A ditopic receptor for cation binding and facilitated transport through a supported liquid membrane

The binding properties of an artificial receptor towards a series of cations including Li⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Ba²⁺, Fe²⁺ and Al³⁺ in acetonitrile are described. The receptor comprises a photo-responsive pyrene unit connected via a short spacer to a 2,2′:6′,2″-terpyridine metal ion binding site. Interaction of cations with the receptor was monitored by changes in absorption profile and the association constants calculated for 1:1 and 1:2 cation:ligand binding fall within the range log β = 3-12. The receptor is highly fluorescent and quenching of the emission is observed upon cation binding. The potassium picrate transport properties of the membrane-bound receptor are also described. This receptor when immobilised in a polymer support, which separates two aqueous solutions, has been shown to transport potassium ions in the dark with a flux rate of 1.5 × 10⁸ mol/s m². In contrast, when the membrane-bound receptor is selectively illuminated with light (λ > 400 nm), the flux increases to 2.0 × 10⁸ mol/s m². The transport efficiency depends on the nature of the trap used in the receiver phase.     

Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma

Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs. Twenty-seven hypermethylated and 13 hypomethylated potential promoter regions of microRNAs, known to be associated with cancer-related pathways like Wnt, ErbB, and PI3K-Akt signaling, were identified. Selected DMRs were confirmed in 2 independent patient cohorts. Inverse correlation between promoter methylation and expression suggested miR-129-2 and members of the miR-200 family (miR-200a, miR-200b, and miR-429) as novel tumor suppressors and oncomiRs, respectively, in CC. Tumor suppressor genes deleted in liver cancer 1 (DLC1), F-box/WD-repeat-containing protein 7 (FBXW7), and cadherin-6 (CDH6) were identified as presumed targets in CC. Tissue microarrays of a representative and well-characterized cohort of biliary tract cancers (n=212) displayed stepwise downregulation of CDH6 and association with poor patient outcome. Ectopic expression of CDH6 on the other hand, delayed growth in the CC cell lines EGI-1 and TFK-1, together suggesting a tumor suppressive function of CDH6. Our work represents a valuable repository for the study of epigenetically altered miRNAs in cholangiocarcinogenesis and novel putative, CC-related tumor suppressive miRNAs and oncomiRs.     

Health Literacy Measure for Adolescents (HELMA): Development and Psychometric Properties

Background

Health literacy refers to personal competencies for the access to, understanding of, appraisal of and application of health information in order to make sound decisions in everyday life. The aim of this study was to develop and evaluate the psychometric properties of an instrument for the measurement of health literacy among adolescents (the Health Literacy Measure for Adolescents-HELMA).

Methods

This study was made up of two phases, qualitative and quantitative, which were carried out in 2012–2014 in Tehran, Iran. In the qualitative part of the study, in-depth interviews with 67 adolescents aged 15–18 were carried out in 4 high schools to generate the initial item pool for the survey. The content validity of the items was then assessed by an expert panel review (n = 13) and face validity was assessed by interviewing adolescents (n = 16). In the quantitative part of the study, in order to describe the psychometric properties of the scale, validity, reliability (internal consistency and test-retest) and factor analysis were assessed.

Results

An item pool made up of 104 items was generated at the qualitative stage. After content validity was considered, this decreased to 47 items. In the quantitative stage, 582 adolescents aged 15–18 participated in the study with a mean age of 16.2 years. 51.2% of participants were females. In principal component factor analysis, 8 factors were loaded, which accounted for 53.37% of the variance observed. Reliability has been approved by α = 0.93 and the test-retest of the scale at two-week intervals indicated an appropriate stability for the scale (ICC = 0.93). The final questionnaire was approved with 44 items split into eight sections. The sections were titled: gain access to, reading, understanding, appraise, use, communication, self-efficacy and numeracy.

Conclusion

The Health Literacy Measure for Adolescents (HELMA) is a valid and reliable tool for the measurement of the health literacy of adolescents aged 15–18 and can be used to evaluate different levels of functional, interactive, and critical health literacy in adolescents.     

Role of hydrogen peroxide during the interaction between the hemibiotrophic fungal pathogen Septoria tritici and wheat

Hydrogen peroxide (H(2)O(2)) is reported to inhibit biotrophic but benefit necrotrophic pathogens. Infection by necrotrophs can result in a massive accumulation of H(2)O(2) in hosts. Little is known of how pathogens with both growth types are affected (hemibiotrophs). The hemibiotroph, Septoria tritici, infecting wheat (Triticum aestivum) is inhibited by H(2)O(2) during the biotrophic phase, but a large H(2)O(2) accumulation occurs in the host during reproduction. Here, we infiltrated catalase, H(2)O(2) or water into wheat during the biotrophic or the necrotrophic phase of S. tritici and studied the effect of infection on host physiology to get an understanding of the survival strategy of the pathogen. H(2)O(2) removal by catalase at both early and late stages made plants more susceptible, whereas H(2)O(2) made them more resistant. H(2)O(2) is harmful to S. tritici throughout its life cycle, but it can be tolerated. The late accumulation of H(2)O(2) is unlikely to result from down-regulation of photosynthesis, but probably originates from damage to the peroxisomes during the general tissue collapse, which is accompanied by release of soluble sugars in a susceptible cultivar.     

Mesenchymal stem cell mediated effects on microglial phenotype in cuprizone-induced demyelination model

Microglial cells have an essential role in neurodegenerative disorders, such as multiple sclerosis. They are divided into two subgroups: M1 and M2 phenotypes. Mesenchymal stem cells (MSC), with neuroprotective and immunomodulating properties, could improve these diseases. We evaluate the immunomodulating effects of MSC on microglial phenotypes and the improvement of demyelination in a cuprizone (CPZ) model of multiple sclerosis (MS). For inducing the chronic demyelination model, C57BL6 mice were given a diet with 0.2% CPZ (w/w) for 12 weeks. In the MSC group, cells were transplanted into the right lateral ventricle of mice. The expression of targeted genes was assessed by real-time polymerase chain reaction. M1 and M2 microglial phenotypes were assessed by immunohistochemistry of inducible nitric oxide synthase (iNOS) and Arg-1, respectively. Remyelination was studied by luxal fast blue (LFB) staining and electron microscopy (EM). We found that MSC transplantation reduced the expression level of M1-specific messenger RNA (mRNA; iNOS and CD86) but increased the expression level of M2 specific genes (CD206, Arg-1, and CX3CR1) in comparison to the CPZ group. Moreover, cell therapy significantly decreased the M1 marker (iNOS⁺ cells), but M2 marker (Arg-1⁺ cells) significantly increased in comparison with the CPZ group. In addition, MSC treatment significantly increased the CX3CL1 expression level in comparison with the CPZ group and led to improvement in remyelination, which was confirmed by LFB and EM images. The results showed that MSC transplantation increases the M2 and decreases the M1 phenotype in MS. This change was accompanied by decrease in demyelination and axonal injury and indicated that MSCs have a positive effect on MS by modification of microglia cells.     

A fluorescent aptasensor for sensitive analysis oxytetracycline based on silver nanoclusters

A fluorescent aptasensor for detection of oxytetracycline (OTC) was presented based on fluorescence quenching of DNA aptamer‐templated silver nanoclusters (AgNCs). The specific DNA scaffolds with two different nucleotides fragments were used: one was enriched with a cytosine sequence fragment (C12) that could produce DNA–AgNCs via a chemical reduction method, and another was the OTC aptamer fragment that could selectively bind to the OTC antibiotic. Thus, the as‐prepared AgNCs could exhibit quenched fluorescence after binding to the target OTC. The fluorescence ratio of the DNA–AgNCs was quenched in a linearly proportional manner to the concentration of the target in the range of 0.5 nM to 100 nM with a detection limit of 0.1 nM. This proposed nanobiosensor was demonstrated to be sensitive, selective, and simple, introducing a viable alternative for rapid determination of toxin OTC in honey and water samples. Copyright © 2016 John Wiley & Sons, Ltd.     

Serum nitric oxide metabolite levels in a general healthy population: relation to sex and age

This study aims at determining serum nitrite/nitrate (NO(x)) levels in healthy subjects within the framework of a population-based study. NO(x) concentration was measured in 3505 subjects aged >/=20 years. Subjects with diabetes, renal dysfunction, those undergoing treatment for dyslipidemia and hypertension, were excluded; also excluded were smokers, pregnant women, and subjects with cardiovascular and infectious diseases or cancer; leaving 1983 (667 men, 1316 women) asymptomatic non-smoking subjects for the analysis. NO(x) concentrations were determined in serum and compared in different age groups. Mean+/-SE of NO(x) concentration was 24.8+/-0.02 and 24.4+/-0.01 micromol/l in men and women respectively. Men aged 20-29 years had significantly higher NO(x) levels compared to corresponding women (25.1+/-0.03 vs. 22.7+/-0.02). Serum NO(x) concentration peaked at 50-59 years in both genders. Comparison between lower and upper quartiles of NO(x) levels was performed in both genders. Women with high serum NO(x) were older and had significantly higher body mass index and fasting plasma glucose. The results of this study determine the normal levels of serum NO(x) concentrations in asymptomatic non-smoker subjects; also show that serum NO(x) concentrations indicate sex and age differences in these subjects.     

MgHog1 regulates dimorphism and pathogenicity in the fungal wheat pathogen Mycosphaerella graminicola

The dimorphic ascomycete pathogen Mycosphaerella graminicola switches from a yeastlike form to an infectious filamentous form that penetrates the host foliage through stomata. We examined the biological function of the mitogen-activated protein kinase-encoding gene MgHog1 in M. graminicola. Interestingly, MgHog1 mutants were unable to switch to filamentous growth on water agar that mimics the nutritionally poor conditions on the foliar surface and, hence, exclusively developed by a yeastlike budding process. Consequently, due to impaired initiation of infectious germ tubes, as revealed by detailed in planta cytological analyses, the MgHog1 mutants failed to infect wheat leaves. We, therefore, conclude that MgHog1 is a new pathogenicity factor involved in the regulation of dimorphism in M. graminicola. Furthermore, MgHog1 mutants are osmosensitive, resistant to phenylpyrrole and dicarboximide fungicides, and do not melanize.