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https://www.readbyqxmd.com/read/29439563/co-compartmentation-of-terpene-biosynthesis-and-storage-via-synthetic-droplet
#1
Cheng Zhao, Yongkyoung Kim, Yining Zeng, Man Li, Xin Wang, Cheng Hu, Connor Gorman, Susie Y Dai, Shi-You Ding, Joshua S Yuan
Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene...
February 13, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29408882/modeling-for-influenza-vaccines-and-adjuvants-profile-for-safety-prediction-system-using-gene-expression-profiling-and-statistical-tools
#2
Eita Sasaki, Haruka Momose, Yuki Hiradate, Keiko Furuhata, Mamiko Takai, Hideki Asanuma, Ken J Ishii, Takuo Mizukami, Isao Hamaguchi
Historically, vaccine safety assessments have been conducted by animal testing (e.g., quality control tests and adjuvant development). However, classical evaluation methods do not provide sufficient information to make treatment decisions. We previously identified biomarker genes as novel safety markers. Here, we developed a practical safety assessment system used to evaluate the intramuscular, intraperitoneal, and nasal inoculation routes to provide robust and comprehensive safety data. Influenza vaccines were used as model vaccines...
2018: PloS One
https://www.readbyqxmd.com/read/29396745/high-level-recombinant-production-of-squalene-using-selected-saccharomyces-cerevisiae-strains
#3
Jong Yun Han, Sung Hwa Seo, Jae Myeong Song, Hongweon Lee, Eui-Sung Choi
For recombinant production of squalene, which is a triterpenoid compound with increasing industrial applications, in microorganisms generally recognized as safe, we screened Saccharomyces cerevisiae strains to determine their suitability. A strong strain dependence was observed in squalene productivity among Saccharomyces cerevisiae strains upon overexpression of genes important for isoprenoid biosynthesis. In particular, a high level of squalene production (400 ± 45 mg/L) was obtained in shake flasks with the Y2805 strain overexpressing genes encoding a bacterial farnesyl diphosphate synthase (ispA) and a truncated form of hydroxyl-3-methylglutaryl-CoA reductase (tHMG1)...
February 2, 2018: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29386070/down-selecting-adjuvanted-vaccine-formulations-a-comparative-method-for-harmonized-evaluation
#4
Sumera Y Younis, Christophe Barnier-Quer, Simon Heuking, Vinod Sommandas, Livia Brunner, Nicole Vd Werff, Patrice Dubois, Martin Friede, Clemens Kocken, Nicolas Collin, Ed Remarque
BACKGROUND: The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a harmonized fashion. Three reference antigens: Plasmodium falciparum apical membrane antigen 1 (AMA1), hepatitis B virus surface antigen (HBsAg), and Mycobacterium tuberculosis antigen 85A (Ag85A), were selected as model antigens and were each formulated with three adjuvants: aluminium oxyhydroxide, squalene-in-water emulsion, and a liposome formulation mixed with the purified saponin fraction QS21...
January 31, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29382150/cloning-expression-analysis-and-functional-characterization-of-squalene-synthase-sqs-from-tripterygium-wilfordii
#5
Bin Zhang, Yan Liu, Mengmeng Chen, Juntao Feng, Zhiqing Ma, Xing Zhang, Chuanshu Zhu
Celastrol is an active triterpenoid compound derived from Tripterygium wilfordii which is well-known as a traditional Chinese medicinal plant. Squalene synthase has a vital role in condensing two molecules of farnesyl diphosphate to form squalene, a key precursor of triterpenoid biosynthesis. In the present study, T. wilfordii squalene synthase (TwSQS) was cloned followed by prokaryotic expression and functional verification. The open reading frame cDNA of TwSQS was 1242 bp encoding 413 amino acids. Bioinformatic and phylogenetic analysis showed that TwSQS had high homology with other plant SQSs...
January 29, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29374458/unique-depot-formed-by-an-oil-based-vaccine-facilitates-active-antigen-uptake-and-provides-effective-tumour-control
#6
Kimberly D Brewer, Genevieve M Weir, Iulia Dude, Christa Davis, Cathryn Parsons, Andrea Penwell, Rajkannan Rajagopalan, Leeladhar Sammatur, Chris V Bowen, Marianne M Stanford
BACKGROUND: Oil emulsions are commonly used as vaccine delivery platforms to facilitate slow release of antigen by forming a depot at the injection site. Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the antigen is passively released. DepoVax™ is a unique oil based delivery system that directly suspends the vaccine components in the oil diluent that forces immune cells to actively take up components from the formulation in the absence of passive release...
January 27, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29362090/nerolidol-production-in-agroinfiltrated-tobacco-impact-of-protein-stability-and-membrane-targeting-of-strawberry-fragraria-ananassa-nerolidol-synthase1
#7
Paola Andrade, David Manzano, Karla Ramirez-Estrada, Daniel Caudepon, Montserrat Arro, Albert Ferrer, Michael A Phillips
The sesquiterpene alcohol nerolidol, synthesized from farnesyl diphosphate (FDP), mediates plant-insect interactions across multiple trophic levels with major implications for pest management in agriculture. We compared nerolidol engineering strategies in tobacco using agroinfiltration to transiently express strawberry (Fragraria ananassa) linalool/nerolidol synthase (FaNES1) either at the endoplasmic reticulum (ER) or in the cytosol as a soluble protein. Using solid phase microextraction and gas chromatography-mass spectrometry (SPME-GCMS), we have determined that FaNES1 directed to the ER via fusion to the transmembrane domain of squalene synthase or hydroxymethylglutaryl - CoA reductase displayed significant improvements in terms of transcript levels, protein accumulation, and volatile production when compared to its cytosolic form...
February 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29355536/a-mathematical-model-of-the-mevalonate-cholesterol-biosynthesis-pathway
#8
Frances Pool, Richard Currie, Peter K Sweby, José Domingo Salazar, Marcus J Tindall
We formulate, parameterise and analyse a mathematical model of the mevalonate pathway, a key pathway in the synthesis of cholesterol. Of high clinical importance, the pathway incorporates rate limiting enzymatic reactions with multiple negative feedbacks. In this work we investigate the pathway dynamics and demonstrate that rate limiting steps and negative feedbacks within it act in concert to tightly regulate intracellular cholesterol levels. Formulated using the theory of nonlinear ordinary differential equations and parameterised in the context of a hepatocyte, the governing equations are analysed numerically and analytically...
January 17, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29340843/phytoene-production-utilizing-the-isoprenoid-biosynthesis-capacity-of-thermococcus-kodakarensis
#9
Tsubasa Fuke, Takaaki Sato, Savyasachee Jha, Myra L Tansengco, Haruyuki Atomi
Phytoene (C40H64) is an isoprenoid and a precursor of various carotenoids which are of industrial value. Archaea can be considered to exhibit a relatively large capacity to produce isoprenoids, as they are components of their membrane lipids. Here, we aimed to produce isoprenoids such as phytoene in the hyperthermophilic archaeon Thermococcus kodakarensis. T. kodakarensis harbors a prenyltransferase gene involved in the biosynthesis of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are precursors of squalene and phytoene, respectively...
January 16, 2018: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/29337601/mango-kernel-fat-fractions-as-potential-healthy-food-ingredients-a-review
#10
Jun Jin, Qingzhe Jin, Casimir C Akoh, Xingguo Wang
Mango kernel fat (MKF) has been reported to have high functional and nutritional potential. However, its application in food industry has not been fully explored or developed. In this review, the chemical compositions, physical properties and potential health benefits of MKF are described. MKF is a unique fat consisting of 28.9-65.0% of 1,3-distearoyl-2-oleoyl-glycerol with excellent oxidative stability index (58.8-85.2 h at 110 °C), making the fat and its fractions suitable for use as high-value added food ingredients such as cocoa butter alternatives, trans-free shortenings, and a source of natural antioxidants (e...
January 16, 2018: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/29332796/direct-olive-oil-analysis-by-mass-spectrometry-a-comparison-of-different-ambient-ionization-methods
#11
Felipe J Lara-Ortega, Miriam Beneito-Cambra, José Robles-Molina, Juan F García-Reyes, Bienvenida Gilbert-López, Antonio Molina-Díaz
Analytical methods based on ambient ionization mass spectrometry (AIMS) combine the classic outstanding performance of mass spectrometry in terms of sensitivity and selectivity along with convenient features related to the lack of sample workup required. In this work, the performance of different mass spectrometry-based methods has been assessed for the direct analyses of virgin olive oil for quality purposes. Two sets of experiments have been setup: (1) direct analysis of untreated olive oil using AIMS methods such as Low-Temperature Plasma Mass Spectrometry (LTP-MS) or paper spray mass spectrometry (PS-MS); or alternatively (2) the use of atmospheric pressure ionization (API) mass spectrometry by direct infusion of a diluted sample through either atmospheric pressure chemical ionization (APCI) or electrospray (ESI) ionization sources...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29331331/interaction-of-ceramides-and-tear-lipocalin
#12
Ben J Glasgow, Adil R Abduragimov
The distribution of lipids in tears is critical to their function. Lipids in human tears may retard evaporation by forming a surface barrier at the air interface. Lipids complexed with the major lipid binding protein in tears, tear lipocalin, reside in the bulk (aqueous) and may have functions unrelated to the surface. Many new lipids species have been revealed through recent mass spectrometric studies. Their association with lipid binding proteins has not been studied. Squalene, (O-acyl) omega-hydroxy fatty acids (OAHFA) and ceramides are examples...
January 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29327259/5-aminolevulinic-acid-squalene-nanoassemblies-for-tumor-photodetection-and-therapy-in-vitro-studies
#13
Andrej Babič, V Herceg, E Bastien, H-P Lassalle, L Bezdetnaya, Norbert Lange
Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and photodynamic therapy of several cancers. However, broader use of 5-ALA in oncology is hampered by its charge and polarity that result in its reduced capacity for passing biological barriers and reaching the tumor tissue. Advanced drug delivery platforms are needed to improve the biodistribution of 5-ALA. Here, we report a new approach for the delivery of 5-ALA...
January 11, 2018: Nanoscale Research Letters
https://www.readbyqxmd.com/read/29314179/an-in-vitro-oxidation-model-for-uhmwpe-incorporating-synovial-fluid-lipids
#14
Ebru Oral, Mitchell Fung, Shannon L Rowell, Orhun K Muratoglu
Post-irradiation melting of ultra-high molecular weight polyethylene (UHMWPE) reduced the oxidation potential of UHMWPE in vivo. After mid-term (5- 10 yrs) use in vivo, there is detectable oxidation in irradiated and melted joint implant retrievals. The absorption of the synovial fluid lipid squalene was identified as a possible factor initiating oxidation. We investigated the role of lipids in UHMWPE oxidation by asking: (1) Do other synovial fluid lipids initiate oxidation in irradiated and melted UHMWPE?; (2) What is the effect of the absorption of multiple lipids on UHMWPE oxidation?; (3) How does lipid-initiated oxidation in vitro compare to what is observed in long-term retrievals? We diffused emulsified single and mixed lipids into irradiated and melted UHMWPE and accelerated aged them...
January 4, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29311242/vaccine-linked-chemotherapy-improves-benznidazole-efficacy-for-acute-chagas-disease
#15
Kathryn Jones, Leroy Versteeg, Ashish Damania, Brian Keegan, April Kendricks, Jeroen Pollet, Julio Vladimir Cruz-Chan, Fabian Gusovsky, Peter J Hotez, Maria Elena Bottazzi
Chagas disease affects 6-7 million people worldwide, resulting in significant disease burdens and healthcare costs in endemic countries. Chemotherapeutic treatment is restricted to two parasiticidal drugs benznidazole and nifurtimox. Both drugs are highly effective during acute disease, but are only minimally effective during chronic disease and fraught with significant adverse clinical effects. In experimental models, vaccines can be used to induce parasite specific balanced TH1/TH2 immune responses that effectively reduce parasite burdens and associated inflammation while minimizing adverse effects...
January 8, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29310516/assessment-of-squalene-eligibility-in-bettering-some-maternal-and-fetal-disorders-instigated-by-gamma-irradiation-of-rats-at-mid-gestation
#16
M F Ibrahim, N Abdelaziz
Squalene is an eminent vital part of the synthesis of steroid hormones in the body as well as the first specific intermediate in cholesterol biosynthesis that plays an essential role in normal embryogenesis. PURPOSE: The present work was designed to test the maternal and embryonic response to the modulating capacity of Squalene (0.4 mL/kg/day), when supplemented to rats from Day 1-18 of pregnancy, against the damaging consequences induced by maternal subjection to 3 Gy gamma irradiation on Day 10 post conception...
January 9, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29298487/low-density-lipoproteins-and-human-serum-albumin-as-the-carriers-of-squalenoylated-drugs-insights-from-molecular-simulations
#17
Semen O Yesylevskyy, Christophe Ramseyer, Mariia Savenko, Simona Mura, Patrick Couvreur
We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs accumulated inside the LDL particles. This effect is promoted by the squalene moiety, which acts as an anchor and drives the hydrophilic drugs into the hydrophobic core of the LDL lipid droplet. Our data suggest that LDL particles could be a universal carriers of squalenoylated drugs in the blood stream...
January 4, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29237267/unsaturated-squalene-content-in-emulsion-vaccine-adjuvants-plays-a-crucial-role-in-ros-mediated-antigen-uptake-and-cellular-immunity
#18
Chung-Hsiung Huang, Chiung-Yi Huang, Ming-Hsi Huang
Emulsion-based adjuvants have been demonstrated to be an effective tool in increasing vaccine efficacy. Here, we aimed to launch a mechanistic study on how emulsion adjuvants interacting with immune cells and to elucidate the roles of the core oil in vaccine immunogenicity. Our results showed that treatment of dendritic cells (DCs) and splenocytes with a squalene-based emulsion (referred as SqE) induced reactive oxidative species (ROS) production and resulted in an increase in apoptotic and necrotic cells in a concentration- and time-dependent manner...
December 13, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29235288/-prokaryotic-expression-functional-identification-of-squalene-synthase-in-alisma-orientale-and-its-immunoassay-study
#19
Qing-Zhi Liu, Wei Gu, Qi-Nan Wu, Jian-Guo Chao, Xiao-Hua Sang, Qi Liu, Xiao-Hao Wang
Squalene synthase of Alisma orientale catalyzes farnesyl diphosphate (FPP) to form squalene, which is the key regulatory enzyme of the carbon source flow to protostane triterpenes biosynthesis. For further research on the function and expression of AoSS gene, the open reading frame (ORF) of squalene synthase gene (accession no. JX866770) from A. orientale was subcloned into a prokaryotic expression vector pCzn1 and induced the expression of AoSS gene in Escherichia coli BL21(Roseta). The fusion protein was mainly in the form of inclusion bodies and purified to obtain high purity protein...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29232007/increased-oxidative-protection-by-high-active-vitamin-e-content-and-partial-radiation-crosslinking-of-uhmwpe
#20
Jia-Zhuang Xu, Keith K Wannomae, Orhun K Muratoglu, Ebru Oral
Vitamin E stabilization successfully improved long-term oxidation resistance of wear-resistant ultra-high-molecular-weight polyethylene (UHMWPE) used for joint implants. Stabilization can be achieved by blending an antioxidant into the UHMWPE resin powder before consolidation and irradiation. Balancing the wear resistance and vitamin E content in the blend is the current challenge with this approach, because vitamin E hinders crosslinking of UHMWPE during irradiation, which decreases wear resistance. The vitamin E concentration in the blend is generally limited to less than 0...
December 12, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
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