Ligation of protease-activated receptor 1 enhances alpha(v)beta(6) integrin-dependent TGF-beta activation and promotes acute lung injury

Activation of latent TGF-beta by the alpha(v)beta(6) integrin is a critical step in the development of acute lung injury. However, the mechanism by which a alpha(v)beta(6)-mediated TGF-beta activation is regulated has not been identified. We show that thrombin, and other agonists of protease-activated receptor 1(PAR1), activate TGF-beta in an alpha(v)beta(6) integrin-specific manner. This effect is PART specific and is mediated by RhoA and Rho kinase. Intratracheal instillation of the PART-specific peptide TFLLRN increases lung edema during high-tidal-volume ventilation, and this effect is completely inhibited by a blocking antibody against the alpha(v)beta(6) integrin. Instillation of TFLLRN during high-tidal-volume ventilation is associated with increased pulmonary TGF-beta activation; however, this is not observed in Itgb6(-/-) mice. Furthermore, Itgb6(-/-) mice are also protected from ventilator-induced lung edema. We also demonstrate that pulmonary edema and TGF-beta activity are similarly reduced in Par1(-/-) mice following bleomycin-induced lung injury. These results suggest that PART-mediated enhancement of a alpha(v)beta(6)-dependent TGF-beta activation could be one mechanism by which activation of the coagulation cascade contributes to the development of acute lung injury, and they identify PART and the alpha(v)beta(6) integrin as potential therapeutic targets in this condition

Parental Verbal Communication and Sexual Knowledge of Senior Secondary School Students in South East, Nigeria

BACKGROUND: Parental verbal communication may influence the sexual knowledge of senior secondary school students in Enugu State, Nigeria.METHODS: This study utilized a school based cross-sectional study design and was conducted across the six education zones of Enugu State using three-stage sampling technique. A total of 400 respondents completed the interviewer administered questionnaires on their socio-demographics, sexual knowledge and parents’ information on verbal communication skills. Obtainable knowledge scores for sexuality ranged between 0-10; scores of 1-5 were classified as poor and 6-10 as good. Data analysis for the quantitative data was done using IBM SPSS; version 22. Chi square test of statistical significance and multivariate analysis using binary logistic regression were used in the analysis, and the level of significance was set at a p value of less than 0.05.RESULTS: Out of the 400 respondents, 55.5% were girls. The mean age (SD) of the respondents was 15.9 ± 1.3 years. Although 15.5% and 8.8% of the respondents were very comfortable discussing sexually related matters with their mothers and fathers only 34.8% and 16.0% of mothers and fathers were comfortable discussing such matters with the respondents. Less than half of the respondents (42.5%) had good sexual knowledge. Verbal sexual communication between parents and respondents and age above 16 years were found to be predictors of good sexual knowledge.CONCLUSIONS: Poor parental verbal communication led to the poor knowledge of sexuality among the respondents. Parents should be encouraged to discuss sexuality matters with their children

Design of bolted side-plated reinforced-concrete beams with partial interaction

Existing reinforced-concrete (RC) beams can be effectively strengthened by anchoring steel plates to the side faces of the beams using bolts, which is known as the bolted side-plating (BSP) technique. Previous studies have found that the performance of BSP beams is primarily controlled by the degree of partial interaction at the steel-RC interface, which can be conveniently quantified by the strain and curvature factors. In this paper, a new simplified flexural design procedure for BSP beams taking into account partial interaction is presented. Some optimum ranges of strain and curvature factors are first introduced to the flexural design of BSP beams. By ensuring the flexural capacity of a BSP beam is higher than the design moment, the preliminary size of steel plates and the arrangement of bolts can be determined. Following this, the maximum design slips and minimum design strain and curvature factors are calculated and back-checked to ensure the target flexural capacity of the BSP beam has been achieved. An example is presented to illustrate the effectiveness of the optimised design method for BSP beams, considering the effect of partial interaction under realistic loading conditions.published_or_final_versio

Characterization of damage in shielding structures of space vehicles under hypervelocity impact

6th Asia Pacific Workshop on Structural Health Monitoring, APWSHM, Hobart, Tasmania, Australia, 7-9 December 2016Version of RecordPublishe

Secondary structure in the core of amyloid fibrils formed from human βm and its truncated variant Δn6

Amyloid fibrils formed from initially soluble proteins with diverse sequences are associated with an array of human diseases. In the human disorder, dialysis-related amyloidosis (DRA), fibrils contain two major constituents, full-length human β-microglobulin (hβm) and a truncation variant, ΔN6 which lacks the N-terminal six amino acids. These fibrils are assembled from initially natively folded proteins with an all antiparallel β-stranded structure. Here, backbone conformations of wild-type hβm and ΔN6 in their amyloid forms have been determined using a combination of dilute isotopic labeling strategies and multidimensional magic angle spinning (MAS) NMR techniques at high magnetic fields, providing valuable structural information at the atomic-level about the fibril architecture. The secondary structures of both fibril types, determined by the assignment of ∼80% of the backbone resonances of these 100- and 94-residue proteins, respectively, reveal substantial backbone rearrangement compared with the location of β-strands in their native immunoglobulin folds. The identification of seven β-strands in hβm fibrils indicates that approximately 70 residues are in a β-strand conformation in the fibril core. By contrast, nine β-strands comprise the fibrils formed from ΔN6, indicating a more extensive core. The precise location and length of β-strands in the two fibril forms also differ. The results indicate fibrils of ΔN6 and hβm have an extensive core architecture involving the majority of residues in the polypeptide sequence. The common elements of the backbone structure of the two proteins likely facilitates their ability to copolymerize during amyloid fibril assembly

Characterizing hypervelocity impact (HVI)-induced pitting damage using active guided ultrasonic waves : from linear to nonlinear

2016-2017 > Academic research: refereed > Publication in refereed journal201804_a bcmaVersion of RecordPublishe

Solution-Processed Epitaxial Growth of Arbitrary Surface Nanopatterns on Hybrid Perovskite Monocrystalline Thin Films.

Semiconductor surface patterning at the nanometer scale is crucial for high-performance optical, electronic, and photovoltaic devices. To date, surface nanostructures on organic-inorganic single-crystal perovskites have been achieved mainly through destructive methods such as electron-beam lithography and focused ion beam milling. Here, we present a solution-based epitaxial growth method for creating nanopatterns on the surface of perovskite monocrystalline thin films. We show that high-quality monocrystalline arbitrary nanopatterns can form in solution with a low-cost simple setup. We also demonstrate controllable photoluminescence from nanopatterned perovskite surfaces by adjusting the nanopattern parameters. A seven-fold enhancement in photoluminescence intensity and a three-time reduction of the surface radiative recombination lifetime are observed at room temperature for nanopatterned MAPbBr3 monocrystalline thin films. Our findings are promising for the cost-effective fabrication of monocrystalline perovskite on-chip electronic and photonic circuits down to the nanometer scale with finely tunable optoelectronic properties

IL11 (Interleukin-11) causes emphysematous lung disease in a mouse model of marfan syndrome.

BACKGROUND: Marfan Syndrome (MFS) is an inherited connective tissue disorder caused by mutations in the FBN1 (fibrillin-1) gene. Lung abnormalities are common in MFS, but their pathogenesis is poorly understood. IL11 (interleukin-11) causes aortic disease in a mouse model of MFS and was studied here in the lung. METHODS: We examined histological and molecular phenotypes in the lungs of Fbn1C1041G/+ mice (mouse model of Marfan Syndrome [mMFS]), an established mouse model of MFS. To identify IL11-expressing cells, we used immunohistochemistry on lungs of 4- and 16-week-old Fbn1C1041G/+:Il11EGFP/+ reporter mice. We studied the effects of IL11 inhibition by RT-qPCR, immunoblots and histopathology in lungs from genetic or pharmacologic models: (1) 16-week-old IL11 receptor (IL11RA) knockout mMFS mice (Fbn1C1041G/+:Il11ra1-/- mice) and (2) in mMFS mice administered IgG control or interleukin-11 receptor antibodies twice weekly from 4 to 24 weeks of age. RESULTS: mMFS lungs showed progressive loss and enlargement of distal airspaces associated with increased proinflammatory and profibrotic gene expression as well as matrix metalloproteinases 2, 9, and 12. IL11 was increased in mMFS lungs and localized to smooth muscle and endothelial cells in young mMFS mice in the Fbn1C1041G/+:Il11EGFP/+ reporter strain and in fibroblasts, in older mice. In mMFS mice, genetic (Fbn1C1041G/+:Il11ra1-/-) or pharmacologic (anti-interleukin-11 receptor) inhibition of IL11 signaling reduced lung emphysema, fibrosis, and inflammation. This protective effect was associated with reduced pathogenic ERK1/2 signaling and lower metalloproteinase 2, 9, and 12 expression. CONCLUSIONS: IL11 causes lung disease in mMFS. This reveals a shared IL11-driven disease mechanism in lung and aorta in MFS and suggests inhibition of IL11 signaling as a holistic approach for treating multiorgan morbidity in MFS