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Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma
Yang, Y.,Kelly, P.,Shaffer, A.L.,Schmitz, R.,Yoo, H.M.,Liu, X.,Huang, D.W.,Webster, D.,Young, R.M.,Nakagawa, M.,Ceribelli, M.,Wright, G.W.,Yang, Y.,Zhao, H.,Yu, X.,Xu, W.,Chan, W.C.,Jaffe, E.S.,Gascoy Cell Press 2016 CANCER CELL Vol.29 No.4
Chronic active B cell receptor (BCR) signaling, a hallmark of the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activate IκB kinase (IKK) and the classical NF-κB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-κB activity in ABC DLBCL. cIAP½ attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation. SMAC mimetics target cIAP½ for destruction, and consequently suppress NF-κB and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL.
Synthesis of TiO<sub>2</sub> Nanotubes and Their Sensitivity for Toluene Gas
Yue, H.Y.,Huang, S.,Guo, E.J.,Wang, L.P.,Kang, F.W.,Yu, Z.M.,Guo, Y.K.,Sun, F.L. The Korean Powder Metallurgy Institute 2011 한국분말재료학회지 (KPMI) Vol.18 No.1
$TiO_2$ nanopowders with anatase structure were firstly prepared by controlling the pH value of a precursor solution without any heat-treatment at room temperature. The prepared $TiO_2$ nanopowders were hydrothermally treated in 10M NaOH solution at $170^{\circ}C$. Then, the samples were washed in DI water or 0.1M HCl. The $TiO_2$ nanotubes were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM). The gas sensitivity of $TiO_2$ nanotubes for toluene gas was also investigated. The results show that $TiO_2$ nanotubes can be prepared by hydrothermal treatment. The morphology of $TiO_2$ nanotubes prepared by 0.1M HCl washing is destroyed to some extent. $TiO_2$ nanotubes with DI water washing show better sensitivity than that with 0.1M HCl washing.
Chacon-Heszele, Maria F.,Zuo, Xiaofeng,Hellman, Nathan E.,McKenna, Sarah,Choi, Soo Young,Huang, Liwei,Tobias, John W.,Park, Kwon Moo,Lipschutz, Joshua H. American Physiological Society 2014 American Journal of Physiology Vol.306 No.9
<P>Cystogenesis and tubulogenesis are basic building blocks for many epithelial organs, including the kidney. Most researchers have used two-dimensional (2D) cell culture to investigate signaling pathways downstream of hepatocyte growth factor (HGF). We hypothesize that three-dimensional (3D) collagen-grown Madin-Darby canine kidney (MDCK) cells, which form cysts and then tubulate in response to HGF, are a much more in vivo-like system for the identification of novel tubulogenes. With the use of a canine microarray containing over 20,000 genes, 2,417 genes were identified as potential tubulogenes that were differentially regulated, exclusively in 3D-grown MDCK cells. Among these, 840 were dependent on MAPK signaling. Importantly, this work shows that many putative tubulogenes, previously identified via microarray analysis of 2D cultures, including by us, do not change in 3D culture and vice versa. The use of a 3D-culture system allowed for the identification of novel MAPK-dependent and -independent genes that regulate early renal tubulogenesis in vitro, e.g., matrix metalloproteinase 1 (MMP1). Knockdown of MMP1 led to defects in cystogenesis and tubulogenesis in 3D-grown MDCK cells, most likely due to problems establishing normal polarity. We suggest that data obtained from 2D cultures, even those using MDCK cells treated with HGF, should not be automatically extrapolated to factors important for cystogenesis and tubulogenesis. Instead, 3D culture, which more closely replicates the biological environment and is therefore a more accurate model for identifying tubulogenes, is preferred. Results from the present analysis will be used to build a more accurate model of the signaling pathways that control cystogenesis and tubulogenesis.</P>
Evolution of asexual and sexual reproduction in the aspergilli
Ojeda-Ló,pez, M.,Chen, W.,Eagle, C.E.,Gutié,rrez, G.,Jia, W.L.,Swilaiman, S.S.,Huang, Z.,Park, H.-S.,Yu, J.-H.,Cá,novas, D.,Dyer, P.S. CBS Fungal Biodiversity Centre 2018 Studies in mycology Vol.91 No.-
<P><I>Aspergillus nidulans</I> has long-been used as a model organism to gain insights into the genetic basis of asexual and sexual developmental processes both in other members of the genus <I>Aspergillus</I>, and filamentous fungi in general. Paradigms have been established concerning the regulatory mechanisms of conidial development. However, recent studies have shown considerable genome divergence in the fungal kingdom, questioning the general applicability of findings from <I>Aspergillus</I>, and certain longstanding evolutionary theories have been questioned. The phylogenetic distribution of key regulatory elements of asexual reproduction in <I>A. nidulans</I> was investigated in a broad taxonomic range of fungi. This revealed that some proteins were well conserved in the <I>Pezizomycotina</I> (<I>e.g.</I> AbaA, FlbA, FluG, NsdD, MedA, and some velvet proteins), suggesting similar developmental roles. However, other elements (<I>e.g.</I> BrlA) had a more restricted distribution solely in the <I>Eurotiomycetes</I>, and it appears that the genetic control of sporulation seems to be more complex in the aspergilli than in some other taxonomic groups of the <I>Pezizomycotina</I>. The evolution of the velvet protein family is discussed based on the history of expansion and contraction events in the early divergent fungi. Heterologous expression of the <I>A. nidulans abaA</I> gene in <I>Monascus ruber</I> failed to induce development of complete conidiophores as seen in the aspergilli, but did result in increased conidial production. The absence of many components of the asexual developmental pathway from members of the <I>Saccharomycotina</I> supports the hypothesis that differences in the complexity of their spore formation is due in part to the increased diversity of the sporulation machinery evident in the <I>Pezizomycotina</I>. Investigations were also made into the evolution of sex and sexuality in the aspergilli. <I>MAT</I> loci were identified from the heterothallic <I>Aspergillus</I> (<I>Emericella</I>) <I>heterothallicus</I> and <I>Aspergillus</I> (<I>Neosartorya</I>) <I>fennelliae</I> and the homothallic <I>Aspergillus pseudoglaucus</I> (=<I>Eurotium repens</I>). A consistent architecture of the <I>MAT</I> locus was seen in these and other heterothallic aspergilli whereas much variation was seen in the arrangement of <I>MAT</I> loci in homothallic aspergilli. This suggested that it is most likely that the common ancestor of the aspergilli exhibited a heterothallic breeding system. Finally, the supposed prevalence of asexuality in the aspergilli was examined. Investigations were made using <I>A. clavatus</I> as a representative ‘asexual’ species. It was possible to induce a sexual cycle in <I>A. clavatus</I> given the correct <I>MAT1-1</I> and <I>MAT1-2</I> partners and environmental conditions, with recombination confirmed utilising molecular markers. This indicated that sexual reproduction might be possible in many supposedly asexual aspergilli and beyond, providing general insights into the nature of asexuality in fungi.</P>
Huang, S.Y.,Song, H.L.,Lin, E.-C.,Lee, W.C.,Chiang, J.C.,Tsou, H.L. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.6
The quality characteristics of semen are important indicators of the fertility of a boar. Development of genetic markers for the semen quality in boars will be beneficial to the improvement of porcine fertility. We investigated the relationship between the polymorphisms of epidermal growth factor (EGF), prostaglandin-endoperoxide synthase 2 (PTGS2) and prolactin receptor (PRLR) genes, and semen quality traits in boars. The genomic DNA of 233 boars (157 Duroc and 86 Landrace) from a central testing station was subjected to genotyping for surveying gene frequency. The EGF, PTGS2 and PRLR genotypes were determined using the restriction fragment length polymorphism method. Thirty-seven normal, mature Duroc boars from an AI center were also genotyped and their semen quality traits were collected. The effect of genotype on semen quality traits was analyzed by the least-squares means method using data corrected for season. The frequencies of the AA genotype of EGF, PTGS2 and PRLR in Duroc boars were 0.14, 0.01 and 0.66, respectively. In Landrace, the frequencies of the AA genotype were 0.03, 0.09 and 0.62, respectively. Boars with the BB genotype in EGF, with the AB genotype in PTGS2 and with the AA genotype in PRLR had significantly better semen quality with a higher percentage of normal sperm and a lower percentage of immature sperm than those with other genotypes. These findings imply that polymorphisms of EGF, PTGS2 and PRLR genes might be used as markers for improving the semen quality of boars.