Oxygen-regulated transcription factors and their role in pulmonary disease

The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, which may have anti-inflammatory activity by counteracting effects of IL-1 and IL-8. EGR-1 controls the production of tissue factor by macrophages, which triggers fibrin deposition in the pulmonary vasculature. HIF-1 activates the expression of the vasoconstrictor endothelin-1 in vascular endothelial cells. Angiotensin II induces HIF-1 expression and hypertrophy of pulmonary arterial smooth muscle cells. HIF-1 might therefore have multiple roles in the pathogenesis of pulmonary vascular remodeling

Molecular characterizations of PCR-positive Mycoplasma pneumoniae specimen collected from Australia and China.

Mycoplasma pneumoniaeis an important cause of community-acquired pneumonia (CAP). In this study,M. pneumoniae strains in PCR-positive specimens collected from patients in Sydney, Australia (30 samples), and Beijing, China (83 samples), were characterized using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA), P1-restriction fragment length polymorphism (RFLP) analysis, and sequencing of domain V of the 23S rRNA gene to compare genotype distribution and macrolide resistance rates between locations. Eighteen distinct MLVA types were identified in specimens from Sydney, of which 10 were known (types E, G, J, M, N, P, U, V, S, and X) and 8 previously unknown. Strains were equally distributed between P1-RFLP type 1 and type 2 variants. Among samples from Beijing, MLVA types E, G, J, P, U, X, and Z and four new types were identified. Most specimens belonged to P1-RFLP type 1. A nomenclature based on five VNTR loci is proposed to designate MLVA patterns. Macrolide resistance-associated mutations were identified in only 1 of 30 specimens (3.3%) from Sydney and 71 of 83 (85.5%) from Beijing (P<0.05). This study demonstrated that although multiple individualM. pneumoniaestrains were circulating in Beijing, the genotypes were less diverse than those in Sydney. However, the greatest regional difference was in the incidence of macrolide resistance, which may reflect differences in antibiotic use and/or measures in resistance controlthe Beijing Natural Science Foundation (7112019) and the Beijing City talent training project fund (20071 A0303200118

Down-expression of inducible nitric oxide synthase (iNOS) and endothelial (Enos) proteins and mRNA iNOS in bronchiectasis in vivo

published_or_final_versio

Polymorphisms of two histamine-metabolizing enzymes genes and childhood allergic asthma: a case control study

<p>Abstract</p> <p>Background</p> <p>Histamine-metabolizing enzymes (N-methyltransferase and amiloride binding protein 1) are responsible for histamine degradation, a biogenic amine involved in allergic inflammation. Genetic variants of <it>HNMT </it>and <it>ABP1 </it>genes were found to be associated with altered enzyme activity. We hypothesized that alleles leading to decreased enzyme activity and, therefore, decreased inactivation of histamine may be responsible for altered susceptibility to asthma.</p> <p>Methods</p> <p>The aim of this study was to analyze polymorphisms within the <it>HNMT </it>and <it>ABP1 </it>genes in the group of 149 asthmatic children and in the group of 156 healthy children. The genetic analysis involved four polymorphisms of the <it>HNMT </it>gene: rs2071048 (-1637T/C), rs11569723 (-411C/T), rs1801105 (Thr105Ile = 314C/T) and rs1050891 (1097A/T) and rs1049793 (His645Asp) polymorphism for <it>ABP1 </it>gene. Genotyping was performed with use of PCR-RFLP. Statistical analysis was performed using Statistica software; linkage disequilibrium analysis was done with use of Haploview software.</p> <p>Results</p> <p>We found an association of TT genotype and T allele of Thr105Ile polymorphism of <it>HNMT </it>gene with asthma. For other polymorphisms for <it>HNMT </it>and <it>ABP1 </it>genes, we have not observed relationship with asthma although the statistical power for some SNPs might not have been sufficient to detect an association. In linkage disequilibrium analysis, moderate linkage was found between -1637C/T and -411C/T polymorphisms of <it>HNMT </it>gene. However, no significant differences in haplotype frequencies were found between the group of the patients and the control group.</p> <p>Conclusions</p> <p>Our results indicate modifying influence of histamine N-methyltransferase functional polymorphism on the risk of asthma. The other HNMT polymorphisms and ABP1 functional polymorphism seem unlikely to affect the risk of asthma.</p

Bacterial sex in dental plaque

Genes are transferred between bacteria in dental plaque by transduction, conjugation, and transformation. Membrane vesicles can also provide a mechanism for horizontal gene transfer. DNA transfer is considered bacterial sex, but the transfer is not parallel to processes that we associate with sex in higher organisms. Several examples of bacterial gene transfer in the oral cavity are given in this review. How frequently this occurs in dental plaque is not clear, but evidence suggests that it affects a number of the major genera present. It has been estimated that new sequences in genomes established through horizontal gene transfer can constitute up to 30% of bacterial genomes. Gene transfer can be both inter- and intrageneric, and it can also affect transient organisms. The transferred DNA can be integrated or recombined in the recipient&#x0027;s chromosome or remain as an extrachromosomal inheritable element. This can make dental plaque a reservoir for antimicrobial resistance genes. The ability to transfer DNA is important for bacteria, making them better adapted to the harsh environment of the human mouth, and promoting their survival, virulence, and pathogenicity

Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)

Theories for influencer identification in complex networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure

Aquaporin 3 expression in respiratory mucosa is down-regulated in bronchiectasis in vivo

published_or_final_versio

Overexpression of matrix metalloproteinase-8 (MMP-8) and -9 (MMP-9) in bronchiectatic airways in vivo

published_or_final_versio