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The article deals with the longitudinal waves in a nonlocal elastic rod. Regarding the nonlocal elasticity the Eringeen model has been assumed; the novelty is that this model is described in terms of the fractional Laplace operator. The standing waves are obtained by numerical solutions of the fractional differential equation in one-dimensional continuum. The obtained results are in accordance with the ones reported in the literature and highlight the dispersion phenomenon. The effects of the nonlocal contribution and of the fractional Laplacian order are also analyzed. [ABSTRACT FROM AUTHOR]

The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy. We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis ( p < 0.001), fatigue ( p < 0.001), purpura ( p = 0.01), Raynaud phenomenon ( p = 0.003), and hypergammaglobulinemia ( p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: The use of indwelling medical devices is associated with a significant risk of infections by Staphylococcus aureus (S. aureus) which possesses a variety of virulence factors including many toxins and the ability to invade eukaryotic cells or to form biofilm on biotic and abiotic surfaces. The virulence factors above described are often related to proteins exposed on the bacterial surface. Blocking S. aureus colonization may reduce the incidence of invasive infectious diseases. Previously reports evaluated the anti-infective properties of serratiopeptidase (Spep), an extracellular metalloprotease produced by Serratia marcescens ATCC 21074 (E-15), in impairing virulence-related staphylococcal properties, such as attachment to inert surfaces and adhesion/invasion on eukaryotic cells. However, to date its mechanism of action is unknown. Methods: Spep gene was PCR amplified and cloned into expression vector pET28b(+). The mutant EspepA was constructed from plasmid pET28b-Spep applying the one-step overlap extension PCR strategy. There sulting plasmids were costransformed in EcBL21(DE3) cells with the plasmid pRuW4inh1 harboring the Erwinia chrysanthemi secretion system. Bacterial pellets and supernatants were collected and analyzed by SDS-PAGE and zymography. The unambiguous identification and a detailed structure characterization of both the wild type and the mutant Spep were obtained by mass spectrometric analyses. The resultant supernatants sterilized by filtration were separately used to condition biofilm formation of S. aureus. Quantification was based on crystal violet method. Results: In this work we constructed Spep mutant by substituting the glutamic acid in the catalytic site with a residue of alanine. In this manner we were able to evaluate the anti-biofilm activity of Spep mutant in absence of proteolytic activity. As expected, this mutant did not display protease activity but it retained its anti-biofilm properties, suggesting that this action is independent by enzymatic activity. Conclusions: New knowledge obtained from data reported in this paper calls attention to a novel mechanism of action of Spep. This protein could be developed as a potential "antipathogenic agent" capable to impair the ability of S. aureus to form biofilm on prostheses, catheters and medical devices, exploiting a mechanism different from the proteolytic activity. [ABSTRACT FROM AUTHOR]

Aims The purpose of this study was to evaluate the antimicrobial efficacy of five different proteases belonging to two different families on Staphylococcus aureus and Staphylococcus epidermidis strains. Methods and Results We used three serine proteases and two metalloproteases in single species biofilm formation assays and in human cell invasion processes. Following each protease incubation with bacterial cells, surface protein patterns were analysed by SDS- PAGE and zymography. Some differently expressed proteins were identified by mass spectrometry. Conclusions The effect of tested proteases on biofilm formation was not related to the protease category but was strain-dependent and was related to the biofilm formation capacity of each staphylococcal strain. Some proteases showed a nonspecific and indiscriminate effect on surface proteins, while others induced a discrete and reproducible action on protein profiles. Significance and Impact of the Study The inhibition of the surface-related virulence factors is a promising avenue to overcome persistent infections caused by bacterial biofilms. To this end, we show here that proteases, in particular the metalloprotease serratiopeptidase, can interfere with adhesion and invasion of eukaryotic cells and biofilm formation in staphylococci and their use could represent a viable treatment for the development of novel combination therapies. [ABSTRACT FROM AUTHOR]

This article concerns the blow up at infinity of global solutions of strongly damped polyharmonic Kirchhoff systems, involving lower order terms, a time dependent nonlinear dissipative function Q and a driving force f, under homogeneous Dirichlet boundary conditions. Some applications are presented in special subcases of f and Q. [ABSTRACT FROM AUTHOR]

We deal with the question of global and local asymptotic stabilities, as time tends to infinity, of solutions of dissipative anisotropic Kirchhoff systems, governed by the p(x)-Laplacian operator, in the framework of the variable exponent Sobolev spaces. Concrete applications are presented in special subcases of the external force f and the distributed damping Q involved in the systems. [ABSTRACT FROM AUTHOR]

The paper presents a model of virus mutations and evolution of epidemics in a system of interacting individuals, where the intensity of the pathology, described by a real discrete positive variable, is heterogeneously distributed, and the virus is in competition with the immune system or therapeutical actions. The model is developed within the framework of the Kinetic Theory of Active Particles. The paper also presents a qualitative analysis developed to study the well-posedness of the mathematical problem associated to the general framework. Finally, simulations show the ability of the model to predict some interesting emerging phenomena, such as the mutation to a subsequent virus stage, the heterogeneous evolution of the pathology with the co-presence of individual carriers of the virus at different levels of progression, and the presence of oscillating time phases with either virus prevalence or immune system control. [ABSTRACT FROM AUTHOR]

In this article we treat the question of local asymptotic stability for polyharmonic Kirchhoff systems, governed by time-dependent source forces and nonlinear damping terms. Even the simplest case (P3) studied here includes several systems of great interest, as the physical models for vibrating beams of the Woinowsky-Krieger type. This article extends and generalizes some local stability results of Autuori et al. [Asymptotic stability for anisotropic Kirchhoff systems, J. Math. Anal. Appl. 352 (2009), pp. 149-165] to higher order systems, and also of Nakao and Zhu [Decay rate of solutions of a wave equation with damping and external force, Nonlinear Anal. 46 (2001), pp. 335-345; An attractor for a nonlinear dissipative wave equation of Kirchho type, J. Math. Anal. Appl. 353 (2009), pp. 652-659]. [ABSTRACT FROM AUTHOR]

In this study, a proteomic approach that combines selective labelling of proteins containing reduced cysteine residues with two-dimensional electrophoresis/mass spectrometry was used to evaluate the redox state of protein cysteines during chronological ageing in Saccharomyces cerevisiae. The procedure was developed on the grounds that biotinconjugated iodoacetamide (BIAM) specifically reacts with reduced cysteine residues. BIAM-labelled proteins can then be selectively isolated by streptavidin affinity capture. We compared cells grown on 2% glucose in the exponential phase and during chronological ageing and we found that many proteins undergo cysteine oxidation. The target proteins include enzymes involved in glucose metabolism. Both caloric restriction and growth on glycerol resulted in a decrease in the oxidative modification. Furthermore, in these conditions a reduced production of ROS and a more negative glutathione half cell redox potential were observed. [ABSTRACT FROM AUTHOR]

Indole-3-acetic acid (IAA) is a ubiquitous molecule playing regulatory roles in many living organisms. To elucidate the physiological changes induced by IAA treatment, we used Escherichia coli K-12 as a model system. By microarray analysis we found that 16 genes showed an altered expression level in IAA-treated cells. One-third of these genes encode cell envelope components, or proteins involved in bacterial adaptation to unfavourable environmental conditions. We thus investigated the effect of IAA treatment on some of the structural components of the envelope that may be involved in cellular response to stresses. This showed that IAA-treated cells had increased the production of trehalose, lipopolysaccharide (LPS), exopolysaccharide (EPS) and biofilm. We demonstrated further that IAA triggers an increased tolerance to several stress conditions (heat and cold shock, UV-irradiation, osmotic and acid shock and oxidative stress) and different toxic compounds (antibiotics, detergents and dyes) and this correlates with higher levels of the heat shock protein DnaK. We suggest that IAA triggers an increased level of alert and protection against external adverse conditions by coordinately enhancing different cellular defence systems. [ABSTRACT FROM AUTHOR]

The interaction between the negative cis-element (AldA-NRE) and p97 repressor nuclear protein is a key step in modulating transcription of the human and mouse aldolase A (AldA) gene during the cell cycle and differentiation. In an attempt to clarify the role of transcriptional repression in regulating gene expression, we purified, from HeLa cells, the nuclear protein that specifically binds to the AldA negative regulatory element (NRE). Matrix-assisted laser desorption ionization-time of flight analysis and examination of protein profiles from the SwissProt database revealed that the previously defined p97 repressor is ZNF224, a zinc finger protein. We demonstrate that ZNF224, a Kruppel-like zinc finger transcription factor, is the repressor protein that specifically binds to the negative cis-element AldA-NRE and affects the AldA-NRE-mediated transcription. [Copyright &y& Elsevier]

We use maximum principle techniques to obtain a Harnack inequality for two-dimensional elliptic operators [ABSTRACT FROM AUTHOR]

The solution structure and stability of N-terminally truncated ²2-microglobulin (”N6²2-m), the major modification in ex vivo fibrils, have been investigated by a variety of biophysical techniques. The results show that ”N6²2-m has a free energy of stabilization that is reduced by 2.5 kcal/mol compared to the intact protein. Hydrogen exchange of a mixture of the truncated and full-length proteins at ¼M concentrations at pH 6.5 monitored by electrospray mass spectrometry reveals that ”N6²2-m is significantly less protected than its wild-type counterpart. Analysis of ”N6²2-m by NMR shows that this loss of protection occurs in ² strands I, III, and part of II. At mM concentration gel filtration analysis shows that ”N6²2-m forms a series of oligomers, including trimers and tetramers, and NMR analysis indicates that strand V is involved in intermolecular interactions that stabilize this association. The truncated species of ²2-microglobulin was found to have a higher tendency to self-associate than the intact molecule, and unlike wild-type protein, is able to form amyloid fibrils at physiological pH. Limited proteolysis experiments and analysis by mass spectrometry support the conformational modifications identified by NMR and suggest that ”N6²2-m could be a key intermediate of a proteolytic pathway of ²2-microglobulin. Overall, the data suggest that removal of the six residues from the N-terminus of ²2-microglobulin has a major effect on the stability of the overall fold. Part of the tertiary structure is preserved substantially by the disulfide bridge between Cys25 and Cys80, but the pairing between ²-strands far removed from this constrain is greatly perturbed. [ABSTRACT FROM PUBLISHER]

The preparation of new Certified Reference Materials (CRMs) of antarctic matrices forms the backbone of an ongoing project in the framework of the Italian National Program for Antarctic Research. The first CRM of this kind (MURST-ISS-A1 Antarctic Marine Sediment) is already available. The second phase focuses on the certification of antarctic krill, a small shrimp extremely abundant in the Southern Ocean. The total mass of krill available for this purpose is approximately 44 kg and results from the combination of three different catches (Ross Sea, Marguerite Bay and Livingston Island, respectively). The quantification of the following elements in the raw mass appears to be affordable by current analytical techniques, values being in the range of (in μg/g) 0.11–0.30 for As, 0.03–0.12 for Cd, 0.06–0.23 for Cr, 6.1–21 for Cu, 5.7–7.6 for Fe, 0.005–0.008 for Hg, 0.7–1.2 for Mn, 0.013– 0.077 for Ni, 0.04–0.57 for Pb and 12–16 for Zn. On the other hand, the average values ascertained in freeze-dried krill are as a rule one order of magnitude higher, i.e., (in μg/g), 3.2 for As, 0.6 for Cd, 1.8 for Cr, 75 for Cu, 61 for Fe, 0.025 for Hg, 4.6 for Mn, 0.7 for Ni, 2.1 for Pb and 81 for Zn. Information on the pretreatment of krill and details on the planned certification campaign are also given. [ABSTRACT FROM AUTHOR]

Structural analogues of syringomycin and syringotoxin were produced by fermentation, characterized by FAB-MS and amino acid analysis and compared to the parent compounds in the antibiosis test against Rhodotorula pilimanae. The C-terminal residue was shown to be important for the activity. [ABSTRACT FROM AUTHOR]

The acute effects on exercise tolerance and electrocardiographic ischaemia of felodipine and diltiazem, alone or in combination, were investigated in 12 patients with documented stable effort-induced angina pectoris. After being withdrawn from their previous antianginal treatments, patients received a single oral dose of felodipine 10 mg, diltiazem 60 mg, their combination or placebo on four different days, according to a double-blind, 4 × 4 latin-square design. Exercise time to ischaemic threshold (ST-segment depression = 1 mm) and to peak exercise was significantly prolonged by the felodipine-diltiazem combination (492 and 504s, respectively) against placebo (301 and 370s, both P <0.01), felodipine alone (381 and 428. s, both P <0.01) and diltiazem alone (367 and 422 s, both P<0.01). The effects on total work followed a similar pattern. In comparison with placebo, the administration of felodipine and diltiazem alone significantly increased exercise duration as well as total work to ischaemic threshold and to peak exercise, with no differences between the two drugs. Systolic blood pressure during exercise was not affected by any of the treatments. However, in comparison with both placebo and diltiazem, the combination induced an increase (P < 0.01) in heart rate during exercise. One patient suffered from symptomatic hypotension with the combination, and another had sinus tachycardia after felodipine. In conclusion, the acute concomitant administration of felodipine and diltiazem in patients with stable effort angina induces a marked improvement in exercise tolerance in comparison with placebo, felodipine alone and diltiazem alone. However, the benefit/risk profile of such a combination requires further, long-term investigation. [ABSTRACT FROM PUBLISHER]