Mechanisms Of Telomere Maintenance In Trypanosoma Brucei

Telomeres are a nucleoprotein structure at the end of the chromosome and are essential for genome integrity and chromosome stability. Telomere lengths are primarily maintained by a telomerase-mediated pathway but can be maintained by a homologous recombination-mediated pathway. However, detailed mechanisms of telomere maintenance are still unclear in many eukaryotes, including an important human pathogen, Trypanosoma brucei. Telomeres can be elongated by telomerase in T. brucei, a causative agent of fatal sleeping sickness in humans and nagana in cattle. T. brucei evades host immune response by regularly switching its major surface antigen, variant surface glycoprotein (VSG), a process known as antigenic variation. The telomere structure and telomere proteins play critical roles in T. brucei pathogenesis. In mammalian, yeast, and plant cells, ssDNA binding proteins with OB-fold domains play important roles in coordinating telomere G- and C-strand syntheses. However, no such protein has been described in T. brucei to be specifically associated with the telomere. We identified POLIE, an A-type DNA polymerase, as a crucial telomere complex component in T. brucei and essential in maintaining telomere integrity in T. brucei. Depletion of POLIE in T. brucei leads to an increased amount of DNA damage at telomere/subtelomere, increased frequency of gene conversion-mediated VSG switching, and an increased amount of the telomeric circles (T-circles), suggesting a potential role of POLIE in suppressing DNA recombination at the telomere and the subtelomere. However, I find that telomeric and subtelomeric DNA recombination is unlikely to be mediated by the increased telomeric R-loop level as the telomeric repeat-containing RNA (TERRA) level is significantly lower in POLIE-depleted cells. The telomere G-rich 3’overhangs are dramatically elongated in POLIE-depleted cells, indicating a potential role of POLIE to coordinate telomere G- and C-strand syntheses and suggesting that the long telomere 3’ overhang can induce more telomeric and subtelomeric recombination. In addition, I find that POLIE inhibits telomerase-dependent telomere G-strand extension, identifying POLIE as the first telomere protein that potentially suppresses telomerase in T. brucei. Moreover, depletion of POLIE greatly increases the amount of telomeric C-circles which can be derived from replication stress in the telomere C-strand. Importantly, the elongated telomere 3’ overhang and elevated telomeric C-circle level phenotypes are independent of the telomerase, which suggests that POLIE may promote the telomere C-strand synthesis. Therefore, we identified that POLIE plays a major role in suppressing telomere recombination, coordinating telomerase-mediated telomere G-strand extension, and telomere C-strand synthesis, and maintaining telomere integrity in T. brucei

Formulation and characterization of modified release tablets containing ionizid using swellable polymers

The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12th hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.Keywords: Isoniazid, Polyvinyl acetate, Sodium-carboxymethylcellulose, Modified release tablets

Lessons Learned Through the Follow-up of the Long-Term Effects of Over-Exposure to an Ir192 Industrial Radiography Source in Bangladesh

An industrial radiographer was accidentally over-exposed while taking the radiograph of weld-joints of gas pipe-lines in 1985 in Bangladesh. Symptoms of high radiation exposure occurred immediately after the accident and skin erythema developed leading to progressive tissue deterioration. The consequences of this over-exposure is being followed up to assess the long-term effects of ionizing radiation on the victim. Progressive tissue deteriorations have already led to multiple surgeries and successive amputations of the finger-tips so far. Lessons learned from this accident are also reported in this paper

Effect of Permeation Enhancers on the Release Behavior and Permeation Kinetics of Novel Tramadol Lotions

Purpose: The aim of this research work was to formulate, characterize and evaluate the in vitro permeation behavior of tramadol lotion containing propylene glycol (PG) and polyethylene glycol (PEG) as permeation enhancers.Methods: The permeation experiments were conducted in vitro using full thickness rabbit skin in Franz diffusion cells. The donor compartment was filled with PBS (phosphate buffered saline) at pH 7.4 ± 0.1. The receptor phase was continuously stirred PBS (pH 7.4) at 37 °C ± 0.5. The amount of tramadol permeated into the receptor phase was determined spectrophotometrically at 271 nm. Various permeation parameters such as permeation coefficient (Kp), diffusion coefficient (D), flux (J), input rate,and enhancement ratio were obtained using Fick’s diffusion laws.Results: Permeation increased with increase in the concentrations of both enhancers tested. Maximum cumulative amount permeated for control lotion (Lc) was 357 ìg/cm2/min with input rate 0.574 ìg/min and lag time (tlag) of 34.93 min, while for the optimum test lotion (L4, containing 8 % PG/PEG in ratio of 1:1 v/v), it was 926 ìg/cm2/min, 1.482 ìg/min and 58.36 min, respectively. The significantly (p < 0.05) higher permeability shown by the test lotion L4 can be attributed, in part, to the interaction of PG withintercellular lipids leading to the disruption of their organization and increasing their fluidity, and also partly as a result of solubilization of lipid bilayers by PEG.Conclusion: A binary system of PG and PEG in lotion can be successfully utilized for the permeation enhancement of tramadol.Keyword: Tramadol, Transdermal delivery, Permeation, Propylene glycol, Polyethylene glycol, Rabbit skin

A genetic algorithm based approach for solving optimal power flow problem

200

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET‐DD) study, a collaborative study carried out in 14 countries

Aims To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. Methods People with diabetes aged 18–65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. Results A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (PPPPP<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0–29.6%). Conclusions Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes

Improvement of power system dynamics using superconducting magnetic energy storage unit

9th February, 200

Matlab based fault analysis toolbox for electrical power system

19-21 December, 200

Estimation of genetic diversity in a natural population of cambui tree (Myrciaria tenella O. Berg) using ISSR markers.

Cambui (Myrciaria tenella O. Berg) is a native species from Brazil, which belongs to the family Myrtaceae. Molecular characterization is one of the most used tools for the study of the biotechnological potential of species because the diversity level between individuals can be inferred. Analysis of enetic diversity is fundamental to the direction of the strategies necessary to form and maintain a germplasm. This study aimed to evaluate the genetic diversity in a natural population of cambui using inter-simple sequence repeat (ISSR) molecular markers. The natural population, which provided the plant material, is found at the Private Reserve of Natural Heritage of Caju, which belongs to the experimental field of Embrapa Tabuleiros Costeiros, in the municipality of Itaporanga d’Ajuda, SE, Brazil. Young leaves of each individual were collected for DNA extraction and analysis of PCR-ISSR. Thirty primers were tested and the top 10 were selected. The use of these primers resulted in 71 fragments with 98.3% polymorphism. Similarity of individuals ranged between 0.30 and 0.92. The most similar individuals were C13 and C17 and the most distant were C1 and C41. Through UPGMA, six distinct groups were identified. This information may be used for conservation of these genetic resources, germplasm exchange, creation of germplasm bank and in future studies with this species