Possible role of Krüppel-like factor 5 in the remodeling of small airways and pulmonary vessels in chronic obstructive pulmonary disease

BACKGROUND: Small airway remodeling is an important cause of the airflow limitation in chronic obstructive pulmonary disease (COPD). A large population of patients with COPD also have pulmonary hypertension. Krüppel-like factor 5 (KLF5) is a zinc-finger transcription factor that contributes to tissue remodeling in cardiovascular diseases. Here, we evaluate the possible involvement of KLF5 in the remodeling of small airways and pulmonary vessels in COPD. METHODS: Lung tissues were obtained from 23 control never-smokers, 17 control ex-smokers and 24 ex-smokers with COPD. The expression of KLF5 in the lung tissues was investigated by immunohistochemistry. We investigated whether oxidative/nitrosative stress, which is a major cause of the pathogenesis in COPD, could augment the production of KLF5. We examined the role of KLF5 in the stress-mediated tissue remodeling responses. We also investigated the susceptibility of KLF5 expression to nitrosative stress using bronchial fibroblasts isolated from the lung tissues. RESULTS: The expression of KLF5 was up-regulated in the small airways and pulmonary vessels of the COPD patients and it was mainly expressed in bronchial fibroblasts and cells of the pulmonary vessels. The extent of the KLF5 expression in the small airway of the COPD group had a significant correlation with the severity of the airflow limitation. Oxidative/nitrosative stress augmented the production of KLF5 in lung fibroblasts as well as the translocation of KLF5 into the nuclei. Silencing of KLF5 suppressed the stress-augmented differentiation into myofibroblasts, the release of collagens and metalloproteinases. Bronchial fibroblasts from the patients with COPD highly expressed KLF5 compared to those from the control subjects under basal condition and were more susceptible to the induction of KLF5 expression by nitrosative stress compared to those from the control subjects. CONCLUSION: We provide the first evidence that the expression of KLF5 is up-regulated in small airways and pulmonary vessels of patients with COPD and may be involved in the tissue remodeling of COPD

Pembentukan Monolayer Azobenzen Disulfida dan Karakterisasinya

Dalam penelitian ini dilakukan studi kinetik adsorpsi pembentukan monolayer azobenzen disulfida pada substrat Au. Ada tiga jenis molekul azobenzen disulfida yang digunakan yaitu HAzC12SSC12, C6AzC12SSC18, dan CNAzC12SSC12. Pengkajian tersebut dilakukan dengan pengukuran kinetik adsorpsi monolayer azobenzen disulfida dan spektrum SPR dengan menggunakan spektroskopi surface plasmon resonance (SPR). Hasil yang didapat menunjukkan molekul C6AzC12SSC18 memiliki potensi yang lebih baik untuk membentuk self-assembled monolayer (SAMs), karena memiliki tahapan adsorpsi yang cepat dengan ketebalan yang optimal dan penyusunan molekul yang teratur

Oscillatory oblique stagnation-point flow toward a plane wall

Two-dimensional oscillatory oblique stagnation-point flow toward a plane wall is investigated. The problem is a eneralisation of the steady oblique stagnation-point flow examined by previous workers. Far from the wall, the flow is composed of an irrotational orthogonal stagnation-point flow with a time-periodic strength, a simple shear flow of constant vorticity, and a time-periodic uniform stream. An exact solution of the Navier-Stokes equations is sought for which the flow streamfunction depends linearly on the coordinate parallel to the wall. The problem formulation reduces to a coupled pair of partial differential equations in time and one spatial variable. The first equation describes the oscillatory orthogonal stagnation-point flow discussed by previous workers. The second equation, which couples to the first, describes the oblique component of the flow. A description of the flow velocity field, the instantaneous streamlines, and the particle paths is sought through numerical solutions of the governing equations and via asymptotic analysis

Prevalence of Hepatitis C Virus and its genotypes among a cohort of drug users in Kenya

Background: Prevalence of hepatitis C virus and that of its main genotypes varies between the worlds geographic regions. The risk factors for infection with HCV include blood transfusion, tattoing and injecting drug use. Objectives: To examine the prevalence of HCV and determine its main genotypes among a cohort of drug users in Kenya. Design: A laboratory based study. Setting: Hepatitis research laboratory in the Centre for Virus Research at the Kenya Medical Research Institute, Nairobi. Subjects: Three hundred and fourteen male and 19 female intravenous and non-intravenous drug users aged between 15-55 years. Results: Seventy four (22.2%) out of 333 samples tested positive for anti-HCV. Sixty nine out of the 74 serum samples were assayed for HCV RNA and 38 (55.5%) were positive. The RNA positive samples were further subjected to sequencing and 19 (73%) of the samples were classified as genotype la, while seven (27%) samples were classified as genotype 4. Genotypes 2, 3, 5 and 6 were not identified in this study. Conclusions: These results demonstrate a high HCV infection prevalence among this cohort of drug users (22.2 %) as compared to that of the general population, which is estimated to be 0.2- 0.9%. The study also confirms the presence of at least two major genotypes among Kenyan drug users (genotypes 1 and 4). East African Medical Journal Vol. 85 (7) 2008: pp. 318-32

Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale

The detection of sound begins when energy derived from acoustic stimuli deflects the hair bundles atop hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors stabilize the structure, further reducing the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please see the online version of the article at http://www.nature.com/natur

A systematic study of the hybrid experiment at Mt.Chacaltaya

In the hybrid experiment on Mt.Chacaltaya, we can observe three different components of airshowers, that is, air-shower size, burst-density and high energy families (a bundle of high energy particles). Burst-density in each block of hadron calorimeters are newly recalculated in simulations in oder to compare directly to the experimental data. Energy deposits in the scintillators of the hadron calorimeters are calculated using GEANT4 for every particle, incident upon the hadron calorimeter, in the air-showers simulated using CORSIKA, and are converted into burst-density, taking into consideration the exact structure of experimental hadron calorimeter. We study correlations among three observable components in the air-showers. Correlations between air-shower size and burst-density and those between air-shower size and accompanied family energy can be explained by model calculations by adjusting primary particle composition, the former correlation is in favor of proton-primaries but the latter iron-primaries. No model can describe well observed correlations between burst-density and family energy. That is, the observed family energy accompanied by the air-showers with larger burst-density is systematically smaller than that expected in the simulated events. Effects of a fluctuation in the cross-section of hadronic interactions are studied to settle the disagreement between experimental data and simulations