PubMed

Related Articles Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection. JCI Insight. 2018 Mar 08;3(5): Authors: Cikach FS, Koch CD, Mead TJ, Galatioto J, Willard BB, Emerton KB, Eagleton MJ, Blackstone EH, Ramirez F, Roselli EE, Apte SS Abstract Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair. PMID: 29515038 [PubMed - as supplied by publisher]

Related Articles Liver Metabolic Perturbations of Heat-Stressed Lactating Dairy Cows. Asian-Australas J Anim Sci. 2018 Mar 02;: Authors: Fan C, Su D, Tian H, Li X, Li Y, Ran L, Hu R, Cheng J Abstract Objective: The objective of the present study was to elucidate the mechanism underlying liver metabolic perturbations in dairy cows exposed to heat stress (HS). Method: Liquid chromatography mass spectrometry (LC-MS) was used to analyze metabolic differences in livers of 20 dairy cows, with and without exposure to HS. Results: The results revealed 33 potential metabolite candidate biomarkers for the detection of HS in dairy cows. Fifteen of these metabolites (glucose, lactate, pyruvate, acetoacetate, β-hydroxybutyrate (BHBA), fumaric acid, citric acid, choline, glycine, proline, isoleucine, leucine, urea, creatinine, and orotic acid) were previously found to be potential biomarkers of HS in plasma or milk, discriminating dairy cows with and without HS. Conclusion: All the potential diagnostic biomarkers were involved in glycolysis, amino acid, ketone, tricarboxylic acid (TCA), or nucleotide metabolism, indicating that HS mainly affected energy and nucleotide metabolism in lactating dairy cows. PMID: 29514433 [PubMed - as supplied by publisher]

Related Articles Mass spectrometry in epidemiological studies: What are the key considerations? Eur J Epidemiol. 2016 08;31(8):715-6 Authors: Dehghan A PMID: 27565981 [PubMed - indexed for MEDLINE]

Related Articles Transcriptome and metabolome of synthetic Solanum autotetraploids reveal key genomic stress events following polyploidization. New Phytol. 2016 Jun;210(4):1382-94 Authors: Fasano C, Diretto G, Aversano R, D'Agostino N, Di Matteo A, Frusciante L, Giuliano G, Carputo D Abstract Polyploids are generally classified as autopolyploids, derived from a single species, and allopolyploids, arising from interspecific hybridization. The former represent ideal materials with which to study the consequences of genome doubling and ascertain whether there are molecular and functional rules operating following polyploidization events. To investigate whether the effects of autopolyploidization are common to different species, or if species-specific or stochastic events are prevalent, we performed a comprehensive transcriptomic and metabolomic characterization of diploids and autotetraploids of Solanum commersonii and Solanum bulbocastanum. Autopolyploidization remodelled the transcriptome and the metabolome of both species. In S. commersonii, differentially expressed genes (DEGs) were highly enriched in pericentromeric regions. Most changes were stochastic, suggesting a strong genotypic response. However, a set of robustly regulated transcripts and metabolites was also detected, including purine bases and nucleosides, which are likely to underlie a common response to polyploidization. We hypothesize that autopolyploidization results in nucleotide pool imbalance, which in turn triggers a genomic shock responsible for the stochastic events observed. The more extensive genomic stress and the higher number of stochastic events observed in S. commersonii with respect to S. bulbocastanum could be the result of the higher nucleoside depletion observed in this species. PMID: 26915816 [PubMed - indexed for MEDLINE]

DNA distribution pattern and metabolite profile of wild edible lobster mushroom (Hypomyces lactifluorum/Russula brevipes). Genome. 2018 Mar 07;: Authors: Laperriere G, Desgagné-Penix I, Germain H Abstract Lobster mushroom is a wild edible mushroom with potential commercial value. It is the product resulting of the infection, most commonly of Russula brevipes by Hypomyces lactifluorum. This study undertook quantitative polymerase chain reaction analysis of tissues sampled at different infection stages, to investigate R. brevipes/H. lactifluorum interaction. We followed the colonization of R. brevipes sporocarps by H. lactifluorum which leads to the edible lobster mushrooms. In parallel, metabolomics analysis was performed to detect differences in metabolite profile among non-infected R. brevipes sporocarp and lobster mushroom. The results show that H. lactifluorum's DNA is not restricted to the margin, but is distributed relatively evenly across the sporocarp of the lobster mushroom. DNA of R. brevipes was also present throughout the sporocarp, but was less abundant at the margins and increased inwards. R. brevipes' DNA also declined as the infection progressed. Metabolomics analysis revealed that the flesh of lobster mushroom, which remains identical in appearance to the flesh of the host, undergoes transformation that alters its metabolite profile, most notably of lipids and terpene compounds. These results define a parasitic relationship between the two species which entails a decline of R. brevipes' DNA and a modification of its metabolite profile. PMID: 29514010 [PubMed - as supplied by publisher]

Augmented frontal cortex diacylglycerol levels in Parkinson's disease and Lewy Body Disease. PLoS One. 2018;13(3):e0191815 Authors: Wood PL, Tippireddy S, Feriante J, Woltjer RL Abstract BACKGROUND: Research from our laboratory, and that of other investigators, has demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of subjects with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). We have extended these observations to investigate the frontal cortex of subjects with Parkinson's disease (PD) and Lewy Body Disease (LBD), with and without coexisting pathologic features of AD. METHODS/PRINCIPAL FINDINGS: Utilizing a high-resolution mass spectrometry analytical platform, we clearly demonstrate that DAG levels are significantly increased in the frontal cortex of subjects with PD, LBD with intermediate neocortical AD neuropathology, and in LBD with established neocortical AD neuropathology. In the case of the PD cohort, increases in cortical DAG levels were detected in cases with no neocortical pathology but were greater in subjects with neocortical pathology. These data suggest that DAG changes occur early in the disease processes and are amplified as cortical dysfunction becomes more established. CONCLUSIONS: These findings suggest that altered DAG synthesis/metabolism is a common feature of neurodegenerative diseases, characterized by proteinopathy, that ultimately result in cognitive deficits. With regard to the mechanism responsible for these biochemical alterations, selective decrements in cortical levels of phosphatidylcholines in LBD and PD suggest that augmented degradation and/or decreased synthesis of these structural glycerophospholipids may contribute to increases in the pool size of free DAGs. The observed augmentation of DAG levels may be phospholipase-driven since neuroinflammation is a consistent feature of all disease cohorts. If this conclusion can be validated it would support utilizing DAG levels as a biomarker of the early disease process and the investigation of early intervention with anti-inflammatory agents. PMID: 29513680 [PubMed - in process]

Metabolic Profiling of Amino Acids Associated with Mortality in Patients with Acute Paraquat Poisoning. Med Sci Monit. 2018 Mar 07;24:1397-1407 Authors: Wan X, Zhou C, Kang X, Hu D, Xue W, Li X, Bao H, Peng A Abstract BACKGROUND Paraquat is a major cause of fatal poisoning after ingestion in many parts of Asia and the Pacific nations. However, optimal prognostic indicators to evaluate patient mortality have not been unequivocally established. Following acute paraquat poisoning, a number of amino acids (AA), are abnormally expressed in metabolic pathways. However, the alterations in AA metabolite levels after paraquat poisoning remain unknown in humans. MATERIAL AND METHODS In the present study, 40 patients were enrolled, of whom 16 survived and 24 died. A metabolomics approach was used to assess changes in AA metabolites in plasma and its potential prognostic value following paraquat poisoning. Mass spectrometry (MS) based on metabolite identification was conducted. RESULTS Twenty-five AA levels in plasma were abnormally expressed in non-survivor patients. Among them, creatinine, indolelactate, and 3-(4-hydroxyphenyl)lactate were found to be highly correlated with paraquat death prediction. It was noted that the intensity levels of these 3 AA metabolites in the non-survivor group were substantially higher than in the survivor group. Furthermore, we examined receiver operating characteristic (ROC) curves for clinical validation. ROC results showed that 3-(4-hydroxyphenyl)lactate had the highest AUC of 0.84, while indolelactate and creatinine had AUCs of 0.75 and 0.83, respectively, suggesting that they can be used to predict the clinical outcome (although this methodology is expensive to implement). CONCLUSIONS Metabolic profiling of AA levels could be a reliable tool to identify effective indicators for the early high precision prognosis of paraquat poisoning. PMID: 29513648 [PubMed - in process]

Integrating Proteomics and Targeted Metabolomics to Understand Global Changes in Histone Modifications. Proteomics. 2018 Mar 07;: Authors: Simithy J, Sidoli S, Garcia BA Abstract The chromatin fiber is the control panel of eukaryotic cells. Chromatin is mostly composed of DNA, which contains the genetic instruction for cell phenotype, and histone proteins, which provide the scaffold for chromatin folding and part of the epigenetic inheritance. Histone writers/erasers "flag" chromatin regions by catalyzing/removing covalent histone post-translational modifications (PTMs). Histone PTMs chemically contribute to chromatin relaxation or compaction and recruit histone readers to modulate DNA readout. The precursors of protein PTMs are mostly small metabolites. For instance, acetyl-CoA is used for acetylation, ATP for phosphorylation, and S-adenosyl methionine for methylation. Interestingly, PTMs such as acetylation can occur at neutral pH also without their respective enzyme when the precursor is sufficiently concentrated. Therefore, it is essential to differentially quantify the contribution of histone writers/erasers vs the effect of local concentration of metabolites to understand the primary regulation of histone PTM abundance. Aberrant phenotypes such as cancer cells have misregulated metabolism and thus the composition and the modulation of chromatin is not only driven by enzymatic tuning. In this review, we discuss the latest advances in mass spectrometry (MS) to analyze histone PTMs and the most adopted quantification methods for related metabolites, both necessary to understand PTM relative changes. This article is protected by copyright. All rights reserved. PMID: 29512899 [PubMed - as supplied by publisher]

Unbiased Lipidomics and Metabolomics of Human Brain Samples. Methods Mol Biol. 2018;1750:255-269 Authors: Astarita G, Stocchero M, Paglia G Abstract Mass spectrometry (MS)-based lipidomics and metabolomics approaches have been used to discover new diagnostic and therapeutic targets of neurodegenerative disorders. Here, we describe a protocol to conduct an integrated metabolomics and lipidomics profiling of postmortem brains of frozen tissue samples from clinically characterized patients and age-matched controls. Metabolites and lipids can be extracted from each brain tissue sample, using a biphasic liquid/liquid extraction method. An unbiased liquid chromatography MS-based lipidomics and metabolomics workflows allows to screen for the content and composition of lipids and polar metabolites for each brain tissue. Data processing and statistical analysis are then used to compare the molecular content of all the samples, grouping them into cluster based on molecular similarities. The final results highlight classes of metabolites and biochemical pathways that are altered in brain samples from diseased brains compared to those from healthy subjects, helping to generate novel hypotheses on their mechanistic and functional significance. PMID: 29512078 [PubMed - in process]

Mass Spectrometry-Based Metabolomic Multiplatform for Alzheimer's Disease Research. Methods Mol Biol. 2018;1750:125-137 Authors: González-Domínguez R, González-Domínguez Á, Sayago A, Fernández-Recamales Á Abstract The integration of complementary analytical platforms has emerged as a suitable strategy to perform a comprehensive metabolomic characterization of complex biological systems. In this work, we describe the most important issues to be considered for the application of a mass spectrometry multiplatform in Alzheimer's disease research, which combines direct analysis with electrospray and atmospheric pressure photoionization sources, as well as orthogonal hyphenated approaches based on reversed-phase ultrahigh-performance liquid chromatography and gas chromatography. These procedures have been optimized for the analysis of multiple biological samples from human patients and transgenic animal models, including blood serum, various brain regions (e.g., hippocampus, cortex, cerebellum, striatum, olfactory bulbs), and other peripheral organs (e.g., liver, kidney, spleen, thymus). It is noteworthy that the metabolomic pipeline here detailed has demonstrated a great potential for the investigation of metabolic perturbations underlying Alzheimer's disease pathogenesis. PMID: 29512069 [PubMed - in process]

CSF Lipidomics Analysis: High-Resolution Mass Spectrometry Analytical Platform. Methods Mol Biol. 2018;1750:69-74 Authors: Wood PL, Woltjer RL Abstract High-resolution mass spectrometry provides the resolution required for direct infusion allowing detection and characterization of a vast array of lipids with a single injection. This chapter presents the methodology utilized for both unbiased and targeted lipidomics of cerebrospinal fluid. PMID: 29512065 [PubMed - in process]

Epidemiology of Dementia: The Burden on Society, the Challenges for Research. Methods Mol Biol. 2018;1750:3-14 Authors: Wolters FJ, Arfan Ikram M Abstract Dementia is among the leading causes of death and disability. Due to the ageing population, its prevalence is expected to nearly triple worldwide by 2050, urging the development of preventive and curative interventions. Various modifiable risk factors have been identified in community-based cohort studies, but insight into the underlying pathophysiological mechanisms is lacking. Clinical trials have thus far failed in the development of disease-modifying therapy in patients with dementia, thereby triggering a shift of focus toward the presymptomatic phase of disease. The extensive preclinical disease course of Alzheimer's disease warrants reliable, easily obtainable biomarkers to aid in timely application of preventive strategies, selecting participants for neuroprotective trials, and disease monitoring in trials and clinical practice. Biomarker and drug discovery may yield the fruits from technology-driven developments in the field of genomics, epigenetics, metabolomics, and brain imaging. In that context, bridging the gap between translational and population research may well prove a giant leap toward development of successful preventive and curative interventions against dementia. PMID: 29512062 [PubMed - in process]

PROM and Labour Effects on Urinary Metabolome: A Pilot Study. Dis Markers. 2018;2018:1042479 Authors: Meloni A, Palmas F, Barberini L, Mereu R, Deiana SF, Fais MF, Noto A, Fattuoni C, Mussap M, Ragusa A, Dessì A, Pintus R, Fanos V, Melis GB Abstract Since pathologies and complications occurring during pregnancy and/or during labour may cause adverse outcomes for both newborns and mothers, there is a growing interest in metabolomic applications on pregnancy investigation. In fact, metabolomics has proved to be an efficient strategy for the description of several perinatal conditions. In particular, this study focuses on premature rupture of membranes (PROM) in pregnancy at term. For this project, urine samples were collected at three different clinical conditions: out of labour before PROM occurrence (Ph1), out of labour with PROM (Ph2), and during labour with PROM (Ph3). GC-MS analysis, followed by univariate and multivariate statistical analysis, was able to discriminate among the different classes, highlighting the metabolites most involved in the discrimination. PMID: 29511388 [PubMed - in process]

The Use of Metabolomics and Inflammatory Mediator Profiling Provides a Novel Approach to Identifying Pediatric Appendicitis in the Emergency Department. Sci Rep. 2018 Mar 06;8(1):4083 Authors: Shommu NS, Jenne CN, Blackwood J, Martin DA, Joffe AR, Eccles R, Brindle M, Khanafer I, Vogel HJ, Thompson GC Abstract Multiplexed profiling approaches including various 'omics' platforms are becoming a new standard of biomarker development for disease diagnosis and prognosis. The present study applied an integrated metabolomics and cytokine profiling approach as a potential aid to the identification of pediatric appendicitis. Metabolic analysis using serum (n = 121) and urine (n = 102) samples, and cytokine analysis using plasma (n = 121) samples from children presenting to the Emergency Department with abdominal pain were performed. Comparisons between children with appendicitis vs. non-appendicitis abdominal pain, and with perforated vs. non-perforated appendicitis were made using multivariate statistics. Serum and urine biomarker patterns were statistically significantly different between groups. The combined serum metabolomics and inflammatory mediator model revealed clear separation between appendicitis and non-appendicitis abdominal pain (AUROC: 0.92 ± 0.03) as well as for perforated and non-perforated appendicitis (AUROC: 0.88 ± 0.05). Urine metabolic analysis also demonstrated distinction between the groups appendicitis and non-appendicitis abdominal pain (AUROC: 0.85 ± 0.04), and perforated and non-perforated appendicitis (AUROC: 0.98 ± 0.02). In children presenting to the Emergency Department with abdominal pain, metabolomics and inflammatory mediator profiling are capable of distinguishing children with appendicitis from those without. The approach also differentiates between severities of disease. These results provide an important first step towards a potential aid for improving appendicitis identification. PMID: 29511263 [PubMed - in process]

1H NMR-based metabolomics reveals the effect of maternal habitual dietary patterns on human amniotic fluid profile. Sci Rep. 2018 Mar 06;8(1):4076 Authors: Fotiou M, Fotakis C, Tsakoumaki F, Athanasiadou E, Kyrkou C, Dimitropoulou A, Tsiaka T, Chatziioannou AC, Sarafidis K, Menexes G, Theodoridis G, Biliaderis CG, Zoumpoulakis P, Athanasiadis AP, Michaelidou AM Abstract Maternal diet may influence offspring's health, even within well-nourished populations. Amniotic fluid (AF) provides a rational compartment for studies on fetal metabolism. Evidence in animal models indicates that maternal diet affects AF metabolic profile; however, data from human studies are scarce. Therefore, we have explored whether AF content may be influenced by maternal diet, using a validated food-frequency questionnaire and implementing NMR-based metabolomics. Sixty-five AF specimens, from women undergoing second-trimester amniocentesis for prenatal diagnosis, were analysed. Complementary, maternal serum and urine samples were profiled. Hierarchical cluster analysis identified 2 dietary patterns, cluster 1 (C1, n = 33) and cluster 2 (C2, n = 32). C1 was characterized by significantly higher percentages of energy derived from refined cereals, yellow cheese, red meat, poultry, and "ready-to-eat" foods, while C2 by higher (P < 0.05) whole cereals, vegetables, fruits, legumes, and nuts. 1H NMR spectra allowed the identification of metabolites associated with these dietary patterns; glucose, alanine, tyrosine, valine, citrate, cis-acotinate, and formate were the key discriminatory metabolites elevated in C1 AF specimens. This is the first evidence to suggest that the composition of AF is influenced by maternal habitual dietary patterns. Our results highlight the need to broaden the knowledge on the importance of maternal nutrition during pregnancy. PMID: 29511239 [PubMed - in process]

Metabolic Profiling of Dendrobium officinale in Response to Precursors and Methyl Jasmonate. Int J Mol Sci. 2018 Mar 03;19(3): Authors: Jiao C, Song C, Zheng S, Zhu Y, Jin Q, Cai Y, Lin Y Abstract Alkaloids are the main active ingredients in the medicinal plant Dendrobium officinale. Based on the published genomic and transcriptomic data, a proposed terpenoid indole alkaloid (TIA) biosynthesis pathway may be present in D. officinale. In this study, protocorm-like bodies (PLBs) with a high-yielding production of alkaloids were obtained by the optimization of tryptophan, secologanin and methyl jasmonate (MeJA) treatment. The results showed that the total alkaloid content was 2.05 times greater than that of the control group when the PLBs were fed with 9 µM tryptophan, 6 µM secologanin and 100 µM MeJA after 36 days. HPLC analysis showed that strictosidine synthase (STR) activity also increased in the treated plants. A total of 78 metabolites were identified using gas chromatography-mass spectrometry (GC-MS) in combination with liquid chromatography-mass spectrometry (LC-MS) methods; 29 differential metabolites were identified according to the multivariate statistical analysis. Among them, carapanaubine, a kind of TIA, exhibited dramatically increased levels. In addition, a possible underlying process of the metabolic flux from related metabolism to the TIA biosynthetic pathway was enhanced. These results provide a comprehensive view of the metabolic changes related to alkaloid biosynthesis, especially TIA biosynthesis, in response to tryptophan, secologanin and MeJA treatment. PMID: 29510516 [PubMed - in process]

Related Articles Postoperative Echocardiographic Reduction of Right Ventricular Function: Is Pericardial Opening Modality the Main Culprit? Biomed Res Int. 2017;2017:4808757 Authors: Zanobini M, Saccocci M, Tamborini G, Veglia F, Di Minno A, Poggio P, Pepi M, Alamanni F, Loardi C Abstract Echocardiographic reduction of RV function, measured using TAPSE, is a well described phenomenon after cardiac surgery. The aim of the present study was to investigate the relation between the modality of pericardial opening (lateral versus anterior) and the postoperative right ventricular systolic function by comparing echocardiographic parameters in patients undergoing minimally invasive or traditional mitral valve repair. 34 patients with severe mitral regurgitation due to mitral valve prolapse underwent traditional (sternotomy) operation (Group A) or minimally invasive surgery with right anterolateral thoracotomy (Group B). A postoperative TAPSE fall was found in both groups. Group A experienced a significant postoperative TAPSE fall versus Group B with p < 0.0001. PMID: 28589141 [PubMed - indexed for MEDLINE]

Related Articles Pattern recognition analysis of proton nuclear magnetic resonance spectra of postmortem cerebrospinal fluid from rats with drug-induced seizure or coma. Leg Med (Tokyo). 2017 Mar;25:52-58 Authors: Kanawaku Y, Hirakawa K, Koike K, Kanetake J, Ohno Y Abstract Cerebrospinal fluid (CSF) is routinely subjected to gross evaluation in postmortem investigations; however, its use in chemical evaluations has not been fully realized. Analysis of nuclear magnetic resonance (NMR) spectra with pattern recognition methods was applied to CSF samples. Rats were treated with pentylenetetrazol (PTZ) to induce seizure or pentobarbital (PB) to induce coma, and postmortem CSF was collected after CO2 gas euthanization. Pattern recognition analysis of the NMR data was performed on individual postmortem CSF samples. The aim of this study was to determine if pattern recognition analysis of NMR data could be used to classify the rats according to their drug treatment. The applicability of NMR data with pattern recognition analysis using postmortem CSF was also assessed. Partial Least Squares-Discriminant Analysis (PLS-DA) score plots indicated that the PTZ, PB, and NS (control) groups were clustered and clearly separated. PLS-DA correlation loading plots showed respective spectral and category variances of 41% and 42% for factor 1, and 17% and 27% for factor 2. Thus, factors 1 and 2 together described 58% (41%+17%) and 69% (42%+27%) of the variation, respectively. NMR study of postmortem CSF has the potential to be utilized as both a novel forensic neurochemistry method and in the clinical setting. PMID: 28457510 [PubMed - indexed for MEDLINE]

Related Articles Characterization of a New Pink-Fruited Tomato Mutant Results in the Identification of a Null Allele of the SlMYB12 Transcription Factor. Plant Physiol. 2016 Jul;171(3):1821-36 Authors: Fernandez-Moreno JP, Tzfadia O, Forment J, Presa S, Rogachev I, Meir S, Orzaez D, Aharoni A, Granell A Abstract The identification and characterization of new tomato (Solanum lycopersicum) mutants affected in fruit pigmentation and nutritional content can provide valuable insights into the underlying biology, as well as a source of new alleles for breeding programs. To date, all characterized pink-pigmented tomato fruit mutants appear to result from low SlMYB12 transcript levels in the fruit skin. Two new mutant lines displaying a pink fruit phenotype (pf1 and pf2) were characterized in this study. In the pf mutants, SlMYB12 transcripts accumulated to wild-type levels but exhibited the same truncation, which resulted in the absence of the essential MYB activation domain coding region. Allelism and complementation tests revealed that both pf mutants were allelic to the y locus and showed the same recessive null allele in homozygosis: Δy A set of molecular and metabolic effects, reminiscent of those observed in the Arabidopsis (Arabidopsis thaliana) myb11 myb12 myb111 triple mutant, were found in the tomato Δy mutants. To our knowledge, these have not been described previously, and our data support the idea of their being null mutants, in contrast to previously described transcriptional hypomorphic pink fruit lines. We detected a reduction in the expression of several flavonol glycosides and some associated glycosyl transferases. Transcriptome analysis further revealed that the effects of the pf mutations extended beyond the flavonoid pathway into the interface between primary and secondary metabolism. Finally, screening for Myb-binding sites in the candidate gene promoter sequences revealed that 141 of the 152 co-down-regulated genes may be direct targets of SlMYB12 regulation. PMID: 27208285 [PubMed - indexed for MEDLINE]

Application of metabolomics in prediction of lymph node metastasis in papillary thyroid carcinoma. PLoS One. 2018;13(3):e0193883 Authors: Seo JW, Han K, Lee J, Kim EK, Moon HJ, Yoon JH, Park VY, Baek HM, Kwak JY Abstract PURPOSE: The aim of this study was to find useful metabolites to predict lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC) through a metabolomics approach and investigate the potential role of metabolites as a novel prognostic marker. MATERIALS AND METHODS: Fifty-two consecutive patients (median age: 41.5 years, range 15-74 years) were enrolled who underwent total thyroidectomy and central LN dissection with or without lateral LN dissection in Severance Hospital between October 2013 and July 2015. The study specimens were provided by the Severance Hospital Gene Bank, and consisted of PTC from each patient. The specimens were prepared for proton nuclear magnetic resonance (1H-NMR) spectroscopy. Spectral data by 1H-NMR spectroscopy were acquired, processed, and analyzed. Patients were grouped in three ways, according to the presence of LN metastasis, central LN metastasis and lateral LN metastasis. Chi-square test and the student t-test were used to analyze categorical variables and continuous variables, respectively. The Mann-Whitney U test was used for univariate analysis of metabolites. Orthogonal projections to latent structure discriminant analysis (OPLS-DA) was used for multivariate analysis to discriminate metabolic differences between the two groups. RESULTS: Among 52 patients, 32 had central LN metastasis and 19 had lateral LN metastasis. No clinical or histopathological characteristic was significantly different for all comparisons. On univariate analysis, no metabolite showed significant difference for all comparisons. On multivariate analysis, OPLS-DA did not discriminate the presence and absence of LN metastasis. Lactate was found to be the most promising metabolite. CONCLUSIONS: No metabolite could discriminate the presence of LN metastasis. However, lactate was found to be the most promising metabolite for discrimination. Further studies with larger sample sizes are needed to elucidate significant metabolites which can indicate the presence of LN metastasis in patients with PTC. PMID: 29509799 [PubMed - in process]