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https://www.readbyqxmd.com/read/27909940/enhancement-of-rapamycin-production-by-metabolic-engineering-in-streptomyces-hygroscopicus-based-on-genome-scale-metabolic-model
#1
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/27908785/disco-interacting-protein-2-regulates-axonal-bifurcation-and-guidance-of-drosophila-mushroom-body-neurons
#2
Yohei Nitta, Daisuke Yamazaki, Atsushi Sugie, Makoto Hiroi, Tetsuya Tabata
Axonal branching is one of the key processes within the enormous complexity of the nervous system to enable a single neuron to send information to multiple targets. However, the molecular mechanisms that control branch formation are poorly understood. In particular, previous studies have rarely addressed the mechanisms underlying axonal bifurcation, in which axons form new branches via splitting of the growth cone. We demonstrate that DISCO Interacting Protein 2 (DIP2) is required for precise axonal bifurcation in Drosophila mushroom body (MB) neurons by suppressing ectopic bifurcation and regulating the guidance of sister axons...
November 28, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27908688/increased-production-of-l-serine-in-escherichia-coli-through-adaptive-laboratory-evolution
#3
Hemanshu Mundhada, Jose S Miguel, Konstantin Schneider, Anna Koza, Hanne B Christensen, Tobias Klein, Patrick V Phaneuf, Markus Herrgard, Adam M Feist, Alex T Nielsen
L-serine is a promising building block biochemical with a high theoretical production yield from glucose. Toxicity of L-serine is however prohibitive for high-titer production in E. coli. Here, E. coli lacking L-serine degradation pathways was evolved for improved tolerance by gradually increasing L-serine concentration from 3 to 100g/L using adaptive laboratory evolution (ALE). Genome sequencing of isolated clones revealed multiplication of genetic regions, as well as mutations in thrA, thereby showing a potential mechanism of serine inhibition...
November 28, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27908343/a%C3%AE-amyloid-pathology-affects-the-hearts-of-patients%C3%A2-with%C3%A2-alzheimer-s-disease-mind%C3%A2-the-heart
#4
Luca Troncone, Marco Luciani, Matthew Coggins, Elissa H Wilker, Cheng-Ying Ho, Kari Elise Codispoti, Matthew P Frosch, Rakez Kayed, Federica Del Monte
BACKGROUND: Individually, heart failure (HF) and Alzheimer's disease (AD) are severe threats to population health, and their potential coexistence is an alarming prospect. In addition to sharing analogous epidemiological and genetic profiles, biochemical characteristics, and common triggers, the authors recently recognized common molecular and pathological features between the 2 conditions. Whereas cognitive impairment has been linked to HF through perfusion defects, angiopathy, and inflammation, whether patients with AD present with myocardial dysfunction, and if the 2 conditions bear a common pathogenesis as neglected siblings are unknown...
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27908266/is-metformin-a-perfect-drug-updates-in-pharmacokinetics-and-pharmacodynamics
#5
Magdalena Markowicz-Piasecka, Kristiina Maria Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. In this review, we present the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27906997/role-of-genetic-polymorphisms-in-the-development-and-prognosis-of-sporadic-and-familial-prostate-cancer
#6
Sabrina T Reis, Nayara I Viana, Katia R M Leite, Erico Diogenes, Alberto A Antunes, Alexandre Iscaife, Adriano J Nesrallah, Carlo C Passerotti, Victor Srougi, José Pontes-Junior, Mary Ellen Salles, William C Nahas, Miguel Srougi
BACKGROUNDS: Our aim was to evaluate the role of 20 genetic polymorphisms in the development and prognosis of sporadic and familial PC. A case-control study of 185 patients who underwent radical prostatectomy from 1997 to 2011. These patients were divided into two groups based on their family history. Gleason grade, PSA value and pathological TNM 2002 stage were used as prognostic factors. Blood samples from 70 men without PC were used as controls. The SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit...
2016: PloS One
https://www.readbyqxmd.com/read/27906114/p38%C3%AE-mapk-disables-kmt1a-mediated-repression-of-myogenic-differentiation-program
#7
Biswanath Chatterjee, David W Wolff, Mathivanan Jothi, Munmun Mal, Asoke K Mal
BACKGROUND: Master transcription factor MyoD can initiate the entire myogenic gene expression program which differentiates proliferating myoblasts into multinucleated myotubes. We previously demonstrated that histone methyltransferase KMT1A associates with and inhibits MyoD in proliferating myoblasts, and must be removed to allow differentiation to proceed. It is known that pro-myogenic signaling pathways such as PI3K/AKT and p38α MAPK play critical roles in enforcing associations between MyoD and transcriptional activators, while removing repressors...
August 22, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905614/methanobactins-from-genome-to-function
#8
Laura M K Dassama, Grace E Kenney, Amy C Rosenzweig
Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptide (RiPP) natural products that bind copper with high affinity using nitrogen-containing heterocycles and thioamide groups. In some methanotrophic bacteria, Mbns are secreted under conditions of copper starvation and then re-internalized as a copper source for the enzyme particulate methane monooxygenase (pMMO). Genome mining studies have led to the identification and classification of operons encoding the Mbn precursor peptide (MbnA) as well as a number of putative transport, regulatory, and biosynthetic proteins...
December 1, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27905213/hepatic-lipid-and-genetic-factors-associated-with-obesity-crosstalk-with-alcohol-dependence
#9
Kimberly Goodyear, Mary R Lee, Melanie L Schwandt, Colin A Hodgkinson, Lorenzo Leggio
OBJECTIVES: Alcohol dependence represents a leading cause of mortality and morbidity. Understanding the variables that contribute to this diagnosis and its severity is critical. An overlap between factors that may predispose people to become obese and those that may increase the risk of alcohol dependence may exist. However, data in the literature are not conclusive. Therefore, this study aimed to identify the association between alcohol dependence and obesity-related factors, including biochemical and genetic factors...
December 1, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27904882/first-case-of-actinomycetoma-in-france-due-to-a-novel-nocardia-species-nocardia-boironii-sp-nov
#10
Jacques M Gilquin, Brigitte Riviere, Valme Jurado, Bernard Audouy, Jean-Baptiste Kouatche, Emmanuelle Bergeron, Delphine Mouniée, Thierry Molina, Philippe Faure, Cesáreo Saiz-Jimenez, Verónica Rodríguez-Nava
Bacterial mycetoma is a neglected disease mainly observed in tropical area countries and typically associated with rural conditions, making its presence in developed countries of temperate climate areas rare. However, we report the first case of an autochthonous mycetoma case in continental France that originated from a new Nocardia species. A Gram-positive filamentous bacterium (OFN 14.177(T)) was isolated from a pus sample from the mycetoma of a male French patient 92 years old suffering from chronic lymphocytic leukemia...
November 2016: MSphere
https://www.readbyqxmd.com/read/27904153/genotype-and-phenotype-characterization-in-a-spanish-cohort-with-isovaleric-acidemia
#11
María L Couce, Luís Aldamiz-Echevarría, María A Bueno, Patricia Barros, Amaya Belanger-Quintana, Javier Blasco, María-Teresa García-Silva, Ana M Márquez-Armenteros, Isidro Vitoria, Inmaculada Vives, Rosa Navarrete, Ana Fernández-Marmiesse, Belén Pérez, Celia Pérez-Cerdá
Isovaleric acidemia (IVA) is a rare disorder of leucine metabolism. We carried out a multicenter study of IVA patients diagnosed by newborn screening (NBS) or symptoms clinics over a period of 28 years in Spain. Evaluated at diagnosis, data included age, detection method, levels of C5 and IVG, enzymatic studies, clinical presentation parameters and genotype in 16 patients. Follow-up data included C5 levels, intellectual quotient and correlation genotype-phenotype. IVA was detected by NBS in 8 patients (prevalence of 1/326 629)...
December 1, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27903722/adenosine-kinase-deficiency-in-the-brain-results-in-maladaptive-synaptic-plasticity
#12
Ursula S Sandau, Mariana Colino-Oliveira, Abbie Jones, Bounmy Saleumvong, Shayla Q Coffman, Long Liu, Catarina Miranda-Lourenço, Cátia Palminha, Vânia L Batalha, Yiming Xu, Yuqing Huo, Maria J Diógenes, Ana M Sebastião, Detlev Boison
: Adenosine kinase (ADK) deficiency in human patients (OMIM:614300) disrupts the methionine cycle and triggers hypermethioninemia, hepatic encephalopathy, cognitive impairment, and seizures. To identify whether this neurological phenotype is intrinsically based on ADK deficiency in the brain or if it is secondary to liver dysfunction, we generated a mouse model with a brain-wide deletion of ADK by introducing a Nestin-Cre transgene into a line of conditional ADK deficient Adk(fl/fl) mice...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903531/dream-plays-an-important-role-in-platelet-activation-and-thrombogenesis
#13
Kyungho Kim, Alan Tseng, Andrew Barazia, Joseph E Italiano, Jaehyung Cho
Downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, is known to modulate pain responses. However, it is unknown whether DREAM is expressed in anucleate platelets and plays a role in thrombogenesis. By using intravital microscopy with DREAM-null mice and their bone marrow chimeras, we demonstrated that both hematopoietic and non-hematopoietic cell DREAM are required for platelet thrombus formation following laser-induced arteriolar injury. In a FeCl3-induced thrombosis model, we found that compared to WT control and non-hematopoietic DREAM knockout (KO) mice, DREAM KO control and hematopoietic DREAM KO mice showed a significant delay in time to occlusion...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27903453/repair-of-8-oxo-7-8-dihydroguanine-in-prokaryotic-and-eukaryotic-cells-properties-and-biological-roles-of-the-fpg-and-ogg1-dna-n-glycosylases
#14
Serge Boiteux, Franck Coste, Bertrand Castaing
Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases...
November 26, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27903443/biochemical-and-genetic-basis-of-orsellinic-acid-biosynthesis-and-prenylation-in-a-stereaceous-basidiomycete
#15
Jana Braesel, Janis Fricke, Daniel Schwenk, Dirk Hoffmeister
The prenylphenols are a class of natural products that have been frequently isolated from basidiomycetes, e.g., from the genus Stereum (false turkey tail fungi) and other Russulales as well as from ascomycetes. Biosynthetically, these compounds are considered hybrids, as the orsellinic acid moiety is a polyketide and the prenyl side chain originates from the terpene metabolism, although no literature on the genetic and biochemical background of the biosynthesis is available. In a stereaceous basidiomycete, referred to as BY1, a new prenylphenol, now termed cloquetin, was identified and its structure elucidated by mass spectrometry and nuclear magnetic resonance spectroscopy...
November 26, 2016: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/27902860/genetic-and-biochemical-interactions-between-the-bacterial-replication-initiator-dnaa-and-the-nucleoid-associated-protein-rok-in-bacillus-subtilis
#16
Charlotte A Seid, Janet L Smith, Alan D Grossman
We identified interactions between the conserved bacterial replication initiator and transcription factor DnaA and the nucleoid-associated protein Rok of Bacillus subtilis. DnaA binds directly to clusters of DnaA boxes at the origin of replication and elsewhere, including the promoters of several DnaA-regulated genes. Rok, an analog of H-NS from gamma-proteobacteria that affects chromosome architecture and Lsr2 from Mycobacteria, binds A+T-rich sequences throughout the genome and represses expression of many genes...
November 30, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27900439/non-ribosomal-peptide-synthases-from-pseudomonas-aeruginosa-play-a-role-in-cyclodipeptide-biosynthesis-quorum-sensing-regulation-and-root-development-in-a-plant-host
#17
Omar González, Randy Ortíz-Castro, César Díaz-Pérez, Alma L Díaz-Pérez, Viridiana Magaña-Dueñas, José López-Bucio, Jesús Campos-García
Diverse molecules mediate cross-kingdom communication between bacteria and their eukaryotic partners and determine pathogenic or symbiotic relationships. N-acyl-L-homoserine lactone-dependent quorum-sensing signaling represses the biosynthesis of bacterial cyclodipeptides (CDPs) that act as auxin signal mimics in the host plant Arabidopsis thaliana. In this work, we performed bioinformatics, biochemical, and plant growth analyses to identify non-ribosomal peptide synthase (NRPS) proteins of Pseudomonas aeruginosa, which are involved in CDP synthesis...
November 30, 2016: Microbial Ecology
https://www.readbyqxmd.com/read/27900365/genome-sequencing-in-a-case-of-niemann-pick-type-c
#18
Max Dougherty, John Lazar, Jason C Klein, Karina Diaz, Theodore Gobillot, Eli Grunblatt, Nicholas Hasle, Daniel Lawrence, Megan Maurano, Maria Nelson, Gregory Olson, Sanjay Srivatsan, Jay Shendure, C Dirk Keene, Thomas Bird, Marshall S Horwitz, Desiree A Marshall
Adult-onset Niemann-Pick disease type C (NPC) is an infrequent presentation of a rare neurovisceral lysosomal lipid storage disorder caused by autosomal recessive mutations in NPC1 (∼95%) or NPC2 (∼5%). Our patient was diagnosed at age 33 when he presented with a 10-yr history of difficulties in judgment, concentration, speech, and coordination. A history of transient neonatal jaundice and splenomegaly with bone marrow biopsy suggesting a lipid storage disorder pointed to NPC; biochemical ("variant" level cholesterol esterification) and ultrastructural studies in adulthood confirmed the diagnosis...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899559/division-of-labor-among-mycobacterium-smegmatis-rnase-h-enzymes-rnase-h1-activity-of-rnha-or-rnhc-is-essential-for-growth-whereas-rnhb-and-rnha-guard-against-killing-by-hydrogen-peroxide-in-stationary-phase
#19
Richa Gupta, Debashree Chatterjee, Michael S Glickman, Stewart Shuman
RNase H enzymes sense the presence of ribonucleotides in the genome and initiate their removal by incising the ribonucleotide-containing strand of an RNA:DNA hybrid. Mycobacterium smegmatis encodes four RNase H enzymes: RnhA, RnhB, RnhC and RnhD. Here, we interrogate the biochemical activity and nucleic acid substrate specificity of RnhA. We report that RnhA (like RnhC characterized previously) is an RNase H1-type magnesium-dependent endonuclease with stringent specificity for RNA:DNA hybrid duplexes. Whereas RnhA does not incise an embedded mono-ribonucleotide, it can efficiently cleave within tracts of four or more ribonucleotides in duplex DNA...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27894998/push-pull-and-feedback-mechanisms-can-align-signaling-system-outputs-with-inputs
#20
Steven S Andrews, William J Peria, Richard C Yu, Alejandro Colman-Lerner, Roger Brent
Many cell signaling systems, including the yeast pheromone response system, exhibit "dose-response alignment" (DoRA), in which output of one or more downstream steps closely matches the fraction of occupied receptors. DoRA can improve the fidelity of transmitted dose information. Here, we searched systematically for biochemical network topologies that produced DoRA. Most networks, including many containing feedback and feedforward loops, could not produce DoRA. However, networks including "push-pull" mechanisms, in which the active form of a signaling species stimulates downstream activity and the nominally inactive form reduces downstream activity, enabled perfect DoRA...
November 23, 2016: Cell Systems
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