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https://www.readbyqxmd.com/read/28433108/genetic-and-environmental-modifiers-of-wilson-disease
#1
Valentina Medici, Karl-Heinz Weiss
Wilson disease (WD) is characterized by remarkable variety in its phenotypic presentation. Patients with WD can present with hepatic, neurologic, and psychiatric symptoms combined in different and unpredictable ways. Importantly, no convincing phenotype-genotype correlation has ever been identified, opening the possibility that other genes, aside from ATPase copper-transporting beta (ATP7B), are involved in the pathogenesis of this condition. In addition, modifier genes, or genes that can affect the expression of other genes, may be involved...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28430712/apolipoprotein-e-variants-and-genetic-susceptibility-to-combat-related-post-traumatic-stress-disorder-a-meta-analysis
#2
Yang Roby
BACKGROUND: Apolipoprotein E (APOE) has recently been studied as a risk factor for association with developing combat-related post-traumatic stress disorder (PTSD) in the military population. These studies have yielded inconsistent findings. The present study carried out a meta-analysis to establish whether the APOE polymorphism confers increased susceptibility to combat-related PTSD. METHODS: PubMed, Medline, Embase, PsycInfo, and Google Scholar were searched for potential publications relating to patients with PTSD in military settings with combat exposure...
April 18, 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/28429734/neuroprotective-pentapeptide-cn-105-is-associated-with-reduced-sterile-inflammation-and-improved-functional-outcomes-in-a-traumatic-brain-injury-murine-model
#3
Daniel T Laskowitz, Haichen Wang, Tony Chen, David T Lubkin, Viviana Cantillana, Tian Ming Tu, Dawn Kernagis, Guanen Zhou, Gary Macy, Bradley J Kolls, Hana N Dawson
At present, there are no proven pharmacological treatments demonstrated to improve long term functional outcomes following traumatic brain injury(TBI). In the setting of non-penetrating TBI, sterile brain inflammatory responses are associated with the development of cerebral edema, intracranial hypertension, and secondary neuronal injury. There is increasing evidence that endogenous apolipoprotein E(apoE) modifies the neuroinflammatory response through its role in downregulating glial activation, however, the intact apoE holoprotein does not cross the blood-brain barrier due to its size...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425466/crystal-structures-of-the-no-sensor-nsrr-reveal-how-its-iron-sulfur-cluster-modulates-dna-binding
#4
Anne Volbeda, Erin L Dodd, Claudine Darnault, Jason C Crack, Oriane Renoux, Matthew I Hutchings, Nick E Le Brun, Juan C Fontecilla-Camps
NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes through the progressive degradation of its [4Fe-4S] cluster on nitric oxide (NO) exposure. We report the 1.95 Å resolution crystal structure of dimeric holo-ScNsrR and show that the cluster is coordinated by the three invariant Cys residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C variants remain NO sensitive, DNA binding is affected...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28408925/combination-therapy-with-a-sodium-glucose-cotransporter-2-inhibitor-and-a-dipeptidyl-peptidase-4-inhibitor-additively-suppresses-macrophage-foam-cell-formation-and-atherosclerosis-in-diabetic-mice
#5
Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Hideki Kushima, Makoto Ohara, Takuya Watanabe, Olov Andersson, Tsutomu Hirano
Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe(-/-) ) mice...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28406978/combined-assessment-of-serum-folate-and-hemoglobin-as-biomarkers-of-brain-amyloid-%C3%AE-accumulation
#6
Takuma Yoshinaga, Hiroto Nishimata, Yoriko Kajiya, Shunichi Yokoyama
A relationship between Alzheimer's disease (AD) and folate has been reported. Amyloid positron emission tomography (PET) is currently one of the most reliable biomarkers for AD. We investigated the correlation between serum folate levels and amyloid imaging to clarify whether serum folate could be a biomarker for AD. We also examined the usefulness of a combined assessment of serum folate levels and red blood cell hemoglobin content. Apolipoprotein E (APOE) gene polymorphisms were also assessed. Serum folate levels and hemoglobin content were evaluated by receiver operating characteristic analysis for their diagnostic capability as AD biomarkers relating to brain amyloid β accumulation...
2017: PloS One
https://www.readbyqxmd.com/read/28404852/attachment-and-post-attachment-receptors-important-for-hepatitis-c-virus-infection-and-cell-to-cell-transmission
#7
Huahao Fan, Luhua Qiao, Kyung-Don Kang, Junfen Fan, Wensheng Wei, Guangxiang Luo
Hepatitis C virus (HCV) infection requires multiple receptors for its attachment and entry to the cell. Our previous studies found that human syndecan-1 (SDC-1), SDC-2, and T cell immunoglobulin and mucin domain-containing protein 1 (TIM-1) are HCV attachment receptors. Other cell surface molecules such as CD81, CLDN1, OCLN, SR-BI, and LDLR mainly function at post-attachment steps, which are considered post-attachment receptors. The underlying molecular mechanisms of different receptors in HCV cell-free and cell-to-cell transmission remain elusive...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28400210/derepression-of-sapibov1-is-independent-of-%C3%AF-nm1-type-2-dutpase-activity-and-is-inhibited-by-dutp-and-dump
#8
Rosanne L L Hill, Jiri Vlach, Laura K Parker, Gail E Christie, Jamil S Saad, Terje Dokland
Staphylococcus aureus is an opportunistic human pathogen able to transfer virulence genes to other cells through the mobilization of S. aureus pathogenicity islands (SaPIs). SaPIs are derepressed and packaged into phage-like transducing particles by helper phages like 80α or φNM1. Phages 80α and φNM1 encode structurally distinct dUTPases, Dut80α (type 1) and DutNM1 (type 2). Both dUTPases can interact with the SaPIbov1 Stl master repressor, leading to derepression and mobilization. That two structurally distinct dUTPases bind the same repressor led us to speculate that dUTPase activity may be important to the derepression process...
April 8, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28391878/autosomal-dominant-familial-dysbetalipoproteinemia-a-pathophysiological-framework-and-practical-approach-to-diagnosis-and-therapy
#9
REVIEW
Charlotte Koopal, A David Marais, Jan Westerink, Frank L J Visseren
Familial dysbetalipoproteinemia (FD) is a genetic disorder of lipoprotein metabolism associated with an increased risk for premature cardiovascular disease. In about 10% of the cases, FD is caused by autosomal dominant mutations in the apolipoprotein E gene (APOE). This review article provides a pathophysiological framework for autosomal dominant FD (ADFD) and discusses diagnostic challenges and therapeutic options. The clinical presentation and diagnostic work-up of ADFD are illustrated by two cases: a male with premature coronary artery disease and a p...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28389270/combination-of-valproic-acid-and-morpholino-splice-switching-oligonucleotide-produces-improved-outcomes-in-spinal-muscular-atrophy-patient-derived-fibroblasts
#10
Anna Farrelly-Rosch, Chew Ling Lau, Nitin Patil, Bradley J Turner, Fazel Shabanpoor
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality worldwide, is characterised by the homozygous loss of the survival motor neuron 1 (SMN1) gene. The consequent degeneration of spinal motor neurons and progressive atrophy of voluntary muscle groups results in paralysis and eventually premature infantile death. Humans possess a second nearly identical copy of SMN1, known as SMN2. However, SMN2 produces only 10-20% functional SMN protein due to aberrant splicing of its pre-mRNA that leads to the exclusion of exon 7...
April 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28381441/role-of-lrp1-in-the-pathogenesis-of-alzheimer-s-disease-evidence-from-clinical-and-preclinical-studies
#11
Mitsuru Shinohara, Masaya Tachibana, Takahisa Kanekiyo, Guojun Bu
Among the low-density lipoprotein receptor (LDLR) family members, the roles of LDLR-related protein 1 (LRP1 or LRP) in the pathogenesis of Alzheimer's disease (AD), especially late-onset AD, have been the most studied by genetic, neuropathological and biomarker analyses (clinical studies) or cellular and animal model systems (preclinical studies) over the last 25 years. Although there are some conflicting reports, accumulating evidence from preclinical studies indicates that LRP1 not only regulates the metabolism of amyloid-β peptides (Aβ) in the brain and periphery, but also maintains brain homeostasis, impairment of which likely contributes to AD development in Aβ-independent manners...
April 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28379035/polygenic-hypercholesterolemia-examples-of-gwas-results-and-their-replication-in-the-czech-slavonic-population
#12
J A Hubacek, V Adamkova, V Lanska, D Dlouha
Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the "gold standard" for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recognize the importance of new genetic determinants (e...
April 5, 2017: Physiological Research
https://www.readbyqxmd.com/read/28377388/targeting-the-gut-microbiota-with-inulin-type-fructans-preclinical-demonstration-of-a-novel-approach-in-the-management-of-endothelial-dysfunction
#13
Emilie Catry, Laure B Bindels, Anne Tailleux, Sophie Lestavel, Audrey M Neyrinck, Jean-François Goossens, Irina Lobysheva, Hubert Plovier, Ahmed Essaghir, Jean-Baptiste Demoulin, Caroline Bouzin, Barbara D Pachikian, Patrice D Cani, Bart Staels, Chantal Dessy, Nathalie M Delzenne
OBJECTIVE: To investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction. DESIGN: We examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe(-/-)) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days...
April 4, 2017: Gut
https://www.readbyqxmd.com/read/28372324/apolipoprotein-e-isoforms-differentially-regulate-alzheimer-s-disease-and-amyloid-%C3%AE-induced-inflammatory-response-in-vivo-and-in-vitro
#14
Evan Dorey, Michelle Bamji-Mirza, Dema Najem, Yan Li, Hong Liu, Debbie Callaghan, Douglas Walker, Lih-Fen Lue, Danica Stanimirovic, Wandong Zhang
Neuroinflammation plays a critical role in neuronal dysfunction and death of Alzheimer's disease (AD). ApoE4 is a major risk factor of AD, while ApoE2 is neuroprotective. Little is known about the roles of ApoE isoforms in the neuroinflammation seen in AD. Their roles and mechanisms in Aβ-induced/neuroinflammation were investigated in this study using in vivo and in vitro models. Rat astrocytes were treated with lipid-poor recombinant hApoE or/and Aβ42. Mouse astrocyte lines-expressing lipidated hApoE were treated with Aβ42 or/and vitamin D receptor (VDR) agonist, 1α,25-dihydroxyvitamin D3...
March 29, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28364044/high-serum-thrombospondin-1-concentration-is-associated-with-slower-abdominal-aortic-aneurysm-growth-and-deficiency-promotes-angiotensin-ii-induced-aneurysm-in-mice
#15
Smriti M Krishna, Saiwang Seto, Roby Jose, Jiaze Li, Joseph V Moxon, Paula Clancy, David J Crossman, Paul E Norman, Theophilus I Emeto, Jonathan Golledge
Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix remodeling. In this study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeat ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration ( Spearman's rho (-)0...
March 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28355284/differential-action-of-glucocorticoids-on-apolipoprotein-e-gene-expression-in-macrophages-and-hepatocytes
#16
Violeta Georgeta Trusca, Elena Valeria Fuior, Ioana Madalina Fenyo, Dimitris Kardassis, Maya Simionescu, Anca Violeta Gafencu
Apolipoprotein E (apoE) has anti-atherosclerotic properties, being involved in the transport and clearance of cholesterol-rich lipoproteins as well as in cholesterol efflux from cells. We hypothesized that glucocorticoids may exert anti-inflammatory properties by increasing the level of macrophage-derived apoE. Our data showed that glucocorticoids increased apoE expression in macrophages in vitro as well as in vivo. Dexamethasone increased ~6 fold apoE mRNA levels in cultured peritoneal macrophages and RAW 264...
2017: PloS One
https://www.readbyqxmd.com/read/28352998/an-external-substrate-free-blue-white-screening-system-in-escherichia-coli
#17
Zhoujie Xie, Zhao Zhang, Zhenju Cao, Meng Chen, Pengwei Li, Weifeng Liu, Hua Qin, Xuejin Zhao, Yong Tao, Yihua Chen
Since the lacZα-based blue/white screening system was introduced to molecular biology, several different visual reporter systems were developed and used for various purposes in Escherichia coli. A common limit to the existent visual reporter systems is that an extracellular chromogenic substrate has to be added for the visible pigment production. In this study, we developed a new blue/white screening system based on a non-ribosomal peptide synthetase encoded by idgS from Streptomyces and a phosphopantetheinyl transferase encoded by sfp from Bacillus...
March 28, 2017: Applied Microbiology and Biotechnology
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
#18
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
#19
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/28345146/evidence-for-the-generation-of-myristylated-fmn-by-bacterial-luciferase
#20
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) flavin adenine mononucleotide (myrFMN) 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...
March 27, 2017: Molecular Microbiology
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