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Find video protocols related to scientific articles indexed in Pubmed.
Energy Metabolic Re-Programming in the Hypertrophied and Early Stage Failing Heart: A Multi-systems Approach.
Circ Heart Fail
PUBLISHED: 09-18-2014
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-An unbiased systems approach was utilized to define energy metabolic events that occur during the pathologic cardiac remodeling en route to heart failure.
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SEX DIFFERENCES IN BIOMARKERS ASSOCIATED WITH INSULIN RESISTANCE IN OBESE ADOLESCENTS: METABOLOMIC PROFILING AND PRINCIPAL COMPONENTS ANALYSIS.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-10-2014
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OBJECTIVE Obesity and insulin resistance (IR) predispose to T2D. Yet only half of obese adolescents have IR and far fewer progress to T2D. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. RESEARCH DESIGN AND METHODS Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. Principal Components Analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: HOMA-IR, adiponectin, and triglyceride (TG)/HDL ratio. RESULTS Branched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (p<0.01) in males than females with comparable BMI-z. In multivariate analyses, HOMA-IR in males correlated positively with BMI-z and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines, and negatively with by-products of complete fatty acid oxidation (FAO, R(2)=0.659, p<0.0001). In contrast, only BMI-z correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric-acid (R(2)=0.268, p=0.0212) in males but not females. TG/HDL correlated with BMI-z and the BCAA signature in females but not males. CONCLUSIONS BCAA levels and by-products of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI-z. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG/HDL in females and inversely with adiponectin in males but not females. Likewise, byproducts of FAO associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity.
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Long-echo time MR spectroscopy for skeletal muscle acetylcarnitine detection.
J. Clin. Invest.
PUBLISHED: 08-28-2014
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Animal models suggest that acetylcarnitine production is essential for maintaining metabolic flexibility and insulin sensitivity. Because current methods to detect acetylcarnitine involve biopsy of the tissue of interest, noninvasive alternatives to measure acetylcarnitine concentrations could facilitate our understanding of its physiological relevance in humans. Here, we investigated the use of long-echo time (TE) proton magnetic resonance spectroscopy (1H-MRS) to measure skeletal muscle acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1H-MRS to measure acetylcarnitine in endurance-trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1H-MRS protocol was implemented for successful detection of skeletal muscle acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS (31P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle acetylcarnitine concentration showed a reciprocal distribution, with mean acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring acetylcarnitine concentrations with 1H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of acetylcarnitine, possibly underlying decreased insulin sensitivity.
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Extracting patterns of database and software usage from the bioinformatics literature.
Bioinformatics
PUBLISHED: 08-28-2014
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As a natural consequence of being a computer-based discipline, bioinformatics has a strong focus on database and software development, but the volume and variety of resources are growing at unprecedented rates. An audit of database and software usage patterns could help provide an overview of developments in bioinformatics and community common practice, and comparing the links between resources through time could demonstrate both the persistence of existing software and the emergence of new tools.
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Hepatic SRC-1 activity orchestrates transcriptional circuitries of amino acid pathways with potential relevance for human metabolic pathogenesis.
Mol. Endocrinol.
PUBLISHED: 08-22-2014
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Disturbances in amino acid metabolism are increasingly recognized as being associated with, and serving as prognostic markers for chronic human diseases, such as cancer or type 2 diabetes. In the current study, a quantitative metabolomics profiling strategy revealed global impairment in amino acid metabolism in mice deleted for the transcriptional coactivator steroid receptor coactivator (SRC)-1. Aberrations were hepatic in origin, because selective reexpression of SRC-1 in the liver of SRC-1 null mice largely restored amino acids concentrations to normal levels. Cistromic analysis of SRC-1 binding sites in hepatic tissues confirmed a prominent influence of this coregulator on transcriptional programs regulating amino acid metabolism. More specifically, SRC-1 markedly impacted tyrosine levels and was found to regulate the transcriptional activity of the tyrosine aminotransferase (TAT) gene, which encodes the rate-limiting enzyme of tyrosine catabolism. Consequently, SRC-1 null mice displayed low TAT expression and presented with hypertyrosinemia and corneal alterations, 2 clinical features observed in the human syndrome of TAT deficiency. A heterozygous missense variant of SRC-1 (p.P1272S) that is known to alter its coactivation potential, was found in patients harboring idiopathic tyrosinemia-like disorders and may therefore represent one risk factor for their clinical symptoms. Hence, we reinforce the concept that SRC-1 is a central factor in the fine orchestration of multiple pathways of intermediary metabolism, suggesting it as a potential therapeutic target that may be exploitable in human metabolic diseases and cancer.
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A pragmatic approach to measuring, monitoring and evaluating interventions for improved tuberculosis case detection.
Int Health
PUBLISHED: 08-06-2014
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The inability to detect all individuals with active tuberculosis has led to a growing interest in new approaches to improve case detection. Policy makers and program staff face important challenges measuring effectiveness of newly introduced interventions and reviewing feasibility of scaling-up successful approaches. While robust research will continue to be needed to document impact and influence policy, it may not always be feasible for all interventions and programmatic evidence is also critical to understand what can be expected in routine settings. The effects of interventions on early and improved tuberculosis detection can be documented through well-designed program evaluations. We present a pragmatic framework for evaluating and measuring the effect of improved case detection strategies using systematically collected intervention data in combination with routine tuberculosis notification data applying historical and contemporary controls. Standardized process evaluation and systematic documentation of program implementation design, cost and context will contribute to explaining observed levels of success and may help to identify conditions needed for success. Findings can then guide decisions on scale-up and replication in different target populations and settings.
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Republished: Society for Neuroscience in Anesthesiology and Critical Care expert consensus statement: Anesthetic management of endovascular treatment for acute ischemic stroke.
Stroke
PUBLISHED: 07-30-2014
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Literature on the anesthetic management of endovascular treatment of acute ischemic stroke (AIS) is limited. Anesthetic management during these procedures is still mostly dependent on individual or institutional preferences. Thus, the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a task force to provide expert consensus recommendations on anesthetic management of endovascular treatment of AIS. The task force conducted a systematic literature review (up to August 2012). Because of the limited number of research articles relating to this subject, the task force solicited opinions from experts in this area. The task force created a draft consensus statement based on the available data. Classes of recommendations and levels of evidence were assigned to articles specifically addressing anesthetic management during endovascular treatment of stroke using the standard American Heart Association evidence rating scheme. The draft consensus statement was reviewed by the Task Force, SNACC Executive Committee and representatives of Society of NeuroInterventional Surgery (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final document. For this consensus statement the anesthetic management of endovascular treatment of AIS was subdivided into 12 topics. Each topic includes a summary of available data followed by recommendations. This consensus statement is intended for use by individuals involved in the care of patients with acute ischemic stroke, such as anesthesiologists, interventional neuroradiologists, neurologists, neurointensivists and neurosurgeons.
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Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice.
J. Lipid Res.
PUBLISHED: 05-09-2014
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Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. The high-fat lard diet induces obesity and fatty liver in C57BL/6J mice and suppresses expression of the PPAR-target gene, FA elongase 5 (Elovl5). Elovl5 plays a key role in MUFA and PUFA synthesis. Increasing hepatic Elovl5 activity in obese mice lowered hepatic TGs and endoplasmic reticulum stress markers (X-box binding protein 1 and cAMP-dependent transcription factor 6?) and increased TG catabolism and fatty acyl carnitines. Increased hepatic Elovl5 activity did not increase hepatic capacity for ?-oxidation. Elovl5 effects on hepatic TG catabolism were linked to increased protein levels of adipocyte TG lipase (ATGL) and comparative gene identification 58 (CGI58). Elevated hepatic Elovl5 activity also induced the expression of some (pyruvate dehydrogenase kinase 4 and fibroblast growth factor 21), but not other cytochrome P450 4A10 (CYP4A10), PPAR-target genes. FA products of Elovl5 activity increased ATGL, but not CGI58, mRNA through PPAR?-dependent mechanisms in human HepG2 cells. Treatment of mouse AML12 hepatocytes with the PPAR? agonist (GW0742) decreased (14)C-18:2,n-6 in TGs but did not affect ?-oxidation. These studies establish that Elovl5 activity regulates hepatic levels of FAs controlling PPAR? activity, ATGL expression, and TG catabolism, but not FA oxidation.
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Functional recovery after moderate/severe traumatic brain injury: a role for cognitive reserve?
Neurology
PUBLISHED: 04-23-2014
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To evaluate the hypothesis that educational attainment, a marker of cognitive reserve, is a predictor of disability-free recovery (DFR) after moderate to severe traumatic brain injury (TBI).
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Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness.
Diabetologia
PUBLISHED: 04-10-2014
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Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms.
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Small vessel disease and the resting functional architecture of the brain.
J. Cereb. Blood Flow Metab.
PUBLISHED: 03-27-2014
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Small vessel disease (SVD) is linked to cognitive impairment and dementia, yet little is known regarding functional activation in patients with SVD. Resting fMRI recordings suggest reduced connectivity in prefrontal, parietal and cingulate nodes and reciprocally increased connectivity in cerebellum, alterations which predicted neuropsychological test performance. Together with diffusion tensor tensor imaging studies, these data support of a model of disrupted connectivity as a systems-level approach to the cognitive disturbances seen in SVD.
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Society for Neuroscience in Anesthesiology and Critical Care Expert consensus statement: anesthetic management of endovascular treatment for acute ischemic stroke*: endorsed by the Society of NeuroInterventional Surgery and the Neurocritical Care Society.
J Neurosurg Anesthesiol
PUBLISHED: 03-06-2014
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Literature on the anesthetic management of endovascular treatment of acute ischemic stroke (AIS) is limited. Anesthetic management during these procedures is still mostly dependent on individual or institutional preferences. Thus, the Society of Neuroscience in Anesthesiology and Critical Care (SNACC) created a task force to provide expert consensus recommendations on anesthetic management of endovascular treatment of AIS. The task force conducted a systematic literature review (up to August 2012). Because of the limited number of research articles relating to this subject, the task force solicited opinions from experts in this area. The task force created a draft consensus statement based on the available data. Classes of recommendations and levels of evidence were assigned to articles specifically addressing anesthetic management during endovascular treatment of stroke using the standard American Heart Association evidence rating scheme. The draft consensus statement was reviewed by the Task Force, SNACC Executive Committee and representatives of Society of NeuroInterventional Surgery (SNIS) and Neurocritical Care Society (NCS) reaching consensus on the final document. For this consensus statement the anesthetic management of endovascular treatment of AIS was subdivided into 12 topics. Each topic includes a summary of available data followed by recommendations. This consensus statement is intended for use by individuals involved in the care of patients with acute ischemic stroke, such as anesthesiologists, interventional neuroradiologists, neurologists, neurointensivists, and neurosurgeons.
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Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-27-2014
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Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment.
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MRI for coma emergence and recovery.
Curr Opin Crit Care
PUBLISHED: 02-18-2014
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Data from MRI can be used to generate detailed maps of central nervous system anatomy and functional activation. Here, we review new research that integrates advanced MRI acquisition and analysis to predict and track recovery following severe traumatic brain injury (TBI) or anoxic ischemic encephalopathy (AIE) following cardiac arrest.
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Targeted metabolomics connects thioredoxin-interacting protein (TXNIP) to mitochondrial fuel selection and regulation of specific oxidoreductase enzymes in skeletal muscle.
J. Biol. Chem.
PUBLISHED: 01-30-2014
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Thioredoxin-interacting protein (TXNIP) is an ?-arrestin family member involved in redox sensing and metabolic control. Growing evidence links TXNIP to mitochondrial function, but the molecular nature of this relationship has remained poorly defined. Herein, we employed targeted metabolomics and comprehensive bioenergetic analyses to evaluate oxidative metabolism and respiratory kinetics in mouse models of total body (TKO) and skeletal muscle-specific (TXNIP(SKM-/-)) Txnip deficiency. Compared with littermate controls, both TKO and TXNIP(SKM-/-) mice had reduced exercise tolerance in association with muscle-specific impairments in substrate oxidation. Oxidative insufficiencies in TXNIP null muscles were not due to perturbations in mitochondrial mass, the electron transport chain, or emission of reactive oxygen species. Instead, metabolic profiling analyses led to the discovery that TXNIP deficiency causes marked deficits in enzymes required for catabolism of branched chain amino acids, ketones, and lactate, along with more modest reductions in enzymes of ?-oxidation and the tricarboxylic acid cycle. The decrements in enzyme activity were accompanied by comparable deficits in protein abundance without changes in mRNA expression, implying dysregulation of protein synthesis or stability. Considering that TXNIP expression increases in response to starvation, diabetes, and exercise, these findings point to a novel role for TXNIP in coordinating mitochondrial fuel switching in response to nutrient availability.
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Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans.
Am. J. Clin. Nutr.
PUBLISHED: 01-15-2014
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Epidemiologic evidence has suggested that diets with a high ratio of palmitic acid (PA) to oleic acid (OA) increase risk of cardiovascular disease (CVD).
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Neurological examination of critically ill patients: a pragmatic approach. Report of an ESICM expert panel.
Intensive Care Med
PUBLISHED: 01-08-2014
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Many patients admitted to the intensive care unit (ICU) have pre-existing or acquired neurological disorders which significantly affect their short-term and long-term outcomes. The ESICM Neuro Intensive Care Section convened an expert panel to establish a pragmatic approach to neurological examination (NE) of the critically ill patient.
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The quality of methods reporting in parasitology experiments.
PLoS ONE
PUBLISHED: 01-01-2014
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There is a growing concern both inside and outside the scientific community over the lack of reproducibility of experiments. The depth and detail of reported methods are critical to the reproducibility of findings, but also for making it possible to compare and integrate data from different studies. In this study, we evaluated in detail the methods reporting in a comprehensive set of trypanosomiasis experiments that should enable valid reproduction, integration and comparison of research findings. We evaluated a subset of other parasitic (Leishmania, Toxoplasma, Plasmodium, Trichuris and Schistosoma) and non-parasitic (Mycobacterium) experimental infections in order to compare the quality of method reporting more generally. A systematic review using PubMed (2000-2012) of all publications describing gene expression in cells and animals infected with Trypanosoma spp was undertaken based on PRISMA guidelines; 23 papers were identified and included. We defined a checklist of essential parameters that should be reported and have scored the number of those parameters that are reported for each publication. Bibliometric parameters (impact factor, citations and h-index) were used to look for association between Journal and Author status and the quality of method reporting. Trichuriasis experiments achieved the highest scores and included the only paper to score 100% in all criteria. The mean of scores achieved by Trypanosoma articles through the checklist was 65.5% (range 32-90%). Bibliometric parameters were not correlated with the quality of method reporting (Spearman's rank correlation coefficient <-0.5; p>0.05). Our results indicate that the quality of methods reporting in experimental parasitology is a cause for concern and it has not improved over time, despite there being evidence that most of the assessed parameters do influence the results. We propose that our set of parameters be used as guidelines to improve the quality of the reporting of experimental infection models as a pre-requisite for integrating and comparing sets of data.
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The Software Ontology (SWO): a resource for reproducibility in biomedical data analysis, curation and digital preservation.
J Biomed Semantics
PUBLISHED: 01-01-2014
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Biomedical ontologists to date have concentrated on ontological descriptions of biomedical entities such as gene products and their attributes, phenotypes and so on. Recently, effort has diversified to descriptions of the laboratory investigations by which these entities were produced. However, much biological insight is gained from the analysis of the data produced from these investigations, and there is a lack of adequate descriptions of the wide range of software that are central to bioinformatics. We need to describe how data are analyzed for discovery, audit trails, provenance and reproducibility.
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Effects of HIV infection on the metabolic and hormonal status of children with severe acute malnutrition.
PLoS ONE
PUBLISHED: 01-01-2014
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HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood.
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A multi-site evaluation of innovative approaches to increase tuberculosis case notification: summary results.
PLoS ONE
PUBLISHED: 01-01-2014
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Globally, TB notifications have stagnated since 2007, and sputum smear positive notifications have been declining despite policies to improve case detection. We evaluate results of 28 interventions focused on improving TB case detection.
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Thematic series on biomedical ontologies in JBMS: challenges and new directions.
J Biomed Semantics
PUBLISHED: 01-01-2014
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Over the past 15 years, the biomedical research community has increased its efforts to produce ontologies encoding biomedical knowledge, and to provide the corresponding infrastructure to maintain them. As ontologies are becoming a central part of biological and biomedical research, a communication channel to publish frequent updates and latest developments on them would be an advantage. Here, we introduce the JBMS thematic series on Biomedical Ontologies. The aim of the series is to disseminate the latest developments in research on biomedical ontologies and provide a venue for publishing newly developed ontologies, updates to existing ontologies as well as methodological advances, and selected contributions from conferences and workshops. We aim to give this thematic series a central role in the exploration of ongoing research in biomedical ontologies and intend to work closely together with the research community towards this aim. Researchers and working groups are encouraged to provide feedback on novel developments and special topics to be integrated into the existing publication cycles.
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Race and sex differences in small-molecule metabolites and metabolic hormones in overweight and obese adults.
OMICS
PUBLISHED: 10-11-2013
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Abstract In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, p<0.0001), factor 6 (long-chain acylcarnitines, p<0.01), and factor 2 (medium-chain dicarboxylated acylcarnitines, p<0.0001) were higher in males vs. females; factor 6 levels were higher in Caucasians vs. African Americans (p<0.0001). Significant differences were also observed in hormones regulating body weight homeostasis. Among overweight/obese adults, there are significant race and sex differences in small-molecule metabolites and metabolic hormones; these differences may contribute to risk factor heterogeneity across race and sex subgroups and should be considered in future investigations with circulating metabolites and metabolic hormones.
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Pattern of Brain Injury in the Acute Setting of Human Septic Shock.
Crit Care
PUBLISHED: 09-18-2013
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Sepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change.
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SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks.
Cell Metab.
PUBLISHED: 08-29-2013
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Reversible posttranslational modifications are emerging as critical regulators of mitochondrial proteins and metabolism. Here, we use a label-free quantitative proteomic approach to characterize the lysine succinylome in liver mitochondria and its regulation by the desuccinylase SIRT5. A total of 1,190 unique sites were identified as succinylated, and 386 sites across 140 proteins representing several metabolic pathways including ?-oxidation and ketogenesis were significantly hypersuccinylated in Sirt5(-/-) animals. Loss of SIRT5 leads to accumulation of medium- and long-chain acylcarnitines and decreased ?-hydroxybutyrate production in vivo. In addition, we demonstrate that SIRT5 regulates succinylation of the rate-limiting ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) both in vivo and in vitro. Finally, mutation of hypersuccinylated residues K83 and K310 on HMGCS2 to glutamic acid strongly inhibits enzymatic activity. Taken together, these findings establish SIRT5 as a global regulator of lysine succinylation in mitochondria and present a mechanism for inhibition of ketogenesis through HMGCS2.
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Metabolomics reveals broad-scale metabolic perturbations in hyperglycemic mothers during pregnancy.
Diabetes Care
PUBLISHED: 08-29-2013
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OBJECTIVE To characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG). RESEARCH DESIGN AND METHODS We compared fasting serum from an oral glucose tolerance test at ?28 weeks gestation from 67 Northern European ancestry mothers from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with high (>90th percentile) FPG with 50 mothers with low (<10th percentile) FPG but comparable BMI. Metabolic data from biochemical analyses of conventional clinical metabolites, targeted mass spectrometry (MS)-based measurement of amino acids, and nontargeted gas chromatography/MS were subjected to per-metabolite analyses and collective pathway analyses using Unipathway annotation. RESULTS High-FPG mothers had a metabolic profile consistent with insulin resistance including higher triglycerides, 3-hydroxybutyrate, and amino acids including alanine, proline, and branched-chain amino acids (false discovery rate [FDR]-adjusted P < 0.05). Lower 1,5-anhydroglucitol in high-FPG mothers suggested recent hyperglycemic excursions (FDR-adjusted P < 0.05). Pathway analyses indicated differences in amino acid degradation pathways for the two groups (FDR-adjusted P < 0.05), consistent with population-based findings in nonpregnant populations. Exploratory analyses with newborn outcomes indicated positive associations for maternal triglycerides with neonatal sum of skinfolds and cord C-peptide and a negative association between maternal glycine and cord C-peptide (P < 0.05). CONCLUSIONS Metabolomics reveals perturbations in metabolism of major macronutrients and amino acid degradation pathways in high- versus low-FPG mothers.
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The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases.
BMC Bioinformatics
PUBLISHED: 07-21-2013
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Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics data repository for renal diseases.
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Three-dimensional whole-brain perfusion quantification using pseudo-continuous arterial spin labeling MRI at multiple post-labeling delays: accounting for both arterial transit time and impulse response function.
NMR Biomed
PUBLISHED: 06-17-2013
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Measurement of the cerebral blood flow (CBF) with whole-brain coverage is challenging in terms of both acquisition and quantitative analysis. In order to fit arterial spin labeling-based perfusion kinetic curves, an empirical three-parameter model which characterizes the effective impulse response function (IRF) is introduced, which allows the determination of CBF, the arterial transit time (ATT) and T1,eff . The accuracy and precision of the proposed model were compared with those of more complicated models with four or five parameters through Monte Carlo simulations. Pseudo-continuous arterial spin labeling images were acquired on a clinical 3-T scanner in 10 normal volunteers using a three-dimensional multi-shot gradient and spin echo scheme at multiple post-labeling delays to sample the kinetic curves. Voxel-wise fitting was performed using the three-parameter model and other models that contain two, four or five unknown parameters. For the two-parameter model, T1,eff values close to tissue and blood were assumed separately. Standard statistical analysis was conducted to compare these fitting models in various brain regions. The fitted results indicated that: (i) the estimated CBF values using the two-parameter model show appreciable dependence on the assumed T1,eff values; (ii) the proposed three-parameter model achieves the optimal balance between the goodness of fit and model complexity when compared among the models with explicit IRF fitting; (iii) both the two-parameter model using fixed blood T1 values for T1,eff and the three-parameter model provide reasonable fitting results. Using the proposed three-parameter model, the estimated CBF (46?±?14 mL/100 g/min) and ATT (1.4?±?0.3 s) values averaged from different brain regions are close to the literature reports; the estimated T1,eff values (1.9?±?0.4 s) are higher than the tissue T1 values, possibly reflecting a contribution from the microvascular arterial blood compartment.
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bioNerDS: exploring bioinformatics database and software use through literature mining.
BMC Bioinformatics
PUBLISHED: 06-11-2013
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Biology-focused databases and software define bioinformatics and their use is central to computational biology. In such a complex and dynamic field, it is of interest to understand what resources are available, which are used, how much they are used, and for what they are used. While scholarly literature surveys can provide some insights, large-scale computer-based approaches to identify mentions of bioinformatics databases and software from primary literature would automate systematic cataloguing, facilitate the monitoring of usage, and provide the foundations for the recovery of computational methods for analysing biological data, with the long-term aim of identifying best/common practice in different areas of biology.
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Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis.
J. Biol. Chem.
PUBLISHED: 04-03-2013
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The accumulation of long-chain fatty acids (LCFAs) in non-adipose tissues results in lipid-induced cytotoxicity (or lipoapoptosis). Lipoapoptosis has been proposed to play an important role in the pathogenesis of several metabolic diseases, including non-alcoholic fatty liver disease, diabetes mellitus, and cardiovascular disease. In this report, we demonstrate a novel role for caspase-2 as an initiator of lipoapoptosis. Using a metabolomics approach, we discovered that the activation of caspase-2, the initiator of apoptosis in Xenopus egg extracts, is associated with an accumulation of LCFA metabolites. Metabolic treatments that blocked the buildup of LCFAs potently inhibited caspase-2 activation, whereas adding back an LCFA in this scenario restored caspase activation. Extending these findings to mammalian cells, we show that caspase-2 was engaged and activated in response to treatment with the saturated LCFA palmitate. Down-regulation of caspase-2 significantly impaired cell death induced by saturated LCFAs, suggesting that caspase-2 plays a pivotal role in lipid-induced cytotoxicity. Together, these findings reveal a previously unknown role for caspase-2 as an initiator caspase in lipoapoptosis and suggest that caspase-2 may be an attractive therapeutic target for inhibiting pathological lipid-induced apoptosis.
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Prognosis in severe brain injury.
Crit. Care Med.
PUBLISHED: 03-27-2013
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The prediction of neurologic outcome is a fundamental concern in the resuscitation of patients with severe brain injury.
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Continuous electroencephalographic monitoring in critically ill patients: indications, limitations, and strategies.
Crit. Care Med.
PUBLISHED: 02-13-2013
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Continuous electroencephalography as a bedside monitor of cerebral activity has been used in a range of critically ill patients. This review compiles the indications, limitations, and strategies for continuous electroencephalography in the ICU.
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Significance of triphasic waves in patients with acute encephalopathy: a nine-year cohort study.
Clin Neurophysiol
PUBLISHED: 01-24-2013
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Triphasic waves (TWs) are a frequent electroencephalography (EEG) finding in encephalopathy, yet their origin and prognostic significance are not well understood. The aim of this study was to determine the clinical and EEG characteristics in encephalopathic patients with TWs. We hypothesized that specific EEG characteristics are predictive of outcome.
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Clinical review: Neuromonitoring - an update.
Crit Care
PUBLISHED: 01-15-2013
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ABSTRACT: Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required.
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Research resource: tissue- and pathway-specific metabolomic profiles of the steroid receptor coactivator (SRC) family.
Mol. Endocrinol.
PUBLISHED: 01-11-2013
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The rapidly growing family of transcriptional coregulators includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have emerged as important regulators of metabolic homeostasis, including the p160 steroid receptor coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis, fat absorption and storage in the liver, and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of the SRC family members, we performed targeted metabolomic analyses of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockouts (KOs) of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 KO mice and their wild-type littermates under fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC. Specifically, SRC-1 ablation revealed the most significant impact on hepatic metabolism, whereas SRC-2 appeared to impact cardiac metabolism. Conversely, ablation of SRC-3 primarily affected brain and skeletal muscle metabolism. Surprisingly, we identified very few metabolites that changed universally across the three SRC KO models. The findings of this Research Resource demonstrate that coactivator function has very limited metabolic redundancy even within the homologous SRC family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators.
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Proteasix: a tool for automated and large-scale prediction of proteases involved in naturally occurring peptide generation.
Proteomics
PUBLISHED: 01-09-2013
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In this study, we have developed Proteasix, an open-source peptide-centric tool that can be used to predict in silico the proteases involved in naturally occurring peptide generation. We developed a curated cleavage site (CS) database, containing 3500 entries about human protease/CS combinations. On top of this database, we built a tool, Proteasix, which allows CS retrieval and protease associations from a list of peptides. To establish the proof of concept of the approach, we used a list of 1388 peptides identified from human urine samples, and compared the prediction to the analysis of 1003 randomly generated amino acid sequences. Metalloprotease activity was predominantly involved in urinary peptide generation, and more particularly to peptides associated with extracellular matrix remodelling, compared to proteins from other origins. In comparison, random sequences returned almost no results, highlighting the specificity of the prediction. This study provides a tool that can facilitate linking of identified protein fragments to predicted protease activity, and therefore into presumed mechanisms of disease. Experiments are needed to confirm the in silico hypotheses; nevertheless, this approach may be of great help to better understand molecular mechanisms of disease, and define new biomarkers, and therapeutic targets.
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Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness.
Metab. Clin. Exp.
PUBLISHED: 01-06-2013
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To identify novel biomarkers through metabolomic profiles that distinguish metabolically well (MW) from metabolically unwell (MUW) individuals, independent of body mass index (BMI).
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Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects.
PLoS ONE
PUBLISHED: 01-01-2013
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Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5-phosphate (PLP) serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n?=?23) were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (<0.5 mg/d) to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD) to 21.5±4.6 nmol/L (P<0.0001) and increased cystathionine from 131±65 to 199±56 nmol/L (P<0.001). Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by (1)H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS). Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P<0.001) and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P<0.05). Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P<0.05), but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.
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The efficacy of intravenous patient-controlled analgesia after intracranial surgery of the posterior fossa: a prospective, randomized controlled trial.
Anesth. Analg.
PUBLISHED: 12-09-2011
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Surgery of the posterior fossa often produces intense postoperative pain. However, this pain is infrequently treated because of concern that opioid administration may mask the postoperative neurologic examination and/or produce hypercarbia. In this prospective, randomized controlled trial, we sought to determine whether IV patient-controlled analgesia (PCA) would lead to reductions in postoperative pain after neurosurgical procedures of the posterior fossa compared with conventional IV nurse-administered as-needed (PRN) therapy.
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Effect of heparin administration on metabolomic profiles in samples obtained during cardiac catheterization.
Circ Cardiovasc Genet
PUBLISHED: 10-18-2011
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Metabolic profiling holds promise for early detection of coronary artery disease and assessing risk for ischemic events. Heparin is frequently administered (1) to treat acute coronary syndromes; and (2) during routine cardiac catheterization procedures. Because it stimulates lipolysis, heparin is a potential confounder of metabolic profiling in these populations.
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An influenza N1 neuraminidase-specific monoclonal antibody with broad neuraminidase inhibition activity against H5N1 HPAI viruses.
Hum Vaccin
PUBLISHED: 09-20-2011
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H5N1 avian influenza continues to be a potential pandemic threat. Several vaccine candidates based on potentially pandemic influenza strains and antiviral drugs have been tested in preclinical and clinical studies. The data obtained so far have shown some promise, but have also revealed some shortcomings with both of these approaches. We have identified and characterized an H5N1 neuraminidasespecific monoclonal antibody which specifically inhibits N1 neuraminidase activity of highly pathogenic avian influenza (HPAI) strains from clades 1 and 2. We have also shown the protective efficacy of this antibody in animal challenge models using homologous virus. Specific and effective inhibition of N1 NA could make this mAb a useful therapeutic tool in the treatment of human infection, in particular with oseltamivirand zanamivir-resistant strains of HPAI.
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Using semantic web technologies to manage complexity and change in biomedical data.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 08-29-2011
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Data in biomedicine are characterised by their complexity, volatility and heterogeneity. It is these characteristics, rather than size of the data, that make managing these data an issue for their analysis. Any significant data analysis task requires gathering data from many places, organising the relationships between the datas entities and overcoming the issues of recognising the nature of each entity such that this organisation can take place. It is the inter-relationship of these data and the semantic confusion inherent in the data that make the data complex. On top of this we have volatility in the domains data, knowledge and experimental techniques that make the processing of data from the domain a distinct challenge, even before those data are organised. In this article we describe these challenges with respect to a project that is using data mining techniques to analyse data from the kidney and urinary pathway (KUP) domain. We are using Semantic Web technologies to manage the complexity and change in our data and we report on our experiences in this project.
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Walkable new urban LEED_Neighborhood-Development (LEED-ND) community design and childrens physical activity: selection, environmental, or catalyst effects?
Int J Behav Nutr Phys Act
PUBLISHED: 08-19-2011
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Interest is growing in physical activity-friendly community designs, but few tests exist of communities explicitly designed to be walkable. We test whether students living in a new urbanist community that is also a pilot LEED_ND (Leadership in Energy and Environmental Design-Neighborhood Development) community have greater accelerometer-measured moderate-to-vigorous physical activity (MVPA) across particular time periods compared to students from other communities. We test various time/place periods to see if the data best conform to one of three explanations for MVPA. Environmental effects suggest that MVPA occurs when individuals are exposed to activity-friendly settings; selection effects suggest that walkable community residents prefer MVPA, which leads to both their choice of a walkable community and their high levels of MVPA; catalyst effects occur when walking to school creates more MVPA, beyond the school commute, on schooldays but not weekends.
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Neurological complications of transplantation.
J Intensive Care Med
PUBLISHED: 07-19-2011
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Recipients of solid organ or hematopoietic cell transplants are at risk of life-threatening neurological disorders including encephalopathy, seizures, infections and tumors of the central nervous system, stroke, central pontine myelinolysis, and neuromuscular disorders-often requiring admission to, or occurring in, the intensive care unit (ICU). Many of these complications are linked directly or indirectly to immunosuppressive therapy. However, neurological disorders may also result from graft versus host disease, or be an expression of the underlying disease which prompted transplantation, as well as injury induced during radiation, chemotherapy, surgery, and ICU stay. In rare cases, neuroinfectious pathogens may be transmitted with the transplanted tissue or organ. Diagnosis may be a challenge because clinical symptoms and findings on neuroimaging lack specificity, and a biological specimen or tissue diagnosis is often needed for definitive diagnosis. Management is centered on preventing further neurological injury, etiology-targeted therapy, and balancing the benefits and toxicities of specific immunosuppressive agents.
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SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome.
Mol. Cell
PUBLISHED: 06-23-2011
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Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.
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Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system.
Diabetes
PUBLISHED: 05-20-2011
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Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism.
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Developing a kidney and urinary pathway knowledge base.
J Biomed Semantics
PUBLISHED: 05-17-2011
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Chronic renal disease is a global health problem. The identification of suitable biomarkers could facilitate early detection and diagnosis and allow better understanding of the underlying pathology. One of the challenges in meeting this goal is the necessary integration of experimental results from multiple biological levels for further analysis by data mining. Data integration in the life science is still a struggle, and many groups are looking to the benefits promised by the Semantic Web for data integration.
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Automating generation of textual class definitions from OWL to English.
J Biomed Semantics
PUBLISHED: 05-17-2011
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Text definitions for entities within bio-ontologies are a cornerstone of the effort to gain a consensus in understanding and usage of those ontologies. Writing these definitions is, however, a considerable effort and there is often a lag between specification of the main part of an ontology (logical descriptions and definitions of entities) and the development of the text-based definitions. The goal of natural language generation (NLG) from ontologies is to take the logical description of entities and generate fluent natural language. The application described here uses NLG to automatically provide text-based definitions from an ontology that has logical descriptions of its entities, so avoiding the bottleneck of authoring these definitions by hand.
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Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss.
Sci Transl Med
PUBLISHED: 04-29-2011
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Glycemic control is improved more after gastric bypass surgery (GBP) than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus. We applied metabolomic profiling to understand the mechanisms of this better metabolic response after GBP. Circulating amino acids (AAs) and acylcarnitines (ACs) were measured in plasma from fasted subjects by targeted tandem mass spectrometry before and after a matched 10-kilogram weight loss induced by GBP or diet. Total AAs and branched-chain AAs (BCAAs) decreased after GBP, but not after dietary intervention. Metabolites derived from BCAA oxidation also decreased only after GBP. Principal components (PC) analysis identified two major PCs, one composed almost exclusively of ACs (PC1) and another with BCAAs and their metabolites as major contributors (PC2). PC1 and PC2 were inversely correlated with pro-insulin concentrations, the C-peptide response to oral glucose, and the insulin sensitivity index after weight loss, whereas PC2 was uniquely correlated with levels of insulin resistance (HOMA-IR). These data suggest that the enhanced decrease in circulating AAs after GBP occurs by mechanisms other than weight loss and may contribute to the better improvement in glucose homeostasis observed with the surgical intervention.
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Comparison of bulbar and mucosal olfactory ensheathing cells using FACS and simultaneous antigenic bivariate cell cycle analysis.
Glia
PUBLISHED: 04-08-2011
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Transplantation of olfactory ensheathing cells (OECs) is a promising route for CNS repair. There have, however, been major discrepancies between the results from different groups. Part of this can be attributed to variations in cell sources and culture protocols. Accurate estimation of the proportions of OECs and their associated fibroblasts (ONFs) and their evolution with time in culture is an essential baseline for establishing the reparative properties of transplants. In this study, we compare the evolution of cultures from the superficial layers of the olfactory bulb with tissue from the olfactory mucosa, both whole and split into lamina propria and epithelial layer. We used FACS based on p75 and Thy1 to provide a robust and objective numerical estimate of the numbers of OECs and ONFs, respectively in the cultures. A novel four color simultaneous antigenic bivariate cell cycle analysis shows that proliferation of OECs is time-limited, and is unable to prevent an overall loss of OECs with time. Overall, the numbers of OECs in the cultures were inversely correlated with the deposition of fibronectin (FN). Further, culture of the cells purified by flow cytometry shows that, whereas the Thy1 population is terminally differentiated, the p75 population from the mucosal samples generates subpopulations with different antigenic phenotypes, including the reappearance of a subpopulation of p75 cells expressing FN. Culturing epithelial samples at high density reveals an unexpected transient stem cell-like population of rapidly proliferating p75 positive cells.
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Physiological origin for the BOLD poststimulus undershoot in human brain: vascular compliance versus oxygen metabolism.
J. Cereb. Blood Flow Metab.
PUBLISHED: 04-06-2011
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The poststimulus blood oxygenation level-dependent (BOLD) undershoot has been attributed to two main plausible origins: delayed vascular compliance based on delayed cerebral blood volume (CBV) recovery and a sustained increased oxygen metabolism after stimulus cessation. To investigate these contributions, multimodal functional magnetic resonance imaging was employed to monitor responses of BOLD, cerebral blood flow (CBF), total CBV, and arterial CBV (CBV(a)) in human visual cortex after brief breath hold and visual stimulation. In visual experiments, after stimulus cessation, CBV(a) was restored to baseline in 7.9±3.4?seconds, and CBF and CBV in 14.8±5.0?seconds and 16.1±5.8?seconds, respectively, all significantly faster than BOLD signal recovery after undershoot (28.1±5.5?seconds). During the BOLD undershoot, postarterial CBV (CBV(pa), capillaries and venules) was slightly elevated (2.4±1.8%), and cerebral metabolic rate of oxygen (CMRO(2)) was above baseline (10.6±7.4%). Following breath hold, however, CBF, CBV, CBV(a) and BOLD signals all returned to baseline in ?20?seconds. No significant BOLD undershoot, and residual CBV(pa) dilation were observed, and CMRO(2) did not substantially differ from baseline. These data suggest that both delayed CBV(pa) recovery and enduring increased oxidative metabolism impact the BOLD undershoot. Using a biophysical model, their relative contributions were estimated to be 19.7±15.9% and 78.7±18.6%, respectively.
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Time use choices and healthy body weight: a multivariate analysis of data from the American Time Use Survey.
Int J Behav Nutr Phys Act
PUBLISHED: 03-17-2011
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We examine the relationship between time use choices and healthy body weight as measured by survey respondents body mass index (BMI). Using data from the 2006 and 2007 American Time Use Surveys, we expand upon earlier research by including more detailed measures of time spent eating as well as measures of physical activity time and sedentary time. We also estimate three alternative models that relate time use to BMI.
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A clinical description of extubation failure in patients with primary brain injury.
Neurocrit Care
PUBLISHED: 03-12-2011
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Patients with acute brain injury but normal lung function are often intubated for airway protection, but extubation often fails. Currently, no clinical data exist that describe the events leading to extubation failure in this population. We examined the extubation failure rate, reintubation rate, and clinical characteristics of patients whose reason for intubation was a primary neurological injury. We then identified the clinical characteristics of those patients with primary brain injury who were reintubated.
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Mining semantic networks of bioinformatics e-resources from the literature.
J Biomed Semantics
PUBLISHED: 03-07-2011
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There have been a number of recent efforts (e.g. BioCatalogue, BioMoby) to systematically catalogue bioinformatics tools, services and datasets. These efforts rely on manual curation, making it difficult to cope with the huge influx of various electronic resources that have been provided by the bioinformatics community. We present a text mining approach that utilises the literature to automatically extract descriptions and semantically profile bioinformatics resources to make them available for resource discovery and exploration through semantic networks that contain related resources.
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Plasma acylcarnitines are associated with physical performance in elderly men.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 03-02-2011
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Metabolic profiling might provide insight into the biologic underpinnings of disability in older adults.
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Hyperglycaemia and apoptosis of microglial cells in human septic shock.
Crit Care
PUBLISHED: 02-15-2011
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The effect of hyperglycaemia on the brain cells of septic shock patients is unknown. The objective of this study was to evaluate the relationship between hyperglycaemia and apoptosis in the brains of septic shock patients.
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Delirium in the ICU: time to probe the hard questions.
Crit Care
PUBLISHED: 02-04-2011
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Prevalent in critically ill patients, delirium remains poorly understood and difficult to treat. In a cross-sectional study conducted in 12 countries, delirium was identified in close to one third of patients and was independently associated with increased mortality. While such epidemiological accounts represent an important cornerstone for research, scientific efforts are needed to elucidate the causes of delirium and the mechanisms underlying its association with poor outcomes.
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Hormonal status in protracted critical illness and in-hospital mortality.
Crit Care
PUBLISHED: 02-03-2011
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The aim of this study was to determine the relationship between hormonal status and mortality in patients with protracted critical illness.
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Acylcarnitines: analysis in plasma and whole blood using tandem mass spectrometry.
Methods Mol. Biol.
PUBLISHED: 01-06-2011
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The acylcarnitine profile is a diagnostic test for inherited disorders of fatty acid and branched-chain amino acid catabolism. Patients with this type of metabolic disorder accumulate disease-specific acylcarnitines that correlate with the acyl coenzyme A compounds in the affected mitochondrial metabolic pathways. For example, propionylcarnitine accumulates in patients with both propionic and methylmalonic acidemias. The test identifies and quantifies the species of acylcarnitines in the whole blood or blood plasma of patients at risk for or suspected of having such a disorder. The acylcarnitines are analyzed using electrospray ionization-tandem mass spectrometry. The instrument is used in the precursor ion scan mode to record the molecular species giving rise to fragment ions at m/z 99, derived specifically from the methylated acylcarnitines within the specimen. Quantification is based on the principle of stable isotope dilution, whereby concentrations are derived from the response ratio of each acylcarnitine species to that of a deuterium-labeled acylcarnitine standard. Interpretation of the acylcarnitine profile requires recognition of abnormal concentrations of specific analytes or patterns of analytes and knowledge of their metabolic origin.
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Effect of caloric restriction with and without exercise on metabolic intermediates in nonobese men and women.
J. Clin. Endocrinol. Metab.
PUBLISHED: 12-01-2010
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The objective of the study was to evaluate whether serum concentrations of metabolic intermediates are related to adiposity and insulin sensitivity (Si) in overweight healthy subjects and compare changes in metabolic intermediates with similar weight loss achieved by diet only or diet plus exercise.
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Exercise-induced changes in metabolic intermediates, hormones, and inflammatory markers associated with improvements in insulin sensitivity.
Diabetes Care
PUBLISHED: 10-04-2010
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To understand relationships between exercise training-mediated improvements in insulin sensitivity (S(I)) and changes in circulating concentrations of metabolic intermediates, hormones, and inflammatory mediators.
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Septic-associated encephalopathy--everything starts at a microlevel.
Crit Care
PUBLISHED: 09-29-2010
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Sepsis-associated encephalopathy is associated with increased mortality and morbidity. Its pathophysiology remains insufficiently elucidated, although there is evidence for a neuroinflammatory process sequentially involving endothelial activation, blood-brain barrier alteration and cellular dysfunction and alteration in neurotransmission. Experimental studies have shown that microcirculatory dysfunction, a consequence of endothelial activation, is an early pathogenic step. To date, we do not know whether it is present in septic patients, whether it accounts for clinical features and whether it is treatable.
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Acute liver failure: a management challenge for the practicing gastroenterologist.
Gastroenterol Hepatol (N Y)
PUBLISHED: 09-10-2010
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Although comprising a minority of the transplant population, acute liver failure (ALF) patients represent some of the most challenging cases in terms of the level and complexity of care required. An ALF patient requires much more than a single skilled intensivist, gastroenterologist, or surgeon. Successful care of the ALF patient begins with early diagnosis and triage to the appropriate level of care where a multitude of specialties are required to work together to maximize the chance of recovery and/or extend the window of opportunity for transplant.
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Short-term effects of dietary fatty acids on muscle lipid composition and serum acylcarnitine profile in human subjects.
Obesity (Silver Spring)
PUBLISHED: 06-17-2010
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In cultured cells, palmitic acid (PA) and oleic acid (OA) confer distinct metabolic effects, yet, unclear, is whether changes in dietary fat intake impact cellular fatty acid (FA) composition. We hypothesized that short-term increases in dietary PA or OA would result in corresponding changes in the FA composition of skeletal muscle diacylglycerol (DAG) and triacylglycerol (TAG) and/or the specific FA selected for ?-oxidation. Healthy males (N = 12) and females (N = 12) ingested a low-PA diet for 7 days. After fasting measurements of the serum acylcarnitine (AC) profile, subjects were randomized to either high-PA (HI PA) or low-PA/high-OA (HI OA) diets. After 7 days, the fasting AC measurement was repeated and a muscle/fat biopsy obtained. FA composition of intramyocellular DAG and TAG and serum AC was measured. HI PA increased, whereas HI OA decreased, serum concentration of 16:0 AC (P < 0.001). HI OA increased 18:1 AC (P = 0.005). HI PA was associated with a higher PA/OA ratio in muscle DAG and TAG (DAG: 1.03 ± 0.24 vs. 0.46 ± 0.08, P = 0.04; TAG: 0.63 ± 0.07 vs. 0.41 ± 0.03, P = 0.01). The PA concentration in the adipose tissue DAG (µg/mg adipose tissue) was 0.17 ± 0.02 in those receiving the HI PA diet (n = 6), compared to 0.11 ± 0.02 in the HI OA group (n = 4) (P = 0.067). The relative PA concentration in muscle DAG and TAG and the serum palmitoylcarnitine concentration was higher in those fed the high-PA diet.
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Further developments towards a genome-scale metabolic model of yeast.
BMC Syst Biol
PUBLISHED: 06-02-2010
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To date, several genome-scale network reconstructions have been used to describe the metabolism of the yeast Saccharomyces cerevisiae, each differing in scope and content. The recent community-driven reconstruction, while rigorously evidenced and well annotated, under-represented metabolite transport, lipid metabolism and other pathways, and was not amenable to constraint-based analyses because of lack of pathway connectivity.
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Adding a little reality to building ontologies for biology.
PLoS ONE
PUBLISHED: 05-27-2010
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Many areas of biology are open to mathematical and computational modelling. The application of discrete, logical formalisms defines the field of biomedical ontologies. Ontologies have been put to many uses in bioinformatics. The most widespread is for description of entities about which data have been collected, allowing integration and analysis across multiple resources. There are now over 60 ontologies in active use, increasingly developed as large, international collaborations. There are, however, many opinions on how ontologies should be authored; that is, what is appropriate for representation. Recently, a common opinion has been the "realist" approach that places restrictions upon the style of modelling considered to be appropriate.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.