A change in metal cation switches selectivity of a phospholipid sensor from phosphatidic acid to phosphatidylserine.

Phosphatidic acid and phosphatidylserine are anionic phospholipids with emerging signalling roles in cells. Determination of how phosphatidic acid and phosphatidylserine change location and quantity in cells over time requires selective fluorescent sensors that can distinguish these two anionic phospholipids. However, the design of such synthetic sensors that can selectively bind and respond to a single phospholipid within the complex membrane milieu remains challenging. In this work, we present a simple and robust strategy to control the selectivity of synthetic sensors for phosphatidic acid and phosphatidylserine. By changing the coordination metal of a dipicolylamine (DPA) ligand from Zn(II) to Ni(II) on the same synthetic sensor with a peptide backbone, we achieve a complete switch in selectivity from phosphatidic acid to phosphatidylserine in model lipid membranes. Furthermore, this strategy was largely unaffected by the choice and the position of the fluorophores. We envision that this strategy will provide a platform for the rational design of targeted synthetic phospholipid sensors to probe plasma and intracellular membranes.

A macrocyclic fluorescent probe for the detection of citrate.

We present a macrocyclic fluorescent probe for the detection of citrate. This receptor binds citrate through hydrogen-bonding interactions in aqueous solutions, and exhibits a turn-on in fluorescence in response to binding. The presence of common biologically relevant dicarboxylate species does not significantly impact the fluorescence response. We have demonstrated the utility of this probe with the staining of murine splenocytes, and identified different basal levels of citrate present in immune cell subsets via flow cytometry analysis.

Molecular recognition and sensing of dicarboxylates and dicarboxylic acids.

The recognition and detection of dicarboxylic acids and dicarboxylates is of significance for a wide variety of applications, including medical diagnosis, monitoring of health and of environmental contaminants, and in industry. Hence small molecule receptors and sensors for dicarboxylic acids and dicarboxylates have great potential for applications in these fields. This review outlines the challenges faced in the recognition and detection of these species, strategies that have been used to obtain effective and observable interactions with dicarboxylic acids and dicarboxylates, and progress made in this field in the period from 2014 to 2020.

A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism.

Specific forms of the lipid ceramide, synthesized by the ceramide synthase enzyme family, are believed to regulate metabolic physiology. Genetic mouse models have established C16 ceramide as a driver of insulin resistance in liver and adipose tissue. C18 ceramide, synthesized by ceramide synthase 1 (CerS1), is abundant in skeletal muscle and suggested to promote insulin resistance in humans. We herein describe the first isoform-specific ceramide synthase inhibitor, P053, which inhibits CerS1 with nanomolar potency. Lipidomic profiling shows that P053 is highly selective for CerS1. Daily P053 administration to mice fed a high-fat diet (HFD) increases fatty acid oxidation in skeletal muscle and impedes increases in muscle triglycerides and adiposity, but does not protect against HFD-induced insulin resistance. Our inhibitor therefore allowed us to define a role for CerS1 as an endogenous inhibitor of mitochondrial fatty acid oxidation in muscle and regulator of whole-body adiposity.

Antisocial thinking in adolescents: further psychometric development of the Antisocial Beliefs and Attitudes Scale (ABAS).

Investigating the impact of "off-line" cognitive structures on the broad range of antisocial behaviors shown by young people has been hampered by the absence of psychometrically robust measures of antisocial cognitions. This study evaluates the psychometric properties of the Antisocial Beliefs and Attitudes Scale (ABAS), a developmentally sensitive measure of young people's beliefs and attitudes toward social standards of acceptable behavior at home and at school. The reliability and validity of the ABAS was assessed in a sample of British school children (N = 486) aged 9-16 years (M = 12.79, SD = 1.90) and male young offenders (N = 84) aged 13-17 years (M = 15.15, SD = 0.27). Participants completed the ABAS, together with a self-report measure of antisocial behavior; maternal reports of antisocial activity were also collected in the offending sample. Confirmatory factor analysis replicated the 2-factor structure of Rule Noncompliance and Peer Conflict previously derived from a sample of Canadian school children, and these factors showed good test-retest reliability. Rule Noncompliance predicted self-reported antisocial behavior for ages 11-16 years, while Peer Conflict predicted antisocial behavior for ages 9-16 years. Comparisons between young offenders and an age-matched subsample of males from the school group showed significant differences. In young offenders, Rule Noncompliance and Peer Conflict were significantly predictive of self-reported antisocial behavior, while Rule Noncompliance independently predicted mothers' ratings of their sons' antisocial behavior. These findings provide support for the ABAS as a psychometrically sound measure of antisocial thinking.

Distinguishing two types of adolescent sex offenders.

OBJECTIVE: To distinguish between adolescent sex offenders according to nonsexual offense history. METHOD: Thirty-two sex offenders, 48 criminally versatile offenders, and 34 nonaggressive offenders referred by youth courts for mental health assessments in Toronto, Canada between 1994 and 1997 were compared on measures of childhood conduct problems, current behavioral adjustment, antisocial attitudes and beliefs, and risk for future delinquency. Sex offenders were further divided into those without (sex-only) and those with (sex-plus) nonsexual offenses in their criminal histories. RESULTS: Sex offenders were similar to non-sex offenders in their childhood conduct problems, current behavioral adjustment, and antisocial attitudes and beliefs, but they had a lower risk for future delinquency. Sex-only offenders had significantly fewer childhood conduct problems, better current adjustment, more prosocial attitudes, and a lower risk for future delinquency than did the non-sex offender groups, whereas sex-plus offenders resembled criminally versatile offenders. CONCLUSIONS: Differences between sex-only and sex-plus offenders reflect a valid typological distinction. Discrimination between these two groups is important when assigning sex offenders to appropriate interventions.