Patellins 3 and 6, two members of the Plant Patellin family, interact with the movement protein of Alfalfa mosaic virus and interfere with viral movement

This is the accepted version of the following article: Peiró Morell, A.; Izquierdo Garcia, AC.; Sanchez Navarro, JA.; Pallás Benet, V.; Mulet Salort, JM.; Aparicio Herrero, F. (2014). Patellins 3 and 6, two members of the Plant Patellin family, interact with the movement protein of Alfalfa mosaic virus and interfere with viral movement. Molecular Plant Pathology. 15(9):881-891. doi:10.1111/mpp.12146., which has been published in final form at http://dx.doi.org/10.1111/mpp.12146.[EN] Movement proteins (MPs) encoded by plant viruses interact with host proteins to facilitate or interfere with intra- and/or intercellular viral movement. Using yeast two-hybrid and bimolecular fluorescence complementation assays, we herein present invivo evidence for the interaction between Alfalfa mosaic virus (AMV) MP and Arabidopsis Patellin 3 (atPATL3) and Patellin 6 (atPATL6), two proteins containing a Sec14 domain. Proteins with Sec14 domains are implicated in membrane trafficking, cytoskeleton dynamics, lipid metabolism and lipid-mediated regulatory functions. Interestingly, the overexpression of atPATL3 and/or atPATL6 interfered with the plasmodesmata targeting of AMV MP and correlated with reduced infection foci size. Consistently, the viral RNA levels increased in the single and double Arabidopsis knockout mutants for atPATL3 and atPATL6. Our results indicate that, in general, MP-PATL interactions interfere with the correct subcellular targeting of MP, thus rendering the intracellular transport of viral MP-containing complexes less efficient and diminishing cell-to-cell movement.AP was a recipient of a Pre-Doctoral Fellowship from the program JAE Pre-Doc of Consejo superior de Investigaciones Cientificas. ACI-G was a recipient of a Pre-Doctoral Fellowship associated with the project BFU2008-00604. FA was a recipient of a contract Ramon y Cajal (RYC-2010-06169) Program of the Ministerio de Educacion y Ciencia of Spain. We thank L. Corachan for excellent technical assistance. This work was supported by grants BIO2011-25018 from the Direccion General de Investigacion Cientifica y Tecnica, the Prometeo Program GV2011/003 from the Generalitat Valenciana and PAID-06-10-1496 from the Universitat Politecnica de Valencia (Spain).Peiró Morell, A.; Izquierdo García, AC.; Sanchez Navarro, JA.; Pallás Benet, V.; Mulet Salort, JM.; Aparicio Herrero, F. (2014). Patellins 3 and 6, two members of the Plant Patellin family, interact with the movement protein of Alfalfa mosaic virus and interfere with viral movement. Molecular Plant Pathology. 15(9):881-891. https://doi.org/10.1111/mpp.12146S88189115

Search for the Decay τ−→4pi−3π+(π0)ντ\tau^{-}\to 4pi^{-}3\pi^{+}(\pi^{0})\nu_{\tau}

We have searched for the decay of the tau lepton into seven charged particles and zero or one pi0. The data used in the search were collected with the CLEO II detector at the Cornell Electron Storage Ring (CESR) and correspond to an integrated luminosity of 4.61 fb^(-1). No evidence for a signal is found. Assuming all the charged particles are pions, we set an upper limit on the branching fraction, B(tau- -> 4pi- 3pi+ (pi0) nu_tau) < 2.4 x 10^(-6) at the 90% confidence level. This limit represents a significant improvement over the previous limit.Comment: 9 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

MicroRNA Related Polymorphisms and Breast Cancer Risk

Peer reviewe

Breast cancer risk genes: association analysis in more than 113,000 women

BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)Molecular tumour pathology - and tumour geneticsMTG1 - Moleculaire genetica en pathologie van borstkanke