexual functioning and suggest a novel avenue through which the COVID-19 pandemic has disrupted relationships.

Synthesis of non-nucleoside anti-viral cyclopropylcarboxacyl hydrazones and initial anti-HSV-1 structure-activity relationship studies.

The synthesis of a lead anti-viral cyclopropyl carboxy acyl hydrazone 4F17 (5) and three sequential arrays of structural analogues along with the initial assessment and optimization of the antiviral pharmacophore against the herpes simplex virus type 1 (HSV-1) are reported.

The Relationship Problem Solving (RePS) Model: How Partners Influence One Another to Resolve Relationship Problems.

In this article, we synthesize existing literatures across numerous domains to introduce a novel model-the Relationship Problem Solving (RePS) model-for understanding the process through which romantic partners influence one another to resolve relationship problems. The first section briefly describes the key constructs and stages of the model. The second section details the interpersonal behaviors that influence various intrapersonal factors (e.g., affect, self-efficacy) that ultimately influence partners' motivation and ability to progress through the stages of the model. The third section uses the model to generate novel predictions that suggest that the effectiveness of these interpersonal behaviors often depends on contextual factors. Finally, the fourth section discusses the implications of this model for understanding relationship problem solving, highlights the need to consider the role of context in the problem-solving process, and offers numerous specific predictions to be addressed by future research.

Implications of life-history strategies for obesity.

The association between low socioeconomic status (SES) and obesity is well documented. In the current research, a life history theory (LHT) framework provided an explanation for this association. Derived from evolutionary behavioral science, LHT emphasizes how variability in exposure to unpredictability during childhood gives rise to individual differences in a range of social psychological processes across the life course. Consistent with previous LHT research, the current findings suggest that exposure to unpredictability during childhood (a characteristic common to low SES environments) is associated with the adoption of a fast life-history strategy, one marked by impulsivity and a focus on short-term goals. We demonstrate that a fast life-history strategy, in turn, was associated with dysregulated weight-management behaviors (i.e., eating even in the absence of hunger), which were predictive of having a high body mass index (BMI) and being obese. In both studies, findings held while controlling for participants' current socioeconomic status, suggesting that obesity is rooted in childhood experiences. A serial mediation model in study 2 confirmed that effects of childhood SES on adult BMI and obesity can be explained in part by exposure to unpredictability, the adoption of a fast life-history strategy, and dysregulated-eating behaviors. These findings suggest that weight problems in adulthood may be rooted partially in early childhood exposure to unpredictable events and environments. LHT provides a valuable explanatory framework for understanding the root causes of obesity.

Polyphenolic natural products and natural product-inspired steroidal mimics as aromatase inhibitors.

The discovery of biologically active polyphenolic natural products, including chalcones, stilbenes, flavanones, and isoflavones as steroidal mimics has proven to be a subject of considerable importance in medicine. Some of these natural compounds have been shown to modulate key human metabolic processes via steroidal hormone receptors, or to inhibit crucial enzymes involved in the biosynthesis of steroidal hormones themselves. Isoflavone polyphenolics such as genistein are well known for this "phytoestrogenic" biological activity. This review focuses on the ability of select polyphenolics and their synthetic derivatives to function as steroidal mimics in the inhibition of the enzyme aromatase, thereby lowering production of endogenous estrogen growth hormones. The discovery of potent, natural product-based aromatase inhibitors (AIs) as hit compounds has led to the introduction of steroidal-based irreversible inhibitors, such as exemestane and reversible AIs such as anastrozole and letrozole, now standard therapy in the treatment of estrogen receptor-positive breast cancer and other hormone related indications. Pursuit of this strategy over the last few decades has been largely successful although complications and challenges remain. This review highlights the aromatase activity of natural stilbenes, chalcones, and flavanones and synthetically inspired versions thereof and draws attention to new and under-investigated areas within each class worthy of pursuit.

Synthesis of α-methylstilbenes using an aqueous Wittig methodology and application toward the development of potent human aromatase inhibitors.

The development of aqueous Wittig methodology for the synthesis of α-methylstilbenes using tripropylphosphine-derived phosphonium salts is described. The Wittig olefination reaction was high yielding and allowed isolation of stilbenes by simple filtration and washing with water. The novel phosphonium salts employed were accessed via a highly efficient, regioselective addition of hydrogen bromide to styrenes. Application of the α-methylstilbenes toward the synthesis of a collection of stilbenoid-triazoles is reported and their inhibition of CYP450 19A1 (aromatase) investigated. The overall structure-activity profile provided additional evidence on the aryl halide-ketone bioisostere hypothesis and identified 6c as a potent inhibitor of aromatase in vitro (Ki = 8 nM).

Sex-Differentiated Changes in Sexual Desire Predict Marital Dissatisfaction.

Sex is critical to marriage. Yet, there are several reasons to expect spouses to experience declines in the desire for sex over time, and the rates of any declines in sexual desire may differ for men and women. We used two multi-wave, longitudinal studies to test whether male and female members of newlywed couples experienced different rates of change in sexual desire, whether any such changes were accentuated by childbirth, and whether any such changes had implications for marital satisfaction. In both studies, spouses provided multiple reports of sexual desire, marital satisfaction, and childbirth. Results demonstrated that women's sexual desire declined more steeply over time than did men's sexual desire, which did not decline on average. Further, childbirth accentuated this sex difference by partially, though not completely, accounting for declines in women's sexual desire but not men's. Finally, declines in women's but not men's sexual desire predicted declines in both partners' marital satisfaction. These effects held controlling depressive symptoms and stress, including stress from parenthood. The current findings offer novel longitudinal evidence for sex-differentiated changes in sexual desire and therefore suggest an important source of marital discord.

Sex differences in testosterone reactivity during marital conflict.

When attempting to resolve relationship problems, individuals in close relationships sometimes challenge their partners with statements that oppose their partners' point of view. Such oppositional behaviors may undermine those partners' relational value and threaten their status within the relationship. We examined whether perceptions of opposition from a partner during a series of problem-solving interactions were associated with reactivity in testosterone levels and whether those associations were different for men and women. Fifty newlywed couples discussed four marital problems. Each member of the couple reported how much oppositional behavior they perceived from their partner during the discussions. Pre- and post-discussion saliva samples were assayed for testosterone. For men, but not for women, perceptions of oppositional behavior were associated with heightened testosterone reactivity, and this result replicated across three different measures of testosterone reactivity. Findings were specific to men's perceptions of oppositional behavior, and held controlling for objective measures of oppositional behavior coded from videos of the conversations. Results highlight the benefits of considering pair-bonded relationships as a novel context for investigating associations involving hormones and behavior. Findings also raise the possibility that sex differentiated hormonal reactions to opposition partly explain why conflict among heterosexual partners can be so divisive.

Progesterone and women's anxiety across the menstrual cycle.

Animal models and a few human investigations suggest progesterone may be associated with anxiety. Progesterone naturally fluctuates across the menstrual cycle, offering an opportunity to understand how within-person increases in progesterone and average progesterone levels across the cycle correspond to women's anxiety. Across two longitudinal studies, we simultaneously modeled the between- and within-person associations between progesterone and anxiety using multilevel modeling. In Study 1, 100 Polish women provided saliva samples and reported their anxiety at three phases of the menstrual cycle: follicular, peri-ovulatory, and luteal. A significant between-person effect emerged, revealing that women with higher average progesterone levels across their cycles reported higher levels of anxiety than women with lower progesterone cycles. This effect held controlling for estradiol. In Study 2, 61 American women provided saliva samples and reported their attachment anxiety during laboratory sessions during the same three cycle phases. A significant between-person and within-person association emerged: women with higher average progesterone levels reported higher levels of attachment anxiety, and as women's progesterone levels increased across their cycles, so too did their attachment anxiety. These effects held controlling for cortisol. In sum, both studies provide support for a link between menstrual cycle progesterone levels and subjective anxiety.

One-pot, multicomponent synthesis of 2,3-disubstituted quinazolin-ones with potent and selective activity against Toxoplasma gondii.

The discovery of two quinazolinones with selective, single-digit micromolar activity (IC50 = 6-7 µM) against the tachyzoites of the apicomplexan parasite Toxoplasma gondii is reported. These potent and selective third generation derivatives contain a benzyloxybenzyl substituent at C2 and a bulky aliphatic moiety at N3. Here we show that these quinazolinones inhibit T. gondii tachyzoite replication in an established infection, but do not significantly affect host cell invasion by the tachyzoites.

Isolation, Synthesis, and Semisynthesis of Amaryllidaceae Constituents from Narcissus and Galanthus sp.: De Novo Total Synthesis of 2- epi-Narciclasine.

An efficient protocol for the isolation of narciclasine from common Amaryllidaceae bulbs, separation from haemanthamine, and the occurrence of a trace alkaloid, 2- epi-narciclasine, are reported. Attempts to convert natural narciclasine to its C-2 epimer by Mitsunobu inversion or oxidation/reduction sequences were compromised by rearrangement and aromatization processes, through which a synthesis of the alkaloid narciprimine was achieved. The methylation of the 7-hydroxy group of natural narciclasine followed by protection of the 3,4-diol function and oxidation/reduction sequence provided the target C-2 epimer. A de novo chemoenzymatic synthesis of 2- epi-narciclasine from m-dibromobenzene is also described. Haemanthamine and narciprimine were readily detected in the crude extracts of Narcissus and Galanthus bulbs containing narciclasine, and the occurrence of 2- epi-narciclasine as a trace natural product in Galanthus sp. is reported for the first time.

Relative Physical Position as an Impression-Management Strategy: Sex Differences in Its Use and Implications.

People's physical position relative to others may shape how those others perceive them. The research described here suggests that people use relative physical position to manage impressions by strategically positioning themselves either higher or lower relative to ostensible observers. Five studies supported the prediction that women take and display photographs portraying themselves in a low relative physical position to highlight their youthful features and appear attractive, whereas men take and display photographs portraying themselves in a high relative physical position to highlight their size and appear dominant. The effectiveness of these strategies was confirmed in two studies that measured social perceptions of male and female targets who varied in their relative position. In sum, as do members of other social species, people use relative physical position to manage social impressions, and although these impression-management strategies may have deep ancestral roots, they appear to manifest themselves through a contemporary human modality-photographs.

Automatic Associations Between One's Partner and One's Affect as the Proximal Mechanism of Change in Relationship Satisfaction: Evidence From Evaluative Conditioning.

The current study examined whether directly altering affective associations involving a relationship partner through evaluative conditioning can lead to changes in relationship satisfaction. Married couples ( N = 144) were asked to view a brief stream of images once every 3 days for 6 weeks. Embedded in this stream were pictures of the partner, which, according to random assignment of couples to experimental group, were paired with either positive or neutral stimuli. Couples also completed measures of automatic partner attitudes and explicit marital satisfaction at baseline and once every 2 weeks for 8 weeks. Spouses who viewed their partners paired with positive stimuli demonstrated more-positive automatic partner attitudes than did control spouses, and these attitudes predicted increased self-reported marital satisfaction over time. These results provide novel evidence for a mechanism of change in relationship satisfaction, represent a step toward documenting how strong attitudes can evolve through passive exposure to information, and suggest novel avenues for relationship interventions.

Quantifying the Sexual Afterglow: The Lingering Benefits of Sex and Their Implications for Pair-Bonded Relationships.

Sex presumably facilitates pair bonding, but how do partners remain pair-bonded between sexual acts? Evolutionary perspectives suggest that sexual afterglow serves this purpose. We explored how long sexual satisfaction would remain elevated following sex and predicted that stronger sexual afterglow would characterize more satisfying partnerships. We pooled the data from two independent, longitudinal studies of newlywed couples to examine these issues. Spouses reported their daily sexual activity and sexual satisfaction for 14 days and their marital satisfaction at baseline and 4 or 6 months later. Results demonstrated that sexual satisfaction remained elevated approximately 48 hr after sex, and spouses experiencing a stronger afterglow reported higher levels of marital satisfaction both at baseline and over time. We interpret these findings as evidence that sexual afterglow is a proximal cognitive mechanism through which sex promotes pair bonding.

Discovery of potent antiviral (HSV-1) quinazolinones and initial structure-activity relationship studies.

The discovery of antiviral activity of 2,3-disubstituted quinazolinones, prepared by a one-pot, three-component condensation of isatoic anhydride with amines and aldehydes, against Herpes Simplex Virus (HSV)-1 is reported. Sequential iterative synthesis/antiviral assessment allowed structure-activity relationship (SAR) generation revealing synergistic structural features required for potent anti-HSV-1 activity. The most potent derivatives show greater efficacy than acyclovir against acute HSV-1 infections in neurons and minimal toxicity to the host.

Women Like Being Valued for Sex, as Long as it is by a Committed Partner.

How do women respond to being valued for sex by their partners? Although research supporting objectification theory suggests that women's reactions to sexual valuation are primarily negative, a separate body of research indicates that women expend significant effort to enhance their sexual appeal. Evolutionary perspectives suggest that whether women are more or less satisfied with partners who value them for sex may depend on how committed those partners are. Being sexually valued by a relatively uncommitted partner may violate women's desire to avoid short-term sexual relationships and thus may be negatively associated with relationship satisfaction. In contrast, being sexually valued by a highly committed partner may positively influence women's relationship satisfaction because it signals to them that they have successfully attracted a long-term relationship partner. Two studies of newly married couples supported these predictions. In Study 1 (N = 109), husbands' sexual valuation was positively associated with marital satisfaction among wives who perceived that those husbands were highly committed, but negatively associated with marital satisfaction among wives who perceived that those husbands were relatively less committed. Study 2 (N = 99) revealed the same pattern for wives (but not husbands) using a likely manifestation of sexual valuation-engaging in frequent sex. These findings join others to demonstrate that interpersonal processes do not have universally positive or negative implications for relationships; rather, their implications depend on the context in which they occur, including contexts that were reproductively beneficial or costly throughout evolutionary history.