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c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-β Type II Receptor
Zuo, W.,Huang, F.,Chiang, Y.,Li, M.,Du, J.,Ding, Y.,Zhang, T.,Lee, H.,Jeong, L.,Chen, Y.,Deng, H.,Feng, X.H.,Luo, S.,Gao, C.,Chen, Y.G. Cell Press 2013 Molecular cell Vol.49 No.3
Transforming growth factor β (TGF-β) is a potent antiproliferative factor in multiple types of cells. Deregulation of TGF-β signaling is associated with the development of many cancers, including leukemia, though the molecular mechanisms are largely unclear. Here, we show that Casitas B-lineage lymphoma (c-Cbl), a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-β signaling by neddylating and stabilizing the type II receptor (TβRII). Knockout of c-Cbl decreases the TβRII protein level and desensitizes hematopoietic stem or progenitor cells to TGF-β stimulation, while c-Cbl overexpression stabilizes TβRII and sensitizes leukemia cells to TGF-β. c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TβRII at Lys556 and Lys567. Neddylation of TβRII promotes its endocytosis to EEA1-positive early endosomes while preventing its endocytosis to caveolin-positive compartments, therefore inhibiting TβRII ubiquitination and degradation. We have also identified a neddylation-activity-defective c-Cbl mutation from leukemia patients, implying a link between aberrant TβRII neddylation and leukemia development.
ASCL2 Gene Expression Analysis and Its Association with Carcass Traits in Pigs
Cheng, H.C.,Zhang, F.W.,Deng, C.Y.,Jiang, C.D.,Xiong, Y.Z.,Li, F.E.,Lei, M.G. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.10
Achaete-scute like 2 (ASCL2) gene encodes a member of the basic helix-loop-helix transcription factor which is essential for the maintenance of proliferating trophoblasts during placental development. ASCL2 gene preferentially expresses the maternal allele in the mouse. However, it escapes genomic imprinting in the human. In this study, the complete open reading frame consisting of 193 amino acids of ASCL2 gene was obtained. Sequence analysis indicated that a C-G mutation existed in the 3' region between Meishan and Large White pigs. The polymorphism was used to determine the monoallelic or biallelic expression with RT-PCR-RFLP in pigs of Large $White{\times}Meishan$ $F_1$ hybrids. Imprinting analysis indicated that the ASCL2 gene expression was biallelic in all the tested tissues (heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, fat, uterus, ovary and pituitary). PCR-RFLP was used to detect the polymorphism in 270 pigs of the "$Large\;White{\times}Meishan$" $F_2$ resource population. The statistical results showed highly significant associations of the genotypes and fat meat percentage (FMP), lean meat percentage (LMP) and ratio of lean to fat (RLF) (p<0.01), and significant associations of the genotypes and loin eye area (LEA) and internal fat rate (IFR) (p<0.05).
Zhang, B.Z.,Lei, M.G.,Deng, C.Y.,Xiong, Y.H.,Zuo, B.,Li, F.E. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.4
The study was aimed at detecting polymorphism of the fifth intron in lipoprotein lipase (LPL) gene and analyzing association between the polymorphism and productive traits. A pair of primers was designed for amplifying the fifth intron. Sequence analysis indicated that a G1171C substitution existed in Large White breed. The mutation was detected by PCR-AfaI-RFLP. Polymorphism analysis in a pig resource family showed that there existed significant effects on carcass and meat quality traits. Thoraxwaist fat thickness of BB genotype was significantly higher (14.2%, p<0.05) than that of AA on carcass traits, while BB genotype was significantly lower (3.6% p<0.01, 4.1% p<0.01; 2.3% p<0.01, 1.9% p<0.01; 1.8% p<0.01, 1.4% p<0.05) than AA and AB genotype in pH of m. Longissimus Dorsi (LD), m. Biceps Femoris (BF), m. Semipinali Capitis (SC). The allelic frequencies were also significantly different between indigenous Chinese breeds and exotic breeds. Data analyzed revealed that the mutation locus affected production traits mostly by additive effects. Based on these results, it is necessary to do more studies on LPL gene before making the LPL locus into the application of marker-assisted selection (MAS) programs.
Zhang, F.W.,Cheng, H.C.,Deng, C.Y.,Xiong, Y.Z.,Li, F.E.,Lei, M.G. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.9
Pleiomorphic adenoma gene-like1 (PLAGL1) encodes a zinc-finger (ZF) protein with seven ZFs of the C2H2-type which is a regulator of apoptosis and cell cycle arrest, and also regulates the secretion of insulin. In both human and mouse, PLAGL1 is a candidate gene for tumor suppressor and transient neonatal diabetes mellitus (TNDM). In this study, a 2,238 bp fragment covering the complete coding region was obtained and deposited to GenBank (accession number: DQ288899). The reverse transcriptase-polymerase chain reaction (RT-PCR) indicated that PLAGL1 was expressed almost equally in heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, fat, uterus and ovary. Comparing the sequences of Large White and Meishan pigs, a C-T transition in exon 6 was found. The polymorphism could be detected by TaqI and was genotyped in five purebreds (Large White, Landrace, Meishan, Tongcheng and Bamei). Association analysis was performed between the polymorphism and carcass traits in 276 pigs of a "Large White${\times}$Meishan" F2 resource population. As a consequence, significant associations of the genotypes with shoulder backfat thickness (SFT) and internal fat rate (IFR) were observed. Pigs with TT genotype had low SFT and high IFR compared with TC or CC genotypes.
Zhang T.,Du W.Y.,Zhan C.Y.,Wang M.M.,Deng H.W.,Xie Z.M.,Li H. 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.8
The synergistic effect of ZrC nanoparticle pining and Re solution in W matrix on the thermal stability of tungsten was studied by investigating the evolution of the microstructure, hardness and tensile properties after annealing in a temperature range of 1000e1700 C. The results of metallography, electron backscatter diffraction pattern and Vickers micro-hardness indicate that the rolled W-1wt%Re-0.5 wt% ZrC alloy has a higher recrystallization temperature (1600 Ce1700 C) than that of the rolled pure W (1200 C), W-0.5 wt%ZrC (1300 C), W-0.5 wt%HfC (1400e1500 C) and WeK-3wt%Re alloy fabricated by the same technology. The molecular dynamics simulation results indicated that solution Re atoms in W matrix can slow down the self-diffusion of W atoms and form dragging effect to delay the growth of W grain, moreover, the diffusion coefficient decrease with increasing Re content. In addition, the ZrC nanoparticles can pin the grain boundaries and dislocations effectively, preventing the recrystallization. Therefore, synergistic effect of solid solution Re element and dispersed ZrC nanoparticles significantly increase recrystallization temperature
New Evidence of Alleles (V199I and G52S) at the PRKAG3 (RN) Locus Affecting Pork Meat Quality
Chen, J.F.,Dai, L.H.,Peng, J.,Li, J.L.,Zheng, R.,Zuo, B.,Li, F.E.,Liu, M.,Yue, K.,Lei, M.G.,Xiong, Y.Z.,Deng, C.Y.,Jiang, S.W. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.4
The porcine PRKAG3 (RN) gene encodes the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK), which is a good candidate gene affecting meat quality. In this study, the effects of two missense mutations A595G (Ile199Val) and G154A (Gly52Ser) in porcine PRKAG3 gene on meat quality traits were studied in M. Longissimus dorsi (LD), M. Semispinalis capitis (SC) and M. Biceps femoris (BF) from different populations of 326 pigs. The PRKAG3 alleles 199I, 199IV, 52S and 52G were identified with PCR-RFLPs and all genotypes - 199I/199I, 199I/199V, 199V/199V, 52S/52S, 52S/52G and 52G/52G - were found. The frequency of V allele was larger than that of I allele in all populations. I allele frequency was zero in Chinese Meishan pigs (population D) especially. G allele frequency was larger than that of S allele in all populations except Large White (population A). Both variations at the PRKAG3 locus significantly affected these meat quality traits. The pork meat quality has not previously been established in Meishan or crosses thereof. The results suggested that generally pH of LD, SC and BF was higher in Meishan pigs than that in other populations. Moreover, Meishan pigs showed higher water-holding capacity and intramuscular fat (IMF), lower water content and water loss percentage compared to other populations in terms of the two variations. The results present here supply new evidence that alleles V199I and G52S at the PRKAG3 locus affect pork meat quality and provide useful information on pork production.
Association Analyses with Carcass Traits in the Porcine KIAA1717 and HUMMLC2B Genes
Xu, D.Q.,Xiong, Y.Z.,Liu, M.,Lan, J.,Ling, X.F.,Deng, C.Y.,Jiang, S.W. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.11
By screening a subtracted cDNA library constructed with mRNA obtained from the longissimus dorsi muscles of F1 hybrids Landrace${\times}$Yorkshire and their Yorkshire female parents, we isolated two partial sequences coding for the H3-K4-specific methyltransferase (KIAA1717) and skeletal muscle myosin regulatory light chain (HUMMLC2B) genes. In the present work we investigated two SNPs, one (C1354T) at the 3' untranslated region (UTR) of KIAA1717 and one (A345G) at the SINE (PRE-1) element of HUMMLC2B, in a resource population derived from crossing Chinese Meishan and Large White pig. The selected pigs were genotyped by means of a PCR-RFLP protocol. Significant associations were observed for the KIAA1717 C1354T polymorphic site with thorax-waist backfat thickness (p<0.05), buttock backfat thickness (p<0.05), average backfat thickness (p<0.05), loin eye height (p<0.05), loin eye area (p<0.05), carcass length to 1$^{st}$ spondyle (p<0.01) and carcass length to 1st rib (p<0.01). HUMMLC2B A345G were significantly associated with loin eye width (p<0.05), loin eye area (p<0.05). Further studies are needed to confirm these preliminary results.
Mapping of Quantitative Trait Loci on Porcine Chromosome 7 Using Combined Data Analysis
Zuo, B.,Xiong, Y.Z.,Su, Y.H.,Deng, C.Y.,Lei, M.G.,Zheng, R.,Jiang, S.W.,Li, F.E. Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.10
To further investigate the regions on porcine chromosome 7 that are responsible for economically important traits, phenotypic data from a total of 287 F2 individuals were collected and analyzed from 1998 to 2000. All animals were genotyped for eight microsatellite loci spanning the length of chromosome 7. QTL analysis was performed using interval mapping under the line-cross model. A permutation test was used to establish significance levels associated with QTL effects. Observed QTL effects were (chromosomewide significance, position of maximum significance in centimorgans): Birth weight (<0.01, 3); Carcass length (<0.05, 80); Longissimus muscle area (<0.01, 69); Skin percentage (<0.01, 69); Bone percentage (<0.01, 74); Fat depths at shoulder (<0.05, 54);Mean fat depth (<0.05, 81); Moisture in m. Longissimus Dorsi (<0.05, 88). Additional evidence was also found which suggested QTL for dressing percentage and fat depths at buttock. This study offers confirmation of several QTL affecting growth and carcass traits on SSC7 and provides an important step in the search for the actual major genes involved in the traits of economic interest.
Large-Pore Apertures in a Series of Metal-Organic Frameworks
Deng, H.,Grunder, S.,Cordova, K. E.,Valente, C.,Furukawa, H.,Hmadeh, M.,Gandara, F.,Whalley, A. C.,Liu, Z.,Asahina, S.,Kazumori, H.,O'Keeffe, M.,Terasaki, O.,Stoddart, J. F.,Yaghi, O. M. American Association for the Advancement of Scienc 2012 Science Vol.336 No.6084
<P>We report a strategy to expand the pore aperture of metal-organic frameworks (MOFs) into a previously unattained size regime (>32 angstroms). Specifically, the systematic expansion of a well-known MOF structure, MOF-74, from its original link of one phenylene ring (I) to two, three, four, five, six, seven, nine, and eleven (II to XI, respectively), afforded an isoreticular series of MOF-74 structures (termed IRMOF-74-I to XI) with pore apertures ranging from 14 to 98 angstroms. All members of this series have noninterpenetrating structures and exhibit robust architectures, as evidenced by their permanent porosity and high thermal stability (up to 300C). The pore apertures of an oligoethylene glycol-functionalized IRMOF-74-VII and IRMOF-74-IX are large enough for natural proteins to enter the pores.</P>