Exocytotic catecholamine release is not associated with cation flux through channels in the vesicle membrane but Na+ influx through the fusion pore

Release of charged neurotransmitter molecules through a narrow fusion pore requires charge compensation by other ions. It has been proposed that this may occur by ion flow from the cytosol through channels in the vesicle membrane, which would generate a net outward current. This hypothesis was tested in chromaffin cells using cell-attached patch amperometry that simultaneously measured catecholamine release from single vesicles and ionic current across the patch membrane. No detectable current was associated with catecholamine release indicating that <2% of cations, if any, enter the vesicle through its membrane. Instead,we show that flux of catecholamines through the fusion pore, measured as an amperometric foot signal, decreases when the extracellular cation concentration is reduced. The results reveal that the rate of transmitter release through the fusion pore is coupled to net Na+ influx through the fusion pore, as predicted by electrodiffusion theory applied to fusion-pore permeation,and suggest a prefusion rather than postfusion role for vesicular cation channels

Quality of Life and Related Factors among HIV-Positive Spouses from Serodiscordant Couples under Antiretroviral Therapy in Henan Province, China

OBJECTIVE: To describe the quality of life and related factors in HIV-positive spouses undergoing ART from discordant couples. METHODS: A cross-sectional study was conducted among 1,009 HIV-positive spouses from serodiscordant couples in Zhumadian, Henan Province, between October 1, 2008 and March 31, 2009. HIV-positive spouses were interviewed by local health professionals. Quality of life was evaluated by WHOQOL (Chinese Version). A multiple linear regression model was used to analyze the related factors. RESULTS: The majority of subjects were female (56.39%), had received a high school education (44%), were of Han ethnicity (98.41%), and were farmers (90.09%); the median time period of receiving ART was 3.92 years. The physical, psychological, social, and environmental QOL scores of the subjects were 12.91±1.95, 12.35±1.80, 13.96±2.43, and 12.45±1.91 respectively. The multiple linear regression model identified the physical domain related factors to be CD4 count, educational level, and occupation; psychological domain related factors include age, educational level, and reported STD symptom; social domain related factors included education level; and environmental domain related factors included education level, reported STD symptoms, and occupation. CONCLUSION: Being younger, a farmer, having a lower level of education, a reported STD symptom, or lower CD4 count, could decrease one's quality of life, suggesting that the use of blanket ART programs alone may not necessarily improve quality of life. Subjects received lower scores in the psychological domain, suggesting that psychological intervention may also need to be strengthened

Sex differences in money pathology in the general population

This study examined sex differences in money beliefs and behaviours. Over 100,000 British participants completed two measures online, one of which assessed “money pathology” (Forman in Mind over money, Doubleday, Toronto, 1987), and the other four “money types”, based on the emotional associations of money (Furnham et al. in Personal Individ Differ, 52:707–711, 2012). Nearly all measures showed significant sex differences with medium to large effect sizes, and with females exhibiting more “money pathology” than males. The biggest difference on the money types was on money being associated with generosity (money representing love) where men scored much lower than females, and autonomy (money representing freedom) where men scored higher than women. For men, more than women, money represented Power and Security. Men were more likely to be Hoarders while women did more emotional regulatory purchasing. Implications and limitations of this study are discussed

Reproductive health and lifestyle factors associated with health-related quality of life among perinatally HIV-infected adolescents in Uganda

Background With increased survival of perinatally HIV - infected adolescents due to antiretroviral therapy (ART), the focus of HIV care has shifted to health-related quality of life (HRQoL) as a measure of disease progression, effects of ART co-morbidity and prognosis. We assessed factors associated with better HRQoL in perinatally HIV -infected adolescents in Uganda by determining the associations between sexual and reproductive health (SRH) or lifestyle experiences on HRQoL. Methods In a cross-sectional study, data on SRH, lifestyle experiences, socio demographic factors, communication with parents on sexuality and satisfaction of SRH services in ART clinics were collected from 614 HIV perinatally infected adolescents aged 10–19 using an interviewer-administered survey questionnaire. HRQoL data were collected using the Medical Outcomes Study HIV Health Survey instrument (MOS-HIV). Factors associated with better HRQoL were analysed using multiple logistic regression. Results The mean age was 16.2 ± 2.1 years, 362 (58.8 %) were females and 210 (34.2 %) were sexually active. Adolescents on ART were twice likely to present with better physical health (AOR = 2.07, 95 % CI: 1.24–3.46) and four times more likely to present with better mental health (AOR = 3.9, 95 % CI: 2.22–6.92) than those who were not on ART. There were no statistically significant associations between SRH (ever had sex, ever been pregnant, condom use, contraceptive use) or life style factors and physical health or mental health. Those with secondary or tertiary education were more likely to present with a better mental health (AOR = 5.3, 95 % CI: 1.86–15.41) compared those who had attained primary or no education. Participants who desired to have a child in future more likely (AOR 1.7, 95 % CI: 1.05–3.00) to present with a better mental health. Lack of communication with guardians on sexuality (AOR = 0.6, 95 % CI: 0.40–0.89), or dissatisfaction with SRH services (AOR 0.34, 95 % CI: 0.18–0.62) were associated with poorer mental health. Conclusion Among perinatally HIV-infected adolescents in Uganda, being on ART was associated with better physical and mental health while lack of communication with guardians on sexuality or dissatisfaction with SRH services was associated with poor mental health. Adolescents with pregnancy intentions were more likely to have a better mental health

The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling

The Z-disc, appearing as a fine dense line forming sarcomere boundaries in striated muscles, when studied in detail reveals crosslinked filament arrays that transmit tension and house myriads of proteins with diverse functions. At the Z-disc the barbed ends of the antiparallel actin filaments from adjoining sarcomeres interdigitate and are crosslinked primarily by layers of α-actinin. The Z-disc is therefore the site of polarity reversal of the actin filaments, as needed to interact with the bipolar myosin filaments in successive sarcomeres. The layers of α-actinin determine the Z-disc width: fast fibres have narrow (~30–50 nm) Z-discs and slow and cardiac fibres have wide (~100 nm) Z-discs. Comprehensive reviews on the roles of the numerous proteins located at the Z-disc in signalling and disease have been published; the aim here is different, namely to review the advances in structural aspects of the Z-disc

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field