40 research outputs found
Summary: Combating Climate Change with Section 115 of the Clean Air Act
The scale and scope of the climate crisis calls for comprehensive nationwide efforts to reduce greenhouse gas emissions. New legislation, passed by Congress and signed by the President, is the first and best option for climate action at the federal level. This could be a version of the Green New Deal, a carbon tax, sectoral limits, an emissions cap with compliance trading, or another approach. What matters most is that the legislation effectively cut the greenhouse gas emissions driving the world’s temperatures ever higher. Unfortunately, the prospect for federal legislation is uncertain, while strong and decisive action is needed now. A president committed to tackling climate change will need a backup plan in case Congress remains gridlocked, one that relies on existing statutes to achieve the deep emission reductions the science says we need
Preclinical Models for Neuroblastoma: Establishing a Baseline for Treatment
Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system.Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.The studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer
The Death Effector Domains of Caspase-8 Induce Terminal Differentiation
The differentiation and senescence programs of metazoans play key roles in regulating normal development and preventing aberrant cell proliferation, such as cancer. These programs are intimately associated with both the mitotic and apoptotic pathways. Caspase-8 is an apical apoptotic initiator that has recently been appreciated to coordinate non-apoptotic roles in the cell. Most of these functions are attributed to the catalytic domain, however, the amino-terminal death effector domains (DED)s, which belong to the death domain superfamily of proteins, can also play key roles during development. Here we describe a novel role for caspase-8 DEDs in regulating cell differentiation and senescence. Caspase-8 DEDs accumulate during terminal differentiation and senescence of epithelial, endothelial and myeloid cells; genetic deletion or shRNA suppression of caspase-8 disrupts cell differentiation, while re-expression of DEDs rescues this phenotype. Among caspase-8 deficient neuroblastoma cells, DED expression attenuated tumor growth in vivo and proliferation in vitro via disruption of mitosis and cytokinesis, resulting in upregulation of p53 and induction of differentiation markers. These events occur independent of caspase-8 catalytic activity, but require a critical lysine (K156) in a microtubule-binding motif in the second DED domain. The results demonstrate a new function for the DEDs of caspase-8, and describe an unexpected mechanism that contributes to cell differentiation and senescence
The Berkeley Planning Journal: Change and Growth
An essay reflecting upon the the role of student journals in higher education, upon the occasion of BPJ's 25th anniversary
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Phoenix Cities: The Fall and Rise of Great Industrial Cities By Anne Power, Jörg Plöger, and Astrid Winkler
The total damage to human lives and property caused by deindus- trialization in U.S. and European cities over the past forty years has never been fully assessed. What we know and see is that major cities were devastated by the loss of employment and income that accompanied the movement of manufacturing to offshore locations with lower labor costs. Policy makers and planners in cities such as Detroit and Pittsburgh struggled to respond to the crises that they faced, but researchers have tended to be more bemused by new industrial growth, exemplified by Silicon Valley, or by the search for nostrums such as the creative class. Thus, Phoenix Cities comes as a welcome effort to document both the scale of industrial decline and the efforts to alleviate it
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