Positional effect of mutations in 5'UTR of hepatitis C virus 4a on patients' response to therapy

AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS： HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustaIW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing.RESULTS： Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered WatsonCrick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain - were statistically more prevalent in sustained viral response patients （SVR, n = 14） as compared to breakthrough （BT, n = 5） patients.CONCLUSION： The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.

Blurring the Distinction Between ＂High＂ and ＂Low＂ Politics in International Relations Theory： Drifting Players in the Logic of Two-Level Games

Since the beginning of international relations as a formal academic discipline in 1919, the realist paradigm has dominated academic debate, and consequently, major foreign policy decisions. This paradigm focuses on ＂politics＂ as the actions of so-called ＂high politics＂; that is to say, primacy is given to actions between states over the actions that occur within states. This article will aim to demonstrate that the ＂low politics＂ of domestic policy should be considered to a further extent than it currently is in the field of international relations theory. In doing so, this article will focus on sub-unit level factors that have considerable impact on international relations; namely, political parties, terrorist organizations, and lobbying groups. However, it is recognised that proponents of neo-liberal theory, such as Keohane and Nye, and academics studying interest group theory, such as Kabashima and Sato, have done much work to further the idea of international relations theory as more than state-centric analysis. This article will act as an attempt to further this idea both through normative and conceptual analysis. The article uses Putnam＇s concept of two-level games as a basic model of international-domestic relations, hoping to expand on the concept whilst retaining its integrity.

Expression of telomerase hTERT in human non-small cell lung cancer and its correlation with c-myc gene

Objective To investigate the expression of human telomerase catalytic subunit,hTERT, in human non-small cell lung cancer (NSCLC) and its correlations to c-myc gene.Methods hTERT and c-myc mRNA expressions were detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Statistical correlation analysis was made to estimate whether there was interrelation between them.Results Positive rate of hTERT expression in 51 surgically resected lung cancer specimens was 86.3%,significantly higher than that in adjacent non-neoplastic lung tissues and benign lesions,which were 14.3% and 27.3% respectively. No statistical significance was observed between the frequency of hTERT expression and histologic types,degree of differentiation,TNM stages,tumor size or lymph nodes metastases. Correlation analysis revealed that the expression of c-myc gene was significantly related to that of hTERT (correlation coefficient,r =0.633,P <0.001).Conclusions hTERT may be a useful tumor marker in diagnosing lung cancer. Significant correlation between the expression of hTERT and c-myc mRNA indicates that the activation and up-regulation of hTERT might be conferred by over-expression of c-myc gene.