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951.
Judit Kocsis Balázs Madaras Éva Katalin Tóth George Füst Zoltán Prohászka 《Cell stress & chaperones》2010,15(2):143-151
Many findings indicate that measuring the serum concentration of soluble 70-kD heat shock protein (soluble HSP70) may provide
important information in cardiovascular, inflammatory, and pregnancy-related diseases; however, only scarce data are available
in cancer. Therefore, using a commercial ELISA kit, we measured soluble HSP70 concentration in the sera of 179 patients with
colorectal cancer. We investigated the relationship between soluble HSP70 concentration and mortality, during 33.0 (24.4–44.0) months
long follow-up. High (>1.65 pg/ml, median concentration) soluble HSP70 level was a significant (hazard ratio: 1.88 (1.20–2.96,
p = 0.005) predictor of mortality during the follow-up period. When we compared the soluble HSP70 levels in patients with non-resected
primary tumors as compared to those who were recruited into the study 4–6 weeks after the tumor resection they were found
to be significantly (p = 0.020) higher in the former group. Since the patients with non-resected primary tumors had also distant metastasis and
died early, we limited the further analysis to 142 patients with no distant metastasis at the beginning of the follow-up.
This association remained significant even after multiple Cox-regression analysis had been performed to adjust the data for
age and sex (p = 0.028); age, sex, and TNM-T stage (p = 0.041); age, sex, and TNM-N stage (p = 0.021); age, sex, and histological grade (p = 0.023); or age, sex, and tumor localization (p = 0.029). Further analysis showed that the significant association between high HSP70 levels and poor survival is in the
strongest in the group of <70-year-old female patients (HR: 5.52 (2.02-15.15), p = 0.001), as well as in those who were in a less advanced stage of the disease at baseline. These novel findings indicate
that the serum level of soluble HSP70 might prove a useful, stage-independent prognostic marker in colorectal cancer without
distant metastasis. 相似文献
952.
The release of fatty acids from membrane glycerolipids has been implicated in a variety of cellular processes, but the enzymes involved and their regulation are poorly understood in plants. One large group of acyl-hydrolyzing enzymes is structurally related to patatins. Patatins are potato tuber proteins with acyl-hydrolyzing activity, and the patatin catalytic domain is widely spread in bacterial, yeast, plant and animal enzymes. Recent results have indicated that patatin-related enzymes are involved in different cellular functions, including plant responses to auxin, elicitors or pathogens, and abiotic stresses and lipid mobilization during seed germination. In this review, we highlight recent developments regarding these enzymes and propose the nomenclature pPLA for the patatin-related phospholipase A enzyme. 相似文献
953.
Massimiliano Virgilio Thierry Backeljau Bruno Nevado Marc De Meyer 《BMC bioinformatics》2010,11(1):206
Background
Previous studies on insect DNA barcoding provide contradictory results and suggest not consistent performances across orders. This work aims at providing a general evaluation of insect DNA barcoding and "mini-barcoding" by performing simulations on a large database of 15,948 DNA barcodes. We compared the proportions of correctly identified queries across a) six insect orders (Coleoptera, Diptera, Hemiptera, Hymenoptera, Lepidoptera and Orthoptera), b) four identification criteria (Best Match: BM; Best Close Match: BCM; All Species Barcodes: ASB; tree-based identification: NJT), and c) reference databases with different taxon coverage (100, 500, 1,000, 1,500 and 1,995 insect species). 相似文献954.
Hoffmann T Bös M Stadler H Schnider P Hunkeler W Godel T Galley G Ballard TM Higgins GA Poli SM Sleight AJ 《Bioorganic & medicinal chemistry letters》2006,16(5):1362-1365
The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK(1)) receptor antagonists is described. The evaluation of this class is briefly outlined, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration. 相似文献
955.
Laurent Noël Céline Huynh-Delerme Thierry Guérin Hélène Huet Jean-Marc Frémy Martine Kolf-Clauw 《Biometals》2006,19(5):473-481
The influence of long-term exposure to cadmium (Cd) on essential minerals was investigated using a Caco-2 TC7 cells and a
multi-analytical tool: microwave digestion and inductively coupled plasma mass spectrometry. Intracellular levels, effects
on cadmium accumulation, distribution, and reference concentration ranges of the following elements were determined: Na, Mg,
Ca, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mo, and Cd. Results showed that Caco-2 TC7 cells incubated long-term with cadmium concentrations
ranging from 0 to 10 μmol Cd/l for 5 weeks exhibited a significant increase in cadmium accumulation. Furthermore, this accumulation was more marked
in cells exposed long-term to cadmium compared with controls, and that this exposure resulted in a significant accumulation
of copper and zinc but not of the other elements measured. Interactions of Cd with three elements: zinc, copper, and manganese
were particularly studied. Exposed to 30 μmol/l of the element, manganese showed the highest inhibition and copper the lowest on cadmium intracellular accumulation
but Zn, Cu, and Mn behave differently in terms of their mutual competition with Cd. Indeed, increasing cadmium in the culture
medium resulted in a gradual and significant increase in the accumulation of zinc. There was a significant decrease in manganese
from 5 μmol Cd/l exposure, and no variation was observed with copper. 相似文献
956.
In vitro oxidative metabolism study of (-)-rhazinilam 总被引:1,自引:0,他引:1
Décor A Bellocq D Thoison O Lekieffre N Chiaroni A Ouazzani J Cresteil T Guéritte F Baudoin O 《Bioorganic & medicinal chemistry》2006,14(5):1558-1564
Metabolism studies were conducted in order to investigate the reasons for the in vivo lack of activity of (-)-rhazinilam 1, an original poison of the mitotic spindle. Bioconversion by Beauveria bassiana strains, rat and human liver microsomes allowed the identification of metabolites 2, 3, and 4 oxidized in positions 3 and 5 of rhazinilam. Further experiments indicated that CYP2B6 was the main CYP responsible for the oxidation of 1 by human liver microsomes. All isolated metabolites were markedly less active than rhazinilam in vitro, which might explain its in vivo inactivity. 相似文献
957.
Botulinum neurotoxins types B, D, F, and G, and tetanus neurotoxin inhibit vesicular fusion via proteolytic cleavage of VAMP/Synaptobrevin, a core component of the membrane fusion machinery. Thus, these neurotoxins became widely used tools for investigating vesicular trafficking routes. Except for VAMP-1, VAMP-2, and Cellubrevin, no other member of the VAMP family represents a substrate for these neurotoxins. The molecular basis for this discrepancy is not known. A 34 amino acid residue segment of VAMP-2 was previously suggested to mediate the interaction with botulinum neurotoxin B, but the validity of the data was later questioned. To check whether this segment alone controls the susceptibility toward botulinum neurotoxin B, it was used to replace the corresponding segment in TI-VAMP. The resulting VAMP hybrid and VAMP-2 were hydrolysed at virtually identical rates. Resetting the VAMP-2 portion in the hybrid from either end to TI-VAMP residues gradually reduced the cleavability. A hybrid encompassing merely the VAMP-2 segment 71-80 around the Gln76/Phe77 scissile bond was still hydrolysed, albeit at a approximately tenfold lower cleavage rate. The contribution of each non-conserved amino acid of the whole 34-mer segment to the interaction was investigated employing VAMP-2. We find that the eight non-conserved residues of the 71-80 segment are all necessary for efficient cleavage. Mutation of an additional six residues located upstream and downstream of this segment affects substrate hydrolysis as well. Vice versa, a readily cleavable TI-VAMP molecule requires at the least the replacement of Ile158, Thr161, and the section 165-174 by Asp64, Ala67, and the 71-80 segment of VAMP-2, respectively. However, the insensitivity of TI-VAMP to botulinum neurotoxin B relies on at least 12 amino acid changes versus VAMP-2. These are scattered along an interface of 22 amino acid residues in length. 相似文献
958.
Delatte T Umhang M Trevisan M Eicke S Thorneycroft D Smith SM Zeeman SC 《The Journal of biological chemistry》2006,281(17):12050-12059
The aim of this work was to understand the initial steps of starch breakdown inside chloroplasts. In the non-living endosperm of germinating cereal grains, starch breakdown is initiated by alpha-amylase secreted from surrounding cells. However, loss of alpha-amylase from Arabidopsis does not prevent chloroplastic starch breakdown (Yu, T.-S., Zeeman, S. C., Thorneycroft, D., Fulton, D. C., Dunstan, H., Lue, W.-L., Hegemann, B., Tung, S.-Y., Umemoto, T., Chapple, A., Tsai, D.-L., Wang, S.-M, Smith, A. M., Chen, J., and Smith, S. M. (2005) J. Biol. Chem. 280, 9773-9779), implying that other enzymes must attack the starch granule. Here, we present evidence that the debranching enzyme isoamylase 3 (ISA3) acts at the surface of the starch granule. Atisa3 mutants have more leaf starch and a slower rate of starch breakdown than wild-type plants. The amylopectin of Atisa3 contains many very short branches and ISA3-GFP localizes to granule-like structures inside chloroplasts. We suggest that ISA3 removes short branches from the granule surface. To understand how some starch is still degraded in Atisa3 mutants we eliminated a second debranching enzyme, limit dextrinase (pullulanase-type). Atlda mutants are indistinguishable from the wild type. However, the Atisa3/Atlda double mutant has a more severe starch-excess phenotype and a slower rate of starch breakdown than Atisa3 single mutants. The double mutant accumulates soluble branched oligosaccharides (limit dextrins) that are undetectable in the wild-type and the single mutants. Together these results suggest that glucan debranching occurs primarily at the granule surface via ISA3, but in its absence soluble branched glucans are debranched in the stroma via limit dextrinase. Consistent with this model, chloroplastic alpha-amylase AtAMY3, which could release soluble branched glucans, is induced in Atisa3 and in the Atisa3/Atlda double mutant. 相似文献
959.
Loucif AJ Bonnavion P Macri B Golmard JL Boni C Melfort M Leonard G Lesch KP Adrien J Jacquin TD 《Journal of neurobiology》2006,66(13):1475-1488
Agonists at G-protein-coupled receptors in neurons of the dorsal raphe nucleus (DRN) of knock-out mice devoid of the serotonin transporter (5-HTT(-/-)) exhibit lower efficacy to inhibit cellular discharge than in wild-type counterparts. Using patch-clamp whole-cell recordings, we found that a G-protein-gated inwardly rectifying potassium (GIRK) current is involved in the inhibition of spike discharge induced by 5-HT1A agonists (5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT); 50 nM-30 microM) in both wild-type and 5-HTT(-/-) female and male mice. These effects were mimicked by 5'-guanylyl-imido-diphosphate (Gpp(NH)p; 400 microM) dialysis into cells with differences between genders. The 5-HTT(-/-) knock-out mutation reduced the current density induced by Gpp(NH)p in females but not in males. These data suggest that the decreased response of 5-HT1A receptors to agonists in 5-HTT(-/-) mutants reflects notably alteration in the coupling between G-proteins and GIRK channels in females but not in males. Accordingly, gender differences in central 5-HT neurotransmission appear to depend-at least in part-on sex-related variations in corresponding receptor-G protein signaling mechanisms. 相似文献
960.
Ana M. González Thierry C. Marcel Zuzana Kohutova Piet Stam C. Gerard van der Linden Rients E. Niks 《PloS one》2010,5(8)