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https://www.readbyqxmd.com/read/28230977/extracellular-self-assembly-of-functional-and-tunable-protein-conjugates-from-bacillus-subtilis
#1
Charlie Gilbert, Mark Howarth, Colin R Harwood, Tom Ellis
The ability to stably and specifically conjugate recombinant proteins to one another is a powerful approach for engineering multifunctional enzymes, protein therapeutics and novel biological materials. While many of these applications have been illustrated through in vitro and in vivo intracellular protein conjugation methods, extracellular self-assembly of protein conjugates offers unique advantages: simplifying purification, reducing toxicity and burden, and enabling tunability. Exploiting the recently described SpyTag-SpyCatcher system, we describe here how enzymes and structural proteins can be genetically-encoded to covalently conjugate in culture media following programmable secretion from Bacillus subtilis...
February 23, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28230927/crispr-cas9-technologies
#2
Bart O Williams, Matthew L Warman
The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) pathway is revolutionizing biological research. Modifications to this primitive prokaryotic immune system now enable scientists to efficiently edit DNA or modulate gene expression in living eukaryotic cells and organisms. Thus, many laboratories can now perform important experiments that previously were considered scientifically risky or too costly. Here, we describe the components of the CRISPR/Cas system that have been engineered for use in eukaryotes...
February 23, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28230815/conceptual-foundations-of-systems-biology-explaining-complex-cardiac-diseases
#3
REVIEW
George E Louridas, Katerina G Lourida
Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine...
February 21, 2017: Healthcare (Basel, Switzerland)
https://www.readbyqxmd.com/read/28230277/immune-checkpoint-blockade-biology-in-mouse-models-of-glioblastoma
#4
Alan T Yeo, Al Charest
Glioblastoma Multiforme (GBM) is a highly malignant primary brain cancer that is associated with abysmal prognosis. The median survival of GBM patients is ∼15 months and there have not been any significant advance in therapies in over a decade, leaving treatment options limited. There is clearly an unmet need for GBM treatment. Immunotherapies are treatments based on usurping the power of the host's immune system to recognize and eliminate cancer cells. They have recently proven to be a successful strategy for combating a variety of cancers...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230247/digest-less-than-the-sum-of-its-parts-negative-epistasis-in-bacterial-swarming
#5
Sonia Singhal, Katrina van Raay
Understanding how mutations change phenotypes is vital to evolutionary biology. However, predicting evolutionary outcomes is complicated by the fact that a mutation's effect may depend on the individual's genetic background. Epistasis occurs when interactions among different genes or mutations result in phenotypes that differ from the sum of their parts. Uncovering epistasis usually involves genetic engineering of point mutations and then comparing the phenotypic effect of each mutation individually against its effect in combination with others (e...
February 23, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28229928/an-expanded-genetic-code-for-probing-the-role-of-electrostatics-in-enzyme-catalysis-by-vibrational-stark-spectroscopy
#6
REVIEW
Jan-Stefan Völler, Hernan Biava, Peter Hildebrandt, Nediljko Budisa
BACKGROUND: To find experimental validation for electrostatic interactions essential for catalytic reactions represents a challenge due to practical limitations in assessing electric fields within protein structures. SCOPE OF REVIEW: This review examines the applications of non-canonical amino acids (ncAAs) as genetically encoded probes for studying the role of electrostatic interactions in enzyme catalysis. MAJOR CONCLUSIONS: ncAAs constitute sensitive spectroscopic probes to detect local electric fields by exploiting the vibrational Stark effect (VSE) and thus have the potential to map the protein electrostatics...
February 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28229589/production-of-cinnamyl-alcohol-glucoside-from-glucose-in-escherichia-coli
#7
Wei Zhou, Huiping Bi, Yibin Zhuang, Qinglin He, Hua Yin, Tao Liu, Yanhe Ma
Rosin, a cinnamyl alcohol glucoside, is one of the important ingredients in Rhodiola rosea, which is a valuable medicinal herb used for centuries. Rosin displayed multiple biological activities. The traditional method for producing rosin and derivatives is direct extraction from R. rosea, which suffers from limited availability of natural resources and complicated purification procedure. In this work, we achieved de novo biosynthesis of rosin in Escherichia coli. Firstly, a biosynthetic pathway of aglycon cinnamyl alcohol from phenylalanine was constructed...
February 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28228595/hepatitis-c-virus-specific-t-cell-receptor-mrna-engineered-human-t-cells-impact-of-antigen-specificity-on-functional-properties
#8
Anangi Balasiddaiah, Haleh Davanian, Soo Aleman, Anna Pasetto, Lars Frelin, Matti Sällberg, Volker Lohmann, Sarene Koh, Antonio Bertoletti, Margaret Chen
Therapy with genetically modified autologous T cells has shown great promise in cancer therapy. For an efficient control of hepatitis C virus (HCV) infection, cytotoxic T cells (CTL) are pivotal but persistence of activated T cells may lead to liver toxicity. Here, anti-HCV T cell receptors (TCRs) recognising the HCV non-structural (NS) NS3 or NS5 viral peptide target were examined by mRNA transfection of human peripheral blood lymphocytes (PBL) derived from healthy donors as well as chronically infected HCV patients...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228086/clinical-trials-with-oncolytic-measles-virus-current-status-and-future-prospects
#9
Pavlos Msaouel, Mateusz Opyrchal, Angela Dispenzieri, Kah Whye Peng, Mark J Federspiel, Stephen J Russell, Evanthia Galanis
Attenuated Edmonston lineage measles virus (MV-Edm) vaccine strains can preferentially infect and lyse a wide variety of cancer cells. Oncolytic MV-Edm derivatives genetically engineered to expressed the human carcinoembryonic antigen (MV-CEA virus) or the human sodium iodide symporter (MV-NIS virus) and are currently being tested in clinical trials against ovarian cancer, glioblastoma multiforme, multiple myeloma, mesothelioma, head and neck cancer, breast cancer and malignant peripheral nerve sheath tumors...
February 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28226291/cell-free-synthetic-biology-for-environmental-sensing-and-remediation
#10
REVIEW
David K Karig
The fields of biosensing and bioremediation leverage the phenomenal array of sensing and metabolic capabilities offered by natural microbes. Synthetic biology provides tools for transforming these fields through complex integration of natural and novel biological components to achieve sophisticated sensing, regulation, and metabolic function. However, the majority of synthetic biology efforts are conducted in living cells, and concerns over releasing genetically modified organisms constitute a key barrier to environmental applications...
February 19, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28226217/sulfation-of-glycosaminoglycans-and-its-implications-in-human-health-and-disorders
#11
Diana Soares da Costa, Rui L Reis, Iva Pashkuleva
Sulfation is a dynamic and complex posttranslational modification process. It can occur at various positions within the glycosaminoglycan (GAG) backbone and modulates extracellular signals such as cell-cell and cell-matrix interactions; different sulfation patterns have been identified for the same organs and cells during their development. Because of their high specificity in relation to function,GAGsulfation patterns are referred to as the sulfation code. This review explores the role of GAG sulfation in different biological processes at the cell, tissue, and organism levels...
February 2, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28225256/analysis-and-control-of-chain-mobility-in-protein-hydrogels
#12
Peter B Rapp, Ahmad K Omar, Jeff J Shen, Maren E Buck, Zhen-Gang Wang, David A Tirrell
Coiled-coil domains can direct the assembly of protein block copolymers into physically crosslinked, viscoelastic hydrogels. Here we describe the use of fluorescence recovery after photobleaching (FRAP) to probe chain mobility in reversible hydrogels assembled from engineered proteins bearing terminal coiled-coil domains. We show that chain mobility can be related to the underlying dynamics of the coiled-coil domains by application of a 3-state "hopping" model of chain migration. We further show that genetic programming allows the effective mobility of network chains to be varied 500-fold through modest changes in protein sequence...
February 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28225058/superstatistical-model-of-bacterial-dna-architecture
#13
Mikhail I Bogachev, Oleg A Markelov, Airat R Kayumov, Armin Bunde
Understanding the physical principles that govern the complex DNA structural organization as well as its mechanical and thermodynamical properties is essential for the advancement in both life sciences and genetic engineering. Recently we have discovered that the complex DNA organization is explicitly reflected in the arrangement of nucleotides depicted by the universal power law tailed internucleotide interval distribution that is valid for complete genomes of various prokaryotic and eukaryotic organisms. Here we suggest a superstatistical model that represents a long DNA molecule by a series of consecutive ~150 bp DNA segments with the alternation of the local nucleotide composition between segments exhibiting long-range correlations...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224920/genetic-engineering-of-the-biosynthesis-of-glycinebetaine-leads-to-alleviate-salt-induced-potassium-efflux-and-enhances-salt-tolerance-in-tomato-plants
#14
Dandan Wei, Wen Zhang, Cuicui Wang, Qingwei Meng, Gang Li, Tony H H Chen, Xinghong Yang
Tomato (Solanum lycopersicum cv. 'Moneymaker') was transformed with the choline oxidase gene codA from Arthrobacter globiformis, which was modified to allow for targeting to both chloroplasts and the cytosol. Glycine betaine (GB) was accumulated in transformed plants, while no detectable GB was found in wild-type (WT) plants. Compared to WT plants, transgenic lines showed significantly higher photosynthetic rates (Pn) and antioxidant enzyme activities and lower reactive oxygen species (ROS) accumulation in the leaves when exposed to salt stress...
April 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28224230/newly-isolated-bacillus-sp-g51-from-patagonian-wool-produces-an-enzyme-combination-suitable-for-felt-resist-treatments-of-organic-wool
#15
Martín S Iglesias, Cynthia Sequeiros, Sebastián García, Nelda L Olivera
Bacteria from Patagonian Merino wool were isolated to assess their wool-keratinolytic activity and potential for felt-resist treatments. Strains from Bacillus, Exiguobacterium, Deinococcus, and Micrococcus produced wool-degrading enzymes. Bacillus sp. G51 showed the highest wool-keratinolytic activity. LC-MS/MS analysis revealed that G51 secreted two serine proteases belonging to the peptidase family S8 (MEROPS) and a metalloprotease associated with Bacillolysin, along with other enzymes (γ-glutamyltranspeptidase and dihydrolipoyl dehydrogenases) that could be involved in reduction of keratin disulfide bonds...
February 21, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28223994/enhanced-grain-iron-levels-in-rice-expressing-an-iron-regulated-metal-transporter-nicotianamine-synthase-and-ferritin-gene-cassette
#16
Kulaporn Boonyaves, Ting-Ying Wu, Wilhelm Gruissem, Navreet K Bhullar
Micronutrient malnutrition is widespread, especially in poor populations across the globe, and iron deficiency anemia is one of the most prevalent forms of micronutrient deficiencies. Iron deficiency anemia has severe consequences for human health, working ability, and quality of life. Several interventions including iron supplementation and food fortification have been attempted and met with varied degrees of success. Rice, which is a staple food for over half of the world's population, is an important target crop for iron biofortification...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223460/mechanism-of-h2s-oxidation-by-the-dissimilatory-perchlorate-reducing-microorganism-azospira-suillum-ps
#17
Misha G Mehta-Kolte, Dana Loutey, Ouwei Wang, Matthew D Youngblut, Christopher G Hubbard, Kelly M Wetmore, Mark E Conrad, John D Coates
The genetic and biochemical basis of perchlorate-dependent H2S oxidation (PSOX) was investigated in the dissimilatory perchlorate-reducing microorganism (DPRM) Azospira suillum PS (PS). Previously, it was shown that all known DPRMs innately oxidize H2S, producing elemental sulfur (S(o)). Although the process involving PSOX is thermodynamically favorable (ΔG°' = -206 kJ ⋅ mol(-1) H2S), the underlying biochemical and genetic mechanisms are currently unknown. Interestingly, H2S is preferentially utilized over physiological electron donors such as lactate or acetate although no growth benefit is obtained from the metabolism...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28223282/induction-of-nkg2d-ligands-on-solid-tumors-requires-tumor-specific-cd8-t-cells-and-histone-acetyltransferases
#18
Jiemiao Hu, Chantale Bernatchez, Liangfang Zhang, Xueqing Xia, Eugenie S Kleinerman, Mien-Chie Hung, Patrick Hwu, Shulin Li
NKG2D-mediated immune surveillance is crucial for inhibiting tumor growth and metastases. Malignant tumor cells often downregulate NKG2D ligands to escape from immune surveillance. High-profile studies have shown that restoring NKG2D ligand expression via genetic engineering inhibits tumor formation and progression. However, no effective in vivo approaches are available to restore these ligands across different types of solid tumors, because the classic stress signal-dependent induction of this ligand in vitro is transient and has rarely been duplicated in solid tumors in vivo We found that co-administration of an immune stimulatory signal (interleukin-12) and chemotherapy (doxorubicin) restored the NKG2D ligand Rae-1 in multiple tumor types, including a human tumor model...
February 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28223167/intracavitary-t4-immunotherapy-of-malignant-mesothelioma-using-pan-erbb-re-targeted-car-t-cells
#19
Astero Klampatsa, Daniela Y Achkova, David M Davies, Ana C Parente-Pereira, Natalie Woodman, James Rosekilly, Georgina Osborne, Thivyan Thayaparan, Andrea Bille, Michael Sheaf, James F Spicer, Juliet King, John Maher
Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy...
February 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28222737/dynamic-genome-scale-metabolic-modeling-of-the-yeast-pichia-pastoris
#20
Francisco Saitua, Paulina Torres, José Ricardo Pérez-Correa, Eduardo Agosin
BACKGROUND: Pichia pastoris shows physiological advantages in producing recombinant proteins, compared to other commonly used cell factories. This yeast is mostly grown in dynamic cultivation systems, where the cell's environment is continuously changing and many variables influence process productivity. In this context, a model capable of explaining and predicting cell behavior for the rational design of bioprocesses is highly desirable. Currently, there are five genome-scale metabolic reconstructions of P...
February 21, 2017: BMC Systems Biology
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