Electronic cigarette use was not associated with quitting of conventional cigarettes in youth smokers

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The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells

BACKGROUND: Neuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer. The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells.METHODS: NE differentiation of prostate cancer LNCaP cells was induced by serum deprivation or by incubation with interleukin-6, for 6 days. Levels of NE markers and signaling proteins were determined by western blotting. Levels of cannabinoid receptors were determined by quantitative PCR. The involvement of signaling cascades was investigated by pharmacological inhibition and small interfering RNA.RESULTS: The differentiated LNCaP cells exhibited neurite outgrowth, and increased the expression of the typical NE markers neuron-specific enolase and βIII tubulin (βIII Tub). Treatment with 3 μM WIN inhibited NK differentiation of LNCaP cells. The cannabinoid WIN downregulated the PI3K/Akt/mTOR signaling pathway, resulting in NE differentiation inhibition. In addition, an activation of AMP-activated protein kinase (AMPK) was observed in WIN-treated cells, which correlated with a decrease in the NE markers expression. Our results also show that during NE differentiation the expression of cannabinoid receptors CB1 and CB2 dramatically decreases.CONCLUSIONS: Taken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer.Prostate Cancer and Prostatic Diseases advance online publication, 21 June 2016; doi:10.1038/pcan.2016.19.</p

Improvement of Carbon Nanofibers/ZrO2 Composites Properties with a Zirconia Nanocoating on Carbon Nanofibers by Sol–Gel Method

The development of new carbon nanofibers (CNFs)–ceramic nanocomposite materials with excellent mechanical, thermal, and electrical properties is interesting for a wide range of industrial applications. Among the ceramic materials, zirconia stands out for their excellent mechanical properties. The main limitations in the preparation of this kind of nanocomposites are related with the difficulty in obtaining materials with homogeneous distribution of both phases and the dissimilar properties of CNFs and ZrO2 which causes poor interaction between them. CNFs-reinforced zirconia nanocomposites ZrO2/xCNFs (x=1–20 vol%) were prepared by powder mixture and sintered by spark plasma sintering (SPS). ZrO2-reinforced CNFs nanocomposites CNFs/xZrO2 (x=20 vol%) were prepared by powder mixture and a surface coating of CNFs by the wet chemical route with zirconia precursor is proposed as a very effective way to improve the interaction between CNFs and ZrO2. After SPS sintering, an improvement of 50% in fracture strength was found for similar nanocomposite compositions when the surface coating was used. The improved mechanical properties of these nanocomposites are caused by stronger interaction between the CNFs and ZrO2.This work was financially supported by National Plan Projects MAT2006-01783 and MAT2007-30989-E and the Regional Project FICYT PC07-021. A. Borrell, acknowledges the Spanish Ministry of Science and Innovation for her research grant BES2007-15033.Borrell Tomás, MA.; Rocha, VG.; Torrecillas, R.; Fernandez, A. (2011). Improvement of Carbon Nanofibers/ZrO2 Composites Properties with a Zirconia Nanocoating on Carbon Nanofibers by Sol–Gel Method. Journal of the American Ceramic Society. 94(7):2048-2052. https://doi.org/10.1111/j.1551-2916.2010.04354.xS20482052947Iijima, S. (1991). Helical microtubules of graphitic carbon. Nature, 354(6348), 56-58. doi:10.1038/354056a0Merkoçi, A. (2005). Carbon Nanotubes in Analytical Sciences. Microchimica Acta, 152(3-4), 157-174. doi:10.1007/s00604-005-0439-zUchida, T., Anderson, D. P., Minus, M. L., & Kumar, S. (2006). Morphology and modulus of vapor grown carbon nano fibers. Journal of Materials Science, 41(18), 5851-5856. doi:10.1007/s10853-006-0324-0Hvizdoš, P., Puchý, V., Duszová, A., & Dusza, J. (2010). Tribological behavior of carbon nanofiber–zirconia composite. Scripta Materialia, 63(2), 254-257. doi:10.1016/j.scriptamat.2010.03.069Balázsi, C., Kónya, Z., Wéber, F., Biró, L. P., & Arató, P. (2003). Preparation and characterization of carbon nanotube reinforced silicon nitride composites. Materials Science and Engineering: C, 23(6-8), 1133-1137. doi:10.1016/j.msec.2003.09.085Tatami, J., Katashima, T., Komeya, K., Meguro, T., & Wakihara, T. (2005). Electrically Conductive CNT-Dispersed Silicon Nitride Ceramics. Journal of the American Ceramic Society, 88(10), 2889-2893. doi:10.1111/j.1551-2916.2005.00539.xHirota, K., Hara, H., & Kato, M. (2007). Mechanical properties of simultaneously synthesized and consolidated carbon nanofiber (CNF)-dispersed SiC composites by pulsed electric-current pressure sintering. Materials Science and Engineering: A, 458(1-2), 216-225. doi:10.1016/j.msea.2006.12.065Dusza, J., Blugan, G., Morgiel, J., Kuebler, J., Inam, F., Peijs, T., … Puchy, V. (2009). Hot pressed and spark plasma sintered zirconia/carbon nanofiber composites. Journal of the European Ceramic Society, 29(15), 3177-3184. doi:10.1016/j.jeurceramsoc.2009.05.030Lee, S.-Y., Kim, H., McIntyre, P. C., Saraswat, K. C., & Byun, J.-S. (2003). Atomic layer deposition of ZrO2 on W for metal–insulator–metal capacitor application. Applied Physics Letters, 82(17), 2874-2876. doi:10.1063/1.1569985Kobayashi, S., & Kawai, W. (2007). Development of carbon nanofiber reinforced hydroxyapatite with enhanced mechanical properties. Composites Part A: Applied Science and Manufacturing, 38(1), 114-123. doi:10.1016/j.compositesa.2006.01.006Sun, J., Gao, L., Iwasa, M., Nakayama, T., & Niihara, K. (2005). Failure investigation of carbon nanotube/3Y-TZP nanocomposites. Ceramics International, 31(8), 1131-1134. doi:10.1016/j.ceramint.2004.11.010Ukai, T., Sekino, T., Hirvonen, A. T., Tanaka, N., Kusunose, T., Nakayama, T., & Niihara, K. (2006). Preparation and Electrical Properties of Carbon Nanotubes Dispersed Zirconia Nanocomposites. Key Engineering Materials, 317-318, 661-664. doi:10.4028/www.scientific.net/kem.317-318.661Duszová, A., Dusza, J., Tomášek, K., Morgiel, J., Blugan, G., & Kuebler, J. (2008). Zirconia/carbon nanofiber composite. Scripta Materialia, 58(6), 520-523. doi:10.1016/j.scriptamat.2007.11.002Wang, X., Padture, N. P., & Tanaka, H. (2004). Contact-damage-resistant ceramic/single-wall carbon nanotubes and ceramic/graphite composites. Nature Materials, 3(8), 539-544. doi:10.1038/nmat1161Zhan, G.-D., Kuntz, J. D., Garay, J. E., & Mukherjee, A. K. (2003). Electrical properties of nanoceramics reinforced with ropes of single-walled carbon nanotubes. Applied Physics Letters, 83(6), 1228-1230. doi:10.1063/1.1600511Yucheng, W., & Zhengyi, F. (2002). Study of temperature field in spark plasma sintering. Materials Science and Engineering: B, 90(1-2), 34-37. doi:10.1016/s0921-5107(01)00780-2Haase, F., & Sauer, J. (1998). The Surface Structure of Sulfated Zirconia:  Periodic ab Initio Study of Sulfuric Acid Adsorbed on ZrO2(101) and ZrO2(001). Journal of the American Chemical Society, 120(51), 13503-13512. doi:10.1021/ja9825534Matsui, K., Suzuki, H., Ohgai, M., & Arashi, H. (1995). Raman Spectroscopic Studies on the Formation Mechanism of Hydrous-Zirconia Fine Particles. Journal of the American Ceramic Society, 78(1), 146-152. doi:10.1111/j.1151-2916.1995.tb08374.xGateshki, M., Petkov, V., Williams, G., Pradhan, S. K., & Ren, Y. (2005). Atomic-scale structure of nanocrystallineZrO2prepared by high-energy ball milling. Physical Review B, 71(22). doi:10.1103/physrevb.71.224107Pyda, W., Haberko, K., & Bulko, M. M. (1991). Hydrothermal Crystallization of Zirconia and Zirconia Solid Solutions. Journal of the American Ceramic Society, 74(10), 2622-2629. doi:10.1111/j.1151-2916.1991.tb06810.xDell’Agli, G., & Mascolo, G. (2000). Hydrothermal synthesis of ZrO2–Y2O3 solid solutions at low temperature. Journal of the European Ceramic Society, 20(2), 139-145. doi:10.1016/s0955-2219(99)00151-xTai, C. Y., Hsiao, B.-Y., & Chiu, H.-Y. (2007). Preparation of silazane grafted yttria-stabilized zirconia nanocrystals via water/CTAB/hexanol reverse microemulsion. Materials Letters, 61(3), 834-836. doi:10.1016/j.matlet.2006.05.068Tai, C. Y., Lee, M.-H., & Wu, Y.-C. (2001). Control of zirconia particle size by using two-emulsion precipitation technique. Chemical Engineering Science, 56(7), 2389-2398. doi:10.1016/s0009-2509(00)00454-1Tai, C. Y., & Hsiao, B.-Y. (2005). CHARACTERIZATION OF ZIRCONIA POWDER SYNTHESIZED VIA REVERSE MICROEMULSION PRECIPITATION. Chemical Engineering Communications, 192(11), 1525-1540. doi:10.1080/009864490896133Ci, L., Wei, J., Wei, B., Liang, J., Xu, C., & Wu, D. (2001). Carbon nanofibers and single-walled carbon nanotubes prepared by the floating catalyst method. Carbon, 39(3), 329-335. doi:10.1016/s0008-6223(00)00126-3Choi, S. R., & Bansal, N. P. (s. f.). Alumina-Reinforced Zirconia Composites. Handbook of Ceramic Composites, 437-457. doi:10.1007/0-387-23986-3_18Li, W., & Gao, L. (2000). Rapid sintering of nanocrystalline ZrO2(3Y) by spark plasma sintering. Journal of the European Ceramic Society, 20(14-15), 2441-2445. doi:10.1016/s0955-2219(00)00152-7Borrell, A., Fernández, A., Merino, C., & Torrecillas, R. (2010). High density carbon materials obtained at relatively low temperature by spark plasma sintering of carbon nanofibers. International Journal of Materials Research, 101(1), 112-116. doi:10.3139/146.110246Dusza, J., Morgiel, J., Tatarko, P., & Puchy, V. (2009). Characterization of interfaces in ZrO2–carbon nanofiber composite. Scripta Materialia, 61(3), 253-256. doi:10.1016/j.scriptamat.2009.03.052Lauwers, B., Kruth, J. P., Liu, W., Eeraerts, W., Schacht, B., & Bleys, P. (2004). Investigation of material removal mechanisms in EDM of composite ceramic materials. Journal of Materials Processing Technology, 149(1-3), 347-352. doi:10.1016/j.jmatprotec.2004.02.01

Predicting survival of de novo metastatic breast cancer in Asian women: Systematic review and validation study

10.1371/journal.pone.0093755PLoS ONE94-POLN

ICOS regulates the generation and function of human CD4+ Treg in a CTLA-4 dependent manner

Inducible co-stimulator (ICOS) is a member of CD28/Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) family and broadly expressed in activated CD4+ T cells and induced regulatory CD4+ T cells (CD4+ iTreg). ICOS-related signal pathway could be activated by the interaction between ICOS and its ligand (ICOSL). In our previous work, we established a cost-effective system to generate a novel human allo-antigen specific CD4hi Treg by co-culturing their naïve precursors with allogeneic CD40-activated B cells in vitro. Here we investigate the role of ICOS in the generation and function of CD4hi Treg by interrupting ICOS-ICOSL interaction with ICOS-Ig. It is found that blockade of ICOS-ICOSL interaction impairs the induction and expansion of CD4hi Treg induced by allogeneic CD40-activated B cells. More importantly, CD4hi Treg induced with the addition of ICOS-Ig exhibits decreased suppressive capacity on alloantigen-specific responses. Dysfunction of CD4hi Treg induced with ICOS-Ig is accompanied with its decreased exocytosis and surface CTLA-4 expression. Through inhibiting endocytosis with E64 and pepstatin A, surface CTLA-4 expression and suppressive functions of induced CD4hi Treg could be partly reversed. Conclusively, our results demonstrate the beneficial role of ICOS-ICOSL signal pathway in the generation and function of CD4hi Treg and uncover a novel relationship between ICOS and CTLA-4. © 2013 zheng et al.published_or_final_versio

Visual attention and action: How cueing, direct mapping, and social interactions drive orienting

Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another’s goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice

<p>Abstract</p> <p>Background</p> <p>Ginsenoside Rg3, a saponin extracted from ginseng, inhibits angiogenesis. The combination of low-dose chemotherapy and anti-angiogenic inhibitors suppresses growth of experimental tumors more effectively than conventional therapy or anti-angiogenic agent alone. The present study was designed to evaluate the efficacy of low-dose gemcitabine combined with ginsenoside Rg3 on angiogenesis and growth of established Lewis lung carcinoma in mice.</p> <p>Methods</p> <p>C57L/6 mice implanted with Lewis lung carcinoma were randomized into the control, ginsenoside Rg3, gemcitabine and combination group. The quality of life and survival of mice were recorded. Tumor volume, inhibitive rate and necrosis rate were estimated. Necrosis of tumor and signals of blood flow as well as dynamic parameters of arterial blood flow in tumors such as peak systolic velocity (PSV) and resistive index (RI) were detected by color Doppler ultrasound. In addition, expression of vascular endothelial cell growth factor (VEGF) and CD31 were observed by immunohistochemstry, and microvessel density (MVD) of the tumor tissues was assessed by CD31 immunohistochemical analysis.</p> <p>Results</p> <p>Quality of life of mice in the ginsenoside Rg3 and combination group were better than in the control and gemcitabine group. Combined therapy with ginsenoside Rg3 and gemcitabine not only enhanced efficacy on suppression of tumor growth and prolongation of the survival, but also increased necrosis rate of tumor significantly. In addition, the combination treatment could obviously decrease VEGF expression and MVD as well as signals of blood flow and PSV in tumors.</p> <p>Conclusion</p> <p>Ginsenoside Rg3 combined with gemcitabine may significantly inhibit angiogenesis and growth of lung cancer and improve survival and quality of life of tumor-bearing mice. The combination of chemotherapy and anti-angiogenic drugs may be an innovative and promising therapeutic strategy in the experimental treatment of human lung cancer.</p

Structural Elucidation and Functional Characterization of the Hyaloperonospora arabidopsidis Effector Protein ATR13

The oomycete Hyaloperonospora arabidopsidis (Hpa) is the causal agent of downy mildew on the model plant Arabidopsis thaliana and has been adapted as a model system to investigate pathogen virulence strategies and plant disease resistance mechanisms. Recognition of Hpa infection occurs when plant resistance proteins (R-genes) detect the presence or activity of pathogen-derived protein effectors delivered to the plant host. This study examines the Hpa effector ATR13 Emco5 and its recognition by RPP13-Nd, the cognate R-gene that triggers programmed cell death (HR) in the presence of recognized ATR13 variants. Herein, we use NMR to solve the backbone structure of ATR13 Emco5, revealing both a helical domain and a disordered internal loop. Additionally, we use site-directed and random mutagenesis to identify several amino acid residues involved in the recognition response conferred by RPP13-Nd. Using our structure as a scaffold, we map these residues to one of two surface-exposed patches of residues under diversifying selection. Exploring possible roles of the disordered region within the ATR13 structure, we perform domain swapping experiments and identify a peptide sequence involved in nucleolar localization. We conclude that ATR13 is a highly dynamic protein with no clear structural homologues that contains two surface-exposed patches of polymorphism, only one of which is involved in RPP13-Nd recognition specificity

The androgen receptor can signal through Wnt/β-Catenin in prostate cancer cells as an adaptation mechanism to castration levels of androgens

<p>Abstract</p> <p>Background</p> <p>A crucial event in Prostate Cancer progression is the conversion from a hormone-sensitive to a hormone-refractory disease state. Correlating with this transition, androgen receptor (AR) amplification and mutations are often observed in patients failing hormonal ablation therapies. β-Catenin, an essential component of the canonical Wnt signaling pathway, was shown to be a coactivator of the AR signaling in the presence of androgens. However, it is not yet clear what effect the increased levels of the AR could have on the Wnt signaling pathway in these hormone-refractory prostate cells.</p> <p>Results</p> <p>Transient transfections of several human prostate cancer cell lines with the AR and multiple components of the Wnt signaling pathway demonstrate that the AR overexpression can potentiate the transcriptional activities of Wnt/β-Catenin signaling. In addition, the simultaneous activation of the Wnt signaling pathway and overexpression of the AR promote prostate cancer cell growth and transformation at castration levels of androgens. Interestingly, the presence of physiological levels of androgen or other AR agonists inhibits these effects. These observations are consistent with the nuclear co-localization of the AR and β-Catenin shown by immunohistochemistry in human prostate cancer samples. Furthermore, chromatin immunoprecipitation assays showed that Wnt3A can recruit the AR to the promoter regions of Myc and Cyclin D1, which are well-characterized downstream targets of the Wnt signalling pathway. The same assays demonstrated that the AR and β-Catenin can be recruited to the promoter and enhancer regions of a known AR target gene PSA upon Wnt signaling. These results suggest that the AR is promoting Wnt signaling at the chromatin level.</p> <p>Conclusion</p> <p>Our findings suggest that the AR signaling through the Wnt/β-Catenin pathway should be added to the well established functional interactions between both pathways. Moreover, our data show that via this interaction the AR could promote prostate cell malignancy in a ligand-independent manner.</p