Showing papers by "David Baltimore published in 2004"

Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-κB activation pathways

Abstract: B lymphocytes can be activated by many different stimuli. However, the mechanisms responsible for the signaling and functional specificities of individual stimuli remain to be elucidated. Here, we have compared the contribution of the type 1 (p50-dependent) and type 2 (p52-dependent) NF-kappaB activation pathways to cell survival, proliferation, homotypic aggregation, and specific gene regulation of murine primary B lymphocytes. Whereas lipopolysaccharide (LPS) and B cell activation factor (BAFF) mainly activate the type 1 or type 2 pathways, respectively, CD40 ligand (CD40L) strongly activates both. Rescue of spontaneous apoptosis is diminished in p52(-/-) B cells after BAFF stimulation and in p50(-/-)c-Rel(-/-) B cells after LPS stimulation. Interestingly, significant CD40-induced B cell survival is still observed even in p50(-/-)c-Rel(-/-)p65(-/+) B cells, which is correlated with the ability of CD40L to up-regulate Bcl-x(L) expression in these cells. CD40L- and LPS-induced B cell proliferation, as well as up-regulation of proliferation-related genes, however, are greatly reduced in c-Rel(-/-) and p50(-/-)c-Rel(-/-) B cells but are normal in p52(-/-) B cells. We have further demonstrated that both c-Rel and p52 are required for CD40-mediated B cell homotypic aggregation, which explains well why neither LPS nor BAFF has this function. Overall, our studies suggest that both type 1 and type 2 NF-kappaB pathways contribute to the gene expression and biological program unique for CD40 in B cell activation.

Science and the Bush Administration.

Abstract: I n various ways, the scientific community in the United States—and in other nations as well—has expressed concern about the way in which decisions about scientific issues have been subjected to political tests by the Bush administration. For example, the Union of Concerned Scientists (UCS), in

Methods and compositions for inhibiting cell growth and proliferation

Abstract: Compositions, including, for example, soluble Ryk polypeptides and/or agents that selectively bind Ryk, are provided. Methods of using such agents or compositions also are provided, including, for example, methods of using such compositions to inhibit proliferation of a cell exhibiting, or predisposed to exhibiting, unregulated growth. In addition, methods of ameliorating a cancer in a subject are provided.

Compositions for inducing cell growth and differentiation and methods of using same

Abstract: Compositions, including, for example, soluble Ryk polypeptides and Wnt polypeptides, that induce cell growth and/or differentiation, including, for example, neurite outgrowth and hematopoietic cell proliferation and differentiation, are provided. Methods of using such compositions also are provided, including, for example, methods of using such compositions to induce neurite outgrowth (e.g., in a subject having a neuronal disorder). In addition, methods to identify agents that alter Ryk mediated signal transduction in a cell are provided.

The Sudden Death of a Coral Reef - Response

Abstract: As articulated in our policy forum and by Zinkernagel, the development of an HIV vaccine is one of the most complex scientific challenges that modern biomedical research is confronting. However, it is exactly because this effort will be so difficult, and because we recognize that there are few blueprints for how to go about creating successful vaccines for organisms that have the characteristics that Zinkernagel describes, that we have proposed a more interactive systematic scientific approach organized to best support the science, both preclinical and clinical, required to make progress through experimentation. We strongly believe that basic scientific research should be conducted in coordination with well-planned clinical trials, in an iterative process that leads to incremental increase in knowledge and, eventually, to a safe and effective HIV vaccine. We do not believe that “hygienic measures, sufficient nutrition, chemotherapeutic agents … and serious … epidemiological surveys and prevention programs” alone will stop the HIV pandemic, especially in the poorest countries of the world, where 95% of all HIV infections are occurring. An HIV vaccine would be a powerful complement to these interventions and is essential to worldwide control of the pandemic. We, therefore, feel responsible to harness the power of science to accelerate its development.