Some Logical Consequences of Makkai's "Idiomaticity as a Language Universal"

Paper by William J. Sulliva

A latent ability to persist: differentiation in Toxoplasma gondii

A critical factor in the transmission and pathogenesis of Toxoplasma gondii is the ability to convert from an acute disease-causing, proliferative stage (tachyzoite), to a chronic, dormant stage (bradyzoite). The conversion of the tachyzoite-containing parasitophorous vacuole membrane into the less permeable bradyzoite cyst wall allows the parasite to persist for years within the host to maximize transmissibility to both primary (felids) and secondary (virtually all other warm-blooded vertebrates) hosts. This review presents our current understanding of the latent stage, including the factors that are important in bradyzoite induction and maintenance. Also discussed are the recent studies that have begun to unravel the mechanisms behind stage switching

A study to evolve and implement a selection and development program for sales personnel

Thesis (M.B.A.)--Boston Universit

Regulation of arginine transport by GCN2 eIF2 kinase is important for replication of the intracellular parasite Toxoplasma gondii

Toxoplasma gondii is a prevalent protozoan parasite that can infect any nucleated cell but cannot replicate outside of its host cell. Toxoplasma is auxotrophic for several nutrients including arginine, tryptophan, and purines, which it must acquire from its host cell. The demands of parasite replication rapidly deplete the host cell of these essential nutrients, yet Toxoplasma successfully manages to proliferate until it lyses the host cell. In eukaryotic cells, nutrient starvation can induce the integrated stress response (ISR) through phosphorylation of an essential translation factor eIF2. Phosphorylation of eIF2 lowers global protein synthesis coincident with preferential translation of gene transcripts involved in stress adaptation, such as that encoding the transcription factor ATF4 (CREB2), which activates genes that modulate amino acid metabolism and uptake. Here, we discovered that the ISR is induced in host cells infected with Toxoplasma. Our results show that as Toxoplasma depletes host cell arginine, the host cell phosphorylates eIF2 via protein kinase GCN2 (EIF2AK4), leading to induced ATF4. Increased ATF4 then enhances expression of the cationic amino acid transporter CAT1 (SLC7A1), resulting in increased uptake of arginine in Toxoplasma-infected cells. Deletion of host GCN2, or its downstream effectors ATF4 and CAT1, lowers arginine levels in the host, impairing proliferation of the parasite. Our findings establish that Toxoplasma usurps the host cell ISR to help secure nutrients that it needs for parasite replication

Mitochondrial behaviour throughout the lytic cycle of Toxoplasma gondii

Mitochondria distribution in cells controls cellular physiology in health and disease. Here we describe the mitochondrial morphology and positioning found in the different stages of the lytic cycle of the eukaryotic single-cell parasite Toxoplasma gondii. The lytic cycle, driven by the tachyzoite life stage, is responsible for acute toxoplasmosis. It is known that whilst inside a host cell the tachyzoite maintains its single mitochondrion at its periphery. We found that upon parasite transition from the host cell to the extracellular matrix, mitochondrion morphology radically changes, resulting in a reduction in peripheral proximity. This change is reversible upon return to the host, indicating that an active mechanism maintains the peripheral positioning found in the intracellular stages. Comparison between the two states by electron microscopy identified regions of coupling between the mitochondrion outer membrane and the parasite pellicle, whose features suggest the presence of membrane contact sites, and whose abundance changes during the transition between intra- and extra-cellular states. These novel observations pave the way for future research to identify molecular mechanisms involved in mitochondrial distribution in Toxoplasma and the consequences of these mitochondrion changes on parasite physiology

Analyzing Carnegie’s Reach: The Contingent Nature of Innovation

Our interest is curricular innovation, with a focus on the recommendations of the 2007 Carnegie report – Educating Lawyers. Recognizing that meaningful reform requires an institutional commitment, our interest also includes initiatives in the areas of faculty development and faculty incentive structure that would support curricular innovation. Additionally, we are curious as to what might explain change and whether certain school characteristics will do so or whether external factors that challenge legal education offer an explanation. To explore these issues we surveyed law schools (a 60.5% response rate). The results show that while there is much activity in the area of curriculum – including the key matters of lawyering, professionalism, and especially integration – there is much less in the important areas of faculty development and faculty incentive structure. School characteristics, including rank, do not provide a sufficient explanation for the patterns emerging from the survey’s results. Additionally, activity by law schools with regard to curriculum, faculty development, and faculty professional activity is not simply a response to external challenges either. However, it appears that those pressures are providing a potential window of opportunity for innovation, reinforcing the need for change, and accelerating its pace

GCN2-like eIF2α kinase manages the amino acid starvation response in Toxoplasma gondii

The apicomplexan protozoan Toxoplasma gondii is a significant human and veterinary pathogen. As an obligate intracellular parasite, Toxoplasma depends on nutrients provided by the host cell and needs to adapt to limitations in available resources. In mammalian cells, translational regulation via GCN2 phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) is a key mechanism for adapting to nutrient stress. Toxoplasma encodes two GCN2-like protein kinases, TgIF2K-C and TgIF2K-D. We previously showed that TgIF2K-D phosphorylates T. gondii eIF2α (TgIF2α) upon egress from the host cell, which enables the parasite to overcome exposure to the extracellular environment. However, the function of TgIF2K-C remained unresolved. To determine the functions of TgIF2K-C in the parasite, we cloned the cDNA encoding TgIF2K-C and generated knockout parasites of this TgIF2α kinase to study its function during the lytic cycle. The TgIF2K-C knockout did not exhibit a fitness defect compared with parental parasites. However, upon infection of human fibroblasts that were subsequently cultured in glutamine-free medium, the intracellular TgIF2K-C knockout parasites were impeded for induced phosphorylation of TgIF2α and showed a 50% reduction in the number of plaques formed compared with parental parasites. Furthermore, we found that this growth defect in glutamine-free media was phenocopied in parasites expressing only a non-phosphorylatable TgIF2α (TgIF2α-S71A), but not in a TgIF2K-D knockout. These studies suggest that Toxoplasma GCN2-like kinases TgIF2K-C and TgIF2K-D evolved to have distinct roles in adapting to changes in the parasite’s environment

Settlement Predictions in Residual Soils by Dilatometer, Pressuremeter and One-Dimensional Compression Tests: Comparison with Measured Field Response

A case study investigating settlement predictions based on data from one dimensional compression, pressuremeter (PMT) and dilatometer (DMT) tests is presented. A relationship is established between PMT and DMT evaluated moduli and the standard penetration N values. These relationships are utilized in the settlement computations. The predictions obtained by each method are compared to the actual measured settlement. The column location at which settlement observations were made was instrumented with strain gages to measure the actual applied loads. A comparison between actual and design loads is made. Settlement predictions using PMT were performed utilizing two different existing approaches. A distinction is made between the rheological factors, both termed α, used in each of the methods

Introduction

On August 19, 1994, the sponsorship of this Law School was transferred from the University of Puget Sound to a new parent institution, Seattle University, and the school became the Seattle University School of Law. It is now our great pleasure to welcome all past subscribers and supporters to the first issue of the Seattle University Law Review. Seattle University brings to the Law School the tradition of excellence of the Jesuit-sponsored universities and their law schools throughout the nation. From Fordham and Georgetown to Santa Clara and the Loyolas, these law schools have attained uniform reputations of quality and national prominence. Under its new sponsorship, the Seattle University School of Law will maintain the fine teaching and scholarly faculty, and the model clinical and legal writing programs that have brought it accolades in the past. The new partnership with Seattle University provides institutional support and opportunities for our law programs to flourish and to mesh with the other interdisciplinary activities and graduate programs of Seattle University. This merger of a thriving law school with an established and respected full service university is unprecedented, and is full of promise for both institutions. The Law Review will maintain its fine tradition of offering a balance of Symposia Issues, Articles, Notes and Comments that are timely and relevant for readers in both the northwest and the national legal community. We shall appreciate your continued support of the Seattle University Law Review and we promise you a publication that will be of continued and expanded service

Doxycycline alters metabolism and proliferation of human cell lines.

The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism