No description available.

The fourth chromosome mutant cubitus interruptus‐Wallace(ciW) produces leg, wing, and body bristle aberrations. The effect on the wing is similar to that produced by cubitus interruptus‐dominant (ciD) which also has an influence on larval segmentation indicating that it has a regulatory function. Leg morphology of haplo‐4, ciW, and mosaic haplo‐4:diplo‐4, ci/ci+ flies was examined in an attempt to distinguish between a structural and a regulatory function by ciW. Aberrations recovered include failure of segment elongation, intersegmental gaps, duplication of bristles, and segments that are shorter than normal and of greater than normal diameter. Many of these effects are localized, suggesting that ciW may act to maintain cell positional reference. Increased local cell proliferation appears to be one manifestation of loss of the normal function.

The adoption and subsequent retention of distinct cellular fates upon cell division is a critical phenomenon in the development of multicellular organisms. A well-studied example of this process is stem cell divisions; stem cells must possess the capacity to self-renew in order to maintain a stem cell population, as well as to generate differentiated daughters for tissue growth and repair. Drosophila neuroblasts are the neural stem cells of the central nervous system and have emerged as an important model for stem cell divisions and the genetic control of daughter cell identities. Neuroblasts divide asymmetrically to generate daughters with distinct fates; one retains a neuroblast identity and the other, a ganglion mother cell, divides only once more to generate differentiated neurons and glia. Perturbing the asymmetry of neuroblast divisions can result in the failure to self-renew and the loss of the neural stem cell population; alternatively, ectopic self-renewal can occur, resulting in excessive neuroblast proliferation and tumorigenesis. Several genetic lesions have been characterized which cause extensive ectopic self-renewal, resulting in brains composed of neuroblasts at the expense of differentiated cells. This contrasts with wild type brains, which are composed mostly of differentiated cells and only a small pool of neuroblasts. We made use of these mutants by performing a series of microarray experiments comparing mutant brains (consisting mostly of neuroblasts) to wild type brains (which are mostly neurons). Using this approach, we generated lists of over 1000 putatively neuroblast-expressed genes and over 1000 neuronal genes; in addition, we were able to compare the transcriptional output of different mutants to infer the neuroblast subtype specificity of some of the transcripts. Finally, we verified the self-renewal function of a subset of the neuroblast genes using an RNAi-based screen, resulting in the identification of 84 putative self-renewal regulators. We went on to show that one of these genes, midlife crisis (mammals: RNF113a), is a well-conserved RNA splicing regulator which is required in postmitotic neurons for the maintenance of their differentiated state. Our data suggest that the mammalian ortholog performs the same function, implicating RNF113a as an important regulator of neuronal differentiation in humans.

Indiana University-Purdue University Indianapolis (IUPUI) / A hallmark of diabetes is the loss of physical or functional Beta (β) cell mass. Maladaptive intrinsic β cell responses to islet inflammatory stress may exacerbate diabetes development, suggesting that β cells themselves may not be innocent bystanders in diabetes development. MicroRNAs (miRNAs), small RNAs that repress mRNA translation, serve as important regulators of β cell development and function. β cell microRNA 21 (miR-21) is increased in models of diabetes and I have identified Hypoxia Inducible Factor 1 Subunit Alpha (Hif1a) as a regulator of β cell miR-21. However, β cell effects of miR-21, remain poorly defined. To define the effects of miR-21, an in silico analysis of predictive targets of miR-21 identified multiple targets associated with maintenance of β cell identity, including the SMAD Family Member 2 (Smad2) mRNAs in the Transforming Growth Factor Beta 2 (Tgfb2) pathway. Based on this, I hypothesized that β cell miR-21 induces dysfunction via loss of β cell identity. To test this, I developed a tetracycline-on system of miR-21 induction in clonal β cells and human islets, as well as novel transgenic zebrafish and mouse models of inducible β cell specific miR-21 overexpression. β cell miR-21 induction increased aldehyde dehydrogenase (aldh1a3), but reduced expression of transcription factors associated with β cell identity, and glucose stimulated insulin secretion (GSIS), consistent with β cell dedifferentiation and dysfunction. Predicted targets Tgfb2 and Smad2 were reduced by miR-21 overexpression and confirmed to directly bind miR-21 using streptavidin-biotin pulldown. In vivo models of β cell miR-21 induction exhibited hyperglycemia, increased glucagon expression, and decreased insulin expression. These findings implicate miR-21- mediated reduction of mRNAs regulating β cell identity as a contributor to β cell dedifferentiation and dysfunction during islet inflammatory stress. / 2022-05-19

No description available.

Plant growth and development depends on controlled cell expansion. This, in itself, is determined by the plant cell wall, a structural matrix of polysaccharides encasing the plant cell. One line of investigation that has proven particularly successful in elucidating the components of the plant cell wall machinery has been the forward genetic screens of cell wall mutants. In this study, the molecular and cellular characterisation of sloughy, a cell separation mutant in Arabidopsis thaliana, was commenced. This mutant has a striking phenotype, with files of elongating epidermal cells snaking away from the adjacent epidermal cells and from the underlying cortex, loosing contact from the side walls while remaining attached at the cell ends, in a manner reminiscent of border-like cells in the root cap of arabidopsis. The sloughy mutation was fine mapped to a short region on chromosome I using high resolution melt point analysis. On sequencing all five genes in this region, a single nucleotide mutation, introducing a stop codon, was detected in exon 2 in the previously-described heat shock transcription factor SCHIZORIZA that results in a truncated protein missing several conserved domains essential for activity. SCHIZORIZA acts as a cell fate determinate in the root meristem to promote cortex fate, while suppressing epidermal and root cap fate in the mature ground tissue. Although the literature on schizoriza mutants has focused on the developing root meristem, with little documentation on the cell separation phenotype further up in the roots, the investigation of a collection of schizoriza TILLING mutants revealed that aberrant cell separation was ubiquitous to schizoriza mutants with a severely truncated protein. To investigate cell identity in the mature roots, sloughy was crossed to GAL4-GFP enhancer trap lines that act as cell-specific markers. Epidermal identity lines revealed that sloughy possessed a supernumerary ground tissue layer with epidermal identity. A cortex and endodermal line revealed that these two identities are restricted to the endodermal layer and the next ground tissue layer out. There was no indication of root cap identity in the mature root with any of the root cap lines used, although partial lateral root cap identity has been previously described in the epidermal and subepidermal cell layers in the meristem of schizoriza mutants expressing SOMBRERO-GFP, a lateral root cap-specific transcription factor. Immunolabelling of cell wall epitopes revealed that the JIM13 antibody, which specifically labels arabinogalactan-proteins in wild-type root caps, often labelled the epidermal cells and surrounding mucilage further up the in the roots of sloughy. The aberrant cell separation present in sloughy is thought to be a consequence of epidermal cells possessing partial lateral root cap identity. The data on sloughy/schizoriza is sufficient to generate a model on how a meristem developmental gene can generate a cell separation phenotype in the mature roots. Loss of SCHIZORIZA causes confused cell identity in the root meristem that results in an epidermal and subepidermal layer possessing mixed epidermal and lateral root cap identity. The distinctive properties of border-like cells in the root cap of arabidopsis have been linked to unique cell wall maturation and developmental processes, implicating the cellulases CEL3 and CEL5, the pectin glycosyltransferase QUA1, the pectin methyltransferase QUA2 and other pectolytic enzymes. The ectopic expression of these cell wall enzymes in the epidermal and subepidermal layers of sloughy roots result in reduced adhesion along the sides of the cell, while the ends remain attached, causing the observed cell separation phenotype.

Background: The growing needs of communications have a higher demand for data and stream-less services for the users. A unique physical cell identity (PCI) is assigned to transfer data between the cellular base station (gNB) and user equipment (UE). It is used to transmit the data to multiple users simultaneously. In this thesis, a heuristic algorithm is generated, aided by an unsupervised machine learning approach to improve the PCI allocation of a cell for better 5G services such as connectivity and speed.  Objectives: Firstly, performing a literature review to find the appropriate performance metrics to compare both K-means and density-based spatial clustering of applications with noise (DBSCAN) technique on the PCI allocation data provided by Ericsson. Next, the better-clustering method along with heuristic algorithm was implemented to generate a efficient PCI planning. Later, compare the results of previous planning (existing PCI planning approach), proposed planning (results of using the generated heuristic algorithm) based on the ideal planning derived from the experts.  Methods: The literature review is conducted for determining the best metrics for the clustering algorithms mentioned in the objectives. With the use of unsupervised learning the PCI allocation data is clustered based on its distance and neighbors. Subsequently the clusters are used in the heuristic algorithm. The results of proposed planning are compared with previous planning.  Results: The literature review indicated that the silhouette coefficient and davies-bouldin index are most suitable metrics for comparing the clustering algorithms mentioned in the objectives. These two metrics are used to determine the best performing clustering algorithm. The clustering results were given as input for heuristic algorithm to generate a PCI planning. Then, the results stated that the proposed planning is better than previous planning and decreased nearly 70% collisions in the areas: Fresno, San Francisco and San Jose compared to the previous planning. Conclusions: The main goal of this study is to achieve a better PCI planning that can accommodate many users and achieve better 5G services. This PCI planning is helpful for the company to utilize its resources efficiently.

La formation d'un organe repose sur la coordination spatio-temporelle du positionnement et de la différenciation de progéniteurs. La finalité de ces évènements permet la constitution structurelle de l'organe et la production de la diversité cellulaire nécessaire pour assurer ses fonctions. L'épithélium olfactif de l'embryon de poisson-zèbre est issu de la migration de progéniteurs qui vont générer entre autres les neurones olfactifs. Au cours de ma thèse je me suis intéressé aux bases génétiques et moléculaires de la coordination de la morphogenèse et de la neurogenèse de cet épithélium tout en étudiant l'origine de la diversité des types cellulaires olfactifs. L'imagerie en temps réel m'a permis de caractériser la migration de ces progéniteurs en générant une carte morphométrique de leur déplacement. Mon travail de thèse révèle que le proneural Neurog1 régule directement l'expression de cxcr4b, un récepteur au chimiokine, dans les progéniteurs olfactifs assurant leur positionnement. Ainsi, Neurog1 coordonnerait la position et l'identité des progéniteurs olfactifs via ses cibles transcriptionnelles. Au sein de l'épithélium olfactif dans l'embryon, deux populations cellulaires (neurones à GnRH et neurones à microvillosités) ont été décrites comme provenant des crêtes neurales céphaliques (CNC). J'ai pu montrer que l'expression de marqueurs spécifiques de ces populations n'est pas affectée dans un contexte d'absence de différenciation des CNCs (sox10-/-) suggérant que ces types cellulaires ne dérivent pas de ce territoire. Afin d'identifier leur territoire d'origine, j'ai développé une méthode d'imagerie en temps réel, le backtracking, qui m'a permis de déterminer que la région de la placode olfactive, et non les crêtes neurales, génère ces deux types cellulaires. Ainsi j'ai pu définir la source de ces deux populations neuronales tout en minimisant la contribution des crêtes neurales. En conclusion mes résultats suggèrent que la diversité des neurones olfactifs serait produite localement et ceci conjointement à la morphogenèse de l'épithélium. / The correct development of sensory organs relies on the coordination between changes in progenitor positioning over time and the differentiation/specification of different neural subtypes. The outcome of this coordination is proper organ shape and cell diversity, which are required for functionality. The zebrafish embryonic olfactory epithelium arises from progenitor migration and differentiation. During my PhD, I studied the genetic and molecular basis of morphogenesis in this tissue, and how this is coordinated with neurogenesis, as well as revisiting the origin of olfactory cell type diversity.First, I generated a morphometric map of olfactory progenitors through the characterization of their migration in live embryos. Next, I showed that the proneural transcription factor Neurog1 directly regulates cxcr4b expression, a chemokine receptor that has already been shown to govern olfactory progenitor positioning. Thus, Neurog1 orchestrates olfactory progenitor position and the generation of olfactory neurons via distinct transcriptional targets. Secondly, I addressed the origin of olfactory neuron diversity. Within the embryonic olfactory epithelium, two cell populations (GnRH neurons and microvillous neurons) have been described as cephalic neural crest (CNC) derivatives. I found, however, that the expression of specific markers of both populations is unaffected in a genetic context blocking CNC differentiation. To revisit the lineage assignment of these cell types, I developed a backtracking approach through time-lapse live imaging. I found that both populations are derived from classical olfactory placode progenitor and not the CNC. In conclusion, my results indicate that heterogeneity of olfactory cell-types is locally generated, and concomitant with morphogenesis of the placode.

L’ADKP est la 5e cause de décès par cancer dans le monde occidental, et il est estimé qu’il constituera la 2e cause de mort par cancer d’ici à 2030. Le taux de survie à 5 ans est inférieur à 4%, et la médiane de survie est d’environ 6 mois. Ce pronostic sombre est dû à une pathologie asymptomatique dans les phases précoces du développement tumoral, résultant en un diagnostic tardif. Les tumeurs primaires sont constituées de structures épithéliales néoplasiques entourées par un stroma abondant empêchant l’accès des chimiothérapies aux cellules tumorales. La compréhension des mécanismes d’initiation et de progression tumorale est donc primordiale pour développer de nouvelles stratégies visant à la détection et à la prise en charge thérapeutique optimale des patients atteints d’ADKP. Le TGFbeta est une cytokine assurant de nombreuses fonctions physiologiques comme la régulation de l’immunité, la cicatrisation, le développement ou encore l’angiogenèse. Les résultats présentés dans ce manuscrit mettent en évidence que l’activation de la voie de signalisation TGFbeta perturbe la différenciation des cellules acineuses au cours du développement, et perturbe l’identité acineuse lorsqu’elle est activée dans le pancréas chez l’adulte. L’induction en parallèle de l’apoptose des cellules acineuses et d’une métaplasie acino-canalaire (ou ADM) mène à la disparition quasi-totale du tissu acineux au profit de structures canalaires typiques d’un pancréas en régénération. Lorsque l’oncogène KRASG12D est exprimé en parallèle dans le tissu pancréatique chez l’adulte, ce tissu canalaire régénératif est mis à profit par KRAS pour le développement précoce de lésions pré-néoplasiques. Mes travaux au sein de l’équipe du Dr. Laurent BARTHOLIN permettent donc de démontrer in vivo un nouveau rôle du TGFbeta dans la carcinogénèse pancréatique / PDA is the 5th cause of cancer related death in the western countries, and is estimated to move the second rank by 2020. The 5-year survival rate is less than 4%, and the median survival is around 6 months. The poor prognostic of this tumor is due to asymptomatic early phases of the disease, resulting in a late diagnosis. Primary tumors are composed by ductal neoplastic lesions embedded into a highly abundant stroma that prevents the access of chemotherapeutic drugs to the tumor cells. Thus, understanding tumor initiation and progression mechanisms is needed to develop new strategies aiming at detecting and taking care of patients in the most optimal manner. TGFbeta is a cytokine playing several physiological functions such as immunity regulation, wound healing, development or angiogenesis. Results presented in this manuscript demonstrate that activation of TGFbeta signaling disturb acinar cell differentiation during development, and disrupts acinar cell identity when activated in the adult pancreas. The simultaneous induction of acinar cell apoptosis and ADM leads to the massive loss of acinar cells and the emergence of ductal structures typical of pancreas regeneration. When the KRASG12D oncogene is expressed in combination with the activation of TGFbeta signaling, these regenerative duct structures are harnessed by KRASG12D to develop early neoplastic lesions. Thus, my work in Dr. Laurent BARTHOLIN’s team demonstrates a new function of TGFbeta in pancreatic carcinogenesis in vivo

La presente tesina consiste en el diseño de migración de nodos B aplicado para una RNC caída de una red móvil, con la finalidad de solucionar los problemas que se presenten ante un incidente que afecte los servicios de voz y datos de los usurarios de una red móvil. En el desarrollo de la tesina, se describe el planteamiento del problema, el marco teórico de la tecnología UMTS y posteriormente nos centramos en los elementos principales de esta tecnología. También describimos los equipos importantes a utilizar en desarrollo del proyecto, en este caso nos enfocamos en la descripción de la RNC. Y finalmente describimos el desarrollo del proyecto, el diseño de la solución e implementación de la misma, y en donde se presentan los resultados del diseño. This thesis is the design of migration of nodes B and its a applied when RNC fall for a mobile network, in order to solve the problems that arise before an incident affecting voice and data services from a mobile network. In developing the thesis, we describe the theoretical framework of UMTS technology and then we focus on the main elements of this technology. We also describe the important equipment used in project development; in this case we focus on the description of the RNC. And finally we describe the solution of design and implementation .Also, the results of this project.