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91.
92.
Mukherjee A Bilton PR Mackay L Janoschka A Zhu H Rea D Langridge-Smith PR Campopiano DJ Teschner T Trautwein AX Schünemann V Sadler PJ 《Journal of biological inorganic chemistry》2012,17(4):573-588
Isothermal calorimetric studies of the binding of iron(III) citrate to ferric ion binding protein from Neisseria gonorrhoeae suggested the complexation of a tetranuclear iron(III) cluster as a single step binding event (apparent binding constant K(app) (ITC) = 6.0(5) × 10(5) M(-1)). High-resolution Fourier transform ion cyclotron resonance mass spectrometric data supported the binding of a tetranuclear oxo(hydroxo) iron(III) cluster of formula [Fe(4)O(2)(OH)(4)(H(2)O)(cit)](+) in the interdomain binding cleft of FbpA. The mutant H9Y-nFbpA showed a twofold increase in the apparent binding constant [K(app) (ITC) = 1.1(7) × 10(6) M(-1)] for the tetranuclear iron(III) cluster compared to the wild-type protein. M?ssbauer spectra of Escherichia coli cells overexpressing FbpA and cultured in the presence of added (57)Fe citrate were indicative of the presence of dinuclear and polynuclear clusters. FbpA therefore appears to have a strong affinity for iron clusters in iron-rich environments, a property which might endow the protein with new biological functions. 相似文献
93.
Powell NA Kohrt JT Filipski KJ Kaufman M Sheehan D Edmunds JE Delaney A Wang Y Bourbonais F Lee DY Schwende F Sun F McConnell P Catana C Chen H Ohren J Perrin LA 《Bioorganic & medicinal chemistry letters》2012,22(1):190-193
We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall. 相似文献
94.
Zanzonico P 《Radiation research》2012,177(4):349-364
The underlying principles of nuclear medicine imaging involve the use of unsealed sources of radioactivity in the form of radiopharmaceuticals. The ionizing radiations that accompany the decay of the administered radioactivity can be quantitatively detected, measured, and imaged in vivo with instruments such as gamma cameras. This paper reviews the design and operating principles, as well as the capabilities and limitations, of instruments used clinically and preclinically for in vivo radionuclide imaging. These include gamma cameras, single-photon emission computed tomography (SPECT) scanners, and positron emission tomography (PET) scanners. The technical basis of autoradiography is reviewed as well. 相似文献
95.
Peter M Szabó Miklós Pintér Diana Rita Szabó Adrienn Zsippai Attila Patócs András Falus Károly Rácz Peter Igaz 《BMC medical genomics》2012,5(1):1-19
Background
Pheochromocytoma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. We have performed a large-scale in silico analysis of altogether 1784 neuroblastoma and 531 pheochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatics analysis based on cooperative game theory.Methods
Datasets obtained from Gene Expression Omnibus and ArrayExpress have been subjected to a complex bioinformatics analysis using GeneSpring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own software.Results
Comparison of neuroblastoma and pheochromocytoma with other tumors revealed the overexpression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b in pheochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and pheochromocytoma revealed the same anti-apoptotic strategies in these tumors. Cancer regulation by stathmin turned out to be the major difference between pheochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavorable neuroblastoma. By the comparison of hypoxia- and Ras-associated pheochromocytoma, we have found that enhanced insulin like growth factor 1 signaling may be responsible for the activation of Src homology 2 domain containing transforming protein 1, the main co-factor of RET. Hypoxia induced factor 1?? and vascular endothelial growth factor signaling included the most prominent gene expression changes between von Hippel-Lindau- and multiple endocrine neoplasia type 2A-associated pheochromocytoma.Conclusions
These pathways include previously undescribed pathomechanisms of neuroblastoma and pheochromocytoma and associated gene products may serve as diagnostic markers and therapeutic targets. 相似文献96.
D Haddad CH Chen S Carlin G Silberhumer NG Chen Q Zhang V Longo SG Carpenter A Mittra J Carson J Au M Gonen PB Zanzonico AA Szalay Y Fong 《PloS one》2012,7(8):e41647
Introduction
Oncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS.Methods
GLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide 131I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via 124I-positron emission tomography (PET). Detection of systemic administration of virus was investigated with both 124I-PET and 99m-technecium gamma-scintigraphy.Results
GLV-1h153 successfully facilitated time-dependent intracellular uptake of 131I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 109 plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82±0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via 124I-PET and 99m-technecium-scintigraphy.Conclusion
GLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic cancer cells, facilitating detection by PET with both intratumoral and systemic administration. Therefore, GLV-1h153 is a promising candidate for the noninvasive imaging of virotherapy and warrants further study into longterm monitoring of virotherapy and potential radiocombination therapies with this treatment and imaging modality. 相似文献97.
Isabella Maiellaro Konstantinos Lefkimmiatis Mary Pat Moyer Silvana Curci Aldebaran M. Hofer 《Journal of cellular and molecular medicine》2012,16(11):2715-2725
Diverse pathophysiological processes (e.g. obesity, lifespan determination, addiction and male fertility) have been linked to the expression of specific isoforms of the adenylyl cyclases (AC1‐AC10), the enzymes that generate cyclic AMP (cAMP). Our laboratory recently discovered a new mode of cAMP production, prominent in certain cell types, that is stimulated by any manoeuvre causing reduction of free [Ca2+] within the lumen of the endoplasmic reticulum (ER) calcium store. Activation of this ‘store‐operated’ pathway requires the ER Ca2+ sensor, STIM1, but the identity of the enzymes responsible for cAMP production and how this process is regulated is unknown. Here, we used sensitive FRET‐based sensors for cAMP in single cells combined with silencing and overexpression approaches to show that store‐operated cAMP production occurred preferentially via the isoform AC3 in NCM460 colonic epithelial cells. Ca2+ entry via the plasma membrane Ca2+ channel, Orai1, suppressed cAMP production, independent of store refilling. These findings are an important first step towards defining the functional significance and to identify the protein composition of this novel Ca2+/cAMP crosstalk system. 相似文献
98.
99.
Pat B Killingsworth C Denney T Zheng J Powell P Tillson M Dillon AR Dell'Italia LJ 《American journal of physiology. Heart and circulatory physiology》2008,295(6):H2321-H2327
The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that beta1-adrenergic receptor blockade (beta1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. beta1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by beta1-RB. However, beta1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171+/-5 microm, P<0.05) compared with normal (156+/-3 microm) and MR (165+/-4 microm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73+/-0.31 vs. 5.02+/-0.26%, P<0.05) and normalized with beta1-RB (4.73+/-0.48%). In addition, stimulation with the beta-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% (P<0.05) in beta1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, beta1-RB improved LV cardiomyocyte function and beta-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization. 相似文献
100.
Peter A. Pridmore Thomas H. Rich Pat Vickers-Rich Petr P. Gambaryan 《Journal of Mammalian Evolution》2005,12(3-4):359-378
A partial right humerus has been recovered from the Early Cretaceous (Albian) Eumeralla Formation at Dinosaur Cove in south-eastern
Australia. General morphology, size and the presence of a single epicondylar foramen (the entepicondylar) suggest that the
bone is from a mammal or an advanced therapsid reptile. The humerus is similar in size, shape and torsion to the equivalent
bone of extant and late Neogene echidnas (Tachyglossidae) but, contrary to the situation in extant monotremes, in which the
ulna and radius articulate with a single, largely bulbous condyle, it bears a shallow, pulley-shaped (i.e. trochlear-form)
ulnar articulation that is confluent ventro-laterally with the bulbous radial condyle. This form of ulnar articulation distinguishes
this bone from the humeri of most advanced therapsids and members of several major groups of Mesozoic mammals, which have
a condylar ulnar articulation, but parallels the situation found in therian mammals and in some other lineages of Mesozoic
mammals. As in extant monotremes the distal humerus is greatly expanded transversely and humeral torsion is strong. Transverse
expansion of the distal humerus is evident in the humeri of the fossorial docodont Haldanodon, highly-fossorial talpids and some clearly fossorial dicynodont therapsids, but the fossil shows greatest overall similarity
to extant monotremes and it is possible that the peculiar elbow joint of extant monotremes evolved from a condition approximating
that of the fossil. On the basis of comparisons with Mesozoic and Cainozoic mammalian taxa in which humeral morphology is
known, the Dinosaur Cove humerus is tentatively attributed to a monotreme. However, several apparently primitive features
of the bone exclude the animal concerned from the extant families Tachyglossidae and Ornithorhynchidae and suggest that, if
it is a monotreme, it is a stem-group monotreme. Whatever, the animal's true affinity, the gross morphology of its humerus
indicates considerable capacity for rotation-thrust digging. 相似文献