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1.
Plant Biotechnol J ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39403866

RESUMEN

Maize lethal necrosis (MLN), which is caused by maize chlorotic mottle virus along with a potyvirus, has threatened the food security of smallholders in sub-Saharan Africa. Mutations in eukaryotic translation initiation factors (eIFs), which also facilitate virus genome translation, are known to confer variable resistance against viruses. Following phylogenetic analysis, we selected two eIF4E proteins from maize as the most likely candidates to facilitate MLN infection. A knockout (KO) of each of the corresponding genes in elite but MLN-susceptible maize lines conferred only partial protection. Our inability to knockout both the genes together suggested that at least one was required for survival. When we edited (ED) the eIF4E genes in Mini Maize, however, the plants with the eif4e1-KO became highly resistant, whereas those with the eif4e2-KO remained susceptible. Neither of the causal viruses could be detected in the MLN-inoculated eif4e1-KO plants. The eIF4E2 cDNA in Mini Maize lacked the entire 4th exon, causing a 22-amino acid in-frame deletion, which shortened the protein to 198 amino acids. When we introduced mutations in the 4th exon of the eIF4E2 gene in two elite, MLN-susceptible lines pre-edited for an eif4e1-KO, we obtained as strong resistance against MLN as in eif4e1-KO Mini Maize. The MLN-inoculated lines with eif4e1-KO/eIF4E2-exon-4ED performed as well as the uninoculated wild-type lines. We demonstrate that the C-terminal 38 amino acids of eIF4E2 are dispensable for normal plant growth but are required for the multiplication of MLN viruses. Our discovery has wide applications across plant species for developing virus-resistant varieties.

2.
Arch. cardiol. Méx ; Arch. cardiol. Méx;94(2): 141-150, Apr.-Jun. 2024. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1556910

RESUMEN

Resumen Objetivo: Determinar las características clínico-epidemiológicas, viabilidad diagnóstica de la poligrafía respiratoria domiciliaria y el tratamiento de pacientes con sospecha de apnea obstructiva del sueño (AOS) en riesgo cardiovascular. Métodos: Se realizó estudio observacional, transversal, descriptivo en pacientes atendidos en un servicio de consulta externa de cardiología con sospecha de AOS, de enero de 2015 a diciembre de 2019. La información se obtuvo de los expedientes médicos, se aplicó análisis estadístico descriptivo. Resultados: Se examinaron 138 expedientes, de las poligrafías respiratorias domiciliarias fueron descartadas solo el 8% por no cumplir con los estándares de calidad requeridos. Se demostró que el 89% padecían AOS, un 60% moderada a severa; predominó en hombres después de los 50 años. El principal ractores de riesgo cardiovascular fue hipertensión (89%). La cardiopatía más prevalente fue la hipertensiva (52%). Se optimizó tratamiento farmacológico cardiovascular en el 82% de los casos. Rehabilitación cardiaca en el 30%, ventilación mecánica no invasiva 41%, modalidad fija 33% y autoajustable 9%, todos con telemetría. Conclusiones: La prevalencia y severidad de la AOS es mayor en presencia de riesgo o enfermedad cardiovascular establecida. Ante la sospecha clínica es factible confirmar el diagnóstico con poligrafía respiratoria domiciliaria por el nivel de precisión y la menor infraestructura requerida. Es necesaria una mayor participación del cardiólogo en el diagnóstico y tratamiento de este trastorno por el riesgo significativo de enfermedad cardiovascular que representa.


Abstract Objective: To determine the clinical-epidemiological characteristics, diagnostic feasibility of home respiratory polygraphy and treatment of patients with suspected obstructive sleep apnea (OSA) at cardiovascular risk. Methods: An observational, cross-sectional, descriptive study was conducted in patients seen in a cardiology outpatient service with suspected OSA, from January 2015 to December 2019. The information was obtained from medical records, and a descriptive statistical analysis was applied to this information. Results: 138 files were reviewed; only 8% of the home respiratory polygraphs were discarded, because they did not meet the required quality standards. It was demonstrated that 89% suffered from OSA, 60% moderate to severe; in men after 50 years of age. The main cardiovascular risk factors was hypertension (89%). The most prevalent heart disease was hypertension (52%). Cardiovascular pharmacological treatment was improved in 82% of the cases. Cardiac rehabilitation in 30%, noninvasive mechanical ventilation 41%, fixed modality 33%, and self-adjustable 9%, all with telemetry. Conclusions: The prevalence and severity of OSA is higher in the presence of risk or established cardiovascular disease. In the presence of clinical suspicion, it is feasible to confirm the diagnosis with home respiratory poligrafy due to the level of precision and the lower infrastructure required. Greater involvement of the cardiologist in the diagnosis and treatment of this disorder is necessary due to the significant risk of cardiovascular disease it represents.

3.
Arch Cardiol Mex ; 94(2): 141-150, 2024 02 02.
Artículo en Español | MEDLINE | ID: mdl-38306451

RESUMEN

Objective: To determine the clinical-epidemiological characteristics, diagnostic feasibility of home respiratory polygraphy and treatment of patients with suspected obstructive sleep apnea (OSA) at cardiovascular risk. Methods: An observational, cross-sectional, descriptive study was conducted in patients seen in a cardiology outpatient service with suspected OSA, from January 2015 to December 2019. The information was obtained from medical records, and a descriptive statistical analysis was applied to this information. Results: 138 files were reviewed; only 8% of the home respiratory polygraphs were discarded, because they did not meet the required quality standards. It was demonstrated that 89% suffered from OSA, 60% moderate to severe; in men after 50 years of age. The main cardiovascular risk factors was hypertension (89%). The most prevalent heart disease was hypertension (52%). Cardiovascular pharmacological treatment was improved in 82% of the cases. Cardiac rehabilitation in 30%, noninvasive mechanical ventilation 41%, fixed modality 33%, and self-adjustable 9%, all with telemetry. Conclusions: The prevalence and severity of OSA is higher in the presence of risk or established cardiovascular disease. In the presence of clinical suspicion, it is feasible to confirm the diagnosis with home respiratory poligrafy due to the level of precision and the lower infrastructure required. Greater involvement of the cardiologist in the diagnosis and treatment of this disorder is necessary due to the significant risk of cardiovascular disease it represents.


Objetivo: Determinar las características clínico-epidemiológicas, viabilidad diagnóstica de la poligrafía respiratoria domiciliaria y el tratamiento de pacientes con sospecha de apnea obstructiva del sueño (AOS) en riesgo cardiovascular. Métodos: Se realizó estudio observacional, transversal, descriptivo en pacientes atendidos en un servicio de consulta externa de cardiología con sospecha de AOS, de enero de 2015 a diciembre de 2019. La información se obtuvo de los expedientes médicos, se aplicó análisis estadístico descriptivo. Resultados: Se examinaron 138 expedientes, de las poligrafías respiratorias domiciliarias fueron descartadas solo el 8% por no cumplir con los estándares de calidad requeridos. Se demostró que el 89% padecían AOS, un 60% moderada a severa; predominó en hombres después de los 50 años. El principal ractores de riesgo cardiovascular fue hipertensión (89%). La cardiopatía más prevalente fue la hipertensiva (52%). Se optimizó tratamiento farmacológico cardiovascular en el 82% de los casos. Rehabilitación cardiaca en el 30%, ventilación mecánica no invasiva 41%, modalidad fija 33% y autoajustable 9%, todos con telemetría. Conclusiones: La prevalencia y severidad de la AOS es mayor en presencia de riesgo oenfermedad cardiovascular establecida. Ante la sospecha clínica es factible confirmar el diagnóstico con poligrafía respiratoria domiciliaria por el nivel de precisión y la menor infraestructura requerida. Es necesaria una mayor participación del cardiólogoen el diagnóstico y tratamiento de este trastorno por el riesgo significativo de enfermedad cardiovascular que representa.

4.
Plants (Basel) ; 12(12)2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37375939

RESUMEN

Doubled haploid (DH) technology has become integral to maize breeding programs to expedite inbred line development and increase the efficiency of breeding operations. Unlike many other plant species that use in vitro methods, DH production in maize uses a relatively simple and efficient in vivo haploid induction method. However, it takes two complete crop cycles for DH line generation, one for haploid induction and the other one for chromosome doubling and seed production. Rescuing in vivo induced haploid embryos has the potential to reduce the time for DH line development and improve the efficiency of DH line production. However, the identification of a few haploid embryos (~10%) resulting from an induction cross from the rest of the diploid embryos is a challenge. In this study, we demonstrated that an anthocyanin marker, namely R1-nj, which is integrated into most haploid inducers, can aid in distinguishing haploid and diploid embryos. Further, we tested conditions that enhance R1-nj anthocyanin marker expression in embryos and found that light and sucrose enhance anthocyanin expression, while phosphorous deprivation in the media had no affect. Validating the use of the R1-nj marker for haploid and diploid embryo identification using a gold standard classification based on visual differences among haploids and diploids for characteristics such as seedling vigor, erectness of leaves, tassel fertility, etc., indicated that the R1-nj marker could lead to significantly high false positives, necessitating the use of additional markers for increased accuracy and reliability of haploid embryo identification.

5.
Front Plant Sci ; 13: 830147, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35242157

RESUMEN

Biofortification of cereal grains offers a lasting solution to combat micronutrient deficiency in developing countries where it poses developmental risks to children. Breeding efforts thus far have been directed toward increasing the grain concentrations of iron (Fe) and zinc (Zn) ions. Phytic acid (PA) chelates these metal ions, reducing their bioavailability in the digestive tract. We present a high-throughput assay for quantification of PA and its application in screening a breeding population. After extraction in 96-well megatiter plates, PA content was determined from the phosphate released after treatment with a commercially available phytase enzyme. In a set of 330 breeding lines of wheat grown in the field over 3 years as part of a HarvestPlus breeding program for high grain Fe and Zn, our assay unraveled variation for PA that ranged from 0.90 to 1.72% with a mean of 1.24%. PA content was not associated with grain yield. High yielding lines were further screened for low molar PA/Fe and PA/Zn ratios for increased metal ion bioavailability, demonstrating the utility of our assay. Genome-wide association study revealed 21 genetic associations, six of which were consistent across years. Five of these associations mapped to chromosomes 1A, 2A, 2D, 5A, and 7D. Additivity over four of these haplotypes accounted for an ∼10% reduction in PA. Our study demonstrates it is possible to scale up assays to directly select for low grain PA in forward breeding programs.

6.
Neural Process Lett ; 54(1): 559-580, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34580573

RESUMEN

Deep learning models, such as convolutional neural networks (CNN), have been successfully applied in pattern recognition and system identification recent years. But for the cases of missing data and big noises, CNN does not work well for dynamic system modeling. In this paper, complex valued convolution neural network (CVCNN) is presented for modeling nonlinear systems with large uncertainties. Novel training methods are proposed for CVCNN. Comparisons with other classical neural networks are made to show the advantages of the proposed methods.

7.
Acta Crystallogr E Crystallogr Commun ; 77(Pt 7): 749-754, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34513024

RESUMEN

A new RuII-ReII complex salt, µ-cyanido-κ2 C:N-bis-[(η5-cyclo-penta-dien-yl)bis(3,5,7-tri-aza-phosphaadamantane-κP)ruthenium(II)] tetra-bromido-(ethanol/methanol-κO)nitrosylrhenate(II), [Ru(CN)(C5H5)2(C6H12N3P)4][ReBr4(NO)(CH4O)0.5(C2H6O)0.5] or [RuCp(PTA)2-µ-CN-1κC:2κ2 N-RuCp(PTA)2][Re(NO)Br4(EtOH)0.5(MeOH)0.5] (PTA = 3,5,7-tri-aza-phosphaadaman-tane) was obtained and characterized by single-crystal X-ray diffraction, elemental analysis and infrared spectroscopy. The title salt was obtained by liquid-liquid diffusion of methanol/DMSO solutions of (NBu4)[Re(NO)Br4(EtOH)] and [(PTA)2CpRu-µ-CN-1κC:2κ2 N-RuCp(PTA)2](CF3SO3). The RuII and ReII independent moieties correspond to a binuclear and mononuclear complex ion, respectively. A deep geometrical parameter analysis was performed, and no significant differences were found with earlier reports containing similar mol-ecules. The magnetic properties were investigated in the temperature range 2.0-300 K, and the complex behaves as a quasi-magnetically isolated spin doublet with weak anti-ferromagnetic inter-actions.

8.
Inquiry ; 57: 46958020976826, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33243056

RESUMEN

This study analyzes whether hospitals accredited by the Joint Commission International in outpatient medical care protocols located in Colombia achieve a higher quality perception from foreign patients compared to others treated in a non-accredited one. A t-test with Welch correction, chi-square test, correlation coefficient of Tau Kendall, pre-test, post-test, complementary questionnaire and a 2 focus groups were used in 178 foreign patients. It was observed that patients treated in accredited hospitals had a higher quality perception than the non-accredited group. However, it was found that an unbalanced application of the 3 variables negatively alters quality judgment. Findings contributes to understanding the Colombian medical tourism in depth using non-conventional instruments.


Asunto(s)
Proyectos de Investigación , Turismo , Acreditación , Atención Ambulatoria , Colombia , Humanos , Percepción
9.
Educ. med. super ; 34(1): e1716, ene.-mar. 2020. tab
Artículo en Español | LILACS, CUMED | ID: biblio-1124658

RESUMEN

Introducción: Los contextos geográficos e institucionales diferenciados suponen la necesidad de analizar la efectividad de las metodologías de enseñanza desde enfoques no convencionales, a fin de contrastar asunciones generalistas. Una vía es el análisis de la valoración de los estudiantes sobre el método de aprendizaje que se les aplica y su relación con el cumplimiento de los objetivos de los cursos que reciben. Objetivo: Evaluar la percepción estudiantil sobre la efectividad del método de aprendizaje basado en proyectos en el Caribe colombiano en la asignatura Gerencia de la Salud para las carreras de medicina y enfermería. Métodos: Se aplicó un cuestionario de percepción estudiantil sobre la efectividad del método aprendizaje basado en proyectos a dos grupos de trabajo. Se utilizó una prueba chi cuadrado y de correlación de variables independientes en 340 estudiantes del curso de pregrado de Gerencia de la Salud. Se compararon la valoración estudiantil acerca del aprendizaje basado en proyectos y el método de enseñanza convencional para el cumplimiento de los objetivos del curso, y se identificaron las competencias trasversales que fueron mejor y peor valoradas durante el proceso de aprendizaje. Resultados: Se encontró que solo las competencias "Resolución de problemas" y "Trabajo en equipo" tuvieron percepciones positivas significativas cuando se usó el aprendizaje basado en proyectos, y que la valoración estudiantil era un instrumento idóneo que aporta al análisis de la eficacia de los métodos de enseñanza en contextos geográficos diferenciados. Conclusiones: La utilización de este instrumento permite conocer con mayor profundidad la efectividad del aprendizaje basado en proyectos en diferentes contextos. Los resultados demuestran que la percepción estudiantil sobre el aprendizaje basado en proyectos es pertinente. Este estudio exploratorio favorece otras investigaciones que analizarán el impacto de la aplicación de este método, a través de la percepción de los estudiantes sobre el desarrollo de competencias trasversales(AU)


Introduction: Differentiated geographical and institutional contexts imply the need to analyze the effectiveness of teaching methodologies from unconventional approaches, in order to contrast generalist assumptions. One way is the analysis of the students' assessment of the learning method that is applied to them and their relationship with the fulfillment of the objectives of the courses they receive. Objective: To evaluate the student's perception on the effectiveness of the project-based learning method in the Colombian Caribbean in the Health Management course for the medical and nursing majors. Methods: A student's perception questionnaire on the effectiveness of the project-based learning method was applied to two work groups. A chi-square and correlation of independent variables test was used in 340 students of the undergraduate course in Health Management. The student's assessment about project-based learning and the conventional teaching method for meeting the objectives of the course were compared, and the transversal competencies that were assessed as better and worse during the learning process were identified. Results: Only the competencies problem solving and teamwork were found to have significant positive perceptions when project-based learning was used, together with the fact that student assessment was an ideal instrument that contributes to the analysis of the effectiveness of teaching methods in differentiated geographical contexts. Conclusions: The use of this instrument allows to know, in greater depth, the effectiveness of project-based learning in different contexts. The results demonstrate that student perception of project-based learning is relevant. This exploratory study favors other research that will analyze the impact of the application of this method, through the students' perception of the development of transversal skills(AU)


Asunto(s)
Humanos , Percepción , Enseñanza , Efectividad , Gestión en Salud , Aprendizaje
10.
Mol Cell Biochem ; 415(1-2): 119-31, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27015684

RESUMEN

During the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca(2+)] i was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X.


Asunto(s)
Caspasas/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Melanoma/patología , Mitocondrias/efectos de los fármacos , Neoplasias Pancreáticas/patología , Proteínas y Péptidos Salivales/farmacología , Proteínas de Artrópodos , Línea Celular Tumoral , Chaperón BiP del Retículo Endoplásmico , Activación Enzimática , Humanos , Proteínas Recombinantes/farmacología
11.
Exp Cell Res ; 340(2): 248-58, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26748183

RESUMEN

The Kunitz-type recombinant protein, Amblyomin-X, is an antitumor recombinant molecule from a cDNA library prepared from the salivary glands of the tick Amblyomma cajennense. The primary target of this protein appears to be the proteasome. Amblyomin-X increased gene and protein expression of distinct subunits of the molecular motor dynein, which plays a key role in the intracellular transport. Herein, Amblyomin-X was specifically taken up by tumor cells through lipid-raft endocytic pathways, but not by fibroblasts. Moreover, dynein inhibitor, ciliobrevin A, decreased Amblyomin-X uptake by tumor cells. Furthermore, incubation of tumor cells with Amblyomin-X inhibited trypsin-like activity of the proteasome, which was restored upon pretreatment with ciliobrevin A. Only in tumor cells treated with Amblyomin-X, we identified proteins bounds to dynein that are related to aggresome formation, autophagy inhibition, and early and recycling endosome markers. In addition, Amblyomin-X was found to interact with dynein, increased Rab11A protein expression and Rab11A co-localization with the light-intermediate chain 2 (LIC2) of dynein. Thereby, the results provide new insights on the antitumor mechanism of Amblyomin-X and reveal an unsuspected role of cytoplasmic dynein in its uptake, intracellular trafficking and pro-apoptotic action.


Asunto(s)
Apoptosis/efectos de los fármacos , Dineínas Citoplasmáticas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas y Péptidos Salivales/farmacología , Animales , Apoptosis/fisiología , Proteínas de Artrópodos , Autofagia/fisiología , Línea Celular Tumoral , Humanos , Proteínas Recombinantes/metabolismo , Garrapatas
12.
Dalton Trans ; 44(25): 11636-48, 2015 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-26042855

RESUMEN

The novel Re(II) complex NBu4[Re(NO)Br4(Hnic)] (1) and the heterodinuclear compounds [Re(NO)Br4(µ-nic)Ni(dmphen)2]·½CH3CN (2), [Re(NO)Br4(µ-nic)Co(dmphen)2]·½MeOH (3), [Re(NO)Br4(µ-nic)Mn(dmphen)(H2O)2]·dmphen (4), [Re(NO)Br4(µ-nic)Cu(bipy)2] (5) [Re(NO)Br4(µ-nic)Cu(dmphen)2] (5') (NBu4(+) = tetra-n-butylammonium cation, Hnic = 3-pyridinecarboxylic acid, dmphen = 2,9-dimethyl-1,10-phenanthroline, bipy = 2,2'-bipyridine) have been prepared and the structures of 1-5 determined using single crystal X-ray diffraction. The structure of 1 consists of [Re(NO)Br4(Hnic)](-) anions and NBu4(+) cations. Each Re(II) is six-coordinate with four bromide ligands, a linear nitrosyl group and a nitrogen atom from the Hnic molecule, in a distorted octahedral surrounding. The structures of 2-5 are made up of discrete heterodinuclear Re(II)M(II) units where the fully deprotonated [Re(NO)Br4(nic)](2-) entity acts as a didentate ligand through the carboxylate group towards the [Ni(dmphen)2](2+) (2), [Co(dmphen)2](2+) (3), [Mn(dmphen)(H2O)2](2+) (4) and [Cu(bipy)2](2+) (5) fragments, the Re-M separation across the nic bridge being 7.8736(8) (2), 7.9632(10) (3), 7.7600(6) (4) and 8.2148(7) Å (5). The environment of the Re(II) ion in 2-5 is the same as 1 that in and all M(II) are six-coordinate in highly distorted octahedral surroundings, the main source of the distortion being due to the reduced bite of the chelating carboxylate. The magnetic properties of 1-5' were investigated in the temperature range 1.9-300 K. 1 behaves as a quasi-magnetically isolated spin doublet with very weak antiferromagnetic interactions through space Br···Br contacts. Its magnetic susceptibility data were successfully modeled through a deep analysis of the influence of the ligand field, spin-orbit coupling, tetragonal distortion and covalence effects as variable parameters. Compounds 2-5' exhibit weak antiferromagnetic interactions. The intramolecular exchange pathway in this family being discarded because of the symmetry of magnetic orbitals of the Re(II) ion (d(xy)) precludes any spin delocalization on the bridging nic orbitals, the observed magnetic interactions are most likely mediated by π-π type interactions between the peripheral ligands which occur in them. Only in the case of 4, short through space Br···Br contacts of ca. 4.03 Å (values larger than 5.5 Å in 2, 3 and 5) could be involved in the exchange coupling.

13.
São Paulo; 2015. 197 p.
Tesis en Portugués | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3271

RESUMEN

Hematophagous animals are sources of natural anticoagulants, since, for feeding, they need to maintain fluid blood in their digestive tract and therefore may contain a series of physiologically active molecules. From the construction of a cDNA library from the salivary glands of the Amblyomma cajennense tick, it was identified a transcript that encodes a serine protease inhibitor with a Kunitz-type domain similar to the endogenous TFPI inhibitor. The protein showed an inhibitory effect on the coagulation factor FXa and was isolated and produced in recombinant form, being named Amblyomin-X. Furthermore, the recombinant protein exerted pro-apoptotic effects in tumor cells as well as anti-angiogenic activity, tumor regression and decreased metastasis. Until now, it was not identified cytotoxic effects of AmblyominX in non-malignant or normal cells, such as fibroblasts. Among the activities described in this new molecule, we emphasize its ability to inhibit the proteasome system and to induce an increase in gene expression of the dynein cytoplasmic 1 light-intermediate chain 2 in microarray analysis in melanoma (SK-MEL-28) and pancreatic adenocarcinoma (MIA PaCa-2) human cells. The dynein is a molecular motor that plays an important role in all eukaryotic cells in transport of proteins, organelles and vesicles, and also the positioning of the nucleus, and the mitotic spindle pole and microtubules. This study is proposed to investigate the role of dynein in the antitumor mechanism of action of Amblyomin-X, from its uptake by the cell towards to its target as well as the biological effects triggered by this novel molecule linked to the proteasome inhibition.


Animais hematófogos são fontes de anticoagulantes naturais, visto que, para se alimentarem, necessitam manter o sangue fluido no seu trato digestivo e assim,podem conter uma série de moléculasfisiologicamente ativas. A partir da construçãode uma biblioteca de cDNA da glândula salivar do carrapato-estrela Amblyomma cajennense, foi identificado um transcrito que codifica um inibidor de serino protease com um domínio tipo Kunitz semelhante ao inibidor endógeno TFPI. A proteína apresentou efeito inibidor sobre o fator FXa da coagulação e foi isolada e produzida na sua forma recombinante, sendo denominada Amblyomin-X. Além disso, a proteína recombinante exerceu efeitos pró-apoptóticos em células tumorais e também atividade anti-angiogênica, regressão da massa tumoral e diminuição de metástases. Até o momento, não foi identificado efeitos citotóxicos do Amblyomin-X em linhagens celulares não-tumorais ou normais, como por exemplo, fibroblastos. Dentre as atividades descritas desta nova molécula, destaca-se sua capacidade de inibição do sistema proteassomo e indução do aumento de expressão gênica da cadeia leve-intermediária 2 da dineína citoplasmática 1 em análise de microarray em células de melanoma (SK-MEL-28) e adenocarcinoma de pâncreas (MIA PaCa-2) humano. A dineína é um motor molecular que desempenha um papel importante em todas as células eucarióticas no transporte de proteínas, vesículas e organelas e também no posicionamento do núcleo, do fuso mitótico e dos microtúbulos. O presente trabalho é proposto para investigar o papel da dineína no mecanismo de ação antitumoral do Amblyomin-X, desde sua entrada na célula até o seu alvo e os efeitos biológicos desencadeados por esta nova molécula relacionados à inibição proteassomal.

14.
PLoS One ; 9(12): e111907, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25479096

RESUMEN

Amblyomin-X is a Kunitz-type recombinant protein identified from the transcriptome of the salivary glands of the tick Amblyomma cajennense and has anti-coagulant and antitumoral activity. The supposed primary target of this molecule is the proteasome system. Herein, we elucidated intracellular events that are triggered by Amblyomin-X treatment in an attempt to provide new insight into how this serine protease inhibitor, acting on the proteasome, could be comparable with known proteasome inhibitors. The collective results showed aggresome formation after proteasome inhibition that appeared to occur via the non-exclusive ubiquitin pathway. Additionally, Amblyomin-X increased the expression of various chains of the molecular motor dynein in tumor cells, modulated specific ubiquitin linkage signaling and inhibited autophagy activation by modulating mTOR, LC3 and AMBRA1 with probable dynein involvement. Interestingly, one possible role for dynein in the mechanism of action of Amblyomin-X was in the apoptotic response and its crosstalk with autophagy, which involved the factor Bim; however, we observed no changes in the apoptotic response related to dynein in the experiments performed. The characteristics shared among Amblyomin-X and known proteasome inhibitors included NF-κB blockage and nascent polypeptide-dependent aggresome formation. Therefore, our study describes a Kunitz-type protein that acts on the proteasome to trigger distinct intracellular events compared to classic known proteasome inhibitors that are small-cell-permeable molecules. In investigating the experiments and literature on Amblyomin-X and the known proteasome inhibitors, we also found differences in the structures of the molecules, intracellular events, dynein involvement and tumor cell type effects. These findings also reveal a possible new target for Amblyomin-X, i.e., dynein, and may serve as a tool for investigating tumor cell death associated with proteasome inhibition.


Asunto(s)
Dineínas/metabolismo , Inhibidores de Proteasoma/administración & dosificación , Proteínas y Péptidos Salivales/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Proteínas de Artrópodos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Dineínas/química , Humanos , Ixodidae/química , Ixodidae/genética , Complejo de la Endopetidasa Proteasomal/efectos de los fármacos , Inhibidores de Proteasoma/metabolismo , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/metabolismo
15.
Dalton Trans ; 42(43): 15361-71, 2013 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-24005773

RESUMEN

Four novel Re(II) complexes of formula NBu4[Re(NO)Br4(L)] [NBu4(+) = tetra-n-butylammonium cation and L = pyridine (1), pyrazine (2), pyrimidine (3), pyridazine (4)] have been prepared by a substitution reaction involving NBu4[Re(NO)Br4(EtOH)] and L. Their crystal structures have been determined by single crystal X-ray diffraction. They are all mononuclear complexes whose structure is made up of [Re(NO)Br4L](-) anions and NBu4(+) cations. Each Re(II) ion is six-coordinate with four bromide ligands, a linear nitrosyl group and one monodentate nitrogen donor L building a tetragonally distorted octahedral surrounding. The Re-Br bond distances cover a narrow range [2.5048(8)-2.5333(5) Å] and they are longer than the Re-NO [1.688(15)-1.736(3) Å] and Re-N bonds [2.219(4)-2.234(3) Å]. The magnetic properties of 1-4 have been investigated in the temperature range 1.9-295 K. They behave like quasi magnetically isolated spin doublets with very weak antiferromagnetic interactions through intermolecular BrBr contacts. Their magnetic properties are discussed through a deep analysis of the influence of the ligand field, spin-orbit coupling, tetragonal distortion and covalence effects. The values of the temperature-independent paramagnetism for 1-4 are also substantiated and compared to those previously reported in related systems.

16.
Ann Fam Med ; 8(1): 73-81, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20065282

RESUMEN

The Agricultural Cooperative Extension Service model offers academic health centers methodologies for community engagement that can address the social determinants of disease. The University of New Mexico Health Sciences Center developed Health Extension Rural Offices (HEROs) as a vehicle for its model of health extension. Health extension agents are located in rural communities across the state and are supported by regional coordinators and the Office of the Vice President for Community Health at the Health Sciences Center. The role of agents is to work with different sectors of the community in identifying high-priority health needs and linking those needs with university resources in education, clinical service and research. Community needs, interventions, and outcomes are monitored by county health report cards. The Health Sciences Center is a large and varied resource, the breadth and accessibility of which are mostly unknown to communities. Community health needs vary, and agents are able to tap into an array of existing health center resources to address those needs. Agents serve a broader purpose beyond immediate, strictly medical needs by addressing underlying social determinants of disease, such as school retention, food insecurity, and local economic development. Developing local capacity to address local needs has become an overriding concern. Community-based health extension agents can effectively bridge those needs with academic health center resources and extend those resources to address the underlying social determinants of disease.


Asunto(s)
Centros Médicos Académicos , Relaciones Comunidad-Institución , Regionalización , Servicios de Salud Rural , Servicios de Salud Comunitaria , Humanos , Evaluación de Necesidades , New Mexico , Salud Rural
17.
Toxicon ; 53(6): 652-9, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19673080

RESUMEN

Lopap (Lonomia obliqua prothrombin activator protease) is a member of the lipocalin family isolated from the extract of L obliqua bristles. Lopap displays serine protease-like activities, including coagulation disturbance, cytokine secretion and antiapoptotic activity in human cultured endothelial cells. Here, we have investigated the effects of the recombinant protein (rLopap) on the inflammatory and apoptotic processes of neutrophils and endothelial cells from male Wistar rats. We found that rLopap did not induce in vivo leukocyte-endothelial interactions in the microvasculature, initial steps of leukocyte recruitment during inflammation. Incubation of rLopap with neutrophils or endothelial cells prevented apoptosis evoked by serum deprivation and induced nitric oxide (NO) production in both cell types, and increased the expression of ICAM-1 by endothelial cells. Simultaneous incubation of endothelial cells or neutrophils with rLopap and N omega-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthases, inhibited NO production and impaired the protection on apoptosis. Differently, incubation of endothelial cells with monoclonal antibody anti ICAM-1 did not change the protection on apoptosis evoked by rLopap. Together, these results indicate that rLopap does not display inflammatory properties in vivo but inhibits apoptosis of neutrophils and endothelial cells depending, at least in part, on NO production.


Asunto(s)
Citoprotección , Células Endoteliales/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Serina Endopeptidasas/farmacología , Animales , Apoptosis/efectos de los fármacos , Comunicación Celular/efectos de los fármacos , Células Endoteliales/fisiología , Inflamación/inducido químicamente , Interleucina-6/biosíntesis , Masculino , Neutrófilos/fisiología , Óxido Nítrico/biosíntesis , Ratas , Ratas Wistar , Proteínas Recombinantes/farmacología , Factor de Necrosis Tumoral alfa/biosíntesis
18.
Acad Med ; 80(8): 739-44, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16043528

RESUMEN

PURPOSE: To determine the impact on rural New Mexico of the large, decentralized University of New Mexico (UNM) family medicine residency. METHOD: A cross-sectional study was conducted of all 317 residency's graduates from 1974 to 2004. Location of current practice was correlated with the residents' gender, ethnicity, medical school of origin, and whether most training took place in the urban program or one of three rural programs. The residency's impact on rural communities was assessed. RESULTS: There was no significant gender difference between graduates who went into urban or rural practice. Compared with non-minority graduates, a significantly greater percentage of ethnic minority graduates were in rural and urban New Mexico practices and fewer in out-of-state practices. A greater percentage of graduates who had been medical students in New Mexico practiced in both rural and urban New Mexico areas compared with graduates of out of state medical schools. Finally, a greater percentage of graduates from the three rural family medicine residencies remained in the state and practiced in rural areas compared with graduates from the urban program. The graduates' contributions to the school of medicine and to rural New Mexico are described. CONCLUSIONS: Graduates of UNM's family medicine residency have contributed significantly to the state's rural health workforce. Ethnic minority status, graduation from New Mexico's medical school, and training in one of the three rurally based residencies favored in-state and rural retention, while gender had no significant effect. The rural orientation of the residencies offered rural communities economic benefits.


Asunto(s)
Medicina Familiar y Comunitaria/educación , Internado y Residencia/organización & administración , Médicos de Familia/provisión & distribución , Ubicación de la Práctica Profesional/estadística & datos numéricos , Servicios de Salud Rural , Selección de Profesión , Estudios Transversales , Etnicidad , Femenino , Geografía , Humanos , Masculino , New Mexico , Atención Primaria de Salud , Población Rural , Facultades de Medicina/estadística & datos numéricos , Recursos Humanos
19.
Genome ; 47(3): 493-500, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15190366

RESUMEN

One of the major environmental factors limiting plant productivity is lack of water. This is especially true for the major cereals maize, rice, and wheat, which demonstrate a range of susceptibility to moisture deficit. Although conventional breeding and marker-assisted selection are being used to develop varieties more tolerant to water stress, these methods are time and resource consuming and germplasm dependent. Genetic engineering is attractive because of its potential to improve abiotic stress tolerance more rapidly. Transcription factors have been shown to produce multiple phenotypic alterations, many of which are involved in stress responses. DREB1A, a transcription factor that recognizes dehydration response elements, has been shown in Arabidopsis thaliana to play a crucial role in promoting the expression of drought-tolerance genes. In our efforts to enhance drought tolerance in wheat, the A. thaliana DREB1A gene was placed under control of a stress-inducible promoter from the rd29A gene and transferred via biolistic transformation into bread wheat. Plants expressing the DREB1A gene demonstrated substantial resistance to water stress in comparison with checks under experimental greenhouse conditions, manifested by a 10-day delay in wilting when water was withheld.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Genes de Plantas , Factores de Transcripción/genética , Agua , Arabidopsis/fisiología , Secuencia de Bases , Southern Blotting , Cartilla de ADN , Plantas Modificadas Genéticamente , Reacción en Cadena de la Polimerasa , Transgenes
20.
La Paz; Fundacion Milenio; 2000. 400 p. (Serie: Temas de la mordenización).
Monografía en Español | LIBOCS, LIBOSP | ID: biblio-1305786

RESUMEN

La Fundación Milenio presenta la segunda parte de las Reformas Estructurales en Bolivia, trabajo que permite completar ese primer esfuerzo y de esa manera culminar el análisis de las principales reformas ejecutadas


Asunto(s)
Modernización del Sector Público , Bolivia
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