Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells.

Thymic epithelial cells play a crucial role in the selection of developing thymocytes. Thymocyte-epithelial cell interactions involve a number of adhesion molecules, including members of the integrin and immunoglobulin superfamilies. We found that human thymic epithelial cells synthesize an endogenous lectin, galectin-1, which binds to oligosaccharide ligands on the surface of thymocytes and T lymphoblastoid cells. Binding of T lymphoblastoid cells to thymic epithelial cells was inhibited by antibody to galectin-1 on the epithelial cells, and by two antibodies, T305 and 2B11, that recognize carbohydrate epitopes on the T cell surface glycoproteins CD43 and CD45, respectively. T lymphoblastoid cells and thymocytes bound recombinant galectin-1, as demonstrated by flow cytometric analysis, and lectin binding was completely inhibited in the presence of lactose. The degree of galectin-1 binding to thymocytes correlated with the maturation stage of the cells, as immature thymocytes bound more galectin-1 than did mature thymocytes. Preferential binding of galectin-1 to immature thymocytes may result from regulated expression of preferred oligosaccharide ligands on those cells, since we found that the epitope recognized by the T305 antibody, the core 2 O-glycan structure on CD43, was expressed on cortical, but not medullary cells. The level of expression of the UDP-GlcNAc:Gal beta 1,3GalNAc-R beta 1, 6GlcNAc transferase (core 2 beta 1, 6 GlcNAc transferase, or C2GnT), which creates the core 2 O-glycan structure, correlated with the glycosylation change between cortical and medullary cells. Expression of mRNA encoding the C2GnT was high in subcapsular and cortical thymocytes and low in medullary thymocytes, as demonstrated by in situ hybridization. These results suggest that galectin-1 participates in thymocyte-thymic epithelial cell interactions, and that this interaction may be regulated by expression of relevant oligosaccharide ligands on the thymocyte cell surface

Linguistic Abilities and Identity in a Globalizing World: Perspectives of Proficient Taiwanese English Users

Ph.DDOCTOR OF PHILOSOPH

The Oxytricha trifallax Mitochondrial Genome

The Oxytricha trifallax mitochondrial genome contains the largest sequenced ciliate mitochondrial chromosome (∼70 kb) plus a ∼5-kb linear plasmid bearing mitochondrial telomeres. We identify two new ciliate split genes (rps3 and nad2) as well as four new mitochondrial genes (ribosomal small subunit protein genes: rps- 2, 7, 8, 10), previously undetected in ciliates due to their extreme divergence. The increased size of the Oxytricha mitochondrial genome relative to other ciliates is primarily a consequence of terminal expansions, rather than the retention of ancestral mitochondrial genes. Successive segmental duplications, visible in one of the two Oxytricha mitochondrial subterminal regions, appear to have contributed to the genome expansion. Consistent with pseudogene formation and decay, the subtermini possess shorter, more loosely packed open reading frames than the remainder of the genome. The mitochondrial plasmid shares a 251-bp region with 82% identity to the mitochondrial chromosome, suggesting that it most likely integrated into the chromosome at least once. This region on the chromosome is also close to the end of the most terminal member of a series of duplications, hinting at a possible association between the plasmid and the duplications. The presence of mitochondrial telomeres on the mitochondrial plasmid suggests that such plasmids may be a vehicle for lateral transfer of telomeric sequences between mitochondrial genomes. We conjecture that the extreme divergence observed in ciliate mitochondrial genomes may be due, in part, to repeated invasions by relatively error-prone DNA polymerase-bearing mobile elements

Family History of Alcoholism and Childhood Adversity: Joint Effects on Alcohol Consumption and Dependence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65494/1/j.1530-0277.1994.tb00085.x.pd

Design of Group IIA Secreted/Synovial Phospholipase A2 Inhibitors: An Oxadiazolone Derivative Suppresses Chondrocyte Prostaglandin E2 Secretion

Group IIA secreted/synovial phospholipase A2 (GIIAPLA2) is an enzyme involved in the synthesis of eicosanoids such as prostaglandin E2 (PGE2), the main eicosanoid contributing to pain and inflammation in rheumatic diseases. We designed, by molecular modeling, 7 novel analogs of 3-{4-[5(indol-1-yl)pentoxy]benzyl}-4H-1,2,4-oxadiazol-5-one, denoted C1, an inhibitor of the GIIAPLA2 enzyme. We report the results of molecular dynamics studies of the complexes between these derivatives and GIIAPLA2, along with their chemical synthesis and results from PLA2 inhibition tests. Modeling predicted some derivatives to display greater GIIAPLA2 affinities than did C1, and such predictions were confirmed by in vitro PLA2 enzymatic tests. Compound C8, endowed with the most favorable energy balance, was shown experimentally to be the strongest GIIAPLA2 inhibitor. Moreover, it displayed an anti-inflammatory activity on rabbit articular chondrocytes, as shown by its capacity to inhibit IL-1β-stimulated PGE2 secretion in these cells. Interestingly, it did not modify the COX-1 to COX-2 ratio. C8 is therefore a potential candidate for anti-inflammatory therapy in joints

Integrated Lipidomics in the Secreted Phospholipase A2 Biology

Mammalian genomes encode genes for more than 30 phospholipase A2s (PLA2s) or related enzymes, which are subdivided into several subgroups based on their structures, catalytic mechanisms, localizations and evolutionary relationships. More than one third of the PLA2 enzymes belong to the secreted PLA2 (sPLA2) family, which consists of low-molecular-weight, Ca2+-requiring extracellular enzymes, with a His-Asp catalytic dyad. Individual sPLA2 isoforms exhibit unique tissue and cellular localizations and enzymatic properties, suggesting their distinct pathophysiological roles. Recent studies using transgenic and knockout mice for several sPLA2 isoforms, in combination with lipidomics approaches, have revealed their distinct contributions to various biological events. Herein, we will describe several examples of sPLA2-mediated phospholipid metabolism in vivo, as revealed by integrated analysis of sPLA2 transgenic/knockout mice and lipid mass spectrometry. Knowledge obtained from this approach greatly contributes to expanding our understanding of the sPLA2 biology and pathophysiology

Letter Written by William R. Seilhamer to the Bryant College Service Club Dated July 27, 1942

[Transcription begins] Wm. R. Seilhamer Sea. 2c. U.S.N.R. 403 Mangum Hall U.S. Navy Pre-Flight School Chapel Hill, North Carolina July 27, 1942 Sunday, 11:30 A.M. Gentlemen: I want to express my sincere thanks for the 2 flat fifties of cigarettes I received yesterday. The gift came as a complete surprise and to say that such a gift is welcome is to express it inadequately. You are doing a wonderful job and I know of no other college that is doing anything of a similar nature for either undergraduates or graduates. As far as life goes down here we are the most confined outfit anywhere in the service. We had Saturday and Sunday afternoons off but cannot go outside of an eight block square. They keep us on the go from 5:45 A.M. to 9:25 P.M. and out of the entire day have 25 minutes to ourselves. Would advise anyone contemplating the Navy Air Service to try and get down here after Sept. as the heat runs about 110° and you really bake and sweat as you labor now. As ever, and thanks again, Bill Seilhamer [Transcription ends

Etextbook Access, Usage, And Beliefs: Implications For Adoption In Higher Education

Purpose – Dynamic features of eTextbooks, such as taking interactive quizzes and sharing notes can make the practice of reading a textbook more supportive and engaging than before. While promising, challenges exist regarding the integration of eTextbooks in higher education, such as cost, usability, and lack of instructor development. There is a need for a more informed understanding of how instructors and learners are integrating eTextbooks to revolutionize learning spaces, in order to formulate next steps of action on a university level. While studies exist regarding universities with eTextbook initiatives, there is little empirical data concerning universities that offer eTextbooks without a focussed initiative. This paper aims to fill this gap. Design/methodology/approach – In this paper, the results of a university-wide student survey are shared, which provide insight into factors such as the selection and use of eTextbooks, access, and beliefs regarding eTextbook use and learning. Findings – Generally, we found that in a university setting without an eTextbook initiative, eTextbook use is relatively low and their features are not being effectively utilized by students or instructors. In any university that offers eTextbooks, instructor development is critical. Originality/value – Findings from this survey guide the instructional design of instructor development. The findings also identify pertinent issues that any university is likely to face when considering an eTextbook initiative, such as raising student awareness, working with publishers, and providing effective technical and pedagogical support