Analisis kode etik dosen dan implementasinya di IAIN Padangsidimpuan

Skripsi ini berjudul “Analisis Kode Etik Dosen dan Implementasinya di IAIN Padangsidimpuan”, penelitian ini membahas tentang kode etik dosen dalam berbagai perspektif dan implementasinya di IAIN Padangsidimpuan. Terkait implementasi kode etik dalam penelitian ini dibatasi kepada implementasi norma berpakaian, kewajiban dosen terhadap diri sendiri, kewajiban dosen terhadap institusi, hak dosen dan hukuman dosen di IAIN Padangsidimpuan. Penelitian ini menggunakan metode kualitatif. Analisis data yang digunakan menggunakan model Miles and Huberman, yaitu reduksi data, penyajian data dan penarikan kesimpulan. Penelitian ini menyimpulkan bahwa secara teologis, kode etik dosen mengandung nilai-nilai ketuhanan. Secara filosofis kode etik ini sudah mengarahkan dosen kepada tugas pokok dan fungsi dosen sebagaimana mestinya. Dalam perspektif yuridis kode etik ini membuktikan telah menjunjung tinggi hukum. Secara sosiologis kode etik dosen mengatur tugas sosial dosen. Terkait dengan implementasi kode etik, peneliti menyimpulkan yaitu sebagai berikut: Pertama, Implementasi norma berpakaian dosen dikategorikan dalam 4 kategori yaitu supra normatif, relevan dengan kode etik, mendekati kode etik dan melanggar kode etik. Kedua, Implementasi kewajiban dosen terhadap diri sendiri sudah berjalan dengan baik, semua dosen telah mempertanggung jawabkan apa yang seharusnya menjadi kewajiban mereka sebagai seorang dosen. Ketiga, Implementasi kewajiban dosen terhadap institusi sudah terpenuhi dan terlaksanakan dengan baik dengan segala aspek yang didalamnya. Keempat, Implementasi hak dosen itu sudah diberikan sesuai dengan apa yang diterapkan dan sudah berjalan dengan sebaik-baiknya di IAIN Padangsidimpuan. Kelima, Implementasi penerapan sanksi kode etik dapat dikategorikan dalam 3 kategori, yaitu hukuman disiplin ringan, hukuman disiplin sedang dan hukuman disiplin berat

HoxA9 binds and represses the Cebpa +8 kb enhancer

C/EBPα plays a key role in specifying myeloid lineage development. HoxA9 is expressed in myeloid progenitors, with its level diminishing during myeloid maturation, and HOXA9 is over-expressed in a majority of acute myeloid leukemia cases, including those expressing NUP98-HOXD13. The objective of this study was to determine whether HoxA9 directly represses Cebpa gene expression. We find 4-fold increased HoxA9 and 5-fold reduced Cebpa in marrow common myeloid and LSK progenitors from Vav-NUP98-HOXD13 transgenic mice. Conversely, HoxA9 decreases 5-fold while Cebpa increases during granulocytic differentiation of 32Dcl3 myeloid cells. Activation of exogenous HoxA9-ER in 32Dcl3 cells reduces Cebpa mRNA even in the presence of cycloheximide, suggesting direct repression. Cebpa transcription in murine myeloid cells is regulated by a hematopoietic-specific +37 kb enhancer and by a more widely active +8 kb enhancer. ChIP-Seq analysis of primary myeloid progenitor cells expressing exogenous HoxA9 or HoxA9-ER demonstrates that HoxA9 localizes to both the +8 kb and +37 kb Cebpa enhancers. Gel shift analysis demonstrates HoxA9 binding to three consensus sites in the +8 kb enhancer, but no affinity for the single near-consensus site present in the +37 kb enhancer. Activity of a Cebpa +8 kb enhancer/promoter-luciferase reporter in 32Dcl3 or MOLM14 myeloid cells is increased ~2-fold by mutation of its three HOXA9-binding sites, suggesting that endogenous HoxA9 represses +8 kb Cebpa enhancer activity. In contrast, mutation of five C/EBPα-binding sites in the +8 kb enhancer reduces activity 3-fold. Finally, expression of a +37 kb enhancer/promoter-hCD4 transgene reporter is reduced ~2-fold in marrow common myeloid progenitors when the Vav-NUP98-HOXD13 transgene is introduced. Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9

Depletion of Cytotoxic T-Cells Does Not Protect NUP98-HOXD13 Mice from Myelodysplastic Syndrome but Reveals a Modest Tumor Immunosurveillance Effect

Myelodysplastic syndrome (MDS) and aplastic anemia (AA) patients both present with symptoms of bone marrow failure. In many AA patients, these features are thought to result from an oligoclonal expansion of cytotoxic T-cells that destroy haematopoietic stem or progenitor cells. This notion is supported by the observation that AA patients respond to immunosuppressive therapy. A fraction of MDS patients also respond well to immunosuppressive therapy suggesting a similar role for cytotoxic T-cells in the etiology of MDS, however the role of cytotoxic T-cells in MDS remains unclear. Mice that express a NUP98-HOXD13 (NHD13) transgene develop a MDS that closely mimics the human condition in terms of dysplasia, ineffective hematopoiesis, and transformation to acute myeloid leukemia (AML). We followed a cohort of NHD13 mice lacking the Rag1 protein (NHD13/Rag1KO) to determine if the absence of lymphocytes might 1) delay the onset and/or diminish the severity of the MDS, or 2) effect malignant transformation and survival of the NHD13 mice. No difference was seen in the onset or severity of MDS between the NHD13 and NHD13/Rag1KO mice. However, NHD13/Rag1KO mice had decreased survival and showed a trend toward increased incidence of transformation to AML compared to the NHD13 mice, suggesting protection from AML transformation by a modest immuno-surveillance effect. In the absence of functional Tcrb signaling in the NHD13/Rag1KO T-cell tumors, Pak7 was identified as a potential Tcrb surrogate survival signal

Generation of Gross Chromosomal Rearrangements by a Single Engineered DNA Double Strand Break

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Unsuspected role of the brain morphogenetic gene Otx1 in hematopoiesis

Otx1 belongs to the paired class of homeobox genes and plays a pivotal role in brain development. Here, we show that Otx1 is expressed in hematopoietic pluripotent and erythroid progenitor cells. Moreover, bone marrow cells from mice lacking Otx1 exhibit a cell-autonomous impairment of the erythroid compartment. In agreement with these results, molecular analysis revealed decreased levels of erythroid genes that include the SCL and GATA-1 transcription factors. Accordingly, a gain of function of SCL rescues the erythroid deficiency in Otx1-/- mice. Taken together, our findings indicate a function for Otx1 in the regulation of blood cell production. There is growing evidence suggesting that common cellular and molecular mechanisms orchestrate differentiation in various tissues. Homeobox-containing genes seem to be strong candidate genes to regulate a number of developmental processes, including neurogenesis and hematopoiesis. Members of the Otx family (Otx1, Otx2, Otx3, and Crx) are the vertebrate homologues of the Drosophila head gap gene orthodenticle and encode transcription factors containing a bicoid-like homeodomain. They are temporally and spatially regulated during development and seem to be required for proper head and sense organ patterning. Otx1, Otx2, and Otx3 show partially overlapping, but distinct expression patterns, and Otx2, the first to be activated during development, plays a major role in gastrulation and in the early specification of the anterior neural plate. In contrast, Otx1 shows a later onset and is involved in corticogenesis, sense organ development, and pituitary function. Mice bearing targeted deletion of Otx1 are affected by a permanent epileptic phenotype and show multiple brain abnormalities and morphological defects of the acoustic and visual sense organs. In addition, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism because of low levels of pituitary hormones. In the present study, we have investigated whether Otx1 also plays a role in blood cell production, as several homeobox genes of different families are involved in normal and/or malignant hematopoiesis

Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models

Disulfiram (DS), a clinically used drug to control alcoholism, has displayed promising anti-cancer activity against a wide range of tumors. Here, we demonstrated that DS/copper (Cu) complex effectively eliminated adult B-ALL cells in vitro and in vivo in patient-derived xenograft (PDX) humanized mouse models, reflected by inhibition of cell proliferation, induction of apoptosis, suppression of colony formation, and reduction of PDX tumor growth, while sparing normal peripheral blood mononuclear cells. Mechanistically, these events were associated with disruption of mitochondrial membrane potential and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Further analysis on B-ALL patients’ clinical characteristics revealed that the ex vivo efficacy of DS/Cu in primary samples was significantly correlated to p16 gene deletion and peripheral blood WBC counts at diagnosis, while age, LDH level, extramedullary infiltration, status post intensive induction therapy, immune phenotype, risk category, and Ph chromosome had no effect. Together, these findings indicate that disulfiram, particularly when administrated in combination with copper, might represent a potential repurposing agent for treatment of adult B-ALL patients, including those clinically characterized by one or more adverse prognostic factors