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11.
Yahya Elsayed Constantina Lekakou Paul Tomlins 《Biotechnology and bioengineering》2019,116(6):1509-1522
The paper presents a transient, continuum, two-phase model of the tissue engineering in fibrous scaffolds, including transport equations for the flowing culture medium, nutrient and cell concentration with transverse and in-plane diffusion and cell migration, a novel feature of local in-plane transport across a phenomenological pore and innovative layer-by-layer cell filling approach. The model is successfully validated for the smooth muscle cell tissue engineering of a vascular graft using crosslinked, electrospun gelatin fiber scaffolds for both static and dynamic cell culture, the latter in a dynamic bioreactor with a rotating shaft on which the tubular scaffold is attached. Parametric studies evaluate the impact of the scaffold microstructure, cell dynamics, oxygen transport, and static or dynamic conditions on the rate and extent of cell proliferation and depth of oxygen accessibility. An optimized scaffold of 75% dry porosity is proposed that can be tissue engineered into a viable and still fully oxygenated graft of the tunica media of the coronary artery within 2 days in the dynamic bioreactor. Such scaffold also matches the mechanical properties of the tunica media of the human coronary artery and the suture retention strength of a saphenous vein, often used as a coronary artery graft. 相似文献
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Adarichev VA Bárdos T Christodoulou S T Phillips M Mikecz K Glant TT 《Immunogenetics》2002,54(3):184-192
Collagen-induced arthritis (CIA) in DBA/1 and proteoglycan-induced arthritis (PGIA) in BALB/c mice are the most frequently used mouse models for studying clinical, immunological and genetic factors contributing to rheumatoid arthritis. DBA/1 ( H2(q)) mice are susceptible to CIA but resistant to PGIA, whereas BALB/c mice ( H2 (d)) are susceptible to PGIA and resistant to CIA. To gain insight into the mechanisms of how the major clinical (disease susceptibility, severity and onset of arthritis) and immunological traits (antigen-specific T- and B-cell responses) are influenced by the major histocompatibility complex (MHC), we have generated a unique intercross of BALB/c and DBA/1 parent strains, and the F1 and F2 hybrids were immunized for either CIA or PGIA. The major clinical and immunological traits were identified as either binary (qualitative) or quantitative traits on Chromosome 17 with a peak at MHC when the entire population was analyzed. In contrast, when only arthritic (susceptible) mice were selected and analyzed, the major clinical traits (severity and onset) 'lost' the linkage to MHC. Thus, MHC dictates disease susceptibility, but not the severity of arthritis. This was even more evident in the case of the H2(q) allele, which was clearly responsible for the dominant inheritance of arthritis in F2 hybrids (either CIA or PGIA). In conclusion, while certain MHC alleles strongly affect disease susceptibility and determine the mode of inheritance of a polygenic autoimmune disease, neither the type of inheritance (dominant vs recessive) nor other MHC components have evident effects upon the clinical symptoms of arthritis. 相似文献
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Sze Chern Lim Katherine R. Smith David A. Stroud Alison G. Compton Elena J. Tucker Ayan Dasvarma Luke C. Gandolfo Justine E. Marum Matthew McKenzie Heidi L. Peters David Mowat Peter G. Procopis Bridget Wilcken John Christodoulou Garry K. Brown Michael T. Ryan Melanie Bahlo David R. Thorburn 《American journal of human genetics》2014
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The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase
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Yu Z Genest PA ter Riet B Sweeney K DiPaolo C Kieft R Christodoulou E Perrakis A Simmons JM Hausinger RP van Luenen HG Rigden DJ Sabatini R Borst P 《Nucleic acids research》2007,35(7):2107-2115
Trypanosomatids contain an unusual DNA base J (beta-d-glucosylhydroxymethyluracil), which replaces a fraction of thymine in telomeric and other DNA repeats. To determine the function of base J, we have searched for enzymes that catalyze J biosynthesis. We present evidence that a protein that binds to J in DNA, the J-binding protein 1 (JBP1), may also catalyze the first step in J biosynthesis, the conversion of thymine in DNA into hydroxymethyluracil. We show that JBP1 belongs to the family of Fe(2+) and 2-oxoglutarate-dependent dioxygenases and that replacement of conserved residues putatively involved in Fe(2+) and 2-oxoglutarate-binding inactivates the ability of JBP1 to contribute to J synthesis without affecting its ability to bind to J-DNA. We propose that JBP1 is a thymidine hydroxylase responsible for the local amplification of J inserted by JBP2, another putative thymidine hydroxylase. 相似文献
17.
An integrative approach combining ion mobility mass spectrometry,X-ray crystallography,and nuclear magnetic resonance spectroscopy to study the conformational dynamics of α1-antitrypsin upon ligand binding
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Mun Peak Nyon Tanya Prentice Jemma Day John Kirkpatrick Ganesh N Sivalingam Geraldine Levy Imran Haq James A Irving David A Lomas John Christodoulou Bibek Gooptu Konstantinos Thalassinos 《Protein science : a publication of the Protein Society》2015,24(8):1301-1312
Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whereas ion mobility (IM)-MS can report on conformational behavior of specific states. We used IM-MS to study a conformationally labile protein (α1-antitrypsin) that undergoes pathological polymerization in the context of point mutations. The folded, native state of the Z-variant remains highly polymerogenic in physiological conditions despite only minor thermodynamic destabilization relative to the wild-type variant. Various data implicate kinetic instability (conformational lability within a native state ensemble) as the basis of Z α1-antitrypsin polymerogenicity. We show the ability of IM-MS to track such disease-relevant conformational behavior in detail by studying the effects of peptide binding on α1-antitrypsin conformation and dynamics. IM-MS is, therefore, an ideal platform for the screening of compounds that result in therapeutically beneficial kinetic stabilization of native α1-antitrypsin. Our findings are confirmed with high-resolution X-ray crystallographic and nuclear magnetic resonance spectroscopic studies of the same event, which together dissect structural changes from dynamic effects caused by peptide binding at a residue-specific level. IM-MS methods, therefore, have great potential for further study of biologically relevant thermodynamic and kinetic instability of proteins and provide rapid and multidimensional characterization of ligand interactions of therapeutic interest.PDB Code(s): 4PYW 相似文献
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Maraki MI Aggelopoulou N Christodoulou N Anastasiou CA Toutouza M Panagiotakos DB Kavouras SA Magkos F Sidossis LS 《Obesity (Silver Spring, Md.)》2011,19(5):968-976
Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m(-2)), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age-matched healthy lean men (BMI: 24.7 ± 0.6 kg·m(-2)). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27-46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m(-2)). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = -0.714, P = 0.047). We conclude that moderate weight loss induced by a low-carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet-induced negative energy balance, and possibly through enhancement of insulin action. 相似文献
20.
Lundwall A Band V Blaber M Clements JA Courty Y Diamandis EP Fritz H Lilja H Malm J Maltais LJ Olsson AY Petraki C Scorilas A Sotiropoulou G Stenman UH Stephan C Talieri M Yousef GM 《Biological chemistry》2006,387(6):637-641
The human kallikrein locus on chromosome 19q13.3-13.4 contains kallikrein 1--the tissue kallikrein--and 14 related serine proteases. Recent investigations into their function and evolution have indicated that the present nomenclature for these proteins is inadequate or insufficient. Here we present a new nomenclature in which proteins without proven kininogenase activity are denoted kallikrein-related peptidase. Names are also given to the unique rodent proteins that are closely related to kallikrein 1. 相似文献