ROLE OF THE SNF2 HOMOLOG, IRC20, IN YEAST GENOME MAINTENANCE

In eukaryotes, DNA is wrapped around histone proteins forming a highly compact structure, the chromatin. All DNA-based processes must occur within the complex organization of the chromatin, and this requires modulation of its structure when needed. This is accomplished by covalent histone modifications that alter histone-DNA contacts, as well as through the actions of ATP-dependent chromatin remodelers. These multi-subunit complexes play major roles in transcription regulation, replication and repairing DNA damage. This thesis aims to characterize a poorly studied member of the SWI/SNF family of ATPases/helicases, Irc20, from Saccharomyces cerevisiae. Previously, Irc20 has been shown to be involved in recombinational repair and to possess ubiquitin ligase (E3) activity. The human homolog of Irc20, SHPRH, has also been implicated in repair via the poly-ubiquitylation of PCNA, the sliding clamp of the DNA polymerase. Loss of heterozygosity in the region containing the SHPRH gene is seen in a wide variety of cancers. In this study, using purified Irc20, we showed that it possesses DNA and nucleosome binding activities, as well as an ATP-hydrolyzing activity. However, despite homology to Snf2 catalytic domain, Irc20 did not have the ability to alter chromatin structure. Using point mutations in different Irc20 domains, we identified that the increased recombination centers observed in irc20 null mutants is dependent on both its ATPase and ubiquitin ligase activities. Consistent with this, we observed higher recruitment or retention of the recombination repair factor Rad52 at a single induced double strand break in Δirc20 mutant, suggesting a regulatory role for Irc20 in DNA repair. Furthermore, we observed a previously unidentified function for Irc20 in regulating the levels of the endogenous yeast 2-μm plasmid. In irc20 null mutant, we observed a three to four-fold increase in 2-μm levels, forming high molecular weight forms in a manner dependent on homologous recombination. We suggest this is, at least partially, through regulating the levels of Flp1 recombinase since we observed higher levels of Flp1 in Δirc20 mutant after shutting off expression from a repressible promoter. Collectively, our results show a regulatory role for Irc20 in recombination underlying its role in stabilizing the genome and regulating the 2-μm plasmid levels

Immunotherapy for B-Cell Neoplasms using T Cells expressing Chimeric Antigen Receptors : From antigen choice to clinical implementation

Immunotherapy with T cells expressing chimeric antigen receptors (CAR) is being evaluated as a potential treatment for B-cell neoplasms. In recent clinical trials it has shown promising results. As the number of potential candidate antigens expands, the choice of suitable target antigens becomes more challenging to design studies and to assess optimal efficacy of CAR. Careful evaluation of candidate target antigens is required to ensure that T cells expressing CAR will preferentially kill malignant cells with a minimal toxicity against normal tissues. B cells express specific surface antigens that can theoretically act as targets for CAR design. Although many of these antigens can stimulate effective cellular immune responses in vivo, their implementation in clinical settings remains a challenge. Only targeted B-cell antigens CD19 and CD20 have been tested in clinical trials. This article reviews exploitable B cell surface antigens for CAR design and examines obstacles that could interfere with the identification of potentially useful cellular targets

Synthesis and anti-Aphid Aphis gossypii (Glover) activity of some new quinoline derivatives

A series of quinoline derivatives have been elaborated fromreaction of 2-(m- and p-acetylanilino)-quinolines 6a-b withaldehydes under Claisen-Schmidt conditions followed by cyclization with phenyl hydrazine and hydroxylamine. Reaction of  6a and 6b with hydrazine, semicarbazide and thiosemicarbazide, cyanoacetylhydrazide and subsequent some condensation reactions led to diverse quinoline derivatives. Anti aphid  Aphis gossypii that harm cotton cropin Egypt was screened. Compound  12 showed an LC50 value of 19429E-10 ppm which is very more active than Marshal (Carbosulfan), one of the broad spectrum insecticides widely used in this field

Pleural manometry in pleural effusion

AbstractPleural manometry is a valuable tool to determine lung expansibility and helps to avoid unsafe pressure changes during thoracentesis.Study designCross-sectional descriptive study.Aim of the workTo measure the pleural pressure during thoracocentesis in patients with pleural effusion and the value of their measurement in both diagnostic and therapeutic decisions.Patients and methodsForty-four patients with pleural effusion were included. Thoracocentesis was performed for all patients. End-expiratory pleural pressure values were recorded after the withdrawal of 5ml of fluid (initial pleural pressure), after the removal of every 500ml for the first liter then after the withdrawal of every 250ml for the second liter, and every 100ml thereafter until the procedure completed. The last recorded pressure was used as the closing pressure. Comparisons were done according to the etiology and character of the effusion (transudate or exudate). The pressure/volume curves were done and studied.ResultsTwenty out of 34 patients with exudative pleural effusion having a pleural space elastance >14.5 cm H2O/L were identified. These patients had a diagnosis of malignant effusion either primary or secondary (14/20 patients), or inflammatory causes (6/20 patients). All the 10 patients with transudative effusion had an elastance <14.5 cm H2O/L. The study revealed a statistically significant decrease in closing pressure in the symptomatic group when compared to non-symptomatic group (p value=0.022), none of our patients (including symptomatic patients) had exceeded the proposed cutoff value for unsafe pleural pressures (−20cm H2O).ConclusionPleural manometry is proved a useful tool to differentiate freely expandable lungs from lungs with entrapment. It is proved as a useful guide as to when to terminate thoracentesis in large volume thoracentesis

Serum Activins and Follistatin during the Treatment of Chronic Hepatitis C Genotypes 1 and 4 and Their Correlations with Viral Load and Liver Enzymes: A Preliminary Report

Aims. To measure the effect of pegylated interferon-α therapy on serum activin-A, activin-B, and follistatin and their correlation with viral load and liver fibrosis in chronic hepatitis C (CHC). Methods. This study was cross-sectional and sera were collected from 165 participants classified into 7 groups: 40 healthy negative control, 33 treatment naïve patients as positive control, 19 patients at week 4, 22 at week 12, and 19 at week 24 of treatment initiation and 21 responders and 11 nonresponders at the end of 48-week treatment protocol. Serum candidate proteins were measured using ELISA and liver fibrosis was assessed by AST platelet ratio index (APRI). Results. CHC significantly increased activins and decreased follistatin compared to negative control (P<0.05). Activin-A and follistatin levels returned to the levels of negative control group at weeks 4, 12, and 24 following treatment initiation and were significantly different from positive control (P<0.05). Both proteins were significantly different between responders and nonresponders. Activin-A correlated positively and significantly with the viral load and APRI. Conclusion. CHC modulates serum activin-A and follistatin and they appear to be influenced by pegylated interferon-α therapy. Further studies are needed to explore the role of activins in CHC

Effect of planting date and sowing method on yield and grain quality of soybean (Glycine max L.) under North Sudan conditions

This study aimed to assess the effect of different planting dates and sowing methods on yield and grain quality of soybean. A split plot arrangement using randomized complete block with three replications was used to layout the experiment. The studied traits determining yield and grain quality, included height to first pod, no of pods/plant, 100-seed weight, harvest index, straw yield, seed yield, grain protein and oil contents. The results showed significant differences between planting dates in height to first pod, 100-seed weight, harvest index, grain yield and grain protein. Planting date in the 1st July produced 72% more grain yield than delaying planting date (15th July). Early planting date (15th June) and mid-planting date (1st July) increased grain protein of soybean by 5% than delaying planting date (15th July). Results revealed that soybean yield components were not affected by sowing methods except that of straw yield. Interaction between planting date and sowing method was significant for grain oil content. Keywords: Soybean, planting date, sowing method, grain protein, grain yield, oil conten

Multi-parametric arterial spin labelling and diffusion-weighted magnetic resonance imaging in differentiation of grade II and grade III gliomas

Purpose: To assess arterial spin labelling (ASL) perfusion and diffusion MR imaging (DWI) in the differentiation of grade II from grade III gliomas. Material and methods: A prospective cohort study was done on 36 patients (20 male and 16 female) with diffuse gliomas, who underwent ASL and DWI. Diffuse gliomas were classified into grade II and grade III. Calculation of tumoural blood flow (TBF) and apparent diffusion coefficient (ADC) of the tumoral and peritumoural regions was made. The ROC curve was drawn to differentiate grade II from grade III gliomas. Results: There was a significant difference in TBF of tumoural and peritumoural regions of grade II and III gliomas (p = 0.02 and p =0.001, respectively). Selection of 26.1 and 14.8 ml/100 g/min as the cut-off for TBF of tumoural and peritumoural regions differentiated between both groups with area under curve (AUC) of 0.69 and 0.957, and accuracy of 77.8% and 88.9%, respectively. There was small but significant difference in the ADC of tumoural and peritumoural regions between grade II and III gliomas (p = 0.02 for both). The selection of 1.06 and 1.36 × 10-3 mm2/s as the cut-off of ADC of tumoural and peritumoural regions was made, to differentiate grade II from III with AUC of 0.701 and 0.748, and accuracy of 80.6% and 80.6%, respectively. Combined TBF and ADC of tumoural regions revealed an AUC of 0.808 and accuracy of 72.7%. Combined TBF and ADC for peritumoural regions revealed an AUC of 0.96 and accuracy of 94.4%. Conclusion: TBF and ADC of tumoural and peritumoural regions are accurate non-invasive methods of differentiation of grade II from grade III gliomas

Role of diffusion-weighted magnetic resonance imaging in the differentiation of benign and malignant pulmonary lesions

Purpose: To evaluate the role of magnetic resonance (MRI) diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) measurement of solid and cystic pulmonary masses in differentiating benign from malignant lesions. Material and methods: The study included 41 patients with pulmonary masses, who underwent conventional MRI and DWI (b value 0, 500, and 1000 s/mm²) examinations with 1.5-T MRI. The diffusion signal and the mean ADC values of the solid and cystic lesions were obtained. Statistical analyses were performed with the Mann-Whitney U test (z), Pearson's chi-square test, and receiver operating characteristic (ROC) analysis. Results: Thirty-three lesions were malignant, and eight lesions were benign. The malignant masses showed significantly higher signal intensity on DWI than benign masses (p = 0.006), and the mean ADC value of malignant solid lesions was significantly lower than that of benign lesions (p = 0.02). By ROC analysis, an ADC cut-off value of 1.4 × 10-3 mm2/s was considered the threshold value, and the sensitivity and specificity were 93.8% and 75%, respectively. There was no significant difference between the ADC value of the cystic parts inside the benign and the malignant lesions. Conclusions: Diffusion-weighted MRI and measurement of ADC value can significantly differentiate between solid benign and malignant pulmonary masses