RESUMEN
Self-assembly of peptides is closely related to many diseases, including Alzheimer's, Parkinson's, and prion diseases. Understanding the basic mechanism of this assembly is essential for designing ultimate cure and preventive measures. Template-assisted self-assembly (TASA) of peptides on inorganic substrates can provide fundamental understanding of substrate-dependent peptides assemble, including the role of hydrophobic interface on the peptide fibrillization. Here, we have studied the self-assembly process of a potential pentapeptide inhibitor on the surface of highly oriented pyrolytic graphite (HOPG) using real time atomic force microscopy (RT-AFM) as well as molecular dynamics (MD) simulation. Experimental and simulation results show nanofilament formation consisting of ß-sheet structures and epitaxial growth on HOPG. Height analysis of the nanofilaments and MD simulation indicate that the peptides adopt a lying down configuration of double-layered antiparallel ß-sheets for its epitaxial growth, and the number of nanofilament layers is concentration-dependent. These findings provide new perspective for the mechanism of peptide-based fibrillization in amyloid diseases as well as for designing well-ordered micrometrical and nanometrical structures.
Asunto(s)
Nanoestructuras , Enfermedad de Alzheimer , Amiloide , Péptidos beta-Amiloides , Grafito , Humanos , Microscopía de Fuerza Atómica , Simulación de Dinámica MolecularRESUMEN
Owing to the inevitability of nanoparticles encountering proteins/peptides in current bio-nano-medicine development, it is important to know how they interact with each other in vitro before developing in vivo applications. To this end, a model de novo ß-sheet-forming peptide and typical biocompatible nanoparticles were selected to study thermodynamic aspects of their interactions via a fluorescence quenching method. The results showed that Pep11 and AuNPs spontaneously formed conjugates, mainly driven by a coulombic interaction with a binding affinity of ~ 0.1 µM(-1); the physical adsorption process was cooperative. These results deepen our quantitative understanding of nanoparticle-peptide interactions. The results may also be helpful in further nanoparticle-peptide hybrid nanofabrication and also useful for the application of nanoparticles in the treatment of amyloid diseases.
Asunto(s)
Fluorometría , Oro/química , Nanopartículas del Metal/química , Péptidos/química , Polímeros/química , Tensoactivos/química , Triptófano/química , Tamaño de la Partícula , Propiedades de Superficie , TermodinámicaRESUMEN
Some syphilis patients do not exhibit an appropriate serological response after treatment despite the absence of any clinical evidence of treatment failure or reinfection. This condition is called "serofast syphilis" or "serological non-response syphilis." This study explored the incidence of asymptomatic neurosyphilis (ANS) and related factors in 324 asymptomatic patients with serological non-response syphilis. We analyzed descriptive statistics stratified by the presence of asymptomatic neurosyphilis for the basic characteristics of samples. Bivariate analysis was conducted to assess correlations between outcomes and potential predictors. Variables significant in the bivariate analysis (p<0.1) were entered into multivariable logistic regression models. All p-values were two-sided with a significance threshold of p<0.05. The results indicated that 89 of 324 patients had ANS (incidence of 27.5%), and the greatest risk factors were a < fourfold decrease in serum rapid plasma reagin (RPR) titers after treatment and current serum RPR titers >1:32. Our findings suggest that ANS is common among syphilis patients, and patients with a fourfold decrease in serum RPR titers after treatment and current serum RPR titers >1:32 are more likely to develop ANS.
Asunto(s)
Infecciones Asintomáticas/epidemiología , Líquido Cefalorraquídeo/microbiología , Seronegatividad para VIH , Neurosífilis/microbiología , Sífilis/diagnóstico , Treponema pallidum/aislamiento & purificación , Adulto , Anciano , Pruebas de Aglutinación/métodos , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neurosífilis/sangre , Neurosífilis/líquido cefalorraquídeo , Estudios Retrospectivos , Sífilis/epidemiología , Serodiagnóstico de la SífilisRESUMEN
Background: Anxiety and depression continue to be significant comorbidities for people with HIV infection. We investigated the prevalence of and factors associated with anxiety and depression among adult HIV-infected patients across China. Methods: In this cross-sectional study, we described clinical and psychosocial variables related to depression and anxiety in 4103 HIV-infected persons. Doctors assessed anxiety and depression by asking patients whether they had experienced anxiety or depression in the prior month. Patients also self-administered the Hospital Anxiety and Depression (HAD) scale; those with score ≥8 on HAD-A/D were considered to be at high risk of anxiety or depression. Results: Associations between socio-demographic, psychosocial, and ART-related clinical factors and risk of depression or anxiety were investigated using multivariable logistic regression. Among patients assessed between 9/2014 and 11/2015, 27.4% had symptoms of anxiety, 32.9% had symptoms of depression, and 19.0% had both. Recentness of HIV diagnoses (P = 0.046) was associated with elevated odds of anxiety. Older age (P = 0.004), higher educational attainment (P < 0.001), employment (P = 0.001), support from family / friends (P < 0.001), and sleep disturbance (P < 0.001), and number of ART regimen switches (P = 0.046) were associated with risk of depression, while neither sex nor transmission route showed any associations. There were no significant associations with HIV-specific clinical factors including current CD4+ T cell count and current viral load. Conclusions: Prevalence of symptoms of anxiety and depression is high in this cohort of treatment-experienced HIV patients. Psychological and social-demographic factors, rather than HIV disease status, were associated with risk of depression and anxiety. This finding highlights the need to deliver interventions to address the mental health issues affecting HIV-infected persons with fully successful immune restoration across China.
RESUMEN
Muscovite mica is a widely used substrate because of its flatness. The large scale anomalous patterns of muscovite have been discovered by atomic force microscopy (AFM). These patterns distribute around the defects of the muscovite surface. By using different imaging modes and analyzing functions of AFM, these extraordinary patterns are thoroughly characterized, and it was revealed that some selected regularly aligned patterns mimic 2-D orthorhombic crystal systems surrounding the regular structure. However, such patterned nanostructures have no effects on the template-assisted self-assembly (or epitaxial growth) of a disease-related peptide GAV-9.
RESUMEN
In the past years the self-assembly of amyloid-like peptides has attracted increasing attentions, because it is highly related to neurodegenerative diseases and has a potential for serving as nanomaterial to fabricate novel and useful nanostructures. In this paper, we focused on the role of interfacial conditions in the self-assembly of an amyloid-like peptide, termed Pep11. It was found that, when dissolved in bulk solutions, Pep11 formed into ß-sheet structures and assembled into long filaments in several hours, as revealed by Thioflavin T fluorescence and transmission electron microscopy (TEM) morphology characterization, respectively. When the peptide solution was added onto a mica/HOPG substrate, peptide filaments with three preferred orientations with an angle of 60° to each other were formed immediately, as imaged in situ by atomic force microscopy (AFM). However, the kinetics in filament formation and the morphologies of the formed beta sheet either on HOPG and mica or in bulk solutions were quite different. These results indicate that the interfacial properties dramatically affect the peptide self-assembly process.