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181.
Vidal A Sabatini M Rolland-Valognes G Renard P Madelmont JC Mounetou E 《Bioorganic & medicinal chemistry》2007,15(6):2368-2374
Among other non-antibiotic properties, tetracyclines inhibit matrix metalloproteinases and are currently under study for the treatment of osteoarthritis. Quaternary ammonium conjugates of tetracyclines were synthesized by direct alkylation of the amine function at the 4-position with methyl iodide. When tested in vitro, they inhibited cytokine-induced MMP expression to a lesser extent than parent tetracyclines. This was compensated by an improved inhibition of MMP catalytic activity. Since inhibition of collagen degradation was maintained these derivatives could be potent drug candidates for cartilage-targeted chondroprotective treatment. 相似文献
182.
Fatty acid composition of the amphipod Dikerogammarus villosus: feeding strategies and trophic links
Maazouzi C Masson G Izquierdo MS Pihan JC 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,147(4):868-875
Fatty acid (FA) compositions were determined for the invader amphipod Dikerogammarus villosus collected from July to September 2002, in an overheated, high-conductivity dammed reservoir in north-eastern France. Predominant fatty acids were the polyunsaturated fatty acids (PUFA): eicosapentaenoic acid (EPA), linoleic acid (LA), arachidonic acid (ARA), linolenic acid (LNA) together with the monounsaturated fatty acid 18:1omega9 and the saturated fatty acid 16:0. FA markers indicated that available food was constituted of incompletely degraded phytodetritus and terrestrial inputs, as well as animal remains. PUFA contents depended on the diet and the capacity of animals to desaturate and elongate LNA and LA in long chain PUFA as EPA and ARA respectively. Based on their FA compositions, we showed that gammarids represent naturally-occurring freshwater sources of essential PUFA, and could play a fundamental role in pelagic-benthic coupling and energy recycling in the ecosystem. The complexity of the feeding strategies of D. villosus--detritivorous, omnivorous, carnivorous--makes this species efficient at exploiting different components of the available food and may be a key factor in its high invasive success. 相似文献
183.
Radiolabeled somatostatin analogues have been successfully used for targeted radiotherapy and for imaging of somatostatin receptor (sst1-5)-positive tumors. Nevertheless, these analogues are subject to improving their tumor-to-nontarget ratio to enhance their diagnostic or therapeutic properties, preventing nephrotoxicity. In order to understand the influence of lipophilicity and charge on the pharmacokinetic profile of [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)]-somatostatin-based radioligands such as [DOTA,1-Nal3]-octreotide (DOTA-NOC), different spacers (X) based on 8-amino-3,6-dioxaoctanoic acid (PEG2), 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG4), N-acetyl glucosamine (GlcNAc), triglycine, beta-alanine, aspartic acid, and lysine were introduced between the chelator DOTA and the peptide NOC. All DOTA-X-NOC conjugates were synthesized by Fmoc solid-phase synthesis. The partition coefficient (log D) at pH = 7.4 indicated that higher hydrophilicity than [111In-DOTA]-NOC was achieved with the introduction of the mentioned spacers, except with triglycine and beta-alanine. The high affinity of [InIII-DOTA]-NOC for human sst2 (hsst2) was preserved with the structural modifications, while an overall drop for hsst3 affinity was observed, except in the case of [InIII-DOTA]-beta-Ala-NOC. The new conjugates preserved the good affinity for hsst5, except for [InIII-DOTA]-Asn(GlcNAc)-NOC, which showed decreased affinity. A significant 1.2-fold improvement in the specific internalization rate in AR4-2J rat pancreatic tumor cells (sst2 receptor expression) at 4 h was achieved with the introduction of Asp as a spacer in the parent compound. In sst3-expressing HEK cells, the specific internalization rate at 4 h for [111In-DOTA]-NOC (13.1% +/- 0.3%) was maintained with [111In-DOTA]-beta-Ala-NOC (14.0% +/- 1.8%), but the remaining derivatives showed <2% specific internalization. Biodistribution studies were performed with Lewis rats bearing the AR4-2J rat pancreatic tumor. In comparison to [111In-DOTA]-NOC (2.96% +/- 0.48% IA/g), the specific uptake in the tumor at 4 h p.i. was significantly improved for the 111In-labeled sugar analogue (4.17% +/- 0.46% IA/g), which among all the new derivatives presented the best tumor-to-kidney ratio (1.9). 相似文献
184.
Lamarche F Mével M Montier T Burel-Deschamps L Giamarchi P Tripier R Delépine P Le Gall T Cartier D Lehn P Jaffrès PA Clément JC 《Bioconjugate chemistry》2007,18(5):1575-1582
The DNA compacting properties of polyamines (especially spermine) are well-known, hence the use of spermine as the cationic part in several synthetic DNA carriers. Here, we describe the synthesis of modified spermines, with a "lipophosphoramidate" as the lipidic part, and their use for efficient in vitro transfection. Physicochemical measurements (particle size, zeta potentials, pKa determination) and gel retardation assays were also performed. Theoretical membrane-disrupting ability was established by FRET. Taken together, our results indicate that lipophosphoramidates constitute an interesting alternative to "classical" lipidic parts of cationic lipids used as DNA carriers. 相似文献
185.
Camponova P Baud S Mattras H Duroux-Richard I Bonnafous JC Marie J 《Protein expression and purification》2007,55(2):300-311
The B(2) bradykinin receptor belongs to the G-protein coupled receptor family. Development of new drugs for this important therapeutic target requires structural information on the receptor. The main goal of the present work was to overexpress the human B(2) receptor for future biophysical studies. Different tagged B(2) receptors were engineered and their properties were evaluated by transient expression in HEK293S cells. A B(2) receptor tagged with a hexahistidine at the N-terminus and a nonapeptide at the C-terminus was selected for high expression level and preserved ligand-binding characteristics. First, we generated a HEK293S stable cell line expressing the receptor constitutively at a level of 60pmol/mg of crude membrane protein. However, the decrease of expression level with cell passages led us to express the B(2) receptor in a HEK293S tetracycline-inducible stable cell line. Induction of expression of the B(2) receptor with tetracycline and sodium butyrate led to a level of 100pmol/mg of membrane protein, which is the highest level reported so far for this receptor. The expression level was stable with cell passages and the ligand-binding and signal transduction properties of the receptor were unaltered. The receptor was purified to near homogeneity by solubilization with n-dodecyl-beta-d-maltoside followed by a two-step purification procedure combining hydroxyapatite and immunoaffinity chromatography. Although the purified receptor is not functional, the purification of the B(2) receptor to near homogeneity from a stable cell line overexpressing this receptor pave the way for future structural studies of this receptor. 相似文献
186.
Rekangalt D Verner MC Kües U Walser PJ Marmeisse R Debaud JC Fraissinet-Tachet L 《FEMS microbiology letters》2007,274(1):67-72
The symbiotic basidiomycete Hebeloma cylindrosporum is a model fungal species used to study ectomycorrhizal symbiosis at the molecular level. In order to have a vital marker, we developed a green fluorescent protein (GFP) reporter system efficiently expressed in H. cylindrosporum using the sgfp coding region bordered by two introns fused to the saprophytic basidiomycete Coprinopsis cinerea cgl1 promoter. Expression of this reporter system was tested under different environmental conditions in two transformants, and glucose was shown to repress gfp expression. Such a reporter system will be used in plant-fungus interaction to evaluate sugar supply by the plant to the compatible mycorrhizal symbiont and to compare the expression of various genes of interest in the free-living mycelia, in the symbiotic (mycorrhizas) and the reproductive (fruit bodies) structures formed by H. cylindrosporum. 相似文献
187.
Fouron JC 《Médecine sciences : M/S》2007,23(11):950-956
The new physiological concept: because of the parallel disposition of the fetal ventricles and of their respective arterial outlet, the flow through the aortic isthmus represents the only arterial shunt in the fetal circulation. The low resistance of the placental circulation explains the forward systolic and diastolic flows normally observed through the isthmus. Clinical implications: (1) assessment of individual performances of each ventricle : left ventricle causes forward flow while the right ventricle has a retrograde influence; (2) any changes of flow and/or resistances affecting one of the two fetal arterial systems organized in parallel should influence the flow pattern within the isthmus. Examples : peripheral arterio-venous fistula, increase in placental vascular resistance leading to intra-uterine growth restriction, etc. Conclusion: doppler flow recordings in the fetal aortic isthmus: (1) provides information on the global condition of the fetal cardiocirculatory system; (2) is a good indicator of fetal individual ventricular performance; (3) allows assessment of hemodynamic consequences of abnormalities of the peripheral circulatory systems. 相似文献
188.
Said Aoufouchi Annie De Smet Frédéric Delbos Camille Gelot Ida Chiara Guerrera Jean-Claude Weill Claude-Agnès Reynaud 《Molecular and cellular biology》2015,35(17):3059-3070
Mice derived from the 129 strain have a nonsense codon mutation in exon 2 of the polymerase iota (Polι) gene and are therefore considered Polι deficient. When we amplified Polι mRNA from 129/SvJ or 129/Ola testes, only a small fraction of the full-length cDNA contained the nonsense mutation; the major fraction corresponded to a variant Polι isoform lacking exon 2. Polι mRNA lacking exon 2 contains an open reading frame, and the corresponding protein was detected using a polyclonal antibody raised against the C terminus of the murine Polι protein. The identity of the corresponding protein was further confirmed by mass spectrometry. Although the variant protein was expressed at only 5 to 10% of the level of wild-type Polι, it retained de novo DNA synthesis activity, the capacity to form replication foci following UV irradiation, and the ability to rescue UV light sensitivity in Polι−/− embryonic fibroblasts derived from a new, fully deficient Polι knockout (KO) mouse line. Furthermore, in vivo treatment of 129-derived male mice with Velcade, a drug that inhibits proteasome function, stabilized and restored a substantial amount of the variant Polι in these animals, indicating that its turnover is controlled by the proteasome. An analysis of two xeroderma pigmentosum-variant (XPV) cases corresponding to missense mutants of Polη, a related translesion synthesis (TLS) polymerase in the same family, similarly showed a destabilization of the catalytically active mutant protein by the proteasome. Collectively, these data challenge the prevailing hypothesis that 129-derived strains of mice are completely deficient in Polι activity. The data also document, both for 129-derived mouse strains and for some XPV patients, new cases of genetic defects corresponding to the destabilization of an otherwise functional protein, the phenotype of which is reversible by proteasome inhibition. 相似文献
189.
Modifications of cell wall pectin in tomato cell suspension in response to cadmium and zinc 总被引:1,自引:0,他引:1
Aurélie?Muschitz Catherine?Riou Jean-Claude?Mollet Vincent?Gloaguen Céline?FaugeronEmail author 《Acta Physiologiae Plantarum》2015,37(11):245
Retention of metal cations by the cell wall is a common process found in plants in response to stress induced by the presence of trace metals (TMs). In this study conducted on a tomato cell suspension culture, cadmium (Cd) and zinc (Zn) were added to the medium at maximal concentrations of 0.5 and 2 mM, respectively. We showed that around 50 % of Zn or Cd was confined into the cell wall of tomato cells. Besides, their accumulation in the cell wall increased with the exogenous concentration in the culture medium. Characterization of cell wall pectins showed a decrease in the highly methylesterified pectin fraction whereas the weakly methylesterified pectin remained stable in response to Cd. Moreover, a significant increase in the degree of methylesterification was observed in both fractions. This was probably associated to the reduced pectin methylesterase (PME) activity in the treated cells. Furthermore, linked to a reduction of pectin content we showed a reduced expression of the galacturonosyltransferase QUA1 gene whereas PME1 expression remained unchanged. Taking together, these data strongly suggest that pectin biosynthesis and its modification in the cell wall are strongly regulated in response to TM exposure in tomato cells. 相似文献
190.