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71.

Introduction

First/Second-hand cigarette-smoke (FHS/SHS) exposure weakens immune defenses inducing chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are not fully understood. Hence, we evaluated if SHS induced changes in membrane/lipid-raft (m-/r)-CFTR (cystic fibrosis transmembrane conductance regulator) expression/activity is a potential mechanism for impaired bacterial phagocytosis in COPD.

Methods

RAW264.7 murine macrophages were exposed to freshly prepared CS-extract (CSE) containing culture media and/or Pseudomonas-aeruginosa-PA01-GFP for phagocytosis (fluorescence-microscopy), bacterial survival (colony-forming-units-CFU), and immunoblotting assays. The CFTR-expression/activity and lipid-rafts were modulated by transient-transfection or inhibitors/inducers. Next, mice were exposed to acute/sub-chronic-SHS or room-air (5-days/3-weeks) and infected with PA01-GFP, followed by quantification of bacterial survival by CFU-assay.

Results

We investigated the effect of CSE treatment on RAW264.7 cells infected by PA01-GFP and observed that CSE treatment significantly (p<0.01) inhibits PA01-GFP phagocytosis as compared to the controls. We also verified this in murine model, exposed to acute/sub-chronic-SHS and found significant (p<0.05, p<0.02) increase in bacterial survival in the SHS-exposed lungs as compared to the room-air controls. Next, we examined the effect of impaired CFTR ion-channel-activity on PA01-GFP infection of RAW264.7 cells using CFTR172-inhibitor and found no significant change in phagocytosis. We also similarly evaluated the effect of a CFTR corrector-potentiator compound, VRT-532, and observed no significant rescue of CSE impaired PA01-GFP phagocytosis although it significantly (p<0.05) decreases CSE induced bacterial survival. Moreover, induction of CFTR expression in macrophages significantly (p<0.03) improves CSE impaired PA01-GFP phagocytosis as compared to the control. Next, we verified the link between m-/r-CFTR expression and phagocytosis using methyl-β-cyclodextran (CD), as it is known to deplete CFTR from membrane lipid-rafts. We observed that CD treatment significantly (p<0.01) inhibits bacterial phagocytosis in RAW264.7 cells and adding CSE further impairs phagocytosis suggesting synergistic effect on CFTR dependent lipid-rafts.

Conclusion

Our data suggest that SHS impairs bacterial phagocytosis by modulating CFTR dependent lipid-rafts.  相似文献   
72.

Aim

To measure and compare the head scatter factor for 7 MV unflattened and 6 MV flattened photon beam using a home-made designed mini phantom.

Background

The head scatter factor (Sc) is one of the important parameters for MU calculation. There are multiple factors that influence the Sc values, like accelerator head, flattening filter, primary and secondary collimators.

Materials and methods

A columnar mini phantom was designed as recommended by AAPM Task Group 74 with high and low atomic number material for measurement of head scatter factors at 10 cm and dmax dose water equivalent thickness.

Results

The Sc values measured with high-Z are higher than the low-Z mini phantoms observed for both 6MV-FB and 7MV-UFB photon energies. Sc values of 7MV-UFB photon beams were smaller than those of the 6MV-FB photon beams (0.6–2.2% (Primus), 0.2–1.4% (Artiste) and 0.6–3.7% (Clinac iX (2300CD))) for field sizes ranging from 10 cm × 10 cm to 40 cm × 40 cm. The SSD had no influence on head scatter for both flattened and unflattened beams. The presence of wedge filters influences the Sc values. The collimator exchange effects showed that the opening of the upper jaw increases Sc irrespective of FF and FFF.

Conclusions

There were significant differences in Sc values measured for 6MV-FB and unflattened 7MV-UFB photon beams over the range of field sizes from 10 cm × 10 cm to 40 cm × 04 cm. Different results were obtained for measurements performed with low-Z and high-Z mini phantoms.  相似文献   
73.
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels.  相似文献   
74.
The efficiency of phenol degradation via Fenton reaction using mixture of heterogeneous goethite catalyst with homogeneous ferrous ion was analyzed as a function of three independent variables, initial concentration of phenol (60 to 100 mg /L), weight ratio of initial concentration of phenol to that of H2O2 (1: 6 to 1: 14) and, weight ratio of initial concentration of goethite catalyst to that of H2O2 (1: 0.3 to 1: 0.7). More than 90 % of phenol removal and more than 40% of TOC removal were achieved within 60 minutes of reaction. Two separate models were developed using artificial neural networks to predict degradation percentage by a combination of Fe3+ and Fe2+ catalyst. Five operational parameters were employed as inputs while phenol degradation and TOC removal were considered as outputs of the developed models. Satisfactory agreement was observed between testing data and the predicted values (R2 Phenol = 0.9214 and R2TOC= 0.9082).  相似文献   
75.

Introduction

The microeconomic impact of surgery for congenital heart disease is unexplored, particularly in resource limited environments. We sought to understand the direct and indirect costs related to congenital heart surgery and its impact on Indian households from a family perspective.

Methods

Baseline and first follow-up data of 644 consecutive children admitted for surgery for congenital heart disease (March 2013 – July 2014) in a tertiary referral hospital in Central Kerala, South India was collected prospectivelyfrom parents through questionnaires using a semi-structured interview schedule.

Results

The median age was 8.2 months (IQR: 3.0– 36.0 months). Most families belonged to upper middle (43.0%) and lower middle (35.7%) socioeconomic class. Only 3.9% of families had some form of health insurance. The median expense for the admission and surgery was INR 201898 (IQR: 163287–266139) [I$ 11989 (IQR: 9696–15804)], which was 0.93 (IQR: 0.52–1.49) times the annual family income of affected patients. Median loss of man-days was 35 (IQR: 24–50) and job-days was 15 (IQR: 11–24). Surgical risk category and hospital stay duration significantly predicted higher costs. One in two families reported overwhelming to high financial stress during admission period for surgery. Approximately half of the families borrowed money during the follow up period after surgery.

Conclusion

Surgery for congenital heart disease results in significant financial burden for majority of families studied. Efforts should be directed at further reductions in treatment costs without compromising the quality of care together with generating financial support for affected families.  相似文献   
76.
The measurement of viscoelasticity of cells in physiological environments with high spatio-temporal resolution is a key goal in cell mechanobiology. Traditionally only the elastic properties have been measured from quasi-static force-distance curves using the atomic force microscope (AFM). Recently, dynamic AFM-based methods have been proposed to map the local in vitro viscoelastic properties of living cells with nanoscale resolution. However, the differences in viscoelastic properties estimated from such dynamic and traditional quasi-static techniques are poorly understood. In this work we quantitatively reconstruct the local force and dissipation gradients (viscoelasticity) on live fibroblast cells in buffer solutions using Lorentz force excited cantilevers and present a careful comparison between mechanical properties (local stiffness and damping) extracted using dynamic and quasi-static force spectroscopy methods. The results highlight the dependence of measured viscoelastic properties on both the frequency at which the chosen technique operates as well as the interactions with subcellular components beyond certain indentation depth, both of which are responsible for differences between the viscoelasticity property maps acquired using the dynamic AFM method against the quasi-static measurements.  相似文献   
77.
Landscape simplification has been clearly demonstrated to have negative impacts on the in-crop density and biological-control activity of natural enemies in agricultural landscapes. The role of spatial arrangement of the landscape, however, has not been investigated in agroecosystems. We applied cost–distance modeling to investigate the relationship between the in-crop density of natural enemies and the structural connectivity of non-crop land uses surrounding crops within Australian cotton landscapes. We further compared the explanatory power of this approach with the more commonly used spatially specific proportional-area approach, which considers landscape composition in terms of the proportional area of a given land use within a given radius. Cost–distance metrics offered a more significant explanation of in-crop density for the predatory beetle Dicranolaius bellulus (Coleoptera: Melyridae) than did the proportional-area approach. The in-crop density for this species was positively and significantly correlated with the connectivity of wooded land uses within a 3000 m radius. However, for natural enemy taxa that responded to landscape characteristics at smaller spatial scales (within a 750 m radius), namely Oxyopes spp. (Araneae: Oxyopidae) and Trichogramma spp., (Hymenoptera: Trichogrammatidae), the proportional-area approach gave a more significant explanation of in-crop density. Herbivore taxa responded weakly to proportional area at all scales and showed no correlation to cost–distance metrics. Findings indicate potential for simplified agricultural landscapes to be ‘selectively’ manipulated to enhance colonization of the crop by natural enemies, but not herbivores, by improving connectivity between crops and non-crop resources, through the presence of woody vegetation.  相似文献   
78.
Aluminium (Al3+) toxicity restricts productivity and profitability of wheat (Triticum aestivum L.) crops grown on acid soils worldwide. Continued gains will be obtained by identifying superior alleles and novel Al3+ resistance loci that can be incorporated into breeding programs. We used association mapping to identify genomic regions associated with Al3+ resistance using 1055 accessions of common wheat from different geographic regions of the world and 178 polymorphic diversity arrays technology (DArT) markers. Bayesian analyses based on genetic distance matrices classified these accessions into 12 subgroups. Genome-wide association analyses detected markers that were significantly associated with Al3+ resistance on chromosomes 1A, 1B, 2A, 2B, 2D, 3A, 3B, 4A, 4B, 4D, 5B, 6A, 6B, 7A, and 7B. Some of these genomic regions correspond to previously identified loci for Al3+ resistance, whereas others appear to be novel. Among the markers targeting TaALMT1 (the major Al3+-resistance gene located on chromosome 4D), those that detected alleles in the promoter explained most of the phenotypic variance for Al3+ resistance, which is consistent with this region controlling the level of TaALMT1 expression. These results demonstrate that genome-wide association mapping cannot only confirm known Al3+-resistance loci, such as those on chromosomes 4D and 4B, but they also highlight the utility of this technique in identifying novel resistance loci.  相似文献   
79.
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