106 research outputs found

    Dynamic Image-Based Modelling of Kidney Branching Morphogenesis

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    Kidney branching morphogenesis has been studied extensively, but the mechanism that defines the branch points is still elusive. Here we obtained a 2D movie of kidney branching morphogenesis in culture to test different models of branching morphogenesis with physiological growth dynamics. We carried out image segmentation and calculated the displacement fields between the frames. The models were subsequently solved on the 2D domain, that was extracted from the movie. We find that Turing patterns are sensitive to the initial conditions when solved on the epithelial shapes. A previously proposed diffusion-dependent geometry effect allowed us to reproduce the growth fields reasonably well, both for an inhibitor of branching that was produced in the epithelium, and for an inducer of branching that was produced in the mesenchyme. The latter could be represented by Glial-derived neurotrophic factor (GDNF), which is expressed in the mesenchyme and induces outgrowth of ureteric branches. Considering that the Turing model represents the interaction between the GDNF and its receptor RET very well and that the model reproduces the relevant expression patterns in developing wildtype and mutant kidneys, it is well possible that a combination of the Turing mechanism and the geometry effect control branching morphogenesis

    Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning

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    The renal stroma is an embryonic cell population located in the cortex that provides a structural framework as well as a source of endothelial progenitors for the developing kidney. The exact role of the renal stroma in normal kidney development hasn't been clearly defined. However, previous studies have shown that the genetic deletion of Foxd1, a renal stroma specific gene, leads to severe kidney malformations confirming the importance of stroma in normal kidney development. This study further investigates the role of renal stroma by ablating Foxd1-derived stroma cells themselves and observing the response of the remaining cell populations. A Foxd1cre (renal stroma specific) mouse was crossed with a diphtheria toxin mouse (DTA) to specifically induce apoptosis in stromal cells. Histological examination of kidneys at embryonic day 13.5-18.5 showed a lack of stromal tissue, mispatterning of renal structures, and dysplastic and/or fused horseshoe kidneys. Immunofluorescence staining of nephron progenitors, vasculature, ureteric epithelium, differentiated nephron progenitors, and vascular supportive cells revealed that mutants had thickened nephron progenitor caps, cortical regions devoid of nephron progenitors, aberrant vessel patterning and thickening, ureteric branching defects and migration of differentiated nephron structures into the medulla. The similarities between the renal deformities caused by Foxd1 genetic knockout and Foxd1DTA mouse models reveal the importance of Foxd1 in mediating and maintaining the functional integrity of the renal stroma. © 2014 Hum et al

    A case study of a mother's intertwining experiences with incest and postpartum depression

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    The association between childhood sexual abuse (CSA) and major depression disorder (MDD) gives reason to suspect that many mothers with postpartum depression (PPD) have a history of CSA. However, few studies have investigated how CSA and PPD are related. In this case study we explore how the experience of incest intertwines with the experience of postpartum depression. We focus on participant subject “Nina,” who has experienced both. We interviewed her three times and we analysed the interviews with Giorgi's phenomenological descriptive method to arrive at a contextualised meaning structure. Nina's intruding fantasies of men who abuse her children merge with her recollections of her own incest experiences. She may succeed in forcing these fantasies out of her consciousness, but they still alter her perceptions, thoughts, and emotions. She feels overwhelmed and succumbs to sadness, while she also is drawn towards information about CSA, which in turn feeds her fantasies. The psychodynamic concepts of repetition compulsion, transference, and projection may provide some explanation of Nina's actions, thoughts, and emotions through her past experiences. With our phenomenological stance, we aim to acknowledge Nina's descriptions of her everyday life here and now. With reference to Husserl, Heidegger, Merleau-Ponty, and Minkowski, we show that Nina's past is not a dated memory; rather it determines the structure of her consciousness that constitutes her past as her true present and future. Incest dominates Nina's world, and her possibilities for action are restricted by this perceived world. Any suspension of action implies anguish, and she resolves this by incest-structured action that in turn feeds and colours her expectations. Thus anxiety and depression are intertwined in the structure of this experience

    Engineering kidneys from simple cell suspensions:an exercise in self-organization

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    Increasing numbers of people approaching and living with end-stage renal disease and failure of the supply of transplantable kidneys to keep pace has created an urgent need for alternative sources of new organs. One possibility is tissue engineering of new organs from stem cells. Adult kidneys are arguably too large and anatomically complex for direct construction, but engineering immature kidneys, transplanting them, and allowing them to mature within the host may be more feasible. In this review, we describe a technique that begins with a suspension of renogenic stem cells and promotes these cells’ self-organization into organ rudiments very similar to foetal kidneys, with a collecting duct tree, nephrons, corticomedullary zonation and extended loops of Henle. The engineered rudiments vascularize when transplanted to appropriate vessel-rich sites in bird eggs or adult animals, and show preliminary evidence for physiological function. We hope that this approach might one day be the basis of a clinically useful technique for renal replacement therapy

    International Alliance Strategies: A Case Study of the Indonesian Medical Device Industry

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    This study aims to investigate how the multinational corporations form alliance strategies with local businesses under the dynamic institutional environment in the Indonesian context. We used a qualitative approach with a case study of the medical device industry to examine how the institutional environment affects the choice of the strategic alliance. By collecting the qualitative data, including interviews, observations and archival data, the interpretive approach was adopted to understand social worlds from the point of view of participants. We identified five types of alliance strategies: the wholly owned subsidiary with contractual collaboration, the wholly owned subsidiary with the licence agreement, the international trade with the licence agreement, joint venture and outsourcing. There are also two main issues of the institutional environments that determine the choice of alliance strategic: the restriction for foreign companies to carry out direct selling and the new policy that introduces the electronic procurement system. This study provides evidence of the role of the institutional environment on collaboration strategies between the multinational enterprises from the developed countries and the local distributors from Indonesia. The results extend the concept of international business in the Asian context
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