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31.
Caruana M Neuner J Högen T Schmidt F Kamp F Scerri C Giese A Vassallo N 《Biochimica et biophysica acta》2012,1818(11):2502-2510
Cumulative evidence now suggests that the abnormal aggregation of the protein α-synuclein (αS) is a critical factor in triggering neurodegeneration in Parkinson's disease (PD). In particular, a fundamental pathogenetic mechanism appears to involve targeting of neuronal membranes by soluble oligomeric intermediates of αS, leading to their disruption or permeabilisation. Therefore, a model assay was developed in which fluorophore-loaded unilamellar vesicles were permeabilised by soluble oligomers, the latter formed by aggregation of human recombinant αS protein. The αS oligomers induced an impairment of membrane integrity similar to that of the pore-forming bacterial peptide gramicidin. The lipid vesicle permeabilisation assay was then utilised to screen 11 natural polyphenolic compounds, 8 synthetic N'-benzylidene-benzohydrazide compounds and black tea extract for protection against membrane damage by wild-type and mutant (A30P, A53T) synuclein aggregates. A select group of potent inhibitory compounds included apigenin, baicalein, morin, nordihydroguaiaretic acid, and black tea extract. Structure-activity analysis further suggests that a 5,7-dihydroxy-chromen-4-one moiety appears to be favourable for the inhibition reaction. In conclusion, we have identified a group of polyphenols that can effectively hinder membrane damage by αS aggregates. These may serve as a viable source of lead compounds for the development and design of novel therapeutic agents in PD. 相似文献
32.
Mapping a songbird fauna with pupils How to induce pupils aged 13 to 14 years to successfully map the songbird fauna of a city park? The mapping project took place within 1.5 hours on an April morning. Pupils were organized as small working groups using maps, binoculars, and field guides produced by themselves. The project had been prepared by a 6 lesson course. Results were later discussed with nature conservancy officials. Pupils having participated in the project displayed increased knowledge of birds and motivation to observe them. 相似文献
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34.
Monaci P Luzzago A Santini C De Pra A Arcuri M Magistri F Bellini A Ansuini H Ambrosio M Ammendola V Bigotti MG Cirillo A Nuzzo M Nasti AA Neuner P Orsatti L Pezzanera M Sbardellati A Silvestre G Uva P Viti V Barbato G Colloca S Demartis A De Rinaldis E Giampaoli S Lahm A Palombo F Talamo F Vitelli A Nicosia A Cortese R 《PloS one》2008,3(1):e1508
A novel and efficient tagArray technology was developed that allows rapid identification of antibodies which bind to receptors with a specific expression profile, in the absence of biological information. This method is based on the cloning of a specific, short nucleotide sequence (tag) in the phagemid coding for each phage-displayed antibody fragment (phage-Ab) present in a library. In order to set up and validate the method we identified about 10,000 different phage-Abs binding to receptors expressed in their native form on the cell surface (10 k Membranome collection) and tagged each individual phage-Ab. The frequency of each phage-Ab in a given population can at this point be inferred by measuring the frequency of its associated tag sequence through standard DNA hybridization methods. Using tiny amounts of biological samples we identified phage-Abs binding to receptors preferentially expressed on primary tumor cells rather than on cells obtained from matched normal tissues. These antibodies inhibited cell proliferation in vitro and tumor development in vivo, thus representing therapeutic lead candidates. 相似文献
35.
Surmann-Schmitt C Dietz U Kireva T Adam N Park J Tagariello A Onnerfjord P Heinegård D Schlötzer-Schrehardt U Deutzmann R von der Mark K Stock M 《The Journal of biological chemistry》2008,283(11):7082-7093
Here we report on the structure, expression, and function of a novel cartilage-specific gene coding for a 17-kDa small, highly charged, and secreted protein that we termed Ucma (unique cartilage matrix-associated protein). The protein is processed by a furin-like protease into an N-terminal peptide of 37 amino acids and a C-terminal fragment (Ucma-C) of 74 amino acids. Ucma is highly conserved between mouse, rat, human, dog, clawed frog, and zebrafish, but has no homology to other known proteins. Remarkable are 1-2 tyrosine sulfate residues/molecule and dense clusters of acidic and basic residues in the C-terminal part. In the developing mouse skeleton Ucma mRNA is expressed in resting chondrocytes in the distal and peripheral zones of epiphyseal and vertebral cartilage. Ucma is secreted into the extracellular matrix as an uncleaved precursor and shows the same restricted distribution pattern in cartilage as Ucma mRNA. In contrast, antibodies prepared against the processed C-terminal fragment located Ucma-C in the entire cartilage matrix, indicating that it either diffuses or is retained until chondrocytes reach hypertrophy. During differentiation of an MC615 chondrocyte subclone in vitro, Ucma expression parallels largely the expression of collagen II and decreases with maturation toward hypertrophic cells. Recombinant Ucma-C does not affect expression of chondrocyte-specific genes or proliferation of chondrocytes, but interferes with osteogenic differentiation of primary osteoblasts, mesenchymal stem cells, and MC3T3-E1 pre-osteoblasts. These findings suggest that Ucma may be involved in the negative control of osteogenic differentiation of osteochondrogenic precursor cells in peripheral zones of fetal cartilage and at the cartilage-bone interface. 相似文献
36.
Waldecker M Kautenburger T Daumann H Busch C Schrenk D 《The Journal of nutritional biochemistry》2008,19(9):587-593
Colorectal cancer is the most abundant cause of cancer mortality in the Western world. Nutrition and the microbial flora are considered to have a marked influence on the risk of colorectal cancer, the formation of butyrate and other short-chain fatty acids (SCFAs) possibly playing a major role as chemopreventive products of microbial fermentation in the colon. In this study, we investigated the effects of butyrate, other SCFAs, and of a number of phenolic SCFA and trans-cinnamic acid derivatives formed during the intestinal degradation of polyphenolic constituents of fruits and vegetables on global histone deacetylase (HDAC) activity in nuclear extracts from colon carcinoma cell cultures using tert-butoxycarbonyl-lysine (acetylated)-4-amino-7-methylcoumarin (Boc-Lys(Ac)-AMC) as substrate. Inhibition of HDAC activity, e.g., by butyrate, is related to a suppression of malignant transformation and a stimulation of apoptosis of precancerous colonic cells. In nuclear extracts from HT-29 human colon carcinoma cells, butyrate was found to be the most potent HDAC inhibitor (IC(50)=0.09 mM), while other SCFAs such as propionate were less potent. In the same assay, p-coumaric acid (IC(50)=0.19 mM), 3-(4-OH-phenyl)-propionate (IC(50)=0.62 mM) and caffeic acid (IC(50)=0.85 mM) were the most potent HDAC inhibitors among the polyphenol metabolites tested. Interestingly, butyrate was also the most potent HDAC inhibitor in a whole-cell HeLa Mad 38-based reporter gene assay, while all polyphenol metabolites and all other SCFAs tested were much less potent; some were completely inactive. The findings suggest that butyrate plays an outstanding role as endogenous HDAC inhibitor in the colon, and that other SCFAs and HDAC-inhibitory polyphenol metabolites present in the colon seem to play a much smaller role, probably because of their limited levels, their marked cytotoxicity and/or their limited intracellular availability. 相似文献
37.
The species specific response of photosystem 2 (PS2) efficiency and its thermotolerance to diurnal and seasonal alterations in leaf temperature, irradiance, and water relations were investigated under alpine field conditions (1 950 m) and in response to an in situ long-term heat treatment (+3 K). Three plant species were compared using the naturally occurring microstratification of alpine environments, i.e. under contrasting leaf temperatures but under similar macroclimatic conditions. Thermotolerance of PS2 showed a high variability in all three species of up to 9.6 K. Diumal changes (increases or even decreases) in PS2 thermotolerance occurred frequently with a maximum increase of +4.8 K in Loiseleuria procumbens. Increasing leaf temperatures and photosynthetic photon flux density influenced thermotolerance adjustments. Under long-term heating (+3 K) of L. procumbens canopies with infra-red lamps, the maxima of the critical (Tc) and the lethal (Tp) temperature of PS2 increased by at least 1 K. Thermotolerance of the leaf tissue (LT50) increased significantly by +0.6 K. The effects of slight water stress on thermotolerance of PS2 were species specific. High temperature thresholds for photoinhibition were significantly different between species and increased by 9 K from the species in the coldest microhabitat to the species in the warmest. Experimental heating of L. procumbens canopies by +3 K caused a significant (p>0.01) upward shift of the high temperature threshold for photoinhibition by +3 K. Each species appeared to be very well adapted to the thermal conditions of its microhabitat as under the most frequently experienced daytime leaf temperatures no photoinhibition occurred. The observed fine scale thermal adjustment of PS2 in response to increased leaf temperatures shows the potential to optimise photosynthesis under varying environmental conditions as long as the upper thermal limits are not exceeded. 相似文献
38.
Cordula I. Jörgens Nora Grünewald Martin Hülskamp Joachim F. Uhrig 《The Plant journal : for cell and molecular biology》2010,62(6):925-935
Actin nucleation facilitated by the ARP2/3 complex plays a central role in plant cell shape development. The molecular characterization of the distorted class of trichome mutants has recently revealed the SCAR/WAVE complex as an essential upstream activator of ARP2/3 function in plants. The SCAR/WAVE complex is conserved from animals to plants and, generally, is composed of the five subunits SCAR/WAVE, PIR121, NAP125, BRICK and ABI. In plants, four of the five subunits have been shown to participate in trichome and pavement morphogenesis. Plant ABI‐like proteins (ABIL), however, which constitute a small four‐member protein family in Arabidopsis thaliana, have not been characterized functionally, so far. Here we demonstrate that microRNA knock‐down of the ABIL3 gene leads to a distorted trichome phenotype reminiscent of ARP2/3 mutant phenotypes and consistent with a crucial role of the ABIL3 protein in an ARP2/3‐activating SCAR/WAVE complex. In contrast to ARP2/3 mutants, however, the ABIL3 knock‐down stimulated cell elongation in the root, indicating distinct functions of the ABIL3 protein in different tissues. Furthermore, we provide evidence that ABIL3 associates with microtubules in vivo, opening up the intriguing possibility that ABI‐like proteins have a function in linking SCAR/WAVE‐dependent actin nucleation with organization of the microtubule cytoskeleton. 相似文献
39.
Brian S. Sproat Barbro Beijer Peter Rider Philippe Neuner 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):651-653
Abstract Modified building blocks have been synthesised and used to prepare 5′- amino and 5′-mercapto-oligodeoxyribonucleotides. Subsequent labelling with fluorophores or metal cluster derivatives generates a range of very useful probes. 相似文献
40.
Vanessa Drendel Bianca Heckelmann Christoph Schell Lucas Kook Martin L. Biniossek Martin Werner Cordula A. Jilg Oliver Schilling 《Clinical proteomics》2018,15(1):25