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Apoe-/- cx3cr1

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https://www.readbyqxmd.com/read/29341140/lipoprotein-modifications-by-gingipains-of-porphyromonas-gingivalis
#1
J Lönn, S Ljunggren, K Klarström-Engström, I Demirel, T Bengtsson, H Karlsson
BACKGROUND AND OBJECTIVE: Several studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low-density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown...
January 17, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29341070/personality-changes-during-the-transition-from-cognitive-health-to-mild-cognitive-impairment
#2
Richard J Caselli, Blake T Langlais, Amylou C Dueck, Bruce R Henslin, Travis A Johnson, Bryan K Woodruff, Charlene Hoffman-Snyder, Dona E C Locke
BACKGROUND/OBJECTIVES: Behavioral problems in individuals with Alzheimer's disease (AD) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI). DESIGN: Longitudinal observational cohort study...
January 17, 2018: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/29340220/multilocus-analysis-of-genetic-susceptibility-to-myocardial-infarction-in-russians-replication-study
#3
N G Kukava, B V Titov, G J Osmak, N A Matveeva, O G Kulakova, A V Favorov, R M Shakhnovich, M Ya Ruda, O O Favorova
In search of genetic markers of myocardial infarction (MI) risk, which have prognostic significance for Russians, we performed a replication study of MI association with genetic variants of PCSK9 (rs562556), APOE (epsilon polymorphism, rs7412 and rs429358), LPL (rs320), MTHFR (rs1801133), eNOS (rs2070744), and the 9p21 region (rs1333049) in 405 patients with MI and 198 controls. Significant MI association was observed with variants of the lipid metabolism genes (PCSK9, APOE and LPL), and of eNOS. The SNPs in the MTHFR gene and the 9p21 region were not significantly associated with MI one by one but were included in several different MI-associated allelic combinations identified by multilocus analysis...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29339490/structural-basis-of-sterol-recognition-and-nonvesicular-transport-by-lipid-transfer-proteins-anchored-at-membrane-contact-sites
#4
Junsen Tong, Mohammad Kawsar Manik, Young Jun Im
Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338257/a-dynamic-protein-protein-coupling-between-the-tonb-dependent-transporter-fhua-and-tonb
#5
Jessica Sarver, Michael Zhang, Lishan Liu, David Nyenhuis, David S Cafiso
Bacterial outer membrane TonB-dependent transporters function by executing cycles of binding and unbinding to the inner membrane protein TonB. In the vitamin B12 transporter BtuB and the ferric citrate transporter FecA, substrate binding increases the periplasmic exposure of the Ton box, an energy-coupling segment. This increased exposure appears to enhance the affinity of the transporter for TonB. Here, continuous wave and pulse EPR spectroscopy were used to examine the state of the Ton box in the Escherichia coli ferrichrome transporter, FhuA...
January 17, 2018: Biochemistry
https://www.readbyqxmd.com/read/29338009/anti-angiogenic-drug-loaded-liposomes-nanotherapy-for-early-atherosclerotic-lesions-in-mice
#6
Isabel Pont, Aracely Calatayud-Pascual, Alicia López-Castellano, Elena P Albelda, Enrique García-España, Luis Martí-Bonmatí, Juan C Frias, M Teresa Albelda
Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment.
2018: PloS One
https://www.readbyqxmd.com/read/29337899/synergistic-effects-of-copper-sites-on-apparent-stability-of-multicopper-oxidase-fet3p
#7
Erik Sedlák, Gabriel Žoldák, Pernilla Wittung-Stafshede
Saccharomyces cerevisiae Fet3p is a multicopper oxidase that contains three cupredoxin-like domains and four copper ions located in three distinct metal sites (T1 in domain 3; T2 and the binuclear T3 at the interface between domains 1 and 3). To probe the role of the copper sites in Fet3p thermodynamic stability, we performed urea-induced unfolding experiments with holo-, apo- and three partially-metallated (T1, T2 and T1/T2 sites depleted of copper) forms of Fet3p. Using a combination of spectroscopic probes (circular dichroism, fluorescence intensity and maximum, 8-anilinonaphthalene-1-sulfonic acid (ANS) emission, oxidase activity and blue color), we reveal that all forms of Fet3p unfold in a four-state reaction with two partially-folded intermediates...
January 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29336888/lxr-apoe-activation-restricts-innate-immune-suppression-in-cancer
#8
Masoud F Tavazoie, Ilana Pollack, Raissa Tanqueco, Benjamin N Ostendorf, Bernardo S Reis, Foster C Gonsalves, Isabel Kurth, Celia Andreu-Agullo, Mark L Derbyshire, Jessica Posada, Shugaku Takeda, Kimia N Tafreshian, Eric Rowinsky, Michael Szarek, Roger J Waltzman, Elizabeth A Mcmillan, Connie Zhao, Monica Mita, Alain Mita, Bartosz Chmielowski, Michael A Postow, Antoni Ribas, Daniel Mucida, Sohail F Tavazoie
Therapeutic harnessing of adaptive immunity via checkpoint inhibition has transformed the treatment of many cancers. Despite unprecedented long-term responses, most patients do not respond to these therapies. Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and pharmacological approaches, we uncovered a pathway governing MDSC abundance in multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients treated in a first-in-human dose escalation phase 1 trial...
January 9, 2018: Cell
https://www.readbyqxmd.com/read/29335837/backbone-chemical-shift-assignments-of-the-glycine-cleavage-complex-h-protein-of-escherichia-coli
#9
Usha Yadav, Monica Sundd
Glycine cleavage complex H protein (GcvH) is one of the four components that form the glycine cleavage complex (GCS), essential for the synthesis of C1 (one-carbon units) for cell metabolism, by the oxidative cleavage of glycine. The activity of this complex is induced in the presence of exogenous glycine, and is repressed by purines. GCS, in cooperation with GCA (serine hydroxymethyltransferase) regulates the endogenous levels of glycine and C1 units in the cell. GcvH, the lipoamide containing component of the complex, plays an indispensable role in this reaction, as its prosthetic group shuttles between the active site of the three other components of the GCS complex sequentially...
January 15, 2018: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29335450/copper-sulfide-nanoparticles-as-a-photothermal-switch-for-trpv1-signaling-to-attenuate-atherosclerosis
#10
Wen Gao, Yuhui Sun, Michelle Cai, Yujie Zhao, Wenhua Cao, Zhenhua Liu, Guanwei Cui, Bo Tang
Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29335389/checklist-in-colorectal-surgery-proposal-of-experts-of-the-polish-club-of-coloproctology-and-national-consultant-in-general-surgery
#11
Tomasz Banasiewicz, Łukasz Krokowicz, Piotr Richter, Adam Dziki, Piotr Krokowicz, Zbigniew Lorenc, Marek Szczepkowski, Michał Drews, Grzegorz Wallner
A checklist is a collection of information that helps reduce the risk of failure due to limitations in human memory and attention. In surgery, the first Surgical Safety Checklist (SSC), created under the supervision of WHO (World Health Organization), was established in 2007 and covers three stages related to the patient's stay in the operating theater and operation: 1. Prior to initiation (induction) of anesthesia; 2. before cutting the skin; 3. before the patient leaves the operating room Colorectal surgery is particularly at high risk for complications and relatively high mortality...
December 30, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/29335318/longitudinal-effect-of-stroke-on-cognition-a-systematic-review
#12
REVIEW
Eugene Yh Tang, Obreniokibo Amiesimaka, Stephanie L Harrison, Emma Green, Christopher Price, Louise Robinson, Mario Siervo, Blossom Cm Stephan
BACKGROUND: Stroke is associated with an increased risk of dementia; however, the impact of stroke on cognition has been found to be variable, such that stroke survivors can show decline, remain stable, or revert to baseline cognitive functioning. Knowing the natural history of cognitive impairment after stroke is important for intervention. The aim of this systematic review is to investigate the longitudinal course of cognitive function in stroke survivors. METHODS AND RESULTS: Three electronic databases (Medline, Embase, PsycINFO) were searched using OvidSP from inception to July 15, 2016...
January 15, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29334727/apob-apoa-i-ratio-is-independently-associated-with-carotid-atherosclerosis-in-type-2-diabetes-mellitus-with-well-controlled-ldl-cholesterol-levels
#13
Ji Eun Jun, Young Ju Choi, Yong-Ho Lee, Dae Jung Kim, Seok Won Park, Byung Wook Huh, Eun Jig Lee, Sun-Ha Jee, Kyu Yeon Hur, Sung Hee Choi, Kap Bum Huh
BACKGROUND/AIMS: This study aimed to investigate whether the apolipoprotein (Apo) B/ApoA-I ratio is associated with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM) subjects with low density lipoprotein cholesterol (LDL-C) levels less than 100 mg/dL. METHODS: This cross-sectional study included 845 subjects aged with T2DM 40 to 75 years who had visited Huh's Diabetes Center in Seoul, Republic of Korea for CIMT measurement. Traditional fasting lipid profiles, ApoB and ApoA-I levels were examined...
January 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29334498/evidence-based-interpretation-of-amyloid-%C3%AE-pet-results-a-clinician-s-tool
#14
David Bergeron, Rik Ossenkoppele, Robert Jr Laforce
BACKGROUND: Amyloid-β positron emission tomography (PET) allows for in vivo detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer's disease (AD). However, amyloid-β PET interpretation is limited by the imperfect correlation between PET and autopsy, and the fact that it is positive in about 20% to 30% of cognitively normal individuals and non-AD dementias, especially when older or carrying the ε4 allele of apolipoprotein E (ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the probability of a pathologic false positive as well as the probability of amyloid positivity being age-related, comorbid to a primary non-AD dementia (clinicopathologic false positive)...
January 12, 2018: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/29334455/modulating-the-molybdenum-coordination-sphere-of-escherichia-coli-trimethylamine-n-oxide-reductase
#15
Paul Kaufmann, Benjamin R Duffus, Biljana Mitrova, Chantal Iobbi-Nivol, Christian Teutloff, Manfred Nimtz, Lothar Jänsch, Ulla Wollenberger, Silke Leimkühler
The well-studied enterobacterium Escherichia coli present in the human gut is able to reduce TMAO to trimethylamine (TMA) during anaerobic respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor-containing enzyme belonging to the dimethylsulfoxide (DMSO) reductase family of molybdoenzymes. We report on a system for the in vitro reconstitution of TorA with molybdenum cofactors (Moco) from different sources. Higher TMAO reductase activities for TorA were obtained when using Moco-sources containing a sulfido ligand at the molybdenum atom...
January 15, 2018: Biochemistry
https://www.readbyqxmd.com/read/29334311/the-surface-chemistry-determines-the-spatio-temporal-interaction-dynamics-of-quantum-dots-in-atherosclerotic-lesions
#16
Bernd Uhl, Stephanie Hirn, Karina Mildner, Raffaele Coletti, Steffen Massberg, Christoph A Reichel, Markus Rehberg, Dagmar Zeuschner, Fritz Krombach
AIM: To optimize the design of nanoparticles for diagnosis or therapy of vascular diseases, it is mandatory to characterize the determinants of nano-bio interactions in vascular lesions. MATERIALS & METHODS: Using ex vivo and in vivo microscopy, we analyzed the interactive behavior of quantum dots with different surface functionalizations in atherosclerotic lesions of ApoE-deficient mice. RESULTS: We demonstrate that quantum dots with different surface functionalizations exhibit specific interactive behaviors with distinct molecular and cellular components of the injured vessel wall...
January 15, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29332579/alzheimer-s-disease-a-systemic-review-of-substantial-therapeutic-targets-and-the-leading-multi-functional-molecules
#17
Tarana Umar, Nasimul Hoda
Alzheimer's disease (AD) is a fatal neurodegenerative disorder, having a complex aetiology with numerous possible drug targets. There are targets that have been known for years while more new targets and theories have also emerged. Beta amyloid and cholinesterases are the most significant biological targets for finding curative treatment of AD. The major class of drugs used for AD till now has been the Cholinesterase (ChE) inhibitors. Other prevailing models of molecular pathogenesis in AD include neurofibrillary tangles (NFTs) and amyloid deposition, tryptophan degradation pathway, kinase and phosphatase activity imbalance and neuroinflammation...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29331631/the-edinburgh-ct-and-genetic-diagnostic-criteria-for-lobar-intracerebral-haemorrhage-associated-with-cerebral-amyloid-angiopathy-model-development-and-diagnostic-test-accuracy-study
#18
Mark A Rodrigues, Neshika Samarasekera, Christine Lerpiniere, Catherine Humphreys, Mark O McCarron, Philip M White, James A R Nicoll, Cathie L M Sudlow, Charlotte Cordonnier, Joanna M Wardlaw, Colin Smith, Rustam Al-Shahi Salman
BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype. METHODS: We identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort...
January 10, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29331531/profiles-of-%C3%AE-amyloid-peptides-and-key-secretases-in-brain-autopsy-samples-differ-with-sex-and-apoe-%C3%AE%C2%B54-status-impact-for-risk-and-progression-of-alzheimer-disease
#19
Jennifer N K Nyarko, Maa O Quartey, Paul R Pennington, Ryan M Heistad, Doris Dea, Judes Poirier, Glen B Baker, Darrell D Mousseau
The APOE ε 4 allele was originally reported to contribute to risk of Alzheimer disease (AD) in women, yet male and female AD patient-derived data are routinely pooled. Histopathological hallmarks of AD include neurofibrillary tangles centered on hyperphosphorylated Tau and plaques composed of the β -amyloid (A β) peptide that is derived by sequential secretase-mediated cleavage of the Amyloid Protein Precursor (APP). We chose to examine profiles of A β (1-40), A β (1-42), and N-truncated (i.e. p3-related) fragments in the plaque-associated fraction of autopsied cortical and corresponding hippocampal samples from donors with a diagnosis of early-onset (EOAD) and late-onset (LOAD) AD...
January 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29330760/oxidized-phospholipids-stimulate-production-of-stem-cell-factor-via-nrf2-dependent-mechanisms
#20
Taras Afonyushkin, Olga V Oskolkova, Valery N Bochkov
Receptor tyrosine kinase c-Kit and its ligand stem cell factor (SCF) regulate resident vascular wall cells and recruit circulating progenitors. We tested whether SCF may be induced by oxidized palmitoyl-arachidonoyl-phosphatidylcholine (OxPAPC) known to accumulate in atherosclerotic vessels. Gene expression analysis demonstrated OxPAPC-induced upregulation of SCF mRNA and protein in different types of endothelial cells (ECs). Elevated levels of SCF mRNA were observed in aortas of ApoE-/- knockout mice. ECs produced biologically active SCF because conditioned medium from OxPAPC-treated cells stimulated activation (phosphorylation) of c-Kit in naïve ECs...
January 12, 2018: Angiogenesis
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