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131.
To develop a molecular probe for detection of hydroxyl radicals in the vicinity of DNA, the coumarin-polyamine complexes, N(1),N(12)-bis[2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (5) and tris[2-(2-oxo-2H-chromene-3-carboxamido)ethyl]amine (7), and their hydroxylated derivatives, N(1),N(12)-bis[7-hydroxy-2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (6) and tris[2-(7-hydroxy-2-oxo-2H-chromene-3-carboxamido)ethyl]amine (8), have been synthesized. Using computer-generated molecular modeling, the derivatives have been docked onto DNA dodecamer d(CGCGAATTCGCG)(2), the ligand-DNA complexes have been minimized, and the free binding energies (DeltaG(binding)) and inhibition constants (K(i)) have been calculated. Compound 7 is not water-soluble at the concentrations required for the project. When aqueous solutions of 5 are irradiated with gamma rays, the relationship between induced fluorescence and dose is linear in the range of 0 to 10 Gy. The fluorescence emission spectrum of irradiated 5 is similar to that of its dihydroxy derivative 6, indicating conversion of 5 to 6, and induction of fluorescence records formation of hydroxyl radicals in aqueous solution. The dicoumarin-polyamine 5, a novel compound for the detection of hydroxyl radicals close to DNA, is a sensitive and quantitative probe with potential for applications in biological systems. 相似文献
132.
Rodríguez FA Cai Y Lin C Tang Y Kolbanovskiy A Amin S Patel DJ Broyde S Geacintov NE 《Nucleic acids research》2007,35(5):1555-1568
The environmental carcinogen benzo[a]pyrene (BP) is metabolized to reactive diol epoxides that bind to cellular DNA by predominantly forming N2-guanine adducts (G*). Mutation hotspots for these adducts are frequently found in 5′-···GG··· dinucleotide sequences, but their origins are poorly understood. Here we used high resolution NMR and molecular dynamics simulations to investigate differences in G* adduct conformations in 5′-···CG*GC··· and 5′-···CGG*C··· sequence contexts in otherwise identical 12-mer duplexes. The BP rings are positioned 5′ along the modified strand in the minor groove in both cases. However, subtle orientational differences cause strong distinctions in structural distortions of the DNA duplexes, because the exocyclic amino groups of flanking guanines on both strands compete for space with the BP rings in the minor groove, acting as guideposts for placement of the BP. In the 5′-···CGG*C··· case, the 5′-flanking G · C base pair is severely untwisted, concomitant with a bend deduced from electrophoretic mobility. In the 5′-···CG*GC··· context, there is no untwisting, but there is significant destabilization of the 5′-flanking Watson–Crick base pair. The minor groove width opens near the lesion in both cases, but more for 5′-···CGG*C···. Differential sequence-dependent removal rates of this lesion result and may contribute to the mutation hotspot phenomenon. 相似文献
133.
The Aer receptor guides Escherichia coli to specific oxygen and energy-generating niches. The input sensor in Aer is a flavin adenine dinucleotide-binding PAS domain, which is separated from a HAMP/signaling output domain by two membrane-spanning segments that flank a short (four-amino-acid) periplasmic loop. In this study, we determined the overall membrane organization of Aer by introducing combinations of residues that allowed us to differentiate intradimeric collisions from interdimeric collisions. Collisions between proximal residues in the membrane anchor were exclusively intra- or interdimeric but, with one exception, not both. Cross-linking profiles were consistent, with a rigid rather than flexible periplasmic loop and a tilted TM2 helix that crossed TM2' at residue V197C, near the center of the lipid bilayer. The periplasmic loop formed a stable neighborhood that (i) included a maximum of three Aer dimers, (ii) did not swap neighbors over time, and (iii) appeared to be constrained by interactions in the cytosolic signaling domain. 相似文献
134.
Josien H Bara T Rajagopalan M Asberom T Clader JW Favreau L Greenlee WJ Hyde LA Nomeir AA Parker EM Pissarnitski DA Song L Wong GT Zhang L Zhang Q Zhao Z 《Bioorganic & medicinal chemistry letters》2007,17(19):5330-5335
The design and development of a new class of small 2,6-disubstituted piperidine N-arylsulfonamide gamma-secretase inhibitors is reported. Lowering molecular weight including the use of conformational constraint led to compounds with less CYP 3A4 liability compared to early leads. Compounds active orally in lowering Abeta levels in Tg CRND8 mice were identified as potential treatments for Alzheimer's disease. 相似文献
135.
OBJECTIVE: Periodontoid pseudotumours are lesions of presumed degenerative aetiology which typically occur in elderly patients with cervical myelopathy. The clinical and radiological differential diagnosis includes neoplastic and inflammatory lesions, and the exclusion of such lesions may be of value in the intra-operative management of the patient. This audit aimed to examine the value of intra-operative smear cytology in the management of this condition. METHODS: The intra-operative smear cytological features of four cases of periodontoid pseudotumour were reviewed. RESULTS: In each case the intra-operative cytological interpretation was in keeping with a non-neoplastic and non-inflammatory process. CONCLUSION: These results suggest that intra-operative smear cytology can provide information on the value in the intra-operative management of patients with this lesion. 相似文献
136.
137.
Annemarie MM Vlaar Angela EP Bouwmans Marinus JPG van Kroonenburgh Werner H Mess Selma C Tromp Piet GWM Wuisman Alfons GH Kessels Ania Winogrodzka Wim EJ Weber 《BMC neurology》2007,7(1):28
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD. 相似文献138.
This study communicates the molecular design, preparation, and biological application of novel symmetric amphiphilic polycationic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) D2-LLA15-D2 bearing two two-generation poly(L-lysine) PLL dendrons D2 and a central hydrophobic biodegradable poly(L-lactide) block LLA15. First, an amino-protected precursor of L1-OH was designed and synthesized and was further employed to prepare L1-LLA15 with an organic 4-(dimethylamino)-pyridine-mediated living-ring-opening polymerization of l-lactide. Subsequently, the hydroxy end-capped L1-LLA15 was coupled to synthesize a new triblock L1-LLA15-L1 with two one-generation amino-protected PLL dendrons L1. Furthermore, with a repeated trifluoroacetic-acid-mediated amino deprotection-protection cycle, new amphiphilic triblock D2-LLA15-D2 was successfully prepared. By means of NMR, mass spectrometry, and gel permeation chromatography, these synthetic precursors and final amphiphilic product were characterized to bear well-defined triblock structures. In addition, this synthesized amphiphilic triblock polycationic macromolecule was applied as a new polycationic plasmid DNA carrier, and its DNA binding affinity was examined via an agarose electrophoresis and a fluorescence titration assay along with two important references of hydrophilic dendritic D2-HEX-D2 and double-hydrophilic D2-PEG-4K-D2 bearing the same two D2 dendrons; much enhanced DNA binding affinity was interestingly revealed for the new amphiphilic structural D2-LLA15-D2. Moreover, the assembled polyplex microparticles of plasmid DNA/polycationic carrier were further analyzed by dynamic light scattering and transmission electron microscopy, indicating their averaged nanoparticle size around 150-200 nm. As for the cytotoxicity of the new D2-LLA15-D2, MTT assays were conducted with a human hepatocellular carcinoma cell line (SMMC-7721), indicating a very low cytotoxicity as compared with commercial linear PLL-23K and PEI-2K, and a DNase I degradation of the assembled polyplex particles was also done in the HBS buffer solution to evaluate their stabilities. Finally, employing the new amphiphilic D2-LLA15-D2 as gene carrier, in vitro gene transfection experiments were conducted with the SMMC-7721 cell line, indicating a transfection efficiency increase of at least 10 times higher than that of the naked plasmid DNA under a N/P charge ratio of 10. Therefore, these interesting results may provide a new possible way to construct efficient polycationic macromolecular gene carriers with low toxicity and less expensive low-generation PLL dendrons. 相似文献
139.
Length‐weight and length‐length relationships of two tropical fish Secutor megalolepis (Mochizuki & Hayashi, 1989) and Rhabdamia gracilis (Bleeker, 1856) from Sabah,Malaysia 下载免费PDF全文
M. A. M. Siddique A. Arshad S. M. N. Amin 《Zeitschrift fur angewandte Ichthyologie》2015,31(3):574-575
Length‐weight relationships (LWRs) and length‐length relationships (LLRs) for two tropical fish species from Marudu Bay, Sabah were studied. Specimens were caught with the traditional ‘Bagan net’ fishing gear from October 2012 to September 2013, using the light trap method. The maximum total length for Rhabdamia gracilis (7.4 cm) reported in this study is a new record for this species. No information regarding length‐weight relationships was reported previously in FishBase for either Secutor megalolepis or Rhabdamia gracilis. 相似文献
140.
Paulo FP Pimenta Alessandra S Orfano Ana C Bahia Ana PM Duarte Claudia M Ríos-Velásquez Fabrício F Melo Felipe AC Pessoa Giselle A Oliveira Keillen MM Campos Luis Martínez Villegas Nilton Barnabé Rodrigues Rafael Nacif-Pimenta Rejane C Sim?es Wuelton M Monteiro Rogerio Amino Yara M Traub-Cseko José BP Lima Maria GV Barbosa Marcus VG Lacerda Wanderli P Tadei Nágila FC Secundino 《Memórias do Instituto Oswaldo Cruz》2015,110(1):23-47
In the Americas, areas with a high risk of malaria transmission are mainly located in
the Amazon Forest, which extends across nine countries. One keystone step to
understanding the Plasmodium life cycle in Anopheles species from the Amazon Region
is to obtain experimentally infected mosquito vectors. Several attempts to colonise
Ano- pheles species have been conducted, but with only short-lived success or no
success at all. In this review, we review the literature on malaria transmission from
the perspective of its Amazon vectors. Currently, it is possible to develop
experimental Plasmodium vivax infection of the colonised and field-captured vectors
in laboratories located close to Amazonian endemic areas. We are also reviewing
studies related to the immune response to P. vivax infection of Anopheles aquasalis,
a coastal mosquito species. Finally, we discuss the importance of the modulation of
Plasmodium infection by the vector microbiota and also consider the anopheline
genomes. The establishment of experimental mosquito infections with Plasmodium
falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide
interesting models for studying malaria in the Amazonian scenario is important.
Understanding the molecular mechanisms involved in the development of the parasites
in New World vectors is crucial in order to better determine the interaction process
and vectorial competence. 相似文献