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https://www.readbyqxmd.com/read/28222519/genetic-stratification-to-identify-risk-groups-for-alzheimer-s-disease
#1
Riccardo E Marioni, Archie Campbell, Saskia P Hagenaars, Reka Nagy, Carmen Amador, Caroline Hayward, David J Porteous, Peter M Visscher, Ian J Deary
Stratification by genetic risk factors for Alzheimer's disease (AD) may help identify groups with the greatest disease risk. Biological changes that cause late-onset AD are likely to occur years, if not decades prior to diagnosis. Here, we select a subset of the Generation Scotland: Scottish Family Health Study cohort in a likely preclinical age-range of 60-70 years (subset n = 3,495 with cognitive and genetic data). We test for cognitive differences by polygenic risk scores for AD. The polygenic scores are constructed using all available SNPs, excluding those within a 500 kb distance of the APOE locus...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222301/impact-of-home-visit-capacity-on-genetic-association-studies-of-late-onset-alzheimer-s-disease
#2
David W Fardo, Laura E Gibbons, Shubhabrata Mukherjee, M Maria Glymour, Wayne McCormick, Susan M McCurry, James D Bowen, Eric B Larson, Paul K Crane
INTRODUCTION: Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits. METHODS: We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308)...
February 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28222243/studies-on-the-binding-of-modest-modulators-of-the-human-enzyme-sirtuin-6-using-std-nmr
#3
Beatriz E Bolívar, John T Welch
Pyrazinamide (PZA), an essential constituent of short course tuberculosis chemotherapy, binds weakly but selectively to Sirtuin 6 (SIRT6). Despite structural similarities between nicotinamide (NAM), PZA, and pyrazinoic acid (POA), these inhibitors modulate SIRT6 via different mechanisms and binding sites, as suggested by Saturation Transfer Difference (STD) Nuclear Magnetic Resonance (NMR). Available experimental evidence, such as that derived from crystal structures and kinetic experiments, is of only limited utility in the elucidation of the mechanistic details of sirtuin inhibition by NAM or other inhibitors...
February 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28222187/a-purified-maa-based-elisa-is-a-useful-tool-for-determining-anti-maa-antibody-titer-with-high-sensitivity
#4
Takasumi Shimomoto, Leonard B Collins, Xianwen Yi, Darcy W Holley, Zhenfa Zhang, Xu Tian, Koji Uchida, Chunguang Wang, Sohvi Hörkkö, Monte S Willis, Avram Gold, Scott J Bultman, Jun Nakamura
Atherosclerosis is widely accepted to be a chronic inflammatory disease, and the immunological response to the accumulation of LDL is believed to play a critical role in the development of this disease. 1,4-Dihydropyridine-type MAA-adducted LDL has been implicated in atherosclerosis. Here, we have demonstrated that pure MAA-modified residues can be chemically conjugated to large proteins without by-product contamination. Using this pure antigen, we established a purified MAA-ELISA, with which a marked increase in anti-MAA antibody titer was determined at a very early stage of atherosclerosis in 3-month ApoE-/- mice fed with a normal diet...
2017: PloS One
https://www.readbyqxmd.com/read/28220880/parenteral-administration-of-factor-xa-iia-inhibitors-limits-experimental-aortic-aneurysm-and-atherosclerosis
#5
Corey S Moran, Sai-Wang Seto, Smriti M Krishna, Surabhi Sharma, Roby J Jose, Erik Biros, Yutang Wang, Susan K Morton, Jonathan Golledge
Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE(-/-)) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE(-/-) mice...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220571/genetic-risk-factors-for-cognitive-decline-in-parkinson-s-disease-a-review-of-the-literature
#6
REVIEW
E S Fagan, L Pihlstrøm
Parkinson's disease is a highly heterogeneous disorder, where genetic factors are likely to contribute to clinical variability, including susceptibility to cognitive impairment and dementia. Monogenic forms of parkinsonism show distinct cognitive profiles, yet less is known about the impact of common genetic variants on cognition in sporadic Parkinson's disease. In a systematic review of the literature, the current results from genetic association studies of cognitive outcomes are summarized and prospects and challenges for future studies are discussed...
February 21, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28220068/reduced-activity-in-the-right-inferior-frontal-gyrus-in-elderly-apoe-e4-carriers-during-a-verbal-fluency-task
#7
Andrea Katzorke, Julia B M Zeller, Laura D Müller, Martin Lauer, Thomas Polak, Andreas Reif, Jürgen Deckert, Martin J Herrmann
Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer's disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28219919/dickkopf-3-ablation-attenuates-the-development-of-atherosclerosis-in-apoe-deficient-mice
#8
Wen-Lin Cheng, Yang Yang, Xiao-Jing Zhang, Junhong Guo, Jun Gong, Fu-Han Gong, Zhi-Gang She, Zan Huang, Hao Xia, Hongliang Li
BACKGROUND: Dickkopf-3 (DKK3) is a negative regulator of the Wnt/β-catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis. The aim of the present study was to define the role of DKK3 and its potential mechanism in the development of atherosclerosis. METHODS AND RESULTS: Immunofluorescence analysis showed that DKK3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice...
February 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28219797/spectroscopy-analysis-and-molecular-dynamics-studies-on-the-binding-of-penicillin-v-and-sulbactam-to-beta-lactamase-ii-from-bacillus-cereus
#9
Penghui Shi, Pan Qiao, Yeli Zhang, Shuaihua Li, Xuan Feng, Liujiao Bian
The molecular recognition and interaction of beta-lactamase II from Bacillus cereus (Bc II) with penicillin V (PV) and sulbactam (Sul) especially conformational changes of Bc II in the binding process were studied through spectroscopy analysis in combination with molecular dynamics (MD) simulation. The results show that in the binding process, a new coordination bond is observed between the Zn2 of Bc II and the carboxyl-O of PV or Sul by replacing His204. Electrostatic interaction between Zn2 and the ligand provide main driving force for the binding affinity...
February 11, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28219318/gender-and-pathology-specific-effect-of-apolipoprotein-e-genotype-on-psychosis-in-alzheimer-s-disease
#10
Julia Kim, Corinne E Fischer, Tom A Schweizer, David G Munoz
BACKGROUND: Symptoms of psychosis is one of the common clinical manifestations of Alzheimer's disease (AD). However, the pathophysiology behind psychosis is unknown. OBJECTIVE: The aim of the present study was to explore the relationship between Apolipoprotein E (APOE) genotype, Lewy body pathology, and psychosis in AD. METHODS: The data was obtained from the National Alzheimer's disease Coordinating Centre (NACC), using the Uniform Data Set and the Neuropathology Data Set...
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28218841/the-mechanism-of-human-apohemoglobin-unfolding
#11
Premila P Samuel, William Christopher Ou, George N Phillips, John Steven Olson
Removal of heme from human hemoglobin (Hb) results in formation of an apoglobin heterodimer. Titration of this apo-dimer with GdnHCl leads to biphasic unfolding curves indicating two distinct steps. Initially the heme pocket unfolds and generates a dimeric intermediate in which ~50% of the original helicity is lost, but the α1β1 interface is still intact. At higher [GdnHCl], this intermediate dissociates into unfolded monomers. This structural interpretation was verified by comparing GdnHCl titrations for adult human hemoglobin A (HbA), recombinant fetal human hemoglobin (HbF), recombinant Hb crosslinked with a single glycine linker between the α chains (rHb0...
February 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28218786/gene-expressions-levels-of-14-3-3a-nkccla-apo-14-and-na-k-atpase%C3%AE-in-gill-tissue-of-mugil-cephalus-acclimated-to-low-salinity
#12
L Li, M Jiang, X Q Shen
Fishes adapt to salinity changes primarily through osmotic pressure regulation, a process often associated with several genes, including 14-3-3a, NKCCla, APO-14, and Na(+)-K(+)-ATPaseβ. The present study investigated the differential expression of genes 14-3-3a, NKCCla, APO-14, and Na(+)-K(+)-ATPaseβ in the gill tissue of Mugil cephalus acclimated to low salinity. Susceptibility relationships between the four gene expressions levels and salinity were detected and analyzed using polymerase chain reaction-restriction fragment length polymorphism...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28218653/proteomic-analysis-of-mitochondria-enriched-fraction-isolated-from-the-frontal-cortex-and-hippocampus-of-apolipoprotein-e-knockout-mice-treated-with-alda-1-an-activator-of-mitochondrial-aldehyde-dehydrogenase-aldh2
#13
Aneta Stachowicz, Rafał Olszanecki, Maciej Suski, Katarzyna Głombik, Agnieszka Basta-Kaim, Dariusz Adamek, Ryszard Korbut
The role of different genotypes of apolipoprotein E (apoE) in the etiology of Alzheimer's disease is widely recognized. It has been shown that altered functioning of apoE may promote 4-hydroxynonenal modification of mitochondrial proteins, which may result in mitochondrial dysfunction, aggravation of oxidative stress, and neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme considered to perform protective function in mitochondria by the detoxification of the end products of lipid peroxidation, such as 4-hydroxynonenal and other reactive aldehydes...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28217556/group-b-streptococcus-induces-neutrophil-recruitment-to-gestational-tissues-and-elaboration-of-extracellular-traps-and-nutritional-immunity
#14
Vishesh Kothary, Ryan S Doster, Lisa M Rogers, Leslie A Kirk, Kelli L Boyd, Joann Romano-Keeler, Kathryn P Haley, Shannon D Manning, David M Aronoff, Jennifer A Gaddy
Streptococcus agalactiae, or Group B Streptococcus (GBS), is a gram-positive bacterial pathogen associated with infection during pregnancy and is a major cause of morbidity and mortality in neonates. Infection of the extraplacental membranes surrounding the developing fetus, a condition known as chorioamnionitis, is characterized histopathologically by profound infiltration of polymorphonuclear cells (PMNs, neutrophils) and greatly increases the risk for preterm labor, stillbirth, or neonatal GBS infection...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28217507/stronger-relationship-of-serum-apolipoprotein-a-1-and-b-with-diabetic-retinopathy-than-traditional-lipids
#15
B S Ankit, G Mathur, R P Agrawal, K C Mathur
AIM: Diabetic retinopathy (DR) is the most common preventable cause of blindness where early detection and treatment can be sight-saving. Search for biomarkers of the disease has been relentless. We aimed to determine whether lipoproteins apolipoproteins A1 and B1 (Apo-A1 and Apo-B1) have stronger associations with DR in contrast to conventionally measured low-density lipoprotein (LDL) and high-density lipoprotein cholesterol levels. MATERIALS AND METHODS: We performed a cross-sectional study and studied 117 patients...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28216341/mechanisms-of-protection-against-irreversible-oxidation-of-the-catalytic-cysteine-of-aldh-enzymes-possible-role-of-vicinal-cysteines
#16
Rosario A Muñoz-Clares, Lilian González-Segura, Dario S Murillo-Melo, Héctor Riveros-Rosas
The catalytic mechanism of the NAD(P)(+)-dependent aldehyde dehydrogenases (ALDHs) involves the nucleophilic attack of the essential cysteine (Cys302, mature HsALDH2 numbering) on the aldehyde substrate. Although oxidation of Cys302 will inactivate these enzymes, it is not yet well understood how this oxidation is prevented. In this work we explore possible mechanisms of protection by systematically analyzing the reported three-dimensional structures and amino acid sequences of the enzymes of the ALDH superfamily...
February 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28215291/crystal-structures-of-neurotrophin-receptors-kinase-domain
#17
T Bertrand
Neurotrophins and their receptors (Trk) play key roles in the development of the nervous system and in cell survival. Trk receptors are therefore attractive pharmacological targets for brain disorders as well as for cancers. While the druggability of the extracellular domain of the receptors, that specifically binds neurotrophins, is yet to be proven, the intracellular kinase domains are attractive targets for small-molecule binding. The recent crystal structures of the three isoforms of the Trk family, TrkA, TrkB, and TrkC have been described in their apo forms and in complex with potent and selective pan-Trk inhibitors...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28214534/demographic-phenotypic-and-genetic-characteristics-of-centenarians-in-okinawa-and-honshu-japan-part-2-honshu-japan
#18
REVIEW
Yasumichi Arai, Takashi Sasaki, Nobuyoshi Hirose
The scope and purpose of this review was to summarize the aims, methods, findings, and future of centenarian and (semi)-supercentenarian studies in Japan, particularly those from our own interdisciplinary laboratory. Medically, approximately 97% of centenarians contract chronic diseases including hypertension and gastrointestinal disease; however, they present with few cardiovascular risk factors. The low prevalence of diabetes mellitus and carotid atherosclerotic plaques are peculiarities of centenarians, which could be associated with high adiponectin levels...
February 15, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28213977/mitochondria-targeted-esculetin-inhibits-pai-1-levels-by-modulating-stat3-activation-and-mir-19b-via-sirt3-role-in-acute-coronary-artery-syndrome
#19
Sujana Katta, Santosh Karnewar, Devayani Panuganti, Mahesh Kumar Jerald, Sastry B K, Srigiridhar Kotamraju
In this study, we explored the microRNAs responsible for the regulation of PAI-1 during LPS-stimulated inflammation in human aortic endothelial cells, subsequently studied the effect of a newly synthesized mitochondria-targeted esculetin (Mito-Esc) that was shown for its anti-atherosclerotic potential in modulating PAI-1 levels and its targeted miRs during angiotensin-II-induced atherosclerosis in ApoE(-/-) mice. LPS-stimulated PAI-1 was accompanied with an upregulation of miR-19b and down-regulation of miR-30c...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213371/polygenic-risk-scores-in-familial-alzheimer-disease
#20
Giuseppe Tosto, Thomas D Bird, Debby Tsuang, David A Bennett, Bradley F Boeve, Carlos Cruchaga, Kelley Faber, Tatiana M Foroud, Martin Farlow, Alison M Goate, Sarah Bertlesen, Neill R Graff-Radford, Martin Medrano, Rafael Lantigua, Jennifer Manly, Ruth Ottman, Roger Rosenberg, Daniel J Schaid, Nicole Schupf, Yaakov Stern, Robert A Sweet, Richard Mayeux
OBJECTIVE: To investigate the association between a genetic risk score (GRS) and familial late-onset Alzheimer disease (LOAD) and its predictive value in families multiply affected by the disease. METHODS: Using data from the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease (National Institute on Aging-Late-Onset Alzheimer's Disease Family Study), mixed regression models tested the association of familial LOAD with a GRS based on single nucleotide polymorphisms (SNPs) previously associated with LOAD...
February 17, 2017: Neurology
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