Mechanism of T-Cell Lymphomagenesis: Transformation of Growth-Factor-Dependent T-Lymphoblastoma Cells to Growth-Factor-Independent T-Lymphoma Cells

In a previous paper we described the induction by x-irradiation or radiation-induced leukemia virus-in-oculation of two classes of lymphoid T-cell neoplasms: The first class, designated T-cell lymphoblastoma (TCLB), consists of growth-factor-dependent eudiploid cells that home to the spleen and give rise to splenic tumors on injection into syngeneic mice; the second class, designated T-cell lymphoma (TCL), consists of growth-factor-independent aneuploid or pseudodiploid cells that give rise to local tumors at the site of subcutaneous injection. This paper describes the generation of a family of growth-factor-independent aneuploid or pseudodiploid TCL cells after the injection into the thymus of growth-factor-dependent diploid TCLB cells. In contrast to the donor TCLB cells, the resulting TCL cells could be cloned in semisolid medium, produced local tumors at the site of subcutaneous injection, and proliferated in a growth-factor-independent fashion in vitro. The induced growth-factor-independent TCL cells were chromosomally and phenotypically unstable and continued to evolve both in vivo and in vitro. After propagation in the thymus, the cells often showed stable translocations in addition to the evolving aneuploidy. We propose that the chromosome abnormalities induced during the proliferation of growth-factor-dependent TCLB cells in the thymus constitute a general mechanism by which neoplastic cells progress from growth-factor dependency to independency

Civil society leadership in the struggle for AIDS treatment in South Africa and Uganda

Includes abstract.Includes bibliographical references.This thesis is an attempt to theorise and operationalise empirically the notion of ‘civil society leadership’ in Sub-Saharan Africa. ‘AIDS leadership,’ which is associated with the intergovernmental institutions charged with coordinating the global response to HIV/AIDS, is both under-theorised and highly context-specific. In this study I therefore opt for an inclusive framework that draws on a range of approaches, including the literature on ‘leadership’, institutions, social movements and the ‘network’ perspective on civil society mobilisation. This framework is employed in rich and detailed empirical descriptions (‘thick description’) of civil society mobilisation around AIDS, including contentious AIDS activism, in the key case studies of South Africa and Uganda. South Africa and Uganda are widely considered key examples of poor and good leadership (from national political leaders) respectively, while the Treatment Action Campaign (TAC) and The AIDS Support Organisation (TASO) are both seen as highly effective civil society movements. These descriptions emphasise ‘transnational networks of influence’ in which civil society leaders participated (and at times actively constructed) in order to mobilise both symbolic and material resources aimed at exerting influence at the transnational, national and local levels

The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences

Radiation leukemia virus and X-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: A growth factor-dependent lymphoma and a growth factor-independent lymphoma

Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. FD-TCL cells were often eudiploid and could be grown in pure culture only at high concentrations, or on stromal feeder layers. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. Single cell cloning of FD-TCL cells in semisolid medium required the addition of exogenous conditioned medium. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. FD-TCL cells did not produce local tumors at the site of subcutaneous injection. The isolation and study of FD-TCL cells were facilitated by their cultivation on stromal hemotopoietic monolayers in supplemented “lymphocyte medium”, until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4–6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype (in some cases trisomic for chromosome No. 15), and produced local tumors at the site of subcutaneous injection. These cells could be cloned in semisolid medium without addition of exogenous factor(s). The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines

Lunchtime School Water Availability and Water Consumption Among California Adolescents

PURPOSE: To examine the potential impact of California SB1413, which required school districts to provide free, fresh drinking water during mealtimes in food service areas by July 1, 2011, on greater water consumption among California adolescents. METHODS: Data were drawn from the 2012 and 2013 state-representative California Health Interview Survey. A total of 2,665 adolescents aged 12-17 were interviewed regarding their water consumption and availability of free water during lunchtime at their school. RESULTS: Three-fourths reported that their school provided free water at lunchtime, mainly via fountains. In a multivariate model that controlled for age, gender, income, race/ethnicity, BMI, and school type, adolescents in schools that provided free water consumed significantly more water than adolescents who reported that water was not available, b (SE) = 0.67 (0.28), p = .02. School water access did not significantly vary across the two years. CONCLUSIONS: Lunchtime school water availability was related to water consumption, but a quarter of adolescents reported that their school did not provide free water at lunch. Future research should explore what supports and inducements might facilitate provision of drinking water during school mealtimes