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Volume 1, Emitir 1 (2012)

Artigo de Pesquisa

Mixed Inbred FVB;B6 Background Strain Attenuates Kidney Disease and Improves Survival of GneM712T/M712T Mice

Yadira Valles-Ayoub, Arman Haghighatgoo, Chai Saechao, Zeshan Khokher, Christopher Creencia, Oscar Scremin, Gregory Lawson, DVM, Babak Darvish and Daniel Darvish

Recessive form of Hereditary Inclusion Body Myopathy (HIBM, IBM2, MIM:600737) is an adult onset muscle wasting disorders caused by hypomorphic GNE, the rate-limiting enzyme of sialic acid (Sia) biosynthesis. Unlike human patients, mice bearing the GneM712T/M712T genotype in C57BL/6 background strain suffer severe glomerular hematuria, incomplete podocyte development, and do not survive beyond the first few days of life. We crossed heterozygous mice (GneM712T/+) of B6 strain with FVB strain mice. In mixed inbred FVB;B6 background, the homozygous mice show attenuated glomerular disease and survive longer (mean survival 22±13 weeks, n=26). Paradoxically, the homozygous mice showed increased total Sia levels in serum (2x control), and Neu5Ac:Neu5Gc ratios are slightly shifted towards Neu5Ac in serum and towards Neu5Gc in muscle tissue. Increase in serum Sia levels may be caused by altered glomerular filtration. This paradoxical increase in serum Sia may contribute to Sia pools of muscle, and exert a potential beneficial effect. In summary, the background strain of mouse model can significantly affect the disease phenotype.

Artigo de Pesquisa

Regulation of Myf5 Early Enhancer by Histone Acetyltransferase p300 during Stem Cell Differentiation

Tanja Francetic, Melanie Le May, Munerah Hamed, Hymn Mach, David Meyers, Philip A Cole, Jihong Chen and Qiao Li

Skeletal myogenesis is an intricate process coordinated temporally by multiple myogenic regulatory factors (MRF) including Myf5, which is the first MRF expressed and marks the commitment of skeletal muscle lineage. The expression of Myf5 gene during early embryogenesis is controlled by a set of enhancer elements, and requires the histone acetyltransferase (HAT) activity of transcriptional coactivator p300. However, it is unclear as to how different regulatory signals converge at enhancer elements to regulate early Myf5 gene expression, and if p300 is directly involved. We show here that p300 associates with the Myf5 early enhancer at the early stage of stem cell differentiation, and its HAT activity is important for the recruitment of β-catenin to this early enhancer. In addition, histone H3-K27 acetylation, but not H3-K9/14, is intimately connected to the p300 HAT activity. Thus, p300 is directly involved in the regulation of the Myf5 early enhancer, and is important for specific histone acetylation and transcription factor recruitment. This connection of p300 HAT activity with H3-K27 acetylation and β-catenin signalling during myogenic differentiation in vitro offers a molecular insight into the enhancer-elements participation observed in embryonic development. In addition, pluripotent stem cell differentiation is a valuable system to dissect the signal-dependent regulation of specific enhancer element during cell fate determinations.

Artigo de Pesquisa

ALK Folic Acid Transport and Integrin Signal Induced-Angiogenesis Network in Human Hepatocellular Carcinoma (HCC) by Systems-Theoretical Analysis

Lin Wang, Juxiang Huang and Hong Lin

We constructed the high-expression ALK activated transport and signal network in human hepatocellular carcinoma (HCC) compared with low-expression (fold change ≥2) no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) in GEO data set, by using integration of gene regulatory activated and inhibited network inference method with gene ontology (GO) analysis. Our result showed that ALK transport and signal upstream network ECT2, FOLR1, GNAZ, GRM1, ITGA2, LEF1, NR5A1, PTHLH, RIMS3, SORT1, SOX2 activated ALK, and downstream ALK-activated BAP1, CAD, CDH13, CNTNAP2, GRM1, ITGA2, LAPTM4B, MAP2K6, NR5A1, STMN1 in HCC. We obtained that the different biological processes of ALK activated network consisted of folic acid transport, cell surface receptor linked signal transduction, cell-cell signaling, G-protein coupled receptor protein signaling pathway, integrin-mediated signaling pathway, intracellular signaling cascade, low density lipoprotein mediated signaling, Rac protein signal transduction, Rho protein signal transduction in HCC compared with the activated network of no-tumor hepatitis/cirrhotic tissues, as a result of inducing folic acid transport and integrin signal induced-angiogenesis in HCC. Our hypothesis was verified by the different and the same biological processes of ALK activated transport and signal network of HCC compared with the corresponding inhibited network of no-tumor hepatitis/cirrhotic tissues and HCC, respectively.

Artigo de Pesquisa

Malt Genotypic Screening of Polymorphism Information Content (PIC) of SSR Markers Based on Physiological Traits in Barley

Gang Qian, Junjiao Ping, Dazhong Wang, Zhen Zhang, Suyuan Luo and Mingzhen Yang

Brewing genotypes were described by polymorphism information content (PIC) of 22 SSR markers in barley (Hordeum vulgare L.), associated with malt quality. Notably, the values of diastatic power set ranged from 5.53 to 24.13 U/Kg in these samples, suitable to assess the relative importance of biochemical components of malt variations and genetic characteristics. Cluster analysis revealed a significant correlation between eco-geographic origin and SSR marker clustering, resolving the accessions into four subgroups. Moreover, SSRs with higher PIC values and higher average number of alleles per marker in the population with higher values of diastatic power were found to be an efficient utility for distinguishing brewing genotypes in barley. These results possibly indicated that SSRs linked to brewing traits could be very useful for application in monitoring malt traits, evaluating genetic diversity, and determining the sampled eco-geographic origins in barley.

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