Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells

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Elucidation of the anticancer potential and tubulin isotype-specific interactions of β-sitosterol

Beta-sitosterol (β-SITO), a phytosterol present in many edible vegetables, has been reported to possess antineoplastic properties and cancer treatment potential. We have shown previously that it binds at a unique site (the ‘SITO-site’) compared to the colchicine binding site at the interface of α- and β-tubulin. In this study, we investigated the anticancer efficacy of β-SITO against invasive breast carcinoma using MCF-7 cells. Since ‘isotypes’ of β-tubulin show tissue-specific expression and many are associated with cancer drug resistance, using computer-assisted docking and atomistic molecular dynamic simulations, we also examined its binding interactions to all known isotypes of β-tubulin in αβ-tubulin dimer. β-SITO inhibited MCF-7 cell viability by up to 50%, compared to vehicle-treated control cells. Indicating its antimetastatic potential, the phytosterol strongly inhibited cell migration. Immunofluorescence imaging of β-SITO-treated MCF-7 cells exhibited disruption of the microtubules and chromosome organization. Far-UV circular dichroism spectra indicated loss of helical stability in tubulin when bound to β-SITO. Docking and MD simulation studies, combined with MM-PBSA and MM-GBSA calculations revealed that β-SITO preferentially binds with specific β-tubulin isotypes (β_II and β_III) in the αβ-tubulin dimer. Both these β-tubulin isotypes have been implicated in drug resistance against tubulin-targeted chemotherapeutics. Our data show the tubulin-targeted anticancer potential of β-SITO, and its potential clinical utility against β_II and β_III isotype-overexpressing neoplasms.     

Influence of a developing tree canopy on the yield of Pennisetum pedicellatum sown on a mine spoil

Abstract. Shoot and root biomass yield of a sown grass, Pennisetum pedicellatum, were measured at below-canopy, canopy edge and open locations in young monoculture stands of eight tree species planted on a coalmine spoil. Incident light as percentage of full sunlight decreased from open to canopy edge to below-canopy locations. The shoot and root weights of Pennisetum in different tree stands for each of the three locations were significantly different and were significantly related to each other, and to percentage sunlight across all tree species plots and locations. The gradient of incident light was the principal factor governing the gradient of grass biomass under developing canopies of tree plantations on the mine spoil.     

Metal(II) complexes of 1-formylisoquinoline thiosemicarbazone: their preparation,characterization and antitumour activity

Complexes of Co(II), Ni(lI), Cu(II), Zn(II) and Pt(II) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H) were prepared and characterized by elemental analyses, conductance measurement and spectral studies. On the basis of these studies a distorted octahedral structure for [Co(1-iqtsc)₂]·2H₂O, a distorted trigonal-bipyramidal structure for [Ni- (1-iqtsc-H)Cl₂], [Cu(1-iqtsc-H)Cl₂] and [Zn(1-iqtsc- H)(OAc)₂]·H₂O and a square-planar structure for [Pt(1-iqtsc)Cl] are suggested. All these metal(II) complexes were screened for their antitumour activity in the P388 lymphocytic leukaemia test system in mice. Except for Pt(Il), the complexes were found to possess significant activity; the Ni(II) complex showed a T/C value of 161 at the optimum dosage.     

Antifungal activity of soybean and chickpea isoflavones and their reduced derivatives

The fungicidal activity of the isoflavones from soybean (Glycine max) and chickpea (Cicer arietinum) has been studied on three food and forage contaminating fungi, Aspergillus ochraceus, Penicillium digitatum and Fusarium culmorum. The reduced derivatives of the corresponding isoflavones—the isoflavanones and the isoflavans—were also included in the investigation. For the first time in a comparative study it is shown that isoflavones and isoflavanones are variable in their activity whereas the isoflavans are moderately active inhibitors of fungal growth.     

Association of <Emphasis Type="Italic">p</Emphasis>53 codon 72 polymorphism and survival of North Indian lung cancer patients treated with platinum-based chemotherapy

p53 helps in maintaining genomic stability by undergoing cellular arrest, DNA repair or cellular apoptosis during DNA damage. So, as to find the association of p53Arg ⁷² Pro towards lung carcinogenesis and overall survival of North Indian lung cancer patients, single nucleotide polymorphic variant (rs1042522) was analyzed. 840 subjects including 420 cases and 420 controls were recruited and genotyped using PCR-RFLP technique for p53Arg ⁷² Pro polymorphic site. Association was analyzed using adjusted odds ratio along with its confidence intervals (95?% CI) and p value predicted from logistic regression whereas overall survival for lung cancer patients was obtained using Kaplan–Meir and Cox regression model for different parameters to obtain hazard ratio and survival time with statistical significance (log-rank p value). None of the variant genotypes for p53Arg ⁷² Pro showed any association towards lung cancer risk or any specific histological subtype. Lung cancer subjects with Pro/Pro genotype had better median survival time as compared to Arg/Pro genotype (10 months; HR?=?0.65; 95?% CI?=?0.45–0.95; p?=?0.03). Furthermore, female lung cancer patients with Arg/Pro (HR?=?0.08; 95?% CI?=?0.02–0.34; p?=?0.0005) and Pro/Pro (HR?=?0.21; 95?% CI?=?0.06–0.67; p?=?0.008) genotypes showed a better overall survival and hence a better prognosis as compared to males. Our data also reveals that lung cancer patients with ECOG scores between 0 and 1 and carrying the Pro/Pro had better chances of survival. p53 codon 72 polymorphism could play a role as a prognostic marker in lung cancer patients.     

Agency,intimacy, and rape jokes: an ethnographic study of young women and sexual risk in Chennai

In this article, I examine the circulation of jokes about sexual violence among young middle‐class women in the South Indian city of Chennai. Drawing on ethnographic research with undergraduate students in this city, I locate the rape joke in an ambivalent discourse of risk that conflates the possibility of sexual assault with the perceived ‘risks’ of women's sexual autonomy. In this context, I argue that humour about sexual violence functions as a form of lateral agency, facilitating a break from the task of reproducing middle‐class respectability.     

Polypeptide motions are dominated by peptide group oscillations resulting from dihedral angle correlations between nearest neighbors

To identify basic local backbone motions in unfolded chains, simulations are performed for a variety of peptide systems using three popular force fields and for implicit and explicit solvent models. A dominant "crankshaft-like" motion is found that involves only a localized oscillation of the plane of the peptide group. This motion results in a strong anticorrelated motion of the phi angle of the ith residue (phi(i)) and the psi angle of the residue i - 1 (psi(i-1)) on the 0.1 ps time scale. Only a slight correlation is found between the motions of the two backbone dihedral angles of the same residue. Aside from the special cases of glycine and proline, no correlations are found between backbone dihedral angles that are separated by more than one torsion angle. These short time, correlated motions are found both in equilibrium fluctuations and during the transit process between Ramachandran basins, e.g., from the beta to the alpha region. A residue's complete transit from one Ramachandran basin to another, however, occurs in a manner independent of its neighbors' conformational transitions. These properties appear to be intrinsic because they are robust across different force fields, solvent models, nonbonded interaction routines, and most amino acids.