Short‐term effects of a modified A lt‐ RAMEC protocol for early treatment of C lass III malocclusion: a controlled study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109361/1/ocr12051.pd

Are periodontitis and psoriasis associated? A pre-clinical murine model

Aim: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models. Materials and Methods: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm(2)]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-alpha) were collected. Results: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm(2)) compared to the control group (p <.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p <.05). Conclusions: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation

Skin rash and response to cetuximab treatment: a retrospective single-center analysis

Background: The standard of care for patients with recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) not susceptible for surgery or reirradiation is chemotherapy with 5-FU and cisplatin plus cetuximab. Skin rash (SR) is a common adverse event of cetuximab. In patients treated with cetuximab for colorectal cancer there is strong evidence of a better outcome in those who undergo moderate or high grade of SR, and some retrospective data seem to confirm this finding in HNSCC. We report our experience. Materials and methods: We retrospectively reviewed 107 patients treated with cetuximab for R/M HNSCC from January 2014 to December 2016. Patients were divided in two groups by the grade of SR (G0-1 and G2-4), conforming to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Progression-free survival (PFS) was computed as time of progression or death since the date of assessment of recurrent/metastatic disease. Overall response rate (ORR) was computed as the sum of partial and complete responses and evaluated according to RECIST 1.1. PFS and ORR were correlated to the grade of rash. Results: 67 patients were evaluable for PFS: among them PFS was significantly longer (p 0.0014) in those who underwent a G2-4 rash (9,3 months) vs G0-1 (4,9 months). Hazard Ratio was 2,445 (CI 1.412-4.232). 95 patients were evaluable for ORR: among them G0-1 group had 4,2%, while G2-4 group had 36,8% of ORR. Conclusions: Our results support data of literature on improved outcome according to the development of skin rash in HNSCC. SR might be considered a predictive marker of response in these patients; nonetheless further ad hoc studies would be interesting

Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity

Recent studies have revealed an important role for hormones in plant immunity. We are now beginning to understand the contribution of crosstalk among different hormone signaling networks to the outcome of plant–pathogen interactions. Cytokinins are plant hormones that regulate development and responses to the environment. Cytokinin signaling involves a phosphorelay circuitry similar to two-component systems used by bacteria and fungi to perceive and react to various environmental stimuli. In this study, we asked whether cytokinin and components of cytokinin signaling contribute to plant immunity. We demonstrate that cytokinin levels in Arabidopsis are important in determining the amplitude of immune responses, ultimately influencing the outcome of plant–pathogen interactions. We show that high concentrations of cytokinin lead to increased defense responses to a virulent oomycete pathogen, through a process that is dependent on salicylic acid (SA) accumulation and activation of defense gene expression. Surprisingly, treatment with lower concentrations of cytokinin results in increased susceptibility. These functions for cytokinin in plant immunity require a host phosphorelay system and are mediated in part by type-A response regulators, which act as negative regulators of basal and pathogen-induced SA–dependent gene expression. Our results support a model in which cytokinin up-regulates plant immunity via an elevation of SA–dependent defense responses and in which SA in turn feedback-inhibits cytokinin signaling. The crosstalk between cytokinin and SA signaling networks may help plants fine-tune defense responses against pathogens

An allele of Arabidopsis COI1 with hypo- and hypermorphic phenotypes in plant growth, defence and fertility

Resistance to biotrophic pathogens is largely dependent on the hormone salicylic acid (SA) while jasmonic acid (JA) regulates resistance against necrotrophs. JA negatively regulates SA and is, in itself, negatively regulated by SA. A key component of the JA signal transduction pathway is its receptor, the COI1 gene. Mutations in this gene can affect all the JA phenotypes, whereas mutations in other genes, either in JA signal transduction or in JA biosynthesis, lack this general effect. To identify components of the part of the resistance against biotrophs independent of SA, a mutagenised population of NahG plants (severely depleted of SA) was screened for suppression of susceptibility. The screen resulted in the identification of intragenic and extragenic suppressors, and the results presented here correspond to the characterization of one extragenic suppressor, coi1-40. coi1-40 is quite different from previously described coi1 alleles, and it represents a strategy for enhancing resistance to biotrophs with low levels of SA, likely suppressing NahG by increasing the perception to the remaining SA. The phenotypes of coi1-40 lead us to speculate about a modular function for COI1, since we have recovered a mutation in COI1 which has a number of JA-related phenotypes reduced while others are equal to or above wild type levels.This work was supported by grant BIO201018896 from "Ministerio de Economia y Competitividad" (MINECO) of Spain and by grant ACOMP/2012/105 from "Generalitat Valenciana" to PT, a JAE-CSIC Fellowship to JVC, a FPI-MINECO to AD, and Fellowships from the European Molecular Biology Organization and the Human Frontier Science Program to BBHW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Dobón Alonso, A.; Wulff, BBH.; Canet Perez, JV.; Fort Rausell, P.; Tornero Feliciano, P. (2013). An allele of Arabidopsis COI1 with hypo- and hypermorphic phenotypes in plant growth, defence and fertility. PLoS ONE. 1(8):55115-55115. https://doi.org/10.1371/journal.pone.0055115S551155511518Vlot, A. C., Dempsey, D. A., & Klessig, D. F. (2009). Salicylic Acid, a Multifaceted Hormone to Combat Disease. Annual Review of Phytopathology, 47(1), 177-206. doi:10.1146/annurev.phyto.050908.135202Mauch, F., Mauch-Mani, B., Gaille, C., Kull, B., Haas, D., & Reimmann, C. (2001). Manipulation of salicylate content in Arabidopsis thaliana by the expression of an engineered bacterial salicylate synthase. The Plant Journal, 25(1), 67-77. doi:10.1046/j.1365-313x.2001.00940.xGaffney, T., Friedrich, L., Vernooij, B., Negrotto, D., Nye, G., Uknes, S., … Ryals, J. (1993). Requirement of Salicylic Acid for the Induction of Systemic Acquired Resistance. Science, 261(5122), 754-756. doi:10.1126/science.261.5122.754Delaney, T. P., Uknes, S., Vernooij, B., Friedrich, L., Weymann, K., Negrotto, D., … Ryals, J. (1994). A Central Role of Salicylic Acid in Plant Disease Resistance. Science, 266(5188), 1247-1250. doi:10.1126/science.266.5188.1247Lawton, K. (1995). Systemic Acquired Resistance inArabidopsisRequires Salicylic Acid but Not Ethylene. Molecular Plant-Microbe Interactions, 8(6), 863. doi:10.1094/mpmi-8-0863Ross, A. F. (1961). Systemic acquired resistance induced by localized virus infections in plants. Virology, 14(3), 340-358. doi:10.1016/0042-6822(61)90319-1Pieterse, C. M. ., & van Loon, L. C. (1999). Salicylic acid-independent plant defence pathways. Trends in Plant Science, 4(2), 52-58. doi:10.1016/s1360-1385(98)01364-8Fonseca, S., Chico, J. M., & Solano, R. (2009). The jasmonate pathway: the ligand, the receptor and the core signalling module. Current Opinion in Plant Biology, 12(5), 539-547. doi:10.1016/j.pbi.2009.07.013Ton, J., De Vos, M., Robben, C., Buchala, A., Métraux, J.-P., Van Loon, L. C., & Pieterse, C. M. J. (2002). Characterization ofArabidopsisenhanced disease susceptibility mutants that are affected in systemically induced resistance. The Plant Journal, 29(1), 11-21. doi:10.1046/j.1365-313x.2002.01190.xCui, J., Bahrami, A. K., Pringle, E. G., Hernandez-Guzman, G., Bender, C. L., Pierce, N. E., & Ausubel, F. M. (2005). Pseudomonas syringae manipulates systemic plant defenses against pathogens and herbivores. Proceedings of the National Academy of Sciences, 102(5), 1791-1796. doi:10.1073/pnas.0409450102Robert-Seilaniantz, A., Navarro, L., Bari, R., & Jones, J. D. (2007). Pathological hormone imbalances. Current Opinion in Plant Biology, 10(4), 372-379. doi:10.1016/j.pbi.2007.06.003Garcion, C., Lohmann, A., Lamodière, E., Catinot, J., Buchala, A., Doermann, P., & Métraux, J.-P. (2008). Characterization and Biological Function of the ISOCHORISMATE SYNTHASE2 Gene of Arabidopsis. Plant Physiology, 147(3), 1279-1287. doi:10.1104/pp.108.119420Tornero, P., Chao, R. A., Luthin, W. N., Goff, S. A., & Dangl, J. L. (2002). Large-Scale Structure –Function Analysis of the Arabidopsis RPM1 Disease Resistance Protein. The Plant Cell, 14(2), 435-450. doi:10.1105/tpc.010393Bowling, S. A., Guo, A., Cao, H., Gordon, A. S., Klessig, D. F., & Dong, X. (1994). A mutation in Arabidopsis that leads to constitutive expression of systemic acquired resistance. The Plant Cell, 6(12), 1845-1857. doi:10.1105/tpc.6.12.1845Bowling, S. A., Clarke, J. D., Liu, Y., Klessig, D. F., & Dong, X. (1997). The cpr5 mutant of Arabidopsis expresses both NPR1-dependent and NPR1-independent resistance. The Plant Cell, 9(9), 1573-1584. doi:10.1105/tpc.9.9.1573Yu, I. -c., Parker, J., & Bent, A. F. (1998). Gene-for-gene disease resistance without the hypersensitive response in Arabidopsis dnd1 mutant. Proceedings of the National Academy of Sciences, 95(13), 7819-7824. doi:10.1073/pnas.95.13.7819Dietrich, R. A., Delaney, T. P., Uknes, S. J., Ward, E. R., Ryals, J. A., & Dangl, J. L. (1994). Arabidopsis mutants simulating disease resistance response. Cell, 77(4), 565-577. doi:10.1016/0092-8674(94)90218-6Rivas-San Vicente, M., & Plasencia, J. (2011). Salicylic acid beyond defence: its role in plant growth and development. Journal of Experimental Botany, 62(10), 3321-3338. doi:10.1093/jxb/err031Wang, D. (2005). Induction of Protein Secretory Pathway Is Required for Systemic Acquired Resistance. Science, 308(5724), 1036-1040. doi:10.1126/science.1108791Ritter, C. (1995). TheavrRpm1Gene ofPseudomonas syringaepv.maculicolaIs Required for Virulence on Arabidopsis. Molecular Plant-Microbe Interactions, 8(3), 444. doi:10.1094/mpmi-8-0444Debener, T., Lehnackers, H., Arnold, M., & Dangl, J. L. (1991). Identification and molecular mapping of a single Arabidopsis thaliana locus determining resistance to a phytopathogenic Pseudomonas syringae isolate. The Plant Journal, 1(3), 289-302. doi:10.1046/j.1365-313x.1991.t01-7-00999.xGrant, M., Godiard, L., Straube, E., Ashfield, T., Lewald, J., Sattler, A., … Dangl, J. (1995). Structure of the Arabidopsis RPM1 gene enabling dual specificity disease resistance. Science, 269(5225), 843-846. doi:10.1126/science.7638602Mindrinos, M., Katagiri, F., Yu, G.-L., & Ausubel, F. M. (1994). The A. thaliana disease resistance gene RPS2 encodes a protein containing a nucleotide-binding site and leucine-rich repeats. Cell, 78(6), 1089-1099. doi:10.1016/0092-8674(94)90282-8Coego, A., Ramirez, V., Gil, M. J., Flors, V., Mauch-Mani, B., & Vera, P. (2005). An Arabidopsis Homeodomain Transcription Factor, OVEREXPRESSOR OF CATIONIC PEROXIDASE 3, Mediates Resistance to Infection by Necrotrophic Pathogens. The Plant Cell, 17(7), 2123-2137. doi:10.1105/tpc.105.032375Pieterse, C. M. J., van Wees, S. C. M., van Pelt, J. A., Knoester, M., Laan, R., Gerrits, H., … van Loon, L. C. (1998). A Novel Signaling Pathway Controlling Induced Systemic Resistance in Arabidopsis. The Plant Cell, 10(9), 1571-1580. doi:10.1105/tpc.10.9.1571Berger, S., Bell, E., & Mullet, J. E. (1996). Two Methyl Jasmonate-Insensitive Mutants Show Altered Expression of AtVsp in Response to Methyl Jasmonate and Wounding. Plant Physiology, 111(2), 525-531. doi:10.1104/pp.111.2.525Attaran, E., Zeier, T. E., Griebel, T., & Zeier, J. (2009). Methyl Salicylate Production and Jasmonate Signaling Are Not Essential for Systemic Acquired Resistance in Arabidopsis. The Plant Cell, 21(3), 954-971. doi:10.1105/tpc.108.063164Yan, J., Zhang, C., Gu, M., Bai, Z., Zhang, W., Qi, T., … Xie, D. (2009). The Arabidopsis CORONATINE INSENSITIVE1 Protein Is a Jasmonate Receptor. The Plant Cell, 21(8), 2220-2236. doi:10.1105/tpc.109.065730Mittal, S. (1995). Role of the Phytotoxin Coronatine in the Infection ofAmbidopsis thalianabyPseudomonas syringaepv.tomato. Molecular Plant-Microbe Interactions, 8(1), 165. doi:10.1094/mpmi-8-0165Genoud, T., & Métraux, J.-P. (1999). Crosstalk in plant cell signaling: structure and function of the genetic network. Trends in Plant Science, 4(12), 503-507. doi:10.1016/s1360-1385(99)01498-3Lawton, K. A., Friedrich, L., Hunt, M., Weymann, K., Delaney, T., Kessmann, H., … Ryals, J. (1996). Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway. The Plant Journal, 10(1), 71-82. doi:10.1046/j.1365-313x.1996.10010071.xFeys, B., Benedetti, C. E., Penfold, C. N., & Turner, J. G. (1994). Arabidopsis Mutants Selected for Resistance to the Phytotoxin Coronatine Are Male Sterile, Insensitive to Methyl Jasmonate, and Resistant to a Bacterial Pathogen. The Plant Cell, 751-759. doi:10.1105/tpc.6.5.751Sun, J., Xu, Y., Ye, S., Jiang, H., Chen, Q., Liu, F., … Li, C. (2009). Arabidopsis ASA1 Is Important for Jasmonate-Mediated Regulation of Auxin Biosynthesis and Transport during Lateral Root Formation. The Plant Cell, 21(5), 1495-1511. doi:10.1105/tpc.108.064303He, Y., Fukushige, H., Hildebrand, D. F., & Gan, S. (2002). Evidence Supporting a Role of Jasmonic Acid in Arabidopsis Leaf Senescence. Plant Physiology, 128(3), 876-884. doi:10.1104/pp.010843Shan, X., Zhang, Y., Peng, W., Wang, Z., & Xie, D. (2009). Molecular mechanism for jasmonate-induction of anthocyanin accumulation in Arabidopsis. Journal of Experimental Botany, 60(13), 3849-3860. doi:10.1093/jxb/erp223Yoshida, Y., Sano, R., Wada, T., Takabayashi, J., & Okada, K. (2009). Jasmonic acid control of GLABRA3 links inducible defense and trichome patterning in Arabidopsis. Development, 136(6), 1039-1048. doi:10.1242/dev.030585Borevitz, J. O., Xia, Y., Blount, J., Dixon, R. A., & Lamb, C. (2000). Activation Tagging Identifies a Conserved MYB Regulator of Phenylpropanoid Biosynthesis. The Plant Cell, 12(12), 2383-2393. doi:10.1105/tpc.12.12.2383Berger, S., Bell, E., Sadka, A., & Mullet, J. E. (1995). Arabidopsis thaliana Atvsp is homologous to soybean VspA and VspB, genes encoding vegetative storage protein acid phosphatases, and is regulated similarly by methyl jasmonate, wounding, sugars, light and phosphate. Plant Molecular Biology, 27(5), 933-942. doi:10.1007/bf00037021Feng, S., Ma, L., Wang, X., Xie, D., Dinesh-Kumar, S. P., Wei, N., & Deng, X. W. (2003). The COP9 Signalosome Interacts Physically with SCFCOI1 and Modulates Jasmonate Responses. The Plant Cell, 15(5), 1083-1094. doi:10.1105/tpc.010207Nawrath C, Métraux JP, Genoud T (2005) Chemical signals in plant resistance: salicylic acid. . In: Tuzun S, Bent E, editors. Multigenic and Induced Systemic Resistance in Plants. Dordrecht, Netherlands.: Springer US. pp. pp. 143–165.Kunkel, B. N., & Brooks, D. M. (2002). Cross talk between signaling pathways in pathogen defense. Current Opinion in Plant Biology, 5(4), 325-331. doi:10.1016/s1369-5266(02)00275-3Truman, W., Bennett, M. H., Kubigsteltig, I., Turnbull, C., & Grant, M. (2007). Arabidopsissystemic immunity uses conserved defense signaling pathways and is mediated by jasmonates. Proceedings of the National Academy of Sciences, 104(3), 1075-1080. doi:10.1073/pnas.0605423104Canet, J. V., Dobón, A., Ibáñez, F., Perales, L., & Tornero, P. (2010). Resistance and biomass in Arabidopsis: a new model for Salicylic Acid perception. Plant Biotechnology Journal, 8(2), 126-141. doi:10.1111/j.1467-7652.2009.00468.xCasimiro, I., Marchant, A., Bhalerao, R. P., Beeckman, T., Dhooge, S., Swarup, R., … Bennett, M. (2001). Auxin Transport Promotes Arabidopsis Lateral Root Initiation. The Plant Cell, 13(4), 843-852. doi:10.1105/tpc.13.4.843Celenza, J. L., Grisafi, P. L., & Fink, G. R. (1995). A pathway for lateral root formation in Arabidopsis thaliana. Genes & Development, 9(17), 2131-2142. doi:10.1101/gad.9.17.2131Traw, M. B., & Bergelson, J. (2003). Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis. Plant Physiology, 133(3), 1367-1375. doi:10.1104/pp.103.027086Kloek, A. P., Verbsky, M. L., Sharma, S. B., Schoelz, J. E., Vogel, J., Klessig, D. F., & Kunkel, B. N. (2001). Resistance to Pseudomonas syringae conferred by an Arabidopsis thaliana coronatine-insensitive (coi1) mutation occurs through two distinct mechanisms. The Plant Journal, 26(5), 509-522. doi:10.1046/j.1365-313x.2001.01050.xXie, D. (1998). COI1: An Arabidopsis Gene Required for Jasmonate-Regulated Defense and Fertility. Science, 280(5366), 1091-1094. doi:10.1126/science.280.5366.1091Ellis, C., & Turner, J. (2002). A conditionally fertile coi1 allele indicates cross-talk between plant hormone signalling pathways in Arabidopsis thaliana seeds and young seedlings. Planta, 215(4), 549-556. doi:10.1007/s00425-002-0787-4Fernández-Arbaizar, A., Regalado, J. J., & Lorenzo, O. (2011). Isolation and Characterization of Novel Mutant Loci Suppressing the ABA Hypersensitivity of the Arabidopsis coronatine insensitive 1-16 (coi1-16) Mutant During Germination and Seedling Growth. Plant and Cell Physiology, 53(1), 53-63. doi:10.1093/pcp/pcr174He, Y., Chung, E.-H., Hubert, D. A., Tornero, P., & Dangl, J. L. (2012). Specific Missense Alleles of the Arabidopsis Jasmonic Acid Co-Receptor COI1 Regulate Innate Immune Receptor Accumulation and Function. PLoS Genetics, 8(10), e1003018. doi:10.1371/journal.pgen.1003018Xu, L., Liu, F., Lechner, E., Genschik, P., Crosby, W. L., Ma, H., … Xie, D. (2002). The SCFCOI1 Ubiquitin-Ligase Complexes Are Required for Jasmonate Response in Arabidopsis. The Plant Cell, 14(8), 1919-1935. doi:10.1105/tpc.003368Chini, A., Fonseca, S., Fernández, G., Adie, B., Chico, J. M., Lorenzo, O., … Solano, R. (2007). The JAZ family of repressors is the missing link in jasmonate signalling. Nature, 448(7154), 666-671. doi:10.1038/nature06006Grunewald, W., Vanholme, B., Pauwels, L., Plovie, E., Inzé, D., Gheysen, G., & Goossens, A. (2009). Expression of the Arabidopsis jasmonate signalling repressor JAZ1/TIFY10A is stimulated by auxin. EMBO reports, 10(8), 923-928. doi:10.1038/embor.2009.103Cao, H., Glazebrook, J., Clarke, J. D., Volko, S., & Dong, X. (1997). The Arabidopsis NPR1 Gene That Controls Systemic Acquired Resistance Encodes a Novel Protein Containing Ankyrin Repeats. Cell, 88(1), 57-63. doi:10.1016/s0092-8674(00)81858-9Century, K. S., Holub, E. B., & Staskawicz, B. J. (1995). NDR1, a locus of Arabidopsis thaliana that is required for disease resistance to both a bacterial and a fungal pathogen. Proceedings of the National Academy of Sciences, 92(14), 6597-6601. doi:10.1073/pnas.92.14.6597Wildermuth, M. C., Dewdney, J., Wu, G., & Ausubel, F. M. (2001). Isochorismate synthase is required to synthesize salicylic acid for plant defence. Nature, 414(6863), 562-565. doi:10.1038/35107108Lu, M., Tang, X., & Zhou, J.-M. (2001). Arabidopsis NHO1 Is Required for General Resistance against Pseudomonas Bacteria. The Plant Cell, 13(2), 437-447. doi:10.1105/tpc.13.2.437Ritter, C., & Dangl, J. L. (1996). Interference between Two Specific Pathogen Recognition Events Mediated by Distinct Plant Disease Resistance Genes. The Plant Cell, 251-257. doi:10.1105/tpc.8.2.251Tornero, P., & Dangl, J. L. (2002). A high-throughput method for quantifying growth of phytopathogenic bacteria in Arabidopsis thaliana. The Plant Journal, 28(4), 475-481. doi:10.1046/j.1365-313x.2001.01136.xMacho, A. P., Guevara, C. M., Tornero, P., Ruiz-Albert, J., & Beuzón, C. R. (2010). The Pseudomonas syringae effector protein HopZ1a suppresses effector-triggered immunity. New Phytologist, 187(4), 1018-1033. doi:10.1111/j.1469-8137.2010.03381.xTon, J., & Mauch-Mani, B. (2004). β-amino-butyric acid-induced resistance against necrotrophic pathogens is based on ABA-dependent priming for callose. The Plant Journal, 38(1), 119-130. doi:10.1111/j.1365-313x.2004.02028.xCANET, J. V., DOBÓN, A., ROIG, A., & TORNERO, P. (2010). Structure-function analysis of npr1 alleles in Arabidopsis reveals a role for its paralogs in the perception of salicylic acid. Plant, Cell & Environment, 33(11), 1911-1922. doi:10.1111/j.1365-3040.2010.02194.xJohnson, C. M., Stout, P. R., Broyer, T. C., & Carlton, A. B. (1957). Comparative chlorine requirements of different plant species. Plant and Soil, 8(4), 337-353. doi:10.1007/bf01666323Dobón, A., Canet, J. V., Perales, L., & Tornero, P. (2011). Quantitative genetic analysis of salicylic acid perception in Arabidopsis. Planta, 234(4), 671-684. doi:10.1007/s00425-011-1436-6Mehrtens, F., Kranz, H., Bednarek, P., & Weisshaar, B. (2005). The Arabidopsis Transcription Factor MYB12 Is a Flavonol-Specific Regulator of Phenylpropanoid Biosynthesis. Plant Physiology, 138(2), 1083-1096. doi:10.1104/pp.104.058032Konieczny, A., & Ausubel, F. M. (1993). A procedure for mapping Arabidopsis mutations using co-dominant ecotype-specific PCR-based markers. The Plant Journal, 4(2), 403-410. doi:10.1046/j.1365-313x.1993.04020403.xBell, C. J., & Ecker, J. R. (1994). Assignment of 30 Microsatellite Loci to the Linkage Map of Arabidopsis. Genomics, 19(1), 137-144. doi:10.1006/geno.1994.1023Swarbreck, D., Wilks, C., Lamesch, P., Berardini, T. Z., Garcia-Hernandez, M., Foerster, H., … Huala, E. (2007). The Arabidopsis Information Resource (TAIR): gene structure and function annotation. Nucleic Acids Research, 36(Database), D1009-D1014. doi:10.1093/nar/gkm965Jürgens G, Mayer U, Torres Ruiz RA, Berleth T, Mísera S (1991) Genetic analysis of pattern formation in the Arabidopsis embryo. Development (Supplement 1) : 27–38.Huang, W. E., Wang, H., Zheng, H., Huang, L., Singer, A. C., Thompson, I., & Whiteley, A. S. (2005). Chromosomally located gene fusions constructed in Acinetobacter sp. ADP1 for the detection of salicylate. Environmental Microbiology, 7(9), 1339-1348. doi:10.1111/j.1462-5822.2005.00821.xDeFraia, C. T., Schmelz, E. A., & Mou, Z. (2008). A rapid biosensor-based method for quantification of free and glucose-conjugated salicylic acid. Plant Methods, 4(1), 28. doi:10.1186/1746-4811-4-28Chenna, R. (2003). Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Research, 31(13), 3497-3500. doi:10.1093/nar/gkg50

Loss of a Conserved tRNA Anticodon Modification Perturbs Plant Immunity

[EN] tRNA is the most highly modified class of RNA species, and modifications are found in tRNAs from all organisms that have been examined. Despite their vastly different chemical structures and their presence in different tRNAs, occurring in different locations in tRNA, the biosynthetic pathways of the majority of tRNA modifications include a methylation step(s). Recent discoveries have revealed unprecedented complexity in the modification patterns of tRNA, their regulation and function, suggesting that each modified nucleoside in tRNA may have its own specific function. However, in plants, our knowledge on the role of individual tRNA modifications and how they are regulated is very limited. In a genetic screen designed to identify factors regulating disease resistance and activation of defenses in Arabidopsis, we identified SUPPRESSOR OF CSB3 9 (SCS9). Our results reveal SCS9 encodes a tRNA methyltransferase that mediates the 2'-O-ribose methylation of selected tRNA species in the anticodon loop. These SCS9-mediated tRNA modifications enhance during the course of infection with the bacterial pathogen Pseudomonas syringae DC3000, and lack of such tRNA modification, as observed in scs9 mutants, severely compromise plant immunity against the same pathogen without affecting the salicylic acid (SA) signaling pathway which regulates plant immune responses. Our results support a model that gives importance to the control of certain tRNA modifications for mounting an effective immune response in Arabidopsis, and therefore expands the repertoire of molecular components essential for an efficient disease resistance response.This work was supported by the National Science Foundation of China (grant 31100268 to PC) and the Spanish MINECO (BFU2012 to PV) and Generalitat Valenciana (Prometeo2014/020 to PV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ramirez Garcia, V.; González-García, B.; López Sánchez, A.; Castelló Llopis, MJ.; Gil, M.; Zheng, B.; Cheng, P.... (2015). Loss of a Conserved tRNA Anticodon Modification Perturbs Plant Immunity. PLoS Genetics. 11(10):1-27. https://doi.org/10.1371/journal.pgen.1005586S127111

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Stability of rapid maxillary expansion and facemask therapy: a long-term controlled study

The aim of this prospective controlled study was to evaluate the long-term effects of rapid maxillary expansion and facemask therapy in Class III subjects. METHODS: Twenty-two subjects (9 boys, 13 girls; mean age, 9.2 years ± 1.6) with Class III disharmony were treated consecutively with rapid maxillary expansion and facemask therapy followed by fixed appliances. The patients were reevaluated at the end of the 2-phase treatment (mean age, 14.5 years ± 1.9) and then recalled about 8.5 years after the end of rapid maxillary expansion and facemask treatment (mean age, 18.7 years ± 2.1). Two groups of controls with untreated Class III malocclusion were used for statistical comparisons of the short-term and long-term intervals. Statistical comparisons were performed with the Mann-Whitney U test. RESULTS: In the long term, no significant differences in maxillary changes were recorded, whereas the treatment group showed significantly smaller increases in mandibular protrusion. The sagittal maxillomandibular skeletal variables maintained significant improvements in the treatment group vs the control groups. CONCLUSIONS: In the long term, rapid maxillary expansion and facemask therapy led to successful outcomes in about 73% of the Class III patients. Favorable skeletal changes were mainly due to significant improvements in the sagittal position of the mandibl