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

Sustained remission in a case of lupus nephritis with cyclosporin therapy

Systemic lupus erythematosus (SLE) in severe form still presents a major therapeutic challenge. Aggressive treatment of severe renal lesions has improved the prognosis of renal disease over the last decade. However, this benefit is quite frequently offset by the side effects and toxicity of the treatment. Moreover, the disease may appear to be poorly responsive to treatment with steroids and cytotoxic drugs. We report a case of lupus nephritis that relapsed despite having adequate steroid and cytotoxic therapy, but later was successfully treated with cyclosporin. Fifteen months after discontinuing the treatment with cyclosporin, the patient continued to remain in remission

Cutaneous manifestations of systemic lupus erythematosus in Pakistani patients

Objective: Systemic Lupus Erythematosus (SLE) is an autoimmune process in which cutaneous lesions occur in majority of patients. This study from Karachi, Pakistan was conducted to determine the pattern and prevalence of such lesions in SLE in Pakistani patients.Methods: One hundred ninety eight patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatology Association were examined between 1986 and 2001 for the presence of cutaneous manifestations.Results: Skin changes noted were: noncicatricial diffuse alopecia (22%), malar rash (31%), mucosal lesions (20%), discoid eruptions (15%), photosensitivity (33%), vascular lesions (20%), pruritus (17%), and pigmentary changes (22%). Peripheral gangrene, chronic ulcers, Raynauds phenomenon, urticaria, chilblains, thrombophlebitis, palmar erythema, and erythema multiform were rare. Anti ANA and anti dsDNA were positive in 93% and 83% patients respectively.CONCLUSION: A different clinical pattern was noted in our patients than reported previously

Comparative effects of pure spirulina powder and other diets on larval growth and survival of green tiger shrimp, Peneaus semisulcatus

This experiment was carried out in Bandargah Station in Bushehr province. Peneaus semisulcatus larvae were fed on Spirulina platensis as supplementation microalgae. In order to use Spirulina platensis in this study, we have to produce biomass and dry production of this microalga. Determination of length and survival rate of Peneaus semisulcatus larvae was carried out as the objective of the study. Treatments including Z plus (as a supplementation without spirulina), M.C.F (as an imported enriched spirulina), the powder combination of Spirulina platensis with Z plus and Spirulina platensis as live food were compared to Cheatocerus microalgae as a control. The experiment was carried out from nauplii stage to early post larvae. The results of the experiment indicated that the powder combination of Spirulina platensis with Z plus treatment has the most survival rate (76.5%). The maximum of length (4.3mm) observed in control (Cheatocerus spp.). The maximum mortality was observed in zoa stage in spirulina microalgae treatment, because the spiral filamentous of Spirulina sp. was large

Heavy metal flocculation at Pirbazar River, Banadar Anzali, south west Caspian Sea

Heavy metal flocculation process was studied in the year 2002 in order to determine the interaction of water in Pirbazar River with Caspian Sea water. The effects of various salinity concentrations of Caspian Sea water were studied on determined heavy metals including Fe, Zn, Pb, Cu, Cd and Cr level of Pirbazar River using APHA method of extraction and measurement. The results illustrated that the level of heavy metal concentration in Pirbazar River were above standard limits and the extent of flocculation depended on both the salinity level and the heavy metal itself. The maximum flocculation for Cd and Cr were recorded at 7.65ppt, for Zn and Fe at 9.35ppt while for Pb and Cd were at 2.55ppt salinity. The order of flocculation with respect to percentage of original concentrations was found to be Zn > Fe > Cr> Cu > Cd> Pb

Evaluation of the anxiolytic effect of Nepeta persica Boiss. in mice

The aim of the present study was to evaluate the anxiolytic effects of hydroalcoholic extract (HE) of Nepeta persica Boiss. (Lamiaceae) on the elevated plus-maze (EPM) model of anxiety. The extract of arial parts of the plant was administered intraperitoneally to male NMRI mice, at various doses, 30 min before behavioural evaluation. The HE extract of N. persica at the dose of 50 mg kg−1 significantly increased the percentage of time spent and percentage of arm entries in the open arms of the EPM. This dose of plant extract affected neither animal's locomotor activity nor ketamine-induced sleeping time. The 50 mg kg−1 dose of the plant extract seemed to be the optimal dose in producing the anxiolytic effects, lower or higher doses of the plant produce either sedative or stimulant effects. At 100 mg kg−1, the plant extract increased the locomotor activity. These results suggested that the extract of N. persica at dose of 50 mg kg−1 possess anxiolytic effect with less sedative and hypnotic effects than that of diazepam and causes a non-specific stimulation at 100 mg kg−1

Mutation Analysis of the CYP21A2 Gene in the Iranian Population

Background: Defects in the CYP21A2 gene cause steroid 21-hydroxylase deficiency, which is the most frequent cause of congenital adrenal hyperplasia. Forty four affected families were investigated to identify the mutation spectrum of the CYP21A2 gene. Methods: Families were subjected to clinical, biochemical, and molecular analyses. Allele-specific polymerase chain reaction amplification was used for eight common mutations followed by dosage analysis to exclude CYP21A2 deletions. Results: The most frequent mutations detected were gene deletions and chimera (31.8). Other mutation frequencies were as follows: Q318X, 15.9; I2G, 14.8; I172N, 5.8; gene duplication, 5.7; R356W, 8; and E6 cluster mutations, 2.3. Direct sequencing of the CYP21A2 gene revealed R316X, P453S, c.484insT, and a change at the start codon. Different modules carried by patients were classified into five different haplotypes. The genotype phenotype correlation (positive predictive value) for group null, A, B, and C were 92.3, 85.7, 100, and 0, respectively. Conclusions: Methods used will be helpful for carrier detection and antenatal diagnosis, especially with inclusion of the multiplex ligation probe dependent amplification technique, which is easier for routine tests in comparison with other methods. Mutation frequencies indicate that Iranians are possible descendants of Asians and Europeans

Determination of nutrient values of the bivalve Anodonta cygnea in Selkeh area of the Anzali Lagoon during autumn and spring

Anzali Lagoon is one of the most important aquatic ecosystems of Iran which was registered as a Ramsar Convention site in 1999. This valuable ecosystem is located in the south west shores of the Caspian Sea, in Guilan Province. We randomly collected 30 and 20 samples of the bivalve Anodonta cygnea in autumn 2004 and spring 2005 respectively. The Selkeh area was chosen for the sampling because of its availability during autumn. The area receives water from the southern part of the lagoon basin. Nutrient content of the soft tissue of the bivalve was measured. Live sampled bivalves were transferred to laboratory and their length, width, height; total body weight and wet weight of the internal soft part were measured. Moisture, ash, protein, T.V.N, lipid and amino acid contents in soft tissue were also determined. Moisture content in spring and autumn samples were 84.84% and 83.6%, respectively. Ash content in autumn samples was higher than spring samples, being 4% and 2.32%, respectively. Assessment showed protein content in the autumn samples to be 12% while in spring samples this was 10.5%. T.V.N content in autumn and spring samples were 0.031 and 0.003% respectively. Measurements showed that autumn bivalves had 4% lipid content whereas this value in spring samples was 3%. We found Sixtheen amino acids, including seven essential ones in the samples

Dynamic model for price of wheat in Bangladesh

Wheat is the second staple food of Bangladesh. In this paper we constructed a dynamic model for wheat price. Basically we constructed a single equation autoregressive integrated moving average (ARIMA) model of the price (quarterly wholesale wheat price). Standard ARIMA analysis rests on the simplifying assumption that the time series is stationary. So, at first stationary of the series is checked. An ARIMA (1,1,0) (2,1,1)4 model is constructed based on the autocorrelation and partial autocorrelation functions. Finally, forecasts are made based on the model developed