Immunogenicity evaluation of a DNA vaccine expressing the hepatitis C virus non-structural protein 2 gene in C57BL/6 Mice

Backgrounds: Most of the hepatitis C virus (HCV) infections elicit poor immune responses and 75% to 85% of cases become chronic; therefore, the development of an effective vaccine against HCV is of paramount importance. In this study, we aimed to evaluate co-administration of HCV non-Structural Protein 2 and IL-12 DNA vaccines in C57BL/6 mice. Methods: A plasmid encoding full-length HCV NS2 protein (non-structural protein 2) was generated and used to vaccinate mice. Negative control (an empty expression vector) was also employed to evaluate the background response. To investigate immune responses against vaccine, C57BL/6 mice received three doses of the vaccine with a two-week interval. Cellular immunity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay for lymphocyte proliferation, lactate dehydrogenase release for cytotoxic T lymphocyte (CTL) activity and cytokine assay. Results: The findings demonstrated that immunization of mice with plasmid expressing HCV NS2 induced CTL response, interferon gamma production, and lymphocyte proliferation compared to negative control. The results also demonstrated that co-administration of IL-12 with the HCV NS2 plasmid induced significantly better immune response in C57BL/6 mice. Conclusion: DNA vaccine encoding HCV NS2 is an effective candidate that can trigger CTL-based immune response against HCV. In addition, the results suggested that combining the DNA vaccine approach with immune stimulatory cytokines may significantly enhance antigen-specific immune responses

Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran

Objective(s): It has been reported that the mutation of the pre-core (PC) and basal-core promoter (BCP) may play an important role in the development of HBV-related hepatocellular carcinoma (HCC). In this study the PC and BCP mutations were investigated in chronic HBV patients. Materials and Methods: In this study, 120 chronic HBV patients from Golestan, Northeast of Iran who were not vaccinated against HBV, were recruited from the year 2008 to 2012. HBV-DNA extraction from plasma and PCR were performed and positive PCR products were subjected to automated sequencing. Results: One hundred out of 120 (83.3%) patients were HBeAg negative. Comparison of our nucleotide sequences with reference sequence showed high rate mutation in BCP and PC region (96.66%). Frame shift mutation was found in 78 (65%) of patients in BCP region, among them 8 (6.6%) patients showed mutation in PC region. Conclusion: Our results demonstrated high rate of mutations in BCP and PC regions among HBV chronic patients in Northeast of Iran

Antimicrobial effects of folk medicinal plants from the North of Iran against Mycobacterium tuberculosis

Background: Medicinal plants have been used traditionally in Golestan province (north of Iran), against Mycobacterium tuberculosis or the clinical signs of tuberculosis (TB). Objectives: This study aimed to define the inhibitory effects of ethanolic extracts of six of these medicinal plants against Mycobacterium tuberculosis. Materials and Methods: Peganum harmala (seed extract), Punica granatum (peel extract), Digitalis sp. (leaf extract), fruit extract of Citrus lemon, Rosa canina and Berberis vulgaris were extracted in ethanol and their activity against M. tuberculosis isolates were determined by the agar diffusion method. The zone of inhibition (at 200 to 1.6 mg/mL) was measured and the results were compared with isoniazid and rifampin as standard positive controls. Also the concentration of vitamin C of each the extracts was evaluated. Results: The ethanolic extract of Peganum harmala seed and Punica granatum peel exhibited potential activity against all M. tuberculosis isolates with mean inhibitory zone of 18.7 and 18.8 mm, at 200 mg/mL concentration. The mean inhibitory zone around isoniazid and rifampinwere 19.2 and 18.8 mm. Ethanolic extract of Citrus lemon showed moderate inhibitory activity only against sensitive (non MDR; non multi drug resistant) strains of M. tuberculosis, and Digitalis sp. showed inhibitory effects on five isolates. Ascorbic acid content was 43.3 mg/dL in Punica granatum and Digitalis sp. and only 9.1 mg/dL in ethanolic extract of Peganum harmala. Conclusions: The highest content of vitamin C was observed in the extract of Punica granatum, which was observed to be highly active against Mycobacterium tuberculosis, while the P. harmala must have contained other phytochemical constituents that contributed to the anti-tuberculosis effects of this plant. Our findings showed that ethanolic extracts of P. granatum and P. harmala had anti-TB effects comparable to isoniazid and rifampin and can be good candidates for novel and safe natural products against tuberculosis. © 2015, Pediatric Infections Research Center

Mutations in the S gene region of hepatitis B virus genotype D in Golestan Province-Iran

Mutations of HBsAg especially within the "a" determinant could alter the antigenicity of the protein causing failure of HBsAg neutralization and escaping from the host's immune system, resulting in active viral replication and liver disease. This project aimed to investigate mutation in the S gene region of HBV infected patients in Golestan Province-Iran. HBV-DNA extractions from plasma and PCR of 100 patients were performed. Direct sequencing and alignment of S gene were applied using reference sequence from Gene Bank database. All isolates were belonged to genotype D, subgenotype D1, subtype ayw2. Overall 92 point mutations occurred. Of them, 40 (43.47%) were missense and 52 (56.52%) were silent. Mutations were detected in 95 cases (95%). Five of 40 mutations (12.5%) occurred in "a" determinant and 13 (32.5%), 17 (42.5%), and 2 (5%) were seen in antigenic epitope regions of B cell, CD4⁺ and CTL, respectively. Frame shift mutations were seen in 22 cases (22%). 14% of mutations occurred at Major Hydrophilic Region(MHR) area which P120T/S and R122K/T substitutions were the most frequent ones (4%). Mutation in G145R of the S gene was observed in one case. A large number of MHR mutants are in association with failure of HBsAg detection, vaccine, and immunotherapy escape. This study showed "a" determinant S gene mutations in HBV infected people with HBsAg positivity in Golestan Province-Iran. The rate of mutation in our study was 95%. Collectively, the results of this project exhibited that most of mutations were clustered in CD4⁺ antigenic epitopes. © Springer Science+Business Media, LLC 2012

Convergence science in the Anthropocene: Navigating the known and unknown

Rapidly changing ecological and social systems currently pose significant societal challenges. Navigating the complexity of social-ecological change requires ap- proaches able to cope with, and potentially solve, both foreseen and unforeseen societal challenges. The emergent field of convergence addresses the intricacies of such challenges, and is thus relevant to a broad range of interdisciplinary issues. This paper suggests a way to conceptualize convergence research. It discusses how it relates to two major societal challenges (adaptation, transformation), and to the generation of policy-relevant science. It also points out limitations to the further development of convergence research

The prevalence and predictors of comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review and meta-analysis

Abstract Background: Although some authors have recently investigated the co-occurrence of anxiety and bipolar disorders, the topic remains insufficiently studied. Defining the prevalence and predictors of BD-OCD comorbidity has important nosological, clinical and therapeutic implications. Methods: A systematic review and meta-analysis was conducted on the prevalence and predictors of comorbid BD-OCD. Relevant papers published through March 30th, 2015 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. Results: 46 articles met inclusion criteria. The pooled prevalence of OCD in BD was 17.0% (95% CI 12.7-22.4%), which was comparable to the results reported by the pooled prevalence of BD in OCD (18.35%, 95% CI 13.2-24.8%). With regard to OCD-BD predictors, a higher mean age predicted a lower prevalence of OCD in BD patients. Sub group meta-analyses reported higher OCD prevalence rates in BD children and adolescents (24.2%, compared to 13.5% in adults), in BD-I patients (24.6%, compared to 13.6% in mixed BD patients), and among population-based studies (22.2%, compared to 13.2% in hospital-based studies). Limitations: Most studies use retrospective assessment scales with low sensitivity in discriminating true ego-dystonic obsessions from depressive ruminations that may bias results towards an overestimation of obsessive symptom prevalence. Conclusions: This first systematic review and meta-analysis of the prevalence and predictors of comorbid BD-OCD confirms that BD-OCD comorbidity is a common condition in psychiatry with children and adolescents and BD-I patients as the most affected subgroups

Maternal serum copper concentration in premature rupture of membrane: A case-control study

Copper is an integrated parts of metal-protein required far varieties of oxide-reductive metabolic pathways in human. Copper deficiency is considered as risk factors in some pregnancies. Premature rupture of membrane is a pregnancy complication with major adverse effects and is believed maternal Copper deficiency can also be considered as interventional factors. This study was done to evaluate if there is a correlation between maternal serum Copper concentration and premature rupture of membrane in pregnancy. In this case-control study 60 pregnant women with Premature Rupture of Membrane (PROM) were selected as case group including term and pre term the control group consist of 60 pregnant women with normal delivery of term and pre term states. Both group were matched for maternal and pregnancy age. In case and control group the pregnancy at term and pre-term were grouped independently as well. In general the maternal mean serum Copper concentration were 192.4±78.2 and 201.08±82.06 in case and control groups, respectively but this differences statistically was not significant. Data in this study revealed that the absolute value of maternal serum Copper concentration of term or pre term in case groups was slightly lower than related controls. Drop in maternal Copper concentration in some disturbed pregnancies such as premature rupture of membrane is previously demonstrated and based on our data the absolute Copper serum concentration of women with premature rupture of membrane was also slightly lower compared to healthy pregnancy but it was not statistically significant. © Asian Network for Scientific Information

Luminescence from Semiconductor Quantum Wires, Quantum Dots, and Monolayer Quantum Wells: Bottleneck and Localization Issues

Semiconductors nanostructures are fabricated using a range of techniques which inevitably have an impact in the resulting optical properties. Multilayers are grown by epitaxial techniques with a varying degree of uniformity in thickness, composition, etc., all leading to localisation effects in two-dimension. These multilayers are patterned to fabricate wires and dots using, in this case, electron beam lithography and dry etching. The fabrication steps contribute to modifications of the optical properties, beyond the expected purely confinement-related effects. An overview of linear and modulation spectroscopy is presented to demonstrate the impact of fabrication steps as well as of lateral confinement upon the emission from wires and dots. We focus on photoreflectance of GaAs-GaA1As dots and Si-SiGe wires as a probe of strain relaxation. Near-field scanning optical microscopy of single dots of GaAs-GaA1As at helium temperatures illustrates the potentials of using scanning probe techniques to study the underlying quantum mechanics of nanostructures. Finally, we suggest that a combination of lateral exciton confinement and exciton localization is a possible way forward to realise high emission efficiency nanostructures

Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of < 5 years in the Iranian population

This is the final version. Available on open access from Wiley via the DOI in this recordAim To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non‐European population. Methods We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next‐generation sequencing of 35 monogenic diabetes genes. We measured three islet autoantibodies (islet antigen 2, glutamic acid decarboxylase and zinc transporter 8) and generated a Type 1 diabetes genetic risk score in all children. Results We identified six children with monogenic diabetes, including four novel mutations: homozygous mutations in WFS1 (n=3), SLC19A2 and SLC29A3, and a heterozygous mutation in GCK. All clinical features were similar in children with monogenic diabetes (n=6) and in the rest of the cohort (n=121). The Type 1 diabetes genetic risk score discriminated children with monogenic from Type 1 diabetes [area under the receiver‐operating characteristic curve 0.90 (95% CI 0.83–0.97)]. All children with monogenic diabetes were autoantibody‐negative. In children with no mutation, 59 were positive to glutamic acid decarboxylase, 39 to islet antigen 2 and 31 to zinc transporter 8. Measuring zinc transporter 8 increased the number of autoantibody‐positive individuals by eight. Conclusions The present study provides the first evidence that Type 1 diabetes genetic risk score can be used to distinguish monogenic from Type 1 diabetes in an Iranian population with a large number of consanguineous unions. This test can be used to identify children with a higher probability of having monogenic diabetes who could then undergo genetic testing. Identification of these individuals would reduce the cost of treatment and improve the management of their clinical course.Wellcome TrustDiabetes U