PubMed

Metabolic responses of clams, Ruditapes decussatus and Ruditapes philippinarum, to short-term exposure to lead and zinc. Mar Pollut Bull. 2016 Apr 5; Authors: Aru V, Sarais G, Savorani F, Engelsen SB, Cesare Marincola F Abstract This study investigated the effects of 48h heavy metal exposure upon the metabolic profiles of Ruditapes decussatus and Ruditapes philippinarum using (1)H NMR metabolomics. Both species were exposed to increasing concentrations of lead nitrate (10, 40, 60 and 100μg/L) and zinc chloride (20, 50, 100 and 150μg/L), under laboratory conditions. ICP-OES analysis was further performed on the clams' samples in order to verify the occurrence of heavy metal bioaccumulation. With respect to the controls, the metabolic profiles of treated R. decussatus exhibited higher levels of organic osmolytes and lower contents of free amino acids. An opposite behavior was shown by R. philippinarum. In terms of heavy metal, the exposure effects were more evident in the case of Pb rather than Zn. These findings show that NMR-based metabolomics has the required sensitivity and specificity for the identification of metabolites that can act as sensitive indicators of contaminant-induced stress. PMID: 27058966 [PubMed - as supplied by publisher]

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 2016/04/09PubMed 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.

Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever. PLoS Negl Trop Dis. 2016 Apr;10(4):e0004607 Authors: Cui L, Lee YH, Thein TL, Fang J, Pang J, Ooi EE, Leo YS, Ong CN, Tannenbaum SR Abstract Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism-serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved the prognosis performance (AUC = 0.92, sensitivity = 77.8%, specificity = 95.8%), suggesting this duplex panel as accurate metrics for the early prognosis of DHF. PMID: 27055163 [PubMed - as supplied by publisher]

Effects of petrochemical contamination on caged marine mussels using a multi-biomarker approach: Histological changes, neurotoxicity and hypoxic stress. Mar Environ Res. 2016 Mar 31; Authors: Maisano M, Cappello T, Natalotto A, Vitale V, Parrino V, Giannetto A, Oliva S, Mancini G, Cappello S, Mauceri A, Fasulo S Abstract This work was designed to evaluate the biological effects of petrochemical contamination on marine mussels. Mytilus galloprovincialis, widely used as sentinel organisms in biomonitoring studies, were caged at the "Augusta-Melilli-Priolo" industrial site (eastern Sicily, Italy), chosen as one of the largest petrochemical areas in Europe, and Brucoli, chosen as reference site. Chemical analyses of sediments at the polluted site revealed high levels of PAHs and mercury, exceeding the national and international guideline limits. In mussels from the polluted site, severe morphological alterations were observed in gills, mainly involved in nutrient uptake and gas exchange. Changes in serotonergic and cholinergic systems, investigated through immunohistochemical, metabolomics and enzymatic approaches, were highlighted in gills, as well as onset of hypoxic adaptive responses with up-regulation of hypoxia-inducible factor transcript. Overall, the application of a multi-biomarker panel results effective in assessing the biological effects of petrochemical contamination on the health of aquatic organisms. PMID: 27053509 [PubMed - as supplied by publisher]

Evaluation of 2,4-dichlorophenol exposure of Japanese medaka, Oryzias latipes, using a metabolomics approach. Environ Sci Pollut Res Int. 2016 Apr 7; Authors: Kokushi E, Shintoyo A, Koyama J, Uno S Abstract In this study, the metabolic effects of waterborne exposure of medaka (Oryzias latipes) to nominal concentrations of 20 (L group) and 2000 μg/L (H group) 2,4-dichlorophenol (DCP) were examined using a gas chromatography/mass spectroscopy (GC/MS) metabolomics approach. A principal component analysis (PCA) separated the L, H, and control groups along PC1 to explain the toxic effects of DCP at 24 h of exposure. Furthermore, the L and H groups were separated along PC1 at 96 h on the PCA score plots. These results suggest that the effects of DCP depended on exposure concentration and time. Changes in tricarboxylic cycle metabolites suggested that fish exposed to 2,4-DCP require more energy to metabolize and eliminate DCP, particularly at 96 h of exposure. A time-dependent response in the fish exposed to DCP was observed in the GC/MS data, suggesting that the higher DCP concentration had greater effects at 24 h than those observed in response to the lower concentration. In addition, several essential amino acids (arginine, histidine, lysine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, and valine) decreased after DCP exposure in the H group, and starvation condition and high concentration exposure of DCP could consume excess energy from amino acids. PMID: 27053050 [PubMed - as supplied by publisher]

Reply to the commentary by Law and Han: the importance of suitable GC-MS date processing and analysis for plant and environmental metabolomics, with references to: changes in the abundance of sugars and sugar-like compounds in tall fescue (Festuca arundinacea) due to growth in naphthalene-treated sand. Environ Sci Pollut Res Int. 2016 Apr 7; Authors: Balasubramaniyam A, Harvey PJ PMID: 27053046 [PubMed - as supplied by publisher]

HDL functionality in South Asians as compared to white Caucasians. Nutr Metab Cardiovasc Dis. 2016 Feb 19; Authors: Bakker LE, Boon MR, Annema W, Dikkers A, van Eyk HJ, Verhoeven A, Mayboroda OA, Jukema JW, Havekes LM, Meinders AE, Willems van Dijk K, Jazet IM, Tietge UJ, Rensen PC Abstract BACKGROUND AND AIMS: South Asians have an exceptionally high risk of developing cardiovascular disease compared to white Caucasians. A contributing factor might be dysfunction of high density lipoprotein (HDL). We aimed to compare HDL function in different age groups of both ethnicities. METHODS AND RESULTS: HDL functionality with respect to cholesterol efflux, anti-oxidation and anti-inflammation was determined using fasting, apoB-depleted, plasma samples from South Asian and white Caucasian neonates (n = 14 each), adolescent healthy men (n = 12 each, 18-25 y), and adult overweight men (n = 12 each, 40-50 y). Adolescents were subjected to a 5-day high fat high calorie diet (HCD) and adults to an 8-day very low calorie diet (LCD). Additionally, HDL composition was measured in adolescents and adults using (1)H-NMR spectroscopy. Anti-oxidative capacity was lower in South Asian adults before LCD (19.4 ± 2.1 vs. 25.8 ± 1.2%, p = 0.045, 95%-CI = [0.1; 12.7]) and after LCD (16.4 ± 2.4 vs. 27.6 ± 2.7%, p = 0.001, 95%-CI = [4.9; 17.5]). Anti-inflammatory capacity was reduced in South Asian neonates (23.8 ± 1.2 vs. 34.9 ± 1.3%, p = 0.000001, 95%-CI = [-14.6; -7.5]), and was negatively affected by an 8-day LCD only in South Asian adults (-12.2 ± 4.3%, p = 0.005, 95%-CI = [-5.9; -1.2]). Cholesterol efflux capacity was increased in response to HCD in adolescents (South Asians: +6.3 ± 2.9%, p = 0.073, 95%-CI = [-0.02; 0.46], Caucasians: +11.8 ± 3.4%, p = 0.002, 95%-CI = [0.17;0.65]) and decreased after LCD in adults (South Asians: -10.3 ± 2.4%, p < 0.001, 95%-CI = [-0.57; -0.20], Caucasians: -13.7 ± 1.9%, p < 0.00001, 95%-CI = [-0.67; -0.33]). Although subclass analyses of HDL showed no differences between ethnicities, cholesterol efflux correlated best with cholesterol and phospholipid within small HDL compared to other HDL subclasses and constituents. CONCLUSION: Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. CLINICAL TRIAL REGISTRATION: NTR 2473 (URL: http://www.trialregister.nl/). PMID: 27052926 [PubMed - as supplied by publisher]

Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. J Nutr. 2016 Apr 6; Authors: Trammell SA, Yu L, Redpath P, Migaud ME, Brenner C Abstract BACKGROUND: Nicotinamide riboside (NR) is a recently discovered NAD(+)precursor vitamin with a unique biosynthetic pathway. Although the presence of NR in cow milk has been known for more than a decade, the concentration of NR with respect to the other NAD(+)precursors was unknown. OBJECTIVE: We aimed to determine NAD(+)precursor vitamin concentration in raw samples of milk from individual cows and from commercially available cow milk. METHODS: LC tandem mass spectrometry and isotope dilution technologies were used to quantify NAD(+)precursor vitamin concentration and to measure NR stability in raw and commercial milk. Nuclear magnetic resonance (NMR) spectroscopy was used to test for NR binding to substances in milk. RESULTS: Cow milk typically contained ∼12 μmol NAD(+)precursor vitamins/L, of which 60% was present as nicotinamide and 40% was present as NR. Nicotinic acid and other NAD(+)metabolites were below the limits of detection. Milk from samples testing positive forStaphylococcus aureuscontained lower concentrations of NR (Spearman ρ = -0.58,P= 0.014), and NR was degraded byS. aureus Conventional milk contained more NR than milk sold as organic. Nonetheless, NR was stable in organic milk and exhibited an NMR spectrum consistent with association with a protein fraction in skim milk. CONCLUSIONS: NR is a major NAD(+)precursor vitamin in cow milk. Control ofS. aureusmay be important to preserve the NAD(+)precursor vitamin concentration of milk. PMID: 27052539 [PubMed - as supplied by publisher]

Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice. J Nutr. 2016 Apr 6; Authors: Preidis GA, Ajami NJ, Wong MC, Bessard BC, Conner ME, Petrosino JF Abstract BACKGROUND: Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. Mechanisms by which metabolic abnormalities persist despite catch-up growth are poorly understood. OBJECTIVE: We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth. METHODS: Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. Both groups were weaned simultaneously to a standard unpurified diet. At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing. RESULTS: Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinaryp-cresol sulfate concentrations than did controls. Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multipleN-linked glycans. Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). Abundances of the mucolytic organismsAkkermansia muciniphilaandMucispirillum schaedleriwere altered at 0 and 1 wk. Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P= 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P= 0.0006) than did controls. CONCLUSION: Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice. PMID: 27052538 [PubMed - as supplied by publisher]

Related Articles Study of Phospholipids in Single Cells Using an Integrated Microfluidic Device Combined with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal Chem. 2015 Jul 21;87(14):7052-9 Authors: Xie W, Gao D, Jin F, Jiang Y, Liu H Abstract Single-cell trapping and high-throughput mass spectrometry analysis remain challenging now. Current technologies for single-cell analysis have several limitations, such as throughput, space resolution, and multicomponent analysis. In this study, we demonstrate, for the first time, the combination of microfluidic chip and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for high-throughput and automatic single-cell phospholipids analysis. A microwell-array-based microfluidic chip was designed and fabricated for cell array formation on an indium tin oxide (ITO)-coated glass slide. Mass spectrometry imaging measurement with 25 μm pixel size was performed with a MALDI ion source. Eight phospholipids in a single A549 cell were detected, and their structures were further identified by MS/MS spectra. Selected ion images were generated with a bin width of Δm/z ± 0.005. The selected ion images and optical images of the cell array showed excellent correlation, and mass spectrometry information on phospholipids from 1-3 cells was extracted automatically by selecting pixels with the same fixed interval between microwells on the chip. The measurement and data extraction could be processed in several minutes to achieve a high-throughput analysis. Through the optimization of different microwell sizes and different matrices, this method showed potential for the analysis of other metabolites or metabolic changes at the single-cell level. PMID: 26110742 [PubMed - indexed for MEDLINE]

Related Articles Perilipin 3 modulates specific lipogenic pathways in SZ95 sebocytes. Exp Dermatol. 2014 Oct;23(10):759-61 Authors: Camera E, Dahlhoff M, Ludovici M, Zouboulis CC, Schneider MR Abstract Lipid droplets (LD) are dynamic organelles that manage cellular lipid synthesis, storage and retrieval. Although LD-associated proteins, including the perilipin family (PLIN1-PLIN5), are essential for these functions, they have been poorly characterized in sebocytes. Here, we employed siRNAs to downregulate PLIN3 in SZ95 sebaceous gland cells and evaluated the consequences in lipid accumulation by nile red staining and mass spectrometry. Nile red staining revealed that siRNA-mediated downregulation of PLIN3 significantly impaired linoleic acid-induced lipid accumulation in SZ95 sebocytes. Mass spectrometry revealed that PLIN3 was implicated in the metabolism of linoleic acid, a lipid source used in the build-up of triglycerides, among other acyl lipids. Furthermore, the expression of key enzymes of sebaceous lipogenesis was altered in PLIN3-deficient sebocytes, consistent with the changes observed in the neutral lipid abundance, suggesting that PLIN3 functions are intertwined with the lipogenic pathways implicated in sebaceous lipogenesis, such as desaturation and triglyceride synthesis. PMID: 25039349 [PubMed - indexed for MEDLINE]

Use of Metabolomics to Advance Research on Environmental Exposures and the Human Exposome: Workshop in Brief Book. 2016 03 22Authors: Board on Life Sciences, Division on Earth and Life Studies, National Academies of Sciences, Engineering, and Medicine Abstract Metabolomics, the scientific study of small molecules produced from metabolism (metabolites) is a rapidly expanding area of research that enables scientists to better understand the physiological state of an organism and its response to different types of stimuli, including nutrients and pollutants. Metabolism is the array of chemical reactions that occur within a living organism to support its ability to grow, reproduce, and respond to environmental exposures, among other processes necessary to sustain life. Metabolites can be created in response to chemicals that originate endogenously (inside the body) or exogenously (outside of the body). Preliminary research suggests that metabolomics holds promise to advance understanding of the exposome. The exposome includes all of the environmental compounds an individual is exposed to from conception to death. This environmental correlate to the genome, first described in 2005 by Christopher Wild, includes people's exposure to complex mixtures of chemicals, as well as the substances that can be produced in the body when chemicals are metabolized. For this reason, the National Academies of Sciences, Engineering, and Medicine held a workshop to examine the potential for using metabolomics to characterize human environmental exposures and the exposome. Proofs-of-concept were discussed in two case studies on the cause of human Eosinophilic esophagitis and the effect of toxic pollutants on pregnancy in rats. Key workshop themes included technical capabilities and limitations to collect metabolomics data and the implications of this new source of data for future environmental and public health research and public health policies. PMID: 27054232

Targeted lipidomics distinguishes patient subgroups in mild cognitive impairment (MCI) and late onset Alzheimer's disease (LOAD). BBA Clin. 2016 Jun;5:25-28 Authors: Wood PL, Locke VA, Herling P, Passaro A, Vigna GB, Volpato S, Valacchi G, Cervellati C, Zuliani G Abstract BACKGROUND: Diverse research approaches support the concept that a clinical diagnosis of Late-Onset Alzheimer's Disease (LOAD) does not distinguish between subpopulations with differing neuropathologies, including dementia patients with amyloid deposition and dementia patients without amyloid deposition but with cortical thinning. Mild cognitive impairment (MCI) is generally considered the prodromal phase for LOAD, however, while a number of studies have attempted to define plasma biomarkers for the conversion of MCI to LOAD, these studies have not taken into account the heterogeneity of patient cohorts within a clinical phenotype. METHODS: Studies of MCI and LOAD in several laboratories have demonstrated decrements in ethanolamine plasmalogen levels in plasma and brain and increased levels of diacylglycerols in plasma and brain. To further extend these studies and to address the issue of heterogeneity in MCI and LOAD patient groups we investigated the levels of diacylglycerols and ethanolamine plasmalogens in larger cohorts of patients utilizing, high-resolution (0.2 to 2 ppm mass error) mass spectrometry. RESULTS: For the first time, our lipidomics data clearly stratify both MCI and LOAD subjects into 3 different patient cohorts within each clinical diagnosis. These include i) patients with lower circulating ethanolamine plasmalogen levels; ii) patients with augmented plasma diacylglycerol levels; and iii) patients with neither of these lipid alterations. CONCLUSIONS: These represent the first serum biochemical data to stratify MCI and LOAD patients, advancing efforts to biochemically define patient heterogeneity in cognitive disorders. GENERAL SIGNIFICANCE: Lipidomics offers a new approach for identifying biomarkers and biological targets in cognitive disorders. PMID: 27051586 [PubMed - as supplied by publisher]

Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function. Proc Natl Acad Sci U S A. 2016 Apr 5; Authors: Sadhukhan S, Liu X, Ryu D, Nelson OD, Stupinski JA, Li Z, Chen W, Zhang S, Weiss RS, Locasale JW, Auwerx J, Lin H Abstract Cellular metabolites, such as acyl-CoA, can modify proteins, leading to protein posttranslational modifications (PTMs). One such PTM is lysine succinylation, which is regulated by sirtuin 5 (SIRT5). Although numerous proteins are modified by lysine succinylation, the physiological significance of lysine succinylation and SIRT5 remains elusive. Here, by profiling acyl-CoA molecules in various mouse tissues, we have discovered that different tissues have different acyl-CoA profiles and that succinyl-CoA is the most abundant acyl-CoA molecule in the heart. This interesting observation has prompted us to examine protein lysine succinylation in different mouse tissues in the presence and absence of SIRT5. Protein lysine succinylation predominantly accumulates in the heart whenSirt5is deleted. Using proteomic studies, we have identified many cardiac proteins regulated by SIRT5. Our data suggest that ECHA, a protein involved in fatty acid oxidation, is a major enzyme that is regulated by SIRT5 and affects heart function.Sirt5knockout (KO) mice have lower ECHA activity, increased long-chain acyl-CoAs, and decreased ATP in the heart under fasting conditions.Sirt5KO mice develop hypertrophic cardiomyopathy, as evident from the increased heart weight relative to body weight, as well as reduced shortening and ejection fractions. These findings establish that regulating heart metabolism and function is a major physiological function of lysine succinylation and SIRT5. PMID: 27051063 [PubMed - as supplied by publisher]

Plasma metabolomic changes following PI3K inhibition as pharmacodynamic biomarkers: preclinical discovery to Phase I trial evaluation. Mol Cancer Ther. 2016 Apr 5; Authors: Ang JE, Pandher R, Ang JC, Asad YJ, Henley A, Valenti M, Box G, De Haven Brandon A, Baird RR, Friedman L, Derynck M, Vanhaesebroeck B, Eccles SA, Kaye SB, Workman P, de Bono JS, Raynaud FI Abstract Phosphoinositide-3-kinase (PI3K) plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor bearing controls and in addition were increased following dosing with Class I PI3K inhibitor pictilisib (GDC-0941). These candidate metabolomics biomarkers were evaluated in a Phase I dose-escalation clinical trial of pictilisib. Time- and dose-dependent effects were observed in patients for 22 plasma metabolites. The changes exceeded baseline variability, resolved after drug washout and were recapitulated on continuous dosing. Our study provides a link between modulation of the PI3K pathway and changes in the plasma metabolome and demonstrates that plasma metabolomics is a feasible and promising strategy for biomarker evaluation. Also, our findings provide additional support for an association between insulin resistance, branched-chain amino acids and related metabolites following PI3K inhibition. PMID: 27048952 [PubMed - as supplied by publisher]

Integrated Metabolomics Study of the Milk of Heat-stressed Lactating Dairy Cows. Sci Rep. 2016;6:24208 Authors: Tian H, Zheng N, Wang W, Cheng J, Li S, Zhang Y, Wang J Abstract Heat stress (HS) damages the global dairy industry by reducing milk yields and quality, harming health, and damaging the reproduction of dairy cows, causing huge economic losses each year. However, an understanding of the physiological mechanism of HS lactating dairy cows remains elusive. Here, a metabolomics study using LC-MS and (1)H NMR spectroscopy was performed to analyze the metabolomic differences in the milk between HS-free and HS dairy cows, and discover diagnostic biomarkers and changes in the metabolic pathway. A total of 53 discriminating metabolites were significantly up- or down-regulated in the HS group compared with the HS-free group (P < 0.05). These biomarkers were involved in pathways of carbohydrate, amino acid, lipid, and gut microbiome-derived metabolism. Comparing these potential biomarkers with previously identified HS candidate biomarkers in plasma, significant correlations between the levels of lactate, pyruvate, creatine, acetone, β-hydroxybutyrate, trimethylamine, oleic acid, linoleic acid, lysophosphatidylcholine 16:0, and phosphatidylcholine 42:2 in milk and plasma were found, indicating that the blood-milk barrier became leaky and the levels of these 10 biomarkers in milk can reflect HS-induced metabolomic alterations in blood. These novel findings can support more in-depth research to elucidate the milk-based changes in metabolic pathways in HS lactating dairy cows. PMID: 27048914 [PubMed - in process]

Dysbiosis in gastrointestinal disorders. Best Pract Res Clin Gastroenterol. 2016 Feb;30(1):3-15 Authors: Chang C, Lin H Abstract The recent development of advanced sequencing techniques has revealed the complexity and diverse functions of the gut microbiota. Furthermore, alterations in the composition or balance of the intestinal microbiota, or dysbiosis, are associated with many gastrointestinal diseases. The looming question is whether dysbiosis is a cause or effect of these diseases. In this review, we will evaluate the contribution of intestinal microbiota in obesity, fatty liver, inflammatory bowel disease, and irritable bowel syndrome. Promising results from microbiota or metabolite transfer experiments in animals suggest the microbiota may be sufficient to reproduce disease features in the appropriate host in certain disorders. Less compelling causal associations may reflect complex, multi-factorial disease pathogenesis, in which dysbiosis is a necessary condition. Understanding the contributions of the microbiota in GI diseases should offer novel insight into disease pathophysiology and deliver new treatment strategies such as therapeutic manipulation of the microbiota. PMID: 27048892 [PubMed - in process]

Regulated cell death and adaptive stress responses. Cell Mol Life Sci. 2016 Apr 5; Authors: Galluzzi L, Bravo-San Pedro JM, Kepp O, Kroemer G Abstract Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide. This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis. PMID: 27048813 [PubMed - as supplied by publisher]

Approximating the stabilization of cellular metabolism by compartmentalization. Theory Biosci. 2016 Apr 5; Authors: Fürtauer L, Nägele T Abstract Biochemical regulation in compartmentalized metabolic networks is highly complex and non-intuitive. This is particularly true for cells of higher plants showing one of the most compartmentalized cellular structures across all kingdoms of life. The interpretation and testable hypothesis generation from experimental data on such complex systems is a challenging step in biological research and biotechnological applications. While it is known that subcellular compartments provide defined reaction spaces within a cell allowing for the tight coordination of complex biochemical reaction sequences, its role in the coordination of metabolic signals during metabolic reprogramming due to environmental fluctuations is less clear. In the present study, we numerically analysed the effects of environmental fluctuations in a subcellular metabolic network with regard to the stability of an experimentally observed steady state in the genetic model plant Arabidopsis thaliana. Applying a method for kinetic parameter normalization, several millions of probable enzyme kinetic parameter constellations were simulated and evaluated with regard to the stability information of the metabolic homeostasis. Information about the stability of the metabolic steady state was derived from real parts of eigenvalues of Jacobian matrices. Our results provide evidence for a differential stabilizing contribution of different subcellular compartments. We could identify stabilizing and destabilizing network components which we could classify according to their subcellular localization. The findings prove that a highly dynamic interplay between intracellular compartments is preliminary for an efficient stabilization of a metabolic homeostasis after environmental perturbation. Further, our results provide evidence that feedback-inhibition originating from the cytosol and plastid seem to stabilize the sucrose homeostasis more efficiently than vacuolar control. In summary, our results indicate stabilizing and destabilizing network components in context of their subcellular organization. PMID: 27048513 [PubMed - as supplied by publisher]

The importance of GC-MS date processing and analysis strategies suitable for plant and environmental metabolomics : with references to Changes in the abundance of sugars and sugar-like compounds in tall fescue (Festuca arundinacea) due to growth in naphthalene-treated sand. Environ Sci Pollut Res Int. 2016 Apr 6; Authors: Law KP, Han TL PMID: 27048323 [PubMed - as supplied by publisher]