PubMed

Toxic effects of male Perna viridisgonad exposed to BaP, DDT and their mixture: A metabolomic and proteomic study of the underlying mechanism. Toxicol Lett. 2015 Nov 4; Authors: Song Q, Zheng P, Qiu L, Jiang X, Zhao H, Zhou H, Han Q, Diao X Abstract Benzo(a)pyrene and dichlorodiphenyltrichloroethane are typical persistent organic pollutants, and also the widespread environmental estrogens with known toxicity towards green mussels Perna viridis. In this study, the toxicological effects of BaP and DDT and their mixture were assessed in green mussel gonads using proteomic and metabolomic approaches. Metabolomics by NMR spectroscopy revealed that BaP didn't show obvious metabolite changes in the gonad of male green mussel. DDT mainly caused some disturbance of osmotic regulation and energy metabolism by changing BCAAs, alanine, threonine, arginine, etc., unknown metabolite (3.53ppm), glycine, homarine and ATP at different levels. However, the mixture of BaP and DDT mainly caused some disturbance in osmotic regulation and energy metabolism by differentially altering branched chain amino acids, glutamate, alanine, arginine, unknown metabolite (3.53ppm), glycine, 4-aminobutyrate, dimethylglycine, homarine and ATP. The results suggest that DDT alone may cause most of metabolites changes in the mixture exposed mussel gonad, and the results also show that the male Perna viridis gonad was more sensitive to DDT than BaP exposures. Proteomic study showed that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced signal transduction, oxidative stress, spermatogenesis, etc. in the male green mussel gonad; whereas DDT exposure altered proteins that were associated with signal transduction, oxidative stress, cytoskeleton and cell structure, cellular organization, energy metabolism, etc. However, the mixture of BaP and DDT affected proteins related to cytoskeleton and cell structure, oxidative stress, cellular organization, etc. This research demonstrated that metabolomic and proteomic approaches could better elucidate the underlying mechanism of environmental pollutants gonad toxicity. PMID: 26546779 [PubMed - as supplied by publisher]

Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis. J Biol Chem. 2015 Nov 6; Authors: Poisson LM, Suhail H, Singh J, Datta I, Denic A, Labuzek K, Hoda MN, Shankar A, Kumar A, Cerghet M, Elias S, Mohney RP, Rodriguez M, Rattan R, Mangalam AK, Giri S Abstract We performed untargeted metabolomics of plasma from B6 mice with experimental autoimmune encephalitis (EAE) at the chronic phase of the disease in search of an altered metabolic pathway(s). Of 324 metabolites measured, 100 metabolites that mapped to various pathways (mainly lipids) linked to mitochondrial function, inflammation and membrane stability were observed to be significantly altered between EAE and healthy control (p < 0.05, false discover rate [< 0.10]. Bioinformatics analysis revealed 6 metabolic pathways being impacted and altered in EAE including alpha linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, including omega 3 and omega 6 fatty acids, are commonly decreased in mouse models and in multiple sclerosis patients. Daily oral administration of resolvin D1, a downstream metabolite of omega 3, decreased disease progression by suppressing autoreactive T cells and inducing a M2 phenotype of monocytes/macrophages and resident brain microglial cells. This study provides a proof of principle for the application of a metabolomic approach to identify endogenous metabolite(s) possessing drug-like properties, which is tested for therapy in preclinical mouse models. PMID: 26546682 [PubMed - as supplied by publisher]

1H NMR metabolic profiling of cod (Gadus morhua) larvae: potential effects of temperature and diet composition during early developmental stages. Biol Open. 2015 Nov 6; Authors: Chauton MS, Galloway TF, Kjørsvik E, Størseth TR, Puvanendran V, van der Meeren T, Karlsen Ø, Rønnestad I, Hamre K Abstract Marine aquaculture offers a great source of protein for the increasing human population, and farming of, for example, Atlantic salmon is a global industry. Atlantic cod farming however, is an example of a promising industry where the potential is not yet realized. Research has revealed that a major bottleneck to successful farming of cod is poor quality of the larvae and juveniles. A large research program was designed to increase our understanding of how environmental factors such as temperature and nutrition affects cod larvae development. Data on larvae growth and development were used together with nuclear magnetic resonance. The NMR data indicated that the temperature influenced the metabolome of the larvae; differences were related to osmolytes such as betaine/TMAO, the amino acid taurine, and creatine and lactate which reflect muscle activity. The larvae were fed Artemia from stage 2, and this was probably reflected in a high taurine content of older larvae. Larvae fed with copepods in the nutrition experiment also displayed a high taurine content, together with higher creatine and betaine/TMAO content. Data on the cod larvae metabolome should be coupled to data on gene expression, in order to identify events which are regulated on the genetic level versus regulation resulting from temperature or nutrition during development, to fully understand how the environment affects larval development. PMID: 26545964 [PubMed - as supplied by publisher]

Integration of metabolomics and transcriptomics reveals major metabolic pathways and potential biomarker involved in prostate cancer. Mol Cell Proteomics. 2015 Nov 6; Authors: Ren S, Shao Y, Zhao X, Hong CS, Wang F, Lu X, Li J, Ye G, Zhuang Z, Xu C, Xu G, Sun Y Abstract Prostate cancer is a highly prevalent tumor affecting millions of men world-wide, but poor understanding of its pathogenesis has limited effective clinical management of patients. In addition to transcriptional profiling or transcriptomics, metabolomics is being increasingly utilized to discover key molecular changes underlying tumorigenesis. In this study, we integrated transcriptomics and metabolomics to analyze 25 paired human prostate cancer tissues and adjacent noncancerous tissues, followed by further validation of our findings in an additional cohort of 51 prostate cancer patients and 16 benign prostatic hyperplasia patients. We found several altered pathways aberrantly expressed at both metabolic and transcriptional levels, including cysteine and methionine metabolism, nicotinamide adenine dinucleotide metabolism, and hexosamine biosynthesis. Additionally, the metabolite sphingosine demonstrated high specificity and sensitivity for distinguishing prostate cancer from benign prostatic hyperplasia, particularly for patients with low prostate specific antigen level (0-10 ng/mL). We also found impaired sphingosine-1-phosphate receptor 2 signaling, downstream of sphingosine, representing a loss of tumor suppressor gene and a potential key oncogenic pathway for therapeutic targeting. By integrating metabolomics and transcriptomics, we have provided both a broad picture of the molecular perturbations underlying prostate cancer and a preliminary study of a novel metabolic signature, which may help to discriminate prostate cancer from normal tissue and benign prostatic hyperplasia. PMID: 26545398 [PubMed - as supplied by publisher]

Pioneering ambient mass spectrometry imaging in psychiatry: Potential for new insights into schizophrenia. Schizophr Res. 2015 Nov 3; Authors: Vendramini PH, Gattaz WF, Schmitt A, Falkai P, Eberlin MN, Martins-de-Souza D PMID: 26545296 [PubMed - as supplied by publisher]

Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice. Atherosclerosis. 2015 Oct 26;243(2):598-608 Authors: Rasmiena AA, Barlow CK, Stefanovic N, Huynh K, Tan R, Sharma A, Tull D, de Haan JB, Meikle PJ Abstract BACKGROUND AND AIM: We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress. METHODS AND RESULTS: Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta. CONCLUSION: Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. PMID: 26545014 [PubMed - as supplied by publisher]

High-throughput platforms for metabolomics. Curr Opin Chem Biol. 2015 Nov 3;30:7-13 Authors: de Raad M, Fischer CR, Northen TR Abstract Mass spectrometry has become a choice method for broad-spectrum metabolite analysis in both fundamental and applied research. This can range from comprehensive analysis achieved through time-consuming chromatography to the rapid analysis of a few target metabolites without chromatography. In this review article, we highlight current high-throughput MS-based platforms and their potential application in metabolomics. Although current MS platforms can reach throughputs up to 0.5seconds per sample, the metabolite coverage of these platforms are low compared to low-throughput, separation-based MS methods. High-throughput comes at a cost, as it's a trade-off between sample throughput and metabolite coverage. As we will discuss, promising emerging technologies, including microfluidics and miniaturization of separation techniques, have the potential to achieve both rapid and more comprehensive metabolite analysis. PMID: 26544850 [PubMed - as supplied by publisher]

Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study. PLoS One. 2015;10(11):e0142610 Authors: Alonso A, Yu B, Qureshi WT, Grams ME, Selvin E, Soliman EZ, Loehr LR, Chen LY, Agarwal SK, Alexander D, Boerwinkle E Abstract BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited. METHODS: We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987-1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates. RESULTS: During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12-1.32) for glycolithocholate sulfate and 1.22 (1.10-1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes. CONCLUSION: We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted. PMID: 26544570 [PubMed - as supplied by publisher]

Diabetes and cardiovascular disease: let's push forward with translational research. Cardiovasc Diagn Ther. 2015 Oct;5(5):407-11 Authors: Paneni F, Costantino S Abstract Albeit advances in therapy have reduced morbidity and mortality in patients with diabetes, cardiovascular (CV) risk is far to be eradicated. This is partially due to the fact that breakthrough therapies have yet to be approved to counteract the atherosclerotic burden in this setting. Therefore, it is very important to understand the molecular mechanisms underpinning diabetes-related CV complications. Growing evidence is supporting the concept that translational research is perhaps the best approach to unveil novel insights into disease etiology and its link with CV phenotypes. The recent employment of high throughput "omics" (i.e., metabolomics, transcriptomics, proteomics) is a clinically relevant approach which may provide insightful interpretations of diabetes-related biological signals. The possibility to analyse thousands or more molecules simultaneously has given "omics" the ability to generate enormous quantities of data which may somehow offer a precious "window on the disease". In the present article, we critically discuss the importance of translational research in diabetes, including potential difficulties which may arise in the implementation and development of promising technologies from the laboratory to the marketplace. PMID: 26543828 [PubMed]

Production of hyperpolarized (13)CO2 from [1-(13)C]pyruvate in perfused liver does reflect total anaplerosis but is not a reliable biomarker of glucose production. Metabolomics. 2015 Oct;11(5):1144-1156 Authors: Moreno KX, Moore CL, Burgess SC, Sherry AD, Malloy CR, Merritt ME Abstract In liver, (13)CO2 can be generated from [1-(13)C] pyruvate via pyruvate dehydrogenase or anaplerotic entry of pyruvate into the TCA cycle followed by decarboxylation at phosphoenolpyruvate carboxykinase (PEPCK), the malic enzyme, isocitrate dehydrogenase, or α-ketoglutarate dehydrogenase. The purpose of this study was to determine the relative importance of these pathways in production of hyperpolarized (HP) (13)CO2 after administration of hyper-polarized pyruvate in livers supplied with a fatty acid plus substrates for gluconeogenesis. Isolated mouse livers were perfused with a mixture of thermally-polarized (13)C-enriched pyruvate, lactate and octanoate in various combinations prior to exposure to HP pyruvate. Under all perfusion conditions, HP malate, aspartate and fumarate were detected within ~ 3 s showing that HP [1-(13)C]pyruvate is rapidly converted to [1-(13)C]oxaloacetate which can subsequently produce HP (13)CO2 via decarboxylation at PEPCK. Measurements using HP [2-(13)C]pyruvate allowed the exclusion of reactions related to TCA cycle turnover as sources of HP (13)CO2. Direct measures of O2 consumption, ketone production, and glucose production by the intact liver combined with (13)C isotopomer analyses of tissue extracts yielded a comprehensive profile of metabolic flux in perfused liver. Together, these data show that, even though the majority of HP (13)CO2 derived from HP [1-(13)C]pyruvate in livers exposed to fatty acids reflects decarboxylation of [4-(13)C]oxaloacetate (PEPCK) or [4-(13)C]malate (malic enzyme), the intensity of the HP (13)CO2 signal is not proportional to glucose production because the amount of pyruvate returned to the TCA cycle via PEPCK and pyruvate kinase is variable, depending upon available substrates. PMID: 26543443 [PubMed - as supplied by publisher]

Calcified nodules on fingers in a primary hyperoxaluria type 2. Lancet Diabetes Endocrinol. 2015 Nov 2; Authors: Yamanouchi M, Ubara Y, Takayama T, Kuhara T, Takaichi K PMID: 26542998 [PubMed - as supplied by publisher]

Lessons learned from metabolomics in cystic fibrosis. Mol Cell Pediatr. 2015 Dec;2(1):9 Authors: Muhlebach MS, Sha W Abstract Cystic fibrosis is a mono-genetic multi-system disease; however, respiratory manifestations cause the main morbidity and mortality where chronic bacterial infections lead to bronchiectasis and ultimately respiratory failure. Metabolomics allows a relatively complete snapshot of metabolic processes in a sample using different mass spectrometry methods. Sample types used for discovery of biomarkers or pathomechanisms in cystic fibrosis (CF) have included blood, respiratory secretions, and exhaled breath to date. Metabolomics has shown distinction of CF vs. non-CF for matrices of blood, exhaled breath, and respiratory epithelial cultures, each showing different pathways. Severity of lung disease has been addressed by studies in bronchoalveolar lavage and exhaled breath condensate showing separation by metabolites that the authors of each study related to inflammation; e.g., ethanol, acetone, purines. Lipidomics has been applied to blood and sputum samples showing associations with lung function and Pseudomonas aeruginosa infection status. Finally, studies of bacteria grown in vitro showed differences of bacterial metabolites to be associated with clinical parameters. Metabolomics, in the sense of global metabolomic profiling, is a powerful technique that has allowed discovery of pathways that had not previously been implicated in CF. These may include purines, mitochondrial pathways, and different aspects of glucose metabolism besides the known differences in lipid metabolism in CF. However, targeted studies to validate such potential metabolites and pathways of interest are necessary. Studies evaluating metabolites of bacterial origin are in their early stages. Thus further well-designed studies could be envisioned. PMID: 26542299 [PubMed]

Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015 Nov 5; Authors: Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CP, Poirier-Colame V, Roux A, Becharef S, Formenti S, Golden E, Cording S, Eberl G, Schlitzer A, Ginhoux F, Mani S, Yamazaki T, Jacquelot N, Enot DP, Bérard M, Nigou J, Opolon P, Eggermont A, Woerther PL, Chachaty E, Chaput N, Robert C, Mateus C, Kroemer G, Raoult D, Boneca IG, Carbonnel F, Chamaillard M, Zitvogel L Abstract Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, or by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that anti-CTLA-4 treatment of melanoma patients favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade. PMID: 26541610 [PubMed - as supplied by publisher]

Changes in the NMR Metabolic Profile of Live Human Neuron-Like SH-SY5Y Cells Exposed to Interferon-α2. J Neuroimmune Pharmacol. 2015 Nov 5; Authors: Valeria R, Luisa S, Adele M, Stefania B, Fabio T, Nicoletta B, Carmine PM, Silvia A Abstract Interferon (IFN)-α2 is an extensively therapeutically used pro-inflammatory cytokine. Though its efficacy in controlling viral replication and tumor cells proliferation, administration of IFN-α2 is often associated with the development of central side effects. Magnetic resonance spectroscopy studies have demonstrated that IFN-α2 administration affects brain metabolism, however the exact nature of this effect is not completely known. We hypothesized that IFN-α2 can affect metabolic activity of human neuron-like SH-SY5Y cells which possess many characteristics of neurons and represent one of the most used models for studying mechanisms involved in neurotoxicity or neuroprotection. To test our hypothesis we have characterized the metabolic signature of live SH-SY5Y, and their conditioned media, after 24 and 72 h of exposure to vehicle or IFN-α2 (100 ng/ml) by using High Resolution-Magic Angle Spinning (HR-MAS) Nuclear Magnetic Resonance (NMR) spectroscopy. Our results revealed that 1) the use of HR-MAS NMR is ideally suitable for the characterization of the metabolic profile of live cells and their conditioned media without extraction procedures; and 2) a 72 h exposure to IFN-α2 increases the level of metabolites involved in maintaining energetic (including creatine and lactate) and osmotic (such as myo-inositol, scyllo-inositol, taurine and glycerophosphorylcholine) balances in neuron-like cells and of metabolic waste products (namely lactate, ethanol and acetate), glycine and glutamine in their growth media. These results may contribute to gain more knowledge about the IFN-α2 induced effect on the brain and support the interpretation of magnetic resonance spectroscopy studies performed in humans. PMID: 26541470 [PubMed - as supplied by publisher]

The Cooperative Health Research in South Tyrol (CHRIS) study: rationale, objectives, and preliminary results. J Transl Med. 2015;13(1):348 Authors: Pattaro C, Gögele M, Mascalzoni D, Melotti R, Schwienbacher C, De Grandi A, Foco L, D'Elia Y, Linder B, Fuchsberger C, Minelli C, Egger C, Kofink LS, Zanigni S, Schäfer T, Facheris MF, Smárason SV, Rossini A, Hicks AA, Weiss H, Pramstaller PP Abstract The Cooperative Health Research In South Tyrol (CHRIS) study is a population-based study with a longitudinal lookout to investigate the genetic and molecular basis of age-related common chronic conditions and their interaction with life style and environment in the general population. All adults of the middle and upper Vinschgau/Val Venosta are invited, while 10,000 participants are anticipated by mid-2017. Family participation is encouraged for complete pedigree reconstruction and disease inheritance mapping. After a pilot study on the compliance with a paperless assessment mode, computer-assisted interviews have been implemented to screen for conditions of the cardiovascular, endocrine, metabolic, genitourinary, nervous, behavioral, and cognitive system. Fat intake, cardiac health, and tremor are assessed instrumentally. Nutrient intake, physical activity, and life-course smoking are measured semi-quantitatively. Participants are phenotyped for 73 blood and urine parameters and 60 aliquots per participant are biobanked (cryo-preserved urine, DNA, and whole and fractionated blood). Through liquid-chromatography mass-spectrometry analysis, metabolite profiling of the mitochondrial function is assessed. Samples are genotyped on 1 million variants with the Illumina HumanOmniExpressExome array and the first data release including 4570 fully phenotyped and genotyped samples is now available for analysis. Participants' follow-up is foreseen 6 years after the first visit. The target population is characterized by long-term social stability and homogeneous environment which should both favor the identification of enriched genetic variants. The CHRIS cohort is a valuable resource to assess the contribution of genomics, metabolomics, and environmental factors to human health and disease. It is awaited that this will result in the identification of novel molecular targets for disease prevention and treatment. PMID: 26541195 [PubMed - in process]

Related Articles Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa. J Virol. 2015 Sep;89(18):9427-39 Authors: van der Meijden E, Kazem S, Dargel CA, van Vuren N, Hensbergen PJ, Feltkamp MC Abstract UNLABELLED: The polyomavirus tumor (T) antigens play crucial roles in viral replication, transcription, and cellular transformation. They are encoded by partially overlapping open reading frames (ORFs) located in the early region through alternative mRNA splicing. The T expression pattern of the trichodysplasia spinulosa-associated polyomavirus (TSPyV) has not been established yet, hampering further study of its pathogenic mechanisms and taxonomic relationship. Here, we characterized TSPyV T antigen expression in human cell lines transfected with the TSPyV early region. Sequencing of T antigen-encoded reverse transcription-PCR (RT-PCR) products revealed three splice donor and acceptor sites creating six mRNA splice products that potentially encode the antigens small T (ST), middle T (MT), large T (LT), tiny T, 21kT, and alternative T (ALTO). Except for 21kT, these splice products were also detected in skin of TSPyV-infected patients. At least three splice products were confirmed by Northern blotting, likely encoding LT, MT, ST, 21kT, and ALTO. Protein expression was demonstrated for LT, ALTO, and possibly MT, with LT detected in the nucleus and ALTO in the cytoplasm of transfected cells. Splice site and start codon mutations indicated that ALTO is encoded by the same splice product that encodes LT and uses internal start codons for initiation. The genuineness of ALTO was indicated by the identification of acetylated N-terminal ALTO peptides by mass spectrometry. Summarizing, TSPyV exhibits an expression pattern characterized by both MT and ALTO expression, combining features of rodent and human polyomaviruses. This unique expression pattern provides important leads for further study of polyomavirus-related disease and for an understanding of polyomavirus evolution. IMPORTANCE: The human trichodysplasia spinulosa-associated polyomavirus (TSPyV) is distinguished among polyomaviruses for combining productive infection with cell-transforming properties. In the research presented here, we further substantiate this unique position by indicating expression of both middle T antigen (MT) and alternative T antigen (ALTO) in TSPyV. So far, none of the human polyomaviruses was shown to express MT, which is considered the most important viral oncoprotein of rodent polyomaviruses. Coexpression of ALTO and MT, which involves a conserved, recently recognized overlapping ORF subject to positive selection, has not been observed before for any polyomavirus. As a result of our findings, this study provides valuable new insights into polyomavirus T gene use and expression. Obviously, these insights will be instrumental in further study and gaining an understanding of TSPyV pathogenicity. More importantly, however, they provide important leads with regard to the interrelationship, functionality, and evolution of polyomaviruses as a whole, indicating that TSPyV is a suitable model virus to study these entities further. PMID: 26136575 [PubMed - indexed for MEDLINE]

Related Articles Characterization of ampicillin-stressed proteomics and development of a direct method for detecting drug-binding proteins in Edwardsiella tarda. J Proteomics. 2015 Feb 26;116:97-105 Authors: Liu XJ, Zhu WC, Su YB, Guo C, Zeng ZH, Zhu H, Li H, Peng XX Abstract UNLABELLED: Antibiotic-resistant Edwardsiella tarda poses a severe challenge to aquaculture. An understanding for antibiotic-resistant mechanisms is crucial to control the disease. The present study characterizes E. tarda ampicillin-stressed proteome and shows the importance of energy metabolism including the TCA cycle and glycolysis/gluconeogenesis in the antibiotic resistance. Further combination with antibiotic measurement develops a new method for identification of antibiotic-binding proteins out of differential abundances of proteins and results in determination of ETAE_0175 and ETAE_3367 as ampicillin-binding proteins in E. tarda. Genes of the two proteins are cloned and recombinant proteins are purified for validation of antibiotic-binding capability. Results show that higher binding capability is detected in ETAE_3367 than ETAE_0175. Out of the two proteins, ETAE_3367 is first reported here to be an antibiotic-binding protein, while ETAE_0175 homology in other bacteria has been shown to bind with other antibiotics. Bioinformatics analysis shows that ETAE_3367 may closely interact with aceF and sucA belonging to the TCA cycle and glycolysis/gluconeogenesis, respectively. These results indicate that energy metabolism contributes to ampicillin resistance in E. tarda and a new method to identify antibiotic-binding proteins is developed. These findings highlight the way to an understanding of antibiotic-resistant mechanisms in content of antibiotic-binding proteins. BIOLOGICAL SIGNIFICANCE: Our data characterizes Edwardsiella tarda ampicillin-stressed proteome and shows the importance of energy metabolism including the TCA cycle and glycolysis/gluconeogenesis in the antibiotic resistance. Furthermore, a new method based 2-DE proteomics is developed for identification of antibiotic-binding proteins, which results in determination of ETAE_0175 and ETAE_3367 as ampicillin-binding proteins in E. tarda. ETAE_3367 is closely interacted with proteins of the TCA cycle and glycolysis/gluconeogenesis, suggesting the drug-resistant mechanism. PMID: 25596334 [PubMed - indexed for MEDLINE]

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Molecular Regulation of Circadian Rhythms by Polyamines. Cell Metab. 2015 Nov 3;22(5):757-758 Authors: Galluzzi L, Pietrocola F, Kroemer G Abstract In this issue of Cell Metabolism, Zwighaft and colleagues (Zwighaft et al., 2015) describe a novel mechanism through which intracellular polyamines regulate circadian rhythms. These findings are significant, as they add yet another layer of complexity to the interplay between environmental, dietary, and organismal factors in the molecular control of daily behavioral oscillations. PMID: 26536485 [PubMed - as supplied by publisher]

Quality assurance of metabolomics. ALTEX. 2015;32(4):319-326 Authors: Bouhifd M, Beger R, Flynn T, Guo L, Harris G, Hogberg H, Kaddurah-Daouk R, Kamp H, Kleensang A, Maertens A, Odwin-DaCosta S, Pamies D, Robertson D, Smirnova L, Sun J, Zhao L, Hartung T Abstract Metabolomics promises a holistic phenotypic characterization of biological responses to toxicants. This technology is based on advanced chemical analytical tools with reasonable throughput, including mass-spectroscopy and NMR. Quality assurance, however - from experimental design, sample preparation, metabolite identification, to bioinformatics data-mining - is urgently needed to assure both quality of metabolomics data and reproducibility of biological models. In contrast to microarray-based transcriptomics, where consensus on quality assurance and reporting standards has been fostered over the last two decades, quality assurance of metabolomics is only now emerging. Regulatory use in safety sciences, and even proper scientific use of these technologies, demand quality assurance. In an effort to promote this discussion, an expert workshop discussed the quality assurance needs of metabolomics. The goals for this workshop were 1) to consider the challenges associated with metabolomics as an emerging science, with an emphasis on its application in toxicology and 2) to identify the key issues to be addressed in order to establish and implement quality assurance procedures in metabolomics-based toxicology. Consensus has still to be achieved regarding best practices to make sure sound, useful, and relevant information is derived from these new tools. PMID: 26536290 [PubMed - as supplied by publisher]