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https://www.readbyqxmd.com/read/29151159/enhanced-catalytic-efficiency-and-enantioselectivity-of-epoxide-hydrolase-from-agrobacterium-radiobacter-ad1-by-iterative-saturation-mutagenesis-for-r-epichlorohydrin-synthesis
#1
Shu-Ping Zou, Yu-Guo Zheng, Qun Wu, Zhi-Cai Wang, Ya-Ping Xue, Zhi-Qiang Liu
Enantioselective hydrolysis of epoxides by epoxide hydrolase (EH) is one of the most attractive approaches for the synthesis of chiral epoxides. So far, attempts to develop an efficient epoxide hydrolase -mediated biotransformation have been limited by either the low activity or insufficient enantioselectivity of epoxide hydrolase. In this study, iterative saturation mutagenesis (ISM) of epoxide hydrolase from Agrobacterium radiobacter AD1 (ArEH) was performed for efficient production of (R)-epichlorohydrin...
November 18, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29150773/overexpression-of-a-cellobiose-glucose-halotolerant-endoglucanase-from-scytalidium-thermophilum
#2
Luana Parras Meleiro, Sibeli Carli, Raquel Fonseca-Maldonado, Marcela da Silva Torricillas, Ana Lucia Ribeiro Latorre Zimbardi, Richard John Ward, João Atílio Jorge, Rosa Prazeres Melo Furriel
Enzyme reaction products and by-products from pretreatment steps can inhibit endoglucanases and are major factors limiting the efficiency of enzymatic lignocellulosic biomass hydrolysis. The gene encoding the endoglucanase from Scytalidium thermophilum (egst) was cloned and expressed as a soluble protein in Pichia pastoris GS115. The recombinant enzyme (Egst) was monomeric (66 kDa) and showed an estimated carbohydrate content of 53.3% (w/w). The optimum temperature and pH of catalysis were 60-70 °C and pH of 5...
November 18, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29150589/change-in-hydration-indices-associated-with-an-increase-in-total-water-intake-of-more-than-0-5%C3%A2-l-day-sustained-over-4%C3%A2-weeks-in-healthy-young-men-with-initial-total-water-intake-below-2%C3%A2-l-day
#3
Jodi D Stookey, Janice Hamer, David W Killilea
This secondary data analysis addressed gaps in knowledge about effects of chronic water intake. Longitudinal data from the Adapt Study were used to describe effects of prescribing a sustained increase in water intake relative to baseline, for 4 weeks, on multiple indices of total body water (TBW) flux, regulation, distribution, and volume in five healthy, free-living, young men, with mean total water intake initially below 2 L/day. Indices were measured weekly. Within-person fixed effect models tested for significant changes in indices over time and associations between changes in indices...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29150543/toxicokinetics-and-physiologically-based-pharmacokinetic-modeling-of-the-shellfish-toxin-domoic-acid-in-nonhuman-primates
#4
Jing Jing, Rebekah Petroff, Sara Shum, Brenda Crouthamel, Ariel R Topletz, Kimberly S Grant, Thomas M Burbacher, Nina Isoherranen
Domoic acid (DA), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. However, the toxicokinetics of DA has not been fully evaluated, and information is missing on the disposition of DA following oral exposures at doses that are considered safe for human consumption. In this study, toxicokinetics of DA were investigated in cynomolgus monkeys, following single doses of 5 µg/kg DA iv, 0.075 mg/kg DA po and 0.15 mg/kg DA po. Following iv dosing, DA had a systemic clearance of 124 ± 71 ml/hr/kg, volume of distribution at steady state of 131±71 ml/kg and elimination half-life of 1...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29149425/correction-to-efficacy-and-safety-of-full-length-pegylated-recombinant-factor-viii-with-extended-half-life-in-previously-treated-patients-with-hemophilia-a-comparison-of-data-between-the-general-and-japanese-study-populations
#5
Keiji Nogami, Midori Shima, Katsuyuki Fukutake, Teruhisa Fujii, Masashi Taki, Tadashi Matsushita, Satoshi Higasa, Tetsuji Sato, Michio Sakai, Morio Arai, Haruhiko Uchikawa, Werner Engl, Brigitt Abbuehl, Barbara A Konkle
The authors would like to correct the error in Table 2 in the original publication of the article. The "Blood type" is not described in any part of "Results" and "Discussion" and had no impact on the conclusion hence the bottom of the table is removed.
November 17, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29149420/blood-clearance-and-occupational-exposure-for-177-lu-dotatate-compared-to-177-lu-psma-radionuclide-therapy
#6
Mohammad Abuqbeitah, Mustafa Demir, Lebriz Uslu-Beşli, Nami Yeyin, Kerim Sönmezoğlu
The main target of this work is to examine blood clearance and external exposure for (177)Lu-DOTATATE compared with new emerging (177)Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5 ± 1.1 GBq (177)Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq (177)Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver's cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4-5 days and medical staff's dose was also estimated using electronic personal dosimeters...
November 17, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29147673/the-regulation-of-snail-on-the-ubiquitin-edge
#7
Qian Yu, Binhua P Zhou, Yadi Wu
Metastasis accounts for a majority of cancer death. One key feature during metastasis is epithelial-mesenchymal transition (EMT), which is regulated by transcription factors such as Snail and Twist. In non-malignant cells, Snail has a short half-life and is degraded via ubiquitination, but its stability is increased in cancer cell. However, the mechanism by which Snail escapes ubiquitination and degradation remains unknown. Recently, we found that Dub3 is a deubiquinase of Snail. Most importantly, we determined that Dub3 responded to extracellular signals such as IL-6, and that the resultant signaling prevented Snail degradation, and promoted cancer growth, invasion, and migration...
2017: Cancer Cell & Microenvironment
https://www.readbyqxmd.com/read/29145616/variation-in-methylmercury-metabolism-and-elimination-status-mermes-in-humans-following-fish-consumption
#8
Samuel W Caito, Brian P Jackson, Tracy Punshon, Thomas Scrimale, Alex Grier, Steven R Gill, Tanzy M Love, Gene E Watson, Edwin van Wijngaarden, Matthew D Rand
Evaluating the potential for methylmercury (MeHg) toxicity relies on accurately predicting the mercury (Hg) body burden that results from eating fish. Hg body burden is directly determined by the slow elimination kinetics of MeHg in the human body (kel ∼0.014days-1 or t1/2∼ 50days). Existing studies on MeHg half-life in humans demonstrate a wide range values (t1/2 = 30 to > 150days) and has lead to uncertainty in the derivation of a regulatory standard for acceptable daily oral intake. The causes of variation in MeHg toxicokinetics in humans remain little explored...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29145196/aqp2-abundance-is-regulated-by-the-e3-ligase-chip-via-hsp70
#9
Mariangela Centrone, Marianna Ranieri, Annarita Di Mise, Sante Princiero Berlingerio, Annamaria Russo, Peter M T Deen, Olivier Staub, Giovanna Valenti, Grazia Tamma
BACKGROUND/AIMS: AQP2 expression is mainly controlled by vasopressin-dependent changes in protein abundance which is in turn regulated by AQP2 ubiquitylation and degradation, however the proteins involved in these processes are largely unknown. Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation. METHODS: MCD4 cells and kidney slices were used to study the involvement of the E3 ligase CHIP on AQP2 protein abundance by cell homogenization and immunoprecipitation followed by immunoblotting...
November 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29141139/the-effect-of-synthetic-high-density-lipoproteins-modification-with-polyethylene-glycol-on-pharmacokinetics-and-pharmacodynamics
#10
Dan Li, Maria V Fawaz, Emily E Morin, Ran Ming, Denis Sviridov, Jie Tang, Rose Ackerman, Karl Olsen, Alan T Remaley, Anna Schwendeman
Synthetic high density lipoprotein nanoparticles (sHDL) capable of mobilizing excess cholesterol from atherosclerotic arteries and delivering it to the liver for elimination have been shown to reduce plaque burden in patients. Unfortunately, sHDLs have a narrow therapeutic index and relative to the endogenous HDL shorter circulation half-life. Surface modification with polyethylene glycol (PEG) was investigated for its potential to extend sHDL circulation in vivo. Various amounts (2.5, 5 and 10%) and different chain lengths (2 and 5 kDa) of PEG-modified lipids were incorporated in sHDL's lipid membrane...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29140865/influence-of-syringe-volume-on-foam-stability-in-sclerotherapy-for-varicose-vein-treatment
#11
Taoping Bai, Wentao Jiang, Yubo Fan
BACKGROUND: Despite the popularity of sclerotherapy for treating varicose veins, it still exhibits various problems, such as pulmonary embolism, deep-vein thrombosis, phlebitis, and visual disorders. OBJECTIVE: To investigate syringe volume influence on foam stability, obtain the foam decay rule, and provide a reference for clinics. MATERIALS AND METHODS: Five types of syringes are used to prepare foam at room temperature with various liquid-gas ratios...
November 14, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/29140548/a-phase-ib-open-label-single-arm-study-to-assess-the-safety-pharmacokinetics-and-impact-on-humoral-sensitization-of-sanguinate-infusion-in-patients-with-end-stage-renal-disease
#12
Bassam G Abu Jawdeh, E Steve Woodle, Abbie D Leino, Paul Brailey, Simon Tremblay, Tonya Dorst, Mouhamad H Abdallah, Amit Govil, Daniel Byczkowski, Hemant Misra, Abraham Abuchowski, Rita R Alloway
The endeavor to study desensitization in kidney transplantation hasn't been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive 3 weekly infusions of SG (320mg/Kg)...
November 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29140073/3-dimensional-enzyme-biohydrogel-electrode-for-improved-bioelectrocatalysis
#13
Ananta Ghimire, Ajith Pattammattel, Charles Maher, Rajeswari Kasi, Challa V Kumar
Higher loading of enzymes on electrode and efficient electron transfer from the enzyme to the electrode are urgently needed to enhance the current density of biofuel cells. The two-dimensional nature of electrode surface limits the enzyme loading on the surface and unfavorable interaction with electrode surfaces cause inactivation of the enzyme. Benign biohydrogels are designed here to address enzyme degradation and the three-dimensional nature of the biohydrogel enhanced the enzyme density per unit area. A general strategy is demonstrated here using a redox active enzyme glucose oxidase (GOx) embedded in bovine serum albumin (BSA) biohydrogel on flexible carbon cloth (CC) electrodes...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29139314/cost-utility-analysis-of-life-long-prophylaxis-with-recombinant-factor-viii-fc-vs-recombinant-factor-viii-for-the-management-of-severe-haemophilia-a-in-sweden
#14
Nathaniel Henry, Jelena Jovanović, Max Schlueter, Persefoni Kritikou, Koo Wilson, Karl-Johan Myrén
AIMS: Prophylaxis with recombinant factor VIII (rFVIII) is the standard of care for severe haemophilia A in Sweden. The need for frequent injections with existing rFVIII products may, however, result in poor adherence to prophylaxis leading to increased bleeding and long-term joint damage. Recombinant FVIIIFc (rFVIIIFc) is an extended half-life fusion protein which can offer prolonged protection and reduced dosing frequency. The objective of this study was to evaluate the cost-utility of prophylaxis with rFVIIIFc in severe haemophilia A from the perspective of the Swedish health system...
November 15, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/29139136/tilmicosin-and-florfenicol-loaded-hydrogenated-castor-oil-solid-lipid-nanoparticles-to-pigs-combined-antibacterial-activities-and-pharmacokinetics
#15
Z Ling, L Yonghong, L Junfeng, Z Li, L Xianqiang
The combined antibacterial effects of tilmicosin (TIL) and florfenicol (FF) against Actinobacillus pleuropneumoniae (APP) (n = 2), Streptococcus suis (S. suis) (n = 2), and Haemophilus parasuis (HPS) (n = 2) were evaluated by chekerboard test and time-kill assays. The pharmacokinetics (PKs) of TIL- and FF-loaded hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) were performed in healthy pigs. The results indicated that TIL and FF showed synergistic or additive antibacterial activities against APP, S...
November 15, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29137993/characterization-of-cold-adapted-and-ethanol-tolerant-%C3%AE-glucosidase-from-bacillus-cellulosilyticus-and-its-application-for-directed-hydrolysis-of-cellobiose-to-ethanol
#16
Jian Wu, Alei Geng, Rongrong Xie, Hongcheng Wang, Jianzhong Sun
A β-glucosidase gene from Bacillus cellulosilyticus was expressed in Escherichia coli BL21 and characterized. The recombinant enzyme (BcBgl1A) showed the optimal activity at 40°C, and the half-life of BcBgl1A activity at 40 °C was 24 h. BcBgl1A was sensitive to heat and exhibited obvious cold-adapted activity, retained 27.2% and 46.5% of the optimal activity at 4 and 20°C, respectively. The best activity was observed at pH 7.0 and stable over the range of pH 6.0-8.0. The activity was significantly enhanced by Fe(2+), Fe(3+) and Mn(2+), also showed a high level of NaCl tolerance...
November 11, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29137239/transcriptome-profiling-in-preadipocytes-identifies-long-noncoding-rnas-as-sam68-targets
#17
Naomi Li, Steven Hébert, Jingwen Song, Claudia L Kleinman, Stéphane Richard
The KH-type RNA binding protein Sam68 is required for adipogenesis. We have previously shown that Sam68-deficient mice have a lean phenotype and are protected against dietary-induced obesity due to defects in mTOR and S6K1 alternative splicing. Herein we profiled the transcriptome of Sam68 wild type and deficient 3T3-L1 mouse preadipocytes. We identified 652 protein-coding genes and 9 ncRNAs that were significantly altered with the loss of Sam68. As expected, downregulated genes were significantly associated with GO terms linked to cell migration, motility, and fat cell differentiation, while upregulated genes were mostly associated with GO terms linked to neurogenesis...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137047/massive-neonatal-intracranial-hemorrhage-caused-by-bromadiolone-a-case-report
#18
Mingsheng Ma, Mengqi Zhang, Xiaoyan Tang, Zhenghong Li
RATIONALE: Bromadiolone, often called a super-warfarin, is a potent rodenticide with long half-life. Skin and mucosal bleeding is the most common clinical manifestations of its intoxication. Bromadiolone intoxications in adults and children have been reported, but this phenomenon is rarely seen in fetuses. This paper presents a case of neonate with massive intracranial hemorrhage mediated by bromadiolone intoxication, highlighting that the bromadiolone is potentially lethal to the fetus...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29136641/radioactive-contamination-in-the-tokyo-metropolitan-area-in-the-early-stage-of-the-fukushima-daiichi-nuclear-power-plant-fdnpp-accident-and-its-fluctuation-over-five-years
#19
Masanobu Ishida, Hideo Yamazaki
Radioactive contamination in the Tokyo metropolitan area in the immediate aftermath of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident was analyzed via surface soil sampled during a two-month period after the accident. 131I, 134Cs, and 137Cs were detected in these soil samples. The activity and inventory of radioactive material in the eastern part of Tokyo tended to be high. The 134Cs/137Cs activity ratio in soil was 0.978 ± 0.053. The 131I/137Cs ratio fluctuated widely, and was 19.7 ± 9.0 (weighted average 18...
2017: PloS One
https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#20
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
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