Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription Factor CSL

Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.Here, we utilized protein-binding microarrays (PBMs) to compare the binding site preferences of isolated CSL with the preferred binding sites of CSL when bound to the CSL-binding domains of all four different human Notch receptors. Measurements were taken both in the absence and in the presence of Mastermind-like-1 (MAML1). Our data show no detectable difference in the DNA binding site preferences of CSL before and after loading of Notch and MAML1 proteins.These findings support the conclusion that accrual of Notch and MAML1 promote transcriptional activation without dramatically altering the preferred sites of DNA binding, and illustrate the potential of PBMs to analyze the binding site preferences of multiprotein-DNA complexes

Numerical investigation of heat transfer and entropy generation in a wavy channel

In this thesis, the flow and heat transfer of nanofluid in a wavy channel is investigated numerically. For this purpose, the equations of continuity, momentum, turbulence, and heat transfer in the computational domain are solved numerically. The accurate correlations are used for simulation of nanofluid. The correlations of effective viscosity and effective thermal conductivity are defined. The results in the limiting case are in good agreement with the pervious published results. In this work, various parameters such as entropy generation, kinetic energy, vorticity, pressure parameter, and temperature conditions are investigated. The results show that the value of vorticity increases by approaching to the walls and the value of vorticity becomes maximum where the fluid desert the wavy part of the wall. Also, it can be found that the pressure decreases where the fluid flows through the channel. The results show that the pressure is changed periodically. It can be found that the pressure decreases where the fluid flows in wavy part of the wall and the pressure increases where the fluid flows out of wavy part of wall. It can be seen that the maximum of temperature is happened at the top wall. Also, it can be found that the thermal boundary layer becomes thicker by passing through the flow field. It can be found that the Nusselt number increases with the increase in nanofluid concentration. The variations of entropy generation function are very similar to the function of temperature and it can be found that the maximum of entropy generation is happened at the top wall

Genotypic characterization by multi locus variable number of tandem repeats analysis international Bordetella pertussis vaccine strains

Background: In 1930's first whole cell pertussis vaccines became available to the public heralding a dramatic success in overcoming the global burden of the disease. To date only a handful of B. pertussis strains have been used by international/local pertussis vaccine manufacturers. Inevitable well-documented genetic changes in the world population of this pathogen have prompted serious questions on suitability of traditional vaccine strains protect human against currently circulating wild isolates of Bordetella pertussis. Objective: Analyzing the genetic diversity within the most frequently-used vaccine strains of B. pertussis in the world Methods: A recently developed multi locus variable number of tandem repeats analysis (MLVA) genotyping system along with a bioinforamtic piece of analysis was conducted on 11 strain/sub-strains of B137, B203 (10536), C393, Cs, E476, Tohama I, J445 (134), B202 and J446 (509) plus 2 sub-strains of 134 and 509 that are used at Razi institute for preparation of pertussis vaccine. In this study have used 6 individual loci of VNTR1, VNTR3a, VNTR3b, VNTR4, VNTR5 and VNTR6. Findings: Six distinct genotypes were recognized among the examined strains by comparing our data with the Dutch MLVA databank. These were all new and not reported before in the database. Conclusion: This observation reiterates on necessity for detection of predominant native strains to include in vaccine preparations suitable for different countries. Keywords: Pertussis, Strain, Vaccine, Genotypin

Isolation, identification, and monitoring of antibiotic resistance in Pasteurella multocida and Mannheimia haemolytica isolated from sheep in East Azerbaijan province, Iran

The present study was carried out in order to isolate, identify, and assess the antimicrobial susceptibility of the causative agent(s) of pneumonic pasteurellosis in sheep in East Azerbaijan province, northwest of Iran. Pneumonia was detected in 320 cases, and the affected lungs were sampled in the slaughterhouse. The samples were investigated bacteriologically for the isolation of two microorganisms from the Pasteurellaceae family. Pasteurella multocida was isolated from six (1.87%) samples, while none of the lung tissues were positive for Mannheimia haemolytica. After the isolation and detection of microorganisms via cultural and morphological tests, the bacteria were identified on the basis of biochemical criteria and polymerase chain reaction (PCR) technique. Antimicrobial susceptibility testing was performed on all P. multocida isolates, using broth microdilution method. Evaluation of the minimum inhibitory concentration (MIC) of eight antimicrobial agents against the tested isolates showed that all the organisms were resistant to amoxicillin and relatively susceptible to ceftiofur. In conclusion, P. multocida was introduced as the main cause of ovine pneumonic pasteurellosis in the studied district, and the outbreak frequency significantly varied in different seasons of the year (