OBJECTIVE-To gain structural insights into the autoantigenic properties of GAD65 in type 1 diabetes, we analyzed experimental epitope mapping data in the context of the recently determined crystal structures of GAD65 and GAD67, to allow "molecular positioning" of epitope sites for B-and T-cell reactivity. RESEARCH DESIGN AND METHODS-Datawere assembled from analysis of reported effects of mutagenesis of GAD65 on its reactivity with a panel of 11 human monoclonal antibodies (mAbs), supplemented by use of recombinant Fab to crossinhibit reactivity with GAD65 by radioimmunoprecipitation of the same mAbs. RESULTS-The COOH-terminal region on GAD65 was the major autoantigenic site. B-cell epitopes were distributed within two separate clusters around different faces of the COOHterminal domain. Inclusion of epitope sites in the pyridoxal phosphate-and NH 2 -terminal domains was attributed to the juxtaposition of all three domains in the crystal structure. Epitope preferences of different mAbs to GAD65 aligned with different clinical expressions of type 1 diabetes. Epitopes for four of five known reactive T-cell sequences restricted by HLA DRB1*0401 were aligned to solvent-exposed regions of the GAD65 structure and colocalized within the two B-cell epitope clusters. The continuous COOH-terminal epitope region of GAD65 was structurally highly flexible and therefore differed markedly from the equivalent region of GAD67.CONCLUSIONS-Structural features could explain the differing antigenicity, and perhaps immunogenicity, of GAD65 versus GAD67. The proximity of B-and T-cell epitopes within the GAD65 structure suggests that antigen-antibody complexes may influence antigen processing by accessory cells and thereby T-cell reactivity. Diabetes 57:1293-1301, 2008 T ype 1 diabetes is characterized by autoimmune reactivity to islet cell antigens that include the 65-kDa isoform of GAD (GAD65). Of the two isoforms of GAD, GAD67 and GAD65, only GAD65 is autoantigenic, in diseases that include particularly type 1 diabetes (1,2). Importantly, the specificity of antibodies for particular epitopes on GAD65 rather than their actual levels may be a better indicator of impending or actual destruction of islet ␤-cells. Thus in genetically prone individuals, changes in the focus of autoantibody responses to epitopes of GAD65, i.e., intramolecular epitope shifts during the period of pre-diabetic insulitis, herald the onset of overt type 1 diabetes (3).B-cell/autoantibody epitopes on GAD65 engage conformational determinants that are widely distributed over the linear sequence of the three domains, NH 2 -terminal (amino acids 1-234), pyridoxal phosphate (PLP)-binding (235-442), and COOH-terminal (443-585) domains (4). Presently, unanswered questions include the precise location of epitope sites and critical binding residues for autoantibody recognition, the differing immune reactivity of the GAD65 versus the GAD67 isoform, and the failure of natural immune tolerance to GAD65 in the first place. These questions prompted the recent crystallographic s...

No abstract

Penelitian ini mendiskripsikan tentang peranan kepemimpinan dalam meningkatkan mutu pendidikan melalui Manajemen Berbasis Sekolah yang diterapkan di SD Negeri 14 Betung dengan rumusan masalah penelitiannya. Penelitian ini menggunakan pendekatan penelitian kualitatif dengan jenis fenomenologic naturalistic. Data penelitian diperoleh dengan teknik pengamatan terlibat, wawancara mendalam dan dokumentasi. informan dalam penelitian ini, Kepala Sekolah dan guru. Hasil penelitian menyimpulkan bahwa Kepala Sekolah telah melaksanakan peran utamanya sebagai pemimpin dan manajer dengan baik, di samping peran yang lainnya adalah seorang wirausahawan yang tangguh dalam upaya meningkatkan mutu pendidikan. Strategi yang dilakukan untuk meningkatkan mutu pendidikan di SD Negeri 14 Betung melalui Manajemen Berbasis Sekolah (MBS) cukup bagus, hal ini dapat dilihat dari kinerja kepala sekolah, guru, karyawan,dalam berkolaborasi dan menjalin komunikasi dalam melaksanakan setiap kegiatan yang menjadi tugas dan tanggung jawabnya demi tercapainya tujuan pendidikan yang diharapkan

Penelitian ini bertujuan untuk mengetahui pengaruh supervisi akademik kepala sekolah dan lingkungan kerja terhadap kinerja guru. Penelitian ini menggunakan metode kuantitatif dengan jenis penelitian korelasional. Populasi penelitian sebanyak 30 orang yaitu guru-guru Sekolah Dasar Negeri jalur 8 Kecamatan Air Salek Kabupaten Banyuasin. Teknik pengumpulan data menggunakan kuesioner. Data dianalisis menggunakan teknik analisis korelasi dan regresi ganda. Hasil penelitian menunjukkan bahwa: (1) supervisi akademik kepala sekolah berpengaruh positif dan signifikan terhadap kinerja guru Sekolah Dasar Negeri Jalur 8 Air Salek Banyuasin; (2) Lingkungan kerja berpengaruh positif dan signifikan terhadap kinerja guru Sekolah Dasar Negeri Jalur 8 Air Salek Banyuasin, dan (3) supervisi akademik kepala sekolah dan lingkungan kerja secara bersama-sama berpengaruh positif dan signifikan terhadap kinerja guru Sekolah Dasar Negeri Jalur 8 Air Salek Banyuasin

No abstract