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71.
The Casein Kinase 2‐Dependent Phosphorylation of NS5A Domain 3 from Hepatitis C Virus Followed by Time‐Resolved NMR Spectroscopy 下载免费PDF全文
Erica Secci Dr. Enrico Luchinat Prof. Lucia Banci 《Chembiochem : a European journal of chemical biology》2016,17(4):328-333
Hepatitis C virus (HCV) chronically affects millions of individuals worldwide. The HCV nonstructural protein 5A (NS5A) plays a critical role in the viral assembly pathway. Domain 3 (D3) of NS5A is an unstructured polypeptide responsible for the interaction with the core particle assembly structure. Casein kinase 2 (CK2) phosphorylates NS5A‐D3 at multiple sites that have mostly been predicted and only observed indirectly. In order to identify the CK2‐dependent phosphorylation sites, we monitored the reaction between NS5A‐D3 and CK2 in vitro by time‐resolved NMR. We unambiguously identified four serine residues as substrates of CK2. The apparent rate constant for each site was determined from the reaction curves. Ser408 was quickly phosphorylated, whereas the three other serine residues reacted more slowly. These results provide a starting point from which to elucidate the role of phosphorylation in the mechanisms of viral assembly—and in the modulation of the viral activity—at the molecular level. 相似文献
72.
Alessandro Marchioni Roberto Tonelli Alessandro Andreani Gaia Francesca Cappiello Matteo Fermi Fabiana Trentacosti Ivana Castaniere Riccardo Fantini Luca Tabbì Dario Andrisani Filippo Gozzi Giulia Bruzzi Linda Manicardi Antonio Moretti Serena Baroncini Anna Valeria Samarelli Massimo Pinelli Giorgio De Santis Alessandro Stefani Daniele Marchioni Francesco Mattioli Enrico Clini 《International journal of molecular sciences》2022,23(5)
Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS. 相似文献
73.
Biagio Barone Luigi Napolitano Marco Abate Luigi Cirillo Pasquale Reccia Francesco Passaro Carmine Turco Simone Morra Francesco Mastrangelo Antonio Scarpato Ugo Amicuzi Vincenzo Morgera Lorenzo Romano Francesco Paolo Calace Savio Domenico Pandolfo Luigi De Luca Achille Aveta Enrico Sicignano Massimiliano Trivellato Gianluca Spena Carlo DAlterio Giovanni Maria Fusco Raffaele Vitale Davide Arcaniolo Felice Crocetto 《International journal of molecular sciences》2022,23(7)
Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains. 相似文献
74.
Brian J. Briscoe Enrico Pelillo Sujeet K. Sinha 《Polymer Engineering and Science》1996,36(24):2996-3005
This paper presents results obtained from the scratching of an ultrahigh molecular weight polyethylene (UHMWPE) and a polycarbonate (PC). The data are used to obtain various surface mechanical properties such as the hardness and also the prevailing deformation mechanisms. Scratch results are reported for the case of rigid conical indenters for various tip included angles, bulk temperatures, scratch velocities, and applied normal loads. Scanning electron microscopy (SEM) and laser profilometry data are used to study the surface deformation and damage mechanisms, and to assess the topography of the surfaces after scratching. Deformation maps are provided for these polymers under different experimental conditions, which describe the various deformation characteristics. In general, these polymers show both increasing and decreasing trends for the scratch hardness values with variation of cone angle, (4qW/ηd2; where W is the normal load, d the width of the residual scratch, and q is a characteristic contact parameter, which ranges between 1 and 2). The scratch velocity, which governs the imposed strain rate, imparts an increasing effect on the hardness values, whereas a higher bulk temperature of the material decreases the scratch hardness. The measured responses of the surface properties of these polymers are shown to greatly depend upon the kind of deformation mechanism prevalent during the scratching and associated material removal processes. 相似文献
75.
Dr. Ivan A. Yaremenko Dr. Paolo Coghi Parichat Prommana Congling Qiu Peter S. Radulov Yuanqing Qu Yulia Yu. Belyakova Dr. Enrico Zanforlin Dr. Vladimir A. Kokorekin Yuki Yu Jun Wu Prof. Fabrice Fleury Dr. Chairat Uthaipibull Dr. Vincent Kam Wai Wong Prof. Alexander O. Terent'ev 《ChemMedChem》2020,15(13):1118-1127
This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC50=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma. 相似文献
76.
Antonio Magrì Alessia Munzone Massimiliano Peana Serenella Medici Maria Antonietta Zoroddu Orjan Hansson Cristina Satriano Enrico Rizzarelli Diego La Mendola 《International journal of molecular sciences》2016,17(8)
Angiogenin (Ang) is a potent angiogenic factor, strongly overexpressed in patients affected by different types of cancers. The specific Ang cellular receptors have not been identified, but it is known that Ang–actin interaction induces changes both in the cell cytoskeleton and in the extracellular matrix. Most in vitro studies use the recombinant form (r-Ang) instead of the form that is normally present in vivo (“wild-type”, wt-Ang). The first residue of r-Ang is a methionine, with a free amino group, whereas wt-Ang has a glutamic acid, whose amino group spontaneously cyclizes in the pyro-glutamate form. The Ang biological activity is influenced by copper ions. To elucidate the role of such a free amino group on the protein–copper binding, we scrutinized the copper(II) complexes with the peptide fragments Ang(1–17) and AcAng(1–17), which encompass the sequence 1–17 of angiogenin (QDNSRYTHFLTQHYDAK-NH2), with free amino and acetylated N-terminus, respectively. Potentiometric, ultraviolet-visible (UV-vis), nuclear magnetic resonance (NMR) and circular dichroism (CD) studies demonstrate that the two peptides show a different metal coordination environment. Confocal microscopy imaging of neuroblastoma cells with the actin staining supports the spectroscopic results, with the finding of different responses in the cytoskeleton organization upon the interaction, in the presence or not of copper ions, with the free amino and the acetylated N-terminus peptides. 相似文献
77.
This paper extends a method previously introduced by the authors for building a transparent fault classification algorithm by combining the fuzzy clustering, fuzzy logic and decision trees techniques. The baseline method transforms an opaque, fuzzy clustering-based classification model into a fuzzy logic inference model based on linguistic rules which can be represented by a decision tree formalism. The classification model thereby obtained is transparent in that it allows direct interpretation and inspection of the model. An extension in the procedure for the development of the fuzzy logic inference model is introduced to allow the treatment of more complicated cases, e.g. splitted and overlapping clusters. The corresponding computational tool developed relies on a number of parameters which can be tuned by the user to optimally compromise the level of transparency of the classification process and its efficiency. A numerical application is presented with regards to the fault classification in the Steam Generator of a Pressurized Water Reactor. 相似文献
78.
Filippo Piccinini Michela Pierini Enrico Lucarelli Alessandro Bevilacqua 《Journal of materials science. Materials in medicine》2014,25(10):2395-2410
The analysis of cell confluence and proliferation is essential to design biomaterials and scaffolds to use as bone substitutes in clinical applications. Accordingly, several approaches have been proposed in the literature to estimate the area of the scaffold covered by cells. Nevertheless, most of the approaches rely on sophisticated equipment not employed for routine analyses, while the rest of them usually do not provide significant statistics about the cell distribution. This research aims at studying confluence and proliferation of mesenchymal stromal cells (MSC) adherent on OSPROLIFE®, a commercial biomaterial in the form of granules. In particular, we propose a Computer Vision approach that can routinely be employed to monitor the surface of the single granules covered by cells because only a standard widefield fluorescent microscope is required. In order to acquire significant statistics data, we analyse wide-area images built by using MicroMos v2.0, an updated version of a previously published software specific for stitching brightfield and phase-contrast images manually acquired via a widefield microscope. In particular, MicroMos v2.0 permits to build accurate “mosaics” of fluorescent images, after correcting vignetting and photo-bleaching effects, providing a consistent representation of a sample region containing numerous granules. Then, our method allows to make automatically a statistically significant estimate of the percentage of the area of the single granules covered by cells. Finally, by analysing hundreds of granules at different time intervals we also obtained reliable data regarding cell proliferation, confirming that not only MSC adhere onto the OSPROLIFE® granules, but even proliferate over time. 相似文献
79.
Pascal Steiner Enrico Gnecco Tobin Filleter Nitya Nand Gosvami Sabine Maier Ernst Meyer Roland Bennewitz 《Tribology Letters》2010,39(3):321-327
We review recent friction measurements on ordered superstructures performed by atomic force microscopy. In particular, we
consider ultrathin KBr films on NaCl(001) and Cu(001) surfaces, single and bilayer graphene on SiC(0001), and the herringbone
reconstruction of Au(111). Atomically resolved friction images of these systems show periodic features spanning across several
unit cells. Although the physical mechanisms responsible for the formation of these superstructures are quite different, the
experimental results can be interpreted within the same phenomenological framework. A comparison between experiments and modeling
shows that, in the cases of KBr films on NaCl(001) and of graphene films, the tip-surface interaction is well described by
a potential with the periodicity of the substrate which is modulated or, respectively, superimposed with a potential with
the symmetry of the superstructure. 相似文献
80.
Roberto Chiabrando Enrico Fabrizio Gabriele Garnero 《Renewable & Sustainable Energy Reviews》2009,13(9):2441-2451
The installation and operation of systems that exploit solar energy through photovoltaic conversion, recently promoted in some European countries by new sell-back tariffs, is a relevant transformation of the territory for various reasons (land use, elimination of the existing vegetation, visual impact on the components of the landscape, microclimate change, glare from the reflection of the direct sunlight). The weak energy intensity of the solar source coupled with the low conversion efficiency of the photovoltaic cells, make the physical dimensions of such systems relevant and, with them, also the environmental, territorial and landscape impacts that basically depend on the physical extent of the system. If it is well known that an incentive to the exploitation of renewable sources is one of the features of the policy of land conservation, including the one of the protected areas, at the same time the concerns of local communities and governments about the environmental, territorial and landscape impacts of this technology are increasing rapidly.Given this picture, this work is intended to clarify the territorial impacts of the ground mounted photovoltaic systems. Later, the paper concentrates on a specific impact, which is the assessment of the risk of glare by reflection of direct sunlight from the surfaces of photovoltaic modules. The methodologies that can be used to assess this impact and the outcomes of an evaluation carried out for a 5000 m2 PV system currently designed on a hilly territory in Italy are presented. 相似文献