Lack of association between TLR4 rs4986790 polymorphism and risk of cardiovascular disease in patients with rheumatoid arthritis

This is copy of an article published in the DNA and cell biology 2012 © Mary Ann Liebert, Inc.; DNA and cell bilogy is available online at: http://online.liebertpub.comRheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Toll-like receptor-4 (TLR4) activates the innate immune response via NF-kB pathway and mitogenactivated protein kinase signaling, leading to expression of proinflammatory cytokines and chemokines. The G allele of TLR4 rs4986790 (+ 896A > G, Asp299Gly) gene polymorphism has been implicated in reduction of risk of atherosclerosis. In this study, 1481 RA patients fulfilling the 1987 American College of Rheumatology (ACR) criteria were genotyped for the rs4986790 TLR4 variant to determine the influence of this variant in the risk of CV events in these patients. Also, HLA-DRB1 status was determined using molecular based methods. Moreover, potential influence of rs4986790 variant in the development of subclinical atherosclerosis was assessed in a subgroup of RA patients with no history of CV events by the measurement of surrogate markers of subclinical atherosclerosis. No statistically significant differences in allele or genotype frequencies for the rs4986790 variant between RA patients who experienced CV events or not were found. Likewise, no significant association between this gene variant and any of the surrogate markers of subclinical atherosclerosis was found. In summary, results in our study do not support the hypothesis that the rs4986790 (+ 896A > G, Asp299Gly) TLR4 variant may influence predisposition for subclinical atherosclerosis and clinically evident CV disease in RA patientsThis study was supported by two grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spain). This work was partially supported by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I +D+ i 2008–2011 (FEDER). M.G.B. is supported by a grant from Fundación Española de Reumatología (FER). R.L.M. is supported by a grant by IFIMAV, Santander (Spain)

Efecto de la inoculación con hongos micorrízicos en el rendimiento de avena forrajera

Objective: The objective of the present study was to evaluate the effect of inoculation with two species of mycorrhizal fungi on the yield of forage oats. Design / methodology / approach: The method of pelletization and seed coating was used; The sowing went to volley. A completely randomized design with factorial arrangement (2x3x3) was used as factors: the two varieties, the HMA Glomus cubense and Glomus fasciculatum with a control and fertilization at 50% and 100% with a control with four repetitions. Results: The Chihuahua variety obtained a better yield, leaf stem ratio, leaf area index, number of leaves, leaf death, stem density and leaf death (2.50); in the other variables they were statistically equal. The Glomus cubense species was superior to Glomus fasciculatum in the yield variables (6.92 t DM ha-1) and in the death of leaves (4.68), but in the leaf area index (135.02), Glomus fasciculatum exceeded Glomus cubense. Limitations of the study / implications: yield in fodder production, producers apply high amounts of chemical fertilizers, whose excessive use negatively affects the soil resource. Findings / conclusions: The Chihuahua variety has better behavior and Glomus cubense exceeds Glomus fascicucatum in performanceObjetivo: El objetivo del presente estudio fue evaluar el efecto de inoculación con dos especies de hongos micorrízicos en el rendimiento de avena forrajera. Diseño/metodología/aproximación: Se utilizó el método de peletización y recubrimiento de semilla; la siembra fue al voleo. Se utilizó un diseño completamente al azar con arreglo factorial (2x3x3) se consideró como factores: las dos variedades, los HMA Glomus cubense y Glomus fasciculatum con un testigo y la fertilización al 50% y al 100% con un testigo con cuatro repeticiones. Resultados: La variedad Chihuahua obtuvo un mejor rendimiento, relación hoja tallo, índice de área foliar, número de hojas, muerte de hojas, densidad de tallos y en la muerte de hojas (2.50); en las demás variables fueron estadísticamente iguales. La especie Glomus cubense fue superior al Glomus fasciculatum en las variables rendimiento (6.92 t MS ha-1) y en la muerte de hojas (4.68), pero en el índice de área foliar (135.02), Glomus fasciculatum superó a Glomus cubense. Limitaciones del estudio/implicaciones: el rendimiento en la producción de forraje, los productores aplican cantidades elevadas de fertilizantes químicos, cuyo uso excesivo afecta negativamente el recurso suelo. Hallazgos/conclusiones: La variedad Chihuahua tiene mejor comportamiento y Glomus cubense en supera en rendimiento a Glomus fascicucatu

An investigation of targeted inhibition of transcription factor activity with pyrrole imidazole polyamide (PA) in chronic myeloid leukemia (CML) blast crisis cells

Tyrosine kinase inhibitor (TKI) therapy is the standard treatment for chronic phase (CP)-chronic myeloid leukemia (CML), yet patients in blast crisis (BC) phase of CML are unlikely to respond to TKI therapy. The transcription factor E2F1 is a down-stream target of the tyrosine kinase BCR-ABL1 and is up-regulated in TKI-resistant leukemia stem cells (LSC). Pyrrole imidazole polyamides (PA) are minor groove binders which can be programmed to target DNA sequences in a gene-selective manner. This manuscript describes such an approach with a PA designed to down-regulate E2F1 controlled gene expression by targeting a DNA sequence within 100 base pairs (bp) upstream of the E2F1 consensus sequence. Human BC-CML KCL22 cells were assessed after treatment with PA, TKI or their combination. Our PA inhibited BC-CML cell expansion based on cell density analysis compared to an untreated control after a 48-hour time-course of PA treatment. However, no evidence of cell cycle arrest was observed among BC-CML cells treated with PA, with respect to their no drug control counterparts. Thus, this work demonstrates that PAs are effective in inhibiting E2F1 TF activity which results in a temporal reduction in BC-CML cell number. We envisage that PAs could be used in the future to map genes under E2F1 control in CML LSCs

CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in spanish rheumatoid arthritis patients

This is a copy of an article published in the DNA Cell Biology (01-01-2013) copyright Mary Ann Liebert, Inc. DNA Cell Biology is avalaible online at: http://online.liebertpub.comRheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis, which is the main cause of increased cardiovascular (CV) morbidity and mortality in RA patients. CARD8 is a constituent of inflammasome, which regulates interleukin 1-beta production, and has been associated with a worse disease course in early RA. One thousand six hundred twenty-one patients fulfilling the 1987 ACR classification criteria for RA and 1300 matched controls, were genotyped for the CARD8 rs2043211 (30T > A, p.C10X) single-nucleotide polymorphism (SNP) using predesigned TaqMan SNP genotyping assay. The genotyping success rate in our study was greater than 94%. We assessed CARD8 rs2043211 gene polymorphism results in 1530 Spanish RA patients in whom information on CV disease and CV risk factors was available at the time of the study. Also, a subgroup of patients with no history of CV events (n = 276) was assessed for the potential influence of the rs2043211 variant in the development of subclinical atherosclerosis, by measurement of carotid intima-media thickness (IMT) and presence of carotid plaques. No statistically significant differences in allele or genotype frequencies for the rs2043211 CARD8 gene variant between patients with RA and controls were seen. Similarly, CARD8 rs2043211 (30T > A, p.C10X) SNP did not influence the development of CV events or the risk of CV events throughout the time. Likewise, no significant association between this gene variant and carotid IMT or the presence of plaques was found. In summary, our results do not support a role of the CARD8 rs2043211 gene variant in susceptibility to RA or in the development of CV disease in patients with RAThis work was supported by grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spain), and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I +D+ i 2008–2011 (FEDER). M.G.B. is a beneficiary of a grant from Fundación Española de Reumatología (FER)

¿La deserción y la graduación no diferencian a los programas de pregrado de la Facultad de Ingeniería de la Universidad de Antioquia?

RESUMEN: A las universidades públicas colombianas, llegan mayoritariamente estudiantes provenientes de estratos medios y bajos con las dificultades propias de su condición social, que aunados a los de masificación creciente, se traducen en fenómenos como la deserción y la mayor duración de la carrera, entre otros. El grupo de investigación Ingeniería y Sociedad, acoge como variables de interés la deserción y la graduación del estudiante. En el presente trabajo, se hace un seguimiento desde la cohorte 2005-2 a la 2013-1, con el propósito de analizar en ellas la evolución de dichas variables en los 16 programas de pregrado de la Facultad de Ingeniería (4 programas virtuales y 12 presenciales). Para tal efecto, los datos fueron tomados del sistema de información de Matrícula y Registro Sistematizado (MARES) de la Universidad, los cuales fueron analizados por medio de estadística descriptiva y comparación entre variables. Los resultados estadísticos que se presentan son los valores de los correspondientes parámetros, dado que fueron calculados sobre los registros de la totalidad de los estudiantes. Se encontró que la deserción promedio entre los programas virtuales al cabo de 10 semestres es del 76%, mientras que en los presenciales es del 51%. Por su parte, el porcentaje de estudiantes graduados a los 10 semestres en la modalidad virtual es del 0.4% y, en la presencial, es del 5%; es decir, por cada estudiante que se gradúe de la virtual, se gradúan 10 de la presencial en el tiempo esperado de duración del programa. Esto muestra que la modalidad virtual en la Facultad de Ingeniería presenta indicadores que la hacen distante con respecto a la modalidad presencial, con las consecuencias negativas que esto conlleva en lo personal, familiar, social e inclusive, para la institución misma. De esta manera, este trabajo contribuye a la identificación de factores asociados a la deserción y a la graduación

Identifying non-destructive growth and maturity indexes of Prickly pear (Opuntia albicarpa S. Var. Burrona) and evaluation of freeze-drying conditions

Around the world, prickly pear fruits are valued as a source of dietary functional compounds and ingredients for innovative foods. Growth and physicochemical changes of Opuntia albicarpa S. fruits were recorded from 0 to 132 days-after-flowering (DAF) to identify non-destructive maturity-indices. Optimum-ripened fruits were freeze-dried to study physicochemical and functional characteristics of dried and rehydrated pulp. Principal component analysis confirmed growth turned into fruit ripening in DAF 99, and it lasted until DAF 132. Changes in color parameters of the peel correlated with fruit texture and pulp sugar content and taste index (P < 0.01). During freeze-drying, plate temperature had more significant effects than the thickness (P < 0.05). At 30°C, color ΔE between dried and fresh slices augmented, but, texture Δ´s (medium force) between rehydrated and fresh pulp was lower. Color tests could be used to harvest commercially-ripened fruits. Freeze-drying at 30°C improves the rehydrated slices texture regarding thickness maintaining rehydration coefficients.Las tunas son apreciadas en todo el mundo como fuente de compuestos funcionales dietarios e ingredientes para alimentos innovadores. Para identificar índices de maduración no destructivos, se registraron cambios en el crecimiento y en los parámetros fisicoquímicos de frutos de Opuntia albicarpa S. entre los días después de la floración (DAF) 0 al 132. Frutos con maduración óptima fueron liofilizados para evaluar características fisicoquímicas y funcionales de pulpa seca y rehidratada. El análisis de componentes principales confirmo que el crecimiento dio lugar a la maduración en el DAF 99 y ésta prosiguió hasta el DAF 132. Los cambios en parámetros de color en cáscara correlacionaron con la textura del fruto, y en pulpa, con el contenido de azúcares y el índice de sabor (P< 0.01). Durante la liofilización, la temperatura de placa tiene más efectos significativos que el espesor (P≤ 0.05). A 30°C, el ΔE de color entre la pulpa seca y fresca aumentó, pero, el Δ de textura (fuerza media) fue menor entre la rehidratada y la fresca. Se pueden emplear evaluaciones de color para cosechar frutos en su madurez comercial, y liofilizar estos frutos a 30°C mejora la textura sin importar el espesor, manteniendo los coeficientes de rehidratación.This work was supported by the SIMORELOS program of CONACyT

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis

Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.National Institutes of HealthRevisión por pare

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data