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Myogenesis, or skeletal muscle formation, begins during embryogenesis and involves the proliferation of myoblasts followed by their exit from the cell-cycle to differentiate and form myotubes. This formation of skeletal muscle is a complex process involving many genes and various signalling pathways. Mighty is a novel myogenic gene discovered at AgResearch by the Functional Muscle Genomics (FMG) group in a genetic screen performed on the muscle of myostatin null and wild-type mice. It was found that heavily muscled mice, lacking myostatin, had increased expression of the mighty gene. This gene was found to be conserved, with cognates found in mammals, amphibians, teleosts, and arthropods. Mighty was found to be expressed in a variety of tissues, but only skeletal muscle showed increased mighty mRNA expression in myostatin null mice, indicating the specific regulation of mighty by myostatin in skeletal muscle (Marshall, 2005). The aim of this study was to characterise the mighty protein and examine its role in myogenesis to elucidate mighty's function. To undertake this study, antibodies specific for the full-length mighty protein and antibodies specific for a peptide region of mighty were characterised. Results using these antibodies, showed endogenous mighty, from myoblasts, to be a low-abundant, nuclear protein which shows a mobility of ~52 kDa in SDS gels, different to that of recombinant mighty protein. The mobility difference of endogenous mighty compared to recombinant mighty appears to be due to phosphorylation and may involve other post-translational modifications. In agreement, the determined isoelectric point (~5.7) of endogenous mighty also appears to be the result of phosphorylation. Interestingly, 52 kDa mighty was not detected in muscle extracts, but a ~30 kDa protein was specifically detected, indicating multiple forms, and subsequent roles, for mighty protein. Mass spectrometry (MS) was also performed for further characterisation of the mighty protein and possible post-translational modifications. Although hits were achieved with both recombinant mighty proteins, endogenous mighty MS analysis was not accomplished due to its low-abundance. The function of the mighty protein in myoblasts was investigated during proliferation and differentiation. The results indicate that proliferating myoblasts have low levels of mighty in G0 and increased levels in G1/S during the cell cycle. This differential expression of mighty may involve cell cycle exit at the G1/S phase. Differentiation results showed mighty to be upregulated before MyoD during differentiation, placing mighty very early in the differentiation hierarchy. This agrees with previous results by Marshall (2005) which showed mighty to upregulate MyoD through IGF-II expression. Enhanced differentiation was also seen in double muscle bovine myoblasts concomitantly with increased mighty expression. In conclusion, mighty appears to be a post-translationally modified protein that plays an early role in myogenic differentiation. This role in differentiation appears to be upstream of MyoD through the upregulation of IGF-II and may be linked to cell cycle exit in the G1 phase of the cell cycle.

<p>When studying how companies differentiate from their competitors, corporate image can play a main role in this aspect. The aim of this study is to observe and analyse the perception by the consumers of the corporate image of two groceries companies.This perception can lead to a competitive position in the marketplace by outperforming competitors in all the areas of corporate image. Thus, it can be observed how both companies are differentiated in the mind of the consumers in a different way.</p>

<p>The thesis is an investigateion of Ikea´s strategies on differents markets. The reasearch shows how the company had to adjust to different markets and conditions, in order to achieve competitive advantage.</p>

Modulation of the actin-based cytoskeleton and transcription factor regulation are merely two essential functions in a wide array of cellular activities that the Rho family of small GTPases is responsible for mediating. Aberrations in, or loss of, Rho GTPase signaling has been found to lead to multiple pathologies, including both metastatic progression and lenticular differentiation leading to cataractogenesis. This study has examined the transcriptional regulation of the metastasis suppressor, KiSS-1. Although the mechanism by which KiSS-1 modulates an anti-metastatic effect is not entirely known, it is known that KiSS-1 mediates stress fiber formation, increased adhesion and reduced migratory and invasive properties through modulation of the Rho family of small GTPases. The loss of KiSS-1 that commonly occurs during metastatic progression, leads to a loss of proper Rho GTPase regulation. This study has examined how KiSS-1 is regulated in two tissue types, breast and skin, and how the loss of AP-2(alpha) and DRIP-130, respectively, leads to the progression of breast cancer and melanoma. In addition, this study has also looked at the importance of Rac1 expression and function in the lens epithelium. Activation of Rac1 and its downstream effector, SRF, have been shown to be key regulators in lens cell differentiation, possibly leading to lens opacification via its transcriptional control of the structural crystallins within the lens. The results of this dissertation research have made significant strides in understanding the nature of the anti-metastatic effects registered by the novel KiSS-1 peptide and its cognate GPCR. Additionally, it has shed light on the Rho family regulation of lens epithelial cell differentiation, indicating the elaborate involvement of Rac1 in mediating lens fiber development. In all, this research has determined previously unknown roles of small molecule GTPases in both the progression of metastasis, as well as in normal and abnormal lens cell differentiation.

The thesis is an investigateion of Ikea´s strategies on differents markets. The reasearch shows how the company had to adjust to different markets and conditions, in order to achieve competitive advantage.

When studying how companies differentiate from their competitors, corporate image can play a main role in this aspect. The aim of this study is to observe and analyse the perception by the consumers of the corporate image of two groceries companies.This perception can lead to a competitive position in the marketplace by outperforming competitors in all the areas of corporate image. Thus, it can be observed how both companies are differentiated in the mind of the consumers in a different way.

Staufen1 is a double-stranded RNA-binding protein known to be involved in the transport, localization, decay and increased translation of some mRNAs. The goal of the present study is to determine the role of Staufen1 during myogenic differentiation by characterizing the effects of Staufen1 over-expression in C2C12 cells. Immunofluorescence experiments revealed that Staufen1 over-expression causes a decrease in the fusion and differentiation indices and leads to the formation of myotubes with significantly fewer nuclei. We show, by western blot and qRT-PCR, that the protein expression of MyoD, myogenin and MyHC and the mRNA expression of MyoD, myogenin, Mef2A, Mef2C and p35 are significantly decreased during differentiation when Staufen1 is over-expressed. We then found that c-myc protein expression was increased during proliferation but that its mRNA expression remained unchanged. In this study we propose that Staufen1 negatively regulates skeletal muscle differentiation through the posttranscriptional regulation of c-myc, Mef2A, Mef2C and p35 transcripts.

Much speculation on extraterrestrial life has focused on finding environments where water is present. Heating of smaller icy bodies may create and sustain a possible liquid layer below the surface. If liquid water was sustained for geologically significant times (> 108 years) within the ubiquitous small bodies in the outer solar system, the opportunities for development of simple life are much greater. The lifetime of the liquid water layer will depend on several factors, including the rate of rock/water reaction, which will depend on the rate at which water can be segregated from a melting ice/rock core. For the liquid water phase to migrate toward the surface, the denser rock phase must compact. The primary question that this thesis will answer is how fast melt water can segregate from the core of an ice-rich planetesimal. To answer this question we treat the core as two phase flow problem: a compacting viscous “solid” (ice/rock mixture) and a segregating liquid (melt water). The model developed here is based on the approach derived to study a different partially molten solid: in the viscously deforming partially molten upper mantle. We model a planetesimal core that initially a uniform equal mixture of solid ice and rock. We assume chondritic levels of radiogenic heating as the only heat source, and numerically solve for the evolution of solid and melt velocities and the distribution of melt fraction (“porosity”) during the first few million years after accretion. From a suite of numerical models, we have determined that the meltwater is segregated out of the core as fast as it is created, except in the case of very fast melting times (0.75 My vs. 0.62 My), and small ore radius (~25 to 150 km, depending on the viscosity of the ice/rock mixture in the solid core). In these latter cases, segregation is slower than migration and a high water fraction develops in the core. Heat released by water-rock reactions (not included in this model) will tend to drive up melting rates in all cases, which may favor this latter endmember.

Staufen1 is a double-stranded RNA-binding protein known to be involved in the transport, localization, decay and increased translation of some mRNAs. The goal of the present study is to determine the role of Staufen1 during myogenic differentiation by characterizing the effects of Staufen1 over-expression in C2C12 cells. Immunofluorescence experiments revealed that Staufen1 over-expression causes a decrease in the fusion and differentiation indices and leads to the formation of myotubes with significantly fewer nuclei. We show, by western blot and qRT-PCR, that the protein expression of MyoD, myogenin and MyHC and the mRNA expression of MyoD, myogenin, Mef2A, Mef2C and p35 are significantly decreased during differentiation when Staufen1 is over-expressed. We then found that c-myc protein expression was increased during proliferation but that its mRNA expression remained unchanged. In this study we propose that Staufen1 negatively regulates skeletal muscle differentiation through the posttranscriptional regulation of c-myc, Mef2A, Mef2C and p35 transcripts.