Efficient Generation of iPS Cells from Skeletal Muscle Stem Cells

Reprogramming of somatic cells into inducible pluripotent stem cells generally occurs at low efficiency, although what limits reprogramming of particular cell types is poorly understood. Recent data suggest that the differentiation status of the cell targeted for reprogramming may influence its susceptibility to reprogramming as well as the differentiation potential of the induced pluripotent stem (iPS) cells that are derived from it. To assess directly the influence of lineage commitment on iPS cell derivation and differentiation, we evaluated reprogramming in adult stem cell and mature cell populations residing in skeletal muscle. Our data using clonal assays and a second-generation inducible reprogramming system indicate that stem cells found in mouse muscle, including resident satellite cells and mesenchymal progenitors, reprogram with significantly greater efficiency than their more differentiated daughters (myoblasts and fibroblasts). However, in contrast to previous reports, we find no evidence of biased differentiation potential among iPS cells derived from myogenically committed cells. These data support the notion that adult stem cells reprogram more efficiently than terminally differentiated cells, and argue against the suggestion that “epigenetic memory” significantly influences the differentiation potential of iPS cells derived from distinct somatic cell lineages in skeletal muscle

The Turtle Garden: Tan Kah Kee’s last spiritual world

This paper explores the role of diasporic subjects in China’s heritage-making through a case study of the Turtle Garden built by Tan Kah Kee in Xiamen, China. Tan is the first person with Overseas Chinese background who built museums in the P.R. China and has been regarded as a symbol of Overseas Chinese patriotism. This paper argues that the Turtle Garden, conceptualised as a postcolonial ‘carnivalesque’ space, is more than a civic museum for public education. It reflects the owner’s highly complex and sometimes conflicting museum outlook embedded in his life experience as a migrant, his encounter with (British) colonialism in Malaya, and integrated with his desire and despair about the Chinese Communist Party’s nation-building project in the 1950s. Rather than a sign of devotion to the socialist motherland as simplistically depicted in China’s discourse, the garden symbolises Tan’s last ‘spiritual world’ where he simultaneously engaged with soul-searching as a returned Overseas Chinese and alternative diasporic imagining of Chinese identities and nation. It brings to light the value of heritage-making outside centralised heritage discourses, and offers an invaluable analytical lens to disentangle the contested and ever shifting relationship between diasporic subjects, cultural heritage and nation-(re)building in the Chinese context and beyond

Branch retinal vein occlusion associated with quetiapine fumarate

<p>Abstract</p> <p>Background</p> <p>To report a case of branch retinal vein occlusion in a young adult with bipolar mood disorder treated with quetiapine fumarate.</p> <p>Case Presentation</p> <p>A 29 years old gentleman who was taking quetiapine fumarate for 3 years for bipolar mood disorder, presented with sudden vision loss. He was found to have a superior temporal branch retinal vein occlusion associated with hypercholesterolemia.</p> <p>Conclusion</p> <p>Atypical antipsychotic drugs have metabolic side effects which require regular monitoring and prompt treatment.</p

Cell Type of Origin Influences the Molecular and Functional Properties of Mouse Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.Stem Cell and Regenerative Biolog

Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function

Skeletal muscle is a highly regenerative tissue, but muscle repair potential is increasingly compromised with advancing age. In this study, we demonstrate that increased NF-κB activity in aged muscle fibers contributes to diminished myogenic potential of their associated satellite cells. We further examine the impact of genetic modulation of NF-κB signaling in muscle satellite cells or myofibers on recovery after damage. These studies reveal that NF-κB activity in differentiated myofibers is sufficient to drive dysfunction of muscle regenerative cells via cell-non-autonomous mechanisms. Inhibition of NF-κB, or its downstream target Phospholipase A2, in myofibers rescued muscle regenerative potential in aged muscle. Moreover, systemic administration of sodium salicylate, an FDA-approved NF-κB inhibitor, decreased inflammatory gene expression and improved repair in aged muscle. Together, these studies identify a unique NF-κB regulated, non-cell autonomous mechanism by which stem cell function is linked to lipid signaling and homeostasis, and provide important new targets to stimulate muscle repair in aged individuals

Design of a wide input supply range buck-boost converter

Master'sMASTER OF ENGINEERIN

Stem Cell-Based Strategies to Enhance Muscle Regeneration through Extrinsic and Intrinsic Regulators

Skeletal muscle has a remarkable capacity for regeneration, mediated by muscle stem cells that can self-renew or differentiate to form the mature myofibers of the tissue. Several human diseases are characterized by a loss of function and strength in skeletal muscle, with impairments in the ability to regenerate and consequent decreases in quality of life and increases in mortality. The work in this dissertation has focused on developing methods for combating muscle disease. This goal has been approached through attempts at cell replacement therapy - by generating muscle cells that can be engrafted in vivo. I also investigated the influence on regeneration of the skeletal muscle microenvironment (skeletal muscle-resident fibroblasts), and systemic environment (inflammation in myogenic and non-myogenic tissues), both of which were found to affect skeletal muscle stem cell behavior and the efficiency of myogenic regeneration. Ultimately, these studies identified novel factors that impair or improve skeletal muscle differentiation, and that offer the potential to modulate the process of muscle regeneration. In the process of investigating if induced pluripotent stem cells from skeletal muscle retain an epigenetic memory conducive to myogenic differentiation, I discovered that precursor cells in skeletal muscle reprogram to a pluripotent state more efficiently. However, these induced pluripotent stem cells, like embryonic stem cells, retain strong barriers to skeletal muscle differentiation. Together, these findings offer insights into the process of muscle regeneration, and suggest new potential pathways towards treatment of muscle disease

Evaluation of externally bonded CFRP systems for the strengthening of RC slabs

This paper presents an experimental study on flexural strengthening of reinforced concrete (RC) slabs with three different commercially available carbon FRP (CFRP) systems, prefabricated laminate plate, fiber laminate sheet and prefabricated laminate bar, using four different EBR techniques involving cold cured adhesive bonding, prestressing, manual wet lay-up and near surface mounted (NSM) technique. --Abstract, page iii

Canaliculitis in supernumerary puncta and canaliculi

We report the first case of supernumerary puncta and canaliculi presented with canaliculitis. A-59 year-old gentleman presented with painful swelling of the left lower lid for a week, which was associated with epiphora. The swelling was confined to the nasal aspect of the left lower lid (0.5¥0.5 mm) with inflamed overlying skin. Two puncta (0.5 mm apart) were noted. The outer punctum at the normal anatomical position was a cul-de-sac while the inner punctum it the caruncle was patent. We described the embryology leading to supernumerary puncta and canaliculi to explain the paradoxical patency of the abnormally located punctum as well as the pathomechanism leading to canaliculitis. The patient was treated with oral cloxacillin 500 mg, 6 hourly for 5 days; the cellulitis subsided after three days