This is the first study performed in population from Bosnia & Herzegovina (BH), in which we analysed a significance of genetic variations in drug-metabolising enzyme, cytochrome P450 (CYP), in pathogenesis of Type 2 diabetes. We have determined allele frequencies for CYP2C9*2, CYP2C19*2, and CYP2D6*4 in diabetic patients and nondiabetic controls. Genomic DNA was extracted from blood samples collected from 37 diabetic and 44 nondiabetic subjects. A real-time polymerase chain reaction was used for the detection of specific CYP polymorphisms, with the application of the specific TaqMan® SNP genotyping tests (Applied Biosystems). Interestingly, results from this study have demonstrated that frequencies of CYP2C19*2 and CYP2D6*4 variants were in line, while frequency of CYP2C9*2 polymorphism seemed to be lower in this sample of BH population as compared to the Caucasians genotype data. Furthermore, no significant difference in allele frequencies for CYP2C9*2, CYP2C19*2, and CYP2D6*4 was demonstrated between diabetic and nondiabetic subjects. Thus, results form this study seem to indicate no relationship between CYP2C9, CYP2C19, and CYP2D6 genotype and diabetes susceptibility in Bosnian population. This in part may reflect a limited study population included in our study and would require larger cohorts to reveal potential relationships between analysed CYP genetic variants and diabetes risk. In addition, it would be pertinent to further explore possible effects of CYP genetic variations on therapeutic and adverse outcomes of oral antidiabetics, which might be the key in optimising therapy for individual patient with Type 2 diabetes.
Genus Artemisia is thought to have reached the Americas across the Bering Strait from Asia during the late Tertiary, but the systematic position of the South American endemic species and the migration routes towards the south have not yet been studied. We used nuclear DNA sequences to unravel the interspecific relationships among the South American Artemisia and their connections with the remaining species of the genus, as well as using fluorescent in situ hybridisation and genome size assessments to characterise this polyploid complex. Most of the species are clustered in a monophyletic clade, nested within the American endemic clade, with the exception of A. magellanica Sch. Bip., which appears segregated from the other American species and constitutes a clade together with A. biennis Willd. Fluorescent in situ hybridisation and genome size data revealed that monoploid genome size remains quite constant across ploidy levels and a proportional increase of ribosomal loci was detected, a dynamic not usually found in this genus. The results are discussed in the light of evolutionary processes which occur in plants, and plausible origins for the South American endemic species are hypothesised.
We present explicit formulae for the eccentric connectivity index and Wiener index of 2-dimensional square and comb lattices with open ends. The formulae for these indices of 2-dimensional square lattices with ends closed at themselves are also derived. The index for closed ends case divided by the same index for open ends case in the limit N →∞ defines a novel quantity we call compression factor. This factor was calculated for both eccentric connectivity and Wiener index for 2- dimensional square lattice.
Human epidermal growth factor receptor 2 (HER2) overexpression stimulates cell growth in p53-mutated cells while it inhibits cell proliferation in those with wild-type p53, but the molecular mechanism is unknown. The Dmp1 promoter was activated by HER2/neu through the phosphatidylinositol-3'-kinase-Akt-NF-κB pathway, which in turn stimulated Arf transcription. Binding of p65 and p52 subunits of NF-κB was shown to the Dmp1 promoter and that of Dmp1 to the Arf promoter on HER2/neu overexpression. Both Dmp1 and p53 were induced in premalignant lesions from mouse mammary tumor virus-neu mice, and mammary tumorigenesis was significantly accelerated in both Dmp1+/- and Dmp1-/- mice. Selective deletion of Dmp1 and/or overexpression of Tbx2/Pokemon was found in >50% of wild-type HER2/neu carcinomas, although the involvement of Arf, Mdm2, or p53 was rare. Tumors from Dmp1+/-, Dmp1-/-, and wild-type neu mice with hemizygous Dmp1 deletion showed significant downregulation of Arf and p21Cip1/WAF1, showing p53 inactivity and more aggressive phenotypes than tumors without Dmp1 deletion. Notably, endogenous hDMP1 mRNA decreased when HER2 was depleted in human breast cancer cells. Our study shows the pivotal roles of Dmp1 in HER2/neu-p53 signaling and breast carcinogenesis.
The paper also synthesizes a feasible process structure that can be applied for the process of fractional crystallization, and gives a simulation of the process by calculating the material balance of the process. The parameters of relevant process paths that were obtained prove that the process presented in this paper is feasible in practice and applicable in industry.
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