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https://www.readbyqxmd.com/read/28214511/identification-of-a-degradation-signal-sequence-within-substrates-of-the-mitochondrial-i-aaa-protease
#1
Anthony J Rampello, Steven E Glynn
The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by disruption of conserved disulfide bonds within the substrate...
February 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28214350/upregulation-of-microrna-15a-contributes-to-pathogenesis-of-abdominal-aortic-aneurysm-aaa-by-modulating-the-expression-of-cyclin-dependent-kinase-inhibitor-2b-cdkn2b
#2
Peng Gao, Jiyuan Si, Bin Yang, Jixiang Yu
BACKGROUND The objective of the present study was to identify the association between miR-15a-5p and CDKN2B, and their roles in regulating the development of abdominal aortic aneurysm (AAA). MATERIAL AND METHODS We searched the miRNA database online (www.mirdb.org) and used a luciferase reporter assay system to study the regulatory relationship between miR-15a-5p and CDKN2B. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CDKN2B among different patient groups (participants with abdominal aortic aneurysm (AAA) and normal controls) or cells treated with scramble control, miR-15a-5p mimics, CDKN2B siRNA, and miR-15a-5p inhibitors...
February 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28213405/inhibition-of-the-mtor-pathway-in-abdominal-aortic-aneurysm-implication-of-smooth-muscle-cell-contractile-phenotype-inflammation-and-aneurysm-expansion
#3
Guangxin Li, Lingfeng Qin, Lei Wang, Xuan Li, Alexander W Caulk, Jian Zhang, Pei-Yu Chen, Shijie Xin
The development of effective pharmacological treatment of abdominal aortic aneurysm (AAA) potentially offers great benefit to patients with pre-aneurysmal aortic dilation by slowing the expansion of aneurysms and reducing the need for surgery. To date, therapeutic targets for slowing aortic dilation have had low efficacy. Thus, in this study, we aim to elucidate possible mechanisms driving aneurysm progression in order to identify potential targets for pharmacological intervention. We demonstrate that mTOR signaling is over activated in aortic smooth muscle cells (SMCs) which contributes to murine AAA...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28212412/a-mathematical-model-of-aortic-aneurysm-formation
#4
Wenrui Hao, Shihua Gong, Shuonan Wu, Jinchao Xu, Michael R Go, Avner Friedman, Dai Zhu
Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient's aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6...
2017: PloS One
https://www.readbyqxmd.com/read/28210435/role-of-thr399ile-and-asp299gly-polymorphisms-of-toll-like-receptor-4-gene-in-acute-dental-abscess
#5
Ebrahim Miri-Moghaddam, Narges Farhad-Mollashahi, Elnaz Baghaee, Ali Bazi, Yasaman Garme
BACKGROUND: Apical Periodontitis (AP) is an inflammatory disease that affects the tissues surrounding the root end of a tooth. The disease which is caused by endodontic infections presents in different clinical ways including development of an acute abscess. Recent studies have provided information suggesting role of a multitude of factors in pathogenesis of acute apical abscess (AAA). In this case-control study, our goal was to evaluate the frequency and potential role of two common polymorphisms of toll like receptor-4 (TLR-4) gene; Thr399Ile (1196 C>T) and Asp299Gly (+896 A>G), in 50 patients with AAA as cases and 50 patients with asymptomatic apical periodontitis (AAP) as controls...
February 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28209269/association-of-matrix-metalloproteinase-levels-with-collagen-degradation-in-the-context-of-abdominal-aortic-aneurysm
#6
V Klaus, F Tanios-Schmies, C Reeps, M Trenner, E Matevossian, H-H Eckstein, J Pelisek
OBJECTIVE/BACKGROUND: Matrix metalloproteinases (MMPs) have already been identified as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the current data remain inconclusive. In this study, the expression of MMPs at mRNA and protein levels were investigated in relation to the degradation of collagen I and collagen III. METHODS: Tissue samples were obtained from 40 patients with AAA undergoing open aortic repair, and from five healthy controls during kidney transplantation...
February 10, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28205175/membrane-extraction-of-hmg-coa-reductase-as-determined-by-susceptibility-of-lumenal-epitope-to-in-vitro-protease-digestion
#7
Lindsey L Morris, Russell A DeBose-Boyd
Although many aspects of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway have been elucidated, methods to detect and examine intermediate steps in the process are lacking. Here, we describe the use of a protease protection assay to study the metabolically regulated ERAD substrate HMG CoA reductase. Studies utilizing this assay reveal that ubiquitinated reductase becomes extracted across the ER membrane prior to its cytosolic release and proteasomal degradation through reactions mediated by distinct AAA-ATPases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28205095/tetramerization-of-satb1-is-essential-for-regulating-of-gene-expression
#8
Minying Zheng, Wancai Xing, Yabing Liu, Meng Li, Hao Zhou
Special AT-rich sequence-binding protein 1 (SATB1) functions as a 'genome organizer' in tumorigenesis. Our previous report showed that SATB1 forms a tetramer through its N-terminal ubiquitin like domain rather than the proposed PDZ domain. In the present study, we aim to illustrate whether this oligomerization is critical to its function as a global repressor of gene expression in vivo. Luciferase and GST pull-down assays demonstrated that disrupting SATB1's tetramerization not only affects the activities of promoters but also influences the recruitment of interaction partners...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28198175/early-intervention-effects-of-or-and-evar-on-young-patients-suffering-from-40-54mm-aaas-single-center-experience
#9
Jian Qui, Chang Shu, Wenwu Cai, Ming Li, Quanming Li
BACKGROUND: We conducted this study to explore the early intervention effects of OR and EVAR in treating young AAA patients (maximum diameter 40~54mm). METHODS: We retrospectively analyzed patients under 65 years old with maximum AAA diameter 40-54mm in our hospital from Jan. 2010 to Jan. 2016 (among which there are 38 EVAR cases and 18 OR cases) and compared their short-mid term operation effects. RESULTS: The time of the operation, bleeding volume and volume of blood transfusion during operation in the EVAR group are significantly lower than those in the OR group; differences are statistically significant (P<0...
February 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28196857/deletion-of-hypoxia-inducible-factor-1%C3%AE-in-myeloid-lineage-exaggerates-angiotensin-ii-induced-formation-of-abdominal-aortic-aneurysm
#10
Yusuke Takahara, Tomotake Tokunou, Hiroshi Kojima, Yoshitaka Hirooka, Toshihiro Ichiki
Hypoxia-inducible factor (HIF)-1α is a transcription factor that regulates various genes responding to hypoxic conditions. We previously reported that myeloid-specific activation of HIF-1α had protective effects on hypertensive cardiovascular remodeling in mice. However the role of myeloid lineage HIF-1α in the development of abdominal aortic aneurysm (AAA) has not been determined. Myeloid-specific HIF-1α knockout (HIF-1KO) mice were created using a Cre-lox recombination system in the background of apolipoprotein E-deficient mice...
February 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28193267/abdominal-ultrasound-scanning-versus-non-contrast-computed-tomography-as-screening-method-for-abdominal-aortic-aneurysm-a-validation-study-from-the-randomized-dancavas-study
#11
Mads Liisberg, Axel C Diederichsen, Jes S Lindholt
BACKGROUND: Validating non-contrast-enhanced computed tomography (nCT) compared to ultrasound sonography (US) as screening method for abdominal aortic aneurysm (AAA) screening. METHODS: Consecutively attending men (n = 566) from the pilot study of the randomized Danish CardioVascular Screening trial (DANCAVAS trial), underwent nCT and US examination. Diameters were measured in outer-to-outer fashion. Sensitivity and specificity were done testing each modality against each other as reference standard...
February 14, 2017: BMC Medical Imaging
https://www.readbyqxmd.com/read/28193091/abdominal-aortic-aneurysm-screening-reduces-all-cause-mortality
#12
Hisato Takagi, Tomo Ando, Takuya Umemoto
We performed an updated meta-analysis of the longest (≥13 years) follow-up results from 4 randomized controlled trials of abdominal aortic aneurysm (AAA) screening in ≥64-year-old men. Invitation to screening reduced all-cause mortality significantly according to time-to-event data (hazard ratio: 0.98; 95% confidence interval [CI]: 0.96-0.99; P = .003) despite no reduction according to dichotomous data (odds ratio [OR]: 0.99; 95% CI: 0.96-1.01; P = .23). Invitation to screening reduced AAA-related mortality significantly (OR: 0...
January 1, 2017: Angiology
https://www.readbyqxmd.com/read/28191893/structural-basis-of-mcm2-7-replicative-helicase-loading-by-orc-cdc6-and-cdt1
#13
Zuanning Yuan, Alberto Riera, Lin Bai, Jingchuan Sun, Saikat Nandi, Christos Spanos, Zhuo Angel Chen, Marta Barbon, Juri Rappsilber, Bruce Stillman, Christian Speck, Huilin Li
To initiate DNA replication, the origin recognition complex (ORC) and Cdc6 load an Mcm2-7 double hexamer onto DNA. Without ATP hydrolysis, ORC-Cdc6 recruits one Cdt1-bound Mcm2-7 hexamer, thus forming an ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) helicase-loading intermediate. Here we report a 3.9-Å structure of Saccharomyces cerevisiae OCCM on DNA. Flexible Mcm2-7 winged-helix domains (WHDs) engage ORC-Cdc6. A three-domain Cdt1 configuration embraces Mcm2, Mcm4, and Mcm6, thus comprising nearly half of the hexamer. The Cdt1 C-terminal domain extends to the Mcm6 WHD, which binds the Orc4 WHD...
February 13, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28190808/quantification-of-triacylglycerol-molecular-species-in-edible-fats-and-oils-by-gas-chromatographyflame-ionization-detector-using-correction-factors
#14
Kazuaki Yoshinaga, Junji Obi, Toshiharu Nagai, Hiroyuki Iioka, Akihiko Yoshida, Fumiaki Beppu, Naohiro Gotoh
In the present study, the resolution parameters and correction factors (CFs) of triacylglycerol (TAG) standards were estimated by gas chromatography-flame ionization detector (GC-FID) to achieve the precise quantification of the TAG composition in edible fats and oils. Forty seven TAG standards comprising capric acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, and/or linolenic acid were analyzed, and the CFs of these TAGs were obtained against tripentadecanoyl glycerol as the internal standard...
February 10, 2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28190712/effect-of-antiplatelet-therapy-on-aneurysmal-sac-expansion-associated-with-type-ii-endoleaks-after-endovascular-aneurysm-repair
#15
Francisco Álvarez Marcos, José Manuel Llaneza Coto, Francisco José Franco Meijide, Ahmad Amer Zanabili Al-Sibbai, Jorge Vilariño Rico, Manuel Alonso Pérez, Santiago Caeiro Quinteiro
OBJECTIVE: Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) has gained widespread use through a solid reputation of safety and effectiveness. However, some issues, such as endoleaks and sac growth over time, still arise as important concerns. Antiplatelet therapy, mandatory as secondary prevention of cardiovascular disease, may play a role in both phenomena by interfering with blood clotting properties and the inflammatory process associated with AAA. We analyzed whether different antiplatelet therapies were independent risk factors for type II endoleak (T2E) persistence and midterm sac growth after EVAR...
February 9, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28189002/abdominal-aortic-aneurysm-an-independent-disease-to-atherosclerosis
#16
REVIEW
Bradley J Toghill, Athanasios Saratzis, Matthew J Bown
Atherosclerosis and abdominal aortic aneurysms (AAAs) are multifactorial and polygenic diseases with known environmental and genetic risk factors that contribute toward disease development. Atherosclerosis represents an important independent risk factor for AAA, as people with AAA often have atherosclerosis. Studies have shown that comorbidity is usually between ~25% and 55%, but it is still not fully known whether this association is causal or a result of common shared risk profiles. Most recent epidemiological, clinical, and biological evidence suggests that the two pathologies are more distinct than traditionally thought...
January 29, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28188183/variants-of-the-sir4-coiled-coil-domain-improve-binding-to-sir3-for-heterochromatin-formation-in-saccharomyces-cerevisiae
#17
Anke Samel, Adam Rudner, Ann E Ehrenhofer-Murray
Heterochromatin formation in the yeast Saccharomyces cerevisiae is characterized by the assembly of the Silent Information Regulator (SIR) complex, which consists of the histone deacetylase Sir2 and the structural components Sir3 and Sir4 and binds to unmodified nucleosomes to provide gene silencing. Sir3 contains an AAA(+) ATPase-like domain, and mutations in an exposed loop on the surface of this domain abrogate Sir3 silencing function in vivo as well in vitro binding to the Sir2/ Sir4 subcomplex. Here, we found that the removal of a single methyl group in the C-terminal coiled-coil domain (mutation T1314S) of Sir4 was sufficient to restore silencing at the silent mating-type loci HMR and HML to a Sir3 version with a mutation in this loop...
February 10, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28186202/inhibition-of-receptor-interacting-protein-kinase-1-with-necrostatin-1s-ameliorates-disease-progression-in-elastase-induced-mouse-abdominal-aortic-aneurysm-model
#18
Qiwei Wang, Ting Zhou, Zhenjie Liu, Jun Ren, Noel Phan, Kartik Gupta, Danielle M Stewart, Stephanie Morgan, Carmel Assa, K Craig Kent, Bo Liu
Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s)...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28183702/glycated-hemoglobin-is-associated-with-the-growth-rate-of-abdominal-aortic-aneurysms-a-substudy-from-the-viva-viborg-vascular-randomized-screening-trial
#19
Katrine Lawaetz Kristensen, Marie Dahl, Lars Melholt Rasmussen, Jes Sanddal Lindholt
OBJECTIVE: An inverse association between abdominal aortic aneurysms (AAAs) and diabetes mellitus exists; however, the cause remains unknown. This study aimed to evaluate whether the degree of glycemia is associated with aneurysm growth. APPROACH AND RESULTS: The study was based on VIVA trial (Viborg Vascular), the randomized clinically controlled screening trial for abdominal aortic aneurysm in men aged 65 to 74 years in the Central Denmark Region. The screening included measurement of the abdominal aorta by ultrasound, analysis of glycated hemoglobin (HbA1c), and follow-up for ≤5 years for aneurysms <5 cm...
February 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28183566/relationship-between-normal-preoperative-white-blood-cell-count-and-major-adverse-events-after-endovascular-repair-for-abdominal-aortic-aneurysm-results-of-a-pilot-study
#20
Eleni Arnaoutoglou, George Kouvelos, Petros Tzimas, Eleni Laou, Vasilios Bouris, George Papadopoulos, Miltiadis Matsagkas
STUDY OBJECTIVE: To examine the association between preoperative white blood cell (WBC) count within the reference range and major adverse events (MAEs) following endovascular repair of abdominal aortic aneurysms (AAA). DESIGN: Prospective observational study. SETTING: Vascular surgery clinic in a tertiary university hospital. PATIENTS: One hundred fifty-three consecutive patients. INTERVENTION: Endovascular repair of AAA...
February 2017: Journal of Clinical Anesthesia
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