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排序方式: 共有261条查询结果,搜索用时 31 毫秒
71.
Gentile G Merlo G Pozzan A Bernasconi G Bax B Bamborough P Bridges A Carter P Neu M Yao G Brough C Cutler G Coffin A Belyanskaya S 《Bioorganic & medicinal chemistry letters》2012,22(5):1989-1994
5-Aryl-4-carboxamide-1,3-oxazoles are a novel, potent and selective series of GSK-3 inhibitors. The optimization of the series to yield compounds with cell activity and brain permeability is described. 相似文献
72.
Sfondrini L Rossini A Besusso D Merlo A Tagliabue E Mènard S Balsari A 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(11):6624-6630
Flagellin, the structural protein subunit of the bacterial flagellum, is specifically recognized by TLR-5 and has potent immunomodulatory effects. The antitumor effects of purified Salmonella typhimurium flagellin were evaluated in mice transplanted s.c. with a weakly immunogenic murine tumor or with its variant stably transfected to express the highly antigenic human HER-2 oncoprotein. Peritumoral administration of flagellin 8-10 days after tumor implantation did not affect the growth rate of the weakly immunogenic tumor but significantly inhibited growth of the antigenic variant tumor. In contrast, flagellin administered at the time of implantation of the antigenic tumor led to accelerated tumor growth. These contrasting effects of flagellin on tumor growth correlated with the type of immune response induced; i.e., late flagellin administration was associated with an increased IFN-gamma:IL-4 ratio and the decreased frequency of CD4+CD25+ T regulatory cells, whereas flagellin treatment at the time of tumor implantation decreased the IFN-gamma:IL-4 ratio and increased CD4+CD25+ T cell frequency. When the early flagellin treatment was combined with administration of CpG-containing oligodeoxynucleotides, tumor growth was completely suppressed, indicating synergy between flagellin and CpG-containing oligodeoxynucleotides. Together, these data provide evidence that flagellin can have contrasting effects on tumor growth. 相似文献
73.
Fiorella Fontana Pasquale Bernardi Carmine Pizzi Santi Spampinato Andrea Bedini Emilio Merlo Pich 《Peptides》2009,30(9):1705-1709
The aim of our study was to evaluate the effects of repeated episodes of angina and induced myocardial ischemia on plasma nociceptin/orphanin FQ (N/OFQ) levels. Patients with unstable angina (23 with new onset severe angina or accelerated angina and 18 with subacute angina at rest) who had had repeated spontaneous episodes of chest pain in the last week before the study underwent myocardial perfusion single-photon emission computed tomography using adenosine infusion. Twenty subjects without clinical symptoms of angina matched for age, sex and cardiac risk factors served as a control group. N/OFQ levels were significantly (P < 0.01) higher in the patients (15.2 ± 2.1 pg/ml) than in the control group (8.5 ± 2.6 pg/ml). Blood pressure and heart rate did not significantly differ. All patients showed transient adenosine infusion myocardial ischemia that did not induce chest pain or significantly modify plasma N/OFQ levels or hemodynamic parameters. Our findings show that unstable angina is associated with a significant increase in circulating N/OFQ levels unrelated to intervening transient myocardial ischemia or hemodynamic changes. This increase is probably related to the chest pain repeatedly occurring in the course of coronary artery disease, but absent during transient adenosine-induced myocardial ischemia. 相似文献
74.
Serdar Korur Roland M. Huber Balasubramanian Sivasankaran Michael Petrich Pier Morin Jr Brian A. Hemmings Adrian Merlo Maria Maddalena Lino 《PloS one》2009,4(10)
Cancers are driven by a population of cells with the stem cell properties of self-renewal and unlimited growth. As a subpopulation within the tumor mass, these cells are believed to constitute a tumor cell reservoir. Pathways controlling the renewal of normal stem cells are deregulated in cancer. The polycomb group gene Bmi1, which is required for neural stem cell self-renewal and also controls anti-oxidant defense in neurons, is upregulated in several cancers, including medulloblastoma. We have found that Bmi1 is consistently and highly expressed in GBM. Downregulation of Bmi1 by shRNAs induced a differentiation phenotype and reduced expression of the stem cell markers Sox2 and Nestin. Interestingly, expression of glycogen synthase kinase 3 beta (GSK3β), which was found to be consistently expressed in primary GBM, also declined. This suggests a functional link between Bmi1 and GSK3β. Interference with GSK3β activity by siRNA, the specific inhibitor SB216763, or lithium chloride (LiCl) induced tumor cell differentiation. In addition, tumor cell apoptosis was enhanced, the formation of neurospheres was impaired, and clonogenicity reduced in a dose-dependent manner. GBM cell lines consist mainly of CD133-negative (CD133-) cells. Interestingly, ex vivo cells from primary tumor biopsies allowed the identification of a CD133- subpopulation of cells that express stem cell markers and are depleted by inactivation of GSK3β. Drugs that inhibit GSK3, including the psychiatric drug LiCl, may deplete the GBM stem cell reservoir independently of CD133 status. 相似文献
75.
Isabella Campanini Andrea Merlo Dario Farina 《Journal of electromyography and kinesiology》2009,19(1):22-29
Motor unit properties were analyzed in patients with upper motor neuron syndrome (UMNS). Multi-channel surface electromyographic (EMG) signals were recorded for 300 s from the biceps brachii muscle of seven male subacute patients (time from lesion, mean ± SE, 4.9 ± 1.0 months). In three patients, both arms were investigated, leading to 10 recorded muscles. Patients were analyzed in rest-like condition with motor units activated due to pathological muscle overactivity. For a total of 12 motor units, the complete discharge pattern was extracted from EMG decomposition. Interpulse interval variability was 7.8 ± 0.9%. At minimum discharge rate (6.4 ± 0.4 pulses per second, pps), conduction velocity was smaller than at maximum discharge rate (12.0 ± 0.9 pps) in all motor units (3.60 ± 0.21 m/s vs. 3.84 ± 0.20 m/s). Conduction velocity changed by 1.35 ± 0.48% (different from zero, P < 0.01) for each increase of 1 pps in discharge rate. It was concluded that conduction velocity of low-threshold motor units in subacute patients with UMNS had similar values as reported in healthy subjects and was positively correlated to instantaneous discharge rate (velocity recovery function of muscle fibers). 相似文献
76.
An optimal protocol for cat semen cryopreservation has not yet been defined. Addition of Equex STM Paste has been tested for epididymal cat spermatozoa but not for ejaculated cat spermatozoa. Furthermore, the effect of Equex STM Paste on fertilizing ability of cryopreserved semen has never been evaluated in that species. Therefore, the aims of the current study were to investigate if addition of Equex STM Paste to a freezing extender for electroejaculated cat (Felis catus) semen would improve postthaw sperm quality and if sperm fertilizing ability after cryopreservation with or without Equex STM Paste was preserved. Semen was collected by electroejaculation and frozen in a Tris-glucose-citrate egg yolk extender supplemented with (0.5% vol/vol) or without Equex STM Paste. In Experiment 1, sperm motility, membrane integrity, and acrosomal status were determined immediately after collection and at 0, 3, and 6 h postthaw. In Experiment 2, frozen semen from the two groups was used for in vitro fertilization (IVF) of in vitro-matured cat oocytes. Cleavage rate was recorded 30 h after IVF, and embryo development was evaluated on Days 6 and 7 of culture. In Experiment 1, the rate of motile spermatozoa after freezing-thawing was higher when Equex STM Paste was added to the freezing extender, but progressive motility score was not influenced (P > 0.05). Sperm membrane integrity was positively affected (P < 0.05) by the addition of the detergent. Intact acrosomes after thawing were similar (P > 0.05) between groups. Even if the decreasing rates of motility and membrane integrity were more rapid in presence of Equex than those in controls, total motility and sperm viability were similar at 3 and 6 h after thawing (P > 0.05). In Experiment 2, there was no difference in fertilizing ability and embryo development between the two groups (P > 0.05). The results of this study demonstrate that the addition of Equex STM Paste in the freezing extender avoids the loss of motile spermatozoa and maintains fertilizing ability of frozen-thawed spermatozoa. 相似文献
77.
María Úbeda-Manzanaro Manuel A. Merlo José L. Palazón Ismael Cross Carmen Sarasquete Laureana Rebordinos 《Genetica》2010,138(7):787-794
In the present study dual-colour fluorescence in situ hybridization (FISH) was performed to study the chromosomal distribution
of 18S and 5S rDNAs, (GATA)n and 5S rDNA, and U2 snRNA and 18S rDNA in four species of Batrachoididae family: Amphichthys cryptocentrus, Batrachoides manglae, Porichthys plectrodon and Thalassophryne maculosa. The 18S rDNA signals were present in only one pair of chromosomes in all the four Batrachoididae species. The 5S rDNA was
mapped on one pair of chromosomes, except in B. manglae, which showed a hybridization signal in two pairs. The two ribosomal genes are located on different chromosome pairs, except
in A. cryptocentrus, in which they appear co-located. In all the cases, the (GATA)n probe produced disperse hybridization signals in all four species. The U2 snRNA signals appear very widely scattered in A. cryptocentrus, P. plectrodon, but show a degree of clustering in a specific chromosome pair in B. manglae. In T.
maculosa, they are thinly dispersed and strong hybridization signals are observed co-located to the 18S rDNA-bearing chromosomes.
Finally, a double-colour FISH with U2 snRNA and 5S rDNA probes was performed in B. manglae, and this showed that these genes were not co-located. These results have been compared with those from another Batrachoididae
species, and evolutive processes of these species are discussed. 相似文献
78.
Discovery and structure–activity relationship of a novel spirocarbamate series of NPY Y5 antagonists
Colin P. Leslie Jonathan Bentley Matteo Biagetti Stefania Contini Romano Di Fabio Daniele Donati Thorsten Genski Sebastien Guery Angelica Mazzali Giancarlo Merlo Domenica A. Pizzi Fabiola Sacco Catia Seri Michela Tessari Laura Zonzini Laura Caberlotto 《Bioorganic & medicinal chemistry letters》2010,20(20):6103-6107
A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5]decan-2-one derivatives was identified with potent NPY Y5 antagonist activity. Optimization of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar Y5 activity with metabolic stability, oral bioavailability, brain penetration and strong preclinical profile for development. Both compounds significantly inhibited the food intake induced by a Y5 selective agonist with minimal effective doses of 3 mg/kg po. 相似文献
79.
L. Mesin E. Merlo R. Merletti C. Orizio 《Journal of electromyography and kinesiology》2010,20(4):580-589
This work investigated motor unit (MU) recruitment during transcutaneous electrical stimulation (TES) of the tibialis anterior (TA) muscle, using experimental and simulated data. Surface electromyogram (EMG) and torque were measured during electrically-elicited contractions at different current intensities, on eight healthy subjects.EMG detected during stimulation (M-wave) was simulated selecting the elicited MUs on the basis of: (a) the simulated current density distribution in the territory of each MU and (b) the excitation threshold characteristic of the MU. Exerted force was simulated by adding the contribution of each of the elicited MUs. The effects of different fat layer thickness (between 2 and 8 mm), different distributions of excitation thresholds (random excitation threshold, higher threshold for larger MUs or smaller MUs), and different MU distributions within the muscle (random distribution, larger MU deeper in the muscle, smaller MU deeper) on EMG variables and torque were tested.Increase of the current intensity led to a first rapid increase of experimental M-wave amplitude, followed by a plateau. Further increases of the stimulation current determined an increase of the exerted force, without relevant changes of the M-wave. Similar results were obtained in simulations.Rate of change of conduction velocity (CV) and leading coefficient of the second order polynomial interpolating the force vs. stimulation level curve were estimated as a function of increasing current amplitudes. Experimental data showed an increase of estimated CV with increasing levels of the stimulation current (for all subjects) and a positive leading coefficient of force vs. stimulation current curve (for five of eight subjects). Simulations matched the experimental results only when larger MUs were preferably located deeper in the TA muscle (in line with a histochemical study). Marginal effect of MU excitation thresholds was observed, suggesting that MUs closer to the stimulation electrode are recruited first during TES regardless of their excitability. 相似文献
80.
Mohammad Tauqeer Alam Maria Elena Merlo Eriko Takano Rainer Breitling 《Molecular phylogenetics and evolution》2010,54(3):763-772
MotivationStreptomyces is one of the best-studied genera of the order Actinomycetales due to its great importance in medical science, ecology and the biotechnology industry. A comprehensive, detailed and robust phylogeny of Streptomyces and its relatives is needed for understanding how this group emerged and maintained such a vast diversity throughout evolution and how soil-living mycelial forms (e.g., Streptomyces s. str.) are related to parasitic, unicellular pathogens (e.g., Mycobacterium tuberculosis) or marine species (e.g., Salinispora tropica). The most important application area of such a phylogenetic analysis will be in the comparative re-annotation of genome sequences and the reconstruction of Streptomyces metabolic networks for biotechnology.MethodsClassical 16S-rRNA-based phylogenetic reconstruction does not guarantee to produce well-resolved robust trees that reflect the overall relationship between bacterial species with widespread horizontal gene transfer. In our study we therefore combine three whole genome-based phylogenies with eight different, highly informative single-gene phylogenies to determine a new robust consensus tree of 45 Actinomycetales species with completely sequenced genomes.ResultsNone of the individual methods achieved a resolved phylogeny of Streptomyces and its relatives. Single-gene approaches failed to yield a detailed phylogeny; even though the single trees are in good agreement among each other, they show very low resolution of inner branches. The three whole genome-based methods improve resolution considerably. Only by combining the phylogenies from single gene-based and genome-based approaches we finally obtained a consensus tree with well-resolved branches for the entire set of Actinomycetales species. This phylogenetic information is stable and informative enough for application to the system-wide comparative modeling of bacterial physiology. 相似文献