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81.
82.
Igor F. Tsigelny Valentina L. Kouznetsova Nilima Biswas Sushil K. Mahata Daniel T. O’Connor 《Bioorganic & medicinal chemistry》2013,21(18):5855-5869
The endogenous catecholamine release-inhibitory peptide catestatin (CST) regulates events leading to hypertension and cardiovascular disease. Earlier we studied the structure of CST by NMR, molecular modeling, and amino acid scanning mutagenesis. That structure has now been exploited for elucidation of interface pharmacophores that mediate binding of CST to its target, with consequent secretory inhibition. Designed pharmacophore models allowed screening of 3D structural domains. Selected compounds were tested on both cultured catecholaminergic cells and an in vivo model of hypertension; in each case, the candidates showed substantial mimicry of native CST actions, with preserved or enhanced potency and specificity. The approach and compounds have thus enabled rational design of novel drug candidates for treatment of hypertension or autonomic dysfunction. 相似文献
83.
Simone Guglielmetti Roberto Basilico Valentina Taverniti Stefania Arioli Claudia Piagnani Andrea Bernacchi 《World journal of microbiology & biotechnology》2013,29(11):2025-2032
In order to preserve environmental quality, alternative strategies to chemical-intensive agriculture are strongly needed. In this study, we characterized in vitro the potential plant growth promoting (PGP) properties of a gamma-proteobacterium, named MIMR1, originally isolated from apple shoots in micropropagation. The analysis of the 16S rRNA gene sequence allowed the taxonomic identification of MIMR1 as Luteibacter rhizovicinus. The PGP properties of MIMR1 were compared to Pseudomonas chlororaphis subsp. aurantiaca DSM 19603T, which was selected as a reference PGP bacterium. By means of in vitro experiments, we showed that L. rhizovicinus MIMR1 and P. chlororaphis DSM 19603T have the ability to produce molecules able to chelate ferric ions and solubilize monocalcium phosphate. On the contrary, both strains were apparently unable to solubilize tricalcium phosphate. Furthermore, the ability to produce 3-indol acetic acid by MIMR1 was approximately three times higher than that of DSM 19603T. By using fluorescent recombinants of strains MIMR1 and DSM 19603T, we also demonstrated that both bacteria are able to abundantly proliferate and colonize the barley rhizosphere, preferentially localizing on root tips and in the rhizoplane. Finally, we observed a negative effect of DSM 19603T on barley seed germination and plant growth, whereas MIMR1, compared to the control, determined a significant increase of the weight of aerial part (+22 %), and the weight and length of roots (+53 and +32 %, respectively). The results obtained in this work make L. rhizovicinus MIMR1 a good candidate for possible use in the formulation of bio-fertilizers. 相似文献
84.
Valentina D.A. Corino Frida Sandberg Federico Lombardi Luca T. Mainardi Leif Sörnmo 《Biomedical signal processing and control》2013,8(6):1017-1025
Statistical modeling of atrioventricular (AV) nodal function during atrial fibrillation (AF) is revisited for the purpose of defining model properties and improving parameter estimation. The characterization of AV nodal pathways is made more detailed and the number of pathways is now determined by the Bayesian information criterion, rather than just producing a probability as was previously done. Robust estimation of the shorter refractory period (i.e., of the slow pathway) is accomplished by a Hough-based technique which is applied to a Poincaré plot of RR intervals. The performance is evaluated on simulated data as well as on ECG data acquired from AF patients during rest and head-up tilt test. The simulation results suggest that the refractory period of the slow pathway can be accurately estimated even in the presence of many artifacts. They also show that the number of pathways can be accurately determined. The results from ECG data show that the refined AV node model provides significantly better fit than did the original model, increasing from 85 ± 5% to 88 ± 4% during rest, and from 86 ± 5% to 87 ± 3% during tilt. When assessing the effect of sympathetic stimulation, the AF frequency increased significantly during tilt (6.25 ± 0.58 Hz vs. 6.32 ± 0.61 Hz, p < 0.05, rest vs. tilt) and the prolongation of the refractory periods of both pathways decreased significantly (slow pathway: 0.23 ± 0.20 s vs. 0.11 ± 0.10 s, p < 0.001, rest vs. tilt; fast pathway: 0.24 ± 0.31 s vs. 0.16 ± 0.19 s, p < 0.05, rest vs. tilt). The results show that AV node characteristics can be assessed noninvasively for the purpose of quantifying changes induced by autonomic stimulation. 相似文献
85.
Mohammed Sherif Debbie Waung Bihter Korbeci Valentina Mavisakalyan Robert Flick Greg Brown Mamdouh Abou‐Zaid Alexander F. Yakunin Emma R. Master 《Microbial biotechnology》2013,6(5):588-597
Multicopper oxidases can act on a broad spectrum of phenolic and non‐phenolic compounds. These enzymes include laccases, which are widely distributed in plants and fungi, and were more recently identified in bacteria. Here, we present the results of biochemical and mutational studies of small laccase (SLAC), a multicopper oxidase from Streptomyces coelicolor (SCO6712). In addition to typical laccase substrates, SLAC was tested using phenolic compounds that exhibit antioxidant activity. SLAC showed oxidase activity against 12 of 23 substrates tested, including caffeic acid, ferulic acid, resveratrol, quercetin, morin, kaempferol and myricetin. The kinetic parameters of SLAC were determined for 2,2′‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulphonic acid), 2,6‐dimethoxyphenol, quercetin, morin and myricetin, and maximum reaction rates were observed with myricetin, where kcat and Km values at 60°C were 8.1 (± 0.8) s?1 and 0.9 (± 0.3) mM respectively. SLAC had a broad pH optimum for activity (between pH 4 and 8) and temperature optimum at 60–70°C. It demonstrated remarkable thermostability with a half‐life of over 10 h at 80°C and over 7 h at 90°C. Site‐directed mutagenesis revealed 17 amino acid residues important for SLAC activity including the 10 His residues involved in copper coordination. Most notably, the Y229A and Y230A mutant proteins showed over 10‐fold increase in activity compared with the wild‐type SLAC, which was correlated to higher copper incorporation, while kinetic analyses with S929A predicts localization of this residue near the meta‐position of aromatic substrates. 相似文献
86.
Emanuele Lombardo Cristian Sabellico Jan Hájek Veronika Staňková Tomá? Filipsky Valentina Balducci Paolo De Vito Stefano Leone Eugenia I. Bavavea Ilaria Proietti Silvestri Giuliana Righi Paolo Luly Luciano Saso Paolo Bovicelli Jens Z. Pedersen Sandra Incerpi 《PloS one》2013,8(4)
Natural polyphenol compounds are often good antioxidants, but they also cause damage to cells through more or less specific interactions with proteins. To distinguish antioxidant activity from cytotoxic effects we have tested four structurally related hydroxyflavones (baicalein, mosloflavone, negletein, and 5,6-dihydroxyflavone) at very low and physiologically relevant levels, using two different cell lines, L-6 myoblasts and THP-1 monocytes. Measurements using intracellular fluorescent probes and electron paramagnetic resonance spectroscopy in combination with cytotoxicity assays showed strong antioxidant activities for baicalein and 5,6-dihydroxyflavone at picomolar concentrations, while 10 nM partially protected monocytes against the strong oxidative stress induced by 200 µM cumene hydroperoxide. Wide range dose-dependence curves were introduced to characterize and distinguish the mechanism and targets of different flavone antioxidants, and identify cytotoxic effects which only became detectable at micromolar concentrations. Analysis of these dose-dependence curves made it possible to exclude a protein-mediated antioxidant response, as well as a mechanism based on the simple stoichiometric scavenging of radicals. The results demonstrate that these flavones do not act on the same radicals as the flavonol quercetin. Considering the normal concentrations of all the endogenous antioxidants in cells, the addition of picomolar or nanomolar levels of these flavones should not be expected to produce any detectable increase in the total cellular antioxidant capacity. The significant intracellular antioxidant activity observed with 1 pM baicalein means that it must be scavenging radicals that for some reason are not eliminated by the endogenous antioxidants. The strong antioxidant effects found suggest these flavones, as well as quercetin and similar polyphenolic antioxidants, at physiologically relevant concentrations act as redox mediators to enable endogenous antioxidants to reach and scavenge different pools of otherwise inaccessible radicals. 相似文献
87.
Fernanda S. Giudice Decio S. Pinto Jr Jacques E. N?r Cristiane H. Squarize Rogerio M. Castilho 《PloS one》2013,8(3)
The genome is organized and packed into the nucleus through interactions with core histone proteins. Emerging evidence suggests that tumors are highly responsive to epigenetic alterations that induce chromatin-based events and dynamically influence tumor behavior. We examined chromatin organization in head and neck squamous cell carcinoma (HNSCC) using acetylation levels of histone 3 as a marker of chromatin compaction. Compared to control oral keratinocytes, we found that HNSCC cells are hypoacetylated and that microenvironmental cues (e.g., microvasculature endothelial cells) induce tumor acetylation. Furthermore, we found that chemical inhibition of histone deacetylases (HDAC) reduces the number of cancer stem cells (CSC) and inhibits clonogenic sphere formation. Paradoxically, inhibition of HDAC also induced epithelial-mesenchymal transition (EMT) in HNSCC cells, accumulation of BMI-1, an oncogene associated with tumor aggressiveness, and expression of the vimentin mesenchymal marker. Importantly, we observed co-expression of vimentin and acetylated histone 3 at the invasion front of human HNSCC tumor tissues. Collectively, these findings suggest that environmental cues, such as endothelial cell-secreted factors, modulate tumor plasticity by limiting the population of CSC and inducing EMT. Therefore, inhibition of HDAC may constitute a novel strategy to disrupt the population of CSC in head and neck tumors to create a homogeneous population of cancer cells with biologically defined signatures and predictable behavior. 相似文献
88.
Valentina Robol Marc S. Tibber Elaine J. Anderson Tracy Bobin Patricia Carlin Sukhwinder S. Shergill Steven C. Dakin 《PloS one》2013,8(4)
Background
Detection of visual contours (strings of small oriented elements) is markedly poor in schizophrenia. This has previously been attributed to an inability to group local information across space into a global percept. Here, we show that this failure actually originates from a combination of poor encoding of local orientation and abnormal processing of visual context.Methods
We measured the ability of observers with schizophrenia to localise contours embedded in backgrounds of differently oriented elements (either randomly oriented, near-parallel or near-perpendicular to the contour). In addition, we measured patients’ ability to process local orientation information (i.e., report the orientation of an individual element) for both isolated and crowded elements (i.e., presented with nearby distractors).Results
While patients are poor at detecting contours amongst randomly oriented elements, they are proportionally less disrupted (compared to unaffected controls) when contour and surrounding elements have similar orientations (near-parallel condition). In addition, patients are poor at reporting the orientation of an individual element but, again, are less prone to interference from nearby distractors, a phenomenon known as visual crowding.Conclusions
We suggest that patients’ poor performance at contour perception arises not as a consequence of an “integration deficit” but from a combination of reduced sensitivity to local orientation and abnormalities in contextual processing. We propose that this is a consequence of abnormal gain control, a phenomenon that has been implicated in orientation-selectivity as well as surround suppression. 相似文献89.
Lorenzo Tancioni Tommaso Russo Stefano Cataudella Valentina Milana Anne Kathrin Hett Elisa Corsi Anna Rita Rossi 《PloS one》2013,8(4)
Leuciscine fishes represent an important component of freshwater ichthyofauna endemic to northern Mediterranean areas. This lineage shows high intra-specific morphological variability and exhibits high levels of hybridization, two characteristics that contribute to systematic uncertainties, misclassification of taxa and, potentially, the mismanagement of biodiversity. This study focused on brook chub, Squalius lucumonis, an endemic taxon of Central Italy. The taxonomic status of this species has long been questioned, and a hybrid origin from sympatric leusciscines (S. squalus x Rutilus rubilio, or S. squalus x Telestes muticellus) has been hypothesised. A phenotypic (evaluating shape and meristic counts) and genetic (using mitochondrial and nuclear markers) investigation of these four taxa was conducted to test species delimitation in sympatric areas and to evaluate the taxonomic status of S. lucumonis. One hundred and forty-five individuals of all four taxa were collected within streams of the lowest portion of the Tiber River basin and analysed; this region encompasses a large portion of the S. lucumonis distribution. The different morphological and genetic approaches were individually examined, compared, and then combined in a quantitative model to both investigate the limits of each approach and to identify cases of misclassification. The results obtained confirm the cladogenetic non-hybrid origin of S. lucumonis, highlight the need for immediate conservation actions and emphasise the value of an integrated approach in the study of leuciscines evolution. 相似文献
90.
Vitantonio Di Bello Iacopo Fabiani Lorenzo Conte Valentina Barletta Maria Grazia Delle Donne Cucco Cuono Laura Anna Leo Frank Lloyd Dini Mario Marzilli Aldo Pinchera Ferruccio Santini 《Obesity (Silver Spring, Md.)》2013,21(5):881-892