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Synthetic biology

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https://www.readbyqxmd.com/read/29149479/cripsr-cas-expands-dynamic-range-of-gene-expression-from-t7rnap-promoters
#1
Sean R McCutcheon, Kwan Lun Chiu, Daniel D Lewis, Cheemeng Tan
BACKGROUND: Reducing leaky gene expression is critical for improving protein yield of recombinant bacteria and stability of engineered cellular circuits in synthetic biology. Leaky gene expression occurs when a genetic promoter is not fully repressed, leading to unintended protein synthesis in the absence of stimuli. Existing work has devised specific molecular strategies for reducing leaky gene expression of each promoter. Main Method and Results: In contrast, we describe a repurposed, modular CRISPRi system that attenuates leaky gene expression using a series of single-guide RNAs targeting the PT7/LacO1 ...
November 17, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29149042/comparative-study-of-biological-activities-of-venom-from-colubrid-snakes-rhabdophis-tigrinus-yamakagashi-and-rhabdophis-lateralis
#2
Yumiko Komori, Toru Hifumi, Akihiko Yamamoto, Atsushi Sakai, Manabu Ato, Kyoko Sawabe, Toshiaki Nikai
Rhabdophis lateralis, a colubrid snake distributed throughout the continent of Asia, has recently undergone taxonomic revisions. Previously, Rhabdophis lateralis was classified as a subspecies of R. tigrinus (Yamakagashi) until 2012, when several genetic differences were discovered which classified this snake as its own species. To elucidate the toxicity of venom from this poorly studied colubrid, various biological activities were compared between the venom from the two snake species. The components of their venom were compared by the elution profiles of reversed-phase HPLC and SDS-PAGE, and gel filtrated fractions were tested for effects on blood coagulation...
November 17, 2017: Toxins
https://www.readbyqxmd.com/read/29148614/double-regioselective-asymmetric-c-allylation-of-isoxazolinones-iridium-catalyzed-n-allylation-followed-by-an-aza-cope-rearrangement
#3
Stefan Rieckhoff, Jan Meisner, Johannes Kästner, Wolfgang Frey, René Peters
Isoxazolinones are biologically and synthetically interesting densely functionalized heterocycles, which for a long time were not accessible in enantioenriched form by asymmetric catalysis. Next to the deficit of enantioselective methods, the functionalization of isoxazolinones is often plagued by regioselectivity issues due to the competition of various nucleophilic centers within the heterocycles. Here we report the first regio- and enantioselective C-allylations of isoxazolinones. They also allowed for high regioselectivity in favor of the linear allylation products, although Ir phosphoramidite catalysts were used, which commonly result in branched isomers...
November 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29148403/treatment-patterns-in-rheumatoid-arthritis-after-discontinuation-of-methotrexate-data-from-the-ontario-best-practices-research-initiative-obri
#4
Janet E Pope, Emmanouil Rampakakis, Mohammad Movahedi, Angela Cesta, Xiuying Li, Sandra Couto, John S Sampalis, Claire Bombardier
OBJECTIVES: In active rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), guidelines support adding or switching to another conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) and/or a biologic DMARD (bDMARD). The purpose of this analysis was to describe treatment practices in routine care and to evaluate determinants of regimen selection after MTX discontinuation. METHODS: Biologic-naïve patients in the Ontario Best Practice Research Initiatives registry discontinuing MTX due to primary/secondary failure, adverse events, or patient/physician decision were included...
October 23, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29148257/multiscale-memory-and-bioelectric-error-correction-in-the-cytoplasm-cytoskeleton-membrane-system
#5
REVIEW
Chris Fields, Michael Levin
A fundamental aspect of life is the modification of anatomy, physiology, and behavior in the face of changing conditions. This is especially illustrated by the adaptive regulation of growth and form that underlies the ability of most organisms-from single cells to complex large metazoa-to develop, remodel, and regenerate to specific anatomical patterns. What is the relationship of the genome and other cellular components to the robust computations that underlie this remarkable pattern homeostasis? Here we examine the role of constraints defined at the cellular level, especially endogenous bioelectricity, in generating and propagating biological information...
November 17, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/29148012/use-of-bovine-carotid-artery-for-buttonhole-technique-hemodialysis
#6
Earl Schuman, Philip Alexander, Amy Ronfeld
PURPOSE: Assess the feasibility of using a bovine carotid artery graft for buttonhole technique hemodialysis in patients who are not candidates for a native fistula. METHODS: Case reports used to demonstrate selection criteria and results for this approach. Criteria include: knowledgeable patient with prior dialysis experience, stable graft in place for 3 months minimum, not a candidate for a native fistula, and able to maintain close follow-up. RESULTS: Both grafts were based on axillary vessels and have been in place for a total of 64 months...
November 8, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/29147712/a-biocompatible-betaine-functionalized-polycation-for-coacervation
#7
Mintai P Hwang, Xiaochu Ding, Jin Gao, Abhinav P Acharya, Steven R Little, Yadong Wang
The aqueous nature of complex coacervates provides a biologically-relevant context for various therapeutic applications. In this sense, biological applications demand a corresponding level of biocompatibility from the polyelectrolytes that participate in complex coacervation. Continued development with naturally-occurring polyelectrolytes such as heparin and chitosan underscore such aims. Herein, we design a synthetic polycation, in which betaine is conjugated to a biodegradable polyester backbone. Betaine is a naturally-occurring methylated amino acid that is ubiquitously present in human plasma...
November 17, 2017: Soft Matter
https://www.readbyqxmd.com/read/29147558/discovery-and-design-of-self-assembling-peptides
#8
REVIEW
Shuguang Zhang
Peptides are ubiquitous in nature and useful in many fields, from agriculture as pesticides, in medicine as antibacterial and antifungal drugs founded in the innate immune systems, to medicinal chemistry as hormones. However, the concept of peptides as materials was not recognized until 1990 when a self-assembling peptide as a repeating segment in a yeast protein was serendipitously discovered. Peptide materials are so called because they have bona fide materials property and are made from simple amino acids with well-ordered nanostructures under physiological conditions...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29147556/mechanism-of-biosurfactant-adsorption-to-oil-water-interfaces-from-millisecond-scale-tensiometry-measurements
#9
Lingling Kong, Kadi Liis Saar, Raphael Jacquat, Liu Hong, Aviad Levin, Hongze Gang, Ruqiang Ye, Bozhong Mu, Tuomas P J Knowles
Many biological molecules are by their nature amphiphilic and have the ability to act as surfactants, stabilizing interfaces between aqueous and immiscible oil phases. In this paper, we explore the adsorption kinetics of surfactin, a naturally occurring cyclic lipopeptide, at hexadecane/water interfaces and compare and contrast its adsorption behaviour with that of synthetic alkyl benzene sulfonate isomers, through direct measurements of changes in interfacial tension upon surfactant adsorption. We access millisecond time resolution in kinetic measurements by making use of droplet microfluidics to probe the interfacial tension of hexadecane droplets dispersed in a continuous water phase through monitoring their deformation when the droplets are exposed to shear flows in a microfluidic channel with regular corrugations...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29147532/copper-catalyzed-cyanothiolation-to-incorporate-a-sulfur-substituted-quaternary-carbon-center
#10
Yubing Huang, Xianwei Li, Xu Wang, Yue Yu, Jia Zheng, Wanqing Wu, Huanfeng Jiang
Sulfur-containing nitriles have important research value in the life sciences due to their diverse biological activities resulting from the sulfur and cyano functional groups. Herein, a copper-catalyzed cyanothiolation of N-tosylhydrazones with thiocyanates to generate α-arylthioalkanenitriles bearing sulfur-substituted quaternary carbon center atoms has been described. This novel protocol involves the procedure of copper carbene species promoting S-CN bond cleavage and C-CN/C-S bond reconstruction to introduce both sulfur and cyano groups onto a single carbon center...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29144600/engineering-mammalian-designer-cells-for-the-treatment-of-metabolic-diseases
#11
REVIEW
Yidan Wang, Meiyan Wang, Kaili Dong, Haifeng Ye
Synthetic biology applies engineering principles to biological systems and has significantly advanced the design of synthetic gene circuits that can reprogram cell activities to perform new functions. The ability to engineer mammalian designer cells with robust therapeutic behaviors has brought new opportunities for treating metabolic diseases. In this review, we highlight the most recent advances in the development of synthetic designer cells uploaded with open-loop gene circuits or closed-loop gene circuits for the treatment of metabolic disorders including diabetes, hypertension, hyperuricemia and obesity, and discuss the current technologies and future perspectives in applying these designer cells for clinical applications...
November 16, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29144523/protein-templated-gold-nanoparticle-synthesis-protein-organization-controlled-gold-sequestration-and-unexpected-reaction-products
#12
Cassidy Hart, Nouf Abuladel, Madeleine Bee, Megan C Kreider, Alexander C CVitan, Moira M Esson, Andrew Farag, Trisha Ibeh, Eleni N Kalivas, Daniel-Mario Larco, Andrew Walker Long, Loukas Lymperopoulos, Zachary Mendel, Nancy Miles, Carly M Zareba, James C Schwabacher, Helen Slucher, Javier Vinals, John M Heddleston, Wenyue Li, Douglas M Fox, Matthew R Hartings
Emerging applications that exploit the properties of nanoparticles for biotechnology require that the nanoparticles be biocompatible or support biological recognition. These types of particles can be produced through syntheses that involve biologically relevant molecules (proteins or natural extracts, for example). Many of the protocols that rely on these molecules are performed without a clear understanding of the mechanism by which the materials are produced. We have investigated a previously described reaction in which gold nanoparticles are produced from the reaction of chloroauric acid and proteins in solution...
November 16, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29143781/biological-properties-of-low-toxic-plga-and-plga-phb-fibrous-nanocomposite-scaffolds-for-osseous-tissue-regeneration-evaluation-of-potential-bioactivity
#13
Boguslawa Żywicka, Izabella Krucińska, Jerzy Garcarek, Maria Szymonowicz, Agnieszka Komisarczyk, Zbigniew Rybak
Abstracts: The aim of the study was to evaluate the biocompatibility and bioactivity of two new prototype implants for bone tissue regeneration made from biodegradable fibrous materials. The first is a newly developed poly(l-lactide-co-glycolide), (PLGA), and the second is a blend of PLGA with synthetic poly([R,S]-3-hydroxybutyrate) (PLGA/PHB). The implant prototypes comprise PLGA or PLGA/PHB nonwoven fabrics with designed pore structures to create the best conditions for cell proliferation. The bioactivity of the proposed implants was enhanced by introducing a hydroxyapatite material and a biologically active agent, namely, growth factor IGF1, encapsulated in calcium alginate microspheres...
October 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29143537/camphor-sulphonic-acid-mediated-quantitative-1-3-diol-protection-of-major-labdane-diterpenes-isolated-from-andrographis-paniculata
#14
Venu Sharma, Kamal K Kapoor, Debaraj Mukherjee, Vivek K Gupta, Manoj K Dhar, Sanjana Kaul
Phytochemical survey of the methanol extract of the dried aerial parts of Andrographis paniculata led to the isolation of major labdane diterpenes, namely 14-deoxy-11,12-didehydroandrographolide, andrographolide and neoandrographolide. Andrographolide was found to be the major phytoconstituent of the plant which was biologically active. For better physiochemical characteristics and bioefficacy, andrographolide is subjected to semi-synthetic modifications. However, presence of several free hydroxyl groups associated with this molecule make it quite polar and poorly soluble in many organic solvents and hence unsuitable for synthetic modifications...
November 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/29143361/2-alkylsulfanyl-4-5-aryl-5-4-heteroarylimidazoles-an-overview-on-synthetic-strategies-and-biological-activity
#15
REVIEW
Pierre Koch, Francesco Ansideri
2-Alkylsulfanyl-4(5)-aryl-5(4)-heteroarylimidazoles represent an important class of ATP-competitive protein kinase inhibitors, offering the possibility of multiple interactions with different regions of the target enzyme. The necessity of exploring the effects of diverse chemical decorations around the imidazole core prompted the design of several synthetic routes aimed at achieving both efficiency and flexibility. Additionally, the optimization of established protocols and the extensive use of transition metal-catalyzed cross-coupling reactions have been broadening the spectrum of preparative methodologies within the last decade...
November 16, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29142167/synergistic-cytotoxicity-caused-by-forming-a-complex-of-copper-and-2-9-dimethyl-1-10-phenanthroline-in-cultured-vascular-endothelial-cells
#16
Takehiro Nakamura, Eiko Yoshida, Tomoya Fujie, Fumihiko Ogata, Chika Yamamoto, Naohito Kawasaki, Toshiyuki Kaji
Organic-inorganic hybrid molecules, which are composed of organic-ligand(s) and metal(s), are indispensable as synthetic reagents in chemistry, but they have made very little in the way of contributions to biological research. Previously, we reported that the cytotoxicity of organic-inorganic hybrid molecules in vascular endothelial cells depends on interactions between the intramolecular metal and ligand, but remains independent of the hydrophobicity of the intramolecular metal(s). Herein, we show a synergistic cytotoxicity produced by forming a complex of copper and 2,9-dimethyl-1,10-phenanthroline in vascular endothelial cells that depends on the intracellular accumulation of copper...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142040/use-of-disease-modifying-antirheumatic-drugs-for-inflammatory-arthritis-in-us-veterans-effect-of-specialty-care-and-geographic-distance
#17
Jessica A Walsh, Shaobo Pei, Zachary Burningham, Gopi Penmetsa, Grant W Cannon, Daniel O Clegg, Brian C Sauer
OBJECTIVE: To evaluate the effect of access to and distance from rheumatology care on the use of disease-modifying antirheumatic drugs (DMARD) in US veterans with inflammatory arthritis (IA). METHODS: Provider encounters and DMARD dispensations for IA (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) were evaluated in national Veterans Affairs (VA) datasets between January 1, 2015, and December 31, 2015. RESULTS: Among 12,589 veterans with IA, 23...
November 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/29142036/effect-of-glucocorticoids-on-the-clinical-and-radiographic-efficacy-of-tofacitinib-in-patients-with-rheumatoid-arthritis-a-posthoc-analysis-of-data-from-6-phase-iii-studies
#18
Christina Charles-Schoeman, Désirée van der Heijde, Gerd R Burmester, Peter Nash, Cristiano A F Zerbini, Carol A Connell, Haiyun Fan, Kenneth Kwok, Eustratios Bananis, Roy Fleischmann
OBJECTIVE: Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies. METHODS: Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440)...
November 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/29141677/factors-associated-with-oral-glucocorticoid-use-in-patients-with-rheumatoid-arthritis-a-drug-use-study-from-a-prospective-national-biologics-registry
#19
Rachel J Black, Susan Lester, Rachelle Buchbinder, Claire Barrett, Marissa Lassere, Lyn March, Samuel Whittle, Catherine L Hill
BACKGROUND: Glucocorticoids (GCs) are used in ~ 60% of patients with rheumatoid arthritis (RA). Although disease-modifying, they also have significant adverse effects. Understanding factors associated with GC use may help minimise exposure. The aims of the present study were to describe oral GC use in RA; determine any change in use over time; and determine factors associated with oral GC use, commencement or cessation. METHODS: Adult patients with RA were identified in the Australian Rheumatology Association Database (ARAD), a national Australian registry that collects long-term outcome data from patients with inflammatory arthritis...
November 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29140977/low-cost-and-open-source-multi-fluorescence-imaging-system-for-teaching-and-research-in-biology-and-bioengineering
#20
Isaac Nuñez, Tamara Matute, Roberto Herrera, Juan Keymer, Timothy Marzullo, Timothy Rudge, Fernán Federici
The advent of easy-to-use open source microcontrollers, off-the-shelf electronics and customizable manufacturing technologies has facilitated the development of inexpensive scientific devices and laboratory equipment. In this study, we describe an imaging system that integrates low-cost and open-source hardware, software and genetic resources. The multi-fluorescence imaging system consists of readily available 470 nm LEDs, a Raspberry Pi camera and a set of filters made with low cost acrylics. This device allows imaging in scales ranging from single colonies to entire plates...
2017: PloS One
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