A genetically humanized mouse model for hepatitis C virus infection

Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mouse cells permissive to HCV entry in vitro, we attempted murine humanization via a genetic approach. Here we show that expression of two human genes is sufficient to allow HCV infection of fully immunocompetent inbred mice. We establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class I for HCV uptake. We demonstrate that HCV can be blocked by passive immunization, as well as showing that a recombinant vaccinia virus vector induces humoral immunity and confers partial protection against heterologous challenge. This system recapitulates a portion of the HCV life cycle in an immunocompetent rodent for the first time, opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing HCV entry inhibitors in vivo

High Hopes, Few Opportunities (Full Report): The Status of Elementary Science Education in California

This report, produced by the Center for the Future of Teaching and Learning at WestEd, Lawrence Hall of Science at University of California, Berkeley, and SRI International,?addresses how well California is doing to prepare its young people for the evolving economy and societal challenges. Specifically, it describes the status of science teaching and learning in California public elementary schools

High hopes few opportunities: The status of elementary science education in California

This report, produced by the Center for the Future of Teaching and Learning at WestEd, Lawrence Hall of Science at University of California, Berkeley, and SRI International, addresses how well California is doing to prepare its young people for the evolving economy and societal challenges. Specifically, it describes the status of science teaching and learning in California public elementary schools.Among the findings:- Forty percent of elementary teachers say they spend 60 minutes or less teaching science each week- Only one third of elementary teachers say they feel prepared to teach science- Eighty-five percent of teachers say they have not received any professional development in science during the last three years- 9 in 10 principals say science education is very important and should start early- Less than half of principals (44%) believe it is likely that a student would receive high-quality science instruction in his or her schoolThe reasons underlying the lack of high-quality learning opportunities in the state's elementary schools are many. For example:- Teachers do not feel prepared to teach science -- especially in comparison to their preparation to teach English language arts and mathematics.- Districts and schools do not have the resources (staff, time, or funds) to provide the needed professional development.- High-quality science teaching requires specialized materials, which teachers also say they lack, and districts and schools are strapped to provide these resources.These shortcomings are rooted in part in the state and federal accountability systems that place the greatest emphasis on English language arts and mathematics, which receive the lion's share of political and practical attention. The end result? California does not have a coherent system that enables teachers and schools to consistently provide students with high-quality science learning

High Hopes, Few Opportunities (Summary Report & Recommendations): The Status of Elementary Science Education in California

This report, prepared by the Center for the Future of Teaching and Learning at WestEd, summarizes extensive new research examining science education in California's classrooms, schools, and school districts. A key finding? Students have little access to high-quality science education

SCID repopulating cells derived from unmobilised adult human peripheral blood

Severe combined immunodeficient (SCID)-repopulating cells (termed SRC) with lymphohaematopoietic differentiation potential reside at an extremely low frequency in unmobilised adult human peripheral blood. Recently, an ex vivo method of increasing the relative numbers of at least four distinct human stem cell classes, that include CD34+ haematopoietic progenitor cells, in mononuclear cells (MNC) obtained from unmobilised adult human peripheral blood has been described. This process is triggered by a monoclonal antibody (mAb) against the human monomorphic region of the beta chain of HLA-DP, DQ and DR (clone CR3/43). Herein, we assess the ability of human male donor-derived MNC, following ex vivo culturing for 3 hr in haematopoietic-conducive conditions (HCC) (3-hr MNC/HCC), to form SRC in female non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. All 3-hr MNC/HCC-recipient animals exhibited significant levels (\u3e 0.5%) of human cell engraftment in the bone marrow, thymus and spleen when compared to animals receiving MNC cultured in the absence of CR3/43. Phenotypic characterisation of the bone marrow cell populations of engrafted mice demonstrated significant levels of human lymphohaematopoietic cell lineages, comprised of T lymphocytes, monocytes, erythrocytes and megakaryocytes, including platelets. In addition, significant levels of clonogenic human CD34+ cells were also detected by in vitro surrogate assay. The thymi of engrafted animals contained maturating human thymocytes, while the spleen consisted mainly of T lymphocytes. Fluorescence in situ hybridisation (FISH) further identified the presence of human male X and Y chromosomes at engrafted sites, whilst the human origin of the cells was confirmed by a specific PCR assay for the human Cart-1 gene. In conclusion, the conversion of MNC to SRC in response to treatment with CR3/43 for 3 hr could have far-reaching clinical implications especially where time and donor-histocompatibility are limiting factors