PubMed

Related Articles A coastal and an interior Douglas fir provenance exhibit different metabolic strategies to deal with drought stress. Tree Physiol. 2016 Feb;36(2):148-63 Authors: Du B, Jansen K, Kleiber A, Eiblmeier M, Kammerer B, Ensminger I, Gessler A, Rennenberg H, Kreuzwieser J Abstract Drought is a major environmental stress affecting growth and vitality of forest ecosystems. In the present study, foliar nitrogen (N) and carbon (C) metabolism of two Douglas fir (Pseudotsuga menziesii) provenances with assumed different drought tolerance were investigated. We worked with 1-year-old seedlings of the interior provenance Fehr Lake (FEHR) originating from a dry environment and the coastal provenance Snoqualmie (SNO) from a more humid origin. Total C and N, structural N and the concentrations of soluble protein, total amino acids (TAAs) and individual amino acids as well as the relative abundance of polar, low-molecular-weight metabolites including antioxidants were determined in current-year needles exposed either to 42 days of drought or to 42 days drought plus 14 days of rewatering. The seedlings reacted in a provenance-specific manner to drought stress. Coastal provenance SNO showed considerably increased contents of TAAs, which were caused by increased abundance of the quantitatively most important amino acids arginine, ornithine and lysine. Additionally, the polyamine putrescine accumulated exclusively in drought-stressed trees of this provenance. In contrast, the interior provenance FEHR showed the opposite response, i.e., drastically reduced concentrations of these amino acids. However, FEHR showed considerably increased contents of pyruvate-derived and aromatic amino acids, and also higher drought-induced levels of the antioxidants ascorbate and α-tocopherol. In response to drought, both provenances produced large amounts of carbohydrates, such as glucose and fructose, most likely as osmolytes that can readily be metabolized for protection against osmotic stress. We conclude that FEHR and SNO cope with drought stress in a provenance-specific manner: the coastal provenance SNO was mainly synthesizing N-based osmolytes, a reaction not observed in the interior provenance FEHR; instead, the latter increased the levels of scavengers of reactive oxygen species. Our results underline the importance of provenance-specific reactions to abiotic stress. PMID: 26491053 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic study of urinary polyamines in rat exposed to 915 MHz radiofrequency identification signal. Amino Acids. 2016 Jan;48(1):213-7 Authors: Paik MJ, Kim HS, Lee YS, Choi HD, Pack JK, Kim N, Ahn YH Abstract Metabolomic analysis of urinary polyamines (PAs) from rat exposed to 915 MHz radiofrequency identification (RFID) signal for 8 h/day for 2 weeks was performed by gas chromatography-mass spectrometry as N-ethoxycarbonyl/N-pentafluoropropionyl derivatives. Large alterations in nine PA levels including four aliphatic and five acetylated PAs were monitored in sham-exposed and RFID-exposed groups. Total PA and urinary levels of N (1)-acetylputrescine, N (1)-acetylcadaverine, putrescine, cadaverine, N (1)-acetylspermidine, N (8)-acetylspermidine, spermidine and spermine were reduced, whereas N (1)-acetylspermine was significantly increased after sham and RFID exposure compared with those before exposure. Their levels were normalized to the corresponding group means before exposure and then plotted into star symbol patterns. N (1)-Acetylspermine after RFID exposure was 54 % higher compared to the level before RFID exposure, while it was elevated by only 17 % in the sham group. The results suggest that 915 MHz RFID exposure may induce metabolic disturbance of PA. It may also elevate spermidine/spermine acetyltransferase (SSAT) activity. Thus, the present metabolic profiling combined with star pattern recognition method might be useful for understanding the complexity of biochemical events after exposure to RFID signal. PMID: 26319644 [PubMed - indexed for MEDLINE]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/11/02PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/11/01PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/10/30PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolic phenotyping of urine for discriminating alcohol-dependent from social drinkers and alcohol-naive subjects. Drug Alcohol Depend. 2016 Oct 18;169:80-84 Authors: Mostafa H, Amin AM, Teh CH, Murugaiyah V, Arif NH, Ibrahim B Abstract BACKGROUND: Alcohol-dependence (AD) is a ravaging public health and social problem. AD diagnosis depends on questionnaires and some biomarkers, which lack specificity and sensitivity, however, often leading to less precise diagnosis, as well as delaying treatment. This represents a great burden, not only on AD individuals but also on their families. Metabolomics using nuclear magnetic resonance spectroscopy (NMR) can provide novel techniques for the identification of novel biomarkers of AD. These putative biomarkers can facilitate early diagnosis of AD. OBJECTIVES: To identify novel biomarkers able to discriminate between alcohol-dependent, non-AD alcohol drinkers and controls using metabolomics. METHOD: Urine samples were collected from 30 alcohol-dependent persons who did not yet start AD treatment, 54 social drinkers and 60 controls, who were then analysed using NMR. Data analysis was done using multivariate analysis including principal component analysis (PCA) and orthogonal partial least square-discriminate analysis (OPLS-DA), followed by univariate and multivariate logistic regression to develop the discriminatory model. The reproducibility was done using intraclass correlation coefficient (ICC). RESULTS: The OPLS-DA revealed significant discrimination between AD and other groups with sensitivity 86.21%, specificity 97.25% and accuracy 94.93%. Six biomarkers were significantly associated with AD in the multivariate logistic regression model. These biomarkers were cis-aconitic acid, citric acid, alanine, lactic acid, 1,2-propanediol and 2-hydroxyisovaleric acid. The reproducibility of all biomarkers was excellent (0.81-1.0). CONCLUSION: This study revealed that metabolomics analysis of urine using NMR identified AD novel biomarkers which can discriminate AD from social drinkers and controls with high accuracy. PMID: 27788404 [PubMed - as supplied by publisher]

Assessment of key plasma metabolites in combat casualties. J Trauma Acute Care Surg. 2016 Oct 25; Authors: Lusczek ER, Muratore SL, Dubick MA, Beilman GJ Abstract BACKGROUND: Previous studies have indicated that hemorrhagic shock and injury cause significant early changes in metabolism. Recently, global changes in metabolism have been described using metabolomics in animal models and civilian trauma. We evaluated metabolic changes associated with combat injury to identify early biomarkers and aid in triage. METHODS: Plasma obtained at Emergency Department (ED) presentation and intervals thereafter from patients injured during combat operations in Iraq (n=78) were compared to healthy control subjects (n=40). Using proton Nuclear Magnetic Resonance, water-soluble metabolites were detected and quantified. Resulting metabolic profiles were analyzed with partial least squares discriminant analysis (PLS-DA), ROC, and cluster analyses to identify features of combat injury and mortality. RESULTS: Significant alterations to metabolism resulted from traumatic injury. Metabolic profiles of injured patients differed from those of healthy controls, driven by increased 5-aminolevulinate and hypoxanthine that persisted through 24 hours. Among combat-injured patients, increased succinate and malonate best discriminated between those who survived from those who did not. Higher levels of succinate and hypoxanthine were associated with increased injury severity. ROC analysis showed that these metabolites had equivalent or superior performance to lactate in distinguishing the presence of trauma, injury severity, and mortality. CONCLUSIONS: Combat injury is associated with several changes at the metabolic level compared to healthy individuals. Novel potential biomarkers of mortality (succinate, malonate), injury severity (succinate, hypoxanthine), and the presence of trauma (hypoxanthine, 5-aminolevulinate) perform as well as or better than the common clinical standard, lactate. LEVEL OF EVIDENCE: Level III STUDY TYPE: Prognostic. PMID: 27787435 [PubMed - as supplied by publisher]

Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors. Genes Immun. 2016 Oct 27;: Authors: Stoll ML, Kumar R, Lefkowitz EJ, Cron RQ, Morrow CD, Barnes S Abstract We have previously shown alterations in the composition of the gut microbiota in children with enthesitis-related arthritis (ERA). To explore the mechanisms by which an altered microbiota might predispose to arthritis, we performed metabolomic profiling of fecal samples of children with ERA. Fecal samples were collected from two cohorts of children with ERA and healthy control subjects. Nano-liquid chromatography-mass spectroscopy (LC-MS) was performed on the fecal water homogenates with identification based upon mass: charge ratios. Sequencing of the 16S ribosomal DNA (rDNA) on the same stool specimens was performed. In both sets of subjects, patients demonstrated lower diversity of ions and under-representation of multiple metabolic pathways, including the tryptophan metabolism pathway. For example, in the first cohort, out of 1500 negatively charged ions, 154 were lower in ERA patients, compared with only one that was higher. Imputed functional annotation of the 16S ribosomal DNA sequence data demonstrated significantly fewer microbial genes associated with metabolic processes in the patients compared with the controls (77 million versus 58 million, P=0.050). Diminished metabolic diversity and alterations in the tryptophan metabolism pathway may be a feature of ERA.Genes and Immunity advance online publication, 27 October 2016; doi:10.1038/gene.2016.38. PMID: 27786174 [PubMed - as supplied by publisher]

Related Articles Cardiovascular Risk Factors Associated with Blood Metabolite Concentrations and Their Alterations over a 4-Year Period in a Population-Based Cohort. Circ Cardiovasc Genet. 2016 Oct 26;: Authors: Lacruz ME, Kluttig A, Tiller D, Medenwald D, Giegling I, Rujescu D, Prehn C, Adamski J, Frantz S, Greiser KH, Emeny RT, Kastenmüller G, Haerting J Abstract BACKGROUND: -The effects of lifestyle risk-factors considered collectively on the human metabolism are so far unknown. We aim to investigate the association of these risk-factors with metabolites and their changes over 4 years. METHODS AND RESULTS: -163 metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45-83 at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lyso-phosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (BMI, alcohol consumption, smoking, diet and exercise). Multilevel or simple linear regression modelling adjusted for relevant covariates was used for the evaluation of cross-sectional and longitudinal associations respectively, multiple testing correction was based on false discovery rate. BMI, alcohol and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk-factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI, and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. CONCLUSIONS: -This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences. PMID: 27784734 [PubMed - as supplied by publisher]

Related Articles Preanalytics in urinalysis. Clin Biochem. 2016 Oct 23;: Authors: Delanghe JR, Speeckaert MM Abstract Urine contains an enormous amount of information. Well-standardized procedures for collection, transport, sample preparation and analysis should become the basis of an effective diagnostic strategy for urinalysis. As reproducibility of urinalysis has been greatly improved due to recent technological progress, preanalytical requirements of urinalysis have gained importance and have become stricter. Since the patients themselves often collect urine specimens, urinalysis is very susceptible to preanalytical issues. Various collection methods and inappropriate specimen transport can cause important preanalytical errors. In addition to the insurance of correct collection, the clinical laboratory should optimize transport and sample preservation. Errors due to variation in diuresis may be corrected by recalculating the results using dilution parameters (e.g. osmolality, creatinine, conductivity, urine density). Next to the use of a primary urine container, it is recommended to split the original urine sample into various smaller aliquots for morphological, microbiological and chemical analyses, decreasing the risk of contamination. The use of preservatives may be helpful for particular analytes. A universal urine preservative however does not exist. Preanalytical aspects are also of major importance for newer urinalysis applications (e.g. metabolomics). PMID: 27784640 [PubMed - as supplied by publisher]

Related Articles Gas chromatography/mass spectrometry-based urine metabolome study in children for inborn errors of metabolism: An Indian experience. Clin Biochem. 2016 Oct 23;: Authors: Hampe MH, Panaskar SN, Yadav AA, Ingale PW Abstract OBJECTIVE: The present study highlights the feasibility of gas chromatography/mass spectrometry (GC/MS)-based analysis for simultaneous detection of >200 marker metabolites in urine found in characteristic pattern in inborn errors of metabolism (IEM) in India. DESIGN AND METHODS: During this retrospective study conducted from July 2013 to January 2016, we collected urine specimens on filter papers from Indian children across the country along with relevant demographic and clinical data. The laboratory technique involved urease pretreatment followed by deproteinization, derivatization, and subsequent computer-aided analysis of organic acids, amino acids, fatty acids, and sugars by GC/MS, which enable chemical diagnosis of IEM. RESULTS: Totally 23,140 patients were investigated for IEM with an estimated frequency of about 1.40%, that is, 323 positive cases. Most frequent disorders observed were of primary lactic acidemia (27.2%) and organic acidemia (methylmalonic aciduria, glutaric acidemia type I, propionic aciduria, etc.) followed by aminoacidopathies (maple syrup urine disease, phenylketonuria, tyrosinemia, etc.). Furthermore, alkaptonuria, canavan disease, and 4-hydroxybutyric aciduria were also diagnosed. Prompt treatment following diagnosis led to a better outcome in a considerable number of patients. CONCLUSIONS: GC/MS with one-step metabolomics enables quick detection, accurate identification, and precise quantification of a wide range of urinary markers that may not be discovered using existing newborn screening programs. The technique is effective as a second-tier test to other established screening technologies, as well as one-step primary screening tool for a wide spectrum of IEM. PMID: 27784639 [PubMed - as supplied by publisher]

Related Articles Screening and verifying endometrial carcinoma diagnostic biomarkers based on a urine metabolomic profiling study using UPLC-Q-TOF/MS. Clin Chim Acta. 2016 Oct 23;: Authors: Shao X, Wang K, Liu X, Gu C, Zhang P, Xie J, Liu W, Sun L, Chen T, Li Y Abstract BACKGROUND: Endometrial carcinoma (EOC) is a gynecological disease with one of the highest worldwide incidences. Due to the lack of typical clinical symptoms and limited sensitive screening methods used to diagnose endometrial carcinoma, the disease is easily neglected before patients are aware of its presence. Therefore, EOC results in serious impacts on women's lives and health. We screened diagnostic biomarkers of EOC with a noninvasive method that compared healthy individuals and endometrial hyperplasia (EOH) patients. METHODS: The morning urine of 25 healthy individuals, 25 patients with EOC and 10 patients with EOH were analyzed using an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) platform. Metabolomics data were used to screen the different metabolites according to PCA and PLS-DA analyses. Furthermore, the screened biomarkers of the newly diagnosed EOC and EOH candidates and healthy individuals were verified using the predictive model of the support vector machine (SVM) to obtain EOC diagnostic biomarkers. RESULTS: An EOC diagnostic biomarker group was found according to the metabolomics method. Five diagnostic biomarkers, including porphobilinogen, acetylcysteine, N-acetylserine, urocanic acid and isobutyrylglycine, were significantly changed in the EOC patients. Among them, porphobilinogen and acetylcysteine were significantly down-regulated, while N-acetylserine, urocanic acid and isobutyrylglycine were significantly up-regulated. CONCLUSIONS: Disturbances in these biomarkers have negative impacts on the body's metabolic functioning. The EOC diagnostic biomarker group can provide a clinical reference for diagnosing EOC and insight into the diagnosis of other diseases in the clinic. PMID: 27784637 [PubMed - as supplied by publisher]

Recent advances in CE-MS coupling: Instrumentation, methodology, and applications. Electrophoresis. 2016 Oct 26;: Authors: Týčová A, Ledvina V, Klepárník K Abstract This review focuses on the latest development of microseparation electromigration methods in capillaries and microfluidic devices coupled with MS for detection and identification of important analytes. It is a continuation of the review article on the same topic by Kleparnik (Electrophoresis 2015, 36, 159-178). A wide selection of 161 relevant articles covers the literature published from June 2014 till May 2016. New improvements in the instrumentation and methodology of MS interfaced with capillary or microfluidic versions of zone electrophoresis, isotachophoresis, and isoelectric focusing are described in detail. The most frequently implemented MS ionization methods include electrospray ionization, matrix-assisted desorption/ionization and inductively coupled plasma ionization. Although the main attention is paid to the development of instrumentation and methodology, representative examples illustrate also applications in the proteomics, glycomics, metabolomics, biomarker research, forensics, pharmacology, food analysis, and single-cell analysis. The combinations of MS with capillary versions of electrochromatography, and micellar electrokinetic chromatography are not included. PMID: 27783411 [PubMed - as supplied by publisher]

Use of Ion Chromatography/Mass Spectrometry for Targeted Metabolite Profiling of Polar Organic Acids. Anal Chem. 2016 Oct 26; Authors: Petucci C, Zelenin A, Culver JA, Gabriel M, Kirkbride K, Christison TT, Gardell SJ Abstract Organic acids (OAs) serve as metabolites that play pivotal roles in a host of different metabolic and regulatory pathways. The polar nature of many OAs poses a challenge to their measurement using widely-practiced analytical methods. In this study, a targeted metabolomics method was developed using ion chromatography/triple quadrupole mass spectrometry (IC/MS) to quantitate 28 polar OAs with limits of quantitation ranging from 0.25-50 µM. The inter-day assay precisions ranged from 1-19%, with accuracies ranging from 82 to 115%. The IC/MS assay was used to quantitate OAs in quadriceps muscle from sedentary mice compared to fatigued mice subjected to either a low intensity, long duration (LILD) or high intensity, short duration (HISD) forced treadmill regimen. Among the OAs examined, significant differences were detected for hippuric acid, malic acid, fumaric acid, and 2-ketoglutaric acid between the sedentary and fatigued mice. In conclusion, the IC/MS method enabled the separation and quantitative survey of a broad range of polar OAs that are difficult to analyze by chromatographic techniques. PMID: 27782384 [PubMed - as supplied by publisher]

Detecting beer intake by unique metabolite patterns. J Proteome Res. 2016 Oct 26; Authors: Gürdeniz G, Jensen MG, Meier S, Bech L, Lund E, Dragsted LO Abstract Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and production process (i.e. pyro-glutamyl proline and 2-ethyl malate) were selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption. PMID: 27781435 [PubMed - as supplied by publisher]

Related Articles Analysis of Ca(2+) mediated signalling regulating Toxoplasma infectivity reveals complex relationships between key molecules. Cell Microbiol. 2016 Oct 26;: Authors: Stewart RJ, Whitehead L, Nijagal B, Sleebs BE, Lessene G, McConville MJ, Rogers KL, Tonkin CJ Abstract Host cell invasion, exit and parasite dissemination is critical to the pathogenesis of apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. These processes are regulated by intracellular Ca(2+) signalling although the temporal dynamics of Ca(2+) fluxes and down-stream second messenger pathways are poorly understood. Here we use a genetically encoded biosensor, GFP-Calmodulin-M13-6 (GCaMP6), to capture Ca(2+) flux in live Toxoplasma and investigate the role of Ca(2+) signalling in egress and motility. Our analysis determines how environmental cues and signal activation influence intracellular Ca(2+) flux, allowing placement of effector molecules within this pathway. Importantly, we have identified key interrelationships between cGMP and Ca(2+) signalling that are required for activation of egress and motility. Furthermore, we extend this analysis to show that the Ca(2+) Dependent Protein Kinases - TgCDPK1 and TgCDPK3 - play a role in signal quenching before egress. This work highlights the interrelationships of second messenger pathways of Toxoplasma in space and time, which is likely required for pathogenesis of all apicomplexan species. PMID: 27781359 [PubMed - as supplied by publisher]

Related Articles Effects of 14-day oral low dose selenium nanoparticles and selenite in rat-as determined by metabolite pattern determination. PeerJ. 2016;4:e2601 Authors: Hadrup N, Loeschner K, Skov K, Ravn-Haren G, Larsen EH, Mortensen A, Lam HR, Frandsen HL Abstract Selenium (Se) is an essential element with a small difference between physiological and toxic doses. To provide more effective and safe Se dosing regimens, as compared to dosing with ionic selenium, nanoparticle formulations have been developed. However, due to the nano-formulation, unexpected toxic effects may occur. We used metabolite pattern determination in urine to investigate biological and/or toxic effects in rats administered nanoparticles and for comparison included ionic selenium at an equimolar dose in the form of sodium selenite. Low doses of 10 and 100 fold the recommended human high level were employed to study the effects at borderline toxicity. Evaluations of all significantly changed putative metabolites, showed that Se nanoparticles and sodium selenite induced similar dose dependent changes of the metabolite pattern. Putative identified metabolites included increased decenedioic acid and hydroxydecanedioic acid for both Se formulations whereas dipeptides were only increased for selenite. These effects could reflect altered fatty acid and protein metabolism, respectively. PMID: 27781177 [PubMed - in process]

Related Articles Sucrose Non-Fermenting Related Kinase Enzyme Mediated Rho-Associated Kinase Signaling is Responsible for Cardiac Function. Circ Cardiovasc Genet. 2016 Oct 25;: Authors: Cossette SM, Bhute VJ, Bao X, Harmann LM, Horswill MA, Sinha I, Gastonguay A, Pooya S, Bordas M, Kumar SN, Mirza SP, Palecek S, Strande J, Ramchandran R Abstract BACKGROUND: -Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our lab has previously shown that sucrose non-fermenting related kinase (SNRK) enzyme, which belongs to the AMP-activated kinase (AMPK) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure, and death by 8-10 months. METHODS AND RESULTS: -We performed additional cardiac functional studies using echocardiography (ECHO), and identified further cardiac functional deficits in Snrk cmcKO mice. NMR-based metabolomics analysis identified key metabolic pathway deficits in SNRK knockdown cardiomyocytes (CMs) in vitro Specifically, metabolites involved in lipid metabolism and oxidative phosphorylation are altered and perturbations in these pathways can result in cardiac function deficits and heart failure. A phosphopeptide-based proteomic screen identified Rho-associated kinase (ROCK) as a putative substrate for SNRK and mass spec-based fragment analysis confirmed key amino acid residues on ROCK that are phosphorylated by SNRK. Western blot analysis on heart lysates from Snrk cmcKO adult mice and SNRK knockdown CMs showed increased ROCK activity. In addition, in vivo inhibition of ROCK partially rescued the in vivo Snrk cmcKO cardiac function deficits. CONCLUSIONS: -Collectively, our data suggests that SNRK in CMs is responsible for maintaining cardiac metabolic homeostasis, which is mediated in part by ROCK and alteration of this homeostasis influences cardiac function in the adult heart. PMID: 27780848 [PubMed - as supplied by publisher]

Related Articles Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2016 Oct 17;: Authors: Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G Abstract Immunogenicity depends on two key factors: antigenicity and adjuvanticity. The presence of exogenous or mutated antigens explains why infected cells and malignant cells can initiate an adaptive immune response provided that the cells also emit adjuvant signals as a consequence of cellular stress and death. Several infectious pathogens have devised strategies to control cell death and limit the emission of danger signals from dying cells, thereby avoiding immune recognition. Similarly, cancer cells often escape immunosurveillance owing to defects in the molecular machinery that underlies the release of endogenous adjuvants. Here, we review current knowledge on the mechanisms that underlie the activation of immune responses against dying cells and their pathophysiological relevance. PMID: 27748397 [PubMed - as supplied by publisher]

Related Articles Complete metabolome and lipidome analysis reveals novel biomarkers in the human diabetic corneal stroma. Exp Eye Res. 2016 Oct 11;153:90-100 Authors: Priyadarsini S, McKay TB, Sarker-Nag A, Allegood J, Chalfant C, Ma JX, Karamichos D Abstract Prolonged hyperglycemia during diabetes mellitus can cause severe ophthalmic complications affecting both the anterior and posterior ocular segments leading to impaired vision or blindness. Diabetes-induced corneal pathologies are associated with decreased wound healing capacity, corneal edema, and altered epithelial basement membrane. The mechanism by which diabetes modulates structure and function within the corneal stroma are unknown. In our study, we characterized the effects of diabetes on extracellular matrix, lipid transport, and cellular metabolism by defining the entire metabolome and lipidome of Type 1 and Type 2 human diabetic corneal stroma. Significant increases in Collagen I and III were found in diabetic corneas suggesting that diabetes promotes defects in matrix structure leading to scarring. Furthermore, increased lipid content, including sphingosine-1-phosphate and dihydrosphingosine, in diabetic corneas compared to healthy controls were measured suggesting altered lipid retention. Metabolomics analysis identified elevated tryptophan metabolites, independent of glucose metabolism, which correlated with upregulation of the Kynurenine pathway in diabetic corneas. We also found significant upregulation of novel biomarkers aminoadipic acid, D,L-pipecolic acid, and dihydroorotate. Our study links aberrant tryptophan metabolism to end-stage pathologies associated with diabetes indicating the potential of the Kynurenine pathway as a therapeutic target for inhibiting diabetes-associated defects in the eye. PMID: 27742548 [PubMed - as supplied by publisher]