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https://www.readbyqxmd.com/read/28823028/backbone-resonance-assignments-of-complexes-of-human-voltage-dependent-sodium-channel-nav1-2-iq-motif-peptide-bound-to-apo-calmodulin-and-to-the-c-domain-fragment-of-apo-calmodulin
#1
Ryan Mahling, Adina M Kilpatrick, Madeline A Shea
Human voltage-gated sodium channel NaV1.2 has a single pore-forming α-subunit and two transmembrane β-subunits. Expressed primarily in the brain, NaV1.2 is critical for initiation and propagation of action potentials. Milliseconds after the pore opens, sodium influx is terminated by inactivation processes mediated by regulatory proteins including calmodulin (CaM). Both calcium-free (apo) CaM and calcium-saturated CaM bind tightly to an IQ motif in the C-terminal tail of the α-subunit. Our thermodynamic studies and solution structure (2KXW) of a C-domain fragment of apo (13)C,(15)N- CaM (CaMC) bound to an unlabeled peptide with the sequence of rat NaV1...
August 19, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28810853/acute-effects-of-reducing-sitting-time-in-adolescents-a-randomized-cross-over-study
#2
Anisse Penning, Anthony D Okely, Stewart G Trost, Jo Salmon, Dylan P Cliff, Marijka Batterham, Steven Howard, Anne-Maree Parrish
BACKGROUND: Levels of sitting among adolescents are high, especially during the school day. The acute cognitive and health consequences associated with prolonged sitting are poorly understood in adolescents. This randomized crossover design study examined the acute effects of a simulated school day with reduced sitting or usual sitting on adolescents' cognitive function and cardiometabolic biomarkers. METHODS: Eighteen healthy school aged adolescents were recruited from the community to the study (11 males; 7 females; mean age [SD] = 13...
August 15, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#3
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28808293/targeting-apolipoprotein-e-amyloid-%C3%AE-binding-by-peptoid-cpo_a%C3%AE-17-21%C3%A2-p-ameliorates-alzheimer-s-disease-related-pathology-and-cognitive-decline
#4
Shan Liu, Shinae Park, Grant Allington, Frances Prelli, Yanjie Sun, Mitchell Martá-Ariza, Henrieta Scholtzova, Goutam Biswas, Bernard Brown, Philip B Verghese, Pankaj D Mehta, Yong-Uk Kwon, Thomas Wisniewski
Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807493/homocysteine-and-cognitive-function-in-parkinson-s-disease
#5
Nicole Licking, Charles Murchison, Brenna Cholerton, Cyrus P Zabetian, Shu-Ching Hu, Thomas J Montine, Amie L Peterson-Hiller, Kathryn A Chung, Karen Edwards, James B Leverenz, Joseph F Quinn
INTRODUCTION: Increased plasma homocysteine (HC) is a risk factor for dementia in the general population. Levodopa therapy causes increased plasma HC, but it remains unclear whether elevated plasma HC is associated with cognitive impairment in Parkinson's disease (PD). METHODS: The study population includes all participants in the Pacific Northwest Udall Center (PANUC) Clinical cohort at the time of the study, consisting of 294 individuals with PD who had a standardized neuropsychological assessment and plasma collection for HC measurement...
August 9, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28804682/effects-of-intensive-pitavastatin-therapy-on-glucose-control-in-patients-with-non-st-elevation-acute-coronary-syndrome
#6
Yan-Bo Wang, Xiang-Hua Fu, Xin-Shun Gu, Wei-Ze Fan, Yun-Fa Jiang, Guo-Zhen Hao, Qing Miao, Jie Cao, Bing Fu, Yi Li
Objective: This study aimed to investigate the effects of intensive pitavastatin therapy on glucose control in patients with non-ST elevation acute coronary syndrome (ACS). Methods: Patients who had ACS with significant stenosis on initial coronary angiography and received successful percutaneous coronary intervention (PCI) in the Second Hospital of Hebei Medical University, Shijiazhuang, China from August 2015 to January 2016 were enrolled in this study. The patients were randomized to receive pitavastatin (4 mg daily) or atorvastatin (20 mg daily)...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28800603/genetic-variants-specific-to-aging-related-verbal-memory-insights-from-gwass-in-a-population-based-cohort
#7
Thalida E Arpawong, Neil Pendleton, Krisztina Mekli, John J McArdle, Margaret Gatz, Chris Armoskus, James A Knowles, Carol A Prescott
Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60...
2017: PloS One
https://www.readbyqxmd.com/read/28799493/association-between-apo-b-levels-in-mothers-and-in-their-pre-school-age-offspring
#8
Valeria Hirschler, Maximiliano Maximiliano Martin, Karen Oestreicher, Claudia Molinari, Laura Boero, Tetzlaff Walter, Fernando Brites
OBJECTIVE: To determine the association between apo B levels in mothers and their pre-school offspring. METHODS: BMI, lipids, and apo B levels were obtained in mothers and their children in November 2015 in Buenos Aires. RESULTS: Eighty-four children (42M) aged 5.3±1.6 years and their mothers aged 33.8±7.2 years were examined. The prevalence of overweight was 39.2% (33) in mothers and 22.6%(19) in children, and the prevalence of obesity was 38...
August 11, 2017: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28798155/ifn-%C3%AE-aggravates-neointimal-hyperplasia-by-inducing-endoplasmic-reticulum-stress-and-apoptosis-in-macrophages-by-promoting-ubiquitin-dependent-liver-x-receptor-%C3%AE-degradation
#9
Qiang Zhao, Dong Zhou, Hongjun You, Bowen Lou, Yan Zhang, Yuling Tian, Ning Guo, Xiaoli Chen, Yan Liu, Yue Wu, Zuyi Yuan, Juan Zhou
Neointimal hyperplasia is the main cause of restenosis after percutaneous coronary interventions (PCIs). Both IFN-γ and macrophages play nonredundant roles in the pathogenesis of vascular intimal hyperplasia; however, the underlying mechanisms remain elusive and must be further investigated. In mouse peritoneal macrophages, IFN-γ significantly accelerated degradation and up-regulated polyubiquitination of liver X receptor (LXR)-α. Signal transducer and activator of transcription 1 (STAT1) inhibitor, fludarabine, and PIAS1 knockdown reduced ubiquitination and increased the expression of LXR-α in IFN-γ-treated macrophages...
August 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28797250/omega-3-fatty-acids-eicosapentaenoic-acid-and-docosahexaenoic-acid-and-their-mechanisms-of-action-on-apolipoprotein-b-containing-lipoproteins-in-humans-a-review
#10
REVIEW
Jan Oscarsson, Eva Hurt-Camejo
BACKGROUND: Epidemiological and genetic studies suggest that elevated triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hypertriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies...
August 10, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28795598/inhibition-studies-of-dna-methyltransferases-by-maleimide-derivatives-of-rg108-as-non-nucleoside-inhibitors
#11
Grégoire Rondelet, Laurence Fleury, Céline Faux, Véronique Masson, Jean Dubois, Paola B Arimondo, Luc Willems, Johan Wouters
AIM: DNA methyltransferases (DNMTs) are important drug targets for epigenetic therapy of cancer. Nowadays, non-nucleoside DNMT inhibitors are in development to address high toxicity of nucleoside analogs. However, these compounds still have low activity in cancer cells and mode of action of these compounds remains unclear. MATERIALS & METHODS: In this work, we studied maleimide derivatives of RG108 by biochemical, structural and computational approaches to highlight their inhibition mechanism on DNMTs...
August 10, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28795506/oral-apolipoprotein-a-i-mimetic-d-4f-lowers-hdl-inflammatory-index-in-high-risk-patients-a-first-in-human-multiple-dose-randomized-controlled-trial
#12
Richard L Dunbar, Rajesh Movva, LeAnne T Bloedon, Danielle Duffy, Robert B Norris, Mohamad Navab, Alan M Fogelman, Daniel J Rader
A single dose of the apolipoprotein (apo)A-I mimetic peptide D-4F rendered high-density lipoprotein (HDL) less inflammatory, motivating the first multiple-dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D-4F. High-risk coronary heart disease (CHD) subjects added double-blinded placebo or D-4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D-4F was safe and well-tolerated...
August 9, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28783817/associations-between-midlife-vascular-risk-factors-and-25-year-incident-dementia-in-the-atherosclerosis-risk-in-communities-aric-cohort
#13
Rebecca F Gottesman, Marilyn S Albert, Alvaro Alonso, Laura H Coker, Josef Coresh, Sonia M Davis, Jennifer A Deal, Guy M McKhann, Thomas H Mosley, A Richey Sharrett, Andrea L C Schneider, B Gwen Windham, Lisa M Wruck, David S Knopman
Importance: Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment. Objectives: To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence. Design, Setting, and Participants: This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013...
August 7, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28768281/%C3%AE-sarcoglycan-deficiency-reduces-atherosclerotic-plaque-development-in-apoe-null-mice
#14
Vignesh Murugesan, Eva Degerman, Ann-Kristin Holmen-Pålbrink, Pontus Duner, Anki Knutsson, Anna Hultgårdh-Nilsson, Uwe Rauch
BACKGROUND: Smooth muscle cells are important for atherosclerotic plaque stability. Their proper ability to communicate with the extracellular matrix is crucial for maintaining the correct tissue integrity. In this study, we have investigated the role of β-sarcoglycan within the matrix-binding dystrophin-glycoprotein complex in the development of atherosclerosis. RESULTS: Atherosclerotic plaque development was significantly reduced in ApoE-deficient mice lacking β-sarcoglycan, and their plaques contained an increase in differentiated smooth muscle cells...
July 29, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28763372/xinxuekang-regulates-reverse-cholesterol-transport-by-improving-high-density-lipoprotein-synthesis-maturation-and-catabolism
#15
Guang-Xin Dong, Wen-Wen Li, Ruo-Zhu Wang, Wen-Jun Zou, Zhen-Dong Zhong, Bo-Gang Li
Di'ao Xinxuekang (XXK) is an herbal product in China and the Netherlands that has been clinically shown to attenuate atherosclerosis; however, the underlying antiatherosclerotic mechanism remains unclear. Because of its role in cholesterol homeostasis, reverse cholesterol transport (RCT) is a potential target for these beneficial effects. This study investigated the effects of XXK on RCT and related proteins. After treating ApoE-deficient mice with XXK for 8 weeks, we observed an increase in the expression level of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which in turn stimulated cholesterol efflux and reduced aortic atherosclerotic lesion area...
August 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28762722/posttranslational-modification-of-heme-b-in-a-bacterial-peroxidase-the-role-of-heme-to-protein-ester-bonds-in-ligand-binding-and-catalysis
#16
Andrea Nicolussi, Markus Auer, Julia Weissensteiner, Georg Schütz, Sonja Katz, Daniel Maresch, Stefan Hofbauer, Marzia Bellei, Gianantonio Battistuzzi, Paul G Furtmüller, Christian Obinger
The existence of covalent heme to protein bonds is the most striking structural feature of mammalian peroxidases, including myeloperoxidase and lactoperoxidase (LPO). These autocatalytic posttranslational modifications (PTMs) were shown to strongly influence the biophysical and biochemical properties of these oxidoreductases. Recently, we reported the occurrence of stable LPO-like counterparts with two heme to protein ester linkages in bacteria. This study focuses on the model wild-type peroxidase from the cyanobacterium Lyngbya sp...
August 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28761931/unc5c-variants-are-associated-with-cerebral-amyloid-angiopathy
#17
Hyun-Sik Yang, Charles C White, Lori B Chibnik, Hans-Ulrich Klein, Julie A Schneider, David A Bennett, Philip L De Jager
OBJECTIVE: To determine whether common genetic variants in UNC5C, a recently identified late-onset Alzheimer disease (LOAD) dementia susceptibility gene, are associated with AD susceptibility or AD-related clinical/pathologic phenotypes. METHODS: We used data from deceased individuals of European descent who participated in the Religious Orders Study or the Rush Memory and Aging Project (n = 1,288). We examined whether there were associations between single nucleotide polymorphisms (SNPs) within ±100 kb of the UNC5C gene and a diagnosis of AD dementia, global cognitive decline, a pathologic diagnosis of AD, β-amyloid load, neuritic plaque count, diffuse plaque count, paired helical filament tau density, neurofibrillary tangle count, and cerebral amyloid angiopathy (CAA) score...
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28760743/hypoxia-inducible-protein-2-hig2-hilpda-mediates-neutral-lipid-accumulation-in-macrophages-and-contributes-to-atherosclerosis-in-apolipoprotein-e-deficient-mice
#18
Anja Maier, Hao Wu, Nada Cordasic, Peter Oefner, Barbara Dietel, Christoph Thiele, Alexander Weidemann, Kai-Uwe Eckardt, Christina Warnecke
Recently we identified hypoxia-inducible protein 2 (HIG2)/hypoxia-inducible lipid droplet associated (HILPDA) as lipid droplet (LD) protein. Because HILPDA is highly expressed in atherosclerotic plaques, we examined its regulation and function in murine macrophages, compared it to the LD adipose differentiation-related protein (Adrp)/perilipin 2 (Plin2), and investigated its effects on atherogenesis in apolipoprotein E-deficient (ApoE(-/-)) mice. Tie2-Cre-driven Hilpda knockout (cKO) did not affect viability, proliferation, and ATP levels in macrophages...
July 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28759039/elevated-tumor-ldlr-expression-accelerates-ldl-cholesterol-mediated-breast-cancer-growth-in-mouse-models-of-hyperlipidemia
#19
E J Gallagher, Z Zelenko, B A Neel, I M Antoniou, L Rajan, N Kase, D LeRoith
Obesity is associated with an increase in cancer-specific mortality in women with breast cancer. Elevated cholesterol, particularly low-density lipoprotein cholesterol (LDL-C), is frequently seen in obese women. Here, we aimed to determine the importance of elevated circulating LDL, and LDL receptor (LDLR) expression in tumor cells, on the growth of breast cancer using mouse models of hyperlipidemia. We describe two novel immunodeficient mouse models of hyperlipidemia (Rag1(-/)(-)/LDLR(-/)(-) and Rag1(-/)(-)/ApoE (apolipoprotein E)(-/)(-) mice) in addition to established immunocompetent LDLR(-/)(-) and ApoE(-/)(-) mice...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28757643/birth-by-cesarean-section-in-relation-to-adult-offspring-overweight-and-biomarkers-of-cardiometabolic-risk
#20
S Hansen, T I Halldorsson, S F Olsen, D Rytter, B H Bech, C Granström, T B Henriksen, J E Chavarro
BACKGROUND: Birth by Cesarean section (C-section) may increase the risk for non-communicable diseases. We aimed to examine the relation of birth by C-section with offspring overweight and markers of cardio-metabolic risk in a prospective observational cohort with 20-years of follow-up. METHODS: The Danish Fetal Origins Cohort enrolled 965 pregnant women in 1988-1989. In 2008, a follow-up study of the offspring was completed. The offspring were invited to participate in a clinical examination with measurements of anthropometry and a fasting blood sample (n=443)...
July 31, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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