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https://www.readbyqxmd.com/read/28350817/differential-associations-of-plasma-lipids-with-incident-dementia-and-dementia-subtypes-in-the-3c-study-a-longitudinal-population-based-prospective-cohort-study
#1
Sabrina Schilling, Christophe Tzourio, Aïcha Soumaré, Sara Kaffashian, Jean-François Dartigues, Marie-Laure Ancelin, Cécilia Samieri, Carole Dufouil, Stéphanie Debette
BACKGROUND: Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons. METHODS AND FINDINGS: Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28350795/fine-mapping-of-the-human-leukocyte-antigen-locus-as-a-risk-factor-for-alzheimer-disease-a-case-control-study
#2
Natasha Z R Steele, Jessie S Carr, Luke W Bonham, Ethan G Geier, Vincent Damotte, Zachary A Miller, Rahul S Desikan, Kevin L Boehme, Shubhabrata Mukherjee, Paul K Crane, John S K Kauwe, Joel H Kramer, Bruce L Miller, Giovanni Coppola, Jill A Hollenbach, Yadong Huang, Jennifer S Yokoyama
BACKGROUND: Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28346846/dna-methylation-of-the-pdgfd-gene-promoter-increases-the-risk-for-intracranial-aneurysms-and-brain-arteriovenous-malformations
#3
Shengjun Zhou, Xiang Gao, Jie Sun, Zhiqing Lin, Yi Huang
The aim of this study was to determine the role of DNA methylation of the platelet-derived growth factor-D (PDGFD) gene promoter in the development of intracranial aneurysms (IAs) and brain arteriovenous malformations (BAVMs). A total of 70 patients with IAs or BAVMs and 26 control individuals were enrolled for this study. The PDGFD level in the plasma was determined using enzyme-linked immunosorbent assay. DNA methylation levels of seven cytosine-phosphate-guanine (CpG) dinucleotides present in the PDGFD gene promoter were measured using bisulfite pyrosequencing technology...
March 27, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28346588/association-between-childhood-onset-epilepsy-and-amyloid-burden-5-decades-later
#4
Juho Joutsa, Juha O Rinne, Bruce Hermann, Mira Karrasch, Anu Anttinen, Shlomo Shinnar, Matti Sillanpää
Importance: The effect of childhood epilepsy on later-life cognitive and brain health is an unclear and little-explored issue. Objective: To determine whether adults with a history of childhood-onset epilepsy exhibit increased brain amyloid accumulation, possibly predisposing to accelerated cognitive impairment or even frank cognitive disorders in later life. Design, Setting, and Participants: Forty-one adults from a population-based cohort of individuals with childhood-onset epilepsy in southwestern Finland, together with 46 matched population-based controls, underwent amyloid ligand carbon 11-labeled Pittsburgh Compound B (PiB) positron emission tomography after long-term prospective follow-up...
March 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28346566/gene-gene-interaction-between-pparg-and-apoe-gene-on-late-onset-alzheimer-s-disease-a-case-control-study-in-chinese-han-population
#5
S Wang, L Guan, D Luo, J Liu, H Lin, X Li, X Liu
AIMS: The aim was to investigate the impact of PPARG and APOE gene single nucleotide polymorphisms (SNPs) and additional gene- gene interaction on late-onset Alzheimer's disease (LOAD) risk based on Chinese Han population. METHODS: A total of 928 participants (466 males, 462 females), with a mean age of 81.3 ± 16.4 years old, were included in the study, including 460 LOAD patients and 468 normal controls participants. Logistic regression was performed to investigate association between SNP and LOAD risk and generalized multifactor dimensionality reduction (GMDR) was used to analysis the gene-gene interaction...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28346407/insights-into-activity-and-inhibition-from-the-crystal-structure-of-human-o-glcnacase
#6
Nathaniel L Elsen, Sangita B Patel, Rachael E Ford, Dawn L Hall, Fred Hess, Hari Kandula, Maria Kornienko, John Reid, Harold Selnick, Jennifer M Shipman, Sujata Sharma, Kevin J Lumb, Stephen M Soisson, Daniel J Klein
O-GlcNAc hydrolase (OGA) catalyzes removal of βα-linked N-acetyl-D-glucosamine from serine and threonine residues. We report crystal structures of Homo sapiens OGA catalytic domain in apo and inhibited states, revealing a flexible dimer that displays three unique conformations and is characterized by subdomain α-helix swapping. These results identify new structural features of the substrate-binding groove adjacent to the catalytic site and open new opportunities for structural, mechanistic and drug discovery activities...
March 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28345659/oral-chromium-picolinate-impedes-hyperglycemia-induced-atherosclerosis-and-inhibits-proatherogenic-protein-tsp-1-expression-in-stz-induced-type-1-diabetic-apoe-mice
#7
Rituparna Ganguly, Soumyadip Sahu, Vahagn Ohanyan, Rebecca Haney, Ronaldo J Chavez, Shivani Shah, Siri Yalamanchili, Priya Raman
Increasing evidence suggests thrombospondin-1 (TSP-1), a potent proatherogenic matricellular protein, as a putative link between hyperglycemia and atherosclerotic complications in diabetes. We previously reported that the micronutrient chromium picolinate (CrP), with long-standing cardiovascular benefits, inhibits TSP-1 expression in glucose-stimulated human aortic smooth muscle cells in vitro. Here, we investigated the atheroprotective action of orally administered CrP in type 1 diabetic apolipoprotein E-deficient (ApoE(-/-)) mice and elucidated the role of TSP-1 in this process...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345146/evidence-for-the-generation-of-myristylated-fmn-by-bacterial-luciferase
#8
Chaitanya R Tabib, Eveline Brodl, Peter Macheroux
The genes responsible for the light production in bioluminescent bacteria are present as an operon, luxCDABEG. Many strains of Photobacteria carry an additional gene, termed luxF. X-ray crystallographic analysis of LuxF revealed the presence of four molecules of a flavin derivative, i.e. 6-(3'-(R)-myristyl) FMN non-covalently bound to the homodimer. In the present study, we exploited the binding of myrFMN to recombinant apo-LuxF to explore the occurrence of myrFMN in various bioluminescent bacteria. MyrFMN was detected in all bacterial strains tested including Vibrio and Aliivibrio indicating that it is more widely occurring in bioluminescent bacteria than previously assumed...
March 27, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28345116/oligomeric-state-and-thermal-stability-of-apo-and-holo-human-ornithine-%C3%AE-aminotransferase
#9
Riccardo Montioli, Carlotta Zamparelli, Carla Borri Voltattorni, Barbara Cellini
Human ornithine δ-aminotransferase (hOAT) (EC 2.6.1.13) is a mitochondrial pyridoxal 5'-phosphate (PLP)-dependent aminotransferase whose deficit is associated with gyrate atrophy, a rare autosomal recessive disorder causing progressive blindness and chorioretinal degeneration. Here, both the apo- and holo-form of recombinant hOAT were characterized by means of spectroscopic, kinetic, chromatographic and computational techniques. The results indicate that apo and holo-hOAT (a) show a similar tertiary structure, even if apo displays a more pronounced exposure of hydrophobic patches, (b) exhibit a tetrameric structure with a tetramer-dimer equilibrium dissociation constant about fivefold higher for the apoform with respect to the holoform, and (c) have apparent Tm values of 46 and 67 °C, respectively...
March 27, 2017: Protein Journal
https://www.readbyqxmd.com/read/28345008/insights-into-the-mechanism-of-membrane-pyrophosphatases-by-combining-experiment-and-computer-simulation
#10
Nita R Shah, Craig Wilkinson, Steven P D Harborne, Ainoleena Turku, Kun-Mou Li, Yuh-Ju Sun, Sarah Harris, Adrian Goldman
Membrane-integral pyrophosphatases (mPPases) couple the hydrolysis of pyrophosphate (PPi) to the pumping of Na(+), H(+), or both these ions across a membrane. Recently solved structures of the Na(+)-pumping Thermotoga maritima mPPase (TmPPase) and H(+)-pumping Vigna radiata mPPase revealed the basis of ion selectivity between these enzymes and provided evidence for the mechanisms of substrate hydrolysis and ion-pumping. Our atomistic molecular dynamics (MD) simulations of TmPPase demonstrate that loop 5-6 is mobile in the absence of the substrate or substrate-analogue bound to the active site, explaining the lack of electron density for this loop in resting state structures...
May 2017: Structural Dynamics (Melville, N.Y.)
https://www.readbyqxmd.com/read/28344760/severe-pulmonary-hypertension-in-aging-female-apolipoprotein-e-deficient-mice-is-rescued-by-estrogen-replacement-therapy
#11
Soban Umar, Rod Partow-Navid, Gregoire Ruffenach, Andrea Iorga, Shayan Moazeni, Mansoureh Eghbali
BACKGROUND: Apolipoprotein E (ApoE) is a multifunctional protein, and its deficiency leads to the development of atherosclerosis in mice. Patients with pulmonary hypertension (PH) have reduced expression of ApoE in lung tissue. ApoE is known to inhibit endothelial and smooth muscle cell proliferation and has anti-inflammatory and anti-platelet aggregation properties. Young ApoE-deficient mice have been shown to develop PH on high fat diet. The combined role of female sex and aging in the development of PH has not been investigated before...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28344553/youthful-processing-speed-in-older-adults-genetic-biological-and-behavioral-predictors-of-cognitive-processing-speed-trajectories-in-aging
#12
Nicholas T Bott, Brianne M Bettcher, Jennifer S Yokoyama, Darvis T Frazier, Matthew Wynn, Anna Karydas, Kristine Yaffe, Joel H Kramer
Objective: To examine the impact of genetic, inflammatory, cardiovascular, lifestyle, and neuroanatomical factors on cognitive processing speed (CPS) change over time in functionally intact older adults. Methods: This observational study conducted over two time points, included 120 community dwelling cognitively normal older adults between the ages of 60 and 80 from the University of California San Francisco Memory and Aging Center. Participants were followed with composite measures of CPS, calculated based on norms for 20-30 year-olds...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28344552/adding-recognition-discriminability-index-to-the-delayed-recall-is-useful-to-predict-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease-in-the-alzheimer-s-disease-neuroimaging-initiative
#13
María J Russo, Jorge Campos, Silvia Vázquez, Gustavo Sevlever, Ricardo F Allegri
Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28344547/app-function-and-lipids-a-bidirectional-link
#14
REVIEW
Marcus O W Grimm, Janine Mett, Heike S Grimm, Tobias Hartmann
Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28343238/visualization-of-endothelial-barrier-damage-prior-to-formation-of-atherosclerotic-plaques
#15
Heike Bömmel, Florian Kleefeldt, Alma Zernecke, Sharang Ghavampour, Nicole Wagner, Stefanie Kuerten, Süleyman Ergün
En-face fat staining is frequently used to visualize atherosclerotic lesions. This method, however, is not suitable to visualize endothelial barrier damage prior to microscopically detectable morphological alterations of the arterial wall such as sub-endothelial lipid deposition. To enable the investigation of early endothelial barrier damage and in particular the initial steps of atherosclerosis, a new method has to fulfill three requirements: (i) easy and fast to perform, (ii) low cost of applicability without requirement for highly sophisticated technical equipment, and (iii) reliable reproducibility of valid results...
March 25, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28343066/calcium-triggers-reversal-of-calmodulin-on-nested-anti-parallel-sites-in-the-iq-motif-of-the-neuronal-voltage-dependent-sodium-channel-nav1-2
#16
Liam Hovey, C Andrew Fowler, Ryan Mahling, Zesen Lin, Mark Stephen Miller, Dagan C Marx, Jesse B Yoder, Elaine H Kim, Kristin M Tefft, Brett C Waite, Michael D Feldkamp, Liping Yu, Madeline A Shea
Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel NaV1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca(2+))4-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca(2+))4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1...
March 9, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28341860/high-plasma-lipid-levels-reduce-efficacy-of-adenovirus-mediated-gene-therapy
#17
A M Kivelä, J Huusko, E Gurzeler, A Laine, M H Dijkstra, G Dragneva, C B F Andersen, S K Moestrup, S Ylä-Herttuala
Adenoviruses are very efficient vectors for delivering therapeutic genes in preclinical and clinical trials. However, randomized controlled human trials have often been lacking clear clinically relevant results. We hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral transduction efficiency in vivo. Here we demonstrate that mice on a high fat diet have lower transgene expression compared to mice on a regular chow. In addition, on a high fat diet, ApoE(-/-) mice have much higher plasma transgene levels compared to LDLR-deficient mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341847/apoe-genotype-effects-on-intrinsic-brain-network-connectivity-in-patients-with-amnestic-mild-cognitive-impairment
#18
Zan Wang, Zhengjia Dai, Hao Shu, Xuhong Liao, Chunxian Yue, Duan Liu, Qihao Guo, Yong He, Zhijun Zhang
Whether and how the apolipoprotein E (APOE) ε4 genotype specifically modulates brain network connectivity in patients with amnestic mild cognitive impairment (aMCI) remain largely unknown. Here, we employed resting-state ('task-free') functional MRI and network centrality approaches to investigate local (degree centrality, DC) and global (eigenvector centrality, EC) functional integrity in the whole-brain connectome in 156 older adults, including 66 aMCI patients (27 ε4-carriers and 39 non-carriers) and 90 healthy controls (45 ε4-carriers and 45 non-carriers)...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341122/molecular-dynamics-simulations-of-zika-virus-ns3-helicase-insights-into-rna-binding-site-activity
#19
Melina Mottin, Rodolpho C Braga, Roosevelt A da Silva, Joao H Martins da Silva, Alexander L Perryman, Sean Ekins, Carolina Horta Andrade
America is still suffering with the outbreak of Zika virus (ZIKV) infection. Congenital ZIKV syndrome has already caused a public health emergency of international concern. However, there are still no vaccines to prevent or drugs to treat the infection caused by ZIKV. The ZIKV NS3 helicase (NS3h) protein is a promising target for drug discovery due to its essential role in viral genome replication. NS3h unwinds the viral RNA to enable the replication of the viral genome by the NS5 protein. NS3h contains two important binding sites: the NTPase binding site and the RNA binding site...
March 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28340945/plasma-levels-of-apolipoprotein-e-apoe-genotype-and-risk-of-dementia-and-ischemic-heart-disease-a-review
#20
REVIEW
Katrine Laura Rasmussen
Dementia is one of the major causes of disability in later life, and ischemic heart disease is a leading cause of morbidity and mortality. Apolipoprotein E (apoE) plays a pivotal role in lipoprotein metabolism in the brain and in the periphery, and is implicated in both dementia and ischemic heart disease. Peripherally, liver-derived apoE is the main source of plasma apoE. Approximately half of plasma apoE is associated with triglyceride-rich lipoproteins, where apoE serves as the main ligand for the low density lipoprotein (LDL) receptor and the LDL receptor Related Protein (LRP)...
December 2016: Atherosclerosis
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