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Lorenzato A.,University of Turin | Lorenzato A.,Institute for Cancer Research at Candiolo | Martino C.,University of Turin | Martino C.,Institute for Cancer Research at Candiolo | And 11 more authors.
FASEB Journal | Year: 2012

The cellular apoptosis susceptibility gene CAS/CSE1L is overexpressed in cancer, although it was originally identified as a gene that renders cells vulnerable to apoptotic stimuli. CAS/CSE1L has roles in the nucleocytoplasmic recycling of importin-α and in the regulation of gene expression, cell migration, and secretion. We identified CAS/CSE1L as a survival factor for ovarian cancer cells in vitro and in vivo. In 3/3 ovarian cancer cell lines, CAS/CSE1L was down-modulated by the unorthodox proapoptotic signaling of the MET receptor. CAS/CSE1L knockdown with RNA interference committed the ovarian cancer cells to death, but not immortalized normal cells and breast and colon cancer cells. In 70 and 95% of these latter cells, respectively, CAS/CSE1L was localized in the cytoplasm, while it accumulated in the nucleus in >90% of ovarian cancer cells. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells. In the nucleus, CAS/CSE1L regulated the expression of the proapoptotic Ras-association domain family 1 gene products RASSF1C and RASSF1A, which mediated death signals evoked by depletion of CAS/CSE1L. Our data show that CAS/CSE1L protects ovarian cancer cells from death through transcriptional suppression of a proapoptotic gene and suggest that the localization of CAS/CSE1L dictates its function. © FASEB. Source

Adams III W.W.,University of Colorado at Boulder | Cohu C.M.,University of Colorado at Boulder | Amiard V.,Genomics and Bioinformatics Unit | Demmig-Adams B.,University of Colorado at Boulder
Frontiers in Plant Science | Year: 2014

The companion cells (CCs) and/or phloem parenchyma cells (PCs) in foliar minor veins of some species exhibit invaginations that are amplified when plants develop in high light (HL) compared to low light (LL). Leaves of plants that develop under HL also exhibit greater maximal rates of photosynthesis compared to those that develop under LL, suggesting that the increased membrane area of CCs and PCs of HL-acclimated leaves may provide for greater levels of transport proteins facilitating enhanced sugar export. Furthermore, the degree of wall invagination in PCs (Arabidopsis thaliana) or CCs (pea) of fully expanded LL-acclimated leaves increased to the same level as that present in HL-acclimated leaves 7 days following transfer to HL, and maximal photosynthesis rates of transferred leaves of both species likewise increased to the same level as in HL-acclimated leaves. In contrast, transfer of Senecio vulgaris from LL to HL resulted in increased wall invagination in CCs, but not PCs, and such leaves furthermore exhibited only partial upregulation of photosynthetic capacity following LL to HL transfer. Moreover, a significant linear relationship existed between the level of cell wall ingrowths and maximal photosynthesis rates across all three species and growth light regimes. A positive linear relationship between these two parameters was also present for two ecotypes (Sweden, Italy) of the winter annual A. thaliana in response to growth at different temperatures, with significantly greater levels of PC wall ingrowths and higher rates of photosynthesis in leaves that developed at cooler versus warmer temperatures. Treatment of LL-acclimated plants with the stress hormone methyl jasmonate also resulted in increased levels of wall ingrowths in PCs of A. thaliana and S. vulgaris but not in CCs of pea and S. vulgaris. The possible role of PC wall ingrowths in sugar export versus as physical barriers to the movement of pathogens warrants further attention. © 2014 Adams III, Cohu, Amiard and Demmig-Adams. Source

Soto-Cerda B.J.,University of Manitoba | Soto-Cerda B.J.,Agriculture and Agri Food Canada | Soto-Cerda B.J.,Genomics and Bioinformatics Unit | Duguid S.,Agriculture and Agri Food Canada | And 5 more authors.
Theoretical and Applied Genetics | Year: 2014

Key message: The identification of stable QTL for seed quality traits by association mapping of a diverse panel of linseed accessions establishes the foundation for assisted breeding and future fine mapping in linseed. Linseed oil is valued for its food and non-food applications. Modifying its oil content and fatty acid (FA) profiles to meet market needs in a timely manner requires clear understanding of their quantitative trait loci (QTL) architectures, which have received little attention to date. Association mapping is an efficient approach to identify QTL in germplasm collections. In this study, we explored the quantitative nature of seed quality traits including oil content (OIL), palmitic acid, stearic acid, oleic acid, linoleic acid (LIO) linolenic acid (LIN) and iodine value in a flax core collection of 390 accessions assayed with 460 microsatellite markers. The core collection was grown in a modified augmented design at two locations over 3 years and phenotypic data for all seven traits were obtained from all six environments. Significant phenotypic diversity and moderate to high heritability for each trait (0.73-0.99) were observed. Most of the candidate QTL were stable as revealed by multivariate analyses. Nine candidate QTL were identified, varying from one for OIL to three for LIO and LIN. Candidate QTL for LIO and LIN co-localized with QTL previously identified in bi-parental populations and some mapped nearby genes known to be involved in the FA biosynthesis pathway. Fifty-eight percent of the QTL alleles were absent (private) in the Canadian cultivars suggesting that the core collection possesses QTL alleles potentially useful to improve seed quality traits. The candidate QTL identified herein will establish the foundation for future marker-assisted breeding in linseed. © 2014 The Author(s). Source

Gilli F.,Regional Center for Multiple Sclerosis e and Clinical Neurobiology | Lindberg R.L.P.,University of Basel | Valentino P.,Regional Center for Multiple Sclerosis e and Clinical Neurobiology | Marnetto F.,Regional Center for Multiple Sclerosis e and Clinical Neurobiology | And 8 more authors.
PLoS ONE | Year: 2010

Background: Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. Methodology: We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26). Principal Findings: Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to "normal" already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month. Conclusions: Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies. © 2010 Gilli et al. Source

Soto-Cerda B.J.,Agriculture and Agri Food Canada | Soto-Cerda B.J.,Genomics and Bioinformatics Unit | Westermeyer F.,Genomics and Bioinformatics Unit | Iniguez-Luy F.,Genomics and Bioinformatics Unit | And 3 more authors.
Euphytica | Year: 2014

High prices of fish oil make linseed attractive for aquaculture and animal feed. To ensure a constant supply of linseed, the development of stable cultivars is of strategic importance. In this study, 35 linseed genotypes were evaluated in five Chilean environments (E) from 2009 to 2012. The additive main effect and multiplicative interaction analysis (AMMI), genotype (G) plus genotype by environment (GE) interaction (GGE) biplot analysis and three stability parameters were tested with the aim of identifying adapted genotypes for the development of linseed cultivars. An association mapping (AM) analysis was also conducted for four agronomic traits and the stability of the associated markers was evaluated using the QQE (QTL main effect and QTL by environment interaction) approach. Combined analysis of variance for yield, seeds per boll (SPB), plant height (PH) and days to flowering (DTF) were significant for G, E and GE (P < 0.001). The combined stability analysis identified some Canadian, Argentinean and Chilean accessions to be the best adapted and highest yielding genotypes. Coancestry analysis indicated that crossing Canadian and Chilean genotypes could maximize transgressive segregation for yield. Significant associations for DTF, PH and SPB explained up to 59 % of the phenotypic variation for these traits. The QQE and AM analyses were consistent in identifying marker LGM27B as the most stable and significant across all environments with the largest effect in reducing DTF. The combined application of the stability, AM and QQE analyses could accelerate the development of marketable linseed cultivars adapted to Southern Chile. © 2013 Her Majesty the Queen in Right of Canada. Source

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