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71.
Background
It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems. 相似文献72.
Ana Paula F Trombone Celio L Silva Luciana P Almeida Rogerio S Rosada Karla M Lima Constance Oliver Maria C Jamur Arlete AM Coelho-Castelo 《Genetic vaccines and therapy》2007,5(1):1-8
Background
Mucopolysaccharidosis type IIIA (MPS IIIA) is the most common of the mucopolysaccharidoses. The disease is caused by a deficiency of the lysosomal enzyme sulphamidase and results in the storage of the glycosaminoglycan (GAG), heparan sulphate. MPS IIIA is characterised by widespread storage and urinary excretion of heparan sulphate, and a progressive and eventually profound neurological course. Gene therapy is one of the few avenues of treatment that hold promise of a sustainable treatment for this disorder.Methods
The murine sulphamidase gene cDNA was cloned into a lentiviral vector and high-titre virus produced. Human MPS IIIA fibroblast cultures were transduced with the sulphamidase vector and analysed using molecular, enzymatic and metabolic assays. High-titre virus was intravenously injected into six 5-week old MPS IIIA mice. Three of these mice were pre-treated with hyperosmotic mannitol. The weight of animals was monitored and GAG content in urine samples was analysed by polyacrylamide gel electrophoresis.Results
Transduction of cultured MPS IIIA fibroblasts with the sulphamidase gene corrected both the enzymatic and metabolic defects. Sulphamidase secreted by gene-corrected cells was able to cross correct untransduced MPS IIIA cells. Urinary GAG was found to be greatly reduced in samples from mice receiving the vector compared to untreated MPS IIIA controls. In addition, the weight of treated mice became progressively normalised over the 6-months post-treatment.Conclusion
Lentiviral vectors appear promising vehicles for the development of gene therapy for MPS IIIA. 相似文献73.
Marek Cie?lak Joanna Czarnecka Katarzyna Roszek Micha? Komoszyński 《Purinergic signalling》2015,11(3):307-316
Etiopathogenesis of migraine involves different structures of the central nervous system: the trigeminal nerve with nuclei located in the brain stem, vascular system, and the cerebral cortex as well as diverse mechanisms and pathological processes. The multidirectional action of purines in different cell types (blood vessels, neurons, and satellite glial cells) and through different types of purinergic receptors contributes to the etiopathogenesis of migraine pain. Adenosine triphosphate (ATP) and its derivatives are involved in initiation and propagation of migrenogenic signals in several ways: they participate in vasomotor mechanism, cortical spreading depression, and in fast transmission or cross-excitation based on the satellite glial cells in trigeminal ganglion. Contribution of purinergic signaling in the conduction of pain is realized through the activation of P1 and P2 receptors expressed widely in the central nervous system: on the neurons and glial cells as well as on the smooth muscles and endothelium in the vascular system. Therefore, the purinergic receptors can be an excellent target for pharmacologists constructing new antimigraine therapeutics. Moreover, the mechanisms facilitating ATP and adenosine degradation may prevent vasodilatation and thus avoid a secondary central sensitization during a migraine attack. Thus, agonists and antagonists of P receptors as well as ecto-enzymes metabolizing nucleotides/nucleosides could gain the growing attention as therapeutic agents. 相似文献
74.
75.
Cliona delitrix is a very destructive coral-excavating sponge in Caribbean coral reef systems, particularly for Montastraea species. Little is known about how these excavating sponges propagate across coral reefs. In this study a hypothesis was tested that coral breakage caused by the bioeroding activity facilitates the asexual propagation of this sponge and in turn favors the spread of the most aggressive sponge genotypes. An allozyme analysis, involving 12 loci systems of 52 sponge individuals from a total of 13 Montastraea heads, found that no two sponges possessed identical multi-locus genotypes. Contrary to the pattern expected for fragmenting species, the incidence of clonality and asexual propagation at the population level was minimal. The lack of correlation between genetic and physical distances for the studied sponges also suggests that population maintenance appears to derive from larval dispersal, with a spatial range of dispersal larger than the average distance between the coral heads (10–102 m). 相似文献
76.
The role of solid waste materials as habitats for macroinvertebrates in a lowland dam reservoir 总被引:2,自引:1,他引:1
Magdalena Czarnecka Małgorzata Poznańska Jarosław Kobak Norbert Wolnomiejski 《Hydrobiologia》2009,634(1):125-135
Eight hypereutrophic phytoplankton dominated ponds from the Brussels Capital Region (Belgium) were biomanipulated (emptied
with fish removal) to restore their ecological quality and reduce the risk of cyanobacterial bloom formation. Continuous monitoring
of the ponds before and after the biomanipulation allowed the effects of the management intervention on different compartments
of pond ecosystems (phytoplankton, zooplankton, submerged vegetation and nutrients) to be assessed. Fish removal resulted
in a drastic reduction in phytoplankton biomass and a shift to the clear-water state in seven out of eight biomanipulated
ponds. The reduction in phytoplankton biomass was associated with a marked increase in density and size of large cladocerans
in six ponds and a restoration of submerged macrophytes in five ponds. The phytoplankton biomass in the ponds with extensive
stands of submerged macrophytes was less affected by planktivorous fish recolonisation of some of the ponds later in the summer.
The two non-vegetated ponds as well as one pond with sparse submerged vegetation showed a marked increase in phytoplankton
biomass associated with the appearance of fish. Phytoplankton biomass increase coincided with the decrease in large Cladocera
density and size. One pond lacking submerged macrophytes could maintain very low phytoplankton biomass owing to large Cladocera
grazing alone. The results of this study confirmed the importance of large zooplankton grazing and revegetation with submerged
macrophytes for the maintenance of the clear-water state and restoration success in hypereutrophic ponds. They also showed
that large Cladocera size is more important than their number for efficient phytoplankton control and when cladocerans are
large enough, they can considerably restrain phytoplankton growth, including bloom-forming cyanobacteria, even when submerged
vegetation is not restored. The positive result of fish removal in seven out of eight biomanipulated ponds clearly indicated
that such management intervention can be used, at least, for the short-term restoration of ecological water quality and prevention
of noxious cyanobacterial bloom formation. The negative result of biomanipulation in one pond seems to be related to the pollution
by sewage water.
Guest editors: B. Oertli, R. Cereghino, A. Hull & R. Miracle
Pond Conservation: From Science to Practice. 3rd Conference of the European Pond Conservation Network, Valencia, Spain, 14–16
May 2008 相似文献
77.
78.
Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides 总被引:2,自引:0,他引:2
Background
The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.Results
EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.Conclusion
DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress. 相似文献79.
Corry-Anke Brandsma Machteld N Hylkema Marie Geerlings Wouter H van Geffen Dirkje S Postma Wim Timens Huib AM Kerstjens 《Respiratory research》2009,10(1):108
There is increasing evidence that a specific immune response contributes to the pathogenesis of COPD. B-cell follicles are present in lung tissue and increased anti-elastin titers have been found in plasma of COPD patients. Additionally, regulatory T cells (Tregs) have been implicated in its pathogenesis as they control immunological reactions. We hypothesize that the specific immune response in COPD is smoke induced, either by a direct effect of smoking or as a result of smoke-induced lung tissue destruction (i.e. formation of neo-epitopes or auto antigens). Furthermore, we propose that Tregs are involved in the suppression of this smoke-induced specific immune response.The presence of B cells, memory B cells and Tregs was assessed by flow cytometry in peripheral blood of 20 COPD patients and 29 healthy individuals and related to their current smoking status.COPD patients had lower (memory) B-cell percentages and higher Treg percentages in peripheral blood than healthy individuals, with a significant negative correlation between these cells. Interestingly, current smokers had higher percentages of (class-switched) memory B cells than ex-smokers and never smokers, irrespective of COPD.This increase in (class-switched) memory B cells in current smokers is intriguing and suggests that smoke-induced neo-antigens may be constantly induced in the lung. The negative correlation between B cells and Tregs in blood is in line with previously published observations that Tregs can suppress B cells. Future studies focusing on the presence of these (class switched) memory B cells in the lung, their antigen specificity and their interaction with Tregs are necessary to further elucidate the specific B-cell response in COPD. 相似文献
80.
A Luquita L Urli MJ Svetaz AM Gennaro ME Giorgetti G Pistone R Volpintesta S Palatnik M Rasia 《Journal of biomedical science》2010,17(1):8