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
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

metabolomics; +27 new citations

Sat, 30/01/2021 - 12:59
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 2021/01/30PubMed 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.

metabolomics; +34 new citations

Fri, 29/01/2021 - 15:53
34 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 2021/01/29PubMed 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; +34 new citations

Fri, 29/01/2021 - 12:48
34 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 2021/01/29PubMed 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; +36 new citations

Thu, 28/01/2021 - 15:41
36 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 2021/01/28PubMed 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; +36 new citations

Thu, 28/01/2021 - 12:35
36 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 2021/01/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +21 new citations

Wed, 27/01/2021 - 15:24
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +21 new citations

Wed, 27/01/2021 - 12:24
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/27PubMed 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; +40 new citations

Tue, 26/01/2021 - 15:18
40 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 2021/01/26PubMed 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.

Complete Reduction to Amplitude Frequency Table (CRAFT) - A Perspective.

Tue, 26/01/2021 - 09:15
Related Articles Complete Reduction to Amplitude Frequency Table (CRAFT) - A Perspective. Magn Reson Chem. 2021 Jan 24;: Authors: Krishnamurthy K Abstract The CRAFT (Complete Reduction to Amplitude Frequency Table) technique, based on Bayesian analysis approach, converts FID and/or interferogram (time domain) to a frequency-amplitude table (tabular domain) in a robust, automated, and time-efficient fashion. This mini review/perspective presents an introduction to CRAFT as a processing workflow followed by a discussion of several practical 1D and 2D examples of its applicability and associated benefit. CRAFT provides high quality quantitative results for complex systems without any need for conventional preprocessing steps, such as phase and baseline corrections. Two-dimensional time domain data are typically truncated, particularly in the evolution dimension, and conventional processing after zero-filling and t1max -matched apodization masks potentially available peak resolution. The line broadening introduced by extensive zero-filling and severe apodization functions leads to the lack of clear resolution of cross peaks. CRAFT decimation of interferograms, on the other hand, requires minimal or no apodization prior to extraction of the NMR parameters and significantly improves the spectral linewidth of the cross peaks along F1 dimension compared to conventional (FT) processing. The tabular representation of the CRAFT2d cross peaks information can be visualized in a variety of frequency domain formats for conventional spectral interpretation as well as quantitative applications. A simple workflow to generate in-silico oversampled interferogram (iSOS) is presented and its potential benefit in CRAFT decimation of highly crowded 2D NMR is demonstrated. This report is meant as a collective thesis to present a potentially new paradigm in data processing that questions the need for hitherto unchallenged preprocessing steps, such as phase and baseline correction in 1D and zero-fill/severe apodization in 2D. PMID: 33486830 [PubMed - as supplied by publisher]

Aberrant and glutamate metabolism linked to regional neurodegeneration in a mouse model of Leigh syndrome.

Tue, 26/01/2021 - 09:15
Related Articles Aberrant and glutamate metabolism linked to regional neurodegeneration in a mouse model of Leigh syndrome. Biochim Biophys Acta Mol Basis Dis. 2021 Jan 21;:166082 Authors: Terburgh K, Coetzer J, Lindeque JZ, van der Westhuizen FH, Louw R Abstract The dysfunction of respiratory chain complex I (CI) is the most common form of mitochondrial disease that most often presents as Leigh syndrome (LS) in children - a severe neurometabolic disorder defined by progressive focal lesions in specific brain regions. The mechanisms underlying this region-specific vulnerability to CI deficiency, however, remain elusive. Here, we examined brain regional respiratory chain enzyme activities and metabolic profiles in a mouse model of LS with global CI deficiency to gain insight into regional vulnerability to neurodegeneration. One lesion-resistant and three lesion-prone brain regions were investigated in Ndufs4 knockout (KO) mice at the late stage of LS. Enzyme assays confirmed significantly decreased (60-80%) CI activity in all investigated KO brain regions, with the lesion-resistant region displaying the highest residual CI activity (38% of wild type). A higher residual CI activity, and a less perturbed NADH/NAD+ ratio, correlate with less severe metabolic perturbations in KO brain regions. Moreover, less perturbed BCAA oxidation and increased glutamate oxidation seem to distinguish lesion-resistant from -prone KO brain regions, thereby identifying key areas of metabolism to target in future therapeutic intervention studies. PMID: 33486097 [PubMed - as supplied by publisher]

Enhancement of the flavone contents of Scutellaria baicalensis hairy roots via metabolic engineering using maize Lc and Arabidopsis PAP1 transcription factors.

Tue, 26/01/2021 - 09:15
Related Articles Enhancement of the flavone contents of Scutellaria baicalensis hairy roots via metabolic engineering using maize Lc and Arabidopsis PAP1 transcription factors. Metab Eng. 2021 Jan 21;: Authors: Park CH, Xu H, Yeo HJ, Park YE, Hwang GS, Park NI, Park SU Abstract Baicalin, baicalein, and wogonin are valuable natural flavonoid compounds produced by Scutellaria baicalensis. In this study, we showed that the maize transcription factor Lc can enhance the production of these three flavonoids in hairy root cultures of S. baicalensis by comprehensively upregulating flavonoid biosynthesis pathway genes (SbPAL1, SbC4H, and Sb4CL) and baicalein 7-O-glucuronosyltransferase (UBGAT), ultimately yielding total flavonoid contents of up to 80.5 ± 6.15 mg g-1 dry weight, which was 322% greater than the average value of total flavonoid contents produced by three GUS-overexpressing lines. Similarly, the Arabidopsis transcription factor PAP1 was found to enhance flavonoid accumulation by upregulating SbPAL1, SbPAL2, SbPAL3, SbC4H, Sb4CL, SbCHI, and UBGAT, ultimately yielding total flavonoid contents of up to 133 ± 7.66 mg g-1 dry weight, which was 532% greater than the average value of total flavonoid contents produced by three GUS-overexpressing lines. These findings indicate that metabolic engineering in S. baicalensis can be achieved using Agrobacterium rhizogenes-mediated transformation and that the production of baicalin, baicalein, and wogonin can be enhanced via the overexpression of ZmLc and AtPAP1 in hairy root cultures. These results also indicate that ZmLc and AtPAP1 can be used as positive regulators of the flavonoid biosynthetic pathway of S. baicalensis hairy root cultures. PMID: 33486093 [PubMed - as supplied by publisher]

Altered plasma serine and 1-deoxydihydroceramide profiles are associated with diabetic neuropathy in type 2 diabetes and obesity.

Tue, 26/01/2021 - 09:15
Related Articles Altered plasma serine and 1-deoxydihydroceramide profiles are associated with diabetic neuropathy in type 2 diabetes and obesity. J Diabetes Complications. 2021 Jan 09;:107852 Authors: Fridman V, Zarini S, Sillau S, Harrison K, Bergman BC, Feldman EL, Reusch JEB, Callaghan BC Abstract Recent studies suggest that the accumulation of atypical, 1-deoxysphingolipids that lack the C1 hydroxyl group may be associated with diabetic neuropathy (DN). We hypothesized that specific plasma 1-deoxysphingolipids associate with DN severity, and that alterations in plasma serine and alanine associate with 1-deoxysphingolipid elevation in patients with type 2 diabetes (T2D). We examined individual 1-deoxysphingolipid species using LC/MS/MS in plasma samples from 75 individuals including lean controls (LC, n = 19), those with obesity (n = 19), obesity with T2D without DN (ob/T2D, n = 18), and obesity with T2D with DN (Ob/T2D/DN, n = 19). We observed a step wise increase in 1-deoxydihydroceramides across these four groups (spearman correlation coefficient r = 0.41, p = 0.0002). Mean total concentrations of 1-deoxydihydroceramides, and most individual 1-deoxydihydroceramide species, were higher in ob/T2D/DN versus LC group (8.939 vs. 5.195 pmol/100 μL for total 1-deoxydihydroceramides p = 0.005). No significant differences in 1-deoxydihydroceramides were observed between the ob/T2D and ob/T2D/DN groups. l-alanine was higher and l-serine lower in ob/T2D/DN versus LC groups (326.2 vs. 248.0 μM, p = 0.0086 and 70.2 vs. 89.8 μM, p = 0.0110), consistent with a potential contribution of these changes to the observed 1-deoxysphingolipids profiles. 1-deoxydihydroceramides correlated inversely with leg intraepidermal nerve fiber density (CC -0.40, p = 0.003). These findings indicate that 1-deoxydihydroceramides may be important biomarkers and/or mediators of DN. PMID: 33485750 [PubMed - as supplied by publisher]

Reviewing the metabolome coverage provided by LC-MS: Focus on sample preparation and chromatography-A tutorial.

Tue, 26/01/2021 - 09:15
Related Articles Reviewing the metabolome coverage provided by LC-MS: Focus on sample preparation and chromatography-A tutorial. Anal Chim Acta. 2021 Feb 22;1147:38-55 Authors: Roca M, Alcoriza MI, Garcia-Cañaveras JC, Lahoz A Abstract Metabolomics has become an invaluable tool for both studying metabolism and biomarker discovery. The great technical advances in analytical chemistry and bioinformatics have considerably increased the number of measurable metabolites, yet an important part of the human metabolome remains uncovered. Among the various MS hyphenated techniques available, LC-MS stands out as the most used. Here, we aimed to show the capabilities of LC-MS to uncover part of the metabolome and how to best proceed with sample preparation and LC to maximise metabolite detection. The analyses of various open metabolite databases served us to estimate the size of the already detected human metabolome, the expected metabolite composition of most used human biospecimens and which part of the metabolome can be detected when LC-MS is used. Based on an extensive review and on our experience, we have outlined standard procedures for LC-MS analysis of urine, cells, serum/plasma, tissues and faeces, to guide in the selection of the sample preparation method that best matches with one or more LC techniques in order to get the widest metabolome coverage. These standard procedures may be a useful tool to explore, at a glance, the wide spectrum of possibilities available, which can be a good starting point for most of the LC-MS metabolomic studies. PMID: 33485584 [PubMed - in process]

Comprehensive metabolic profiling of Parkinson's disease by liquid chromatography-mass spectrometry.

Tue, 26/01/2021 - 09:15
Related Articles Comprehensive metabolic profiling of Parkinson's disease by liquid chromatography-mass spectrometry. Mol Neurodegener. 2021 Jan 23;16(1):4 Authors: Shao Y, Li T, Liu Z, Wang X, Xu X, Li S, Xu G, Le W Abstract BACKGROUND: Parkinson's disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. METHODS: We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts (n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. RESULTS: A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. CONCLUSIONS: This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future. PMID: 33485385 [PubMed - in process]

Metabolomics analysis of the effects of temperature on the growth and development of juvenile European seabass (Dicentrarchus labrax).

Sun, 24/01/2021 - 14:54
Related Articles Metabolomics analysis of the effects of temperature on the growth and development of juvenile European seabass (Dicentrarchus labrax). Sci Total Environ. 2021 Jan 14;769:145155 Authors: Zhang Z, Zhou C, Fan K, Zhang L, Liu Y, Liu PF Abstract Temperature variations have significant impacts on the growth and development of fish. In this study, the effects of temperature on the growth and development of European seabass (Dicentrarchus labrax) were investigated using ultra-performance liquid chromatography-tandem mass spectrometry-based metabolomics. Three groups of fish were exposed to various temperatures for 60 days: T1-E (10 °C), T2-E (15 °C), and T3-E (20 °C). Afterward, the temperature of all groups was increased to 20 °C and maintained for 62 days (T1-S, T2-S, T3-S). The livers were extracted for subsequent analysis. In the first stage of the experiment, the growth rate was highest in the T3-E group, followed by the T1-E and T2-E groups. The following metabolites identified by comparative analysis were found to be elevated: L-thyroxine, cysteamine, uridine diphosphate (UDP)-glucose, α-ketoglutaric acid, carbamoyl phosphate, and guanidine acetic acid of the T1-E group. Pathway analysis of the altered metabolites suggested changes in glucose metabolism, arginine and proline metabolism, the tricarboxylic acid cycle, the ornithine cycle, histidine metabolism, and taurine metabolism, which were involved with growth and development. Meanwhile, partial compensatory growth was observed in fish in the T1-S and T2-S groups. Metabolites identified as potential markers of growth included L-cysteine, taurocholic acid, UDP-glucose, and L-thyroxine. The significantly changed metabolic pathways were cysteine and methionine metabolism, bile secretion, tyrosine metabolism, and hypotaurine metabolism. We screened out the marker metabolites and metabolic pathway could provide important insights into the potential mechanisms of temperature affects the growth and development of European seabass. All in all, our research can provide theoretical basis and technical guidance for efficiently culturing European seabass. PMID: 33485208 [PubMed - as supplied by publisher]

Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment.

Sun, 24/01/2021 - 14:54
Related Articles Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment. Mitochondrion. 2021 Jan 20;: Authors: Chitturi J, Santhakumar V, Kannurpatti SS Abstract Ru360, a mitochondrial Ca2+ uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 to 72 hours, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD+ depletion across both hemispheres. While neural viability improved ipsilaterally, it reduced contralaterally. Ru360 treatment, overall, had a global impact with most benefit near the strongest injury impact areas, while perturbing mitochondrial oxidative energetics in the milder TBI impact areas. PMID: 33484870 [PubMed - as supplied by publisher]

Dietary table grape protects against UV photodamage in humans: 2. molecular biomarker studies.

Sun, 24/01/2021 - 14:54
Related Articles Dietary table grape protects against UV photodamage in humans: 2. molecular biomarker studies. J Am Acad Dermatol. 2021 Jan 20;: Authors: Oak ASW, Shafi R, Elsayed M, Mishra B, Bae S, Barnes S, Kashyap MP, Slominski AT, Wilson LS, Athar M, Elmets CA PMID: 33484768 [PubMed - as supplied by publisher]

Oxoeicosanoid receptor inhibition alleviates acute myocardial infarction through activation of BCAT1.

Sun, 24/01/2021 - 14:54
Related Articles Oxoeicosanoid receptor inhibition alleviates acute myocardial infarction through activation of BCAT1. Basic Res Cardiol. 2021 Jan 23;116(1):3 Authors: Lai Q, Yuan G, Shen L, Zhang L, Fu F, Liu Z, Zhang Y, Kou J, Liu S, Yu B, Li F Abstract 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is an arachidonic acid metabolite produced along with leukotrienes via the 5-lipoxygenase pathway. Metabolomics studies have shown that 5-oxo-ETE level is elevated in the serum in acute myocardial infarction (AMI). The actions of 5-oxo-ETE are mediated by the highly selective oxoeicosanoid receptor (OXE-R). Moreover, increased OXE-R content was verified in AMI patients and mice. However, the precise role of OXE-R in AMI is unclear. In the present study, we demonstrate that 5-oxo-ETE triggered myocardial injury in mice. Pathway enrichment analysis identified branched chain amino acid transaminase 1/2 (BCAT1/2) as potential mediators of this effect. Western blot and immunohistochemical analyses showed that BCAT1/BCAT2 expression was significantly reduced by AMI in vitro and in vivo, while pharmacologic inhibition of BCAT1/BCAT2 accelerated myocardial injury. Conversely, heart-specific overexpression of BCAT1/BCAT2 in mice protected against ischemic myocardial injury. Treatment with the selective OXE-R inhibitor Gue1654 alleviated coronary artery ligation-induced ischemic myocardial injury in mice and oxygen/glucose deprivation-induced injury in cardiomyocytes through activation of BCAT1, while inhibiting OXE-R suppressed protein kinase C-ε (PKC-ε)/nuclear factor κB (NF-κB) signaling and cardiomyocyte apoptosis. Overall, our study confirmed a novel target OXE-R for the treatment of AMI based on metabolomics, and targeting OXE-R may represent unrecognized therapeutic intervention for cardiovascular diseases through activation of BCAT1. PMID: 33484341 [PubMed - as supplied by publisher]

Correction to: Metabolic characterisation of disturbances in the APOC3/triglyceride‑rich lipoprotein pathway through sample‑based recall by genotype.

Sun, 24/01/2021 - 14:54
Related Articles Correction to: Metabolic characterisation of disturbances in the APOC3/triglyceride‑rich lipoprotein pathway through sample‑based recall by genotype. Metabolomics. 2021 Jan 23;17(2):15 Authors: Corbin LJ, Hughes DA, Chetwynd AJ, Taylor AE, Southam AD, Jankevics A, Weber RJM, Groom A, Dunn WB, Timpson NJ PMID: 33484338 [PubMed - as supplied by publisher]

Lilikoi V2.0: a deep learning-enabled, personalized pathway-based R package for diagnosis and prognosis predictions using metabolomics data.

Sun, 24/01/2021 - 14:54
Related Articles Lilikoi V2.0: a deep learning-enabled, personalized pathway-based R package for diagnosis and prognosis predictions using metabolomics data. Gigascience. 2021 Jan 23;10(1): Authors: Fang X, Liu Y, Ren Z, Du Y, Huang Q, Garmire LX Abstract BACKGROUND: previously we developed Lilikoi, a personalized pathway-based method to classify diseases using metabolomics data. Given the new trends of computation in the metabolomics field, it is important to update Lilikoi software. RESULTS: here we report the next version of Lilikoi as a significant upgrade. The new Lilikoi v2.0 R package has implemented a deep learning method for classification, in addition to popular machine learning methods. It also has several new modules, including the most significant addition of prognosis prediction, implemented by Cox-proportional hazards model and the deep learning-based Cox-nnet model. Additionally, Lilikoi v2.0 supports data preprocessing, exploratory analysis, pathway visualization, and metabolite pathway regression. CONCULSION: Lilikoi v2.0 is a modern, comprehensive package to enable metabolomics analysis in R programming environment. PMID: 33484242 [PubMed - as supplied by publisher]

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