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

PubMed

Recommendations and Best Practices for Standardizing the Pre-Analytical Processing of Blood and Urine Samples in Metabolomics.

Sun, 07/06/2020 - 13:10
Related Articles Recommendations and Best Practices for Standardizing the Pre-Analytical Processing of Blood and Urine Samples in Metabolomics. Metabolites. 2020 Jun 03;10(6): Authors: González-Domínguez R, González-Domínguez Á, Sayago A, Fernández-Recamales Á Abstract Metabolomics can be significantly influenced by a range of pre-analytical factors, such as sample collection, pre-processing, aliquoting, transport, storage and thawing. This therefore shows the crucial need for standardizing the pre-analytical phase with the aim of minimizing the inter-sample variability driven by these technical issues, as well as for maintaining the metabolic integrity of biological samples to ensure that metabolomic profiles are a direct expression of the in vivo biochemical status. This review article provides an updated literature revision of the most important factors related to sample handling and pre-processing that may affect metabolomics results, particularly focusing on the most commonly investigated biofluids in metabolomics, namely blood plasma/serum and urine. Finally, we also provide some general recommendations and best practices aimed to standardize and accurately report all these pre-analytical aspects in metabolomics research. PMID: 32503183 [PubMed - as supplied by publisher]

metabolomics; +27 new citations

Sat, 06/06/2020 - 16:02
27 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 2020/06/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +27 new citations

Sat, 06/06/2020 - 13:02
27 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 2020/06/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +25 new citations

Fri, 05/06/2020 - 15:54
25 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 2020/06/05PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +25 new citations

Fri, 05/06/2020 - 12:53
25 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 2020/06/05PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +39 new citations

Thu, 04/06/2020 - 15:47
39 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 2020/06/04PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +39 new citations

Thu, 04/06/2020 - 12:46
39 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 2020/06/04PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +19 new citations

Wed, 03/06/2020 - 15:37
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 2020/06/03PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +19 new citations

Wed, 03/06/2020 - 12:37
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 2020/06/03PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +33 new citations

Tue, 02/06/2020 - 15:25
33 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 2020/06/02PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +33 new citations

Tue, 02/06/2020 - 12:23
33 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 2020/06/02PubMed 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.

Antioxidant vitamins and lysophospholipids are critical for inducing mouse spermatogenesis under organ culture conditions.

Mon, 01/06/2020 - 12:20
Antioxidant vitamins and lysophospholipids are critical for inducing mouse spermatogenesis under organ culture conditions. FASEB J. 2020 May 31;: Authors: Sanjo H, Yao T, Katagiri K, Sato T, Matsumura T, Komeya M, Yamanaka H, Yao M, Matsuhisa A, Asayama Y, Ikeda K, Kano K, Aoki J, Arita M, Ogawa T Abstract In vitro mouse spermatogenesis using a classical organ culture method became possible by supplementing basal culture medium with only the product of bovine serum albumin purified by chromatography (AlbuMAX), which indicated that AlbuMAX contained every chemical factor necessary for mouse spermatogenesis. However, since the identity of these factors was unclear, improvements in culture media and our understanding of the nutritional and signal substances required for spermatogenesis were hindered. In the present study, chemically defined media (CDM) without AlbuMAX was used to evaluate each supplementary factor and their combinations for the induction of spermatogenesis. Similar to in vivo conditions, retinoic acid, triiodothyronine (T3 ), and testosterone (T) were needed. Based on differences in spermatogenic competence between AlbuMAX, fetal bovine serum, and adult bovine serum, we identified α-tocopherol, which strongly promoted spermatogenesis when combined with ascorbic acid and glutathione. Differences were also observed in the abilities of lipids extracted from AlbuMAX using two different methods to induce spermatogenesis. This led to the identification of lysophospholipids, particularly lysophosphatidylcholine, lysophosphatidic acid, and lysophosphatidylserine, as important molecules for spermatogenesis. New CDM formulated based on these results induced and promoted spermatogenesis as efficiently as AlbuMAX-containing medium. In vitro spermatogenesis with CDM may provide a unique experimental system for research on spermatogenesis that cannot be performed in in vivo experiments. PMID: 32474967 [PubMed - as supplied by publisher]

Omics research in diabetic kidney disease: new biomarker dimensions and new understandings?

Mon, 01/06/2020 - 12:20
Omics research in diabetic kidney disease: new biomarker dimensions and new understandings? J Nephrol. 2020 May 30;: Authors: Tofte N, Persson F, Rossing P Abstract The use of "omics" is increasing in research areas looking to identify biomarkers or early preclinical signs of disease or to increase understanding of complex pathological processes that determines prognosis of the disease. Diabetic kidney disease is no exception as it is an area in need of further improvement of both understanding and prognosis. In addition, there is a notion that pretreatment investigations using techniques like proteomics, lipidomics and metabolomics can help individualize therapy thus fulfilling the wish for personalized medicine. An increasing number of cohort studies using these techniques are published, but only few have been validated in external cohorts or even replicated by other groups. In essence, to achieve clinical impact and usefulness, prospective validation is needed. So far, only the urinary proteomics based PRIORITY study has tried to do this, as discussed in this review. Other areas are promising, but are currently lacking such efforts. In this review we report and discuss the current status of urinary proteomics as well as plasma metabolomics and lipidomics with an overview of the results so far, and with some comments and perspectives regarding future developments and implementation. As is evident, these techniques are promising, but there is still some way before widespread clinical use can be foreseen. PMID: 32474762 [PubMed - as supplied by publisher]

UHPLC-QqQ-MS/MS method development and validation with statistical analysis: Determination of raspberry ketone metabolites in mice plasma and brain.

Mon, 01/06/2020 - 12:20
UHPLC-QqQ-MS/MS method development and validation with statistical analysis: Determination of raspberry ketone metabolites in mice plasma and brain. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 May 19;1149:122146 Authors: Yuan B, Zhao D, Kshatriya D, Bello NT, Simon JE, Wu Q Abstract Raspberry ketone (RK) (4-(4-hydroxyphenyl)-2-butanone) is the major compound responsible for the characteristic aroma of red raspberries, and has long been used commercially as a flavoring agent and recently as a weight loss supplement. A targeted UHPLC-QqQ-MS/MS method was developed and validated for analysis of RK and 25 associated metabolites in mouse plasma and brain. Dispersion and projection analysis and central composite design were used for method optimization. Random effect analysis of variance was applied for validation inference and variation partition. Within this framework, repeatability, a broader sense of precision, was calculated as fraction of accuracy variance, reflecting instrumental imprecision, compound degradation and carry-over effects. Multivariate correlation analysis and principle component analysis were conducted, revealing underlying association among the manifold of method traits. R programming was engaged in streamlined statistical analysis and data visualization. Two particular phenomena, the analytes' background existence in the enzyme solution used for phase II metabolites deconjugation, and the noted lability of analytes in pure solvent at 4 ℃ vs. elevated stability in biomatrices, were found critical to method development and validation. The approach for the method development and validation provided a foundation for experiments that examine RK metabolism and bioavailability. PMID: 32474352 [PubMed - as supplied by publisher]

The use of non-targeted metabolomics to assess the toxicity of bifenthrin to juvenile Chinook salmon (Oncorhynchus tshawytscha).

Mon, 01/06/2020 - 12:20
The use of non-targeted metabolomics to assess the toxicity of bifenthrin to juvenile Chinook salmon (Oncorhynchus tshawytscha). Aquat Toxicol. 2020 May 23;224:105518 Authors: Magnuson JT, Giroux M, Cryder Z, Gan J, Schlenk D Abstract An increase in urban and agricultural application of pyrethroid insecticides in the San Francisco Bay Estuary and Sacramento San Joaquin Delta has raised concern for the populations of several salmonids, including Chinook salmon (Oncorhynchus tshawytscha). Bifenthrin, a type I pyrethroid, is among the most frequently detected pyrethroids in the Bay-Delta watershed, with surface water concentrations often exceeding chronic toxicity thresholds for several invertebrate and fish species. To better understand the mechanisms of bifenthrin-induced neurotoxicity, juvenile Chinook salmon were exposed to concentrations of bifenthrin previously measured in the Delta. Non-targeted metabolomic profiles were used to identify transcriptomic changes in the brains of bifenthrin-exposed fish. Pathway analysis software predicted increased apoptotic, inflammatory, and reactive oxygen species (ROS) responses in Chinook following exposure to 0.15 and 1.50 μg/L bifenthrin for 96 h. These responses were largely driven by reduced levels of inosine, hypoxanthine, and guanosine. Subsequently, in the brain, the expression of caspase 3, a predominant effector for apoptosis, was significantly upregulated following exposure to 1.50 μg/L bifenthrin. This data suggests that metabolites involved in inflammatory and apoptotic responses, as well as those involved in maintaining proper neuronal function may be disrupted following sublethal exposure to bifenthrin and further suggests that additional population studies should focus on behavioral responses associated with impaired brain function. PMID: 32474292 [PubMed - as supplied by publisher]

Metabolic variation in Cistus monspeliensis L. ecotypes correlated to their plant-fungal interactions.

Mon, 01/06/2020 - 12:20
Metabolic variation in Cistus monspeliensis L. ecotypes correlated to their plant-fungal interactions. Phytochemistry. 2020 May 28;176:112402 Authors: Salomé-Abarca LF, Mandrone M, Sanna C, Poli F, van der Hondel CAMJJ, Klinkhamer PGL, Choi YH Abstract The effect of environmental factors on the chemical composition of plants eventually resulting in plant growth regulation is an age-old issue in plant biology. Nowadays, the acceleration in changes in environmental conditions (e.g. global warming) can act as an incentive to investigate their correlation with metabolic changes. In this study, Cistus monspeliensis plants grown on the island of Sardinia (Italy) were used to explore the geographical-mediated metabolic variation and its repercussion on plant-fungus interactions. Samples of different ecotypes of C. monspeliensis were collected and chemically profiled by 1H NMR and HPTLC-based metabolomics and the relationship between the variations of biological activity was examined by multivariate data analysis. The ecotypes, collected from different geographical zones and altitudes, exhibited clearly distinguishable chemical profiles, particularly in their terpene and phenolic contents. In particular, multivariate data analysis revealed several diterpenes of the labdane and clerodane series among the terpenes and methoxyflavonoids to be responsible for the differentiation. The antifungal activity of the plants was used to explore the correlation between chemical variation and biological activity. Results showed that there was a strong correlation between the metabolic profiles and the antifungal activity, revealing terpenes and methoxylated flavonoids as the main involved metabolites. This demonstrated that environmental factors can influence the chemical variation of plant ecotypes, resulting in the generation of chemotypes that are potentially adapted to their niche conditions including the plant-fungal interactions. PMID: 32474264 [PubMed - as supplied by publisher]

First-principles identification of C-methyl-scyllo-inositol (mytilitol) - A new species-specific metabolite indicator of geographic origin for marine bivalve molluscs (Mytilus and Ruditapes spp.).

Mon, 01/06/2020 - 12:20
First-principles identification of C-methyl-scyllo-inositol (mytilitol) - A new species-specific metabolite indicator of geographic origin for marine bivalve molluscs (Mytilus and Ruditapes spp.). Food Chem. 2020 Apr 30;328:126959 Authors: Aru V, Motawie MS, Khakimov B, Sørensen KM, Møller BL, Engelsen SB Abstract This study presents a level-1 identification of the seven carbon (7-C) sugar C-methyl-scyllo-inositol (mytilitol) in mussels and clams (Mytilus and Ruditapes spp., respectively) purchased in Denmark and Italy. For each sample, the hydrophilic extract of the soft tissue was analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy using a 600 MHz NMR spectrometer. A first tentative identification of mytilitol was carried out by computing a statistical total correlation spectroscopy (STOCY) analysis of the 1H NMR spectra, followed by a level-1 identification based on first-principles methods including chemical synthesis, structure elucidation and standard-addition experiments. Mytilitol was quantified in the 1H NMR spectra and its average relative concentration turned out to be significantly lower in clams than in mussels (p-value < 0.001), with Danish mussels having the highest mytilitol concentration. Principal component analysis (PCA) of the NMR dataset brought further evidence to a species-specific and geographic-dependent content of mytilitol in mussels and clams. PMID: 32474235 [PubMed - as supplied by publisher]

Ectomycorrhizal fungi induce systemic resistance against insects on a non-mycorrhizal plant in a CERK1-dependent manner.

Sun, 31/05/2020 - 12:13
Ectomycorrhizal fungi induce systemic resistance against insects on a non-mycorrhizal plant in a CERK1-dependent manner. New Phytol. 2020 May 30;: Authors: Vishwanathan K, Zienkiewicz K, Liu Y, Janz D, Feussner I, Polle A, Haney CH Abstract Below-ground microbes can induce systemic resistance (ISR) against foliar pests and pathogens on diverse plant hosts. The prevalence of ISR among plant-microbe-pest systems raises the question of host specificity in microbial induction of ISR. To test whether ISR is limited by plant host range, we tested the ISR-inducing ectomycorrhizal fungus Laccaria bicolor on the non-mycorrhizal plant Arabidopsis thaliana. We used the cabbage looper Trichoplusia ni and bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pto) as readouts for ISR on Arabidopsis. We found that root inoculation with L. bicolor triggered ISR against T. ni and induced systemic susceptibility (ISS) against the bacterial pathogen Pto. We found that L. bicolor-triggered ISR against T. ni was dependent on jasmonic acid signaling and salicylic acid biosynthesis and signaling. Heat-killed L. bicolor and chitin were sufficient to trigger ISR against T. ni and ISS against Pto. The chitin receptor CERK1 was necessary for L. bicolor-mediated effects on systemic immunity. Collectively our findings suggest that some ISR responses might not require intimate symbiotic association, but rather might be the result of root perception of conserved microbial signals. PMID: 32473606 [PubMed - as supplied by publisher]

Metabolomics in the Development and Progression of rheumatoid arthritis: A Systematic Review.

Sun, 31/05/2020 - 12:13
Metabolomics in the Development and Progression of rheumatoid arthritis: A Systematic Review. Joint Bone Spine. 2020 May 27;: Authors: Li C, Chen B, Fang Z, Leng YF, Wang DW, Chen FQ, Xiao X, Sun ZL Abstract OBJECTIVE: A systematic review and analysis of data from several rheumatoid arthritis metabolomics studies attempts to determine which metabolites can be used as potential biomarkers for the diagnosis of rheumatoid arthritis and to explore the pathogenesis of rheumatoid arthritis. METHODS: We searched all the subject-related documents published by EMBASE, PubMed, Web of Science, and Cochrane Library from the database to the September 2019 publication. Two researchers independently screened the literature and extracted the data. QUADOMICS tool was used to assess the quality of studies included in this systematic review. RESULTS: A total of 10 studies met the inclusion criteria of systematic review, including 502 patients with Rheumatoid arthritis and 373 healthy people. Among them, the biological samples utilized for metabolomic analysis include: serum (n = 8), urine (n = 1) and synovial fluid(n = 1). Some metabolites play an important role in rheumatoid arthritis: glucose, lactic acid, citric acid, leucine, methionine, isoleucine, valine, phenylalanine, threonine, serine, proline, glutamate, histidine, alanine, cholesterol, glycerol, ribose. CONCLUSIONS: Metabolomics provides important new opportunities for further research in rheumatoid arthritis and is expected to elucidate the pathogenesis of rheumatoid arthritis that has not been fully understood before. PMID: 32473419 [PubMed - as supplied by publisher]

STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue.

Sun, 31/05/2020 - 12:13
STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue. Mol Metab. 2020 May 27;:101026 Authors: Kaltenecker D, Spirk K, Ruge F, Grebien F, Herling M, Rupprecht A, Kenner L, Pohl EE, Mueller KM, Moriggl R Abstract OBJECTIVE: Increasing energy expenditure through activation of brown adipose tissue (BAT) thermogenesis is an attractive approach to counteract obesity. Thus, it is essential to understand the molecular mechanisms that control BAT functions. Until now several members of the Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway have been implicated to be relevant for BAT physiology. Yet, whether the STAT family member STAT5 is important for the thermogenic property of adipose tissues is unknown. Here, we investigate the role of STAT5 in thermogenic fat. METHODS: Using mice that harbour an adipocyte-specific deletion of Stat5a/b alleles, we performed metabolic and molecular analyses. RESULTS: We found that STAT5 is necessary for acute cold-induced temperature maintenance and the induction of lipid mobilization in BAT following β3-adrenergic stimulation. Moreover, mitochondrial respiration of primary differentiated brown adipocytes lacking STAT5 was diminished. Increased sensitivity to cold stress upon STAT5 deficiency was associated with reduced expression of thermogenic markers including uncoupling protein 1 (UCP1), while decreased stimulated lipolysis was linked to decreased protein kinase A (PKA) activity. In addition, brown remodeling of white adipose tissue was diminished following chronic β3-adrenergic stimulation, which was accompanied by a decrease in mitochondrial performance. CONCLUSION: We conclude that STAT5 is essential for the functionality and the β-adrenergic responsiveness of thermogenic adipose tissue. PMID: 32473405 [PubMed - as supplied by publisher]

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