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

metabolomics; +24 new citations

Sat, 04/07/2020 - 13:54
24 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 2020/07/04PubMed 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; +23 new citations

Fri, 03/07/2020 - 13:46
23 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 2020/07/03PubMed 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; +29 new citations

Thu, 02/07/2020 - 16:31
29 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 2020/07/02PubMed 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; +29 new citations

Thu, 02/07/2020 - 13:29
29 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 2020/07/02PubMed 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; +53 new citations

Wed, 01/07/2020 - 16:08
53 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 2020/07/01PubMed 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; +53 new citations

Wed, 01/07/2020 - 13:06
53 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 2020/07/01PubMed 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.

Obligatory Metabolomic Profiling of Gene-edited Crops is Risk Disproportionate.

Sun, 28/06/2020 - 12:11
Obligatory Metabolomic Profiling of Gene-edited Crops is Risk Disproportionate. Plant J. 2020 Jun 27;: Authors: Fedorova M, Herman RA Abstract It has been argued that the application of metabolomics to gene-edited crops would present value in three areas: 1) detection of gene-edited crops, 2) characterization of unexpected changes that might affect safety, and 3) building on the track record of rigorous government regulation in supporting consumer acceptance of GMOs. Here, we offer a different perspective relative to each of these areas. 1) Metabolomics is unable to differentiate if a mutation has resulted from gene editing or traditional breeding techniques. 2) It is risk-disproportionate to apply metabolomics for regulatory purposes to search for possible compositional differences within crops developed using the least likely technique to generate unexpected compositional changes. 3) Onerous regulations for genetically engineered crops have only contributed to unwarranted public fears, and repeating this approach for gene-edited crops is unlikely to result in a different outcome. It is also suggested that manuscripts proposing the utility of specific analytical techniques to support risk assessment would benefit from input from scientists with risk assessment subject-matter expertise. PMID: 32593232 [PubMed - as supplied by publisher]

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients.

Sun, 28/06/2020 - 12:11
Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients. Liver Int. 2020 Jun 27;: Authors: Salgüero S, Rojo D, Berenguer J, González-García J, Fernández-Rodríguez A, Brochado-Kith O, Díez C, Hontañon V, Virseda-Berdices A, Martínez J, Ibañez-Samaniego L, Llop-Herrera E, Barbas C, Resino S, Jiménez-Sousa MA, ESCORIAL Study Group Abstract BACKGROUND & AIMS: Hepatitis C virus (HCV), human immunodeficiency virus (HIV), and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child-Turcotte-Pugh (CTP) score and hepatic decompensation in HIV/HCV-coinfected and HCV-monoinfected patients with advanced cirrhosis. METHODS: Observational study in 62 HIV/HCV-coinfected and 28 HCV-monoinfected patients. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS-DA) and generalized linear model (GLM) with binomial distribution (to analyze HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyze different stages of cirrhosis (CTP score). RESULTS: The statistical analysis identified plasma metabolites associated to HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulfur amino acids, butyrate derivatives, oxidized phospholipids, energy-related metabolites, and bacterial fermentation-related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched-chain amino acids (BCAA), and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV and HCV infected patients. Glycolic acid, LPC(16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥7). CONCLUSION: Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV-coinfected and HCV-monoinfected patients. PMID: 32593189 [PubMed - as supplied by publisher]

Cold acclimation and freezing tolerance in three Eucalyptus species: A metabolomic and proteomic approach.

Sun, 28/06/2020 - 12:11
Cold acclimation and freezing tolerance in three Eucalyptus species: A metabolomic and proteomic approach. Plant Physiol Biochem. 2020 May 26;154:316-327 Authors: Oberschelp GPJ, Guarnaschelli AB, Teson N, Harrand L, Podestá FE, Margarit E Abstract The ability of plants to cope with frost events relies on the physiological and molecular responses triggered by cold temperatures. This process, named acclimation, involves reprogramming gene expression in order to adjust metabolism. Planted Eucalyptus species are highly productive but most of them are frost sensitive. However, acclimation process varies among species and environmental conditions, promoting more or less frost damage in young plantations of frost-prone areas. To identify metabolites and proteins responsible for these differences, two acclimation regimes were imposed to seedling of Eucalyptus grandis Hill ex Maiden (Eg), Eucalyptus dunnii Maiden (Ed) and Eucalyptus benthamii Maiden Cambage (Eb), and leaves submitted to biochemical and molecular analyses. Further, seedlings were used for simulated frosts in order to test the acclimation status effect on frost tolerance. Eb showed higher frost tolerance than Ed and Eg under control and acclimation scenarios, possibly due to its higher accumulation of phenolics, anthocyanins and soluble sugars as well as lower levels of photosynthetic pigments and related proteins. Also, a rise in frost tolerance and in osmoprotectants and antioxidants was observed for all the species due to cold acclimation treatment. Interestingly, metabolic profiles differed among species, suggesting different mechanisms to endure frosts and, probably, different requirements for cold acclimation. Shotgun proteomics reinforced differences and commonalities and supported metabolome observations. An in depth understanding of these responses could help to safeguard planted forests productivity through breeding of tolerant genetic material. PMID: 32593088 [PubMed - as supplied by publisher]

Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retina pigment epithelium.

Sun, 28/06/2020 - 12:11
Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retina pigment epithelium. Biochim Biophys Acta Mol Basis Dis. 2020 Jun 24;:165883 Authors: Zhong Y, Mohan K, Liu J, Al-Attar A, Lin P, Flight RM, Sun Q, Warmoes MO, Deshpande RR, Liu H, Jung KS, Mitov MI, Lin N, Butterfield DA, Lu S, Liu J, Moseley HNB, Fan TWM, Kleinman ME, Wang QJ Abstract Juvenile neuronal ceroid lipofuscinosis (JNCL, aka. juvenile Batten disease or CLN3 disease) is a lysosomal storage disease characterized by progressive blindness, seizures, cognitive and motor failures, and premature death. JNCL is caused by mutations in the Ceroid Lipofuscinosis, Neuronal 3 (CLN3) gene, whose function is unclear. Although traditionally considered a neurodegenerative disease, CLN3 disease displays eye-specific effects: JNCL often first presents as vision loss; and vision loss has also been reported in non-syndromic CLN3 disease. Here we described the roles of CLN3 protein in maintaining healthy retinal pigment epithelium (RPE) and normal vision. Using electroretinogram, fundoscopy and microscopy, we showed impaired visual function, retinal autofluorescent lesions, and RPE disintegration and metaplasia/hyperplasia in a Cln3 ~ 1 kb-deletion mouse model [1] on C57BL/6J backgroun. Utilizing a combination of biochemical analyses, RNA-Seq, Seahorse XF bioenergetic analysis, and Stable Isotope Resolved Metabolomics (SIRM), we further demonstrated that loss of CLN3 increased autophagic flux, suppressed mTORC1 and Akt activities, enhanced AMPK activity, and up-regulated gene expression of the autophagy-lysosomal system in RPE-1 cells, suggesting autophagy induction. This CLN3 deficiency induced autophagy induction coincided with decreased mitochondrial oxygen consumption, glycolysis, the tricarboxylic acid (TCA) cycle, and ATP production. We also report for the first time that loss of CLN3 led to glycogen accumulation despite of impaired glycogen synthesis. Our comprehensive analyses shed light on how loss of CLN3 affect autophagy and metabolism. This work suggests possible links among metabolic impairment, autophagy induction and lysosomal storage, as well as between RPE atrophy/degeneration and vision loss in JNCL. PMID: 32592935 [PubMed - as supplied by publisher]

Activation of glycogenolysis and glycolysis in breast cancer stem cell models.

Sun, 28/06/2020 - 12:11
Activation of glycogenolysis and glycolysis in breast cancer stem cell models. Biochim Biophys Acta Mol Basis Dis. 2020 Jun 24;:165886 Authors: Abad E, Samino S, Yanes O, Potesil D, Zdrahal Z, Lyakhovich A PMID: 32592934 [PubMed - as supplied by publisher]

Global Metabolomics in Allogeneic Hematopoietic Cell Transplant Recipients Discordant for Chronic Graft-versus-Host Disease.

Sun, 28/06/2020 - 12:11
Global Metabolomics in Allogeneic Hematopoietic Cell Transplant Recipients Discordant for Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2020 Jun 24;: Authors: Kelly DL, Farharfar N, Starkweather A, Garrett TJ, Yao Y, Wingard JR, Mahmud I, Menzies V, Patel P, Alabasi KM, Lyon D Abstract BACKGROUND: Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation survivors contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Due to lack of early diagnostic tests and pathophysiology ambiguity, there remain limited targeted treatments. Biomarkers for prediction, control response or prognostication are not yet identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD however not known in this population. This study examined global metabolites of stored plasma to examine differentially expressed metabolites of individuals discordant for cGVHD following allogeneic HCT. METHODS: A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from two parent studies approved by the Institutional Review Board. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed using R statistical software version 3.4.3 by a PhD prepared, trained bioinformatics statistician. RESULTS: There were 10 differentially expressed metabolites between those with and without cGVHD. Differential metabolites included those related to energy metabolism (n=3), amino acid metabolism (n=3), lipid metabolism (n=2), caffeine metabolism (n=1), and neurotransmission (n=1). Serotonin had the greatest fold change (FC) (FC = 21.01). CONCLUSION: This study suggests cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that need to be further explored as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomics risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD. PMID: 32592859 [PubMed - as supplied by publisher]

Rationale and design of "Hearts & Parks": study protocol for a pragmatic randomized clinical trial of an integrated clinic-community intervention to treat pediatric obesity.

Sun, 28/06/2020 - 12:11
Related Articles Rationale and design of "Hearts & Parks": study protocol for a pragmatic randomized clinical trial of an integrated clinic-community intervention to treat pediatric obesity. BMC Pediatr. 2020 Jun 26;20(1):308 Authors: Armstrong SC, Windom M, Bihlmeyer NA, Li JS, Shah SH, Story M, Zucker N, Kraus WE, Pagidipati N, Peterson E, Wong C, Wiedemeier M, Sibley L, Berchuck SI, Merrill P, Zizzi A, Sarria C, Dressman HK, Rawls JF, Skinner AC Abstract BACKGROUND: The prevalence of child and adolescent obesity and severe obesity continues to increase despite decades of policy and research aimed at prevention. Obesity strongly predicts cardiovascular and metabolic disease risk; both begin in childhood. Children who receive intensive behavioral interventions can reduce body mass index (BMI) and reverse disease risk. However, delivering these interventions with fidelity at scale remains a challenge. Clinic-community partnerships offer a promising strategy to provide high-quality clinical care and deliver behavioral treatment in local park and recreation settings. The Hearts & Parks study has three broad objectives: (1) evaluate the effectiveness of the clinic-community model for the treatment of child obesity, (2) define microbiome and metabolomic signatures of obesity and response to lifestyle change, and (3) inform the implementation of similar models in clinical systems. METHODS: Methods are designed for a pragmatic randomized, controlled clinical trial (n = 270) to test the effectiveness of an integrated clinic-community child obesity intervention as compared with usual care. We are powered to detect a difference in body mass index (BMI) between groups at 6 months, with follow up to 12 months. Secondary outcomes include changes in biomarkers for cardiovascular disease, psychosocial risk, and quality of life. Through collection of biospecimens (serum and stool), additional exploratory outcomes include microbiome and metabolomics biomarkers of response to lifestyle modification. DISCUSSION: We present the study design, enrollment strategy, and intervention details for a randomized clinical trial to measure the effectiveness of a clinic-community child obesity treatment intervention. This study will inform a critical area in child obesity and cardiovascular risk research-defining outcomes, implementation feasibility, and identifying potential molecular mechanisms of treatment response. CLINICAL TRIAL REGISTRATION: NCT03339440 . PMID: 32590958 [PubMed - as supplied by publisher]

Associations between Dietary Fiber, the Fecal Microbiota and Estrogen Metabolism in Postmenopausal Women with Breast Cancer.

Sun, 28/06/2020 - 12:11
Related Articles Associations between Dietary Fiber, the Fecal Microbiota and Estrogen Metabolism in Postmenopausal Women with Breast Cancer. Nutr Cancer. 2020 Jun 26;:1-10 Authors: Zengul AG, Demark-Wahnefried W, Barnes S, Morrow CD, Bertrand B, Berryhill TF, Frugé AD Abstract Breast cancer is a hormonally-driven cancer, and various dietary factors are associated with estrogen metabolism, including dietary fiber. Several studies report associations between dietary fiber and breast cancer; however, research on whether fiber influences circulating estrogens through the gut microbiota is rare. The objective of this cross-sectional study among 29 newly-diagnosed (stage 0-II), post-menopausal breast cancer patients is to examine associations between dietary fiber and the gut microbiota that are linked with β-glucuronidase activity, and purportedly increase circulating estrogens. Spearman's and partial correlations controlling for body mass index and age were performed using dietary recall data, Illumina MiSeq generated microbiota relative abundance, and HPLC-mass spectrometry-derived estradiol and estrone levels.Major findings are: (1) total dietary fiber is inversely associated with Clostridium hathewayi (r= -0.419; p = 0.024); (2) soluble fiber is inversely associated with Clostridium (r=-0.11; p = 0.02); (3) insoluble fiber is positively associated with Bacteroides uniformis sp. (r = 0.382; p = 0.041); and (4) serum estradiol and estrone levels are not correlated with species/genera or dietary fiber, though there is a trend toward an inverse association between soluble fiber and estradiol levels (r= -0.30; p = 0.12). More studies are needed to understand the complex interaction between dietary fiber, intestinal microbiota, and hormonal levels in older females. PMID: 32590914 [PubMed - as supplied by publisher]

metabolomics; +21 new citations

Sat, 27/06/2020 - 15:00
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 2020/06/27PubMed 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; +28 new citations

Fri, 26/06/2020 - 14:46
28 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 2020/06/26PubMed 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.

metabolomics; +22 new citations

Thu, 25/06/2020 - 14:30
22 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 2020/06/25PubMed 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, 24/06/2020 - 14:05
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 2020/06/24PubMed 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; +23 new citations

Tue, 23/06/2020 - 13:56
23 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 2020/06/23PubMed 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.

Different Malabsorptive Obesity Surgery Interventions Result in Distinct Postprandial Amino Acid Metabolomic Signatures.

Mon, 22/06/2020 - 13:44
Related Articles Different Malabsorptive Obesity Surgery Interventions Result in Distinct Postprandial Amino Acid Metabolomic Signatures. Obes Surg. 2020 Jun 20;: Authors: Pereira SS, Jarak I, Carvalho RA, Oliveira PF, Alves MG, Guimarães M, Almeida R, Pereira AM, Wewer Albrechtsen NJ, Holst JJ, Nora M, Monteiro MP Abstract PURPOSE: Biliopancreatic diversion with duodenal switch (BPD-DS) is an effective weight loss surgical procedure. Yet, BPD-DS is technically difficult to perform and carries a higher risk of nutrient deficiencies as compared with other surgical interventions. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modified BPD-DS procedure conceived with the aim of decreasing the technical complexity, while retaining the weight loss efficiency. Whether the two surgical procedures diverge in nutrient absorption rates and malnutrition risk is still matter of debate. Our aim was to determine if postprandial nutrient absorption rates are different in patients subjected to BPD-DS or SADI-S for weight loss. MATERIALS AND METHODS: Plasma amino acid metabolomic profiling during mixed-meal tolerance test (MMTT) was performed in subjects (N = 18) submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.6 ± 0.1 years earlier. RESULTS: Patients submitted to SADI-S or BPD-DS presented distinct postprandial metabolomic profiles. Postprandial excursions of total and essential amino acids-leucine, isoleucine, and valine-were higher after SADI-S as compared with BPD-DS. CONCLUSION: Our study demonstrates that a simplified malabsorptive bariatric surgery procedure SADI-S results in greater essential branched-chain amino acid absorption when compared with the classical BPD-DS intervention. These findings suggest that SADI-S can potentially lower lifetime risk of postoperative protein malnutrition, as well as have a positive impact on systemic metabolism and glucose homeostasis. PMID: 32564307 [PubMed - as supplied by publisher]

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