Database : MEDLINE
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[PMID]: 29524844
[Au] Autor:Cheng Z; Shen X; Jiang X; Shan H; Cimini M; Fang P; Ji Y; Park JY; Drosatos K; Yang X; Kevil CG; Kishore R; Wang H
[Ad] Address:Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, 3500 Broad Street, Philadelphia, PA 19140, USA. Electronic address: zjcheng@temple.edu.
[Ti] Title:Hyperhomocysteinemia potentiates diabetes-impaired EDHF-induced vascular relaxation: Role of insufficient hydrogen sulfide.
[So] Source:Redox Biol;16:215-225, 2018 Feb 14.
[Is] ISSN:2213-2317
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Insufficient hydrogen sulfide (H S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively), and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF)-induced endothelium-dependent relaxation to acetylcholine (ACh), determined by the presence of eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and prostacyclin (PGI ) inhibitor indomethacin (INDO), in SMA from db/db mice but not that from db/+ mice. A non-selective Ca -active potassium channel (K ) opener NS309 rescued T2DM/HHcy-impaired EDHF-mediated vascular relaxation to ACh. EDHF-induced relaxation to ACh was inhibited by a non-selective K blocker TEA and intermediate-conductance K blocker (IK ) Tram-34, but not by small-conductance K (SK ) blocker Apamin. HHcy potentiated the reduction of free sulfide, H S and cystathionine γ-lyase protein, which converts L-cysteine to H S, in SMA of db/db mice. Importantly, a stable H S donor DATS diminished the enhanced O production in SMAs and lung endothelial cells of T2DM/HHcy mice. Antioxidant PEG-SOD and DATS improved T2DM/HHcy impaired relaxation to ACh. Moreover, HHcy increased hyperglycemia-induced IK tyrosine nitration in human micro-vascular endothelial cells. EDHF-induced vascular relaxation to L-cysteine was not altered, whereas such relaxation to NaHS was potentiated by HHcy in SMA of db/db mice which was abolished by ATP-sensitive potassium channel blocker Glycolamide but not by K blockers. CONCLUSIONS: Intermediate HHcy potentiated H S reduction via CSE-downregulation in microvasculature of T2DM mice. H S is justified as an EDHF. Insufficient H S impaired EDHF-induced vascular relaxation via oxidative stress and IK inactivation in T2DM/HHcy mice. H S therapy may be beneficial for prevention and treatment of micro-vascular complications in patients with T2DM and HHcy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 63935 MEDLINE  
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[PMID]: 29180119
[Au] Autor:Xu W; Mukherjee S; Ning Y; Hsu FF; Zhang K
[Ad] Address:Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.
[Ti] Title:Cyclopropane fatty acid synthesis affects cell shape and acid resistance in Leishmania mexicana.
[So] Source:Int J Parasitol;48(3-4):245-256, 2018 Mar.
[Is] ISSN:1879-0135
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Cyclopropane fatty acid synthase (CFAS) catalyzes the transfer of a methylene group from S-adenosyl methionine to an unsaturated fatty acid, generating a cyclopropane fatty acid (CFA). The gene encoding CFAS is present in many bacteria and several Leishmania spp. including Leishmania mexicana, Leishmania infantum and Leishmania braziliensis. In this study, we characterised the CFAS-null and -overexpression mutants in L. mexicana, the causative agent for cutaneous leishmaniasis in Mexico and central America. Our data indicate that L. mexicana CFAS modifies the fatty acid chain of plasmenylethanolamine (PME), the dominant class of ethanolamine glycerophospholipids in Leishmania, generating CFA-PME. While the endogenous level of CFA-PME is extremely low in wild type L. mexicana, overexpression of CFAS results in a significant increase. CFAS-null mutants (cfas ) exhibit altered cell shape, increased sensitivity to acidic pH, and aberrant growth in serum-free media. In addition, the CFAS protein is preferentially expressed during the proliferative stage of L. mexicana and is required for the cell membrane targeting of lipophosphoglycan. Finally, the maturation and localization of CFAS protein are dependent upon the downstream sequence of the CFAS coding region. Without the downstream sequence, the mis-localised CFAS protein cannot fully rescue the defects of cfas . Our data suggest that CFA modification of phospholipids can significantly affect the parasite's response to certain adverse conditions. These findings are distinct from the roles of CFAS in L. infantum, highlighting the functional divergence in lipid modification among Leishmania spp.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review

  3 / 63935 MEDLINE  
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[PMID]: 29523717
[Au] Autor:Guo J; Wang S; Yu X; Dong R; Li Y; Mei X; Shen Y
[Ad] Address:Beijing University of Agriculture CITY: Beijing China [CN].
[Ti] Title:Polyamines Regulate Strawberry Fruit Ripening by ABA, IAA, and Ethylene.
[So] Source:Plant Physiol;, 2018 Mar 09.
[Is] ISSN:1532-2548
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Polyamines (PAs) participate in many plant growth and developmental processes, including fruit ripening. However, it is not clear whether PAs play a role in the ripening of strawberry (Fragaria ananassa), a model non-climacteric plant. Here, we found that the content of the PA spermine (Spm) increased more sharply after the onset of fruit coloration than did that of the PAs putrescine (Put) or spermidine (Spd). Spm dominance in ripe fruit resulted from abundant transcripts of a strawberry S-adenosyl-L-methionine decarboxylase gene (FaSAMDC), which encodes an enzyme that generates a residue needed for PA biosynthesis. Exogenous Spm and Spd promoted fruit coloration, while exogenous Put and a SAMDC inhibitor inhibited coloration. Based on transcriptome data, up- and downregulation of FaSAMDC expression promoted and inhibited ripening, respectively, which coincided with changes in several physiological parameters and their corresponding gene transcripts, including firmness, anthocyanin content, sugar content, polyamine content, auxin (IAA) content, abscisic acid (ABA) content, and ethylene emission. Using isothermal titration calorimetry, we found that FaSAMDC also had a high enzymatic activity with a Kd of 1.7 × 10-3 M. In conclusion, PAs, especially Spm, regulate strawberry fruit ripening in an ABA-dominated, IAA-participating and ethylene-coordinated manner, and FaSAMDC plays an important role in ripening.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  4 / 63935 MEDLINE  
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[PMID]: 29523205
[Au] Autor:Moore SJ; Vrentas CE; Hwang S; West Greenlee MH; Nicholson EM; Greenlee JJ
[Ad] Address:USDA, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, USA.
[Ti] Title:Pathologic and biochemical characterization of PrP from elk with PRNP polymorphisms at codon 132 after experimental infection with the chronic wasting disease agent.
[So] Source:BMC Vet Res;14(1):80, 2018 Mar 09.
[Is] ISSN:1746-6148
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: The Rocky Mountain elk (Cervus elaphus nelsoni) prion protein gene (PRNP) is polymorphic at codon 132, with leucine (L132) and methionine (M132) allelic variants present in the population. In elk experimentally inoculated with the chronic wasting disease (CWD) agent, different incubation periods are associated with PRNP genotype: LL132 elk survive the longest, LM132 elk are intermediate, and MM132 elk the shortest. The purpose of this study was to investigate potential mechanisms underlying variations in incubation period in elk of different prion protein genotypes. Elk calves of three PRNP genotypes (n = 2 MM132, n = 2 LM132, n = 4 LL132) were orally inoculated with brain homogenate from elk clinically affected with CWD. RESULTS: Elk with longer incubation periods accumulated relatively less PrP in the brain than elk with shorter incubation periods. PrP accumulation in LM132 and MM132 elk was primarily neuropil-associated while glial-associated immunoreactivity was prominent in LL132 elk. The fibril stability of PrP from MM132 and LM132 elk were similar to each other and less stable than that from LL132 elk. Real-time quaking induced conversion assays (RT-QuIC) revealed differences in the ability of PrP seed from elk of different genotypes to convert recombinant 132 M or 132 L substrate. CONCLUSIONS: This study provides further evidence of the importance of PRNP genotype in the pathogenesis of CWD of elk. The longer incubation periods observed in LL132 elk are associated with PrP that is more stable and relatively less abundant at the time of clinical disease. The biochemical properties of PrP from MM132 and LM132 elk are similar to each other and different to PrP from LL132 elk. The shorter incubation periods in MM132 compared to LM132 elk may be the result of genotype-dependent differences in the efficiency of propagation of PrP moieties present in the inoculum. A better understanding of the mechanisms by which the polymorphisms at codon 132 in elk PRNP influence disease pathogenesis will help to improve control of CWD in captive and free-ranging elk populations.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Process
[do] DOI:10.1186/s12917-018-1400-9

  5 / 63935 MEDLINE  
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[PMID]: 29400461
[Au] Autor:Kelly KL; Dalton SR; Wai RB; Ramchandani K; Xu RJ; Linse S; Londergan CH
[Ad] Address:Department of Chemistry , Haverford College , Haverford , Pennsylvania 19041 , United States.
[Ti] Title:Conformational Ensembles of Calmodulin Revealed by Nonperturbing Site-Specific Vibrational Probe Groups.
[So] Source:J Phys Chem A;, 2018 Mar 09.
[Is] ISSN:1520-5215
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Seven native residues on the regulatory protein calmodulin, including three key methionine residues, were replaced (one by one) by the vibrational probe amino acid cyanylated cysteine, which has a unique CN stretching vibration that reports on its local environment. Almost no perturbation was caused by this probe at any of the seven sites, as reported by CD spectra of calcium-bound and apo calmodulin and binding thermodynamics for the formation of a complex between calmodulin and a canonical target peptide from skeletal muscle myosin light chain kinase measured by isothermal titration. The surprising lack of perturbation suggests that this probe group could be applied directly in many protein-protein binding interfaces. The infrared absorption bands for the probe groups reported many dramatic changes in the probes' local environments as CaM went from apo- to calcium-saturated to target peptide-bound conditions, including large frequency shifts and a variety of line shapes from narrow (interpreted as a rigid and invariant local environment) to symmetric to broad and asymmetric (likely from multiple coexisting and dynamically exchanging structures). The fast intrinsic time scale of infrared spectroscopy means that the line shapes report directly on site-specific details of calmodulin's variable structural distribution. Though quantitative interpretation of the probe line shapes depends on a direct connection between simulated ensembles and experimental data that does not yet exist, formation of such a connection to data such as that reported here would provide a new way to evaluate conformational ensembles from data that directly contains the structural distribution. The calmodulin probe sites developed here will also be useful in evaluating the binding mode of calmodulin with many uncharacterized regulatory targets.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1021/acs.jpca.8b00475

  6 / 63935 MEDLINE  
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[PMID]: 28463369
[Au] Autor:Ndagi U; Mhlongo NN; Soliman ME
[Ad] Address:Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa. soliman@ukzn.ac.za.
[Ti] Title:The impact of Thr91 mutation on c-Src resistance to UM-164: molecular dynamics study revealed a new opportunity for drug design.
[So] Source:Mol Biosyst;13(6):1157-1171, 2017 May 30.
[Is] ISSN:1742-2051
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The emergence of a drug resistant non-receptor tyrosine kinase (c-Src) in triple-negative breast cancer (TNBC) remains a prime concern in relation to the burden of TNBC among people living with breast cancer and drug development. Thr91 mutation was found to induce a complete loss of protein conformation required for drug fitness. Herein, we provide the first account of the molecular impact of the Thr91 mutation on c-Src resistance to experimental drug UM-164 using various computational approaches, namely molecular dynamics simulation, principal component analysis (PCA), dynamic cross-correlation matrices (DCCM) analysis, hydrogen bond occupancy, thermodynamics calculation, ligand-residue interaction and residue interaction networks (RINs). Findings from this study revealed that Thr91 mutation leads to a steric conflict between UM-164 and the side chain of methionine (Met91); this mutation distorts the UM-164 optimum orientation on the conformational space of mutant c-Src compared to the wild-type; decreases hydrogen bond formation between the residues in the mutant protein structure; decreases the UM-164 binding energy in the mutant by -13.416 kcal mol ; reduces the residue correlation in the mutant protein structure; induces a change in the overall protein structure conformation from an inactive to active conformation; and distorts the ligand atomic interaction network and the residue interaction network. This report provides important insights that will assist in the further design of novel dual kinase inhibitors to minimise the chances of drug resistance in triple negative breast cancer.
[Mh] MeSH terms primary: Molecular Dynamics Simulation
Triple Negative Breast Neoplasms/genetics
[Mh] MeSH terms secundary: Drug Design
Drug Resistance, Viral/genetics
Humans
Hydrogen Bonding
Mutation
Principal Component Analysis
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:170503
[St] Status:MEDLINE
[do] DOI:10.1039/c6mb00848h

  7 / 63935 MEDLINE  
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[PMID]: 29521488
[Au] Autor:Testino G; Leone S; Fagoonee S; Pellicano R
[Ad] Address:Alcohological Regional Centre, Liguria Region, ASL3 Genovese c/o Ospedale Policlinico San Martino, Genova, Italy.
[Ti] Title:The role of adenosyl-methionine in alcoholic liver disease and intrahepatic cholestasis.
[So] Source:Minerva Gastroenterol Dietol;, 2018 Mar 08.
[Is] ISSN:1827-1642
[Cp] Country of publication:Italy
[La] Language:eng
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.23736/S1121-421X.18.02484-4

  8 / 63935 MEDLINE  
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[PMID]: 29518953
[Au] Autor:Bekeschus S; Lackmann JW; Gümbel D; Napp M; Schmidt A; Wende K
[Ad] Address:Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK Plasmatis, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany. sander.bekeschus@inp-greifswald.de.
[Ti] Title:A Neutrophil Proteomic Signature in Surgical Trauma Wounds.
[So] Source:Int J Mol Sci;19(3), 2018 Mar 07.
[Is] ISSN:1422-0067
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates. Among them were expected targets belonging to the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200 post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine trioxidation) to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually collected exudates, we confirmed presence of neutrophils and their products, such as microparticles and fragments containing myeloperoxidase and DNA. These data confirmed known and identified less known wound proteins and their PTMs, which may serve as resource for future studies on human wound healing.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

  9 / 63935 MEDLINE  
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[PMID]: 29518784
[Au] Autor:Furuta C; Murakami H
[Ti] Title:A Novel Concept of Amino Acid Supplementation to Improve the Growth of Young Malnourished Male Rats.
[So] Source:Ann Nutr Metab;72(3):231-240, 2018 Mar 08.
[Is] ISSN:1421-9697
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:BACKGROUNDS/AIMS: This study was aimed at understanding the relationship between plasma amino acids and protein malnutrition and at determining whether amino acid supplementation associated with malnutrition and growth improves linear growth in growing rats. METHODS: Body length and plasma amino acids were measured in young male rats that were fed the following diet for 3 weeks, mimicking a low and imbalanced protein diets based on maize, a major staple consumed in developing countries: a 70% calorically restricted cornmeal-based diet (C), C + micronutrients (CM), CM + casein (CMC), CM + soy protein (CMS) or CMS + 0.3% lysine. RESULTS: A correlation analysis of linear growth and plasma amino acids indicated that lysine, tryptophan, branched-chain amino acids, methionine, and phenylalanine significantly correlated with body length. Supplementation with these 5 amino acids (AA1) significantly improved the body length in rats compared to CMC treatment whereas, nitrogen-balanced amino acid supplemented controls (AA2) did not (CM +1.2 ± 0.2, CMC +2.7 ± 0.3, CMS +2.1 ± 0.3, AA1 +2.8 ± 0.2, and AA2 +2.5 ± 0.3 cm). CONCLUSION: With securing proper amino acid balance, supplementing growth-related amino acids is more effective in improving linear growth in malnourished growing male rats. Analysis of the correlation between plasma amino acids and growth represents a powerful tool to determine candidate amino acids for supplementation to prevent malnutrition. This technology is adaptable to children in developing countries.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1159/000487603

  10 / 63935 MEDLINE  
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[PMID]: 29504255
[Au] Autor:Wanders D; Forney LA; Stone KP; Hasek BE; Johnson WD; Gettys TW
[Ad] Address:Department of Nutrition, Georgia State University, Atlanta, Georgia, USA.
[Ti] Title:The Components of Age-Dependent Effects of Dietary Methionine Restriction on Energy Balance in Rats.
[So] Source:Obesity (Silver Spring);, 2018 Mar 04.
[Is] ISSN:1930-739X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Dietary methionine restriction (MR) improves biomarkers of metabolic health, in part through coordinated increases in energy intake and energy expenditure (EE). Some metabolic benefits of dietary MR are secondary to its effects on energy balance, so this study's purpose was to examine how age at initiation of MR influences its effects on energy balance and body composition. METHODS: Energy balance was examined in rats provided control or MR diets for 9 months after weaning or in rats between 6 and 12 months of age. RESULTS: Rats provided the control diet for 9 months after weaning increased their body weight (BW) and fat mass by five- and eightfold, respectively, while BW and fat accumulation in the MR group were reduced to 50% of that of controls. In adult rats fed the respective diets between 6 and 12 months of age, dietary MR increased energy intake by ∼23%, but the 15% increase in EE was sufficient to prevent increases in BW or fat mass. CONCLUSIONS: Dietary MR produces comparable increases in EE in young, growing animals and in mature animals, but young animals continue to deposit new tissue because of the proportionately larger effect of MR on energy intake relative to maintenance requirements.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1002/oby.22146


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