The utility of nostalgia for unhealthy populations: A systematic review and narrative analysis.

Nostalgic reverie (i.e. sentimental longing) has received increased attention as a predictor of health and well-being, but only a handful of reviews have summarized this literature. The available reviews (Dementia: The International Journal of Social Research and Practice, 19, 2020, 330; Intimations of nostalgia: Multidisciplinary explorations of an enduring emotion, Bristol University Press, 2022) left a critical gap in explicating the function of nostalgia among people engaged in unhealthy behaviour. In the current systematic review and narrative analysis, we sought to answer whether and under what conditions emotion serves to help or hinder people engaged in unhealthy behaviours in terms of taking action to change. We identified 14 studies and categorized them into two themes. In Theme I, nostalgising about a time in one's life when one was healthier motivated both readiness to change and action to change unhealthy behaviour. In Theme II, nostalgizing about the perceived benefits of engaging in unhealthy behaviour (e.g. social connectedness related to drinking) was associated with the continuance or acceleration of the unhealthy behaviour. This review highlights not only the presence of a link between nostalgia and unhealthy behaviour but also that the content of one's nostalgising matters for understanding whether the unhealthy behaviour is undermined or bolstered.

Advancing the Pathways Model: Financially Focused Self-concept and Erroneous Beliefs as Core Psychopathologies in Disordered Gambling.

In the Pathways Model, there are three distinct etiological subtypes of disordered gambling (Behaviourally Conditioned, Emotionally Vulnerable, and Anti-Social Impulsive Risk-Taker). The Pathways Model also posits that erroneous gambling beliefs are a maintenance factor of disordered gambling across the subtypes. Yet, etiological factors and erroneous beliefs have largely been examined separately when determining disordered gambling subtype. Moreover, there may be heretofore unexamined maintenance factors that span the disordered gambling subtypes. In the current research, we addressed this gap by using latent profile analyses to assess the role both erroneous beliefs and financially focused self-concept (a novel maintenance factor) play in the determination of disordered gambling subtype. In Study 1, community members with gambling problems (n = 215) completed the Gambling Pathways Questionnaire and Financially Focused Self-Concept Scale. In Study 2 (n = 290), participants also completed the Gambling Beliefs Questionnaire. Results from both studies revealed three profiles that coincide with the subtypes in the Pathways Model as providing the best fit to the data. The three profiles were largely distinguished by low, medium, or high scores on the etiological factors, which is consistent with the disordered gambling subtypes being on different parts of the same continuum of psychopathology severity. Financial focus (Studies 1 and 2) and erroneous gambling beliefs (Study 2) were elevated across the three profiles, and both were higher among profiles with more severe psychopathology. Findings support a dimensional understanding of gambling disorder psychopathology and suggest that a financially focused self-concept may be a maintenance factor of disordered gambling.

Understanding Lower-Risk Cannabis Consumption from the Consumers' Perspective: A Rapid Evidence Assessment.

Background: In the current rapid evidence assessment, we summarize the existing research on lower-risk cannabis consumption as understood by those who consume cannabis. Methods: We identified 7111 unique articles published between 1900 and 2021 using search terms related to a) cannabis consumption, b) beliefs and behaviors, and c) positive outcomes. Results: Twelve articles met our inclusion criteria. Three themes emerged that reflect lower-risk cannabis beliefs and behaviors (informed self-regulation, protective behavioral strategies, and the normalization of cannabis consumption) and one theme reflected motivations that undermine lower-risk cannabis consumption (e.g., using cannabis to cope). Conclusions: Results suggest a need for targeted lower-risk cannabis consumption research-research focused on how those who consume cannabis do so in a positive, non-problematic manner. Such research would help to inform policy and practice and, ultimately, help promote lower-risk cannabis consumption strategies.

Artemisia annua L. plants lacking Bornyl diPhosphate Synthase reallocate carbon from monoterpenes to sesquiterpenes except artemisinin.

The monoterpene camphor is produced in glandular secretory trichomes of the medicinal plant Artemisia annua, which also produces the antimalarial drug artemisinin. We have found that, depending on growth conditions, camphor can accumulate at levels ranging from 1- 10% leaf dry weight (LDW) in the Artemis F1 hybrid, which has been developed for commercial production of artemisinin at up to 1% LDW. We discovered that a camphor null (camphor-0) phenotype segregates in the progeny of self-pollinated Artemis material. Camphor-0 plants also show reduced levels of other less abundant monoterpenes and increased levels of the sesquiterpene precursor farnesyl pyrophosphate plus sesquiterpenes, including enzymatically derived artemisinin pathway intermediates but not artemisinin. One possible explanation for this is that high camphor concentrations in the glandular secretory trichomes play an important role in generating the hydrophobic conditions required for the non-enzymatic conversion of dihydroartemisinic acid tertiary hydroperoxide to artemisinin. We established that the camphor-0 phenotype associates with a genomic deletion that results in loss of a Bornyl diPhosphate Synthase (AaBPS) gene candidate. Functional characterization of the corresponding enzyme in vitro confirmed it can catalyze the first committed step in not only camphor biosynthesis but also in a number of other monoterpenes, accounting for over 60% of total volatiles in A. annua leaves. This in vitro analysis is consistent with loss of monoterpenes in camphor-0 plants. The AaBPS promoter drives high reporter gene expression in A. annua glandular secretory trichomes of juvenile leaves with expression shifting to non-glandular trichomes in mature leaves, which is consistent with AaBPS transcript abundance.

Structure of a cereal purple acid phytase provides new insights to phytate degradation in plants.

Grain phytate, a mixed metal ion salt of inositol hexakisphosphate, accounts for 60%-80% of stored phosphorus in plants and is a potent antinutrient of non-ruminant animals including humans. Through neofunctionalization of purple acid phytases (PAPhy), some cereals such as wheat and rye have acquired particularly high mature grain phytase activity. As PAPhy activity supplies phosphate, liberates metal ions necessary for seedling emergence, and obviates antinutrient effects of phytate, its manipulation and control are targeted crop traits. Here we show the X-ray crystal structure of the b2 isoform of wheat PAPhy induced during germination. This high-resolution crystal structure suggests a model for phytate recognition that, validated by molecular dynamics simulations, implicates elements of two sequence inserts (termed PAPhy motifs) relative to a canonical metallophosphoesterase (MPE) domain in forming phytate-specific substrate specificity pockets. These motifs are well conserved in PAPhys from monocot cereals, enzymes which are characterized by high specificity for phytate. Tested by mutagenesis, residues His229 in PAPhy motif 4 and Lys410 in the MPE domain, both conserved in PAPhys, are found to strongly influence phytase activity. These results explain the observed phytase activity of cereal PAPhys and open the way to the rational engineering of phytase activity in planta.

Longing for the Past and Longing for the Future: A Phenomenological Assessment of the Relation Between Temporal Focus and Readiness to Change Among People Living With Addiction.

At present, the dominant motivational strategy to facilitate behavior change among those living with addiction is to focus one's attention on the better possible future that may result from cutting down or cessation. However, research is now emerging that suggests nostalgic reverie (i.e., sentimental longing) for life lived before addiction can also motivate behavior change. In the current research, we explore the conditions in which longing for a better future free of addiction and longing for one's past that was free of addition might motivate change. To this end, we assessed first-person experiential narratives of problem gamblers to better understand how they feel about their past or future without gambling, and how those feelings may relate to motivation to change. Problem gamblers were randomly assigned to either write about their lived past before gambling (n = 31) or their expected future without gambling (n = 26). Each narrative was systematically examined to identify recurrent themes and cluster these narratives according to similarly expressed themes. In the past condition, participants reported their life before gambling was either positive (Cluster P1) or difficult (Cluster P2). Gamblers with a positive past described how their life, character, close relationships, and the activities they engaged in before gambling were more meaningful. Importantly, these gamblers also reported feeling more nostalgic for life without gambling and were more ready to change their behavior than gamblers with a difficult past. In the future condition, participants were either positive (Cluster F1) or ambivalent (Cluster F2) about a future free from gambling. Gamblers who expected a positive future described how they expect their emotions, finances, and the activities they will engage in to be more positive without gambling. Compared to those ambivalent about their future, these gamblers also reported a future without addiction to be more vivid and had more desire to change their behavior, but there were no between-cluster differences in readiness to change. These findings demonstrate unique differences in how gamblers perceive their past and future without gambling, and shed a novel light on how each temporal focus might motivate behavior change among those living with addiction.

Sparse Epistatic Patterns in the Evolution of Terpene Synthases.

We explore sequence determinants of enzyme activity and specificity in a major enzyme family of terpene synthases. Most enzymes in this family catalyze reactions that produce cyclic terpenes-complex hydrocarbons widely used by plants and insects in diverse biological processes such as defense, communication, and symbiosis. To analyze the molecular mechanisms of emergence of terpene cyclization, we have carried out in-depth examination of mutational space around (E)-ß-farnesene synthase, an Artemisia annua enzyme which catalyzes production of a linear hydrocarbon chain. Each mutant enzyme in our synthetic libraries was characterized biochemically, and the resulting reaction rate data were used as input to the Michaelis-Menten model of enzyme kinetics, in which free energies were represented as sums of one-amino-acid contributions and two-amino-acid couplings. Our model predicts measured reaction rates with high accuracy and yields free energy landscapes characterized by relatively few coupling terms. As a result, the Michaelis-Menten free energy landscapes have simple, interpretable structure and exhibit little epistasis. We have also developed biophysical fitness models based on the assumption that highly fit enzymes have evolved to maximize the output of correct products, such as cyclic products or a specific product of interest, while minimizing the output of byproducts. This approach results in nonlinear fitness landscapes that are considerably more epistatic. Overall, our experimental and computational framework provides focused characterization of evolutionary emergence of novel enzymatic functions in the context of microevolutionary exploration of sequence space around naturally occurring enzymes.

Snapshots during the catalytic cycle of a histidine acid phytase reveal an induced-fit structural mechanism.

Highly engineered phytases, which sequentially hydrolyze the hexakisphosphate ester of inositol known as phytic acid, are routinely added to the feeds of monogastric animals to improve phosphate bioavailability. New phytases are sought as starting points to further optimize the rate and extent of dephosphorylation of phytate in the animal digestive tract. Multiple inositol polyphosphate phosphatases (MINPPs) are clade 2 histidine phosphatases (HP2P) able to carry out the stepwise hydrolysis of phytate. MINPPs are not restricted by a strong positional specificity making them attractive targets for development as feed enzymes. Here, we describe the characterization of a MINPP from the Gram-positive bacterium Bifidobacterium longum (BlMINPP). BlMINPP has a typical HP2P-fold but, unusually, possesses a large α-domain polypeptide insertion relative to other MINPPs. This insertion, termed the U-loop, spans the active site and contributes to substrate specificity pockets underpopulated in other HP2Ps. Mutagenesis of U-loop residues reveals its contribution to enzyme kinetics and thermostability. Moreover, four crystal structures of the protein along the catalytic cycle capture, for the first time in an HP2P, a large ligand-driven α-domain motion essential to allow substrate access to the active site. This motion recruits residues both downstream of a molecular hinge and on the U-loop to participate in specificity subsites, and mutagenesis identified a mobile lysine residue as a key determinant of positional specificity of the enzyme. Taken together, these data provide important new insights to the factors determining stability, substrate recognition, and the structural mechanism of hydrolysis in this industrially important group of enzymes.

When do gamblers help themselves? Self-discontinuity increases self-directed change over time.

Most disordered gamblers fail to take the necessary action to change their behavior. When action is taken, it is typically done under self-direction. Yet, little is known about what motivates gamblers to engage in self-directed change as researchers have focused almost exclusively on barriers to treatment seeking. Herein, we tested whether self-discontinuity (i.e., the notion that the self has undergone fundamental changes as a result of one's gambling) predicts self-directed change among gamblers experiencing sub-clinical levels of disordered gambling. Further, we tested whether this relationship would hold when controlling for feelings of shame and guilt about one's gambling as well as self-stigma as a disordered gambler (i.e., known barriers to change). To this end, 195 gamblers from the community completed a questionnaire battery that contained the variables of interest. Six months later, participants were re-contacted to assess whether they engaged in self-directed change. As hypothesized, the likelihood that self-directed change was attempted increased to the extent participants reported feeling self-discontinuous - an effect that remained significant when controlling for shame, guilt, and self-stigma. Results suggest that heightening the awareness that the gambling has fundamentally changed the self increases the likelihood of gamblers taking action to change their disordered gambling behaviors.

Discovery of germacrene A synthases in Barnadesia spinosa: The first committed step in sesquiterpene lactone biosynthesis in the basal member of the Asteraceae.

The Andes-endemic Barnadesioideae lineage is the oldest surviving and phylogenetically basal subfamily of the Asteraceae (Compositae), a prolific group of flowering plants with world-wide distribution (∼24,000 species) marked by a rich diversity of sesquiterpene lactones (STLs). Intriguingly, there is no evidence that members of the Barnadesioideae produce STLs, specialized metabolites thought to have contributed to the adaptive success of the Asteraceae family outside South America. The biosynthesis of STLs requires the intimate expression and functional integration of germacrene A synthase (GAS) and germacrene A oxidase (GAO) to sequentially cyclize and oxidize farnesyl diphosphate into the advanced intermediate germacrene A acid leading to diverse STLs. Our previous discovery of GAO activity conserved across all major subfamilies of Asteraceae, including the phylogenetically basal lineage of Barnadesioideae, prompted further investigation of the presence of the gateway GAS in Barnadesioideae. Herein we isolated two terpene synthases (BsGAS1/BsGAS2) from the basal Barnadesia spinosa (Barnadesioideae) that displayed robust GAS activity when reconstituted in yeast and characterized in vitro. Despite the apparent lack of STLs in the Barnadesioideae, this work unambiguously confirms the presence of GAS in the basal genera of the Asteraceae. Phylogenetic analysis reveals that the two BsGASs fall into two distinct clades of the Asteraceae's GASs, and BsGAS1 clade is only retained in the evolutionary closer Cichorioideae subfamily, implicating BsGAS2 is likely the ancestral base of most GASs found in the lineages outside the Barnadesioideae. Taken together, these results show the enzymatic capacities of GAS and GAO emerged prior to the subsequent radiation of STL-producing Asteraceae subfamilies.

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases.

Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.

A dangerous cocktail: Alcohol consumption increases suicidal ideations among problem gamblers in the general population.

The current research examined whether alcohol consumption exacerbates suicidal ideations among gamblers in the general population. While prior research suggests problem gambling severity and excessive alcohol consumption are unique predictors of suicidal behaviors, the extant literature as almost exclusively focused on gamblers in treatment. This represents a significant gap in the literature as less than 10% of gamblers seek treatment. Furthermore, gamblers in treatment are not representative of gamblers in the general population, precluding a simple generalization of research findings. We address this gap using data obtained from the Canadian Community Health Survey (Cycle 4.1)--a cross-sectional national survey that assesses health-related information among the Canadian population. To this end, we conducted a moderation analysis with problem gambling severity as the independent variable, weekly alcohol consumption as the moderator variable and suicidal ideations (in the past 12 months) as the dependent variable. The results found that alcohol consumption alone did not reliably predict suicidal ideation among gamblers who did not gamble problematically. However, as predicted, the odds of suicidal ideation were greatest among problem gamblers who frequently consumed alcohol. Thus, it may behoove policy makers to re-visit the availability of alcohol in gambling venues. Moreover, responsible gambling-oriented education initiatives may be advanced by informing gamblers about the increased risk of suicidal ideations when problematic gambling is combined with frequent alcohol consumption.

Emergence of terpene cyclization in Artemisia annua.

The emergence of terpene cyclization was critical to the evolutionary expansion of chemical diversity yet remains unexplored. Here we report the first discovery of an epistatic network of residues that controls the onset of terpene cyclization in Artemisia annua. We begin with amorpha-4,11-diene synthase (ADS) and (E)-ß-farnesene synthase (BFS), a pair of terpene synthases that produce cyclic or linear terpenes, respectively. A library of ~27,000 enzymes is generated by breeding combinations of natural amino-acid substitutions from the cyclic into the linear producer. We discover one dominant mutation is sufficient to activate cyclization, and together with two additional residues comprise a network of strongly epistatic interactions that activate, suppress or reactivate cyclization. Remarkably, this epistatic network of equivalent residues also controls cyclization in a BFS homologue from Citrus junos. Fitness landscape analysis of mutational trajectories provides quantitative insights into a major epoch in specialized metabolism.

Do Social Casino Gamers Migrate to Online Gambling? An Assessment of Migration Rate and Potential Predictors.

Social casino games (i.e., free-to-play online gambling games) are enjoyed by millions of players worldwide on a daily basis. Despite being free to play, social casino games share many similarities to traditional casino games. As such, concerns have been raised as to whether social casino games influences the migration to online gambling among people who have not engaged in such activity (see Griffiths in World Online Gambl 9:12-13, 2010). To date, however, no empirical research has assessed this possibility. Thus, the purpose of the present research was to assess the extent to which social casino gamers migrate to online gambling and potential predictors (time spent on social casino games, skill building, enhancement and micro-transactions) of such migration. To this end, social casino gamers who never gambled online (N = 409) completed a questionnaire battery assessing our variables of interest and were re-contacted 6-months later to see if they had engaged in online gambling during the intervening months. Approximately 26% of social casino gamers reported having migrated to online gambling. Importantly, engagement in micro-transactions was the only unique predictor of migration from social casino gaming to online gambling. The implications for the potential harms associated with social casino gaming are discussed.

Comparative analysis and validation of the malachite green assay for the high throughput biochemical characterization of terpene synthases.

Terpenes are the largest group of natural products with important and diverse biological roles, while of tremendous economic value as fragrances, flavours and pharmaceutical agents. Class-I terpene synthases (TPSs), the dominant type of TPS enzymes, catalyze the conversion of prenyl diphosphates to often structurally diverse bioactive terpene hydrocarbons, and inorganic pyrophosphate (PPi). To measure their kinetic properties, current bio-analytical methods typically rely on the direct detection of hydrocarbon products by radioactivity measurements or gas chromatography-mass spectrometry (GC-MS). In this study we employed an established, rapid colorimetric assay, the pyrophosphate/malachite green assay (MG), as an alternative means for the biochemical characterization of class I TPSs activity.•We describe the adaptation of the MG assay for turnover and catalytic efficiency measurements of TPSs.•We validate the method by direct comparison with established assays. The agreement of k cat/K M among methods makes this adaptation optimal for rapid evaluation of TPSs.•We demonstrate the application of the MG assay for the high-throughput screening of TPS gene libraries.