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991.
Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression 总被引:2,自引:0,他引:2
Lam SH Wu YL Vega VB Miller LD Spitsbergen J Tong Y Zhan H Govindarajan KR Lee S Mathavan S Murthy KR Buhler DR Liu ET Gong Z 《Nature biotechnology》2006,24(1):73-75
The zebrafish (Danio rerio) has been long advocated as a model for cancer research, but little is known about the real molecular similarities between zebrafish and human tumors. Comparative analysis of microarray data from zebrafish liver tumors with those from four human tumor types revealed molecular conservation at various levels between fish and human tumors. This approach provides a useful strategy for identifying an expression signature that is strongly associated with a disease phenotype. 相似文献
992.
993.
Rowan S Hardy Andrew Filer Mark S Cooper Greg Parsonage Karim Raza Debbie L Hardie Elizabeth H Rabbitt Paul M Stewart Christopher D Buckley Martin Hewison 《Arthritis research & therapy》2006,8(4):R108-10
Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation.
We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of
the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed
in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid
arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were
higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative
to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis
factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold;
synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1
expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the
presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly
reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor,
emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences
in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations
may play a key role in the predeliction of certain tissues to develop persistent inflammation. 相似文献
994.
Qu X Khutoryanskiy VV Stewart A Rahman S Papahadjopoulos-Sternberg B Dufes C McCarthy D Wilson CG Lyons R Carter KC Schätzlein A Uchegbu IF 《Biomacromolecules》2006,7(12):3452-3459
Amphiphilic chitosan-based polymers (Mw < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension. 相似文献
995.
A recent Cold Spring Harbour meeting(*) reviewed the latest progress on telomeres (the specialized structures that form the ends of chromosomes) and telomerase (the enzyme primarily responsible for their replication). Among the many aspects of telomere biology covered were strong sessions elaborating telomere replication and length regulation, telomerase structure and function, end-binding and telomere-associated proteins, DNA-damage-response proteins and telomerase-independent telomere maintenance. 相似文献
996.
Directed evolution of toluene dioxygenase from Pseudomonas putida for improved selectivity toward cis-indandiol during indene bioconversion 总被引:2,自引:0,他引:2
Zhang N Stewart BG Moore JC Greasham RL Robinson DK Buckland BC Lee C 《Metabolic engineering》2000,2(4):339-348
Toluene dioxygenase (TDO) from Pseudomonas putida F1 converts indene to a mixture of cis-indandiol (racemic), 1-indenol, and 1-indanone. The desired product, cis-(1S,2R)-indandiol, is a potential key intermediate in the chemical synthesis of indinavir sulfate (Crixivan), Merck's HIV-1 protease inhibitor for the treatment of AIDS. To reduce the undesirable byproducts 1-indenol and 1-indanone formed during indene bioconversion, the recombinant TDO expressed in Escherichia coli was evolved by directed evolution using the error-prone polymerase chain reaction (epPCR) method. High-throughput fluorometric and spectrophotometric assays were developed for rapid screening of the mutant libraries in a 96-well format. Mutants with reduced 1-indenol by-product formation were identified, and the individual indene bioconversion product profiles of the selected mutants were confirmed by HPLC. Changes in the amino acid sequence of the mutant enzymes were identified by analyzing the nucleotide sequence of the genes. A mutant with the most desirable product profile from each library, defined as the most reduced 1-indenol concentration and with the highest cis-(1S,2R)-indandiol enantiomeric excess, was used to perform each subsequent round of mutagenesis. After three rounds of mutagenesis and screening, mutant 1C4-3G was identified to have a threefold reduction in 1-indenol formation over the wild type (20% vs 60% of total products) and a 40% increase of product (cis-indandiol) yield. 相似文献
997.
In a pilot study, we examined whether frost boils grossly mask the effect of site by comparing physical, chemical and microbial
soil properties between the middle and edge of frost boils on remote and understudied Browning Peninsula, Antarctica. In addition,
we determined the degree to which soil microbial community structure can be attributed to frost boil physical and chemical
soil properties. Principle components (PCs) of physical and chemical soil properties and of microbial soil properties were
compared between the middle and edge of frost boils and between frost boil replicates. Despite higher soil moisture, % C,
% S and % N, pH, total DNA, 16S copy number, total phospholipid fatty acids, bacteria, fungi, proteobacteria, anaerobes, gram-positive
bacteria and eukaryotes at frost boil edges, PCs were not significantly different between edge and middle positions. Physical
and chemical soil properties between frost boil replicates differed significantly, but not microbial communities. In non-metric
multidimensional scaling (NMS) ordinations, soil microbial community structure was affected by differences in frost boil replicates
and some frost boil replicates were well separated. Therefore, site factors may play a critical role in determining the soil
characteristics of frost boils. It remains to be seen whether stronger gradients in physical, chemical and microbial soil
properties will develop across frost boils with continued warming of Antarctic soils. Frost boils may have subtle effects
and require consideration in long-term sampling design for understanding the effects of climate change. 相似文献
998.
999.
Miller LJ 《Zoo biology》2012,31(2):242-248
Many publications within the field of zoo animal welfare have stated the importance of decreasing stereotypic behavior (e.g., pacing) to help ensure a positive visitor experience. The idea behind these statements is that visitors want to see animals engaged in natural behavior. Additionally, it is thought that watching an animal exhibit species-appropriate behavior could help increase a visitor's connection to wildlife and ultimately their interest in conservation. However, until recently, no information was available to validate such statements. The purpose of this research was to examine people's reaction to viewing an animal engaged in pacing behavior. Participants were randomly selected to fill out a survey after watching a short video of either a tiger pacing or resting (control). Results indicate that having viewed a tiger pacing significantly decreases people's perception of the level of care animals receive at that facility. In addition, people's interest in supporting zoos decreased as a result of viewing this behavior. Results are discussed from an animal welfare, business, and conservation perspective. 相似文献
1000.
Stewart PS 《Biofouling》2012,28(2):187-198
Water that flows around a biofilm influences the transport of solutes into and out of the biofilm and applies forces to the biofilm that can cause it to deform and detach. Engineering approaches to quantifying and understanding these phenomena are reviewed in the context of biofilm systems. The slow-moving fluid adjacent to the biofilm acts as an insulator for diffusive exchange. External mass transfer resistance is important because it can exacerbate oxygen or nutrient limitation in biofilms, worsen product inhibition, affect quorum sensing, and contribute to the development of tall, fingerlike biofilm clusters. Measurements of fluid motion around biofilms by particle velocimetry and magnetic resonance imaging indicate that water flows around, but not through biofilm cell clusters. Moving fluid applies forces to biofilms resulting in diverse outcomes including viscoelastic deformation, rolling, development of streamers, oscillatory movement, and material failure or detachment. The primary force applied to the biofilm is a shear force in the main direction of fluid flow, but complex hydrodynamics including eddies, vortex streets, turbulent wakes, and turbulent bursts result in additional force components. 相似文献