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    Photosensitised pyrimidine dimerisation in DNA

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    Triplet-mediated pyrimidine (Pyr) dimerisation is a key process in photochemical damage to DNA. It may occur in the presence of a photosensitiser, provided that a number of requirements are fulfilled, such as favourable intersystem crossing quantum yield and high triplet energy. The attention has been mainly focused on cyclobutane pyrimidine dimers, as they are by far the most relevant Pyr photoproducts obtained by sensitisation. The present perspective deals with the involved chemistry, not only in DNA but also in its simple building blocks. It also includes the photophysical characterisation of the Pyr triplet excited states, as well as a brief discussion of the theoretical aspects.Financial support from the Spanish Government (CTQ2009-13699, CTQ2009-14196, JAE Doc fellowship for M. C. C. and Ramon y Cajal contract for V. L.-V.) and EU (CM0603) is gratefully acknowledged.Bosca Mayans, F.; Lhiaubet, VL.; Cuquerella Alabort, MC.; Miranda Alonso, MÁ. (2011). Photosensitised pyrimidine dimerisation in DNA. Chemical Science. 2(7):1219-1232. https://doi.org/10.1039/c1sc00088h1219123227The Lancet Oncology. (2009). Beauty and the beast. The Lancet Oncology, 10(9), 835. doi:10.1016/s1470-2045(09)70243-8Mouret, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2006). Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proceedings of the National Academy of Sciences, 103(37), 13765-13770. doi:10.1073/pnas.0604213103Setlow, R. B., Grist, E., Thompson, K., & Woodhead, A. D. (1993). Wavelengths effective in induction of malignant melanoma. Proceedings of the National Academy of Sciences, 90(14), 6666-6670. doi:10.1073/pnas.90.14.6666Rochette, P. J. (2003). UVA-induced cyclobutane pyrimidine dimers form predominantly at thymine-thymine dipyrimidines and correlate with the mutation spectrum in rodent cells. Nucleic Acids Research, 31(11), 2786-2794. doi:10.1093/nar/gkg402Mitchell, D. L., Fernandez, A. A., Nairn, R. S., Garcia, R., Paniker, L., Trono, D., 
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    Bridges of biomaterials promote nigrostriatal pathway regeneration

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    [EN] Repair of central nervous system (CNS) lesions is difficulted by the lack of ability of central axons to regrow, and the blocking by the brain astrocytes to axonal entry. We hypothesized that by using bridges made of porous biomaterial and permissive olfactory ensheathing glia (OEG), we could provide a scaffold to permit restoration of white matter tracts. We implanted porous polycaprolactone (PCL) bridges between the substantia nigra and the striatum in rats, both with and without OEG. We compared the number of tyrosine-hydroxylase positive (TH+) fibers crossing the striatal-graft interface, and the astrocytic and microglial reaction around the grafts, between animals grafted with and without OEG. Although TH+ fibers were found inside the grafts made of PCL alone, there was a greater fiber density inside the graft and at the striatal-graft interface when OEG was cografted. Also, there was less astrocytic and microglial reaction in those animals. These results show that these PCL grafts are able to promote axonal growth along the nigrostriatal pathway, and that cografting of OEG markedly enhances axonal entry inside the grafts, growth within them, and re-entry of axons into the CNS. These results may have implications in the treatment of diseases such as Parkinson's and others associated with lesions of central white matter tracts.Contract grant sponsor: Regional Government Health Department (Conselleria de Sanitat, Generalitat Valenciana) and Carlos III Health Institute of the Ministry of Health and Consumer Affairs (Spain) (Regenerative Medicine Programme) Contract grant sponsor: Spanish ministry of Education and Science; contract grant number: MAT 2006-13554-C02-02 Contract grant sponsor: Red de Terapia Celular TERCEL (RETICS), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion (ISCIII); contract grant number: RD12/0019/0010 (to J.A.) Contract grant sponsor: Spanish Science & Innovation Ministery; contract grant number: MAT2008-06434 (to M.M.P.) Contract grant sponsor: "Convenio de Colaboracion para la Investigacion Basica y Traslacional en Medicina Regenerativa," Instituto Nacional de Salud Carlos III, the Conselleria de Sanidad of the Generalitat Valenciana, and the Foundation Centro de Investigacion Principe FelipeGĂłmez Pinedo, U.; Sanchez-Rojas, L.; Vidueira, S.; Sancho, FJ.; MartĂ­nez-Ramos, C.; Lebourg, M.; MonleĂłn Pradas, M.... (2019). Bridges of biomaterials promote nigrostriatal pathway regeneration. Journal of Biomedical Materials Research Part B Applied Biomaterials. 107(1):190-196. https://doi.org/10.1002/jbm.b.34110S1901961071Pekny, M., Wilhelmsson, U., & Pekna, M. (2014). The dual role of astrocyte activation and reactive gliosis. Neuroscience Letters, 565, 30-38. doi:10.1016/j.neulet.2013.12.071Bliss, T. M., Andres, R. H., & Steinberg, G. K. (2010). Optimizing the success of cell transplantation therapy for stroke. Neurobiology of Disease, 37(2), 275-283. doi:10.1016/j.nbd.2009.10.003Tam, R. Y., Fuehrmann, T., Mitrousis, N., & Shoichet, M. S. (2013). Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach. Neuropsychopharmacology, 39(1), 169-188. doi:10.1038/npp.2013.237Skop, N. B., Calderon, F., Cho, C. H., Gandhi, C. D., & Levison, S. W. (2014). Improvements in biomaterial matrices for neural precursor cell transplantation. Molecular and Cellular Therapies, 2(1), 19. doi:10.1186/2052-8426-2-19Yasuhara, T., Kameda, M., Sasaki, T., Tajiri, N., & Date, I. (2017). Cell Therapy for Parkinson’s Disease. Cell Transplantation, 26(9), 1551-1559. doi:10.1177/0963689717735411Orive, G., Anitua, E., Pedraz, J. L., & Emerich, D. F. (2009). Biomaterials for promoting brain protection, repair and regeneration. Nature Reviews Neuroscience, 10(9), 682-692. doi:10.1038/nrn2685Walker, P. A., Aroom, K. R., Jimenez, F., Shah, S. K., Harting, M. T., Gill, B. S., & Cox, C. S. (2009). Advances in Progenitor Cell Therapy Using Scaffolding Constructs for Central Nervous System Injury. Stem Cell Reviews and Reports, 5(3), 283-300. doi:10.1007/s12015-009-9081-1Zhong, Y., & Bellamkonda, R. V. (2008). Biomaterials for the central nervous system. Journal of The Royal Society Interface, 5(26), 957-975. doi:10.1098/rsif.2008.0071PĂ©rez‐GarnezM BarciaJA GĂłmez‐PinedoU MonleĂłn‐PradasM VallĂ©s‐LluchA.Materials for Central Nervous System Tissue Engineering Cells and Biomaterials in Regenerative Medicine. InTech;2014. Chap 7.Sinha, V. R., Bansal, K., Kaushik, R., Kumria, R., & Trehan, A. (2004). Poly-Ï”-caprolactone microspheres and nanospheres: an overview. International Journal of Pharmaceutics, 278(1), 1-23. doi:10.1016/j.ijpharm.2004.01.044Raisman, G. (2001). Olfactory ensheathing cells — another miracle cure for spinal cord injury? Nature Reviews Neuroscience, 2(5), 369-375. doi:10.1038/35072576Raisman, G., & Li, Y. (2007). Repair of neural pathways by olfactory ensheathing cells. Nature Reviews Neuroscience, 8(4), 312-319. doi:10.1038/nrn2099Fairless, R., & Barnett, S. C. (2005). Olfactory ensheathing cells: their role in central nervous system repair. The International Journal of Biochemistry & Cell Biology, 37(4), 693-699. doi:10.1016/j.biocel.2004.10.010Collins, A., Li, D., Mcmahon, S. B., Raisman, G., & Li, Y. (2017). Transplantation of Cultured Olfactory Bulb Cells Prevents Abnormal Sensory Responses during Recovery from Dorsal Root Avulsion in the Rat. Cell Transplantation, 26(5), 913-924. doi:10.3727/096368917x695353Navarro, X., Valero, A., Gudiïżœo, G., Forïżœs, J., Rodrïżœguez, F. J., Verdïżœ, E., 
 Nieto-Sampedro, M. (1999). Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy. Annals of Neurology, 45(2), 207-215. doi:10.1002/1531-8249(199902)45:23.0.co;2-kGĂłmez-Pinedo, U., FĂ©lez, M. C., Sancho-Bielsa, F. J., Vidueira, S., Cabanes, C., Soriano, M., 
 Barcia, J. A. (2008). Improved technique for stereotactic placement of nerve grafts between two locations inside the rat brain. Journal of Neuroscience Methods, 174(2), 194-201. doi:10.1016/j.jneumeth.2008.07.008HowardCV ReedMG.Unbiased Stereology: Three‐Dimensional Measurement in Microscopy. Oxford: Bioimaging Group;1998.Collier, T. J., & Springer, J. E. (1991). Co-grafts of embryonic dopamine neurons and adult sciatic nerve into the denervated striatum enhance behavioral and morphological recovery in rats. Experimental Neurology, 114(3), 343-350. doi:10.1016/0014-4886(91)90160-eBourke, J. L., Coleman, H. A., Pham, V., Forsythe, J. S., & Parkington, H. C. (2014). Neuronal Electrophysiological Function and Control of Neurite Outgrowth on Electrospun Polymer Nanofibers Are Cell Type Dependent. Tissue Engineering Part A, 20(5-6), 1089-1095. doi:10.1089/ten.tea.2013.0295Nga, V. D. W., Lim, J., Choy, D. K. S., Nyein, M. A., Lu, J., Chou, N., 
 Teoh, S.-H. (2015). Effects of Polycaprolactone-Based Scaffolds on the Blood–Brain Barrier and Cerebral Inflammation. Tissue Engineering Part A, 21(3-4), 647-653. doi:10.1089/ten.tea.2013.0779PĂ©rez-GarnĂ©s, M., MartĂ­nez-Ramos, C., Barcia, J. A., Escobar Ivirico, J. L., GĂłmez-Pinedo, U., VallĂ©s-Lluch, A., & MonleĂłn Pradas, M. (2012). One-Dimensional Migration of Olfactory Ensheathing Cells on Synthetic Materials: Experimental and Numerical Characterization. Cell Biochemistry and Biophysics, 65(1), 21-36. doi:10.1007/s12013-012-9399-1Diban, N., Ramos-Vivas, J., Remuzgo-Martinez, S., Ortiz, I., & Urtiaga, A. (2015). Poly(ε-caprolactone) Films with Favourable Properties for Neural Cell Growth. Current Topics in Medicinal Chemistry, 14(23), 2743-2749. doi:10.2174/156802661466614121515393

    On the Number of Edges of Fan-Crossing Free Graphs

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    A graph drawn in the plane with n vertices is k-fan-crossing free for k > 1 if there are no k+1 edges g,e1,...ekg,e_1,...e_k, such that e1,e2,...eke_1,e_2,...e_k have a common endpoint and gg crosses all eie_i. We prove a tight bound of 4n-8 on the maximum number of edges of a 2-fan-crossing free graph, and a tight 4n-9 bound for a straight-edge drawing. For k > 2, we prove an upper bound of 3(k-1)(n-2) edges. We also discuss generalizations to monotone graph properties

    Analogies between the crossing number and the tangle crossing number

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    Tanglegrams are special graphs that consist of a pair of rooted binary trees with the same number of leaves, and a perfect matching between the two leaf-sets. These objects are of use in phylogenetics and are represented with straightline drawings where the leaves of the two plane binary trees are on two parallel lines and only the matching edges can cross. The tangle crossing number of a tanglegram is the minimum crossing number over all such drawings and is related to biologically relevant quantities, such as the number of times a parasite switched hosts. Our main results for tanglegrams which parallel known theorems for crossing numbers are as follows. The removal of a single matching edge in a tanglegram with nn leaves decreases the tangle crossing number by at most n−3n-3, and this is sharp. Additionally, if Îł(n)\gamma(n) is the maximum tangle crossing number of a tanglegram with nn leaves, we prove 12(n2)(1−o(1))≀γ(n)<12(n2)\frac{1}{2}\binom{n}{2}(1-o(1))\le\gamma(n)<\frac{1}{2}\binom{n}{2}. Further, we provide an algorithm for computing non-trivial lower bounds on the tangle crossing number in O(n4)O(n^4) time. This lower bound may be tight, even for tanglegrams with tangle crossing number Θ(n2)\Theta(n^2).Comment: 13 pages, 6 figure
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