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Previous experiments and simulations have shown that acetonitrile organizes into a lipid-like bilayer at the liquid/silica interface. Recent simulations have further suggested that this bilayer structure persists in mixtures of acetonitrile with water, even at low acetonitrile concentrations. This behavior is indicative of microscopic phase separation of these liquids near silica interfaces and may have important ramifications for the use of acetonitrile in chromatography and heterogeneous catalysis. To explore this phenomenon, we have used vibrational sum-frequency-generation spectroscopy to probe acetonitrile/water mixtures at a silica interface. Our spectra provide evidence that acetonitrile partitions to the hydrated silica interface even when the mole fraction of acetonitrile is as low as 10%. A blue shift is observed in the spectrum of the methyl symmetric stretch upon increasing water mole fraction, in agreement with vibrational spectra of bulk mixtures. Line shape analysis suggests that acetonitrile may exist in the form of bilayer patches at high water mole fractions.
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(1) Background: Few qualitative studies address diverse older adults' perceptions of COVID-19 vaccination in the United States, including non-English speakers and immigrant populations. This study aims to understand the attitudes of diverse, primarily immigrant older adults in the U.S. toward the COVID-19 vaccine and its influences on their vaccination decision-making. (2) Methods: The research team conducted semi-structured interviews (N = 100) in 2021 focused on understanding ethnically/racially diverse older adults' perceptions of the COVID-19 vaccine. Interviews were recorded, coded, and analyzed using a thematic analysis approach. (3) Results: Thematic analyses identified three themes. (1) Older adults showed mixed attitudes toward the COVID-19 vaccine associated with information consumed and trust in healthcare systems; (2) health concerns and underlying medical conditions were the most influential factors of vaccine uptake; and (3) systemic barriers and trusted figures impacted vaccination decision-making of older adults. (4) Conclusions: Accessible information in diverse languages tailored to the community's fears is needed to combat vaccine mistrust. Vaccine rollout programs need to tackle the fear of vaccine side effects. Attitudes of religious leaders, family members, and physicians considerably influenced vaccine uptake, suggesting their role as trusted members for vaccine messaging for older, primarily immigrant adults. Systemic barriers, namely lack of transportation and inaccessible vaccination sites, contributed to vaccine deterrence.
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Eubacteria and archaea contain a variety of actin-like proteins (ALPs) that form filaments with surprisingly diverse architectures, assembly dynamics, and cellular functions. Although there is much data supporting differences between ALP families, there is little data regarding conservation of structure and function within these families. We asked whether the filament architecture and biochemical properties of the best-understood prokaryotic actin, ParM from plasmid R1, are conserved in a divergent member of the ParM family from plasmid pB171. Previous work demonstrated that R1 ParM assembles into filaments that are structurally distinct from actin and the other characterized ALPs. They also display three biophysical properties thought to be essential for DNA segregation: 1) rapid spontaneous nucleation, 2) symmetrical elongation, and 3) dynamic instability. We used microscopic and biophysical techniques to compare and contrast the architecture and assembly of these related proteins. Despite being only 41% identical, R1 and pB171 ParMs polymerize into nearly identical filaments with similar assembly dynamics. Conservation of the core assembly properties argues for their importance in ParM-mediated DNA segregation and suggests that divergent DNA-segregating ALPs with different assembly properties operate via different mechanisms.
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Actinas/química , Proteínas de Escherichia coli/metabolismo , Citoesqueleto de Actina/química , Actinas/metabolismo , Adenosina Trifosfato/química , Clonación Molecular , ADN/química , Procesamiento de Imagen Asistido por Computador , Cinética , Modelos Biológicos , Fosfatos/química , Plásmidos/metabolismo , Polímeros/química , Conformación Proteica , Proteínas/química , Dispersión de RadiaciónRESUMEN
The ICN photodissociation reaction is the prototype system for understanding energy disposal and curve crossing in small molecule bond-breaking. The wide knowledge base on this reaction in the gas phase makes it an excellent test case to explore and understand the influence of a liquid solvent on the photo-induced reaction dynamics. Molecular dynamics simulations that include surface-hopping have addressed numerous aspects of how the solvent should influence non-adiabatic transitions and energy flow and ultimately determine product branching for this reaction system. In this paper, we report femtosecond transient absorption work directly combined with new molecular dynamics simulations that make direct connection with the spectroscopic observables. The full spectral evolution after initiating ICN photodissociation at 266 nm in water and ethanol is recorded with unprecedented time resolution, fast enough to see the nascent products emerge before interacting with the solvent cage. Use of a 266 nm pump maximizes the probability of subsequent caging on the upper diabat while launching large rotational energy release for trajectories emerging on the lower diabat. The 2D dataset yields a map of the different products and how they interconvert. In particular, information on the branching ratio and spectral evolution of the product bands is revealed as the products relax their electronic and rotational degrees of freedom. An evolution from rotationally hot gas-phase like CN (sharp band, at 390 nm) to equilibrated and solvated CN radicals (broad, at 326 nm in water and 415 nm in ethanol) is clearly observed in both solvents, and signals assignable to I* are also captured. The non-adiabatic molecular dynamics simulations focus on identifying when trajectories curve cross, filtering the trajectory ensemble into spectroscopically distinct sub-populations and analyzing the rotational energy for the CN product population. The experimental results, taken together with the MD simulations, establish the initial surface crossing probability and suggest multiple passes through the curve crossing region determine the final product yields and provide a source of freshly torqued CN radicals that continues to top up the population of rotationally hot photoproduct over the first few picoseconds.
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Transcriptomic reconstructions without reference (i.e., de novo) are common for data samples derived from non-model biological systems. These assemblies involve massive parallel short read sequence reconstructions from experiments, but they usually employ ad-hoc bioinformatic workflows that exhibit limited standardization and customization. The increasing number of transcriptome assembly software continues to provide little room for standardization which is exacerbated by the lack of studies on modularity that compare the effects of assembler synergy. We developed a customizable management workflow for de novo transcriptomics that includes modular units for short read cleaning, assembly, validation, annotation, and expression analysis by connecting twenty-five individual bioinformatic tools. With our software tool, we were able to compare the assessment scores based on 129 distinct single-, bi- and tri-assembler combinations with diverse k-mer size selections. Our results demonstrate a drastic increase in the quality of transcriptome assemblies with bi- and tri- assembler combinations. We aim for our software to improve de novo transcriptome reconstructions for the ever-growing landscape of RNA-seq data derived from non-model systems. We offer guidance to ensure the most complete transcriptomic reconstructions via the inclusion of modular multi-assembly software controlled from a single master console.
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Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos , Programas Informáticos , Transcriptoma/genética , Biología Computacional , RNA-Seq/métodosRESUMEN
Typical femtosecond pulse compression of deep ultraviolet radiation consists of prism or diffraction grating pair chirp compensation but, both techniques introduce higher-order dispersion, spatial-spectral beam distortion and poor transmission. While negatively chirped dielectric mirrors have been used to compress near infrared and visible pulses to <10 fs, there has been no extension of this technique below 300 nm. We demonstrate the use of Gires-Tournois interferometer (GTI) negative dispersion multilayer dielectric mirrors designed for pulse compression in the deep ultraviolet region. GTI mirror designs are more robust than chirped mirrors and, can provide sufficient bandwidth for the compression of sub-30-fs pulses in the UV wavelength range. Compression of a 5 nm (FWHM) pulse centered between 266 and 271 nm to 30 fs has been achieved with less pulse broadening due to high-order dispersion and no noticeable spatial deformation, thereby improving the resolution of ultrafast techniques used to study problems such as fast photochemical reaction dynamics.
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Interferometría/métodos , Óptica y Fotónica , Diseño de Equipo , Luz , Ensayo de Materiales , Fotoquímica/métodos , Rayos UltravioletaRESUMEN
Two-photon absorption (2PA) spectroscopy in the range from 7 to 10 eV provides new insight on the electronic structure of liquid water. Continuous 2PA spectra are obtained via the pump-probe technique, using broadband probe pulses to record the absorption at many wavelengths simultaneously. A preresonance enhancement of the absolute 2PA cross section is observed when the pump-photon energy increases from 4.6 to 6.2 eV. The absorption cross section also depends on the relative polarization of the pump and probe photons. The variation of the polarization ratio across the spectrum reveals a detailed picture of the 2PA and indicates that at least four different transitions play a role below 10 eV. Theoretical polarization ratios for the isolated molecule illustrate the value of the experimental polarization measurement in deciphering the 2PA spectrum and provide the framework for a simple simulation of the liquid spectrum. A more comprehensive model goes beyond the isolated molecule picture and connects the 2PA spectrum with previous one-photon absorption, photoelectron, and x-ray absorption spectroscopy measurements of liquid water. Previously unresolved, overlapping transitions are assigned for the first time. Finally, the electronic character of the vertical excited states is related to the energy-dependent ionization mechanism of liquid water.
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Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes the enzyme cholesterol 7alpha-hydroxylase, which catalyzes the initial step in cholesterol catabolism and bile acid synthesis. We report here a new metabolic disorder presenting with hyperlipidemia caused by a homozygous deletion mutation in CYP7A1. The mutation leads to a frameshift (L413fsX414) that results in loss of the active site and enzyme function. High levels of LDL cholesterol were seen in three homozygous subjects. Analysis of a liver biopsy and stool from one of these subjects revealed double the normal hepatic cholesterol content, a markedly deficient rate of bile acid excretion, and evidence for upregulation of the alternative bile acid pathway. Two male subjects studied had hypertriglyceridemia and premature gallstone disease, and their LDL cholesterol levels were noticeably resistant to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. One subject also had premature coronary and peripheral vascular disease. Study of the kindred, which is of English and Celtic background, revealed that individuals heterozygous for the mutation are also hyperlipidemic, indicating that this is a codominant disorder.
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Colesterol 7-alfa-Hidroxilasa/deficiencia , Colesterol 7-alfa-Hidroxilasa/genética , Hiperlipoproteinemia Tipo II/enzimología , Hiperlipoproteinemia Tipo II/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Ácidos y Sales Biliares/metabolismo , Colelitiasis/enzimología , Colelitiasis/genética , Colesterol/metabolismo , ADN/genética , Femenino , Heterocigoto , Homocigoto , Humanos , Hiperlipoproteinemia Tipo II/metabolismo , Hipertrigliceridemia/enzimología , Hipertrigliceridemia/genética , Lipoproteínas LDL/sangre , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Eliminación de SecuenciaRESUMEN
PURPOSE: Students with intellectual disability often struggle with significant language delays or impairments and can require explicit instruction in language skills. The purpose of this study was to investigate the effects of direct instruction on the use of and response to prepositions by 3 elementary school students with intellectual disability. METHOD: A multiple-baseline design across prepositions was used in this study with replication across students. RESULTS: Results of this study found that students were able to use and respond to prepositions consistently after receiving direct instruction on each of the 3 target prepositions. Furthermore, all 3 students demonstrated maintenance and generalization of the prepositions. CONCLUSION: These results have implications for practice that could influence preposition acquisition for students with intellectual disability, providing educators with a simple, efficient instructional approach.
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Educación de las Personas con Discapacidad Intelectual/métodos , Discapacidad Intelectual/terapia , Trastornos del Desarrollo del Lenguaje/terapia , Terapia del Lenguaje/métodos , Niño , Femenino , Humanos , Discapacidad Intelectual/complicaciones , Trastornos del Desarrollo del Lenguaje/etiología , Masculino , Resultado del TratamientoRESUMEN
As a result of their intense physical activity, racehorses suffer high tendon stress which may result in various pathologies. One of these is tendonitis in the tendon of the superficial digital flexor muscle (TSDFM). Conventional treatment with rest, has not shown to be very effective, and regenerative medicine through the application mesenchymal stem cells appears to be a promising therapy. The objective of this work was to assess the effect of the application of autologous MSC on reduction of the scar length in recurrent TSDFM tendinitis in Holsteiner horses, using image analysis. This study included two groups of five animals each: A control group that received conventional treatment (CG) and an experimental group which was also treated with intralesional injections of MSC (EG). Scar evolution was assessed by echographic analysis, with measurements taken of the scar length over a four month period; the length at month zero, was taken as the initial value of 100 %. During the first month, the mean scar length diminished to 81.14 % (EG) and 95.85 % (CG); after the second month, lengths were 64.4 % (EG) and 92.3 % (CG); following the third month lengths were 51.92 % (EG) and 87.42 % (CG); finally at the end of the fourth month the lengths recorded were 26.7 % (EG) and 83.92 % (CG). These results show that treatment with autologous MSC helps TSDFM scar length was significantly reduced, as compared to conventional treatment.
Reducción de la cicatriz de tendinitis recidivante mediante células Madre mesenquimales autólogas derivadas de tejido adiposo de la base de la cola en equinos Holsteiner (Equus ferus caballus). En equinos deportistas, la actividad física intensa ocasiona gran estrés en los tendones, pudiendo ocasionar diversas patologías como la tendinitis del tendón del músculo flexor digital superficial (TMFDS). El tratamiento convencional con reposo es poco eficaz, siendo la medicina regenerativa a través de la aplicación de células madres mesenquimáticas (MSC) una promisoria terapia. El objetivo de este trabajo, fue evaluar el efecto de la aplicación de MSC autólogas, sobre la reducción de la longitud de la cicatriz en tendinopatías recidivantes del TMFDS en equinos Holsteiner, a través del análisis de imagen. Este estudio conto con dos grupos de cinco animales cada uno, el grupo control mantuvo el tratamiento convencional (GC) y el grupo experimental fue tratado adicionalmente con inyección interlesional de MSC (GE). El análisis ecográfico permitió evaluar la evolución de la cicatriz, a través de la medición de su longitud durante los cuatros meses, tomando la longitud del mes cero como la medición inicial del 100 %. Durante el primer mes, la longitud de la cicatriz se redujo a un 81,14 % (GE) y 95,85 % (GC), al segundo mes la longitud fue de un 64,4 % (GE) y de 92,3 % (GC), al tercer mes, la longitud fue de 51,92 (GE) y un 87,42 (GC), finalmente al cuarto mes la longitud fue de 26,7 % (GE) y del 83,92 % (GC). Estos resultados muestran que el tratamiento con MSC autólogas favorece a la disminución de la longitud de la cicatriz del TMFDS de forma significativa respecto al tratamiento convencional.
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Animales , Cicatrización de Heridas , Tejido Adiposo , Tendinopatía/terapia , Células Madre Mesenquimatosas , Recurrencia , Modelos Animales de Enfermedad , Tendinopatía/complicaciones , CaballosRESUMEN
There is a growing appreciation that dynamic processes play an important role in determining the line shape in surface-selective, nonlinear spectroscopies such as vibrational sum-frequency-generation (VSFG). Here we analyze the influence that reorientation can have on VSFG spectra when the vibrational transition frequency is a function of orientation. Under these circumstances, reorientation-induced spectral diffusion (RISD) causes the underlying spectral line shape to become time dependent. Unlike previously reported mechanisms through which reorientation can contribute to the VSFG signal, RISD influences the line shape regardless of the degree of polarization of the Raman transition that is probed. We assess the impact of RISD on VSFG spectra using a model system of liquid acetonitrile at a silica interface. Comparison of delay-time-dependent VSFG spectra with simulations that employ static line shapes suggests that RISD contributes substantially to the spectra, particularly at delay times that are comparable to or greater than the probe pulse duration. The observed behavior is in qualitative agreement with a two-state RISD model that uses orientational distributions determined from previous molecular dynamics simulations.
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We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.
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Variación Genética/fisiología , Hiperlipoproteinemias/genética , Lipoproteínas HDL/sangre , Lipoproteínas/sangre , Proteínas de Transferencia de Fosfolípidos/genética , Adulto , Anciano , Animales , Células COS , Estudios de Casos y Controles , Chlorocebus aethiops , Femenino , Ligamiento Genético , Humanos , Hiperlipoproteinemias/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , TransfecciónRESUMEN
Phospholipid transfer protein (PLTP) participates in key processes in lipoprotein metabolism, including interparticle phospholipid transfer, remodeling of HDL, cholesterol and phospholipid efflux from peripheral tissues, and the production of hepatic VLDL. The impact of PLTP on reverse cholesterol transport suggests that the gene may harbor sequence anomalies that contribute to disorders of HDL metabolism. The human PLTP gene was screened for sequence anomalies by DNA melting analysis in 276 subjects with hypoalphalipoproteinemia (HA) and 364 controls. The association with plasma lipid parameters was evaluated. We discovered 18 sequence variations, including four missense mutations and a novel polymorphism (c.-34G > C). In healthy controls, the c.-34G > C minor allele was associated with higher high density lipoprotein-cholesterol (HDL-C) and was depleted in subjects with HA. Linear regression models predict that possession of the rare allele decreases plasma triglyceride (TG) and TG/HDL-C and increases HDL-C independent of TG. Decreased PLTP activity was observed in one (p.R235W) of four (p.E72G, p.S119A, p.S124Y, and p.R235W) mutations in an in vitro activity assay. These findings indicate that PLTP gene variation is an important determinant of plasma lipoproteins and affects disorders of HDL metabolism.