112 research outputs found

    Caste-Based Exclusion in Nepal’s Communal Micro-Hydro Plants

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    Discriminatory practices rooted in an ethno-caste system have dominated Nepal for centuries. This paper investigates the existence of such practices in Nepal\u27s communal micro-hydro plants. A field research on the role of caste in influencing access to electricity was carried out in Ghandruk, Nepal. The research indicates that although the costs of establishing the micro-hydro plant is shared equally between user-groups, benefit sharing is highly uneven. This analysis demonstrates the need for development projects to be more aligned with socio-economic ground realities

    Targeted Informal Education Promotes Improved Well-Being, Innovation, and Climate-Change Adaptation among Residents in Bajura District, Nepal

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    Western Nepal is a remote region home to a wide variety of traditional small farm and livestock production systems. Communities here lack direct access to a suitable road infrastructure and thus are isolated from the modern world. Farm families are often poverty stricken. Western Nepal is also enduring significant climate change, resulting in warmer and drier conditions that negatively affect crop and livestock productivity. Here we report findings from a novel, quasi-experimental approach where the residents of two communities were provided with an intervention package and their perceptions of change over a 16-month period were contrasted with those from residents of two paired “control” communities that lacked the interventions. The goal was to assess the impact of interventions in promoting well-being, agricultural innovation, and climate-change adaptation. Research efforts included baseline surveys conducted in December, 2013, as well as endline surveys conducted during May, 2015. During the interim period a series of informal, educational inputs and technical demonstrations was implemented based on needs assessments from Participatory Rural Appraisals and expert input. Results indicated that the educational interventions had a very positive impact on nearly all of the 24 attributes that were assessed. The implications are that a concentrated and relatively low-cost educational effort—based on community felt needs—can enhance well-being, innovation, and adaptive capacity of the rural poor in a relatively short period of tim

    Exdpf Is a Key Regulator of Exocrine Pancreas Development Controlled by Retinoic Acid and ptf1a in Zebrafish

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    Both endocrine and exocrine pancreatic cells arise from pancreatic-duodenal homeobox 1 (pdx1)-positive progenitors. The molecular mechanisms controlling cell fate determination and subsequent proliferation, however, are poorly understood. Unlike endocrine cells, less is known about exocrine cell specification. We report here the identification and characterization of a novel exocrine cell determinant gene, exocrine differentiation and proliferation factor (exdpf), which is highly expressed in the exocrine cell progenitors and differentiated cells of the developing pancreas in zebrafish. Knockdown of exdpf by antisense morpholino caused loss or significant reduction of exocrine cells due to lineage-specific cell cycle arrest but not apoptosis, whereas the endocrine cell mass appeared normal. Real-time PCR results demonstrated that the cell cycle arrest is mediated by up-regulation of cell cycle inhibitor genes p21Cip, p27Kip, and cyclin G1 in the exdpf morphants. Conversely, overexpression of exdpf resulted in an overgrowth of the exocrine pancreas and a severe reduction of the endocrine cell mass, suggesting an inhibitory role for exdpf in endocrine cell progenitors. We show that exdpf is a direct target gene of pancreas-specific transcription factor 1a (Ptf1a), a transcription factor critical for exocrine formation. Three consensus Ptf1a binding sites have been identified in the exdpf promoter region. Luciferase assay demonstrated that Ptf1a promotes transcription of the exdpf promoter. Furthermore, exdpf expression in the exocrine pancreas was lost in ptf1a morphants, and overexpression of exdpf successfully rescued exocrine formation in ptf1a-deficient embryos. Genetic evidence places expdf downstream of retinoic acid (RA), an instructive signal for pancreas development. Knocking down exdpf by morpholino abolished ectopic carboxypeptidase A (cpa) expression induced by RA. On the other hand, exdpf mRNA injection rescued endogenous cpa expression in embryos treated with diethylaminobenzaldehyde, an inhibitor of RA signaling. Moreover, exogenous RA treatment induced anterior ectopic expression of exdpf and trypsin in a similar pattern. Our study provides a new understanding of the molecular mechanisms controlling exocrine cell specification and proliferation by a novel gene, exdpf. Highly conserved in mammals, the expression level of exdpf appears elevated in several human tumors, suggesting a possible role in tumor pathogenesis

    All-trans retinoic acid suppresses exocrine differentiation and branching morphogenesis in the embryonic pancreas

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    Recent evidence has shown that retinoic acid (RA) signalling is required for early pancreatic development in zebrafish and frog but its role in later development in mammals is less clear cut. In the present study, we determined the effects of RA on the differentiation of the mouse embryonic pancreas. Addition of all-trans retinoic acid (atRA) to embryonic pancreatic cultures induced a number of changes. Branching morphogenesis and exocrine differentiation were suppressed and there was premature formation of endocrine cell clusters (although the total area of β cells was not different in control and atRA-treated buds). We investigated the mechanism of these changes and found that the premature formation of β cells was associated with the early expression of high-level Pdx1 in the endocrine cell clusters. In contrast, the suppressive effect of RA on exocrine differentiation may be due to a combination of two mechanisms (i) up-regulation of the extracellular matrix component laminin and (ii) enhancement of apoptosis. We also demonstrate that addition of fibroblast growth factor (FGF)-10 is able to partially prevent apoptosis and rescue exocrine differentiation and branching morphogenesis in atRA-treated cultures but not in mice lacking the FGF receptor 2-IIIb, suggesting the effects of FGF-10 are mediated through this receptor

    Retinoic Acid Promotes the Generation of Pancreatic Endocrine Progenitor Cells and Their Further Differentiation into β-Cells

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    The identification of secreted factors that can selectively stimulate the generation of insulin producing β-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based β-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of β-cells during normal pancreatic development such putative factors may be identified. In the mouse, β-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of β-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when β-cells are generated. We also provide evidence that RA induces the generation of Ngn3+ endocrine progenitor cells and stimulates their further differentiation into β-cells by activating a program of cell differentiation that recapitulates the normal temporal program of β-cell differentiation

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    京都大学0048新制・課程博士博士(医学)甲第10685号医博第2669号新制||医||850(附属図書館)UT51-2004-G532京都大学大学院医学研究科分子医学系専攻(主査)教授 清野 裕, 教授 鍋島 陽一, 教授 今村 正之学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA
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