First, few studies analyze the genetic and genomic alterations that emerge at different time points during the entire progressive process of the disease. Second, the limited size of the studies is often a factor that undermines the capability to provide Tipifarnib supplier consistent genomic data[9]. Animal models of hepatocarcinogenesis

summarize the primal biology of liver tumorigenesis and have provided reliable data for understanding the cellular development of HCC in humans[1, 10, 11]. In the present study, the pathologic changes of livers in rats treated by DEN included non-specific injuries, regeneration and repair, fibrosis, and cirrhosis, dysplastic

nodules, early tumorous nodules, advanced tumorous nodules and metastasis foci, resembling the process of human hepatocarcinogenesis. DEGs obtained by compare normal rats with DEN-treated animals at stages from cirrhosis to metastasis allowed us to screen for upregulated and downregulated gene expressional profiles. The number of DEGs at each Protein Tyrosine Kinase inhibitor stage was large and the information obtained was powerful. We were thus able to visualize the complicated process of hepatocarcinogenesis at the genomic level. The annotated information of the DEGs show that extensive and diverse biological processes and molecular functions are involved in hepatocaricnogenesis. Most of the DEGs are involved in metabolism and transport, indicating that significant alterations occurred in the process of metabolism and transport during the developmnet of HCC. For example, tumor cells always perform anaerobic glycolysis, even when there is an adequate oxygen supply[12, 13], partly a result of alterations in the profile of enzymes associated Olopatadine with glycolysis. In this study, the gene expression level of lactate

dehydrogenase B increased from the cirrhosis phase to the metastasis phase. Evidence shows that some genetic changes promoting tumor growth influences glucose energy metabolism directly[14, 15]. Many intermediate products from glycolysis are used to synthesize proteins, nucleic acids and lipids by tumor cells, providing the essential materials for the growth and hyperplasia of tumor cells. For aggressive tumors, increased glycolysis and metabolism alterations often occurred. The microenvironment acidosis provided by the conversion of pyruvic acid to lactic acid promotes invasion and metastasis of tumor cells [16–18].

We observed a strong defect on the ability of Cagup1Δ null mutant strain to form biofilm on an inert substrate (polystyrene wells). The attachment of Cagup1Δ null mutant strain cells to this

surface, i.e. their adherence was nearly one BGB324 solubility dmso third than the parent strain and no differentiated structure was formed. These observations corroborate defects in the 2 first basic stages above mentioned. Additionally, also the 3rd, i.e. extensive filamenttation was highly compromised. Conclusions In conclusion, we demonstrate that in Cagup1Δ null mutant strain the major virulence factors are severely weakened, namely the impaired ability of form true hyphae, to adhere and to invade to different

substrates and form biofilms. Equally important, was the revealing Luminespib supplier role of CaGUP1 gene in the resistance to antifungals. The present work brings cutting-edge insights into the role of Gup1p on the transformation of C. albicans into a pathogen. All taken, and considering the fact that mmGUP1 gene complemented the hyphal morphogenetic defects of Cagup1Δ null mutant (Ferreira, C., unpublished results); we anticipate that Gup1p may be part of a yeast morphogenic pathway parallel to the mammalian Hedgehog. Methods Yeast strains, media and growth conditions C. albicans strains used in this work were BWP17 (ura3Δ::λimm434/ura3Δ ::λimm434his1::hisG/his1::hisGarg4::hisG/arg4::hisG) [73], several clones (3-5)

of homozygous C. albicans gup1Δ/gup1Δ (isogenic to BWP17 but gup1::URA3-dpl200/gup1::ARG4) [74], and CF-Ca001 (isogenic to C. albicans gup1Δ/gup1Δ::GUP1) (this study). DOCK10 All assays were preceded by batch cultures grown on complex medium (YPD: 1% (w/v) yeast extract; 2% (w/v) peptone), supplemented with 2% (w/v) glucose as carbon and energy source, at 26°C to maintain unicellular yeast form. These cultures were continuously inspected as to the absence of hyphae – referred ahead as young cultures. Incubation was done at 160 rpm, orbital shaking with air/liquid ratio 2.5/1. Growth was monitored spectrophotometrically at 600 nm. Solid media were supplemented with 2% (w/v) agar. Induction of hyphal growth was as follows: Young YPD cultures (above) were inoculated into YPD, YPD + 10% FBS or Spider’s medium [1% (w/v) nutrient broth, 1% (w/v) mannitol, 0.2% (w/v) K2HPO4 [75]], supplemented with 1.5% agar, and grown at 37°C for 3-5 days. For time-course induction with FBS in liquid broth, cells from young cultures were washed, resuspended (1 × 107 cell/ml) in YPD supplemented with 10% FBS and incubated at 37°C. Photomicrographs were taken at representative time-points. Strain construction To reintroduce GUP1 into C.

J Bacteriol 2006,188(21):7396–7404.PubMedCrossRef 30. Hinderhofer M, Walker CA, Friemel A, Stuermer CA, Moller HM, Reuter A: Evolution of prokaryotic SPFH proteins. BMC Evol Biol 2009, 9:10.PubMedCrossRef 31. Donovan C, Bramkamp M: Characterization and subcellular localization of a bacterial flotillin homologue. Microbiology 2009,155(Pt 6):1786–1799.PubMedCrossRef BMN 673 ic50 32. Glebov OO, Bright NA, Nichols BJ: Flotillin-1 defines a clathrin-independent endocytic pathway in mammalian cells. Nat Cell Biol

2006,8(1):46–54.PubMedCrossRef 33. Wu LJ, Errington J: Coordination of cell division and chromosome segregation by a nucleoid occlusion protein in bacillus subtilis . Cell 2004,117(7):915–925.PubMedCrossRef

34. Dempwolff F, Moller HM, Graumann PL: Synthetic motility and cell shape defects associated with deletions of flotillin/reggie paralogs in bacillus subtilis and interplay of these proteins with NfeD proteins. J Bacteriol 2012,194(17):4652–4661.PubMedCrossRef 35. Defeu Soufo HJ, Graumann PL: Actin-like proteins MreB and Mbl from bacillus subtilis are required for MG-132 price bipolar positioning of replication origins. Curr Biol 2003,13(21):1916–1920.CrossRef 36. Formstone A, Errington J: A magnesium-dependent mreB null mutant: implications for the role of mreB in bacillus subtilis . Mol Microbiol 2005,55(6):1646–1657.PubMedCrossRef 37. Lee YH, Kingston AW, Helmann JD: Glutamate dehydrogenase affects resistance to cell wall antibiotics in bacillus subtilis . J Bacteriol 2011,194(5):993–1001.PubMedCrossRef 38. Jaacks KJ, Healy J, Losick R, Grossman AD: Identification and characterization of

genes controlled by the sporulation regulatory gene spo0H in bacillus subtilis . J Bacteriol 1989, 171:4121–4129.PubMed 39. Feucht A, Lewis PJ: Improved plasmid vectors for the production of multiple fluorescent protein fusions in Bacillus subtilis . Gene 2001,264(2):289–297.PubMedCrossRef 40. Defeu Soufo HJ, Graumann PL: Dynamic localization and interaction with other bacillus subtilis actin-like science proteins are important for the function of MreB. Mol Microbiol 2006, 62:1340–1356.PubMedCrossRef 41. Gueiros-Filho FJ, Losick R: A widely conserved bacterial cell division protein that promotes assembly of the tubulin-like protein FtsZ. Genes Dev 2002,16(19):2544–2556.PubMedCrossRef 42. Dempwolff F, Reimold C, Reth M, Graumann PL: Bacillus subtilis MreB orthologs self-organize into filamentous structures underneath the cell membrane in a heterologous cell system. PLoS One 2011,6(11):e27035.PubMedCrossRef 43. Kidane D, Sanchez H, Alonso JC, Graumann PL: Visualization of DNA double-strand break repair in live bacteria reveals dynamic recruitment of bacillus subtilis RecF, RecO and RecN proteins to distinct sites on the nucleoids. Mol Microbiol 2004,52(6):1627–1639.PubMedCrossRef 44.

They also suggest that genes with relatively stable expression are more likely to evolve slowly when compared with VEG. Gene expression level and functional necessity independently influence core genome stabilization It is well established that the core genome contains more indispensible genes that play central metabolic roles [11, 12]. This results in a lower mutation rate than in the flexible genome. To define essential genes, we searched for homologs of all selleck compound MED4 coding

genes in the Database of Essential Genes (DEG8.0), a database that collects all indispensible genes measured in laboratory by far [39]. Using BLASTx (E-value = 1 × 10-4), we found homologs for 871 MED4 coding genes. A total of 767 genes were distributed in the core genome, representing 61.3% of core genes. This was a significantly higher proportion of genes than those distributed in the flexible genome (14.6%; P < 0.001; Figure 4a). These data support the hypothesis that core genes are responsible for central cell metabolism in Prochlorococcus. Figure 4 Gene necessity analysis and COG functional enrichment of HEG. All coding-sequence genes were searched on the Database of Essential Genes (DEG8.0 [39]) using BLASTx CHIR99021 (E-value = 1 × 10-4). (a) Comparison of the DEG-hit genes in the core and flexible genomes. (b) Comparisons of gene expression subclasses

between DEG-hit and DEG-miss genes. (c) COG functional enrichment of HEG in the core genome. Statistic significance was

performed by Fisher’s exact test (one-tailed). P-value ≤ 0.05 was indicated in figure. COG, clusters of orthologous groups; Core, the core genome; DEG-hit, genes with homologs identified in the database; DEG-miss, genes without any known homologs; Flexible, the flexible genome; Unk, unknown function. We also compared the expression levels of the core MED4 genes that had homologs in the DEG database (DEG-hit) with those genes that did not have any known homologs (DEG-miss). HEG, LEG, and NEG had no enrichment for either DEG-hit or DEG-miss genes (P > 0.1; Figure 4b). Although the MEG subclass had a Dimethyl sulfoxide significantly higher rate of DEG-hit genes (P < 0.001; Figure 4b), the mean expression level of the DEG-hit genes (mean RPKM = 602.62) was not significantly different from that of the DEG-miss genes (mean RPKM = 874.81; Student’s t-test, two-tailed P = 0.084). Therefore, as previous works reported [14, 40, 41], this suggests that essential genes are not necessarily highly expressed and that gene expression levels relatively independently affect sequence evolution in Prochlorococcus MED4. We also performed functional enrichment analysis on each gene expression subclass. As most of the genes in the flexible genome have no COG categories [42], we mainly focused on the core genes’ expression subclasses, especially the HEG.

Table 1 outlines the findings of employment social support for risk and prognosis for the included studies. Table 1 Outcomes of low levels RAD001 in vitro of employment social support on risk and prognosis for back pain Outcome Study Study quality  (%) Strong support Moderate support Weak support No support Risk of occurrence for back pain Andersen et al. 100       × (SS, CWS) Clays et al. 79     + (GWS males) × (GWS females) Elfering et al. 64       × (GWS) Feuerstein et al.

85     + (SS)   Fransen et al. 50       × (GWS) Ghaffari et al. 64       × (GWS) Gheldof et al. 86       × (GWS) Gonge et al. 79       × (GWS) Harkness et al. 64       × (GWS) Hoogendoorn et al. 71       × (CWS, SS) Ijzelenberg and Burdorf 79 + (SS)     × (CWS) Josephson and Vingard 78       × (GWS) Kaila-Kangas et al. 64 + (SS)     × (CWS) Kerr et al. 92   − (CWS)     Krause et al. 86       × (CWS, SS) Larsman and Hanse 64       × (GWS) Leino and Hanninen 71   + (GWS)     Rugulies and Krause 93       × (CWS, SS) Shannon et al. 79       × (GWS) Stevenson et al. 50 + (CWS)       Return to work/recovery Dionne et al. 93       × (GWS) Gheldof et al. 86       × (GWS) Helmhout et al. 79       × (CWS,

SS) Heymans et al. Selleck SCH727965 86     + (GWS)   Karlsson et al. 79       × (GWS) Lotters and Burdorf 71       × (GWS) Mielenz et al. 78   + (CWS)   × (SS) Morken et al. 78     + (GWS short term absence) × (GWS long term absence) Schultz et

al. 86   − (CWS)     Soucy et al. 79     + (GWS)   Tubach et al. 86 + (GWS, long term absence)     × (GWS, short term absence) van der Giezen et al. 79     + (GWS)   van den Heuvel et al. 79 + (CWS)     × (SS) LBP Low back pain, SS supervisor support, CWS Co-worker support, GWS General work selleck screening library support, + positive association, − negative association, × (no association) Employment social support and risk of occurrence of back pain In total, 20 studies report on 27 findings on the association of employment social support and occurrence of back pain. Of those findings, 20 reported no significant associations, one reported a strong reverse effect (a greater level of employment support increased the risk of back pain) and six reported an effect whereby lower levels of employment support increased the risk of back pain (Table 1). Of those six findings, three were judged as weak associations, one of moderate strength and two judged as strong effects. Co-worker support (CWS) Seven studies were included within this analysis, six of those studies reporting no effect (Andersen et al. 2007; Hoogendoorn et al. 2001; Ijzelenberg and Burdorf 2005; Kaila-Kangas et al. 2004; Krause et al. 1998; Rugulies and Krause 2005) and one study reporting a reverse effect of higher CWS increasing the risk of LBP (Kerr et al. 2001).

The results were comparable to those of the analyses of the complete protein sequences. Similarly, comparing only the C-termini, AIDA-I clusters in one phylogenetic

branch with AatA, thus the C-terminus of AatA seems to be most related to that of AIDA-I (Figure 3B). The amino acid residue alignment of the C-termini of AIDA-I and AatA revealed a number of identical residues as shown in Figure 3C. Comparing only the C-terminus one has to keep in mind that this part contains the transmembrane domain to span the bacterial membrane, thus it is likely to be the most conserved part among all autotransporter adhesins. Figure 3 see more Phylogenetic tree of autotransporter adhesins including AatA. The phylogenetic trees were calculated with the Neighbor-Joining-Algorithm Antiinfection Compound Library cost on the basis of a ClustalW multiple alignment of 24 protein sequences from known adhesins of the autotransporter family including AatA. The percentages of replicate trees in which the associated taxa clustered together in the bootstrap test (1000 replicates) are shown next to the branches. Protein sequences were obtained from the NCBI database. A: Phylogenetic tree (NJ-tree) obtained using the complete 24 protein sequences. B: NJ-tree obtained using only the last 256 amino acid residues according to the smallest protein HadA

in ClustalW analyses. Here, only proteins clustering in one phylogenetic branch with AatA are shown. C: The amino acid residue PtdIns(3,4)P2 alignment of the C-termini of AIDA-I and AatA are shown highlighting identical residues (*indicates fully conserved residues, :indicates fully conserved strong groups, .indicates fully conserved weaker groups). Symbols indicate the species: *Escherichia coli, # Neisseria meningitidis, °Haemophilus influenzae, + Yersinia enterocolitica, ‘Moraxella catarrhalis, ´´Helicobacter pylori, $ Xylella fastidiosa, **Salmonella Typhimurium, and & Bordetella pertussis. We also examined the amino acid differences of the conserved AatA proteins in E. coli IMT5155, APEC_O1 and BL21 and B_REL606, respectively. The AatA of the latter two strains are 100% identical. In

total, 19 amino acid substitutions were found in the C-terminus containing the transmembrane domain; 3 variable positions lie within the passenger domain and 13 differences in amino acid sequence were found in the N-termini of the AatA proteins (Figure 4). Interestingly, the transmembrane domains of BL21 and IMT5155 are 100% identical and the 19 C-terminal amino acid differences occur in APEC_O1 compared to these two strains. Also the majority of amino acid substitutions within the N-terminus (10 of 13) occur in APEC_O1 in contrast to the almost identical AatA proteins from BL21 and IMT5155 (only 3 substitutions). Taken together, the adhesins of the two APEC strains differ more than the AatA proteins of IMT5155 and the non-pathogenic BL21 strain.

Kiziltan ME, Gunduz A, Kiziltan G, et al. Peripheral neuropathy in patients with diabetic foot ulcera: clinical and nerve conduction study. J Neurol Sci 2007; 258: 75–9PubMedCrossRef 26. Shaikh AS, Somani RS. Animal models and biomarkers of neuropathy in diabetic rodents. Indian J Pharmacol 2010; 42 (3): 129–34PubMedCrossRef 27. Edwards JL, Vincent CH5424802 chemical structure AM, Cheng HT, et al. Diabetic neuropathy: mechanisms to management. Pharmacol

Ther 2008; 120: 1–34PubMedCrossRef 28. Ziegler D, Nowak H, Kempler P, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med 2004; 21: 114–21PubMedCrossRef 29. Vincent AM, Russell JW, Sullivan KA, et al. SOD2 protects neurons Acalabrutinib mouse from injury in cell culture and animal models of diabetic neuropathy. Exper Neurol 2007; 208: 216–27CrossRef 30. Ziegler D. Painful diabetic neuropathy. Diabetes Care 2009; Suppl. 2 (32): S414–9CrossRef”
“Introduction Asthma disproportionately affects racial and ethnic populations. In the US in 2006, the age-adjusted, asthma-related mortality rates were approximately 3 times higher in non-Hispanic Blacks than in non-Hispanic Whites and Hispanics.[1] Although typical safety

and efficacy studies are underpowered or too short in duration to make definitive conclusions regarding severe asthma exacerbations (i.e. those requiring systemic corticosteroids), important insight into the efficacy of medications can be gained from analyzing related moderate exacerbation events characterized by a sustained loss of asthma control (beyond normal day-to-day SPTBN5 variation) that does not meet the definition of a severe exacerbation.[2] For the purpose of asthma research protocol development, moderate exacerbation events

have been captured using various terminology, such as asthma deterioration,[3] asthma worsenings,[4] and asthma events.[5] Few US studies have evaluated the safety and efficacy of an inhaled corticosteroid (ICS)/long-acting β2-adrenergic agonist (LABA) combination therapy in Black or Hispanic patients with asthma. The efficacy of budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) has been evaluated in randomized, double-blind studies in predominantly White patients with mild to moderate asthma[6] and predominantly White,[5] Black,[7] and Hispanic[8] patients with moderate to severe asthma. Results for a predefined asthma event definition, which encompass moderate to severe asthma deteriorations, are presented as these findings have not been presented previously in detail or compared across patient populations. Methods Table I includes a brief summary of the studies that were included in this exploratory analysis. Additional details of the individual studies, including study design and methods, have been previously described.

The only species that contains a locus identical in content and arrangement to S. meliloti is the closely related Sinorhizobium medicae. The locus of Sinorhizobium fredii NGR234, contains all but one of the genes (fucA1) found in the other Sinorhizobium loci (Figure  2). Figure 2 The phylogenetic tree of erythritol proteins does

not correlate with species phylogeny; evidence for horizontal gene transfer. EryA phylogenetic tree (Left) and RpoD species tree (Right) were constructed using ML and Bayesian analysis. Support for each clade is expressed as a percentage (Bayesian/ML, ie. posterior probability and bootstrap values respectively) adjacent AG-014699 molecular weight to the nodes that supports the monophyly of various clades. V. eiseniae was used as an outgroup for both trees since it was the most phylogenetically distant organism. A tree including branch lengths for EryA is included as Additional file 1: Figure S1. The loci of Mesorhizobium species were varied, however all three Mesorhizobium sp. contained an independent locus

with homologs to lalA and rbtBC elsewhere in the genome (Figure  1). Interestingly, while Mesorhizobium loti and Mesorhizobium opportunism both contain transporters homologous to mptABCDE, Mesorhizobium ciceri bv. biserrulae contains a transporter homologous to eryEFG. This operon also contains the same hypothetical gene that is found at the beginning of the R. leguminosarum eryEFG transcript. The transporters however, are arranged check details in a manner similar to that seen in S. meliloti and the gene encoding the regulator eryD, is found ahead of the transporter genes, whereas in R. leguminosarum and Brucella, eryD is found following eryC (Figure  1). We also note that whereas M. loti and M. opportunism both contain a putative fructose 1,6 bis phosphate aldolase gene between the eryR-tpiB-rpiB operon and eryC, a homolog to this is also gene is found adjacent

to the rpiB in Brucella. Bradyrhizobium sp. BTAi1, and ORS278, A. cryptum and V. eiseniae Isoconazole all have similar genetic arrangement to that of S. meliloti, except that they do not contain a homolog to eryC, or an associated eryR-tpiB-rpiB operon. These loci also differ primarily in their arrangement of lalA-rbtBC (Figure  1). The phylogenies of erythritol proteins do not correlate with species phylogeny The DNA sequences of 16S rDNA (data not shown) as well as the amino acid sequences of RpoD were extracted from GenBank to analyze the phylogenetic relationships of the organisms examined in this study, using the most phylogenetically distant organism Verminephrobacter eiseniae as an out-group. The results of the 16S rDNA and RpoD sequence analyses were in concordance with each other and are consistent with phylogenies that have been previously generated [42]. Initial comparison of the operon structures with the generated phylogenies suggested that the operon structure(s) did not correlate with the species phylogeny.

The SEM and TEM images (Figure 2a,b) show that the as-synthesized product consists of hexagonal nanoplates. These nanoplates have a diameter of 70 to 350 nm and a thickness of ca. 20 nm. As shown in Figure 2c, the HRTEM image taken from the face of nanoplates exhibits clear lattice fringes with spacings of 0.33 nm, assigning to (10–10) planes of wurtzite CGS. The corresponding FFT pattern (Figure 2d) displays the bright spots with sixfold symmetry, consistent with the hexagonal wurtzite structure of CGS. Furthermore,

HRTEM image was also CHIR-99021 mouse taken from the sides of nanoplates, as shown in Figure 2e. The AB-stacking of the layers in the hexagonal domains and the ABC-stacking in the cubic domains are clearly distinguishable in the HRTEM image shown in Figure 2e, which suggests the coexistence of wurtzite and zincblende structures within each nanoplate. Therefore, the crystal phase of the as-synthesized

nanoplates is wurtzite-zincblende polytypism, wherein the hexagonal wurtzite domains are interfaced with the cubic zincblende domains across (0002)WZ/(111)ZB stacking faults. This crystal structure of CGS nanoplates is similar selleck kinase inhibitor to that of our previously synthesized CuInS2 nanoplates [23]. Figure 2 SEM (a), TEM (b), and HRTEM (c,e) images of as-synthesized product and FFT pattern (d) of (c). In particular, the HRTEM image (c) was taken from the face of nanoplates while the HRTEM image (e) was taken from the sides of nanoplates. The valence states and composition of the as-synthesized nanoplates were studied by XPS, as shown

in Figure 3. The full-scan spectra (Figure 3a) show the presence of the Cu 2p, Ga 2p and S 2p peaks, confirming the presence of these elements in as-synthesized ID-8 nanoplates. The Cu 2p, Ga 2p and S 2p core levels were also examined, respectively. The peaks observed at 931.9 and 951.7 eV, with a peak splitting of 19.8 eV, are indicative of monovalent Cu [23]. The two peaks centered at 1,117 and 1,144 eV, with a peak separation of 27 eV, are attributed to trivalent Ga [20]. The two peaks of S 2p were located at 162.4 and 163.6 eV, with a peak splitting of 1.2 eV, which are consistent with the literature values in metal sulfides [24]. Through quantification of peaks, the molar ratio of Cu/Ga/S of 1.22:1:1.93 is given, indicating that the as-synthesized nanoplates are Cu-rich with respect to the stoichiometric CGS. Figure 3 XPS of as-synthesized nanoplates: (a) a survey spectrum, (b) Cu 2 p , (c) Ga 2 p , and (d) S 2 p . In our synthesis, metal chlorides (CuCl and GaCl3) could react with 1-dodecanethiol to form metal thiolates, which then decomposed into nanocrystals at elevated temperature [9, 23]. When heating a mixture of CuCl, GaCl3, 1-dodecanethiol, and 1-octadecene to 140°C, a clear yellow solution formed, suggesting the formation of metal thiolates because of the reaction between metal chlorides and 1-dodecanethiol.

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P-glycoprotein in rat astrocyte cultures. J Neurochem 2004, 89:788–800.PubMedCrossRef 15. Smart EJ, Ying YS, Mineo C, Anderson RG: A detergent-free method for purifying caveolae membrane from tissue culture cells. Proc Natl Acad Sci USA 1995, 92:10104–10108.PubMedCrossRef 16. Ahmed SN, Brown DA, London E: On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes:physiological concentrations of cholesterol and sphingolipid induce formation of a detergent-insoluble, Isotretinoin liquid-ordered lipid phase in model membranes.

check details Biochemistry 1997, 36:10944–10953.PubMedCrossRef 17. Hansen CG, Nichols BJ: Exploring the caves: cavins, caveolins and caveolae. Trends Cell Biol 2010,20(4):177–86.PubMedCrossRef 18. Stan RV: Structure of caveolae. Biochim Biophys Acta 2005,1746(3):334–348.PubMedCrossRef 19. Lavie Y, Liscovitch M: Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences. Glycoconj J 2000,17(3–4):253–259.PubMedCrossRef 20. Barakat S, Turcotte S, Demeule M, Lachambre MP, Régina A, Baggetto LG, Béliveau R: Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction. Biochem Biophys Res Commun 2008,372(3):440–6.PubMedCrossRef 21. Schlachetzki F, Pardridge WM: P-glycoprotein and caveolin-1α in endothelium and astrocytes of primate brain. Neuroreport 2003,14(16):2041–2046.PubMedCrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions ZG collected the clinical datas and samples, participated in the immunohistochemistry and drafted the manuscript. JZ carried out the immunohistochemistry. LZ performed the statistical analysis. QL participated in the design of the study. XJ conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript.