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151.
Maria A. Argiriadi Anna M. Ericsson Christopher M. Harris David L. Banach David W. Borhani David J. Calderwood Megan D. Demers Jennifer DiMauro Richard W. Dixon Jennifer Hardman Silvia Kwak Biqin Li John A. Mankovich Douglas Marcotte Kelly D. Mullen Baofu Ni M. Pietras Ramkrishna Sadhukhan Silvino Sousa Medha J. Tomlinson Robert V. Talanian 《Bioorganic & medicinal chemistry letters》2010,20(1):330-333
MK2 is a Ser/Thr kinase of significant interest as an anti-inflammatory drug discovery target. Here we describe the development of in vitro tools for the identification and characterization of MK2 inhibitors, including validation of inhibitor interactions with the crystallography construct and determination of the unique binding mode of 2,4-diaminopyrimidine inhibitors in the MK2 active site. Use of these tools in the optimization of a potent and selective inhibitor lead series is described in the accompanying Letter. 相似文献
152.
The forests surrounding Bossou, Guinea, are home to a small, semi-isolated chimpanzee community studied for over three decades [1]. In 1992, Matsuzawa [2] reported the death of a 2.5-year-old chimpanzee (Jokro) at Bossou from a respiratory illness. The infant's mother (Jire) carried the corpse, mummified in the weeks following death, for at least 27 days. She exhibited extensive care of the body, grooming it regularly, sharing her day- and night-nests with it, and showing distress whenever they became separated. The carrying of infants' corpses has been reported from a number of primate species, both in captivity and the wild [3-7] - albeit usually lasting a few days only - suggesting a phylogenetic continuity for a behavior that is poignant testament to the close mother-infant bond which extends across different primate taxa. In this report we recount two further infant deaths at Bossou, observed over a decade after the original episode but with striking similarities. 相似文献
153.
Erin Milner William McCalmont Jayendra Bhonsle Diana Caridha Dustin Carroll Sean Gardner Lucia Gerena Montip Gettayacamin Charlotte Lanteri ThuLan Luong Victor Melendez Jay Moon Norma Roncal Jason Sousa Anchalee Tungtaeng Peter Wipf Geoffrey Dow 《Bioorganic & medicinal chemistry letters》2010,20(4):1347-1351
Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product profile for malaria chemoprophylaxis while reducing permeability across the blood–brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure–activity relationship for this library of quinoline methanols. 相似文献
154.
Jiang Wu Peter Warren Quazi Shakey Eric Sousa Andrew Hill Terence E. Ryan Tao He 《Proteomics》2010,10(11):2224-2234
Recent advances in MS instrumentation and progresses in phosphopeptide enrichment, in conjunction with more powerful data analysis tools, have facilitated unbiased characterization of thousands of site‐specific phosphorylation events. Combined with stable isotope labeling by amino acids in cell culture metabolic labeling, these techniques have made it possible to quantitatively evaluate phosphorylation changes in various physiological states in stable cell lines. However, quantitative phosphoproteomics in primary cells and tissues remains a major technical challenge due to the lack of adequate techniques for accurate quantification. Here, we describe an integrated strategy allowing for large scale quantitative profiling of phosphopeptides in complex biological mixtures. In this technique, the mixture of proteolytic peptides was subjected to phosphopeptide enrichment using a titania affinity column, and the purified phosphopeptides were subsequently labeled with iTRAQ reagents. After further fractionation by strong‐cation exchange, the peptides were analyzed by LC‐MS/MS on an Orbitrap mass spectrometer, which collects CID and high‐energy collisional dissociation (HCD) spectra sequentially for peptide identification and quantitation. We demonstrate that direct phosphopeptide enrichment of protein digests by titania affinity chromatography substantially improves the efficiency and reproducibility of phosphopeptide proteomic analysis and is compatible with downstream iTRAQ labeling. Conditions were optimized for HCD normalized collision energy to balance the overall peptide identification and quantitation using the relative abundances of iTRAQ reporter ions. Using this approach, we were able to identify 3557 distinct phosphopeptides from HeLa cell lysates, of which 2709 were also quantified from HCD scans. 相似文献
155.
Apuleia Mart., a genus of the Leguminosae native to South America, is revised. Species limits within the genus were tested using
morphometrics and shape analysis of leaflets and fruits. Morphological evidence indicates that although there is great variation
in Apuleia, the genus cannot be reliably separated into different species or infraspecific taxa. Apuleia is monospecific, comprising the single species A. leiocarpa (Vogel) J. F. Macbr. 相似文献
156.
I. García-Ispierto C. Nogareda S. Almería N.M. de Sousa F. López-Gatius 《Theriogenology》2010,74(2):212-220
Q fever is a zoonotic infection caused by Coxiella burnetii that is endemic worldwide. Domestic ruminants are a source of infection for humans. Given the suggestion that the bacterium recrudesces during pregnancy in cattle, this study was designed to determine whether C. burnetii infection affects hormonal patterns, such as progesterone, cortisol, pregnancy associated glycoproteins (PAG), and prolactin during gestation in lactating cows. Possible interactions with Neospora caninum were also explored. The study was performed on 58 gestating non-aborting cows. Blood samples for hormone determinations were collected on Days 40, 90, 120, 150, 180, and 210 of gestation. For antibody determinations, blood was collected at day 40 postinsemination and postpartum. By GLM repeated measures analysis of variance, we established the effects of production and reproductive variables as well as Coxiella and Neospora seropositivity related to changes on cortisol, PAG, progesterone, and prolactin levels. Coxiella antibody levels were significantly related to cortisol, PAG, and plasma progesterone concentrations, whereas Neospora seropositivity was linked to plasma progesterone concentrations. The interaction between Coxiella and Neospora seropositivity was correlated with cortisol and plasma progesterone levels, whereas the interaction seropositivity against C. burnetii-plasma cortisol concentration was related to plasma PAG levels. Finally, an effect of lactation number only was observed on plasma prolactin. Our findings suggest that both the N. caninum and C. burnetii infection or the presence of both modify endocrine patterns throughout gestation. Cows seropositive to both, Neospora and Coxiella, showed higher plasma progesterone levels than the remaining animals examined. Seropositivity to C. burnetii was associated with placental damage and diminishing PAG levels throughout the second half of gestation, along with increased plasma cortisol levels on Day 180 of gestation. 相似文献
157.
158.
Andrea Vivian Alvarez-Oxiley Noelita Melo de Sousa Jean-Luc Hornick Kamal Touati Gysbert C van der Weijden Marcel AM Taverne Otto Szenci Jean-François Beckers 《Acta veterinaria Scandinavica》2010,52(1):9
Background
The involvement of placental lactogen (PL) in the regulation of foetal growth has been investigated in different species by in vivo immunomodulation techniques. However, when circulating antibodies are present together with the hormone, the procedure for hormonal measurement becomes considerably complex. The aim of this study was the immunoneutralization of bovine placental lactogen (bPL) concentrations in bovine foetal circulation by direct infusion of rabbit anti-bPL purified immunoglobulins (IgG) via a foetal catheter (in vivo study). The ability of a RIA based on guinea pig anti-bPL antiserum, for the measurement of bPL concentrations in samples containing exogenous rabbit anti-bPL immunoglobulins, was also analyzed in in vitro and in vivo conditions. 相似文献159.
Deyze Alencar Soares Rosângela Vieira de Andrade Simoneide Sousa Silva Anamélia Lorenzetti Bocca Sueli Maria Soares Felipe Silvana Petrofeza 《BMC microbiology》2010,10(1):241
Background
Phospholipase B (PLB) has been reported to be one of the virulence factors for human pathogenic fungi and has also been described as necessary for the early events in infection. Based on these data, we investigated the role of PLB in virulence and modulation of the alveolar pulmonary immune response during infection using an in-vitro model of host-pathogen interaction, i.e. Paracoccidioides brasiliensis yeast cells infecting alveolar macrophage (MH-S) cells. 相似文献160.
Tailane Sant’Anna Moreira Valéria Pereira de Sousa Maria Bernadete Riemma Pierre 《AAPS PharmSciTech》2010,11(2):621-629
Transdermal delivery of non-steroidal anti-inflammatory drugs may be an interesting strategy for delivering these drugs to
the diseased site, but it would be ineffective due to low skin permeability. We investigated whether oleic acid (OA), a lipid
penetration enhancer in poloxamer gels named poloxamer-based delivery systems (PBDS), can improve lumiracoxib (LM) delivery
to/through the skin. The LM partition coefficient (K) studies were carried out in order to evaluate the drug lipophilicity grade (K
octanol/buffer), showing values >1 which demonstrated its high lipophilicity. Both in vitro percutaneous absorption and skin retention studies of LM were measured in the presence or absence of OA (in different concentrations)
in PBDS using porcine ear skin. The flux of in vitro percutaneous absorption and in vitro retention of LM in viable epidermis increased in the presence of 10.0% (w/w) OA in 25.0% (w/w) poloxamer gel. In vivo cutaneous irritation potential was carried out in rabbits showing that this formulation did not provide primary or cumulative
cutaneous irritability in animal model. The results showed that 25.0% poloxamer gel containing 10.0% OA is potential transdermal
delivery system for LM. 相似文献