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.

Nutritive Values of Chinese Peanut Meal for Growing-Finishing Pigs

Li, Defa,Xu, X.X.,Qiao, S.Y.,Zheng, C.T.,Chen, Y.,Piao, X.S.,Han, In K.,Thacker, P. Asian Australasian Association of Animal Productio 2000 Animal Bioscience Vol.13 No.3

Two experiments were conducted to determine the apparent ileal digestibility of the amino acids contained in peanut meal using the regression technique and then applying the values obtained, in a growth trial, using growing-finishing pigs. For the digestibility trial, four 20 kg crossbred (Yorkshire${\times}$Landrace${\times}$Beijing Black) barrows were fitted with simple T-cannula in the terminal ileum. After recovery, the barrows were fed one of four experimental diets according to a $4{\times}4$ Latin Square design. The pigs were fed corn-soybean meal based diets supplemented with 0, 25, 50 or 75% peanut meal. For the growth trial, 200 crossbred (Yorkshire${\times}$Landrace${\times}$Beijing Black) growing pigs (20.9 kg) were fed corn-soybean meal diets supplemented with 0, 5, 10, 15 or 20% peanut meal. Five pens (4 gilts and 4 castrates) were assigned to each treatment. With the exception of arginine, histidine and phenylalanine, the digestibility coefficients for the indispensible amino acids declined as the level of peanut meal in the diet increased. There was a good agreement between the amino acid digestibilities for lysine, methionine, threonine and tryptophan determined using the regression technique and amino acid digestibilities previously published for peanut meal. During both the growing (21-54 kg) and finishing (54-99 kg) periods, the addition of peanut meal decreased average daily gain (p=0.01) and feed conversion in a linear manner (p<0.05). Feed intake was not significantly different among treatments. The overall results suggest that peanut meal can be used at levels up to 15% in diets fed to growing-finishing pigs provided that the diet has been balanced for digestible amino acids.

Growth Performance of Growing-Finishing Pigs Fed Diets Supplemented with Chinese Cottonseed Meal Based on Amino Acid Digestibilities

Li, Deta,Xn, X.X.,Qiao, S.Y.,Zheng, C.T.,Chen, Y.,Piao, X.S.,Han, In K.,Thacker, P. Asian Australasian Association of Animal Productio 2000 Animal Bioscience Vol.13 No.4

Two experiments were conducted to determine the ileal digestibility of the amino acids contained in cottonseed meal using the regression technique and then applying the values obtained, in a growth trial, using growing-finishing pigs. For the digestibility trial, four 20 kg crossbred ($Yorkshire{\times}Landrace{\times}Beijing$ Black) barrows were fitted with simple T-cannula in the terminal ileum. After recovery, the barrows were fed one of four experimental diets according to a $4{\times}4$ Latin Square design. The pigs were fed com-soybean meal based diets supplemented with 0, 25, 50 or 75% cottonseed meal. For the growth trial, 128 crossbred ($Yorkshire{\times}Landrace{\times}Beijing$ Black) growing pigs (21 kg) were fed com-soybean meal diets supplemented with 0, 4, 8 or 12% cottonseed meal. Four pens (4 gilts and 4 castrates) were assigned to each treatment. The digestibility coefficients for the indispensible amino acids declined as the level of cottonseed meal in the diet increased. There was good agreement between the amino acid digestibilities for methionine, threonine and tryptophan determined using the regression technique and amino acid digestibilities previously published for cottonseed meal. However, for lysine, the value of 67% ileal digestibility obtained in the present experiment was higher than most previously published estimates which ranged from 42 to 73%. During both the growing (21-43 kg) and finishing (43-84 kg) periods, the addition of cottonseed meal decreased average daily gain and feed conversion in a linear manner (p<0.05). Feed intake was not significantly different between treatments. The overall results suggest that cottonseed meal can be used at levels of up to 8% in diets fed to growing-finishing pigs provided that the diet. has been balanced for digestible amino acids.

Vector prime protein boost vaccination in the setting of myeloablative-induced lymphopenia suppresses growth of leukemia and solid tumors

Han, T H,Tang, Y,Park, Y H,Maynard, J,Li, P,Akbulut, H,Petersen, L,Deisseroth, A Macmillan Publishers Limited 2010 Bone marrow transplantation Vol.45 No.3

We have developed a vaccine, which is designed to induce tumor-associated antigen (TAA)-specific T cells and antibodies in the setting of profound lymphopenia induced by myeloablative therapy and T-cell-depleted bone marrow transplantation. Test mice were injected subcutaneously (sc) with the 32DP210Bcr-Abl cell line, which is positive for the p210Bcr-Abl protein (Group 1). In Group 2, 7 days after injection of the 32DP210Bcr-Abl positive cell line, the mice received 900 cGy total body irradiation (TBI) followed in 1 h by the intravenous infusion of 10 million T-cell-depleted syngeneic bone marrow cells (TCDBMT) (Group 2). The leukemia-bearing group received an intravenous injection of 10 million spleen cells (donor lymphocyte infusions) from unvaccinated (Group 3) and TAA/ecdCD40L-vaccinated (Group 4) syngeneic mice 3 days after completion of the TBI and TCDBMT. Groups 3 and 4 mice received three additional sc vaccinations at 7-day intervals with the TAA/ecdCD40L vaccine, in which the TAA was taken from the junctional peptide of the P210bcr-Abl protein. The survival of Groups 3 and 4 mice was significantly longer than that in Groups 1 and 2 mice. Vaccinated mice from Group 4, which developed complete responses, survived up to 350 days post-injection of the leukemia cells without any evidence of leukemia regrowth.

Coronary Atherosclerosis T₁-Weighed Characterization With Integrated Anatomical Reference

Xie, Y.,Kim, Y.J.,Pang, J.,Kim, J.S.,Yang, Q.,Wei, J.,Nguyen, C.T.,Deng, Z.,Choi, B.W.,Fan, Z.,Bairey Merz, C.N.,Shah, P.K.,Berman, D.S.,Chang, H.J.,Li, D. Elsevier Science B.V. Amsterdam 2017 JACC CARDIOVASCULAR IMAGING Vol.10 No.6

Objectives: The aim of this work is the development of coronary atherosclerosis T<SUB>1</SUB>-weighted characterization with integrated anatomical reference (CATCH) technique and the validation by comparison with high-risk plaque features (HRPF) observed on intracoronary optical coherence tomography (OCT) and invasive coronary angiography. Background: T<SUB>1</SUB>-weighted cardiac magnetic resonance with or without contrast media has been used for characterizing coronary atherosclerosis showing promising prognostic value. Several limitations include: 1) coverage is limited to proximal coronary segments; 2) spatial resolution is low and often anisotropic; and 3) a separate magnetic resonance angiography acquisition is needed to localize lesions. Methods: CATCH acquired dark-blood T<SUB>1</SUB>-weighted images and bright-blood anatomical reference images in an interleaved fashion. Retrospective motion correction with 100% respiratory gating efficiency was achieved. Reference control subjects (n = 13) completed both pre- and post-contrast scans. Stable angina patients (n = 30) completed pre-contrast scans, among whom 26 eligible patients also completed post-contrast scans. After cardiac magnetic resonance, eligible patients (n = 22) underwent invasive coronary angiography and OCT for the interrogation of coronary atherosclerosis. OCT images were assessed and scored for HRPF (lipid-richness, macrophages, cholesterol crystals, and microvessels) by 2 experienced analysts blinded to magnetic resonance results. Results: Per-subject analysis showed none of the 13 reference control subjects had coronary hyperintensive plaques (CHIP) in either pre-contrast or post-contrast CATCH. Five patients had CHIP on pre-contrast CATCH and 5 patients had CHIP on post-contrast CATCH. Patients with CHIP had greater lipid abnormality than those without. Per-segment analysis showed elevated pre- and post-contrast plaque to myocardium signal ratio in the lesions with HRPF versus those without. Positive correlation was observed between plaque to myocardium signal ratio and OCT HRPF scoring. CHIP on pre-contrast CATCH were associated with significantly higher stenosis level than non-CHIP on invasive coronary angiography. Conclusions: CATCH provided accelerated whole heart coronary plaque characterization with simultaneously acquired anatomical reference. CHIP detected by CATCH showed positive association with high-risk plaque features on invasive imaging studies.

Energy and Ileal Digestible Amino Acid Concentrations for Growing Pigs and Performance of Weanling Pigs Fed Fermented or Conventional Soybean Meal

Wang, Y.,Lu, W.Q.,Li, D.F.,Liu, X.T.,Wang, H.L.,Niu, S.,Piao, X.S. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.5

A new strategy of co-inoculating Bacillus subtilis MA139 with Streptococcus thermophilus and Saccharomyces cerevisiae was used to produce fermented soybean meal (FSBM). Three experiments were conducted to determine the concentration of digestible energy (DE) and metabolizable energy (ME) (Exp. 1), apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of amino acids (AA) (Exp. 2), and feeding value (Exp. 3) of FSBM produced by this new strategy (NFSB) compared with soybean meal (SBM) and conventionally available FSBM (Suprotein). In Exp. 1, twenty-four barrows (initial body weight [BW] of $32.2{\pm}1.7kg$) were randomly allotted to 1 of 4 diets with 6 replicates per diet. A corn basal diet and 3 diets based on a mixture of corn and 1 of 3 soybean products listed above were formulated and the DE and ME contents were determined by the difference method. The results showed that there were no differences in DE and ME between SBM and either FSBM product (p>0.05). In Exp. 2, eight barrows (initial BW of $26.8{\pm}1.5kg$) were fitted with ileal T-cannulaes and used in a replicated $4{\times}4$ Latin square design. Three corn-starch-based diets were formulated using each of the 3 soybean products as the sole source of AA. A nitrogen-free diet was also formulated to measure endogenous losses of AA. The results showed that the SID of all AA except arginine and histidine was similar for NFSB and SBM (p>0.05), but Suprotein had greater (p<0.05) SID of most AA except lysine, aspartate, glycine and proline than NFSB. In Exp. 3, a total of 144 piglets (initial BW of $8.8{\pm}1.2$ kg) were blocked by weight and fed 1 of 4 diets including a control diet with 24% SBM as well as diets containing 6% and 12% NFSB or 12% Suprotein added at the expense of SBM. During d 15 to 28, replacing SBM with 6% NFSB significantly improved average daily gain (ADG) and average daily feed intake (ADFI) (p<0.05) for nursery piglets. During the overall experiment, ADG of piglets fed diets containing 6% NFSB was significantly greater (p<0.05) than that of piglets fed SBM. In conclusion, fermentation with the new strategy did not affect the energy content or the AID and the SID of AA in SBM. However, inclusion of 6% NFSB in diets fed to nursery piglets improved performance after weaning likely as a result of better nutritional status and reduced immunological challenge.

Investigation of PCR-RFLPs within Major Histocompatibility Complex B-G Genes Using Two Restriction Enzymes in Eight Breeds of Chinese Indigenous Chickens

R. F. Xu,K. Li,G. H. Chen,B. Y. Z. Qiang,D. L. Mo,B. Fan,C. C. Li,M. Yu,M. J. Zhu,T. A. Xiong,B. Liu 아세아·태평양축산학회 2005 Animal Bioscience Vol.18 No.7

New polymorphism of major histocompatibility complex B-G genes was investigated by amplification and digestion of a 401bp fragment including intron 1 and exon 2 using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique with two restriction enzymes of Msp I and Tas I in eight breeds of Chinese indigenous chickens and one exotic breed. In the fragment region of the gene, three novel single nucleotide polymorphisms (SNPs) were detected at the two restriction sites. We found the transition of two nucleotides of A294G and T295C occurred at Tas I restriction site, and consequently led to a nonsynonymous substitution of asparagine into serine at position 54 within the deduced amino acid sequence of immunoglobulin variableregion- like domain encoded by the exon 2 of B-G gene. It was observed at rare frequency that a single mutation of A294G occurring at the site, also caused an identical substitution of amino acid, asparagine 54-to-serine, to that we described previously. And the transversion of G319C at Msp I site led to a non-synonymous substitution, glutamine 62-to-histidine. The new alleles and allele frequencies identified by the PCR-RFLP method with the two enzymes were characterized, of which the allele A and B frequencies at Msp I and Tas I loci were given disequilibrium distribution either in the eight Chinese local breeds or in the exotic breed. By comparison, allele A at Msp I locus tended to be dominant, while, the allele B at Tas I locus tended to be dominant in all of the breeds analyzed. In Tibetan chickens, the preliminary association analysis revealed that no significant difference was observed between the different genotypes identified at the Msp I and Tas I loci and the laying performance traits, respectively.

재래 흑돼지와 중국 재래돈간의 Melanocortin Receptor 1(MC1R) 유전자의 유전자형 분석

이성수,양보석,정진관,고서봉,오성종,양영훈,김규일,이찬동,풍서당 한국동물자원과학회 2001 한국축산학회지 Vol.43 No.1

PCR-RFLP analysis of Melanocortin receptor 1 (MC1R) gene was carried out to investigate the genotype distribution in Korean-Native and Chinese-Native pig breeds(Neijiang, Putian, Wannanhua and Jinhua). Allelic variants of MC1R in pigs were analyzed by digestion of BspH I , AccII and Hha I . Ncijiang. Wannanhua and Jinhua had only MC1R*2 allele which is considered to be typical genotype for Meishan and Large Black. Among 20 Korean-Native Pigs and 5 Putian pigs, 10 and 2 heads had the MC1R*3 allele (*2/3 or 3/3), respectively, which was detected in European pig breeds such as Hampshire, Large White, and Pietrain. The remaining animals possessed the genotype MC1R*2/2, probably reflecting the genetic introgression of MC1R*3 allele into Korean-Native and Putian pig breeds by the crossbreeding for improvement. The alleles MC1R*l and MC1R*4, which are considered to be typical allele for European Wild Boar with wild-type coat color and Duroc with red coat color, respectively, were not detected in pig breeds used in this experiment. These results indicate that the analysis of genotype frequencies of MC1R gene may be a useful tool for the conservation of Korean-Native and Chinese-Native pig breeds.

The effect of spin reorientation transition of antiferromagnetic NiO on the Py magnetic anisotropy in Py/NiO/CoO/MgO(0 0 1)

Yang, M.,Li, Q.,N'Diaye, A.T.,Dong, Q.Y.,Gao, N.,Arenholz, E.,Hwang, C.,Wu, Y.Z.,Qiu, Z.Q. Elsevier 2018 Journal of magnetism and magnetic materials Vol.460 No.-

<P><B>Abstract</B></P> <P>Using X-ray Magnetic Linear Dichroism (XMLD) measurement, we investigate the antiferromagnetic (AFM) NiO spin reorientation transition (SRT) in epitaxial NiO/CoO/MgO(0 0 1) system at room temperature and constructed a complete NiO spin phase diagram. Then utilizing Magneto-Optic Kerr Effect (MOKE) combined with a rotation magnetic field (ROTMOKE), we investigated the effect of NiO SRT on the magnetic anisotropy of a ferromagnetic (FM) Py overlayer in Py/NiO/CoO/MgO(0 0 1) system. We find that the Py coercivity and anisotropy only slightly enhanced for Py on top of out-of-plane NiO spins but greatly enhanced for Py on top of in-plane NiO spins. Both the uniaxial and fourfold anisotropies of the Py showed a clear dependence on the NiO spin orientation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Spin reorientation transition (SRT) of antiferromagnetic NiO. </LI> <LI> Direct measurement of antiferromagnetic spins using XMLD. </LI> <LI> Quantitative determination of Py magnetic anisotropy using ROTMOKE. </LI> <LI> Demonstration of the effect of the NiO SRT on the Py magnetic anisotropy. </LI> </UL> </P>

Dietary Requirement of True Digestible Phosphorus and Total Calcium for Growing Pigs

Ruan, Z.,Zhang, Y.-G.,Yin, Y.-L.,Li, T.-J.,Huang, R.-L.,Kim, S.W.,Wu, G.Y.,Deng, Z.Y. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.8

Sixty healthy growing pigs ($Duroc{\times}Landrace{\times}Yorkshire$ with an average BW of 21.4 kg) were used to determine the true digestible phosphorus (TDP) requirement of growing pigs on the basis of growth performance and serum biochemical indices. Pigs were assigned randomly to one of five dietary treatments (12 pigs/diet), representing five levels of TDP (0.16%, 0.20%, 0.23%, 0.26% and 0.39%). There were three replications per treatment, with four pigs (2 barrows and 2 gilts) in each replication (2 pigs/pen) A randomized-block design was used, with pen as the experimental unit. Experimental diets were formulated to provide the 5 TDP levels with a total calcium (Ca) to TDP ratio of 2:1, and offered to pigs at 5% BW for 28 d. The total Ca contents of the five diets were 0.33, 0.38, 0.45, 0.51 and 0.79%, respectively. During the 28-d experimental period, the ADG of pigs was affected by dietary TDP levels as described by Equation 1: y = $-809,532x^4+788,079x^3-276,250x^2+42,114x-1$,759; ($R^2$ = 0.99; p<0.01; y = ADG, g/d; x = dietary TDP, %). The feed:gain ratio for pigs was affected by dietary TDP levels as described by Equation 2: y = $3,651.1x^4-3,480.4x^3+1,183.8x^2-172.5x+10.9$ ($R^2$ = 0.99; p<0.01; y = feed:gain ratio; x = dietary TDP, %). Total P concentrations in serum were affected by dietary TDP levels as described by Equation 3: y = $-3,311.7x^4+3,342.7x^3-1,224.6x^2+195.6x-8.7$ ($R^2$ = 0.99; p<0.01; y = total serum P concentration and x = dietary TDP, %). The highest ADG (782 g/d), the lowest feed:gain ratio (1.07), and the highest total serum P concentration (3.1 mmol/L) were obtained when dietary TDP level was 0.34%. Collectively, these results indicate that the optimal TDP requirement of growing pigs is 0.34% of the diet (e.g., 5.1 g/day for a 30-kg pig that consumed 1.5 kg feed daily) at a total Ca to TDP ratio of 2:1.