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We tested the effects of prolonged voluntary wheel running on the muscle function of mdx mice treated with one of two different microdystrophin constructs. At 7 weeks of age mdx mice were injected with a single dose of AAV9-CK8-microdystrophin with (gene therapy 1, GT1) or without (gene therapy 2, GT2) the nNOS-binding domain and were assigned to one of four gene therapy treated groups: mdxRGT1 (run, GT1), mdxGT1 (no run, GT1), or mdxRGT2 (run,GT2), mdxGT2 (no run, GT2). There were two mdx untreated groups injected with excipient: mdxR (run, no gene therapy) and mdx (no run, no gene therapy). A third no treatment group, Wildtype (WT) received no injection and did not run. mdxRGT1, mdxRGT2 and mdxR performed voluntary wheel running for 52 weeks; WT and remaining mdx groups were cage active. Robust expression of microdystrophin occurred in diaphragm, quadriceps, and heart muscles of all treated mice. Dystrophic muscle pathology was high in diaphragms of non-treated mdx and mdxR mice and improved in all treated groups. Endurance capacity was rescued by both voluntary wheel running and gene therapy alone, but their combination was most beneficial. All treated groups increased in vivo plantarflexor torque over both mdx and mdxR mice. mdx and mdxR mice displayed â¼3-fold lower diaphragm force and power compared to WT values. Treated groups demonstrated partial improvements in diaphragm force and power, with mdxRGT2 mice experiencing the greatest improvement at â¼60% of WT values. Evaluation of oxidative red quadriceps fibers revealed the greatest improvements in mitochondrial respiration in mdxRGT1 mice, reaching WT levels. Interestingly, mdxGT2 mice displayed diaphragm mitochondrial respiration values similar to WT but mdxRGT2 animals showed relative decreases compared to the no run group. Collectively, these data demonstrate that either microdystrophin construct combined with voluntary wheel running increased in vivo maximal muscle strength, power, and endurance. However, these data also highlighted important differences between the two microdystrophin constructs. GT1, with the nNOS-binding site, improved more markers of exercise-driven adaptations in metabolic enzyme activity of limb muscles, while GT2, without the nNOS-binding site, demonstrated greater protection of diaphragm strength after chronic voluntary endurance exercise but decreased mitochondrial respiration in the context of running.
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BACKGROUND: Chronic venous leg ulcers pose a significant burden to healthcare systems, and predicting wound healing is challenging. The aim of this study was to develop a genetic test to evaluate the propensity of a chronic ulcer to heal. METHODS: Sequential refinement and testing of a gene expression signature was conducted using three distinct cohorts of human wound tissue. The expression of candidate genes was screened using a cohort of acute and chronic wound tissue and normal skin with quantitative transcript analysis. Genes showing significant expression differences were combined and examined, using receiver operating characteristic (ROC) curve analysis, in a controlled prospective study of patients with venous leg ulcers. A refined gene signature was evaluated using a prospective, blinded study of consecutive patients with venous ulcers. RESULTS: The initial gene signature, comprising 25 genes, could identify the outcome (healing versus non-healing) of chronic venous leg ulcers (area under the curve (AUC) 0·84, 95 per cent c.i. 0·73 to 0·94). Subsequent refinement resulted in a final 14-gene signature (WD14), which performed equally well (AUC 0·88, 0·80 to 0·97). When examined in a prospective blinded study, the WD14 signature could also identify wounds likely to demonstrate signs of healing (AUC 0·73, 0·62 to 0·84). CONCLUSION: A gene signature can identify people with chronic venous leg ulcers that are unlikely to heal.
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Testes Genéticos/métodos , Úlcera da Perna/genética , Transcriptoma , Cicatrização/genética , Adulto , Biópsia , Humanos , Úlcera da Perna/patologia , Úlcera da Perna/fisiopatologia , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
AIMS To investigate the effects of sporidesmin on cells cultured from the epithelial surface of sheep gallbladder walls, and to examine cellular responses to sporidesmin using cultures prepared from the gallbladders of sheep from selection lines that differed in sensitivity to sporidesmin-induced liver damage. METHODS Gallbladders were obtained following slaughter of lambs that were selected for resistance or susceptibility to sporidesmin-induced liver damage, or were not selected (controls). Monolayer cell cultures were established after incubation of excised gallbladders with protease to detach the lining epithelial cells from the muscular and connective tissue of the gallbladder wall. Released cells were harvested and transferred to culture flasks or dishes, then incubated with 1â µg/mL sporidesmin and were examined at 5 minute intervals, up to 3 hours, using light microscopy to monitor loss of attachment of cultured cells. Immunofluorescence staining of cell cultures was used to identify cytokeratin 19 as a marker for biliary epithelial cells, and to characterise sporidesmin-induced change in the cellular distribution of actin microfilaments. Gallbladder size was also measured. RESULTS In cultures incubated with sporidesmin, cells at the margins of sheets of cells showed the first signs of change, becoming unanchored from the culture vessels while remaining attached to the cell mass. This was followed by progressive detachment of sheets of cells and clumps of rounded cells. Disruption of cytoplasmic actin microfilaments with accumulation of actin in the cytoplasm adjacent to the plasma membrane preceded major detachment of cells. Cells from susceptible line lambs were extensively rounded up within 1 hour with complete or almost complete detachment within 2 hours, whereas cultures from resistant line lambs generally only contained detaching rounded-up cells at the periphery of monolayers within 2 hours; detachment observed in cells from the control line lambs was intermediate. There was a trend for gallbladders to be smaller in male lambs from the resistant line compared to the control or susceptible lines. CONCLUSIONS Altered cell adhesion and disruption of microfilament actin in biliary cell cultures incubated with sporidesmin suggest that biliary tract pathology may be due to the effects of the toxin on cytoplasmic and cell surface protein networks that affect the integrity of the epithelial lining of the biliary tract. These effects can be interpreted in terms of the hepatobiliary pathology of facial eczema, including potential differences in sensitivity of biliary tract cells that may contribute to inherited resistance and susceptibility to sporidesmin and hence facial eczema.
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Vesícula Biliar/efeitos dos fármacos , Vesícula Biliar/patologia , Esporidesminas/toxicidade , Matadouros , Análise de Variância , Animais , Sistema Biliar , Técnicas de Cultura de Células , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Fotomicrografia , Ovinos , Doenças dos Ovinos , Esporidesminas/administração & dosagemRESUMO
Ryegrass staggers (RGS) is a metabolic disease of herbivores, caused by the ingestion of perennial ryegrass (Lolium perenne L.) containing a fungal endophyte (Neotyphodium lolii) which produces a tremorgenic toxin, lolitrem B. RGS has a major economic impact for agriculture in New Zealand as well as internationally. Management of RGS in grazing sheep can be problematic, and there is an incomplete knowledge of the interaction between the toxin and the grazing animal. This review is focused on recent advances in understanding the molecular physiology of RGS in the affected animal as well as the influence of animal genetics on the degree of susceptibility to RGS. Investigations to date suggest that the primary target for toxin is the large conductance, calcium-activated, potassium (BK) channel, resulting in disruption of neuromuscular junction signalling. Genetic investigation has established the existence of genes influencing resistance to RGS, however their identity has not been confirmed and their impact has not been established. Studies to date suggest that a multi-gene selection approach will be necessary in order to develop an effective selection tool for use in the agricultural industries.
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Resistência à Doença/genética , Lolium/microbiologia , Doenças dos Ovinos , Animais , Humanos , Alcaloides Indólicos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta , Camundongos , Mutação , Micotoxinas , Neotyphodium/patogenicidade , Ovinos , Doenças dos Ovinos/genética , Doenças dos Ovinos/microbiologia , Doenças dos Ovinos/fisiopatologiaRESUMO
Duchenne muscular dystrophy is caused by mutations in the DYSTROPHIN gene. Although primarily associated with muscle wasting, a significant portion of patients (approximately 25%) are also diagnosed with autism spectrum disorder. We describe social behavioral deficits in dystrophin-deficient mice and present evidence of cerebellar deficits in cGMP production. We demonstrate therapeutic potential for selective inhibitors of the cGMP-specific PDE5A and PDE9A enzymes to restore social behaviors in dystrophin-deficient mice.
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Human adipose-derived stromal/stem cells (ASCs) display potential to be used in regenerative stem cell therapies and as treatments for inflammatory and autoimmune disorders. Despite promising use of ASCs as therapeutics, little is known about their susceptibility to infectious agents. In this study, we demonstrate that ASCs are highly susceptible to human cytomegalovirus (HCMV) infection and permissive for replication leading to release of infectious virions. Additionally, many basic ASC functions are inhibited during HCMV infection, such as differentiation and immunomodulatory potential. To our knowledge this is the first study examining potential adverse effects of HCMV infection on ASC biology. Our results suggest, that an active HCMV infection during ASC therapy may result in a poor clinical outcome due to interference by the virus.
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The goal was to estimate the heritabilities and genetic variances for pregnancy rate (PR) and calving date (CD) in Angus cattle along with the effect of weight, age, and sire on PR and CD. The data consisted of 4,999 records on PR and CD. Statistical models included year as a fixed effect; premating/postmating weight and age as covariates; and sire of embryo, maternal grandsire (MGS), and permanent maternal environmental effects as random effects. The models also included the interactions between herd and weight (weight change). Direct and maternal effects on PR and CD were estimated using sire MGS and animal models in REML. Pregnancy rate increased from age 2 to 6 and decreased from age 7 to 11 (P < 0.01) and this effect was independent of the culling strategy. There was a quadratic effect of premating cow weight independent of age on PR, with lower PR for low weights (P < 0.01). Overall, cows with a premating weight of 550 kg had the greatest PR. Cows that lost weight during mating had lower PR (P < 0.01). The maternal additive heritability for PR was 0.001 ± 0.012 and the direct additive heritability was 0.024 ± 0.020. The ratio of permanent maternal environmental variance to phenotypic variance was significant (0.048 ± 0.017; P < 0.01). This demonstrates that permanent maternal environmental effects play a major role in the repeatability of PR (0.049 ± 0.015; P < 0.01). The maternal additive heritability for CD was 0.040 ± 0.022, and the direct additive heritability was 0.076 ± 0.045. The ratio of permanent maternal environmental variance to phenotypic variance was low (0.014 ± 0.017) and the repeatability for CD was significant (0.0544 ± 0.0180; P < 0.01). This suggests that maternal genetic effects are as important as direct genetic effects on CD. There was a positive quadratic relationship between premating cow weight and CD with delayed calving for low/high weights (P < 0.01). Cows that lost weight over mating also had a later CD (P < 0.01). Comparisons of a weight-selected herd to the control herd showed differences (P < 0.05) in the optimal premating weight for early calving (control, 480 kg, and weight selected, 615 kg). Calving date was also more sensitive to changes in weight over mating in the weight selection herd (P < 0.05). Therefore, the set point in the weight-fertility axis and the sensitivity of fertility to changes in weight both changed in the weight selection herd.
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Envelhecimento/fisiologia , Peso Corporal/fisiologia , Cruzamento/métodos , Bovinos/genética , Bovinos/fisiologia , Taxa de Gravidez , Prenhez/genética , Prenhez/fisiologia , Animais , Meio Ambiente , Feminino , Fertilidade/genética , Fertilidade/fisiologia , Masculino , Modelos Biológicos , Modelos Estatísticos , Nova Zelândia , Fenótipo , Gravidez , Reprodução/genética , Reprodução/fisiologia , Comportamento Sexual Animal/fisiologia , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Williams syndrome, a rare genetic disorder with a striking neurobehavioral profile characterized by extreme sociability and impaired visuospatial construction abilities, is caused by a hemideletion that includes the elastin gene, resulting in frequent supravavular aortic stenosis and other stenotic arterial lesions. Strokes have been reported in Williams syndrome. Although the extracranial carotid artery has been studied in a sample of patients with Williams syndrome, proximal intracranial arteries have not. MATERIALS AND METHODS: Using MRA, we studied the intracranial vessels in 27 participants: 14 patients with Williams syndrome (age range, 18-44 years; mean age, 27.3 ± 9.1; 43% women) and 13 healthy control participants with similar age and sex distribution (age range, 22-52 years; mean age, 33.4 ± 7.6; 46% women). All participants with Williams syndrome had hemideletions of the elastin gene. Blinded to group allocation or to any other clinical data, a neuroradiologist determined the presence of intracranial vascular changes in the 2 groups. RESULTS: The Williams syndrome group and the healthy control group had similar patency of the proximal intracranial arteries, including the internal carotid and vertebral arteries; basilar artery; and stem and proximal branches of the anterior cerebral artery, MCA, and posterior cerebral arteries. The postcommunicating segment of the anterior cerebral artery was longer in the Williams syndrome group. CONCLUSIONS: Despite the elastin haploinsufficiency, the proximal intracranial arteries in Williams syndrome preserve normal patency.
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Doenças Arteriais Cerebrais/patologia , Artérias Cerebrais/patologia , Elastina/genética , Angiografia por Ressonância Magnética/métodos , Síndrome de Williams/genética , Síndrome de Williams/patologia , Adolescente , Adulto , Doenças Arteriais Cerebrais/fisiopatologia , Artérias Cerebrais/fisiopatologia , Deleção de Genes , Predisposição Genética para Doença/genética , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Grau de Desobstrução Vascular , Adulto JovemRESUMO
A V-ATPase subunit A protein (VHA-A) transcript together with a variant (C793 to U), which introduces a stop codon truncating the subunit immediately downstream of its ATP binding site, was identified within a Fucus vesiculosus cDNA from a heavy metal contaminated site. This is intriguing because the VHA-A subunit is the crucial catalytic subunit responsible for the hydrolysis of ATP that drives ion transport underlying heavy metal detoxification pathways. We employed a chemiluminescent hybridization protection assay to quantify the proportion of both variants directly from mRNA while performing quantification of total transcript using Q-PCR. Polyclonal antisera raised against recombinant VHA-A facilitated simultaneous detection of parent and truncated VHA-A and revealed its cellular and subcellular localization. By exploiting laboratory exposures and samples from an environmental copper gradient, we showed that total VHA-A transcript and protein, together with levels of the truncated variant, were induced by copper. The absence of a genomic sequence representing the truncated variant suggests a RNA editing event causing the production of the truncated VHA-A. Based on these observations, we propose RNA editing as a novel molecular process underpinning VHA trafficking and intracellular sequestration of heavy metals under stress.
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Adenosina Trifosfatases/metabolismo , Proteínas de Algas/metabolismo , Cobre/metabolismo , Fucus/enzimologia , Edição de RNA , Adenosina Trifosfatases/genética , Proteínas de Algas/genética , Sequência de Aminoácidos , DNA Complementar/genética , Fucus/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica , Dados de Sequência Molecular , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA/genética , RNA/metabolismo , Proteínas Recombinantes , Alinhamento de SequênciaRESUMO
Genetic selection for enhanced levels of protective antibody to specific nematode antigens may be a more user-friendly means of selecting animals for resistance to gastrointestinal nematodes than obtaining faecal samples and selecting on the basis of faecal egg counts. Saliva IgA antibody levels to the L3-specific surface glycan known as carbohydrate larval antigen were measured on six occasions over a 5 month period in approximately 350 lambs. The carbohydrate larval antigen IgA response increased markedly with time as the lambs grazed on pasture naturally contaminated with nematode parasite larvae. The monthly loge transformed carbohydrate larval antigen IgA levels were moderately heritable at all samplings, with a combined value of 0.28±0.10 and a repeatability of 0.35±0.03. The genetic correlations between all samplings were high (0.86), suggesting that testing for a carbohydrate larval antigen IgA response could be carried out at any time in the 5 months post-weaning. The transformed carbohydrate larval antigen IgA levels were genetically and phenotypically correlated negatively with loge transformed (faecal egg count+50), averaging -0.57±0.20 and -0.12±0.03 (P<0.05), respectively. The correlations between carbohydrate larval antigen IgA and breech-soiling (dag score) never reached significance. However, genetic correlations between carbohydrate larval antigen IgA and live weight were always positive and significantly so, especially at the beginning and end of the trial, indicating that carbohydrate larval antigen IgA production may be an important genetic determinant of growth rate for lambs experiencing a larval challenge. The data suggest that the ideal time to sample for a carbohydrate larval antigen IgA response and maximise selection for lowered faecal egg count and increased live-weight would be in the first 2 months after weaning.
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Antígenos de Helmintos/imunologia , Carboidratos/imunologia , Resistência à Doença , Imunoglobulina A/imunologia , Infecções por Nematoides/veterinária , Doenças dos Ovinos/imunologia , Ovinos/crescimento & desenvolvimento , Animais , Peso Corporal , Nematoides/imunologia , Infecções por Nematoides/genética , Infecções por Nematoides/imunologia , Ovinos/imunologia , Doenças dos Ovinos/genética , DesmameRESUMO
A quantitative trait locus (QTL) study of the concentrations of 14 trace and macro elements (minerals) in tissues of beef cattle was conducted in New Zealand. Back-cross calves with Jersey and Limousin ancestry (202 heifers and 211 steers) were generated using first-cross sires. This paper reports on testing for effects of QTL on the concentrations of minerals in liver, kidney and muscle in cattle at slaughter, following a growth phase during which rearing and finishing stages were on pasture. Fifteen QTL were identified (P < 0.05) on a genome-wide basis in combined-sire and within-sire analyses. In addition, the possible effect of the Limousin myostatin F94L allele was tested by fitting each calf's myostatin genotype, and 16 QTL were identified. Twelve were in common with those QTL identified previously, comprising six affecting the liver (copper and zinc, on two chromosomes each; plus iron and molybdenum), three affecting the kidney (calcium, copper and iron), and three affecting muscle (iron, strontium and zinc).
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Bovinos/genética , Minerais/análise , Miostatina/genética , Locos de Características Quantitativas/genética , Oligoelementos/análise , Alelos , Substituição de Aminoácidos , Animais , Bovinos/metabolismo , Mapeamento Cromossômico/veterinária , Cruzamentos Genéticos , Feminino , Genótipo , Rim/química , Fígado/química , Masculino , Músculos/química , Nova Zelândia , Especificidade de ÓrgãosRESUMO
Infection with gastrointestinal nematodes (GIN) is a major constraint on the productivity of grazing livestock. The development of selection methods to quickly and accurately identify animals capable of developing an effective natural immunity to infection would contribute to the development of sustainable worm control programs. A carbohydrate larval surface antigen (CarLA), present on the infective-stage larvae (L3) of all trichostrongylid nematodes, is a target antigen for host antibody (Ab). The levels of various Ab isotypes in serum and/or saliva of field-grazed lambs were assessed by ELISA, and Ab titres compared with parasite faecal egg counts (FECs) and a range of animal productivity parameters. Levels of anti-CarLA IgA in saliva proved to be the most heritable (h(2)=0.3), and had the closest genetic correlation with FEC (r=-0.5). Those animals identified as having 'high levels' of anti-CarLA IgA typically have 20-30% lower FEC than animals with low or undetectable titres. Furthermore, animals with 'high levels' of anti-CarLA IgA tend to have improved growth rates post-weaning, and have no tendency for increased breech-soiling. The assay performed well regardless of parasite genera present on pasture. The saliva assay has a number of key practical advantages over the use of FEC for selection purposes: animals can be identified without a requirement to withhold anthelmintic treatment; sampling is rapid and easy and there is a significantly reduced barrier to adoption within the farming community. Measurement of anti-CarLA IgA in saliva by ELISA offers a practical, rapid and easy method of selecting for natural immunity to GIN in sheep.
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Anticorpos Anti-Helmínticos/análise , Gastroenteropatias/veterinária , Imunoglobulina A Secretora/análise , Nematoides/imunologia , Infecções por Nematoides/veterinária , Doenças dos Ovinos/imunologia , Animais , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Fezes/parasitologia , Feminino , Gastroenteropatias/imunologia , Gastroenteropatias/parasitologia , Imunidade Inata , Larva , Infecções por Nematoides/imunologia , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas/veterinária , Saliva/imunologia , Ovinos , Doenças dos Ovinos/parasitologia , Carneiro DomésticoRESUMO
A whole-genome scan was carried out in New Zealand and Australia to detect quantitative trait loci (QTL) for live animal and carcass composition traits and meat quality attributes in cattle. Backcross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin backgrounds. The New Zealand cattle were reared and finished on pasture, whilst Australian cattle were reared on grass and finished on grain for at least 180 days. This paper reports on meat quality traits (tenderness measured as shear force at 4-5 ages on two muscles as well as associated traits of meat colour, pH and cooking loss) and a number of metabolic traits. For meat quality traits, 18 significant QTL (P < 0.05), located in nine linkage groups, were detected on a genome-wise basis, in combined-sire (seven QTL) or within-sire analyses (11 QTL). For metabolic traits, 11 significant QTL (P < 0.05), located in eight linkage groups, were detected on a genome-wise basis, in combined-sire (five QTL) or within-sire analyses (six QTL). BTA2 and BTA3 had QTL for both metabolic traits and meat quality traits. Six significant QTL for meat quality and metabolic traits were found at the proximal end of chromosome 2. BTA2 and BTA29 were the most common chromosomes harbouring QTL for meat quality traits; QTL for improved tenderness were associated with Limousin-derived and Jersey-derived alleles on these two chromosomes, respectively.
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Bovinos/genética , Carne , Músculo Esquelético/metabolismo , Locos de Características Quantitativas , Animais , Cruzamentos Genéticos , Estudo de Associação Genômica AmplaRESUMO
A trial was carried out over a 7-year period (1999 to 2005 calf crops) to compare indicators of seasonality in Angus cattle, which were part of a long-term genetic selection experiment. Divergent selection was applied for early ('AGE-') or late ('AGE+') age at puberty (AP) in heifers, and selection lines differed over the 7-year period by 62 days (15% of the mean). The primary measures of seasonality studied in 629 heifer progeny (59 sire groups) were serum concentration of prolactin (PRL), and winter and summer hair growth. Serial samples were obtained for PRL from 11 to 18 months of age, and data were analysed with adjustment for cortisol concentration. Using restricted maximum likelihood procedures with an animal model, heritability estimates were: AP, 0.26 ± 0.03; log(e)PRL concentration, 0.23 ± 0.07; log(e)cortisol concentration, 0.22 ± 0.07; hair weight, 0.21 ± 0.04; and hair length, 0.09 ± 0.05. Corresponding repeatability estimates for the last four traits were 0.49 ± 0.03, 0.38 ± 0.03, 0.21 ± 0.04, and 0.64 ± 0.02, respectively. The genetic correlation between AP and log(e)PRL concentration was estimated at -0.29 ± 0.13 (P < 0.05). PRL concentration in the AGE- line after passing through puberty was 11 ± 5% lower than in the AGE+ line (P < 0.05). Line effects were not significant for hair weight or hair length. It was concluded that divergent selection for AP changed PRL concentration, which may partly reflect sensitivity to changing day length.
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Bowman-Birk inhibitor concentrate (BBIC), a serine protease inhibitor, has been shown to diminish disuse atrophy of skeletal muscle. Duchenne muscular dystrophy (DMD) results from a loss of dystrophin protein and involves an ongoing inflammatory response, with matrix remodeling and activation of transforming growth factor (TGF)-ß(1) leading to tissue fibrosis. Inflammatory-mediated increases in extracellular protease activity may drive much of this pathological tissue remodeling. Hence, we evaluated the ability of BBIC, an extracellular serine protease inhibitor, to impact pathology in the mouse model of DMD (mdx mouse). Mdx mice fed 1% BBIC in their diet had increased skeletal muscle mass and tetanic force and improved muscle integrity (less Evans blue dye uptake). Importantly, mdx mice treated with BBIC were less susceptible to contraction-induced injury. Changes consistent with decreased degeneration/regeneration, as well as reduced TGF-ß(1) and fibrosis, were observed in the BBIC-treated mdx mice. While Akt signaling was unchanged, myostatin activitation and Smad signaling were reduced. Given that BBIC treatment increases mass and strength, while decreasing fibrosis in skeletal muscles of the mdx mouse, it should be evaluated as a possible therapeutic to slow the progression of disease in human DMD patients.
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Músculo Esquelético/efeitos dos fármacos , Distrofia Muscular de Duchenne/tratamento farmacológico , Inibidor da Tripsina de Soja de Bowman-Birk/farmacologia , Administração Oral , Animais , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Contração Muscular/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Miostatina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Inibidor da Tripsina de Soja de Bowman-Birk/administração & dosagemRESUMO
A QTL study of live animal and carcass traits in beef cattle was carried out in New Zealand and Australia. Back-cross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin backgrounds. This paper reports on weights of eight organs (heart, liver, lungs, kidneys, spleen, gastro-intestinal tract, fat, and rumen contents) and 12 fat composition traits (fatty acid (FA) percentages, saturated and monounsaturated FA subtotals, and fat melting point). The New Zealand cattle were reared and finished on pasture, whilst Australian cattle were reared on grass and finished on grain for at least 180 days. For organ weights and fat composition traits, 10 and 12 significant QTL locations (P<0.05), respectively, were detected on a genome-wide basis, in combined-sire or within-sire analyses. Seven QTL significant for organ weights were found at the proximal end of chromosome 2. This chromosome carries a variant myostatin allele (F94L), segregating from the Limousin ancestry, and this is a positional candidate for the QTL. Ten significant QTL for fat composition were found on chromosomes 19 and 26. Fatty acid synthase and stearoyl-CoA desaturase (SCD1), respectively, are positional candidate genes for these QTL. Two FA QTL found to be common to sire groups in both populations were for percentages of C14:0 and C14:1 (relative to all FAs) on chromosome 26, near the SCD1 candidate gene.
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Tecido Adiposo/química , Composição Corporal/genética , Bovinos/genética , Ácidos Graxos/química , Tamanho do Órgão/genética , Locos de Características Quantitativas/genética , Alelos , Animais , Austrália , Mapeamento Cromossômico/veterinária , Cruzamentos Genéticos , Ácido Graxo Sintases/genética , Feminino , Genótipo , Masculino , Miostatina/genética , Nova Zelândia , Fenótipo , Estearoil-CoA Dessaturase/genéticaRESUMO
beta, beta-carotene-9', 10'-dioxygenase (BCO2) plays a role in cleaving beta-carotene eccentrically, and may be involved in the control of adipose and milk colour in cattle. The bovine BCO2 gene was sequenced as a potential candidate gene for a beef fat colour QTL on chromosome (BTA) 15. A single nucleotide base change located in exon 3 causes the substitution of a stop codon (encoded by the A allele) for tryptophan(80) (encoded by the G allele) (c. 240G>A, p.Trp80stop, referred to herein as SNP W80X). Association analysis showed significant differences in subcutaneous fat colour and beta-carotene concentration amongst cattle with different BCO2 genotypes. Animals with the BCO2 AA genotype had more yellow beef fat and a higher beta-carotene concentration in adipose tissues than those with the GA or GG genotype. QTL mapping analysis with the BCO2 SNP W80X fitted as a fixed effect confirmed that this SNP is likely to represent the quantitative trait nucleotide (QTN) for the fat colour-related traits on BTA 15. Moreover, animals with the AA genotype had yellower milk colour and a higher concentration of beta-carotene in the milk.
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Bovinos/genética , Variação Genética , Carne/análise , Leite/química , Oxigenases/genética , beta Caroteno/análise , Tecido Adiposo/anatomia & histologia , Animais , Feminino , Frequência do Gene , Masculino , Locos de Características QuantitativasRESUMO
A quantitative trait locus (QTL) study was carried out in two countries, recording live animal and carcass composition traits. Back-cross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin breed backgrounds. The New Zealand cattle were reared on pasture to carcass weights averaging 229 kg, whilst the Australian cattle were reared on grass and finished on grain (for at least 180 days) to carcass weights averaging 335 kg. From 11 live animal traits and 31 carcass composition traits respectively, 5 and 22 QTL were detected in combined-sire analyses, which were significant (P < 0.05) on a genome-wise basis. Fourteen significant traits for carcass composition QTL were on chromosome 2 and these were traits associated with muscling and fatness. This chromosome carried a variant myostatin allele (F94L), segregating from the Limousin ancestry. Despite very different cattle management systems between the two countries, the two populations had a large number of QTL in common. Of the 18 traits which were common to both countries, and which had significant QTL at the genome-wise level, eight were significant in both countries.
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Composição Corporal/genética , Bovinos/genética , Dieta , Fenótipo , Locos de Características Quantitativas , Animais , Austrália , Cruzamento , Mapeamento Cromossômico/veterinária , Genótipo , Miostatina/genética , Nova Zelândia , Especificidade da EspécieRESUMO
This study set out to determine if ultimate pH (pH(u)) affected the performance of intracellular small heat shock protein and endopeptidase dynamics in muscle during beef ageing. Longissimus dorsi muscles from 39 Angus or Limousin×Angus bulls were examined to see if pH(u) achieved at 22h post mortem (rigor) affected tenderness and water holding capacity of beef. Samples were segregated into three pH(u) groups termed high (pH>6.3), intermediate (5.7
RESUMO
Facial eczema (FE) is a secondary photosensitization disease arising from liver cirrhosis caused by the mycotoxin sporidesmin. The disease affects sheep, cattle, deer and goats, and costs the New Zealand sheep industry alone an estimated NZ$63M annually. A long-term sustainable solution to this century-old FE problem is to breed for disease-resistant animals by marker-assisted selection. As a step towards finding a diagnostic DNA test for FE sensitivity, we have conducted a genome-scan experiment to screen for quantitative trait loci (QTL) affecting this trait in Romney sheep. Four F(1) sires, obtained from reciprocal matings of FE resistant and susceptible selection-line animals, were used to generate four outcross families. The resulting half-sib progeny were artificially challenged with sporidesmin to phenotype their FE traits measured in terms of their serum levels of liver-specific enzymes, namely gamma-glutamyl transferase and glutamate dehydrogenase. In a primary screen using selective genotyping on extreme progeny of each family, a total of 244 DNA markers uniformly distributed over all 26 ovine autosomes (with an autosomal genome coverage of 79-91%) were tested for linkage to the FE traits. Data were analysed using Haley-Knott regression. The primary screen detected one significant and one suggestive QTL on chromosomes 3 and 8 respectively. Both the significant and suggestive QTL were followed up in a secondary screen where all progeny were genotyped and analysed; the QTL on chromosome 3 was significant in this analysis.