Publications by authors named "James McNulty"

168 Publications

Metabolite profiling reveals a role for intercellular dihydrocamalexic acid in the response of mature Arabidopsis thaliana to Pseudomonas syringae.

Phytochemistry 2021 Apr 3;187:112747. Epub 2021 Apr 3.

Vineland Research and Innovation Centre, 4890 Victoria Ave North Box 4000, Vineland Station, Ontario, L0R 2E0, Canada; Brock University, 1812 Sir Isaac Brock Way, St Catharines, Ontario, L2S 3A1, Canada. Electronic address:

The leaf intercellular space is a site of plant-microbe interactions where pathogenic bacteria such as Pseudomonas syringae grow. In Arabidopsis thaliana, the biosynthesis of tryptophan-derived indolic metabolites is induced by P. syringae infection. Using high-resolution mass spectrometry-based profiling and biosynthetic mutants, we investigated the role of indolic compounds and other small molecules in the response of mature Arabidopsis to P. syringae. We observed dihydrocamalexic acid (DHCA), the precursor to the defense-related compound camalexin, accumulating in intercellular washing fluids (IWFs) without further conversion to camalexin. The indolic biosynthesis mutant cyp71a12/cyp71a13 was more susceptible to P. syringae compared to mature wild-type plants displaying age-related resistance (ARR). DHCA and structural analogs inhibit P. syringae growth (MIC ~ 500 μg/mL), but not at concentrations found in IWFs, and DHCA did not inhibit biofilm formation in vitro. However, infiltration of exogenous DHCA enhanced resistance in mature cyp71a12/cyp71a13. These results provide evidence that DHCA derived from CYP71A12 and CYP71A13 activity accumulates in the intercellular space and contributes to the resistance of mature Arabidopsis to P. syringae without directly inhibiting bacterial growth.
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http://dx.doi.org/10.1016/j.phytochem.2021.112747DOI Listing
April 2021

CD38 is associated with bonding-relevant cognitions and relationship satisfaction over the first 3 years of marriage.

Sci Rep 2021 Feb 3;11(1):2965. Epub 2021 Feb 3.

Department of Psychology, Florida State University, 1107 W. Call St, Tallahassee, FL, 32306, USA.

Although there are numerous benefits to having a satisfying romantic relationship, maintaining high levels of relationship satisfaction is difficult. Many couples experience declines in relationship satisfaction in the early years of marriage, and such declines predict not only relationship dissolution but also poor mental and physical health. Several recent studies indicate that genetic variation on the CD38 gene (CD38), at the single nucleotide polymorphism (SNP) rs3796863, is associated with cognitions and behaviors related to pair bonding; we thus leveraged longitudinal data from a sample of newlywed couples (N = 139 genotyped individuals; 71 couples) to examine whether rs3796863 is associated with relationship maintenance processes and, in turn, relationship satisfaction in the early years of marriage. Replicating and extending prior research, we found that individuals with the CC genotype (vs. AC/AA) of rs3796863 reported higher levels of gratitude, trust, and forgiveness and that trust mediated the association between rs3796863 and marital satisfaction. Moreover, the benefits conferred to CC individuals lasted over the first 3 years of marriage. To our knowledge, this is the first study to examine the link between variation in CD38 rs3796863 and marital functioning over time.
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http://dx.doi.org/10.1038/s41598-021-82307-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859203PMC
February 2021

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

Bioorg Med Chem Lett 2020 12 19;30(24):127559. Epub 2020 Sep 19.

Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bmcl.2020.127559DOI Listing
December 2020

Do people realize how their partners make them feel? Relationship enhancement motives and stress determine the link between implicitly assessed partner attitudes and relationship satisfaction.

J Pers Soc Psychol 2021 Feb 27;120(2):335-369. Epub 2020 Jul 27.

Department of Psychology.

Do people realize the evaluative feelings that are spontaneously activated by their partner? If so, do they use those evaluations when judging their romantic relationships? To answer these questions, we investigated the association between automatic partner attitudes and judgments of relationship satisfaction in 7 studies. Study 1 was a meta-analysis of 86 correlations that revealed a very weak association between implicitly and explicitly assessed relationship evaluations, and Studies 2a-2c revealed that people failed to accurately report their automatic partner attitudes even when specifically asked to do so. Consistent with the idea that such inaccuracy emerged in part because motivational factors led people to override their automatic attitudes, Studies 3 and 4 demonstrated that automatic partner attitudes better aligned with relationship judgments when people were incentivized with money (Study 3) and had dissolved their relationship (Study 4). Nevertheless, consistent with the idea that overriding automatic attitudes requires the opportunity to deliberate, Studies 4 and 5 demonstrated that automatic partner attitudes better aligned with relationship judgments when people experienced more stress at the daily level (Study 4) and yearly for two years (Study 5). In Study 5, the interaction between stress and automatic attitudes emerged controlling indicators of negativity and was further moderated by relationship enhancing motivations among wives. These studies (a) help explain why automatic partner attitudes predict self-reported relationship satisfaction over time and (b) provide support for theories of social cognition suggesting that people have access to implicitly assessed attitudes that is obscured by motivations and opportunities to deliberate. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/pspi0000247DOI Listing
February 2021

Automatic partner attitudes and daily experiences of mood and relationship satisfaction.

J Fam Psychol 2020 Dec 20;34(8):1036-1045. Epub 2020 Apr 20.

Department of Psychology.

Automatic partner attitudes can be conceptualized as associations stored in memory between a partner and one's evaluation of that partner that are spontaneously activated upon thoughts of or encounters with the partner. Although more negative automatic partner attitudes have been shown to predict worse relationship outcomes over extended periods of time, it is less clear how such attitudes are related to personal and relationship well-being on a daily basis. Using a sample of newlywed couples, we assessed automatic partner attitudes implicitly and then assessed relationship evaluations, positive mood, and negative mood every day for 14 days. On average, more negative automatic partner attitudes were associated with more negative and less positive daily mood but unrelated to daily relationship evaluations. Nevertheless, the association between automatic partner attitudes and daily relationship evaluations was moderated by relationship length, such that more negative automatic partner attitudes were associated with more negative daily relationship evaluations among people in longer relationships, but with more positive daily relationship evaluations among people in shorter relationships. These findings suggest that people experience evaluative feelings activated by their partners as mood on a daily basis and, as the relationship lengthens, they may learn to use this affect to evaluate their relationships. The latter possibility may help explain why automatic partner attitudes predict relationship outcomes over time and suggests that effectively maintaining positive relationship evaluations requires cognitive and behavioral strategies that minimize negative associations involving the partner. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/fam0000665DOI Listing
December 2020

A comparison of Bayesian synthesis approaches for studies comparing two means: A tutorial.

Res Synth Methods 2020 Jan 29;11(1):36-65. Epub 2019 Nov 29.

Psychology, University of California, Los Angeles, California.

Researchers often seek to synthesize results of multiple studies on the same topic to draw statistical or substantive conclusions and to estimate effect sizes that will inform power analyses for future research. The most popular synthesis approach is meta-analysis. There have been few discussions and applications of other synthesis approaches. This tutorial illustrates and compares multiple Bayesian synthesis approaches (i.e., integrative data analyses, meta-analyses, data fusion using augmented data-dependent priors, and data fusion using aggregated data-dependent priors) and discusses when and how to use these Bayesian synthesis approaches to combine studies that compare two independent group means or two matched group means. For each approach, fixed-, random-, and mixed-effects models with other variants are illustrated with real data. R code is provided to facilitate the implementation of each method and each model. On the basis of these analyses, we summarize the strengths and limitations of each approach and provide recommendations to guide future synthesis efforts.
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http://dx.doi.org/10.1002/jrsm.1365DOI Listing
January 2020

The risk-benefit ratio of studying psychiatric symptoms via daily diary methods.

Account Res 2019 11 21;26(8):498-511. Epub 2019 Nov 21.

Department of Psychology, University of Tennessee, Knoxville, TN, USA.

Ethics committee members and researchers have deliberated about the risk-benefit ratio of researching sensitive issues such as psychiatric symptoms. Although research has suggested that inquiring about psychiatric symptoms in research generally does not cause harm, these findings have primarily arisen from cross-sectional studies. We examined whether this generalized to repeated, daily assessments of psychiatric symptoms. We collected daily survey data on psychiatric symptoms over 90 days from a sample of 206 college students. A subset of the sample ( = 80) provided reactions to study participation administered on the 90 day. Individuals who did not complete the 90 day survey reported higher levels of suicidal ideation and hopelessness than those who did. For individuals who completed the 90, final assessment, reactions primarily fell within the neutral to positive range, with variation depending on their baseline levels of psychiatric symptoms and identification as religious. This study adds to past work by demonstrating that individuals who remained in the study had neutral to positive experiences. However, participants with greater suicidal ideation and hopelessness were likely to attrit, warranting caution in assuming a low risk-benefit ratio of these studies. Management of risks involved in repeated assessment studies may be informed by this work.
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http://dx.doi.org/10.1080/08989621.2019.1694913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913872PMC
November 2019

Association between measured teamwork and medical errors: an observational study of prehospital care in the USA.

BMJ Open 2019 10 31;9(10):e025314. Epub 2019 Oct 31.

Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA

Objectives: The goal of this study was to examine the relationship between measured teamwork and adverse safety events in the prehospital emergency care of children using high-fidelity simulation. We posit that non-technical skills such as leadership, teamwork, situation awareness and decision-making are associated with the clinical success of teams.

Design: Observational study.

Setting: Emergency medical services (EMS) responders were recruited from public fire and private transport agencies in Oregon State to participate in four simulations of paediatric emergencies using high-fidelity patient simulators, scene design, and professional actors playing parents and bystanders.

Participants: Forty-four fire/transport teams consisting of 259 EMS professionals consented to participate and completed simulations.

Primary And Secondary Outcome Measures: Teams were assessed using the Clinical Teamwork Scale (CTS), a validated instrument that measures overall teamwork and 15 specific elements in five overarching domains: communication, decision-making, role responsibility (leadership and followership), situational awareness/resource management and patient-friendliness. We used generalised estimating equations to estimate the odds of error with increasing overall CTS teamwork score while adjusting for clinical scenario and potential clustering by team.

Results: Across 176 simulations, the mean overall score on the CTS was 6.04 (SD 2.10; range 1=poor to 10=perfect) and was normally distributed. The distribution of scores was similar across the four clinical scenarios. At least one error was observed in 82% of the simulations. In simulations with at least one observed error, the mean CTS score was 5.76 (SD 2.04) compared with 7.16 (SD 1.95) in scenarios with no observed error. Logistic regression analysis accounting for clustering at the team level revealed that the odds of an error decreased 28% with each unit increase in CTS (OR 0.72, 95% CI 0.59 to 0.88).

Conclusions: This study found that overall teamwork among care delivery teams was strongly associated with the risk of serious adverse events in simulated scenarios of caring for critically ill and injured children.
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http://dx.doi.org/10.1136/bmjopen-2018-025314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830602PMC
October 2019

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

Pers Soc Psychol Rev 2020 02 29;24(1):53-77. Epub 2019 Oct 29.

Florida State University, Tallahassee, USA.

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 personal behaviors that influence various personal 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.
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http://dx.doi.org/10.1177/1088868319881243DOI Listing
February 2020

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

Pers Soc Psychol Rev 2020 02 29;24(1):53-77. Epub 2019 Oct 29.

Florida State University, Tallahassee, USA.

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 personal behaviors that influence various personal 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.
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http://dx.doi.org/10.1177/1088868319881243DOI Listing
February 2020

Sex-Differentiated Changes in Sexual Desire Predict Marital Dissatisfaction.

Arch Sex Behav 2019 11 30;48(8):2473-2489. Epub 2019 Aug 30.

School of Psychology, University of Queensland, St. Lucia, QLD, Australia.

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.
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http://dx.doi.org/10.1007/s10508-019-01471-6DOI Listing
November 2019

The synthesis of densely functionalised α-acyloxy enaminals and enaminones via a novel homogeneous silver(i) catalysed rearrangement.

Chem Commun (Camb) 2019 Sep;55(73):10868-10871

Department of Chemistry & Chemical Biology, McMaster University, Hamilton, Ontario L8S 4M1, Canada.

A synthesis of densely functionalised α-acyloxy enaminals and enaminones via a novel homogeneous silver(i) catalyzed rearrangement of 1-acyloxy-3-azido ketones is reported. This silver catalyzed reaction involves an internal redox process comprised of four net transformations: loss of nitrogen, reductive cleavage of the azide, 1,2-acyl migration and oxidation of the acyloxy position to an aldehyde (enaminal) or ketone (enaminone). These mild reaction conditions have been applied to acyclic, cyclic, and chiral substrates yielding the rearranged enaminals or enaminones in up to 91% yield, all of which prove to be stable, isolatable products.
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http://dx.doi.org/10.1039/c9cc05614aDOI Listing
September 2019

Impact of a pharmacist-directed pain management service on inpatient opioid use, pain control, and patient safety.

Am J Health Syst Pharm 2019 Jan;76(1):17-25

Kaweah Delta Healthcare Healthcare District, Visalia, CA.

Purpose: To evaluate the impact of a pharmacy-directed pain management service (PPMS) designed to optimize analgesic pharmacotherapy, minimize adverse events, and improve patients' experience of pain management.

Methods: A retrospective analysis was conducted to evaluate the PPMS consisting of 3 dedicated pain management clinical pharmacists who perform both consult-based and stewardship functions. Multiple measures of opioid use and associated patient satisfaction outcomes during 3-year periods before and after implementation of the PPMS were compared.

Results: Significant decreases in use of institutionally defined high-risk opioid medications (e.g., parenteral hydromorphone, fentanyl, transdermal fentanyl patches), a decrease in total institutional opioid use, increased coanalgesic and adjunctive medication use, and a decrease in rapid response team (RRT) and code blue events associated with opioid-induced oversedation were seen after service implementation. Despite decreased opioid use, available patient satisfaction data suggested ongoing improvement in associated Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey domains.

Conclusion: Our data highlights the impact of a pharmacy directed pain management service on institutional opioid use with available data suggesting improved patient satisfaction scores and indirect cost savings. Despite decreased opioid use, available patient satisfaction data suggested ongoing improvement in associated HCAHPS survey pain management domains.
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http://dx.doi.org/10.1093/ajhp/zxy003DOI Listing
January 2019

A dyadic perspective on gratitude sheds light on both its benefits and its costs: Evidence that low gratitude acts as a "weak link".

J Fam Psychol 2019 Oct 15;33(7):876-881. Epub 2019 Apr 15.

Department of Psychology.

Research suggests gratitude benefits close relationships. However, relationships involve 2 people, and the interpersonal implications of mismatches in gratitude remain unclear. Is it sufficient for 1 partner to be high in gratitude, or does low gratitude in at least 1 partner act as a "weak link" that disrupts both partners' relational well-being? We asked both members of 120 newlywed couples to report their tendencies to feel and express gratitude for their partner every year for 2 years and their marital satisfaction every 4 months for 3 years. Initial levels of own and partner gratitude interacted to predict initial levels of marital satisfaction and changes in marital satisfaction over time. Although own and partner gratitude were associated with higher levels of initial marital satisfaction when both spouses were high in gratitude, own and partner gratitude were unassociated with initial satisfaction if either spouse was low in gratitude. Further, gratitude was associated with more stable marital satisfaction when both partners were high in gratitude, partner gratitude was unassociated with changes in satisfaction when own gratitude was low and own gratitude was associated with in satisfaction when partner gratitude was low. In fact, although initial gratitude was positively associated with marital satisfaction 3 years later if both spouses were high in gratitude, own initial gratitude was associated with later satisfaction when partner gratitude was relatively low. These findings suggest low gratitude in one partner acts as a weak link that is sufficient to disrupt both partners' relationship satisfaction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/fam0000533DOI Listing
October 2019

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

Bioorg Med Chem Lett 2019 06 26;29(11):1395-1398. Epub 2019 Mar 26.

Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ont. L8S 4M1, Canada. Electronic address:

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 (K = 8 nM).
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http://dx.doi.org/10.1016/j.bmcl.2019.03.033DOI Listing
June 2019

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

Bioorg Med Chem Lett 2019 06 26;29(11):1395-1398. Epub 2019 Mar 26.

Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ont. L8S 4M1, Canada. Electronic address:

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 (K = 8 nM).
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http://dx.doi.org/10.1016/j.bmcl.2019.03.033DOI Listing
June 2019

An interdependence account of sexism and power: Men's hostile sexism, biased perceptions of low power, and relationship aggression.

J Pers Soc Psychol 2019 Aug 26;117(2):338-363. Epub 2018 Nov 26.

Department of Psychology, Florida State University.

Protecting men's power is fundamental to understanding the origin, expression, and targets of hostile sexism, yet no prior theoretical or empirical work has specified how hostile sexism is related to experiences of power. In the current studies, we propose that the interdependence inherent in heterosexual relationships will lead men who more strongly endorse hostile sexism to perceive they have lower power in their relationship, and that these perceptions will be biased. We also predicted that lower perceptions of power would in turn promote aggression toward intimate partners. Across 4 studies, men who more strongly endorsed hostile sexism perceived lower power in their relationships. Comparisons across partners supported that these lower perceptions of power were biased; men who more strongly endorsed hostile sexism underestimated the power they had compared with their partners' reports of that power (Studies 1 and 2). These lower perceptions of power, in turn, predicted greater aggression toward female partners during couples' daily interactions (Study 1), observed during couples' video-recorded conflict discussions (Study 2), and reported over the last year (Studies 3 and 4). Moreover, the associations between hostile sexism, power, and aggression were specific to men perceiving lower relationship power rather than desiring greater power in their relationships (Studies 3 and 4), and they were not the result of generally being more dominant and aggressive (Studies 3 and 4), or more negative relationship evaluations from either partner (Studies 1-4). The findings demonstrate the importance of an interdependence perspective in understanding the experiences, aggressive expressions, and broader consequences associated with hostile sexism. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/pspi0000167DOI Listing
August 2019

R430: A potent inhibitor of DNA and RNA viruses.

Sci Rep 2018 11 9;8(1):16662. Epub 2018 Nov 9.

Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.

Acyclovir (ACV) is an effective antiviral agent for treating lytic Herpes Simplex virus, type 1 (HSV-1) infections, and it has dramatically reduced the mortality rate of herpes simplex encephalitis. However, HSV-1 resistance to ACV and its derivatives is being increasingly documented, particularly among immunocompromised individuals. The burgeoning drug resistance compels the search for a new generation of more efficacious anti-herpetic drugs. We have previously shown that trans-dihydrolycoricidine (R430), a lycorane-type alkaloid derivative, effectively inhibits HSV-1 infections in cultured cells. We now report that R430 also inhibits ACV-resistant HSV-1 strains, accompanied by global inhibition of viral gene transcription and enrichment of H3K27me3 methylation on viral gene promoters. Furthermore, we demonstrate that R430 prevents HSV-1 reactivation from latency in an ex vivo rodent model. Finally, among a panel of DNA viruses and RNA viruses, R430 inhibited Zika virus with high therapeutic index. Its therapeutic index is comparable to standard antiviral drugs, though it has greater toxicity in non-neuronal cells than in neuronal cells. Synthesis of additional derivatives could enable more efficacious antivirals and the identification of active pharmacophores.
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http://dx.doi.org/10.1038/s41598-018-33904-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226428PMC
November 2018

Asymmetric Entry into 10-aza-Analogues of Alkaloids Reveals a Pronounced Electronic Effect on Antiviral Activity.

ACS Omega 2018 Sep 20;3(9):11469-11476. Epub 2018 Sep 20.

Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213, United States.

Development of a chiral pool-based synthesis of 10-aza-analogues of biologically active alkaloids is described, involving a concise reductive amination and condensation sequence, leading to ring-B/C-modified, fully functionalized ring-C derivatives. Differentiated anticancer and antiviral activities of these analogues are presented. Despite complete conformational and functional group overlap, the 10-aza-analogues have diminished anticancer activity and no antiviral activity. These unprecedented electronic effects suggest a possible role for π-type secondary orbital interactions with the biological target.
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http://dx.doi.org/10.1021/acsomega.8b01987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173499PMC
September 2018

Behavioral immune system activity predicts downregulation of chronic basal inflammation.

PLoS One 2018 20;13(9):e0203961. Epub 2018 Sep 20.

Department of Psychology, Texas Christian University, Fort Worth, Texas, United States of America.

Here, we present a mechanistically grounded theory detailing a novel function of the behavioral immune system (BIS), the psychological system that prompts pathogen avoidance behaviors. We propose that BIS activity allows the body to downregulate basal inflammation, preventing resultant oxidative damage to DNA and promoting longevity. Study 1 investigated the relationship between a trait measure of pathogen avoidance motivation and in vitro and in vivo proinflammatory cytokine production. Study 2 examined the relationship between this same predictor and DNA damage often associated with prolonged inflammation. Results revealed that greater trait pathogen avoidance motivation predicts a) lower levels of spontaneous (but not stimulated) proinflammatory cytokine release by peripheral blood mononuclear cells (PBMCs), b) lower plasma levels of the proinflammatory cytokine interleukin-6 (IL-6), and c) lower levels of oxidative DNA damage. Thus, the BIS may promote health by protecting the body from the deleterious effects of inflammation and oxidative stress.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203961PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147464PMC
March 2019

Does support need to be seen? Daily invisible support promotes next day relationship well-being.

J Fam Psychol 2018 Oct 13;32(7):882-893. Epub 2018 Sep 13.

School of Psychology.

Direct and overt promotes recipients' relationship satisfaction but can also exacerbate negative mood. In contrast, subtle and indirect can bypass costs to mood, but it is unclear whether it undermines or boosts relationship satisfaction. Because invisible support is not perceived by recipients, its relational impact may be delayed across time. Thus, the current research used three dyadic daily diary studies (total = 322 married couples) to explore, for the first time, both the immediate (same day) and lagged (next day) effects of visible and invisible support on recipients' mood and relationship satisfaction. Consistent with prior research, visible support was associated with recipients reporting greater relationship satisfaction and greater anxiety the same day. In contrast, but also consistent with prior research, invisible support had no significant same-day effects, and thus avoided mood costs. Nevertheless, invisible support was associated with recipients reporting greater relationship satisfaction the next day. Study 3 provided evidence that such effects emerged because invisible support was also associated with greater satisfaction with partners' helpful behaviors (e.g., household chores) and relationship interactions (e.g., time spent together) on the next day. These studies demonstrate the importance of assessing different temporal effects associated with support acts (which may otherwise go undetected) and provide the first evidence that invisible support enhances relationship satisfaction but does so across days. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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http://dx.doi.org/10.1037/fam0000453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205907PMC
October 2018

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

Med Res Rev 2019 07 1;39(4):1274-1293. Epub 2018 Sep 1.

Department of Chemistry & Chemical Biology, McMaster University, Hamilton, Ontario, Canada.

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.
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http://dx.doi.org/10.1002/med.21536DOI Listing
July 2019

Sex differences in testosterone reactivity during marital conflict.

Horm Behav 2018 09 24;105:22-27. Epub 2018 Jul 24.

Florida State University, United States of America.

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.
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http://dx.doi.org/10.1016/j.yhbeh.2018.07.007DOI Listing
September 2018

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

J Nat Prod 2018 06 22;81(6):1451-1459. Epub 2018 May 22.

Department of Chemistry and Centre for Biotechnology , Brock University , 1812 Sir Isaac Brock Way , St. Catharines , ON L2S 3A1 , Canada.

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.
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http://dx.doi.org/10.1021/acs.jnatprod.8b00218DOI Listing
June 2018

Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections.

Stem Cell Res Ther 2018 05 11;9(1):134. Epub 2018 May 11.

Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.

Background: A variety of neurological disorders including neurodegenerative diseases and infection by neurotropic viruses can cause structural and functional changes in the central nervous system (CNS), resulting in long-term neurological sequelae. An improved understanding of the pathogenesis of these disorders is important for developing efficacious interventions. Human induced pluripotent stem cells (hiPSCs) offer an extraordinary window for modeling pathogen-CNS interactions, and other cellular interactions, in three-dimensional (3D) neuronal cultures that can recapitulate several aspects of in vivo brain tissue.

Methods: Herein, we describe a prototype of scaffold-free hiPSC-based adherent 3D (A-3D) human neuronal cultures in 96-well plates. To test their suitability for drug screening, A-3D neuronal cultures were infected with herpes simplex virus type 1 (HSV-1) with or without acyclovir.

Results: The half maximal inhibitory concentration (IC50) of acyclovir was 3.14 μM and 3.12 μM determined using flow cytometry and the CX7 High Content Screening platform, respectively.

Conclusions: Our A-3D neuronal cultures provide an unprecedented opportunity for high-content drug screening programs to treat human CNS infections.
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http://dx.doi.org/10.1186/s13287-018-0881-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948884PMC
May 2018

"You're forgiven, but don't do it again!" Direct partner regulation buffers the costs of forgiveness.

J Fam Psychol 2018 06 30;32(4):435-444. Epub 2018 Apr 30.

Department of Psychology, University of Auckland.

Although forgiveness can have numerous benefits, it can also have a notable cost-forgiveness can allow transgressors to continue behaving in ways that can be hurtful (McNulty, 2010, 2011). Accordingly, two studies tested the prediction that the implications of forgiveness for whether the partner transgresses or fails to behave benevolently depend on whether forgivers regulate partners away from future transgressions and toward benevolent behaviors. Study 1 was an experimental study of emerging adult couples in which participants were (a) asked to report their partners' tendencies to engage in partner-regulation behaviors, (b) led to believe their partners were either forgiving or unforgiving, and (c) given the opportunity to transgress against their partners. Study 2 was a longitudinal study of newlywed couples in which participants were (a) asked to report their tendencies to forgive their partners, (b) observed during problem-solving discussions, and then (c) asked to report their satisfaction with their partners' considerateness every 6 months for 4 years. Both studies provided evidence that direct oppositional partner-regulation behaviors moderate the implications of forgiveness for partner behavior. Among intimates who demanded more change, forgiveness was associated with the partner transgressing less (Study 1) and compromising more (Study 2), as well as participants being more satisfied with their partners' considerateness over time (Study 2); among intimates who demanded less change, forgiveness was associated with these outcomes in the opposite direction. These findings suggest that supplementing forgiveness with partner-regulation behaviors can help nondistressed couples avoid the undesirable outcomes and maximize desirable outcomes associated with forgiveness. (PsycINFO Database Record
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http://dx.doi.org/10.1037/fam0000409DOI Listing
June 2018

Progesterone and women's anxiety across the menstrual cycle.

Horm Behav 2018 06 24;102:34-40. Epub 2018 Apr 24.

Department of Psychology, Florida State University, 1107 W. Call St., Tallahassee, FL 32304, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.yhbeh.2018.04.008DOI Listing
June 2018

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

Bioorg Med Chem Lett 2018 05 16;28(9):1642-1646. Epub 2018 Mar 16.

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8S 4M1, Canada. Electronic address:

The discovery of two quinazolinones with selective, single-digit micromolar activity (IC = 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.
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http://dx.doi.org/10.1016/j.bmcl.2018.03.036DOI Listing
May 2018