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https://www.readbyqxmd.com/read/28340083/evaluating-the-patterns-of-aging-related-tau-astrogliopathy-unravels-novel-insights-into-brain-aging-and-neurodegenerative-diseases
#1
Gabor G Kovacs, John L Robinson, Sharon X Xie, Edward B Lee, Murray Grossman, David A Wolk, David J Irwin, Dan Weintraub, Christopher F Kim, Theresa Schuck, Ahmed Yousef, Stephanie T Wagner, Eunran Suh, Vivianna M Van Deerlin, Virginia M-Y Lee, John Q Trojanowski
The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania...
March 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28337704/analysis-of-traditional-and-emerging-risk-factors-in-premenopausal-women-with-coronary-artery-disease-a-pilot-scale-study-from-north-india
#2
Rajesh Vijayvergiya, Divya Kapoor, Ajay Aggarwal, Sonal Sangwan, Vanita Suri, Veena Dhawan
Premenopausal women are known to have less heart disease than their menopausal counterparts and men. However, there is a rising prevalence of coronary artery disease (CAD) in premenopausal females, which necessitates determination of risk factors that negate the effects of hormonal protection. There are few studies describing the prevalence of traditional and emerging risk factors in premenopausal women with CAD. Thus, our objective was to explore the prevalence of traditional and emerging risk factors and features of coronary lesions in premenopausal women with CAD in an Indian population...
March 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28337631/upregulation-of-mineralocorticoid-receptor-in-the-hypothalamus-associated-with-a-high-anxiety-like-level-in-apolipoprotein-e4-transgenic-mice
#3
Fan-Tao Meng, Jun Zhao, Hui Fang, Li-Feng Zhang, Hui-Mei Wu, Ya-Jing Liu
Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3 months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice...
March 24, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28337214/crystal-structure-of-the-chloroplastic-oxoene-reductase-ceqorh-from-arabidopsis-thaliana
#4
Sarah Mas Y Mas, Gilles Curien, Cécile Giustini, Norbert Rolland, Jean-Luc Ferrer, David Cobessi
Enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids give rise to accumulation of aldehydes, ketones, and α,β-unsaturated carbonyls of various lengths, known as oxylipins. Oxylipins with α,β-unsaturated carbonyls are reactive electrophile species and are toxic. Cells have evolved several mechanisms to scavenge reactive electrophile oxylipins and decrease their reactivity such as by coupling with glutathione, or by reduction using NAD(P)H-dependent reductases and dehydrogenases of various substrate specificities...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28336922/novel-and-traditional-lipid-related-biomarkers-and-their-combinations-in-predicting-coronary-severity
#5
Sha Li, Yuan-Lin Guo, Xi Zhao, Yan Zhang, Cheng-Gang Zhu, Na-Qiong Wu, Rui-Xia Xu, Ping Qing, Ying Gao, Xiao-Lin Li, Jing Sun, Geng Liu, Qian Dong, Jian-Jun Li
We investigated simultaneously traditional and novel lipid indices, alone or in combination, in predicting coronary severity assessed by Gensini score (GS) in 1605 non-lipid-lowering-drug-treated patients undergoing coronary angiography. Firstly, levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), non high density lipoprotein cholesterol (non-HDL-C), apolipoprotein (apo) B, lipoprotein (a) [Lp(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoC3, small dense LDL (sdLDL) and large HDL were increased, while HDL-C and apoA1 levels were decreased as GS status (all p for trend <0...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336560/lipoprotein-a-and-hiv-allele-specific-apolipoprotein-a-levels-predict-carotid-intima-media-thickness-in-hiv-infected-young-women-in-the-women-s-interagency-hiv-study
#6
Enkhmaa Byambaa, Anuurad Erdembileg, Wei Zhang, Chin-Shang Li, Robert Kaplan, Jason Lazar, Dan Merenstein, Roksana Karim, Brad Aouizerat, Mardge Cohen, Kenneth Butler, Savita Pahwa, Igho Ofotokun, Adaora A Adimora, Elizabeth Golub, Lars Berglund
OBJECTIVE: In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. APPROACH AND RESULTS: The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study)...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28336528/platelet-cd36-promotes-thrombosis-by-activating-redox-sensor-erk5-in-hyperlipidemic-conditions
#7
Moua Yang, Brian C Cooley, Wei Li, Yiliang Chen, Jeannette Vasquez-Vivar, Na'il O Scoggins, Scott J Cameron, Craig N Morrell, Roy L Silverstein
Atherothrombosis is a process mediated by dysregulated platelet activation that can cause life-threatening complications and is the leading cause of death by cardiovascular disease. Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in LDL particles, a process which induces an overt prothrombotic phenotype. The mechanisms by which CD36 promotes platelet activation and thrombosis remain incompletely defined. In this study, we identify a mechanism for CD36 to promote thrombosis by increasing activation of MAP kinase ERK5, a protein kinase known to be exquisitely sensitive to redox stress, through a signaling pathway requiring Src kinases, NADPH oxidase, superoxide radical anion and hydrogen peroxide...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28336201/a-facile-method-for-isolation-of-recombinant-human-apolipoprotein-a-i-from-e-coli
#8
Nikita Ikon, Jennifer Shearer, Jianfang Liu, Jesse J Tran, ShiBo Feng, Ayako Kamei, Jennifer A Beckstead, Robert S Kiss, Paul M Weers, Gang Ren, Robert O Ryan
Apolipoprotein (apo) A-I is the major protein component of high-density lipoprotein (HDL) and plays key roles in the Reverse Cholesterol Transport pathway. In the past decade, reconstituted HDL (rHDL) has been employed as a therapeutic agent for treatment of atherosclerosis. The ability of rHDL to promote cholesterol efflux from peripheral cells has been documented to reduce the size of atherosclerotic plaque lesions. However, development of apoA-I rHDL-based therapeutics for human use requires a cost effective process to generate an apoA-I product that meets "Good Manufacturing Practice" standards...
March 20, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28336061/enzymes-as-sensors
#9
Maria Staiano, Angela Pennacchio, Antonio Varriale, Alessandro Capo, Adelia Majoli, Clotilde Capacchione, Sabato D'Auria
Over the last few decades the development of new technologies, the fabrication of new materials, and the introduction of nanotechnologies created new trends in a series of advances that produced innovations in biological sensing devices with a wide range of application from health, security, defense, food, and medicine, to the environment. Specificity, low cost, rapidity, sensitivity, and multiplicity are some of the reasons for their growth, and their commercial success is expected to increase in the next future...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28335828/dha-brain-uptake-and-apoe4-status-a-pet-study-with-1-11-c-dha
#10
Hussein N Yassine, Etienne Croteau, Varun Rawat, Joseph R Hibbeln, Stanley I Rapoport, Stephen C Cunnane, John C Umhau
BACKGROUND: The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes. METHODS: Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-(11)C]-DHA (J in), and regional cerebral blood flow using [(15)O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19-65 years)...
March 23, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28334939/association-between-tau-deposition-and-antecedent-amyloid-%C3%AE-accumulation-rates-in-normal-and-early-symptomatic-individuals
#11
Duygu Tosun, Susan Landau, Paul S Aisen, Ronald C Petersen, Mark Mintun, William Jagust, Michael W Weiner
A long-term goal of our field is to determine the sequence of pathological events, which ultimately lead to cognitive decline and dementia. In this study, we first assessed the patterns of brain tau tangle accumulation (measured with the positron emission tomography tracer 18F-AV-1451) associated with well-established Alzheimer's disease factors in a cohort including cognitively healthy elderly individuals and individuals at early symptomatic stages of Alzheimer's disease. We then explored highly associated patterns of greater 18F-AV-1451 binding and increased annualized change in cortical amyloid-β plaques measured as florbetapir positron emission tomography binding antecedent to 18F-AV-1451 positron emission tomography scans, and to what extent these multimodal pattern associations explained the variance in cognitive performance and clinical outcome measures, independently and jointly...
March 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334117/a-generalized-association-test-based-on-u-statistics
#12
Changshuai Wei, Qing Lu
Motivation: Second generation sequencing technologies are being increasingly used for genetic association studies, where the main research interest is to identify sets of genetic variants that contribute to various phenotypes. The phenotype can be univariate disease status, multivariate responses and even high-dimensional outcomes. Considering the genotype and phenotype as two complex objects, this also poses a general statistical problem of testing association between complex objects...
February 17, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28333036/apoe-%C3%AE%C2%B54-specific-imbalance-of-arachidonic-acid-and-docosahexaenoic-acid-in-serum-phospholipids-identifies-individuals-with-preclinical-mild-cognitive-impairment-alzheimer-s-disease
#13
Laila Abdullah, James E Evans, Tanja Emmerich, Gogce Crynen, Ben Shackleton, Andrew P Keegan, Cheryl Luis, Leon Tai, Mary J LaDu, Michael Mullan, Fiona Crawford, Corbin Bachmeier
This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers...
March 23, 2017: Aging
https://www.readbyqxmd.com/read/28332978/structural-reorganization-of-the-chromatin-remodeling-enzyme-chd1-upon-engagement-with-nucleosomes
#14
Ramasubramanian Sundaramoorthy, Amanda L Hughes, Vijender Singh, Nicola Wiechens, Daniel P Ryan, Hassane El-Mkami, Maxim Petoukhov, Dmitri I Svergun, Barbara Treutlein, Salina Quack, Monika Fischer, Jens Michaelis, Bettina Böttcher, David G Norman, Tom Owen-Hughes
The yeast Chd1 protein acts to position nucleosomes across genomes. Here we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state the DNA binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.5 helical turns from the dyad axis of symmetry. Binding in this conformation involves unravelling the outer turn of nucleosomal DNA and requires substantial reorientation of the DNA binding domain with respect to the ATPase domains...
March 23, 2017: ELife
https://www.readbyqxmd.com/read/28332615/integrative-variants-haplotypes-and-diplotypes-of-the-capn3-and-frmd5-genes-and-several-environmental-exposures-associate-with-serum-lipid-variables
#15
Tao Guo, Rui-Xing Yin, Ling Pan, Shuo Yang, Liu Miao, Feng Huang
To determine whether the integrative variants, haplotypes and diplotypes of the calpain 3 (CAPN3) and the FERM domain containing 5 genes (FRMD5) and several environmental exposures are associated with an implication in lipid homeostasis, which are associated with cardiovascular risk. Genotyping of the CAPN3 rs4344713 and FRMD5 rs524908 was performed by Sanger sequencing in 1,640 subjects (Jing, 819 and Han, 821). Multivariate analyses of covariance models that adjusted by age, gender, body mass index (BMI), blood pressure and lifestyle (smoking and drinking), were constructed using variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908 as predictors and changes in lipid variables...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331223/therapeutic-efficacy-and-safety-of-pcsk9-monoclonal-antibodies-on-familial-hypercholesterolemia-and-statin-intolerant-patients-a-meta-analysis-of-15-randomized-controlled-trials
#16
Li Jun Qian, Yao Gao, Yan Mei Zhang, Ming Chu, Jing Yao, Di Xu
Proprotein convertase subtilisin/kexin9 monoclonal antibodies (PCSK9-mAb) have been studied intensively to identify their effect in lowering levels of low density lipoprotein cholesterol (LDL-C). However, the applicable target of PCSK9-mAbs remains inconclusive so far. Therefore, this first meta-analysis was carried out to clarify the therapeutic efficacy and safety of PCSK9-mAbs on the potential patients: familial hypercholesterolemia and statin-intolerant patients. All randomized controlled trials that met the search terms were retrieved in multiple databases...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330873/amp-activated-protein-kinase-%C3%AE-1-promotes-atherogenesis-by-increasing-monocyte-to-macrophage-differentiation
#17
Miao Zhang, Huaiping Zhu, Ye Ding, Zhaoyu Liu, Zhejun Cai, Ming-Hui Zou
Monocyte-to-macrophage differentiation, which can be initiated by physiological or atherogenic factors, is a pivotal process in atherogenesis, a disorder in which monocytes adhere to endothelial cells and subsequently migrate into the sub-endothelial spaces, where they differentiate into macrophages and macrophage-derived foam cells and cause atherosclerotic lesions. However, the monocyte-differentiation signaling pathways that are activated by atherogenic factors are poorly defined. Here we report that the AMP- activated protein kinase (AMPK) α1 in monocytes promotes atherosclerosis by increasing monocyte differentiation and survival...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28330871/human-mitochondrial-cytochrome-c-oxidase-assembly-factor-cox18-acts-transiently-as-a-membrane-insertase-within-the-subunit-2-maturation-module
#18
Myriam Bourens, Antoni Barrientos
Defects in mitochondrial cytochrome c oxidase or respiratory chain complex IV (CIV) assembly are a frequent cause of human mitochondrial disorders. Specifically, mutations in four conserved assembly factors impinging the biogenesis of the mitochondrion-encoded catalytic core subunit 2 (COX2) result in myopathies. These factors afford stability of newly-synthesized COX2 (the dystonia-ataxia syndrome protein COX20), a protein with two transmembrane domains, and maturation of its copper center CuA (cardiomyopathy proteins SCO1, SCO2 and COA6)...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28330175/exploration-of-the-binding-modes-of-l-asparaginase-complexed-with-its-amino-acid-substrates-by-molecular-docking-dynamics-and-simulation
#19
Erva Rajeswara Reddy, Rajulapati Satish Babu, Potla Durthi Chandrasai, Pola Madhuri
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-glutamine (L-Gln) deamination plays crucial role in ALL treatment. Role of Erwinaze(®) (L-asparaginase from Erwinia chrysanthemi) in regulation of L-Asn and L-Gln has been confirmed by the experimental studies. Therapeutic research against ALL remained elusive with the lack of structural information on Erwinaze(®) enzyme. In this present study, homology model of the Erwinaze(®) was developed using MODELLER and the same was validated by various quality indexing tools...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330072/molecular-dynamic-simulations-of-escherichia-coli-l-asparaginase-to-illuminate-its-role-in-deamination-of-asparagine-and-glutamine-residues
#20
Rajeswara Reddy Erva, Satish Babu Rajulapati, Chandrasai Potla Durthi, Mayuri Bhatia, Madhuri Pola
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-Glutamine (L-Gln) deamination play a crucial role in ALL treatment. Role of Elspar(®) (L-asparaginase from Escherichia coli) in regulation of L-Asn and L-Gln has been confirmed by the other researchers through experimental studies. Therapeutic research against ALL remained elusive with the lack of information on molecular interactions of Elspar(®) with amino acid substrates. In the present study, using different docking tools binding cavities, key residues in binding and ligand binding mechanisms were identified...
June 2016: 3 Biotech
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