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1.
Int J Infect Dis ; : 107089, 2024 May 09.
Article En | MEDLINE | ID: mdl-38734058

BACKGROUND: Listeria monocytogenes (LM) is a health treat worldwide given its high mortality and the growing of high-risk susceptible populations. METHODS: All hospitalizations with a diagnosis of LM in the National Registry of Hospital Discharges were examined in Spain from 2000 to 2021. RESULTS: A total of 8,152 hospital admissions with LM were identified. The mean age was 59.5 years and 48% were immunosuppressed (IS). The rate of LM hospitalizations increased from 5 per 1 million population in 2000 to 8.9 in 2021 (p<0.001). A foodborne outbreak in Andalusia determined a sharp increase of admissions with LM during 2019. The COVID-19 pandemic and lockdowns were associated with a fall in LM admissions. The overall in-hospital mortality was 16.7%. The number of deaths in patients hospitalized with LM rose from 7.8 per 100,000 deceased in 2000 to 18 in 2021 (p<0.001). After adjustment, age >65 years-old (Odds ratio [OR]=2.16), sepsis (OR=2.60), meningoencephalitis (OR=1.72), endocarditis (OR=2.0), neonatal listeriosis (OR=2.10) and IS (OR=2.09) were associated with mortality. CONCLUSIONS: The number of patients hospitalized with LM in Spain has risen significantly from 2000 to 2021. The increase in the rate of admissions and deaths was largely driven by the growing proportion of elderly and of immunosuppressed patients.

2.
Sci Total Environ ; 934: 173260, 2024 May 16.
Article En | MEDLINE | ID: mdl-38761933

The LIFE SURFING Project was carried out at the Bailin Landfill in Sabiñánigo, Spain (2020-2022), applying Surfactant Enhanced Aquifer Remediation (SEAR) and In Situ Chemical Oxidation (S-ISCO) in a 60-meter test cell beneath the old landfill, to remediate a contaminated aquifer with dense non-aqueous phase liquid (DNAPL) from nearby lindane production. The project overcame traditional extraction limitations, successfully preventing groundwater pollution from reaching the river. In spring 2022, two SEAR interventions involved the injection of 9.3 m3 (SEAR-1) and 6 m3 (SEAR-2) of aqueous solutions containing 20 g/L of the non-ionic surfactant E-Mulse 3®, with bromide (around 150 mg/L) serving as a conservative tracer. 7.1 and 6.0 m3 were extracted in SEAR-1 and SEAR-2, respectively, recovered 60-70 % of the injected bromide and 30-40 % of the surfactant, confirming surfactant adsorption by the soil. Approximately 130 kg of DNAPL were removed, with over 90 % mobilized and 10 % solubilized. A surfactant-to-DNAPL recovery mass ratio of 2.6 was obtained, a successful value for a fractured aquifer. In September 2022, the S-ISCO phase entailed injecting 22 m3 of a solution containing persulfate (40 g/L), E-Mulse 3® (4 g/L), and NaOH (8.75 g/L) in pulses over 48 h, oxidizing around 20 kg of DNAPL and ensuring low toxicity levels after that. Preceding the SEAR and S-ISCO trials, 2020 and 2021 were dedicated to detailed groundwater flow characterizations, including hydrological and tracer studies. These preliminary investigations allowed the design of a barrier zone between 317 and 557 m from the test cell and the river, situated 900 m away. This zone, integrating alkali dosing, aeration, vapor extraction, and oxidant injection, effectively prevented the escape of fluids to the river. Neither surfactants nor contaminants were detected in river waters post-treatment. The absence of residual phase in test cell wells and reduction of chlorinated compound levels in groundwater were noticed till one year after S-ISCO.

3.
Article En | MEDLINE | ID: mdl-38738641

AIMS: The study aimed to determine the dimensionality of the Spanish version of the PQ-16 among Colombian adolescent school students. METHODS: A validation study was designed with the participation of 334 Colombian adolescent students aged between 13 and 17 (M = 15.2, SD = 1.1); 171 (52.1%) were girls, and 163 (47.9%) were boys, 229 (68.6%) were ninth-grade students and 105 (31.4%) were tenth-grade students. Confirmatory factor analysis was performed, internal consistency was calculated with the Kuder-Richardson and McDonald's omega tests, and correlation with suicide ideation was computed with the Kendall correlation (r). RESULTS: The confirmatory factor analysis showed that the PQ-16 adequately fit a unidimensional structure: RMSEA = 0.05 (90%CI 0.04-0.06), CFI = 0.91, TLI = 0.90, SRMR = 0.05, chi-squared = 193.18 (df = 102, p < 0.001) and normalized chi-squared = 1.89. This factor presented high internal consistency: Kuder-Richardson test and McDonald's omega of 0.83. The correlation between the PQ-16 and suicide ideation was r = 0.45 (p < 0.001). CONCLUSION: The PQ-16 is a one-dimensional tool with high internal consistency and correlation with suicide ideation among schooled adolescents. Further research should explore the PQ-16 performance against a structured clinical interview.

4.
Small Methods ; : e2400251, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38607949

The advent of biomedical applications of soft bioinspired materials has entailed an increasing demand for streamlined and expedient characterization methods meant for both research and quality control objectives. Here, a novel measurement system for the characterization of biological hydrogels with volumes as low as 75 µL was developed. The system is based on an indentation platform equipped with micrometer drive actuators that allow the determination of both the fracture points and Young's moduli of relatively stiff polymers, including agarose, as well as the measurements of viscosity for exceptionally soft and viscous hydrogels, such as DNA hydrogels. The sensitivity of the method allows differentiation between DNA hydrogels produced by rolling circle amplification based on different template sequences and synthesis protocols. In addition, the polymerization kinetics of the hydrogels can be determined by time-resolved measurements, and the apparent viscosities of even more complex DNA-based nanocomposites can be measured. The platform presented here thus offers the possibility to characterize a broad variety of soft biomaterials in a targeted, fast, and cost-effective manner, holding promises for applications in fundamental materials science and ensuring reproducibility in the handling of complex materials.

5.
Med. clín. soc ; 8(1)abr. 2024.
Article Es | LILACS-Express | LILACS | ID: biblio-1550538

Introducción: durante las últimas dos décadas, el concepto de capital social se ha utilizado con creciente frecuencia en las ciencias de la salud debido a las relaciones directas e indirectas entre el capital social y la salud física y mental de las poblaciones. Por tanto, es necesario construir un instrumento para cuantificar este concepto con seguridad y confiabilidad. Objetivo: analizar la consistencia interna y dimensionalidad de una escala de siete ítems para medir el capital social en adultos de la población general de Colombia. Metodología: se realizó un estudio de validación en línea, que incluyó una muestra de 700 adultos de entre 18 y 76 años, el 68 % eran mujeres. Los participantes completaron una escala de siete ítems llamada Escala de Capital Social Cognitivo (ECSC). El alfa de Cronbach y el omega de McDonald se calcularon para probar la consistencia interna. Se realizaron análisis factoriales exploratorios y confirmatorios para explorar la dimensionalidad de la ECSC. Resultados: la ECSC presentó una consistencia interna baja (alfa de Cronbach de 0,56 y omega de McDonald de 0,59) y pobre dimensionalidad. Seguidamente, se probó una versión de cinco ítems (ECSC-5). La ECSC-5 mostró una alta consistencia interna (alfa de Cronbach de 0,79 y omega de McDonald de 0,80) y una estructura unidimensional con indicadores de bondad de ajuste aceptables. Discusión: la ECSC-5 presenta alta consistencia interna y una estructura unidimensional para medir el capital cognitivo social en adultos colombianos. Se recomienda la ECSC-5 para la medición del capital social en la población general colombiana. Futuras investigaciones deben corroborar estos hallazgos en aplicaciones de lápiz y papel y explorar otros indicadores de confiabilidad y validez.


Introduction: During the last two decades, the concept of social capital has been used increasingly frequently in health sciences due to the direct and indirect relationships between social capital and populations' physical and mental health. Therefore, it is necessary to build an instrument to quantify this concept confidently and reliably. Objective: The study aimed to internal consistency and dimensionality of a seven-item scale to measure social capital in Colombia's general population of adults. Methods: An online validation study included a sample of 700 adults aged between 18 and 76 years; 68% were females. Participants completed a seven-item scale called the Cognitive Social Capital Scale (CSCS). Cronbach's alpha and McDonald's omega were computed to test internal consistency. The authors explore the internal consistency and dimensionality of the CSCS. Results: The CSCS presented a low internal consistency (Cronbach's alpha of 0.56 and McDonald's omega of 0.59) and poor dimensionality. Then, the researchers tested a five-item version (CSCS-5). The CSCS-5 showed high internal consistency (Cronbach's alpha of 0.79 and McDonald's omega of 0.80) and a one-dimension structure with acceptable goodness-of-fit indicators. Discussion: The CSCS-5 presents high internal consistency and a one-dimensional structure to measure cognitive capital social in the Colombian sample. Authors can recommend measuring social capital in the general Colombian population. Further research should corroborate this pencil and paper application findings and explore other reliability and validity indicators.

6.
Angew Chem Int Ed Engl ; : e202318805, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38687094

The adhesion of circulating tumor cells (CTCs) to the endothelial lumen and their extravasation to surrounding tissues are crucial in the seeding of metastases and remain the most complex events of the metastatic cascade to study. Integrins expressed on CTCs are major regulators of the extravasation process. This knowledge is primarily derived from animal models and biomimetic systems based on artificial endothelial layers, but these methods have ethical or technical limitations. We present a versatile microfluidic device to study cancer cell extravasation that mimics the endothelial barrier by using a porous membrane functionalized with DNA origami nanostructures (DONs) that display nanoscale patterns of adhesion peptides to circulating cancer cells. The device simulates physiological flow conditions and allows direct visualization of cell transmigration through microchannel pores using 3D confocal imaging. Using this system, we studied integrin-specific adhesion in the absence of other adhesive events. Specifically, we show that the transmigration ability of the metastatic cancer cell line MDA-MB-231 is influenced by the type, distance, and density of adhesion peptides present on the DONs. Furthermore, studies with mixed ligand systems indicate that integrins binding to RGD (arginine-glycine-aspartic acid) and IDS (isoleucine-aspartic acid-serine) did not synergistically enhance the extravasation process of MDA-MB-231 cells.

7.
Sci Total Environ ; 926: 171848, 2024 May 20.
Article En | MEDLINE | ID: mdl-38518821

This work studies the remediation of groundwater saturated with dense non-aqueous phase liquid (DNAPL) from lindane production wastes by electrochemical oxidation. DNAPL-saturated groundwater contains up to 26 chlorinated organic compounds (COCs), including different isomers of hexachlorocyclohexane (HCH). To do this, polluted groundwater was electrolysed using boron-doped diamond (BDD) and stainless steel (SS) as anode and cathode, respectively, and the influence of the current density on COCs removal was evaluated in the range from 5 to 50 mA cm-2. Results show that current densities higher than 25 mA cm-2 lead to the complete removal and mineralisation of all COCs identified in groundwater. The higher the current density, the higher the COCs removal rate. At lower current densities (5 mA cm-2), chlorobenzenes were completely removed, and degradations above 90 % were reached for COCs with more than five chlorine atoms in their molecules. The use of BDD anodes promotes the electrochemical generation of powerful reactive species, such as persulfate, hypochlorite or hydroxyl radicals, that contribute to the degradation and mineralisation of COCs. The applied current density also influences the generation of these species. Finally, no acute toxicity towards Vibrio fischeri was observed for the treated groundwater after the electrochemical oxidation performed at 5 and 10 mA cm-2. These findings demonstrate that electrochemical oxidation with BDD anodes at moderate current densities is a promising alternative for the remediation of actual groundwater contaminated with DNAPLs.

8.
Healthcare (Basel) ; 12(3)2024 Feb 05.
Article En | MEDLINE | ID: mdl-38338293

BACKGROUND: The widespread adoption of mobile devices by adolescents underscores the potential to harness these tools to instill healthy habits into their daily lives. An exemplary manifestation of this initiative is the Healthy Jeart app, crafted with the explicit goal of fostering well-being. METHODOLOGY: This study, framed within an applied investigation, adopts an exploratory and descriptive approach, specifically delving into the realm of user experience analysis. The focus of this research is a preliminary examination aimed at understanding users' perceived usability of the application. To glean insights, a comprehensive questionnaire was administered to 101 teenagers, seeking their evaluations on various usability attributes. The study took place during 2022. RESULTS: The findings reveal a considerable consensus among users regarding the evaluated usability aspects. However, the areas for improvement predominantly revolve around managing the information density, particularly for a subset of end users grappling with overwhelming content. Additionally, recommendations are put forth to streamline the confirmation process for user suggestions and comments. CONCLUSION: This analysis illuminates both the strengths of the app and areas ripe for refinement, paving the way for a more user-centric and efficacious Healthy Jeart application.

9.
J Child Sex Abus ; 33(2): 229-242, 2024 Feb.
Article En | MEDLINE | ID: mdl-38351595

Sexual abuse is a public health problem due to its negative impact on physical and mental health. This study aimed to determine the association between sexual abuse and the use of psychoactive substances among high-school adolescents in Colombia. A cross-sectional analytical study was designed in which tenth and eleventh-grade students were included. Overall, a history of sexual abuse was explored with the Trauma Symptom Checklist, and lifetime substance use was assessed with the United States Centers for Disease Control Youth Risk Behavior Questionnaire. The prevalence of sexual abuse was 17.4%, lifetime alcohol use was 77.4%, cigarette 22.4%, cannabis 11.6%, cocaine 2.7%, and other substances 5.1%. History of sexual abuse was associated with alcohol use (OR = 1.59, 95% CI 1.10-2.30), cigarette (OR = 2.08, 95% CI 1.51-2.85), cannabis (OR = 2.43, 95% CI 1.66-3.56), cocaine (OR = 2.51, 95% CI 1.25-5.04) and use of other substances (OR = 2.33, 95% CI 1.31-4.13). The history of sexual abuse is related to the use of substances in high school adolescents in the Caribbean Region of Colombia. More studies are needed to identify the impact of sexual abuse on short-term and lifelong mental health.


Child Abuse, Sexual , Cocaine , Substance-Related Disorders , Adolescent , Child , Humans , Colombia/epidemiology , Cross-Sectional Studies , Substance-Related Disorders/epidemiology , Substance-Related Disorders/psychology , Students/psychology , Surveys and Questionnaires , Caribbean Region , Prevalence
10.
Nano Lett ; 24(5): 1611-1619, 2024 Feb 07.
Article En | MEDLINE | ID: mdl-38267020

The nanoscale arrangement of ligands can have a major effect on the activation of membrane receptor proteins and thus cellular communication mechanisms. Here we report on the technological development and use of tailored DNA origami-based molecular rulers to fabricate "Multiscale Origami Structures As Interface for Cells" (MOSAIC), to enable the systematic investigation of the effect of the nanoscale spacing of epidermal growth factor (EGF) ligands on the activation of the EGF receptor (EGFR). MOSAIC-based analyses revealed that EGF distances of about 30-40 nm led to the highest response in EGFR activation of adherent MCF7 and Hela cells. Our study emphasizes the significance of DNA-based platforms for the detailed investigation of the molecular mechanisms of cellular signaling cascades.


Epidermal Growth Factor , ErbB Receptors , Humans , DNA/chemistry , Epidermal Growth Factor/chemistry , Epidermal Growth Factor/metabolism , ErbB Receptors/metabolism , HeLa Cells , Ligands , Signal Transduction
11.
Sci Rep ; 13(1): 21746, 2023 12 08.
Article En | MEDLINE | ID: mdl-38066027

This paper presents a new procedure for vaccine design against highly variable viruses such as Hepatitis C. The procedure uses an optimization algorithm to design vaccines that maximize the coverage of epitopes across different virus variants. Weighted epitopes based on the success ratio of immunological assays are used to prioritize the selection of epitopes for vaccine design. The procedure was successfully applied to design DC vaccines loaded with two HCV peptides, STG and DYP, which were shown to be safe, immunogenic, and able to induce significant levels of anti-viral cytokines, peptide-specific cellular immune responses and IgG antibodies. The procedure could potentially be applied to other highly variable viruses that currently lack effective vaccines.


Hepatitis C , Viral Hepatitis Vaccines , Humans , Hepacivirus , Epitopes , Immunity, Cellular
12.
Article Es | LILACS-Express | LILACS | ID: biblio-1535414

Introducción: La exposición a la violencia afecta la salud mental. Sin embargo, existen pocos estudios sobre este fenómeno en estudiantes universitarios. Objetivo: Establecer la asociación entre la exposición a la violencia e ideación suicida en universitarios de Santa Marta, Colombia. Metodología: Se realizó un estudio cuantitativo, analítico y transversal. Participaron 1647 estudiantes entre 16 y 24 años (M=20,58, DT=1,715), quienes completaron la Escala de Exposición a la Violencia (α = 0,87) y la Escala de Ideación Suicida de Roberts (α =0,74). Resultados: El modelo de regresión logística ajustado indicó que la exposición directa a la violencia en el colegio (OR=2,02; IC95 %=1,28-3,16) y casa (OR=1,53; IC95 %=1,02-2,29), e indirecta en colegio (OR=1,34; IC95 %= 11,06-1,70) y casa (OR=1,91; IC95 %=1,27-2,88), incrementan la ideación suicida. Conclusiones: La exposición a la violencia en el colegio y en la casa, de forma directa e indirecta, son factores de riesgo para la ideación suicida en estudiantes universitarios.


Introduction: Exposure to violence affects mental health; however, there are few studies on this phenomenon in university students. Objective: To establish the association between exposure to violence and suicidal ideation in university students from Santa Marta, Colombia. Methodology: A quantitative, analytical, and cross-sectional study was carried out involving 1,647 students between 16 and 24 years old (M=20.58, SD=1.715), who completed the violence exposure Scale (α =0.87) and the Roberts suicidal ideation scale (α =0.74). Results: The adjusted logistic regression model indicated that direct exposure to violence at school (OR=2.02; 95% CI=1.28-3.16) and home (OR=1.53; 95% CI=1.02 -2.29), and indirect exposure at school (OR=1.34; CI95%= 1.06-1.70) and home (OR=1.91; CI95%=1.27-2.88), increased suicidal ideation. Conclusion: Direct and indirect exposure to violence at school and at home are risk factors for suicidal ideation in university students.

14.
Chem Commun (Camb) ; 59(81): 12184-12187, 2023 Oct 10.
Article En | MEDLINE | ID: mdl-37750315

Accurate quantification of polymerized DNA in rolling circle amplification (RCA)-based hydrogels is challenging due to the high viscosity of these materials, however, it can be achieved with a photometric nucleotide depletion assay or qPCR. We show that the DNA content strongly depends on the template sequence and correlates with the mechanical properties of the hydrogels.

16.
Nanoscale Adv ; 5(15): 3914-3923, 2023 Jul 25.
Article En | MEDLINE | ID: mdl-37496619

Microfluidic droplets are an important tool for studying and mimicking biological systems, e.g., to examine with high throughput the interaction of biomolecular components and the functionality of natural cells, or to develop basic principles for the engineering of artificial cells. Of particular importance is the approach to generate a biomimetic membrane by supramolecular self-assembly of nanoparticle components dissolved in the aqueous phase of the droplets at the inner water/oil interface, which can serve both to mechanically reinforce the droplets and as an interaction surface for cells and other components. While this interfacial assembly driven by electrostatic interaction of surfactants is quite well developed for water/mineral oil (W/MO) systems, no approaches have yet been described to exploit this principle for water/fluorocarbon oil (W/FO) emulsion droplets. Since W/FO systems exhibit not only better compartmentalization but also gas solubility properties, which is particularly crucial for live cell encapsulation and cultivation, we report here the investigation of charged fluorosurfactants for the self-assembly of DNA-modified silica nanoparticles (SiNP-DNA) at the interface of microfluidic W/FO emulsions. To this end, an efficient multicomponent Ugi reaction was used to synthesize the novel fluorosurfactant M4SURF to study the segregation and accumulation of negatively charged SiNP-DNA at the inner interface of microfluidic droplets. Comparative measurements were performed with the negatively charged fluorosurfactant KRYTOX, which can also induce SiNP-DNA segregation in the presence of cations. The segregation dynamics is characterized and preliminary results of cell encapsulation in the SiNP-DNA functionalized droplets are shown.

17.
Sci Rep ; 13(1): 9561, 2023 06 12.
Article En | MEDLINE | ID: mdl-37308689

Originally considered to act as a transcriptional co-factor, Pirin has recently been reported to play a role in tumorigenesis and the malignant progression of many tumors. Here, we have analyzed the diagnostic and prognostic value of Pirin expression in the early stages of melanoma, and its role in the biology of melanocytic cells. Pirin expression was analyzed in a total of 314 melanoma biopsies, correlating this feature with the patient's clinical course. Moreover, PIR downregulated primary melanocytes were analyzed by RNA sequencing, and the data obtained were validated in human melanoma cell lines overexpressing PIR by functional assays. The immunohistochemistry multivariate analysis revealed that early melanomas with stronger Pirin expression were more than twice as likely to develop metastases during the follow-up. Transcriptome analysis of PIR downregulated melanocytes showed a dampening of genes involved in the G1/S transition, cell proliferation, and cell migration. In addition, an in silico approach predicted that JARID1B as a potential transcriptional regulator that lies between PIR and its downstream modulated genes, which was corroborated by co-transfection experiments and functional analysis. Together, the data obtained indicated that Pirin could be a useful marker for the metastatic progression of melanoma and that it participates in the proliferation of melanoma cells by regulating the slow-cycling JARID1B gene.


Melanoma , Humans , Prognosis , Melanocytes , Biopsy , Transcription Factors , Cell Proliferation , Nuclear Proteins , Repressor Proteins , Jumonji Domain-Containing Histone Demethylases
18.
Biotechnol Adv ; 66: 108168, 2023 09.
Article En | MEDLINE | ID: mdl-37146921

Grasses, legumes and green plant wastes represent a ubiquitous feedstock for developing a bioeconomy in regions across Europe. These feedstocks are often an important source of ruminant feed, although much remains unused or underutilised. In addition to proteins, these materials are rich in fibres, sugars, minerals and other components that could also be used as inputs for bio-based product development. Green Biorefinery processes and initiatives are being developed to better capitalise on the potential of these feedstocks to produce sustainable food, feed, materials and energy in an integrated way. Such systems may support a more sustainable primary production sector, enable the valorisation of green waste streams, and provide new business models for farmers. This review presents the current developments in Green Biorefining, focusing on a broad feedstock and product base to include different models of Green Biorefinery. It demonstrates the potential and wide applicability of Green Biorefinery systems, the range of bio-based product opportunities and highlights the way forward for their broader implementation. While the potential for new products is extensive, quality control approval will be required prior to market entry.


Fabaceae , Poaceae , Food , Biofuels , Biomass
19.
J Med Virol ; 95(3): e28602, 2023 03.
Article En | MEDLINE | ID: mdl-36880164

The aim of this study was to assess the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among people living with HIV (PLWH) with severe immunosuppression, after a booster dose. The design was a case-control study nested in a prospective cohort of PLWH. All patients with CD4 cell count <200 cells/mm3 who had received additional dose of messenger RNA (mRNA) COVID-19 vaccine, after a standard immunization scheme were included. Control group: patients age- and sex-matched, with CD4 ≥ 200 cells/mm3 , in the ratio of 2:1. Antibody response to a booster dose (anti-S levels 33.8 ≥ BAU/mL) and neutralizing activity against SARS-CoV-2 B.1, B.1.617.2, and Omicron BA.1, BA.2, and BA.5 strains were assessed after the booster shot. Fifty-four PLWH were included, 18 with CD4 counts < 200 cells/mm3 . Fifty-one (94%) showed response to a booster dose. Response was less frequent in PLWH with CD4 < 200 cells/mm3 than in those with CD4 counts ≥ 200 cells/mm3 (15 [83%] vs. 36 [100%], p = 0.033). In the multivariate analysis, CD4 counts ≥ 200 cells/mm3 [incidence rate ratio (IRR) = 18.1 (95% confidence interval [CI]: 16.8-19.5), p < 0.001] was associated with a higher probability of showing antibody response. Neutralization activity against SARS-CoV-2 B.1, B.1.617, BA.1, and BA.2 strains was significantly inferior among individuals with CD4 counts < 200 cells/mm3 . In conclusion, among PLWH with CD4 counts < 200 cells/mm3 , the immune response elicited by mRNA additional vaccine dose is reduced.


COVID-19 , HIV Infections , Humans , COVID-19 Vaccines , Antibodies, Neutralizing , Antibody Formation , Case-Control Studies , Prospective Studies , COVID-19/prevention & control , SARS-CoV-2 , Immunosuppression Therapy , RNA, Messenger , Antibodies, Viral
20.
ACS Nano ; 17(7): 6719-6730, 2023 04 11.
Article En | MEDLINE | ID: mdl-36990450

The immunological response of mast cells is controlled by the multivalent binding of antigens to immunoglobulin E (IgE) antibodies bound to the high-affinity receptor FcεRI on the cell membrane surface. However, the spatial organization of antigen-antibody-receptor complexes at the nanometer scale and the structural constraints involved in the initial events at the cell surface are not yet fully understood. For example, it is unclear what influence the affinity and nanoscale distance between the binding partners involved have on the activation of mast cells to degranulate inflammatory mediators from storage granules. We report the use of DNA origami nanostructures (DON) functionalized with different arrangements of the haptenic 2,4-dinitrophenyl (DNP) ligand to generate multivalent artificial antigens with full control over valency and nanoscale ligand architecture. To investigate the spatial requirements for mast cell activation, the DNP-DON complexes were initially used in surface plasmon resonance (SPR) analysis to study the binding kinetics of isolated IgE under physiological conditions. The most stable binding was observed in a narrow window of approximately 16 nm spacing between haptens. In contrast, affinity studies with FcεRI-linked IgE antibodies on the surface of rat basophilic leukemia cells (RBL-2H3) indicated virtually no distance-dependent variations in the binding of the differently structured DNP-DON complexes but suggested a supramolecular oligovalent nature of the interaction. Finally, the use of DNP-DON complexes for mast cell activation revealed that antigen-directed tight assembly of antibody-receptor complexes is the critical factor for triggering degranulation, even more critical than ligand valence. Our study emphasizes the significance of DNA nanostructures for the study of fundamental biological processes.


Mast Cells , Nanostructures , Rats , Animals , Mast Cells/physiology , Ligands , Antigens , Haptens/chemistry , Immunoglobulin E/metabolism , Receptors, IgE , Nanostructures/chemistry , DNA
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