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- Knutsen Rydberg, Ellen, 1969, et al.
(author)
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Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
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In: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
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| 3. |
- Lansner, A, et al.
(author)
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Modulating the calcium dependent potassium conductance in a model of the lamprey CPG
- 1997
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Conference paper (pop. science, debate, etc.)abstract
- The lampery is a primitive water-living vertebrate that moves by means of undulatory swimming. It is of particular interest as an experimental model for the neural generation of locomotin [Grillner et al..,,, 1995] a major advantage of this system is that the motor pattern underlying swimming can be elicited in an isolated piece of spinal cord. Being one of the best characterized vertebrate neuronal systems, the lampery spinal CPG has been the subject of a number of modelling and simulation studies.
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| 4. |
- Ullström, M, et al.
(author)
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Activity-dependent modulation of adaptation produces a constant burst proportion in a model of the lamprey spinal locomotor generator.
- 1998
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In: Biological Cybernetics. - : Springer Science and Business Media LLC. - 0340-1200 .- 1432-0770. ; 79:1, s. 1-14
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Journal article (peer-reviewed)abstract
- The neuronal network underlying lamprey swimming has stimulated extensive modelling on different levels of abstraction. The lamprey swims with a burst frequency ranging from 0.3 to 8-10 Hz with a rostrocaudal lag between bursts in each segment along the spinal cord. The swimming motor pattern is characterized by a burst proportion that is independent of burst frequency and lasts around 30%-40% of the cycle duration. This also applies in preparations in which the reciprocal inhibition in the spinal cord between the left and right side is blocked. A network of coupled excitatory neurons producing hemisegmental oscillations may form the basis of the lamprey central pattern generator (CPG). Here we explored how such networks, in principle, could produce a large frequency range with a constant burst proportion. The computer simulations of the lamprey CPG use simplified, graded output units that could represent populations of neurons and that exhibit adaptation. We investigated the effect of an active modulation of the degree of adaptation of the CPG units to accomplish a constant burst proportion over the whole frequency range when, in addition, each hemisegment is assumed to be self-oscillatory. The degree of adaptation is increased with the degree of stimulation of the network. This will make the bursts terminate earlier at higher burst rates, allowing for a constant burst proportion. Without modulated adaptation the network operates in a limited range of swimming frequencies due to a progressive increase of burst duration with increasing background stimulation. By introducing a modulation of the adaptation, a broad burst frequency range can be produced. The reciprocal inhibition is thus not the primary burst terminating factor, as in many CPG models, and it is mainly responsible for producing alternation between the left and right sides. The results are compared with the Morris-Lecar oscillator model with parameters set to produce a type A and type B oscillator, in which the burst durations stay constant or increase, respectively, when the background stimulation is increased. Here as well, burst duration can be controlled by modulation of the slow variable in a similar way as above. When oscillatory hemisegmental networks are coupled together in a chain a phase lag is produced. The production of a phase lag in chains of such oscillators is compared with chains of Morris-Lecar relaxation oscillators. Models relating to the intact versus isolated spinal cord preparation are discussed, as well as the role of descending inhibition.
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