Evaluating the Impact of Hydrophobic Silicon Dioxide in the Interfacial Properties of Lung Surfactant Films

CRUE-CSIC (Acuerdos Transformativos 2022)The interaction of hydrophobic silicon dioxide particles (fumed silicon dioxide), as model air pollutants, and Langmuir monolayers of a porcine lung surfactant extract has been studied in order to try to shed light on the physicochemical bases underlying the potential adverse effects associated with pollutant inhalation. The surface pressure−area isotherms of lung surfactant (LS) films including increasing amounts of particles revealed that particle incorporation into LS monolayers modifies the organization of the molecules at the water/vapor interface, which alters the mechanical resistance of the interfacial films, hindering the ability of LS layers for reducing the surface tension, and reestablishing the interface upon compression. This influences the normal physiological function of LS as is inferred from the analysis of the response of the Langmuir films upon the incorporation of particles against harmonic changes of the interfacial area (successive compression−expansion cycles). These experiments evidenced that particles alter the relaxation mechanisms of LS films, which may be correlated to a modification of the transport of material within the interface and between the interface and the adjacent fluid during the respiratory cycle.Depto. de Química FísicaFac. de Ciencias QuímicasTRUEUnión Europea. Horizonte 2020Ministerio de Ciencia e Innovación (MICINN)pu

Effect of Silica Nanoparticles on Rheological and Structural Properties of DPPC Langmuir Monolayers

The study of the interaction between nanoparticles and model of lung surfactant is of great relevance to understand possible adverse effects of inhalable nanoparticles on the respiratory function [1,2]. We report therefore a study on the interfacial properties, structure and dilational rheology of monolayers of the major lipidic component of the lung surfactant, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), in the presence of silica nanoparticles. Investigations are performed by a Langmuir trough equipped with Brewster Angle Microscopy

The display makes a difference: A mobile eye tracking study on the perception of art before and after a museum’s rearrangement

There is increasing awareness that the perception of art is affected by the way it is presented. In 2018, the Austrian Gallery Belvedere redisplayed its permanent collection. Our multi-disciplinary team seized this opportunity to investigate the viewing behavior of specific artworks both before and after the museum’s rearrangement. In contrast to previous mobile eye tracking (MET) studies in museums, this study benefits from the comparison of two realistic display conditions (without any research interference), an unconstrained study design (working with regular museum visitors), and a large data sample (comprising 259 participants). We employed a mixed-method approach that combined mobile eye tracking, subjective mapping (a drawing task in conjunction with an open interview), and a questionnaire in order to relate gaze patterns to processes of meaning-making. Our results show that the new display made a difference in that it 1) generally increased the viewing times of the artworks; 2) clearly extended the reading times of labels; and 3) deepened visitors’ engagement with the artworks in their exhibition reflections. In contrast, interest in specific artworks and art form preferences proved to be robust and independent of presentation modes

Interaction of Particles with Langmuir Monolayers of 1,2-Dipalmitoyl-Sn-Glycero-3-Phosphocholine: A Matter of Chemistry?

Lipid layers are considered among the first protective barriers of the human body against pollutants, e.g., skin, lung surfactant, or tear film. This makes it necessary to explore the physico-chemical bases underlying the interaction of pollutants and lipid layers. This work evaluates using a pool of surface-sensitive techniques, the impact of carbon black and fumed silica particles on the behavior of Langmuir monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The results show that the incorporation of particles into the lipid monolayers affects the surface pressure–area isotherm of the DPPC, modifying both the phase behavior and the collapse conditions. This is explained considering that particles occupy a part of the area available for lipid organization, which affects the lateral organization of the lipid molecules, and consequently the cohesion interactions within the monolayer. Furthermore, particles incorporation worsens the mechanical performance of lipid layers, which may impact negatively in different processes presenting biological relevance. The modification induced by the particles has been found to be dependent on their specific chemical nature. This work tries to shed light on some of the most fundamental physico-chemical bases governing the interaction of pollutants with lipid layers, which plays an essential role on the design of strategies for preventing the potential health hazards associated with pollution

Molecular engineering of Ghfp, the gonococcal orthologue of neisseria meningitidis factor H binding protein

Knowledge of the sequences and structures of proteins produced by microbial pathogens is continuously increasing. Besides offering the possibility of unraveling the mechanisms of pathogenesis at the molecular level, structural information provides new tools for vaccine development, such as the opportunity to improve viral and bacterial vaccine candidates by rational design. Structure-based rational design of antigens can optimize the epitope repertoire in terms of accessibility, stability, and variability. In the present study, we used epitope mapping information on the well-characterized antigen of Neisseria meningitidis factor H binding protein (fHbp) to engineer its gonococcal homologue, Ghfp. Meningococcal fHbp is typically classified in three distinct antigenic variants. We introduced epitopes of fHbp variant 1 onto the surface of Ghfp, which is naturally able to protect against meningococcal strains expressing fHbp of variants 2 and 3. Heterologous epitopes were successfully transplanted, as engineered Ghfp induced functional antibodies against all three fHbp variants. These results confirm that structural vaccinology represents a successful strategy for modulating immune responses, and it is a powerful tool for investigating the extension and localization of immunodominant epitopes

Non-invasive evaluation of ventricular refractoriness and its dispersion during ventricular fibrillation in patients with implantable cardioverter defibrillator

BACKGROUND: Local ventricular refractoriness and its dispersion during ventricular fibrillation (VF) have not been well evaluated, due to methodological difficulties. METHODS: In this study, a non-invasive method was used in evaluation of local ventricular refractoriness and its dispersion during induced VF in 11 patients with VF and/or polymorphic ventricular tachycardia (VT) who have implanted an implantable cardioverter defibrillator (ICD). Bipolar electrograms were simultaneously recorded from the lower oesophagus behind the posterior left ventricle (LV) via an oesophageal electrode and from the right ventricular (RV) apex via telemetry from the implanted ICD. VF intervals were used as an estimate of the ventricular effective refractory period (VERP). In 6 patients, VERP was also measured during sinus rhythm at the RV apex and outflow tract (RVOT) using conventional extra stimulus technique. RESULTS: Electrograms recorded from the RV apex and the lower esophagus behind the posterior LV manifested distinct differences of the local ventricular activities. The estimated VERPs during induced VF in the RV apex were significantly shorter than that measured during sinus rhythm using extra stimulus technique. The maximal dispersion of the estimated VERPs during induced VF between the RV apex and posterior LV was that of 10 percentile VF interval (40 ± 27 ms), that is markedly greater than the previously reported dispersion of ventricular repolarization without malignant ventricular arrhythmias (30–36 ms). CONCLUSIONS: This study verified the feasibility of recording local ventricular activities via oesophageal electrode and via telemetry from an implanted ICD and the usefulness of VF intervals obtained using this non-invasive technique in evaluation of the dispersion of refractoriness in patients with ICD implantation

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p 10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features

Data for a meta-analysis of the adaptive layer in adaptive large neighborhood search.

Meta-analysis, a systematic statistical examination that combines the results of several independent studies, has the potential of obtaining problem- and implementation-independent knowledge and understanding of metaheuristic algorithms, but has not yet been applied in the domain of operations research. To illustrate the procedure, we carried out a meta-analysis of the adaptive layer in adaptive large neighborhood search (ALNS). Although ALNS has been widely used to solve a broad range of problems, it has not yet been established whether or not adaptiveness actually contributes to the performance of an ALNS algorithm. A total of 134 studies were identified through Google Scholar or personal e-mail correspondence with researchers in the domain, 63 of which fit a set of predefined eligibility criteria. The results for 25 different implementations of ALNS solving a variety of problems were collected and analyzed using a random effects model. This dataset contains a detailed comparison of ALNS with the non-adaptive variant per study and per instance, together with the meta-analysis summary results. The data enable to replicate the analysis, to evaluate the algorithms using other metrics, to revisit the importance of ALNS adaptive layer if results from more studies become available, or to simply consult the ready-to-use formulas in the summary file to carry out a meta-analysis of any research question. The individual studies, the meta-analysis and its results are described and interpreted in detail in Renata Turkeš, Kenneth Sörensen, Lars Magnus Hvattum, Meta-analysis of Metaheuristics: Quantifying the Effect of Adaptiveness in Adaptive Large Neighborhood Search, in the European Journal of Operational Research

DNA and histone deacetylases as targets for neuroblastoma treatment

Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death from neoplasia in infancy. Still little improvement in therapeutic options has been made, requiring a need for the development of new therapies. In our laboratory, we address still unsettled questions, which of mechanisms of action of DNA-damaging drugs both currently use for treatment of human neuroblastomas (doxorubicin, cis-platin, cyclophosphamide and etoposide) and another anticancer agent decreasing growth of neuroblastomas in vitro, ellipticine, are predominant mechanism(s) responsible for their antitumor action in neuroblastoma cell lines in vitro. Because hypoxia frequently occurs in tumors and strongly correlates with advanced disease and poor outcome caused by chemoresistance, the effects of hypoxia on efficiencies and mechanisms of actions of these drugs in neuroblastomas are also investigated. Since the epigenetic structure of DNA and its lesions play a role in the origin of human neuroblastomas, pharmaceutical manipulation of the epigenome may offer other treatment options also for neuroblastomas. Therefore, the effects of histone deacetylase inhibitors on growth of neuroblastoma and combination of these compounds with doxorubicin, cis-platin, etoposide and ellipticine as well as mechanisms of such effects in human neuroblastona cell lines in vitro are also investigated. Such a study will increase our knowledge to explain the proper function of these drugs on the molecular level, which should be utilized for the development of new therapies for neuroblastomas