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1.
Animal ; 18(9): 101259, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39137614

RESUMEN

In pigs, meat quality depends markedly on the fatty acid (FA) content and composition of the intramuscular fat, which is partly determined by the gene expression in this tissue. The aim of this work was to identify the link between muscle gene expression and its FA composition. In an (Iberian × Duroc) × Duroc backcrossed pig population, we identified modules of co-expressed genes, and correlation analyses were performed for each of them versus the phenotypes, finding four relevant modules. Two of the modules were positively correlated with saturated FAs (SFAs) and monounsaturated FAs (MUFAs), while negatively correlated with polyunsaturated FAs (PUFAs) and the omega-6/omega-3 ratio. The gene-enrichment analysis showed that these modules had over-representation of pathways related with the biosynthesis of unsaturated FAs, the Peroxisome proliferator-activated receptor signalling pathway and FA elongation. The two other relevant modules were positively correlated with PUFA and the n-6/n-3 ratio, but negatively correlated with SFA and MUFA. In this case, they had an over-representation of pathways related with fatty and amino acid degradation, and with oxidative phosphorylation. Using a graphical Gaussian model, we inferred a network of connections between the genes within each module. The first module had 52 genes with 87 connections, and the most connected genes were ADIPOQ, which is related with FA oxidation, and ELOVL6 and FABP4, both involved in FA metabolism. The second module showed 196 genes connected by 263 edges, being FN1 and MAP3K11 the most connected genes. On the other hand, the third module had 161 genes connected by 251 edges and ATG13 was the top neighbouring gene, while the fourth module had 224 genes and 655 connections, and its most connected genes were related with mitochondrial pathways. Overall, this work successfully identified relevant muscle gene networks and modules linked with FA composition, providing further insights on how the physiology of the pigs influences FA composition.

2.
Animal ; 17(12): 101033, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38064855

RESUMEN

The intramuscular fat content and fatty acid composition of porcine meat have a significant impact on its quality and nutritional value. This research aimed to investigate the expression of 45 genes involved in lipid metabolism in the longissimus dorsi muscle of three experimental pig backcrosses, with a 25% of Iberian background. To achieve this objective, we conducted an expression Genome-Wide Association Study (eGWAS) using gene expression levels in muscle measured by high-throughput real-time qPCR for 45 target genes and genotypes from the PorcineSNP60 BeadChip or Axiom Porcine Genotyping Array and 65 single nucleotide polymorphisms (SNPs) located in 20 genes genotyped by a custom-designed Taqman OpenArray in a cohort of 354 animals. The eGWAS analysis identified 301 eSNPs associated with 18 candidate genes (ANK2, APOE, ARNT, CIITA, CPT1A, EGF, ELOVL6, ELOVL7, FADS3, FASN, GPAT3, NR1D2, NR1H2, PLIN1, PPAP2A, RORA, RXRA and UCP3). Three cis-eQTL (expression quantitative trait loci) were identified for GPAT3, RXRA, and UCP3 genes, which indicates that a genetic polymorphism proximal to the same gene is affecting its expression. Furthermore, 24 trans-eQTLs were detected, and eight candidate regulatory genes were located in these genomic regions. Additionally, two trans-regulatory hotspots in Sus scrofa chromosomes 13 and 15 were identified. Moreover, a co-expression analysis performed on 89 candidate genes and the fatty acid composition revealed the regulatory role of four genes (FABP5, PPARG, SCD, and SREBF1). These genes modulate the levels of α-linolenic, arachidonic, and oleic acids, as well as regulating the expression of other candidate genes associated with lipid metabolism. The findings of this study offer novel insights into the functional regulatory mechanism of genes involved in lipid metabolism, thereby enhancing our understanding of this complex biological process.


Asunto(s)
Redes Reguladoras de Genes , Estudio de Asociación del Genoma Completo , Humanos , Animales , Estudio de Asociación del Genoma Completo/veterinaria , Metabolismo de los Lípidos/genética , Genómica , Músculo Esquelético/metabolismo , Ácidos Grasos/análisis , Polimorfismo de Nucleótido Simple , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo
4.
Sci Rep ; 11(1): 23488, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-34873196

RESUMEN

Weaning is a critical period in the life of pigs with repercussions on their health and welfare and on the economy of the swine industry. This study aimed to assess the effect of the commercial early weaning on gut microbiota, intestinal gene expression and serum metabolomic response via an integrated-omic approach combining 16S rRNA gene sequencing, the OpenArray gene expression technology and 1H-NMR spectroscopy. Fourteen piglets from different litters were sampled for blood, jejunum tissue and caecal content two days before (- 2d), and three days after (+ 3d) weaning. A clearly differential ordination of caecal microbiota was observed. Higher abundances of Roseburia, Ruminococcus, Coprococcus, Dorea and Lachnospira genera in weaned piglets compared to prior to weaning showed the quick microbial changes of the piglets' gut microbiota. Downregulation of OCLN, CLDN4, MUC2, MUC13, SLC15A1 and SLC13A1 genes, also evidenced the negative impact of weaning on gut barrier and digestive functions. Metabolomic approach pinpointed significant decreases in choline, LDL, triglycerides, fatty acids, alanine and isoleucine and increases in 3-hydroxybutyrate after weaning. Moreover, the correlation between microbiota and metabolome datasets revealed the existence of metabolic clusters interrelated to different bacterial clusters. Our results demonstrate the impact of weaning stress on the piglet and give insights regarding the associations between gut microbiota and the animal gene activity and metabolic response.


Asunto(s)
Microbioma Gastrointestinal/genética , Interacciones Microbiota-Huesped/genética , Animales , Bacterias/genética , Ciego/microbiología , Heces/microbiología , Yeyuno/microbiología , Metaboloma/genética , ARN Ribosómico 16S/genética , Porcinos , Destete
5.
Sci Rep ; 11(1): 6113, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731752

RESUMEN

The aim of this study was to determine the possible impact of early socialization and an enriched neonatal environment to improve adaptation of piglets to weaning. We hypothesized that changes in the microbiota colonization process and in their metabolic response and intestinal functionality could help the animals face weaning stress. A total of 48 sows and their litters were allotted into a control (CTR) or an enriched treatment (ENR), in which piglets from two adjacent pens were combined and enriched with toys. The pattern of caecal microbial colonization, the jejunal gene expression, the serum metabolome and the intestinal physiology of the piglets were assessed before (-2 d) and after weaning (+ 3d). A differential ordination of caecal microbiota was observed after weaning. Serum metabolome suggested a reduced energetic metabolism in ENR animals, as evidenced by shifts in triglycerides and fatty acids, VLDL/LDL and creatine regions. The TLR2 gene showed to be downregulated in the jejunum of ENR pigs after weaning. The integration of gene expression, metabolome and microbiota datasets confirmed that differences between barren and enriched neonatal environments were evident only after weaning. Our results suggest that improvements in adaptation to weaning could be mediated by a better response to the post-weaning stress.


Asunto(s)
Ciego/microbiología , Microbioma Gastrointestinal , Yeyuno , Lactancia , Animales , Femenino , Yeyuno/metabolismo , Yeyuno/microbiología , Porcinos , Destete
6.
Sci Rep ; 11(1): 6315, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33737699

RESUMEN

There is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.


Asunto(s)
Pollos/microbiología , Infecciones por Clostridium/microbiología , Enteritis/microbiología , Enfermedades de las Aves de Corral/microbiología , Alimentación Animal/microbiología , Animales , Infecciones por Clostridium/genética , Clostridium perfringens/efectos de los fármacos , Clostridium perfringens/patogenicidad , Coccidiosis/genética , Coccidiosis/microbiología , Coccidiosis/prevención & control , Suplementos Dietéticos , Eimeria/efectos de los fármacos , Eimeria/patogenicidad , Enteritis/genética , Enteritis/prevención & control , Expresión Génica/efectos de los fármacos , Humanos , Enfermedades de las Aves de Corral/genética , Enfermedades de las Aves de Corral/prevención & control , Vacunas/farmacología
7.
Theriogenology ; 113: 63-72, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29475126

RESUMEN

The aim of this study was to characterize and identify causative SNPs in the MTNR1A gene responsible for the reproductive seasonality traits in the Rasa aragonesa sheep breed. A total of 290 ewes (155, 84 and 51 mature, young and ewe lambs, respectively) from one flock were controlled from January to August. The following three reproductive seasonality traits were considered: the total days of anoestrus (TDA) and the progesterone cycling months (P4CM); both ovarian function seasonality traits based on blood progesterone levels; and the oestrus cycling months (OCM) based on oestrous detection, which indicate behavioural signs of oestrous. We have sequenced the total coding region plus 733 and 251 bp from the promoter and 3'-UTR regions, respectively, from the gene in 268 ewes. We found 9 and 4 SNPs associated with seasonality traits in the promoter (for TDA and P4CM) and exon 2 (for the three traits), respectively. The SNPs located in the gene promoter modify the putative binding sites for various trans-acting factors. In exon 2, two synonymous SNPs affect RFLP sites, rs406779174/RsaI (for the three traits) and rs430181568/MnlI (for OCM), and they have been related with seasonal reproductive activity in previous association studies with other breeds. SNP rs400830807, which is located in the 3'-UTR, was associated with the three traits, but this did not modify the putative target sites for ovine miRNAs according to in silico predictions. Finally, the SNP rs403212791 (NW_014639035.1: g.15099004G > A), which is also associated with the three seasonality phenotypes, was the most significant SNP detected in this study and was a non-synonymous polymorphism, leading a change from an Arginine to a Cysteine (R336C). Haplotype analyses confirmed the association results and showed that the effects found for the seasonality traits were caused by the SNPs located in exon 2. We have demonstrated that the T allele in the SNP rs403212791 in the MNTR1A gene is associated with a lower TDA and higher P4CM and OCM values in the Rasa Aragonesa breed.


Asunto(s)
Regulación de la Expresión Génica/fisiología , Polimorfismo de Nucleótido Simple , Receptor de Melatonina MT1/metabolismo , Reproducción/genética , Estaciones del Año , Ovinos/genética , Animales , Haplotipos , Desequilibrio de Ligamiento , Regiones Promotoras Genéticas , Receptor de Melatonina MT1/genética , Reproducción/fisiología , Ovinos/fisiología
8.
Neurología (Barc., Ed. impr.) ; 33(1): 47-58, ene.-feb. 2018. tab, graf
Artículo en Español | IBECS | ID: ibc-172546

RESUMEN

Introducción: La enfermedad de Alzheimer (EA) es el principal trastorno neurodegenerativo que provoca una discapacidad intelectual total en los pacientes que la presentan. La elevada prevalencia a nivel mundial, así como la elevada carga socioeconómica que conlleva la EA para la sociedad en general, hace que sea considerada un importante problema de salud pública en este siglo xxi. En este trabajo se revisan los tratamientos actuales y en fase de desarrollo que actúan principalmente sobre la proteína Beta-amiloide. Discusión: La hipótesis amiloidogénica propone que el péptido β-amiloide tiene un papel clave en esta enfermedad. Se han desarrollado varias estrategias farmacológicas diferentes con el objetivo de inhibir la formación de los péptidos β-amiloides, como son los inhibidores de Beta-secretasa y γ-secretasa. Además, se han desarrollado los tratamientos antiamiloide, que incluyen inmunoterapias pasivas y activas enfocadas a inhibir la agregación del péptido Beta-amiloide. Conclusiones: Los avances en la identificación de las bases moleculares de la EA pueden servir como modelo para comprender las causas de esta enfermedad neurodegenerativa. Sin embargo, los ensayos clínicos más recientes en 2 ensayos de fase iii con solanezumab, un anticuerpo monoclonal humanizado que promueve el aclaramiento del Beta-amiloide en el cerebro, indican que este anticuerpo no muestra eficacia en pacientes con EA leve, sugiriendo que hay que replantearse esta hipótesis amiloidogénica de la EA (AU)


Introduction: Alzheimer disease (AD) is a major neurodegenerative disorder which eventually results in total intellectual disability. The high global prevalence and the socioeconomic burden associated with the disease pose major challenges for public health in the 21st century. In this review we focus on both existing treatments and the therapies being developed, which principally target the Beta-amyloid protein. Discussion: The amyloidogenic hypothesis proposes that Beta-amyloid plays a key role in AD. Several pharmacological approaches aim to reduce the formation of Beta-amyloid peptides by inhibiting the Beta-secretase and γ-secretase enzymes. In addition, both passive and active immunotherapies have been developed for the purpose of inhibiting β-amyloid peptide aggregation. Conclusions: Progress in identifying the molecular basis of AD may provide better models for understanding the causes of this neurodegenerative disease. The lack of efficacy of solanezumab (a humanised monoclonal antibody that promotes Beta-amyloid clearance in the brain), demonstrated by 2 recent Phase III clinical trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs to be revised (AU)


Asunto(s)
Péptidos beta-Amiloides , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/fisiopatología , Secretasas de la Proteína Precursora del Amiloide , Proteínas tau , Enfermedades Neurodegenerativas/tratamiento farmacológico , Endopeptidasas , Factores de Riesgo , Inmunoterapia/métodos
9.
Neurologia (Engl Ed) ; 33(1): 47-58, 2018.
Artículo en Inglés, Español | MEDLINE | ID: mdl-25976937

RESUMEN

INTRODUCTION: Alzheimer disease (AD) is a major neurodegenerative disorder which eventually results in total intellectual disability. The high global prevalence and the socioeconomic burden associated with the disease pose major challenges for public health in the 21st century. In this review we focus on both existing treatments and the therapies being developed, which principally target the ß-amyloid protein. DISCUSSION: The amyloidogenic hypothesis proposes that ß-amyloid plays a key role in AD. Several pharmacological approaches aim to reduce the formation of ß-amyloid peptides by inhibiting the ß-secretase and γ-secretase enzymes. In addition, both passive and active immunotherapies have been developed for the purpose of inhibiting ß-amyloid peptide aggregation. CONCLUSIONS: Progress in identifying the molecular basis of AD may provide better models for understanding the causes of this neurodegenerative disease. The lack of efficacy of solanezumab (a humanised monoclonal antibody that promotes ß-amyloid clearance in the brain), demonstrated by 2 recent Phase III clinical trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs to be revised.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Anticuerpos Monoclonales Humanizados , Humanos
10.
Anim Genet ; 48(6): 660-668, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29076225

RESUMEN

The FABP4 and FABP5 genes, coding for fatty acid transport proteins, have long been studied as positional candidate genes for SSC4 QTL affecting fat deposition and composition traits in pigs. Polymorphisms in these genes, FABP4:g.2634_2635insC and FABP5:g.3000T>G, have previously been associated with fatness traits in an Iberian by Landrace cross (IBMAP). The aim of the present work was to evaluate the functional implication of these genetic variants. For this purpose, FABP4 and FABP5 mRNA expression levels in 114 BC1_LD animals (25% Iberian × 75% Landrace) were analyzed using real-time quantitative PCR in backfat and muscle. FABP4 gene expression in backfat, but not in muscle, was associated with FABP4:g.2634_2635insC. In contrast, FABP5:g.3000T>G was not associated with gene expression levels. An expression-based genome-wide association study highlighted the FABP4:g.2634_2635insC polymorphism as the polymorphism most associated with FABP4 gene expression in backfat. Furthermore, other genomic regions associated in trans with the mRNA expression of FABP4 in backfat and FABP5 in muscle were also identified. Finally, two putative transcription binding sites for PPARG and NR4A2 may be affected by the FABP4:g.2634_2635insC polymorphism, modifying FABP4 gene expression. Our results reinforce FABP4 as a candidate gene for fatness traits on SSC4.


Asunto(s)
Adiposidad/genética , Proteínas de Unión a Ácidos Grasos/genética , Sitios de Carácter Cuantitativo , Sus scrofa/genética , Tejido Adiposo/metabolismo , Animales , Sitios de Unión , Femenino , Expresión Génica , Estudios de Asociación Genética , Genotipo , Masculino , Músculo Esquelético/metabolismo , Factores de Transcripción/metabolismo
11.
Anim Genet ; 48(2): 151-165, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27642173

RESUMEN

RNA-Seq technology is widely used in quantitative gene expression studies and identification of non-annotated transcripts. However this technology also can be used for polymorphism detection and RNA editing in transcribed regions in an efficient and cost-effective way. This study used SNP data from an RNA-Seq assay to identify genes and mutations underlying production trait variations in an experimental pig population. The hypothalamic and hepatic transcriptomes of nine extreme animals for growth and fatness from an (Iberian × Landrace) × Landrace backcross were analyzed by RNA-Seq methodology, and SNP calling was conducted. More than 125 000 single nucleotide variants (SNVs) were identified in each tissue, and 78% were considered to be potential SNPs, those SNVs segregating in the context of this study. Potential informative SNPs were detected by considering those showing a homozygous or heterozygous genotype in one extreme group and the alternative genotype in the other group. In this way, 4396 and 1862 informative SNPs were detected in hypothalamus and liver respectively. Out of the 32 SNPs selected for validation, 25 (80%) were confirmed as actual SNPs. Association analyses for growth, fatness and premium cut yields with 19 selected SNPs were carried out, and four potential causal genes (RETSAT, COPA, RNMT and PALMD) were identified. Interestingly, new RNA editing modifications were detected and validated for the NR3C1:g.102797 (ss1985401074) and ACSM2B:g.13374 (ss1985401075) positions and for the COG3:g3.4525 (ss1985401087) modification previously identified across vertebrates, which could lead to phenotypic variation and should be further investigated.


Asunto(s)
Carne , Polimorfismo de Nucleótido Simple , Edición de ARN , Análisis de Secuencia de ARN/métodos , Sus scrofa/genética , Animales , Cruzamientos Genéticos , Femenino , Masculino , Sus scrofa/fisiología
12.
Anim Genet ; 47(5): 552-9, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27296287

RESUMEN

APOA2 is a protein implicated in triglyceride, fatty acid and glucose metabolism. In pigs, the APOA2 gene is located on pig chromosome 4 (SSC4) in a QTL region affecting fatty acid composition, fatness and growth traits. In this study, we evaluated APOA2 as a candidate gene for meat quality traits in an Iberian × Landrace backcross population. The APOA2:c.131T>A polymorphism, located in exon 3 of APOA2 and determining a missense mutation, was associated with the percentage of hexadecenoic acid [C16:1(n-9)], linoleic acid [C18:2(n-6)], α-linolenic acid [C18:3(n-3)], dihomo-gamma-linolenic acid [C20:3(n-6)] and polyunsaturated fatty acids (PUFAs) in backfat. Furthermore, this SNP was associated with the global mRNA expression levels of APOA2 in liver and was used as a marker to determine allelic expression imbalance by pyrosequencing. We determined an overexpression of the T allele in heterozygous samples with a mean ratio of 2.8 (T/A), observing a high variability in the allelic expression among individuals. This result suggests that complex regulatory mechanisms, beyond a single polymorphism (e.g. epigenetic effects or multiple cis-acting polymorphisms), may be regulating APOA2 gene expression.


Asunto(s)
Apolipoproteína A-II/genética , Ácidos Grasos/química , Carne , Sus scrofa/genética , Tejido Adiposo/química , Alelos , Animales , Cruzamientos Genéticos , Expresión Génica , Estudios de Asociación Genética , Genotipo , Hígado/metabolismo , Mutación Missense , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Sitios de Carácter Cuantitativo , Análisis de Secuencia de ADN
13.
J Nutr Health Aging ; 19(4): 403-12, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25809804

RESUMEN

A growing body of evidence suggests that ß-amyloid peptides (Aß) are unlikely to be the only factor involved in Alzheimer's disease (AD) aetiology. In fact, a strong correlation has been established between AD patients and patients with type 2 diabetes and/or cholesterol metabolism alterations. In addition, a link between adipose tissue metabolism, leptin signalling in particular, and AD has also been demonstrated. In the present study we analyzed the expression of molecules related to metabolism, with the main focus on leptin and prolactin signalling pathways in an APPswe/PS1dE9 (APP/PS1) transgenic mice model, at 3 and 6 months of age, compared to wild-type controls. We have chosen to study 3 months-old APP/PS1 animals at an age when neither the cognitive deficits nor significant Aß plaques in the brain are present, and to compare them to the 6 months-old mice, which exhibit elevated levels of Aß in the hippocampus and memory loss. A significant reduction in both mRNA and protein levels of the prolactin receptor (PRL-R) was detected in the hippocampi of 3 months old APP/PS1 mice, with a decrease in the levels of the leptin receptor (OB-R) first becoming evident at 6 months of age. We proceeded to study the expression of the intracellular signalling molecules downstream of these receptors, including stat (1-5), sos1, kras and socs (1-3). Our data suggest a downregulation in some of these molecules such as stat-5b and socs (1-3), in 3 months-old APP/PS1 brains. Likewise, at the same age, we detected a significant reduction in mRNA levels of lrp1 and cyp46a1, both of which are involved in cholesterol homeostasis. Taken together, these results demonstrate a significative impairment in adipokine receptors signalling and cholesterol regulation pathways in the hippocampus of APP/PS1 mice at an early age, prior to the Aß plaque formation.


Asunto(s)
Adipoquinas/metabolismo , Enfermedad de Alzheimer/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Colesterol/metabolismo , Colesterol 24-Hidroxilasa , Diabetes Mellitus Tipo 2/metabolismo , Ingestión de Alimentos/genética , Hipocampo/fisiopatología , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Masculino , Trastornos de la Memoria , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Obesidad/genética , Placa Amiloide/genética , Placa Amiloide/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de LDL/genética , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Receptores de Prolactina/genética , Receptores de Prolactina/metabolismo , Proteína SOS1/metabolismo , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Esteroide Hidroxilasas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Proteínas Supresoras de Tumor/genética
14.
Free Radic Res ; 48(2): 119-28, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24060108

RESUMEN

Melatonin has been shown to down-regulate inflammatory responses and provide neuroprotection. However, the mechanisms underlying the anti-inflammatory properties of melatonin are poorly understood. In the present work, we studied the modulatory effect of melatonin against pro-inflammatory cytokines in glial cell cultures. Treatment with pro-inflammatory cytokines mainly tumor necrosis factor-alpha, interleukin 1-beta, and interferon-gamma induces an increase in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. Pre-treatment with melatonin produced an inhibitory effect on iNOS expression and NO production. The biochemical studies revealed that cytokine treatment favors the activation of several pathways, such as mitogen-activated protein kinases (MAPKs), STAT1, and STAT3; however, the anti-inflammatory effect of melatonin was accompanied only by a decrease in p38 MAPK activity. Likewise, SB203580 a p38 kinase inhibitor inhibits NO production. These data indicate that the anti-inflammatory action of melatonin in glial cells after stimulation with pro-inflammatory cytokines may be in part, attributable to p38 inhibition which down-regulates iNOS expression and NO production.


Asunto(s)
Antiinflamatorios/farmacología , Citocinas/fisiología , Sistema de Señalización de MAP Quinasas , Melatonina/farmacología , Neuroglía/metabolismo , Óxido Nítrico/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/farmacología , Guanilato Ciclasa , Mediadores de Inflamación/farmacología , Mediadores de Inflamación/fisiología , Ratones , Ratones Endogámicos C57BL , Neuroglía/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
15.
Theriogenology ; 81(2): 347-57, 2014 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-24268018

RESUMEN

Embryo biotechnologies contribute significantly to the genetic enhancement of livestock, although their efficiency remains limited in sheep, mainly owing to variable ovarian responses to gonadotropins. At present, anti-Müllerian hormone (AMH), which is produced by the granulosa cells of the small antral follicles, is a reliable endocrine marker of the ovarian follicle reserve in many species. The expression of AMH in granulosa cells was shown to be stimulated by bone morphogenetic proteins (BMPs) in vitro, so a mutation affecting the BMP15 gene might modulate AMH production in vivo. The present study aimed to assess plasma AMH concentrations before puberty in two groups of Rasa Aragonesa ewes that were carrying (R+) or not carrying (++) the prolific FecX(R) allele and to relate them with their AMH concentrations at adulthood. Additionally, we sought to establish in both genotypes whether AMH measurements during a laparoscopic ovum pick-up (LOPU) program could be predictive of the number of ovarian follicles (≥3 mm) and recovered cumulus-oocyte complexes (COCs). No differences in AMH were found between the R+ and ++ ewes before puberty or during the adult age. Before puberty, the AMH concentration tended to increase from 3 to 4.5 months and to decline at 6 months to levels similar to those observed later in adults (333.8 ± 73.3, 483.2 ± 135.5, and 184.1 ± 38.2 pg/mL, respectively; P < 0.1), showing a large variability between individuals and between ages. A relationship between the AMH concentrations before puberty and during adulthood was not found, likely reflecting different follicular growth dynamics. In adults, the AMH concentration at the beginning of the FSH treatment was strongly correlated with the number of punctured follicles at LOPU in R+ and ++ ewes (r = 0.75 and 0.78, respectively; P < 0.001), and it was possible to accurate determine AMH cutoff values for both genotypes to identify high-responding ewes. On average, 5.1 extra follicles and 2.7 extra COCs were expected per each 100 pg/mL increase in AMH (P < 0.0001 and P < 0.01, respectively). The repeatability of AMH concentration from session to session was 0.70 (P < 0.0001). Our results demonstrated that, regardless of age, the presence of the FecX(R) allele did not affect plasma AMH levels. During adulthood, AMH proved to be a good predictor of the ovarian response to FSH stimulation. Such an indicator could therefore be used to improve the performance of embryo biotechnologies in sheep.


Asunto(s)
Hormona Antimülleriana/sangre , Proteína Morfogenética Ósea 15/genética , Embrión de Mamíferos/fisiología , Ovinos/embriología , Factores de Edad , Animales , Biotecnología/métodos , Progesterona/sangre , Maduración Sexual , Ovinos/sangre , Ovinos/genética
16.
Anim Genet ; 44(6): 648-60, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23826865

RESUMEN

This study aimed at identifying differential gene expression conditional on the fatty acid profile of the longissimus thoracis (Lt) muscle, a prime cut of economic relevance for fresh and cured pork production. A population of 110 Iberian (25%) × Landrace (75%) back-crossed pigs was used, because these two breeds exhibit extreme profiles of intramuscular saturated fatty acid, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) contents. Total RNA from Lt muscle was individually hybridized to GeneChip Porcine Genome arrays (Affymetrix). A principal component analysis was performed with data from the 110 animals to select 40 extreme animals based on the total fatty acid profile and the MUFA composition (MAP). Comparison of global transcription levels between extreme fatty acid profile pigs (n = 40) resulted in 219 differentially expressed probes (false discovery rate <0.10). Gene ontology, pathway and network analysis indicated that animals with higher percentages of PUFA exhibit a shift toward a more oxidative muscular metabolism state, with a raise in mitochondria function (PPARGC1A, ATF2), fatty acid uptake and oxidation (FABP5, MGLL). On the other hand, 87 probes were differentially expressed between MUFA composition groups (n = 40; false discovery rate <0.10). In particular, muscles rich in n-7 MUFA expressed higher levels of genes involved in lipid metabolism (GLUL, CRAT, PLA2G15) and lower levels of fatty acid elongation genes (ELOVL5). Moreover, the chromosomal position of FABP5, PAQR3, MGLL, PPARGC1A, GLUL and ELOVL5 co-localized with very relevant QTL for fat deposition and composition described in the same resource population. This study represents a complementary approach to identifying genes underlying these QTL effects.


Asunto(s)
Composición Corporal/genética , Ácidos Grasos/análisis , Músculo Esquelético/química , Sus scrofa/genética , Sus scrofa/metabolismo , Animales , Cruzamiento/métodos , Cruzamientos Genéticos , Perfilación de la Expresión Génica/veterinaria , Ontología de Genes , Análisis de Secuencia por Matrices de Oligonucleótidos/veterinaria , Análisis de Componente Principal , Sitios de Carácter Cuantitativo/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria
17.
Cir. plást. ibero-latinoam ; 39(1): 9-14, ene.-mar. 2013. ilus
Artículo en Español | IBECS | ID: ibc-113570

RESUMEN

El tratamiento quirúrgico para la corrección de las orejas prominentes o valgas se basa en crear una distancia de entre 17-21 mm entre el hélix y la mastoides, así como recrear unos pliegues auriculares anteriores bien definidos. Desde finales de 1800 hasta la actualidad se han descrito muchas técnicas para corregir las orejas despegadas, prominentes o valgas, cada una de ellas con sus propias características .En el presente trabajo describimos una técnica para estabilizar el resultado quirúrgico cuando se corrige esta entidad y evitar su recidiva. Se trata de un procedimiento de fijación mastoidea de la oreja mediante un colgajo dermo-graso-pericóndrico de sencillo diseño, útil, seguro y fácilmente reproducible. Hemos empleado esta técnica durante más de 15 años y creemos que ha resistido la prueba del tiempo (AU)


The treatment for the correction of prominent or valgusears, is to create a normal distance (17-21 mm) between the mastoid and the helix and a normal appearance of the anterior auricular folds. From late 1800 to the present, many surgical techniques for correcting prominentor valgus ears have been described, each one with its own characteristics. We describe a technique to stabilize the result and prevent recurrence. This technique stabilizes the correction of the ear fixing it to the mastoid fascia using a dermalfat-perichondrium flap of simple design, useful, safe and easily reproducible. We have used it over 15 years, and that makes us believe that has stood the test of time (AU)


Asunto(s)
Humanos , Pabellón Auricular/anomalías , Pabellón Auricular/cirugía , Colgajos Quirúrgicos , Procedimientos de Cirugía Plástica/métodos
18.
Reprod Domest Anim ; 48(5): 717-23, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23438026

RESUMEN

Ewes heterozygous for the FecX(R) allele (R+) in the bone morphogenetic protein 15 (BMP15) gene display increased ovulation rate and prolificacy. Besides this phenotypic advantage, the influence of the FecX(R) allele on follicle number and size, oocyte competence and in vitro production (IVP) remains undefined. With these aims, 8 R+ and 8 wild-type (++) ewes were subjected to 2 laparoscopic ovum pick-up (LOPU) trials (four sessions per trial; two with and two without FSH) and subsequent IVP and fresh embryo transfer. All follicles >3 mm were punctured (n = 1673). Genotype did not significantly affect the number of punctured follicles per ewe and session (10.4 and 10.2 in R+ and ++ untreated ewes, 17.4 and 14.3 in R+ and ++ FSH-treated ewes, respectively), but follicular diameter of R+ ewes was significantly reduced compared with ++ ewes (-0.2 mm in untreated and -0.8 mm in FSH-treated ewes; p < 0.01). R+ ewes showed higher recovery rate and increased numbers of total and suitable cumulus-oocyte complexes for in vitro maturation (IVM). Similar rates of day 8 blastocysts were observed in R+ (36.1%, 147/407) and ++ (32.6%, 100/307) ewes, but the final output of day 8 blastocysts per ewe and session was higher in R+ ewes (+0.75; p < 0.005), without differences in survival rate at birth of the transferred embryos (40.4%, 21/52 vs 36.4%, 16/44, respectively). In conclusion, a higher number of oocytes proven to be competent for in vitro development and embryo survival after transfer are recovered from R+ ewes, despite the lower mean size of their follicles at puncture.


Asunto(s)
Proteína Morfogenética Ósea 15/genética , Transferencia de Embrión/veterinaria , Fertilización In Vitro/veterinaria , Oocitos/fisiología , Ovinos/genética , Alelos , Animales , Cloprostenol/administración & dosificación , Femenino , Acetato de Fluorogestona/administración & dosificación , Hormona Folículo Estimulante/administración & dosificación , Heterocigoto , Hormonas/administración & dosificación , Luteolíticos/administración & dosificación , Recuperación del Oocito/veterinaria , Progestinas/administración & dosificación , Ovinos/fisiología
19.
Anim Genet ; 44(3): 296-304, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23137011

RESUMEN

Suppressive subtractive hybridization libraries from oviduct at 62 h post-mating of two lines of rabbits divergently selected for uterine capacity were generated to identify differentially expressed genes. A total of 438 singletons and 126 contigs were obtained by cluster assembly and sequence alignment of 704 expressed sequence tags (ESTs), of which 54% showed homology to known proteins of the non-redundant NCBI databases. Differential screening by dot blot validated 71 ESTs, of which 47 showed similarity to known genes. Transcripts of genes were functionally annotated in the molecular function and the biological process gene ontology categories using the BLAST2GO software and were assigned to reproductive developmental process, immune response, amino acid metabolism and degradation, response to stress and apoptosis terms. Finally, three interesting genes, PGR, HSD17B4 and ERO1L, were identified as overexpressed in the low line using RT-qPCR. Our study provides a list of candidate genes that can be useful to understanding the molecular mechanisms underlying the phenotypic differences observed in early embryo survival and development traits.


Asunto(s)
Etiquetas de Secuencia Expresada , Hibridación Genética , Oviductos/metabolismo , Animales , Clonación Molecular , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Biblioteca de Genes , Hibridación de Ácido Nucleico , Conejos , Reacción en Cadena en Tiempo Real de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADN
20.
J Anim Sci ; 90(9): 2883-93, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22785162

RESUMEN

The lipid content and fatty acid (FA) profile have an important impact in human health as well as in the technological transformation and nutritional and organoleptic quality of meat. A genome-wide association study (GWAS) on 144 backcross pigs (25% Iberian × 75% Landrace) was performed for 32 traits associated with intramuscular FA composition and indices of FA metabolism. The GWAS was carried out using Qxpak 5.0 and the genotyping information obtained from the Porcine SNP60K BeadChip (Illumina Inc., San Diego, CA). Signals of significant association considering a false- discovery rate (q-value < 0.05) were observed in 15 of the 32 analyzed traits, and a total of 813 trait-associated SNP (TAS), distributed in 43 chromosomal intervals on almost all autosomes, were annotated. According to the clustering analysis based on functional classification, several of the annotated genes are related to FA composition and lipid metabolism. Some interesting positional concordances among TAS and previously reported QTL for FA compositions and/or other lipid traits were also found. These common genomic regions for different traits suggest pleiotropic effects for FA composition and were found primarily on SSC4, SSC8, and SSC16. These results contribute to our understanding of the complex genetic basis of FA composition and FA metabolism.


Asunto(s)
Ácidos Grasos/metabolismo , Porcinos/genética , Porcinos/metabolismo , Animales , Cruzamientos Genéticos , Ácidos Grasos/química , Femenino , Variación Genética , Genoma , Genotipo , Masculino , Sitios de Carácter Cuantitativo
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