Mismatch repair deficiencies transforming stem cells into cancer stem cells and therapeutic implications

For the exceptional self-renewal capacity, regulated cell proliferation and differential potential to a wide variety of cell types, the stem cells must maintain the intact genome. The cells under continuous exogenous and endogenous genotoxic stress accumulate DNA errors, drive proliferative expansion and transform into cancer stem cells with a heterogeneous population of tumor cells. These cells are a common phenomenon for the hematological malignancies and solid tumors. In response to DNA damage, the complex cellular mechanisms including cell cycle arrest, transcription induction and DNA repair are activated. The cells when exposed to cytotoxic agents, the apoptosis lead to cell death. However, the absence of repair machinery makes the cells resistant to tumor sensitizing agents and result in malignant transformation. Mismatch repair gene defects are recently identified in hematopoietic malignancies, leukemia and lymphoma cell lines. This review emphasizes the importance of MMR systems in maintaining the stem cell functioning and its therapeutic implications in the eradication of cancer stem cells and differentiated tumor cells as well. The understanding of the biological functions of mismatch repair in the stem cells and its malignant counterparts could help in developing an effective novel therapies leaving residual non-tumorigenic population of cells resulting in potential cancer cures

Dielectric properties of Li2O-3B2O3 glasses

The frequency and temperature dependence of the dielectric constant and the electrical conductivity of the transparent glasses in the composition Li2O-3B2O3 (LBO) were investigated in the 100 Hz- 10 MHz frequency range. The dielectric constant and the loss in the low frequency regime were electrode material dependent. Dielectric and electrical relaxations were respectively analyzed using the Cole-Cole and electric modulus formalisms. The dielectric relaxation mechanism was discussed in the framework of electrode and charge carrier (hopping of the ions) related polarization using generalized Cole-Cole expression. The frequency dependent electrical conductivity was rationalized using Jonscher's power law. The activation energy associated with the dc conductivity was 0.80 \pm 0.02 eV, which was ascribed to the motion of Li+ ions in the glass matrix. The activation energy associated with dielectric relaxation was almost equal to that of the dc conductivity, indicating that the same species took part in both the processes. Temperature dependent behavior of the frequency exponent (n) suggested that the correlated barrier hopping model was the most apposite to rationalize the electrical transport phenomenon in Li2O-3B2O3 glasses. These glasses on heating at 933 K/10h resulted in the known non-linear optical phase LiB3O5.Comment: 32 pages, 13 figure

Hypervalent Iodine Compounds with Carboxylate and Tetrazolate Ligands

In modern organic chemistry, hypervalent (HV) iodine(III) compounds are frequently used as oxidizing agents but application of λ3-iodanes in polymer and material chemistry is still underexplored. This dissertation describes the preparation of dynamic and self-healing materials by employing ligand exchange reactions involving HV iodine(III) compounds of the type ArIL2 (Ar = Aryl, L = ligand, e.g., carboxylate or (pseudo)halide). These compounds can undergo ligand exchange reactions in presence of nucleophiles (Nu-) to form ArINu2. Diacetoxyiodo benzene was successfully employed as a crosslinker to prepare dynamic and self-healing gels derived from carboxylate-containing polymers. Furthermore, advantage was taken of the ability of diacetoxyiodo benzene to generate radicals upon UV light irradiation in order to convert the dynamic crosslinked structures to permanent (set) networks. Star polymers were prepared by mixing block copolymers Sty/MMA and AA with diacetoxyiodo benzene solution. The star polymers were characterized by dynamic light scattering and diffusion ordered NMR spectroscopy. Besides that, oligomeric and µ-oxo- HV iodine(III) compounds with two I-N bonds, containing 5-substituted tetrazoles as the ligands PhI(N4CR)2 (R = C6H5, and 4-CH3C6H4) were synthesized using PhIO. The crystal structure of one representative compound (an oligomer with three I atoms in the backbone and 5-phenyltetrazole end groups) was solved and refined from synchrotron powder X-ray diffraction. The novel compounds were characterized by cyclic voltammetry and were found to be strong oxidants. An attempt was made to prepare tetrazole based polymer networks. After synthesizing tetrazole containing oligomeric HV iodine(III) compounds, N-heterocycle-stabilized pseudocyclic λ3-iodane with tetrazole as the stabilizing group was synthesized and its thermal stability and redox activity were studied. The oxidative power of the polyvalent iodine compound with a tetrazole ligand was demonstrated by conducting oxidation of thioanisole to sulfoxide and dimerization of thiobenzamide to 3,5-diphenyl-1,2,4-thiadiazole