PubMed

Cancer immunotherapy in 2017: The breakthrough of the microbiota. Nat Rev Immunol. 2018 Jan 30;18(2):87-88 Authors: Kroemer G, Zitvogel L PMID: 29379189 [PubMed - in process]

Alveolar Macrophages Drive Hepatocellular Carcinoma Lung Metastasis by Generating Leukotriene B4. J Immunol. 2018 Jan 29;: Authors: Nosaka T, Baba T, Tanabe Y, Sasaki S, Nishimura T, Imamura Y, Yurino H, Hashimoto S, Arita M, Nakamoto Y, Mukaida N Abstract Macrophages in lungs can be classified into two subpopulations, alveolar macrophages (AMs) and interstitial macrophages (IMs), which reside in the alveolar and interstitial spaces, respectively. Accumulating evidence indicates the involvement of IMs in lung metastasis, but the roles of AMs in lung metastasis still remain elusive. An i.v. injection of a mouse hepatocellular carcinoma (HCC) cell line, BNL, caused lung metastasis foci with infiltration of AMs and IMs. Comprehensive determination of arachidonic acid metabolite levels revealed increases in leukotrienes and PGs in lungs in this metastasis model. A 5-lipoxygenase (LOX) inhibitor but not a cyclooxygenase inhibitor reduced the numbers of metastatic foci, particularly those of a larger size. A major 5-LOX metabolite, LTB4, augmented in vitro cell proliferation of human HCC cell lines as well as BNL cells. Moreover, in this lung metastasis course, AMs exhibited higher expression levels of the 5-LOX and LTB4 than IMs. Consistently, 5-LOX-expressing AMs increased in the lungs of human HCC patients with lung metastasis, compared with those without lung metastasis. Furthermore, intratracheal clodronate liposome injection selectively depleted AMs but not IMs, together with reduced LTB4 content and metastatic foci numbers in this lung metastasis process. Finally, IMs in mouse metastatic foci produced CCL2, thereby recruiting blood-borne, CCR2-expressing AMs into lungs. Thus, AMs can be recruited under the guidance of IM-derived CCL2 into metastatic lungs and can eventually contribute to the progression of lung metastasis by providing a potent arachidonic acid-derived tumor growth promoting mediator, LTB4. PMID: 29378914 [PubMed - as supplied by publisher]

Related Articles Disruption of OsSULTR3;3 reduces phytate and phosphorus concentrations and alters the metabolite profile in rice grains. New Phytol. 2016 Aug;211(3):926-39 Authors: Zhao H, Frank T, Tan Y, Zhou C, Jabnoune M, Arpat AB, Cui H, Huang J, He Z, Poirier Y, Engel KH, Shu Q Abstract Two low phytic acid (lpa) mutants have been developed previously with the aim to improve the nutritional value of rice (Oryza sativa) grains. In the present study, the impacts of lpa mutations on grain composition and underlying molecular mechanisms were investigated. Comparative compositional analyses and metabolite profiling demonstrated that concentrations of both phytic acid (PA) and total phosphorus (P) were significantly reduced in lpa brown rice, accompanied by changes in other metabolites and increased concentrations of nutritionally relevant compounds. The lpa mutations modified the expression of a number of genes involved in PA metabolism, as well as in sulfate and phosphate homeostasis and metabolism. Map-based cloning and complementation identified the underlying lpa gene to be OsSULTR3;3. The promoter of OsSULTR3;3 is highly active in the vascular bundles of leaves, stems and seeds, and its protein is localized in the endoplasmic reticulum. No activity of OsSULTR3;3 was revealed for the transport of phosphate, sulfate, inositol or inositol 1,4,5 triphosphate by heterologous expression in either yeast or Xenopus oocytes. The findings reveal that OsSULTR3;3 plays an important role in grain metabolism, pointing to a new route to generate value-added grains in rice and other cereal crops. PMID: 27110682 [PubMed - indexed for MEDLINE]

19 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 2018/01/30PubMed 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.

19 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 2018/01/30PubMed 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.

Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis. Biochim Biophys Acta. 2018 Jan 24;: Authors: Duta-Mare M, Sachdev V, Leopold C, Kolb D, Vujic N, Korbelius M, Hofer DC, Xia W, Huber K, Auer M, Gottschalk B, Magnes C, Graier WF, Prokesch A, Radovic B, Bogner-Strauss JG, Kratky D Abstract Lysosomal acid lipase (LAL) is the only known enzyme, which hydrolyzes cholesteryl esters and triacylglycerols in lysosomes of multiple cells and tissues. Here, we explored the role of LAL in brown adipose tissue (BAT). LAL-deficient (Lal-/-) mice exhibit markedly reduced UCP1 expression in BAT, modified BAT morphology with accumulation of lysosomes, and mitochondrial dysfunction, consequently leading to regular hypothermic events in mice kept at room temperature. Cold exposure resulted in reduced lipid uptake into BAT, thereby aggravating dyslipidemia and causing life threatening hypothermia in Lal-/- mice. Linking LAL as a potential regulator of lipoprotein lipase activity, we found Angptl4 mRNA expression upregulated in BAT. Our data demonstrate that LAL is critical for shuttling fatty acids derived from circulating lipoproteins to BAT during cold exposure. We conclude that inhibited lysosomal lipid hydrolysis in BAT leads to impaired thermogenesis in Lal-/- mice. PMID: 29374543 [PubMed - as supplied by publisher]

Related Articles Beyond genomics: understanding exposotypes through metabolomics. Hum Genomics. 2018 Jan 26;12(1):4 Authors: Rattray NJW, Deziel NC, Wallach JD, Khan SA, Vasiliou V, Ioannidis JPA, Johnson CH Abstract BACKGROUND: Over the past 20 years, advances in genomic technology have enabled unparalleled access to the information contained within the human genome. However, the multiple genetic variants associated with various diseases typically account for only a small fraction of the disease risk. This may be due to the multifactorial nature of disease mechanisms, the strong impact of the environment, and the complexity of gene-environment interactions. Metabolomics is the quantification of small molecules produced by metabolic processes within a biological sample. Metabolomics datasets contain a wealth of information that reflect the disease state and are consequent to both genetic variation and environment. Thus, metabolomics is being widely adopted for epidemiologic research to identify disease risk traits. In this review, we discuss the evolution and challenges of metabolomics in epidemiologic research, particularly for assessing environmental exposures and providing insights into gene-environment interactions, and mechanism of biological impact. MAIN TEXT: Metabolomics can be used to measure the complex global modulating effect that an exposure event has on an individual phenotype. Combining information derived from all levels of protein synthesis and subsequent enzymatic action on metabolite production can reveal the individual exposotype. We discuss some of the methodological and statistical challenges in dealing with this type of high-dimensional data, such as the impact of study design, analytical biases, and biological variance. We show examples of disease risk inference from metabolic traits using metabolome-wide association studies. We also evaluate how these studies may drive precision medicine approaches, and pharmacogenomics, which have up to now been inefficient. Finally, we discuss how to promote transparency and open science to improve reproducibility and credibility in metabolomics. CONCLUSIONS: Comparison of exposotypes at the human population level may help understanding how environmental exposures affect biology at the systems level to determine cause, effect, and susceptibilities. Juxtaposition and integration of genomics and metabolomics information may offer additional insights. Clinical utility of this information for single individuals and populations has yet to be routinely demonstrated, but hopefully, recent advances to improve the robustness of large-scale metabolomics will facilitate clinical translation. PMID: 29373992 [PubMed - in process]

Related Articles Metabolomics of osteoarthritis: emerging novel markers and their potential clinical utility. Rheumatology (Oxford). 2018 Jan 24;: Authors: Zhai G, Randell EW, Rahman P Abstract OA is a multifactorial and progressive disease with no cure yet. Substantial efforts have been made and several biochemical and genetic markers have been reported, but neither alone nor in combination is adequate to identify early OA changes or determine disease progression with sufficient predictive values. Recent advances in metabolomics and its application to the study of OA have led to elucidation of involvement of several metabolic pathways and new specific metabolic markers for OA. Some of these metabolic pathways affect amino acid metabolism, including branched chain amino acids and arginine, and phospholipid metabolism involving conversion of phosphatidylcholine to lysophosphatidylcholine. These metabolic markers appear to be clinically actionable and may potentially improve the clinical management of OA patients. In this article, we review the recent studies of metabolomics of OA, discuss those novel metabolic markers and their potential clinical utility, and indicate future research directions in the field. PMID: 29373736 [PubMed - as supplied by publisher]

Related Articles Diagnostic metabolite biomarkers of chronic typhoid carriage. PLoS Negl Trop Dis. 2018 Jan 26;12(1):e0006215 Authors: Näsström E, Jonsson P, Johansson A, Dongol S, Karkey A, Basnyat B, Tran Vu Thieu N, Trinh Van T, Thwaites GE, Antti H, Baker S Abstract BACKGROUND: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. METHODOLOGY/PRINCIPAL FINDINGS: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. CONCLUSIONS/SIGNIFICANCE: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings. PMID: 29373578 [PubMed - as supplied by publisher]

Related Articles Tissue Level Diet and Sex-by-Diet Interactions Reveal Unique Metabolite and Clustering Profiles Using Untargeted Liquid Chromatography-Mass Spectrometry on Adipose, Skeletal Muscle, and Liver Tissue in C57BL6/J Mice. J Proteome Res. 2018 Jan 26;: Authors: Wells A, Barrington WT, Dearth S, May A, Threadgill DW, Campagna SR, Voy BH Abstract Dietary intervention is commonly used for weight loss or to improve health, as diet-induced obesity increases risk of developing type 2 diabetes, hypertension, cardiovascular disease, stroke, osteoarthritis, and certain cancers. Various dietary patterns are associated with effects on health, yet little is known about the effects of diet at the tissue level. Using untargeted metabolomics, this study aimed to identify changes in water-soluble metabolites in C57BL/6J males and females, fed one of five diets (Japanese, ketogenic, Mediterranean, American, and standard mouse chow) for seven months. Metabolite abundance was examined in liver, skeletal muscle, and adipose tissue for sex, diet, and sex-by-diet interaction. Analysis of variance (ANOVA) suggests that liver tissue has the most metabolic plasticity under dietary changes compared to adipose and skeletal muscle. The ketogenic diet was distinguishable from other diets for both males and females, according to partial least squares discriminant analysis. Pathway analysis revealed that the majority of pathways affected play an important role in amino acid metabolism in liver tissue. Not surprisingly, amino acid profiles were affected by dietary patterns in skeletal muscle. Few metabolites were significantly altered for adipose tissue relative to skeletal muscle and liver tissue indicating it was largely stable, regardless of diet alterations. The results of this study revealed that the ketogenic diet had the largest affect on physiology, particularly for females. Furthermore, metabolomics revealed that diet affects metabolites in a tissue-specific manner and that liver was most sensitive to dietary changes. PMID: 29373032 [PubMed - as supplied by publisher]

Related Articles [Analysis on metabolites with small molecule of serum in bone marrow suppression model mice with metabolomics method]. Se Pu. 2017 Dec 08;35(12):1312-1316 Authors: Chen J, Liu Y, Xu Y, Wang Y Abstract Bone marrow suppression is a common symptom in patients with malignant tumor after chemotherapy. Studying the changes of metabolites caused by bone marrow depression can provide insights for the diagnosis of bone marrow suppression disease and for the development of drug therapy. Male BalB/C mice were injected with cyclophosphamide to establish a bone marrow suppression model. Gas chromatography-mass spectrometry (GC-MS) with fingerprinting was used to analyze the normal and model mice blood metabolites. Principal component analysis and orthogonal to partial least squares discriminant analysis (OPLS-DA) on metabolomics for data multidimensional statistical analysis was also used. Compared to the normal group in terms of the metabolic profile of bone marrow suppression mice, there were 15 endogenous metabolites in mouse plasma, nine of which were statistically significantly different, including glucose-1-phosphate, 4-nitrophenol, acetanilide, cortisone, nicotinamide, loganin, caffeic acid, linoleic acid and oleic acid (P<0.05). These results indicate that metabolite can be used as an important marker in bone marrow suppression, which can help to reveal the pathogenesis of bone marrow suppression induced by chemotherapy and determine the disease development stage and the effectiveness of follow-up treatment. PMID: 29372783 [PubMed - in process]

Related Articles [Isolation and purification of seven catechin compounds from fresh tea leaves by semi-preparative liquid chromatography]. Se Pu. 2017 Nov 08;35(11):1192-1197 Authors: Gong Z, Chen S, Gao J, Li M, Wang X, Lin J, Yu X Abstract An effective and simple method was established to simultaneously purify seven tea catechins (gallocatechin (GC), epigallocatechin (EGC), catechin (C), epigallocatechin-3-O-gallate (EGCG), epicatechin (EC), epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3"Me) and epicatechin-3-O-gallate (ECG)) from fresh tea leaves by semi-preparative high performance liquid chromatography (HPLC). Fresh leaves of Tieguanyin tea were successively extracted with methanol and chloroform. Then crude catechins were precipitated from the aqueous fraction of chloroform extraction by adding lead subacetate. Crude catechins were used for the isolation of the seven target catechin compounds by semi-preparative HPLC. Methanol-water and acetonitrile-water were sequentially used as mobile phases. After two rounds of semi-preparative HPLC, all target compounds were achieved with high purities (>90%). The proposed method was tested on two additional tea cultivars and showed similar results. This method demonstrated a simple and efficient strategy based on solvent extraction, ion precipitation and semi-preparative HPLC for the preparation of multiple catechins from tea leaves. PMID: 29372766 [PubMed - in process]

Related Articles Exploring traditional aus-type rice for metabolites conferring drought tolerance. Rice (N Y). 2018 Jan 25;11(1):9 Authors: Casartelli A, Riewe D, Hubberten HM, Altmann T, Hoefgen R, Heuer S Abstract BACKGROUND: Traditional varieties and landraces belonging to the aus-type group of rice (Oryza sativa L.) are known to be highly tolerant to environmental stresses, such as drought and heat, and are therefore recognized as a valuable genetic resource for crop improvement. Using two aus-type (Dular, N22) and two drought intolerant irrigated varieties (IR64, IR74) an untargeted metabolomics analysis was conducted to identify drought-responsive metabolites associated with tolerance. RESULTS: The superior drought tolerance of Dular and N22 compared with the irrigated varieties was confirmed by phenotyping plants grown to maturity after imposing severe drought stress in a dry-down treatment. Dular and N22 did not show a significant reduction in grain yield compared to well-watered control plants, whereas the intolerant varieties showed a significant reduction in both, total spikelet number and grain yield. The metabolomics analysis was conducted with shoot and root samples of plants at the tillering stage at the end of the dry-down treatment. The data revealed an overall higher accumulation of N-rich metabolites (amino acids and nucleotide-related metabolites allantoin and uridine) in shoots of the tolerant varieties. In roots, the aus-type varieties were characterised by a higher reduction of metabolites representative of glycolysis and the TCA cycle, such as malate, glyceric acid and glyceric acid-3-phosphate. On the other hand, the oligosaccharide raffinose showed a higher fold increase in both, shoots and roots of the sensitive genotypes. The data further showed that, for certain drought-responsive metabolites, differences between the contrasting rice varieties were already evident under well-watered control conditions. CONCLUSIONS: The drought tolerance-related metabolites identified in the aus-type varieties provide a valuable set of protective compounds and an entry point for assessing genetic diversity in the underlying pathways for developing drought tolerant rice and other crops. PMID: 29372429 [PubMed]

Related Articles Metabolomics diagnostic approach to mustard airway diseases: a preliminary study. Iran J Basic Med Sci. 2018 Jan;21(1):59-69 Authors: Ghoochani BFNM, Aliannejad R, Oskouie AA, Rezaei-Tavirani M, Kalantari S, Naseri MT, Baghban AA, Parastar H, Aliakbarzadeh G Abstract Objectives: This study aims to evaluate combined proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) metabolic profiling approaches, for discriminating between mustard airway diseases (MADs) and healthy controls and for providing biochemical information on this disease. Materials and Methods: In the present study, analysis of serum samples collected from 17 MAD subjects and 12 healthy controls was performed using NMR. Of these subjects, 14 (8 patients and 6 controls) were analyzed by GC-MS. Then, their spectral profiles were subjected to principal component analysis (PCA) and orthogonal partial least squares regression discriminant analysis (OPLS-DA). Results: A panel of twenty eight metabolite biomarkers was generated for MADs, sixteen NMR-derived metabolites (3-methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, lactic acid, lysine, glutamic acid, proline, hydroxyproline, dimethylamine, creatine, citrulline, choline, acetic acid, acetoacetate, cholesterol, alanine, and lipid (mainly VLDL)) and twelve GC-MS-derived metabolites (threonine, phenylalanine, citric acid, myristic acid, pentadecanoic acid, tyrosine, arachidonic acid, lactic acid, propionic acid, 3-hydroxybutyric acid, linoleic acid, and oleic acid). This composite biomarker panel could effectively discriminate MAD subjects from healthy controls, achieving an area under receiver operating characteristic curve (AUC) values of 1 and 0.79 for NMR and GC-MS, respectively. Conclusion: In the present study, a robust panel of twenty-eight biomarkers for detecting MADs was established. This panel is involved in three metabolic pathways including aminoacyl-tRNA biosynthesis, arginine, and proline metabolism, and synthesis and degradation of ketone bodies, and could differentiate MAD subjects from healthy controls with a higher accuracy. PMID: 29372038 [PubMed]

Related Articles Spermidine in health and disease. Science. 2018 Jan 26;359(6374): Authors: Madeo F, Eisenberg T, Pietrocola F, Kroemer G Abstract Interventions that delay aging and protect from age-associated disease are slowly approaching clinical implementation. Such interventions include caloric restriction mimetics, which are defined as agents that mimic the beneficial effects of dietary restriction while limiting its detrimental effects. One such agent, the natural polyamine spermidine, has prominent cardioprotective and neuroprotective effects and stimulates anticancer immunosurveillance in rodent models. Moreover, dietary polyamine uptake correlates with reduced cardiovascular and cancer-related mortality in human epidemiological studies. Spermidine preserves mitochondrial function, exhibits anti-inflammatory properties, and prevents stem cell senescence. Mechanistically, it shares the molecular pathways engaged by other caloric restriction mimetics: It induces protein deacetylation and depends on functional autophagy. Because spermidine is already present in daily human nutrition, clinical trials aiming at increasing the uptake of this polyamine appear feasible. PMID: 29371440 [PubMed - in process]

Related Articles Multi-omics integration reveals the landscape of pro-metastasis metabolism in hepatocellular carcinoma. Mol Cell Proteomics. 2018 Jan 25;: Authors: Li Y, Zhuang H, Zhang X, Li Y, Liu Y, Yi X, Qin G, Wei W, Chen R Abstract The systematic investigation of gene mutation and expression is important to discover novel biomarkers and therapeutic targets in cancers. Here, we integrated genomics, transcriptomics, proteomics, and metabolomics to analyze three hepatocellular carcinoma (HCC) cell lines with differential metastatic potentials. The results revealed the profile of the pro-metastasis metabolism potentially associated with HCC metastasis. The multi-omic analysis identified 12 genes with variations at multiple levels from three metabolic pathways, including glycolysis, starch and sucrose metabolism, and glutathione metabolism. Furthermore, UDP-glucose pyrophosphorylase 2 (UGP2), was observed to be persistently up-regulated with increased metastatic potential. UGP2 overexpression promoted cell migration and invasion, and enhanced glycogenesis in vitro. The role of UGP2 in metastasis was further confirmed using a tumor xenograft mouse model. Taken together, the compendium of multi-omic data provides valuable insights to understand the roles of shifted cellular metabolism in HCC metastasis. PMID: 29371291 [PubMed - as supplied by publisher]

Related Articles New insights into the catalytic mechanism of human glycine N-acyltransferase. J Biochem Mol Toxicol. 2017 Nov;31(11): Authors: van der Sluis R, Ungerer V, Nortje C, A van Dijk A, Erasmus E Abstract Even though the glycine conjugation pathway was one of the first metabolic pathways to be discovered, this pathway remains very poorly characterized. The bi-substrate kinetic parameters of a recombinant human glycine N-acyltransferase (GLYAT, E.C. 2.3.1.13) were determined using the traditional colorimetric method and a newly developed HPLC-ESI-MS/MS method. Previous studies analyzing the kinetic parameters of GLYAT, indicated a random Bi-Bi and/or ping-pong mechanism. In this study, the hippuric acid concentrations produced by the GLYAT enzyme reaction were analyzed using the allosteric sigmoidal enzyme kinetic module. Analyses of the initial rate (v) against substrate concentration plots, produced a sigmoidal curve (substrate activation) when the benzoyl-CoA concentrations was kept constant, whereas the plot with glycine concentrations kept constant, passed through a maximum (substrate inhibition). Thus, human GLYAT exhibits mechanistic kinetic cooperativity as described by the Ferdinand enzyme mechanism rather than the previously assumed Michaelis-Menten reaction mechanism. PMID: 28759163 [PubMed - indexed for MEDLINE]

Related Articles Dioxygenase-encoding AtDAO1 gene controls IAA oxidation and homeostasis in Arabidopsis. Proc Natl Acad Sci U S A. 2016 09 27;113(39):11016-21 Authors: Porco S, Pěnčík A, Rashed A, Voß U, Casanova-Sáez R, Bishopp A, Golebiowska A, Bhosale R, Swarup R, Swarup K, Peňáková P, Novák O, Staswick P, Hedden P, Phillips AL, Vissenberg K, Bennett MJ, Ljung K Abstract Auxin represents a key signal in plants, regulating almost every aspect of their growth and development. Major breakthroughs have been made dissecting the molecular basis of auxin transport, perception, and response. In contrast, how plants control the metabolism and homeostasis of the major form of auxin in plants, indole-3-acetic acid (IAA), remains unclear. In this paper, we initially describe the function of the Arabidopsis thaliana gene DIOXYGENASE FOR AUXIN OXIDATION 1 (AtDAO1). Transcriptional and translational reporter lines revealed that AtDAO1 encodes a highly root-expressed, cytoplasmically localized IAA oxidase. Stable isotope-labeled IAA feeding studies of loss and gain of function AtDAO1 lines showed that this oxidase represents the major regulator of auxin degradation to 2-oxoindole-3-acetic acid (oxIAA) in Arabidopsis Surprisingly, AtDAO1 loss and gain of function lines exhibited relatively subtle auxin-related phenotypes, such as altered root hair length. Metabolite profiling of mutant lines revealed that disrupting AtDAO1 regulation resulted in major changes in steady-state levels of oxIAA and IAA conjugates but not IAA. Hence, IAA conjugation and catabolism seem to regulate auxin levels in Arabidopsis in a highly redundant manner. We observed that transcripts of AtDOA1 IAA oxidase and GH3 IAA-conjugating enzymes are auxin-inducible, providing a molecular basis for their observed functional redundancy. We conclude that the AtDAO1 gene plays a key role regulating auxin homeostasis in Arabidopsis, acting in concert with GH3 genes, to maintain auxin concentration at optimal levels for plant growth and development. PMID: 27651491 [PubMed - indexed for MEDLINE]

Related Articles Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation. Proc Natl Acad Sci U S A. 2016 10 04;113(40):11255-11260 Authors: Sferruzzi-Perri AN, López-Tello J, Fowden AL, Constancia M Abstract Pregnancy success and life-long health depend on a cooperative interaction between the mother and the fetus in the allocation of resources. As the site of materno-fetal nutrient transfer, the placenta is central to this interplay; however, the relative importance of the maternal versus fetal genotypes in modifying the allocation of resources to the fetus is unknown. Using genetic inactivation of the growth and metabolism regulator, Pik3ca (encoding PIK3CA also known as p110α, α/+), we examined the interplay between the maternal genome and the fetal genome on placental phenotype in litters of mixed genotype generated through reciprocal crosses of WT and α/+ mice. We demonstrate that placental growth and structure were impaired and associated with reduced growth of α/+ fetuses. Despite its defective development, the α/+ placenta adapted functionally to increase the supply of maternal glucose and amino acid to the fetus. The specific nature of these changes, however, depended on whether the mother was α/+ or WT and related to alterations in endocrine and metabolic profile induced by maternal p110α deficiency. Our findings thus show that the maternal genotype and environment programs placental growth and function and identify the placenta as critical in integrating both intrinsic and extrinsic signals governing materno-fetal resource allocation. PMID: 27621448 [PubMed - indexed for MEDLINE]

Related Articles Untargeted saliva metabonomics study of breast cancer based on ultra performance liquid chromatography coupled to mass spectrometry with HILIC and RPLC separations. Talanta. 2016 Sep 01;158:351-60 Authors: Zhong L, Cheng F, Lu X, Duan Y, Wang X Abstract Breast cancer (BC) is not only the most frequently diagnosed cancer, but also the leading cause of cancer death among women worldwide. This study aimed to screen the potential salivary biomarkers for breast cancer diagnosis, staging, and biomarker discovery. For the first time, a UPLC-MS based method along with multivariate data analysis, was proposed for the global saliva metabonomics analysis and diagnosis of BC, which used both hydrophilic interaction chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) separations and operated in both positive (ESI+) and negative (ESI-) ionization modes. On account of different polarities of endogenous metabolites, this method was established to overcome the boundedness of a single chromatographic approach. As a result, 18 potential metabolites for diagnosing BC were identified. A nonparametric Mann-Whitney U test, heat map, and the receiver operating characteristic (ROC) were exploited to analyze the data with the purpose of evaluating the predictive power of the 18 biomarkers. Significant differences (P<0.05) were disclosed in terms of the levels of the 18 potential biomarkers between BC patients and healthy controls (HC). Among the 18 biomarkers, three up-regulated metabolites, LysoPC (18:1), LysoPC (22:6) and MG (0:0/14:0/0:0) displayed the area under the curve (AUC) values of 0.920, 0.920 and 0.929, respectively, indicating the high accuracy of this method to predict BC. In this study, an integrated metabonomics analysis in human saliva for identifying potential biomarkers to diagnose and stage BC was successfully eastablished, which was non-invasive, reliable, low-cost, and simple. The HILIC was demonstrated to be essential for a comprehensive saliva metabonomics profiling as well as RPLC separation. This saliva metabonomics technique may provide new insight into the discovery and identification of diagnostic biomarkers for BC. PMID: 27343615 [PubMed - indexed for MEDLINE]