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https://www.readbyqxmd.com/read/29150231/diagnosis-of-hyperferritinemia-in-routine-clinical-practice
#1
Bernard Lorcerie, Sylvain Audia, Maxime Samson, Aurélie Millière, Nicolas Falvo, Vanessa Leguy-Seguin, Sabine Berthier, Bernard Bonnotte
The discovery of hyperferritinemia is often fortuitous, revealed in results from a laboratory screening or follow-up test. The aim of the diagnostic procedure is therefore to identify its cause and to identify or rule out hepatic iron overload, in a three-stage process. In the first step, clinical findings and several simple laboratory tests are sufficient to detect four of the most frequent causes of high ferritin concentrations: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with substantial hepatic iron overload...
November 14, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29141038/depot-specific-inflammation-with-decreased-expression-of-atm2-in-white-adipose-tissues-induced-by-high-margarine-lard-intake
#2
Nannan Wang, Jie Guo, Fuding Liu, Mingxia Wang, Chuntao Li, Lihong Jia, Lingling Zhai, Wei Wei, Yinglong Bai
A high-fat diet has been recognized as an important risk factor of obesity, with variable impacts of different fatty acid compositions on the physiological process. To understand the effects of a high-margarine/lard diet, which is a major source of trans fatty acids (TFAs)/ saturated fatty acids (SFAs), elaidic acid as a biomarker of margarine intake was used to screen affected adipokines on mature human adipocytes in vitro. Weaned male Wistar rats were fed a high-fat diet enriched with margarine/lard to generate obesity-prone (OP) and obesity-resistant (OR) models, which were then used to explore the inflammatory responses of depot-specific white adipose tissue...
2017: PloS One
https://www.readbyqxmd.com/read/29132235/a-cell-based-assay-to-investigate-hypolipidemic-effects-of-nonalcoholic-fatty-liver-disease-therapeutics
#3
Tapan Dave, Arno William Tilles, Muralikrishna Vemula
In the recent past, there has been a growing interest in developing nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) therapeutics. As a result, a need for in vitro cell models of human hepatic steatosis and high-throughput assays to measure intracellular lipid levels has arisen. To address this growing need, we optimized the conditions based on the current literature to fatten HepG2 hepatocytes by adding a mixture of saturated and unsaturated fatty acids (oleate/palmitate, 2:1 molar ratio) without inducing any overt cytotoxicity...
November 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29131645/high-resolution-monitoring-above-and-below-the-groundwater-table-uncovers-small-scale-hydrochemical-gradients
#4
Niklas Gassen, Christian Griebler, Ulrike Werban, Nico Trauth, Christine Stumpp
Hydrochemical solute concentrations in the shallow subsurface can be spatially highly variable within small scales, particularly at interfaces. However, most monitoring systems fail to capture these small scale variations. Within this study, we developed a high resolution multi-level well (HR-MLW) with which we monitored water across the interface of the unsaturated and saturated zone with a vertical resolution of 0.05-0.5 m. We installed three of these 4 m deep HR-MLWs in the riparian zone of a 3rd-order river and analyzed for hydrochemical parameters and stable water isotopes...
November 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29127198/probing-the-metastable-state-of-influenza-hemagglutinin
#5
Carolyn N Kingsley, Aleksandar Antanasijevic, Helena Palka-Hamblin, Matthew Durst, Benjamin Ramirez, Arnon Lavie, Michael Caffrey
Viral entry into host cells is mediated by membrane proteins in a metastable state that transition to a more stable state upon a stimulus. For example, in the influenza envelope protein hemagglutinin (HA), the low pH in the endosome triggers a transition from the metastable prefusion conformation to the stable fusion conformation. To identify probes that interfere with HA function, here we screened a library of H7 HA peptides for inhibition of H7 HA-mediated entry. We discovered a peptide, PEP87 (WSYNAELLVAMENQHTI), that inhibited H7 and H5 HA-mediated entry...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29124283/semi-rational-engineering-of-cyp153a35-to-enhance-%C3%AF-hydroxylation-activity-toward-palmitic-acid
#6
Eunok Jung, Beom Gi Park, Hee-Wang Yoo, Joonwon Kim, Kwon-Young Choi, Byung-Gee Kim
CYP153A35 from Gordonia alkanivorans was recently characterized as fatty acid ω-hydroxylase. To enhance the catalytic activity of CYP153A35 toward palmitic acid, site-directed saturation mutagenesis was attempted using a semi-rational approach that combined structure-based computational analysis and subsequent saturation mutagenesis. Using colorimetric high-throughput screening (HTS) method based on O-demethylation activity of P450, CYP153A35 D131S and D131F mutants were selected. The best mutant, D131S, having a single mutation on BC-loop, showed 13- and 17-fold improvement in total turnover number (TTN) and catalytic efficiency (k cat/K M) toward palmitic acid compared to wild-type, respectively...
November 9, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29113702/mandibular-advancement-for-adult-obstructive-sleep-apnea-a%C3%A2-systematic-review-and-meta-analysis
#7
REVIEW
Michael W Noller, Christian Guilleminault, Christopher J Gouveia, Douglas Mack, Charles Vivian, Jose Abdullatif, Stefano Mangili, Stanley Yung Liu, Soroush Zaghi, Macario Camacho
OBJECTIVES: Patients with mandibular insufficiency can be predisposed to obstructive sleep apnea (OSA). The objective of this study was to systematically review the international literature for mandibular advancement surgeries (MAS) as treatment for adult OSA, and then to perform a meta-analysis. METHODS: Four authors searched five databases from the inception of each database through April 5, 2017. The PRISMA statement was followed. RESULTS: 972 studies were screened, 84 were downloaded, and 11 (57 patients) met criteria...
October 13, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/29110155/streptomyces-swartbergensis-sp-nov-a-novel-tyrosinase-and-antibiotic-producing-actinobacterium
#8
Marilize le Roes-Hill, Alaric Prins, Paul R Meyers
As part of an antibiotic screening program, an actinobacterium, strain HMC13(T), was isolated from soil collected from the banks of the Gamka River, Western Cape Province, South Africa. The isolate was found to produce branched mycelia that differentiated into spiral spore chains with spiny spores. 16S rRNA gene sequence analysis showed the strain to be closely related to Streptomyces caelestis NRRL 2418(T) (99.72%) and Streptomyces azureus NBRC 12744(T) (99.51%). Chemotaxonomic analyses confirmed the classification of the strain as a member of the genus Streptomyces: LL-DAP in the peptidoglycan, no diagnostic sugars in the whole cell sugar pattern, dominant menaquinones including MK9(H8), MK9(H6), and the polar lipids detected included phosphatidylethanolamine...
November 6, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/29108931/binding-of-human-plasminogen-by-the-lipoprotein-lipl46-of-leptospira-interrogans
#9
Jadson V Santos, Priscila R M Pereira, Luis G V Fernandes, Gabriela Hase Siqueira, Gisele O de Souza, Antônio Souza Filho, Silvio A Vasconcellos, Marcos B Heinemann, Erica G B Chapola, Ana L T O Nascimento
Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira. Bacteria disseminate via the bloodstream and colonize the renal tubules of reservoir hosts. Leptospiral surface-exposed proteins are important targets, because due to their location they can elicit immune response and mediate adhesion and invasion processes. LipL46 has been previously reported to be located at the leptospiral outer membrane and recognized by antibodies present in serum of infected hamsters. In this study, we have confirmed the cellular location of this protein by immunofluorescence and FACS...
November 4, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29104937/novel-genes-required-for-the-fitness-of-streptococcus-pyogenes-in-human-saliva
#10
Luchang Zhu, Amelia R L Charbonneau, Andrew S Waller, Randall J Olsen, Stephen B Beres, James M Musser
Streptococcus pyogenes (group A streptococcus [GAS]) causes 600 million cases of pharyngitis each year. Despite this considerable disease burden, the molecular mechanisms used by GAS to infect, cause clinical pharyngitis, and persist in the human oropharynx are poorly understood. Saliva is ubiquitous in the human oropharynx and is the first material GAS encounters in the upper respiratory tract. Thus, a fuller understanding of how GAS survives and proliferates in saliva may provide valuable insights into the molecular mechanisms at work in the human oropharynx...
November 2017: MSphere
https://www.readbyqxmd.com/read/29102990/process-evaluation-of-a-primary-healthcare-validation-study-of-a-culturally-adapted-depression-screening-tool-for-use-by-aboriginal-and-torres-strait-islander-people-study-protocol
#11
Sara Farnbach, John Evans, Anne-Marie Eades, Graham Gee, Jamie Fernando, Belinda Hammond, Matty Simms, Karrina DeMasi, Maree Hackett
INTRODUCTION: Process evaluations are conducted alongside research projects to identify the context, impact and consequences of research, determine whether it was conducted per protocol and to understand how, why and for whom an intervention is effective. We present a process evaluation protocol for the Getting it Right research project, which aims to determine validity of a culturally adapted depression screening tool for use by Aboriginal and Torres Strait Islander people. In this process evaluation, we aim to: (1) explore the context, impact and consequences of conducting Getting It Right, (2) explore primary healthcare staff and community representatives' experiences with the research project, (3) determine if it was conducted per protocol and (4) explore experiences with the depression screening tool, including perceptions about how it could be implemented into practice (if found to be valid)...
November 3, 2017: BMJ Open
https://www.readbyqxmd.com/read/29101207/the-ferroportin-disease-pathogenesis-diagnosis-and-treatment
#12
Antonello Pietrangelo
The Ferroportin Disease is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of commonest cause of genetic hyperferritinemia, regardless of ethnicity. FPN1 transfers iron from the intestine, macrophages and placenta into the bloodstream. In the ferroportin disease, loss-of-function mutations of FPN1 limit but do not impair iron-export in enterocytes, but severely affects iron-transfer in macrophages. This leads to progressive and preferential iron trapping in tissue macrophages, reduced iron release to serum transferrin (i...
November 3, 2017: Haematologica
https://www.readbyqxmd.com/read/29100914/powder-flow-analysis-a-simple-method-to-indicate-the-ideal-amount-of-lactose-fines-in-dry-powder-inhaler-formulations
#13
Mats Hertel, Eugen Schwarz, Mirjam Kobler, Sabine Hauptstein, Hartwig Steckel, Regina Scherließ
Many efforts have been made in the past to understand the function of lactose fines which are given as a ternary component to carrier-based dry powder inhaler formulations. It is undisputed that fines can significantly improve the performance of such formulations, but choosing the right amount of fines is a crucial point, because too high concentrations can have negative effects on the dispersion performance. The aim of this study was to indicate the optimal concentration of fines with a simple test method...
October 31, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29095663/solvent-extraction-and-gas-chromatography-mass-spectrometry-analysis-of-annona-squamosa-l-seeds-for-determination-of-bioactives-fatty-acid-fatty-oil-composition-and-antioxidant-activity
#14
Mohammad Zahid, Muhammad Arif, Md Akhlaquer Rahman, Kuldeep Singh, Mohd Mujahid
The yield and fatty oil components of the seed kernels of Annona squamosa L. (Family: Annonaceae) were determined by solvent extraction method and gas chromatography-mass spectrometry (GC-MS). Seeds were extracted with ethanol and further fractionated with n-hexane. The free radical-scavenging activities of both ethanolic and n-hexane fraction against 1, 1-diphenyl-2-picrylhydrazyl (DPPH) were determined by UV spectrophotometer at 517 nm. Phytochemical screening revealed the presence of numerous bioactive compounds including steroids, flavonoids, terpenoids, fatty acids, and different types of ester compounds...
November 2, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/29091003/american-college-of-radiology-compliant-short-protocol-breast-mri-for-high-risk-breast-cancer-screening-a-prospective-feasibility-study
#15
Basak E Dogan, Marion E Scoggins, Jong Bum Son, Wei Wei, Rosalind Candelaria, Wei T Yang, Jingfei Ma
OBJECTIVE: The purpose of this study was to assess the feasibility of a short protocol for screening breast MRI that is noninferior to standard-of-care (SOC) MRI in image quality that complies with American College of Radiology accreditation requirements. SUBJECTS AND METHODS: In a prospective feasibility trial, 23 women at high risk underwent both an initial SOC MRI examination that included axial iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) and T1-weighted volume imaging for breast assessment (VIBRANT) dynamic contrast-enhanced sequences and a separate short breast MRI protocol comprising a fast spin-echo (FSE) triple-echo Dixon T2 sequence for T2-weighted imaging and a 3D dual-echo fast spoiled gradient-echo two-point Dixon sequence for dynamic contrast-enhanced imaging from October 1, 2015, through May 2, 2016...
November 1, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/29089306/organic-cation-transporter-1-is-responsible-for-hepatocellular-uptake-of-the-tyrosine-kinase-inhibitor-pazopanib
#16
Waleed Elsayed Ahmed Ellawatty, Yusuke Masuo, Ken-Ichi Fujita, Erina Yamazaki, Hiroo Ishida, Hiroshi Arakawa, Noritaka Nakamichi, Ramadan Abdelwahed, Yasutsuna Sasaki, Yukio Kato
Pazopanib is an orally active tyrosine kinase inhibitor that exhibits hepatotoxicity in some patients. Despite the clinical importance of its hepatic distribution, the transporter(s) responsible for hepatic uptake of pazopanib in humans remain undetermined. In order to characterize its hepatic uptake mechanism, we screened the effects of several transporter inhibitors, including tetrapentylammonium (TPeA) for organic cation transporters (OCTs) and cyclosporin A (CsA) for organic anion-transporting polypeptides (OATPs), on both plasma disappearance and hepatic distribution of pazopanib in mice after its intravenous administration...
October 31, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29082489/quality-control-for-high-throughput-imaging-experiments-using-machine-learning-in-cellprofiler
#17
Mark-Anthony Bray, Anne E Carpenter
Robust high-content screening of visual cellular phenotypes has been enabled by automated microscopy and quantitative image analysis. The identification and removal of common image-based aberrations is critical to the screening workflow. Out-of-focus images, debris, and auto-fluorescing samples can cause artifacts such as focus blur and image saturation, contaminating downstream analysis and impairing identification of subtle phenotypes. Here, we describe an automated quality control protocol implemented in validated open-source software, leveraging the suite of image-based measurements generated by CellProfiler and the machine-learning functionality of CellProfiler Analyst...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29082479/visualizing-soluble-protein-mutants-by-using-monomeric-red-fluorescent-protein-as-a-reporter-for-directed-evolution
#18
Xueying Wang, Lei Wang, Xinping Lin, Xiaobing Yang, Wujun Liu, Zongbao K Zhao
Directed evolution-based protein engineering usually generates large library contained insoluble mutants because of structural disturbance by mutation. To reduce the workload and costs, it is crucial to identify and eliminate those insoluble variants prior to dedicated analysis. Here, we demonstrate a method to visualize soluble protein mutants by using monomeric red fluorescent protein (mRFP) as a fusion tag. A plasmid was devised to express nicotinic acid mononucleotide adenylyltransferase (NadD) fused with a GGGS-linked mRFP tag at the C-terminus...
October 30, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29078379/controlling-orientational-order-in-block-copolymers-using-low-intensity-magnetic-fields
#19
Manesh Gopinadhan, Youngwoo Choo, Kohsuke Kawabata, Gilad Kaufman, Xunda Feng, Xiaojun Di, Yekaterina Rokhlenko, Lalit H Mahajan, Dennis Ndaya, Rajeswari M Kasi, Chinedum O Osuji
The interaction of fields with condensed matter during phase transitions produces a rich variety of physical phenomena. Self-assembly of liquid crystalline block copolymers (LC BCPs) in the presence of a magnetic field, for example, can result in highly oriented microstructures due to the LC BCP's anisotropic magnetic susceptibility. We show that such oriented mesophases can be produced using low-intensity fields (<0.5 T) that are accessible using permanent magnets, in contrast to the high fields (>4 T) and superconducting magnets required to date...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29078326/crispr-cas9-mediated-saturated-mutagenesis-screen-predicts-clinical-drug-resistance-with-improved-accuracy
#20
Leyuan Ma, Jeffrey I Boucher, Janet Paulsen, Sebastian Matuszewski, Christopher A Eide, Jianhong Ou, Garrett Eickelberg, Richard D Press, Lihua Julie Zhu, Brian J Druker, Susan Branford, Scot A Wolfe, Jeffrey D Jensen, Celia A Schiffer, Michael R Green, Daniel N Bolon
Developing tools to accurately predict the clinical prevalence of drug-resistant mutations is a key step toward generating more effective therapeutics. Here we describe a high-throughput CRISPR-Cas9-based saturated mutagenesis approach to generate comprehensive libraries of point mutations at a defined genomic location and systematically study their effect on cell growth. As proof of concept, we mutagenized a selected region within the leukemic oncogene BCR-ABL1 Using bulk competitions with a deep-sequencing readout, we analyzed hundreds of mutations under multiple drug conditions and found that the effects of mutations on growth in the presence or absence of drug were critical for predicting clinically relevant resistant mutations, many of which were cancer adaptive in the absence of drug pressure...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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