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11.
The localisation of the vacuolar proton pump (V-H+ -ATPase) and the enzyme carbonic anhydrase II (CAII) was investigated in the human eccrine sweat gland employing standard immunohistochemical techniques after antigen retrieval using microwave heat treatment and high pressure. The high-pressure antigen retrieval unmasked the presence of V-H+ -ATPase in the clear cells of the secretory coil, with a distribution similar to that previously observed for CAII. However, the dark cells were unreactive to both antibodies. In addition, heat and high-pressure antigen retrieval demonstrated the presence of CAII in the apical zone of luminal cells of the reabsorptive duct, a location not previously reported. The localisation of V-H+ -ATPase and CAII in the secretory coil clear cells suggests that the formation of HCO3- and H+ by carbonic anhydrase II and the transport of H+ by V-H+ -ATPase may play an role in sweat fluid secretion. Their presence at the apex of the duct cells indicates involvement in ductal ion reabsorption.  相似文献   
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Background

While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM), is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation.

Methods

CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO) mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation.

Results

Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke.

Conclusions

These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1 inflammatory pathway.  相似文献   
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Background

Chromosomal breakage followed by faulty DNA repair leads to gene amplifications and deletions in cancers. However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). We present here a novel approach to array CGH data analysis, which focuses on putative breakpoints responsible for rearrangements within the genome.

Results

We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. The specimens were flow sorted according to ploidy to increase tumor cell purity prior to array CGH. We describe the number of chromosomal breaks as well as the patterns of breaks on individual chromosomes in each tumor. There were differences in chromosomal breakage patterns between the 3 clinical subtypes of breast cancers, although the highest density of breaks occurred at chromosome 17 in all subtypes, suggesting a particular proclivity of this chromosome for breaks. We also observed chromothripsis affecting various chromosomes in 41% of high risk breast cancers.

Conclusions

Our results provide a new insight into the genomic complexity of breast cancer. Genomic instability dependent on chromosomal breakage events is not stochastic, targeting some chromosomes clearly more than others. We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-579) contains supplementary material, which is available to authorized users.  相似文献   
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Single-walled aluminum nitride nanotubes (AlNNTs) are introduced as an electronic sensor for detection of sulfur dioxide (SO(2)) molecules based on density functional theory calculations. The proposed sensor benefits from several advantages including high sensitivity: HOMO-LUMO energy gap of the AlNNT is appreciably sensitive toward the presence of SO(2) so that it decreases from 4.11?eV in the pristine tube to 1.01?eV in the SO(2)-adsorbed form, pristine application: this nanotube can detect the SO(2) molecule in its pristine type without manipulating its structure through doping, chemical functionalization, making defect, etc., short recovery time: the adsorption energy of SO(2) molecule is not so large to hinder the recovery of AlNNTs and therefore the sensor will possess short recovery times, and good selectivity: the tube can selectively detect the SO(2) molecule in the presence of several molecules such as H(2)O, CO, NH(3), HCOH, CO(2), N(2), and H(2).  相似文献   
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The structural properties, NMR and NQR parameters in the pristine and silicon carbide (SiC) doped boron phosphide nanotubes (BPNTs) were calculated using DFT methods (BLYP, B3LYP/6-31G*) in order to evaluate the influence of SiC-doped on the (4,4) armchair BPNTs. Nuclear magnetic resonance (NMR) parameters including isotropic (CSI) and anisotropic (CSA) chemical shielding parameters for the sites of various 13C, 29Si, 11B, and 31P atoms and quadrupole coupling constant (C Q ), and asymmetry parameter (η Q ) at the sites of various 11B nuclei were calculated in pristine and SiC- doped (4,4) armchair boron phosphide nanotubes models. The calculations indicated that doping of 11B and 31P atoms by C and Si atoms had a more significant influence on the calculated NMR and NQR parameters than did doping of the B and P atoms by Si and C atoms. In comparison with the pristine model, the SiC- doping in SiPCB model of the (4,4) armchair BPNTs reduces the energy gaps of the nanotubes and increases their electrical conductance. The NMR results showed that the B and P atoms which are directly bonded to the C atoms in the SiC-doped BPNTs have significant changes in the NMR parameters with respect to the B and P atoms which are directly bonded to the Si atoms in the SiC-doped BPNTs. The NQR results showed that in BPNTs, the B atoms at the edges of nanotubes play dominant roles in determining the electronic behaviors of BPNTs. Also, the NMR and NQR results detect that the Fig. 1b (SiPCB) model is a more reactive material than the pristine and the Fig. 1a (SiBCp) models of the (4,4) armchair BPNTs.  相似文献   
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Structural, electronic, and electrical responses of the H-capped (6,0) zigzag single-walled aluminum nitride nanotube was studied under the parallel and transverse electric fields with strengths 0-140?×?10(-4)?a.u. by using density functional calculations. Geometry optimizations were carried out at the B3LYP/6-31G* level of theory using a locally modified version of the GAMESS electronic structure program. The dipole moments, atomic charge variations, and total energy of the (6,0) zigzag AlNNT show increases with increase in the applied external electric field strengths. The length, tip diameters, electronic spatial extent, and molecular volume of the nanotube do not significantly change with increasing electric field strength. The energy gap of the nanotube decreases with increases of the electric field strength and its reactivity is increased. Increase of the ionization potential, electron affinity, chemical potential, electrophilicity, and HOMO and LUMO in the nanotube with increase of the applied parallel electric field strengths shows that the parallel field has a much stronger interaction with the nanotube with respect to the transverse electric field strengths. Analysis of the parameters indicates that the properties of AlNNTs can be controlled by the proper external electric field.  相似文献   
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