Cell density-dependent coordination of gene expression in bacteria has been termed "quorum sensing" (QS). 1 N-acyl L-homoserine lactones (AHLs) are produced by over 70 species of Gram-negative bacteria, and structural differences within AHLs occur in the length and oxidation state of the acyl side chain (Figure 1). Upon reaching a critical threshold concentration, AHLs bind to their cognate receptor proteins, triggering the expression of target genes. AHLs have been shown to play an important role in the establishment and course of bacterial infections. One example of a Gram-negative pathogen that employs AHL-based QS to regulate the expression of its pathogenicity factors is Pseudomonas aeruginosa. This common environmental microorganism has acquired the ability to take advantage of weaknesses in the host defenses to become an opportunistic pathogen in humans. Most prominent is the role of P. aeruginosa in patients suffering from cystic fibrosis (CF). Over the last 15 years, much progress has been made in elucidating the molecular mechanisms underlying P. aeruginosa pathogenicity. 2 Two different AHLs, N-(3-oxododecanoyl) homoserine lactone (3-oxo-C 12 -AHL) and N-butyryl homoserine lactone (C 4 -AHL), have been identified as QS signaling molecules in P. aeruginosa. Genes regulated by this QS mechanism encode enzymes such as elastases A and B, catalase, and superoxide dismutase as well as exotoxins. 2Interference with QS signaling has been suggested as a new approach for anti-infective therapy. 3 In fact, this strategy has yielded interesting results using AHL analogs as QS antagonists in P. aeruginosa. 4 Alternatively, we have embarked on a program utilizing antibodies to inhibit AHL-mediated quorum sensing signaling in P. aeruginosa. AHL-based QS systems represent an ideal target for antibody-based anti-infective therapy given the highly conserved molecular scaffold and extracellular distribution of AHLs.Our initial hapten design for the elicitation of anti-AHL antibodies focused on synthesizing a set of molecules highly congruent in structure to AHLs while also possessing a pendant carboxylic acid functionality that would enable carrier proteins BSA or KLH conjugates to be easily accessed. However, we were aware that such molecules might also be prone to hydrolysis (ring opened products) under conditions required for chemical coupling and also immunization. Thus, to guide our hapten design the stability of several AHLs under physiological conditions was investigated; we synthesized a number of AHL analogs and their corresponding ring opened hydrolysis products, both of which contained a 4-methoxyphenyl amide group that allowed for a detailed investigation into the rate of hydrolysis of the AHL analogues using HPLC with UV detection (Figure 2 Each compound was assayed for its hydrolysis rate in phosphate buffer saline (PBS), pH 7.2, at a concentration of 200 μM at 37 °C. The half lives of each of the lactones varied from 13.7 to 18.1 hours. Interestingly, the oxidation state and chain length did not influence...

The present study evaluated the role of distress tolerance (DT), defined as the ability to tolerate negative emotional states, in the use of four specific emotion regulation strategies (suppression, avoidance, rumination, and reappraisal). Undergraduate psychology students (N = 431, 71.7% female; Mage = 19.80 years, SD= 3.71) completed self-report measures online for course credit. It was hypothesized that, after controlling for the effects of anxiety sensitivity and negative affectivity, DT would be negatively associated with suppression, avoidance, and rumination, and positively associated with reappraisal. Consistent with prediction, low DT significantly predicted greater use of suppression, avoidance, and rumination. However, contrary to prediction, DT did not significantly predict reappraisal. These results suggest that individuals who are unable to withstand negative emotions are more likely to use maladaptive regulation strategies.

Social anxiety disorder appears to be a risk factor for cannabis-related problems. Although it is presumed that increases in cannabis craving during elevated social anxiety reflect an intent to cope with greater negative affectivity, it is unclear whether increases in physiological arousal during social stress are related to cannabis craving, especially among those with social anxiety disorder. Similarly, no studies have assessed motivational reasons for cannabis use during elevated social stress. Thus, the current study tested whether increases in state social anxiety (measured subjectively and via physiological arousal) were related to greater cannabis craving among 126 current cannabis users (88.9% with cannabis use disorder, 31.7% with social anxiety disorder, 54.0% non-Hispanic Caucasian) randomly assigned to either a social interaction or reading task. As predicted, cannabis users in the social interaction condition reported greater cannabis craving than those in the reading condition. This effect was particularly evident among those with social anxiety disorder. Although physiological arousal did not moderate the relationship between condition and craving, coping motives were the most common reasons cited for wanting to use cannabis and were reported more among those in the social interaction task. These experimental results uniquely add to a growing literature suggesting the importance of elevated state social anxiety (especially among those with social anxiety disorder) in cannabis use vulnerability processes.

Social anxiety is related to greater suicidality, even after controlling for depression and other psychopathology. The Interpersonal-Psychological Theory of Suicide (IPTS; Joiner, 2005) proposes that people are vulnerable to wanting to die by suicide if they experience both perceived burdensomeness (sense that one is a burden to others) and thwarted belongingness (a greater sense of alienation from others). Socially anxious persons may be especially vulnerable to these interpersonal factors. The current study tested whether interpersonal IPTS components independently and additively mediate the social anxiety-suicidal ideation (SI) relation among 780 (80.5% female) undergraduates. Social anxiety was significantly, robustly related to SI and to thwarted belongingness and perceived burdensomeness. Social anxiety was indirectly related to SI via thwarted belongingness and perceived burdensomeness. The sum of these indirect effects was significant. Moderated mediation analyses indicated that perceived burdensomeness only mediated the relation between social anxiety and SI at higher levels of thwarted belongingness. Findings highlight that difficulties in interpersonal functioning may serve as potential pathways through which social anxiety may lead to greater suicidality.

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Although social anxiety is related to smoking and nicotine dependence, little work has sought to identify factors that contribute to these relations. The current study examined whether social anxiety was associated with cognitive vulnerability factors related to smoking: perceived barriers for quitting, cessation-related problems, negative affect reduction outcome expectancies, and negative affect reduction motives. Further, we tested whether social anxiety was robustly related to these factors after controlling for cigarettes smoked per day, gender, alcohol use frequency, lifetime cannabis use status, panic attack frequency, anxiety sensitivity, and negative affectivity. The sample consisted of 580 (38.6% female) treatment-seeking smokers. Social anxiety was associated with perceived barriers for quitting, cessation-related problems, negative affect reduction outcome expectancies, and negative affect reduction motives. After controlling for covariates, social anxiety was robustly related to perceived barriers for quitting, cessation- related problems, and negative affect reduction outcome expectancies. Social anxiety was robustly related to negative affect reduction motives among men but not women. Results indicate that social anxiety is robustly related to cognitive vulnerability factors associated with poorer cessation outcomes, suggesting that social anxiety may be an important therapeutic target during smoking cessation.

ABSTRACT. Objective: Despite high rates of college cannabis use, little work has identified high-risk cannabis use events. For instance, Mardi Gras (MG) and St. Patrick's Day (SPD) are characterized by more college drinking, yet it is unknown whether they are also related to greater cannabis use. Further, some campuses may have traditions that emphasize substance use during these events, whereas other campuses may not. Such campus differences may affect whether students use cannabis during specific events. The present study tested whether MG and SPD were related to more cannabis use at two campuses with different traditions regarding MG and SPD. Further, given that Campus A has specific traditions regarding MG whereas Campus B has specific traditions regarding SPD, cross-campus differences in event-specific use were examined. Method: Current cannabis-using undergraduates (N = 154) at two campuses completed an online survey of event-specific cannabis use and event-specific cannabis-related problems. Results: Participants used more cannabis during MG and SPD than during a typical weekday, typical day on which the holiday fell, and a holiday unrelated to cannabis use (Presidents' Day). Among those who engaged in event-specific use, MG and SPD cannabis use was greater than typical weekend use. Campus differences were observed. For example, Campus A reported more cannabis-related problems during MG than SPD, whereas Campus B reported more problems during SPD than MG. Conclusions: Specific holidays were associated with more cannabis use and use-related problems. Observed between-campus differences indicate that campus traditions may affect event-specific cannabis use and use-related problems. (J. Stud. Alcohol Drugs, 76, 190-194, 2015)

These findings suggest that mindfulness-based approaches to smoking cessation may be effective because of improvements in distress tolerance. However, future prospective and laboratory-based studies are needed to better understand the mindfulness-distress tolerance link among smokers.