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

The Effectiveness of Subgingival Scaling and Root Planing in Calculus Removal

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141524/1/jper0119.pd

Studying the factors affecting urban dispersion in mashhad metropolis

In recent decades, urban population in the world, especially in southern countries, hasexceeded rural population that has brought about urban land expansion followed bydispersion phenomenon, the result of which has created problems in environmental,economic, social, and physical aspects including increased air pollution, potentialdeterioration within the city, and destruction of farms and open spaces. The aim of thisstudy is to investigate the roots of dispersion in Mashhad metropolis in order to identifysolutions to control this problem. The tools used in this research were GIS software formapping, quantitative methods of Holdren Model, urban primacy index, and area topopulation growth rate for review and analysis, and at first by examining area topopulation growth rate, Mashhad- developmental process map, Holdren model, andgross population-density dispersion model of this city was shown.Then the roots of dispersion including market failure (checking the price of land), technology, natural population-growth process, and migration were analyzed. To study the dispersion in Mashhad metropolis, Holdren model was used, according to which only 34% of dispersion is population growth, and 66% of urban growth is related to horizontal growth. This is indicative of the dispersion in Mashhad metropolis, and the most important reasons are low price of housing in the suburb, ignoring social costs arising from it, increasing percentage of car ownership, gradual population growth inMashhad due to political priority, and the concentration of facilities in it that are thereason of increase in immigration to this metropolis. To deal with this phenomenondispersion, it is proposed that patterns of sustainable development such as  transportbased development and compact city are used.Key words: urban dispersion, technology, roots of Mashhad dispersion, the price ofland, immigratio

Superconducting magnetic energy storage unit for power system application

5-6 January, 200

Application of simultaneous active and reactive power modulation of SMES unit under unequal mode for power system stabilization

Vol.14, No. 2, May 199

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

A new comprehensive framework for ranking accepted orders and supplier selection in make-to-order environments

This paper presents a new decision making framework for supplier selection in a make-to-order-system (MTO) while establishing an information loop between "sale" and "purchasing" functions which play important roles in successful satisfying of customers. The order entry stage outputs, including accepted orders' requirements and their priorities are reflected into the supplier selection phase; and in return, the outputs of the supplier selection model are fed back into the sale department to revise the orders attributes according to the system's supplying capabilities. A ranking procedure using Fuzzy data-envelopment-analysis (DEA) and multi attribute utility model (Le. similarity to ideal solution TOPSIS) is applied to determine the relative ranking of accepted orders; in the next phase a goal programming supplier selection model focusing on three criteria of time, cost and quality is run to determine the best ability of the system in supplying required components and materials of the accepted orders

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