Bidirectional interactions between NOX2‐type NADPH oxidase and the F‐actin cytoskeleton in neuronal growth cones

NADPH oxidases are important for neuronal function but detailed subcellular localization studies have not been performed. Here, we provide the first evidence for the presence of functional NADPH oxidase 2 (NOX2)‐type complex in neuronal growth cones and its bidirectional relationship with the actin cytoskeleton. NADPH oxidase inhibition resulted in reduced F‐actin content, retrograde F‐actin flow, and neurite outgrowth. Stimulation of NADPH oxidase via protein kinase C activation increased levels of hydrogen peroxide in the growth cone periphery. The main enzymatic NADPH oxidase subunit NOX2/gp91^phox localized to the growth cone plasma membrane and showed little overlap with the regulatory subunit p40^phox. p40^phox itself exhibited colocalization with filopodial actin bundles. Differential subcellular fractionation revealed preferential association of NOX2/gp91^phox and p40^phox with the membrane and the cytoskeletal fraction, respectively. When neurite growth was evoked with beads coated with the cell adhesion molecule apCAM, we observed a significant increase in colocalization of p40^phox with NOX2/gp91^phox at apCAM adhesion sites. Together, these findings suggest a bidirectional functional relationship between NADPH oxidase activity and the actin cytoskeleton in neuronal growth cones, which contributes to the control of neurite outgrowth.

     

Childhood ADHD and Risk for Substance Dependence in Adulthood: A Longitudinal,Population-Based Study

Background

Adolescents with attention-deficit/hyperactivity disorder (ADHD) are known to be at significantly greater risk for the development of substance use disorders (SUD) compared to peers. Impulsivity, which could lead to higher levels of drug use, is a known symptom of ADHD and likely accounts, in part, for this relationship. Other factors, such as a biologically increased susceptibility to substance dependence (addiction), may also play a role.

Objective

This report further examines the relationships between childhood ADHD, adolescent- onset SUD, and substance abuse and substance dependence in adulthood.

Method

Individuals with childhood ADHD and non-ADHD controls from the same population-based birth cohort were invited to participate in a prospective outcome study. Participants completed a structured neuropsychiatric interview with modules for SUD and a psychosocial questionnaire. Information on adolescent SUD was obtained retrospectively, in a previous study, from medical and school records. Associations were summarized using odds ratios (OR) and 95% CIs estimated from logistic regression models adjusted for age and gender.

Results

A total of 232 ADHD cases and 335 non-ADHD controls participated (mean age, 27.0 and 28.6 years, respectively). ADHD cases were more likely than controls to have a SUD diagnosed in adolescence and were more likely to have alcohol (adjusted OR 14.38, 95% CI 1.49–138.88) and drug (adjusted OR 3.48, 95% CI 1.38–8.79) dependence in adulthood. The subgroup of participating ADHD cases who did not have SUD during adolescence were no more likely than controls to develop new onset alcohol dependence as adults, although they were significantly more likely to develop new onset drug dependence.

Conclusions

Our study found preliminary evidence that adults with childhood ADHD are more susceptible than peers to developing drug dependence, a disorder associated with neurological changes in the brain. The relationship between ADHD and alcohol dependence appears to be more complex.     

Antibacterial Activity of THAM Trisphenylguanide against Methicillin-Resistant Staphylococcus aureus

This study investigated the potential antibacterial activity of three series of compounds synthesized from 12 linear and branched polyamines with 2–8 amino groups, which were substituted to produce the corresponding guanides, biguanides, or phenylguanides, against Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Antibacterial activity was measured for each compound by determining the minimum inhibitory concentration against the bacteria, and the toxicity towards mammalian cells was determined. The most effective compound, THAM trisphenylguanide, was studied in time-to-kill and cytoplasmic leakage assays against methicillin-resistant Staphylococcus aureus (MRSA, USA300) in comparison to chlorhexidine. Preliminary toxicity and MRSA challenge studies in mice were also conducted on this compound. THAM trisphenylguanide showed significant antibacterial activity (MIC ∼1 mg/L) and selectivity against MRSA relative to all the other bacteria examined. In time-to-kill assays it showed increased antimicrobial activity against MRSA versus chlorhexidine. It induced leakage of cytoplasmic content at concentrations that did not reduce cell viability, suggesting the mechanism of action may involve membrane disruption. Using an intraperitoneal mouse model of invasive MRSA disease, THAM trisphenylguanide reduced bacterial burden locally and in deeper tissues. This study has identified a novel guanide compound with selective microbicidal activity against Staphylococcus aureus, including a methicillin-resistant (MRSA) strain.     

Workplace Social Capital and Mental Health among Chinese Employees: A Multi-Level,Cross-Sectional Study

Background

Whereas the majority of previous research on social capital and health has been on residential neighborhoods and communities, the evidence remains sparse on workplace social capital. To address this gap in the literature, we examined the association between workplace social capital and health status among Chinese employees in a large, multi-level, cross-sectional study.

Methods

By employing a two-stage stratified random sampling procedure, 2,796 employees were identified from 35 workplaces in Shanghai during March to November 2012. Workplace social capital was assessed using a validated and psychometrically tested eight-item measure, and the Chinese language version of the WHO-Five Well-Being Index (WHO-5) was used to assess mental health. Control variables included sex, age, marital status, education level, occupation status, smoking status, physical activity, and job stress. Multilevel logistic regression analysis was conducted to explore whether individual- and workplace-level social capital was associated with mental health status.

Results

In total, 34.9% of workers reported poor mental health (WHO-5<13). After controlling for individual-level socio-demographic and lifestyle variables, compared to workers with the highest quartile of personal social capital, workers with the third, second, and lowest quartiles exhibited 1.39 to 3.54 times greater odds of poor mental health, 1.39 (95% CI: 1.10–1.75), 1.85 (95% CI: 1.38–2.46) and 3.54 (95% CI: 2.73–4.59), respectively. Corresponding odds ratios for workplace-level social capital were 0.95 (95% CI: 0.61–1.49), 1.14 (95% CI: 0.72–1.81) and 1.63 (95% CI: 1.05–2.53) for the third, second, and lowest quartiles, respectively.

Conclusions

Higher workplace social capital is associated with lower odds of poor mental health among Chinese employees. Promoting social capital at the workplace may contribute to enhancing employees’ mental health in China.     

Zika Virus Emergence in Mosquitoes in Southeastern Senegal, 2011

Background

Zika virus (ZIKV; genus Flavivirus, family Flaviviridae) is maintained in a zoonotic cycle between arboreal Aedes spp. mosquitoes and nonhuman primates in African and Asian forests. Spillover into humans has been documented in both regions and the virus is currently responsible for a large outbreak in French Polynesia. ZIKV amplifications are frequent in southeastern Senegal but little is known about their seasonal and spatial dynamics. The aim of this paper is to describe the spatio-temporal patterns of the 2011 ZIKV amplification in southeastern Senegal.

Methodology/Findings

Mosquitoes were collected monthly from April to December 2011 except during July. Each evening from 18∶00 to 21∶00 hrs landing collections were performed by teams of 3 persons working simultaneously in forest (canopy and ground), savannah, agriculture, village (indoor and outdoor) and barren land cover sites. Mosquitoes were tested for virus infection by virus isolation and RT-PCR. ZIKV was detected in 31 of the 1,700 mosquito pools (11,247 mosquitoes) tested: Ae. furcifer (5), Ae. luteocephalus (5), Ae. africanus (5), Ae. vittatus (3), Ae. taylori, Ae. dalzieli, Ae. hirsutus and Ae. metallicus (2 each) and Ae. aegypti, Ae. unilinaetus, Ma. uniformis, Cx. perfuscus and An. coustani (1 pool each) collected in June (3), September (10), October (11), November (6) and December (1). ZIKV was detected from mosquitoes collected in all land cover classes except indoor locations within villages. The virus was detected in only one of the ten villages investigated.

Conclusions/Significance

This ZIKV amplification was widespread in the Kédougou area, involved several mosquito species as probable vectors, and encompassed all investigated land cover classes except indoor locations within villages. Aedes furcifer males and Aedes vittatus were found infected within a village, thus these species are probably involved in the transmission of Zika virus to humans in this environment.