UDP-glucose ceramide glucosyltransferase activates AKT,promoted proliferation,and doxorubicin resistance in breast cancer cells

The UDP-glucose ceramide glucosyltransferase (UGCG) is a key enzyme in the synthesis of glycosylated sphingolipids, since this enzyme generates the precursor for all complex glycosphingolipids (GSL), the GlcCer. The UGCG has been associated with several cancer-related processes such as maintaining cancer stem cell properties or multidrug resistance induction. The precise mechanisms underlying these processes are unknown. Here, we investigated the molecular mechanisms occurring after UGCG overexpression in breast cancer cells. We observed alterations of several cellular properties such as morphological changes, which enhanced proliferation and doxorubicin resistance in UGCG overexpressing MCF-7 cells. These cellular effects seem to be mediated by an altered composition of glycosphingolipid-enriched microdomains (GEMs), especially an accumulation of globotriaosylceramide (Gb3) and glucosylceramide (GlcCer), which leads to an activation of Akt and ERK1/2. The induction of the Akt and ERK1/2 signaling pathway results in an increased gene expression of multidrug resistance protein 1 (MDR1) and anti-apoptotic genes and a decrease of pro-apoptotic gene expression. Inhibition of the protein kinase C (PKC) and phosphoinositide 3 kinase (PI3K) reduced MDR1 gene expression. This study discloses how changes in UGCG expression impact several cellular signaling pathways in breast cancer cells resulting in enhanced proliferation and multidrug resistance.     

Multiple roles of class I HDACs in proliferation, differentiation, and development

Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future.     

Application of an Optical Biosensor to Study the Interaction between Porphyrins and Wheat Germ Agglutinin

0Introduction Porphyrinderivativeshavebeenusedasphotosensitizersinphotodynamictherapy(PDT),anewapproachdevel opedforthetreatmentofcancer[1].Cationwater solublepor phyrinsareofconsiderableinterestowingtotheirpossiblebio medicalapplications[2].Inwhich,theinhibiteffectonthe growthmetabolismofE.coliandcancercellHL60ofmeso tetra(4N ethylacetatepyridyl)porphyrin(H2NEAE pp)and itsZn(Ⅱ)complexform(ZnNEAE pp)havebeenrecentlyin vestigated[3,4].Toenhancetumor locationandanticancerac tivitiesofdr…     

Biochemical,biophysical and molecular dynamics studies on the proteoglycan-like domain of carbonic anhydrase IX

Human carbonic anhydrase IX (hCA IX) is a tumour-associated enzyme present in a limited number of normal tissues, but overexpressed in several malignant human tumours. It is a transmembrane protein, where the extracellular region consists of a greatly investigated catalytic CA domain and a much less investigated proteoglycan-like (PG) domain. Considering its important role in tumour biology, here, we report for the first time the full characterization of the PG domain, providing insights into its structural and functional features. In particular, this domain has been produced at high yields in bacterial cells and characterized by means of biochemical, biophysical and molecular dynamics studies. Results show that it belongs to the family of intrinsically disordered proteins, being globally unfolded with only some local residual polyproline II secondary structure. The observed conformational flexibility may have several important roles in tumour progression, facilitating interactions of hCA IX with partner proteins assisting tumour spreading and progression.     

关于正规双曲方程组的不完全Huygens现象

文中将不完全Ｈｕｙｇｅｎｓ现象这一概念推广到双正规曲型方程组上，并给出了几个定理和例子     

Glucocorticoid localization by radioautography in the rabbit eye following systemic administration of3H-dexamethasone

Summary Dexamethasone was localized radioautographically in the nuclei of target cells of the rabbit eye, following i.v. administration of the labeled steroid. Nuclear receptors in stromal and endothelial cells of the outflow pathway region suggest that glucocorticoids may alter the outflow facility by specific responses of target cells.Acknowledgments. This work was supported by grant EY-01313 of the National Eye Institute, National Institutes of Health, Bethesda, Md, USA.     

黄骅坳陷北大港油田古近系碎屑岩储层成岩作用及其对储层质量的影响

为了明确黄骅坳陷北大港油田古近系碎屑岩储层的成岩作用特征及其影响因素,在综合分析大量岩石薄片、扫描电镜、阴极发光、X衍射及物理性质等分析化验资料的基础上,对研究区古近系碎屑岩储层成岩作用类型及特征、成岩演化阶段及成岩作用影响因素进行了综合研究,并在此基础上划分了成岩相类型,探讨了成岩作用对储层质量的影响作用.结果表明,研究区东营组砂岩主要处于早成岩B期,部分达到中成岩A1期;沙河街组砂岩主要处于中成岩A期,部分达到中成岩B期.压实作用和胶结作用使储层原生孔隙迅速减少,渗透率降低,大大降低了砂岩的储集物性;后期的溶解作用促使砂岩次生孔隙发育,改善了砂岩的储集性能.研究区砂岩可划分为压实固结成岩相、碳酸盐胶结成岩相、弱胶结成岩相和不稳定组分溶蚀成岩相4种成岩相类型,其中不稳定组分溶蚀成岩相控制的储层物性最好,弱胶结成岩相控制的储层物性次之,碳酸盐胶结成岩相和压实固结成岩相控制的储层物性较差.明确研究区成岩作用特征及成岩相分布特点,对寻找该区有利储层具有重要指导意义.     

新疆桑皮纸的口头与非物质文化遗产的价值体现

本文根据《保护非物质文化遗产公约》和《人类口头与非物质文化遗产申报书编写指南》的要求,详细介绍了新疆传统手工艺——桑皮纸的基本情况、独特性、历史传承价值、生活价值、文化价值、艺术价值及保护情况等内容,对新疆桑皮纸的价值体现进行了研究。认为桑皮纸是维吾尔族人民为中华民族留下的宝贵的非物质文化遗产。