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981.
Malgorzata Romanowska Alan Evans David Kellock Susan E. Bray Kathleen McLean Susanne Donandt John Foerster 《PloS one》2009,4(4)
Background
Wnt5a is a member of the wingless-type patterning regulators important in pre-natal development. The expression and distribution of Wnt5a and its receptors frizzled (fzd) 3 and fzd 5 in adult human skin have not been comprehensively studied to date.Methodology/Principal Findings
We here show that Wnt5a, fzd3, fzd5, as well as fzd6 are restricted to specific layers in normal epidermis, analogous to their zonal distribution in hair follicles, suggesting a role in adult skin differentiation. In line, Wnt5a and fzd5 are both overexpressed and re-distributed in the epidermis of psoriasis which involves disturbed keratinocyte differentiation. Functionally, Wnt5a lowers the concentration of IFN required to induce target genes, and increases the magnitude of IFN target gene induction, suggesting a molecular mechanism underlying IFN hypersensitivity in psoriasis. Finally, we identify nedd8 and the amyloid precursor APP, previously shown to be upregulated in psoriasis, as targets of synergistic IFNα/Wnt5a induction.Conclusions/Significance
The present data (i) suggest that Wnt5a regulates epidermal differentiation even in adult skin and (ii) identify synergistic induction of type 1 IFN target genes as a novel mode of Wnt5a action. Targeting Wnt5a in the skin may reduce IFN hypersensitivity and be of therapeutical value. 相似文献982.
Wolfgang Sturm Anton Sandhofer Julia Engl Markus Laimer Clemens Molnar Susanne Kaser Helmut Weiss Herbert Tilg Christoph F. Ebenbichler Josef R. Patsch 《Obesity (Silver Spring, Md.)》2009,17(9):1783-1788
Endothelial dysfunction and increased intima–media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 ± 4.3 kg/m²), we determined (i) endothelial function as flow‐mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = ?0.577, P < 0.0001 and r = ?0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r2 = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r2 = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population. 相似文献
983.
984.
Listeria monocytogenes is a pathogenic bacterium that moves within infected cells and spreads directly between cells by harnessing the cell's dendritic actin machinery. This motility is dependent on expression of a single bacterial surface protein, ActA, a constitutively active Arp2,3 activator, and has been widely studied as a biochemical and biophysical model system for actin-based motility. Dendritic actin network dynamics are important for cell processes including eukaryotic cell motility, cytokinesis, and endocytosis. Here we experimentally altered the degree of ActA polarity on a population of bacteria and made use of an ActA-RFP fusion to determine the relationship between ActA distribution and speed of bacterial motion. We found a positive linear relationship for both ActA intensity and polarity with speed. We explored the underlying mechanisms of this dependence with two distinctly different quantitative models: a detailed agent-based model in which each actin filament and branched network is explicitly simulated, and a three-state continuum model that describes a simplified relationship between bacterial speed and barbed-end actin populations. In silico bacterial motility required a cooperative restraining mechanism to reconstitute our observed speed-polarity relationship, suggesting that kinetic friction between actin filaments and the bacterial surface, a restraining force previously neglected in motility models, is important in determining the effect of ActA polarity on bacterial motility. The continuum model was less restrictive, requiring only a filament number-dependent restraining mechanism to reproduce our experimental observations. However, seemingly rational assumptions in the continuum model, e.g. an average propulsive force per filament, were invalidated by further analysis with the agent-based model. We found that the average contribution to motility from side-interacting filaments was actually a function of the ActA distribution. This ActA-dependence would be difficult to intuit but emerges naturally from the nanoscale interactions in the agent-based representation. 相似文献
985.
Mathematical modelling of aliphatic glucosinolate chain length distribution in Arabidopsis thaliana leaves 总被引:1,自引:0,他引:1
Beate Knoke Susanne Textor Jonathan Gershenzon Stefan Schuster 《Phytochemistry Reviews》2009,8(1):39-51
Aliphatic glucosinolates are a major class of defensive secondary metabolites in plants that are mostly derived from methionine.
Occurring in different chain lengths, they show a structural diversity arising from the variable number of chain elongation
cycles taking place during their biosynthesis. The key enzymes in determining glucosinolate chain length are the methylthioalkylmalate
(MAM) synthases, MAM1 and MAM3, with MAM3 showing a broader substrate specificity than MAM1. A comparison of the measurements
of wild type and MAM1 knockout mutant plants shows the following distinct changes in glucosinolate chain length profiles:
MAM3 knockout mutants on the contrary differ from wild type plants by a pronounced abundance of the second shortest glucosinolate
and the depletion of the two longest glucosinolates. To clarify the contribution of the multifunctional enzymes MAM1 and MAM3
to the glucosinolate profile of Arabidopsis thaliana leaves, we simulated glucosinolate biosynthesis in a kinetic model, taking into account the structure of the pathway and
measured enzymatic properties. The predicted glucosinolate profiles show all characteristics of the actual differences between
wild-type and MAM1 mutants or MAM3 mutants, respectively. The model strongly supports experimental indications that the two MAM activities are not independent
of each other. In particular, it showed that an elevated expression of MAM3 in the MAM1 mutant is critical in determining the glucosinolate profile of this plant line. The simulation was critical for this finding
since it allowed us to assess the individual effects of two processes—the knocking out of MAM1 and the overexpression of MAM3—that
are difficult to separate experimentally. 相似文献
(1) | a reversal of the relative proportions of the two shortest glucosinolates, |
(2) | a significant increase in the concentration of the longest glucosinolate, |
(3) | an increase in total glucosinolate content in the mutant. |
986.
Above ground plant parts of Lolium perenne often harbour endophytic Neotyphodium lolii fungi. These occur both naturally and commercially, as variant strains are introduced to modify the grass metabolic profile.
They reside in the apoplastic spaces and rarely cause visible symptoms of infection. The vast majority of literature has focussed
on the biosynthesis, accumulation, and ecological relevance of a limited number of alkaloids produced by N. lolii which have been shown to negatively affect insect pests and vertebrate herbivores. Much less is known about the effects of
other metabolites in these interactions or the role of resource supply on metabolic profiles, nor critically on the metabolic
consequences of differences in the amount (concentration) of endophyte present. Here, we provide a synthesis of some of our
recently published studies on effects of resource supply (nitrogen, carbohydrates) on concentrations of endophytes and endophyte
specific metabolites in the L. perenne–N. lolii association. We present results of both quantitative PCR and targeted metabolomics studies, using contrasting endophyte strains
in two perennial ryegrass cultivars. We also present and discuss a hypothetical schematic representation of possible links
between plant and fungal metabolic networks. A multiple regression analysis of numerical insect responses and metabolic profiles
indicates that effects of endophyte infection on insect population sizes could be predicted by concentrations of a range of
metabolites other than alkaloids and depended on insect species, fungal strain, and nitrogen supply. 相似文献
987.
Tobias Karlberg Susanne van den Berg Martin Hammarstr?m Johanna Sagemark Ida Johansson Lovisa Holmberg-Schiavone Herwig Schüler 《PloS one》2009,4(10)
Paraplegin is an m-AAA protease of the mitochondrial inner membrane that is linked to hereditary spastic paraplegias. The gene encodes an FtsH-homology protease domain in tandem with an AAA+ homology ATPase domain. The protein is believed to form a hexamer that uses ATPase-driven conformational changes in its AAA-domain to deliver substrate peptides to its protease domain. We present the crystal structure of the AAA-domain of human paraplegin bound to ADP at 2.2 Å. This enables assignment of the roles of specific side chains within the catalytic cycle, and provides the structural basis for understanding the mechanism of disease mutations.
Enhanced version
This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1. 相似文献988.
Activated carbon (AC) is widely used in ecological studies to elucidate the role of allelopathic substances in interspecific
plant competition. However, by adsorbing chemical signalling compounds AC may also have negative effects on plants with symbiosis
partners such as arbuscular mycorrhizal fungi and rhizobia. Here we test whether addition of AC has detrimental effects on
the mycorrhizal root colonization of the native forb Plantago lanceolata and the exotic legume Lupinus polyphyllus, the nodulation of L. polyphyllus, and the nutrient uptake and growth of the plants growing in intra- and interspecific competition. Allelopathic effects probably
occurred in the germination and seedling establishment phase when P. lanceolata suffered from the presence of L. polyphyllus. However, this negative effect of L. polyphyllus on P. lanceolata was not ameliorated by AC addition. AC negatively affected L. polyphyllus root biomass in week 4, and root and shoot biomass of P. lanceolata in week 9 of the experiment; both effects were independent of the presence and absence of the competing plant species. Mycorrhizal
root colonization of both plant species was reduced in the presence of AC, although the effect tended to be stronger for L. polyphyllus. No significant effect of AC on the nodulation of L. polyphyllus was detected. P. lanceolata was the superior competitor and led to reduced biomasses of L. polyphyllus in interspecific competition. We conclude that AC can reduce the mycorrhization and performance of plants which may lead
to changes in interspecific competition without the involvement of allelopathy. Contrary to former studies the AC used in
our study did not enhance the nutrient availability for the plants, but reduced plant growth and mycorrhization. We suggest
that the nutrient properties of the used AC are of crucial importance for the direction and the mechanisms of the effects
and should always be reported. 相似文献
989.
Melanie Zaparty Dominik Esser Susanne Gertig Patrick Haferkamp Theresa Kouril Andrea Manica Trong K. Pham Julia Reimann Kerstin Schreiber Pawel Sierocinski Daniela Teichmann Marleen van Wolferen Mathias von Jan Patricia Wieloch Sonja V. Albers Arnold J. M. Driessen Hans-Peter Klenk Christa Schleper Dietmar Schomburg John van der Oost Phillip C. Wright Bettina Siebers 《Extremophiles : life under extreme conditions》2010,14(1):119-142
990.