| 1. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation.
- 2013
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Ingår i: Developmental biology. - : Elsevier BV. - 1095-564X .- 0012-1606. ; 381:2, s. 377-88
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50-60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions.
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| 2. |
- Ajore, Ram, et al.
(författare)
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The leukemia associated nuclear corepressor ETO homologue genes MTG16 and MTGR1 are regulated differently in hematopoietic cells
- 2012
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Ingår i: BMC Molecular Biology. - : Springer Science and Business Media LLC. - 1471-2199. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: MTG16, MTGR1 and ETO are nuclear transcriptional corepressors of the human ETO protein family. MTG16 is implicated in hematopoietic development and in controlling erythropoiesis/megakaryopoiesis. Furthermore, ETO homologue genes are 3'participants in leukemia fusions generated by chromosomal translocations responsible of hematopoietic dysregulation. We tried to identify structural and functional promoter elements of MTG16 and MTGR1 genes in order to find associations between their regulation and hematopoiesis. Results: 5' deletion examinations and luciferase reporter gene studies indicated that a 492 bp sequence upstream of the transcription start site is essential for transcriptional activity by the MTG16 promoter. The TATA-and CCAAT-less promoter with a GC box close to the start site showed strong reporter activity when examined in erythroid/megakaryocytic cells. Mutation of an evolutionary conserved GATA -301 consensus binding site repressed promoter function. Furthermore, results from in vitro antibody-enhanced electrophoretic mobility shift assay and in vivo chromatin immunoprecipitation indicated binding of GATA-1 to the GATA -301 site. A role of GATA-1 was also supported by transfection of small interfering RNA, which diminished MTG16 expression. Furthermore, expression of the transcription factor HERP2, which represses GATA-1, produced strong inhibition of the MTG16 promoter reporter consistent with a role of GATA-1 in transcriptional activation. The TATA-less and CCAAT-less MTGR1 promoter retained most of the transcriptional activity within a -308 to -207 bp region with a GC-box-rich sequence containing multiple SP1 binding sites reminiscent of a housekeeping gene with constitutive expression. However, mutations of individual SP1 binding sites did not repress promoter function; multiple active SP1 binding sites may be required to safeguard constitutive MTGR1 transcriptional activity. The observed repression of MTG16/MTGR1 promoters by the leukemia associated AML1-ETO fusion gene may have a role in hematopoietic dysfunction of leukemia. Conclusions: An evolutionary conserved GATA binding site is critical in transcriptional regulation of the MTG16 promoter. In contrast, the MTGR1 gene depends on a GC-box-rich sequence for transcriptional regulation and possible ubiquitous expression. Our results demonstrate that the ETO homologue promoters are regulated differently consistent with hematopoietic cell-type-specific expression and function.
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| 3. |
- Bhunya, Pradeep K., et al.
(författare)
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Development of a Regional Non-dimensional Return Period Flood Model
- 2010
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Ingår i: Water Resources Management. - : Springer Science and Business Media LLC. - 0920-4741 .- 1573-1650. ; 24:7, s. 1425-1439
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Tidskriftsartikel (refereegranskat)abstract
- Based on the non-dimensional approach, this study focuses on developing a model to compute design flood for specific return periods whose parameter estimations are done using the Marquardt algorithm considering peak flood data of 100 Indian catchments. The selected flood data varies for majority of the sites for a period of 10 years, and for a few sites up to 36 years; and as a preliminary processing these data are checked for outliers, discordancy, and other errors. The model is calibrated for a variety of situations, and validated on selected gauged catchments. Both the descriptive and predictive goodness-of-fit measures are computed considering the floods of specific return periods estimated from the observed data. The model is found to perform well for the whole study area. Investigations reveal the model to be useful to any catchment within the hydrologically homogeneous region with limited or no flood data conditions.
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| 4. |
- Ohshiro, Kazufumi, et al.
(författare)
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Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator.
- 2010
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Ingår i: EMBO reports. - : EMBO. - 1469-3178 .- 1469-221X. ; 11:9, s. 691-7
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Tidskriftsartikel (refereegranskat)abstract
- High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of Galphai2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the Galphai2 regulatory element and consequently for the repression of Galphai2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time--to the best of our knowledge--evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product.
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