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

Microbial Cleavage of C-F Bonds in Two C6 Per- and Polyfluorinated Compounds via Reductive Defluorination.

Sat, 31/10/2020 - 20:55
Related Articles Microbial Cleavage of C-F Bonds in Two C6 Per- and Polyfluorinated Compounds via Reductive Defluorination. Environ Sci Technol. 2020 Oct 29;: Authors: Yu Y, Zhang K, Li Z, Ren C, Chen J, Lin YH, Liu J, Men Y Abstract The C-F bond is one of the strongest single bonds in nature. Although microbial reductive dehalogenation is well known for the other organohalides, no microbial reductive defluorination has been documented for perfluorinated compounds except for a single, nonreproducible study on trifluoroacetate. Here, we report on C-F bond cleavage in two C6 per- and polyfluorinated compounds via reductive defluorination by an organohalide-respiring microbial community. The reductive defluorination was demonstrated by the release of F- and the formation of the corresponding product when lactate was the electron donor, and the fluorinated compound was the sole electron acceptor. The major dechlorinating species in the seed culture, Dehalococcoides, were not responsible for the defluorination as no growth of Dehalococcoides or active expression of Dehalococcoides-reductive dehalogenases was observed. It suggests that minor phylogenetic groups in the community might be responsible for the reductive defluorination. These findings expand our fundamental knowledge of microbial reductive dehalogenation and warrant further studies on the enrichment, identification, and isolation of responsible microorganisms and enzymes. Given the wide use and emerging concerns of fluorinated organics (e.g., per- and polyfluoroalkyl substances), particularly the perfluorinated ones, the discovery of microbial defluorination under common anaerobic conditions may provide valuable insights into the environmental fate and potential bioremediation strategies of these notorious contaminants. PMID: 33121241 [PubMed - as supplied by publisher]

Effectiveness of Hydrocolloid Dressings for Treating Pressure Ulcers in Adult Patients: A Systematic Review and Meta-Analysis.

Sat, 31/10/2020 - 20:55
Related Articles Effectiveness of Hydrocolloid Dressings for Treating Pressure Ulcers in Adult Patients: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2020 Oct 27;17(21): Authors: Kamińska MS, Cybulska AM, Skonieczna-Żydecka K, Augustyniuk K, Grochans E, Karakiewicz B Abstract The aim of this study was to assess the effectiveness of hydrocolloid dressings in the treatment of grade I, II, III, and IV pressure ulcers in adult patients. We compared the therapeutic effects of hydrocolloids and alternative dressings in pressure ulcer treatment. We conducted a systematic review, using a literature search only in English, from database inception until 20 April 2020, to identify randomized trials comparing various types of dressings applied in the healing of pressure ulcers. The databases were PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The study selection was performed independently by two reviewers. Data were extracted based on the guidelines included in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The risk of bias in the included studies was assessed using a standardized critical appraisal instrument developed by the Cochrane Collaboration. Random-effect meta-analysis of data from three or more studies was performed using meta-analysis software (Comprehensive Meta-Analysis V3, Biostat, New Jersey, USA). A total of 1145 records were identified, of which 223 were qualified after further verification, of which eight were finally included in further analysis. Hydrocolloid dressings were not superior to control therapeutics (p = 0.839; Z = 0.203; CI 95%: 0.791-1.334). They were not associated with higher healing rates (p = 0.718; Z = 0.361; OR: 0.067; CI 95%: 0.297-0.431), nor did they decrease the incidence of adverse events compared with control therapeutics (p = 0.300; Z = -1.036; OR: 0.067; CI 95%: 0.394-1.333). In the above cases, Egger's test also did not indicate publication bias (t value = 0.779, p = 0.465; t value = 1.198, p = 0.442; t value = 0.834, p = 0.465, respectively). The present meta-analysis shows that hydrocolloid dressings are not significantly better than alternative ones in the healing of pressure ulcers in adult patients. PMID: 33121151 [PubMed - in process]

Integration of pluripotency pathways regulates stem cell maintenance in the Arabidopsis shoot meristem.

Sat, 31/10/2020 - 20:55
Related Articles Integration of pluripotency pathways regulates stem cell maintenance in the Arabidopsis shoot meristem. Proc Natl Acad Sci U S A. 2020 09 08;117(36):22561-22571 Authors: Su YH, Zhou C, Li YJ, Yu Y, Tang LP, Zhang WJ, Yao WJ, Huang R, Laux T, Zhang XS Abstract In the shoot meristem, both WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM), two transcription factors with overlapping spatiotemporal expression patterns, are essential for maintaining stem cells in an undifferentiated state. Despite their importance, it remains unclear how these two pathways are integrated to coordinate stem cell development. Here, we show that the WUS and STM pathways in Arabidopsis thaliana converge through direct interaction between the WUS and STM proteins. STM binds to the promoter of CLAVATA3 (CLV3) and enhances the binding of WUS to the same promoter through the WUS-STM interaction. Both the heterodimerization and simultaneous binding of WUS and STM at two sites on the CLV3 promoter are required to regulate CLV3 expression, which in turn maintains a constant number of stem cells. Furthermore, the expression of STM depends on WUS, and this WUS-activated STM expression enhances the WUS-mediated stem cell activity. Our data provide a framework for understanding how spatial expression patterns within the shoot meristem are translated into regulatory units of stem cell homeostasis. PMID: 32839309 [PubMed - indexed for MEDLINE]

Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes.

Sat, 31/10/2020 - 20:55
Related Articles Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes. Sci Rep. 2019 11 08;9(1):16398 Authors: Tofte N, Suvitaival T, Ahonen L, Winther SA, Theilade S, Frimodt-Møller M, Ahluwalia TS, Rossing P Abstract There is an urgent need for a better molecular understanding of the pathophysiology underlying development and progression of diabetic nephropathy. The aim of the current study was to identify novel associations between serum lipidomics and diabetic nephropathy. Non-targeted serum lipidomic analyses were performed with mass spectrometry in 669 individuals with type 1 diabetes. Cross-sectional associations of lipid species with estimated glomerular filtration rate (eGFR) and urinary albumin excretion were assessed. Moreover, associations with register-based longitudinal follow-up for progression to a combined renal endpoint including ≥30% decline in eGFR, ESRD and all-cause mortality were evaluated. Median follow-up time was 5.0-6.4 years. Adjustments included traditional risk factors and multiple testing correction. In total, 106 lipid species were identified. Primarily, alkyl-acyl phosphatidylcholines, triglycerides and sphingomyelins demonstrated cross-sectional associations with eGFR and macroalbuminuria. In longitudinal analyses, thirteen lipid species were associated with the slope of eGFR or albuminuria. Of these lipids, phosphatidylcholine and sphingomyelin species, PC(O-34:2), PC(O-34:3), SM(d18:1/24:0), SM(d40:1) and SM(d41:1), were associated with lower risk of the combined renal endpoint. PC(O-34:3), SM(d40:1) and SM(d41:1) were associated with lower risk of all-cause mortality while an SM(d18:1/24:0) was associated with lower risk of albuminuria group progression. We report distinct associations between lipid species and risk of renal outcomes in type 1 diabetes, independent of traditional markers of kidney function. PMID: 31705008 [PubMed - indexed for MEDLINE]

Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System.

Sat, 31/10/2020 - 20:55
Related Articles Bifidobacterial Dialogue With Its Human Host and Consequent Modulation of the Immune System. Front Immunol. 2019;10:2348 Authors: Alessandri G, Ossiprandi MC, MacSharry J, van Sinderen D, Ventura M Abstract Since bifidobacteria are among the pioneering colonizers of the human infant gut, their interaction with their host is believed to start soon following birth. Several members of the Bifidobacterium genus are purported to exert various health-promoting effects at local and systemic levels, e.g., limiting pathogen colonization/invasion, influencing gut homeostasis, and influencing the immune system through changes in innate and/or adaptive immune responses. This has promoted extensive research efforts to shed light on the precise mechanisms by which bifidobacteria are able to stimulate and interact with the host immune system. These studies uncovered a variety of secreted or surface-associated molecules that act as essential mediators for the establishment of a bifidobacteria-host immune system dialogue, and that allow interactions with mucosa-associated immune cells. Additionally, the by-products generated from bifidobacterial carbohydrate metabolism act as vectors that directly and indirectly trigger the host immune response, the latter by stimulating growth of other commensal microorganisms such as propionate- or butyrate-producing bacteria. This review is aimed to provide a comprehensive overview on the wide variety of strategies employed by bifidobacteria to engage with the host immune system. PMID: 31632412 [PubMed - indexed for MEDLINE]

Characterization of circadian human facial surface lipid composition.

Sat, 31/10/2020 - 20:55
Related Articles Characterization of circadian human facial surface lipid composition. Exp Dermatol. 2019 07;28(7):858-862 Authors: Jia Y, Zhou M, Huang H, Gan Y, Yang M, Ding R Abstract BACKGROUND: The circadian rhythm is an endogenous clock that governs a wide range of physiological functions. In the skin, rhythmic changes in skin barrier function have been investigated at the physiological level; however, few studies at the molecular level have been reported. Additionally, there is no study on lipidomic profile variations of skin surface lipid (SSL), which could potentially explain the rhythmic changes in skin status. OBJECTIVES: The SSL profile of healthy young women was analysed to assess SSL variations and to assess the skin status during the circadian cycle. METHODS: Ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry and multivariate data analysis were performed to assess SSL variations. RESULTS: The lipidomic profile showed significant differences with the circadian rhythm. Multivariate data analysis indicated that glycerolipids were the lipids majorly affected by the circadian rhythm. Additionally, in the SSL profile, both the average chain length and the content of free fatty acids (FFAs) were higher at 20:00 than at 08:00. CONCLUSIONS: The SSL profile significantly varied with respect to the circadian rhythm. The rhythm-altered triacylglycerol level, FFA chain length and FFA content resulted in rhythmic changes in skin barrier function, including transepidermal water loss alteration and pH variation. PMID: 30972810 [PubMed - indexed for MEDLINE]

metabolomics; +27 new citations

Sat, 31/10/2020 - 11:41
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 2020/10/31PubMed 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; +37 new citations

Fri, 30/10/2020 - 14:33
37 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 2020/10/30PubMed 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; +37 new citations

Fri, 30/10/2020 - 11:30
37 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 2020/10/30PubMed 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.

Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes - A nested case-control study.

Thu, 29/10/2020 - 11:18
Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes - A nested case-control study. Environ Int. 2020 Oct 25;146:106180 Authors: Schillemans T, Shi L, Donat-Vargas C, Hanhineva K, Tornevi A, Johansson I, Koponen J, Kiviranta H, Rolandsson O, Bergdahl IA, Landberg R, Åkesson A, Brunius C Abstract Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1-0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3-2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk. PMID: 33113464 [PubMed - as supplied by publisher]

Isoflurane anesthesia disrupts the cortical metabolome.

Thu, 29/10/2020 - 11:18
Isoflurane anesthesia disrupts the cortical metabolome. J Neurophysiol. 2020 Oct 28;: Authors: Baer AG, Bourdon AK, Price JM, Campagna SR, Jacobson DA, Baghdoyan HA, Lydic R Abstract Identifying similarities and differences in the brain metabolome during different states of consciousness has broad relevance for neuroscience and state-dependent autonomic function. This study focused on prefrontal cortex (PFC) as a brain region known to modulate states of consciousness. Anesthesia was used as a tool to eliminate wakefulness. Untargeted metabolomic analyses were performed on microdialysis samples obtained from mouse PFC during wakefulness and during isoflurane anesthesia. Analyses detected 2153 molecules, 91 of which could be identified. Analytes were grouped as detected during both wakefulness and anesthesia (n=61), and as unique to wakefulness (n=23) or anesthesia (n=7). Data were analyzed using univariate and multivariate approaches. Relative to wakefulness, during anesthesia there was a significant (q < 0.0001) four-fold change in 21 metabolites. During anesthesia 11 of these 21 molecules decreased and 10 increased. The Kyoto Encyclopedia of Genes and Genomes database was used to relate behavioral state specific changes in the metabolome to metabolic pathways. Relative to wakefulness, most of the amino acids and analogs measured were significantly decreased during isoflurane anesthesia. Nucleosides and analogs were significantly increased during anesthesia. Molecules associated with carbohydrate metabolism, maintenance of lipid membranes, and normal cell functions were significantly decreased during anesthesia. Significant state-specific changes also were discovered among molecules comprising lipids and fatty acids, monosaccharides, and organic acids. Considered together, these molecules regulate point to point transmission, volume conduction, and cellular metabolism. The results identify a novel ensemble of candidate molecules in PFC as putative modulators of wakefulness and the loss of wakefulness. PMID: 33112692 [PubMed - as supplied by publisher]

Drivers of and Obstacles to the Adoption of Toxicogenomics for Chemical Risk Assessment: Insights from Social Science Perspectives.

Thu, 29/10/2020 - 11:18
Drivers of and Obstacles to the Adoption of Toxicogenomics for Chemical Risk Assessment: Insights from Social Science Perspectives. Environ Health Perspect. 2020 Oct;128(10):105002 Authors: Pain G, Hickey G, Mondou M, Crump D, Hecker M, Basu N, Maguire S Abstract BACKGROUND: Some 20 y ago, scientific and regulatory communities identified the potential of omics sciences (genomics, transcriptomics, proteomics, metabolomics) to improve chemical risk assessment through development of toxicogenomics. Recognizing that regulators adopt new scientific methods cautiously given accountability to diverse stakeholders, the scope and pace of adoption of toxicogenomics tools and data have nonetheless not met the ambitious, early expectations of omics proponents. OBJECTIVE: Our objective was, therefore, to inventory, investigate, and derive insights into drivers of and obstacles to adoption of toxicogenomics in chemical risk assessment. By invoking established social science frameworks conceptualizing innovation adoption, we also aimed to develop recommendations for proponents of toxicogenomics and other new approach methodologies (NAMs). METHODS: We report findings from an analysis of 56 scientific and regulatory publications from 1998 through 2017 that address the adoption of toxicogenomics for chemical risk assessment. From this purposeful sample of toxicogenomics discourse, we identified major categories of drivers of and obstacles to adoption of toxicogenomics tools and data sets. We then mapped these categories onto social science frameworks for conceptualizing innovation adoption to generate actionable insights for proponents of toxicogenomics. DISCUSSION: We identify the most salient drivers and obstacles. From 1998 through 2017, adoption of toxicogenomics was understood to be helped by drivers such as those we labeled Superior scientific understanding, New applications, and Reduced cost & increased efficiency but hindered by obstacles such as those we labeled Insufficient validation, Complexity of interpretation, and Lack of standardization. Leveraging social science frameworks, we find that arguments for adoption that draw on the most salient drivers, which emphasize superior and novel functionality of omics as rationales, overlook potential adopters' key concerns: simplicity of use and compatibility with existing practices. We also identify two perspectives-innovation-centric and adopter-centric-on omics adoption and explain how overreliance on the former may be undermining efforts to promote toxicogenomics. https://doi.org/10.1289/EHP6500. PMID: 33112659 [PubMed - as supplied by publisher]

Toxic Effects of Fine Plant Powder Impregnated With Avermectins on Mosquito Larvae and Nontarget Aquatic Invertebrates.

Thu, 29/10/2020 - 11:18
Toxic Effects of Fine Plant Powder Impregnated With Avermectins on Mosquito Larvae and Nontarget Aquatic Invertebrates. J Med Entomol. 2020 Oct 28;: Authors: Belevich O, Yurchenko Y, Alekseev A, Kotina O, Odeyanko V, Tsentalovich Y, Yanshole L, Kryukov V, Danilov V, Glupov V Abstract The toxic effects of an avermectin-impregnated fine plant powder (AIFP) against larval Aedes aegypti L. (Diptera: Culicidae), Culex modestus Ficalbi (Diptera: Culicidae), and Anopheles messeae Falleroni (Diptera: Culicidae), as well as selected nontarget aquatic invertebrates, were studied under laboratory conditions. The possibility of trophic transfer of avermectins (AVMs) through the food chain and their toxic effects on predaceous species fed AIFP-treated mosquito larvae was also evaluated. Among mosquitoes, Anopheles messeae were the most sensitive to AIFP, while Cx. modestus exhibited the least sensitivity to this formulation. Among nontarget aquatic invertebrates, the greatest toxicity of AIFP was observed for benthic species (larval Chironomus sp. Meigen (Diptera: Chironomidae), whereas predators (dragonflies, water beetles, and water bugs) exhibited the lowest AIFP sensitivity. AIFP sensitivity of the clam shrimp Lynceus brachyurus O. F. Muller (Diplostraca: Lynceidae), the phantom midge Chaoborus crystallinus De Geer (Diptera: Chaoboridae), and the mayfly Caenis robusta Eaton (Ephemeroptera: Caenidae) was intermediate and similar to the sensitivity of the mosquito Cx. modestus. However, these nontarget species were more resistant than An. messeae and Ae. aegypti. Solid-phase extraction of mosquito larvae treated with AIFP and subsequent high-performance liquid chromatography (HPLC) analysis of the extracts revealed an AVM concentration of up to 2.1 ± 0.3 μg/g. Feeding the creeping water bug Ilyocoris cimicoides L. (Hemiptera: Naucoridae) on the AIFP-treated mosquito larvae resulted in 51% mortality of the predaceous species. But no toxicity was observed for Aeshna mixta Latreille (Odonata: Aeshnidae) dragonfly larvae fed those mosquito larvae. The results of this work showed that this AVM formulation can be effective against mosquito larvae. PMID: 33112404 [PubMed - as supplied by publisher]

Tetrahydroxy stilbene glycoside attenuates acetaminophen-induced hepatotoxicity by UHPLC-Q-TOF/MS-based metabolomics and multivariate data analysis.

Thu, 29/10/2020 - 11:18
Tetrahydroxy stilbene glycoside attenuates acetaminophen-induced hepatotoxicity by UHPLC-Q-TOF/MS-based metabolomics and multivariate data analysis. J Cell Physiol. 2020 Oct 28;: Authors: Gao Y, Li JT, Li X, Li X, Yang SW, Chen NH, Li L, Zhang L Abstract Tetrahydroxy stilbene glycoside (TSG) is a main active compound in Polygonum multiflorum. Acetaminophen (APAP) is a well-known analgesic and antipyretic drug. It is considered to be safe within a therapeutic range, in case of acute intoxication hepatotoxicity occurs. This present study aims to observe TSG-provided alleviation on APAP-induced hepatoxicity in C57BL/6 mice. APAP performs extensive necrosis and dissolves nucleus suggesting liver damage from hepatic histopathology. Serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase analysis and liver histological evaluation showed that TSG reduced the hepatotoxicity induced by a toxic dose of APAP. Moreover, TSG alone had no hepatotoxicity. TSG eliminated hepatic glutathione depletion and cysteine adducts formation. It also reduced the expression of interleukin-10 and lowered the production of reactive oxygen species in liver tissues. Luminex was used to detect cytokine production in different groups. Herein, we used an untargeted metabolomics approach by performing ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry on treated mice to identify metabolic disruptions under APAP and TSG. Major alterations were observed for purine metabolism, amino acid metabolism, and fatty acid metabolism. These data provide metabolic evidence and biomarkers in the liver that the ABC transporters, Glycine serine and threonine metabolism, and Choline metabolism in cancer changed the most. These targets of metabolites have the potential to improve our understanding of homeostatic. Meanwhile, these metabolites revealed that TSG can alleviate inflammation caused by APAP and promote the activity of intrinsic antioxidants. In summary, TSG can regulate lipid metabolism, promote the production of antioxidant enzymes, and decrease the inflammatory response. PMID: 33111343 [PubMed - as supplied by publisher]

Serum Metabolomics for Biomarker Screening of Esophageal Squamous Cell Carcinoma and Esophageal Squamous Dysplasia Using Gas Chromatography-Mass Spectrometry.

Thu, 29/10/2020 - 11:18
Serum Metabolomics for Biomarker Screening of Esophageal Squamous Cell Carcinoma and Esophageal Squamous Dysplasia Using Gas Chromatography-Mass Spectrometry. ACS Omega. 2020 Oct 20;5(41):26402-26412 Authors: Zhang S, Lu X, Hu C, Li Y, Yang H, Yan H, Fan J, Xu G, Abnet CC, Qiao Y Abstract BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor diagnosis. Esophageal squamous dysplasia (ESD) is considered as an immediate precancerous lesion of ESCC. Lack of biomarkers for discriminating ESCC and ESD from healthy subjects limits the early diagnosis and treatment of ESCC. Therefore, a serum metabolomic strategy was conducted to identify and validate potential metabolic markers for the screening of ESCC and ESD subjects. METHODS: A total of 74 patients with ESCC, 72 patients with ESD, and 75 normal control (NC) subjects were enrolled in this study. Gas chromatography-mass spectrometry was used to acquire serum metabolic profiles. Pathway analysis was conducted to uncover the fluctuated metabolic pathways during ESCC. Multivariate analyses were used to screen and validate the biomarkers. RESULTS: ESCC, ESD, and NC subjects revealed progressively altered metabolic profiles, in which amino acids globally increased, while fatty acids decreased in ESCCs compared with the control groups. Pathway analysis demonstrated the activated biosynthesis of amino acids and inhibited desaturation of saturated fatty acids. The panel constructed with propanoic acid, linoleic acid, glycerol-3-phosphate, and l-glutamine showed the area under the curve (AUC), sensitivity, and specificity of 0.817, 0.75, and 0.74, respectively, in the discrimination of ESCC/ESD patients from NC subjects. The panel constructed by propanoic acid, l-leucine, and hydroxyproline revealed the AUC, sensitivity, and specificity of 0.819, 0.76, and 0.72, respectively, in the discrimination of ESD from NC subjects. The combination of hypoxanthine, 2-ketoisocaproic acid, l-glutamate, and l-aspartate showed the AUC, sensitivity, and specificity of 0.818, 0.83, and 0.74, respectively, in the discrimination of ESCC patients from ESD subjects. CONCLUSIONS: Our study revealed the systematic landscape for metabolic alterations in sera of ESD and ESCC patients. The defined metabolite markers showed reasonable performance in the discrimination of ESCC and ESD patients, and may provide helpful reference for clinicians and biologists. PMID: 33110968 [PubMed]

Urine metabolomic phenotyping for detection of adrenocortical carcinoma: still a long way to go - Authors' reply.

Thu, 29/10/2020 - 11:18
Related Articles Urine metabolomic phenotyping for detection of adrenocortical carcinoma: still a long way to go - Authors' reply. Lancet Diabetes Endocrinol. 2020 11;8(11):877-878 Authors: Bancos I, Taylor AE, Chortis V, Sitch AJ, Lang K, Prete A, Gilligan LC, Biehl M, Deeks JJ, Arlt W, ENSAT EURINE-ACT Investigators PMID: 33065058 [PubMed - indexed for MEDLINE]

Urine metabolomic phenotyping for detection of adrenocortical carcinoma: still a long way to go.

Thu, 29/10/2020 - 11:18
Related Articles Urine metabolomic phenotyping for detection of adrenocortical carcinoma: still a long way to go. Lancet Diabetes Endocrinol. 2020 11;8(11):876-877 Authors: Anyfanti P, Nikolaidou B, Gkaliagkousi E PMID: 33065057 [PubMed - indexed for MEDLINE]

DRAM for distilling microbial metabolism to automate the curation of microbiome function.

Thu, 29/10/2020 - 11:18
Related Articles DRAM for distilling microbial metabolism to automate the curation of microbiome function. Nucleic Acids Res. 2020 09 18;48(16):8883-8900 Authors: Shaffer M, Borton MA, McGivern BB, Zayed AA, La Rosa SL, Solden LM, Liu P, Narrowe AB, Rodríguez-Ramos J, Bolduc B, Gazitúa MC, Daly RA, Smith GJ, Vik DR, Pope PB, Sullivan MB, Roux S, Wrighton KC Abstract Microbial and viral communities transform the chemistry of Earth's ecosystems, yet the specific reactions catalyzed by these biological engines are hard to decode due to the absence of a scalable, metabolically resolved, annotation software. Here, we present DRAM (Distilled and Refined Annotation of Metabolism), a framework to translate the deluge of microbiome-based genomic information into a catalog of microbial traits. To demonstrate the applicability of DRAM across metabolically diverse genomes, we evaluated DRAM performance on a defined, in silico soil community and previously published human gut metagenomes. We show that DRAM accurately assigned microbial contributions to geochemical cycles and automated the partitioning of gut microbial carbohydrate metabolism at substrate levels. DRAM-v, the viral mode of DRAM, established rules to identify virally-encoded auxiliary metabolic genes (AMGs), resulting in the metabolic categorization of thousands of putative AMGs from soils and guts. Together DRAM and DRAM-v provide critical metabolic profiling capabilities that decipher mechanisms underpinning microbiome function. PMID: 32766782 [PubMed - indexed for MEDLINE]

Gene regulatory network controlling carpel number variation in cucumber.

Thu, 29/10/2020 - 11:18
Related Articles Gene regulatory network controlling carpel number variation in cucumber. Development. 2020 04 06;147(7): Authors: Che G, Gu R, Zhao J, Liu X, Song X, Zi H, Cheng Z, Shen J, Wang Z, Liu R, Yan L, Weng Y, Zhang X Abstract The WUSCHEL-CLAVATA3 pathway genes play an essential role in shoot apical meristem maintenance and floral organ development, and under intense selection during crop domestication. The carpel number is an important fruit trait that affects fruit shape, size and internal quality in cucumber, but the molecular mechanism remains elusive. Here, we found that CsCLV3 expression was negatively correlated with carpel number in cucumber cultivars. CsCLV3-RNAi led to increased number of petals and carpels, whereas overexpression of CsWUS resulted in more sepals, petals and carpels, suggesting that CsCLV3 and CsWUS function as a negative and a positive regulator for carpel number variation, respectively. Biochemical analyses indicated that CsWUS directly bound to the promoter of CsCLV3 and activated its expression. Overexpression of CsFUL1A , a FRUITFULL-like MADS-box gene, resulted in more petals and carpels. CsFUL1A can directly bind to the CsWUS promoter to stimulate its expression. Furthermore, we found that auxin participated in carpel number variation in cucumber through interaction of CsARF14 with CsWUS. Therefore, we have identified a gene regulatory pathway involving CsCLV3, CsWUS, CsFUL1A and CsARF14 in determining carpel number variation in an important vegetable crop - cucumber. PMID: 32165491 [PubMed - indexed for MEDLINE]

Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum.

Thu, 29/10/2020 - 11:18
Related Articles Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum. Sci Rep. 2019 10 28;9(1):15385 Authors: Rajan MR, Sotak M, Barrenäs F, Shen T, Borkowski K, Ashton NJ, Biörserud C, Lindahl TL, Ramström S, Schöll M, Lindahl P, Fiehn O, Newman JW, Perkins R, Wallenius V, Lange S, Börgeson E Abstract The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case. PMID: 31659186 [PubMed - indexed for MEDLINE]

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