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https://www.readbyqxmd.com/read/29779130/the-present-and-the-future-of-genetic-testing-in-familial-hypercholesterolemia-opportunities-and-caveats
#1
REVIEW
Amanda J Hooper, John R Burnett, Damon A Bell, Gerald F Watts
PURPOSE OF REVIEW: We summarize recent advances in the understanding of genetic testing in familial hypercholesterolemia (FH), the use of expanded FH next-generation sequencing panels, and directions for future research. RECENT FINDINGS: The uptake of massively parallel sequencing in research and diagnostic laboratories has enabled expanded testing for FH and its phenocopies, with the added advantage that copy number variants can be detected. However, increasing the number of genes tested increases the number of variants detected, which may or may not be pathogenic...
May 19, 2018: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29779042/combining-theoretical-and-experimental-data-to-decipher-cftr-3d-structures-and-functions
#2
Brice Hoffmann, Ahmad Elbahnsi, Pierre Lehn, Jean-Luc Décout, Fabio Pietrucci, Jean-Paul Mornon, Isabelle Callebaut
Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29778561/severe-xanthomatosis-in-heterozygous-familial-hypercholesterolemia
#3
Sumayah Aljenedil, Isabelle Ruel, Kevin Watters, Jacques Genest
BACKGROUND: Familial hypercholesterolemia is a genetic lipoprotein disorder characterized by elevated plasma low-density lipoprotein cholesterol level, (tendinous xanthomas, xanthelasmas, and premature arcus corneus) and early onset atherosclerotic cardiovascular disease. Familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 genes. Rare mutations in low-density lipoprotein receptor adapter protein 1, APOE p...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29778421/comparison-of-two-groups-for-the-apolipoprotein-e-polymorphisms-by-using-next-generation-sequencing-the-first-group-with-three-consecutive-abortions-and-the-second-group-with-at-most-one-abortion-in-three-consecutive-pregnancies
#4
Evren Gumus
The importance of apolipoprotein E genotypes and allelic polymorphisms in the etiology of recurrent miscarriage is controversial. We plan to investigate this in a two-group study involving more than a thousand participants. In total, 1046 subjects (802 participants in the first group, 244 participants in the second group) were investigated. Women in the first group had a history of ≥3 consecutive spontaneous miscarriage and women in the second group had at most one miscarriage in three consecutive pregnancies...
May 17, 2018: Gene
https://www.readbyqxmd.com/read/29777203/ginkgo-biloba-extracts-prevent-aortic-rupture-in-angiotensin-ii-infused-hypercholesterolemic-mice
#5
Xiao-Fang Huang, Song-Zhao Zhang, Ya-Yu You, Na Zhang, Hong Lu, Alan Daugherty, Xiao-Jie Xie
Abdominal aortic aneurysms (AAAs) are a chronic vascular disease characterized by pathological luminal dilation. Aortic rupture is the fatal consequence of AAAs. Ginkgo biloba extracts (GBEs), a natural herb extract widely used as food supplements, drugs, and cosmetics, has been reported to suppress development of calcium chloride-induced AAAs in mice. Calcium chloride-induced AAAs do not rupture, while angiotensin II (AngII)-induced AAAs in mice have high rate of aortic rupture, implicating potentially different mechanisms from calcium chloride-induced AAAs...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29777060/protease-activated-receptor-1-inhibits-cholesterol-efflux-and-promotes-atherogenesis-via-cullin-3-mediated-degradation-of-the-abca1-transporter
#6
Somasundaram Raghavan, Nikhlesh K Singh, Arul M Mani, Gadiparthi N Rao
Although signaling of thrombin via its receptor protease-activated receptor 1 (Par1) is known to occur in atherothrombosis, its link to the actual pathogenesis of this condition is less clear. To better understand the role of thrombin-Par1 signaling in atherosclerosis, here we have studied their effects on cellular cholesterol efflux in mice. We found that by activating Par1 and cullin 3-mediated ubiquitination and degradation of ATP-binding cassette subfamily A member 1 (ABCA1), thrombin inhibits cholesterol efflux in both murine macrophages and smooth muscle cells...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29776682/the-impact-of-apolipoprotein-e-alleles-on-cognitive-performance-in-patients-with-parkinson-s-disease
#7
Anna Pierzchlińska, Monika Białecka, Mateusz Kurzawski, Jarosław Sławek
Apolipoprotein E (ApoE) is a vital component of several lipoproteins and plays a major role in lipid metabolism. APOE gene comprises of three alleles determined by two single nucleotide polymorphisms (rs429358 and rs7412) resulting in the protein isoforms, among which ApoE4 is a confirmed risk factor for Alzheimer's Disease. However, the impact of APOE genotypes on Parkinson's Disease Dementia (PDD) is still inconclusive. The PDD diagnostic criteria are very inconsistent, and could be complemented with genetic factors...
May 5, 2018: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29776362/apolipoprotein-b-apolipoprotein-a1-ratio-and-mortality-among-incident-peritoneal-dialysis-patients
#8
Xiaojiang Zhan, Yanbing Chen, Caixia Yan, Siyi Liu, Lijuan Deng, Yuting Yang, Panlin Qiu, Dan Pan, Bingxiang Zeng, Qinkai Chen
BACKGROUND: To investigate the association between the ratio of apolipoprotein B (apo B) / apolipoprotein A1 (apo A1) with all-cause mortality and cardiovascular events in peritoneal dialysis (PD) patients. METHODS: Eight hundred and sixty incident PD patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Outcomes were all-cause mortality and cardiovascular events. Associations between the apo B/apo A1 ratio with all-cause mortality and cardiovascular events were evaluated using multivariable-adjusted Cox models...
May 17, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29774596/epidemiological-analysis-of-maternal-lipid-levels-during-the-second-trimester-in-pregnancy-and-the-risk-of-adverse-pregnancy-outcome-adjusted-by-pregnancy-bmi
#9
Chao-Yan Yue, Chun-Mei Ying
BACKGROUND: Pregnancy is accompanied by profound changes in lipid metabolism. We aimed to assess whether effects of second trimester body mass index and maternal lipid concentrations are associated with an increased risk of adverse pregnancy outcomes. METHODS: We investigated the serum levels of maternal lipids during the second trimester in pregnancy, and analyzed associations between the lipid levels and the risk of adverse pregnancy outcome. Seven hundred and seventy-four pregnant women were enrolled in this study between February 2016 and June 2016...
May 17, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29770991/probing-the-interaction-of-l-captopril-with-metallo-%C3%AE-lactamase-ccra-by-fluorescence-spectra-and-molecular-dynamic-simulation
#10
Penghui Shi, Yan Zhang, Yuhua Li, Liujiao Bian
Both the molecular recognition and interaction of metallo-β-lactamase CcrA with l-captopril were studied by the combined use of fluorescence spectra and molecular dynamic simulation. The results showed that the binding constant was 8.89 × 104  L mol-1 at 296 K. Both Zn1 and Zn2 displayed tetrahedral coordination geometries in the CcrA-Lcap complex, the S atom in l-captopril displaced the nucleophilic hydroxide in apo CcrA and occupied the fourth coordination site for each ion, resulting in a competitively inhibited CcrA enzyme...
May 17, 2018: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/29770843/patterns-and-severity-of-vascular-amyloid-in-alzheimer-s-disease-associated-with-duplications-and-missense-mutations-in-app-gene-down-syndrome-and-sporadic-alzheimer-s-disease
#11
David M A Mann, Yvonne S Davidson, Andrew C Robinson, Nancy Allen, Tadafumi Hashimoto, Anna Richardson, Matthew Jones, Julie S Snowden, Neil Pendleton, Marie-Claude Potier, Annie Laquerrière, Vee Prasher, Takeshi Iwatsubo, Andre Strydom
In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD (APPdup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer's disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes...
May 16, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29770778/apolipoprotein-e-in-diet-induced-obesity-a-paradigm-shift-from-conventional-perception
#12
Kyriakos E Kypreos, Eleni A Karavia, Caterina Constantinou, Aikaterini Hatziri, Christina Kalogeropoulou, Eva Xepapadaki, Evangelia Zvintzou
Apolipoprotein E (APOE) is a major protein component of peripheral and brain lipoprotein transport systems. APOE in peripheral circulation does not cross blood brain barrier or blood cerebrospinal fluid barrier. As a result, peripheral APOE expression does not affect brain APOE levels and vice versa. Numerous epidemiological studies suggest a key role of peripherally expressed APOE in the development and progression of coronary heart disease while brain APOE has been associated with dementia and Alzheimer's disease...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29770337/-chlamydia-pneumoniae-infection-exacerbates-atherosclerosis-in-apob100only-ldlr-mouse-strain
#13
Ildikó Lantos, Valéria Endrész, Dezső Péter Virok, Andrea Szabó, Xinjie Lu, Tímea Mosolygó, Katalin Burián
Aims: Hyperlipidaemia model animals have been used to elucidate the role of Chlamydia pneumoniae (Cpn) infection in atherosclerosis. The aims of this study were to investigate the proatherogenic effect of multiple Cpn infections in ApoB100only/LDLR-/- mice which based on lipid profile can be regarded as the most suitable mouse model of human hypercholesterolemia and to compare the lesion development to that in a major atherosclerosis model ApoE-/- mice. Methods and Results: Aorta samples of ApoB100only/LDLR-/- mice infected three times with Cpn were subjected to morphometric analyses...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29769839/a-novel-association-of-polymorphism-in-the-itga4-gene-encoding-the-vla-4-%C3%AE-4-subunit-with-increased-risk-of-alzheimer-s-disease
#14
Vladimira Durmanova, Zuzana Parnicka, Juraj Javor, Gabriel Minarik, Lubomir Vrazda, Barbora Vaseckova, Karin Gmitterova, Maria Kralova, Jan Pecenak, Peter Filipcik, Ivana Shawkatova
Alzheimer's disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α 4 β 1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α 4 subunit of VLA-4 and the risk of AD...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29769483/association-between-serum-apolipoprotein-b-and-acute-ischaemic-stroke
#15
M S Islam, M J Uddin, M Bhattacharjee, M N Farzana, R K Talukder, M A Rahman, M Mohsin, M A Rouf, H Pandit, M R Karim, R Ara, S Akhter, G Saha, M Oliullah, M S Ali, R Parveen
Stroke is one of the leading causes of death and disability in developed as well as developing countries like Bangladesh. There is a crucial need to identify additional risk factors that are easily measurable and treatable in general population. Role of serum lipids, lipoproteins and lipoprotein related variables in the prediction of stroke is less clear. Abnormalities in plasma lipoproteins are the most firmly established and best understood risk factors for atherosclerosis and they are probable risk factors for ischaemic stroke, largely by their link to atherosclerosis...
April 2018: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/29769419/heart-rate-reduction-with-ivabradine-in-the-early-phase-of-atherosclerosis-is-protective-in-the-endothelium-of-apoe-deficient-mice
#16
G Aquila, M B Morelli, F Vieceli Dalla Sega, F Fortini, P Nigro, C Caliceti, M Ferracin, M Negrini, A Pannuti, M Bonora, P Pinton, R Ferrari, P Rizzo
Ivabradine, a heart rate reducing agent, protects the vascular system by unidentified mechanisms. We sought to determine the effects of the treatment with ivabradine, started before plaque formation, on early transcriptional changes and endothelium lesions in regions of aorta subjected to disturbed blood flow. Six week-old apolipoprotein E-deficient (ApoE-/- ) mice, fed a low-fat diet, were treated with ivabradine to determine the effect on transcriptional changes (2-and 4-week treatment) and on lesions formation (19-week treatment) in the endothelium of the aortic arch...
February 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29769126/polymorphism-and-plasma-levels-of-apolipoprotein-e-and-the-risk-of-aneurysmal-subarachnoid-hemorrhage-in-a-chinese-population-a-case-control-study
#17
Xiaofeng Liu, Weiwu Zhan, Qiumei Wu, Fengqing Wang, Bin Yang, Qishui Ou
BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is the most common types of subarachnoid hemorrhage, which is a critical clinical problem with high morbidity, mortality, and economic impact. Recent studies have shown that APOE was a genetic risk factor of aSAH, however, the studies lack consistent conclusions and the evidence from Chinese Han population is rare. OBJECTIVE: To determine the relationship between APOE polymorphism and the incidence of aSAH in Chinese Fujian Han population and explore the possible mechanism of ApoE in the pathogenesis of aSAH...
May 16, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29766364/binding-of-cd-ii-pb-ii-and-zn-ii-to-a-type-1-metallothionein-from-maize-zea-mays
#18
Lian Duan, Jing-Jing Kong, Tong-Qing Wang, Yue Sun
Metallothioneins (MTs) are a family of ubiquitous, low-molecular-mass, cysteine-rich proteins that play a significant role in maintaining intracellular metal homeostasis, eliminating metal toxification, and protecting cells against oxidative damages. Research activity on plant MTs, although known for 30 years, has only moderately increased in the past few years. In this study, a type 1 MT from maize (Zea mays) (ZmMT1) was successfully expressed in Escherichia coli strain BL21 (DE3). The UV absorption spectra recorded after the reconstitution of apo-ZmMT1 with different metals demonstrated that ZmMT1 can coordinate up to six Zn(II) ions, six Cd(II) ions, and even higher amounts of Pb(II)...
May 15, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29766292/gut-derived-lipopolysaccharides-increase-post-prandial-oxidative-stress-via-nox2-activation-in-patients-with-impaired-fasting-glucose-tolerance-effect-of-extra-virgin-olive-oil
#19
Roberto Carnevale, Daniele Pastori, Cristina Nocella, Vittoria Cammisotto, Simona Bartimoccia, Marta Novo, Maria Del Ben, Alessio Farcomeni, Francesco Angelico, Francesco Violi
PURPOSE: Post-prandial phase is characterized by enhanced oxidative stress but the underlying mechanism is unclear. We investigated if gut-derived lipopolysaccharide (LPS) is implicated in this phenomenon and the effect of extra virgin olive oil (EVOO) in patients with impaired fasting glucose (IFG). METHODS: This is a randomized cross-over interventional study including 30 IFG patients, to receive a lunch with or without 10 g of EVOO. Serum LPS, Apo-B48, markers of oxidative stress such as oxidized LDL (oxLDL) and soluble Nox2-derived peptide (sNox2-dp), a marker of nicotinamide-adenine-dinucleotide-phosphate oxidase isoform Nox2 activation, and plasma polyphenols were determined before, 60 and 120 min after lunch...
May 16, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29765610/x-ray-and-cryo-em-structures-of-inhibitor-bound-cytochrome-bc-1-complexes-for-structure-based-drug-discovery
#20
Kangsa Amporndanai, Rachel M Johnson, Paul M O'Neill, Colin W G Fishwick, Alexander H Jamson, Shaun Rawson, Stephen P Muench, S Samar Hasnain, Svetlana V Antonyuk
Cytochrome bc 1 , a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. Structural studies of cytochrome bc 1 from mammalian homologues co-crystallized with lead compounds have underpinned structure-based drug design to develop compounds with higher potency and selectivity. However, owing to the limited amount of cytochrome bc 1 that may be available from parasites, all efforts have been focused on homologous cytochrome bc 1 complexes from mammalian species, which has resulted in the failure of some drug candidates owing to toxicity in the host...
March 1, 2018: IUCrJ
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