Transport into the nucleus is critical for regulation of gene transcription and other intranuclear events. Passage of molecules into the nucleus depends in part upon their size and the presence of appropriate targeting sequences. However, little is known about the effects of hormones or their second messengers on transport across the nuclear envelope. We used localized, two-photon activation of a photoactivatable green fluorescent protein to investigate whether hormones, via their second messengers, could alter nuclear permeability. Vasopressin and other hormones that increase cytosolic Ca 2؉ and activate protein kinase C increased permeability across the nuclear membrane of SKHep1 liver cells in a rapid unidirectional manner. An increase in cytosolic Ca 2؉ was both necessary and sufficient for this process. Furthermore, localized photorelease of caged Ca 2؉ near the nuclear envelope resulted in a local increase in nuclear permeability. Neither activation nor inhibition of protein kinase C affected nuclear permeability. These findings provide evidence that hormones linking to certain G protein-coupled receptors increase nuclear permeability via cytosolic Ca 2؉ . Short term regulation of nuclear permeability may provide a novel mechanism by which such hormones permit transcription factors and other regulatory molecules to enter the nucleus, thereby regulating gene transcription in target cells.The nuclear envelope represents a structural and functional barrier to passage between the nucleus and the cytosol. Regulation of the permeability of this barrier is one potential mechanism to control access to the nucleus for proteins that affect nuclear function, including transcription factors and various kinases and phosphatases. Nucleocytosolic passage generally occurs through the nuclear pore complex (1, 2), a 125-MDa membrane-spanning protein complex consisting of eight ion channels and a large central passage (3). Movement of molecules through the nuclear pore is restricted on the basis of size and the presence or absence of appropriate localization sequences. Studies using electron scanning microscopy (4), fluorescence recovery after photo-bleaching techniques (5), and microinjection of fluorescently labeled dextrans (6) have shown that molecules up to 40 -60 kDa in size can cross the nuclear envelope without a signaling sequence. Proteins less than 4 -10 kDa in size freely pass from cytosol to nucleus (6 -8), while intermediate sized proteins (19 -40 kDa) do not need a targeting sequence to cross the nuclear pore, but the permeability of the pore to such molecules may be modulated (6 -8). One factor that appears to regulate the permeability of the nuclear pore to proteins in this intermediate size range is the amount of Ca 2ϩ within the nuclear envelope (6 -9), although there is now conflicting evidence about this (5). Little is known about the role of cytosolic factors such as second messengers in the regulation of nuclear pore permeability.The spatial pattern of second messenger signals is important for how thes...
For Richard Rorty as well as Stanley Cavell, the realm of the literary carries particular educational force. Literature holds the potential to lead the insensitive and the superficial towards the responsive and the detailed. Literature prompts an interrogation of everyday expressions and the felt meanings we decide to invest or not to invest within them. In this paper, we draw on the work of Rorty and Cavell to highlight the significance of literature for moral education. We argue that both philosophers are committed to the transformative power of literature even if this transformation is conceived in very different ways. Broadening our scope from the Anglo‐American to the European tradition, we propose in the paper's final section that Rorty and Cavell's readings of Derrida can usefully illuminate the fundamental philosophical differences between them.
This paper explores a course design that uses a software drafting program, Revit, as the foundation for community engagement (CE) projects in a required course for civil engineering students. Over four terms, this course has used seven CE projects with three different partners. Local community partners were found through the university's Center for Community Engagement who reached out to community partners that typically host placement-based CE in arts and sciences courses to find spatially based problems that students could address.The course design included several sessions with the students and the community partners, including a preliminary kick-off meeting and a mid-term conceptual design review. After the conceptual design review, students developed several draft drawing sets and calculation documents, which were submitted to the professor as intermediate deliverables. Final drawing sets, calculations, and written explanations of the design were submitted to the professor and the community partner at the end of the quarter. Student teams also presented their work to the community partner. In addition to the final drawings and presentation, students were graded on an individual reflection paper about the design process and given peer evaluations to grade how the team worked together. Because drafting classes (e.g., AutoCAD, Revit, Solidworks) are common among many engineering disciplines, this approach is seen as a model of how CE may be incorporated easily into many engineering programs. In addition to explaining the course design, this paper presents summative reflections from the professor, a community partner, and the Center for Community Engagement coordinator about successes and failures with respect to these projects. These reflections are provided as learning opportunities to help others implement graphics-based CE projects. As a work in progress, this paper only addresses the course design and reflection on implementation and does not focus on student learning or perceptions.
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