Author response

Proteolytic cleavage and release from the cell surface of membrane-tethered ligands is an important mechanism of regulating intercellular signalling. TACE is a major shedding protease, responsible for the liberation of the inflammatory cytokine TNFα and ligands of the epidermal growth factor receptor. iRhoms, catalytically inactive members of the rhomboid-like superfamily, have been shown to control the ER-to-Golgi transport and maturation of TACE. Here, we reveal that iRhom2 remains associated with TACE throughout the secretory pathway, and is stabilised at the cell surface by this interaction. At the plasma membrane, ERK1/2-mediated phosphorylation and 14-3-3 protein binding of the cytoplasmic amino-terminus of iRhom2 alter its interaction with mature TACE, thereby licensing its proteolytic activity. We show that this molecular mechanism is responsible for triggering inflammatory responses in primary mouse macrophages. Overall, iRhom2 binds to TACE throughout its lifecycle, implying that iRhom2 is a primary regulator of stimulated cytokine and growth factor signalling

Environmental Issues and Activities for the Boise Area Earth Science Classroom

Need for the Project Within the past century, human society and civilization have experienced dramatic changes. Today\u27s society is science-technology orientated and modern settlement patterns now include intense urbanization. These changes, as well as increased world population, have resulted in tremendous demands on the natural environment. The solving of problems such as location and recovery of natural resources, waste disposal, pollution, production of energy, and avoiding natural hazards require an adequate number of qualified geoscientists and a scientifically literate public that will make responsible decisions concerning environmental issues. The creation of a scientifically literate, environ-mentally aware citizenry, as well as the production of highly capable geoscientist, hinges on the effectiveness of education. The Earth science course at the secondary school level is a prime opportunity to meet these educational needs. For many nonscience students, the Earth science class is their last formal opportunity to acquire knowledge of critical environmental issues, gain understanding of natural processes (geologic, hydrologic, atmospheric, etc.), develop an awareness of the effects of human interaction with the physical environment, and gain understanding of Earth science methodology and ways of thinking. The Earth science class is also an opportunity for individuals to acquire skills and develop a sense of commitment that will enable them to continue their education in Earth science long after their formal education is complete. It must be recognized, however, that efforts to create a scientifically literate, environmentally aware citizenry and promote the production of needed geoscientists at the secondary school level may be hampered if science and Earth science education is neglected at the primary school level. Purpose The purpose of this project is to develop a resource that will enable Boise area teachers to incorporate into their curriculum effective environmental education based on aspects of the local physical environment. The premise of this project is that effective education begins with students\u27 present environment. The project, therefore provides Boise area teachers with information on local geology, hydrology, meteorology, and other aspects of the physical environment, as well as aspects of human interaction with the environment. projected primary users of this project are secondary level Earth science teachers. However, educators at the primary level are strongly encouraged to study the material included in this project and use it to develop an Earth science curriculum for their students. Limitations of the Project Usefulness of this project, as intended, is limited largely to the Boise School District. Educators within surrounding school districts will need to judge whether the project is sufficiently relevant to their students. In order to incorporate the content of this project into an Earth science course, significant changes in the existing Earth science curriculum may be necessary. For example, where a teacher may normally devote less than one class session to geothermal energy, incorporation of this project would require that the teacher significantly alter the range of content covered to allow students several class periods on geothermal energy. Many important topics/issues are not included in this project. Among those excluded are local waste disposal, water resources, land use, and energy consumption