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1.
Child Dev ; 94(1): 172-186, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36093603

RESUMEN

We investigated children's information seeking in response to a surprising claim (Study 1, N = 109, 54 Female, Range = 4.02-6.94 years, 49% White, 21% Mixed Ethnicity, 19% Southeast Asian, September 2019-March 2020; Study 2, N = 154, 74 Female, Range = 4.09-7.99, 50% White, 20% Mixed Ethnicity, 17% Southeast Asian, September 2020-December 2020). Relative to younger children, older children more often expressed skepticism about the adult's surprising claims (1-year increase, OR = 2.70) and more often suggested exploration strategies appropriate for testing the specific claim they heard (1-year increase, OR = 1.42). Controlling for age, recommending more targeted exploration strategies was associated with a greater likelihood of expressing skepticism about the adult's claim.


Asunto(s)
Desarrollo Infantil , Audición , Humanos , Niño , Adulto , Femenino , Adolescente , Desarrollo Infantil/fisiología , Probabilidad
2.
Chemistry ; 28(58): e202201570, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-35792702

RESUMEN

It is clear that the field of organocatalysis is continuously expanding during the last decades. With increasing computational capacity and new techniques, computational methods have provided a more economic approach to explore different chemical systems. This review offers a broad yet concise overview of current state-of-the-art studies that have employed novel strategies for catalyst design. The evolution of the all different theoretical approaches most commonly used within organocatalysis is discussed, from the traditional approach, manual-driven, to the most recent one, machine-driven.


Asunto(s)
Estereoisomerismo , Catálisis
3.
Faraday Discuss ; 234(0): 349-366, 2022 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-35147145

RESUMEN

Molecular modelling applications in metalloenzyme design are still scarce due to a series of challenges. On top of that, the simulations of metal-mediated binding and the identification of catalytic competent geometries require both large conformational exploration and simulation of fine electronic properties. Here, we demonstrate how the incorporation of new tools in multiscale strategies, namely substrate diffusion exploration, allows taking a step further. As a showcase, the enantioselective profiles of the most outstanding variants of an artificial Rh2-based cyclopropanase (GSH, HFF and RFY) developed by Lewis and co-workers (Nat. Commun., 2015, 6, 7789 and Nat. Chem., 2018, 10, 318-324) have been rationalized. DFT calculations on the free-cofactor-mediated process identify the carbene insertion and the cyclopropanoid formation as crucial events, the latter being the enantiodetermining step, which displays up to 8 competitive orientations easily altered by the protein environment. The key intermediates of the reaction were docked into the protein scaffold showing that some mutated residues have direct interaction with the cofactor and/or the co-substrate. These interactions take the form of a direct coordination of Rh in GSH and HFF and a strong hydrophobic patch with the carbene moiety in RFY. Posterior molecular dynamics sustain that the cofactor induces global re-arrangements of the protein. Finally, massive exploration of substrate diffusion, based on the GPathFinder approach, defines this event as the origin of the enantioselectivity in GSH and RFY. For HFF, fine molecular dockings suggest that it is likely related to local interactions upon diffusion. This work shows how modelling of long-range mutations on the catalytic profiles of metalloenzymes may be unavoidable and software simulating substrate diffusion should be applied.


Asunto(s)
Metaloproteínas , Catálisis , Humanos , Metaloproteínas/química , Metaloproteínas/genética , Metaloproteínas/metabolismo , Simulación de Dinámica Molecular
4.
Genes Dev ; 28(10): 1068-84, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24788092

RESUMEN

The spliceosome machinery is composed of multimeric protein complexes that generate a diverse repertoire of mRNA through coordinated splicing of heteronuclear RNAs. While somatic mutations in spliceosome components have been discovered in several cancer types, the molecular bases and consequences of spliceosome aberrations in cancer are poorly understood. Here we report for the first time that PRPF6, a member of the tri-snRNP (small ribonucleoprotein) spliceosome complex, drives cancer proliferation by preferential splicing of genes associated with growth regulation. Inhibition of PRPF6 and other tri-snRNP complex proteins, but not other snRNP spliceosome complexes, selectively abrogated growth in cancer cells with high tri-snRNP levels. High-resolution transcriptome analyses revealed that reduced PRPF6 alters the constitutive and alternative splicing of a discrete number of genes, including an oncogenic isoform of the ZAK kinase. These findings implicate an essential role for PRPF6 in cancer via splicing of distinct growth-related gene products.


Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/patología , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Empalme Alternativo , Línea Celular , Línea Celular Tumoral , Proliferación Celular , Humanos , Isoformas de Proteínas , Factores de Empalme de ARN , Empalmosomas
5.
J Relig Health ; 60(6): 4014-4028, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34232426

RESUMEN

"Curing" and "healing" are terms frequently used in health care, yet what is actually meant by each? This article asserts that curing pertains exclusively to the corporal while healing is multidimensional-embracing the whole person. Drawing insights from the gospel healing story of the Haemorrhoissa, better known as the bleeding woman or the woman with the issue of blood(Mt 9:20-22; Mk 5:24-34; Lk 8:42-48), this article demonstrates that imitating Christ and partaking in His ministerial mission of healing the sick, demands assisting in the healing process as it expresses authentic Christian love through the patient care provided.


Asunto(s)
Cristianismo , Enfermeras y Enfermeros , Atención a la Salud , Femenino , Humanos
6.
Small ; 15(48): e1902081, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31210002

RESUMEN

Metal-free carbon electrodes with well-defined composition and smooth topography are prepared via sputter deposition followed by thermal treatment with inert and reactive gases. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy show that three carbons of similar N/C content that differ in N-site composition are thus prepared: an electrode consisting of almost exclusively graphitic-N (NG ), an electrode with predominantly pyridinic-N (NP ), and one with ≈1:1 NG :NP composition. These materials are used as model systems to investigate the activity of N-doped carbons in the oxygen reduction reaction (ORR) using voltammetry. Results show that selectivity toward 4e-reduction of O2 is strongly influenced by the NG /NP site composition, with the material possessing nearly uniform NG /NP composition being the only one yielding a 4e-reduction. Computational studies on model graphene clusters are carried out to elucidate the effect of N-site homogeneity on the reaction pathway. Calculations show that for pure NG -doping or NP -doping of model graphene clusters, adsorption of hydroperoxide and hydroperoxyl radical intermediates, respectively, is weak, thus favoring desorption prior to complete 4e-reduction to hydroxide. Clusters with mixed NG /NP sites display synergistic effects, suggesting that co-presence of these sites improves activity and selectivity by achieving high theoretical reduction potentials while facilitating retention of intermediates.

7.
Rev Panam Salud Publica ; 42: e32, 2018.
Artículo en Español | MEDLINE | ID: mdl-31093061

RESUMEN

In Cuba, health research is based on the priorities of national scientific policy, derived from the health status of the population. The objective of this article is to describe the characteristics of the System of Science and Technological Innovation and how the results of its research benefit the health of the population groups. To this end, research related to the generation of products and technologies, diabetes, dengue and disability was selected. This system follows a methodology outlined by the Ministry of Science, Technology and Environment and has 37 research entities. It is organized into programs and projects that favor basic and applied research, with a multidisciplinary and intersectoral approach; these programs and projects are funded mostly by the State and are organized in self-contained cycles, i.e., the same entity is responsible for the entire process, from research to marketing, including market studies and post-marketing surveillance. The selected research shows an alignment between the research, the generalization of the results and its effect in improving health and universal access to health in the population. Positive results were obtained in diagnostic methods, preventive and therapeutic vaccines, warning signs for the prognosis and treatment of dengue, prevention of congenital malformations, and policies and programs that have benefited people with disabilities and their families. The will of the State to develop and fund scientific research, intersectoral action, the definition of research priorities, and the systematic training and attention to human resources have been key factors for the fulfillment of the objectives of the system.


Em Cuba, a pesquisa em saúde baseia-se nas prioridades da política científica nacional, derivadas do estado de saúde da população. O objetivo deste artigo é descrever as características do Sistema de Ciência e Inovação Tecnológica e como os resultados de suas pesquisas beneficiam a saúde dos grupos populacionais. Para este fim, foram selecionadas pesquisas relacionadas à geração de produtos e tecnologias, diabetes, dengue e deficiência. Este sistema segue a metodologia do Ministério da Ciência, Tecnologia e Meio Ambiente e possui 37 entidades de pesquisa. Está organizado em programas e projetos que favorecem pesquisas básicas e aplicadas, com abordagem multidisciplinar e intersetorial; estes são financiados principalmente pelo Estado e organizados em ciclos fechados ou completos, ou seja, a mesma entidade é responsável por todo o processo, desde pesquisa até marketing, incluindo estudos de mercado e vigilância pós-comercialização. As pesquisas selecionadas mostram a harmonia entre a pesquisa, a generalização dos resultados e seus efeitos na melhoria da saúde e no acesso universal à saúde na população. Resultados positivos foram obtidos em métodos de diagnóstico, vacinas preventivas e terapêuticas, sinais de alerta para o prognóstico e tratamento da dengue, prevenção de malformações congênitas e políticas e programas que beneficiaram pessoas com deficiência e suas famílias. A vontade do Estado de desenvolver e financiar pesquisas científicas, ações intersetoriais, a definição de prioridades de pesquisa e o treinamento e atenção sistemática do capital humano têm sido fatores determinantes para o cumprimento dos objetivos do sistema.

8.
Ecotoxicol Environ Saf ; 139: 367-376, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28189778

RESUMEN

As underdeveloped nations continue to industrialize and world population continues to increase, the need for energy, natural resources, and goods will lead to ever increasing inorganic contaminants, such as heavy metals, in various waste streams that can have damaging effects on plant life, wildlife, and human health. This work is focused on the evaluation of the potential of Nannochloropsis salina to be integrated with contaminated water sources for the concurrent production of a biofuel feedstock while providing an environmental service through bioremediation. Individual contaminants (As, Cd, Cr, Co, Cu, Pb, Ni, Hg, Se, and Zn) at various concentrations ranging from a low concentration (1X) to higher concentrations (10X, and 40X) found in contaminated systems (mine tailings, wastewater treatment plants, produced water) were introduced into growth media. Biological growth experimentation was performed in triplicate at the various contaminant concentrations and at 3 different light intensities. Results show that baseline concentrations of each contaminant slightly decreased biomass growth to between 89% and 99% of the control with the exception of Ni which dramatically reduced growth. Increased contaminant concentrations resulted in progressively lower growth rates for all contaminants tested. Lipid analysis shows most baseline contaminant concentrations slightly decrease or have minimal effects on lipid content at all light levels. Trace contaminant analysis on the biomass showed Cd, Co, Cu, Pb, and Zn were sorbed by the microalgae with minimal contaminants remaining in the growth media illustrating the effectiveness of microalgae to bioremediate these contaminants when levels are sufficiently low to not detrimentally impact productivity. The microalgae biomass was less efficient at sorption of As, Cr, Ni, and Se.


Asunto(s)
Biodegradación Ambiental , Metales Pesados/metabolismo , Microalgas/crecimiento & desarrollo , Microalgas/metabolismo , Estramenopilos , Biomasa , Relación Dosis-Respuesta a Droga , Metales Pesados/análisis , Metales Pesados/farmacología , Microalgas/química
9.
J Biol Chem ; 290(43): 25834-46, 2015 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-26342081

RESUMEN

The insulin/insulin-like growth factor (IGF)-1 signaling pathway (ISP) plays a fundamental role in long term health in a range of organisms. Protein kinases including Akt and ERK are intimately involved in the ISP. To identify other kinases that may participate in this pathway or intersect with it in a regulatory manner, we performed a whole kinome (779 kinases) siRNA screen for positive or negative regulators of the ISP, using GLUT4 translocation to the cell surface as an output for pathway activity. We identified PFKFB3, a positive regulator of glycolysis that is highly expressed in cancer cells and adipocytes, as a positive ISP regulator. Pharmacological inhibition of PFKFB3 suppressed insulin-stimulated glucose uptake, GLUT4 translocation, and Akt signaling in 3T3-L1 adipocytes. In contrast, overexpression of PFKFB3 in HEK293 cells potentiated insulin-dependent phosphorylation of Akt and Akt substrates. Furthermore, pharmacological modulation of glycolysis in 3T3-L1 adipocytes affected Akt phosphorylation. These data add to an emerging body of evidence that metabolism plays a central role in regulating numerous biological processes including the ISP. Our findings have important implications for diseases such as type 2 diabetes and cancer that are characterized by marked disruption of both metabolism and growth factor signaling.


Asunto(s)
Glucosa/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Insulina/metabolismo , Fosfofructoquinasa-2/metabolismo , Proteínas Quinasas/metabolismo , Transducción de Señal , Células 3T3-L1 , Animales , Transportador de Glucosa de Tipo 4/metabolismo , Células HeLa , Humanos , Ratones , ARN Interferente Pequeño/genética
10.
Arch Biochem Biophys ; 569: 32-44, 2015 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25668719

RESUMEN

l-Ascorbate, commonly known as vitamin C, serves as an antioxidant and cofactor essential for many biological processes. Distinct ascorbate biosynthetic pathways have been established for animals and plants, but little is known about the presence or synthesis of this molecule in invertebrate species. We have investigated ascorbate metabolism in the nematode Caenorhabditis elegans, where this molecule would be expected to play roles in oxidative stress resistance and as cofactor in collagen and neurotransmitter synthesis. Using high-performance liquid chromatography and gas-chromatography mass spectrometry, we determined that ascorbate is present at low amounts in the egg stage, L1 larvae, and mixed animal populations, with the egg stage containing the highest concentrations. Incubating C. elegans with precursor molecules necessary for ascorbate synthesis in plants and animals did not significantly alter ascorbate levels. Furthermore, bioinformatic analyses did not support the presence in C. elegans of either the plant or the animal biosynthetic pathway. However, we observed the complete (13)C-labeling of ascorbate when C. elegans was grown with (13)C-labeled Escherichia coli as a food source. These results support the hypothesis that ascorbate biosynthesis in invertebrates may proceed by a novel pathway and lay the foundation for a broader understanding of its biological role.


Asunto(s)
Ácido Ascórbico/biosíntesis , Caenorhabditis elegans/metabolismo , Animales , Antioxidantes/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/crecimiento & desarrollo , Isótopos de Carbono , Cromatografía Líquida de Alta Presión , Etanol/toxicidad , Cromatografía de Gases y Espectrometría de Masas , Genes de Helminto , Redes y Vías Metabólicas , Estrés Oxidativo/efectos de los fármacos , Paraquat/toxicidad
11.
J Appl Crystallogr ; 57(Pt 2): 503-508, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38596731

RESUMEN

A systematic procedure is introduced for modeling charge-neutral non-polar surfaces of ionic minerals containing polyatomic anions. By integrating distance- and charge-based clustering to identify chemical species within the mineral bulk, our pipeline, PolyCleaver, renders a variety of theoretically viable surface terminations. As a demonstrative example, this approach was applied to forsterite (Mg2SiO4), unveiling a rich interface landscape based on interactions with formaldehyde, a relevant multifaceted molecule, and more particularly in prebiotic chemistry. This high-throughput method, going beyond techniques traditionally applied in the modeling of minerals, offers new insights into the potential catalytic properties of diverse surfaces, enabling a broader exploration of synthetic pathways in complex mineral systems.

12.
Dalton Trans ; 53(3): 1322-1335, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38116737

RESUMEN

Ion-pairing is a fundamental phenomenon that significantly influences phase-transfer catalysis. In this study, we conduct a comprehensive investigation of ion-pair interactions, aiming to establish a comprehensive understanding of their nature and implications. The study begins with the examination of polar ionic compounds to define the concept of an ion-pair in the context of phase-transfer catalysis. Subsequently, a diverse range of ion-pair catalyst models were explored to gain insight into the factors governing their interactions. Finally, the focus shifts towards the characterisation of real phase-transfer catalysts, bridging the gap between theoretical models and practical applications. Through a combination of computational approaches and theoretical analysis, this work provides valuable insight into the nature of ion-pair interactions within phase-transfer catalysis fields.

13.
Nat Biotechnol ; 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37857725

RESUMEN

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines. To evaluate the potential for immunogenicity, we identified T cell receptors that recognized select neoepitope-HLA pairs and elicited a response after introduction into human T cells. These cellular systems and our data on therapeutically relevant neoepitopes in their HLA contexts will aid researchers studying antigen processing as well as neoepitope targeting therapies.

14.
MicroPubl Biol ; 20222022.
Artículo en Inglés | MEDLINE | ID: mdl-36317086

RESUMEN

Environmental factors such as prenatal stress are hypothesized to contribute to the development of schizophrenia. Lee and colleagues determined rats exposed to prenatal stress exhibited decreased levels of only one protein, DPYSL2, in their prefrontal cortex and hippocampus. DYPSL2, a protein seen to be inactivated in schizophrenic patients, is important for neuronal development. The C. elegans homolog of DPYSL2, UNC-33, is also found to be critical for axonal outgrowth and synapse formation. Herein, we study the effects of environmental stressors such as increasing temperatures and pathogens on the expression of GFP driven by the unc-33 promoter. Results indicate that neuronal GFP expression was lower in C. elegans exposed to these prenatal stressors, making this the first report denoting an environmental regulation of the unc -33 promoter. This study provides insight into unc-33 and the regulation of its expression in relation to temperature and infection.

15.
Chem Sci ; 13(20): 5988-5998, 2022 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-35685808

RESUMEN

Sunlight-driven CO2 reduction to renewable fuels is a promising strategy towards a closed carbon cycle in a circular economy. For that purpose, colloidal quantum dots (QDs) have emerged as a versatile light absorber platform that offers many possibilities for surface modification strategies. Considerable attention has been focused on tailoring the local chemical environment of the catalytic site for CO2 reduction with chemical functionalities ranging from amino acids to amines, imidazolium, pyridines, and others. Here we show that dithiols, a class of organic compounds previously unexplored in the context of CO2 reduction, can enhance photocatalytic CO2 reduction on ZnSe QDs. A short dithiol (1,2-ethanedithiol) activates the QD surface for CO2 reduction accompanied by a suppression of the competing H2 evolution reaction. In contrast, in the presence of an immobilized Ni(cyclam) co-catalyst, a longer dithiol (1,6-hexanedithiol) accelerates CO2 reduction. 1H-NMR spectroscopy studies of the dithiol-QD surface interactions reveal a strong affinity of the dithiols for the QD surface accompanied by a solvation sphere governed by hydrophobic interactions. Control experiments with a series of dithiol analogues (monothiol, mercaptoalcohol) render the hydrophobic chemical environment unlikely as the sole contribution of the enhancement of CO2 reduction. Density functional theory (DFT) calculations provide a framework to rationalize the observed dithiol length dependent activity through the analysis of the non-covalent interactions between the dangling thiol moiety and the CO2 reduction intermediates at the catalytic site. This work therefore introduces dithiol capping ligands as a straightforward means to enhance CO2 reduction catalysis on both bare and co-catalyst modified QDs by engineering the particle's chemical environment.

16.
Chem Sci ; 12(26): 9078-9087, 2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34276937

RESUMEN

Colloidal photocatalysts can utilize solar light for the conversion of CO2 to carbon-based fuels, but controlling the product selectivity for CO2 reduction remains challenging, in particular in aqueous solution. Here, we present an organic surface modification strategy to tune the product selectivity of colloidal ZnSe quantum dots (QDs) towards photocatalytic CO2 reduction even in the absence of transition metal co-catalysts. Besides H2, imidazolium-modified ZnSe QDs evolve up to 2.4 mmolCO gZnSe -1 (TONQD > 370) after 10 h of visible light irradiation (AM 1.5G, λ > 400 nm) in aqueous ascorbate solution with a CO-selectivity of up to 20%. This represents a four-fold increase in CO-formation yield and 13-fold increase in CO-selectivity compared to non-functionalized ZnSe QDs. The binding of the thiolated imidazolium ligand to the QD surface is characterized quantitatively using 1H-NMR spectroscopy and isothermal titration calorimetry, revealing that a subset of 12 to 17 ligands interacts strongly with the QDs. Transient absorption spectroscopy reveals an influence of the ligand on the intrinsic charge carrier dynamics through passivating Zn surface sites. Density functional theory calculations indicate that the imidazolium capping ligand plays a key role in stabilizing the surface-bound *CO2 - intermediate, increasing the yield and selectivity toward CO production. Overall, this work unveils a powerful tool of using organic capping ligands to modify the chemical environment on colloids, thus enabling control over the product selectivity within photocatalyzed CO2 reduction.

17.
Nat Commun ; 10(1): 4993, 2019 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-31704927

RESUMEN

A major roadblock in realizing large-scale production of hydrogen via electrochemical water splitting is the cost and inefficiency of current catalysts for the oxygen evolution reaction (OER). Computational research has driven important developments in understanding and designing heterogeneous OER catalysts using linear scaling relationships derived from computed binding energies. Herein, we interrogate 17 of the most active molecular OER catalysts, based on different transition metals (Ru, Mn, Fe, Co, Ni, and Cu), and show they obey similar scaling relations to those established for heterogeneous systems. However, we find that the conventional OER descriptor underestimates the activity for very active OER complexes as the standard approach neglects a crucial one-electron oxidation that many molecular catalysts undergo prior to O-O bond formation. Importantly, this additional step allows certain molecular catalysts to circumvent the "overpotential wall", leading to enhanced performance. With this knowledge, we establish fundamental principles for the design of ideal molecular OER catalysts.

18.
ACS Nano ; 13(11): 13560-13572, 2019 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-31697474

RESUMEN

Chiroptically active fluorescent semiconductor nanocrystals, quantum dots (QDs), are of high interest from a theoretical and technological point of view, because they are promising candidates for a range of potential applications. Optical activity can be induced in QDs by capping them with chiral molecules, resulting in circular dichroism (CD) signals in the range of the QD ultraviolet-visible (UV-vis) absorption. However, the effects of the chiral ligand concentration and binding modes on the chiroptical properties of QDs are still poorly understood. In the present study, we report the strong influence of the concentration of a chiral amino acid (cysteine) on its binding modes upon the surface of CdSe/CdS QDs, resulting in varying QD chiroptical activity and corresponding CD signals. Importantly, we demonstrate that the increase of cysteine concentration is accompanied by the growth of the QD CD intensity, reaching a certain critical point, after which it starts to decrease. The intensity of the CD signal varies by almost an order of magnitude across this range. Nuclear magnetic resonance and Fourier transform infrared data, supported by density functional theory calculations, reveal a change in the binding mode of cysteine molecules from tridentate to bidentate when going from low to high concentrations, which results in a change in the CD intensity. Hence, we conclude that the chiroptical properties of QDs are dependent on the concentration and binding modes of the capping chiral ligands. These findings are very important for understanding chiroptical phenomena at the nanoscale and for the design of advanced optically active nanomaterials.

19.
Appl Environ Microbiol ; 74(16): 5201-10, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18552183

RESUMEN

The engulfment of Bacillus anthracis spores by macrophages is an important step in the pathogenesis of inhalational anthrax. However, from a quantitative standpoint, the magnitude to which macrophages interact with and engulf spores remains poorly understood, in part due to inherent limitations associated with commonly used assays. To analyze phagocytosis of spores by RAW264.7 macrophage-like cells in a high-throughput, nonsubjective manner, we labeled B. anthracis Sterne 7702 spores prior to infection with an Alexa Fluor 488 amine-reactive dye in a manner that did not alter their germination, growth kinetics, and heat resistance. Using flow cytometry, large numbers of cells exposed to labeled spores were screened to concurrently discriminate infected from uninfected cells and surface-associated from internalized spores. These experiments revealed that spore uptake was not uniform, but instead, highly heterogeneous and characterized by subpopulations of infected and uninfected cells, as well as considerable variation in the number of spores associated with individual cells. Flow cytometry analysis of infections demonstrated that spore uptake was independent of the presence or absence of fetal bovine serum, a germinant that, while routinely used in vitro, complicates the interpretation of the outcome of infections. Two commonly used macrophage cell lines, RAW264.7 and J774A.1 cells, were compared, revealing significant disparity between these two models in the rates of phagocytosis of labeled spores. These studies provide the experimental framework for investigating mechanisms of spore phagocytosis, as well as quantitatively evaluating strategies for interfering with macrophage binding and uptake of spores.


Asunto(s)
Carbunco/inmunología , Bacillus anthracis/crecimiento & desarrollo , Bacillus anthracis/inmunología , Macrófagos/inmunología , Fagocitosis/inmunología , Animales , Línea Celular , Citometría de Flujo , Interacciones Huésped-Patógeno , Macrófagos/microbiología , Ratones , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Esporas Bacterianas/inmunología , Succinimidas
20.
Rev. cuba. pediatr ; 94(2)jun. 2022.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1409127

RESUMEN

RESUMEN Introducción: El dengue es una importante arbovirosis en términos de morbilidad y mortalidad. Objetivo: Caracterizar clínica y epidemiológicamente a un grupo de fallecidos con dengue hemorrágico menores de 15 años durante la epidemia cubana de 1981. Métodos: estudio retrospectivo, descriptivo en una muestra de 67 pacientes. La información se extrajo de las historias clínicas. Resultados: La mayor parte de los pacientes estudiados tenían entre 3 y 10 años de edad, con similar distribución entre ambos sexos, de color de piel blanca en su mayoría, normopesos y con aparente estado de salud. Los síntomas predominantes fueron la fiebre, los vómitos y el sangramiento digestivo, que motivaron el ingreso a partir del 3er. día en la mayoría de las veces. El choque apareció generalmente entre el 4to. y 5to. día, precedido por los vómitos o el dolor abdominal y asociado al aumento del hematocrito y la trombocitopenia. Los referidos signos clínicos de alarma y otros menos frecuentes fueron capaces de anunciar el choque. Los signos radiográficos más encontrados fueron la opacidad y el derrame pleural derecho; en las necropsias predominó el sangramiento gastrointestinal, el derrame seroso y la necrosis hepática medio zonal. Conclusiones: La caracterización clinicoepidemiológica de los casos fallecidos por dengue durante la primera epidemia sufrida en la región de las Américas ha permitido conocer la evolución de la enfermedad y contribuido a la elaboración de las guías para su atención y tratamiento efectivo.


ABSTRACT Introduction: Dengue is an important arbovirus in terms of morbidity and mortality. Objective: Characterize clinically and epidemiologically a group of deceased with hemorrhagic dengue under 15 years of age during the Cuban epidemic of 1981. Methods: Retrospective, descriptive study in a sample of 67 patients. The information was extracted from medical records. Results: Most of the patients studied were between 3 and 10 years old, with similar distribution between both sexes, mostly white skin, normal weight and with apparent good state of health. The predominant symptoms were fever, vomiting and digestive bleeding, which motivated admission at the 3rd day in most cases. The shock usually appeared between the 4th. and 5th. day, preceded by vomiting or abdominal pain, and associated with increased hematocrit and thrombocytopenia. The most commonly found radiographic signs were opacity and right pleural effusion ; necropsies, gastrointestinal bleeding, serous effusion and zonal mid-hepatic necrosis predominated. Conclusions: The clinical-epidemiological study of the cases that died from dengue during the first epidemic suffered in the region of the Americas has made it possible to know the evolutionary particularities of the disease and contributed to the elaboration of guidelines for its care and effective treatment.

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