Analysis of Association between IL-17 gene rs2275913 Single Nucleotide Polymorphism and Chronic Hepatitis B Infection

BACKGROUND AND OBJECTIVE: Hepatitis B disease is one of the main causes of inflammation and liver damage that can lead to chronic hepatitis B virus infection. Single nucleotide polymorphism in the cytokines gene can affect the host immune response. Interleukin 17 produced by Thelper17 cells has been shown to play a role in immune function in infectious and inflammatory diseases. This study was conducted to investigate the association between polymorphism in IL-17 gene (rs2275913) and chronic hepatitis B infection. METHODS: This case-control study was performed on 130 chronic patients as a case group and 130 healthy individuals as control. Patients with positive result of ELISA test for HBsAg and Anti-HBc Ab and control subjects with negative result of this test were enrolled. PCR-RFLP was used to genotype extracted DNA from blood samples. FINDINGS: The genotype frequencies of rs2275913 did not show significant difference between patients and control groups. Distribution of genotypes inpatients were, 40.8% GG, 41.5% AG, 17.7% AA and in control group were, 42.3% GG, 45.4% AG, 12.3% GG (p=0.469). CONCLUSION: The results of study showed no relation between IL-17 gene polymorphism rs2275913 and chronic HBV

Lack of Genetic Association between Interleukin-18 Gene Polymorphism (rs1946518) and Chronic Hepatitis B Infection

BACKGROUND AND OBJECTIVE: Interleukin 18 is a member of the cytokines that play an important role in the Th1-mediated immune response by inducing interferon-gamma activity in collaboration with Interleukin-12 (IL-18). Interleukin 12 and Interleukin 18 can play an important role in purifying viruses. Considering the importance of IL-18, this study was conducted to investigate the relationship between Interleukin-18 Gene polymorphism (-607 C/A: rs1946518) and the susceptibility to chronic hepatitis B infection. METHODS: In this case-control study, the genomic DNA of 115 patients with chronic hepatitis B (with positive results of HBsAg and Anti-HBcAb serology testing) and 115 non-HBV-infected controls (negative results of HBsAg and Anti-HbcAb serology testing and no history of liver disease) was extracted by salting-out method and the genotype of single-nucleotide polymorphism (-607 C / A: rs1946518) was sequenced using PCR-RFLP method. FINDING: The genotype frequency of TT, GT, and GG in patients was 40%, 49.6%, and 10.4% in patients, and 41.7%, 42.6%, and 15.7% in the control group, respectively. No significant difference was found between the patients group and the control group. CONCLUSION: Based on the results of this study, there was no clear relationship between IL-18 polymorphism and the potential for chronic hepatitis B infection. Therefore, this polymorphism cannot be a potential factor for chronic hepatitis B

Role of CAP350 in Centriolar Tubule Stability and Centriole Assembly

BACKGROUND: Centrioles are microtubule-based cylindrical structures composed of nine triplet tubules and are required for the formation of the centrosome, flagella and cilia. Despite theirs importance, centriole biogenesis is poorly understood. Centrosome duplication is initiated at the G1/S transition by the sequential recruitment of a set of conserved proteins under the control of the kinase Plk4. Subsequently, the procentriole is assembled by the polymerization of centriolar tubules via an unknown mechanism involving several tubulin paralogs. METHODOLOGY/PRINCIPAL FINDINGS: Here, we developed a cellular assay to study centrosome duplication and procentriole stability based on its sensitivity to the microtubule-depolymerizing drug nocodazole. By using RNA interference experiments, we show that the stability of growing procentrioles is regulated by the microtubule-stabilizing protein CAP350, independently of hSAS-6 and CPAP which initiate procentriole growth. Furthermore, our analysis reveals the critical role of centriolar tubule stability for an efficient procentriole growth. CONCLUSIONS/SIGNIFICANCE: CAP350 belongs to a new class of proteins which associate and stabilize centriolar tubules to control centriole duplication

Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs.To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria.This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment

Centriole movements in mammalian epithelial cells during cytokinesis

<p>Abstract</p> <p>Background</p> <p>In cytokinesis, when the cleavage furrow has been formed, the two centrioles in each daughter cell separate. It has been suggested that the centrioles facilitate and regulate cytokinesis to some extent. It has been postulated that termination of cytokinesis (abscission) depends on the migration of a centriole to the intercellular bridge and then back to the cell center. To investigate the involvement of centrioles in cytokinesis, we monitored the movements of centrioles in three mammalian epithelial cell lines, HeLa, MCF 10A, and the p53-deficient mouse mammary tumor cell line KP-7.7, by time-lapse imaging. Centrin1-EGFP and α-Tubulin-mCherry were co-expressed in the cells to visualize respectively the centrioles and microtubules.</p> <p>Results</p> <p>Here we report that separated centrioles that migrate from the cell pole are very mobile during cytokinesis and their movements can be characterized as 1) along the nuclear envelope, 2) irregular, and 3) along microtubules forming the spindle axis. Centriole movement towards the intercellular bridge was only seen occasionally and was highly cell-line dependent.</p> <p>Conclusions</p> <p>These findings show that centrioles are highly mobile during cytokinesis and suggest that the repositioning of a centriole to the intercellular bridge is not essential for controlling abscission. We suggest that centriole movements are microtubule dependent and that abscission is more dependent on other mechanisms than positioning of centrioles.</p

Centrioles: active players or passengers during mitosis?

Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as “the organ for cell division”. However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues

Nuclear Import and Export Signals of Human Cohesins SA1/STAG1 and SA2/STAG2 Expressed in Saccharomyces cerevisiae

Abstract Background: Human SA/STAG proteins, homologues of the yeast Irr1/Scc3 cohesin, are the least studied constituents of the sister chromatid cohesion complex crucial for proper chromosome segregation. The two SA paralogues, SA1 and SA2, show some specificity towards the chromosome region they stabilize, and SA2, but not SA1, has been shown to participate in transcriptional regulation as well. The molecular basis of this functional divergence is unknown. Methodology/Principal Findings: In silico analysis indicates numerous putative nuclear localization (NLS) and export (NES) signals in the SA proteins, suggesting the possibility of their nucleocytoplasmic shuttling. We studied the functionality of those putative signals by expressing fluorescently tagged SA1 and SA2 in the yeast Saccharomyces cerevisiae. Only the Nterminal NLS turned out to be functional in SA1. In contrast, the SA2 protein has at least two functional NLS and also two functional NES. Depending on the balance between these opposing signals, SA2 resides in the nucleus or is distributed throughout the cell. Validation of the above conclusions in HeLa cells confirmed that the same N-terminal NLS of SA1 is functional in those cells. In contrast, in SA2 the principal NLS functioning in HeLa cells is different from that identified in yeast and is localized to the C-terminus. Conclusions/Significance: This is the first demonstration of the possibility of non-nuclear localization of an SA protein. The reported difference in the organization between the two SA homologues may also be relevant to their partially divergent functions. The mechanisms determining subcellular localization of cohesins are only partially conserved between yeast and human cells

Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial study with special focus on cataract risk

Because of the increasing application of ionizing radiation in medicine, quantitative data on effects of low-dose radiation are needed to optimize radiation protection, particularly with respect to cataract development. Using mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.125 and 0.5 Gy at 10 weeks of age, determined lens opacities for up to 2 years and compared it with overall survival, cytogenetic alterations and cancer development. The highest dose was significantly associated with increased body weight and reduced survival rate. Chromosomal aberrations in bone marrow cells showed a dose-dependent increase 12 months after irradiation. Pathological screening indicated a dose-dependent risk for several types of tumors. Scheimpflug imaging of the lens revealed a significant dose-dependent effect of 1% of lens opacity. Comparison of different biological end points demonstrated long-term effects of low-dose irradiation for several biological end points