Patients with type-1 diabetes lose their β-cells after autoimmune attack. Islet transplantation is a co-option for curing this disease, but survival of transplanted islets is poor. Thus, methods to enhance β-cell viability and function as well as methods to expand β-cell mass are required. The work presented in this thesis aimed to study the roles of neural crest stem cells or their derivatives in supporting β-cell proliferation, function, and survival. In co-culture when mouse boundary cap neural crest stem cells (bNCSCs) and pancreatic islets were in direct contact, differentiating bNCSCs strongly induced β-cell proliferation, and these proliferating β-cells were glucose responsive in terms of insulin secretion. Moreover, co-culture of murine bNCSCs with β-cell lines RIN5AH and β-TC6 showed partial protection of β-cells against cytokine-induced β-cell death. Direct contacts between bNCSCs and β-cells increased β-cell viability, and led to cadherin and β-catenin accumulations at the bNCSC/β-cell junctions. We proposed that cadherin junctions supported signals which promoted β-cell survival. We further revealed that murine neural crest stem cells harvested from hair follicles were unable to induce β-cell proliferation, and did not form cadherin junctions when cultured with pancreatic islets. Finally, we discovered that the presence of bNCSCs in co-culture counteracted cytokine-mediated insulin-producing human EndoC-βH1 cell death. Furthermore, these two cell types formed N-cadherin, but not E-cadherin, junctions when they were in direct contact. In conclusion, the results of these studies illustrate how neural crest stem cells influence β-cell proliferation, function, and survival which may improve islet transplantation outcome.

The Pacific Crest Trail has become increasingly popular since Clinton Clarke first envisioned such a trail in the 1930’s. By comparing the original motives and experience of the trail to the realities of the trail today, the trail’s fluid narrative becomes apparent. While this narrative is ever changing, over the course of the trail’s history one theme has remained constant – a notably problematic relationship with wilderness rooted in an exaltation of the sublime and post-frontier ideals. This thesis focuses on how the Pacific Crest Trail’s development over the past eighty years has created an experience that, on the surface, is notably different from Clarke’s original vision for the trail, but is still influenced by a perception of wilderness born from a romanticization of nature and a pursuit to preserve the western frontier. Chapter one, The Historic Trail, investigates Clarke’s manners and motives behind promoting the trail. Chapter two, The Popular Trail, examines the visual culture surrounding the trail, from nineteenth century landscape painting to the trail’s presence in social media today. Chapter three, The Trail Community, focuses on the growth of a strong community of hikers, and what this means for the future of the trail.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 3 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (Ph.D. in Neuroscience) -- University of Colorado Denver, 2008. / Includes bibliographical references (leaves 112-120). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph.D.)--Montana State University--Bozeman, 2007. / Typescript. Chairperson, Graduate Committee: Roger Bradley. Includes bibliographical references (leaves 122-140).

Sedan fotbollens början 1863 har sporten idag vuxit till en mångmiljardindustri. Detta innebär att klubbarna framställs mer som företag där den visuella identiteten är en viktig faktor när det kommer till marknadsföring. Syftet med denna studie är att jämföra 98 europeiska fotbollsklubbars logotyper från fem olika ligor för att hitta samband och skillnader i utformningen mellan länder och ligor. Resultatet sammanfattades i form av generiska logotyper för respektive liga. De 98 klubbarna hämtades ur de fem europeiska ligor som 2014 hade störst tv-intäkter. Logotyperna samlades in genom bildsökningar via Google. Logotyperna sorterades efter respektive liga och överskådades för att definiera lämpliga kategorier för en visuell innehållsanalys. Den visuella innehållsanalysen visade att ligorna skiljer sig något vad beträffar logotypernas utformning, men att de har vissa gemensamma grundläggande drag. / Since the beginning of football in 1863 the sport today has grown into a multimillion dollar industry. This means that clubs today are seen as corporations where the visual identity is a major factor when it comes to marketing. The purpose of this study is to compare 98 European football clubs logos from five different leagues to find correlations and differences in design between countries and leagues. The results were summarized in the form of generic logos for each league. The 98 clubs were extracted from the five European leagues, which in 2014 had the largest TV revenues. The logos were collected through image searches using Google and then sorted for each league. The logos were sorted for each league and then beheld to define appropriate categories for a visual content analysis. The visual content analysis showed that the leagues are somewhat different as regards to the design of the logos, but they have some common basic features.

Complex multicellular organisms are composed of at least 200 cell types, which contain the same DNA "black box" of genetic information. It is the precise regime according to which they express their genes, exquisitely controlled by gene regulatory circuits, that defines their cellular identity, morphology and function. We have developed an in vivo biotinylation method that uses genetically encoded components in zebrafish, termed biotagging, for genome-wide regulatory analysis of defined embryonic cell populations. By labelling selected proteins in specific cell types, biotagging eliminates background inherent to analyses of complex embryonic environments via highly stringent biochemical procedures and targeting of specific interactions without the need for cell sorting. We utilised biotagging to characterise the in vivo translational landscape on polysomes as well as the transcriptional regulatory landscape in nuclei of migratory neural crest cells, which intermix with environing tissues during their migration. Our migratory neural crest translatome presented both known and novel players of the neural crest gene regulatory network. An in depth look into the active nuclear transcriptome uncovered a complex world of non-coding regulatory RNAs that potentially specify migratory neural crest identity and present evidence of active bidirectional transcription on regions of open chromatin that include putative cis-regulatory elements. Analysis of our transcribed cis-regulatory modules functionally links these elements to known genes that are key to migratory neural crest function and its derivatives. We also identified a novel cohort of circular RNAs enriched at regions of tandem duplicated genes. Last but not least, we recovered developmentally regulated long non-coding RNAs and transcribed transposable elements. To functionally dissect the biological roles of these factors, we have built two Ac/Ds-mediated in vivo toolkits for efficient screening of putative enhancers and for CRISPR/Cas9-based transcriptional modulation. Overall, our methods and findings present a comprehensive view of the active coding and non-coding landscapes of migratory neural crest on a genome-wide scale that refine the current regulatory architecture underlying neural crest identity.

Branchial arches (BAs) are a series of transient structures that develop on the ventro-lateral surface of the head in vertebrate embryos. BAs initially appear as a series of similar segments; as development proceeds each BA will contribute to different structures. Here, it was investigated the transcriptional mechanisms that instruct the different fates of the BAs in development. Initially, each BA contains a blood vessel, known as aortic arch (AA) artery, that connects the dorsal aorta with the heart. Remodelling of the AAs is crucial to form the adult heart circulation. This process leads to regression of the anterior AAs, running though the first and second BAs (BA1 and BA2), and persistence of the AAs contained in more posterior BAs (PBA). To identify the mechanisms that control remodelling of the AAs, we compared the transcriptomes and epigenomic landscapes of different BAs. Using RNA-seq and H3K27Ac ChIP-seq, we uncovered the activation of a vascular smooth muscle cell (VSMC) differentiation transcriptional program exclusively in the PBAs (and not in BA1/BA2). In support of this finding, we show that VSMC differentiation occurs specifically in the PBAs, but not BA1-2 in mouse embryonic development. Despite the absence of VSMC differentiation in developing BA1-2, cells harvested from these tissues reveal a spontaneous tendency to differentiate towards VSMC fate when grown in vitro, and activate several VSMC-specific genes (Myocd, Acta2, Tagln, Jag1). Together, our results suggest that forming VSMCs is a key process for the persistence of AAs. We also showed that cells derived from all BAs have the potential to differentiate to VSMCs in vitro. However, only cells in the PBAs differentiate to VSMCs in vivo, resulting in the maintenance of posterior AAs. In this study, we also uncovered a novel transcriptional principle that specifies the fate of BA2. Using ChIP-seq, we found that binding of Meis transcription factors establish a ground pattern in the BAs. Hoxa2, which specifies BA2 identity, selects a subset of Meis-bound sites. Meis binding is strongly increased at these sites, which coincide with active enhancers, linked to genes highly expressed in the BA2 and regulated by Hoxa2. Thus, Hoxa2 modifies a ground state binding of Meis to instruct segment-specific transcriptional programs.

Neural crest cells arise during neurulation, a process that occurs during the third week of embryogenesis. These diverse cells then divide into various subtypes including cranial neural crest cells and cardiac neural crest cells. Each of these subtypes gives rise to a wide range of features throughout the fetus. While these cells are extremely diverse, they are also incredibly sensitive to their surrounding environment. Many maternal conditions affect neural crest cell division and migration, but maternal alcohol consumption and hyperglycemia due to gestational diabetes will be discussed in detail, with special attention paid to tissues that derive from cranial neural crest cells. While the initial mechanisms of the pathology vary for both of these conditions, what is remarkable is that they ultimately cause effects in similar ways. Both mechanisms lead to the creation of reactive oxygen species, which in turn trigger apoptotic pathways. Neural crest cell death causes a variety of congenital anomalies in fetuses, including craniofacial defects and cardiac outflow tract defects. Treatment options that have been researched in both conditions also vary, but are based on similar principles. Antioxidant therapies reduce the production of reactive oxygen species, thus reducing the severity of the anomalies affecting the fetus during development. Both maternal alcohol consumption and gestational diabetes are important public health concerns, and their management is of utmost priority in society. By decreasing the rates of women who consume alcohol during pregnancy, and managing gestational diabetes in those at highest risk, the rates of fetal congenital defects could be decreased.