Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Pediatr Res ; 85(3): 398-404, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30555154

RESUMO

BACKGROUND: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time. METHODS: We studied 28 male rhesus monkeys (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 years of uninterrupted dosing. RESULTS: With the exception of serum myoglobin, there were no statistical differences or apparent dose-response trends in clinical pathology, cardiac inflammatory biomarkers, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the control group (2182 ng/mL). The dose response was inversely proportional to dosage (P = .0006). CONCLUSIONS: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Metilfenidato/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Biópsia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Ecocardiografia , Eletrocardiografia , Ventrículos do Coração/efeitos dos fármacos , Inflamação , Macaca mulatta , Masculino , Miocárdio/patologia , Distribuição Aleatória , Risco
2.
Exp Cell Res ; 373(1-2): 164-170, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30342004

RESUMO

Ketamine, an FDA-approved N-methyl-D-aspartate (NMDA) receptor antagonist, is commonly used for general pediatric anesthesia. Accumulating evidence has indicated that prolonged exposure to ketamine induces widespread apoptotic cell death in the developing brains of experimental animals. Although mitochondria are known to play a pivotal role in cell death, little is known about the alterations in mitochondrial ultrastructure that occur during ketamine-induced neurotoxicity. The objective of this pilot study was to utilize classic and contemporary methods in electron microscopy to study the impact of ketamine on the structure of mitochondria in the developing rat brain. While transmission electron microscopy (TEM) was employed to comprehensively study mitochondrial inner membrane topology, serial block-face scanning electron microscopy (SBF-SEM) was used as a complementary technique to compare the overall mitochondrial morphology from a representative treated and untreated neuron. In this study, postnatal day 7 (PND-7) Sprague-Dawley rats were treated with ketamine or saline (6 subcutaneous injections × 20 mg/kg or 10 ml/kg, respectively, at 2-h intervals with a 6-h withdrawal period after the last injection, n=6 each group). Samples from the frontal cortex were harvested and analyzed using TEM or SBF-SEM. While classic TEM revealed that repeated ketamine exposure induces significant mitochondrial swelling in neurons, the newer technique of SBF-SEM confirmed the mitochondrial swelling in three dimensions (3D) and showed that ketamine exposure may also induce mitochondrial fission, which was not observable in the two dimensions (2D) of TEM. Furthermore, 3D statistical analysis of these reconstructed mitochondria appeared to show that ketamine-treated mitochondria had significantly larger volumes per unit surface area than mitochondria from the untreated neuron. The ultrastructural mitochondrial alterations demonstrated here by TEM and SBF-SEM support ketamine's proposed mechanism of neurotoxicity in the developing rat brain.


Assuntos
Analgésicos/toxicidade , Encéfalo/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/toxicidade , Ketamina/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Animais , Encéfalo/ultraestrutura , Feminino , Processamento de Imagem Assistida por Computador , Masculino , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/ultraestrutura , Ratos Sprague-Dawley
3.
Phys Rev Lett ; 112(17): 173901, 2014 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-24836247

RESUMO

We study the cubic- (focusing-)quintic (defocusing) nonlinear Schrödinger equation in two transverse dimensions. We discuss a family of stationary traveling waves, including rarefaction pulses and vortex-antivortex pairs, in a background of critical amplitude. We show that these rarefaction pulses can be generated inside a flattop soliton when a smaller bright soliton collides with it. The fate of the evolution strongly depends on the relative phase of the solitons. Among several possibilities, we find that the dark pulse can reemerge as a bright soliton.

4.
Phys Rev E ; 109(2-1): 024216, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38491634

RESUMO

We investigate the existence of self-trapped nonlinear waves with multiple phase singularities. Working with the cubic-quintic nonlinear Schrödinger equation, we focus on configurations with an antivortex surrounded by a triangular arrangement of vortices within a hosting soliton. We find stationary patterns that can be interpreted as stable self-trapped vortex crystals, constituting the first example of a configuration of this sort with space-independent potentials. Their stability is linked to their norm, transitioning from unstable to stable as their size increases, with an intermediate region where the structure is marginally unstable, undergoing a remarkable and puzzling self-reconstruction during its evolution.

5.
Foods ; 13(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38928770

RESUMO

Campylobacter jejuni is the foodborne pathogen causing most gastrointestinal infections. Understanding its ability to form biofilms is crucial for devising effective control strategies in food processing environments. In this study, we investigated the growth dynamics and biofilm formation of C. jejuni NCTC 11168 in various culture media, including chicken juice (CJ), brain heart infusion (BHI), and Mueller Hinton (MH) broth. Our results demonstrated that C. jejuni exhibited a higher growth rate and enhanced biofilm formation in CJ and in 1:1 mixtures of CJ with BHI or MH broth compared to these measures in BHI or MH broth alone. Electron microscopy unveiled distinct morphological attributes of late-stage biofilm cells in CJ, including the presence of elongated spiral-shaped cells, thinner stretched structures compared to regular cells, and extended thread-like structures within the biofilms. Proteomic analysis identified significant alterations in protein expression profiles in C. jejuni biofilms, with a predominance of downregulated proteins associated with vital functions like metabolism, energy production, and amino acid and protein biosynthesis. Additionally, a significant proportion of proteins linked to biofilm formation, virulence, and iron uptake were suppressed. This shift toward a predominantly coccoid morphology echoed the reduced energy demands of these biofilm communities. Our study unlocks valuable insights into C. jejuni's biofilm in CJ, demonstrating its adaptation and survival.

6.
Front Microbiol ; 15: 1342478, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435692

RESUMO

Salmonella spp. is one of the most isolated microorganisms reported to be responsible for human foodborne diseases and death. Water constitutes a major reservoir where the Salmonella spp. can persist and go undetected when present in low numbers. In this study, we assessed the viability of 12 serotypes of Salmonella enterica subsp. enterica for 160 days in nuclease-free water at 4 and 25°C using flow cytometry and Tryptic Soy Agar (TSA) plate counts. The results show that all 12 serotypes remain viable after 160 days in distilled water using flow cytometry, whereas traditional plate counts failed to detect ten serotypes incubated at 25°C. Moreover, the findings demonstrate that 4°C constitutes a more favorable environment where Salmonella can remain viable for prolonged periods without nutrients. Under such conditions, however, Salmonella exhibits a higher susceptibility to all tested antibiotics and benzalkonium chloride (BZK). The pre-enrichment with Universal Pre-enrichment Broth (UP) and 1/10 × Tryptic Soy broth (1/10 × TSB) resuscitated all tested serotypes on TSA plates, nevertheless cell size decreased after 160 days. Furthermore, phenotype microarray (PM) analysis of S. Inverness and S. Enteritidis combined with principal component analysis (PCA) revealed an inter-individual variability in serotypes with their phenotype characteristics, and the impact of long-term storage at 4 and 25°C for 160 days in nuclease-free water. This study provides an insight to Salmonella spp. long-term survivability at different temperatures and highlights the need for powerful tools to detect this microorganism to reduce the risk of disease transmission of foodborne pathogens via nuclease-free water.

7.
Nanotoxicology ; 18(2): 134-159, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444264

RESUMO

The growing application of silver nanoparticles (AgNPs) in consumer, healthcare, and industrial products has raised concern over potential health implications due to increasing exposure. The evaluation of the immune response to nanomaterials is one of the key criteria to assess their biocompatibility. There are well-recognized sex-based differences in innate and adaptive immune responses. However, there is limited information available using human models. The aim was to investigate the potential sex-based differences in immune functions after exposure to AgNPs using human peripheral blood mononuclear cells (PBMCs) and plasma from healthy donors. These functions include inflammasome activation, cytokine expression, leukocyte proliferation, chemotaxis, plasma coagulation, and complement activation. AgNPs were characterized by dynamic light scattering and transmission electron microscopy. Inflammasome activation by AgNPs was measured after 6- and 24-hours incubations. AgNPs-induced inflammasome activation was significantly higher in the females, especially for the 6-hour exposure. No sex-based differences were observed for Ag ions controls. Younger donors exhibited significantly more inflammasome activation than older donors after 24-hours exposure. IL-10 was significantly suppressed in males and females after exposure. AgNPs suppressed leukocyte proliferation similarly in males and females. No chemoattractant effects, no alterations in plasma coagulation, or activation of the complement were observed after AgNPs exposure. In conclusion, the results highlight that there are distinct sex-based differences in inflammasome activation after exposure to AgNPs in human PBMCs. The results highlight the importance of considering sex-based differences in inflammasome activation induced by exposure to AgNPs in any future biocompatibility assessment for products containing AgNPs.


Assuntos
Leucócitos Mononucleares , Nanopartículas Metálicas , Prata , Humanos , Prata/toxicidade , Prata/química , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Feminino , Masculino , Leucócitos Mononucleares/efeitos dos fármacos , Adulto , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Pessoa de Meia-Idade , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Fatores Sexuais , Adulto Jovem
8.
J Virol ; 86(5): 2390-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22171264

RESUMO

Espirito Santo virus (ESV) is a newly discovered virus recovered as contamination in a sample of a virulent strain of dengue-2 virus (strain 44/2), which was recovered from a patient in the state of Espirito Santo, Brazil, and amplified in insect cells. ESV was found to be dependent upon coinfection with a virulent strain of dengue-2 virus and to replicate in C6/36 insect cells but not in mammalian Vero cells. A sequence of the genome has been produced by de novo assembly and was not found to match to any known viral sequence. An incomplete match to the nucleotide sequence of the RNA-dependent RNA polymerase from Drosophila X virus (DXV), another birnavirus, could be detected. Mass spectrometry analysis of ESV proteins found no matches in the protein data banks. However, peptides recovered by mass spectrometry corresponded to the de novo-assembled sequence by BLAST analysis. The composition and three-dimensional structure of ESV are presented, and its sequence is compared to those of other members of the birnavirus family. Although the virus was found to belong to the family Birnaviridae, biochemical and sequence information for ESV differed from that of DXV, the representative species of the genus Entomobirnavirus. Thus, significant differences underscore the uniqueness of this infectious agent, and its relationship to the coinfecting virus is discussed.


Assuntos
Infecções por Birnaviridae/virologia , Birnaviridae/isolamento & purificação , Birnaviridae/fisiologia , Replicação Viral , Aedes , Sequência de Aminoácidos , Animais , Birnaviridae/classificação , Birnaviridae/genética , Linhagem Celular , Genoma Viral , Humanos , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Proteínas Virais/química , Proteínas Virais/genética , Cultura de Vírus
9.
Phys Rev E ; 107(4-1): 044215, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37198765

RESUMO

We consider a disk-shaped cold atom Bose-Einstein condensate with repulsive atom-atom interactions within a circular trap, described by a two-dimensional time-dependent Gross-Pitaevskii equation with cubic nonlinearity and a circular box potential. In this setup, we discuss the existence of a type of stationary nonlinear waves with propagation-invariant density profiles, consisting of vortices located at the vertices of a regular polygon with or without an antivortex at its center. These polygons rotate around the center of the system and we provide approximate expressions for their angular velocity. For any size of the trap, we find a unique regular polygon solution that is static and is seemingly stable for long evolutions. It consists of a triangle of vortices with unit charge placed around a singly charged antivortex, with the size of the triangle fixed by the cancellation of competing effects on its rotation. There exist other geometries with discrete rotational symmetry that yield static solutions, even if they turn out to be unstable. By numerically integrating in real time the Gross-Pitaevskii equation, we compute the evolution of the vortex structures and discuss their stability and the fate of the instabilities that can unravel the regular polygon configurations. Such instabilities can be driven by the instability of the vortices themselves, by vortex-antivortex annihilation or by the eventual breaking of the symmetry due to the motion of the vortices.

10.
Nanomaterials (Basel) ; 13(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37570524

RESUMO

Spherical copper oxide nanoparticles (CuO/Cu2O NPs) were synthesized by pulsed laser ablation in liquids (PLAL). The copper target was totally submerged in deionized (DI) water and irradiated by an infrared laser beam at 1064 nm for 30 min. The NPs were then characterized by dynamic light scattering (DLS) and atomic emission spectroscopy (AES) to determine their size distribution and concentration, respectively. The phases of copper oxide were identified by Raman spectroscopy. Then, the antibacterial activity of CuO/Cu2O NPs against foodborne pathogens, such as Salmonella enterica subsp. enterica serotype Typhimurium DT7, Escherichia coli O157:H7, Shigella sonnei ATCC 9290, Yersinia enterocolitica ATCC 27729, Vibrio parahaemolyticus ATCC 49398, Bacillus cereus ATCC 11778, and Listeria monocytogenes EGD, was tested. At a 3 ppm concentration, the CuO/Cu2O NPs exhibited an outstanding antimicrobial effect by killing most bacteria after 5 h incubation at 25 °C. Field emission scanning electron microscope (FESEM) confirmed that the CuO/Cu2O NPs destructed the bacterial cell wall.

11.
PLoS One ; 18(5): e0285849, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228105

RESUMO

The joint work of the stomach and the small intestine plays a fundamental role in human digestion. In the stomach, food is turned into a semi-fluid mixture that is slowly released into the small intestine, where most enzymatic reactions occur, and nutrients are absorbed as they become available. This whole process is closely related to glucose homeostasis, mainly because of the appearance of glucose in the portal system and the energetic expenditure of the process itself. The current phenomenological-based model describes such effects of the digestive process on blood glucose concentration. It considers enzymatic and mechanical transformations, energetic expenditure, and the impact of macro-nutrients, fiber, and water on overall digestion and glucose absorption. The model estimates the rate of glucose appearance in the portal vein and is intended to be further integrated into existing models for other human organs and used in model-based systems such as an artificial pancreas with automated insulin delivery.


Assuntos
Glucose , Veia Porta , Humanos , Insulina , Intestino Delgado , Estômago , Glicemia
12.
Phys Rev Lett ; 109(25): 253903, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23368467

RESUMO

We show that extreme vacuum pressures can be measured with current technology by detecting the photons produced by the relativistic Thomson scattering of ultraintense laser light by the electrons of the medium. We compute the amount of radiation scattered at different frequencies and angles when a Gaussian laser pulse crosses a vacuum tube and design strategies for the efficient measurement of pressure. In particular, we show that a single day experiment at a high repetition rate petawatt laser facility such as Vega, that will be operating in 2014 in Salamanca, will be sensitive, in principle, to pressures p as low as 10(-16)Pa, and will be able to provide highly reliable measurements for p >/~ 10(-14)Pa.

13.
Cells ; 11(21)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36359886

RESUMO

Staphylococcus epidermidis is a leading cause of biofilm-associated infections on implanted medical devices. During the treatment of an infection, bacterial cells inside biofilms may be exposed to sublethal concentrations of the antimicrobial agents. In the present study, the effect of subinhibitory concentrations of tigecycline (TC) on biofilms formed by S. epidermidis strain RP62A was investigated using a quantitative global proteomic technique. Sublethal concentrations of TC [1/8 (T1) and 1/4 minimum inhibitory concentration (MIC) (T2)] promoted biofilm production in strain RP62A, but 1/2 MIC TC (T3) significantly inhibited biofilm production. Overall, 413, 429, and 518 proteins were differentially expressed in biofilms grown with 1/8 (T1), 1/4 (T2), and 1/2 (T3) MIC of TC, respectively. As the TC concentration increased, the number of induced proteins in each Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway increased. The TC concentration dependence of the proteome response highlights the diverse mechanisms of adaptive responses in strain RP62A biofilms. In both COG and KEGG functional analyses, most upregulated proteins belong to the metabolism pathway, suggesting that it may play an important role in the defense of strain RP62A biofilm cells against TC stress. Sub-MIC TC treatment of strain RP62A biofilms led to significant changes of protein expression related to biofilm formation, antimicrobial resistance, virulence, quorum sensing, ABC transporters, protein export, purine/pyrimidine biosynthesis, ribosomes, and essential proteins. Interestingly, in addition to tetracycline resistance, proteins involved in resistance of various antibiotics, including aminoglycosides, antimicrobial peptides, ß-lactams, erythromycin, fluoroquinolones, fusidic acid, glycopeptides, lipopeptides, mupirocin, rifampicin and trimethoprim were differentially expressed. Our study demonstrates that global protein expression profiling of biofilm cells to antibiotic pressure may improve our understanding of the mechanisms of antibiotic resistance in biofilms.


Assuntos
Proteoma , Staphylococcus epidermidis , Staphylococcus epidermidis/genética , Tigeciclina/farmacologia , Tigeciclina/metabolismo , Proteoma/metabolismo , Proteômica , Biofilmes , Antibacterianos/farmacologia
14.
Biochemistry ; 50(49): 10598-606, 2011 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-22080766

RESUMO

The glycoprotein Ib-IX (GPIb-IX) complex expressed on platelet plasma membrane is involved in thrombosis and hemostasis via the initiation of adhesion of platelets to von Willebrand factor (VWF) exposed at the injured vessel wall. While most of the knowledge of the GPIb-IX complex was obtained from studies on platelets and transfected mammalian cells expressing the GPIb-IX complex, there is not an in vitro membrane system that allows systematic analysis of this receptor. The phospholipid bilayer Nanodisc composed of a patch of phospholipid surrounded by membrane scaffold protein is an attractive tool for membrane protein study. We show here that the GPIb-IX complex purified from human platelets has been reconstituted into the Nanodisc. The Nanodisc-reconstituted GPIb-IX complex was able to bind various conformation-sensitive monoclonal antibodies. Furthermore, it bound to VWF in the presence of botrocetin with an apparent K(d) of 0.73 ± 0.07 nM. The binding to VWF was inhibited by anti-GPIbα antibodies with epitopes overlapping with the VWF-binding site, but not by anti-GPIbß monoclonal antibody RAM.1. Finally, the Nanodisc-reconstituted GPIb-IX complex exhibited ligand binding activity similar to that of the isolated extracellular domain of GPIbα. In conclusion, the GPIb-IX complex in Nanodiscs adopts a native-like conformation and possesses the ability to bind its natural ligands, thus making a Nanodisc a suitable in vitro platform for further investigation of this hemostatically important receptor complex.


Assuntos
Bicamadas Lipídicas/química , Complexo Glicoproteico GPIb-IX de Plaquetas/química , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Anticorpos Monoclonais/metabolismo , Plaquetas/química , Venenos de Crotalídeos/química , Venenos de Crotalídeos/metabolismo , Humanos , Nanotecnologia , Fosfolipídeos/química , Complexo Glicoproteico GPIb-IX de Plaquetas/isolamento & purificação , Conformação Proteica , Estrutura Terciária de Proteína , Transdução de Sinais , Fator de von Willebrand/metabolismo
15.
Anesth Analg ; 112(6): 1289-95, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21346161

RESUMO

BACKGROUND: The use of plasma-based resuscitation for trauma patients in hemorrhagic shock has been associated with a decrease in mortality. Although some have proposed a beneficial effect through replacement of coagulation proteins, the putative mechanisms of protection afforded by plasma are unknown. We have previously shown in a cell culture model that plasma decreases endothelial cell permeability in comparison with crystalloid. The endothelial glycocalyx consists of proteoglycans and glycoproteins attached to a syndecan backbone, which together protect the underlying endothelium. We hypothesize that endothelial cell protection by plasma is due, in part, to its restoration of the endothelial glycocalyx and preservation of syndecan-1 after hemorrhagic shock. METHODS: Rats were subjected to hemorrhagic shock to a mean arterial blood pressure of 30 mm Hg for 90 minutes followed by resuscitation with either lactated Ringer's (LR) solution or fresh plasma to a mean arterial blood pressure of 80 mm Hg and compared with shams or shock alone. After 2 hours, lungs were harvested for syndecan mRNA, immunostained with antisyndecan-1, or stained with hematoxylin and eosin. To specifically examine the effect of plasma on the endothelium, we infused small bowel mesentery with a lanthanum-based solution, identified venules, and visualized the glycocalyx by electron microscopy. All data are presented as mean ± SEM. Results were analyzed by 1-way analysis of variance with Tukey post hoc tests. RESULTS: Electron microscopy revealed degradation of the glycocalyx after hemorrhagic shock, which was partially restored by plasma but not LR. Pulmonary syndecan-1 mRNA expression was higher in animals resuscitated with plasma (2.76 ± 0.03) in comparison with shock alone (1.39 ± 0.22) or LR (0.82 ± 0.03) and correlated with cell surface syndecan-1 immunostaining. Shock also resulted in significant lung injury by histopathology scoring (1.63 ± 0.26), which was mitigated by resuscitation with plasma (0.67 ± 0.17) but not LR (2.0 ± 0.25). CONCLUSION: The protective effects of plasma may be due in part to its ability to restore the endothelial glycocalyx and preserve syndecan-1 after hemorrhagic shock.


Assuntos
Endotélio/metabolismo , Glicocálix/metabolismo , Ressuscitação/métodos , Choque Hemorrágico/fisiopatologia , Choque Hemorrágico/terapia , Animais , Pressão Sanguínea , Cristalização , Modelos Animais de Doenças , Endotélio/patologia , Lantânio/metabolismo , Masculino , Microscopia Eletrônica/métodos , Ratos , Ratos Sprague-Dawley , Sindecana-1/metabolismo , Fatores de Tempo
16.
Antibiotics (Basel) ; 10(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206280

RESUMO

Pseudomonas aeruginosa is the most common Gram-negative pathogen causing nosocomial multidrug resistant infections. It is a good biofilm producer and has the potential for contaminating medical devices. Despite the widespread use of antibacterial-impregnated catheters, little is known about the impacts of antibacterial coating on the pathogenesis of P. aeruginosa. In this study, we investigated the adaptive resistance potential of P. aeruginosa strain PAO1 in response to continuous antibiotic exposure from clindamycin/rifampicin-impregnated catheters (CR-IC). During exposure for 144 h to clindamycin and rifampicin released from CR-IC, strain PAO1 formed biofilms featuring elongated and swollen cells. There were 545 and 372 differentially expressed proteins (DEPs) identified in the planktonic and biofilm cells, respectively, by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Both Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the planktonic cells responded to the released antibiotics more actively than the biofilm cells, with metabolism and ribosomal biosynthesis-associated proteins being significantly over-expressed. Exposure to CR-IC increased the invasion capability of P. aeruginosa for Hela cells and upregulated the expression of certain groups of virulence proteins in both planktonic and biofilm cells, including the outer membrane associated (flagella, type IV pili and type III secretion system) and extracellular (pyoverdine) virulence proteins. Continuous exposure of P. aeruginosa to CR-IC also induced the overexpression of antibiotic resistance proteins, including porins, efflux pumps, translation and transcription proteins. However, these upregulations did not change phenotypic minimum inhibitory concentration (MIC) during the experimental timeframe. The concerning association between CR-IC and overexpression of virulence factors in P. aeruginosa suggests the need for additional investigation to determine if it results in adverse clinical outcomes.

17.
Rev Med Virol ; 19(5): 257-72, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19475572

RESUMO

Sindbis virus has long been the prototypical alphavirus used in the study of assembly of icosahedral viruses which contain membranes. Much is known about the assembly pathway and molecular architecture of this virus, and models of mechanisms of infection and release of the viral RNA have been proposed. This review will focus on the structural aspects of in vitro antibody neutralisation of a metastable alphavirus, Sindbis virus, which results from antibody induced conformational changes. For the alphaviruses, structures of in vitro antibody induced conformational neutralisation for Sindbis virus, and receptor occlusion for Sindbis and Ross River virus (RRV) have been reported. A model is presented which could extend the mechanism of antibody induced conformational neutralisation to any metastable virus structure.


Assuntos
Infecções por Alphavirus/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Sindbis virus/imunologia , Animais , Testes de Neutralização , Conformação Proteica , Proteínas Virais/química , Proteínas Virais/imunologia , Montagem de Vírus
18.
Microorganisms ; 8(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32369929

RESUMO

Coagulase-negative staphylococci (CoNS) are an important group of opportunistic pathogenic microorganisms that cause infections in hospital settings and are generally resistant to many antimicrobial agents. We report on phenotypic and genotypic virulence characteristics of a select group of clinical, mecA-positive (encoding penicillin-binding protein 2a) CoNS isolates. All CoNS were resistant to two or more antimicrobials with S. epidermidis strain 214EP, showing resistance to fifteen of the sixteen antimicrobial agents tested. Aminoglycoside-resistance genes were the ones most commonly detected. The presence of megaplasmids containing both horizontal gene transfer and antimicrobial resistance genetic determinants indicates that CoNS may disseminate antibiotic resistance to other bacteria. Staphylococcus sciuri species produced six virulence enzymes, including a DNase, gelatinase, lipase, phosphatase, and protease that are suspected to degrade tissues into nutrients for bacterial growth and contribute to the pathogenicity of CoNS. The PCR assay for the detection of biofilm-associated genes found the eno (encoding laminin-binding protein) gene in all isolates. Measurement of their biofilm-forming ability and Spearman's rank correlation coefficient analyses revealed that the results of crystal violet (CV) and extracellular polymeric substances (EPS) assays were significantly correlated (ρ = 0.9153, P = 3.612e-12). The presence of virulence factors, biofilm-formation capability, extracellular enzymes, multidrug resistance, and gene transfer markers in mecA-positive CoNS clinical strains used in this study makes them powerful opportunistic pathogens. The study also warrants a careful evaluation of nosocomial infections caused by CoNS and may be useful in studying the mechanism of virulence and factors associated with their pathogenicity in vivo and developing effective strategies for mitigation.

19.
J Virol ; 82(12): 5750-60, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18417595

RESUMO

A rare Sindbis virus anti-E1 neutralizing monoclonal antibody, Sin-33, was investigated to determine the mechanism of in vitro neutralization. A cryoelectron microscopic reconstruction of Sindbis virus (SVHR) neutralized with FAb from Sin-33 (FAb-33) revealed conformational changes on the surface of the virion at a resolution of 24 A. FAb-33 was found to bind E1 in less than 1:1 molar ratios, as shown by the absence of FAb density in the reconstruction and stoichiometric measurements using radiolabeled FAb-33, which determined that about 60 molecules of FAb-33 bound to the 240 possible sites in a single virus particle. FAb-33-neutralized virus particles became sensitive to digestion by endoproteinase Glu-C, providing further evidence of antibody-induced structural changes within the virus particle. The treatment of FAb-33-neutralized or Sin-33-neutralized SVHR with low pH did not induce the conformational rearrangements required for virus membrane-cell membrane fusion. Exposure to low pH, however, increased the amount of Sin-33 or FAb-33 that bound to the virus particles, indicating the exposure of additional epitopes. The neutralization of SVHR infection by FAb-33 or Sin-33 did not prevent the association of virus with host cells. These data are in agreement with the results of previous studies that demonstrated that specific antibodies can inactivate the infectious state of a metastable virus in vitro by the induction of conformational changes to produce an inactive structure. A model is proposed which postulates that the induction of conformational changes in the infectious state of a metastable enveloped virus may be a general mechanism of antibody inactivation of virus infectivity.


Assuntos
Anticorpos Monoclonais/farmacologia , Glicoproteínas de Membrana/imunologia , Sindbis virus/química , Proteínas do Envelope Viral/imunologia , Animais , Cricetinae , Epitopos , Concentração de Íons de Hidrogênio , Fragmentos Fab das Imunoglobulinas/imunologia , Rim/citologia , Testes de Neutralização , Mapeamento de Peptídeos , Ligação Proteica , Conformação Proteica , Sindbis virus/fisiologia , Sindbis virus/ultraestrutura , Vírion/fisiologia , Vírion/ultraestrutura
20.
Phys Rev E ; 99(6-1): 062211, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31330596

RESUMO

We study the self-trapped vortex-ring eigenstates of the two-dimensional Schrödinger equation with focusing Poisson and cubic nonlinearities. For each value of the topological charge l, there is a family of solutions depending on a parameter that can be understood as the relative importance of the cubic term. We analyze the perturbative stability of the solutions and simulate the fate of the unstable ones. For l=1 and l=2, there is an interval of the family of eigenstates for which the initial profile breaks apart but subsequently reconstructs itself, a process that can be interpreted as a nontrivial nonlinear oscillation between the vortex and an azimuthon. This revival provides a compelling realization of a recurrence of the Fermi-Pasta-Ulam-Tsingou type. Outside this interval, the vortices can be stable (for small cubic terms) or unstable and nonrecurrent (for large cubic terms). We argue that there is a crossover between these regimes that resembles a strong stochasticity threshold. For l≥3, all solutions are unstable and nonrecurrent. Finally, we comment on the possible experimental implementation of this phenomenon in the context of nonlinear laser beam propagation in thermo-optical media.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA