Cooperation of Gq, Gi, and G12/13 in Protein Kinase D Activation and Phosphorylation Induced by Lysophosphatidic Acid

To examine the contribution of different G-protein pathways to lysophosphatidic acid (LPA)-induced protein kinase D (PKD) activation, we tested the effect of LPA on PKD activity in murine embryonic cell lines deficient in Galpha q/11 (Galpha q/11 KO cells) or Galpha 12/13 (Galpha 12/13 KO cells) and used cells lacking rhodopsin kinase (RK cells) as a control. In RK and Galpha 12/13 KO cells, LPA induced PKD activation through a phospholipase C/protein kinase C pathway in a concentration-dependent fashion with maximal stimulation (6-fold for RK cells and 4-fold for Galpha 12/13 KO cells in autophosphorylation activity) achieved at 3 µM. In contrast, LPA did not induce any significant increase in PKD activity in Galpha q/11 KO cells. However, LPA induced a significantly increased PKD activity when Galpha q/11 KO cells were transfected with Galpha q. LPA-induced PKD activation was modestly attenuated by prior exposure of RK cells to pertussis toxin (PTx) but abolished by the combination treatments of PTx and Clostridium difficile toxin B. Surprisingly, PTx alone strikingly inhibited LPA-induced PKD activation in a concentration-dependent fashion in Galpha 12/13 KO cells. Similar results were obtained when activation loop phosphorylation at Ser-744 was determined using an antibody that detects the phosphorylated state of this residue. Our results indicate that Gq is necessary but not sufficient to mediate LPA-induced PKD activation. In addition to Gq, LPA requires additional G-protein pathways to elicit a maximal response with Gi playing a critical role in Galpha 12/13 KO cells. We conclude that LPA induces PKD activation through Gq, Gi, and G12 and propose that PKD activation is a point of convergence in the action of multiple G-protein pathways

The Development and Use of Computational Tools in Forensic Science

Modern computational resources make available a rich toolkit of statistical methods that can be applied to forensic questions. This toolkit is built on the foundation of statistical developments dating back to the 19th century. To fully and effectively exploit these developments, both the makers and users of software must be keenly aware of the quality, i.e., the accuracy and precision, of the data being modeled or analyzed, and end-users must be sufficiently familiar with the underlying theory to understand the process and results of any analysis or software they use. This is especially important for medico-legal personnel who might be called upon to testify in a court of law and be subject to cross-examination. With respect to the development of computational tools, it is increasingly important that they be made available as open-source code to avoid the pitfalls of commercial software support and the potential dependence of end-users on orphaned software

Image data banks and geometric morphometrics

This paper examines the opportunities offered by recent advances in digital image processing to allow access to natural history museum collections without direct handling of specimens. It specifically refers to two- and three-dimensional data recording and analysis in the frame of geometric morphometrics

Athletics, Academics, and the Financial Condition of U.S. Private Colleges

Abstract Many private colleges in the U.S. face financial difficulty. The role of athletics in the financial condition of U.S. colleges is subject to controversy. Supporters argue that collegiate sports draw students, improve student quality, and increase donor support. Detractors argue that athletics are costly and undermine the academic mission of the institution. In this paper, we examine metrics of athletic and academic quality to determine their effects on the financial health of a sample of U.S. private colleges. Our findings indicate that higher spending on athletics reduces an institution’s financial health and that academic quality increases an institution’s financial health

The Mesoamerican Corpus of Formative Period Art and Writing

This project explores the origins and development of the first writing in the New World by constructing a comprehensive database of Formative period, 1500-400 BCE, iconography and a suite of database-driven digital tools. In collaboration with two of the largest repositories of Formative period Mesoamerican art in Mexico, the project integrates the work of archaeologists, art historians, and scientific computing specialists to plan and begin the production of a database, digital assets, and visual search software that permit the visualization of spatial, chronological, and contextual relationships among iconographic and archaeological datasets. These resources will eventually support mobile and web based applications that allow for the search, comparison, and analysis of a corpus of material currently only partially documented. The start-up phase will generate a functional prototype database, project website, wireframe user interfaces, and a report summarizing project development

Anthropology Takes Control of Morphometrics

There has been a startling change over the last decade in the intellectual context of morphometrics. In the 1990’s, this field, which has not altered its focus upon the quantitative analysis of biomedical shape variation and shape change, was principally centered around concerns of medical image analysis; but now it is driven mainly by the demands of researchers in human variability, physical anthropology, primatology, and paleoanthropology instead. This essay celebrates that change and tries to account for it by reference to cognitive and intellectual aspects of the new home