Genetic association between common beta-2 adrenoreceptor polymorphism and asthma severity in school-age children

Recent studies have suggested that polymorphism of the beta-2 adrenergic receptor (β2AR) gene at codon 16 affect an individual’s airway responsiveness. This study aimed to evaluate the association between beta-2 adrenoreceptor genotypes at position 16 and asthma severity among 59 school-aged children. They were divided into two groups: control group including 19 healthy children and 40 asthmatic children as the study group. The study group was also divided into 20 mild asthmatic children and the remaining 20 patients suffered from severe asthma. Blood samples were collected from Chest Department, Pediatrics Hospital, Ain Shams University, from February 2008 to March 2009. Molecular analysis was performed at Science Faculty, Ain Shams University, Cairo, Egypt. Venous blood sample were collected and genotyping of β2AR gene polymorphism at position 16 was identified by polymerase chain reaction– restriction fragment length polymorphism analysis, using the NcoI restriction enzyme. We found a highly statistically significant difference of polymorphisms’ distribution of β2AR gene at codon 16 among asthmatic patients and control subjects (χ2= 11.904; P = 0.0026), also among severe asthmatics and mild/moderate asthmatics(χ2 =10.108;P=0.0064). There was a strong association of heterozygous Arg16Gly of b2AR with severe asthmatics rather than that in control subjects (70% vs. 5.3%, P < 0.001), with odd ratio (OR) 42 (95% confidence interval (CI): 4.520–390.297), the highest OR in heterozygous Arg16Gly (42) suggests a dominant mode of action of the heterozygous Arg16Gly in development of asthma severity. So, we concluded that heterozygous Arg16Gly of b2AR gene appeared to be an important genetic factor in the expression of asthma severity. Keywords: Asthma; Beta-2 adrenoceptor gene polymorphisms; Arginine 16/Glycin

Single-Phase Charging of Six-Phase Integrated On-Board Battery Charger using Predictive Current Control

This work was achieved by the financial support of ITIDAs ITAC collaborative funded project under the category type of advanced research projects (ARP) and Grant Number ARP2020.R29.7.This work was achieved by the financial support of ITIDAs ITAC collaborative funded project under the category type of advanced research projects (ARP) and Grant Number ARP2020.R29.7.Integrated On-Board Battery Chargers (IOBCs) have shown promise as an elegant charging solution for electric vehicles in recent literature. Although the three-phase charging technique of IOBCs has extensively been discussed in the literature, single-phase charging is still a challenging research topic. The Predictive Current Control (PCC) approach has shown many benefits, including a straightforward algorithm, simple implementation, comparatively quick response, and appropriate performance, when compared to conventional control techniques. This paper investigates the impact of single-phase charging of a six-phase-based IOBC system with different winding configurations using PCC, which, up to the best authors’ knowledge, has not been conceived thus far. Under single-phase charging, the zero-sequence current component is utilized to ensure zero torque production during charging mode. Since the impedance of the zero subspace is highly affected by the employed winding design, the performance of PCC with different winding layouts of either induction machine (IM) or permanent magnet synchronous machine (PMSM) is investigated and compared. The proposed method is experimentally validated using a 1.1kW six-phase IM and a 2 kW 12-slot/10-pole PMSM. Finite Element analysis is also carried out to investigate the effect of single-phase charging mode on the induced radial forces and vibration level when PM machine is employed

Frequencies of BCR-ABL1 fusion transcripts among Sudanese chronic myeloid leukaemia patients

The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. In this study we report the frequencies of BCR-ABL1 fusion transcript variants studied in 43 CML patients from Sudan. The study includes 46 Sudanese patients, three of which negative for the BCR-ABL1 fusion transcript. More than half of 43 positive patients showed b2a2 fusion transcript (53.5%), while (41.9%) showed b3a2 transcript and the remaining (4.6%) coexpression of b3a2/ b2a2 and b3a2/b2a2/e19a2. We detected neither coexpression of p210/p190 nor e1a2 alone. Male patients showed a tendency to express b2a2, while female tende to express b3a2 (p = 0.017). Moreover, a single nucleotide polymorphism was detected in BCR exon 13 in one out of four patients and this patient showed only b2a2 expression. In conclusion, we observed a significant correlation between sex and type of BCR-ABL1 transcript, an observation that deserves further investigation

Rhinosinusitis derived Staphylococcal enterotoxin B possibly associates with pathogenesis of ulcerative colitis

BACKGROUND: During clinical practice, we noticed that some patients with both ulcerative colitis (UC) and chronic rhinosinusitis (CRS) showed amelioration of UC after treatment of CRS. This study was designed to identify a possible association between CRS and UC. METHODS: Thirty-two patients with both CRS and UC received treatment with functional endoscopic sinus surgery (FESS) for CRS. Clinical symptom scores for CRS and UC, as well as serum levels of anti-Staphylococcal enterotoxin B (SEB) were evaluated at week 0 and week 12. Sinus wash fluid SEB content was measured with enzyme-linked immunosorbent assay (ELISA). The surgically removed tissues were cultured to identify growth of Staphylococcus. aureus (S. aureus). Immunohistochemistry was employed to identify anti-SEB positive cells in the colonic mucosa. Colonic biopsies were obtained and incubated with SEB. Mast cell activation in the colonic mucosa in response to incubation with SEB was observed with electron microscopy and immunoassay. RESULTS: The clinical symptom scores of CRS and UC severe scores (UCSS) were significantly reduced in the UC-CRS patients after FESS. The number of cultured S. aureus colonies from the surgically removed sinus mucosa significantly correlated with the decrease in UCSS. High levels of SEB were detected in the sinus wash fluids of the patients with UC-CRS. Histamine and tryptase release was significantly higher in the culture supernate in the patients with UC-CRS than the patients with UC-only and normal controls. Anti-SEB positive cells were located in the colonic mucosa. CONCLUSION: The pathogenesis of UC in some patients may be associated with their pre-existing CRS by a mechanism of swallowing sinusitis-derived SEB. We speculate that SEB initiates inappropriate immune reactions and inflammation in the colonic mucosa that further progresses to UC

Combined Inactivation of MYC and K-Ras Oncogenes Reverses Tumorigenesis in Lung Adenocarcinomas and Lymphomas

Conditional transgenic models have established that tumors require sustained oncogene activation for tumor maintenance, exhibiting the phenomenon known as "oncogene-addiction." However, most cancers are caused by multiple genetic events making it difficult to determine which oncogenes or combination of oncogenes will be the most effective targets for their treatment.To examine how the MYC and K-ras(G12D) oncogenes cooperate for the initiation and maintenance of tumorigenesis, we generated double conditional transgenic tumor models of lung adenocarcinoma and lymphoma. The ability of MYC and K-ras(G12D) to cooperate for tumorigenesis and the ability of the inactivation of these oncogenes to result in tumor regression depended upon the specific tissue context. MYC-, K-ras(G12D)- or MYC/K-ras(G12D)-induced lymphomas exhibited sustained regression upon the inactivation of either or both oncogenes. However, in marked contrast, MYC-induced lung tumors failed to regress completely upon oncogene inactivation; whereas K-ras(G12D)-induced lung tumors regressed completely. Importantly, the combined inactivation of both MYC and K-ras(G12D) resulted more frequently in complete lung tumor regression. To account for the different roles of MYC and K-ras(G12D) in maintenance of lung tumors, we found that the down-stream mediators of K-ras(G12D) signaling, Stat3 and Stat5, are dephosphorylated following conditional K-ras(G12D) but not MYC inactivation. In contrast, Stat3 becomes dephosphorylated in lymphoma cells upon inactivation of MYC and/or K-ras(G12D). Interestingly, MYC-induced lung tumors that failed to regress upon MYC inactivation were found to have persistent Stat3 and Stat5 phosphorylation.Taken together, our findings point to the importance of the K-Ras and associated down-stream Stat effector pathways in the initiation and maintenance of lymphomas and lung tumors. We suggest that combined targeting of oncogenic pathways is more likely to be effective in the treatment of lung cancers and lymphomas

Inactivation of [Fe-S] Metalloproteins Mediates Nitric Oxide-Dependent Killing of Burkholderia mallei

BACKGROUND: Much remains to be known about the mechanisms by which O(2)-dependent host defenses mediate broad antimicrobial activity. METHODOLOGY/PRINCIPAL FINDINGS: We show herein that reactive nitrogen species (RNS) generated by inducible nitric oxide (NO) synthase (iNOS) account for the anti-Burkholderia mallei activity of IFNgamma-primed macrophages. Inducible NOS-mediated intracellular killing may represent direct bactericidal activity, because B. mallei showed an exquisite sensitivity to NO generated chemically. Exposure of B. mallei to sublethal concentrations of NO upregulated transcription of [Fe-S] cluster repair genes, while damaging the enzymatic activity of the [Fe-S] protein aconitase. To test whether [Fe-S] clusters are critical targets for RNS-dependent killing of B. mallei, a mutation was constructed in the NO-induced, [Fe-S] cluster repair regulator iscR. Not only was the iscR mutant hypersusceptible to iNOS-mediated killing, but its aconitase pool was readily oxidized by NO donors as compared to wild-type controls. Although killed by authentic H(2)O(2), which also oxidizes [Fe-S] clusters, B. mallei appear to be resilient to NADPH oxidase-mediated cytotoxicity. The poor respiratory burst elicited by this bacterium likely explains why the NADPH oxidase is nonessential to the killing of B. mallei while it is still confined within phagosomes. CONCLUSIONS/SIGNIFICANCE: Collectively, these findings have revealed a disparate role for NADPH oxidase and iNOS in the innate macrophage response against the strict aerobe B. mallei. To the best of our knowledge, this is the first instance in which disruption of [Fe-S] clusters is demonstrated as cause of the bactericidal activity of NO congeners