Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population

NADPH oxidase p22phox subunit is responsible for the production of reactive oxygen species in the vascular tissue. The C242T polymorphism in the p22phox gene has been associated with diverse coronary artery disease phenotypes, but the findings about the protective or harmful effects of the T allele are still controversial. Our main aim was to assess the effect of p22phox C242T genotypes on arterial stiffness, a predictor of late morbidity and mortality, in individuals from the general population. We randomly selected 1,178 individuals from the general population of Vitoria City, Brazil. Genotypes for the C242T polymorphism were detected by PCR-RFLP, and pulse wave velocity (PWV) values were measured with a noninvasive automatic device Complior. p22phox and TNF-α gene expression were quantified by real-time PCR in human arterial mammary smooth muscle cells. In both the entire and nonhypertensive groups: individuals carrying the TT genotype had higher PWV values and higher risk for increased arterial stiffness [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.27-2.92 and OR 1.78, 95% CI 1.07-2.95, respectively] compared with individuals carrying CC+CT genotypes, even after adjustment for covariates. No difference in the p22phox gene expression according C242T genotypes was observed. However, TNF-α gene expression was higher in cells from individual carrying the T allele, suggesting that this genetic marker is associated with functional phenotypes at the gene expression level. In conclusion, we suggest that p22phox C242T polymorphism is associated with arterial stiffness evaluated by PWV in the general population. This genetic association shed light on the understanding of the genetic modulation on vascular dysfunction mediated by NADPH oxidase.     

The combined dexamethasone/TSST paradigm--a new method for psychoneuroendocrinology

The two main physiological systems involved in the regulation of the stress response are the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). However, the interaction of these systems on the stress response remains poorly understood. To better understand the cross-regulatory effects of the different systems involved in stress regulation, we developed a new stress paradigm that keeps the activity of the HPA constant when exposing subjects to psychosocial stress. Thirty healthy male participants were recruited and randomly assigned to either a dexamethasone (DEX; n?=?15) or placebo (PLC; n?=?15) group. All subjects were instructed to take the Dexamethasone (2 mg) or Placebo pill the night before coming to the laboratory to undergo the Trier Social Stress Task (TSST). Salivary cortisol, salivary alpha amylase (sAA), heart rate, blood pressure and subjective stress were assessed throughout the protocol. As expected, the DEX group presented with suppressed cortisol levels. In comparison, their heart rate was elevated by approximately ten base points compared to the PLC group, with increases throughout the protocol and during the TSST. Neither sAA, nor systolic or diastolic blood pressures showed significant group differences. Subjective stress levels significantly increased from baseline, and were found to be higher before and after the TSST after DEX compared to placebo. These results demonstrate a significant interaction between the HPA and the SNS during acute stress. The SNS activity was found to be elevated in the presence of a suppressed HPA axis, with some further effects on subjective levels of stress. The method to suppress the HPA prior to inducing stress was found to completely reliable, without any adverse side effects. Therefore, we propose this paradigm as a new method to investigate the interaction of the two major stress systems in the regulation of the stress response.     

Classification of activity engagement in individuals with severe physical disabilities using signals of the peripheral nervous system

Communication barriers often result in exclusion of children and youth with disabilities from activities and social settings that are essential to their psychosocial development. In particular, difficulties in describing their experiences of activities and social settings hinder our understanding of the factors that promote inclusion and participation of this group of individuals. To address this specific communication challenge, we examined the feasibility of developing a language-free measure of experience in youth with severe physical disabilities. To do this, we used the activity of the peripheral nervous system to detect patterns of psychological arousal associated with activities requiring different patterns of cognitive/affective and interpersonal involvement (activity engagement). We demonstrated that these signals can differentiate among patterns of arousal associated with these activities with high accuracy (two levels: 81%, three levels: 74%). These results demonstrate the potential for development of a real-time, motor- and language-free measure for describing the experiences of children and youth with disabilities.     

Prevalence of and risk factors for trachoma in Kano state, Nigeria

Background

In northern Nigeria, trachoma is an important public health problem, but there are currently few population-based data on prevalence of disease and no formal trachoma control programs.

Methodology / Principal Findings

In Kano state, Nigeria, we conducted a population-based cross-sectional survey using multistage cluster random sampling, combining examination for clinical signs of trachoma and application of questionnaires assessing potential household-level risk factors. A total of 4491 people were examined in 40 clusters, of whom 1572 were aged 1–9 years, and 2407 (53.6%) were female. In 1–9 year-olds, the prevalence of trachomatous inflammation–follicular (TF) was 17.5% (95% CI: 15.7–19.5%). In a multivariate model, independent risk factors for active trachoma were the presence of flies on the face (OR 1.98, 95% CI 1.30–3.02); a dirty face (OR 2.45, 95% CI 1.85–3.25) and presence of animal dung within the compound of residence (OR 3.46, 95% CI 1.62–7.41). The prevalence of trachomatous trichiasis in persons aged ≥15years was 10.9% (95% CI: 9.7–12.2%). Trichiasis was significantly more common in adult females than in adult males.

Conclusion/Significance

There is an urgent need for a trachoma control program in Kano state, with emphasis given to provision of good quality trichiasis surgery. Particular effort will need to be made to identify women with trichiasis and engage them with appropriate services while also taking steps to secure azithromycin for mass treatment and ensuring personal and environmental hygiene.     

Cutting a Drop of Water Pinned by Wire Loops Using a Superhydrophobic Surface and Knife

A water drop on a superhydrophobic surface that is pinned by wire loops can be reproducibly cut without formation of satellite droplets. Drops placed on low-density polyethylene surfaces and Teflon-coated glass slides were cut with superhydrophobic knives of low-density polyethylene and treated copper or zinc sheets, respectively. Distortion of drop shape by the superhydrophobic knife enables a clean break. The driving force for droplet formation arises from the lower surface free energy for two separate drops, and it is modeled as a 2-D system. An estimate of the free energy change serves to guide when droplets will form based on the variation of drop volume, loop spacing and knife depth. Combining the cutting process with an electrofocusing driving force could enable a reproducible biomolecular separation without troubling satellite drop formation.     

Raw attitudes, wetland cultures, life-cycles: socio-cultural dynamics relating to Opisthorchis viverrini in the Mekong Basin

Opisthorchis viverrini is one of the most common and medically important food-borne parasites in the Lower Mekong area of Southeast Asia. As we learn more about its ecology, pathology and epidemiology we see the need to consider more deeply the socio-cultural dynamics with which food-borne species complexes are associated. This paper argues that the Mekong region is characterized by strong livelihoods and life-style associations within wetland ecosystems, which are inseparable from human eating habits (“raw attitudes”). Within the fish-rice economies of the region there are many long-cherished food cultures based on eating raw, semi-cooked and fermented fish dishes, which are known to lead to opisthorchiasis, and potentially cholangiocarcinoma. This paper examines evidence from northeast Thailand showing that dedicated health outreach campaigns do help to reduce prevalence of opisthorchiasis over time. For disease prevention and health education approaches to be most effective, they must be sensitive to culture, livelihood economics, gender, and age. Further integrative, inter-disciplinary and international research must incorporate the complex dynamics of parasite ecology, human behavior, socio-economics, and public health awareness.     

Development of a homogeneous AlphaLISA ubiquitination assay using ubiquitin binding matrices as universal components for the detection of ubiquitinated proteins

The Ubiquitin Proteasome Pathway (UPP) has become a target rich pathway for therapeutic intervention as its role in pathogenic disease is better understood. In particular many E3 ligases within this pathway have been implicated in cancer, inflammation and metabolic diseases. It has been of great interest to develop biochemical assays to identify inhibitors of catalytic E3 ubiquitination activity as a means of abrogating the disease mechanism. Here we describe a homogeneous biochemical assay that utilizes native ubiquitin and Tandem-repeated Ubiquitin-Binding Entities (TUBEs) as a detection technology for ubiquitination activity. We developed a TUBEs based proximity AlphaLisa? assay for Mdm2, which is an E3 ligase that negatively regulates p53 tumor suppressor protein. We further demonstrate that this assay strategy or design can also be applied to the development of assays to detect autoubiquitination of other E3 ligases that are also of interest for therapeutic intervention. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.     

Differential affinity of BsSCO for Cu(II) and Cu(I) suggests a redox role in copper transfer to the Cu(A) center of cytochrome c oxidase

SCO (synthesis of cytochrome c oxidase) proteins are involved in the assembly of the respiratory chain enzyme cytochrome c oxidase acting to assist in the assembly of the Cu(A) center contained within subunit II of the oxidase complex. The Cu(A) center receives electrons from the reductive substrate ferrocytochrome c, and passes them on to the cytochrome a center. Cytochrome a feeds electrons to the oxygen reaction site composed of cytochrome a(3) and Cu(B). Cu(A) consists of two copper ions positioned within bonding distance and ligated by two histidine side chains, one methionine, a backbone carbonyl and two bridging cysteine residues. The complex structure and redox capacity of Cu(A) present a potential assembly challenge. SCO proteins are members of the thioredoxin family which led to the early suggestion of a disulfide exchange function for SCO in Cu(A) assembly, whereas the copper binding capacity of the Bacillus subtilis version of SCO (i.e., BsSCO) suggests a direct role for SCO proteins in copper transfer. We have characterized redox and copper exchange properties of apo- and metalated-BsSCO. The release of copper (II) from its complex with BsSCO is best achieved by reducing it to Cu(I). We propose a mechanism involving both disulfide and copper exchange between BsSCO and the apo-Cu(A) site. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.