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排序方式: 共有1932条查询结果,搜索用时 15 毫秒
51.
Dr. Vladimir O. Talibov Dr. Edoardo Fabini Edward A. FitzGerald Dr. Daniele Tedesco Daniela Cederfeldt Martin J. Talu Moira M. Rachman Filip Mihalic Dr. Elisabetta Manoni Dr. Marina Naldi Dr. Paola Sanese Dr. Giovanna Forte Dr. Martina Lepore Signorile Prof. Xavier Barril Dr. Cristiano Simone Prof. Manuela Bartolini Dr. Doreen Dobritzsch Dr. Alberto Del Rio Prof. U. Helena Danielson 《Chembiochem : a European journal of chemical biology》2021,22(9):1597-1608
SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (KD=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (KD=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action. 相似文献
52.
Paola Songia Mattia Chiesa Valentina Alfieri Ilaria Massaiu Donato Moschetta Veronika Myasoedova Vincenza Valerio Laura Fusini Paola Gripari Marco Zanobini Paolo Poggio 《International journal of molecular sciences》2021,22(4)
Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification. 相似文献
53.
Direct Application of Rep‐PCR on Type I Sourdough Matrix to Monitor the Dominance and Persistence of a Lactobacillus plantarum Starter Throughout Back‐Slopping 下载免费PDF全文
This study describes the optimization and application of repetitive element‐PCR (rep‐PCR) technique directly on microbial DNA extracted from type I sourdoughs for fast monitoring of a Lb. plantarum starter strain (P1FMC) throughout daily back‐slopping. The challenge was to follow and study the performance of a starter culture directly in sourdoughs without cultivation on selective media. The extraction of good quality microbial DNA suitable for amplification from a complex matrix such as dough was the first target. In addition, the objective to obtain a clear rep‐PCR profile referable to a specific starter strain among a microbial community was pursued. Co‐inoculum trials, in flour matrix, with Lb. plantarum P1FMC and L. lactis LC71 strains and, subsequently, type I sourdough back‐slopping trials were performed. The rep‐PCR amplification profiles obtained were clearly referable to that of Lb. plantarum P1FMC starter in both co‐inoculum trials (also when it was present with one order of magnitude less with respect to L. lactis LC71) and back‐slopping trials where it dominated the fermentation process with loads of 108 cfu g?1 and prevailed on the autochthonous microbiota. Thus, the approach proposed in this paper could be considered a methodological advancement, based on a culture‐independent one‐step rep‐PCR, suitable for fast monitoring of starter performance. 相似文献
54.
Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase
Dr. Simone Vitiello Dr. Monica Caselli Dr. Giorgia Pavesi Dr. Matteo Santucci Dr. Stefania Ferrari Prof. Maria Paola Costi Prof. Glauco Ponterini 《Chembiochem : a European journal of chemical biology》2021,22(10):1800-1810
The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided. 相似文献
55.
56.
Paola Riolo Roxana L. Minuz Gianfranco Anfora Marco V. Rossi Stacconi Silvia Carlin Nunzio Isidoro Roberto Romani 《Journal of chemical ecology》2012,38(8):1017-1030
The Palearctic planthopper Hyalesthes obsoletus is the natural vector of the grapevine yellow disease Bois noir. Grapevine is an occasional host plant of this polyphagous planthopper. To deepen our knowledge of the role of plant volatile organic compounds for H. obsoletus host plant searching, we carried out behavioral, morphological, and electrophysiological studies. We tested the attraction of H. obsoletus to nettle, field bindweed, hedge bindweed, chaste tree, and grapevine by using a Y-shaped olfactometer. The results showed a significant attraction of male H. obsoletus to chaste tree, and of the females to nettle. Male H. obsoletus were repelled by odor from hedge bindweed. Ultrastructural studies of the antennae showed at least two types of olfactory sensilla at the antennal pedicel: plaque organs and trichoid sensilla. Volatile organic compounds from nettle and chaste tree were collected, and the extracts were analyzed by coupling gas-chromatography to both mass-spectrometry and electroantennography. The volatile organic compounds that elicited electrophysiological responses in male and female antennae were identified. These findings are discussed with respect to behavior of H. obsoletus males and females in the field. 相似文献
57.
Salvatore Mirabile Dr. Serena Vittorio Prof. Maria Paola Germanò Dr. Ilenia Adornato Dr. Laura Ielo Prof. Antonio Rapisarda Prof. Rosaria Gitto Francesca Pintus Dr. Antonella Fais Prof. Laura De Luca 《ChemMedChem》2021,16(19):3083-3093
There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4-fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4-(4-fluorobenzyl)piperazin-1-yl]-(3-chloro-2-nitro-phenyl)methanone 26 (IC50=0.18 μM) that proved to be ∼100-fold more active than reference compound kojic acid (IC50=17.76 μM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR. 相似文献
58.
Natalia Brossard Beatriz Gonzalez-Muñoz Carolina Pavez Arianna Ricci Xinmiao Wang Fernando Osorio Edmundo Bordeu Giuseppina Paola Parpinello Jianshe Chen 《International Journal of Food Science & Technology》2021,56(10):5382-5394
Astringency is a sensory attribute, related to the quality and mouthfeel of red wines. However, the origin of astringency sub-qualities, such as the typical drying astringency found in immature grapes, is still unknown. Astringency of red wines with similar tannin content but different astringency sub-qualities, from different harvest dates, is studied. Astringency was characterised in terms of friction coefficient, polyphenol content, sensory analysis and tannin/salivary–proteins aggregates characterisation. A different evolution during ripening was found for both Cabernet Sauvignon and Carménère, and tannin–protein aggregates showed differences in size, shape and surface. The velvety sub-quality appears to be related to aggregates with low precipitation, and with specific surface characteristics as roundness and Feret diameter. Results from this work propose an effect of aggregates on sensory perception and opens the possibility to explore their effect on oral lubrication. 相似文献
59.
We investigate the performance of the Mimetic Finite Difference (MFD) method for the approximation of a constraint optimal control problem governed by an elliptic operator. Low-order and high-order mimetic discretizations are considered and a priori error estimates are derived, in a suitable discrete norm, for both the control and the state variables. A wide class of numerical experiments performed on a set of examples selected from the literature assesses the robustness of the MFD method and confirms the convergence analysis. 相似文献
60.
Filippo Fabbri Francesca Rossi Manuela Melucci Ilse Manet Giovanni Attolini Laura Favaretto Massimo Zambianchi Giancarlo Salviati 《Nanoscale research letters》2012,7(1):680
A new class of nanostructured hybrid materials is developed by direct grafting of a model thiophene-based organic dye on the surface of 3C-SiC/SiO2 core/shell nanowires. TEM-EDX analysis reveals that the carbon distribution is more spread than it would be, considering only the SiC core size, suggesting a main contribution from C of the oligothiophene framework. Further, the sulfur signal found along the treated wires is not detected in the as-grown samples. In addition, the fluorescent spectra are similar for the functionalized nanostructures and T3Pyr in solution, confirming homogeneous molecule grafting on the nanowire surface. Chemical and luminescence characterizations confirm a homogeneous functionalization of the nanowires. In particular, the fluorophore retains its optical properties after functionalization. 相似文献