Protecting the Built Environment of Newfoundland and Nova Scotia

For most Canadians, environment is their city or town, where they reside, work, and spend most of their leisure hours. The quality of this urban or semi-urban environment will have a significant impact upon their everyday life, including stress, cultural identity, and sense of historic continuity. Conserving the cultural and aesthetic values represented by the buildings which constitute this environment therefore deserves attention. One way for such buildings to be saved is to be purchased by someone dedicated to their retention; but since it is impossible to thus acquire all valuable buildings, this article looks at alternate approaches. There are legal mechanisms at five levels: international, federal, provincial, municipal, and private. Furthermore, public participation is an important dimension to any discussion of land use controls. The international and federal apsects of protecting the built environment were already described by this writer in a previous publication. 1 The salient features of that detailed description can be summarized as follow

Heparan Sulfate Proteoglycans Mediate Interstitial Flow Mechanotransduction Regulating MMP-13 Expression and Cell Motility via FAK-ERK in 3D Collagen

Interstitial flow directly affects cells that reside in tissues and regulates tissue physiology and pathology by modulating important cellular processes including proliferation, differentiation, and migration. However, the structures that cells utilize to sense interstitial flow in a 3-dimensional (3D) environment have not yet been elucidated. Previously, we have shown that interstitial flow upregulates matrix metalloproteinase (MMP) expression in rat vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts via activation of an ERK1/2-c-Jun pathway, which in turn promotes cell migration in collagen. Herein, we focused on uncovering the flow-induced mechanotransduction mechanism in 3D.Cleavage of rat vascular SMC surface glycocalyx heparan sulfate (HS) chains from proteoglycan (PG) core proteins by heparinase or disruption of HS biosynthesis by silencing N-deacetylase/N-sulfotransferase 1 (NDST1) suppressed interstitial flow-induced ERK1/2 activation, interstitial collagenase (MMP-13) expression, and SMC motility in 3D collagen. Inhibition or knockdown of focal adhesion kinase (FAK) also attenuated or blocked flow-induced ERK1/2 activation, MMP-13 expression, and cell motility. Interstitial flow induced FAK phosphorylation at Tyr925, and this activation was blocked when heparan sulfate proteoglycans (HSPGs) were disrupted. These data suggest that HSPGs mediate interstitial flow-induced mechanotransduction through FAK-ERK. In addition, we show that integrins are crucial for mechanotransduction through HSPGs as they mediate cell spreading and maintain cytoskeletal rigidity.We propose a conceptual mechanotransduction model wherein cell surface glycocalyx HSPGs, in the presence of integrin-mediated cell-matrix adhesions and cytoskeleton organization, sense interstitial flow and activate the FAK-ERK signaling axis, leading to upregulation of MMP expression and cell motility in 3D. This is the first study to describe a flow-induced mechanotransduction mechanism via HSPG-mediated FAK activation in 3D. This study will be of interest in understanding the flow-related mechanobiology in vascular lesion formation, tissue morphogenesis, cancer cell metastasis, and stem cell differentiation in 3D, and also has implications in tissue engineering

Protecting the Built Environment of Newfoundland and Nova Scotia

For most Canadians, environment is their city or town, where they reside, work, and spend most of their leisure hours. The quality of this urban or semi-urban environment will have a significant impact upon their everyday life, including stress, cultural identity, and sense of historic continuity. Conserving the cultural and aesthetic values represented by the buildings which constitute this environment therefore deserves attention. One way for such buildings to be saved is to be purchased by someone dedicated to their retention; but since it is impossible to thus acquire all valuable buildings, this article looks at alternate approaches. There are legal mechanisms at five levels: international, federal, provincial, municipal, and private. Furthermore, public participation is an important dimension to any discussion of land use controls. The international and federal apsects of protecting the built environment were already described by this writer in a previous publication. 1 The salient features of that detailed description can be summarized as follow

The Mechanism of Lithium Zincate-Mediated I/Zn Exchange Revisited: A Computational Micro-Solvation Approach in THF

Lithium trialkylzincate-mediated I/Zn exchange reaction has been revisited computationally through a micro-solvation approach. A never yet investigated iodoaryl derivative bearing a potential bulky para-directing group, namely 4-iodobenzyl mesylate, was considered as a substrate. THF as typical solvent and Et3ZnLi have also been considered for the first time in such a reaction. Four mechanistic pathways have been calculated, including a literature-inspired pathway with preservation of the synergic character of the reagent (pathway 1), an OMs-directed I/Zn exchange pathway (pathway 2), a THF-solvated open complex-promoted pathway (pathway 3) and an anionic pathway (pathway 4). While pathway 4 could be fully precluded, pathway 3 turned out to be the most energetically favoured. Equivalent thermodynamic profiles were found for both pathways 1 and 2, albeit a slight preference can be attributed to the latter through micro-solvation approach. The I/Zn exchange was shown to proceed through a lithium-assisted aryl shuttle-like process. The iodoaryl substrate is first converted into ArLi intermediate which in turns reacts with the remaining diorganozinc reagent