Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype

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Not Availablefile attachedICAR-IIMR, Hyderaba

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Not AvailableThirty seven sorghum germplasm lines were evaluated for resistance to stem borer during kharif 2007 - 2009. Five different parameters viz., deadhearts, stem tunneling, exit holes per stalk, leaf damage score and larvae per stalk were assessed for evaluating resistance. None of these parameters were pronounced in the resistant cultivars. The cluster analysis brought out three discrete categories of entries viz., resistant, moderately resistant and susceptible based on reaction to C. partellus. The entries CJV 25 (IC 308619), GGUB 13 (IC 319859), EC 15 (IC 345717), ES 21 (IC 333366), E 63 (IC 333421), EP 61 (IC 343560), NSJB 6577 (IC 249042), E 56 (IC 333414), GGUB 50 (IC 319892), CJV 11 (IC 308607), NSJB 6585 (IC 249047), NSJB 6662 (IC 249093), GGUB 28 (IC 319871), SEVS 21 (IC 347587), CJV 19 (IC 308614), EG 21 (IC 541328), GGUB 27 (IC 319870), GGUB 61 (IC 319902) and EP 31 (IC 305912) were stable resistant sources, paving way for considering them in future breeding programsNot Availabl

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Not AvailableThe experiments were conducted during khariJ 2007 and 2008 to evaluate resistance for shoot fly Atherigolla soccata (Rondani) and stem borer Chilo parte/lus (Swinhoe) at Directorate of Sorghum and Research, Hyderabad. The trial comprised of 35 entries along with one resistant check each for shoot fly (IS 18551), stem borer (IS 2205) and susceptible check (0.1 6514) and three improved lines viz., ICSV 700,705 and 745. Based upon hierarchical clustering considering parameters viz.; shoot fly oviposition, shoot fly dead-hearts and stem horer induced dead-hearts, the entries were classified into resistant, moderately resistant and susceptible. Eighteen entries viz., AKENT 3, KC 2, GSSV 251, SR 1247-1, SR 1577-1, AKENT 10, KC 4, NSS 104, SR 1532, SEH 03, ST 30 x M 14. GJ 38, ICSV 700, IS 2205, KC I, IS 2312, ICSV 705 and IS 18551 were resistant and fifteen entries viz., SR 1992, GFS 206, GFS 252, ICSV 745, SEH 01, GFS 142, SEH 02, KC 3, AKENT 7, SR 1333, CSH 9, SR 713-5, SR 770-2, SR 806 and SEH 04 were moderately resistant. These entries can be further utilized in developing multiple pest resistant lines with desirable agronomic traits.Not Availabl

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Not AvailableForty seven sweet sorghum genotypes were evaluated for resistance to stem borer during kharif 2007 - 2009. Principal component analysis (PCA) was performed considering five parameters viz., dead-hearts, stem, peduncle tunneling, exit holes/stalk, number of larvae/ stalk. Two principal components (PCs) were extracted explaining a cumulative variation of 71.5 %. PC1 explained 47.7 % of the variation while PC2 explained 23.7 % of variation. PC1 had the loadings for dead-hearts (0.85), stem tunneling (0.73), exit holes/ stalk (0.87) whereas peduncle tunneling (0.82) and larvae/ stalk (0.81) were loaded in PC2 . PCA brought out three characters/variables viz. dead-hearts, stem tunneling and exit holes/ stalk, as most important in explaining variability thus, aiding in deciding reaction to pest. Eleven genotypes viz., E 27, IS 18162, IS 18164, E 38, ICSV 700, ICSV 93046, NSSV 6, GGUB 50, IS 5353, KARS 95 and RSSV 9 were found resistant to stem borer, Chilo partellusNot Availabl

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Not AvailableSorghum shoot fly(Atherigona soccata) is a serious pest that destabilizes the performance of sorghum cultivars and ultimately reduces sorghum production in many parts of the world. Identifying sorghum genotypes with stable resistance to shoot fly is important as it helps to reduce the cost of cultivation and stabilizes yields. In the present study, our objective was to identify stable shoot fly resistant genotypes among 385 recombinant inbred lines (RILs) of a cross between a susceptible parent and a resistant parent. We evaluated this set of RILs in eight environments over three years (2006e2008) for shoot fly resistance and component traits. Non-significant genotypeeenvironment (G E) linear component and significant pooled deviation for deadheart percentage indicated that the performance of genotypes was unpredictable over the environments. However, five lines had deadheart percentages much less than the population meanwith regression coefficient (bi) values close to unity, and non-significant deviation from regression, indicating that they have stable shoot fly resistance and are well adapted to all the environments. Additive main effect and multiplicative interaction (AMMI) analysis partitioned main effects into genotype, environment and G E interacts with all the components showing highly significant effects (p<0.001). Environment had the greatest effect (69.2%) followed by G E interactions (24.6%) and genotype (6.2%). Low heritability and high environmental influence for deadheart percentage suggested that shoot fly resistance is a highly complex character, emphasizing the need for marker assisted selection. We observed transgressive variation in the RIL population for all the traits indicating the contribution of alleles for resistance from both resistant and susceptible parents. Since the alleles for shoot fly resistance are contributed by both resistant and susceptible parents, efforts should be made to capture favourable alleles from resistant and susceptible genotypes.Not Availabl

Identification and validation of genomic regions that affect shoot fly resistance in sorghum [Sorghum bicolor (L.) Moench].

Not AvailableShoot fly is one of the most important pests affecting the sorghum production. The identification of quantitative trait loci (QTL) affecting shoot fly resistance enables to understand the underlying genetic mechanisms and genetic basis of complex interactions among the component traits. The aim of the present study was to detect QTL for shoot fly resistance and the associated traits using a population of 210 RILs of the cross 27B (susceptible) 9 IS2122 (resistant). RIL population was phenotyped in eight environments for shoot fly resistance (deadheart percentage), and in three environments for the component traits, such as glossiness, seedling vigor and trichome density. Linkage map was constructed with 149 marker loci comprising 127 genomic-microsatellite, 21 genic-microsatellite and one morphological marker. QTL analysis was performed by using MQM approach. 25 QTL (five each for leaf glossiness and seedling vigor, 10 for deadhearts, two for adaxial trichome density and three for abaxial trichome density) were detected in individual and across environments. The LOD and R2 (%) values of QTL ranged from 2.44 to 24.1 and 4.3 to 44.1%, respectively. For most of the QTLs, the resistant parent, IS2122 contributed alleles for resistance; while at two QTL regions, the susceptible parent 27B also contributed for resistance traits. Three genomic regions affected multiple traits, suggesting the phenomenon of pleiotrophy or tight linkage. Stable QTL were identified for the traits across different environments, and genetic backgrounds by comparing the QTL in the study with previously reported QTL in sorghum. For majority of the QTLs, possible candidate genes were identified. The QTLs identified will enable marker assisted breeding for shoot fly resistance in sorghum

Leukemic IDH1 and IDH2 Mutations Result in a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation

Cancer-associated IDH mutations are characterized by neomorphic enzyme activity and resultant 2-hydroxyglutarate (2HG) production. Mutational and epigenetic profiling of a large acute myeloid leukemia (AML) patient cohort revealed that IDH1/2-mutant AMLs display global DNA hypermethylation and a specific hypermethylation signature. Furthermore, expression of 2HG-producing IDH alleles in cells induced global DNA hypermethylation. In the AML cohort, IDH1/2 mutations were mutually exclusive with mutations in the alpha-ketoglutarate-dependent enzyme TET2, and TET2 loss-of-function mutations were associated with similar epigenetic defects as IDH1/2 mutants. Consistent with these genetic and epigenetic data, expression of IDH mutants impaired TET2 catalytic function in cells. Finally, either expression of mutant IDH1/2 or Tet2 depletion impaired hematopoietic differentiation and increased stem/progenitor cell marker expression, suggesting a shared proleukemogenic effect