71 research outputs found
Kinetics and mechanism of proton transport across membrane nanopores
We use computer simulations to study the kinetics and mechanism of proton
passage through a narrow-pore carbon-nanotube membrane separating reservoirs of
liquid water. Free energy and rate constant calculations show that protons move
across the membrane diffusively in single-file chains of hydrogen-bonded water
molecules. Proton passage through the membrane is opposed by a high barrier
along the effective potential, reflecting the large electrostatic penalty for
desolvation and reminiscent of charge exclusion in biological water channels.
At neutral pH, we estimate a translocation rate of about 1 proton per hour and
tube.Comment: 4 pages, 4 figure
SÍNTESIS, CARACTERIZACIÓN QUÍMICA Y CRISTALOGRÁFICA DEL N-FUROIL-O-ETIL-SMETILCARBONIMIDOTIOATO
En este trabajo se reporta la síntesis del N-furoil-O-etil-S-metilcarbonimidotioato, así como su caracterización usando IR, RMN-1H y RMN-13C; además se caracterizó cristalográficamente obteniendo los siguientes resultados: a = 9.695 (4) b = 14.011 (5) c = 8.406 (6) A; a = 90.74 (5) 13 = 95.79 (5) y = 77.20 (3) 0 y grupo espacial P-1
Removal of peanut allergen Ara h 1 from common hospital surfaces, toys and books using standard cleaning methods
Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children.
Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma.
Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining.
Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract.
Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes
Mechanisms of Allergen-Antibody Interaction of Cockroach Allergen Bla g 2 with Monoclonal Antibodies That Inhibit IgE Antibody Binding
BACKGROUND: Cockroach allergy is strongly associated with asthma, and involves the production of IgE antibodies against inhaled allergens. Reports of conformational epitopes on inhaled allergens are limited. The conformational epitopes for two specific monoclonal antibodies (mAb) that interfere with IgE antibody binding were identified by X-ray crystallography on opposite sites of the quasi-symmetrical cockroach allergen Bla g 2. METHODOLOGY/PRINCIPAL FINDINGS: Mutational analysis of selected residues in both epitopes was performed based on the X-ray crystal structures of the allergen with mAb Fab/Fab' fragments, to investigate the structural basis of allergen-antibody interactions. The epitopes of Bla g 2 for the mAb 7C11 or 4C3 were mutated, and the mutants were analyzed by SDS-PAGE, circular dichroism, and/or mass spectrometry. Mutants were tested for mAb and IgE antibody binding by ELISA and fluorescent multiplex array. Single or multiple mutations of five residues from both epitopes resulted in almost complete loss of mAb binding, without affecting the overall folding of the allergen. Preventing glycosylation by mutation N268Q reduced IgE binding, indicating a role of carbohydrates in the interaction. Cation-π interactions, as well as electrostatic and hydrophobic interactions, were important for mAb and IgE antibody binding. Quantitative differences in the effects of mutations on IgE antibody binding were observed, suggesting heterogeneity in epitope recognition among cockroach allergic patients. CONCLUSIONS/SIGNIFICANCE: Analysis by site-directed mutagenesis of epitopes identified by X-ray crystallography revealed an overlap between monoclonal and IgE antibody binding sites and provided insight into the B cell repertoire to Bla g 2 and the mechanisms of allergen-antibody recognition, including involvement of carbohydrates
Allergic sensitization: screening methods
Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute
Characterizing first and third person viewpoints and their alternation for embodied interaction in virtual reality
Empirical research on the bodily self has shown that the body representation is malleable, and prone to manipulation when conflicting sensory stimuli are presented. Using Virtual Reality (VR) we assessed the effects of manipulating multisensory feedback (full body control and visuo-tactile congruence) and visual perspective (first and third person perspective) on the sense of embodying a virtual body that was exposed to a virtual threat. We also investigated how subjects behave when the possibility of alternating between first and third person perspective at will was presented. Our results support that illusory ownership of a virtual body can be achieved in both first and third person perspectives under congruent visuo-motor-tactile condition. However, subjective body ownership and reaction to threat were generally stronger for first person perspective and alternating condition than for third person perspective. This suggests that the possibility of alternating perspective is compatible with a strong sense of embodiment, which is meaningful for the design of new embodied VR experiences
Label-free protein detection based on the heat-transfer method-a case study with the peanut allergen Ara h 1 and aptamer-based synthetic receptors
© 2015 American Chemical Society. Aptamers are an emerging class of molecules that, because of the development of the systematic evolution of ligands by exponential enrichment (SELEX) process, can recognize virtually every target ranging from ions, to proteins, and even whole cells. Although there are many techniques capable of detecting template molecules with aptamer-based systems with high specificity and selectivity, they lack the possibility of integrating them into a compact and portable biosensor setup. Therefore, we will present the heat-transfer method (HTM) as an interesting alternative because this offers detection in a fast and low-cost manner and has the possibility of performing experiments with a fully integrated device. This concept has been demonstrated for a variety of applications including DNA mutation analysis and screening of cancer cells. To the best our knowledge, this is the first report on HTM-based detection of proteins, in this case specifically with aptamer-type receptors. For proof-of-principle purposes, measurements will be performed with the peanut allergen Ara h 1 and results indicate detection limits in the lower nanomolar regime in buffer liquid. As a first proof-of-application, spiked Ara h 1 solutions will be studied in a food matrix of dissolved peanut butter. Reference experiments with the quartz-crystal microbalance will allow for an estimate of the areal density of aptamer molecules on the sensor-chip surface
CIRUGÍA MÍNIMAMENTE INVASIVA: PROMONTOFIJACIÓN LAPAROSCÓPICA CON MALLA Y ANCLAJE DE TITANIO PARA PROLAPSO DE CÚPULA VAGINAL
Objetivo: Analizar y evaluar la factibilidad técnica, eficacia y seguridad de la promontofijación laparoscópica con malla y anclajes helicoidales de titanio para el tratamiento del prolapso de cúpula vaginal. Método: Entre noviembre de 2005 y julio de 2006, en el Servicio de Ginecología del Hospital Clínico de la Universidad Católica, se efectuaron 5 promontofijaciones laparoscópicas, utilizando técnica consistente en malla unida al promontorio del sacro con anclajes helicoidales de titanio. El rango de edad de las pacientes fue entre 46 y 65 años, con paridad vaginal entre 2 y 3. Resultados: La técnica quirúrgica logró corregir el defecto en las 5 pacientes. No hubo complicaciones intraoperatorias, ni post operatorias, con rápida recuperación y reintegración a las actividades habituales. Conclusiones: Nos enfrentamos a una novedosa técnica, segura y reproducible, con las ventajas de la laparoscopia, alta precoz y estéticamente óptim
- …