Influence of chondroitin 6-sulfate oligosaccharide unit addition on the immunopathogenicity of human thyroglobulin in cba/j(h-2k) mice. Multiple effects on antigen processing and t cell responses

The site of type D (chondroitin 6-sulfate) oligosaccharide unit addition to human thyroglobulin (hTg) was localized. Furthermore, hTg and its fractions endowed with chondroitin 6-sulfate oligosaccaride units (hTg-CS) and devoid of it (hTg-CS-), were compared, with respect to their ability to induce experimental autoimmune thyroiditis (EAT) in CBA/J(H-2k) mice, by subcutaneous administration, in the presence of complete adjuvant. HTg was chromatographically separated into hTg-CS and hTg-CS- molecules, on the base of their uronic acid content. In an ample number of hTg preparations, the fraction of hTg-CS in total hTg ranged from 32.0 to 71.6 percent. By exploiting the electrophoretic mobility shift and metachromasia conferred by chondrotin-6-sulfate upon the products of limited proteolysis of hTg, chondroitin 6-sulfate was first restricted to a carboxy-terminal region, starting at residue 2513. A single chondroitin 6-sulfate-containing nonapeptide was isolated in pure form from the products of digestion of hTg with endoproteinase Glu-C, and its sequence was determined as being LTAGXGLRE (residues 2725-2733, X being Ser2729 linked to the oligosaccharide chain). In an in vitro assay of enzymatic iodination, hTg-CS produced higher yields of 3,5,5’-triiodothyronine (T3) (171%) and 3,5,3’,5’-tetraiodothyronine (T4) (134%), than hTg-CS-. Unfractionated hTg behaved as hTg-CS. Thus, chondroitin 6-sulfate addition to a subset of hTg molecules enhanced the overall level of T4 and, particularly, T3 formation. Furthermore, the chondroitin 6-sulfate oligosaccharide unit of hTg-CS protected peptide bond Gly2713-Lys2714 from proteolysis, during the limited digestion of hTg-CS with trypsin. Although immunization with all forms of hTg was accompanied by thyroid cell damage, as judged from the increase of T4 in blood, a higher degree of mononuclear infiltration of the thyroid was associated with unfractionated hTg, in comparison both with hTg-CS and with hTg-CS-. Thus, it appears that both hTg subfractions contributed to the immunopathogenic potency of unfractionated hTg, as neither one reproduced fully the histological picture associated with the latter. Significant differences were observed also upon restimulation in vitro of splenic lymphocytes obtained from mice immunized in vivo with the different forms of hTg. Restimulation in vitro with hTg-CS of splenocytes from mice immunized with the same antigen was followed by low-level, dose-dependent proliferation and IFN-γ production, whereas cross-stimulation with hTg-CS- of the same cells was followed by proliferative and secretory responses of even lower degree. On the other hand, restimulation in vitro with hTg-CS- of splenocytes primed in vivo with the same antigen was followed by higher-level, dose-dependent increases of IFN-γ production, accompanied by proliferative responses of low degree and inversely related with the antigen dose, while cross-stimulation with hTg-CS of the same cells was followed by dose-dependent increases, both of proliferation and IFN-γ production, of the highest level observed in this study. Similar results were obtained when splenocytes, primed in vivo with hTg-CS-, were restimulated with purified glycopeptide hTg-CSgp, containing the chondroitin 6-sulfate unit, but not with its non-glycosylated, synthetic homologue. These data indicate that hTg-CS- was more effective than hTg-CS in priming autoreactive T lymphocytes, recognizing thyroiditogenic epitopes shared between murine and human Tg, whereas hTg-CS was a stronger inducer of proliferation of antigen-sensitized T cells. Moreover, different molecular signals, including structural determinant(s) associated with the chondroitin 6-sulfate chain, were required, in addition to epitope recognition, for the activation of T cell proliferation, together with IFN-γ production. These findings provide insights into the molecular mechanism of regulation of the hormonogenic efficiency and of the T4/T3 ratio in hTg, and may bear important implications in the processing and presentation of hTg as an autoantigen, and in the mechanisms of activation of Th-1-mediated and cytotoxic lymphocyte responses involved in EAT

Increased co‐first authorships in biomedical and clinical publications: a call for recognition

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154532/1/fsb2027010039.pd

VuFind - Look & Feel Guerilla Test

The goal for this test was to evaluate how users perceive the catalog when it is and is not embedded into a page with navigation tool bars located at the top of the library's homepage.Usability GroupUsability Task Forcehttp://deepblue.lib.umich.edu/bitstream/2027.42/106795/1/Look_and_feel_guerilla_final.pd

Case Report: Generalized Mutual Information (GMI) Analysis of Sensory Motor Rhythm in a Subject Affected by Facioscapulohumeral Muscular Dystrophy after Ken Ware Treatment

In this case report we study the dynamics of the SMR band in a subject affected from Facioscapulohumeral Muscular Dystrophy and subjected to Ken Ware Neuro Physics treatment. We use the Generalized Mutual Information (GMI) to analyze in detail the SMR band at rest during the treatment. Brain dynamics responds to a chaotic-deterministic regime with a complex behaviour that constantly self-rearranges and self-organizes such dynamics in function of the outside requirements. We demonstrate that the SMR chaotic dynamics responds directly to such regime and that also decreasing in EEG during muscular activity really increases its ability of self-arrangement and self-organization in brain. The proposed novel method of the GMI is arranged by us so that it may be used in several cases of clinical interest. In the case of muscular dystrophy here examined, GMI enables us to quantify with accuracy the improvement that the subject realizes during such treatment

Research by the Numbers: Assessing the Performance of Three Products for Citation Analysis

http://deepblue.lib.umich.edu/bitstream/2027.42/94430/1/research_by_the_numbers_assessing_the_performance_of_three_products_for_citation_analysis.pd

Programa de comprensión, recuerdo y narración : Aplicación en alumnos con síndrome de down

Aunque en los últimos años se ha avanzado considerablemente en la investigación realizada con personas con síndrome de Down, todavía quedan bastantes interrogantes por resolver. Los estudios que han analizado el funcionamiento cognitivo de los niños con síndrome de Down, en tanto que grupo específico y diferenciado, han aportado datos que revelan problemas y déficits en algunos procesos, funciones y estrategias cognitivas en estos niños. También se observan dificultades específicas en determinadas áreas de aprendizaje. Estas peculiaridades cognitivas y de aprendizaje nos permiten afirmar que los niños con síndrome de Down no muestran sólo un retraso en el desarrollo sino que manifiestan un perfil de aprendizaje específico con puntos fuertes y débiles. Ahora bien, este conocimiento va a resultar importante para habilitar programas educativos que permitan un mayor desarrollo de sus capacidades y conocimientos.Eje: Educación especialRed de Universidades con Carreras en Informática (RedUNCI

Programa de comprensión, recuerdo y narración : Aplicación en alumnos con síndrome de down

Aunque en los últimos años se ha avanzado considerablemente en la investigación realizada con personas con síndrome de Down, todavía quedan bastantes interrogantes por resolver. Los estudios que han analizado el funcionamiento cognitivo de los niños con síndrome de Down, en tanto que grupo específico y diferenciado, han aportado datos que revelan problemas y déficits en algunos procesos, funciones y estrategias cognitivas en estos niños. También se observan dificultades específicas en determinadas áreas de aprendizaje. Estas peculiaridades cognitivas y de aprendizaje nos permiten afirmar que los niños con síndrome de Down no muestran sólo un retraso en el desarrollo sino que manifiestan un perfil de aprendizaje específico con puntos fuertes y débiles. Ahora bien, este conocimiento va a resultar importante para habilitar programas educativos que permitan un mayor desarrollo de sus capacidades y conocimientos.Eje: Educación especialRed de Universidades con Carreras en Informática (RedUNCI

The BIG: A Collaborative Librarian Group

http://deepblue.lib.umich.edu/bitstream/2027.42/94427/1/The_Big_A_collaborative_librarian_group.pd

Assessing and Analyzing the Information Needs of Research Complex Tenanta

http://deepblue.lib.umich.edu/bitstream/2027.42/94417/1/assessing_and_analyzing_the_information_needs_of_research_complex_tenants.pd

VuFind - Modified Card Sorting Labels Test

The goals for this test were to solicit suggestions from users for labeling facet categories, determine how users perceive the relative importance of facets, and determine how many narrowing terms users would like to see within each facet.Usability GroupUsability Task Forcehttp://deepblue.lib.umich.edu/bitstream/2027.42/106793/1/VuFind_Card_Sort.pd