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Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs1-3. The high-redshift progenitors of these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter4-6. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts 7 . However, recent detections of possible protoclusters hosting such starbursts8-11 do not support the kind of rapid cluster-core formation expected from simulations 12 : the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.
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Change history: In this Letter, the Acknowledgements section should have included the following sentence: "The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.". This omission has been corrected online.
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According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far. Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey. High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe. These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch.
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Bacterial infection remains the main cause of acute respiratory distress syndrome and is a leading cause of death and disability in critically ill patients. Here we report on the use of purified ß-glucan (lentinan) extracts from Lentinus edodes (Shiitake) mushroom that can reduce infection by a multidrug-resistant clinical isolate of Klebsiella pneumoniae in a rodent pneumonia model, likely through immunomodulation. Adult male Sprague-Dawley rats were subjected to intra-tracheal administration of K. pneumoniae to induce pulmonary sepsis and randomized to three groups; vehicle control (Vehicle, n = 12), commercial lentinan (CL, n = 8) or in-house extracted lentinan (IHL, n = 8) were administered intravenously 1 h postinfection. Physiological parameters and blood gas analysis were measured, bacterial counts from bronchoalveolar-lavage (BAL) were determined, along with differential staining of white cells and measurement of protein concentration in BAL 48 h after pneumonia induction. Use of IHL extract significantly decreased BAL CFU counts. Both CL and IHL extractions reduced protein concentration in BAL. Use of IHL resulted in an improvement in physiological parameters compared to controls and CL. In conclusion, administration of lentinan to treat sepsis-induced lung injury appears safe and effective and may exert its effects in an immunomodulatory manner.
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Antibacterianos/administração & dosagem , Lentinano/administração & dosagem , Pneumopatias/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Sepse/tratamento farmacológico , Cogumelos Shiitake/química , beta-Glucanas/administração & dosagem , Animais , Antibacterianos/química , Farmacorresistência Bacteriana , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/fisiologia , Lentinano/química , Lentinano/farmacologia , Pneumopatias/microbiologia , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Sepse/microbiologiaRESUMO
Massive present-day early-type (elliptical and lenticular) galaxies probably gained the bulk of their stellar mass and heavy elements through intense, dust-enshrouded starbursts--that is, increased rates of star formation--in the most massive dark-matter haloes at early epochs. However, it remains unknown how soon after the Big Bang massive starburst progenitors exist. The measured redshift (z) distribution of dusty, massive starbursts has long been suspected to be biased low in z owing to selection effects, as confirmed by recent findings of systems with redshifts as high as ~5 (refs 2-4). Here we report the identification of a massive starburst galaxy at z = 6.34 through a submillimetre colour-selection technique. We unambiguously determined the redshift from a suite of molecular and atomic fine-structure cooling lines. These measurements reveal a hundred billion solar masses of highly excited, chemically evolved interstellar medium in this galaxy, which constitutes at least 40 per cent of the baryonic mass. A 'maximum starburst' converts the gas into stars at a rate more than 2,000 times that of the Milky Way, a rate among the highest observed at any epoch. Despite the overall downturn in cosmic star formation towards the highest redshifts, it seems that environments mature enough to form the most massive, intense starbursts existed at least as early as 880 million years after the Big Bang.
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The determinants of the structure, functioning and resilience of pelagic ecosystems across most of the polar regions are not well known. Improved understanding is essential for assessing the value of biodiversity and predicting the effects of change (including in biodiversity) on these ecosystems and the services they maintain. Here we focus on the trophic interactions that underpin ecosystem structure, developing comparative analyses of how polar pelagic food webs vary in relation to the environment. We highlight that there is not a singular, generic Arctic or Antarctic pelagic food web, and, although there are characteristic pathways of energy flow dominated by a small number of species, alternative routes are important for maintaining energy transfer and resilience. These more complex routes cannot, however, provide the same rate of energy flow to highest trophic-level species. Food-web structure may be similar in different regions, but the individual species that dominate mid-trophic levels vary across polar regions. The characteristics (traits) of these species are also different and these differences influence a range of food-web processes. Low functional redundancy at key trophic levels makes these ecosystems particularly sensitive to change. To develop models for projecting responses of polar ecosystems to future environmental change, we propose a conceptual framework that links the life histories of pelagic species and the structure of polar food webs.
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Ecossistema , Cadeia Alimentar , Regiões Antárticas , Regiões Árticas , Biodiversidade , Mudança Climática , Oceanos e MaresRESUMO
AIMS/HYPOTHESIS: The primary aim of this completed multicentre randomised, parallel, double-blind placebo-controlled study was to elucidate the mechanisms of glucose-lowering with colesevelam and secondarily to investigate its effects on lipid metabolism (hepatic de novo lipogenesis, cholesterol and bile acid synthesis). METHODS: Participants with type 2 diabetes (HbA(1c) 6.7-10.0% [50-86 mmol/mol], fasting glucose <16.7 mmol/l, fasting triacylglycerols <3.9 mmol/l and LDL-cholesterol >1.55 mmol/l) treated with diet and exercise, sulfonylurea, metformin or a combination thereof, were randomised by a central coordinator to either 3.75 g/day colesevelam (n = 30) or placebo (n = 30) for 12 weeks at three clinical sites in the USA. The primary measure was the change from baseline in glucose kinetics with colesevelam compared to placebo treatment. Fasting and postprandial glucose, lipid and bile acid pathways were measured at baseline and post-treatment using stable isotope techniques. Plasma glucose, insulin, total glucagon-like peptide-1 (GLP-1), total glucose-dependent insulinotropic polypeptide (GIP), glucagon and fibroblast growth factor-19 (FGF-19) concentrations were measured during the fasting state and following a meal tolerance test. Data was collected by people blinded to treatment. RESULTS: Compared with placebo, colesevelam improved HbA(1c) (mean change from baseline of 0.3 [SD 1.1]% for placebo [n = 28] and -0.3 [1.1]% for colesevelam [n = 26]), glucose concentrations, fasting plasma glucose clearance and glycolytic disposal of oral glucose. Colesevelam did not affect gluconeogenesis or appearance rate (absorption) of oral glucose. Fasting endogenous glucose production and glycogenolysis significantly increased with placebo but were unchanged with colesevelam (treatment effect did not reach statistical significance). Compared with placebo, colesevelam increased total GLP-1 and GIP concentrations and improved HOMA-beta cell function while insulin, glucagon and HOMA-insulin resistance were unchanged. Colesevelam increased cholesterol and bile acid synthesis and decreased FGF-19 concentrations. However, no effect was seen on fractional hepatic de novo lipogenesis. CONCLUSIONS/INTERPRETATION: Colesevelam, a non-absorbed bile acid sequestrant, increased circulating incretins and improved tissue glucose metabolism in both the fasting and postprandial states in a manner different from other approved oral agents. TRIAL REGISTRATION: ClinicalTrials.gov NCT00596427 FUNDING: The study was funded by Daiichi Sankyo.
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Ácidos e Sais Biliares/química , Colesterol/metabolismo , Diabetes Mellitus Tipo 2/sangue , Glucose/metabolismo , Lipogênese , Fígado/metabolismo , Administração Oral , Adulto , Idoso , Alilamina/administração & dosagem , Alilamina/análogos & derivados , Anticolesterolemiantes/administração & dosagem , Glicemia/metabolismo , Cloridrato de Colesevelam , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Hemoglobinas Glicadas/biossíntese , Humanos , Insulina/metabolismo , Cinética , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Placebos , Período Pós-PrandialRESUMO
Estimates of genetic diversity represent a valuable resource for biodiversity assessments and are increasingly used to guide conservation and management programs. The most commonly reported estimates of DNA sequence diversity in animal populations are haplotype diversity (h) and nucleotide diversity (π) for the mitochondrial gene cytochrome c oxidase subunit I (cox1). However, several issues relevant to the comparison of h and π within and between studies remain to be assessed. We used population-level cox1 data from peer-reviewed publications to quantify the extent to which data sets can be re-assembled, to provide a standardized summary of h and π estimates, to explore the relationship between these metrics and to assess their sensitivity to under-sampling. Only 19 out of 42 selected publications had archived data that could be unambiguously re-assembled; this comprised 127 population-level data sets (n ≥ 15) from 23 animal species. Estimates of h and π were calculated using a 456-base region of cox1 that was common to all the data sets (median h=0.70130, median π=0.00356). Non-linear regression methods and Bayesian information criterion analysis revealed that the most parsimonious model describing the relationship between the estimates of h and π was π=0.0081 h(2). Deviations from this model can be used to detect outliers due to biological processes or methodological issues. Subsampling analyses indicated that samples of n>5 were sufficient to discriminate extremes of high from low population-level cox1 diversity, but samples of n ≥ 25 are recommended for greater accuracy.
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Ciclo-Oxigenase 1/genética , Variação Genética , Haplótipos , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Genética Populacional , Nucleotídeos/genéticaRESUMO
INTRODUCTION: Clinicians and patients must weigh the benefits of radiological imaging against the risks of radiation exposure in the diagnosis and treatment of scoliosis. This report aims to estimate the cumulative absorbed and equivalent dose of radiation in patients undergoing surgical treatment for scoliosis, and to present this as an estimated risk of cancer compared to background radiation levels. METHODS: Retrospective review of estimated absorbed dose on the Computerised Radiology Information System (CRIS®). Patients undergoing surgical correction of scoliosis (age ≤ 25) from August 2010 to August 2015 investigated. Estimated absorbed dose [milligrays (mGy)] recorded. Pedicle screws inserted using image intensification. Equivalent dose [millisieverts (mSv)] and additional cancer risk calculated from the National Research Council document 'Health risks from exposure to low levels of ionising radiation' (2006). RESULTS: 271 patients identified. Mean age 15 (range 2-25). Mean total absorbed dose 2136 mGy [standard deviation (SD) 1700 mGy]. Mean number of plain spine radiographs was 8 (SD 3) with total 1884 mGy exposure (SD 1609 mGy). Additional dose provided by CT (mean 0.17 episodes), plain chest and abdominal radiographs and image intensification. Mean number of image intensification episodes was 1.1 with mean estimated exposure 180 mGy (SD 238 mGy). Image intensification accounted for 8% of the estimated absorbed dose during treatment. Estimated mean effective dose delivered was 20.952 mSv equating to an additional cancer risk of 0.27-0.45%. CONCLUSION: Additional cancer risk from cumulative imaging is small and equivalent to approximately 8 years of natural background radiation. Use of image intensification for pedicle screw insertion is a minor contribution (8%) to the total patient dose.
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Neoplasias , Escoliose , Adolescente , Criança , Humanos , Doses de Radiação , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Tomografia Computadorizada por Raios X , Raios XRESUMO
The Antarctic krill, Euphausia superba, is an abundant and key species found in the Southern Ocean that forms dense, discrete swarms. Despite over three decades of research on Antarctic krill, the genetics of individual swarms is yet to be specifically investigated. In this study, we address the genetic diversity, population structure and demographic history of nine Antarctic krill swarms by sequencing 1173 bases of the gene cytochrome c oxidase subunit I (cox1, COI) from 504 individuals. Both haplotype diversity (h=0.9974-1.0000) and nucleotide diversity (pi=0.010275-0.011537) of Antarctic krill swarm samples was consistently high compared with populations of other species reported in the literature. Analysis of molecular variance did not show any significant genetic structure, thus implying that the sampled swarms do not appear to reflect discrete genetic units. Fu's Fs and Bayesian Skyride analyses provided strong evidence for a large increase in the population size of Antarctic krill, or selection favouring a particular mitochondrial lineage, within the last few 100,000 years (Pleistocene). The swarm-level results presented in this study not only further our understanding of Antarctic krill biology but, because of the economical importance of this species, also provide data to consider for future krill stock management.
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Complexo IV da Cadeia de Transporte de Elétrons/genética , Euphausiacea/genética , Variação Genética , Animais , Regiões Antárticas , Genética Populacional , População/genéticaRESUMO
Antarctic krill play an important role in biogeochemical cycles and can potentially generate high-particulate organic carbon (POC) fluxes to the deep ocean. They also have an unusual trait of moulting continuously throughout their life-cycle. We determine the krill seasonal contribution to POC flux in terms of faecal pellets (FP), exuviae and carcasses from sediment trap samples collected in the Southern Ocean. We found that krill moulting generated an exuviae flux of similar order to that of FP, together accounting for 87% of an annual POC flux (22.8 g m-2 y-1). Using an inverse modelling approach, we determined the krill population size necessary to generate this flux peaked at 261 g m-2. This study shows the important role of krill exuviae as a vector for POC flux. Since krill moulting cycle depends on temperature, our results highlight the sensitivity of POC flux to rapid regional environmental change.
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Ciclo do Carbono , Carbono/metabolismo , Euphausiacea/fisiologia , Muda/fisiologia , Animais , Biomassa , Geografia , Sedimentos Geológicos/química , Oceanos e Mares , Material Particulado/análise , Dinâmica Populacional , Estações do AnoRESUMO
In this article, we analyze the impacts of climate change on Antarctic marine ecosystems. Observations demonstrate large-scale changes in the physical variables and circulation of the Southern Ocean driven by warming, stratospheric ozone depletion, and a positive Southern Annular Mode. Alterations in the physical environment are driving change through all levels of Antarctic marine food webs, which differ regionally. The distributions of key species, such as Antarctic krill, are also changing. Differential responses among predators reflect differences in species ecology. The impacts of climate change on Antarctic biodiversity will likely vary for different communities and depend on species range. Coastal communities and those of sub-Antarctic islands, especially range-restricted endemic communities, will likely suffer the greatest negative consequences of climate change. Simultaneously, ecosystem services in the Southern Ocean will likely increase. Such decoupling of ecosystem services and endemic species will require consideration in the management of human activities such as fishing in Antarctic marine ecosystems.
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Mudança Climática , Ecossistema , Animais , Regiões Antárticas , Biodiversidade , Pesqueiros , Cadeia Alimentar , Humanos , Oceanos e Mares , Movimentos da ÁguaRESUMO
Earlier work from our laboratory provided evidence for myelin abnormalities (decreased quantities of proteins associated with myelin compaction, decreased sheath thickness) in cortex and hippocampus of Aldh5a1(-/-) mice, which have a complete ablation of the succinate semialdehyde dehydrogenase protein [E.A. Donarum, D.A. Stephan, K. Larkin, E.J. Murphy, M. Gupta, H. Senephansiri, R.C. Switzer, P.L. Pearl, O.C. Snead, C. Jakobs, K.M. Gibson, Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency, J. Inher. Metab. Dis. 29 (2006) 143-156]. In the current report, we have extended these findings via comprehensive analysis of brain phospholipid fractions, including quantitation of fatty acids in individual phospholipid subclasses and estimation of hexose-ceramide in Aldh5a1(-/-) brain. In comparison to wild-type littermates (Aldh5a1(+/+)), we detected a 20% reduction in the ethanolamine glycerophospholipid content of Aldh5a1(-/-)mice, while other brain phospholipids (choline glycerophospholipid, phosphatidylserine and phosphatidylinositol) were within normal limits. Analysis of individual fatty acids in each of these fractions revealed consistent alterations in n-3 fatty acids, primarily increased 22:6n-3 levels (docosahexaenoic acid; DHA). In the phosphatidyl serine fraction there were marked increases in the proportions of polyunsaturated fatty acids with corresponding decreases of monounsaturated fatty acids. Interestingly, the levels of hexose-ceramide (glucosyl- and galactosylceramide, principal myelin cerebrosides) were decreased in Aldh5a1(-/-) brain tissue (one-tailed t test, p=0.0449). The current results suggest that lipid and myelin abnormalities in this animal may contribute to the pathophysiology.
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Encéfalo/metabolismo , Ácidos Graxos/metabolismo , Bainha de Mielina/metabolismo , Fosfolipídeos/metabolismo , Succinato-Semialdeído Desidrogenase/metabolismo , Animais , Camundongos , Camundongos Knockout , Succinato-Semialdeído Desidrogenase/genéticaRESUMO
Enrichment of beef muscle with n-3 fatty acids (FA) is one means to introduce these FA into the diet, but ruminal biohydrogenation limits their bioavailability. To address this problem, we evaluated the ability of condensed tannin (quebracho), in the presence or absence of casein, to protect 18:3n-3 in flaxseed from hydrogenation by ruminal microbes in cattle using an in vitro fermentation approach coupled with evaluation in cattle in vivo. Treated and untreated flaxseed was incubated with bovine rumen fluid for 0 and 24 h. With tannin treated flaxseed, hydrogenation of 18:3n-3 was limited to only 13% over 24 h compared to 43% for untreated flaxseed, while addition of casein to the tannin added no additional protection. To determine if a similar level of protection would occur in vivo, we used two groups of five steers fed either a grain-based or forage-based diet. Five steers were given a grain-based diet during the trial and were fed either ground flaxseed or tannin treated flaxseed for 15 days prior to blood collection for plasma lipid fatty acid analysis. The forage fed steers followed the same regimen. Ingestion of tannin-treated flaxseed did not increase 18:3n-3 and 20:5n-3 in plasma neutral lipids as compared to non-treated flaxseed. Thus, we demonstrated that treating ground flaxseed with quebracho tannin is not useful for increasing 18:3n-3 in the neutral lipid of bovine blood plasma, and suggest caution when interpreting results from in vitro trials that test potential treatments for protecting fatty acids from hydrogenation by ruminal microbes.
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Linho/química , Rúmen/microbiologia , Ácido alfa-Linolênico/química , Ração Animal , Animais , Caseínas/química , Bovinos , Ácidos Graxos Ômega-3/química , Ácidos Graxos Ômega-3/metabolismo , Fermentação , Hidrogenação , Taninos/química , Ácido alfa-Linolênico/metabolismoRESUMO
The clinical course of patients with recently diagnosed early stage chronic lymphocytic leukemia (CLL) is highly variable. We examined the relationship between CLL-cell birth rate and treatment-free survival (TFS) in 97 patients with recently diagnosed, Rai stage 0-II CLL in a blinded, prospective study, using in vivo 2H2O labeling. Birth rates ranged from 0.07 to 1.31% new cells per day. With median follow-up of 4.0 years, 33 subjects (34%) required treatment by NCI criteria. High-birth rate was observed in 44% of subjects and was significantly associated with shorter TFS, unmutated IGHV status and expression of ZAP70 and of CD38. In multivariable modeling considering age, gender, Rai stage, expression of ZAP70 or CD38, IGHV mutation status and FISH cytogenetics, only CLL-cell birth rate and IGHV mutation status met criteria for inclusion. Hazard ratios were 3.51 (P=0.002) for high-birth rate and 4.93 (P<0.001) for unmutated IGHV. The association between elevated birth rate and shorter TFS was observed in subjects with either mutated or unmutated IGHVs, and the use of both markers was a better predictor of TFS than either parameter alone. Thus, an increased CLL birth rate in early stage disease is a strong predictor of disease progression and earlier treatment.
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Biomarcadores Tumorais/genética , Proliferação de Células , Leucemia Linfocítica Crônica de Células B/patologia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
We examined the ability of n-3 FA in flaxseed-supplemented rations to increase the n-3 FA content of bovine muscle. Two groups of animals were used in each of two separate trials: (i) Hereford steers supplemented (or not) with ground flaxseed (907 g/d) for 71 d, and (ii) Angus steers supplemented (or not) with ground flaxseed (454 g/d for 3 d followed by 907 g/d for 110 d). For the Hereford group, flaxseed-supplemented rations increased 18:3n-3 (4.0-fold), 20:5n-3 (1.4-fold), and 22:5n-3 (1.3-fold) mass as compared with the control, and increased total n-3 mass about 1.7-fold. When these data were expressed as mol%, the increase in 18:3n-3 was 3.3-fold and in 20:5n-3 was 1.3-fold in the phospholipid fraction, and 18:3n-3 was increased 4-fold in the neutral lipid fraction. For the Angus group, flaxseed ingestion increased masses and composition of n-3 FA similarly to that for the Herefords and doubled the total n-3 FA mass. The effect of cooking to a common degree of doneness on FA composition was determined using steaks from a third group of cattle, which were Angus steers. We demonstrated no adverse effects on FA composition by grilling steaks to an internal temperature of 64 degrees C. Because n-3 FA may affect gene expression, we used quantitative real-time reverse transcriptase-polymerase chain reaction to quantify the effect of feeding flaxseed on heart-FA binding protein, peroxisome proliferator activated receptor gamma (PPARgamma) and alpha (PPARalpha) gene expression in the muscle tissue. PPARgamma mRNA level was increased 2.7-fold in the flaxseed-fed Angus steers compared with the control. Thus, we demonstrate a significant increase in n-3 FA levels in bovine muscle from cattle fed rations supplemented with flaxseed and increased expression of genes that regulate lipid metabolism.
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Gorduras na Dieta/metabolismo , Ácidos Graxos Ômega-3/biossíntese , Ácidos Graxos Ômega-3/química , Linho/metabolismo , Músculo Esquelético/química , Sementes/metabolismo , Animais , Bovinos , Ácidos Graxos Ômega-3/metabolismo , Linho/química , Masculino , Músculo Esquelético/metabolismoRESUMO
C57BL/6 and Swiss Webster mice are used to study lipid metabolism, although differences in fatty acid uptake between these strains have not been reported. Using a steady state kinetic model, [1-(14)C]16:0, [1-(14)C]20:4n-6, or [1-(14)C]22:6n-3 was infused into awake, adult male mice and uptake into liver, heart, and brain determined. The integrated area of [1-(14)C]20:4n-6 in plasma was significantly increased in C57BL/6 mice, but [1-(14)C]16:0 and [1-(14)C]22:6n-3 were not different between groups. In heart, uptake of [1-(14)C]20:4n-6 was increased 1.7-fold in C57BL/6 mice. However, trafficking of [1-(14)C]22:6n-3 into the organic fraction of heart was significantly decreased 33 % in C57BL/6 mice. Although there were limited differences in fatty acid tracer trafficking in liver or brain, [1-(14)C]16:0 incorporation into liver neutral lipids was decreased 18 % in C57BL/6 mice. In heart, the amount of [1-(14)C]16:0 and [1-(14)C]22:6n-3 incorporated into total phospholipids were decreased 45 and 49 %, respectively, in C57BL/6 mice. This was accounted for by a 53 and 37 % decrease in [1-(14)C]16:0 and 44 and 52 % decrease in [1-(14)C]22:6n-3 entering ethanolamine glycerophospholipids and choline glycerophospholipids, respectively. In contrast, there was a significant increase in [1-(14)C]20:4n-6 esterification into all heart phospholipids of C57BL/6 mice. Although changes in uptake were limited to heart, several significant differences were found in fatty acid trafficking into heart, liver, and brain phospholipids. In summary, our data demonstrates differences in tissue fatty acid uptake and trafficking between mouse strains is an important consideration when carrying out fatty acid metabolic studies.
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Encéfalo/metabolismo , Ácidos Graxos/metabolismo , Fígado/metabolismo , Miocárdio/metabolismo , Animais , Ácido Araquidônico/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Esterificação , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Ácido Palmítico/metabolismo , Fosfolipídeos/metabolismoRESUMO
Astrocytes play a vital role in brain lipid metabolism; however the impact of the phenotypic shift in astrocytes to a reactive state on arachidonic acid metabolism is unknown. Therefore, we determined the impact of dibutyryl-cAMP (dBcAMP) treatment on radiolabeled arachidonic acid ([1-(14)C]20:4n-6) and palmitic acid ([1-(14)C]16:0) uptake and metabolism in primary cultured murine cortical astrocytes. In dBcAMP treated astrocytes, total [1-(14)C]20:4n-6 uptake was increased 1.9-fold compared to control, while total [1-(14)C]16:0 uptake was unaffected. Gene expression of long-chain acyl-CoA synthetases (Acsl), acyl-CoA hydrolase (Acot7), fatty acid binding protein(s) (Fabp) and alpha-synuclein (Snca) were determined using qRT-PCR. dBcAMP treatment increased expression of Acsl3 (4.8-fold) and Acsl4 (1.3-fold), which preferentially use [1-(14)C]20:4n-6 and are highly expressed in astrocytes, consistent with the increase in [1-(14)C]20:4n-6 uptake. However, expression of Fabp5 and Fabp7 were significantly reduced by 25% and 45%, respectively. Acot7 (20%) was also reduced, suggesting dBcAMP treatment favors acyl-CoA formation. dBcAMP treatment enhanced [1-(14)C]20:4n-6 (2.2-fold) and [1-(14)C]16:0 (1.6-fold) esterification into total phospholipids, but the greater esterification of [1-(14)C]20:4n-6 is consistent with the observed uptake through increased Acsl, but not Fabp expression. Although total [1-(14)C]16:0 uptake was not affected, there was a dramatic decrease in [1-(14)C]16:0 in the free fatty acid pool as esterification into the phospholipid pool was increased, which is consistent with the increase in Acsl3 and Acsl4 expression. In summary, our data demonstrates that dBcAMP treatment increases [1-(14)C]20:4n-6 uptake in astrocytes and this increase appears to be due to increased expression of Acsl3 and Acsl4 coupled with a reduction in Acot7 expression.