Striatin knock out induces a gain of function of INa and impaired Ca2+ handling in mESC-derived cardiomyocytes.

AIM: Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its pathogenicity have been poorly investigated. METHODS: We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn-KO and isogenic WT mouse embryonic stem cell lines. RESULTS: The spontaneous beating rate of Strn-KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2-8 Hz) Strn-KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn-KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn-KO CMs than in WT. Indeed, incubation of Strn-KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels. CONCLUSION: Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn-related multi-protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.

HIV awareness: a kap study among students in Italy reveals that preventive campaigns still represent a public health priority.

BACKGROUND: Improving knowledge about HIV/AIDS among young people is crucial for preventing new infections. The aim of the study was to investigate knowledge, attitudes and practices regarding HIV infection among students attending university courses related to the healthcare professions, in order to better target future preventive and informative HIV campaigns tailored for young people. STUDY DESIGN: A knowledge, attitude and practices study was conducted among university students attending the following university courses in Bari (Southern Italy): Medicine and Surgery (MS), Dentistry and Dental Prostheses, Health Assistance, Motor Activities and Sports Sciences, Sciences and Technology of Herbal and Health Products, Nursing, Biomedical Laboratory Techniques, and Dietetics. METHODS: Students completed a self-administered questionnaire designed to assess their knowledge/attitudes re/ HIV and their own sexual practices. The general part of the questionnaire requested information about age, gender, nationality, religion and marital status. The second part included questions asking about knowledge, attitude and practices with respect to HIV, which required true/false answers or graduated answers (reported as agree, quite agree, quite disagree, and disagree). RESULTS: Four hundred students were invited to fill in the questionnaire. The response rate was 91.2% (n=365). Almost all students were aware that HIV is transmitted through sexual intercourse and blood, but only 34% knew that breastfeeding is a route of transmission. Of the respondents, 86.8% referred to previous sexual intercourse (25.8% reported using a condom in all cases of sexual intercourse, 43.5% in most cases, 18.6% rarely and 12.1 never). Sexual intercourse with casual partners was reported by 37.5% of these students and 63.9% of them did not always use a condom. CONCLUSIONS: The results of the study show that knowledge about some aspects of HIV is insufficient even though the students participating in the present study are students attending university courses related to the healthcare professions. Moreover, high-risk behaviors as the lack of the use of condom during sexual intercourse with casual partners are also common among interviewed students. Programs aimed at providing information that can prevent/reduce transmission of HIV in young people and new strategies to improve knowledge should be stressed as a public health priority.

Protein phosphatase-1 and -2A, kinase FA, and casein kinase II in skeletal muscle of streptozotocin diabetic rats.

Protein phosphatase-1 (PP-1) and -2A (PP-2A), two regulatory subunits of PP-1, the glycogen-binding subunit G and inhibitor-2 (I-2), kinase FA, and casein kinase II (CK-II) were investigated in skeletal muscle of diabetic rats 2 days after streptozotocin injection. FA and CK-II activate PP-1 in vitro and might be involved in the activation of PP-1 by insulin. Following muscle fractionation we found that (1) diabetes decreased both basal and trypsin-stimulated PP-1 activities; the decrease was more significant in the glycogen-bound and microsomal fractions than in the cytosol (cytosolic PP-1 decreased as specific activity but not as activity/g of muscle); also PP-2A was lower in diabetic cytosols; (2) less G was immunoprecipitated from diabetic glycogen-bound fractions compared to controls, while I-2 was not significantly changed; (3) diabetes decreased also FA (assayed as PP-1 activator) and CK-II (assayed using a synthetic peptide as substrate); (4) diabetes did not have any effect on phosphorylase (a + b) activity in the glycogen-bound fraction. Altogether the data show that acute diabetes decreased PP-1, one of its regulatory subunits and two potentially physiological regulators of PP-1, in addition to PP-2A. This may indicate that insulin is responsible for the long-term regulation of the same enzymes that are also under acute insulin control.