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https://www.readbyqxmd.com/read/28330175/exploration-of-the-binding-modes-of-l-asparaginase-complexed-with-its-amino-acid-substrates-by-molecular-docking-dynamics-and-simulation
#1
Erva Rajeswara Reddy, Rajulapati Satish Babu, Potla Durthi Chandrasai, Pola Madhuri
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-glutamine (L-Gln) deamination plays crucial role in ALL treatment. Role of Erwinaze(®) (L-asparaginase from Erwinia chrysanthemi) in regulation of L-Asn and L-Gln has been confirmed by the experimental studies. Therapeutic research against ALL remained elusive with the lack of structural information on Erwinaze(®) enzyme. In this present study, homology model of the Erwinaze(®) was developed using MODELLER and the same was validated by various quality indexing tools...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330072/molecular-dynamic-simulations-of-escherichia-coli-l-asparaginase-to-illuminate-its-role-in-deamination-of-asparagine-and-glutamine-residues
#2
Rajeswara Reddy Erva, Satish Babu Rajulapati, Chandrasai Potla Durthi, Mayuri Bhatia, Madhuri Pola
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-Glutamine (L-Gln) deamination play a crucial role in ALL treatment. Role of Elspar(®) (L-asparaginase from Escherichia coli) in regulation of L-Asn and L-Gln has been confirmed by the other researchers through experimental studies. Therapeutic research against ALL remained elusive with the lack of information on molecular interactions of Elspar(®) with amino acid substrates. In the present study, using different docking tools binding cavities, key residues in binding and ligand binding mechanisms were identified...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329797/social-connectedness-perceived-isolation-and-dementia-does-the-social-environment-moderate-the-relationship-between-genetic-risk-and-cognitive-well-being
#3
Judith L Poey, Jeffrey A Burr, J Scott Roberts
Purpose of the Study: This study examined whether the social environment moderates the relationship between the APOE e4 allele and cognitive functioning. Design and Methods: The Aging, Demographics, and Memory Study (ADAMS) data and multinomial logistic regression models were used to investigate these relationships for a nationally representative sample of U.S. adults aged 70 and older (n = 779). Results: Living alone (relative risk ratio [RRR] = 5...
January 24, 2017: Gerontologist
https://www.readbyqxmd.com/read/28328682/early-tranexamic-acid-administration-ameliorates-the-endotheliopathy-of-trauma-and-shock-in-an-in-vitro-model
#4
Lawrence N Diebel, Jonathan V Martin, David M Liberati
BACKGROUND: Systemic vascular endothelial injury is a consequence of trauma-hemorrhagic shock (T/HS) which results in disturbances of coagulation, inflammation and endothelial barrier integrity. The effect of T/HS on the endothelium (Endotheliopathy of Trauma)[EoT] is of intense research interest and may lead to EoT directed therapies. Administration of tranexamic acid (TXA) in trauma patients is associated with a survival benefit and fewer complications if given early after injury. Mechanisms for this protective effect include the anti-fibrinolytic and anti-inflammatory effects of TXA...
March 21, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28327874/left-atrial-deformation-analysis-in-patients-with-corrected-tetralogy-of-fallot-by-3d-speckle-tracking-echocardiography-from-the-magyar-path-study
#5
Kálmán Havasi, Péter Domsik, Anita Kalapos, Jackie S McGhie, Jolien W Roos-Hesselink, Tamás Forster, Attila Nemes
Background: Three-dimensional (3D) echocardiography coupled with speckle-tracking echocardiographic (STE) capability is a novel methodology which has been demontrated to be useful for the assessment of left atrial (LA) volumes and functional properties. There is increased scientific interest on myocardial deformation analysis in adult patients with corrected tetralogy of Fallot (cTOF). Objectives: To compare LA volumes, volume-based functional properties and strain parameters between cTOF patients and age- and gender-matched healthy controls...
February 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28327868/resveratrol-treatment-normalizes-the-endothelial-function-and-blood-pressure-in-ovariectomized-rats
#6
Victor Fabricio, Jorge Camargo Oishi, Bruna Gabriele Biffe, Leandro Dias Gonçalves Ruffoni, Karina Ana da Silva, Keico Okino Nonaka, Gerson Jhonatan Rodrigues
Background: Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). Objective: To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats...
February 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28327740/molecular-dynamics-simulations-elucidate-conformational-selection-and-induced-fit-mechanisms-in-the-binding-of-pd-1-and-pd-l1
#7
Wenping Liu, Bing Huang, Yashu Kuang, Guangjian Liu
Blockage of the interactions between immunologic checkpoint protein PD-1 and its ligand PD-L1 showed efficacy for cancer treatment. X-ray structures have captured static conformational snapshots of PD-1 and revealed that the CC' loop adopts an open conformation in the apo-protein but turns into a closed form and interacts with PD-L1 in the complex. This structural heterogeneity brings difficulties for structure-based drug discovery targeting PD-1. To gain insights into the role of the CC' loop in molecular recognition, we have undertaken a comparative study between the open and closed conformations in apo-PD-1 and the PD-1/PD-L1 complex using molecular dynamics simulations...
March 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28327386/smoking-dependent-effect-of-lpl-and-apo-ciii-genes-on-cad-risk-in-an-african-brazilian-population
#8
Edilene M Q Araújo, Caio C S Cerqueira, Laila Freitas-Santos, Claubert R Coutinho, Ana A L Barbosa, Sandra M B Sousa, Larissa O Guimarães, Lydia L S Korontai, Jamille S Oliveira, Karolline S Silva, Domingos L S Rios
No abstract text is available yet for this article.
December 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28326331/effects-of-apolipoprotein-e-isoforms-in-diabetic-nephropathy-of-chinese-type-2-diabetic-patients
#9
YongWei Jiang, Liang Ma, ChengWu Han, Qian Liu, Xiao Cong, YaPing Xu, TingTing Zhao, Ping Li, YongTong Cao
Diabetic nephropathy (DN) is one of the major chronic complications of diabetes. Genetic polymorphism of Apolipoprotein E (ApoE) has been proposed to participating in DN. The purpose of the study was to evaluate the relationship between ApoE genetic polymorphism and the presence of DN in Chinese type 2 diabetic patients. We studied 845 diabetic patients who were divided into DN group (n = 429) and control group (n = 416). ApoE genotype was determined by ApoE genotyping chip and the plasmatic biochemical characterization was performed on all subjects...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28326151/chronic-porphyromonas-gingivalis-infection-accelerates-the-occurrence-of-age-related-granules-in-apoe-mice-brains
#10
Sim K Singhrao, Sasanka Chukkapalli, Sophie Poole, Irina Velsko, St John Crean, Lakshmyya Kesavalu
This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE(-/-)) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P...
2017: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/28324763/interaction-of-apoe-e4-and-poor-glycemic-control-predicts-white-matter-hyperintensity-growth-from-73-to-76
#11
Simon R Cox, Stuart J Ritchie, David Alexander Dickie, Alison Pattie, Natalie A Royle, Janie Corley, Benjamin S Aribisala, Sarah E Harris, Maria Valdés Hernández, Alan J Gow, Susana Muñoz Maniega, John M Starr, Mark E Bastin, Joanna M Wardlaw, Ian J Deary
We examined whether apolipoprotein E (APOE) status interacts with vascular risk factors (VRFs) to predict the progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when the risk of dementia increases. At age 73 years, baseline VRFs were assessed via self-reported history of diabetes, hypertension, smoking, and hypercholesterolemia, and via objective measures of blood HbA1c, body mass index, diastolic and systolic blood pressure, and blood high-density lipoprotein to total cholesterol (HDL) ratio...
February 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28324341/beta-amyloid-deposition-in-patients-with-major-depressive-disorder-with-differing-levels-of-treatment-resistance-a-pilot-study
#12
Peng Li, Ing-Tsung Hsiao, Chia-Yih Liu, Chia-Hsiang Chen, She-Yao Huang, Tzu-Chen Yen, Kuan-Yi Wu, Kun-Ju Lin
BACKGROUND: Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using (18)F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33)...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28323832/age-related-cognitive-decline-and-associations-with-sex-education-and-apolipoprotein-e-genotype-across-ethnocultural-groups-and-geographic-regions-a-collaborative-cohort-study
#13
Darren M Lipnicki, John D Crawford, Rajib Dutta, Anbupalam Thalamuthu, Nicole A Kochan, Gavin Andrews, M Fernanda Lima-Costa, Erico Castro-Costa, Carol Brayne, Fiona E Matthews, Blossom C M Stephan, Richard B Lipton, Mindy J Katz, Karen Ritchie, Jacqueline Scali, Marie-Laure Ancelin, Nikolaos Scarmeas, Mary Yannakoulia, Efthimios Dardiotis, Linda C W Lam, Candy H Y Wong, Ada W T Fung, Antonio Guaita, Roberta Vaccaro, Annalisa Davin, Ki Woong Kim, Ji Won Han, Tae Hui Kim, Kaarin J Anstey, Nicolas Cherbuin, Peter Butterworth, Marcia Scazufca, Shuzo Kumagai, Sanmei Chen, Kenji Narazaki, Tze Pin Ng, Qi Gao, Simone Reppermund, Henry Brodaty, Antonio Lobo, Raúl Lopez-Anton, Javier Santabárbara, Perminder S Sachdev
BACKGROUND: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. METHODS AND FINDINGS: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323831/genetic-assessment-of-age-associated-alzheimer-disease-risk-development-and-validation-of-a-polygenic-hazard-score
#14
Rahul S Desikan, Chun Chieh Fan, Yunpeng Wang, Andrew J Schork, Howard J Cabral, L Adrienne Cupples, Wesley K Thompson, Lilah Besser, Walter A Kukull, Dominic Holland, Chi-Hua Chen, James B Brewer, David S Karow, Karolina Kauppi, Aree Witoelar, Celeste M Karch, Luke W Bonham, Jennifer S Yokoyama, Howard J Rosen, Bruce L Miller, William P Dillon, David M Wilson, Christopher P Hess, Margaret Pericak-Vance, Jonathan L Haines, Lindsay A Farrer, Richard Mayeux, John Hardy, Alison M Goate, Bradley T Hyman, Gerard D Schellenberg, Linda K McEvoy, Ole A Andreassen, Anders M Dale
BACKGROUND: Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. METHODS AND FINDINGS: Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer's Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10-5)...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323826/apoe-related-risk-of-mild-cognitive-impairment-and-dementia-for-prevention-trials-an-analysis-of-four-cohorts
#15
Jing Qian, Frank J Wolters, Alexa Beiser, Mary Haan, M Arfan Ikram, Jason Karlawish, Jessica B Langbaum, John M Neuhaus, Eric M Reiman, J Scott Roberts, Sudha Seshadri, Pierre N Tariot, Beth McCarty Woods, Rebecca A Betensky, Deborah Blacker
BACKGROUND: With the onset of prevention trials for individuals at high risk for Alzheimer disease, there is increasing need for accurate risk prediction to inform study design and enrollment, but available risk estimates are limited. We developed risk estimates for the incidence of mild cognitive impairment (MCI) or dementia among cognitively unimpaired individuals by APOE-e4 dose for the genetic disclosure process of the Alzheimer's Prevention Initiative Generation Study, a prevention trial in cognitively unimpaired APOE-e4/e4 homozygote individuals...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323660/impact-of-rare-variants-in-autosomal-dominant-hypercholesterolemia-causing-genes
#16
Sebastiano Calandra, Patrizia Tarugi, Stefano Bertolini
PURPOSE OF REVIEW: The systematic analysis of the major candidate genes in autosomal dominant hypercholesterolemia (ADH) and the use of next-generation sequencing (NGS) technology have made possible the discovery of several rare gene variants whose pathogenic effect in most cases remains poorly defined. RECENT FINDINGS: One major advance in the field has been the adoption of a set of international guidelines for the assignment of pathogenicity to low-density lipoprotein receptor (LDLR) gene variants based on the use of softwares, complemented with data available from literature and public databases...
March 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28323160/effect-of-age-and-the-apoe-gene-on-metabolite-concentrations-in-the-posterior-cingulate-cortex
#17
Sana Suri, Uzay Emir, Charlotte J Stagg, Jamie Near, Ralf Mekle, Florian Schubert, E Zsoldos, Abda Mahmood, Archana Singh-Manoux, Mika Kivimäki, Klaus P Ebmeier, Clare E Mackay, Nicola Filippini
Proton magnetic resonance spectroscopy ((1)H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm(3) voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years)...
March 16, 2017: NeuroImage
https://www.readbyqxmd.com/read/28323011/apocynin-protects-against-neurological-damage-induced-by-quinolinic-acid-by-an-increase-in-glutathione-synthesis-and-nrf2-levels
#18
Silvia Cruz-Álvarez, Ricardo Santana-Martínez, Euclides Avila-Chávez, Diana Barrera-Oviedo, Rogelio Hernández-Pando, José Pedraza-Chaverri, Perla D Maldonado
Apocynin (APO) is a well known NADPH oxidase (NOX) inhibitor. However, several studies have reported its ability to increase glutathione (GSH) levels. Due to GSH is a major non-enzymatic antioxidant in brain, the aim of this study was to evaluate, in the striatum of control and quinolinic acid (QUIN) injected rats, the effect of APO administration on: 1) GSH levels, 2) activity of some enzymes involved in the GSH metabolism, and 3) nuclear factor erythroid-2-related factor 2 (Nrf2) mRNA levels. Animals received QUIN 240 nmol in right striatum and APO (5 mg/kg, i...
March 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28322000/postprandial-triglyceride-rich-lipoproteins-promote-lipid-accumulation-and-apolipoprotein-b-48-receptor-transcriptional-activity-in-human-circulating-and-murine-bone-marrow-neutrophils-in-a-fatty-acid-dependent-manner
#19
Almudena Ortega-Gómez, Lourdes M Varela, Sergio Lopez, Sergio Montserrat de la Paz, Rosario Sanchez, Francisco J G Muriana, Beatriz Bermúdez, Rocío Abia
SCOPE: Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of MUFAs, omega-3 PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. METHODS AND RESULTS: Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe-/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs or SFAs...
March 21, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28321820/apolipoprotein-e4-suppresses-neuronal-specific-gene-expression-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#20
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
The apolipoprotein ε4 gene allele and the apolipoprotein E4 protein (ApoE4) are important host susceptibility factors linked to neurocognitive disorders associated with HIV infection or Alzheimer's disease. Our previous studies showed differential effects of the two most common human ApoE genotypes, APOE3/3 and APOE3/4, on gene expression by differentiating human neuroepithelial progenitor cells continuously exposed to HIV. To investigate the effects of ApoE3 versus ApoE4 isoforms specifically on maturing neurons, we adapted a human neuronal progenitor cell line, hNP1, with ApoE genotype APOE3/3...
March 20, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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