The roles of micro RNA in pancreas development and regeneration

Presence of sufficient number of functional glucose responsive β-cells is indispensable for normal glucose homeostasis. Diabetes mellitus is a chronic disease associated with loss or reduction of β-cell mass and not β-cell mass. MicroRNAs are small non-coding RNAs that are involved in different biological processes including development, cell proliferation, stress response, and tumor pathogenesis. MicroRNAs fine-tune the gene expression level post-transcriptionally either by mRNA degradation or translational repression. In the past few years, several miRNAs have been introduced as new critical players for pancreas development, function, and regeneration. Deregulation of several microRNAs is found in animal models of diabetes, as well as in diabetic patients. Therefore, it is essential to understand the roles of these microRNAs in β-cell generation and physiology, as well as the biological consequences of their functional impairment.Biomedical Reviews 2013; 24: 57-65

Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage

<p>Abstract</p> <p>Background</p> <p>Nkx2.2 and Arx represent key transcription factors implicated in the specification of islet cell subtypes during pancreas development. Mice deficient for <it>Arx </it>do not develop any alpha-cells whereas beta- and delta-cells are found in considerably higher numbers. In <it>Nkx2.2 </it>mutant animals, alpha- and beta-cell development is severely impaired whereas a ghrelin-expressing cell population is found augmented.</p> <p>Notably, <it>Arx </it>transcription is clearly enhanced in <it>Nkx2.2</it>-deficient pancreata. Hence in order to precise the functional link between both factors we performed a comparative analysis of <it>Nkx2.2/Arx </it>single- and double-mutants but also of <it>Pax6</it>-deficient animals.</p> <p>Results</p> <p>We show that most of the ghrelin⁺cells emerging in pancreata of <it>Nkx2.2</it>- and <it>Pax6</it>-deficient mice, express the alpha-cell specifier Arx, but also additional beta-cell related genes. In <it>Nkx2.2</it>-deficient mice, Arx directly co-localizes with iAPP, PC1/3 and Pdx1 suggesting an Nkx2.2-dependent control of <it>Arx </it>in committed beta-cells. The combined loss of <it>Nkx2.2 </it>and <it>Arx </it>likewise results in the formation of a hyperplastic ghrelin⁺cell population at the expense of mature alpha- and beta-cells. Surprisingly, such <it>Nkx2.2^-/-Arx^-</it>ghrelin⁺cells also express the somatostatin hormone.</p> <p>Conclusions</p> <p>Our data indicate that Nkx2.2 acts by reinforcing the transcriptional networks initiated by Pax4 and Arx in early committed beta- and alpha-cell, respectively. Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract <it>Arx </it>gene activity in early committed beta-cells.</p

Genetic interplay between the transcription factors Sp8 and Emx2 in the patterning of the forebrain

<p>Abstract</p> <p>Background</p> <p>The forebrain consists of multiple structures necessary to achieve elaborate functions. Proper patterning is, therefore, a prerequisite for the generation of optimal functional areas. Only a few factors have been shown to control the genetic networks that establish early forebrain patterning.</p> <p>Results and conclusion</p> <p>Using conditional inactivation, we show that the transcription factor Sp8 has an essential role in the molecular and functional patterning of the developing telencephalon along the anteroposterior axis by modulating the expression gradients of <it>Emx2 </it>and <it>Pax6</it>. Moreover, Sp8 is essential for the maintenance of ventral cell identity in the septum and medial ganglionic eminence (MGE). This is probably mediated through a positive regulatory interaction with Fgf8 in the medial wall, and Nkx2.1 in the rostral MGE anlage, and independent of SHH and WNT signaling. Furthermore, <it>Sp8 </it>is required during corticogenesis to sustain a normal progenitor pool, and to control preplate splitting, as well as the specification of cellular diversity within distinct cortical layers.</p

Pax7 is requisite for maintenance of a subpopulation of superior collicular neurons and shows a diverging expression pattern to Pax3 during superior collicular development

<p>Abstract</p> <p>Background</p> <p><it>Pax7 </it>encodes a transcription factor well-established as an important determinant of mesencephalic identity and superior collicular development. <it>Pax7 </it>mutant mice, however, present with no obvious morphological impairments to the superior colliculus. This finding is paradoxical and has been attributed to functional redundancy afforded by its paralogue <it>Pax3</it>. Here we utilise <it>Pax7 </it>mutant mice to investigate the precise role of this important developmental regulator during superior collicular development and neuronal specification/differentiation. We also assess its spatiotemporal relationship with <it>Pax3 </it>during embryonic development.</p> <p>Results</p> <p>Analysis of the superior colliculus of <it>Pax7 </it>mutant and wildtype mice at a variety of developmental timepoints revealed that whilst correct initial specification is maintained, a subpopulation of dorsal mesencephalic neurons is lost at early postnatal stages. Moreover, a comparative analysis of embryonic <it>Pax3 </it>and <it>Pax7 </it>expression profiles indicate that <it>Pax3 </it>expression overlaps extensively with that of <it>Pax7 </it>initially, but their expression domains increasingly diverge as development progresses, coinciding spatiotemporally with neuronal differentiation and maturation of the tissue. Furthermore, <it>Pax3 </it>expression is perturbed within the CNS of embryonic <it>Pax7 </it>mutant mice.</p> <p>Conclusion</p> <p>In summary, these results demonstrate that during superior collicular development, <it>Pax7 </it>is required to maintain a subpopulation of dorsal, mesencephalic neurons and partially regulates, spatiotemporally, <it>Pax3 </it>expression within the CNS. The differential nature of <it>Pax7 </it>and <it>Pax3 </it>with respect to neuronal differentiation may have implications for future stem cell therapies aimed at exploiting their developmental capabilities.</p

Three-Dimensional Devices Transport Simulation Lifetime and Relaxation Semiconductor

Our work is to create a three-dimensional Simulator (3D) used for the study of the components to low geometry of design, and to determine in the volume structure  the  potential distributions and densities of free carriers in bias voltage given by solving the system of Poisson  and two  continuities equations. The initial version can simulate components of lifetime semiconductor.  In this study, we make a comparison between the lifetime and relaxation semiconductor in the conduction mode. In order to create a larger Simulator, we'll perform a calculation by varying am bipolar lifetime way to move from lifetime semiconductor to relaxation semiconductor. We consider the case corresponding at two different values of diffusion lifetime τ0 which is corresponding to a measured lifetime in current transport. The method of resolution consists to linearization of the equations transport by the finite differences method. The algorithm for solving linear and strongly coupled equations deduced from the physical model is the Newton-Raphson. However, in order to allow a better convergence and consequently an improvement of time computing 3D, a method combined, incorporating the Newton algorithm and the Gummel method was developed. PIN diodes are used for test of the simulation mode

Corps étranger iléo-caecal mimant une maladie de Crohn: rapport de cas

L'ingestion du corps étranger est une situation fréquente en gastro-entérologie, cependant la localisation iléo-caecale reste très rare. L'objectif de ce travail était de rapporter le cas exceptionnel d'un corps étranger iléo-caecal révélé par des syndromes sub-occlusifs. Il s'agit d'un patient âgé de 22 ans sans antécédents pathologiques notables, qui s'est présenté avec un syndrome de Koening évoluant dans un contexte d'altération de l'état général. Le diagnostic d'un épaississement iléo-caecal inflammatoire réactionnel à un corps étranger est posé grâce à l'étude anatomo-pathologique d'une pièce opératoire de résection iléo-caecale après que l'endoscopie, l'histologie des biopsies et l'imagerie scannographique étaient non contributives. En l'absence d'orientation anamnestique, la localisation iléo-caecale d'un corps étranger pose un réel problème de diagnostic différentiel avec les pathologies inflammatoires, infectieuses et tumorales du carrefour iléo-caecal. Elle peut être révélée par des complications à type d'occlusion ou de perforation où l'imagerie tient une place primordiale. L'endoscopie joue toujours un rôle diagnostique et thérapeutique essentiel dans la prise en charge des corps étrangers ingérés limitant ainsi la morbidité chirurgicale quoique celle-ci demeure parfois incontournable et l'étude anatomo-pathologique met en évidence un granulome à corps étranger constitué. Le corps étranger iléo-caecal est une situation rarement rapportée et doit dorénavant être considéré devant toute symptomatologie du carrefour iléo-caecal afin d'éviter au patient les effets secondaires et les complications des traitements lourds

Neurohypophysial dysmorphogenesis in mice lacking the homeobox gene Uncx4·1

Abstract A number of transcription factors have been implicated in the development of the hypothalamo-neurohypophysial system (HNS). Null mutations for these factors caused severe defects in proliferation, migration and survival during early embryogenesis. While they have informed about early events of HNS developments no insights in mechanisms of late development and maturation of this major peptidergic system have been obtained as yet. In a screen for adult-expressed homeobox genes we identified Uncx4.1 as a gene expressed in adult and embryonic magnocellular neurons of the (HNS). Null mutation of Uncx4.1 left these neurons viable and able to express neuropeptides. However, the connectivity of magnocellular neurons with posterior pituitary elements was compromised. As a consequence neuronal fibres traversed to the adenohypophysis. The penetrance of this phenotype was about 50%. The data show a selective role of Uncx4.1 in controlling the development of connections of hypothalamic neurons to pituitary elements, allowing central neurons to reach the peripheral blood circulation and to deliver hormones for control of peripheral functions

Nonlinear State and Parameter Estimation Using Iterated Sigma Point Kalman Filter: Comparative Studies

In this chapter, iterated sigma‐point Kalman filter (ISPKF) methods are used for nonlinear state variable and model parameter estimation. Different conventional state estimation methods, namely the unscented Kalman filter (UKF), the central difference Kalman filter (CDKF), the square‐root unscented Kalman filter (SRUKF), the square‐root central difference Kalman filter (SRCDKF), the iterated unscented Kalman filter (IUKF), the iterated central difference Kalman filter (ICDKF), the iterated square‐root unscented Kalman filter (ISRUKF) and the iterated square‐root central difference Kalman filter (ISRCDKF) are evaluated through a simulation example with two comparative studies in terms of state accuracies, estimation errors and convergence. The state variables are estimated in the first comparative study, from noisy measurements with the several estimation methods. Then, in the next comparative study, both of states and parameters are estimated, and are compared by calculating the estimation root mean square error (RMSE) with the noise‐free data. The impacts of the practical challenges (measurement noise and number of estimated states/parameters) on the performances of the estimation techniques are investigated. The results of both comparative studies reveal that the ISRCDKF method provides better estimation accuracy than the IUKF, ICDKF and ISRUKF. Also the previous methods provide better accuracy than the UKF, CDKF, SRUKF and SRCDKF techniques. The ISRCDKF method provides accuracy over the other different estimation techniques; by iterating maximum a posteriori estimate around the updated state, it re‐linearizes the measurement equation instead of depending on the predicted state. The results also represent that estimating more parameters impacts the estimation accuracy as well as the convergence of the estimated parameters and states. The ISRCDKF provides improved state accuracies than the other techniques even with abrupt changes in estimated states

Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells

The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7. We show that Pax3, the paralogue of Pax7, is also present in both quiescent and activated satellite cells in many skeletal muscles. Dominant-negative forms of both Pax3 and -7 repress MyoD, but do not interfere with the expression of the other myogenic determination factor, Myf5, which, together with Pax3/7, regulates the myogenic differentiation of these cells. In Pax7 mutants, satellite cells are progressively lost in both Pax3-expressing and -nonexpressing muscles. We show that this is caused by satellite cell death, with effects on the cell cycle. Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7. These findings underline the importance of cell survival in controlling the stem cell populations of adult tissues and demonstrate a role for upstream factors in this context