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https://www.readbyqxmd.com/read/27932576/mammalian-synthetic-biology-for-studying-the-cell
#1
REVIEW
Melina Mathur, Joy S Xiang, Christina D Smolke
Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes...
December 8, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27928578/reporter-gene-assays-in-ecotoxicology
#2
Tal Elad, Shimshon Belkin
The need for simple and rapid means for evaluating the potential toxic effects of environmental samples has prompted the development of reporter gene assays, based on tester cells (bioreporters) genetically engineered to report on sample toxicity by producing a readily quantifiable signal. Bacteria are especially suitable to serve as bioreporters owing to their fast responses, low cost, convenient preservation, ease of handling, and amenability to genetic manipulations. Various bacterial bioreporters have been introduced for general toxicity and genotoxicity assessment, and the monitoring of endocrine disrupting and dioxin-like compounds has been mostly covered by similarly engineered eukaryotic cells...
December 8, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27924160/multivalent-targeting-based-delivery-of-therapeutic-peptide-using-ap1-elp-carrier-for-effective-cancer-therapy
#3
Vijaya Sarangthem, Yunjae Kim, Thoudam Debraj Singh, Bo-Yeon Seo, Sun-Ha Cheon, Young-Jin Lee, Byung-Heon Lee, Rang-Woon Park
Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell-targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities of the drug conjugates. Herein, we described a unique delivery system comprised of genetically engineered ELP incorporated with multiple copies of IL-4 receptor targeting peptide (AP1) periodically and proapoptotic peptide (KLAKLAK)2 referred to as AP1-ELP-KLAK...
2016: Theranostics
https://www.readbyqxmd.com/read/27924150/increasing-n-butanol-production-with-saccharomyces-cerevisiae-by-optimizing-acetyl-coa-synthesis-nadh-levels-and-trans-2-enoyl-coa-reductase-expression
#4
Virginia Schadeweg, Eckhard Boles
BACKGROUND: n-Butanol can serve as an excellent gasoline substitute. Naturally, it is produced by some Clostridia species which, however, exhibit only limited suitability for industrial n-butanol production. The yeast Saccharomyces cerevisiae would be an ideal host due to its high robustness in fermentation processes. Nevertheless, n-butanol yields and titers obtained so far with genetically engineered yeast strains are only low. RESULTS: In our recent work, we showed that n-butanol production via a clostridial acetoacetyl-CoA-derived pathway in engineered yeast was limited by the availability of coenzyme A (CoA) and cytosolic acetyl-CoA...
2016: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/27914702/renal-xenotransplantation-experimental-progress-and-clinical-prospects
#5
Martin Wijkstrom, Hayato Iwase, Wayne Paris, Hidetaka Hara, Mohamed Ezzelarab, David K C Cooper
There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913846/potent-mutagenicity-of-some-non-planar-tri-and-tetrachlorinated-biphenyls-in-mammalian-cells-human-cyp2e1-being-a-major-activating-enzyme
#6
Yungang Liu, Keqi Hu, Hansi Jia, Guifang Jin, Hansruedi Glatt, Hao Jiang
Polychlorinated biphenyls (PCBs) have been classified as human carcinogens. Mutagenicity of lower chlorinated biphenyls as well as activation of transcription factors by some other congeners may contribute to the carcinogenicity of PCBs. Recently, we reported that human CYP2E1 activates mono- and dichlorobiphenyls to mutagens. However, mutagenicity of other PCBs and the involvement of other CYPs remained unknown. In this study, Chinese hamster V79-derived cell lines genetically engineered for expression of individual human CYP enzymes and a human hepatocyte (L-02) line endogenously expressing various CYPs were used to determine the activities of several tri- and tetrachlorobiphenyls to induce micronuclei and gene mutations...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27910951/molecular-imaging-with-engineered-physiology
#7
Mitul Desai, Adrian L Slusarczyk, Ashley Chapin, Mariya Barch, Alan Jasanoff
In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27909940/enhancement-of-rapamycin-production-by-metabolic-engineering-in-streptomyces-hygroscopicus-based-on-genome-scale-metabolic-model
#8
Lanqing Dang, Jiao Liu, Cheng Wang, Huanhuan Liu, Jianping Wen
Rapamycin, as a macrocyclic polyketide with immunosuppressive, antifungal, and anti-tumor activity produced by Streptomyces hygroscopicus, is receiving considerable attention for its significant contribution in medical field. However, the production capacity of the wild strain is very low. Hereby, a computational guided engineering approach was proposed to improve the capability of rapamycin production. First, a genome-scale metabolic model of Streptomyces hygroscopicus ATCC 29253 was constructed based on its annotated genome and biochemical information...
December 1, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27909701/immunological-quality-and-performance-of-tumor-vessel-targeting-car-t-cells-prepared-by-mrna-ep-for-clinical-research
#9
Kanako Inoo, Ryo Inagaki, Kento Fujiwara, Shigemi Sasawatari, Takashi Kamigaki, Shinsaku Nakagawa, Naoki Okada
We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR) specific for vascular endothelial growth factor receptor 2 (VEGFR2), demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6-12 hours after mRNA-EP...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27903826/synthetic-biology-approaches-to-biological-containment-pre-emptively-tackling-potential-risks
#10
REVIEW
Leticia Torres, Antje Krüger, Eszter Csibra, Edoardo Gianni, Vitor B Pinheiro
Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks...
November 30, 2016: Essays in Biochemistry
https://www.readbyqxmd.com/read/27902734/galectin-7-expression-potentiates-her-2-positive-phenotype-in-breast-cancer
#11
Andrée-Anne Grosset, Françoise Poirier, Louis Gaboury, Yves St-Pierre
HER-2 positive tumors are among the most aggressive subtypes of breast cancer and are frequently associated with metastasis and poor outcome. As with other aggressive subtypes of breast cancer, these tumors are associated with abnormally high expression of galectin-7 (gal-7), which confers metastatic breast tumor cells with increased invasive behavior. Although previous studies in the rat model of breast tumorigenesis have shown that gal-7 is also increased in primary breast tumor, its contribution to the development of the primary breast tumors remains unclear...
2016: PloS One
https://www.readbyqxmd.com/read/27899587/temporal-self-regulation-of-transposition-through-host-independent-transposase-rodlet-formation
#12
Lauren E Woodard, Laura M Downes, Yi-Chien Lee, Aparna Kaja, Eyuel S Terefe, Matthew H Wilson
Transposons are highly abundant in eukaryotic genomes, but their mobilization must be finely tuned to maintain host organism fitness and allow for transposon propagation. Forty percent of the human genome is comprised of transposable element sequences, and the most abundant cut-and-paste transposons are from the hAT superfamily. We found that the hAT transposase TcBuster from Tribolium castaneum formed filamentous structures, or rodlets, in human tissue culture cells, after gene transfer to adult mice, and ex vivo in cell-free conditions, indicating that host co-factors or cellular structures were not required for rodlet formation...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27896920/fusion-of-ssm6a-with-a-protein-scaffold-retains-selectivity-on-nav-1-7-and-improves-its-therapeutic-potential-against-chronic-pain
#13
Chuan Wang, Bin Shan, Qiong Wang, Qunyuan Xu, Hailin Zhang, Huimeng Lei
Voltage gated sodium channel NaV 1.7 serves an attractive target for chronic pain treatment. Several venom peptides were found to selectively inhibit NaV 1.7 but with intrinsic problems. Among them, Ssm6a, a recently discovered centipede venom peptide, shows the greatest selectivity against NaV 1.7, but dissociates from the target too fast and loses bioactivity in synthetic forms. As a disulfide-rich venom peptide, it is difficult to optimize Ssm6a by artificial mutagenesis and produce the peptide with common industrial manufacturing methods...
November 29, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27893441/engineering-tumor-cell-targeting-in-nanoscale-amyloidal-materials
#14
Ugutz Unzueta, Joaquin Seras-Franzoso, María Virtudes Céspedes, Paolo Saccardo, Francisco Cortés, Fabián Rueda, Elena Garcia-Fruitós, Neus Ferrer-Miralles, Ramon Mangues, Esther Vázquez, Antonio Villaverde
Bacterial inclusion bodies are non-toxic, mechanically stable and functional protein amyloids within the nanoscale size range that are able to naturally penetrate into mammalian cells, where they deliver the embedded protein in a functional form. The potential use of inclusion bodies in protein delivery or protein replacement therapies is strongly impaired by the absence of specificity in cell binding and penetration, thus preventing targeting. To address this issue, we have here explored whether the genetic fusion of two tumor-homing peptides, the CXCR4 ligands R9 and T22, to an inclusion body-forming green fluorescent protein (GFP), would keep the interaction potential and the functionality of the fused peptides and then confer CXCR4 specificity in cell binding and further uptake of the materials...
January 6, 2017: Nanotechnology
https://www.readbyqxmd.com/read/27892699/genetics-of-consanguinity-and-inbreeding-in-health-and-disease
#15
Mohd Fareed, Mohammad Afzal
CONTEXT: Inbreeding increases the level of homozygotes for autosomal recessive disorders and is the major objective in clinical studies. The prevalence of consanguinity and the degree of inbreeding vary from one population to another depending on ethnicity, religion, culture and geography. Global epidemiological studies have revealed that consanguineous unions have been significantly associated with increased susceptibility to various forms of inherited diseases Objective: The study aimed to determine the role of consanguinity in human health and to highlight the associated risks for various diseases or disorders...
November 28, 2016: Annals of Human Biology
https://www.readbyqxmd.com/read/27886459/standardised-experiments-in-mutant-mice-reveal-behavioural-similarity-on-129s5-and-c57bl-6j-backgrounds
#16
Louie N van de Lagemaat, Lianne E Stanford, Charles Pettit, Douglas J Strathdee, Karen E Strathdee, Kathryn A Elsegood, David G Fricker, Mike D R Croning, Noboru H Komiyama, Seth G N Grant
Behavioural analysis of mice carrying engineered mutations is widely used to identify roles of specific genes in components of the mammalian behavioural repertoire. The reproducibility and robustness of phenotypic measures has become a concern that undermines the use of mouse genetic models for translational studies. Contributing factors include low individual study power, non-standardised behavioural testing, failure to address confounds and differences in genetic background of mutant mice. We have examined the importance of these factors using a statistically robust approach applied to behavioural data obtained from three mouse mutations on 129S5 and C57BL/6J backgrounds generated in a standardised battery of five behavioural assays...
November 25, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27883926/application-of-genetically-engineered-salmonella-typhimurium-for-interferon-gamma-induced-therapy-against-melanoma
#17
Wonsuck Yoon, Yoo Chang Park, Jinseok Kim, Yang Seok Chae, Jung Hye Byeon, Sang-Hyun Min, Sungha Park, Young Yoo, Yong Keun Park, Byeong Mo Kim
Salmonella have been experimentally used as anti-cancer agents, because they show selective growth in tumours. In this study, we genetically modified attenuated Salmonella typhimurium to express and secrete interferon-gamma (IFN-γ) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-γ was fused to the N-terminal region (residues 1-160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-γ (S. typhimurium (IFN-γ)) invaded the melanoma cells and induced cytotoxicity...
November 21, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27883070/ph-responsive-virus-like-nanoparticles-with-enhanced-tumour-targeting-ligands-for-cancer-drug-delivery
#18
Roya Biabanikhankahdani, Noorjahan Banu Mohamed Alitheen, Kok Lian Ho, Wen Siang Tan
Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882538/gene-therapy-with-mesenchymal-stem-cells-expressing-ifn%C3%A3-ameliorates-neuroinflammation-in-experimental-models-of-multiple-sclerosis
#19
C Marin-Bañasco, K Benabdellah, C Melero-Jerez, B Oliver, M J Pinto-Medel, I Hurtado-Guerrero, F de Castro, D Clemente, O Fernández, F Martin, L Leyva, M Suardíaz
BACKGROUND AND PURPOSE: Recombinant IFNß is one of the first line treatments in multiple sclerosis (MS), despite its lack of efficiency in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, taking advantage of their pathotropism ability, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27881659/glycosyl-phosphatidylinositol-gpi-anchored-anti-hiv-scfv-efficiently-protect-cd4-t-cells-from-hiv-1-infection-and-deletion-in-hu-pbl-mice
#20
Chaobaihui Ye, Weiming Wang, Liang Cheng, Guangming Li, Michael Wen, Qi Wang, Qing Zhang, Dan Li, Paul Zhou, Lishan Su
: Despite the success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance of permissive cells...
November 23, 2016: Journal of Virology
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