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https://www.readbyqxmd.com/read/28730450/crispr-cas-rna-scaffolds-for-transcriptional-programming-in-yeast
#1
Jesse G Zalatan
CRISPR scaffold RNAs (scRNAs) provide a modular system for locus-specific transcriptional programming. scRNAs are generated by extending CRISPR guide RNA sequences with domains that recruit RNA-binding proteins, thus physically linking DNA binding and protein recruitment activities. A single scRNA molecule encodes information about the target locus and instructions about what regulatory function to execute at that locus. Sets of scRNA constructs can be used to generate synthetic multigene transcriptional programs in which some genes are activated and others are repressed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28728845/crystal-structure-of-cis-dihydrodiol-naphthalene-dehydrogenase-nahb-from-pseudomonas-sp-mc1-insights-into-the-early-binding-process-of-the-substrate
#2
Ae Kyung Park, Hyun Kim, Il-Sup Kim, Soo Jung Roh, Seung Chul Shin, Jun Hyuck Lee, Hyun Park, Han-Woo Kim
The bacterial strain Pseudomonas sp. MC1 harbors an 81-kb metabolic plasmid, which encodes enzymes involved in the conversion of naphthalene to salicylate. Of these, the enzyme NahB (cis-dihydrodiol naphthalene dehydrogenase), which catalyzes the second reaction of this pathway, binds to various substrates such as cis-1,2-dihydro-1,2-dihydroxy-naphthalene (1,2-DDN), cis-2,3-dihydro-2,3-dihydroxybiphenyl (2,3-DDB), and 3,4-dihydro-3,4-dihydroxy-2,2',5,5'-tetrachlorobiphenyl (3,4-DD-2,2',5-5-TCB). However, the mechanism underlying its broad substrate specificity is unclear owing to the lack of structural information...
July 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28727789/lumpgem-systematic-generation-of-subnetworks-and-elementally-balanced-lumped-reactions-for-the-biosynthesis-of-target-metabolites
#3
Meric Ataman, Vassily Hatzimanikatis
In the post-genomic era, Genome-scale metabolic networks (GEMs) have emerged as invaluable tools to understand metabolic capabilities of organisms. Different parts of these metabolic networks are defined as subsystems/pathways, which are sets of functional roles to implement a specific biological process or structural complex, such as glycolysis and TCA cycle. Subsystem/pathway definition is also employed to delineate the biosynthetic routes that produce biomass building blocks. In databases, such as MetaCyc and SEED, these representations are composed of linear routes from precursors to target biomass building blocks...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28724939/fatty-acid-uptake-in-t-cell-subsets-using-a-quantum-dot-fatty-acid-conjugate
#4
Megan E Muroski, Jason Miska, Alan L Chang, Peng Zhang, Aida Rashidi, Haley Moore, Aurora Lopez-Rosas, Yu Han, Maciej S Lesniak
Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724354/novel-plasmodium-falciparum-metabolic-network-reconstruction-identifies-shifts-associated-with-clinical-antimalarial-resistance
#5
Maureen A Carey, Jason A Papin, Jennifer L Guler
BACKGROUND: Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. RESULTS: Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P...
July 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28723584/the-relationship-between-growth-performance-and-metabolic-rate-flexibility-varies-with-food-availability-in-juvenile-qingbo-spinibarbus-sinensis
#6
Ling-Qing Zeng, Lei Wang, Guan-Nan Wang, Yue Zeng, Shi-Jian Fu
Phenotypic flexibility in traits can allow organisms to cope with environmental challenges. However, the ecological consequences (e.g., growth) of SMR flexibility in fish are poorly understood. Juvenile qingbo (Spinibarbus sinensis) were reared individually with two levels of food resources (satiation or limited) with either continuous feeding (CF) or starvation-refeeding (SR). In the CF experiment, SMR increased when individuals were fed either the satiation or limited diets, but no difference was found in average specific growth rate somatic growth (SGR) between the two food availabilities...
July 16, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28718405/rna-binding-proteins-in-cancer-old-players-and-new-actors
#7
REVIEW
Bruno Pereira, Marc Billaud, Raquel Almeida
RNA-binding proteins (RBPs) are key players in post-transcriptional events. The combination of versatility of their RNA-binding domains with structural flexibility enables RBPs to control the metabolism of a large array of transcripts. Perturbations in RBP-RNA networks activity have been causally associated with cancer development, but the rational framework describing these contributions remains fragmented. We review here the evidence that RBPs modulate multiple cancer traits, emphasize their functional diversity, and assess future trends in the study of RBPs in cancer...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717014/investigating-mixotrophic-metabolism-in-the-model-diatom-phaeodactylum-tricornutum
#8
Valeria Villanova, Antonio Emidio Fortunato, Dipali Singh, Davide Dal Bo, Melissa Conte, Toshihiro Obata, Juliette Jouhet, Alisdair R Fernie, Eric Marechal, Angela Falciatore, Julien Pagliardini, Adeline Le Monnier, Mark Poolman, Gilles Curien, Dimitris Petroutsos, Giovanni Finazzi
Diatoms are prominent marine microalgae, interesting not only from an ecological point of view, but also for their possible use in biotechnology applications. They can be cultivated in phototrophic conditions, using sunlight as the sole energy source. Some diatoms, however, can also grow in a mixotrophic mode, wherein both light and external reduced carbon contribute to biomass accumulation. In this study, we investigated the consequences of mixotrophy on the growth and metabolism of the pennate diatom Phaeodactylum tricornutum, using glycerol as the source of reduced carbon...
September 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28716942/maternal-photoperiod-programs-hypothalamic-thyroid-status-via-the-fetal-pituitary-gland
#9
Cristina Sáenz de Miera, Béatrice Bothorel, Catherine Jaeger, Valérie Simonneaux, David Hazlerigg
In wild mammals, offspring development must anticipate forthcoming metabolic demands and opportunities. Within species, different developmental strategies may be used, dependent on when in the year conception takes place. This phenotypic flexibility is initiated before birth and is linked to the pattern of day length (photoperiod) exposure experienced by the mother during pregnancy. This programming depends on transplacental communication via the pineal hormone melatonin. Here, we show that, in the Siberian hamster (Phodopus sungorus), the programming effect of melatonin is mediated by the pars tuberalis (PT) of the fetal pituitary gland, before the fetal circadian system and autonomous melatonin production is established...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28711730/purification-and-characterization-of-a-long-acting-ciliary-neurotrophic-factor-via-genetically-fused-with-an-albumin-binding-domain
#10
Longfu Xu, Chun Zhang, Liping Liu, Yao Zhang, Qi Wang, Jian Wang, Yongdong Liu, Zhiguo Su
Ciliary neurotrophic factor (CNTF) is a promising candidate for the treatment of neurodegenerative or metabolic diseases, but suffers rapid clearance in body. Herein we constructed a new long-acting recombinant human CNTF (rhCNTF) by genetic fusion with an albumin-binding domain (ABD) through a flexible peptide linker, hoping to endow the new molecule prolonged serum circulation time by binding with endogenous human serum albumin (HSA) and then utilizing the naturally long-half-life property of HSA. This fused protein rhCNTF-ABD was expressed in Escherichia coli mainly in the soluble form and purified through a two-step chromatography, with purity of 95% and a high yield of 90-100 mg/L culture...
July 12, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28710266/specificity-of-subtilin-mediated-activation-of-histidine-kinase-spak
#11
Christoph Geiger, Tobias Spieß, Sophie Marianne Korn, Peter Kötter, Karl-Dieter Entian
Autoinduction via two-component systems is a widespread regulatory mechanism that senses environmental and metabolic changes. Although the lantibiotics nisin and subtilin are closely related and share the same lanthionine ring structure, they autoinduce their biosynthesis in a highly specific manner. Subtilin can only activate the two-component system SpaRK of Bacillus subtilis, whereas nisin activates solely the two-component system NisRK of Lactococcus lactis To identify components that determine the specificity of subtilin autoinduction, several variants of the respective lantibiotic were analyzed for their autoinduction capacity...
July 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28708831/biochem4j-integrated-and-extensible-biochemical-knowledge-through-graph-databases
#12
Neil Swainston, Riza Batista-Navarro, Pablo Carbonell, Paul D Dobson, Mark Dunstan, Adrian J Jervis, Maria Vinaixa, Alan R Williams, Sophia Ananiadou, Jean-Loup Faulon, Pedro Mendes, Douglas B Kell, Nigel S Scrutton, Rainer Breitling
Biologists and biochemists have at their disposal a number of excellent, publicly available data resources such as UniProt, KEGG, and NCBI Taxonomy, which catalogue biological entities. Despite the usefulness of these resources, they remain fundamentally unconnected. While links may appear between entries across these databases, users are typically only able to follow such links by manual browsing or through specialised workflows. Although many of the resources provide web-service interfaces for computational access, performing federated queries across databases remains a non-trivial but essential activity in interdisciplinary systems and synthetic biology programmes...
2017: PloS One
https://www.readbyqxmd.com/read/28701449/the-change-program-exercise-intervention-in-primary-care
#13
Doug Klein, Khursheed Jeejeebhoy, Angelo Tremblay, Matthew Kallio, Caroline Rheaume, Serena Humphries, Dawna Royall, Paula Brauer, Daren Heyland, Rupinder Dhaliwal, David M Mutch
PROBLEM ADDRESSED: Primary care settings require a feasible program for integrating lifestyle interventions, which can reverse metabolic abnormalities, for patients in practice. OBJECTIVE OF PROGRAM: To integrate a lifestyle intervention program into existing primary care clinics with an interprofessional approach that includes dietitians and kinesiologists. PROGRAM DESCRIPTION: Canadian Health Advanced by Nutrition and Graded Exercise (CHANGE) provides a personalized approach to nutrition and exercise modification focusing on patients with metabolic syndrome...
July 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/28689014/poly-pathway-model-a-novel-approach-to-simulate-multiple-metabolic-states-by-reaction-network-based-model-application-to-amino-acid-depletion-in-cho-cell-culture
#14
Erika Hagrot, Hildur Æsa Oddsdóttir, Joan Gonzalez Hosta, Elling W Jacobsen, Véronique Chotteau
Mammalian cell lines are characterized by a complex and flexible metabolism. A single model that could describe the variations in metabolic behavior triggered by variations in the culture conditions would be a precious tool in bioprocess development. In this paper, we introduce an approach to generate a poly-pathway model and use it to simulate diverse metabolic states triggered in response to removal, reduction or doubling of amino acids in the culture medium of an antibody-producing CHO cell line. Macro-reactions were obtained from a metabolic network via elementary flux mode enumeration and the fluxes were modeled by kinetic equations with saturation and inhibition effects from external medium components...
July 5, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28688915/targeted-proteome-analysis-with-isotope-coded-protein-labels-for-monitoring-the-influence-of-dietary-phytochemicals-on-the-expression-of-cytoprotective-proteins-in-primary-human-colon-cells
#15
Christiane Östreicher, Sven Bartenbacher, Monika Pischetsrieder
Cytoprotective effects by upregulating cellular expression levels of antioxidant proteins are attributed to a significant number of food ingredients. Evaluation of those cytoprotective effects and identification of the most active components requires reliable and comprehensive proteomic strategies. Thus, promising potential bioactive ingredients could be determined for the prevention of various diseases, including colon cancer formation. We established a multiplexed nanoLC-MS/MS targeted proteomic method, operated in scheduled selected reaction monitoring mode (sSRM), to record modulation of the expression levels of six major antioxidant proteins induced by dietary phytochemicals...
July 6, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28687587/foxo1-regulates-myocardial-glucose-oxidation-rates-via-transcriptional-control-of-pyruvate-dehydrogenase-kinase-4-expression
#16
Keshav Gopal, Bruno Saleme, Rami Al Batran, Hanin Aburasayn, Amina Eshreif, Kim L Ho, Wayne K Ma, Malak Almutairi, Farah Eaton, Manoj Gandhi, Edwards A Park, Gopinath Sutendra, John R Ussher
Pyruvate dehydrogenase (PDH) is the rate-limiting enzyme for glucose oxidation and a critical regulator of metabolic flexibility during the fasting to feeding transition. PDH is regulated via both PDH kinases (PDHK), and PDH phosphatases, which phosphorylate/inactivate and dephosphorylate/activate PDH, respectively. Our goal was to determine whether the transcription factor, forkhead box O1 (FoxO1) regulates PDH activity and glucose oxidation in the heart via increasing expression of Pdk4, the gene encoding PDHK4...
July 7, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28685754/collagen-derived-proline-promotes-pancreatic-ductal-adenocarcinoma-cell-survival-under-nutrient-limited-conditions
#17
Orianne Olivares, Jared R Mayers, Victoire Gouirand, Margaret E Torrence, Tristan Gicquel, Laurence Borge, Sophie Lac, Julie Roques, Marie-Noëlle Lavaut, Patrice Berthezène, Marion Rubis, Veronique Secq, Stéphane Garcia, Vincent Moutardier, Dominique Lombardo, Juan Lucio Iovanna, Richard Tomasini, Fabienne Guillaumond, Matthew G Vander Heiden, Sophie Vasseur
Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited...
July 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28683921/biology-mechanism-and-structure-of-enzymes-in-the-%C3%AE-d-phosphohexomutase-superfamily
#18
Kyle M Stiers, Andrew G Muenks, Lesa J Beamer
Enzymes in the α-d-phosphohexomutases superfamily catalyze the reversible conversion of phosphosugars, such as glucose 1-phosphate and glucose 6-phosphate. These reactions are fundamental to primary metabolism across the kingdoms of life and are required for a myriad of cellular processes, ranging from exopolysaccharide production to protein glycosylation. The subject of extensive mechanistic characterization during the latter half of the 20th century, these enzymes have recently benefitted from biophysical characterization, including X-ray crystallography, NMR, and hydrogen-deuterium exchange studies...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28683917/striking-diversity-in-holoenzyme-architecture-and-extensive-conformational-variability-in-biotin-dependent-carboxylases
#19
Liang Tong
Biotin-dependent carboxylases are widely distributed in nature and have central roles in the metabolism of fatty acids, amino acids, carbohydrates, and other compounds. The last decade has seen the accumulation of structural information on most of these large holoenzymes, including the 500-kDa dimeric yeast acetyl-CoA carboxylase, the 750-kDa α6β6 dodecameric bacterial propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, and geranyl-CoA carboxylase, the 720-kDa hexameric bacterial long-chain acyl-CoA carboxylase, the 500-kDa tetrameric bacterial single-chain pyruvate carboxylase, the 370-kDa α2β4 bacterial two-subunit pyruvate carboxylase, and the 130-kDa monomeric eukaryotic urea carboxylase...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28680478/a-new-genome-scale-metabolic-model-of-corynebacterium-glutamicum-and-its-application
#20
Yu Zhang, Jingyi Cai, Xiuling Shang, Bo Wang, Shuwen Liu, Xin Chai, Tianwei Tan, Yun Zhang, Tingyi Wen
BACKGROUND: Corynebacterium glutamicum is an important platform organism for industrial biotechnology to produce amino acids, organic acids, bioplastic monomers, and biofuels. The metabolic flexibility, broad substrate spectrum, and fermentative robustness of C. glutamicum make this organism an ideal cell factory to manufacture desired products. With increases in gene function, transport system, and metabolic profile information under certain conditions, developing a comprehensive genome-scale metabolic model (GEM) of C...
2017: Biotechnology for Biofuels
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