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https://www.readbyqxmd.com/read/29150441/co-ii-and-ni-ii-binding-of-the-escherichia-coli-transcriptional-repressor-rcnr-orders-its-n-terminus-alters-helix-dynamics-and-reduces-dna-affinity
#1
Hsin-Ting Huang, Cedric E Bobst, Jeffrey S Iwig, Peter T Chivers, Igor A Kaltashov, Michael J Maroney
RcnR, a transcriptional regulator in Escherichia coli, derepresses the expression of the export proteins RcnAB upon binding Ni(II) or Co(II). Lack of structural information has precluded elucidation of the allosteric basis for the decreased DNA affinity in RcnR's metal-bound states. Here, using hydrogen-deuterium exchange coupled with MS (HDX-MS), we probed the RcnR structure in the presence of DNA, the cognate metal ions Ni(II) and Co(II), or the noncognate metal ion Zn(II). We found that cognate metal binding altered the flexibility from the N-terminus through helix 1 and modulated the RcnR-DNA interaction...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29149817/high-density-lipoprotein-hdl-dysfunction-and-future-of-hdl
#2
Sibel Ertek
Although high density lipoprotein cholesterol (HDL-C) levels are inversely proportional to cardiovascular risk in many studies, recent pharmacological interventional studies with HDL-C raising strategies did not show a benefit in terms of vascular events. The HDL particle is heterogenous with anti-atherogenic functions and non-vascular effects. Many factors affect HDL components and may either cause compositional changes, post-translational modifications of proteins, or alter lipids and other cargo molecules; generally these factors cause more than one of these changes, resulting in functional differences...
November 16, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29147686/lipoprotein-a-associated-molecules-are-prominent-components-in-plasma-and-valve-leaflets-in-calcific-aortic-valve-stenosis
#3
Michael Torzewski, Amir Ravandi, Calvin Yeang, Andrea Edel, Rahul Bhindi, Stefan Kath, Laura Twardowski, Jens Schmid, Xiaohong Yang, Ulrich F W Franke, Joseph L Witztum, Sotirios Tsimikas
The LPA gene is the only monogenetic risk factor for calcific aortic valve stenosis (CAVS). Oxidized phospholipids (OxPL) and lysophosphatidic acid generated by autotaxin (ATX) from OxPL are pro-inflammatory. Aortic valve leaflets were categorized pathologically from Both ATX-apoB and ATX-apo(a) were measureable in plasma. Lp(a), autotaxin, OxPL and MDA epitopes progressively increased in immunostaining (p<0.001 for all). Six species of OxPL and LysoPA were identified following extraction from valve leaflets...
June 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29146892/intermedin-ameliorates-atherosclerosis-by-increasing-cholesterol-efflux-through-the-camp-pka-pathway-in-macrophage-raw264-7-cell-line
#4
Hang Liao, Shixi Wan, Xin Zhang, Di Shi, Xiaojiang Zhu, Xiaoping Chen
BACKGROUND The aim of this study was to explore the role of intermedin and its mechanism in cholesterol efflux of macrophage THP-1 and RAW264.7 cell lines in atherosclerosis (AS). MATERIAL AND METHODS ApoE-/- mice were fed with a high-fat diet, and the concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. The lipidoses of the aortic sinus were analyzed by hematoxylin and eosin staining, and the cAMP level was detected by enzyme-linked immunosorbent assay (ELISA)...
November 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29146749/statins-promote-cardiac-infarct-healing-by-modulating-endothelial-barrier-function-revealed-by-contrast-enhanced-magnetic-resonance-imaging
#5
Geert J Leenders, Mirjam B Smeets, Maaike van den Boomen, Monique Berben, Miranda Nabben, Dianne van Strijp, Gustav J Strijkers, Jeanine J Prompers, Fatih Arslan, Klaas Nicolay, Katrien Vandoorne
OBJECTIVE: The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging...
November 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29144736/inference-of-calmodulin-s-ca2-dependent-free-energy-landscapes-via-gaussian-mixture-model-validation
#6
Annie M Westerlund, Tyler J Harpole, Christian Blau, Lucie Delemotte
A free energy landscape estimation-method based on the well-known Gaussian mixture model (GMM) is used for comparing the efficiency of thermally enhanced sampling methods with respect to regular molecular dynamics. The simulations are carried out on two binding states of calmodulin and the free energy estimation method is compared to other estimators using a toy model. We show that GMM with cross-validation provides a robust estimate that is not subject to overfitting. The continuous nature of Gaussians provides better estimates on sparse data than canonical histogramming...
November 16, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29143599/epistasis-physical-capacity-related-genes-and-exceptional-longevity-fndc5-gene-interactions-with-candidate-genes-foxoa3-and-apoe
#7
Noriyuki Fuku, Roberto Díaz-Peña, Yasumichi Arai, Yukiko Abe, Hirofumi Zempo, Hisashi Naito, Haruka Murakami, Motohiko Miyachi, Carlos Spuch, José A Serra-Rexach, Enzo Emanuele, Nobuyoshi Hirose, Alejandro Lucia
BACKGROUND: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population...
November 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29143455/understanding-the-functional-role-of-microrna-214-3p-in-atherosclerosis-for-the-identification-of-novel-targeted-therapies-to-prevent-or-reverse-endothelial-cell-dysfunction-and-stimulate-autophagy
#8
EDITORIAL
Adriana Georgescu
The original article by Jing Wang and collaborators, entitled "MicroRNA-214-3p: A Link between Autophagy and Endothelial Cell Dysfunction in Atherosclerosis", brings new data concerning molecular mechanisms linking decreased autophagy to endothelial dysfunction in atherosclerosis. In this issue of Acta Physiologica, the authors concluded that microRNA-214-3p (miR-214-3p) controls oxidized low-density lipoprotein (ox-LDL)-induced autophagy in human umbilical vein endothelial cells (HUVECs) by regulating intracellular levels of autophagy-related protein 5 (ATG5), and may have a relevant role in the pathogenesis of atherosclerosis...
November 16, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29142210/millisecond-dynamics-of-btk-reveal-kinome-wide-conformational-plasticity-within-the-apo-kinase-domain
#9
Mohammad M Sultan, Rajiah Aldrin Denny, Ray Unwalla, Frank Lovering, Vijay S Pande
Bruton tyrosine kinase (BTK) is a key enzyme in B-cell development whose improper regulation causes severe immunodeficiency diseases. Design of selective BTK therapeutics would benefit from improved, in-silico structural modeling of the kinase's solution ensemble. However, this remains challenging due to the immense computational cost of sampling events on biological timescales. In this work, we combine multi-millisecond molecular dynamics (MD) simulations with Markov state models (MSMs) to report on the thermodynamics, kinetics, and accessible states of BTK's kinase domain...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138269/irreversible-activation-and-stabilization-of-soluble-guanylate-cyclase-by-the-protoporphyrin-ix-mimetic-cinaciguat
#10
Alexander Kollau, Marissa Opelt, Gerald Wölkart, Antonius C F Gorren, Michael Russwurm, Doris Koesling, Bernd Mayer, Astrid Schrammel
Belonging to the class of so-called sGC activators, cinaciguat and BAY 60-2770 are interesting therapeutic tools for the treatment of various cardiovascular pathologies. The drugs are supposed to preferentially stimulate oxidized or heme-depleted but not native sGC. Since this concept has been challenged by studies demonstrating complete relaxation of non-diseased vessels, this study was designed to re-investigate the mode of action in greater detail. To this purpose, the effect of cinaciguat was studied on vessel tone of porcine coronary arteries and rat thoracic aortas...
November 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29137256/qishenyiqi-pill-attenuates-atherosclerosis-by-promoting-regulatory-t-cells-inhibiting-t-helper-17-cells-and-accelerating-cholesterol-excretion
#11
Li Peng, Chong-Shan Lv, Yun Zhao, Shao-Dong Chen, Yang Huang, Da-Wei Lu, Shu-Qiong Huang, Zong-Bao Yang, Lin-Chao Qian, Lei Wen
Objective: The aim of this study was to explore potential immunoregulatory mechanisms underlying the suppressive effect on atherosclerosis of QiShenYiQi pill (QSYQ). Methods and Results: Male ApoE(-/-) mice were maintained on a Western-type diet and QSYQ treatment for eight weeks. Determination of atherosclerosis demonstrated that QSYQ attenuated plaque formation and decreased the level of blood low-density lipoproteins-cholesterol. QSYQ treatment did not affect body weight but reduced the ratio of liver weight and body weight...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136784/the-alternation-of-autophagy-apoptosis-in-cd4-cd25-foxp3-tregs-on-the-developmental-stages-of-atherosclerosis
#12
Yuling Tian, Xiao Liang, Yue Wu
Naturally regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses in atherosclerosis. However, the regulatory mechanism underlying Tregs upon long-term development of atherosclerosis remains unknown. Therefore, in this study, atherosclerotic model was induced in ApoE-/- mice by feeding fat-diet for 10 weeks. Quantification of atherosclerotic lesions was done by calculating the lesion size in the aortic sinus every 2 weeks. The lipid levels and inflammatory mediators were detected in serum sample...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136780/cml-cd36-accelerates-atherosclerotic-progression-via-inhibiting-foam-cell-migration
#13
Suining Xu, Lihua Li, Jinchuan Yan, Fei Ye, Chen Shao, Zhen Sun, Zhengyang Bao, Zhiyin Dai, Jie Zhu, Lele Jing, Zhongqun Wang
Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136772/trimethylamine-n-oxide-promotes-atherosclerosis-via-cd36-dependent-mapk-jnk-pathway
#14
Jin Geng, Chenchen Yang, Bingjian Wang, Xiwen Zhang, Tingting Hu, Yang Gu, Ju Li
BACKGROUND: Many studies have identified trimethylamine N-oxide (TMAO) as a new risk factor of cardiovascular diseases. It has been suggested that TMAO promotes atherosclerosis development. However, the underlying mechanism is still unclear. METHODS: Apoe-/- mice were fed a high-fat diet and given water with or without TMAO for 8-week. Histological and immunohistological analyses were used to evaluate the atherogenic effect of TMAO in vivo. We also employed peritoneal elicited macrophages and RAW264...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135917/asperlin-inhibits-lps-evoked-foam-cell-formation-and-prevents-atherosclerosis-in-apoe-mice
#15
Yue Zhou, Ran Chen, Dong Liu, Chongming Wu, Peng Guo, Wenhan Lin
Asperlin is a marine-derived natural product with antifungal and anti-inflammatory activities in vitro. In the present study, we isolated asperlin from a marine Aspergillus versicolor LZD4403 fungus and investigated its anti-atherosclerotic effects in vitro and in vivo. Asperlin significantly inhibited lipopolysaccharides (LPS)- but not oxidated low-density lipoprotein (oxLDL)-evoked foam cell formation and promoted cholesterol efflux in RAW264.7 macrophages. Supplementation with asperlin also suppressed LPS-elicited production of pro-inflammatory factors in RAW264...
November 14, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29134505/upregulated-sphingosine-1-phosphate-receptor-1-expression-in-human-and-murine-atherosclerotic-plaques
#16
Hui Liu, Hongjun Jin, Junbin Han, Xuyi Yue, Hao Yang, Mohamed A Zayed, Robert J Gropler, Zhude Tu
PURPOSE: Dysregulation of sphingosine 1-phosphate receptor 1 (S1PR1) signaling contributes to inflammation-related pathophysiological changes in cardiovascular diseases including atherosclerosis (AS). S1PR1-targeting compounds significantly reduce lesion size in murine models of AS. Therefore, characterization of S1PR1 expression in vitro and in vivo in atherosclerotic plaque could enable mechanistic studies and inform S1PR1 targeted therapies. PROCEDURES: H&E staining and immunostaining studies were performed on variably diseased human femoral endarterectomy plaque specimens, as well as mouse aortic sections from ApoE(-/-) mice maintained on a high-fat diet (AS mice)...
November 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29133888/neuronal-hyperactivity-due-to-loss-of-inhibitory-tone-in-apoe4-mice-lacking-alzheimer-s-disease-like-pathology
#17
Tal Nuriel, Sergio L Angulo, Usman Khan, Archana Ashok, Qiuying Chen, Helen Y Figueroa, Sheina Emrani, Li Liu, Mathieu Herman, Geoffrey Barrett, Valerie Savage, Luna Buitrago, Efrain Cepeda-Prado, Christine Fung, Eliana Goldberg, Steven S Gross, S Abid Hussaini, Herman Moreno, Scott A Small, Karen E Duff
The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason APOE4 is associated with increased AD risk remains a source of debate. Neuronal hyperactivity is an early phenotype in both AD mouse models and in human AD, which may play a direct role in the pathogenesis of the disease. Here, we have identified an APOE4-associated hyperactivity phenotype in the brains of aged APOE mice using four complimentary techniques-fMRI, in vitro electrophysiology, in vivo electrophysiology, and metabolomics-with the most prominent hyperactivity occurring in the entorhinal cortex...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29132620/identifying-and-prioritizing-the-tools-techniques-of-knowledge-management-based-on-the-asian-productivity-organization-model-apo-to-use-in-hospitals
#18
Hamid Khajouei, Reza Khajouei
INTRODUCTION: Appropriate knowledge, correct information, and relevant data are vital in medical diagnosis and treatment systems. Knowledge Management (KM) through its tools/techniques provides a pertinent framework for decision-making in healthcare systems. The objective of this study was to identify and prioritize the KM tools/techniques that apply to hospital setting. METHODS: This is a descriptive-survey study. Data were collected using a -researcher-made questionnaire that was developed based on experts' opinions to select the appropriate tools/techniques from 26 tools/techniques of the Asian Productivity Organization (APO) model...
December 2017: International Journal of Medical Informatics
https://www.readbyqxmd.com/read/29132311/weighted-gene-co-expression-network-analysis-of-expression-data-of-monozygotic-twins-identifies-specific-modules-and-hub-genes-related-to-bmi
#19
Weijing Wang, Wenjie Jiang, Lin Hou, Haiping Duan, Yili Wu, Chunsheng Xu, Qihua Tan, Shuxia Li, Dongfeng Zhang
BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. RESULTS: In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29131589/using-tryptophan-mutants-to-probe-the-structural-and-functional-status-of-bssco-a-copper-binding-cytochrome-c-oxidase-assembly-protein-from-bacillus-subtilis
#20
Shina Hussain, Diann Andrews, Bruce C Hill
The synthesis of cytochrome c oxidase protein from Bacillus subtilis (i.e., BsSCO) binds copper with picomolar affinity, which increases the protein's melting temperature (i.e., TM) by 20 °C. Here two native tryptophans (i.e., W36 and W101) are identified as major contributors to BsSCO's structural form, and their contributions to the stability, intrinsic fluorescence, and copper binding properties of BsSCO are explored. Single mutations of tryptophan to phenylalanine decrease the TM by 10 °C and the folding free energy by 3-4 kcal/mol...
November 17, 2017: Biochemistry
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