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991.
Romano Silvestri Alessia Ligresti Giuseppe La Regina Francesco Piscitelli Valerio Gatti Antonella Brizzi Serena Pasquini Antonio Lavecchia Marco Allarà Noemi Fantini Mauro Antonio Maria Carai Ettore Novellino Giancarlo Colombo Vincenzo Di Marzo Federico Corelli 《Bioorganic & medicinal chemistry》2009,17(15):5549-5564
New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized by replacing the 2,4-dichlorobenzyl and cyclohexyl moieties at the 3-carboxamide nitrogen of the previously reported CB1 receptor antagonists/inverse agonists 4 and 5. Several ligands showed potent affinity for the hCB1 receptor, with Ki concentrations comparable to the reference compounds 1, 4 and 5, and exhibited CB1 selectivity comparable to 1 and 2. Docking experiments and molecular dynamics (MD) simulations explained the potent hCB1 binding affinity of compounds 31 and 37. According to our previous studies, 31 and 37 formed a H-bond with K3.28(192), which accounted for the high affinity for the receptor inactive state and the inverse agonist activity. The finding of inhibition of food intake following their acute administration to rats, supported the concept that the CB1 selective compounds 4 and 52 act as antagonists/inverse agonists. 相似文献
992.
Susan Costantini Francesca Capone Marco Miele Eliana Guerriero Maria Napolitano Giovanni Colonna Giuseppe Castello 《Bioinformation》2009,4(3):92-93
Cytokines are subdivided in 12 sub-families and are described as multi-functional
molecules that play an important biological activity in host defense system
against pathogens, in homeostasis, tissue repair, cell growth and development.
CytokineDB is an annotated database that collects biological information
regarding the cytokines family in human and will be periodically updated by
including new biological information. This database is freely available online
and can be accessed at the URL: http://www.cro-m.eu/CytokineDB/ 相似文献
993.
On the hydrophobicity of nitrogen dioxide: Could there be a “lens” effect for NO2 reaction kinetics?
Solvent “lens” effects for the reaction kinetics of NO2 can be evaluated on the basis of published Henry’s law constants for nitrogen dioxide in various solvents. Water-to-organic solvent partition coefficients were derived from Henry’s law constants and used to assess the tendencies of NO2 toward fleeing the aqueous environments and concentrating in biological hydrophobic media. It is concluded, based only on the estimated aqueous medium-to-cell membrane partition coefficient for NO2, that such tendencies will be relatively small, and that they may account for an acceleration of chemical reactions in biological hydrophobic media with reaction kinetics that are first order on NO2 by a factor of approximately 3 ± 1. Thus, kinetic effects due to mass action will be relatively small but it is also important to recognize that because NO2 will tend to dissolve in cell membranes, reactions with cell membrane components will not be hindered by lack of physical solubility at these loci. In comparison to other gases, nitrogen dioxide is less hydrophobic than NO, O2 and N2. 相似文献
994.
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009 总被引:1,自引:0,他引:1
Kroemer G Galluzzi L Vandenabeele P Abrams J Alnemri ES Baehrecke EH Blagosklonny MV El-Deiry WS Golstein P Green DR Hengartner M Knight RA Kumar S Lipton SA Malorni W Nuñez G Peter ME Tschopp J Yuan J Piacentini M Zhivotovsky B Melino G;Nomenclature Committee on Cell Death 《Cell death and differentiation》2009,16(1):3-11
995.
Andrea Tinelli Daniele Vergara Roberta Martignago Giuseppe Leo Maurizio Pisanò Antonio Malvasi 《Current Genomics》2009,10(4):240-249
Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers. Ovarian tumors can be classified on the basis of the cells of origin in epithelial, stromal and germ cell tumors. Epithelial ovarian tumors display great histological heterogeneity and can be further subdivided into benign, intermediate or borderline, and invasive tumors. Several studies on ovarian tumors, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomolecular study and genomic discovery; unfortunately, validity of these should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management. Therefore, considerable interest lies in identifying molecular and protein biomarkers and indicators to guide treatment decisions and clinical follow up. In this review, the current state of knowledge about the genoproteomic and potential clinical value of gene expression profiling in ovarian cancer and ovarian borderline tumors is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian cancers and borderline tumors, identifying different genotypes of ovarian tissue and identifying proteins linked to cancer or tumor development. By these targets, authors focus on the use of novel molecules, developed on the proteomics and genomics researches, as potential protein biomarkers in the management of ovarian cancer or borderline tumor, overlooking on current state of the art and on future perspectives of researches.Key Words: Ovarian cancer, borderline ovarian tumors, markers, genomics, proteomics, oncogenes. 相似文献
996.
Chiara Ciaccio Grazia R. Tundo Giuseppe Grasso Daniela Marasco Magda Gioia Massimo Coletta 《Journal of molecular biology》2009,385(5):1556-1567
Insulin-degrading enzyme (IDE) is an interesting pharmacological target for Alzheimer's disease (AD), since it hydrolyzes β-amyloid, producing non-neurotoxic fragments. It has also been shown that the somatostatin level reduction is a pathological feature of AD and that it regulates the neprilysin activity toward β-amyloid.In this work, we report for the first time that IDE is able to hydrolyze somatostatin [kcat (s− 1) = 0.38 (± 0.05); Km (M) = 7.5 (± 0.9) × 10− 6] at the Phe6-Phe7 amino acid bond. On the other hand, somatostatin modulates IDE activity, enhancing the enzymatic cleavage of a novel fluorogenic β-amyloid through a decrease of the Km toward this substrate, which corresponds to the 10-25 amino acid sequence of the Aβ(1-40). Circular dichroism spectroscopy and surface plasmon resonance imaging experiments show that somatostatin binding to IDE brings about a concentration-dependent structural change of the secondary and tertiary structure(s) of the enzyme, revealing two possible binding sites. The higher affinity binding site disappears upon inactivation of IDE by ethylenediaminetetraacetic acid, which chelates the catalytic Zn2+ ion. As a whole, these features suggest that the modulatory effect is due to an allosteric mechanism: somatostatin binding to the active site of one IDE subunit (where somatostatin is cleaved) induces an enhancement of IDE proteolytic activity toward fluorogenic β-amyloid by another subunit. Therefore, this investigation on IDE-somatostatin interaction contributes to a more exhaustive knowledge about the functional and structural aspects of IDE and its pathophysiological implications in the amyloid deposition and somatostatin homeostasis in the brain. 相似文献
997.
Cell Survival and Polarity of Drosophila Follicle Cells Require the Activity of Ecdysone Receptor B1 Isoform 下载免费PDF全文
Patrizia Romani Fabio Bernardi Jennifer Hackney Leonard Dobens Giuseppe Gargiulo Valeria Cavaliere 《Genetics》2009,181(1):165-175
Proper assembly and maintenance of epithelia are critical for normal development and homeostasis. Here, using the Drosophila ovary as a model, we identify a role for the B1 isoform of the ecdysone receptor (EcR-B1) in this process. We performed a reverse genetic analysis of EcR-B1 function during oogenesis and demonstrate that silencing of this receptor isoform causes loss of integrity and multilayering of the follicular epithelium. We show that multilayered follicle cells lack proper cell polarity with altered distribution of apical and basolateral cell polarity markers including atypical-protein kinase C (aPKC), Discs-large (Dlg), and Scribble (Scrib) and aberrant accumulation of adherens junctions and F-actin cytoskeleton. We find that the EcR-B1 isoform is required for proper follicle cell polarity both during early stages of oogenesis, when follicle cells undergo the mitotic cell cycle, and at midoogenesis when these cells stop dividing and undergo several endocycles. In addition, we show that the EcR-B1 isoform is required during early oogenesis for follicle cell survival and that disruption of its function causes apoptotic cell death induced by caspase. 相似文献
998.
Zhiping Wu Valentin Gogonea Xavier Lee Matthew A. Wagner Xin-Min Li Ying Huang Arundhati Undurti Roland P. May Michael Haertlein Martine Moulin Irina Gutsche Giuseppe Zaccai Joseph A. DiDonato Stanley L. Hazen 《The Journal of biological chemistry》2009,284(52):36605-36619
High density lipoprotein (HDL), the carrier of so-called “good” cholesterol, serves as the major athero-protective lipoprotein and has emerged as a key therapeutic target for cardiovascular disease. We applied small angle neutron scattering (SANS) with contrast variation and selective isotopic deuteration to the study of nascent HDL to obtain the low resolution structure in solution of the overall time-averaged conformation of apolipoprotein AI (apoA-I) versus the lipid (acyl chain) core of the particle. Remarkably, apoA-I is observed to possess an open helical shape that wraps around a central ellipsoidal lipid phase. Using the low resolution SANS shapes of the protein and lipid core as scaffolding, an all-atom computational model for the protein and lipid components of nascent HDL was developed by integrating complementary structural data from hydrogen/deuterium exchange mass spectrometry and previously published constraints from multiple biophysical techniques. Both SANS data and the new computational model, the double superhelix model, suggest an unexpected structural arrangement of protein and lipids of nascent HDL, an anti-parallel double superhelix wrapped around an ellipsoidal lipid phase. The protein and lipid organization in nascent HDL envisages a potential generalized mechanism for lipoprotein biogenesis and remodeling, biological processes critical to sterol and lipid transport, organismal energy metabolism, and innate immunity. 相似文献
999.
Mikko Virmavirta Juha Isolehto Paavo Komi Hermann Schwameder Fabio Pigozzi Giuseppe Massazza 《Journal of biomechanics》2009,42(8):1095-1101
The take-off phase (approximately 6 m) of the jumps of all athletes participating in the individual HS-106 m hill ski jumping competition at the Torino Olympics was filmed with two high-speed cameras. The high altitude of the Pragelato ski jumping venue (1600 m) and slight tail wind in the final jumping round were expected to affect the results of this competition. The most significant correlation with the length of the jump was found in the in-run velocity (r=0.628, p<0.001, n=50). This was a surprise in Olympic level ski jumping, and suggests that good jumpers simply had smaller friction between their skis and the in-run tracks and/or the aerodynamic quality of their in-run position was better. Angular velocity of the hip joint of the best jumpers was also correlated with jumping distance (r=0.651, p<0.05, n=10). The best jumpers in this competition exhibited very different take-off techniques, but still they jumped approximately the same distance. This certainly improves the interests in ski jumping among athletes and spectators. The comparison between the take-off techniques of the best jumpers showed that even though the more marked upper body movement creates higher air resistance, it does not necessarily result in shorter jumping distance if the exposure time to high air resistance is not too long. A comparison between the first and second round jumps of the same jumpers showed that the final results in this competition were at least partly affected by the wind conditions. 相似文献