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https://www.readbyqxmd.com/read/27926730/integrin-yap-taz-jnk-cascade-mediates-atheroprotective-effect-of-unidirectional-shear-flow
#1
Li Wang, Jiang-Yun Luo, Bochuan Li, Xiao Yu Tian, Li-Jing Chen, Yuhong Huang, Jian Liu, Dan Deng, Chi Wai Lau, Song Wan, Ding Ai, King-Lun Kingston Mak, Ka Kui Tong, Kin Ming Kwan, Nanping Wang, Jeng-Jiann Chiu, Yi Zhu, Yu Huang
The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli. However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27925140/tea-consumption-reduces-the-incidence-of-neurocognitive-disorders-findings-from-the-singapore-longitudinal-aging-study
#2
L Feng, M-S Chong, W-S Lim, Q Gao, M S Nyunt, T-S Lee, S L Collinson, T Tsoi, E-H Kua, T-P Ng
OBJECTIVES: To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. DESIGN: Population-based longitudinal study. SETTING: The Singapore Longitudinal Aging Study (SLAS). PARTICIPANTS: 957 community-living Chinese elderly who were cognitively intact at baseline. MEASUREMENTS: We collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010...
2016: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/27924494/characterization-of-membrane-protein-lipid-interactions-by-mass-spectrometry-ion-mobility-mass-spectrometry
#3
Yang Liu, Xiao Cong, Wen Liu, Arthur Laganowsky
Lipids in the biological membrane can modulate the structure and function of integral and peripheral membrane proteins. Distinguishing individual lipids that bind selectively to membrane protein complexes from an ensemble of lipid-bound species remains a daunting task. Recently, ion mobility mass spectrometry (IM-MS) has proven to be invaluable for interrogating the interactions between protein and individual lipids, where the complex undergoes collision induced unfolding followed by quantification of the unfolding pathway to assess the effect of these interactions...
December 6, 2016: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/27924297/datasets-for-the-validation-of-the-in-vivo-sirna-silencing-of-cd40-and-for-the-detection-of-new-markers-of-atherosclerosis-progression-in-apoe-deficient-mice
#4
Miguel Hueso, Laura De Ramon, Estanislao Navarro, Elia Ripoll, Josep M Cruzado, Josep M Grinyo, Joan Torras
Data presented in this Data in Brief article correspond to the article "in vivo" silencing of CD40 reduces progression of experimental atherogenesis through a NFκB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis" (M. Hueso, L. De Ramon, E. Navarro, E. Ripoll, J.M. Cruzado, J.M. Grinyo, J. Torras, 2016) [1]. Here, we describe the validation of the silencing of CD40 expression with a specific siRNA in ApoE(-/-) mouse aortas, and its systemic effects on splenic lymphocytic subpopulations as well as on the infiltration of aortic intima by F4/80(+), galectin-3(+) macrophages or by NF-κB(+) cells...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27923179/structural-dynamics-of-casein-kinase-i-cki-from-malarial-parasite-plasmodium-falciparum-isolate-3d7-insights-from-theoretical-modelling-and-molecular-simulations
#5
Budheswar Dehury, Santosh Kumar Behera, Namita Mahapatra
The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation...
November 21, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27923151/a-novel-role-for-the-kr%C3%A3-ppel-like-factor-14-on-macrophage-inflammatory-response-and-atherosclerosis-development
#6
Xiao Wei, Ruomei Yang, Chengpan Wang, Xun Jian, Ling Li, Hua Liu, Gangyi Yang, Zhiyong Li
Genome-wide association studies have shown that Krüppel-like factor 14 (KLF14) is associated with both Type 2 diabetes mellitus and lipid metabolism. However, its role in chronic inflammatory responses and the pathogenesis of atherosclerosis remains unknown. The present study was designed to investigate both in vivo and in vitro the impact of KLF14 on chronic inflammatory responses and atherosclerosis. ApoE KO mice, a well-established animal model of atherosclerosis, had higher expressions of KLF14 in aorta tissues than that in C57BL/6 J mice when fed the high-fat diet (HFD) or standard chow diet...
November 14, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27922847/apolipoprotein-e-metabolism-and-functions-in-brain-and-its-role-in-alzheimer-s-disease
#7
Fan Liao, Hyejin Yoon, Jungsu Kim
PURPOSE OF REVIEW: APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. RECENT FINDINGS: ApoE isoforms have differential effects on amyloid β metabolism...
December 5, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27922822/serum-protein-mediators-of-dementia-and-aging-proper
#8
Donald R Royall, Safa Al-Rubaye, Ram Bishnoi, Raymond F Palmer
The latent variable "δ" (for "dementia") appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depressive symptoms, gender and the apolipoprotein E (APOE) ε4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of age's specific association with δ in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). 22 serum proteins were recognized as partial mediators of age's association with δ...
December 3, 2016: Aging
https://www.readbyqxmd.com/read/27921997/comparative-molecular-dynamics-study-of-dimeric-and-monomeric-forms-of-hiv-1-protease-in-ligand-bound-and-unbound-state
#9
Monikaben Padariya, Umesh Kalathiya
Human immunodeficiency virus type 1 protease is a viral-encoded enzyme and it is essential for replication and assembly of the virus. Inactivation of HIV-1 protease causes production of immature, noninfectious viral particles and thus HIV-1 protease is an attractive target in anti-AIDS drug design. In our current work, we performed molecular dynamics (MD) calculations (500 ns) for two different ligands (COM5 - designed in our previous study, and Darunavir) and made effort to understand dynamics behaviour of our designed compound COM5...
December 6, 2016: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27919357/lipid-phenotype-and-heritage-pattern-in-families-with-genetic-hypercholesterolemia-not-related-to-ldlr-apob-pcsk9-or-apoe
#10
Estíbaliz Jarauta, María Rosario Pérez-Ruiz, Sofia Pérez-Calahorra, Rocio Mateo-Gallego, Ana Cenarro, Montserrat Cofán, Emilio Ros, Fernando Civeira, Maria Teresa Tejedor
BACKGROUND: A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied. OBJECTIVES: We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH)...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27919352/impact-of-a-1-year-lifestyle-modification-program-on-plasma-lipoprotein-and-pcsk9-concentrations-in-patients-with-coronary-artery-disease
#11
Marjorie Boyer, Valérie Lévesque, Paul Poirier, André Marette, Patrick Mathieu, Jean-Pierre Després, Éric Larose, Benoit J Arsenault
BACKGROUND: Patients with coronary artery disease (CAD) are characterized by an impaired cardiometabolic risk profile including high levels of atherogenic apolipoprotein (apo) B-containing lipoprotein levels. Genetic studies have highlighted a critical role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism and CAD risk. OBJECTIVE: To determine whether improving dietary quality and increasing physical activity levels improve parameters of the cardiometabolic risk profile such as plasma apoB and PCSK9 levels in patients with CAD...
November 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27918234/formation-and-exudation-of-non-volatile-products-of-the-arabidiol-triterpenoid-degradation-pathway-in-arabidopsis-roots
#12
Reza Sohrabi, Tehane Ali, Liva Harinantenaina Rakotondraibe, Dorothea Tholl
Triterpenoids produced by plants play important roles in the protection against biotic stress. Roots of Arabidopsis thaliana produce different triterpenoids, which include the tricyclic triterpene diol, arabidiol. In a degradation reaction induced by infection with the oomycete pathogen, Pythium irregulare, arabidiol is cleaved to the 11-carbon volatile homoterpene, (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), and the 19-carbon ketone, apo-arabidiol. The arabidiol pathway and its volatile breakdown product DMNT have been implicated in the defense against P...
December 5, 2016: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/27917464/relation-of-dysglycemia-to-structural-brain-changes-in-a-multiethnic-elderly-cohort
#13
Christiane Reitz, Vanessa A Guzman, Atul Narkhede, Charles DeCarli, Adam M Brickman, José A Luchsinger
OBJECTIVES: Abnormally high glucose levels (dysglycemia) increase with age. Epidemiological studies suggest that dysglycemia is a risk factor for cognitive impairment but the underlying pathophysiological mechanisms remain unclear. The objective of this study was to examine the relation of dysglycemia clinical categories (normal glucose tolerance (NGT), pre-diabetes, undiagnosed diabetes, known diabetes) with brain structure in older adults. We also assessed the relation between dysglycemia and cognitive performance...
December 5, 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27917297/an-intrinsic-agonist-mechanism-for-activation-of-glucagon-like-peptide-1-receptor-by-its-extracellular-domain
#14
Yanting Yin, X Edward Zhou, Li Hou, Li-Hua Zhao, Bo Liu, Gaihong Wang, Yi Jiang, Karsten Melcher, H Eric Xu
The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27917221/the-influence-of-apoe-genotype-on-the-lipid-profile-and-lipoproteins-during-normal-pregnancy-in-a-southern-african-population
#15
Donald Moshen Tanyanyiwa, Adrian David Marais, Pamela Byrnes, Sheena Jones
BACKGROUND: Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. RESULTS: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy...
September 2016: African Health Sciences
https://www.readbyqxmd.com/read/27916520/water-bridge-mediates-recognition-of-mrna-cap-in-eif4e
#16
Dilraj Lama, Mohan R Pradhan, Christopher J Brown, Rohan S Eapen, Thomas L Joseph, Chee-Keong Kwoh, David P Lane, Chandra S Verma
Ligand binding pockets in proteins contain water molecules, which play important roles in modulating protein-ligand interactions. Available crystallographic data for the 5' mRNA cap-binding pocket of the translation initiation factor protein eIF4E shows several structurally conserved waters, which also persist in molecular dynamics simulations. These waters engage an intricate hydrogen-bond network between the cap and protein. Two crystallographic waters in the cleft of the pocket show a high degree of conservation and bridge two residues, which are part of an evolutionarily conserved scaffold...
November 24, 2016: Structure
https://www.readbyqxmd.com/read/27915184/anti-atherosclerotic-effects-of-pravastatin-in-brachiocephalic-artery-in-comparison-with-en-face-aorta-and-aortic-roots-in-apoe-ldlr-mice
#17
Renata B Kostogrys, Magdalena Franczyk-Zarow, Marlena Gasior-Glogowska, Edyta Kus, Agnieszka Jasztal, Tomasz P Wrobel, Malgorzata Baranska, Izabela Czyzynska-Cichon, Anna Drahun, Angelika Manterys, Stefan Chlopicki
BACKGROUND: Cholesterol-dependent and independent mechanisms were proposed to explain anti-atherosclerotic action of statins in humans. However, their effects in murine models of atherosclerosis have not been consistently demonstrated. Here, we studied the effects of pravastatin on atherosclerosis in ApoE/LDLR(-/-) mice fed a control and atherogenic diet. METHODS: ApoE/LDLR(-/-) mice were fed a control (CHOW) or an atherogenic (Low Carbohydrate High Protein, LCHP) diet...
September 17, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27914062/computational-design-of-ligand-binding-proteins
#18
Christine E Tinberg, Sagar D Khare
The ability to design novel small-molecule binding sites in proteins is a stringent test of our understanding of the principles of molecular recognition, and would have many practical applications, in synthetic biology and medicine. Here, we describe a computational method in the context of the macromolecular modeling suite Rosetta to designing proteins with sites featuring predetermined interactions to ligands of choice. The required inputs for the method are a model of the small molecule and the desired interactions (e...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914033/l-carnitine-simvastatin-reduces-lipoprotein-a-levels-compared-with-simvastatin-monotherapy-a-randomized-double-blind-placebo-controlled-study
#19
M Florentin, M S Elisaf, C V Rizos, V Nikolaou, E Bilianou, C Pitsavos, E N Liberopoulos
Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. L-Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of L-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low-density lipoprotein cholesterol (LDL-C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study...
December 2, 2016: Lipids
https://www.readbyqxmd.com/read/27912196/nox-isoforms-in-the-development-of-abdominal-aortic-aneurysm
#20
Kin Lung Siu, Qiang Li, Yixuan Zhang, Jun Guo, Ji Youn Youn, Jie Du, Hua Cai
Oxidative stress plays an important role in the formation of abdominal aortic aneurysm (AAA), and we have recently established a causal role of uncoupled eNOS in this severe human disease. We have also shown that activation of NADPH oxidase (NOX) lies upstream of uncoupled eNOS. Therefore, identification of the specific NOX isoforms that are required for eNOS uncoupling and AAA formation would ultimately lead to novel therapies for AAA. In the present study, we used the Ang II infused hph-1 mice to examine the roles of NOX isoforms in the development of AAA...
November 19, 2016: Redox Biology
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