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https://www.readbyqxmd.com/read/29777593/degradation-of-recombinant-proteins-by-cho-host-cell-proteases-is-prevented-by-matriptase-1-knock-out
#1
Holger Laux, Sandrine Romand, Sandro Nuciforo, Christopher J Farady, Joel Tapparel, Stine Buechmann-Moeller, Benjamin Sommer, Edward J Oakeley, Ursula Bodendorf
An increasing number of non-antibody format proteins are entering the clinical development. However, one of the major hurdles for the production of non-antibody glycoproteins is host cell-related proteolytic degradation, which can drastically impact developability and timelines of pipeline projects. Chinese hamster ovary (CHO) cells are the preferred production host for recombinant therapeutic proteins. Using protease inhibitors, transcriptomics and genetic knockdowns we have identified, out of the more than 700 known proteases in rodents, Matriptase-1 as the major protease involved in degradation of recombinant proteins expressed in CHO-K1 cells...
May 19, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29774064/tumour-homing-chimeric-polypeptide-conjugated-polypyrrole-nanoparticles-for-imaging-guided-synergistic-photothermal-and-chemical-therapy-of-cancer
#2
Mengmeng Sun, Jianwen Guo, Hanjun Hao, Tong Tong, Kun Wang, Weiping Gao
Near-infrared (NIR)-absorbing conjugated polymer nanoparticles are interesting for imaging-guided combination therapy, especially for synergistic photothermal therapy and chemotherapy; however, most of them target tumours passively through the enhanced permeability and retention (EPR) effect, leading to low utilization efficiency. To address this problem, we report an active tumour-targeting strategy of tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles as a new class of drug nanocarriers for imaging-guided combination therapy of cancer...
2018: Theranostics
https://www.readbyqxmd.com/read/29773767/the-role-of-brincidofovir-in-preparation-for-a-potential-smallpox-outbreak
#3
Scott A Foster, Scott Parker, Randall Lanier
Smallpox (variola) virus is considered a Category A bioterrorism agent due to its ability to spread rapidly and the high morbidity and mortality rates associated with infection. Current recommendations recognize the importance of oral antivirals and call for having at least two smallpox antivirals with different mechanisms of action available in the event of a smallpox outbreak. Multiple antivirals are recommended due in large part to the propensity of viruses to become resistant to antiviral therapy, especially monotherapy...
October 30, 2017: Viruses
https://www.readbyqxmd.com/read/29773074/enhanced-cellulase-production-in-trichoderma-reesei-rut-c30-via-constitution-of-minimal-transcriptional-activators
#4
Jiajia Zhang, Guoxiu Zhang, Wei Wang, Wei Wang, Dongzhi Wei
BACKGROUND: Cellulase can convert lignocellulosic feedstocks into fermentable sugars, which can be used for the industrial production of biofuels and chemicals. The high cost of cellulase production remains a challenge for lignocellulose breakdown. Trichoderma reesei RUT C30 serves as a well-known industrial workhorse for cellulase production. Therefore, the enhancement of cellulase production by T. reesei RUT C30 is of great importance. RESULTS: Two sets of novel minimal transcriptional activators (DBDace2 -VP16 and DBDcre1 -VP16) were designed and expressed in T...
May 17, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29769408/cell-geometry-across-the-ring-structure-of-sitka-spruce
#5
T P S Reynolds, H C Burridge, R Johnston, G Wu, D U Shah, O A Scherman, P F Linden, M H Ramage
For wood to be used to its full potential as an engineering material, it is necessary to quantify links between its cell geometry and the properties it exhibits at bulk scale. Doing so will make it possible to predict timber properties crucial to engineering, such as mechanical strength and stiffness, and the resistance to fluid flow, and to inform strategies to improve those properties as required, as well as to measure the effects of interventions such as genetic manipulation and chemical modification. Strength, stiffness and permeability of timber all derive from the geometry of its cells, and yet current practice is to predict them based on properties, such as bulk density, that do not directly describe the cell structure...
May 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29766029/seizure-suppressant-and-neuroprotective-effects-of-encapsulated-bdnf-producing-cells-in-a-rat-model-of-temporal-lobe-epilepsy
#6
Chiara Falcicchia, Giovanna Paolone, Dwaine F Emerich, Francesca Lovisari, William J Bell, Tracie Fradet, Lars U Wahlberg, Michele Simonato
Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%. These benefits were associated with improved cognitive performance, as epileptic rats treated with BDNF performed significantly better on a novel object recognition test...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29758351/development-of-microreactors-with-surface-immobilized-biocatalysts-for-continuous-transamination
#7
Nataša Miložič, Gorazd Stojkovič, Andreas Vogel, Dominique Bouwes, Polona Žnidaršič-Plazl
The industrial importance of optically pure compounds has thrown a spotlight on ω-transaminases that have shown a high potential for the synthesis of bioactive compounds with a chiral amine moiety. The implementation of biocatalysts in industrial processes relies strongly on fast and cost effective process development, including selection of a biocatalyst form and the strategy for its immobilization. Here, microscale reactors with selected surface-immobilized amine-transaminase (ATA) in various forms are described as platforms for high-throughput process development...
May 11, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29756533/genetic-engineering-of-mesenchymal-stem-cells-for-differential-matrix-deposition-on-3dwoven-scaffold
#8
Nguyen Phuong Thao Huynh, Jonathan Matthew Brunger, Catherine Claire Gloss, Franklin T Moutos, Charles A Gersbach, Farshid Guilak
Tissue engineering approaches for the repair of osteochondral defects using biomaterial scaffolds and stem cells have remained challenging due to the inherent complexities of inducing cartilage-like matrix and bone-like matrix within the same local environment. Members of the transforming growth factor β (TGFβ) family have been extensively utilized in the engineering of skeletal tissues, but have distinct effects on chondrogenic and osteogenic differentiation of progenitor cells. The goal of this study was to develop a method to direct human bone marrow derived mesenchymal stem cells (MSCs) to deposit either mineralized matrix or a cartilaginous matrix rich in glycosaminoglycan and type II collagen within the same biochemical environment...
May 14, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29755309/targeted-delivery-of-crispr-cas9-mediated-cancer-gene-therapy-via-liposome-templated-hydrogel-nanoparticles
#9
Zeming Chen, Fuyao Liu, Yanke Chen, Jun Liu, Xiaoying Wang, Ann T Chen, Gang Deng, Hongyi Zhang, Jie Liu, Zhangyong Hong, Jiangbing Zhou
Due to its simplicity, versatility, and high efficiency, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has emerged as one of the most promising approaches for treatment of a variety of genetic diseases, including human cancers. However, further translation of CRISPR/Cas9 for cancer gene therapy requires development of safe approaches for efficient, highly specific delivery of both Cas9 and single guide RNA to tumors. Here, novel core-shell nanostructure, liposome-templated hydrogel nanoparticles (LHNPs) that are optimized for efficient codelivery of Cas9 protein and nucleic acids is reported...
December 8, 2017: Advanced Functional Materials
https://www.readbyqxmd.com/read/29754773/genome-editing-in-plants-advancing-crop-transformation-and-overview-of-tools
#10
Tariq Shah, Tayyaba Andleeb, Sadia Lateef, Mehmood Ali Noor
Genome manipulation technology is one of emerging field which brings real revolution in genetic engineering and biotechnology. Targeted editing of genomes pave path to address a wide range of goals not only to improve quality and productivity of crops but also permit to investigate the fundamental roots of biological systems. These goals includes creation of plants with valued compositional properties and with characters that confer resistance to numerous biotic and abiotic stresses. Numerous novel genome editing systems have been introduced during the past few years; these comprise zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9)...
May 7, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29754240/engineering-genomes-with-genotype-specification-language
#11
Erin H Wilson, Chris Macklin, Darren Platt
High quality DNA design tools are becoming increasingly important as synthetic biology continues to increase the rate and throughput of building and testing genetic constructs. To make effective use of expanded build and test capacity, genotype design tools must not only be efficient enough to allow for many designs to be easily created, but also expressive enough to support the complex design patterns required by scientists on the frontier of genome engineering. Genotype Specification Language (GSL) is a language-based design tool invented at Amyris that enables scientists to quickly create DNA designs using a familiar syntax...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29751775/cxcl12-engineered-endothelial-progenitor-cells-enhance-neurogenesis-and-angiogenesis-after-ischemic-brain-injury-in-mice
#12
Yaning Li, Shuang Chang, Wanlu Li, Guanghui Tang, Yuanyuan Ma, Yanqun Liu, Fang Yuan, Zhijun Zhang, Guo-Yuan Yang, Yongting Wang
BACKGROUND: Ischemic stroke causes a multitude of brain damage. Neurovascular injury and myelin sheath degradation are two manifestations of ischemic brain damage. Therapeutic strategies aiming only at repairing the neural components or the vessels cannot efficiently restore neurological function. Endothelial progenitor cells (EPCs) have the advantages of both promoting angiogenesis and secreting trophic factors that would promote neurogenesis. Chemokine cxcl12 gene therapy has also been shown to promote angiogenesis, neurogenesis, and remyelination, attracting EPCs, neural progenitor cells, and oligodendrocyte progenitor cells (OPCs) to the injured sites of the brain...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29748134/oxysterol-binding-protein-related-proteins-orps-5-and-8-regulate-calcium-signaling-at-specific-cell-compartments
#13
Ilari Pulli, Taru Lassila, Guoping Pan, Daoguang Yan, Vesa M Olkkonen, Kid Törnquist
Oxysterol-binding protein related-protein 5 and 8 (ORP5/8) localize to the membrane contact sites (MCS) of the endoplasmic reticulum (ER) and the mitochondria, as well as to the ER-plasma membrane (PM) MCS. The MCS are emerging as important regulators of cell signaling events, including calcium (Ca2+ ) signaling. ORP5/8 have been shown to interact with phosphatidylinositol-4,5-bisphosphate (PIP2 ) in the PM, and to modulate mitochondrial respiration and morphology. PIP2 is the direct precursor of inositol trisphosphate (IP3 ), a key second messenger responsible for Ca2+ -release from the intracellular Ca2+ stores...
March 13, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29747585/waveband-specific-transcriptional-control-of-select-genetic-pathways-in-vertebrate-skin-xiphophorus-maculatus
#14
Ronald B Walter, Mikki Boswell, Jordan Chang, William T Boswell, Yuan Lu, Kaela Navarro, Sean M Walter, Dylan J Walter, Raquel Salinas, Markita Savage
BACKGROUND: Evolution occurred exclusively under the full spectrum of sunlight. Conscription of narrow regions of the solar spectrum by specific photoreceptors suggests a common strategy for regulation of genetic pathways. Fluorescent light (FL) does not possess the complexity of the solar spectrum and has only been in service for about 60 years. If vertebrates evolved specific genetic responses regulated by light wavelengths representing the entire solar spectrum, there may be genetic consequences to reducing the spectral complexity of light...
May 10, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29746094/an-engineered-device-for-indoleacetic-acid-production-under-quorum-sensing-signals-enables-cupriavidus-pinatubonensis-jmp134-to-stimulate-plant-growth
#15
Ana Zuniga, Francisco De la Fuente, Fernan Federici, Corinne Lionne, Jerome Bonnet, Victor de Lorenzo, Bernardo Gonzalez
The environmental effects of chemical fertilizers and pesticides have encouraged the quest for new strategies to increase crop productivity with minimal impacts on the natural medium. Plant growth promoting rhizobacteria (PGPR) can contribute to this endeavor by improving fitness through better nutrition acquisition and stress tolerance. Using the neutral (non PGPR) rhizobacterium Cupriavidus pinatubonensis JMP134 as the host, we engineered a regulatory forward loop that triggered the synthesis of the phytohormone indole-3-acetic acid (IAA) in a manner dependent on quorum sensing (QS) signals...
May 10, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29746091/a-framework-for-engineering-stress-resilient-plants-using-genetic-feedback-control-and-regulatory-network-rewiring
#16
Mathias Foo, Iulia Gherman, Peijun Zhang, Declan G Bates, Katherine Denby
Crop disease leads to significant waste world-wide, both pre- and post-harvest, with subsequent economic and sustainability consequences. Disease outcome is determined both by the plants' response to the pathogen and by the ability of the pathogen to suppress defense responses and manipulate the plant to enhance colonization. The defense response of a plant is characterized by significant transcriptional reprogramming mediated by underlying gene regulatory networks and components of these networks are often targeted by attacking pathogens...
May 10, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29742880/diffuse-intrinsic-pontine-glioma-clinical-features-molecular-genetics-and-novel-targeted-therapeutics
#17
REVIEW
Ryan K Mathew, James T Rutka
Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained...
May 2018: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/29740520/the-%C3%AE-bt1-large-serine-recombinase-catalyzes-dna-integration-at-pseudo-attb-sites-in-the-genus-nocardia
#18
Marion Herisse, Jessica L Porter, Romain Guerillot, Takehiro Tomita, Anders Goncalves Da Silva, Torsten Seemann, Benjamin P Howden, Timothy P Stinear, Sacha J Pidot
Plasmid vectors based on bacteriophage integrases are important tools in molecular microbiology for the introduction of foreign DNA, especially into bacterial species where other systems for genetic manipulation are limited. Site specific integrases catalyze recombination between phage and bacterial attachment sites ( attP and attB , respectively) and the best studied integrases in the actinomycetes are the serine integrases from the Streptomyces bacteriophages ΦC31 and ΦBT1. As this reaction is unidirectional and highly stable, vectors containing phage integrase systems have been used in a number of genetic engineering applications...
2018: PeerJ
https://www.readbyqxmd.com/read/29735663/linked-genetic-variation-and-not-genome-structure-causes-widespread-differential-expression-associated-with-chromosomal-inversions
#19
Iskander Said, Ashley Byrne, Victoria Serrano, Charis Cardeno, Christopher Vollmers, Russell Corbett-Detig
Chromosomal inversions are widely thought to be favored by natural selection because they suppress recombination between alleles that have higher fitness on the same genetic background or in similar environments. Nonetheless, few selected alleles have been characterized at the molecular level. Gene expression profiling provides a powerful way to identify functionally important variation associated with inversions and suggests candidate phenotypes. However, altered genome structure itself might also impact gene expression by influencing expression profiles of the genes proximal to inversion breakpoint regions or by modifying expression patterns genome-wide due to rearranging large regulatory domains...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29730661/improvement-of-spinosad-production-upon-utilization-of-oils-and-manipulation-of-%C3%AE-oxidation-in-a-high-producing-saccharopolyspora-spinosa-strain
#20
Ying Huang, Xiaolin Zhang, Chen Zhao, Xuhui Zhuang, Lin Zhu, Chao Guo, Yuan Song
Spinosad, a member of polyketide-derived macrolides produced in the actinomycete Saccharopolyspora spinosa, has been developed as a broad-spectrum and effective insecticide. The β-oxidation pathway could be an important source of building blocks for the biosynthesis of spinosad, thus the effect of vegetable oils on the production of spinosad in a high-yield strain was investigated. The spinosad production increased significantly with the addition of strawberry seed oil (511.64 mg/L) and camellia oil (520.07 mg/L) compared to the control group without oil (285...
May 4, 2018: Journal of Molecular Microbiology and Biotechnology
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