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1.
Ir Med J ; 115(8): 656, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36327969

RESUMO

Introduction Thrombotic Thrombocytopenic Purpura (TTP) is a rare but life-threatening disorder caused by severely reduced activity of ADAMTS13, causing platelet adhesion and formation of small-vessel platelet-rich thrombi, thrombocytopenia, and microangiopathic haemolytic anaemia. Diagnosis A 48-year-old female presented with acute generalized petechial rash, bruises, and fatigue. Bloods revealed thrombocytopenia, anaemia, 10% schistocytes. Her plasmic score was seven, and ADAMT13 was <5. Treatment Patient initially responded to plasma exchange and steroids, but thrombocytopenia recurred on day six of treatment, needing the addition of further immunosuppressive drugs and Caplacizumab. Conclusion TTP cases unresponsive to conventional regimens can represent a challenging situation; however, poor outcomes could potentially be avoided with a novel therapy like Caplacizumab. In our patient, this medication was well tolerated, and platelet count normalized after two days of its introduction.


Assuntos
Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Humanos , Feminino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Anticorpos de Domínio Único/efeitos adversos , Troca Plasmática
2.
Sci Rep ; 12(1): 16361, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180572

RESUMO

Iberian pigs and its crosses are produced to obtain high-quality meat products. The objective of this work was to evaluate a wide panel of DNA markers, selected by biological and functional criteria, for association with traits related to muscle growth, fatness, meat quality and metabolism. We used 18 crossbred Iberian pigs with divergent postnatal growth patterns for whole genome sequencing and SNP discovery, with over 13 million variants being detected. We selected 1023 missense SNPs located on annotated genes and showing different allele frequencies between pigs with makerdly different growth patterns. We complemented this panel with 192 candidate SNPs obtained from literature mining and from muscle RNAseq data. The selected markers were genotyped in 480 Iberian × Duroc pigs from a commercial population, in which phenotypes were obtained, and an association study was performed for the 1005 successfully genotyped SNPs showing segregation. The results confirmed the effects of several known SNPs in candidate genes (such as LEPR, ACACA, FTO, LIPE or SCD on fatness, growth and fatty acid composition) and also disclosed interesting effects of new SNPs in less known genes such as LRIG3, DENND1B, SOWAHB, EPHX1 or NFE2L2 affecting body weight, average daily gain and adiposity at different ages, or KRT10, NLE1, KCNH2 or AHNAK affecting fatness and FA composition. The results provide a valuable basis for future implementation of marker-assisted selection strategies in swine and contribute to a better understanding of the genetic architecture of relevant traits.


Assuntos
Carne , Polimorfismo de Nucleotídeo Único , Animais , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Fenótipo , Suínos/genética
3.
Animal ; 15(12): 100408, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34890881

RESUMO

Low protein diets supplied during the growing period of pigs can diminish their growth rate and increase the intramuscular fat (IMF) content which affects the sensorial and technological characteristics of the products. In the present study, the effects of a low protein diet supplied during the growing period of Duroc × Iberian crossbred pigs on several phenotypic traits and on liver and longissimus dorsi transcriptome were analysed at the beginning (EARLY) and at the end (LATE) of the growing period. Two experimental groups of 10 crossbred pigs each were fed two isocaloric diets with different protein content: control diet (C) with 16.5% protein and 0.8% lysine and low protein diet (LP) with 11% CP and 0.6% lysine. Animals fed LP diet have a slower growth than those fed C diet, but no effect of LP diet was observed on the IMF content. The transcriptomes of liver and longissimus dorsi were characterised and quantified through RNA-sequencing (RNA-seq). In liver, 134 and 480 differentially expressed annotated genes and new isoforms (DEGs) were detected between C and LP diets for EARLY and LATE animals, respectively. In muscle, 128 and 68 DEGs were detected at EARLY and LATE time-points. Functional interpretation revealed that LP diet may inhibit immune system molecules and processes in both tissues at EARLY stage. In liver, the DEGs mainly affect lipid and cholesterol metabolic processes, while in muscle, the expression changes would be involved in growth, development and meat quality. In conclusion, a low protein diet supplied during the growing period seems to slow down the growth of Duroc × Iberian crossbred pigs, but it also seems to affect multiple biological processes that could compromise the immune system of Duroc × Iberian crossbred pigs. Therefore, these results question the adequacy of this type of regime in Duroc × Iberian pigs that must be studied in greater depth before being implemented.


Assuntos
Dieta com Restrição de Proteínas , Transcriptoma , Animais , Dieta/veterinária , Dieta com Restrição de Proteínas/veterinária , Fígado , Lisina , Carne/análise , Músculo Esquelético , Suínos/genética
5.
Anim Genet ; 52(2): 155-170, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33544919

RESUMO

ROHs are long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROHs and their length are indicators of the level and origin of inbreeding. Frequent common ROHs within the same population define ROH islands and indicate hotspots of selection. In this work, we investigated ROHs in a total of 1131 pigs from 20 European local pig breeds and in three cosmopolitan breeds, genotyped with the GGP Porcine HD Genomic Profiler. plink software was used to identify ROHs. Size classes and genomic inbreeding parameters were evaluated. ROH islands were defined by evaluating different thresholds of homozygous SNP frequency. A functional overview of breed-specific ROH islands was obtained via over-representation analyses of GO biological processes. Mora Romagnola and Turopolje breeds had the largest proportions of genome covered with ROH (~1003 and ~955 Mb respectively), whereas Nero Siciliano and Sarda breeds had the lowest proportions (~207 and 247 Mb respectively). The highest proportion of long ROH (>16 Mb) was in Apulo-Calabrese, Mora Romagnola and Casertana. The largest number of ROH islands was identified in the Italian Landrace (n = 32), Cinta Senese (n = 26) and Lithuanian White Old Type (n = 22) breeds. Several ROH islands were in regions encompassing genes known to affect morphological traits. Comparative ROH structure analysis among breeds indicated the similar genetic structure of local breeds across Europe. This study contributed to understanding of the genetic history of the investigated pig breeds and provided information to manage these pig genetic resources.


Assuntos
Endogamia , Sus scrofa/genética , Animais , Europa (Continente) , Genoma , Genótipo , Homozigoto , Polimorfismo de Nucleotídeo Único , Densidade Demográfica
6.
Anim Genet ; 51(4): 541-556, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32510676

RESUMO

In this study, we identified copy number variants (CNVs) in 19 European autochthonous pig breeds and in two commercial breeds (Italian Large White and Italian Duroc) that represent important genetic resources for this species. The genome of 725 pigs was sequenced using a breed-specific DNA pooling approach (30-35 animals per pool) obtaining an average depth per pool of 42×. This approach maximised CNV discovery as well as the related copy number states characterising, on average, the analysed breeds. By mining more than 17.5 billion reads, we identified a total of 9592 CNVs (~683 CNVs per breed) and 3710 CNV regions (CNVRs; 1.15% of the reference pig genome), with an average of 77 CNVRs per breed that were considered as private. A few CNVRs were analysed in more detail, together with other information derived from sequencing data. For example, the CNVR encompassing the KIT gene was associated with coat colour phenotypes in the analysed breeds, confirming the role of the multiple copies in determining breed-specific coat colours. The CNVR covering the MSRB3 gene was associated with ear size in most breeds. The CNVRs affecting the ELOVL6 and ZNF622 genes were private features observed in the Lithuanian Indigenous Wattle and in the Turopolje pig breeds respectively. Overall, the genome variability unravelled here can explain part of the genetic diversity among breeds and might contribute to explain their origin, history and adaptation to a variety of production systems.


Assuntos
Variações do Número de Cópias de DNA , DNA/genética , Sus scrofa/genética , Animais , Cruzamento , Feminino , Itália , Masculino , Fenótipo , Especificidade da Espécie , Sequenciamento Completo do Genoma/veterinária
7.
Meat Sci ; 167: 108152, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32361066

RESUMO

Spanish legislation regulates the labelling of Iberian pig meat and dry-cured products, which are labelled as "Ibérico" or "100% Ibérico" when they come from Duroc x Iberian crossbred or Iberian purebred pigs. Although the analytical authentication of breed origin is not mandatory, a genetic diagnostic tool is demanded by producers and consumers. We have designed a 64 Single Nucleotide Variant genotyping panel displaying extreme allelic frequencies between Duroc and Iberian purebred samples. Average proportions of Iberian alleles of 0.99, 0.01, 0.77 and 0.48 were estimated by admixture clustering analysis of known origin samples, for Iberian and Duroc purebred, 75% Iberian and 50% Iberian classes, respectively. A supervised analysis with 1419 samples showed some overlapping between contiguous classes, but the calculated degrees of separability ranged from 0.800 to 0.996, exceeding the threshold value (0.70) for considering suitable for prediction. Therefore, this panel is a useful genetic tool to infer purebred or crossbred Iberian origin of live animals, meat and dry-cured products.


Assuntos
Produtos da Carne/análise , Carne de Porco/análise , Sus scrofa/genética , Animais , Cruzamento , Polimorfismo de Nucleotídeo Único , Espanha , Sus scrofa/classificação
8.
Enferm. univ ; 16(4): 374-389, oct.-dic. 2019. graf
Artigo em Espanhol | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-1114728

RESUMO

Resumen Introducción: El Proceso de Atención de Enfermería (PAE) como guía para el cuidado, se aplica desde que inicia la formación académica. Comprender el significado que tiene para estudiantes del último curso permite visualizar la importancia y dificultades que se presentan en su aplicación, para proponer estrategias que fortalezcan la calidad educativa. Objetivo: Comprender el significado del PAE que tienen los estudiantes del último curso de Enfermería. Método: Estudio con enfoque cualitativo. Referencial teórico y metodológico fue el Interaccionismo Simbólico y la Teoría Fundamentada en los Datos. Muestra por saturación teórica. Colecta de datos con entrevistas semiestructuradas en 17 estudiantes del 10° ciclo de una universidad privada de Lima Este. Análisis de datos basado en la codificación de Strauss y Corbin posibilitó la identificación de categorías y subcategorías, y el fenómeno central. Resultados: Emergieron cinco categorías: 1) Cuidado enfermero utilizando el PAE desde el inicio de su formación (Condición causal); 2) Satisfacción o insatisfacción al dar cuidado con el PAE (Contexto); 3) PAE como herramienta de investigación en formación profesional (Condiciones Intervinientes); 4) Dificultades en la aplicación del PAE en el cotidiano de los profesionales (Estrategias de Acción/ Interacción) y 5) Mejora de la práctica al dar cuidado con PAE (Consecuencias). Conclusiones: El fenómeno central es el PAE, instrumento que guía el cuidado de enfermería para brindar a las personas atención integral y con fundamento en evidencia científica; a partir de la experiencia profesional con una proyección positiva al campo laboral, no exenta de limitaciones en su aplicación en el campo hospitalario.


Abstract Introduction: The Nursing Process (NP) as the guide to care is encouraged from the beginning of the academic formation; and understanding the meaning which this process has to senior nursing students can yield a more precise visualization of the difficulties regarding its application and, consequently, the possibility to promote strategies aimed at strengthening the related quality of education. Objective: To understand the meaning which NA has to senior nursing students. Method: This is a study with a qualitative focus. The theoretical and methodological references were the Symbolic Interactionism and the Data Grounded Theory. The sample was formed until theoretical saturation was reached. Data were collected using semi-structured interviews on 17 nursing students in the 10th cycle of a private university in Lima Este. Based on the Strauss and Corbin coding, the data analysis yielded the categories, subcategories, and main phenomenon. Results: Five categories emerged: 1) The care using the NP from the beginning of the formation (Causal condition); Satisfaction or insatisfaction while providing care through the NP (Context); NP as a research tool in the professional formation (Intervening conditions); 4) Difficulties while using the NP in the day-to-day activities of the professionals (Action / Interaction strategies); and 5) Improvements in the practice as the result of using the NP (Consequences). Conclusions: The central phenomenon is the NP which guides the nursing care in the provision of integral attention based on scientific and wide in scope projection.


Resumo Introdução: O Processo de Atenção de Enfermagem (PAE) como guia para o cuidado, aplica-se desde que inicia a formação académica. Compreender o significado que tem para estudantes do último curso permite visualizar a importância e dificuldades que se apresentam em sua aplicação, para propor estratégias que fortaleçam a qualidade educativa. Objetivo: Compreender o significado do PAE que têm os estudantes do último curso de Enfermagem. Método: Estudo com enfoque qualitativo. O referencial teórico e metodológico foi o Interacionismo Simbólico e a Teoria Fundamentada nos Dados. Amostra obtida por saturação teórica. Coleta de dados com entrevistas semiestruturadas em 17 estudantes do 10° ciclo de uma universidade privada do leste de Lima. A análise de dados baseada em codificação de Strauss e Corbin, possibilitou a identificação de categorias e subcategorias, e o fenómeno central. Resultados: Emergiram cinco categorias: 1) Cuidado enfermeiro utilizando o PAE desde o início de sua formação (Condição causal); 2) Satisfação ou insatisfação para dar cuidado com o PAE (Contexto); 3) PAE como ferramenta de pesquisa em formação profissional (Condições Interventoras); 4) Dificuldades na aplicação do PAE no cotidiano dos profissionais (Estratégias de Ação/ Interação) e 5) Melhora da prática para dar cuidado com PAE (Consequências). Conclusões: O fenómeno central é o PAE, instrumento que guia o cuidado de enfermagem para proporcionar às pessoas atenção integral e com fundamento na evidência científica; a partir da experiência profissional com uma projeção positiva no campo laboral, não isenta de limitações em sua aplicação no campo hospitalar.

9.
Sci Rep ; 9(1): 13546, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537860

RESUMO

Genetic characterization of local breeds is essential to preserve their genomic variability, to advance conservation policies and to contribute to their promotion and sustainability. Genomic diversity of twenty European local pig breeds and a small sample of Spanish wild pigs was assessed using high density SNP chips. A total of 992 DNA samples were analyzed with the GeneSeek Genomic Profiler (GGP) 70 K HD porcine genotyping chip. Genotype data was employed to compute genetic diversity, population differentiation and structure, genetic distances, linkage disequilibrium and effective population size. Our results point out several breeds, such as Turopolje, Apulo Calabrese, Casertana, Mora Romagnola and Lithuanian indigenous wattle, having the lowest genetic diversity, supported by low heterozygosity and very small effective population size, demonstrating the need of enhanced conservation strategies. Principal components analysis showed the clustering of the individuals of the same breed, with few breeds being clearly isolated from the rest. Several breeds were partially overlapped, suggesting genetic closeness, which was particularly marked in the case of Iberian and Alentejana breeds. Spanish wild boar was also narrowly related to other western populations, in agreement with recurrent admixture between wild and domestic animals. We also searched across the genome for loci under diversifying selection based on FST outlier tests. Candidate genes that may underlie differences in adaptation to specific environments and productive systems and phenotypic traits were detected in potentially selected genomic regions.


Assuntos
Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genética , Suínos/genética , Animais , Animais Domésticos/genética , Cruzamento/métodos , Variação Genética/genética , Genética Populacional/métodos , Genoma , Genômica/métodos , Genótipo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fenótipo , Densidade Demográfica , Análise de Componente Principal/métodos
10.
Mol Psychiatry ; 22(3): 346-352, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28115739

RESUMO

Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the µ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study of usual daily methadone dose. In African-American (AA) OD subjects (n=383), we identified a genome-wide significant association between therapeutic methadone dose (mean=68.0 mg, s.d.=30.1 mg) and rs73568641 (P=2.8 × 10-8), the nearest gene (306 kilobases) being OPRM1. Each minor (C) allele corresponded to an additional ~20 mg day-1 of oral methadone, an effect specific to AAs. In European-Americans (EAs) (n=1027), no genome-wide significant associations with methadone dose (mean=77.8 mg, s.d.=33.9 mg) were observed. In an independent set of opioid-naive AA children being treated for surgical pain, rs73568641-C was associated with a higher required dose of morphine (n=241, P=3.9 × 10-2). Similarly, independent genomic loci previously shown to associate with higher opioid analgesic dose were associated with higher methadone dose in the OD sample (AA and EA: n=1410, genetic score P=1.3 × 10-3). The present results in AAs indicate that genetic variants influencing opioid sensitivity across different clinical settings could contribute to precision pharmacotherapy for pain and addiction.


Assuntos
Analgésicos Opioides/farmacologia , Transtornos Relacionados ao Uso de Opioides/genética , Dor/genética , Adulto , Negro ou Afro-Americano/genética , Alelos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Morfina/uso terapêutico , Dor/tratamento farmacológico , Polimorfismo de Nucleotídeo Único/genética , Receptores Opioides mu/genética , Estados Unidos , População Branca/genética
11.
Anim Genet ; 48(2): 151-165, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27642173

RESUMO

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.


Assuntos
Carne , Polimorfismo de Nucleotídeo Único , Edição de RNA , Análise de Sequência de RNA/métodos , Sus scrofa/genética , Animais , Cruzamentos Genéticos , Feminino , Masculino , Sus scrofa/fisiologia
12.
Animal ; 10(6): 939-46, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27074956

RESUMO

Diet influences animal body and tissue composition due to direct deposition and to the nutrients effects on metabolism. The influence of specific nutrients on the molecular regulation of lipogenesis is not well characterized and is known to be influenced by many factors including timing and physiological status. A trial was performed to study the effects of different dietary energy sources on lipogenic genes transcription in ham adipose tissue of Iberian pigs, at different growth periods and on feeding/fasting situations. A total of 27 Iberian male pigs of 28 kg BW were allocated to two separate groups and fed with different isocaloric feeding regimens: standard diet with carbohydrates as energy source (CH) or diet enriched with high oleic sunflower oil (HO). Ham subcutaneous adipose tissue was sampled by biopsy at growing (44 kg mean BW) and finishing (100 kg mean BW) periods. The first sampling was performed on fasted animals, while the last sampling was performed twice, with animals fasted overnight and 3 h after refeeding. Effects of diet, growth period and feeding/fasting status on gene expression were explored quantifying the expression of a panel of key genes implicated in lipogenesis and lipid metabolism processes. Quantitative PCR revealed several differentially expressed genes according to diet, with similar results at both timings: RXRG, LEP and FABP5 genes were upregulated in HO group while ME1, FASN, ACACA and ELOVL6 were upregulated in CH. The diet effect on ME1 gene expression was conditional on feeding/fasting status, with the higher ME1 gene expression in CH than HO groups, observed only in fasting samples. Results are compatible with a higher de novo endogenous synthesis of fatty acids (FA) in the carbohydrate-supplemented group and a higher FA transport in the oleic acid-supplemented group. Growth period significantly affected the expression of most of the studied genes, with all but PPARG showing higher expression in finishing pigs according to a pattern dissimilar from the usual in cosmopolitan pig breeds. Feeding/fasting status only influenced PPARG gene transcription. The lack of effects of feeding/fasting status on lipogenic gene expression and the higher ME1 response to diet in fasting samples than in postprandial sampling, suggest the persistence of de novo lipogenesis during fasting. Overall results improve the understanding of the influence of different factors on lipid metabolism regulation in Iberian pigs.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Carboidratos da Dieta/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Ácido Oleico/farmacologia , Suínos/genética , Suínos/metabolismo , Transcrição Gênica/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos/metabolismo , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Masculino , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Gordura Subcutânea/metabolismo , Óleo de Girassol , Suínos/crescimento & desenvolvimento , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
13.
Meat Sci ; 102: 59-68, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25549539

RESUMO

The effect of two diets, respectively enriched with SFA (S) and PUFA (P), on FA tissue composition and gene expression was studied in fattened Iberian pigs. The FA composition of adipose, muscular and liver tissues was affected by dietary treatment. S group showed higher MUFA and MUFA/SFA ratio and lower PUFA and n-6/n-3 ratio than P group in all analyzed tissues. In muscle and liver the extracted lipids were separated into neutral lipids and polar lipid fractions which showed significantly different responses to the dietary treatment, especially in liver where no significant effect of diet was observed in NL fraction. The expression of six candidate genes related to lipogenesis and FA oxidation was analyzed by qPCR. In liver, stearoyl CoA desaturase (SCD), acetyl CoA carboxylase alpha (ACACA) and malic enzyme 1 (ME1) genes showed higher expression in S group. SCD, ACACA, ME1, and fatty acid synthase (FASN) gene expression levels showed a wide variation across the tested tissues, with much higher expression levels observed in adipose tissue than other tissues. Tissue FA profile and gene expression results support the deposition of dietary FA, the lipogenic effect of dietary saturated fat in liver and the employment of saturated dietary fat for endogenous synthesis of MUFA in all the analyzed tissues.


Assuntos
Dieta/veterinária , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/análise , Regulação Enzimológica da Expressão Gênica , Carne/análise , Óleos de Plantas/administração & dosagem , Animais , Animais Endogâmicos , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados/análise , Ácidos Graxos Monoinsaturados/metabolismo , Lipogênese , Fígado/química , Fígado/metabolismo , Masculino , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Orquiectomia , Especificidade de Órgãos , Óleos de Plantas/metabolismo , Espanha , Gordura Subcutânea Abdominal/química , Gordura Subcutânea Abdominal/metabolismo , Óleo de Girassol , Sus scrofa , Transcrição Gênica
14.
Mol Psychiatry ; 20(11): 1350-65, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25385366

RESUMO

An increasing number of genetic variants have been implicated in autism spectrum disorders (ASDs), and the functional study of such variants will be critical for the elucidation of autism pathophysiology. Here, we report a de novo balanced translocation disruption of TRPC6, a cation channel, in a non-syndromic autistic individual. Using multiple models, such as dental pulp cells, induced pluripotent stem cell (iPSC)-derived neuronal cells and mouse models, we demonstrate that TRPC6 reduction or haploinsufficiency leads to altered neuronal development, morphology and function. The observed neuronal phenotypes could then be rescued by TRPC6 complementation and by treatment with insulin-like growth factor-1 or hyperforin, a TRPC6-specific agonist, suggesting that ASD individuals with alterations in this pathway may benefit from these drugs. We also demonstrate that methyl CpG binding protein-2 (MeCP2) levels affect TRPC6 expression. Mutations in MeCP2 cause Rett syndrome, revealing common pathways among ASDs. Genetic sequencing of TRPC6 in 1041 ASD individuals and 2872 controls revealed significantly more nonsynonymous mutations in the ASD population, and identified loss-of-function mutations with incomplete penetrance in two patients. Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model. This is the first study to use iPSC-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.


Assuntos
Transtorno Autístico/patologia , Neurônios/patologia , Canais de Cátion TRPC/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Transtorno Autístico/genética , Transtorno Autístico/fisiopatologia , Carboplatina/metabolismo , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/genética , Células Cultivadas , Criança , Modelos Animais de Doenças , Embrião de Mamíferos , Etoposídeo/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Técnicas In Vitro , Células-Tronco Pluripotentes Induzidas/fisiologia , Potenciais Pós-Sinápticos Inibidores/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitoxantrona/metabolismo , Mutação/genética , Neurônios/metabolismo , Prednisolona/metabolismo , Transdução de Sinais/genética , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6
15.
J Anim Sci ; 92(3): 939-54, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24492573

RESUMO

A trial was performed to compare the effects of different dietary sources of MUFA on the fatty acid (FA) composition, lipid metabolism, and gene transcription in different tissues of Iberian pigs. Twenty-seven Iberian male pigs of 28 kg live weight (LW) were divided in 2 groups and fed with 1 of 2 isocaloric diets: a standard diet with carbohydrates as energy source (CH) and a diet enriched with high-oleic sunflower oil (HO). Ham adipose tissue was sampled by biopsy at 44 and 70 kg LW. At 110 kg LW pigs were slaughtered and backfat, loin, and liver tissues were sampled. Animals of the HO group showed higher MUFA content and lower SFA in all the analyzed tissues (P < 0.001). These main effects were established early during the treatment and increased only slightly along time. Small diet effects were also detected on PUFA, which showed differences according to sampling time, tissue, and lipid fraction. Effects of diet on gene expression were explored with a combined approach analyzing adipose tissue transcriptome and quantifying the expression of a panel of key genes implicated in lipogenesis and lipid metabolism processes in backfat, muscle, and liver. Backfat transcriptome showed small effects of diet on gene expression, in number and magnitude. According to the posterior probabilities (PP) of the probe-specific expression differences between dietary groups (PP < 0.01), 37 genes were considered differentially expressed (DE). Gene ontology allowed relating them with several biological functions including lipid metabolic processes. Quantitative PCR confirmed several DE genes in adipose tissue (RXRG, LEP, and ME1; P < 0.0001, P < 0.05, and P < 0.0001, respectively), but no DE gene was found in loin or liver tissues. Joint results agree with a metabolic adjustment of adipose tissue FA levels by the subtle effect of the diet on the regulation of several lipid metabolism pathways, mainly FA oxidation and prostanoid synthesis, with LEP, RXRG, and PTGS2 genes playing mayor roles.


Assuntos
Ração Animal/análise , Dieta/veterinária , Ácidos Graxos/química , Suínos/metabolismo , Transcrição Gênica/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Composição Corporal/efeitos dos fármacos , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos
16.
J Food Sci ; 77(8): M499-504, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22860598

RESUMO

UNLABELLED: In the present work, 3 different yeast strains (1, 2, and 3) were used to elaborate white wines using Albariño must. The concentration of polymeric mannose was determined using a method based on the mannoprotein precipitation, hydrolysis and analysis of sylylated mannose derivatives by gas chromatography. Wines elaborated with the strain 1 (W1) presented a higher mannoprotein concentration than the other wines. The analysis of the volatile composition of wines showed significant differences (P < 0.05) among them, being W1 which presented the highest concentration of aroma compounds, mainly terpens and norisoprenoids. The sensorial analysis of wines also showed that W1 had the best quality. The results obtained from this work demonstrate that mannoproteins could be involved in the behavior observed. Some evidences were obtained using a model wine, where 2 major terpens in W1 were preferentially retained by the colloids rich in mannoproteins released by strain 1. PRACTICAL APPLICATION: White wines elaborated with yeast strains overproducing mannoproteins could have better quality than others. Mannoproteins could contribute to aroma enhancement of Albariño white wines.


Assuntos
Microbiologia de Alimentos , Proteínas Fúngicas/biossíntese , Glicoproteínas de Membrana/biossíntese , Saccharomyces cerevisiae/metabolismo , Vinho/microbiologia , Monoterpenos Acíclicos , Cromatografia Gasosa , Proteínas Fúngicas/análise , Humanos , Manose/análise , Glicoproteínas de Membrana/análise , Monoterpenos/isolamento & purificação , Monoterpenos/metabolismo , Odorantes/análise , Olfato , Terpenos/isolamento & purificação , Terpenos/metabolismo , Vitis/química , Vitis/microbiologia , Compostos Orgânicos Voláteis/análise , Vinho/análise
17.
J Dent Res ; 91(9): 853-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22837552

RESUMO

White-spot lesions (WSL) associated with orthodontic appliances are a cosmetic problem and increase risk for cavities. We characterized the microbiota of WSL, accounting for confounding due to gingivitis. Participants were 60 children with fixed appliances, aged between 10 and 19 yrs, half with WSL. Plaque samples were assayed by a 16S rRNA-based microarray (HOMIM) and by PCR. Mean gingival index was positively associated with WSL (p = 0.018). Taxa associated with WSL by microarray included Granulicatella elegans (p = 0.01), Veillonellaceae sp. HOT 155 (p < 0.01), and Bifidobacterium Cluster 1 (p = 0.11), and by qPCR, Streptococcus mutans (p = 0.008) and Scardovia wiggsiae (p = 0.04) Taxa associated with gingivitis by microarray included: Gemella sanguinis (p = 0.002), Actinomyces sp. HOT 448 (p = 0.003), Prevotella cluster IV (p = 0.021), and Streptococcus sp. HOT 071/070 (p = 0.023); and levels of S. mutans (p = 0.02) and Bifidobacteriaceae (p = 0.012) by qPCR. Species' associations with WSL were minimally changed with adjustment for gingivitis level. Partial least-squares discriminant analysis yielded good discrimination between children with and those without WSL. Granulicatella, Veillonellaceae and Bifidobacteriaceae, in addition to S. mutans and S. wiggsiae, were associated with the presence of WSL in adolescents undergoing orthodontic treatment. Many taxa showed a stronger association with gingivitis than with WSL.


Assuntos
Cárie Dentária/microbiologia , Placa Dentária/microbiologia , Gengivite/microbiologia , Metagenoma , Aparelhos Ortodônticos/efeitos adversos , Adolescente , Bifidobacterium/genética , Criança , Fatores de Confusão Epidemiológicos , Índice CPO , DNA Bacteriano/genética , Cárie Dentária/etiologia , Análise Discriminante , Feminino , Bactérias Gram-Positivas/genética , Humanos , Análise dos Mínimos Quadrados , Modelos Logísticos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Streptococcus mutans/genética , Veillonellaceae/genética
19.
J Food Prot ; 71(7): 1496-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18680954

RESUMO

A wine model was evaluated to determine the influence of aging on the ability of whole yeast cells (WY) and yeast cell walls (YCW) to remove ochratoxin A (OTA). Aging and autolysis were monitored for 214 h in the model wine. The original concentration of OTA in the model wine was 10 microg/liter, and WY and YCW were added at a final concentration of 1 g/liter. YCW mannoproteins were involved in the removal of OTA from the model wine through adsorption mechanisms. Aging affected the capacity of WY to remove OTA, but YCW removal capacity remained constant during aging. A previous heat treatment (85 degrees C for 10 min) of WY and YCW increased their removal capacity and increased the efficiency of the decontamination process.


Assuntos
Descontaminação/métodos , Contaminação de Alimentos/análise , Ocratoxinas/análise , Saccharomyces cerevisiae/fisiologia , Vinho/análise , Adsorção , Autólise , Temperatura Alta , Humanos , Microbiologia Industrial , Fatores de Tempo , Vitis/química , Vitis/microbiologia , Vinho/microbiologia
20.
Acta otorrinolaringol ; 18(2): 55-62, oct. 2006. tab, graf
Artigo em Espanhol | LILACS | ID: lil-508694

RESUMO

Para el año 2002 LA World Health Organization (WHO), estimó que aproximadamente unos 250 millones de personas sufrifrían de trastornos auditivos incapacitantes; que dos terceras partes de estas pesonas vivirían en países en vías de desarrollo, y que la mitad de estas pérdidas auditivas podrían ser evitables. Los programas de WHO, (Healthy People 200) iniciados en 1.990, tenían como objetivo fundamental lograr la identificación de pérdidas auditivas severas en niños antes del primer año de edad, sin embargo, los programas de Joint Comittee of Infant Hearing (1.994) fueron mas ambiciosos y redujeron la identificación del problema a los 6 meses de nacido. El propósito de este trabajo es mostrar los resultados de una encuesta epidemiológica aplicada en las Unidades de Educación Especial (UEE) del estado Sucre: Cumaná (UEE Cumaná), Carúpano (UEE Libertador) y Cumanocoa (UEE Cumanacoa y taller de educación especial Cumanacoa). El objetivo funadmental de esta encuesta era el de establecer las posibles causas que originaron el problema en la población de 3 a 25 años de edad que asisten a estos centros educativos, la edad a la cual se realizó el diagnóstico, el grado de perdida auditiva de los mismos, así como las características de su amplificación aural y escolaridad


Assuntos
Humanos , Masculino , Feminino , Lactente , Transtornos da Audição , Perda Auditiva , Otolaringologia , Venezuela
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