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1.
Clin Exp Rheumatol ; 38 Suppl 124(2): 112-119, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32441643

RESUMEN

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

2.
Crit Rev Eukaryot Gene Expr ; 30(1): 57-75, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32421985

RESUMEN

INTRODUCTION: Various pathologies and lifestyle factors, such as nutritional factors and physical exercises, can alter the gene expression of proteins related to synthesis and degradation. AIM: We performed a systematic review of atrophy models, cancer models, burn models, sepsis models, cardiac insufficiency models, amino acid supplementation models, protein supplementation models, and miscellaneous models that have altered the gene expression of MTOR, MURF-1, or MAFBX in rats and mice. MATERIALS AND METHODS: We searched the literature in the following databases: Medline, Scielo.org, Scielo.br, Redib, Lilacs, and the Periodicos Capes. RESULTS: We selected 56 articles for this review. DISCUSSION: Several conditions can alter the gene expression of muscle proteins under conditions that stimulate muscle degradation pathways. Therefore, treatments must normalize the expression of the degradation pathways and potentiate the synthesis pathways so the muscular tissue confers an increase in functional capacity and thus, survival in diseased patients. Therefore, the reversal of the mechanisms that promote its depletion must be achieved. CONCLUSION: Identification of the atrophic mechanisms present in pathologies and other conditions of muscular disuse in the scientific literature is fundamental for the adoption of clinical strategies to prevent protein degradation and to promote the maintenance and/or increase of muscle tissue. Such strategies include physical exercise, protein supplementation, and/or pharmacological applications, aimed toward restoring the fullness of functional capacity.

3.
Cells ; 9(5)2020 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-32365557

RESUMEN

The pathogenesis of Crohn's disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn's disease (CD) fistulas. Succinate levels and SUCNR1-expression were analyzed in intestinal resections from non-Inflammatory Bowel Disease (non-IBD) subjects and CD patients with stenosing-B2 or penetrating-B3 complications and in a murine heterotopic-transplant model of intestinal fibrosis. EMT, as increased expression of Snail1, Snail2 and vimentin and reduction in E-cadherin, was analyzed in tissues and succinate-treated HT29 cells. The role played by SUCNR1 was studied by silencing its gene. Succinate levels and SUCNR1 expression are increased in B3-CD patients and correlate with EMT markers. SUCNR1 is detected in transitional cells lining the fistula tract and in surrounding mesenchymal cells. Grafts from wild type (WT) mice present increased succinate levels, SUCNR1 up-regulation and EMT activation, effects not observed in SUCNR1-/- tissues. SUCNR1 activation induces the expression of Wnt ligands, activates WNT signaling and induces a WNT-mediated EMT in HT29 cells. In conclusion, succinate and its receptor are up-regulated around CD-fistulas and activate Wnt signaling and EMT in intestinal epithelial cells. These results point to SUCNR1 as a novel pharmacological target for fistula prevention.

4.
Nutrients ; 12(4)2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32244667

RESUMEN

Vitamin D (VD) deficiency has been associated to Crohn's disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression of VDR in intestinal tissue, epithelial cells, and fibroblasts from CD patients. The effects of VD on a fibroblast wound healing assay and murine intestinal fibrosis are also analyzed. Our data show diminished VDR protein levels in surgical resections and epithelial cells from CD patients. In intestinal fibroblasts isolated from damaged tissue of CD patients, we detected enhanced migration and decreased VDR expression compared with both fibroblasts from non-damaged tissue of the same CD patient or control fibroblasts. Treatment with VD increased VDR protein levels, avoided the accelerated migration in CD fibroblasts, and prevented murine intestinal fibrosis induced by the heterotopic transplant model. In conclusion, our study demonstrates diminished VDR protein levels associated with enhanced migration in intestinal fibroblasts from damaged tissue of CD patients. In these cells, VD accumulates VDR and normalizes migration, which supports that CD patients would benefit from the VD anti-fibrotic therapeutic value that we demonstrate in a murine experimental model.

6.
Polymers (Basel) ; 12(3)2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32110932

RESUMEN

Aiming to gain knowledge in the epoxy-bitumen modification mechanisms, this work explores the effects that epoxy concentration and ambient curing exert on the physico-chemistry and thermo-rheological properties of epoxy-modified binders. Process rheokinetics of epoxy-bitumen blends indicates that binder short-term modification (i.e., during processing) is accelerated by epoxy concentration. Furthermore, a synergistic effect of epoxy concentration and ambient curing is found during long-term modification (i.e., during curing at ambient conditions). As a result, viscous and viscoelastic rheological properties of binders are enhanced at medium/high in-service temperatures, at least, after one month of curing. FTIR (Fourier Transform Infrared spectroscopy) tests and SARAs (Saturates, Aromatics, Resins and Asphaltenes) analysis confirm the existence of esterification/etherification reactions between epoxy oxirane groups and the carbonyl groups available in aromatic and resin molecules. Thus, the new high molecular weight compounds increase the asphaltenic fraction of modified bitumen. Likewise, nonreversing heat flow curves obtained by modulated calorimetry corroborate the formation of such highly structured domains responsible for the final binder performance.

7.
Artículo en Inglés | MEDLINE | ID: mdl-32152799

RESUMEN

The use of bryophytes as an indicator of environmental quality has been addressed on numerous occasions and in different places of the world under a variety of conditions. However, in Latin America their use is still limited. In the study described here, the presence and distribution of the bioaccumulation of lead in bryophytes has been evaluated in both contaminated and uncontaminated sites in Villavicencio (Colombia) and its surroundings. Villavicencio is a medium-sized city that is similar in size to many other cities in Latin America. A total of 52 samples of bryophytes were collected, of which 43 belong to points distributed in urban areas of the city (residential, commercial, highway), and the remaining nine are from uncontaminated areas (reference) taken in the surroundings of the city. The samples were treated with acid (nitric and hydrochloric) and subsequently measured by atomic absorption spectrometry. It was found that Pb concentrations in the commercial sector are between 1 and 6 times higher than in the residential and highway sectors. Spatial distribution maps of lead over the sampled territory were created using Arc-GIS 10.1. It is noteworthy that the values obtained are higher than those found in European cities.

8.
Dev Comp Immunol ; 108: 103666, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32126244

RESUMEN

Psoriasis is a skin inflammatory disorder that affects 3% of the human population. Although several therapies based on the neutralization of proinflammatory cytokines have been used with relative success, additional treatments are required. The in silico analysis of gene expression data of psoriasis lesional skin and an analysis of vitamin B6 metabolites in the sera of psoriasis patients point to altered vitamin B6 metabolism at both local and systemic levels. Functional studies showed that vitamin B6 vitamers reduced skin neutrophil infiltration, oxidative stress and Nfkb activity in two zebrafish models of skin inflammation. Strikingly, inhibition of glycogen phosphorylase L (Pygl) and glucose-6-phosphate dehydrogenase (G6pd), two vitamin B6-regulated enzymes, alleviated oxidative-stress induced inflammation in zebrafish skin inflammation models. Despite the central role of G6pd in antioxidant defenses, the results of the study demonstrate that glycogen stores and G6pd fuel NADPH oxidase to promote skin inflammation, revealing novel targets for the treatment of skin inflammatory disorders.

9.
Ecology ; 101(2): e02940, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31749146

RESUMEN

A major goal in ecology is to understand mechanisms that influence patterns of biodiversity and community assembly at various spatial and temporal scales. Understanding how community composition is created and maintained also is critical for natural resource management and biological conservation. In this study, we investigated environmental and spatial factors influencing beta diversity of local fish assemblages along the longitudinal gradient of a nearly pristine Neotropical river in the Colombian Llanos. Standardized surveys were conducted during the low-water season at 34 sites within the Bita River Basin. Physical, chemical, and landscape parameters were recorded at each site, and asymmetric eigenvector maps were used as spatial variables. To examine the relative influence of dispersal and environmental variables on beta diversity and its components, distance-based redundancy analysis (db-RDA) and variation partitioning analysis were conducted. We proposed that spatial scale of analysis and position within the river network would constrain patterns of beta diversity in different ways. However, results indicated that in this system, high beta diversity was consistent among species assemblages no matter the scale of analysis or position within the river network. Species replacement (turnover) dominated beta diversity, an indication of the importance of species sorting. These findings suggested that conservation of fish diversity in tropical rivers requires maintenance of both habitat heterogeneity (spatial variation in habitat conditions) and connectivity at the scale of entire river basins.

10.
Sci Total Environ ; 704: 135393, 2020 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-31831245

RESUMEN

Afforestation or secondary succession after cropland abandonment are different strategies to restore soil ecosystem services such as nutrient cycling, soil conservation, and carbon sequestration. However, the studies on the effects on soil-property dynamics after land-use changes are limited in semiarid regions. In this context, an experimental area with a semiarid climate allowed the assessment and comparison of physicochemical soil properties (soil organic C [SOC], soil total N [TN], available P [AP], available K [AK], cation-exchange capacity [CEC], bulk density [BD], pH, available water-holding capacity [AWHC], and C:N ratio) after Pinus halepensis afforestation and secondary succession following agriculture abandonment in 1994. The impact of 12 soil-preparation treatments for planting on soil properties was also evaluated. For this, soil samples (0-10 cm deep) from the afforestation were taken in 1998, 2002, 2007, 2010, 2013, and 2016, and from abandoned cropland in 2010, 2013, and 2016. In afforestation, soil-preparation treatments did not alter differentially the soil properties after 22 years. Significant differences among years were found in SOC, TN, AP, AK, CEC, pH, and C:N. BD changes were detected neither in afforestation nor in abandoned cropland. After 22 years, only SOC, AK and the C:N ratio proved significantly higher in afforestation than in abandoned cropland. In general, soil properties improvement (i.e. SOC, TN, AP, AK, and CEC) was slow after afforestation and abandoned cropland likely due to the legacy of the previous land use (cereal crops) and the semiarid climate influence.

11.
Dev Comp Immunol ; 105: 103583, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31862296

RESUMEN

The zebrafish has become an excellent model for the study of inflammation and immunity. Its unique advantages for in vivo imaging and gene and drug screening have allowed the visualization of dual oxidase 1 (Duox1)-derived hydrogen peroxide (H2O2) tissue gradients and its crosstalk with neutrophil infiltration to inflamed tissue. Thus, it has been shown that H2O2 directly recruits neutrophils via the Src-family tyrosine kinase Lyn and indirectly by the activation of several signaling pathways involved in inflammation, such as nuclear factor κB (NF-κB), mitogen activated kinases and the transcription factor AP1. In addition, this model has also unmasked the unexpected ability of H2O2 to induce the expression of the gene encoding the key neutrophil chemoattractant CXC chemokine ligand 8 by facilitating the accessibility of transcription factors to its promoter through histone covalent modifications. Finally, zebrafish models of psoriasis have shown that a H2O2/NF-κB/Duox1 positive feedback inflammatory loop operates in this chronic inflammatory disorder and that pharmacological inhibition of Duox1, but not of downstream mediators, inhibits inflammation and restores epithelial homeostasis. Therefore, these results have pointed out DUOX1 and H2O2 as therapeutic targets for the treatment of skin inflammatory disorders, such as psoriasis.

12.
Polymers (Basel) ; 11(12)2019 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-31801302

RESUMEN

Hybrid modification is a relatively new concept of incorporating two or more polymeric modifiers of different nature to a bitumen, in order to take advantage of their complementary features. Aiming to this, in this paper, the so-called Hybrid Systems (HSs) were prepared by the addition of an ethylene-based copolymer (reactive or non-reactive) to a model rubberised binder (Crumb Tyre Rubber Modified Bitumen). The resulting binders (referred to as reactive and non-reactivate HSs, depending on copolymer used) were evaluated by means of thermorheological analysis, technological characterisation, fluorescence microscopy and modulated differential scanning calorimetry. From the experimental results, it may be deduced a positive synergistic effect of non-dissolved Crumb Tyre Rubber (CTR) particles and a second polymeric phase that not only improves the in-service performance but also the high-temperature storage stability. This enhancement is attributed to the development of a multiphasic system composed of non-dissolved CTR particles, a polymer-rich phase and an asphaltene-rich phase. In the case of non-reactive HSs, droplets of swollen ethylene copolymer form a well-defined dispersed phase. By contrast, reactive HSs display a different morphology, almost invisible by optical microscopy, related to the development of a chemical network that yields, by far, the highest degree of modification.

13.
Zootaxa ; 4668(4): zootaxa.4668.4.8, 2019 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-31716611

RESUMEN

A new species of Pimelodella is described from northern coastal drainages of the Sierra Nevada de Santa Marta (SNSM), Colombia. The new species is diagnosed from all trans-Andean congeners by the following unique combination of characters: head length 22.2-23.7% SL, bony interorbital width 17.6-21.6% HL, maxillary barbels length 53.0-68.3% SL, inner mental-barbels length 14.4-20.0% SL, body width 17.6-21.1% SL, dorsal-fin spine length 8.3-13.7% SL, dorsal-fin base 12.3-14.9% SL, pectoral-fin spine length 12.9-14.5% SL, pectoral-fin spine length without dentations on the distal posterior margin 21.6-29.8% in pectoral-fin spine length, maximum depth of dentations in posterior margin of pectoral-fin spine 1.40-1.68 times in the width of the spine at its base, adipose-fin base length 22.8-26.4% SL, caudal-peduncle depth 9.2-10.5% SL, 40 vertebrae, having a conspicuous paired dark brown stripe on the dorsal surface of body, extending from posterior margin of head to caudal-fin insertion and a wide dark brown midlateral stripe present. The isolated occurrence of this new taxon living in allopatry in coastal drainages of the SNSM could have interesting biogeographic implications for dispersal and vicariance processes of the ichthyofauna from northern South America.


Asunto(s)
Bagres , Animales , Colombia , Nevada , América del Norte , América del Sur
14.
Rev. bras. med. esporte ; 25(5): 413-417, Sept.-Oct. 2019. tab, graf
Artículo en Inglés | LILACS-Express | ID: biblio-1042344

RESUMEN

ABSTRACT Introduction Aging is a natural process and marked by changes and adaptations of both a biological and physiological nature. As regards adaptations, there are numerous works that address these responses following various types of training programs. Resistance training (RT) can be assessed by biochemical parameters such as creatine kinase (CK), which is a major marker of stress in the skeletal muscles. C-reactive protein (CRP) is a biochemical marker used to assess damage to the cardiac muscles. Objective To evaluate the influence of CK on CRP in elderly female subjects undergoing RT. Methods An experimental study was carried out with 10 elderly women (61 ± 1.8 years). Peripheral venous blood was collected for the CK and CRP analysis both before and 24 hours after 8 weeks of RT. Anthropometric measurements involved BMI (Body Mass Index), WHR (waist-to-hip ratio) and body composition. The RT involved combined series - Bi-Set. For statistical analysis, the Shapiro-Wilk normality test was conducted first and presented p >0.05, confirming the use of parametric tests. Group variables were presented as mean and standard deviation. To compare the load-dependent samples, the repeated measures one-way ANOVA was performed first, followed by Tukey's post hoc test. For CK and CRP variables, we conducted the paired Student's t-test for the timepoints pre- and post-eight weeks of RT along with the one-way ANOVA test, also conducting Tukey's post-test when necessary. The level of significance was set at p ≤0.05. Results There was a statistically significant decrease in both serum CK and CRP, which indicated a reduction of 73.14% and 75%, respectively. Conclusion Long-term RT promoted influences among biomarkers assessed through skeletal muscle (CK) and cardiac muscle (CRP) damage, determining adaptation and muscle remodeling in any age group. Level of evidence II, Investigation of treatment results.


RESUMO Introdução O envelhecimento é um processo natural e marcado por mudanças e adaptações, tanto biológicas quanto fisiológicas. Com relação às adaptações, existem inúmeros trabalhos que abordam essas respostas decorrente a vários tipos de treinamento. O treinamento resistido (TR) pode ser avaliado por parâmetros bioquímicos, como a creatina quinase (CK), que é um grande marcador de estresse da musculatura esquelética. A proteína C-reativa (PCR) é um marcador bioquímico utilizado para avaliar o dano no sistema muscular cardíaco. Objetivo Avaliar a influência da CK sob a PCR em idosas em TR. Métodos Estudo do tipo experimental com dez idosas (61 ± 1,8 anos). As análises de CK e PCR foram coletadas em sangue venoso periférico antes e 24 horas após as 8 semanas de TR. Medidas antropométricas foram realizadas: índice de massa corporal (IMC), relação da cintura e o quadril (RCQ) e composição corporal. O TR foi realizado por série combinada (Bi-Set). Para análise estatística, primeiramente foi realizado o teste de normalidade de Shapiro-Wilk, apresentando p > 0,05) e comprovando a utilização de testes paramétricos. As variáveis do grupo foram apresentadas como média e desvio padrão. Para comparação das amostras dependentes de evolução das cargas foi realizado a ANOVA one-way pareada para medidas repetidas, seguida de pós-teste de Tukey. Para variáveis de CK e PCR, foi realizado teste t de Student pareado para os momentos pré e pós-8 semanas de TR, assim como o ANOVA one-way e, quando necessário, o pós-teste de Tukey. O nível de significância adotado foi de p ≤ 0,05. Resultados Houve diminuição estatisticamente significativa, tanto para as concentrações séricas de CK, quanto para PCR, o que indicou redução de 73,14% e 75%, respectivamente. Conclusão O TR de longa duração promoveu influências entre biomarcadores avaliados por meio do dano do músculo esquelético (CK) e dano do músculo cardíaco (PCR), determinando adaptação e remodelamento muscular em qualquer faixa etária. Nível de evidência II; Investigação dos resultados do tratamento.


RESUMEN Introducción El envejecimiento es un proceso natural y marcado por cambios y adaptaciones, tanto biológicas como fisiológicas. Con respecto a las adaptaciones, existen innumerables trabajos que abordan esas respuestas derivadas de varios tipos de entrenamiento. El Entrenamiento Resistido (ER) puede ser evaluado por parámetros bioquímicos, como la creatina quinasa (CK) que es un gran marcador de estrés de la musculatura esquelética. La proteína C-reactiva (PCR) es un marcador bioquímico utilizado para evaluar el daño en el sistema muscular cardíaco. Objetivo Evaluar la influencia de la CK bajo la PCR en ancianas en ER. Métodos Estudio de tipo experimental con 10 ancianas (61 ± 1,8 años). Los análisis de CK y PCR fueron recolectados en sangre venosa periférica antes y 24 horas después de las 8 semanas de ER. Se realizaron mediciones antropométricas: IMC (Índice de Masa Corporal), RCC (Relación Cintura / Cadera) y Composición Corporal. El ER fue realizado por Serie Combinada (Bi-Set). Para análisis estadístico, primero se realizó la prueba de normalidad de Shapiro-Wilk presentando p> 0,05 y comprobando el uso de pruebas paramétricas. Las variables del grupo se mostraron como promedio y desviación estándar. Para comparación de las muestras dependientes de evolución de las cargas se realizó el Test one-way ANOVA pareado para medidas repetidas, seguido de post-test de Tukey. Para variables de CK y PCR se realizó el Test t de Student pareado para los momentos pre y post ocho semanas de ER, así como el ANOVA one-way y cuando necesario, el post-test de Tukey. El nivel de significancia adoptado fue de p ≤ 0,05. Resultados Hubo disminución estadísticamente significativa, tanto para las concentraciones séricas de CK, como para PCR, lo que indicó reducción del 73,14% y el 75%, respectivamente. Conclusión El ER de larga duración promovió influencias entre biomarcadores evaluados a través del daño del músculo esquelético (CK) y daño del músculo cardíaco (PCR) determinando adaptación y remodelación muscular en cualquier grupo de edad. Nivel de evidencia II; Investigación de los resultados del tratamiento.

15.
Cells ; 8(9)2019 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-31540207

RESUMEN

We recently observed reduced autophagy in Crohn's disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn's disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against intestinal fibrosis.

16.
Rev. bras. ciênc. esporte ; 41(3): 298-307, jul.-set. 2019. tab, graf
Artículo en Portugués | LILACS-Express | ID: biblio-1042069

RESUMEN

Resumo Foram avaliados os efeitos do destreinamento sobre parâmetros cardiovasculares em idosas. Idosas foram submetidas a oito semanas de treinamento resistido seguidas de oito semanas de destreinamento. Foram avaliadas nove mulheres idosas (idade 62 ± 2,30). Foram feitas coletas de sangue venoso periférico e avaliação da composição corporal antes do início de treinamento, após o treinamento e após a fase de destreinamento. Não houve aumento significativo da PCR na fase de destreino, porém observamos alterações negativas para colesterol total e composição corporal, representada pelo peso gordo. Os resultados sugerem que oito semanas de destreinamento não aumentaram significativamente a PCR, porém influenciaram negativamente em outros parâmetros relacionados aos riscos cardiovasculares, como valores antropométricos e bioquímicos representados pelo colesterol total e massa gorda, respectivamente. De fato, a continuidade do treinamento físico é essencial para adquirir e manter uma boa saúde, caso contrário os benefícios alcançados regridem aos valores iniciais.


Abstract The detraining effects on cardiovascular parameters in the elderly women (EW) were evaluated. EW underwent 8 weeks of resistance training, followed by eight weeks of detraining. 9 EW were evaluated (age 62 ± 2.30). Peripheral venous blood collections and body composition evaluation were performed before training, after training and after the detraining phase. There was no significant increase in CRP in detraining phase, but we observed negative changes for total cholesterol and body composition, represented by fat weight. The results suggest that 8 weeks of detraining did not significantly increase CRP, but had a negative influence on other parameters related to cardiovascular risks, as anthropometric and biochemical values represented by total cholesterol and fat mass, respectively. In fact, continuity of physical training is essential to acquiring and maintaining good health, otherwise the beneficial adaptations achieved will return to initial values.


Resumen Se evaluaron los efectos de la falta de entrenamiento sobre los parámetros cardiovasculares de mujeres mayores. Estas siguieron un entrenamiento resistido durante 8 semanas, seguidas de 8 semanas de falta de entrenamiento. Se evaluó a 9 mujeres de edad avanzada (edad de 62 ± 2,30). Se realizaron extracciones de sangre venosa periférica y evaluación de la composición corporal antes del inicio del entrenamiento, después del entrenamiento y después de la fase de falta de entrenamiento. No hubo un aumento considerable de la PCR en la fase de falta de entrenamiento, pero observamos alteraciones negativas del colesterol total y composición corporal, representada por la grasa. Los resultados sugieren que 8 semanas de falta de entrenamiento no aumentaron considerablemente la PCR, pero influyeron negativamente en otros parámetros relacionados con los riesgos cardiovasculares, como valores antropométricos y bioquímicos representados por el colesterol total y la masa grasa, respectivamente. De hecho, la continuidad del entrenamiento físico es esencial para adquirir y mantener una buena salud; de lo contrario, las adaptaciones beneficiosas alcanzadas vuelven a los valores iniciales.

17.
Nucleic Acids Res ; 47(18): 9524-9541, 2019 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-31392315

RESUMEN

Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4-Not complex conditions its post-transcriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 action in gene transcription. This double strategy brought us to conclude that both Xrn1-decaysome and Ccr4-Not regulate RNAPII elongation, and that they do it in parallel. We validated this conclusion measuring TFIIS genome-wide recruitment to elongating RNAPII. We found that xrn1Δ and ccr4Δ exhibited very different patterns of TFIIS versus RNAPII occupancy, which confirmed their distinct role in controlling transcription elongation. We also found that the relative influence of Xrn1 and Ccr4 is different in the genes encoding ribosomal proteins as compared to the rest of the genome.


Asunto(s)
Exorribonucleasas/genética , ARN Polimerasa II/genética , Estabilidad del ARN/genética , Ribonucleasas/genética , Proteínas de Saccharomyces cerevisiae/genética , Regulación Fúngica de la Expresión Génica , Genoma Fúngico/genética , Impresión Genómica , Proteínas Ribosómicas/genética , Saccharomyces cerevisiae/genética , Factores de Elongación Transcripcional/genética
18.
Sci Rep ; 9(1): 11091, 2019 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-31366981

RESUMEN

The unicellular green alga Chlamydomonas reinhardtii is evolutionarily divergent from higher plants, but has a fully functional silencing machinery including microRNA (miRNA)-mediated translation repression and mRNA turnover. However, distinct from the metazoan machinery, repression of gene expression is primarily associated with target sites within coding sequences instead of 3'UTRs. This feature indicates that the miRNA-Argonaute (AGO) machinery is ancient and the primary function is for post transcriptional gene repression and intermediate between the mechanisms in the rest of the plant and animal kingdoms. Here, we characterize AGO2 and 3 in Chlamydomonas, and show that cytoplasmically enriched Cr-AGO3 is responsible for endogenous miRNA-mediated gene repression. Under steady state, mid-log phase conditions, Cr-AGO3 binds predominantly miR-C89, which we previously identified as the predominant miRNA with effects on both translation repression and mRNA turnover. In contrast, the paralogue Cr-AGO2 is nuclear enriched and exclusively binds to 21-nt siRNAs. Further analysis of the highly similar Cr-AGO2 and Cr-AGO 3 sequences (90% amino acid identity) revealed a glycine-arginine rich N-terminal extension of ~100 amino acids that, given previous work on unicellular protists, may associate AGO with the translation machinery. Phylogenetic analysis revealed that this glycine-arginine rich N-terminal extension is present outside the animal kingdom and is highly conserved, consistent with our previous proposal that miRNA-mediated CDS-targeting operates in this green alga.

19.
Immunity ; 51(1): 50-63.e5, 2019 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-31174991

RESUMEN

Chronic inflammatory diseases are associated with altered hematopoiesis that could result in neutrophilia and anemia. Here we report that genetic or chemical manipulation of different inflammasome components altered the differentiation of hematopoietic stem and progenitor cells (HSPC) in zebrafish. Although the inflammasome was dispensable for the emergence of HSPC, it was intrinsically required for their myeloid differentiation. In addition, Gata1 transcript and protein amounts increased in inflammasome-deficient larvae, enforcing erythropoiesis and inhibiting myelopoiesis. This mechanism is evolutionarily conserved, since pharmacological inhibition of the inflammasome altered erythroid differentiation of human erythroleukemic K562 cells. In addition, caspase-1 inhibition rapidly upregulated GATA1 protein in mouse HSPC promoting their erythroid differentiation. Importantly, pharmacological inhibition of the inflammasome rescued zebrafish disease models of neutrophilic inflammation and anemia. These results indicate that the inflammasome plays a major role in the pathogenesis of neutrophilia and anemia of chronic diseases and reveal druggable targets for therapeutic interventions.


Asunto(s)
Anemia/inmunología , Enfermedades de los Peces/inmunología , Factor de Transcripción GATA1/metabolismo , Inflamasomas/metabolismo , Inflamación/inmunología , Neutrófilos/inmunología , Proteínas de Pez Cebra/metabolismo , Pez Cebra/fisiología , Animales , Animales Modificados Genéticamente , Caspasa 1/genética , Caspasa 1/metabolismo , Diferenciación Celular , Células Eritroides/citología , Factor de Transcripción GATA1/genética , Regulación del Desarrollo de la Expresión Génica , Hematopoyesis , Humanos , Inflamasomas/genética , Células K562 , Masculino , Ratones , Ratones Endogámicos C57BL , Proteolisis , Proteínas de Pez Cebra/genética
20.
Phys Rev Lett ; 122(4): 041302, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30768344

RESUMEN

Using N-body simulations with massive neutrino density perturbations, we detect the scale-dependent linear halo bias with high significance. This is the first time that this effect is detected in simulations containing neutrino density perturbations on all scales, confirming the same finding from separate universe simulations. The scale dependence is the result of the additional scale in the system, i.e., the massive neutrino free-streaming length, and it persists even if the bias is defined with respect to the cold dark matter plus baryon (instead of total matter) power spectrum. The separate universe approach provides a good model for the scale-dependent linear bias, and the effect is approximately 0.25f_{ν} and 0.43f_{ν} for halos with bias of 1.7 and 3.5, respectively. While the size of the effect is small, it is not insignificant in terms of f_{ν} and should therefore be included to accurately constrain neutrino mass from clustering statistics of biased tracers. More importantly, this feature is a distinct signature of free-streaming particles and cannot be mimicked by other components of the standard cosmological model.

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