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[PMID]: 29483297
[Au] Autor:Qiu Y; Perry RJ; Camporez JG; Zhang XM; Kahn M; Cline GW; Shulman GI; Vatner DF
[Ad] Address:Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States.
[Ti] Title: Studies on the Mechanism of Methylenecyclopropylacetic acid and Methylenecyclopropylglycine-Induced Hypoglycemia.
[So] Source:Biochem J;, 2018 Feb 26.
[Is] ISSN:1470-8728
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Exposure to the toxins methylene cyclopropyl acetic acid (MCPA) and methylene cyclopropyl glycine (MCPG) of unripe ackee and litchi fruit can lead to hypoglycemia and death; however, the molecular mechanisms by which MCPA and MCPG cause hypoglycemia have not been established To determine the mechanisms of action of these toxins we infused them into conscious rodents and assessed rates of hepatic gluconeogenesis and ketogenesis, hepatic acyl-CoA and hepatic acetyl-CoA content, and hepatocellular energy charge. MCPG suppressed rates of hepatic ß-oxidation as reflected by reductions in hepatic ketogenesis, reducing both short- and medium-chain hepatic acyl-CoA concentrations. Hepatic acetyl-CoA content decreased, and hepatic glucose production was inhibited. MCPA also suppressed ß-oxidation of short chain acyl-CoAs, rapidly inhibiting hepatic ketogenesis and hepatic glucose production, depleting hepatic acetyl-CoA content and ATP content, while increasing other short chain acyl CoAs. Utilizing a recently-developed positional isotopomer NMR tracer analysis (PINTA) method we demonstrated that MCPA-induced reductions in hepatic acetyl-CoA content were associated with a marked reduction of hepatic pyruvate carboxylase flux. Taken together, these data reveal the mechanisms of action of MCPA and MCPG: the hypoglycemia associated with ingestion of these toxins can be ascribed mostly to MCPA- or MCPG- induced reductions in hepatic pyruvate carboxylase flux due to inhibition of ß-oxidation of short chain acyl-CoAs by MCPA or inhibition of both short and medium chain acyl-CoAs by MCPG with resultant reductions in hepatic acetyl-CoA content, with an additional contribution to hypoglycemia through reduced hepatic ATP stores by MCPA.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher

  2 / 130 MEDLINE  
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[PMID]: 29176509
[Au] Autor:Cauwenberghs N; Knez J; Boggia J; D'hooge J; Yang WY; Wei FF; Thijs L; Staessen JA; Kuznetsova T
[Ad] Address:Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
[Ti] Title:Doppler indexes of left ventricular systolic and diastolic function in relation to haemodynamic load components in a general population.
[So] Source:J Hypertens;36(4):867-875, 2018 Apr.
[Is] ISSN:1473-5598
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: The contribution of central pulsatility to left ventricular (LV) dysfunction might be mediated by the haemodynamic loads of forward (Pf) and backward (Pb) pulse waves. We investigated the relation between echocardiographic indexes of LV function and pulsatile loads derived by wave separation analysis (WSA). METHODS: In 755 participants, we assessed LV dimensions, transmitral blood flow and mitral annular tissue velocities. We derived central pulse pressure (cPP) from radial tonometric recordings and calculated Pf, Pb and their ratio (reflection magnitude) using an automated, pressure-based WSA algorithm. Despite good quality recordings, WSA failed to derive Pf and Pb in 139 participants (18.4%), in particular in older women with unfavourable haemodynamics. Thus, our analysis included 616 participants (46.1% women; mean age, 49.2 years). RESULTS: Age and age explained most of the variance in cPP (36.9%), Pf (18.6%), Pb (41.5%) and reflection magnitude (36.7%; P < 0.0001) and altered the direct correlation between Pf and Pb (Pint < 0.0001). Haemodynamic loads were independently associated with sex, BMI, heart rate, mean arterial pressure, history of diabetes and use of antihypertensive drugs. In multivariable-adjusted analyses, transmitral velocities and E/e' ratio increased with higher cPP, Pf and Pb in men and women. We also observed an age-dependent association of LV radial strain with cPP, Pf and Pb. CONCLUSION: The commercial WSA algorithm holds limited clinical utility given its low feasibility in older participants with unfavourable haemodynamics. LV function indexes were similarly associated with Pf and Pb, favouring the use of the composite cPP for prediction of LV dysfunction.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 180228
[Lr] Last revision date:180228
[St] Status:In-Data-Review
[do] DOI:10.1097/HJH.0000000000001623

  3 / 130 MEDLINE  
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[PMID]: 29386503
[Au] Autor:Perry RJ; Peng L; Cline GW; Butrico GM; Wang Y; Zhang XM; Rothman DL; Petersen KF; Shulman GI
[Ad] Address:Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.
[Ti] Title:Publisher Correction: Non-invasive assessment of hepatic mitochondrial metabolism by positional isotopomer NMR tracer analysis (PINTA).
[So] Source:Nat Commun;9(1):498, 2018 Jan 31.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The originally published version of this Article contained an error in Equation 30, which was inadvertently introduced during the production process. This has now been corrected in the PDF and HTML versions of the Article.
[Pt] Publication type:PUBLISHED ERRATUM
[Em] Entry month:1802
[Cu] Class update date: 180203
[Lr] Last revision date:180203
[St] Status:In-Data-Review
[do] DOI:10.1038/s41467-018-03023-3

  4 / 130 MEDLINE  
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[PMID]: 29136137
[Au] Autor:Macias-Muñoz A; McCulloch KJ; Briscoe AD
[Ad] Address:Ecology and Evolutionary Biology, University of California, Irvine, CA, 92697 U.S.A.
[Ti] Title:Copy number variation and expression analysis reveals a non-orthologous pinta gene family member involved in butterfly vision.
[So] Source:Genome Biol Evol;, 2017 Nov 09.
[Is] ISSN:1759-6653
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Vertebrate (CRALBP) and Drosophila (PINTA) proteins with a CRAL-TRIO domain transport retinal-based chromophores that bind to opsin proteins and are necessary for phototransduction. The CRAL-TRIO domain gene family is composed of genes that encode proteins with a common N-terminal structural domain. While there is an expansion of this gene family in Lepidoptera, there is no lepidopteran ortholog of pinta. Further, the function of these genes in lepidopterans has not yet been established. Here we explored the molecular evolution and expression of CRAL-TRIO domain genes in the butterfly Heliconius melpomene in order to identify a member of this gene family as a candidate chromophore transporter. We generated and searched a four tissue transcriptome and searched a reference genome for CRAL-TRIO domain genes. We expanded an insect CRAL-TRIO domain gene phylogeny to include H. melpomene and used 18 genomes from 4 subspecies to assess copy number variation. A transcriptome-wide differential expression analysis comparing four tissue types identified a CRAL-TRIO domain gene, Hme CTD31, upregulated in heads suggesting a potential role in vision for this CRAL-TRIO domain gene. RT-PCR and immunohistochemistry confirmed that Hme CTD31 and its protein product are expressed in the retina, specifically in primary and secondary pigment cells and in tracheal cells. Sequencing of eye protein extracts that fluoresce in the ultraviolet identified Hme CTD31 as a possible chromophore binding protein. Although we found several recent duplications and numerous copy number variants in CRAL-TRIO domain genes, we identified a single copy pinta paralog that likely binds the chromophore in butterflies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 171114
[Lr] Last revision date:171114
[St] Status:Publisher
[do] DOI:10.1093/gbe/evx230

  5 / 130 MEDLINE  
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[PMID]: 29070788
[Au] Autor:Desgeorges MM; Devillard X; Toutain J; Castells J; Divoux D; Arnould DF; Haqq C; Bernaudin M; Durieux AC; Touzani O; Freyssenet DG
[Ad] Address:Université de Lyon, Laboratoire Interuniversitaire de Biologie de la Motricité, Saint Etienne, F-42023, Lyon, France.
[Ti] Title:Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke.
[So] Source:Sci Rep;7(1):14000, 2017 Oct 25.
[Is] ISSN:2045-2322
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal muscle mass and function after cerebral ischemia. Cerebral ischemia (45 minutes) was induced by intraluminal right middle cerebral artery occlusion (MCAO). Swiss male mice were randomly assigned to Sham-operated mice (n = 10), MCAO mice receiving the vehicle (n = 15) and MCAO mice receiving an anti-myostatin PINTA745 (n = 12; subcutaneous injection of 7.5 mg.kg PINTA745 immediately after surgery, 3, 7 and 10 days after MCAO). PINTA745 reduced body weight loss and improved body weight recovery after cerebral ischemia, as well as muscle strength and motor function. PINTA745 also increased muscle weight recovery 15 days after cerebral ischemia. Mechanistically, the better recovery of skeletal muscle mass in PINTA745-MCAO mice involved an increased expression of genes encoding myofibrillar proteins. Therefore, an anti-myostatin strategy can improve skeletal muscle recovery after cerebral ischemia and may thus represent an interesting strategy to combat skeletal muscle loss and weakness in stroke patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1710
[Cu] Class update date: 171101
[Lr] Last revision date:171101
[St] Status:In-Data-Review
[do] DOI:10.1038/s41598-017-13912-0

  6 / 130 MEDLINE  
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[PMID]: 28986525
[Au] Autor:Perry RJ; Peng L; Cline GW; Butrico GM; Wang Y; Zhang XM; Rothman DL; Petersen KF; Shulman GI
[Ad] Address:Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.
[Ti] Title:Non-invasive assessment of hepatic mitochondrial metabolism by positional isotopomer NMR tracer analysis (PINTA).
[So] Source:Nat Commun;8(1):798, 2017 Oct 06.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of hepatic mitochondrial citrate synthase flux (V ) and pyruvate carboxylase flux (V ) in vivo. Here, we show that a positional isotopomer NMR tracer analysis (PINTA) method can be used to non-invasively assess rates of V and V fluxes using a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3- C]lactate and glucose tracer. PINTA measures V and V fluxes over a wide range of physiological conditions with minimal pyruvate cycling and detects increased hepatic V following treatment with a liver-targeted mitochondrial uncoupler. Finally, validation studies in humans demonstrate that the V /V ratio measured by PINTA is similar to that determined by in vivo NMR spectroscopy. This method will provide investigators with a relatively simple tool to non-invasively examine the role of altered hepatic mitochondrial metabolism.Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1710
[Cu] Class update date: 171018
[Lr] Last revision date:171018
[St] Status:In-Data-Review
[do] DOI:10.1038/s41467-017-01143-w

  7 / 130 MEDLINE  
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[PMID]: 28272233
[Au] Autor:Li L; Hu B; Gong S; Yu Y; Yan J
[Ad] Address:aIntensive Care Unit and Zheiiang Provincial Key Laboratory of Geriatrics, Zhejiang Hospital bIntensive Care Unit, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
[Ti] Title:Age and cigarette smoking modulate the relationship between pulmonary function and arterial stiffness in heart failure patients.
[So] Source:Medicine (Baltimore);96(10):e6262, 2017 Mar.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The aim of this study was to assess the relationship between arterial stiffness and pulmonary function in chronic heart failure (CHF).Outpatients previously diagnosed as CHF were enrolled between April 2008 and March 2010, and submitted to arterial stiffness measurement and lung function assessment. Spirometry was performed by measuring forced vital capacity (FVC), the fraction of predicted FVC, forced expiratory volume in 1 second (FEV1), the percentage of predicted FEV1 in 1 second, FEV1 to FVC ratio, and the percentage of predicted FEV1/FVC. Cardio-ankle vascular index (CAVI) was considered for the estimation of arterial stiffness.The 354 patients assessed included 315 nonsmokers, and were 68.2 ±â€Š7.2 years' old. Unadjusted correlation analyses demonstrated CAVI was positively related to age (r = 0.3664, P < 0.0001), and negatively related to body mass index (BMI, r = -0.2040, P = 0.0001), E/A ratio (r = -0.1759, P = 0.0010), and FEV1 (r = -0.2987, P < 0.0001). Stepwise multivariate regression analyses showed age (r = 0.2391, P < 0.0001), BMI (r = -0.2139, P < 0.0001), smoking (r = 0.1211, P = 0.0130), E/A ratio (r = -0.1082, P = 0.0386), and FEV1 (r = -0.2550, P < 0.0001) were independent determinants of CAVI. In addition, there is a significant interaction between CAVI and forced expiratory volume in 1 second (FEV1) in relation to age (Pint < 0.0001) and smoking (Pint = 0.0001). Meanwhile, pulmonary function was not associated with BMI or E/A ratio.These findings demonstrated that reduced pulmonary function is associated with the increased CAVI, and had an interactive effect with age and smoking on CAVI in patients with CHF.
[Mh] MeSH terms primary: Aging/physiology
Heart Failure/physiopathology
Lung/physiopathology
Smoking/physiopathology
Vascular Stiffness
[Mh] MeSH terms secundary: Aged
Female
Humans
Male
Middle Aged
Respiratory Function Tests
[Pt] Publication type:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Em] Entry month:1703
[Cu] Class update date: 170324
[Lr] Last revision date:170324
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:170309
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006262

  8 / 130 MEDLINE  
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[PMID]: 28168761
[Au] Autor:Brautigam CA; Deka RK; Liu WZ; Tomchick DR; Norgard MV
[Ad] Address:Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
[Ti] Title:Functional clues from the crystal structure of an orphan periplasmic ligand-binding protein from Treponema pallidum.
[So] Source:Protein Sci;26(4):847-856, 2017 Apr.
[Is] ISSN:1469-896X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The spirochete Treponema pallidum is the causative agent of syphilis, a sexually transmitted infection of major global importance. Other closely related subspecies of Treponema also are the etiological agents of the endemic treponematoses, such as yaws, pinta, and bejel. The inability of T. pallidum and its close relatives to be cultured in vitro has prompted efforts to characterize T. pallidum's proteins structurally and biophysically, particularly those potentially relevant to treponemal membrane biology, with the goal of possibly revealing the functions of those proteins. This report describes the structure of the treponemal protein Tp0737; this polypeptide has a fold characteristic of a class of periplasmic ligand-binding proteins associated with ABC-type transporters. Although no ligand for the protein was observed in electron-density maps, and thus the nature of the native ligand remains obscure, the structural data described herein provide a foundation for further efforts to elucidate the ligand and thus the function of this protein in T. pallidum.
[Mh] MeSH terms primary: ATP-Binding Cassette Transporters/chemistry
Periplasmic Proteins/chemistry
Treponema pallidum/chemistry
[Mh] MeSH terms secundary: ATP-Binding Cassette Transporters/genetics
ATP-Binding Cassette Transporters/metabolism
Crystallography, X-Ray
Periplasmic Proteins/genetics
Periplasmic Proteins/metabolism
Protein Domains
Structure-Activity Relationship
Treponema pallidum/genetics
Treponema pallidum/metabolism
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Periplasmic Proteins)
[Em] Entry month:1707
[Cu] Class update date: 171109
[Lr] Last revision date:171109
[Js] Journal subset:IM
[Da] Date of entry for processing:170208
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3133

  9 / 130 MEDLINE  
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[PMID]: 27498082
[Au] Autor:Gogarten JF; Düx A; Schuenemann VJ; Nowak K; Boesch C; Wittig RM; Krause J; Calvignac-Spencer S; Leendertz FH
[Ad] Address:Epidemiology of Highly Pathogenic Microorganisms, Germany; Primatology Department, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany; Department of Biology, McGill University, Montreal, Quebec, Canada.
[Ti] Title:Tools for opening new chapters in the book of Treponema pallidum evolutionary history.
[So] Source:Clin Microbiol Infect;22(11):916-921, 2016 Nov.
[Is] ISSN:1469-0691
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Treponema pallidum infections causing yaws disease and venereal syphilis are globally widespread in human populations, infecting hundreds of thousands and millions annually respectively; endemic syphilis is much less common, and pinta has not been observed in decades. We discuss controversy surrounding the origin, evolution and history of these pathogens in light of available molecular and anthropological evidence. These bacteria (or close relatives) seem to affect many wild African nonhuman primate (NHP) species, though to date only a single NHP Treponema pallidum genome has been published, hindering detection of spillover events and our understanding of potential wildlife reservoirs. Similarly, only ten genomes of Treponema pallidum infecting humans have been published, impeding a full understanding of their diversity and evolutionary history. Research efforts have been hampered by the difficulty of culturing and propagating Treponema pallidum. Here we highlight avenues of research recently opened by the coupling of hybridization capture and next-generation sequencing. We present data generated with such an approach suggesting that asymptomatic bones from NHP occasionally contain enough treponemal DNA to recover large fractions of their genomes. We expect that these methods, which naturally can be applied to modern biopsy samples and ancient human bones, will soon considerably improve our understanding of these enigmatic pathogens and lay rest to old yet unresolved controversies.
[Mh] MeSH terms primary: Bone and Bones/microbiology
Syphilis/history
Treponema pallidum/genetics
Yaws/history
[Mh] MeSH terms secundary: Evolution, Molecular
High-Throughput Nucleotide Sequencing/methods
History, 15th Century
Humans
Phylogeny
Sequence Analysis, DNA/methods
Syphilis/microbiology
Treponema pallidum/classification
Treponema pallidum/isolation & purification
Yaws/microbiology
[Pt] Publication type:HISTORICAL ARTICLE; JOURNAL ARTICLE; REVIEW
[Em] Entry month:1702
[Cu] Class update date: 170223
[Lr] Last revision date:170223
[Js] Journal subset:IM
[Da] Date of entry for processing:160808
[St] Status:MEDLINE

  10 / 130 MEDLINE  
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[PMID]: 27294610
[Au] Autor:Hirko KA; Fortner RT; Hankinson SE; Wu T; Eliassen AH
[Ad] Address:Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, 909 Fee Road, East Lansing, MI, 48824, USA. khirko@epi.msu.edu.
[Ti] Title:Plasma fluorescent oxidation products and risk of estrogen receptor-negative breast cancer in the Nurses' Health Study and Nurses' Health Study II.
[So] Source:Breast Cancer Res Treat;158(1):149-55, 2016 Jul.
[Is] ISSN:1573-7217
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Findings from epidemiologic studies of oxidative stress biomarkers and breast cancer have been mixed, although no studies have focused on estrogen receptor-negative (ER-) tumors which may be more strongly associated with oxidative stress. We examined prediagnostic plasma fluorescent oxidation products (FlOP), a global biomarker of oxidative stress, and risk of ER- breast cancer in a nested case-control study in the Nurses' Health Study and Nurses' Health Study II. ER- breast cancer cases (n = 355) were matched to 355 controls on age, month/time of day of blood collection, fasting status, menopausal status, and menopausal hormone use. Conditional logistic regression models were used to examine associations of plasma FlOP at three emission wavelengths (FlOP_360, FlOP_320, and FlOP_400) and risk of ER- breast cancer. We did not observe any significant associations between FlOP measures and risk of ER- breast cancer overall; the RRQ4vsQ1 (95 %CI) 0.70 (0.43-1.13), p trend = 0.09 for FlOP_360; 0.91(0.56-1.46), p trend = 0.93 for FlOP_320; and 0.62 (0.37-1.03), p trend = 0.10 for FlOP_400. Results were similar in models additionally adjusted for total carotenoid levels and in models stratified by age and total carotenoids. Although high (vs. low) levels of FIOP_360 and FIOP_400 were associated with lower risk of ER- breast cancer in lean women (body mass index (BMI) < 25 kg/m(2)) but not in overweight/obese women, these differences were not statistically significant (pint = 0.23 for FlOP_360; pint = 0.37 for FlOP_400). Our findings suggest that positive associations of plasma FlOP concentrations and ER- breast cancer risk are unlikely.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1606
[Cu] Class update date: 170220
[Lr] Last revision date:170220
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1007/s10549-016-3861-5


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