Abstract: The present invention relates to a novel human orphan nuclear receptor that binds to a cytochrome P-450 monooxygenase (CYP) promoter and that is activated by compounds that induce CYP gene expression. The invention further relates to nucleic acid sequences encoding such a receptor, to methods of making the receptor and to methods of using the receptor and nucleic acid sequences encoding same. The invention also relates to non-human animals transformed to express the human receptor and to methods of using such animals to screen compounds for drug interactions and toxicities.

Abstract: The invention provides methods and compositions for modulating hepsin activity and the MSP/Ron pathway, in particular by regulating pro-MSP activation by hepsin.

Abstract: A fusion protein that includes a polypeptide binding specifically to a constant region of an antibody and a stabilization protein linked to a terminus of the polypeptide, a polynucleotide encoding the fusion protein, a cell including the polynucleotide, a method of preparing the fusion protein, and a method of isolating an antibody by using the fusion protein.

Abstract: This document provides methods and materials related to treating liver conditions. For example, the methods and materials relating to the use of cAMP inhibitors to treat liver conditions are provided.

Abstract: IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpaha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

Abstract: The invention relates to a recombinant human factor IX (FIX) characterized in that said factor is obtained by a preparation method comprising, or even consisting of, the steps which consist in causing the genetic material encoding the FIX to be expressed in vitro in a human hepatocyte cell line Huh7, recovering the cellular supernatant in which the FIX was secreted and, optionally, purifying the synthesized FIX.

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: The present invention relates to a composition for preserving cells, tissues and organs, comprising as an active ingredient indole and indazole compounds of formula (1), or a pharmaceutically acceptable salt or isomer thereof, which are effective for preventing injury of organs, isolated cell systems or tissues caused by cold storage, transplant operation or post-transplantation reperfusion; a preservation method; and a preparation method of the composition.

Abstract: A serum-free, synthetic tissue culture media is described which is completely defined chemically. The media do not require any supplementation with serum to support growth of cells. The media and methods described herein can also be used for growing all types of mammalian cell lines in culture without addition of transferrin protein. The media include a basal medium and an activator of iron uptake. The media also include a defined cell culture media that includes an iron-containing compound, which is capable of supporting the growth of mammalian cells in culture, increasing the level of expression of recombinant protein in cultured cells, and/or increasing virus production in cultured cells.

Abstract: Neuroinvasive and neurovirulent strain of the West Nile virus, named IS-98-ST1, nucleic acid molecules derived from its genome, proteins and peptides encoded by said nucleic acid molecules, and uses thereof.

Abstract: The present invention relates to methods of host cell transduction utilising ecotropic retroviral vector particles. The retroviral vector particle may comprise an envelope of Friend murine leukaemia virus, in particular the envelope encoded by molecular clone PVC-211 and the host cell may be engineered to recombinantly express the Reel receptor. The retroviral vector particles and methods of the invention can be used to introduce expressible polynucleotide sequences of interest into host cells with high efficiency. This results in protein production methods with higher yield (mg/L) and a reduction in manufacturing costs that could be used in a range of applications including for example, the production of therapeutic proteins, vaccines and antibodies.

Abstract: A substantially enriched mammalian hepatic liver engrafting cell population is provided. Methods are provided for the isolation and culture of this liver engrafting cell, for example, a cell population containing human liver engrafting cells wherein at least one cell in the population is HLAlow/neg; and expresses at least one marker selected from the group consisting of albumin; 5E12; Ep-Cam; CD49f; and E-Cadherin. The progenitor cells are obtained from a variety of sources, including fetal and adult tissues. The cells are useful in transplantation, for experimental evaluation, and as a source of lineage and cell specific products, including mRNA species useful in identifying genes specifically expressed in these cells, and as targets for the discovery of factors or molecules that can affect them.

Abstract: A herpes simplex virus is disclosed in which the herpes simplex virus genome comprises a nucleic acid sequence encoding an ING4 polypeptide.

Abstract: The present disclosure provides isolated binding molecules that bind to the human OX40R, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.

Abstract: A polynucleotide encoding the amino acid shown in SEQ ID NO:2 or SEQ ID NO: 5, or encoding an amino acid sequence having not less than 98% identity thereto; preferably a polynucleotide comprising replacement of the amino acid corresponding to glutamic acid at position 1202 of SEQ ID NO:2 (position 177 of SEQ ID NO:5) with glycine, replacement of the amino acid corresponding to glutamic acid at position 1056 (position 31 of SEQ ID NO:5) with valine, and replacement of the amino acid corresponding to alanine at position 2199 (position 1174 of SEQ ID NO:5) with threonine.

Abstract: The invention provides anti-PCSK9 antibodies and methods of using the same.

Abstract: The invention relates to newly identified selectable marker systems, cells for use in a selectable marker system, and methods for using the selectable marker systems.

Abstract: Compositions and methods for making and using anti-LPA agents, for example, monoclonal antibodies, are described.

Abstract: The present invention discloses a method for inducing the differentiation of embryonic stem cells (ESC) or induced pluripotent stem cells (iPS cells) into hepatocytes, a method for inducing the differentiation of embryonic stem cells or induced pluripotent stem cells into hepatic endoderm cells, and a method for inducing the differentiation of embryonic stem cells (ESC) or induced pluripotent stem cells into hepatic progenitor cells. The present invention also provides the hepatocytes, hepatic endoderm cells and hepatic progenitor cells obtained by above methods, and the uses of these cells.

Abstract: Synthetic cell culture surfaces, including a hydrophobe modified cellulose or an hydroxylated acrylate polymer composition and optionally including a silica source, cell culture coating and cell culture articles incorporating the composition, and methods of making and using the articles for cell culture, as defined herein.

Abstract: The invention relates to fusion proteins that bind the enzyme thrombin and enhance the activation of the substrate Factor VII to the product Factor VIIa. The invention is also directed to polynucleotides, vectors, host cells, pharmaceutical compositions, and methods of treatment.

Abstract: The present invention provides compositions comprising cells that can effectively produce HCV after HCV infection, compositions for culturing the cells, methods for making the composition and methods for infecting the cells in the composition with HCV. The present invention also provides methods for assaying HCV production and methods for evaluating compounds that affect the production of HCV.

Abstract: Methods are provided for producing a human embryo capable of developing to the blastocyst stage. The method includes transferring a human somatic cell genome into a mature human oocyte by nuclear transfer and activating the oocyte, without removing the oocyte genome. Pluripotent human embryonic stem cells, and methods of obtaining these, are also provided.

Abstract: The present invention pertains to an auxin receptor protein involved in activation of proton pump in plasma membrane of a plant derived from rice, a gene encoding the protein, a recombinant vector comprising the gene, a host cell transformed with the recombinant vector, a method of improving traits of a plant by transforming the plant with the recombinant plant expression vector, a plant having improved traits by transformation with the recombinant plant expression vector and seeds of the plant, and a composition comprising the gene of the invention for improving traits of a plant.

Abstract: The present disclosure relates to the use and methods of manufacture of bicyclic nucleosides and nucleotides for the treatment and prevention of infectious and proliferative diseases, including microbial infections and cancer.

Abstract: The present invention provides methods for stabilizing a biological sample for analysis. The invention more particularly provides methods combining heat treatment and chemical fixation of biological samples in order to maintain protein primary structure and post-translational modifications, such as protein phosphorylations.

Abstract: A mouse model is provided which is directed to mice bred to have a disruption in the TGF-? signaling pathways which causes tumorigenesis in the liver and gut of the developing mice. The mice models of the invention include those mice whose genome include at least one mutant allele of a protein involved in the TGF-? signaling pathway, such as the elf protein or to the Smad proteins, and such models are advantageous in that they allow the study of tumor suppression and development in the liver and gut and can thus be used to study, assess and treat a variety of forms of hepatocellular and gastrointestinal cancer. Use of the Elf and Smad proteins and antibodies thereto in the diagnosis and treatment of liver and gut tumors is also provided.

Abstract: The present invention concerns human hepatocyte cell line cultures and their use in bioartificial liver (BAL) systems. These systems are used to treat subjects suffering from liver failure to temporarily compensate for loss of hepatocellular function and generally comprise a bioreactor loaded with functional liver cells. Until now, it has been problematic to acquire cells with a broad spectrum metabolic functionality, resembling that of freshly isolated human hepatocytes, to the extent that they are in fact suitable for successful clinical BAL application The present inventors have managed to develop human hepatocyte cell line cultures that display broad-spectrum metabolic functionality such as to render them particularly suitable for effective clinical BAL application.

Abstract: Cytomegalovirus (CMV) Intron A fragments for expressing gene products are disclosed. Also described are expression vectors including the fragments, as well as methods of using the same.

Abstract: The disclosure provides methods and materials for increasing the expression of a protein of interest such as an antibody by a cell. ABC50 expression or activity is increased which increases expression of the protein or antibody of interest. The disclosure also provides methods and materials for increasing the sensitivity of a cell to an endoplasmic reticulum stress agent such as Econozole by decreasing the level of ABC50.

Abstract: Compositions and methods for stimulating an immune response against Shiga toxin-producing Escherichia coli (STEC) antigens are disclosed. The compositions include a multiple epitope fusion protein comprising more than one epitope of an immunogenic STEC protein from more than one STEC serotype. Additional compositions include at least two purified STEC proteins, wherein the STEC proteins are selected from a full-length STEC protein, an immunogenic fragment or variant thereof, wherein at least one of the STEC proteins generates antibodies that react with STEC O157 and at least one other STEC serotype.

Abstract: The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the present invention produced increased lean muscle mass when administered to animals and decreased fat to muscle ratios. Therapeutic compositions containing the binding agents of the present invention are useful for treating muscle-wasting disorders and metabolic disorders including diabetes and obesity.

Abstract: Methods for differentiating primate pluripotent stem cells into hepatocyte-lineage cells are provided. In certain embodiments, the methods utilize sequential culturing of the primate pluripotent stem cells in certain growth factors to produce hepatocyte-lineage cells. In certain embodiments, the population of cells produced by the methods is further enriched for hepatocyte-lineage cells.

Abstract: The cryopreservation of cells and tissue cultures for long term storage of cells, cell constructs or three-dimensional complex tissues assemblies is based on the use of a collagen cell carrier (CCC) having a specific composition and thickness and appropriate mechanical properties which are maintained after thawing. The collagen cell carrier provides a suitable support for the cryopreservation resulting in high survival rates after thawing and providing cells and tissue assemblies already adhered to a mechanically stable and biocompatible support. Frozen collagen carrier-cells assemblies, the frozen artificial cell constructs or three-dimensional complex tissue assemblies obtainable by the method and the use thereof after thawing are also disclosed.

Abstract: The present invention relates to a method for producing infectious hepatitis C virus (HCV) particles, comprising a step of introducing an expression vector into a cell that allows HCV proliferation, such expression vector comprising: DNA sequences encoding the 5? untranslated region, structural proteins, and, if necessary, non-structural proteins of HCV and DNA sequences encoding non-structural proteins and the 3? untranslated region derived from the HCV JFH1 strain, which are located downstream of a polymerase I promoter; and a DNA fragment containing an RNA polymerase I terminator, which is located further downstream thereof.

Abstract: The invention describes novel virus-like particles for use as vaccines, diagnostic tools and R&D tools based on recombinant DNA and cell cultivation techniques for production. The recombinant virus-like particles of the invention are assembled by polypeptide chains that incorporate several, in particular two or more, different epitopes which are selected either (a) from different viral strains of the same virus and/or (b) from different serotypes of the same virus and/or (c) from different viral strains specific for different hosts. These epitopes are then displayed on the particle surface.

Abstract: The invention provides a method for preparing a perfusion based 3D cell culture system, a recellularized matrix culture system, and methods of using the culture system.

Abstract: The use of the liver cell line QSG-7701 for HBV infection includes the following steps: directly infecting QSG-7701 cells with purified HBV particles and facilitating the infection by DMSO and/or PEG treatment. The easily available QSG-7701 liver cell line may not require pre-differentiation induction and is naturally susceptible for HBV infection. This cell line provides near normal physiological conditions for HBV infection, especially the infection conditions that are characterized with Chinese origin. This cell line is suitable for investigating the life cycle of HBV. Therefore, this cell line is useful for the investigation of viral infection processes and for the development of drugs that specifically target these processes.

Abstract: Described herein is a method of expanding human hepatocytes in vivo using an immunodeficient mouse which is further deficient in fumarylacetoacetate hydrolase (Fah). The method comprises transplanting human hepatocytes into the immunodeficient and Fah-deficient mice, administering an IL-1R antagonist to the mouse and allowing the hepatocytes to expand. Alternatively, the method includes transplanting human hepatocytes into the immunodeficient and Fah-deficient mice, wherein the mouse is further deficient for IL-1R and allowing the hepatocytes to expand. The method also allows serial transplantation of the human hepatocytes into secondary, tertiary, quaternary or additional mice.

Abstract: The method is based on the use of expression vectors coding for the sense and anti-sense mRNA of the Phase I and Phase II drug biotransformation enzymes showing a greatest variability in humans for transforming cells expressing reductase activity. Such vectors can modulate (increase or decrease) the individualized expression of an enzyme without affecting the other enzymes. This singular cell model can reproduce in vitro the metabolic idiosyncrasy of humans. It is applicable in the study of development of new drugs, specifically in the study of metabolism, potential idiosyncratic hepatotoxicity, medicament interactions, etc., of new drugs.

Abstract: The present invention relates to precursor cells to hepatic stellate cells, compositions comprising same and methods of isolating same. The surface antigenic profile of the precursors is MHC class Ia negative, ICAM-1+, VCAM-1+, ?3-integrin+. In addition to expression of these surface markers, the cells also express the intracellular markers desmin, vimentin, smooth muscle ?-actin, nestin, hepatocyte growth factor, stromal derived factor-1? and Hlx homeobox transcriptional factor.

Abstract: The present invention relates to novel adenovirus strains with an improved sero-prevalence. In one aspect, the present invention relates to isolated polypeptides of adenoviral capsid proteins such as hexon, penton and fiber protein and fragments thereof and polynucleotides encoding the same. Also provided is a vector comprising the isolated polynucleotide according to the invention and adenoviruses comprising the isolated polynucleotides or polypeptides according to the invention and a pharmaceutical composition comprising said vector, adenovirus, polypeptide and/or polynucleotide. The invention also relates to the use of the isolated polynucleotides, the isolated polypeptides, the vector, the adenoviruses and/or the pharmaceutical composition for the therapy or prophylaxis of a disease.

Abstract: An extracorporeal filtration and detoxification system and method generally comprise separating ultrafiltrate from cellular components of blood, treating the ultrafiltrate independently of the cellular components in a recirculation circuit, recombining treated ultrafiltrate and the cellular components, and returning whole blood to the patient. A recirculation circuit generally comprises an active cartridge including active cells operative to effectuate a selected treatment; in some embodiments, the active cells are the C3A cell line.

Abstract: The invention is directed to methods for culturing cells so that the cells are induced to differentiate into cells that express a hepatic stellate phenotype and cells that express a hepatic sinusoidal endothelial phenotype. The invention is also directed to cells produced by the methods of the invention. The cells are useful, among other things, for treatment of liver deficiency, liver metabolism studies, and liver toxicity studies.

Abstract: The present invention provides a nucleic acid comprises a 5? untranslated region, an NS3 protein coding region, an NS4A protein coding region, an NS4B protein coding region, an NS5A protein coding region, an NS5B protein coding region, and a 3? untranslated region of a hepatitis C virus genome, wherein the nucleic acid has nucleotide substitutions causing one or more amino acid substitutions selected from the group consisting of M(1205)K, F(1548)L, C(1615)W, T(1652)N, A(2196)T, A(2218)S, H(2223)Q, Q(2281)R, K(2520)N, and G(2374)S, as defined using the amino acid sequence shown in SEQ ID NO: 6 in the Sequence Listing as a reference sequence, in the NS3 protein coding region, the NS5A protein coding region, or the NS5B protein coding region.

Abstract: The present inventors used the previously developed H77/JFH1T27OOC,A4O8OT (1a/2a), J4/JFH1T2996C,A4827T,?HVRI (1b/2a), J6/JFH1?HVRI (2a/2a), J8/JFH1?HVRI (2b/2a), S52/JFH1T27i8G,?7i6oc (3a/2a), SA13/JFH1C34O5G,A3696G (5a/2a) and HK6a/JFH1T1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH1 (geno-type 2a) based, genomes. The present inventors serially passaged the viruses in cell culture obtaining relatively high HCV RNA titers and infectivity titers. Sequence analysis of the viruses identified mutations adapting H77/JFH1T27OOC,A4O8OT,?HVR1 (1a/2a), J8/JFH1?HVR1 (2b/2a), S52/JFH1T2718G,T716OC,?HVR1 (3a/2a) and J4/JFH1T2996C,A4827T,?HVR1 (1b/2a) to the HVR1 deletion.

Abstract: The present inventors developed hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A. The inventors have identified a deletion upstream of the inserted reporter gene sequence, which conferred favourable growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. Drugs could be evaluated for their potential to prevent infection or cure infected cells. The neutralizing capacity of antibodies induced by vaccine candidates could be evaluated in order to define successful vaccination strategies. Broadly neutralizing antibodies could be identified testing engineered antibodies and antibodies derived from serum of HCV infected individuals; thus this technique could contribute to the development of immunotherapy.

Abstract: The present disclosure provides compositions, pharmaceutical preparations, kits and methods for inhibiting cell proliferation by contacting a cell expressing Fzd8 with a truncated Wnt2 polypeptide which acts as a dominant negative inhibitor of Fzd8 signaling. The present disclosure provides compositions, kits and methods for the detection of cancer by determining the level of Fzd8 and/or Wnt2 expression in a cell.

Abstract: In certain embodiments this invention this invention pertains to the discovery that inhibition of myosin light chain interacting protein (Mylip) can mitigate one or more symptoms of hypercholesterolemia. Methods of treating hypercholesterolemia and methods of screening for agents to treat hypercholesterolemia are provided.

Abstract: Cell cultures are provided that include a population of micropatterened hepatocytes and one or more non-parenchymal cell populations, where the hepatocytes are infected with a virus or parasite and include a reporter of virus or parasite infection. Methods of making and using the cell cultures are also provided.