E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Quantitative analysis of dribble volumes and rates using three-dimensional reconstruction of X-ray and diffused back-illumination images of diesel sprays

[EN] Post-injection fuel dribble is known to lead to incomplete atomisation and combustion due to the release of slow-moving, and often surface-bound, liquid fuel after the end of injection. This can have a negative effect on engine emissions, performance and injector durability. To better quantify this phenomenon, we developed an image-processing approach to measure the volume of ligaments produced during the end of injection. We applied our processing approach to an Engine Combustion Network 'Spray B' 3-hole injector, using datasets from 220 injections generated by different research groups, to decouple the effect of gas temperature and pressure on the fuel dribble process. High-speed X-ray phase-contrast images obtained at room temperature conditions (297 K) at the Advanced Photon Source at Argonne National Laboratory, together with diffused back-illumination images captured at a wide range of temperature conditions (293-900 K) by CMT Motores Termicos were analysed and compared quantitatively. We found a good agreement between image sets obtained by Argonne National Laboratory and CMT Motores Termicos using different imaging techniques. The maximum dribble volume within the field of view of the imaging system and the mean rate of fuel dribble were considered as characteristic parameters of the fuel dribble process. Analysis showed that the absolute mean dribble rate increases with temperature when injection pressure is higher than 1000 bar and slightly decreases at high injection pressures (>500 bar) when temperature is close to 293 K. Larger maximum volumes of the fuel dribble were observed at lower gas temperatures (similar to 473 K) and low gas pressures (<30 bar), with a slight dependence on injection pressure.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The image processing research was supported by the United Kingdom's Engineering and Physical Science Research Council (Grants EP/K020528/1 and EP/M009424/1) and BP Formulated Products Technology. The X-ray measurements were performed at the Advanced Photon Source at Argonne National Laboratory. Use of the Advanced Photon Source (APS) is supported by the U.S. Department of Energy (DOE) under Contract No. DEAC02-06CH11357. The X-ray component of this research was partially funded by DOE's Vehicle Technologies Program, Office of Energy Efficiency and Renewable Energy.Sechenyh, V.; Duke, DJ.; Swantek, AB.; Matusik, KE.; Kastengren, AL.; Powell, CF.; Viera, A.... (2020). Quantitative analysis of dribble volumes and rates using three-dimensional reconstruction of X-ray and diffused back-illumination images of diesel sprays. International Journal of Engine Research. 21(1):43-54. https://doi.org/10.1177/1468087419860955S4354211Örley, F., Hickel, S., Schmidt, S. J., & Adams, N. A. (2016). Large-Eddy Simulation of turbulent, cavitating fuel flow inside a 9-hole Diesel injector including needle movement. International Journal of Engine Research, 18(3), 195-211. doi:10.1177/1468087416643901Benajes, J., Novella, R., De Lima, D., & Tribotté, P. (2014). Analysis of combustion concepts in a newly designed two-stroke high-speed direct injection compression ignition engine. International Journal of Engine Research, 16(1), 52-67. doi:10.1177/1468087414562867Moon, S., Huang, W., Li, Z., & Wang, J. (2016). End-of-injection fuel dribble of multi-hole diesel injector: Comprehensive investigation of phenomenon and discussion on control strategy. Applied Energy, 179, 7-16. doi:10.1016/j.apenergy.2016.06.116Kook, S., Pickett, L. M., & Musculus, M. P. B. (2009). Influence of Diesel Injection Parameters on End-of-Injection Liquid Length Recession. SAE International Journal of Engines, 2(1), 1194-1210. doi:10.4271/2009-01-1356Kastengren, A., Powell, C. F., Tilocco, F. Z., Liu, Z., Moon, S., Zhang, X., & Gao, J. (2012). End-of-Injection Behavior of Diesel Sprays Measured With X-Ray Radiography. Journal of Engineering for Gas Turbines and Power, 134(9). doi:10.1115/1.4006981Manin, J., Bardi, M., Pickett, L. M., & Payri, R. (2016). Boundary condition and fuel composition effects on injection processes of high-pressure sprays at the microscopic level. International Journal of Multiphase Flow, 83, 267-278. doi:10.1016/j.ijmultiphaseflow.2015.12.001Payri, R., Bracho, G., Marti-Aldaravi, P., & Viera, A. (2017). NEAR FIELD VISUALIZATION OF DIESEL SPRAY FOR DIFFERENT NOZZLE INCLINATION ANGLES IN NON-VAPORIZING CONDITIONS. Atomization and Sprays, 27(3), 251-267. doi:10.1615/atomizspr.2017017949Gimeno, J., Martí-Aldaraví, P., Carreres, M., & Peraza, J. E. (2018). Effect of the nozzle holder on injected fuel temperature for experimental test rigs and its influence on diesel sprays. International Journal of Engine Research, 19(3), 374-389. doi:10.1177/1468087417751531Payri, R., Salvador, F. J., Manin, J., & Viera, A. (2016). Diesel ignition delay and lift-off length through different methodologies using a multi-hole injector. Applied Energy, 162, 541-550. doi:10.1016/j.apenergy.2015.10.118Duke, D. J., Matusik, K. E., Kastengren, A. L., Swantek, A. B., Sovis, N., Payri, R., … Powell, C. F. (2017). X-ray radiography of cavitation in a beryllium alloy nozzle. International Journal of Engine Research, 18(1-2), 39-50. doi:10.1177/1468087416685965Duke, D., Swantek, A., Kastengren, A., Fezzaa, K., & Powell, C. (2015). Recent Developments in X-ray Diagnostics for Cavitation. SAE International Journal of Fuels and Lubricants, 8(1), 135-146. doi:10.4271/2015-01-0918Walko, D. A., Adams, B. W., Doumy, G., Dufresne, E. M., Li, Y., March, A. M., … Zhu, Y. (2016). Developments in time-resolved x-ray research at APS beamline 7ID. doi:10.1063/1.4952871Fessler, J. A., & Macovski, A. (1991). Object-based 3-D reconstruction of arterial trees from magnetic resonance angiograms. IEEE Transactions on Medical Imaging, 10(1), 25-39. doi:10.1109/42.75608Canny, J. (1986). A Computational Approach to Edge Detection. IEEE Transactions on Pattern Analysis and Machine Intelligence, PAMI-8(6), 679-698. doi:10.1109/tpami.1986.4767851Kastengren, A. L., Tilocco, F. Z., Duke, D. J., Powell, C. F., Zhang, X., & Moon, S. (2014). TIME-RESOLVED X-RAY RADIOGRAPHY OF SPRAYS FROM ENGINE COMBUSTION NETWORK SPRAY A DIESEL INJECTORS. Atomization and Sprays, 24(3), 251-272. doi:10.1615/atomizspr.2013008642Edelsbrunner, H., & Mücke, E. P. (1994). Three-dimensional alpha shapes. ACM Transactions on Graphics, 13(1), 43-72. doi:10.1145/174462.156635Lafarge, T., Pateiro-López, B., Possolo, A., & Dunkers, J. P. (2014). RImplementation of a Polyhedral Approximation to a 3D Set of Points Using theα-Shape. Journal of Statistical Software, 56(4). doi:10.18637/jss.v056.i04Koci, C., Dempsey, A., Nudd, J., & Knier, B. (2017). Understanding Hydrocarbon Emissions in Heavy Duty Diesel Engines Combining Experimental and Computational Methods. SAE International Journal of Engines, 10(3), 1093-1109. doi:10.4271/2017-01-070

Designing and evaluation of sodium selenite nanoparticles in vitro to improve selenium absorption in ruminants

Sodium selenite is used to prevent selenium deficiency known as nutritional muscular dystrophy or white muscle disease. In ruminants, selenium supplements are transformed partiality in insoluble form by ruminal microorganisms and its process decrease the selenium absorption in digestive gastrointestinal. However, the objective in this research was focused in encapsulated sodium selenite to be release into of a pH less than four, similarity to an intestinal environment. It was encapsulated by nanoprecipitation and emulsion–evaporation methods, within polymeric nanoparticles. The effect of these methods, polymer proportion (Eudragit RL and RS) and solvent (ethanol and acetone) on the physicochemical (drug entrapment, polidispersity index (PDI) and z potential) and morphological characteristics (particle morphology and particle size) were evaluated. Particle size from each nanoparticles, formulation ranged from 36.64 to 213.86 nm. Particle size, z potential and PDI increased (P ≤ 0.01) when nanoprecipitation and ethanol were used. No significant differences (P > 0.05) were observed when different polymeric proportions were used. Selenium entrapment was 26% when emulsion–evaporation method was used and 78% with nanoprecipitation. Nanoparticles produced by nanoprecipitation were spherical and had a great variation in particle size; on the other hand, nanoparticles produced by emulsion–evaporation were spherical as well as amorphous and presented a homogeneous nanopartcicle size distribution. The release of selenium from nanoparticles was higher in acid pH (less than 4), this condition may represent a better availability of the mineral in the small intestine

Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells

High-grade osteosarcoma occurs predominantly in adolescents and young adults and has an overall survival rate of about 60%, despite chemotherapy and surgery. Therefore, novel treatment modalities are needed to prevent or treat recurrent disease. Natural killer (NK) cells are lymphocytes with cytotoxic activity toward virus-infected or malignant cells. We explored the feasibility of autologous and allogeneic NK cell–mediated therapies for chemotherapy-resistant and chemotherapy-sensitive high-grade osteosarcoma. The expression by osteosarcoma cells of ligands for activating NK cell receptors was studied in vitro and in vivo, and their contribution to NK cell–mediated cytolysis was studied by specific antibody blockade. Chromium release cytotoxicity assays revealed chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cell lines and osteosarcoma primary cultures to be sensitive to NK cell–mediated cytolysis. Cytolytic activity was strongly enhanced by IL-15 activation and was dependent on DNAM-1 and NKG2D pathways. Autologous and allogeneic activated NK cells lysed osteosarcoma primary cultures equally well. Osteosarcoma patient–derived NK cells were functionally and phenotypically unimpaired. In conclusion, osteosarcoma cells, including chemoresistant variants, are highly susceptible to lysis by IL-15-induced NK cells from both allogeneic and autologous origin. Our data support the exploitation of NK cells or NK cell–activating agents in patients with high-grade osteosarcoma

Liver Cancer-Derived Hepatitis C Virus Core Proteins Shift TGF-Beta Responses from Tumor Suppression to Epithelial-Mesenchymal Transition

International audienceBACKGROUND: Chronic hepatitis C virus (HCV) infection and associated liver cirrhosis represent a major risk factor for hepatocellular carcinoma (HCC) development. TGF-beta is an important driver of liver fibrogenesis and cancer; however, its actual impact in human cancer progression is still poorly known. The aim of this study was to investigate the role of HCC-derived HCV core natural variants on cancer progression through their impact on TGF-beta signaling. PRINCIPAL FINDINGS: We provide evidence that HCC-derived core protein expression in primary human or mouse hepatocyte alleviates TGF-beta responses in terms or growth inhibition or apoptosis. Instead, in these hepatocytes TGF-beta was still able to induce an epithelial to mesenchymal transition (EMT), a process that contributes to the promotion of cell invasion and metastasis. Moreover, we demonstrate that different thresholds of Smad3 activation dictate the TGF-beta responses in hepatic cells and that HCV core protein, by decreasing Smad3 activation, may switch TGF-beta growth inhibitory effects to tumor promoting responses. CONCLUSION/SIGNIFICANCE: Our data illustrate the capacity of hepatocytes to develop EMT and plasticity under TGF-beta, emphasize the role of HCV core protein in the dynamic of these effects and provide evidence for a paradigm whereby a viral protein implicated in oncogenesis is capable to shift TGF-beta responses from cytostatic effects to EMT development

Age-dependent alteration of TGF-β signalling in osteoarthritis

Osteoarthritis (OA) is a disease of articular cartilage, with aging as the main risk factor. In OA, changes in chondrocytes lead to the autolytic destruction of cartilage. Transforming growth factor-β has recently been demonstrated to signal not only via activin receptor-like kinase 5 (ALK5)-induced Smad2/3 phosphorylation, but also via ALK1-induced Smad1/5/8 phosphorylation in articular cartilage. In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the expression of ALK1 is correlated with matrix metalloproteinase-13 expression. The age-dependent shift towards Smad1/5/8 signalling might trigger the differentiation of articular chondrocytes with an autolytic phenotype

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

The supportive care needs of women experiencing gynaecological cancer: a Western Australian cross-sectional study

Background: Women diagnosed with gynaecological cancer experience supportive care needs that require care provision to reduce the impact on their lives. International evidence suggests supportive care needs of women with gynaecological cancer are not being met and provision of holistic care is a priority area for action. Knowledge on gynaecological cancer supportive care needs is limited, specifically comparison of needs and cancer gynaecological subtype. Our aim was to identify supportive care needs of Western Australian women experiencing gynaecological cancer, their satisfaction with help and explore associations between participant’s demographic characteristics and identified needs. Methods: A cross-sectional design incorporating a modified version of the Supportive Care Needs Survey - short form (SCNS-SF34) assessed 37 supportive care needs under five domains in conjunction with demographic data. Three hundred and forty three women with gynaecological cancer attending a tertiary public referral hospital completed the survey over 12 months. Statistical analysis was performed using the R environment for statistical computing. A linear regression model was fitted with factor scores for each domain and demographic characteristics as explanatory variables. Results: Three hundred and three women (83%) identified at least one moderate or high level supportive care need. The five highest ranked needs were, ‘being informed about your test results as soon as feasible’ (54.8%), ‘fears about cancer spreading’ (53.7%), ‘being treated like a person not just another case’ (51.9%), ‘being informed about cancer which is under control or diminishing (that is, remission)’ (50.7%), and ‘being adequately informed about the benefits and side-effects of treatments before you choose to have them’ (49.9%). Eight of the top ten needs were from the ‘health system and information’ domain. Associations between supportive care items and demographic variables revealed ‘cancer type’, and ‘time since completion of treatment’ had no impact on level of perceived need for any domain. Conclusions: Western Australian women with gynaecological cancer identified a high level of supportive care needs. The implementation of a supportive care screening tool is recommended to ensure needs are identified and care is patient-centred. Early identification and management of needs may help to reduce the burden on health system resources for managing ongoing needs