2,444 research outputs found

    One-dimensional migration of olfactory ensheathing cells on synthetic materials: Experimental and numerical characterization

    Full text link
    Olfactory ensheathing cells (OECs) are of great interest for regenerative purposes since they are believed to aid axonal growth. With the view set on the strategies to achieve reconnection between neuronal structures, it is of great importance to characterize the behaviour of these cells on long thread-like structures that may efficiently guide cell spread in a targeted way. Here, rat OECs were studied on polycaprolactone (PCL) long monofilaments, on long bars and on discs. PCL turns out to be an excellent substrate for OECs. The cells cover long distances along the monofilaments and colonize completely these struc- tures. With the help of a one-dimensional (1D) analytical model, a migration coefficient, a net proliferation rate constant and the fraction of all cells which undergo migration were obtained. The separate effect of the three phenomena summarized by these parameters on the colo- nization patterns of the 1D path was qualitatively dis- cussed. Other features of interest were also determined, such as the speed of the advance front of colonization and the order of the kinetics of net cell proliferation. Charac- terizing migration by means of these quantities may be useful for comparing and predicting features of the colo- nization process (such as times, patterns, advance fronts and proportion of motile cells) of different cell substrate combinations.Support of the Spanish Science & Innovation Ministery through project MAT2008-06434 is acknowledged. MMP and CMR acknowledge partial funding through the "Convenio de Colaboracion para la Investigacion Basica y Traslacional en Medicina Regenerativa" between the Instituto Nacional de Salud Carlos III, the Conselleria de Sanidad of the Generalitat Valenciana and the Foundation Centro de Investigacion Principe Felipe.Perez Garnes, M.; Martínez Ramos, C.; Barcia, JA.; Escobar Ivirico, JL.; Gomez Pinedo, UA.; Vallés Lluch, A.; Monleón Pradas, M. (2013). One-dimensional migration of olfactory ensheathing cells on synthetic materials: Experimental and numerical characterization. Cell Biochemistry and Biophysics. 65:21-36. https://doi.org/10.1007/s12013-012-9399-1S213665Stokols, S., Sakamoto, J., Breckon, C., Holt, T., Weiss, J., & Tuszynski, M. H. (2006). Templated agarose scaffolds support linear axonal regeneration. Tissue Engineering, 12(10), 2777–2787.Wei, Y. T., Tian, W. M., Yu, X., Cui, F. Z., Hou, S. P., Xu, Q. Y., et al. (2007). Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain. Biomedical Materials, 2(3), 142–146.Yao, L., Wang, S., Cui, W., Sherlock, R., O’Connell, C., Damodaran, G., et al. (2009). Effect of functionalized micropatterned PLGA on guided neurite growth. Acta Biomaterialia, 5(2), 580–588.Chehrehasa, F., Windus, L. C. E., Ekberg, J. A. K., Scott, S. E., Amaya, D., Mackay-Sim, A., et al. (2010). Olfactory glia enhance neonatal axon regeneration. Molecular and Cellular Neuroscience, 45(3), 277–288.Chen, B. K., Knight, A. M., de Ruiter, G. C., Spinner, R. J., Yaszemski, M. J., Currier, B. L., et al. (2009). Axon regeneration through scaffold into distal spinal cord after transection. Journal of Neurotrauma, 26(10), 1759–1771.Goto, E., Mukozawa, M., Mori, H., & Hara, M. (2010). A rolled sheet of collagen gel with cultured Schwann cells: Model of nerve conduit to enhance neurite growth. Journal of Bioscience and Bioengineering, 109(5), 512–518.Lietz, M., Dreesmann, L., Hoss, M., Oberhoffner, S., & Schlosshauer, B. (2006). Neuro tissue engineering of glial nerve guides and the impact of different cell types. Biomaterials, 27(8), 1425–1436.Radtke, C., Sasaki, M., Lankford, K. L., Vogt, P. M., & Kocsis, J. D. (2008). Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury. Journal of Rehabilitation Research and Development, 45(1), 141–151.Wei, Y., Miao, X., Xian, M., Zhang, C., Liu, X., Zhao, H., et al. (2008). Effects of transplanting olfactory ensheathing cells on recovery of olfactory epithelium after olfactory nerve transection in rats. Medical Science Monitor, 14(10), 198–204.Tennent, R., & Chuah, M. I. (1996). Ultrastructural study of ensheathing cells in early development of olfactory axons. Brain Research, Developmental Brain Research, 95(1), 135–139.Doucette, R. (1990). Glial influences on axonal growth in the primary olfactory system. Glia, 3(6), 433–449.Field, P., Li, Y., & Raisman, G. (2003). Ensheathment of the olfactory nerves in the adult rat. Journal of Neurocytology, 32(3), 317–324.Boyd, J. G., Doucette, R., & Kawaja, M. D. (2005). Defining the role of olfactory ensheathing cells in facilitating axon remyelination following damage to the spinal cord. Faseb Journal, 19(7), 694–703.Franklin, R. J., Gilson, J. M., Franceschini, I. A., & Barnett, S. C. (1996). Schwann cell-like myelination following transplantation of an olfactory bulb-ensheathing cell line into areas of demyelination in the adult CNS. Glia, 17(3), 217–224.Imaizumi, T., Lankford, K. L., Waxman, S. G., Greer, C. A., & Kocsis, J. D. (1998). Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord. Journal of Neuroscience, 18(16), 6176–6185.Raisman, G. (2001). Olfactory ensheathing cells - another miracle cure for spinal cord injury? Nature Reviews Neuroscience, 2(5), 369–375.Ramón-Cueto, A., Cordero, M. I., Santos-Benito, F. F., & Avila, J. (2000). Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron, 25(2), 425–435.Chuah, M. I., Choi-Lundberg, D., Weston, S., Vincent, A. J., Chung, R. S., Vickers, J. C., et al. (2004). Olfactory ensheathing cells promote collateral axonal branching in the injured adult rat spinal cord. Experimental Neurology, 185(1), 15–25.Bellamkonda, R. V. (2006). Peripheral nerve regeneration: An opinion on channels, scaffolds and anisotropy. Biomaterials, 27(19), 3515–3518.Liu, Y., Gong, Z., Liu, L., & Sun, H. (2010). Combined effect of olfactory ensheathing cell transplantation and glial cell line-derived neurotrophic factor (GDNF) intravitreal injection on optic nerve injury in rats. Molecular Vision, 16, 2903–2910.Zhu, Y., Cao, L., Su, Z., Mu, L., Yuan, Y., Gao, L., et al. (2010). Olfactory ensheathing cells: Attractant of neural progenitor migration to olfactory bulb. Glia, 58(6), 716–729.Basiri, M., & Doucette, R. (2010). Sensorimotor cortex aspiration: A model for studying Wallerian degeneration-induced glial reactivity along the entire length of a single CNS axonal pathway. Brain Research Bulletin, 81(1), 43–52.Li, Y., Carlstedt, T., Berthold, C.-H., & Raisman, G. (2004). Interaction of transplanted olfactory-ensheathing cells and host astrocytic processes provides a bridge for axons to regenerate across the dorsal root entry zone. Experimental Neurology, 188(2), 300–308.Li, Y., Yamamoto, M., Raisman, G., Choi, D., & Carlstedt, T. (2007). An experimental model of ventral root repair showing the beneficial effect of transplanting olfactory ensheathing cells. Neurosurgery, 60(4), 734–741.Ramón-Cueto, A., Plant, G. W., Avila, J., & Bunge, M. B. (1998). Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. The Journal of Neuroscience, 18(10), 3803–3815.Gómez-Pinedo, U., Vidueira, S., Sancho, F. J., García-Verdugo, J. M., Matías-Guiu, J., & Barcia, J. A. (2011). Olfactory ensheathing glia enhances reentry of axons into the brain from peripheral nerve grafts bridging the substantia nigra with the striatum. Neuroscience Letters, 494(2), 104–108.Graziadei, P. P., Levine, R. R., & Graziadei, G. A. (1978). Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice. Proceedings of the National academy of Sciences of the United States of America, 75(10), 5230–5234.Cao, L., Liu, L., Chen, Z. Y., Wang, L. M., Ye, J. L., Qiu, H. Y., et al. (2004). Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair. Brain, 127(3), 535–549.Cao, L., Su, Z., Zhou, Q., Lv, B., Liu, X., Jiao, L., et al. (2006). Glial cell line-derived neurotrophic factor promotes olfactory ensheathing cells migration. Glia, 54(6), 536–544.Woodhall, E., West, A. K., & Chuah, M. I. (2001). Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors. Brain Research. Molecular Brain Research, 88(1–2), 203–213.Cao, L., Zhu, Y. L., Su, Z., Lv, B., Huang, Z., Mu, L., et al. (2007). Olfactory ensheathing cells promote migration of Schwann cells by secreted nerve growth factor. Glia, 55(9), 897–904.Doucette, R. (1996). Immunohistochemical localization of laminin, fibronectin and collagen type IV in the nerve fiber layer of the olfactory bulb. International Journal of Developmental Neuroscience, 14(7–8), 945–959.Franceschini, I. A., & Barnett, S. C. (1996). Low-affinity NGF-receptor and E-N-CAM expression define two types of olfactory nerve ensheathing cells that share a common lineage. Developmental Biology, 173(1), 327–343.Runyan, S. A., & Phelps, P. E. (2009). Mouse olfactory ensheathing glia enhance axon outgrowth on a myelin substrate in vitro. Experimental Neurology, 216(1), 95–104.Shen, Y., Qian, Y., Zhang, H., Zuo, B., Lu, Z., Fan, Z., et al. (2010). Guidance of olfactory ensheathing cell growth and migration on electrospun silk fibroin scaffolds. Cell Transplantation, 19(2), 147–157.Li, B.-C., Jiao, S.-S., Xu, C., You, H., & Chen, J.-M. (2010). PLGA conduit seeded with olfactory ensheathing cells for bridging sciatic nerve defect of rats. Journal of Biomedical Materials Research, Part A, 94(3), 769–780.Clements, I. P., Kim, Y. T., English, A. W., Lu, X., Chung, A., & Bellamkonda, R. V. (2009). Thin-film enhanced nerve guidance channels for peripheral nerve repair. Biomaterials, 30(23–24), 3834–3846.Martín-López, E., Nieto-Díaz, M., & Nieto-Sampedro, M. (2012). Differential adhesiveness and neurite-promoting activity for neural cells of chitosan, gelatin, and poly-l-lysine films. Journal of Biomaterials Applications, 26(7), 791–809.Cai, J., Peng, X., Nelson, K. D., Eberhart, R., & Smith, G. M. (2005). Permeable guidance channels containing microfilament scaffolds enhance axon growth and maturation. Journal of Biomedical Material Research Part A, 75(2), 374–386.Novikova, L. N., Mosahebi, A., Wiberg, M., Terenghi, G., Kellerth, J. O., & Novikov, L. N. (2006). Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation. Journal of Biomedical Materials Research, Part A, 77(2), 242–252.Tang, Z. P., Liu, N., Li, Z. W., Xie, X. W., Chen, Y., Shi, Y. H., et al. (2010). In vitro evaluation of the compatibility of a novel collagen-heparan sulfate biological scaffold with olfactory ensheathing cells. Chinese Medical Journal (English), 123(10), 1299–1304.Wang, B., Zhao, Y., Lin, H., Chen, B., Zhang, J., Zhang, J., et al. (2006). Phenotypical analysis of adult rat olfactory ensheathing cells on 3-D collagen scaffolds. Neuroscience Letters, 401(1–2), 65–70.Guarnieri, D., De Capua, A., Ventre, M., Borzacchiello, A., Pedone, C., Marasco, D., et al. (2010). Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell migration parameters. Acta Biomaterialia, 6(7), 2532–2539.Ngo, T. T., Waggoner, P. J., Romero, A. A., Nelson, K. D., Eberhart, R. C., & Smith, G. M. (2003). Poly(l-lactide) microfilaments enhance peripheral nerve regeneration across extended nerve lesions. Journal of Neuroscience Research, 72(2), 227–238.Schnell, E., Klinkhammer, K., Balzer, S., Brook, G., Klee, D., Dalton, P., et al. (2007). Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-e-caprolactone and a collagen/poly-e-caprolactone blend. Biomaterials, 28(19), 3012–3025.Lim, S. H., Liu, X. Y., Song, H., Yarema, K. J., & Mao, H. Q. (2010). The effect of nanofiber-guided cell alignment on the preferential differentiation of neural stem cells. Biomaterials, 31(34), 9031–9039.Wong, D. Y., Hollister, S. J., Krebsbach, P. H., & Nosrat, C. (2007). Poly(epsilon-caprolactone) and poly (l-lactic-co-glycolic acid) degradable polymer sponges attenuate astrocyte response and lesion growth in acute traumatic brain injury. Tissue Engineering, 13(10), 2515–2523.Wong, D. Y., Krebsbach, P. H., & Hollister, S. J. (2008). Brain cortex regeneration affected by scaffold architectures. Journal of Neurosurgery, 109(4), 715–722.Wong, D. Y., Leveque, J. C., Brumblay, H., Krebsbach, P. H., Hollister, S. J., & Lamarca, F. (2008). Macro-architectures in spinal cord scaffold implants influence regeneration. Journal of Neurotrauma, 25(8), 1027–1037.Pierucci, A., de Duek, E. A., & de Oliveira, A. L. (2008). Peripheral nerve regeneration through biodegradable conduits prepared using solvent evaporation. Tissue Engineering Part A, 14(5), 595–606.Vleggeert-Lankamp, C. L., de Ruiter, G. C., Wolfs, J. F., Pego, A. P., van den Berg, R. J., Feirabend, H. K., et al. (2007). Pores in synthetic nerve conduits are beneficial to regeneration. Journal of Biomedical Material Research Part A, 80(4), 965–982.Cai, A. Q., Landman, K. A., & Hughes, B. D. (2007). Multi-scale modeling of a wound-healing cell migration assay. Journal of Theoretical Biology, 245(3), 576–594.Maini, P. K., McElwain, D. L., & Leavesley, D. I. (2004). Traveling wave model to interpret a wound-healing cell migration assay for human peritoneal mesothelial cells. Tissue Engineering, 10(3–4), 475–482.Dokukina, I. V., & Gracheva, M. E. (2010). A model of fibroblast motility on substrates with different rigidities. Biophysical Journal, 98(12), 2794–2803.Schneider, I. C., & Haugh, J. M. (2004). Spatial analysis of 3′ phosphoinositide signaling in living fibroblasts: II. Parameter estimates for individual cells from experiments. Biophysical Journal, 86(1), 599–608.Marcy, Y., Prost, J., Carlier, M.-F., & Sykes, C. C. (2004). Forces generated during actin-based propulsion: A direct measurement by micromanipulation. Proceedings of the National academy of Sciences of the United States of America, 101(16), 5992–5997.Mogilner, A., & Oster, G. (2003). Polymer motors: Pushing out the front and pulling up the back. Current Biology, 13(18), R721–R733.Cheng, G., Youssef, B. B., Markenscoff, P., & Zygourakis, K. (2006). Cell population dynamics modulate the rates of tissue growth processes. Biophysical Journal, 90(3), 713–724.Galbusera, F., Cioffi, M., Raimondi, M. T., & Pietrabissa, R. (2007). Computational modeling of combined cell population dynamics and oxygen transport in engineered tissue subject to interstitial perfusion. Computer Methods Biomechanics and Biomedical Engineering, 10(4), 279–287.Hatzikirou, H., & Deutsch, A. (2008). Cellular automata as microscopic models of cell migration in heterogeneous environments. Current Topics in Developmental Biology, 81, 401–434.Reffay, M., Petitjean, L., Coscoy, S., Grasland-Mongrain, E., Amblard, F., Buguin, A., et al. (2011). Orientation and polarity in collectively migrating cell structures: Statics and dynamics. Biophysical Journal, 100(11), 2566–2575.Chung, C. A., Yang, C. W., & Chen, C. W. (2006). Analysis of cell growth and diffusion in a scaffold for cartilage tissue engineering. Biotechnology and Bioengineering, 94(6), 1138–1146.Dunn, J. C., Chan, W. Y., Cristini, V., Kim, J. S., Lowengrub, J., Singh, S., et al. (2006). Analysis of cell growth in three-dimensional scaffolds. Tissue Engineering, 12(4), 705–716.Harms, B. D., Bassi, G. M., Horwitz, A. R., & Lauffenburger, D. A. (2005). Directional persistence of EGF-induced cell migration is associated with stabilization of lamellipodial protrusions. Biophysical Journal, 88(2), 1479–1488.Lemon, G., & King, J. (2007). Travelling-wave behaviour in a multiphase model of a population of cells in an artificial scaffold. Journal of Mathematical Biology, 55(4), 449–480.Fisher, R. (1937). The wave of advance of advantageous genes. Annals of Eugenics, 7, 355–369.Graner, F.o., & Glazier, J. A. (1992). Simulation of biological cell sorting using a two-dimensional extended Potts model. Physical Review Letters, 69(13), 2013–2016.Ouaknin, G. Y., & Bar-Yoseph, P. Z. (2009). Stochastic collective movement of cells and fingering morphology: No maverick cells. Biophysical Journal, 97(7), 1811–1821.Savill, N. J., & Hogeweg, P. (1997). Modelling morphogenesis: From single cells to crawling slugs. Journal of Theoretical Biology, 184(3), 229–235.Brockes, J. P., Fields, K. L., & Raff, M. C. (1979). Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. Brain Research, 165, 105–118.Selinummi, J., Seppala, J., Yli-Harja, O., & Puhakka, J. A. (2005). Software for quantification of labeled bacteria from digital microscope images by automated image analysis. BioTechniques, 39(6), 859–863.Gupta, D., Venugopal, J., Prabhakaran, M. P., Dev, V. R., Low, S., Choon, A. T., et al. (2009). Aligned and random nanofibrous substrate for the in vitro culture of Schwann cells for neural tissue engineering. Acta Biomaterialia, 5(7), 2560–2569.Nisbet, D. R., Yu, L. M., Zahir, T., Forsythe, J. S., & Shoichet, M. S. (2008). Characterization of neural stem cells on electrospun poly(epsilon-caprolactone) submicron scaffolds: Evaluating their potential in neural tissue engineering. Journal of Biomaterials Science, Polymer Edition, 19(5), 623–634.Huang, Z. H., Wang, Y., Cao, L., Su, Z. D., Zhu, Y. L., Chen, Y. Z., et al. (2008). Migratory properties of cultured olfactory ensheathing cells by single-cell migration assay. Cell Research, 18, 479–490.Ekberg, J. A. K., Amaya, D., Mackay-Sim, A., & St. John, J. A. (2012). The migratory of olfactory ensheathing cells during development and regeneration. Neurosignals. doi: 10.1159/000330895 .Ruitenberg, M. J., Vukovic, J., Sarich, J., Busfield, S. J., & Plant, G..W. (2006). Olfactory ensheathing cells: characteristics, genetic engineering, and therapeutic potential. Journal of Neurotrauma, 23, 468–478.Chaikin, P. M., & Lubensky, T. C. (1995). Principles of condensed matter physics (p. 371). Cambridge, UK: Cambridge University Press.Simpson, M. J., Landman, K. A., & Hughes, B. D. (2010). Cell invasion with proliferation mechanisms motivated by time-lapse data. Physica A, 389, 3779–3790

    New Species in the Old World: Europe as a Frontier in Biodiversity Exploration, a Test Bed for 21st Century Taxonomy

    Get PDF
    The number of described species on the planet is about 1.9 million, with ca. 17,000 new species described annually, mostly from the tropics. However, taxonomy is usually described as a science in crisis, lacking manpower and funding, a politically acknowledged problem known as the Taxonomic Impediment. Using data from the Fauna Europaea database and the Zoological Record, we show that contrary to general belief, developed and heavily-studied parts of the world are important reservoirs of unknown species. In Europe, new species of multicellular terrestrial and freshwater animals are being discovered and named at an unprecedented rate: since the 1950s, more than 770 new species are on average described each year from Europe, which add to the 125,000 terrestrial and freshwater multicellular species already known in this region. There is no sign of having reached a plateau that would allow for the assessment of the magnitude of European biodiversity. More remarkably, over 60% of these new species are described by non-professional taxonomists. Amateurs are recognized as an essential part of the workforce in ecology and astronomy, but the magnitude of non-professional taxonomist contributions to alpha-taxonomy has not been fully realized until now. Our results stress the importance of developing a system that better supports and guides this formidable workforce, as we seek to overcome the Taxonomic Impediment and speed up the process of describing the planetary biodiversity before it is too late

    Describing the status of reproductive ageing simply and precisely: A reproductive ageing score based on three questions and validated with hormone levels

    Get PDF
    Equation 6. Quadratic logistic function approximating the function mu(B)(with age in years). Equation 1. Proportion of women who have regular menstruation for each number of reported menstruations in the last year(with period = number of periods per year, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months" and z = number of women answering "No, my periods have stopped", e.g. x(11) = number of women reporting regular menstruation among those who report 11 menstruations in the last 12 months). Equation 5. Biquadratic exponential function mu(A)depending of the number of periods. Equation 3. Age modification by smoking and oophorectomy. Equation 2. Proportion of women whose menstruations have already stopped, for each reported year of age(with age = age in years, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months", z = number of women answering "No, my periods have stopped", e.g. x(40) = number of women reporting regular menstruations among those who are 40 years old). Equation 7. Final formula to calculate the reproductive ageing score (RAS)(with period being the number of periods per year and age as the age in years, modified according to smoking status and oophorectomy). Objective Most women live to experience menopause and will spend 4-8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause;categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers. Methods Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17 beta-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC). Results The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90-0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83-0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women. Conclusions: The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials. Equation 4. The reproductive ageing score as an aggregation function of mu(A)and mu(B)

    Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models

    Get PDF
    Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments. In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors. SIGNIFICANCE: Delta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs

    Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

    Get PDF
    OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

    The state of the Martian climate

    Get PDF
    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Overview of recent TJ-II stellarator results

    Get PDF
    The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

    Peripheral and central arterial pressure and its relationship to vascular target organ damage in carotid artery, retina and arterial stiffness. Development and validation of a tool. The Vaso risk study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Ambulatory blood pressure monitoring (ABPM) shows a better correlation to target organ damage and cardiovascular morbidity-mortality than office blood pressure. A loss of arterial elasticity and an increase in carotid artery intima-media thickness (IMT) has been associated with increased cardiovascular morbidity-mortality. Tools have been developed that allow estimation of the retinal arteriovenous index but not all studies coincide and there are contradictory results in relation to the evolution of the arteriosclerotic lesions and the caliber of the retinal vessels. The purpose of this study is to analyze the relationship between peripheral and central arterial pressure (clinic and ambulatory) and vascular structure and function as evaluated by the carotid artery intima-media thickness, retina arteriovenous index, pulse wave velocity (PWV) and ankle-brachial index in patients with and without type 2 diabetes. In turn, software is developed and validated for measuring retinal vessel thickness and automatically estimating the arteriovenous index.</p> <p>Methods/Design</p> <p>A cross-sectional study involving a control group will be made, with a posterior 4-year follow-up period in primary care. The study patients will be type 2 diabetics, with a control group of non-diabetic individuals. Consecutive sampling will be used to include 300 patients between 34-75 years of age and no previous cardiovascular disease, one-half being assigned to each group. Main measurements: age, gender, height, weight and abdominal circumference. Lipids, creatinine, microalbuminuria, blood glucose, HbA1c, blood insulin, high sensitivity C-reactive protein and endothelial dysfunction markers. Clinic and ambulatory blood pressure monitoring. Carotid ultrasound to evaluate IMT, and retinography to evaluate the arteriovenous index. ECG to assess left ventricle hypertrophy, ankle-brachial index, and pulse wave analysis (PWA) and pulse wave velocity (PWV) with the Sphigmocor System.</p> <p>Discussion</p> <p>We hope to obtain information on the correlation of different ABPM-derived parameters and PWA to organ target damage - particularly vascular structure and function evaluated from the IMT and PWV - and endothelial dysfunction in patients with and without type 2 diabetes. We also hope to demonstrate the usefulness of the instrument developed for the automated evaluation of retinal vascularization in the early detection of alterations in vascular structure and function and in the prognosis of middle-term cardiovascular morbidity.</p> <p>Trial Registration</p> <p>Clinical Trials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01325064">NCT01325064</a></p
    corecore