Targeting Duplex and Higher Order Nucleic Acids Using Neomycin / Neomycin-Hoechst 33258 Conjugates

Small molecules have provided means to combat many diseases caused by pathogens. In the last six decades, advances in the structural and biological understanding of nucleic acid functions have led to rational drug design programs in order to solve current therapeutic challenges. The work described in this dissertation addresses discovery of aminoglycosides as novel binders to G-quadruplex nucleic acids. Understanding of effect of linker length on the B-DNA binding of a series of Hoechst 33258 derivatives have been provided. Novel Hoechst 33258 based monobenzimidazoles have been synthesized and their biological properties have been compared with the bisbenzimidazoles. The bisbenzimidazoles have been designed to be useful towards click chemistry applications. These clickable Hoechst 33258 derivatives were then used to prepare neomycin-Hoechst 33258 conjugates with varied linker spacing between them. The binding studies of these novel neomycin-Hoechst 33258 conjugates show intercalative binding of bisbenzimidazole moiety of the ligand to an RNA duplex. Finally, the novel neomycin-Hoechst 33258 conjugates have been screened against G-quadruplex forming promoter sequences and biophysical characterization to its binding has been provided. Overall, these studies have led to synthesis of novel small molecules that bind to various nucleic acids and their new binding modes have been discovered. The studies presented here are expected to help in the design of novel therapeutics

Contemporary Problems in Hindu Religious Endowments.

The prime object of this thesis is to find out various problems of Hindu religious endowments in general, and private Hindu religious trusts in particular, and to provide suggestions which may be useful for any future comprehensive legislation in that field. Though the thesis is on Hindu religious endowments, section 1 of the first chapter, providing a background to the main contention, deals with the provisions of the Constitution of India, which guarantees every individual in India the right to freedom of religion and management of religious affairs. The purpose of section 2 of the chapter is to show how far a Civil Court can intervene in religious affairs. The second chapter deals with trusts in both English and Hindu law. The objects of this chapter are to enquire into those areas in which the influence of English concepts of law in the Indian field are evident and to make a brief comparative study between the two systems. The main contention, which is related to various problems of private Hindu religious endowments or private debutters is expressed in the third, fourth and fifth chapters. The sixth chapter deals with Hindu public religious trusts called maths; these are unique and one of the oldest Hindu religious institutions. Moreover, it is the problems existing in those institutions which have been investigated. The seventh, and concluding chapter advances propositions relating to the contents of the thesis, in the hope that, if any future statute is introduced, the Indian Parliament will take into consideration the suggestions put forward by way of those propositions

Weight loss during prolonged lactation in rural Bangladeshi mothers

To determine the duration of lactation which is associated with weight loss in rural Bangladeshi mothers and also to determine the relationship with consumption patterns of principal food items, a cross-sectional study was carried out among 791 lactating rural Bangladeshi mothers aged 18-40 years. Results were compared with 333 non-pregnant and non-lactating mothers of a similar age group. The duration of lactation was up to 60 months. The mean difference in body-weight and body mass index (BMI) of lactating mothers who breastfed their children up to 24 months was significantly lower compared to non-lactating mothers of the same age group, but no differences were observed for those who breastfed beyond 24 months. The frequency of consumption of principal food items was comparable between the non-lactating and the lactating mothers who breastfed beyond 24 months. Results of multiple linear regression analysis showed that body-weight of mothers was negatively correlated with 1-12 month(s) and 13-24 months of lactation after controlling for height, education, and food consumption (slope -1.04, p < 0.05 and slope -1.23, p < 0.05 respectively). Height and consumption of meat and milk were significantly positively correlated with body-weight (slope 0.53, p < 0.001; slope 1.44, p < 0.001; and slope 0.75, p < 0.05 respectively). The study concluded that Bangladeshi women who breastfed up to 24 months were of lower weight than non-lactating mothers, most likely due to the effect of lactation. These mothers were not taking any additional foods during their lactating period. Based on the findings of the study, it is recommended that mothers consume additional energy-rich foods during the first 24 months of lactation to prevent weight loss