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101.
Franco Chimenti Daniela Secci Adriana Bolasco Paola Chimenti Arianna Granese Simone Carradori Elias Maccioni M. Cristina Cardia Matilde Yáñez Francisco Orallo Stefano Alcaro Francesco Ortuso Roberto Cirilli Rosella Ferretti Simona Distinto Johannes Kirchmair Thierry Langer 《Bioorganic & medicinal chemistry》2010,18(14):5063-5070
The present study reports on synthesis in high yields (70–99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1–45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds. 相似文献
102.
Sudano MJ Paschoal DM Rascado Tda S Magalhães LC Crocomo LF de Lima-Neto JF Landim-Alvarenga Fda C 《Theriogenology》2011,75(7):1211-1220
The objective was to evaluate supplementation of fetal calf serum (FCS) and phenazine ethosulfate (PES), a metabolic regulator that inhibits fatty acid synthesis, in culture media during in vitro production (IVP) of bovine embryos. Taking oocyte fertilization (n = 4,320) as Day 0, four concentrations of FCS (0, 2.5, 5, and 10%) and three periods of exposure to PES (without addition—Control; after 60 h—PES Day 2.5 of embryo culture; and after 96 h—PES Day 4) were evaluated. Increasing FCS concentration in the culture media enhanced lipid accumulation (P < 0.05), increased apoptosis in fresh (2.5%: 19.1 ± 1.8 vs 10%: 28.4 ± 2.3, P < 0.05; mean ± SEM) and vitrified (2.5%: 42.8 ± 2.7 vs 10%: 69.2 ± 3.4, P < 0.05) blastocysts, and reduced blastocoele re-expansion after vitrification (2.5%: 81.6 ± 2.5 vs 10%: 67.3 ± 3.5, P < 0.05). The addition of PES in culture media, either from Days 2.5 or 4, reduced lipid accumulation (P < 0.05) and increased blastocoele re-expansion after vitrification (Control: 72.0 ± 3.0 vs PES Day 2.5: 79.9 ± 2.8 or PES Day 4: 86.2 ± 2.4, P < 0.05). However, just the use of PES from D4 reduced apoptosis in vitrified blastocysts (Control: 52.0 ± 3.0 vs PES Day 4: 39.2 ± 2.4, P < 0.05). Independent of FCS withdrawal or PES addition to culture media, the in vivo control group had lesser lipid accumulation, a lower apoptosis rate, and greater cryotolerance (P < 0.05). The increased lipid content was moderately correlated with apoptosis in vitrified blastocysts (r = 0.64, P = 0.01). In contrast, the increased apoptosis in fresh blastocysts was strongly correlated with apoptosis in vitrified blastocysts (r = 0.94, P < 0.0001). Therefore, using only 2.5% FCS and the addition of PES from Day 4, increased the survival of IVP embryos after vitrification. Moreover, embryo quality, represented by the fresh apoptosis rate, was better than lipid content for predicting embryo survival after vitrification. 相似文献
103.
Daniela S. Carneiro-Torres Inês Cordeiro Ana Maria Giulietti Paul E. Berry Ricarda Riina 《Brittonia》2011,63(1):122-132
While conducting a floristic inventory of Croton from the Brazilian Caatinga, three new species were discovered. Croton arenosus, Croton glandulosobracteatus, and Croton harleyi are described and illustrated here. Based on morphological characters, Croton glandulosobracteatus is proposed to belong to section Barhamia, and C. arenosus and C. harleyi to section Geiseleria. 相似文献
104.
Individual mouse strains differ significantly in terms of behavior and cognitive function. Strain-specific variation of metabolic
protein levels in the hippocampus among various commonly used mouse strains, however, has not been investigated yet. A proteomic
approach based on two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry [high capacity ion trap (HCT)]
has been chosen to address this question by determining strain-dependent levels of metabolic proteins in hippocampal tissue
of four inbred and one outbred mouse strain. Statistical analysis of protein spots on 2-DE gels of the individual strains
(n = 10) revealed significant strain-dependent differences in densities of 39 spots. Subsequent HCT analysis led to the identification
of 22 different metabolic proteins presenting with differential protein levels among the five mouse strains investigated.
Among those are proteins concerned with the metabolism of amino acid, nucleic acid, carbohydrate and energy. Moreover, proteins
known to play a pivotal role in the processes of learning and memory, such as calcium/calmodulin-dependent protein kinase type II alpha chain, were found to present with significant inter-strain variability, which is also in agreement with our previous reports. Strain-specific
protein levels of metabolic proteins in the mouse hippocampus may provide some insight into the molecular underpinnings and
genetic determination of strain-dependent neuronal function. Furthermore, data presented herein emphasize the significance
of the genetic background for the analysis of metabolic pathways in the hippocampus in wild-type mice as well as in gene-targeting
experiments. 相似文献
105.
Vasiliu D Razi N Zhang Y Jacobsen N Allin K Liu X Hoffmann J Bohorov O Blixt O 《Carbohydrate research》2006,341(10):1447-1457
Poly-N-acetyllactosamines (pLNs) are common terminal sugars of many N- and O-linked glycan structures present in glycoproteins and glycolipids. Utilizing various glycosyltransferases, we developed new and efficient chemoenzymatic methods for the synthesis of pLNs in gram-scale. Specifically, the use of sialyltransferases and fucosyltransferases enabled us to synthesize and purify 24 blood group and tumor-associated pLN derivatives with alpha-(2-->3)- and alpha-(2-->6)-linked sialic acid, as well as with alpha-(1-->2)- and alpha-(1-->3)-linked fucose. All synthesized derivatives were linked to a short 2-azidoethyl spacer for further modification. 相似文献
106.
Ng CA Hunter MJ Perry MD Mobli M Ke Y Kuchel PW King GF Stock D Vandenberg JI 《PloS one》2011,6(1):e16191
The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS) domain (residues 26-135) as well as an amphipathic α-helix (residues 13-23) and an initial unstructured segment (residues 2-9). Deletion of residues 2-25, only the unstructured segment (residues 2-9) or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel. 相似文献
107.
CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers 总被引:1,自引:0,他引:1
Filaci G Fenoglio D Fravega M Ansaldo G Borgonovo G Traverso P Villaggio B Ferrera A Kunkl A Rizzi M Ferrera F Balestra P Ghio M Contini P Setti M Olive D Azzarone B Carmignani G Ravetti JL Torre G Indiveri F 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(7):4323-4334
Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8+ CD28- T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8+ CD28- T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4+ CD25+ T regulatory lymphocytes associate with CD8+ CD28- T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer. 相似文献
108.
Daniele De Simone Lorella D’Amico Daniela Bressanin Emma Motta Tiziana Annesi 《Mycological Progress》2011,10(3):301-306
Thirteen isolates of Inonotus rickii/Ptychogaster cubensis, from different geographic provenances, were analyzed by sequencing ITS1, ITS 2 and 5,8S ribosomal RNA region. A phylogenetic
tree, also including sequences available in Genbank database, showed that the strains enclosed in this study fall into two
well-separated groups, one formed by isolates from Florida (USA) and the other one by isolates from Europe, Argentina and
China. Differences were also highlighted on the growth rate of mycelial cultures at different temperatures. In fact, although
the tested isolates generally attained the best growth at 30°C, isolates from Europe seem well adapted to higher temperatures
and went on growing at 40°C whilst the growth of isolates from Florida significantly decreased at 35°C. Since the teleomorph
I. rickii was never detected in Florida, and in this study noticeable differences were detected by analysis of ITS region, the existence
of two possible distinct species, not discriminated solely on the basis of morphological characters, could be suggested. 相似文献
109.
Dissecting the contributions of GC content and codon usage to gene expression in the model alga Chlamydomonas reinhardtii
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Rouhollah Barahimipour Daniela Strenkert Juliane Neupert Michael Schroda Sabeeha S. Merchant Ralph Bock 《The Plant journal : for cell and molecular biology》2015,84(4):704-717
The efficiency of gene expression in all organisms depends on the nucleotide composition of the coding region. GC content and codon usage are the two key sequence features known to influence gene expression, but the underlying molecular mechanisms are not entirely clear. Here we have determined the relative contributions of GC content and codon usage to the efficiency of nuclear gene expression in the unicellular green alga Chlamydomonas reinhardtii. By comparing gene variants that encode an identical amino acid sequence but differ in their GC content and/or codon usage, we show that codon usage is the key factor determining translational efficiency and, surprisingly, also mRNA stability. By contrast, unfavorable GC content affects gene expression at the level of the chromatin structure by triggering heterochromatinization. We further show that mutant algal strains that permit high‐level transgene expression are less susceptible to epigenetic transgene suppression and do not establish a repressive chromatin structure at the transgenic locus. Our data disentangle the relationship between GC content and codon usage, and suggest simple strategies to overcome the transgene expression problem in Chlamydomonas. 相似文献
110.