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排序方式: 共有130条查询结果,搜索用时 281 毫秒
81.
Wang J Panáková D Kikuchi K Holdway JE Gemberling M Burris JS Singh SP Dickson AL Lin YF Sabeh MK Werdich AA Yelon D Macrae CA Poss KD 《Development (Cambridge, England)》2011,138(16):3421-3430
Natural models of heart regeneration in lower vertebrates such as zebrafish are based on invasive surgeries causing mechanical injuries that are limited in size. Here, we created a genetic cell ablation model in zebrafish that facilitates inducible destruction of a high percentage of cardiomyocytes. Cell-specific depletion of over 60% of the ventricular myocardium triggered signs of cardiac failure that were not observed after partial ventricular resection, including reduced animal exercise tolerance and sudden death in the setting of stressors. Massive myocardial loss activated robust cellular and molecular responses by endocardial, immune, epicardial and vascular cells. Destroyed cardiomyocytes fully regenerated within several days, restoring cardiac anatomy, physiology and performance. Regenerated muscle originated from spared cardiomyocytes that acquired ultrastructural and electrophysiological characteristics of de-differentiation and underwent vigorous proliferation. Our study indicates that genetic depletion of cardiomyocytes, even at levels so extreme as to elicit signs of cardiac failure, can be reversed by natural regenerative capacity in lower vertebrates such as zebrafish. 相似文献
82.
Washburn WN Sun CQ Bisacchi G Wu G Cheng PT Sher PM Ryono D Gavai AV Poss K Girotra RN McCann PJ Mikkilineni AB Dejneka TC Wang TC Merchant Z Morella M Arbeeny CM Harper TW Slusarchyk DA Skwish S Russell AD Allen GT Tesfamariam B Frohlich BH Abboa-Offei BE Cap M Waldron TL George RJ Young D Dickinson KE Seymour AA 《Bioorganic & medicinal chemistry letters》2004,14(13):3525-3529
A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human beta3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent beta3 full agonist (Ki = 93 nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation. 相似文献
83.
Pitts WJ Vaccaro W Huynh T Leftheris K Roberge JY Barbosa J Guo J Brown B Watson A Donaldson K Starling GC Kiener PA Poss MA Dodd JH Barrish JC 《Bioorganic & medicinal chemistry letters》2004,14(11):2955-2958
A series of purine based inhibitors of PDE7 has been derived from screening lead 1a. The synthesis, structure-activity relationships (SAR), and selectivity against several other PDE family members are described. 相似文献
84.
Chen P Norris D Iwanowicz EJ Spergel SH Lin J Gu HH Shen Z Wityak J Lin TA Pang S De Fex HF Pitt S Shen DR Doweyko AM Bassolino DA Roberge JY Poss MA Chen BC Schieven GL Barrish JC 《Bioorganic & medicinal chemistry letters》2002,12(10):1361-1364
We have identified a novel series of 1,5-imidazoquinoxalines as inhibitors of Lck with excellent potency (IC50s<5 nM) as well as good cellular activity against T-cell proliferation (IC50s<1 microM). Structure-activity studies demonstrate the requirement for the core heterocycle in addition to an optimal 2,6-disubstituted aniline group. 相似文献
85.
Martin B Possémé F Le Barbier C Carreaux F Carboni B Seiler N Moulinoux JP Delcros JG 《Bioorganic & medicinal chemistry》2002,10(9):2863-2871
Polyamine vectors are attractive for tumor targeting. We envisaged (Z)-1,4-diamino-2-butene (Z-DAB), an unsaturated analogue of putrescine as vector of (10)B, (18)F and (131)I for boron neutron capture therapy (BNCT), and tumor imaging by positron emission tomography or scintigraphy respectively. In the present work, the synthesis and characterization of new derivatives of Z-DAB were reported. Z-DAB was actively transported in cells via the polyamine transport system and converted into the spermidine analogue.(E)-2-iodo-1,4-diamino-2-butene (E-I-DAB) was not taken up by the polyamine transport system and may not be suitable for tumor imaging. In contrast, (Z)-2-[4-(5,5-dimethyl-dioxaborinan-2-yl)phenyl]methyl-1,4-diamino-2-butene (Z-4-Bbz-DAB) was a substrate of the transport system and allowed significant boron accumulation in 3LL cells. Its potential in BNCT will be evaluated. 相似文献
86.
M Deleers P Chatelain A Poss J M Ruysschaert 《Biochemical and biophysical research communications》1979,89(4):1102-1106
A specific interaction was demonstrated between a monosialo-ganglioside (galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide) incorporated in glycerol monoleate planar bilayer membranes and follitropin. Conductance of glycerol monoleate planar bilayer membranes containing gangliosides were measured before and after addition of follitropin in the aqueous phase. A 5 fold increase of membrane conductance was observed in presence of a specific monosialo-ganglioside. No significant effect was obtained with di- and trisialogangliosides. Membrane conductance changes were suppressed by the presence of an equimolar mixture of the saccharide residues (galactose, N-acetylgalactosamine and N-acetylneuraminic acid) present in the hydrophilic moeity of the ganglioside. The results favour the hypothesis that gangliosides may contribute to the formation of functional glycoproteins receptors. 相似文献
87.
Diversity in virus populations from genital secretions and peripheral blood from women recently infected with human immunodeficiency virus type 1. 总被引:6,自引:4,他引:2
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M Poss H L Martin J K Kreiss L Granville B Chohan P Nyange K Mandaliya J Overbaugh 《Journal of virology》1995,69(12):8118-8122
In order to develop a human immunodeficiency virus type 1 vaccine with global efficacy, it is important to evaluate the virus populations that are transmitted to individuals living in high-incidence areas. To determine the nature of the human immunodeficiency virus type 1 population transmitted to women during heterosexual contact, we examined the diversity of the proviral envelope gene in infected cells in both genital secretions and peripheral blood from six recently seroconverted Kenyan women. Heterogeneous virus populations were present in cervical secretions and/or peripheral blood shortly after seroconversion for five of six infected individuals, and tissue-specific variants were identified in several cases. 相似文献
88.
Rajeev S. Bhide Alec Keon Carolyn Weigelt John S. Sack Robert J. Schmidt Shuqun Lin Hai-Yun Xiao Steven H. Spergel James Kempson William J. Pitts Julie Carman Michael A. Poss 《Bioorganic & medicinal chemistry letters》2017,27(21):4908-4913
The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4. Optimization efforts were aided by X-ray crystal structures of inhibitors bound to IRAK4. Structure activity relationship (SAR) studies led to the identification of compound 29 which exhibited sub-micromolar potency in a LTA stimulated cellular assay. 相似文献
89.
Maria Brüggemann Arabella Gromes Mirjam Poss Doris Schmidt Niklas Klümper Yuri Tolkach Dimo Dietrich Glen Kristiansen Stefan C Müller Jörg Ellinger 《Translational oncology》2017,10(4):661-668
Mitochondrial dysfunction is common in cancer and the mitochondrial electron transport chain is often affected in carcinogenesis. To date, little is known about the expression of the ATP synthase subunits in clear cell renal cell carcinoma (ccRCC). The NextBio database was used to determine an expression profile of the ATP synthase subunits based on published microarray studies. We observed down-regulation of 23 out of 29 subunits of the ATP synthase. Differential expression was validated exemplarily for 12 genes (ATP5A1, ATP5B, ATPAF1, ATP5C1, ATP5D, ATP5O, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5I, ATP5S; screening cohort ccRCC n = 18 and normal renal tissue n = 10) using real-time PCR. Additional eight genes (ATP5A1, ATP5B, ATPAF1, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5S) were internally validated within an enlarged cohort (ccRCC n = 74; normal renal tissue n = 36). Furthermore, down-regulation of ATP5A1, ATPAF1, ATP5G1/G2/G3 was confirmed on the protein level using Western Blot and immunohistochemistry. We observed that altered expression of ATPAF1 and ATP5G1/G2/G3 was correlated with overall survival in patients with ccRCC. In conclusion, down-regulation of many ATP Synthase subunits occurs in ccRCC and is the basis for the reduced activity of the mitochondrial electron chain. Alteration of the expression of ATP5A1, ATPAF1, and ATP5G1/G2/G3 is characteristic for ccRCC and may be prognostic for ccRCC patients' outcome. 相似文献
90.
Unlike adult mammals, adult zebrafish vigorously regenerate lost heart muscle in response to injury. The epicardium, a mesothelial cell layer enveloping the myocardium, is activated to proliferate after cardiac injury and can contribute vascular support cells or provide mitogens to regenerating muscle. Here, we applied proteomics to identify secreted proteins that are associated with heart regeneration. We found that Fibronectin, a main component of the extracellular matrix, is induced and deposited after cardiac damage. In situ hybridization and transgenic reporter analyses indicated that expression of two fibronectin paralogues, fn1 and fn1b, are induced by injury in epicardial cells, while the itgb3 receptor is induced in cardiomyocytes near the injury site. fn1, the more dynamic of these paralogs, is induced chamber-wide within one day of injury before localizing epicardial Fn1 synthesis to the injury site. fn1 loss-of-function mutations disrupted zebrafish heart regeneration, as did induced expression of a dominant-negative Fibronectin cassette, defects that were not attributable to direct inhibition of cardiomyocyte proliferation. These findings reveal a new role for the epicardium in establishing an extracellular environment that supports heart regeneration. 相似文献