Role of the N-terminus in permeability of chicken connexin45.6 gap junctional channels

Previous studies have shown that gap junctional channels formed from the lens connexins Cx50 (or its chicken orthologue, Cx45.6) and Cx43 exhibit marked differences in transjunctional voltage gating and unitary conductance. In the present study, we used the negatively charged dye, Lucifer Yellow (LY), to examine and compare quantitative differences in dye transfer between pairs of HeLa cells stably transfected with Cx45.6 or Cx43. Our results show that Cx45.6 gap junctional channels are three times less permeable to LY than Cx43 channels. Replacement of the N-terminus of Cx45.6 with the corresponding domain of Cx43 increased LY permeability, reduced the transjunctional voltage ( V _j) gating sensitivity, and reduced the unitary conductance of Cx45.6–43N gap junctional channels. Further experiments, using a series of Alexa probes that had similar net charge but varied in size showed that the Cx45.6–43N had a significantly higher permeability for the two largest Alexa dyes than Cx45.6. These data suggest that the N-terminus plays a critical role in determining many of biophysical properties of Cx45.6 gap junctional channels, including molecular permeability and voltage gating.     

Substance use and perceived symptom improvement among patients with bipolar disorder and substance dependence

BACKGROUND: Bipolar disorder (BPD) is the Axis I disorder with the highest risk for coexisting substance use disorder. One explanation for this phenomenon is the 'self-medication hypothesis', which states that some patients experience improvement in psychiatric symptoms as a result of substance use. We thus investigated reasons for substance use and perceived substance-induced improvement in BPD symptoms among patients with current BPD and substance dependence. METHODS: A total of 45 patients received six monthly assessments; 21 also received integrated group therapy (IGT), focusing simultaneously on BPD and substance dependence, while 24 did not receive IGT. Patients reported at intake their current reasons for initiating substance use (including BPD symptoms) and the effects of substance use on those symptoms. RESULTS: Nearly all patients initiated substance use because of at least one BPD symptom, especially depression (77.8%) and racing thoughts (57.8%); most (66.7%) reported improvement in at least one BPD symptom as a result of substance use. Among patients reporting substance-induced improvement in BPD symptoms, those receiving IGT reported fewer days of drug use over the 6-month study period than those not receiving IGT; this difference was not significant among patients without substance-induced improvement in BPD symptoms. LIMITATIONS: The study is limited by its small sample size and by the potential inaccuracy of self-reports regarding the effects of substance use on mood. CONCLUSIONS: Substance dependent patients who report that substance use improves their BPD symptoms may benefit from treatment that focuses simultaneously on both disorders.     

The outcome of T-cell costimulation through intercellular adhesion molecule-1 differs from costimulation through leucocyte function-associated antigen-1

Optimal T-cell activation requires both an antigen-specific and a costimulatory signal. The outcome of T-cell activation can be influenced by the nature of the costimulatory signal the T cell receives. We recently demonstrated the ability of stimulation through intercellular adhesion molecule-1 (ICAM-1), resident on the T-cell surface, to provide a second signal for T-cell activation, and have extended that work here to begin an examination of the functional outcome of this set of signals. Costimulation through ICAM-1 resulted in a greater percentage of cells having undergone more than three divisions when compared to costimulation through leucocyte function-associated antigen-1 (LFA-1). Costimulation through ICAM-1 also had an effect similar to costimulation through CD28 in its ability to down-regulate the cyclin dependent kinase inhibitor p27kip1. Costimulation through ICAM-1 provided greater protection from apoptosis than costimulation through LFA-1, especially in cells having divided more than three times. This was supported by the ability of costimulation through ICAM-1 to up-regulate the anti-apoptotic protein Bcl-2. Finally, costimulation through ICAM-1 or CD28 produced a greater number of T cells with a memory phenotype than costimulation through LFA-1.     

Aspects of social and emotional competence in adult attention-deficit/hyperactivity disorder

Social and emotional competence were evaluated using self-report and behavioral measures in adults with attention-deficit/hyperactivity disorder (ADHD) and controls. Adults with ADHD viewed themselves as less socially competent but more sensitive toward violations of social norms than controls. Films depicting emotional interactions were used to assess linguistic properties of free recall and perceived emotional intensity. Although adults with ADHD used more words to describe the scenes, they used fewer emotion-related words, despite rating the emotions depicted as more intense than did controls. In contrast, no group differences for words depicting social or cognitive processes were observed. Overall, adults with ADHD appear more aware of their problems in social versus emotional skills. Findings may have implications for improving the psychosocial functioning of these adults.     

Psychiatric disorders associated with risk for the development of eating disorders during adolescence and early adulthood

Longitudinal data were used to investigate whether anxiety, depressive, disruptive, personality, or substance use disorders are associated with risk for the development of eating disorders during adolescence or early adulthood. Psychiatric disorders were assessed among 726 youths from a random community sample during adolescence and early adulthood. Depressive disorders during early adolescence were associated with elevated risk for the onset of eating disorders, dietary restriction, purging behavior, and recurrent weight fluctuations after preexisting eating problems and other psychiatric disorders were controlled statistically. Disruptive and personality disorders were independently associated with elevated risk for specific eating or weight problems. The present findings suggest that depressive disorders during early adolescence may contribute to the development of eating disorders during middle adolescence or early adulthood.     

Comparison of an immunochromatography test with multiplex reverse transcription-PCR for rapid diagnosis of respiratory syncytial virus infections

A new commercial rapid 10-min one-step immunochromatography (IC) test, SAS RSV test, was compared to another IC test, Directigen EZ RSV, employing RT-PCR as the "gold standard" for detecting respiratory syncytial virus. Of 102 clinical samples, 79 were positive by RT-PCR, 66 (82.5%) were positive with the SAS RSV test, and 55 (69.6%) were positive with Directigen EZ RSV. The specificity of the new test was 91.3% (21 of 23), similar to that of Directigen EZ RSV (100% [23 of 23]). This test performs well enough to be used for patient care.