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31.
TT Chowdhury S Arghandawi J Brand OO Akanji DL Bader DM Salter DA Lee 《Arthritis research & therapy》2008,10(2):R35
Background
Nitric oxide and prostaglandin E2 (PGE2play pivotal roles in both the pathogenesis of osteoarthritis and catabolic processes in articular cartilage. These mediators are influenced by both IL-1β and mechanical loading, and involve alterations in the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX)-2 enzymes. To identify the specific interactions that are activated by both types of stimuli, we examined the effects of dynamic compression on levels of expression of iNOS and COX-2 and involvement of the p38 mitogen-activated protein kinase (MAPK) pathway. 相似文献32.
The complexity of genetic pathways for hearing is beginning to be amenable to unraveling by systematic functional genomic analysis. Genome-wide mutagenesis studies in the mouse are beginning to shed further light on the structure and regulation of the machinery of hearing. 相似文献
33.
Daniel J. Leong Xiang I. Gu Yonghui Li Jonathan Y. Lee Damien M. Laudier Robert J. Majeska Mitchell B. Schaffler Luis Cardoso Hui B. Sun 《Matrix biology》2010,29(5):420-426
Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6 h that was sustained throughout the 21 day immobilization period. MMP-3 upregulation was higher in the medial condyle than the lateral, and was greatest in the superficial cartilage zone, followed by middle and deep zones. These areas also showed decreases in safranin O staining, consistent with reduced cartilage proteoglycan content, as early as 7 days after immobilization. One hour of daily moderate mechanical loading, applied as passive joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from immobilization, and also prevented changes in safranin O staining. Intra-articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic effects of a 7 day immobilization period, indicating a likely requirement for MMP-3 in the regulation of proteoglycan levels through ADAMTS-5. These results suggest that biomechanical forces have the potential to combat cartilage destruction and can be critical in developing effective therapeutic strategies. 相似文献
34.
Cytosolic isocitrate dehydrogenase in humans, mice, and voles and phylogenetic analysis of the enzyme family 总被引:3,自引:0,他引:3
Nekrutenko A; Hillis DM; Patton JC; Bradley RD; Baker RJ 《Molecular biology and evolution》1998,15(12):1674-1684
In this study, we report cDNA sequences of the cytosolic NADP-dependent
isocitrate dehydrogenase for humans, mice, and two species of voles
(Microtus mexicanus and Microtus ochrogaster). Inferred amino acid
sequences from these taxa display a high level of amino acid sequence
conservation, comparable to that of myosin beta heavy chain, and share
known structural features. A Caenorhabditis elegans enzyme that was
previously identified as a protein similar to isocitrate dehydrogenase is
most likely the NADP-dependent cytosolic isocitrate dehydrogenase enzyme
equivalent, based on amino acid similarity to mammalian enzymes and
phylogenetic analysis. We also suggest that NADP-dependent isocitrate
dehydrogenases characterized from alfalfa, soybean, and eucalyptus are most
likely cytosolic enzymes. The phylogenetic tree of various isocitrate
dehydrogenases from eukaryotic sources revealed that independent gene
duplications may have given rise to the cytosolic and mitochondrial forms
of NADP-dependent isocitrate dehydrogenase in animals and fungi. There
appears to be no statistical support for a hypothesis that the
mitochondrial and cytosolic forms of the enzyme are orthologous in these
groups. A possible scenario of the evolution of NADP-dependent isocitrate
dehydrogenases is proposed.
相似文献
35.
Faecal pellet counts have been widely used to monitor the abundances of introduced ungulates in New Zealand, but ground-based sampling cannot be conducted safely in the steep non-forest habitats that are common in New Zealand's Southern Alps. Helicopter counts may be an effective technique for monitoring ungulates in steep non-forest habitat. We evaluated the relationship between faecal pellet and helicopter counts of ungulates (primarily feral goat Capra hircus) at 12 non-forest sites in the Southern Alps. Within each site we counted the numbers of ungulates from a helicopter on three occasions and the number of intact faecal pellets along 30 transects. Mean observed densities of feral goats derived from helicopter counts ranged from 0.0 to 20.2 km?2. There was a positive curvilinear (concave down) relationship between faecal pellet and helicopter counts. Compared with faecal pellet counts, helicopter counts were cheaper, could identify ungulate species and provided estimates of absolute density. Helicopter counts are a cost-effective method for monitoring ungulates in the steep non-forest habitats of New Zealand's Southern Alps. 相似文献
36.
Erik T Jansson Carolina L Trkulja Aikeremu Ahemaiti Maria Millingen Gavin DM Jeffries Kent Jardemark Owe Orwar 《Molecular pain》2013,9(1):1-8
The TRPV1 ion channel is expressed in nociceptors, where pharmacological modulation of its function may offer a means of alleviating pain and neurogenic inflammation processes in the human body. The aim of this study was to investigate the effects of cholesterol depletion of the cell on ion-permeability of the TRPV1 ion channel. The ion-permeability properties of TRPV1 were assessed using whole-cell patch-clamp and YO-PRO uptake rate studies on a Chinese hamster ovary (CHO) cell line expressing this ion channel. Prolonged capsaicin-induced activation of TRPV1 with N-methyl-D-glucamine (NMDG) as the sole extracellular cation, generated a biphasic current which included an initial outward current followed by an inward current. Similarly, prolonged proton-activation (pH 5.5) of TRPV1 under hypocalcemic conditions also generated a biphasic current including a fast initial current peak followed by a larger second one. Patch-clamp recordings of reversal potentials of TRPV1 revealed an increase of the ion-permeability for NMDG during prolonged activation of this ion channel under hypocalcemic conditions. Our findings show that cholesterol depletion inhibited both the second current, and the increase in ion-permeability of the TRPV1 channel, resulting from sustained agonist-activation with capsaicin and protons (pH 5.5). These results were confirmed with YO-PRO uptake rate studies using laser scanning confocal microscopy, where cholesterol depletion was found to decrease TRPV1 mediated uptake rates of YO-PRO. Hence, these results propose a novel mechanism by which cellular cholesterol depletion modulates the function of TRPV1, which may constitute a novel approach for treatment of neurogenic pain. 相似文献
37.
Roderic DM Page 《BMC bioinformatics》2007,8(1):158
Background
TreeBASE is currently the only available large-scale database of published organismal phylogenies. Its utility is hampered by a lack of taxonomic consistency, both within the database, and with names of organisms in external genomic, specimen, and taxonomic databases. The extent to which the phylogenetic knowledge in TreeBASE becomes integrated with these other sources is limited by this lack of consistency. 相似文献38.
Cancer is a heterogeneous disease with different combinations of genetic alterations driving its development in different individuals. We introduce CoMEt, an algorithm to identify combinations of alterations that exhibit a pattern of mutual exclusivity across individuals, often observed for alterations in the same pathway. CoMEt includes an exact statistical test for mutual exclusivity and techniques to perform simultaneous analysis of multiple sets of mutually exclusive and subtype-specific alterations. We demonstrate that CoMEt outperforms existing approaches on simulated and real data. We apply CoMEt to five different cancer types, identifying both known cancer genes and pathways, and novel putative cancer genes.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0700-7) contains supplementary material, which is available to authorized users. 相似文献39.
Background
Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma.Methods
To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response.Results
We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines.Conclusion
We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2. 相似文献40.