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101.
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The translocator protein (TSPO) is an attractive target for tumor imaging due to its up-regulation in numerous cancer cell types. Here, we report a series of functional TSPO ligands, n-TSPOmbb732, which can be conjugated to a variety of signaling moieties and are widely applicable in TSPO-targeted molecular imaging. Two fluorescent dye-labeled 6-TSPOmbb732 displayed nanomolar binding affinities to TSPO and were successfully imaged in vitro. 相似文献
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Konstantinos Sombolos Demitrios Tsakiris John Boletis Demetrios Vlahakos Kostas C. Siamopoulos Vassilios Vargemezis Pavlos Nikolaidis Christos Iatrou Eugene Dafnis Konstantinos Xynos Christos Argyropoulos 《PloS one》2014,9(11)
Background
Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD.Methods
Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement.Results
A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR<40 ml/min/1.73 m2) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers.Conclusions
In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage. 相似文献106.
Using the crystal structure of the uracil transporter UraA of Escherichia coli, we constructed a 3D model of the Aspergillus nidulans uric acid-xanthine/H(+) symporter UapA, which is a prototype member of the Nucleobase-Ascorbate Transporter (NAT) family. The model consists of 14 transmembrane segments (TMSs) divided into a core and a gate domain, the later being distinctly different from that of UraA. By implementing Molecular Mechanics (MM) simulations and quantitative structure-activity relationship (SAR) approaches, we propose a model for the xanthine-UapA complex where the substrate binding site is formed by the polar side chains of residues E356 (TMS8) and Q408 (TMS10) and the backbones of A407 (TMS10) and F155 (TMS3). In addition, our model shows several polar interactions between TMS1-TMS10, TMS1-TMS3, TMS8-TMS10, which seem critical for UapA transport activity. Using extensive docking calculations we identify a cytoplasm-facing substrate trajectory (D360, A363, G411, T416, R417, V463 and A469) connecting the proposed substrate binding site with the cytoplasm, as well as, a possible outward-facing gate leading towards the substrate major binding site. Most importantly, re-evaluation of the plethora of available and analysis of a number of herein constructed UapA mutations strongly supports the UapA structural model. Furthermore, modeling and docking approaches with mammalian NAT homologues provided a molecular rationale on how specificity in this family of carriers might be determined, and further support the importance of selectivity gates acting independently from the major central substrate binding site. 相似文献
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Bioactivity-guided separation of the aqueous methanolic extract of Yucca desmettiana leaves, which in a preliminary screening exhibited significant molluscicidal activity, led to the isolation and structure elucidation of two new steroidal saponins (1 and 2). The structures of desmettianosides A and B, identified as bisdesmosidic furostanol glycosides with six and five sugar units, respectively, were established by detailed spectroscopic analyses of their NMR and MS data. Compounds 1 and 2 exhibited high molluscicidal activity against Biomphalaria alexandrina snails with LC100 values of 6 and 11 mg/L, respectively. 相似文献
109.
Chochlakis D Ioannou I Sandalakis V Dimitriou T Kassinis N Papadopoulos B Tselentis Y Psaroulaki A 《Microbial ecology》2012,63(2):314-323
In two surveys conducted from March 1999 to March 2001 and from January 2004 to December 2006, a total of 3,950 ticks (belonging
to ten different species) were collected from seven domestic and wild animals (goat, sheep, cattle, dog, fox, hare, and mouflon)
from different localities throughout Cyprus. In order to establish their infection rate with Spotted Fever Rickettsiae (SFG), ticks were pooled and tested by polymerase chain reaction targeting gltA and ompA genes, followed by sequencing analysis. When tick pools tested positive, individual ticks were then tested one by one, and
of the 3,950 ticks screened, rickettsial DNA was identified in 315 ticks (infection rate, 8%). Five SFG Rickettsiae were identified: Rickettsia aeschlimannii in Hyalomma marginatum marginatum, Rickettsia massiliae in Rhipicephalus turanicus and Rhipicephalus sanguineus, Rickettsia sibirica mongolotimonae in Hyalomma anatolicum excavatum, and a Rickettsia endosymbiont of Haemaphysalis sulcata (later described as Rickettsia hoogstraalii) in Haemaphysalis punctata. Two additional genes, 17 kDa and ompB, were targeted to characterize a new genotype of “Candidatus Rickettsia barbariae” genotype in R. turanicus, designated here as “Candidatus Rickettsia barbariae” Cretocypriensis. These results confirm the presence of a spectrum of SFG Rickettsiae on the island. Further studies are necessary to gain better knowledge on the epidemiology of SFG Rickettsiae in Cyprus. 相似文献
110.
Grégory Genta-Jouve Efstathia Ioannou Véronique Mathieu Céline Bruyère Florence Lefranc Olivier P. Thomas Robert Kiss Vassilios Roussis 《Phytochemistry letters》2012,5(4):747-751
The absolute configuration of dilospirane B (1), a diterpene featuring a novel carbon framework recently isolated from the brown alga Dilophus spiralis, was established on the basis of theoretical calculations of its electronic circular dichroism spectra applying the time-dependent density functional theory method. Metabolite 1, evaluated for its in vitro antitumor activity against six human cancer cell lines displaying various levels of sensitivity to pro-apoptotic stimuli, exhibited growth inhibitory activity with a mean IC50 value of 66 μM. Quantitative videomicroscopy analyses indicated that 1 initially displays cytostatic effects which later become cytotoxic. 相似文献