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Now showing items 1 - 16 of 4211

  • Fetal gene therapy of alpha-thalassemia in a mouse model

    Han, Xiao-Dong   Lin, Chin   Chang, Judy   Sadelain, Michel   Kan, Y. W.  

    Fetuses with homozygous a-thalassemia usually die at the third trimester of pregnancy or soon after birth. Hence, the disease could potentially be a target for fetal gene therapy. We have previously established a mouse model of a-thalassemia. These mice mimic the human a-thalassemic conditions and can be used as preclinical models for fetal gene therapy. We tested a lentiviral vector containing the HS 2, 3, and 4 of the P-LCR, a central polypurine tract element, and the beta-globin gene promoter directing either the EGFP or the human a-globin gene. We showed that the GFP expression was erythroid-specific and detected in BFU-E colonies and the erythroid progenies of CFU-GEMM. For in utero gene delivery, we did yolk sac vessel injection at midgestation of mouse embryos. The recipient mice were analyzed after birth for human a-globin gene expression. In the newborn, human a-globin gene expression was detected in the liver, spleen, and peripheral blood. The human a-globin gene expression was at the peak at 3-4 months, when it reached 20% in some recipients. However, the expression declined at 7 months. Colony-forming assays in these mice showed low abundance of the transduced human a-globin gene in their BFU-E and CFU-GEMM and the lack of its transcript. Thus, lentiviral vectors can be an effective vehicle for delivering the human a-globin gene into erythroid cells in utero, but, in the mouse model, delivery at late midgestation could not transduce hematopoietic stem cells adequately to sustain gene expression.
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  • Development of human single-chain antibodies against SARS-associated coronavirus RID A-9674-2008

    Leung, K. M.   Feng, D. X.   Lou, Jianlong   Zhou, Yu   Fung, K. P.   Waye, Mary M. Y.   Tsui, Stephen K. W.   Chan, Paul K. S.   Marks, James D.   Pang, S. F.   Kan, Y. W.  

    The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as well as North America. Over 1,000 patients died of the SARS virus, representing 10% of infected people. Like other coronaviruses, the SARS virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. The spike protein of SARS virus consists of 1,255 amino acid residues and can be divided into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus to its receptor angiotensin-converting enzyme 2, which is abundantly distributed on the surface of human lung cells. The S2 domain mediates membrane fusion between the virus and the host cell. Hence two strategies can be used to block the infection of the SARS virus, either by interfering with the binding of the S1 domain to the receptor or by blocking the fusion of the virus with the cell membrane mediated by the S2 domain. Several antibodies against the S1 domain have been generated and all of them are able to neutralize the virus in vitro and in vivo using animal models. Unfortunately, point mutations have been identified in the S1 domain, so that the virus isolated in the future may not be recognized by these antibodies. As no mutation has been found in the S2 domain indicating that this region is more conserved than the S1 domain, it may be a better target for antibody binding. After predicting the immunogenicity of the epitopes of the S2 domain, we chemically synthesized two peptides and also expressed one of them using a recombinant DNA method. We screened a phage displaying library of human single-chain antibodies (ScFv) against the predicted epitopes and obtained a human ScFv which can recognize the SARS virus in vitro. Copyright (C) 2008 S. Karger AG, Basel.
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  • AAV serotype 1 mediates more efficient gene transfer to pig myocardium than AAV serotype 2 and plasmid

    Yeghiazarians, Y.   Lee, A.   Huang, Y.   Arakawa-Hoyt, J.   Ye, J.   Orcino, G.   Grossman, W.   Kan, Y. W.  

    Adeno-associated virus (AAV) has many properties of an ideal vector for delivery of therapeutic genes into the myocardium. Previous studies in a mouse model of myocardial infarction showed that AAV serotype 1 (AAV1) is superior to AAV serotypes 2-5 to transfer genes into the myocardium by direct injection. Since vectors may behave differently in humans and because the human and the pig hearts resemble each other closely, we tested whether AAVI is also superior to AAV2 in transferring genes into the pig myocardium. We also compared gene transduction efficiency between AAV vectors and plasmid. We injected CMVLacZ and CMVVEGF (vectors with the cytomegalovirus (CMV) promoter driving LacZ and VEGF gene expression) unpackaged or packaged in AAV serotypes I or 2 capsids into pig myocardium. Hearts were collected 3, 14 and 28 days after the injection. Gene expression was analyzed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and histological staining. Capillaries and smooth muscle a-actin (SMA)-positive vessels were quantified. Potential lymphocyte infiltration at the injection sites was analyzed by immunostaining using specific antibodies. As in the mouse, AAVI mediated better gene transduction than AAV2. Plasmid mediated minimal gene expression only. More capillaries and SMA-positive vessels were detected at AAV1CMVVEGF- and AAV2CMVVEGF-injected than AAV1CMVLacZ-injected sites. We did not detect inflammatory cell infiltration at the injection sites. in conclusion, by direct injection, AAVI is more efficient than AAV2, and plasmid is inefficient in mediating gene transfer into the pig myocardium. AAV-mediated VEGF gene transfer can also induce neovascular formation in the pig myocardium. Copyright (c) 2007 John Wiley & Sons, Ltd.
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  • The equation (w+x+y+z)(1/w+1/x+1/y+1/z)=3Dn

    Bremner, Andrew   Tho Nguyen Xuan  

    Bremner, Guy and Nowakowski [Which integers are representable as the product of the sum of three integers with the sum of their reciprocals? Math. Compos. 61(203) (1993) 117130] investigated the Diophantine problem of representing integers n in the form (x+y+z)(1/x+1/y+1/z) for rationals x, y, z. For fixed n, the equation represents an elliptic curve, and the existence of solutions depends upon the rank of the curve being positive. They observed that the corresponding equation in four variables, the title equation here (representing a surface), has infinitely many solutions for each n, and remarked that it seemed plausible that there were always solutions with positive w, x, y, z when n >=3D 16. This is false, and the situation is quite subtle. We show that there cannot exist such positive solutions when n is of the form 4m(2), 4m(2) + 4, where m not equivalent to 2 (mod 4). Computations within our range seem to indicate that solutions exist for all other values of n.
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  • (W, Y, X)-Gorenstein complexes

    Zhao, Renyu   Ding, Nanqing  

    Let W, Y, X be three classes of left R-modules. In this paper, we introduce and study (W, Y, X)-Gorenstein complexes as a common generalization of completely W-resolved complexes [26], Gorenstein projective (resp., injective) complexes [8], Ding projective (resp., injective) complexes [32] and Gorenstein AC-projective (resp., AC-injective) complexes [4]. It is shown that under certain hypotheses, a complex C is (W, Y, X)-Gorenstein if and only if each C-n is a (W, Y, X)-Gorenstein module and Hom(R)(Y, C), Hom(R)(C, X) are exact for any Y is an element of (Y) over tilde, X is an element of (X) over tilde X. This result unifies the corresponding results of the aforementioned complexes. As applications, the stability of (W, Y, X)Gorenstein complexes and modules are explored.
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  • The equation (w + x + y + z)(1/w + 1/x + 1/y + 1/z) = n

    Bremner, Andrew   Xuan, Tho Nguyen  

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  • CHANGING W > Y IN SYRIAC

    Aim, Emmanuel  

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  • On the Pair of Equations x+y=z+w,y+z=(x-w)^2

    A.Vijayasankar   Sharadha Kumar   M.A.Gopalan  

    The system of double equations given by x+y=z+w,y+z=(x-w)^2,is studied for obtaining its non-zero distinct solutions in integers.
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  • Astma u kobiet w ci??y

    Rogala   Barbara  

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  • Y and W Chromosome Assemblies: Approaches and Discoveries

    Tomaszkiewicz, Marta   Medvedev, Paul   Makova, Kateryna D.  

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  • Y and W Chromosome Assemblies: Approaches and Discoveries

    Tomaszkiewicz, Marta   Medvedev, Paul  

    Hundreds of vertebrate genomes have been sequenced and assembled to date. However, most sequencing projects have ignored the sex chromosomes unique to the heterogametic sex - Y and W - that are known as sex-limited chromosomes (SLCs). Indeed, haploid and repetitive Y chromosomes in species with male heterogamety (XY), and W chromosomes in species with female heterogamety (ZW), are difficult to sequence and assemble. Nevertheless, obtaining their sequences is important for understanding the intricacies of vertebrate genome function and evolution. Recent progress has been made towards the adaptation of next-generation sequencing (NGS) techniques to deciphering SLC sequences. We review here currently available methodology and results with regard to SLC sequencing and assembly. We focus on vertebrates, but bring in some examples from other taxa.
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  • Ni W/nano zeolite Y catalysts for n-heptane hydrocracking

    Anis, Shaheen Fatima   Singaravel, Gnanapragasam   Hashaikeh, Raed  

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  • Evolutionary interaction between W/Y chromosome and transposable elements

    Sliwinska, Ewa B.   Martyka, Rafal   Tryjanowski, Piotr  

    The W/Y chromosome is unique among chromosomes as it does not recombine in its mature form. The main side effect of cessation of recombination is evolutionary instability and degeneration of the W/Y chromosome, or frequent W/Y chromosome turnovers. Another important feature of W/Y chromosome degeneration is transposable element (TEs) accumulation. Transposon accumulation has been confirmed for all W/Y chromosomes that have been sequenced so far. Models of W/Y chromosome instability include the assemblage of deleterious mutations in protein coding genes, but do not include the influence of transposable elements that are accumulated gradually in the non-recombining genome. The multiple roles of genomic TEs, and the interactions between retrotransposons and genome defense proteins are currently being studied intensively. Small RNAs originating from retrotransposon transcripts appear to be, in some cases, the only mediators of W/Y chromosome function. Based on the review of the most recent publications, we present knowledge on W/Y evolution in relation to retrotransposable element accumulation.
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  • Evolutionary interaction between W/Y chromosome and transposable elements

    ?liwińska, Ewa B.   Martyka, Rafa?   Tryjanowski, Piotr  

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  • Le changement\r w>y\r en Syriaque

    A?m   Emmanuel  

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  • Przewlek?y kaszel w praktyce otorynolaryngologicznej

    Arcimowicz, Magdalena   Niemczyk, Kazimierz  

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