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https://www.readbyqxmd.com/read/29353324/stromalized-microreactor-supports-murine-hematopoietic-progenitor-enrichment
#1
Danika Khong, Matthew Li, Amy Singleton, Ling-Yee Chin, Biju Parekkadan
There is an emerging need to process, expand, and even genetically engineer hematopoietic stem and progenitor cells (HSPCs) prior to administration for blood reconstitution therapy. A closed-system and automated solution for ex vivo HSC processing can improve adoption and standardize processing techniques. Here, we report a recirculating flow bioreactor where HSCs are stabilized and enriched for short-term processing by indirect fibroblast feeder coculture. Mouse 3 T3 fibroblasts were seeded on the extraluminal membrane surface of a hollow fiber micro-bioreactor and were found to support HSPC cell number compared to unsupported BMCs...
January 20, 2018: Biomedical Microdevices
https://www.readbyqxmd.com/read/29353309/methods-for-enhancing-cyanobacterial-stress-tolerance-to-enable-improved-production-of-biofuels-and-industrially-relevant-chemicals
#2
REVIEW
Rebecca L Kitchener, Amy M Grunden
Cyanobacteria are photosynthetic prokaryotes that can fix atmospheric CO2 and can be engineered to produce industrially important compounds such as alcohols, free fatty acids, alkanes used in next-generation biofuels, and commodity chemicals such as ethylene or farnesene. They can be easily genetically manipulated, have minimal nutrient requirements, and are quite tolerant to abiotic stress making them an appealing alternative to other biofuel-producing microbes which require additional carbon sources and plants which compete with food crops for arable land...
January 20, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29353158/quantification-of-light-induced-minisog-superoxide-production-using-the-selective-marker-2-hydroxyethidium
#3
Miriam E Barnett, Timothy M Baran, Thomas H Foster, Andrew P Wojtovich
Genetically-encoded photosensitizers produce reactive oxygen species (ROS) in response to light. Transgenic expression of fusion proteins can target the photosensitizers to specific cell regions and permit the spatial and temporal control of ROS production. These ROS-generating proteins (RGPs) are widely used for cell ablation, mutagenesis and chromophore-assisted light inactivation of target proteins. However, the species produced by RGPs are unclear due to indirect measures with confounding interpretations...
January 17, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29352128/phosphorylation-of-the-transient-receptor-potential-ankyrin-1-by-cyclin-dependent-kinase-5-affects-chemo-nociception
#4
Bradford E Hall, Michaela Prochazkova, Matthew R Sapio, Paul Minetos, Natalya Kurochkina, B K Binukumar, Niranjana D Amin, Anita Terse, John Joseph, Stephen J Raithel, Andrew J Mannes, Harish C Pant, Man-Kyo Chung, Michael J Iadarola, Ashok B Kulkarni
Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and this interaction was blocked by TFP5, an inhibitor that prevents activation of Cdk5...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351990/saa3-is-a-key-mediator-of-the-protumorigenic-properties-of-cancer-associated-fibroblasts-in-pancreatic-tumors
#5
Magdolna Djurec, Osvaldo Graña, Albert Lee, Kevin Troulé, Elisa Espinet, Lavinia Cabras, Carolina Navas, María Teresa Blasco, Laura Martín-Díaz, Miranda Burdiel, Jing Li, Zhaoqi Liu, Mireia Vallespinós, Francisco Sanchez-Bueno, Martin R Sprick, Andreas Trumpp, Bruno Sainz, Fátima Al-Shahrour, Raul Rabadan, Carmen Guerra, Mariano Barbacid
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351356/epha2-ephrin-a1-mediate-corneal-epithelial-cell-compartmentalization-via-adam10-regulation-of-egfr-signaling
#6
Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios
Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29351237/bioengineering-of-rfviia-biopharmaceutical-and-structure-characterization-for-biosimilarity-assessment
#7
Othman Montacir, Houda Montacir, Murat Eravci, Andreas Springer, Stephan Hinderlich, Fereidoun Mahboudi, Amirhossein Saadati, Maria Kristina Parr
Eptacog alfa (NovoSeven®) is a vitamin K-dependent recombinant Factor VIIa produced by genetic engineering from baby hamster kidney (BHK) cells as a single peptide chain of 406 residues. After activation, it consists of a light chain (LC) of 152 amino and a heavy chain (HC) of 254 amino acids. Recombinant FVIIa undergoes many post-translational modifications (PTMs). The first ten glutamic acids of the N-terminal moiety are γ-carboxylated, Asn145 and Asn322 are N-glycosylated, and Ser52 and Ser60 are O-glycosylated...
January 19, 2018: Bioengineering
https://www.readbyqxmd.com/read/29351064/molecular-target-analysis-of-stearoyl-coa-desaturase-genes-of-protozoan-parasites
#8
He Lu, Xin Qin, Jing Zhang, Shuang Zhang, Yu Zhu, Wei Hua Wu
Protozoan parasites can synthesize polyunsaturated fatty acids. They possess stearoyl-CoA desaturase to convert stearate into oleate and linoleate. Stearoyl-CoA desaturase are the key enzymes required for the synthesis of unsaturated fatty acids. It seems attractive to evaluate the possibility of using unsaturated fatty acid biosynthesis pathways as drug targets. In this study, the authors investigate codon usage bias, base composition variations and protein sequence in ten available complete stearoyl-CoA desaturase gene sequences from Toxoplasma gondii, Neospora caninum etc...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29351057/global-gene-expression-response-in-mouse-models-of-dna-repair-deficiency-after-gamma-irradiation
#9
Nils Rudqvist, Evagelia C Laiakis, Shanaz A Ghandhi, Suresh Kumar, Jeffrey D Knotts, Mashkura Chowdhury, Albert J Fornace, Sally A Amundson
In the event of an improvised nuclear device or "dirty bomb" in a highly populated area, potentially hundreds of thousands of people will require screening to ensure that exposed individuals receive appropriate treatment. For this reason, there is a need to develop tools for high-throughput radiation biodosimetry. Gene expression represents an emerging approach to biodosimetry and could potentially provide an estimate of both absorbed dose and individual radiation-induced injury. Since approximately 2-4% of humans are thought to be radiosensitive, and would suffer greater radiological injury at a given dose than members of the general population, it is of interest to explore the potential impact of such sensitivity on the biodosimetric gene expression signatures being developed...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29350142/lethal-respiratory-disease-associated-with-human-rhinovirus%C3%A2-c-in-wild-chimpanzees-uganda-2013
#10
Erik J Scully, Sarmi Basnet, Richard W Wrangham, Martin N Muller, Emily Otali, David Hyeroba, Kristine A Grindle, Tressa E Pappas, Melissa Emery Thompson, Zarin Machanda, Kelly E Watters, Ann C Palmenberg, James E Gern, Tony L Goldberg
We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in 2013 for which molecular and epidemiologic analyses implicate human rhinovirus C as the cause. Postmortem samples from an infant chimpanzee yielded near-complete genome sequences throughout the respiratory tract; other pathogens were absent. Epidemiologic modeling estimated the basic reproductive number (R0) for the epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3 CDHR3-Y529 allele, which increases risk for rhinovirus C infection and asthma in human children...
February 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29348238/phosphoethanolamine-cellulose-a-naturally-produced-chemically-modified-cellulose
#11
Wiriya Thongsomboon, Diego O Serra, Alexandra Possling, Chris Hadjineophytou, Regine Hengge, Lynette Cegelski
Cellulose is a major contributor to the chemical and mechanical properties of plants and assumes structural roles in bacterial communities termed biofilms. We find that Escherichia coli produces chemically modified cellulose that is required for extracellular matrix assembly and biofilm architecture. Solid-state nuclear magnetic resonance spectroscopy of the intact and insoluble material elucidates the zwitterionic phosphoethanolamine modification that had evaded detection by conventional methods. Installation of the phosphoethanolamine group requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane signaling pathway...
January 19, 2018: Science
https://www.readbyqxmd.com/read/29345968/mature-gastric-chief-cells-are-not-required-for-the-development-of-metaplasia
#12
Hiroto Kinoshita, Yoku Hayakawa, Zhengchuan Niu, Mitsuru Konishi, Masahiro Hata, Mayo Tsuboi, Yuki Hayata, Yohko Hikiba, Sozaburo Ihara, Hayato Nakagawa, Yoshihiro Hirata, Timothy C Wang, K Koike
During human gastric carcinogenesis, intestinal metaplasia (IM) is frequently seen in the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and genetically engineered models. Given the diversity of long- and short-term models of mouse SPEM, it remains unclear whether all models have a shared or distinct molecular mechanism. The origin of SPEM in mice is currently under debate. It is postulated that stem or progenitor cells acquire genetic alterations that then supply metaplastic cell clones, while the possibility of transdifferentiation or dedifferentiation from mature gastric chief cells has also been suggested...
January 18, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29345898/engineered-phage-matrix-stiffness-modulating-osteogenic-differentiation
#13
Hee-Sook Lee, Jeong-In Kang, Woo-Jae Chung, Do Hoon Lee, Byung Yang Lee, Seung-Wuk Lee, So Young Yoo
Herein, we demonstrate an engineered phage mediated matrix for osteogenic differentiation with controlled stiffness by crosslinking the engineered phage displaying RGD and HPQ with various concentrations of streptavidin or polymer, PDDA. Osteogenic gene expressions showed that they were specifically increased when MC3T3 cells were cultured on the stiffer phage matrix than softer one. Our phage matrices can be easily functionalized using chemical/genetic engineering and used as a stem cell tissue matrix stiffness platform for modulating differential cell expansion and differentiation...
January 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29344676/application-of-genome-editing-techniques-in-immunology
#14
REVIEW
Agata O Zych, Malgorzata Bajor, Radoslaw Zagozdzon
The idea of using the effector immune cells to specifically fight cancer has recently evolved into an exciting concept of adoptive cell therapies. Indeed, genetically engineered T cells expressing on their surface recombinant, cancer-targeted receptors have been shown to induce promising response in oncological patients. However, in addition to exogenous expression of such receptors, there is also a need for disruption of certain genes in the immune cells to achieve more potent disease-targeted actions, to produce universal chimeric antigen receptor-based therapies or to study the signaling pathways in detail...
January 17, 2018: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29343642/mechanogenetics-for-the-remote-and-noninvasive-control-of-cancer-immunotherapy
#15
Yijia Pan, Sangpil Yoon, Jie Sun, Ziliang Huang, Changyang Lee, Molly Allen, Yiqian Wu, Ya-Ju Chang, Michel Sadelain, K Kirk Shung, Shu Chien, Yingxiao Wang
While cell-based immunotherapy, especially chimeric antigen receptor (CAR)-expressing T cells, is becoming a paradigm-shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and noninvasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that is activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK293T cells to convert the ultrasound-activated Piezo1 into transcriptional activities...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343520/evidence-for-the-isg15-specific-deubiquitinase-usp18-as-an-antineoplastic-target
#16
REVIEW
Lisa Maria Mustachio, Yun Lu, Masanori Kawakami, Jason Roszik, Sarah J Freemantle, Xi Liu, Ethan Dmitrovsky
Ubiquitination and ubiquitin-like posttranslational modifications (PTM) regulate activity and stability of oncoproteins and tumor suppressors. This implicates PTMs as antineoplastic targets. One way to alter PTMs is to inhibit activity of deubiquitinases (DUB) that remove ubiquitin or ubiquitin-like proteins from substrate proteins. Roles of DUBs in carcinogenesis have been intensively studied, yet few inhibitors exist. Prior work provides a basis for the ubiquitin-specific protease 18 (USP18) as an antineoplastic target...
January 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29343191/thermophilic-xylanases-from-bench-to-bottle
#17
Abdul Basit, Junquan Liu, Kashif Rahim, Wei Jiang, Huiqiang Lou
Lignocellulosic biomass is a valuable raw material. As technology has evolved, industrial interest in new ways to take advantage of this raw material has grown. Biomass is treated with different microbial cells or enzymes under ideal industrial conditions to produce the desired products. Xylanases are the key enzymes that degrade the xylosidic linkages in the xylan backbone of the biomass, and commercial enzymes are categorized into different glycoside hydrolase families. Thermophilic microorganisms are excellent sources of industrially relevant thermostable enzymes that can withstand the harsh conditions of industrial processing...
January 17, 2018: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/29343065/perfect-adaptation-and-optimal-equilibrium-productivity-in-a-simple-microbial-biofuel-metabolic-pathway-using-dynamic-integral-control
#18
Corentin Briat, Mustafa H Khammash
The production of complex biomolecules by genetically engineered organisms is one of the most promising applications of metabolic engineering and synthetic biology. To obtain processes with high productivity, it is therefore crucial to design and implement efficient dynamic in-vivo regulation strategies. We consider here the microbial biofuel production model of Dunlop et al. (2010) for which we demonstrate that an antithetic dynamic integral control strategy can achieve robust perfect adaptation for the intracellular biofuel concentration in presence of poorly known network parameters and implementation errors in certain rate parameters of the controller...
January 17, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29343055/genetically-encoded-circuit-for-remote-regulation-of-cell-migration-by-magnetic-fields
#19
Abdullah Al Mosabbir, Kevin Truong
Magneto-reception can be generally defined as the ability to transduce the effects of a magnetic field into a cellular response. Magnetic stimulation at the cellular level is particularly attractive due to its ability for deep penetration and minimal invasiveness, allowing remote regulation of engineered biological processes. Previously, a magnetic-responsive genetic circuit was engineered using the transient receptor potential vanilloid 1 (TRPV1) and the iron containing ferritin protein (i.e. the TF circuit)...
January 17, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29342501/selective-activation-of-tumor-necrosis-factor-receptor-2-induces-anti-inflammatory-responses-and-alleviates-experimental-arthritis
#20
Roman Fischer, Marcel Proske, Maëlle Duffey, Hubert Stangl, George F Martinez, Nathalie Peters, Alexandra Kraske, Rainer H Straub, John R Bethea, Roland E Kontermann, Klaus Pfizenmaier
OBJECTIVES: Regulatory T cells (Tregs) modulate immune responses and can suppress the development of autoimmune diseases. Tumor necrosis factor receptor 2 (TNFR2) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD4+ Tregs. Here, we investigated the therapeutic activity of a novel TNFR2 agonist in experimental arthritis and the role of different Treg subsets. METHODS: A novel mouse TNFR2-selective fusion protein (EHD2-sc-mTNFR2 ) was generated by genetic engineering...
January 17, 2018: Arthritis & Rheumatology
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