Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

metabolomics; +21 new citations

Sun, 22/07/2018 - 16:04
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 2018/07/22PubMed comprises more than millions of 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.

metabolomics; +21 new citations

Sun, 22/07/2018 - 13:00
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 2018/07/22PubMed comprises more than millions of 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.

Highly Accurate Detection and Identification Methodology of Xenobiotic Metabolites Using Stable Isotope Labeling, Data Mining Techniques, and Time-Dependent Profiling Based on LC/HRMS/MS.

Fri, 20/07/2018 - 12:06
Highly Accurate Detection and Identification Methodology of Xenobiotic Metabolites Using Stable Isotope Labeling, Data Mining Techniques, and Time-Dependent Profiling Based on LC/HRMS/MS. Anal Chem. 2018 Jul 19;: Authors: Takahashi M, Izumi Y, Iwahashi F, Nakayama Y, Iwakoshi M, Nakao M, Yamato S, Fukusaki E, Bamba T Abstract A generally applicable method to discover xenobiotic metabolites is important to safely and effectively develop xenobiotics. We propose an advanced method to detect and identify comprehensive xenobiotic metabolites using stable isotope labeling, liquid chromatography coupled with benchtop quadrupole Orbitrap high-resolution tandem mass spectrometry (LC/HRMS/MS), data mining techniques (alignment, peak picking, and paired-peaks filtering), in silico metabolism prediction, and time-dependent profiling. The LC/HRMS analysis was carried out using Arabidopsis T87 cultured cells treated with unlabeled or with 13C- or 2H-labeled 2,4-dichlorophenoxyacetic acid (2,4-D). Paired-peak filtering enabled the accurate detection of 83 candidates for 2,4-D metabolites without any false positive peaks derived from solvents or the biological matrix. We confirmed 10 previously reported 2,4-D metabolites and identified 16 novel 2,4-D metabolites. Our method provides accurate detection and identification of comprehensive xenobiotic metabolites and represents a potentially useful tool for elucidating xenobiotic metabolism. PMID: 30024726 [PubMed - as supplied by publisher]

The integration of LC-MS and NMR for the analysis of low molecular weight trace analytes in complex matrices.

Fri, 20/07/2018 - 12:06
The integration of LC-MS and NMR for the analysis of low molecular weight trace analytes in complex matrices. Mass Spectrom Rev. 2018 Jul 19;: Authors: Gathungu RM, Kautz R, Kristal BS, Bird SS, Vouros P Abstract This review discusses the integration of liquid chromatography (LC), mass spectrometry (MS), and nuclear magnetic resonance (NMR) in the comprehensive analysis of small molecules from complex matrices. We first discuss the steps taken toward making the three technologies compatible, so as to create an efficient analytical platform. The development of online LC-MS-NMR, highlighted by successful applications in the profiling of highly concentrated analytes (LODs 10 μg) is discussed next. This is followed by a detailed overview of the alternative approaches that have been developed to overcome the challenges associated with online LC-MS-NMR that primarily stem from the inherently low sensitivity of NMR. These alternative approaches include the use of stop-flow LC-MS-NMR, loop collection of LC peaks, LC-MS-SPE-NMR, and offline NMR. The potential and limitations of all these approaches is discussed in the context of applications in various fields, including metabolomics and natural product discovery. PMID: 30024655 [PubMed - as supplied by publisher]

Effects of cold exposure on metabolites in brown adipose tissue of rats.

Fri, 20/07/2018 - 12:06
Effects of cold exposure on metabolites in brown adipose tissue of rats. Mol Genet Metab Rep. 2018 Jun;15:36-42 Authors: Hiroshima Y, Yamamoto T, Watanabe M, Baba Y, Shinohara Y Abstract Brown adipose tissue (BAT) plays an important role in regulation of energy expenditure while adapting to a cold environment. BAT thermogenesis depends on uncoupling protein 1 (UCP1), which is expressed in the inner mitochondrial membranes of BAT. Gene expression profiles induced by cold exposure in BAT have been studied, but the metabolomic biological pathway that contributes to the activation of thermogenesis in BAT remains unclear. In this study, we comprehensively compared the relative levels of metabolites between the BAT of rats kept at room temperature (22 °C) and of those exposed to a cold temperature (4 °C) for 48 h using capillary electrophoresis (CE) time-of-flight mass spectrometry (TOFMS) and liquid chromatography (LC)-TOFMS. We identified 218 metabolites (137 cations and 81 anions) by CE-TOFMS and detected 81 metabolites (47 positive and 34 negative) by LC-TOFMS in BAT. We found that cold exposure highly influenced the BAT metabolome. We showed that the cold environment lead to lower levels of glycolysis and gluconeogenesis intermediates and higher levels of the tricarboxylic acid (TCA) cycle metabolites, fatty acids, and acyl-carnitine metabolites than control conditions in the BAT of rats. These results indicate that glycolysis and β-oxidation of fatty acids in BAT are positive biological pathways that contribute to the activation of thermogenesis by cold exposure, thereby facilitating the generation of heat by UCP1. These data provide useful information for understanding the basal metabolic functions of BAT thermogenesis in rats in response to cold exposure. PMID: 30023288 [PubMed]

Storage conditions modulate the metabolomic profile of a black raspberry nectar with minimal impact on bioactivity.

Fri, 20/07/2018 - 12:06
Related Articles Storage conditions modulate the metabolomic profile of a black raspberry nectar with minimal impact on bioactivity. Food Funct. 2018 Jul 19;: Authors: Teegarden MD, Knobloch TJ, Weghorst CM, Cooperstone JL, Peterson DG Abstract Pre-clinical and clinical studies suggest black raspberries (BRBs) may inhibit the development of oral cancer. Lyophilized BRB powder is commonly used in these studies, but processed BRB products are more often consumed. The objective of this work was to understand how storage conditions influence the phytochemical profile and anti-proliferative activity of a BRB nectar beverage. Untargeted UHPLC-Q-TOF-MS based metabolomics analyses demonstrated that large chemical variation was introduced by storage above -20 °C over 60 days. However, minimal change in anti-proliferative activity was observed when stored nectar extracts were applied to SCC-83-01-82 premalignant oral epithelial cells. As proof of concept, cyanidin-3-O-rutinoside and its degradation product, protocatechuic acid, were administered in different ratios maintaining an equimolar dose, and anti-proliferative activity was maintained. This study shows the utility of metabolomics to profile global chemical changes in foods, while demonstrating that isolated phytochemicals do not explain the complete bioactivity of a complex food product. PMID: 30022172 [PubMed - as supplied by publisher]

Accumulation of succinate controls activation of adipose tissue thermogenesis.

Fri, 20/07/2018 - 12:06
Related Articles Accumulation of succinate controls activation of adipose tissue thermogenesis. Nature. 2018 Jul 18;: Authors: Mills EL, Pierce KA, Jedrychowski MP, Garrity R, Winther S, Vidoni S, Yoneshiro T, Spinelli JB, Lu GZ, Kazak L, Banks AS, Haigis MC, Kajimura S, Murphy MP, Gygi SP, Clish CB, Chouchani ET Abstract Thermogenesis by brown and beige adipose tissue, which requires activation by external stimuli, can counter metabolic disease1. Thermogenic respiration is initiated by adipocyte lipolysis through cyclic AMP-protein kinase A signalling; this pathway has been subject to longstanding clinical investigation2-4. Here we apply a comparative metabolomics approach and identify an independent metabolic pathway that controls acute activation of adipose tissue thermogenesis in vivo. We show that substantial and selective accumulation of the tricarboxylic acid cycle intermediate succinate is a metabolic signature of adipose tissue thermogenesis upon activation by exposure to cold. Succinate accumulation occurs independently of adrenergic signalling, and is sufficient to elevate thermogenic respiration in brown adipocytes. Selective accumulation of succinate may be driven by a capacity of brown adipocytes to sequester elevated circulating succinate. Furthermore, brown adipose tissue thermogenesis can be initiated by systemic administration of succinate in mice. Succinate from the extracellular milieu is rapidly metabolized by brown adipocytes, and its oxidation by succinate dehydrogenase is required for activation of thermogenesis. We identify a mechanism whereby succinate dehydrogenase-mediated oxidation of succinate initiates production of reactive oxygen species, and drives thermogenic respiration, whereas inhibition of succinate dehydrogenase supresses thermogenesis. Finally, we show that pharmacological elevation of circulating succinate drives UCP1-dependent thermogenesis by brown adipose tissue in vivo, which stimulates robust protection against diet-induced obesity and improves glucose tolerance. These findings reveal an unexpected mechanism for control of thermogenesis, using succinate as a systemically-derived thermogenic molecule. PMID: 30022159 [PubMed - as supplied by publisher]

Menthol, a unique urinary volatile compound, is associated with chronic inflammation in interstitial cystitis.

Fri, 20/07/2018 - 12:06
Related Articles Menthol, a unique urinary volatile compound, is associated with chronic inflammation in interstitial cystitis. Sci Rep. 2018 Jul 18;8(1):10859 Authors: Shahid M, Lee MY, Yeon A, Cho E, Sairam V, Valdiviez L, You S, Kim J Abstract Chronic inflammation is a potential systemic risk factor for many bladder dysfunctions, including interstitial cystitis (IC). However, the underlying mechanism through which a healthy bladder protects itself from inflammatory triggers remains unknown. In this study, we identified odor compounds in urine obtained from IC patients and healthy controls. Using comprehensive solid-phase microextraction-gas chromatography-time-of-flight-mass spectrometry (SPME-GC-TOF-MS) profiling and bioinformatics, we found that levels of urinary volatile metabolites, such as menthol, were significantly reduced in IC patients, compared to healthy controls. In an attempt to understand the mechanistic meaning of our volatile metabolites data and the role of menthol in the immune system, we performed two independent experiments: (a) cytokine profiling, and (b) DNA microarray. Our findings suggest that lipopolysaccharide (LPS)-stimulated inflammatory events, such as the production and secretion of inflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β) and the activation of NF-κB and associated proteins within a large signaling network (e.g., Akt, TLR1, TNFAIP3, and NF-κB), are suppressed by the presence of menthol. These findings broaden our knowledge on the role of urinary menthol in suppressing inflammatory events and provide potential new strategies for alleviating both the odor and inflammation associated with IC. PMID: 30022124 [PubMed - in process]

Natural menstrual rhythm and oral contraception diversely affect exhaled breath compositions.

Fri, 20/07/2018 - 12:06
Related Articles Natural menstrual rhythm and oral contraception diversely affect exhaled breath compositions. Sci Rep. 2018 Jul 18;8(1):10838 Authors: Sukul P, Schubert JK, Trefz P, Miekisch W Abstract Natural menstrual cycle and/or oral contraception diversely affect women metabolites. Longitudinal metabolic profiling under constant experimental conditions is thereby realistic to understand such effects. Thus, we investigated volatile organic compounds (VOCs) exhalation throughout menstrual cycles in 24 young and healthy women with- and without oral contraception. Exhaled VOCs were identified and quantified in trace concentrations via high-resolution real-time mass-spectrometry, starting from a menstruation and then repeated follow-up with six intervals including the next bleeding. Repeated measurements within biologically comparable groups were employed under optimized measurement setup. We observed pronounced and substance specific changes in exhaled VOC concentrations throughout all cycles with low intra-individual variations. Certain blood-borne volatiles changed significantly during follicular and luteal phases. Most prominent changes in endogenous VOCs were observed at the ovulation phase with respect to initial menstruation. Here, the absolute median abundances of alveolar ammonia, acetone, isoprene and dimethyl sulphide changed significantly (P-value ≤ 0.005) by 18.22↓, 13.41↓, 18.02↑ and 9.40↓%, respectively. These VOCs behaved in contrast under the presence of combined oral contraception; e.g. isoprene decreased significantly by 30.25↓%. All changes returned to initial range once the second bleeding phase was repeated. Changes in exogenous benzene, isopropanol, limonene etc. and smoking related furan, acetonitrile and orally originated hydrogen sulphide were rather nonspecific and mainly exposure dependent. Our observations could apprehend a number of known/pre-investigated metabolic effects induced by monthly endocrine regulations. Potential in vivo origins (e.g. metabolic processes) of VOCs are crucial to realize such effects. Despite ubiquitous confounders, we demonstrated the true strength of volatolomics for metabolic monitoring of menstrual cycle and contraceptives. These outcomes may warrant further studies in this direction to enhance our fundamental and clinical understanding on menstrual metabolomics and endocrinology. Counter-effects of contraception can be deployed for future noninvasive assessment of birth control pills. Our findings could be translated toward metabolomics of pregnancy, menopause and post-menopausal complications via breath analysis. PMID: 30022081 [PubMed - in process]

Rifampin- or Capreomycin-Induced Remodeling of the Mycobacterium smegmatis Mycolic Acid Layer Is Mitigated in Synergistic Combinations with Cationic Antimicrobial Peptides.

Fri, 20/07/2018 - 12:06
Related Articles Rifampin- or Capreomycin-Induced Remodeling of the Mycobacterium smegmatis Mycolic Acid Layer Is Mitigated in Synergistic Combinations with Cationic Antimicrobial Peptides. mSphere. 2018 Jul 18;3(4): Authors: Man DK, Kanno T, Manzo G, Robertson BD, Lam JKW, Mason AJ Abstract The mycobacterial cell wall affords natural resistance to antibiotics. Antimicrobial peptides (AMPs) modify the surface properties of mycobacteria and can act synergistically with antibiotics from differing classes. Here, we investigate the response of Mycobacterium smegmatis to the presence of rifampin or capreomycin, either alone or in combination with two synthetic, cationic, α-helical AMPs that are distinguished by the presence (D-LAK120-HP13) or absence (D-LAK120-A) of a kink-inducing proline. Using a combination of high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) metabolomics, diphenylhexatriene (DPH) fluorescence anisotropy measurements, and laurdan emission spectroscopy, we show that M. smegmatis responds to challenge with rifampin or capreomycin by substantially altering its metabolism and, in particular, by remodeling the cell envelope. Overall, the changes are consistent with a reduction of trehalose dimycolate and an increase of trehalose monomycolate and are associated with increased rigidity of the mycolic acid layer observed following challenge by capreomycin but not rifampin. Challenge with D-LAK120-A or D-LAK120-HP13 induced no or modest changes, respectively, in mycomembrane metabolites and did not induce a significant increase in the rigidity of the mycolic acid layer. Furthermore, the response to rifampin or capreomycin was significantly reduced when these were combined with D-LAK120-HP13 and D-LAK120-A, respectively, suggesting a possible mechanism for the synergy of these combinations. The remodeling of the mycomembrane in M. smegmatis is therefore identified as an important countermeasure deployed against rifampin or capreomycin, but this can be mitigated and the efficacy of rifampin or capreomycin potentiated by combining the drug with AMPs.IMPORTANCE We have used a combined NMR metabolomics/biophysical approach to better understand differences in the mechanisms of two closely related antimicrobial peptides, as well as the response of the model organism Mycobacterium smegmatis to challenge with first- or second-line antibiotics used against mycobacterial pathogens. We show that, in addition to membrane damage, the triggering of oxidative stress may be an important part of the mechanism of action of one AMP. The metabolic shift that accompanied rifampin and, particularly, capreomycin challenge was associated with modest and more dramatic changes, respectively, in the mycomembrane, providing a rationale for how the response to one antibiotic may affect bacterial penetration and, hence, the action of another. This study presents the first insights into how antimicrobial peptides may operate synergistically with existing antibiotics whose efficacy is waning or sensitize MDR mycobacteria and/or latent mycobacterial infections to them, prolonging the useful life of these drugs. PMID: 30021876 [PubMed - in process]

[Comparation and utilization of crop-omics databases].

Fri, 20/07/2018 - 12:06
Related Articles [Comparation and utilization of crop-omics databases]. Yi Chuan. 2018 Jul 20;40(7):534-545 Authors: Song J, Wu YB, Zhou YH, Liu BJ, Wang N, Hao ZF, Wu YQ Abstract Omics plays an important role in life sciences, which studies all the components and their interrelations as a whole. The omics databases collected and sorted out the relevant information to support omics research. The crop-omics database, based on the major food crop information, especially on the sequencing information and data mining, is set up to improve the basic research level of crop sciences and production, which potentially benefit our grain stock. Here, we summarize crop genomics, transcriptomics, proteomics, metabolomics and phenomics, explore the development and utilization status of crop-omics, and reveal that the comprehensive utilization of multiple omics databases has become an important research method for crop sciences in the era of high throughput information. PMID: 30021717 [PubMed - in process]

Sodium-glucose cotransporter 2 inhibition normalizes glucose metabolism and suppresses oxidative stress in the kidneys of diabetic mice.

Fri, 20/07/2018 - 12:06
Related Articles Sodium-glucose cotransporter 2 inhibition normalizes glucose metabolism and suppresses oxidative stress in the kidneys of diabetic mice. Kidney Int. 2018 Jul 13;: Authors: Tanaka S, Sugiura Y, Saito H, Sugahara M, Higashijima Y, Yamaguchi J, Inagi R, Suematsu M, Nangaku M, Tanaka T Abstract It is unclear whether long-term sodium-glucose cotransporter 2 (SGLT2) inhibition such as that during the treatment of diabetes has deleterious effects on the kidney. Therefore, we first sought to determine whether abnormal glucose metabolism occurs in the kidneys of 22-week-old BTBR ob/ob diabetic mice. Second, the cumulative effect of chronic SGLT2 inhibition by ipragliflozin and 30% calorie restriction, either of which lowered blood glucose to a similar extent, on renal glucose metabolism was evaluated. Mass spectrometry-based metabolomics demonstrated that these diabetic mice exhibited an abnormal elevation in the renal pools of tricarboxylic acid cycle metabolites. This was almost completely nullified by SGLT2 inhibition and calorie restriction. Moreover, imaging mass spectrometry indicated an increased level of the tricarboxylic acid cycle intermediate, citrate, in the cortex of the diabetic mice. SGLT2 inhibition as well as calorie restriction almost completely eliminated citrate accumulation in the cortex. Furthermore, imaging mass spectrometry revealed that the accumulation of oxidized glutathione in the cortex of the kidneys, prominent in the glomeruli, was also canceled by SGLT2 inhibition and calorie restriction. Effects of these beneficial interventions were consistent with improvements in glomerular damage, such as albuminuria, glomerular hyperfiltration, and mesangial expansion. Tubulointerstitial macrophage infiltration and fibrosis were ameliorated only by calorie restriction, which may have been due to autophagy activation, which was observed only with calorie restriction. Thus, chronic SGLT2 inhibition is efficient in normalizing the levels of accumulated tricarboxylic acid cycle intermediates and increased oxidative stress in the kidneys of diabetic mice. PMID: 30021702 [PubMed - as supplied by publisher]

Physiological responses to cold stress in the gills of discus fish (Symphysodon aequifasciatus) revealed by conventional biochemical assays and GC-TOF-MS metabolomics.

Fri, 20/07/2018 - 12:06
Related Articles Physiological responses to cold stress in the gills of discus fish (Symphysodon aequifasciatus) revealed by conventional biochemical assays and GC-TOF-MS metabolomics. Sci Total Environ. 2018 Nov 01;640-641:1372-1381 Authors: Wen B, Jin SR, Chen ZZ, Gao JZ Abstract Discus fish (Symphysodon aequifasciatus) is a cichlid that is among the most popular fish for warm-water aquaria and also frequently used as the model animal for environmental science. However, little is known about the responses of S. aequifasciatus to low temperatures caused by environmental variation. Here, by using conventional biochemical assays and gas chromatography time-of-flight mass spectrometry metabolomics, we investigated the physiological responses of S. aequifasciatus gills exposed for 30 days to two temperature regimes: 28 °C and 20 °C. Low temperature resulted in elevated production of reactive oxygen species but not increased malondialdehyde. This might be partially related to protective responses in the antioxidant system, revealed by increased activities of superoxide dismutase and glutathione peroxidase, and level of reduced glutathione (GSH), compensating for the depletion of catalase activity. A total of 35 metabolites were identified as potential biomarkers of cold stress, showing the most influenced pathways including starch and sucrose metabolism, pentose phosphate pathway, glycerolipid metabolism, sphingolipid metabolism, glutathione metabolism, and arginine and proline metabolism. Moreover, the activation of glutathione metabolism agreed with the increased GSH level detected by biochemical assays. Overall, the results of this study suggest that low temperature can activate a protective antioxidant defence response and modify the metabolic pathways in gills of S. aequifasciatus, providing insights into the physiological regulation in response to cold stress in this tropical fish. PMID: 30021304 [PubMed - in process]

A simple HPLC-DAD method for simultaneous detection of two organophosphates, profenofos and fenthion, and validation by soil microcosm experiment.

Fri, 20/07/2018 - 12:06
Related Articles A simple HPLC-DAD method for simultaneous detection of two organophosphates, profenofos and fenthion, and validation by soil microcosm experiment. Environ Monit Assess. 2018 May 05;190(6):327 Authors: Mahajan R, Chatterjee S Abstract Indiscriminate use of two broad spectrum pesticides, profenofos and fenthion, in agricultural system, often results in their accumulation in a non-target niche and leaching into water bodies. The present study, therefore, aims at developing a simple and rapid HPLC method that allows simultaneous extraction and detection of these two pesticides, especially in run-off water. Extraction of the two pesticides from spiked water samples using dichloromethane resulted in recovery ranging between 80 and 90%. An HPLC run of 20 min under optimized chromatographic parameters (mobile phase: methanol (75%) and water (25%); flow rate of 0.8 ml min-1; diode array detector at wavelength 210 nm) resulted in a significant difference in retention times of two pesticides (4.593 min) which allows a window of opportunity to study any possible intermediates/transformants of the parent compounds while evaluating run-off waters from agricultural fields. The HPLC method developed allowed simultaneous detection of profenofos and fenthion with a single injection into the HPLC system with 0.0328 mg l-1 (32.83 ng ml-1) being the limit of detection (LOD) and 0.0995 mg l-1 (99.5 ng ml-1) as the limit of quantification (LOQ) for fenthion; for profenofos, LOD and LOQ were 0.104 mg l-1 (104.50 ng ml-1) and 0.316 mg l-1 (316.65 ng ml-1), respectively. The findings were further validated using the soil microcosm experiment that allowed simultaneous detection and quantification of profenofos and fenthion. The findings indicate towards the practical significance of the methodology developed as the soil microcosm experiment closely mimics the agricultural run-off water under natural environmental conditions. PMID: 29730742 [PubMed - indexed for MEDLINE]

Metabolite profiling and gene expression of Na/K transporter analyses reveal mechanisms of the difference in salt tolerance between barley and rice.

Thu, 19/07/2018 - 14:49
Related Articles Metabolite profiling and gene expression of Na/K transporter analyses reveal mechanisms of the difference in salt tolerance between barley and rice. Plant Physiol Biochem. 2018 Jul 15;130:248-257 Authors: Fu L, Shen Q, Kuang L, Yu J, Wu D, Zhang G Abstract Barley (Hordeum vulgare) and rice (Oryza sativa) differ greatly in their salt tolerance, although both species belong to the Poaceae family. To understand the mechanisms in the difference of salt tolerance between the two species, the responses of ionome, metabolome and gene expression of Na and K transporters to the different salt treatments were analyzed using 4 barley and 4 rice genotypes differing in salt tolerance. In comparison with 4 rice genotypes, four barley genotypes showed better plant growth, lower shoot Na concentration and higher K concentration at the 9 day after salt treatments. There was a dramatic difference in absolute expression levels of SOS, HKT and NHX family genes between barley and rice, which might account for their difference in Na/K homeostasis and salt tolerance. Moreover, rice leaves accumulated excess Na under salt treatments, which caused serious damages to physiological metabolisms based on metabolomic analysis, but barley leaves had lower Na concentration and small changes in the most metabolites. These results provide useful insights into the molecular mechanism in the difference of salt tolerance between rice and barley. PMID: 30021179 [PubMed - as supplied by publisher]

Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit.

Thu, 19/07/2018 - 14:49
Related Articles Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit. Immunity. 2018 Jul 17;49(1):33-41.e7 Authors: Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L, Schneider C, Miller CN, Pollack JL, Nagana Gowda GA, Fontana MF, Erle DJ, Anderson MS, Locksley RM, Raftery D, von Moltke J Abstract In the small intestine, type 2 responses are regulated by a signaling circuit that involves tuft cells and group 2 innate lymphoid cells (ILC2s). Here, we identified the microbial metabolite succinate as an activating ligand for small intestinal (SI) tuft cells. Sequencing analyses of tuft cells isolated from the small intestine, gall bladder, colon, thymus, and trachea revealed that expression of tuft cell chemosensory receptors is tissue specific. SI tuft cells expressed the succinate receptor (SUCNR1), and providing succinate in drinking water was sufficient to induce a multifaceted type 2 immune response via the tuft-ILC2 circuit. The helminth Nippostrongylus brasiliensis and a tritrichomonad protist both secreted succinate as a metabolite. In vivo sensing of the tritrichomonad required SUCNR1, whereas N. brasiliensis was SUCNR1 independent. These findings define a paradigm wherein tuft cells monitor microbial metabolites to initiate type 2 immunity and suggest the existence of other sensing pathways triggering the response to helminths. PMID: 30021144 [PubMed - in process]

AMPK-ACC signaling modulates platelet phospholipids content and potentiates platelet function and thrombus formation.

Thu, 19/07/2018 - 14:49
Related Articles AMPK-ACC signaling modulates platelet phospholipids content and potentiates platelet function and thrombus formation. Blood. 2018 Jul 17;: Authors: Lepropre S, Kautbally S, Octave M, Ginion A, Onselaer MB, Steinberg GR, Kemp BE, Hego A, Wéra O, Brouns S, Swieringa F, Giera M, Darley-Usmar VM, Ambroise J, Guigas B, Heemskerk J, Bertrand L, Oury C, Beauloye C, Horman S Abstract AMP-activated protein kinase (AMPK) α1 is activated in platelets upon thrombin or collagen stimulation, and as consequence phosphorylates and inhibits acetyl-CoA carboxylase (ACC). Since ACC is crucial for the synthesis of fatty acids, which are essential for platelet activation, we hypothesized that this enzyme plays a central regulatory role in platelet function. To investigate this, we used a double knock-in (DKI) mouse model in which the AMPK phosphorylation sites Ser79 on ACC1 and Ser212 on ACC2 were mutated to prevent AMPK-signaling to ACC. Suppression of ACC phosphorylation promoted injury-induced arterial thrombosis in vivo and enhanced thrombus growth ex vivo on collagen-coated surfaces under flow. After collagen stimulation, loss of AMPK-ACC signaling was associated with amplified thromboxane generation and dense granule secretion. ACC DKI platelets had increased arachidonic acid-containing phosphatidylethanolamine plasmalogen lipids. In conclusion, AMPK-ACC signaling is coupled to the control of thrombosis by specifically modulating thromboxane and granule release in response to collagen. It appears to achieve this by increasing platelet phospholipid content required for the generation of arachidonic acid, a key mediator of platelet activation. PMID: 30018077 [PubMed - as supplied by publisher]

Fenofibrate prevents skeletal muscle loss in mice with lung cancer.

Thu, 19/07/2018 - 14:49
Related Articles Fenofibrate prevents skeletal muscle loss in mice with lung cancer. Proc Natl Acad Sci U S A. 2018 01 23;115(4):E743-E752 Authors: Goncalves MD, Hwang SK, Pauli C, Murphy CJ, Cheng Z, Hopkins BD, Wu D, Loughran RM, Emerling BM, Zhang G, Fearon DT, Cantley LC Abstract The cancer anorexia cachexia syndrome is a systemic metabolic disorder characterized by the catabolism of stored nutrients in skeletal muscle and adipose tissue that is particularly prevalent in nonsmall cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments and increased mortality. The aim of the present study was to characterize the changes in systemic metabolism in a genetically engineered mouse model of NSCLC. We show that a portion of these animals develop loss of skeletal muscle, loss of adipose tissue, and increased inflammatory markers mirroring the human cachexia syndrome. Using noncachexic and fasted animals as controls, we report a unique cachexia metabolite phenotype that includes the loss of peroxisome proliferator-activated receptor-α (PPARα) -dependent ketone production by the liver. In this setting, glucocorticoid levels rise and correlate with skeletal muscle degradation and hepatic markers of gluconeogenesis. Restoring ketone production using the PPARα agonist, fenofibrate, prevents the loss of skeletal muscle mass and body weight. These results demonstrate how targeting hepatic metabolism can prevent muscle wasting in lung cancer, and provide evidence for a therapeutic strategy. PMID: 29311302 [PubMed - indexed for MEDLINE]

Applications of prebiotics in food industry: A review.

Thu, 19/07/2018 - 14:49
Related Articles Applications of prebiotics in food industry: A review. Food Sci Technol Int. 2017 Dec;23(8):649-667 Authors: Singla V, Chakkaravarthi S Abstract Benefits of prebiotics for stimulating a healthy intestinal tract are well known. From suppression of pathogens to proliferation of indigenous bacteria of intestines, prebiotics have it all. Since the research on the scope of prebiotics is expanding, new applications are coming up every day thus upgrading the choices consumer has for a healthy living. Incorporation of prebiotics in a wide range of products that food industry offers on shelf is an innovative way to replace fat and sugars along with enhancing the mouthfeel by providing better tongue lubrication. In some cases, the thermal stability of the product is improved along with other sensory, textural and physiological benefits. This paper gives an overview of the various prebiotics available from different sources and their applications in various segments of food industry, notably dairy, beverage, processed fruit-vegetable, bakery, confectionary, extruded snack, sweetener, infant formula, pet food and livestock industry. The effects observed on addition of various prebiotics are also elaborated. PMID: 28762780 [PubMed - indexed for MEDLINE]

Depletion of carbohydrate reserves limits nitrate uptake during early regrowth in Lolium perenne L.

Thu, 19/07/2018 - 14:49
Related Articles Depletion of carbohydrate reserves limits nitrate uptake during early regrowth in Lolium perenne L. J Exp Bot. 2017 Mar 01;68(7):1569-1583 Authors: Guo Q, Turnbull MH, Song J, Roche J, Novak O, Späth J, Jameson PE, Love J Abstract The mechanisms linking C/N balance to N uptake and assimilation are central to plant responses to changing soil nutrient levels. Defoliation and subsequent regrowth of grasses both impact C partitioning, thereby creating a significant point of interaction with soil N availability. Using defoliation as an experimental treatment, we investigated the dynamic relationships between plant carbohydrate status and NO3--responsive uptake systems, transporter gene expression, and nitrate assimilation in Lolium perenne L. High- and low-affinity NO3- uptake was reduced in an N-dependent manner in response to a rapid and large shift in carbohydrate remobilization triggered by defoliation. This reduction in NO3- uptake was rescued by an exogenous glucose supplement, confirming the carbohydrate dependence of NO3- uptake. The regulation of NO3- uptake in response to the perturbation of the plant C/N ratio was associated with changes in expression of putative high- and low-affinity NO3- transporters. Furthermore, NO3- assimilation appears to be regulated by the C-N status of the plant, implying a mechanism that signals the availability of C metabolites for NO3- uptake and assimilation at the whole-plant level. We also show that cytokinins may be involved in the regulation of N acquisition and assimilation in response to the changing plant C/N ratio. PMID: 28379423 [PubMed - indexed for MEDLINE]

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