Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme

Vitamin D and its analogs have been shown to display anti-proliferative effects in a wide variety of cancer types including glioblastoma multiforme (GBM). These anticancer effects are mediated by its active metabolite, 1α, 25-dihydroxyvitamin D3 (calcitriol) acting mainly through vitamin D receptor (VDR) signaling. In addition to its involvement in calcitriol action, VDR has also been demonstrated to be useful as a prognostic factor for some types of cancer. However, to our knowledge, there are no studies evaluating the expression of VDR protein and its association with outcome in gliomas. Therefore, we investigated VDR expression by using immunohistochemical analysis in human glioma tissue microarrays, and analyzed the association between VDR expression and clinico-pathological parameters. We further investigated the effects of genetic and pharmacologic modulation of VDR on survival and migration of glioma cell lines. Our data demonstrate that VDR is increased in tumor tissues when compared with VDR in non-malignant brains, and that VDR expression is associated with an improved outcome in patients with GBM. We also show that both genetic and pharmacologic modulation of VDR modulates GBM cellular migration and survival and that VDR is necessary for calcitriol-mediated effects on migration. Altogether these results provide some limited evidence supporting a role for VDR in glioma progression.Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Ferronato, María Julia. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Arevalo, Julian. Hospital Municipal General de Agudos Doctor José Penna; ArgentinaFil: Blasco, J.. Hospital Int. Gral. de Agudos Dr. Jose Penna. Servicio de Patologia; ArgentinaFil: Andrés, Nancy Carolina. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Zenklusen, Jean C.. National Institutes of Health. National Cancer Institute; Estados UnidosFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentin

Measure-Based Inconsistency-Tolerant Maintenance of Database Integrity

[EN] To maintain integrity, constraint violations should be prevented or repaired. However, it may not be feasible to avoid inconsistency, or to repair all violations at once. Based on an abstract concept of violation measures, updates and repairs can be checked for keeping inconsistency bounded, such that integrity violations are guaranteed to never get out of control. This measure-based approach goes beyond conventional methods that are not meant to be applied in the presence of inconsistency. It also generalizes recently introduced concepts of inconsistency-tolerant integrity maintenance.Partially supported by FEDER and the Spanish grants TIN2009-14460-C03 and TIN2010-17139Decker, H. (2013). Measure-Based Inconsistency-Tolerant Maintenance of Database Integrity. Lecture Notes in Computer Science. 7693:149-173. https://doi.org/10.1007/978-3-642-36008-4_7S1491737693Abiteboul, S., Hull, R., Vianu, V.: Foundations of Databases. Addison-Wesley (1995)Abiteboul, S., Vianu, V.: A transaction-based approach to relational database specification. JACM 36(4), 758–789 (1989)Afrati, F., Kolaitis, P.: Repair checking in inconsistent databases: algorithms and complexity. In: 12th ICDT, pp. 31–41. ACM Press (2009)Arenas, M., Bertossi, L., Chomicki, J.: Consistent query answers in inconsistent databases. In: PODS 1999, pp. 68–79. ACM Press (1999)Arieli, O., Denecker, M., Bruynooghe, M.: Distance semantics for database repair. Ann. Math. Artif. Intell. 50, 389–415 (2007)Arni-Bloch, N., Ralyté, J., Léonard, M.: Service–Driven Information Systems Evolution: Handling Integrity Constraints Consistency. In: Persson, A., Stirna, J. (eds.) PoEM 2009. LNBIP, vol. 39, pp. 191–206. Springer, Heidelberg (2009)Bauer, H.: Maß- und Integrationstheorie, 2. Auflage. De Gruyter (1992)Besnard, P., Hunter, A.: Quasi-Classical Logic: Non-Trivializable Classical Reasoning from Inconsistent Information. In: Froidevaux, C., Kohlas, J. (eds.) ECSQARU 1995. LNCS, vol. 946, pp. 44–51. Springer, Heidelberg (1995)Bohanon, P., Fan, W., Flaster, M., Rastogi, R.: A Cost-Based Model and Effective Heuristic for Repairing Constraints by Value Modification. In: Proc. SIGMOD 2005, pp. 143–154. ACM Press (2005)Ceri, S., Cochrane, R., Widom, J.: Practical Applications of Triggers and Constraints: Success and Lingering Issues. In: Proc. 26th VLDB, pp. 254–262. Morgan Kaufmann (2000)Chakravarthy, U., Grant, J., Minker, J.: Logic-based Approach to Semantic Query Optimization. Transactions on Database Systems 15(2), 162–207 (1990)Chomicki, J.: Consistent Query Answering: Five Easy Pieces. In: Schwentick, T., Suciu, D. (eds.) ICDT 2007. LNCS, vol. 4353, pp. 1–17. Springer, Heidelberg (2006)Christiansen, H., Martinenghi, D.: On simplification of database integrity constraints. Fundamenta Informaticae 71(4), 371–417 (2006)Clark, K.: Negation as Failure. In: Gallaire, H., Minker, J. (eds.) Logic and Data Bases, pp. 293–322. Plenum Press (1978)Curino, C., Moon, H., Deutsch, A., Zaniolo, C.: Update Rewriting and Integrity Constraint Maintenance in a Schema Evolution Support System: PRISM++. PVLDB 4, 117–128 (2010)Dawson, J.: The compactness of first-order logic: From Gödel to Lindström. History and Philosophy of Logic 14(1), 15–37 (1993)Decker, H.: The Range Form of Databases and Queries or: How to Avoid Floundering. In: Proc. 5th ÖGAI. Informatik-Fachberichte, vol. 208, pp. 114–123. Springer (1989)Decker, H.: Drawing Updates From Derivations. In: Kanellakis, P.C., Abiteboul, S. (eds.) ICDT 1990. LNCS, vol. 470, pp. 437–451. Springer, Heidelberg (1990)Decker, H.: Extending Inconsistency-Tolerant Integrity Checking by Semantic Query Optimization. In: Bhowmick, S.S., Küng, J., Wagner, R. (eds.) DEXA 2008. LNCS, vol. 5181, pp. 89–96. Springer, Heidelberg (2008)Decker, H.: Answers That Have Integrity. In: Schewe, K.-D., Thalheim, B. (eds.) SDKB 2010. LNCS, vol. 6834, pp. 54–72. Springer, Heidelberg (2011)Decker, H.: Causes of the Violation of Integrity Constraints for Supporting the Quality of Databases. In: Murgante, B., Gervasi, O., Iglesias, A., Taniar, D., Apduhan, B.O. (eds.) ICCSA 2011, Part V. LNCS, vol. 6786, pp. 283–292. Springer, Heidelberg (2011)Decker, H.: Inconsistency-tolerant Integrity Checking based on Inconsistency Metrics. In: König, A., Dengel, A., Hinkelmann, K., Kise, K., Howlett, R.J., Jain, L.C. (eds.) KES 2011, Part II. LNCS, vol. 6882, pp. 548–558. Springer, Heidelberg (2011)Decker, H.: Partial Repairs that Tolerate Inconsistency. In: Eder, J., Bielikova, M., Tjoa, A.M. (eds.) ADBIS 2011. LNCS, vol. 6909, pp. 389–400. Springer, Heidelberg (2011)Decker, H.: Consistent Explanations of Answers to Queries in Inconsistent Knowledge Bases. In: Roth-Berghofer, T., Tintarev, N., Leake, D. (eds.) Explanation-aware Computing, Proc. IJCAI 2011 Workshop ExaCt 2011, pp. 71–80 (2011), http://exact2011.workshop.hm/index.phpDecker, H., Martinenghi, D.: Classifying integrity checking methods with regard to inconsistency tolerance. In: Proc. PPDP 2008, pp. 195–204. ACM Press (2008)Decker, H., Martinenghi, D.: Modeling, Measuring and Monitoring the Quality of Information. In: Heuser, C.A., Pernul, G. (eds.) ER 2009. LNCS, vol. 5833, pp. 212–221. Springer, Heidelberg (2009)Decker, H., Martinenghi, D.: Inconsistency-tolerant Integrity Checking. IEEE TKDE 23(2), 218–234 (2011)Decker, H., Muñoz-Escoí, F.D.: Revisiting and Improving a Result on Integrity Preservation by Concurrent Transactions. In: Meersman, R., Dillon, T., Herrero, P. (eds.) OTM 2010 Workshops. LNCS, vol. 6428, pp. 297–306. Springer, Heidelberg (2010)Dung, P., Kowalski, R., Toni, F.: Dialectic Proof Procedures for Assumption-based Admissible Argumentation. Artificial Intelligence 170(2), 114–159 (2006)Ebbinghaus, H.-D., Flum, J.: Finite Model Theory, 2nd edn. Springer (2006)Embury, S., Brandt, S., Robinson, J., Sutherland, I., Bisby, F., Gray, A., Jones, A., White, R.: Adapting integrity enforcement techniques for data reconciliation. Information Systems 26, 657–689 (2001)Enderton, H.: A Mathematical Introduction to Logic, 2nd edn. Academic Press (2001)Eiter, T., Fink, M., Greco, G., Lembo, D.: Repair localization for query answering from inconsistent databases. ACM TODS 33(2), article 10 (2008)Furfaro, F., Greco, S., Molinaro, C.: A three-valued semantics for querying and repairing inconsistent databases. Ann. Math. Artif. Intell. 51(2-4), 167–193 (2007)Grant, J., Hunter, A.: Measuring the Good and the Bad in Inconsistent Information. In: Proc. 22nd IJCAI, pp. 2632–2637 (2011)Greco, G., Greco, S., Zumpano, E.: A logical framework for querying and repairing inconsistent databases. IEEE TKDE 15(6), 1389–1408 (2003)Guessoum, A., Lloyd, J.: Updating knowledge bases. New Generation Computing 8(1), 71–89 (1990)Guessoum, A., Lloyd, J.: Updating knowledge bases II. New Generation Computing 10(1), 73–100 (1991)Gupta, A., Sagiv, Y., Ullman, J., Widom, J.: Constraint checking with partial information. In: Proc. PODS 1994, pp. 45–55. ACM Press (1994)Hunter, A.: Measuring Inconsistency in Knowledge via Quasi-Classical Models. In: Proc. 18th AAAI &14th IAAI, pp. 68–73 (2002)Hunter, A., Konieczny, S.: Approaches to Measuring Inconsistent Information. In: Bertossi, L., Hunter, A., Schaub, T. (eds.) Inconsistency Tolerance. LNCS, vol. 3300, pp. 191–236. Springer, Heidelberg (2005)Hunter, A., Konieczny, S.: Measuring inconsistency through minimal inconsistent sets. In: Brewka, G., Lang, J. (eds.) Principles of Knowledge Representation and Reasoning (Proc. 11th KR), pp. 358–366. AAAI Press (2008)Hunter, A., Konieczny, S.: On the measure of conflicts: Shapley Inconsistency Values. Artificial Intelligence 174, 1007–1026 (2010)Kakas, A., Mancarella, P.: Database updates through abduction. In: Proc. 16th VLDB, pp. 650–661. Morgan Kaufmann (1990)Kakas, A., Kowalski, R., Toni, F.: The role of Abduction in Logic Programming. In: Gabbay, D., Hogger, C., Robinson, J.A. (eds.) Handbook of Logic in Artificial Intelligence and Logic Programming, vol. 5, pp. 235–324. Oxford University Press (1998)Lee, S.Y., Ling, T.W.: Further improvements on integrity constraint checking for stratifiable deductive databases. In: Proc. VLDB 1996, pp. 495–505. Morgan Kaufmann (1996)Lehrer, K.: Relevant Deduction and Minimally Inconsistent Sets. Journal of Philosophy 3(2,3), 153–165 (1973)Mu, K., Liu, W., Jin, Z., Bell, D.: A Syntax-based Approach to Measuring the Degree of Inconsistency for Belief Bases. J. Approx. Reasoning 52(7), 978–999 (2011)Lloyd, J., Sonenberg, L., Topor, R.: Integrity constraint checking in stratified databases. J. Logic Programming 4(4), 331–343 (1987)Lozinskii, E.: Resolving contradictions: A plausible semantics for inconsistent systems. J. Automated Reasoning 12(1), 1–31 (1994)Ma, Y., Qi, G., Hitzler, P.: Computing inconsistency measure based on paraconsistent semantics. J. Logic Computation 21(6), 1257–1281 (2011)Martinenghi, D., Christiansen, H.: Transaction Management with Integrity Checking. In: Andersen, K.V., Debenham, J., Wagner, R. (eds.) DEXA 2005. LNCS, vol. 3588, pp. 606–615. Springer, Heidelberg (2005)Martinenghi, D., Christiansen, H., Decker, H.: Integrity Checking and Maintenance in Relational and Deductive Databases and Beyond. In: Ma, Z. (ed.) Intelligent Databases: Technologies and Applications, pp. 238–285. IGI Global (2006)Martinez, M.V., Pugliese, A., Simari, G.I., Subrahmanian, V.S., Prade, H.: How Dirty Is Your Relational Database? An Axiomatic Approach. In: Mellouli, K. (ed.) ECSQARU 2007. LNCS (LNAI), vol. 4724, pp. 103–114. Springer, Heidelberg (2007)Meyer, J., Wieringa, R. (eds.): Deontic Logic in Computer Science. Wiley (1994)Nicolas, J.M.: Logic for improving integrity checking in relational data bases. Acta Informatica 18, 227–253 (1982)Plexousakis, D., Mylopoulos, J.: Accommodating Integrity Constraints During Database Design. In: Apers, P.M.G., Bouzeghoub, M., Gardarin, G. (eds.) EDBT 1996. LNCS, vol. 1057, pp. 495–513. Springer, Heidelberg (1996)Rahm, E., Do, H.: Data Cleaning: Problems and Current Approaches. Data Engineering Bulletin 23(4), 3–13 (2000)Sadri, F., Kowalski, R.: A theorem-proving approach to database integrity. In: Minker, J. (ed.) Foundations of Deductive Databases and Logic Programming, pp. 313–362. Morgan Kaufmann (1988)Thimm, M.: Measuring Inconsistency in Probabilistic Knowledge Bases. In: Proc. 25th UAI, pp. 530–537. AUAI Press (2009)Vardi, M.: On the integrity of databases with incomplete information. In: Proc. 5th PODS, pp. 252–266. ACM Press (1986)Wijsen, J.: Database repairing using updates. ACM Trans. Database Syst. 30(3), 722–768 (2005

Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed

Hemoxygenase-1 Promotes Head and Neck Cancer Cell Viability

Head and neck squamous cell carcinoma (HNSCC) is a remarkably heterogeneous disease with around 50% mortality, a fact that has prompted researchers to try new approaches to improve patient survival. Hemoxygenase-1 (HO-1) is the rate-limiting step for heme degradation into carbon monoxide, free iron and biliverdin. We have previously reported that HO-1 protein is upregulated in human HNSCC samples and that it is localized in the cytoplasmic and nuclear compartments; additionally, we have demonstrated that HO-1 nuclear localization is associated with malignant progression. In this work, by using pharmacological and genetic experimental approaches, we begin to elucidate the mechanisms through which HO-1 plays a role in HNSCC. We found that high HO-1 mRNA was associated with decreased patient survival in early stages of HNSCC. In vitro experiments have shown that full-length HO-1 localizes in the cytoplasm, and that, depending on its enzymatic activity, it increases cell viability and promotes cell cycle progression. Instead, HO-1 does not alter migration capacity. Furthermore, we show that C-terminal truncated HO-1 localizes into the nucleus, increases cell viability and promotes cell cycle progression. In conclusion, we herein demonstrate that HO-1 displays protumor activities in HNSCC that depend, at least in part, on the nuclear localization of HO-1.Centro de Investigaciones Inmunológicas Básicas y Aplicada

Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer

We thank the patients who participated in this study; Professor Gerry Thomas and the Imperial College Healthcare NHS Trust, Human Biomaterials Resource Centre (Tissue Bank); Professor Clare M Isacke (Institute of Cancer Research, London) for Endo180 antibodies; Dr Richard Harvey (Department of Medical Oncology, Imperial College Healthcare NHS Trust) for CA 15-3 antigen measurement. The Division of Cancer at Imperial College London, Imperial College Healthcare NHS Trust is an Experimental Cancer Medicine Centre (ECMC) supported by funds from Cancer Research UK and the Department of Health (C37/A7283) and forms part of Imperial Cancer Research UK Centre (C42671/A12196). CP is recipient of a CRUK Clinician Scientist award. JW is The Flow Foundation Professor of Oncology at Imperial College London. MPC and GK were supported by donations from Tony and Rita Gallagher and Imperial College NHS Healthcare Trust Special Trustees (to JW and JS). MPC was funded by The Rosetrees Trust (Grant JS16/M59; to JW and JS). A-VF was funded by Fundação para a Ciência e Tecnologia fellowship (project supervisor: JS) and Imperial College NHS Healthcare Special Trustees (to JW and JS). MR-T was funded by the Association of International Cancer Research (Grant 08-0803 to JS)