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131.
Monica A Farcas Leonie Rouleau Richard Fraser Richard L Leask 《Biomedical engineering online》2009,8(1):30-11
The response of the vascular endothelium to wall shear stress plays a central role in the development and progression of atherosclerosis.
Current studies have investigated endothelial response using idealized in vitro flow chambers. Such cell culture models are unable to accurately replicate the complex in vivo wall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both
simplified/tubular and anatomically realistic in vitro endothelial flow models of the human right coronary artery. A post-mortem vascular cast of the human left ventricular outflow
tract was used to create geometrically accurate silicone elastomer models. Straight, tubular models were created using a custom
made mold. Following the culture of human abdominal aortic endothelial cells within the inner lumen, cells were exposed to
steady flow (Re = 233) for varying time periods. The resulting cell morphology was analyzed in terms of shape index and angle
of orientation relative to the flow direction. In both models a progressive elongation and alignment of the endothelium in
the flow direction was observed following 8, 12, and 24 hours. This change, however, was significantly less pronounced in
the anatomical model (as observed from morphological variations indicative of localized flow features). Differences were also
observed between the inner and outer walls at the disease-prone proximal region. Since morphological adaptation is a visual
indication of endothelial shear stress activation, the use of anatomical models in endothelial genetic and biochemical studies
may offer better insight into the disease process. 相似文献
132.
Ferron M Boudiffa M Arsenault M Rached M Pata M Giroux S Elfassihi L Kisseleva M Majerus PW Rousseau F Vacher J 《Cell metabolism》2011,14(4):466-477
Osteoporosis is a multifactorial genetic disease characterized by reduction of bone mass due to dysregulation of osteoclast differentiation or maturation. Herein, we identified a regulator of osteoclastogenesis, the murine homolog of inositol polyphosphate 4-phosphatase type IIα (Inpp4bα). Expression of Inpp4bα is detected from early osteoclast differentiation to activation stage. Targeted expression of native Inpp4bα ex?vivo repressed whereas phosphatase-inactive Inpp4bα stimulated osteoclast differentiation. Inpp4bα acts on intracellular calcium level that modulates NFATc1 nuclear translocation and activation. In?vivo mice deficient in Inpp4b displayed increased osteoclast differentiation rate and potential resulting in decreased bone mass and osteoporosis. Importantly, INPP4B in human was identified as a susceptibility locus for osteoporosis. This study defined Inpp4b as a major modulator of the osteoclast differentiation and as a gene linked to variability of bone mineral density in mice and humans. 相似文献
133.
Monica Dalidowicz 《The journal of the Royal Anthropological Institute》2015,21(4):838-854
Through a phenomenological account of apprenticeship in the North Indian dance form of kathak, I show how skills are adapted and changed through the ingenuity and innovation required in teaching to new generations of students. The traditional pedagogical model for learning in the Indian arts, the guru‐shishya parampara (master‐disciple relationship), has historically been based on imitative and repetitive pedagogies. Yet close examination reveals less conspicuous forms of creativity at work in the process of reproducing the tradition with fidelity; this improvisational work is further heightened in the demands of teaching in the diaspora. As teachers create opportunities for experiential learning, a spectrum of pedagogical tactics, scaffolding strategies, and coaching competencies are developed and accumulate as this tradition is passed on from one generation to the next. The pedagogical work in crafting fidelity can, in fact, produce its own kind of knowledge, which, ironically, can add new elements to the tradition in unexpected ways. In one unique case – the example of ‘kathak yoga’ – the pedagogical adaptations of kathak artist Pandit Chitresh Das elicited a creative response, a new scaffolding technique that would eventually be incorporated into the repertoire as a skill in itself. Pedagogical process, in this sense, was creative process. 相似文献
134.
Moza M Mologni L Trokovic R Faulkner G Partanen J Carpén O 《Molecular and cellular biology》2007,27(1):244-252
Myotilin, palladin, and myopalladin form a novel small subfamily of cytoskeletal proteins that contain immunoglobulin-like domains. Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells. The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere. Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myofibrillar myopathy. Here we describe the generation and analysis of mice that lack myotilin, myo(-/-) mice. Surprisingly, myo(-/-) mice maintain normal muscle sarcomeric and sarcolemmal integrity. Also, loss of myotilin does not cause alterations in the heart or other organs of newborn or adult myo(-/-) mice. The mice develop normally and have a normal life span, and their muscle capacity does not significantly differ from wild-type mice even after prolonged physical stress. The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent. 相似文献
135.
Riley M 《Structure (London, England : 1993)》2007,15(1):1-2
In this issue of Structure, examine in detail the functions of selected domains within proteins both when they are alone and when in combination with others. Domain function is relevant to molecular evolution and to annotation of proteins known only by sequence. 相似文献
136.
Sondhi SM Jain S Dinodia M Shukla R Raghubir R 《Bioorganic & medicinal chemistry》2007,15(10):3334-3344
A number of pyrimidine derivatives (1-10) have been synthesized by condensation of 4-isothiocyanato-4-methylpentan-2-one with furfurylamine, histamine, 1-(3-aminopropyl)imidazole, 1-(3-aminopropyl)-2-pyrrolidinone, 2-aminobenzonitrile and 3-isothiocyanatobutanal with 1-(3-aminopropyl)-2-pyrrolidinone and 2-hydrazinopyridine under different reaction conditions. Various bispyrimidine derivatives (11-15) were obtained by condensation of 4-isothiocyanato-4-methylpentan-2-one with 2,4,8,10-tetraoxaspiro[5,5]undecane3,9-dipropamine (11'), 1,4-bis(3-aminopropyl)piperazine (13'), 3,5-diamino 1,2,4-triazole (15') and 3-isothiocyanatobutanal with 2,4,8,10-tetraoxaspiro[5,5]undecane 3,9-dipropamine, 1,4-bis(3-aminopropyl)piperazine. All these compounds were characterized by correct FT-IR, (1)H NMR, MS and elemental analysis. These compounds were screened for anti-inflammatory and analgesic activities. Anti-inflammatory activity of 3 is comparable while analgesic activity was found to be better than that of standard drug. 相似文献
137.
Reulen SW Brusselaars WW Langereis S Mulder WJ Breurken M Merkx M 《Bioconjugate chemistry》2007,18(2):590-596
Liposomes have become popular drug delivery vehicles and have more recently also been applied as contrast agents for molecular imaging. Most current methods for functionalization of liposomes with targeting proteins rely on reactions of amine or thiol groups at the protein exterior, which generally result in nonspecific conjugation at multiple sites on the protein. In this study, we present native chemical ligation (NCL) as a general method to covalently couple recombinant proteins in a highly specific and chemoselective way to liposomes containing cysteine-functionalized phospholipids. A cysteine-functionalized phospholipid (Cys-PEG-DSPE) was prepared and shown to readily react with the MESNA thioester of EYFP, which was used as a model protein. Characterization of the EYFP-liposomes using fluorescence spectroscopy showed full retention of the fluorescent properties of conjugated EYFP and provides a lower limit of 120 proteins per liposome. The general applicability of NCL was further tested using CNA35, a collagen-binding protein recently applied in fluorescent imaging of collagen. NCL of CNA35 thioester yielded liposomes containing approximately 100 copies of CNA35 per liposome. The CNA35-liposomes were shown to be fully functional and bind collagen with a 150-fold higher affinity compared to CNA35. Our results show that NCL is an attractive addition to existing conjugation methods that allows direct, covalent, and highly specific coupling of recombinant proteins to liposomes and other lipid-based assemblies. 相似文献
138.
Stenoien DL Knyushko TV Londono MP Opresko LK Mayer MU Brady ST Squier TC Bigelow DJ 《American journal of physiology. Cell physiology》2007,292(6):C2084-C2094
Phospholamban (PLB) associates with the Ca2+-ATPase in sarcoplasmic reticulum (SR) membranes to permit the modulation of contraction in response to -adrenergic signaling. To understand how coordinated changes in the abundance and intracellular trafficking of PLB and the Ca2+-ATPase contribute to the maturation of functional muscle, we measured changes in abundance, location, and turnover of endogenous and tagged proteins in myoblasts and during their differentiation. We found that PLB is constitutively expressed in both myoblasts and differentiated myotubes, whereas abundance increases of the Ca2+-ATPase coincide with the formation of differentiated myotubes. We observed that PLB is primarily present in highly mobile vesicular structures outside the endoplasmic reticulum, irrespective of the expression of the Ca2+-ATPase, indicating that PLB targeting is regulated through vesicle trafficking. Moreover, using pulse-chase methods, we observed that in myoblasts, PLB is trafficked through directed transport through the Golgi to the plasma membrane before endosome-mediated internalization. The observed trafficking of PLB to the plasma membrane suggests an important role for PLB during muscle differentiation, which is distinct from its previously recognized role in the regulation of the Ca2+-ATPase. sarco(endo)plasmic reticulum calcium-adenosine triphosphatase; differentiation; C2C12 myocytes; vesicle trafficking 相似文献
139.
Jason Y. Chuei Cheryl S. Asa Monica Hall‐Woods Jonathon Ballou Kathy Traylor‐Holzer 《Zoo biology》2007,26(4):275-288
The need for contraception in the successful management of captive wild animals is becoming increasingly apparent. Because concerns exist regarding the reversibility of the contraceptive implant melengestrol acetate (MGA), reproductive data for 94 female Amur (Panthera tigris altaica) and Sumatran tigers (Panthera tigris sumatrae) were analyzed using survival analyses to evaluate return to reproductive status after implant removal or assumed expiration. Females placed in potential breeding situations after MGA implants were surgically removed showed a 62% return to reproduction by 5.25 years, whereas females with implants that were assumed to have expired showed only a 30% return to reproduction by 6 years. Implanted females did not reproduce as successfully as non‐implanted control females, which showed an 85% probability of reproducing after placement in a new breeding situation by 2.66 years. Parturition increased the probability of reproducing in non‐implanted females, but not in implanted females. Litter size, stillbirths, and offspring survival were not significantly different between non‐implanted, implant‐removed and implant‐expired female tigers. Ten female tigers reproduced both before and after implant placement, and the differences in litter size, stillbirths, and offspring survival were not significant, nor were they significantly different from non‐implanted females. Prior parturition, age when implant was removed, and duration of implantation did not affect the probability of reproducing for females after implant removal. These results show substantial reversibility of MGA implants, leading to 62% successful reproduction after implant removal. The reasons for lower successful reproduction in animals previously treated with the contraceptive compared to non‐implanted females are not known, but a greater delay in reversibility was seen when implants were left in place and only presumed expired. Zoo Biol 26:275–288, 2007. © 2007 Wiley‐Liss, Inc. 相似文献
140.
We have sequenced the O-antigen gene clusters for the Escherichia coli O98 and Yersinia kristensenii O11 O antigens. The basic structures of these O antigens are identical, and the sequence data indicate that Y. kristensenii O11 gained its O-antigen gene cluster by lateral gene transfer (LGT). Escherichia coli O98 has a typical O-antigen gene cluster between galF and gnd as is usual in E. coli. However, the O-antigen gene cluster of Y. kristensenii O11 is not located at the traditional Yersinia O-antigen gene cluster locus, between hemH and gsk, but at a novel chromosomal locus between aroA and cmk where it is flanked by remnant galF and gnd genes that indicate the probable source of the gene cluster. Phylogenetic analysis indicated that the source was not E. coli itself but a species in the Escherichia, Salmonella, and Klebsiella group of genera. Although other O-antigen studies imply LGT on the basis of the hypervariability of the loci and GC content, this report also identifies a potential donor and provides evidence for the mechanism involved. Remnant insertion sequence (IS) sequences flank the galF and gnd remnants and suggest that LGT of the gene cluster was IS mediated. 相似文献