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991.
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
992.
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
993.
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
994.
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
995.
Silvia De Francia Antonio D’Avolio Francesca De Martino Elisa Pirro Lorena Baietto Marco Siccardi Marco Simiele Silvia Racca Giuseppe Saglio Francesco Di Carlo Giovanni Di Perri 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2009,877(18-19):1721-1726
A new method using high performance liquid chromatography coupled with electrospray mass spectrometry is described for the quantification of plasma concentration of tyrosine kinase inhibitors imatinib, dasatinib and nilotinib. A simple protein precipitation extraction procedure was applied on 250 μl of plasma aliquots. Chromatographic separation of drugs and Internal Standard (quinoxaline) was achieved with a gradient (acetonitrile and water + formic acid 0.05%) on a C18 reverse phase analytical column with 20 min of analytical run, at flow rate of 1 ml/min. Mean intra-day and inter-day precision for all compounds were 4.3 and 11.4%; mean accuracy was 1.5%; extraction recovery ranged within 95 and 114%. Calibration curves ranged from 10,000 to 62.5 ng/ml. The limit of quantification was set at 78.1 ng/ml for imatinib and at 62.5 ng/ml for dasatinib and nilotinib. This novel developed methodology allows a specific, sensitive and reliable simultaneous determination of the three tyrosine kinase inhibitors imatinib, dasatinib and nilotinib in a single chromatographic run, useful for drugs estimation in plasma of patients affected by chronic myeloid leukemia. 相似文献
996.
Jon Bielby Stefano Bovero Giuseppe Sotgiu Giulia Tessa Marco Favelli Claudio Angelini Stefano Doglio Frances C. Clare Enrico Gazzaniga Federica Lapietra Trenton W. J. Garner 《EcoHealth》2009,6(1):27-32
Batrachochytrium dendrobatidis (Bd), the causative agent of the amphibian disease chytridiomycosis, is an important factor in the global decline of amphibians. Within Europe, animals that exhibit clinical signs of the disease have only been reported in Spain despite the pathogen’s wide, but patchy, distribution on the continent. Recently, another occurrence of chytridiomycosis was reported in Euproctus platycephalus, the Sardinian brook newt, on the Mediterranean island of Sardinia, but without any evidence of fatal disease. We report further evidence of the emergence of Bd on Sardinia and the first evidence of lethal chytridiomycosis outside of Spain. Unusual mortalities of the Tyrrhenian painted frog (Discoglossus sardus) were found at three sites in the Limbara mountains of northern Sardinia. Molecular and histological screens of corpses, frogs, and tadpoles from these sites revealed infection with Bd. Infection and mortality occurred at locations that are unusual in terms of the published habitat requirements of the pathogen. Given the endemicity, the IUCN Red List status of the amphibian species on Sardinia, and the occurrence of infection and mortality caused by chytridiomycosis, there is serious reason for concern for the impact that disease emergence may have on the conservation of the amphibians of the island. 相似文献
997.
Based on traditional techniques and confocal laser scanning microscopy for external morphology, and immunohistochemistry for the muscular system, we describe here the segmental features of the antennal exopod of Artemia nauplii. Two kinds of serial elements are present, i.e. setae (with cuticular folds at their base) and ringlets (serially arranged sclerites separated by joint-like cuticular folds not extending to form complete rings around the appendage). The two series are usually not in register. The cuticular folds of the setae and of the ringlets are also sites of intermediate insertions of the three exopod muscles: as the two tegumentary structures are discordant in periodicity, this is also mirrored in the pattern of muscle insertions on the two sides of the appendage. Similar cases of segmental mismatch are known for the trunk of several arthropods, but segmental mismatch along the appendages has received very little attention. The occurrence of segmental mismatch in the naupliar appendages of both extant and fossil crustaceans is reviewed and it is suggested here to be a primitive feature of the exopods of both second antennae and mandibles. Problems in the interpretation of morphological evidence are discussed, also in relation to development and evolution of segmentation of naupliar appendages. 相似文献
998.
Anna U?arowska Giuseppe Dionisio Barbara Sarholz Hans-Peter Piepho Mingliang Xu Christina R?nn Ingvardsen Gerhard Wenzel Thomas Lübberstedt 《BMC plant biology》2009,9(1):15
Background
The potyviruses sugarcane mosaic virus (SCMV) and maize dwarf mosaic virus (MDMV) are major pathogens of maize worldwide. Two loci, Scmv1 and Scmv2, have ealier been shown to confer complete resistance to SCMV. Custom-made microarrays containing previously identified SCMV resistance candidate genes and resistance gene analogs were utilised to investigate and validate gene expression and expression patterns of isogenic lines under pathogen infection in order to obtain information about the molecular mechanisms involved in maize-potyvirus interactions. 相似文献999.
Johannes Voortman Thang V Pham Jaco C Knol Giuseppe Giaccone Connie R Jimenez 《Proteome science》2009,7(1):34-14
Background
Only a minority of patients with advanced non-small cell lung cancer (NSCLC) benefit from chemotherapy. Serum peptide profiling of NSCLC patients was performed to investigate patterns associated with treatment outcome. 相似文献1000.
Oliaro-Bosso S Taramino S Viola F Tagliapietra S Ermondi G Cravotto G Balliano G 《Journal of enzyme inhibition and medicinal chemistry》2009,24(2):589-598
Human and murine lanosterol synthases (EC 5.4.99.7) were studied as targets of a series of umbelliferone aminoalkyl derivatives previously tested as inhibitors of oxidosqualene cyclases from other eukaryotes. Tests were carried out on cell cultures of human keratinocytes and mouse 3T3 fibroblasts incubated with radiolabeled acetate, and on homogenates prepared from yeast cells expressing human lanosterol synthase, incubated with radiolabeled oxidosqualene. In cell cultures of both human keratinocytes and mouse 3T3 fibroblasts, the observed inhibition of cholesterol biosynthesis was selective for oxidosqualene cyclase. The most active compounds bear an allylmethylamino chain in position-7 of the coumarin ring. The inhibition was critically dependent on the position and length of the inhibitor side chain, as well as on the type of aminoalkyl group inserted at the end of the same chain. Molecular docking analyses, carried out to clarify details of inhibitors/enzyme interactions, proved useful to explain the observed differences in inhibitory activities. 相似文献