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91.
An M. De Schryver Mark J. Goedkoop Rob S. E. W. Leuven Mark A. J. Huijbregts 《The International Journal of Life Cycle Assessment》2010,15(7):682-691
Purpose
Uncertainties in land use damage modeling are recognized, but hardly quantified in life cycle assessment (LCA). The objective of this study is to analyze the influence of various key assumptions and uncertainties within the development of characterisation factors (CFs) for land use in LCA. We assessed the influence on land use CFs of (1) parameter uncertainty and (2) the choice for a constant or land use-specific species accumulation factor z and including or excluding regional effects. 相似文献92.
Role of alpha(2)-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice
Gourine AV Gourine VN Tesfaigzi Y Caluwaerts N Van Leuven F Kluger MJ 《American journal of physiology. Regulatory, integrative and comparative physiology》2002,283(1):R218-R226
Alpha(2)-macroglobulin (alpha(2)M) is not only a proteinase inhibitor in mammals, but it is also a specific cytokine carrier that binds pro- and anti-inflammatory cytokines implicated in fever, including interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). To define the role of alpha(2)M in regulation of febrile and cytokine responses, wild-type mice and mice deficient in alpha(2)M (alpha(2)M -/-) were injected with lipopolysaccharide (LPS). Changes in body temperature as well as plasma levels of IL-1beta, IL-6, and TNF-alpha and hepatic TNF-alpha mRNA level during fever in alpha(2)M -/- mice were compared with those in wild-type control mice. The alpha(2)M -/- mice developed a short-term markedly attenuated (ANOVA, P < 0.05) fever in response to LPS (2.5 mg/kg ip) compared with the wild-type mice. At 1.5 h after injection of LPS, the plasma concentration of TNF-alpha, but not IL-1beta or IL-6, was significantly lower (by 58%) in the alpha(2)M -/- mice compared with their wild-type controls (ANOVA, P < 0.05). There was no difference in hepatic TNF-alpha mRNA levels between alpha(2)M -/- and wild-type mice 1.5 h after injection of LPS. These data support the hypotheses that 1) alpha(2)M is important for the normal development of LPS-induced fever and 2) a putative mechanism of alpha(2)M involvement in fever is through the inhibition of TNF-alpha clearance. These findings indicate a novel physiological role for alpha(2)M. 相似文献
93.
Jung CK Fuhrmann M Honarnejad K Van Leuven F Herms J 《Journal of neurochemistry》2011,119(5):1064-1073
Mutations in presenilins are the major cause of familial Alzheimer's disease (FAD), leading to impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Presenilins are the catalytic subunits of γ-secretase, which itself is critically involved in the processing of amyloid precursor protein to release neurotoxic amyloid β (Aβ). Besides Aβ generation, there is growing evidence that presenilins play an essential role in the formation and maintenance of synapses. To further elucidate the effect of presenilin1 (PS1) on synapses, we performed longitudinal in vivo two-photon imaging of dendritic spines in the somatosensory cortex of transgenic mice over-expressing either human wild-type PS1 or the FAD-mutated variant A246E (FAD-PS1). Interestingly, the consequences of transgene expression were different in two subtypes of cortical dendrites. On apical layer 5 dendrites, we found an enhanced spine density in both mice over-expressing human wild-type presenilin1 and FAD-PS1, whereas on basal layer 3 dendrites only over-expression of FAD-PS1 increased the spine density. Time-lapse imaging revealed no differences in kinetically distinct classes of dendritic spines nor was the shape of spines affected. Although γ-secretase-dependent processing of synapse-relevant proteins seemed to be unaltered, higher expression levels of ryanodine receptors suggest a modified Ca(2+) homeostasis in PS1 over-expressing mice. However, the conditional depletion of PS1 in single cortical neurons had no observable impact on dendritic spines. In consequence, our results favor the view that PS1 influences dendritic spine plasticity in a gain-of-function but γ-secretase-independent manner. 相似文献
94.
95.
Abstract— The influence of hypercapnia on the metabolism of glutamic acid, aspartic acid, glutamine and GABA in rat brain was studied using three different precursors. Acute hypercapnia induced a fall in the concentration of glutamic and aspartic acid, and a rise in the concentration of glutamine and GABA. Acute hypercapnia had a profound effect on the relative specific radioactivity of glutamine indicating that the excess glutamine, present in the brain in hypercapnia, was synthetized from glutamic acid in the compartment where it could become quickly labelled from butyric and glutamic acid, but not from glucose. This effect was maintained in chronic hypercapnia. 相似文献
96.
Barre A Peumans WJ Menu-Bouaouiche L Van Damme EJ May GD Herrera AF Van Leuven F Rougé P 《Planta》2000,211(6):791-799
The pulp of ripe bananas (Musa acuminata) contains an abundant thaumatin-like protein (TLP). Characterization of the protein and molecular cloning of the corresponding
gene from banana demonstrated that the native protein consists of a single polypeptide chain of 200 amino acid residues. Molecular
modelling further revealed that the banana thaumatin-like protein (Ban-TLP) adopts an overall fold similar to that of thaumatin
and thaumatin-like PR-5 proteins. Although the banana protein exhibits an electrostatically polarized surface, which is believed
to be essential for the antifungal properties of TLPs, it is apparently devoid of antifungal activity towards pathogenic fungi.
It exhibits a low but detectable in vitro endo-β-1,3-glucanase (EC 3.2.1.x) activity. As well as being present in fruits,
Ban-TLP also occurs in root tips where its accumulation is enhanced by methyl jasmonate treatment of plants. Pulp of plantains
(Musa acuminata) also contains a very similar TLP, which is even more abundant than its banana homologue. Our results demonstrate for the
first time that fruit-specific (abundant) TLPs are not confined to dicots but occur also in fruits of monocot species. The
possible role of the apparent widespread accumulation of fruit-specific TLPs is discussed.
Received: 7 January 2000 / Accepted: 26 April 2000 相似文献
97.
Priller C Dewachter I Vassallo N Paluch S Pace C Kretzschmar HA Van Leuven F Herms J 《The Journal of biological chemistry》2007,282(2):1119-1127
Mutations in presenilins are the major cause of familial Alzheimer disease, but the precise pathogenic mechanism by which presenilin (PS) mutations cause synaptic dysfunction leading to memory loss and neurodegeneration remains unclear. Using autaptic hippocampal cultures from transgenic mice expressing human PS1 with the A246E mutation, we demonstrate that mutant PS1 significantly depressed the amplitude of evoked alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptor-mediated synaptic currents. Analysis of the spontaneous miniature synaptic activity revealed a lower frequency of miniature currents but normal miniature amplitude. Both alterations could be rescued by the application of a gamma-secretase blocker. On the other hand, the application of synthetic soluble Abeta42 in wild-type neurons induced the PS1 mutant phenotype on synaptic strength. Together, these findings strongly suggest that the expression of mutant PS1 in cultured neurons depresses synaptic transmission by causing a physical reduction in the number of synapses. This hypothesis is consistent with morphometic and semiquantitative immunohistochemical analysis, revealing a decrease in synaptophysin-positive puncta in PS1 mutant hippocampal neurons. 相似文献
98.
N Boisset J C Taveau M Barray F Van Leuven E Delain J N Lamy 《Biology of the cell / under the auspices of the European Cell Biology Organization》1988,64(1):45-55
Alpha 2-macroglobulin (alpha 2M) is a plasma inhibitor of proteinases, the steric mechanism of which is based on a considerable conformational change. The typical and distinct H-like shape of alpha 2M-chymotrypsin (alpha 2M-chy) complexes seen by electron microscopy led us to an ultrastructural study of the binding of a monoclonal antibody (Mab) specific for this conformation of alpha 2M. The epitope of this Mab is located near the extremities of the 4 arms of the H-like alpha 2M-chy, at a site that is not accessible on the native molecule. The identical binding of the Mab on the 4 arms of the tetrameric molecule demonstrates that these arms are equivalent portions of the 4 monomers. Various types of immune complexes between alpha 2M and IgG are described, and images of individual immune complexes were processed by correspondence analysis. This extracts new information concerning the organization of chymotrypsin-transformed alpha 2M. The molecule appears asymmetrical, presents 2 conformational states (which we describe as relaxed and twisted), and has flexible arms. These intramolecular motions are supposed to be related to IgG binding. The results are discussed in comparison with previously published models of proteinase-transformed alpha 2M. 相似文献
99.
Association between coding variability in the LRP gene and the risk of late-onset Alzheimer’s disease 总被引:3,自引:0,他引:3
Fabienne Wavrant-DeVrièze Jean-Charles Lambert L. Stas Richard Crook Dominique Cottel Florence Pasquier Bernard Frigard Martine Lambrechts E. Thiry Philippe Amouyel J. Pérez-Tur M. C. Chartier-Harlin John Hardy Fred Van Leuven 《Human genetics》1999,104(5):432-434
We have sequenced the entire (89 exons) open reading frame of the LRP gene in 12 cases of Alzheimer’s disease (AD) from Northern
France. We have found no novel changes but confirm the occurrence of a polymorphism in exon 6 of the gene (A216V). This polymorphism
is rare (2.8% of controls) and is in linkage equilibrium with previously reported polymorphisms. The V216 allele is negatively
associated with the disease in a large case-controlled series. These data suggest that the LRP receptor may be involved in
the pathobiology of AD, but the association that we report here cannot explain the previously reported genetic data implicating
the LRP gene in AD. If the LRP gene is a major site of genetic variability leading to AD, there must be other biologically
relevant variability in promoter or other regulatory elements of this large gene.
Received: 28 December 1998 / Accepted: 1 March 1999 相似文献
100.
Developmental expression of wild-type and mutant presenilin-1 in hippocampal neurons from transgenic mice: evidence for novel species-specific properties of human presenilin-1. 下载免费PDF全文
L. L
vesque W. Annaert K. Craessaerts P. M. Mathews M. Seeger R. A. Nixon F. Van Leuven S. Gandy D. Westaway P. St George-Hyslop B. De Strooper P. E. Fraser 《Molecular medicine (Cambridge, Mass.)》1999,5(8):542-554
Presenilins 1 (PS1) and 2 (PS2) are multispanning transmembrane proteins associated with familial Alzheimer disease (FAD). They are developmentally regulated, being expressed at highest levels during neuronal differentiation and are sustained at a lower level throughout life. We investigated the distribution and metabolism of endogenous murine PS1 as well as human wild-type (wtPS1) and the familial AD Met146Leu (M146L) mutant presenilins in dissociated cultures of hippocampal neurons derived from control and transgenic mice. We found that the PS1 endoproteolytic fragments and, to a lesser extent, the full-length protein, were expressed as early as day 3 post-plating. Both species increased until the cells were fully differentiated at day 12. Confocal microscopy revealed that presenilin is present in the Golgi and endoplasmic reticulum and, as in punctate, vesicle-like structures within developing neurites and growth cones. Using a human-specific PS1 antibody, we were able to independently examine the distribution of the transgenic protein which, although similar to the endogenous, showed some unique qualities. These included (i) some heterogeneity in the proteolytic fragments of human PS1; (ii) significantly reduced levels of full-length human PS1, possibly as a result of preferential processing; and (iii) a more discrete intracellular distribution of human PS1. Colocalization with organelle-specific proteins revealed that PS1 was located in a diffuse staining pattern in the MAP2-positive dendrites and in a punctate manner in GAP43-positive axons. PS1 showed considerable overlap with GAP43, particularly at the growth cones. Similar patterns of PS1 distribution were detected in cultures derived from transgenic animals expressing human wild-type or mutant presenilins. The studies demonstrate that mutant presenilins are not grossly different in their processing or distribution within cultured neurons, which may represent more physiological models as compared to transfection systems. Our data also suggest that the molecular pathology associated with PS1 mutations results from subtle alterations in presenilin function, which can be further investigated using these transgenic neuronal cell culture models. 相似文献