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https://www.readbyqxmd.com/read/28240912/domain-targeted-metabolomics-delineates-the-heterocycle-assembly-steps-of-colibactin-biosynthesis
#1
Eric Trautman, Alan R Healy, Emilee Shine, Seth B Herzon, Jason M Crawford
Modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) comprise giant multidomain enzymes responsible for the "assembly line" biosynthesis of many genetically-encoded small molecules. Site-directed mutagenesis, protein biochemical, and structural studies have focused on elucidating the catalytic mechanisms of individual multidomain proteins and protein domains within these megasynthases. Probing their functions at the cellular level typically has invoked the complete deletion (or overexpression) of multidomain-encoding genes or combinations of genes and comparing those mutants to a control pathway...
February 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28239534/transcriptome-and-metabolome-analysis-of-liver-and-kidneys-of-rats-chronically-fed-nk603-roundup-tolerant-genetically-modified-maize
#2
Robin Mesnage, Matthew Arno, Gilles-Eric Séralini, Michael N Antoniou
BACKGROUND: A previous 2-year rat feeding trial assessing potential toxicity of NK603 Roundup-tolerant genetically modified maize revealed blood and urine biochemical changes indicative of liver and kidney pathology. In an effort to obtain deeper insight into these findings, molecular profiling of the liver and kidneys from the same animals was undertaken. RESULTS: Transcriptomics showed no segregation of NK603 maize and control feed groups with false discovery rates ranging from 43 to 83% at a cut-off p value of 1%...
2017: Environmental Sciences Europe
https://www.readbyqxmd.com/read/28239189/pyrrolysyl-trna-synthetase-an-aminoacyl-trna-synthetase-for-genetic-code-expansion
#3
Ana Crnković, Tateki Suzuki, Dieter Söll, Noah M Reynolds
Genetic code expansion (GCE) has become a central topic of synthetic biology. GCE relies on engineered aminoacyl-tRNA synthetases (aaRSs) and a cognate tRNA species to allow codon reassignment by co-translational insertion of non-canonical amino acids (ncAAs) into proteins. Introduction of such amino acids increases the chemical diversity of recombinant proteins endowing them with novel properties. Such proteins serve in sophisticated biochemical and biophysical studies both in vitro and in vivo, they may become unique biomaterials or therapeutic agents, and they afford metabolic dependence of genetically modified organisms for biocontainment purposes...
June 2016: Croatica Chemica Acta. Arhiv za Kemiju
https://www.readbyqxmd.com/read/28237815/antiepileptic-action-of-c-jun-n-terminal-kinase-jnk-inhibition-in-an-animal-model-of-temporal-lobe-epilepsy
#4
Tina Y Tai, Lindsay N Warner, Terrance D Jones, Sangwook Jung, Francis A Concepcion, David W Skyrud, Jason Fender, Yusha Liu, Aaron D Williams, John F Neumaier, Raimondo D'Ambrosio, Nicholas P Poolos
Several phosphorylation signaling pathways have been implicated in the pathogenesis of epilepsy arising from both genetic causes and acquired insults to the brain. Identification of dysfunctional signaling pathways in epilepsy may provide novel targets for antiepileptic therapies. We previously described a deficit in phosphorylation signaling mediated by p38 mitogen-activated protein kinase (p38 MAPK) that occurs in an animal model of temporal lobe epilepsy, and that produces neuronal hyperexcitability measured in vitro...
February 22, 2017: Neuroscience
https://www.readbyqxmd.com/read/28237109/monitoring-the-formation-of-autophagosomal-precursor-structures-in-yeast-saccharomyces-cerevisiae
#5
R Gómez-Sánchez, J Sánchez-Wandelmer, F Reggiori
The budding yeast Saccharomyces cerevisiae is a powerful and versatile model organism for studying multiple aspects of the biology of eukaryotic cells, including the molecular principles underlying autophagy. One of the unique advantages of this unicellular system is its amenability to genetic and biochemical approaches, which had a pivotal role in the discovery and characterization of most of the autophagy-related (Atg) proteins, the central players of autophagy. The relevance of investigating autophagy in this cell model lies in the high conservation of this pathway among eukaryotes, i...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28236971/ligand-receptor-mediated-regulation-of-growth-in-plants
#6
Miyoshi Haruta, Michael R Sussman
Growth and development of multicellular organisms are coordinately regulated by various signaling pathways involving the communication of inter- and intracellular components. To form the appropriate body patterns, cellular growth and development are modulated by either stimulating or inhibiting these pathways. Hormones and second messengers help to mediate the initiation and/or interaction of the various signaling pathways in all complex multicellular eukaryotes. In plants, hormones include small organic molecules, as well as larger peptides and small proteins, which, as in animals, act as ligands and interact with receptor proteins to trigger rapid biochemical changes and induce the intracellular transcriptional and long-term physiological responses...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28236196/erratum-to-genetic-and-biochemical-characterization-of-rhizobacterial-strains-and-their-potential-use-in-combination-with-chelants-for-assisted-phytoremediation
#7
Angela Cicatelli, Francesco Guarino, Enrico Baldan, Stefano Castiglione
No abstract text is available yet for this article.
February 24, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28231254/rapid-generation-of-drug-resistance-alleles-at-endogenous-loci-using-crispr-cas9-indel-mutagenesis
#8
Jonathan J Ipsaro, Chen Shen, Eri Arai, Yali Xu, Justin B Kinney, Leemor Joshua-Tor, Christopher R Vakoc, Junwei Shi
Genetic alterations conferring resistance to the effects of chemical inhibitors are valuable tools for validating on-target effects in cells. Unfortunately, for many therapeutic targets such alleles are not available. To address this issue, we evaluated whether CRISPR-Cas9-mediated insertion/deletion (indel) mutagenesis can produce drug-resistance alleles at endogenous loci. This method takes advantage of the heterogeneous in-frame alleles produced following Cas9-mediated DNA cleavage, which we show can generate rare alleles that confer resistance to the growth-arrest caused by chemical inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28231061/role-of-treatment-modifying-mthfr677c-t-and-1298a-c-polymorphisms-in-metformin-treated-puerto-rican-patients-with-type-2-diabetes-mellitus-and-peripheral-neuropathy
#9
Francisco J Jiménez-Ramírez, Liza M Castro, Clarymar Ortiz, Jennifer Concepción, Jessicca Y Renta, Raúl H Morales-Borges, Jorge R Miranda-Massari, Jorge Duconge
BACKGROUND: The study was conducted to investigate potential association between MTHFR genotypes and diabetic peripheral neuropathy (DPN) in Puerto Ricans with type-2 diabetes mellitus (T2DM) treated with metformin. The prevalence of major MTHFR polymorphisms in this cohort was also ascertained. METHODS: DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C>T and 1298A>C polymorphisms. Frequency distributions of these variants in the study cohort were compared to those reported for three reference populations (HapMap project) and controls (400 newborn specimens)...
February 23, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28229507/a-samhd1-mutation-associated-with-aicardi-gouti%C3%A3-res-syndrome-uncouples-the-ability-of-samhd1-to-restrict-hiv-1-from-its-ability-to-downmodulate-type-i-interferon-in-humans
#10
Tommy E White, Alberto Brandariz-Nuñez, Alicia Martinez-Lopez, Caitlin Knowlton, Gina Lenzi, Baek Kim, Dmitri Ivanov, Felipe Diaz-Griffero
Mutations in the human SAMHD1 gene are known to correlate with the development of the Aicardi-Goutières Syndrome (AGS), which is an inflammatory encephalopathy that exhibits neurological dysfunction characterized by increased production of type I interferon (IFN); this evidence has lead to the concept that the SAMHD1 protein negatively regulates the type I IFN response. Additionally, the SAMHD1 protein has been shown to prevent efficient HIV-1 infection of macrophages, dendritic cells and resting CD4+ T cells...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28229243/correlation-of-insulin-resistance-and-motor-function-in-spinal-and-bulbar-muscular-atrophy
#11
Hideaki Nakatsuji, Amane Araki, Atsushi Hashizume, Yasuhiro Hijikata, Shinichiro Yamada, Tomonori Inagaki, Keisuke Suzuki, Haruhiko Banno, Noriaki Suga, Yohei Okada, Manabu Ohyama, Tohru Nakagawa, Ken Kishida, Tohru Funahashi, Iichiro Shimomura, Hideyuki Okano, Masahisa Katsuno, Gen Sobue
This study aimed to evaluate various metabolic parameters in patients with spinal and bulbar muscular atrophy (SBMA), to investigate the association between those indices and disease severity, and to explore the underlying molecular pathogenesis. We compared the degree of obesity, metabolic parameters, and blood pressure in 55 genetically confirmed SBMA patients against those in 483 age- and sex-matched healthy control. In SBMA patients, we investigated the correlation between these factors and motor functional indices...
February 22, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28228528/clinical-genetic-and-structural-basis-of-congenital-adrenal-hyperplasia-due-to-11%C3%AE-hydroxylase-deficiency
#12
Ahmed Khattab, Shozeb Haider, Ameet Kumar, Samarth Dhawan, Dauood Alam, Raquel Romero, James Burns, Di Li, Jessica Estatico, Simran Rahi, Saleel Fatima, Ali Alzahrani, Mona Hafez, Noha Musa, Maryam Razzghy Azar, Najoua Khaloul, Moez Gribaa, Ali Saad, Ilhem Ben Charfeddine, Berenice Bilharinho de Mendonça, Alicia Belgorosky, Katja Dumic, Miroslav Dumic, Javier Aisenberg, Nurgun Kandemir, Ayfer Alikasifoglu, Alev Ozon, Nazli Gonc, Tina Cheng, Ursula Kuhnle-Krahl, Marco Cappa, Paul-Martin Holterhus, Munier A Nour, Daniele Pacaud, Assaf Holtzman, Sun Li, Mone Zaidi, Tony Yuen, Maria I New
Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28226784/parameter-estimation-for-gene-regulatory-networks-a-two-stage-mcmc-bayesian-approach
#13
Niannan Xue, Wei Pan, Yike Guo, Niannan Xue, Wei Pan, Yike Guo, Wei Pan, Yike Guo, Niannan Xue
Genetic regulatory networks have emerged as a useful way to elucidate the biochemical pathways for biological functions. Yet, determination of the exact parametric forms for these models remain a major challenge. In this paper, we present a novel computational approach implemented in C++ to solve this inverse problem. This takes the form of an optimization stage first after which Bayesian filtering takes place. The key advantage of such a flexible, general and robust approach is that it provides us with a joint probability distribution of the model parameters instead of single estimates, which we can propagate to final predictions...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28224003/darwinism-for-the-genomic-age-connecting-mutation-to-diversification
#14
Xia Hua, Lindell Bromham
A growing body of evidence suggests that rates of diversification of biological lineages are correlated with differences in genome-wide mutation rate. Given that most research into differential patterns of diversification rate have focused on species traits or ecological parameters, a connection to the biochemical processes of genome change is an unexpected observation. While the empirical evidence for a significant association between mutation rate and diversification rate is mounting, there has been less effort in explaining the factors that mediate this connection between genetic change and species richness...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28223996/untargeted-metabotyping-lolium-perenne-reveals-population-level-variation-in-plant-flavonoids-and-alkaloids
#15
Mingshu Cao, Karl Fraser, Chris Jones, Alan Stewart, Thomas Lyons, Marty Faville, Brent Barrett
Metabolomics provides a powerful platform to characterize plants at the biochemical level, allowing a search for underlying genes and associations with higher level complex traits such as yield and nutritional value. Efficient and reliable methods to characterize metabolic variation in economically important species are considered of high value to the evaluation and prioritization of germplasm and breeding lines. In this investigation, a large-scale metabolomic survey was performed on a collection of diverse perennial ryegrass (Lolium perenne L...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223908/elevated-urinary-glyphosate-and-clostridia-metabolites-with-altered-dopamine-metabolism-in-triplets-with-autistic-spectrum-disorder-or-suspected-seizure-disorder-a-case-study
#16
William Shaw
CONTEXT: Autism is a neurodevelopmental disorder for which a number of genetic, environmental, and nutritional causes have been proposed. Glyphosate is used widely as a crop desiccant and as an herbicide in fields of genetically modified foods that are glyphosate resistant. Several researchers have proposed that it may be a cause of autism, based on epidemiological data that correlates increased usage of glyphosate with an increased autism rate. OBJECTIVE: The current study was intended to determine if excessive glyphosate was present in the triplets and their parents and to evaluate biochemical findings for the family to determine the potential effects of its presence...
February 2017: Integrative Medicine
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/28223017/novel-bcl2-inhibitor-disarib-induces-apoptosis-by-disruption-of-bcl2-bak-interaction
#18
Supriya V Vartak, Divyaanka Iyer, T R Santhoshkumar, Sheetal Sharma, Archita Mishra, Gunaseelan Goldsmith, Mrinal Srivastava, Shikha Srivastava, Subhas S Karki, Avadhesha Surolia, Bibha Choudhary, Sathees C Raghavan
Apoptosis is a highly regulated pathway of programmed cell death relying on the fine balance between pro and antiapoptotic binding partners. Overexpression of the antiapoptotic protein BCL2 in several cancers makes it an ideal target for chemotherapy, with minimum side effects. In one of our previous studies, we designed, synthesized and characterized Disarib, a BCL2-specific small molecule inhibitor. Interestingly, Disarib showed a novel mode of BCL2 inhibition, by predominantly binding to its BH1 domain, as compared to the BH3-specific action of other known BCL2 inhibitors...
February 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28222780/advanced-biosensors-for-detection-of-pathogens-related-to-livestock-and-poultry
#19
REVIEW
Jasmina Vidic, Marisa Manzano, Chung-Ming Chang, Nicole Jaffrezic-Renault
Infectious animal diseases caused by pathogenic microorganisms such as bacteria and viruses threaten the health and well-being of wildlife, livestock, and human populations, limit productivity and increase significantly economic losses to each sector. The pathogen detection is an important step for the diagnostics, successful treatment of animal infection diseases and control management in farms and field conditions. Current techniques employed to diagnose pathogens in livestock and poultry include classical plate-based methods and conventional biochemical methods as enzyme-linked immunosorbent assays (ELISA)...
February 21, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28222408/severe-osteoporosis-with-multiple-spontaneous-vertebral-fractures-in-a-young-male-carrying-triple-polymorphisms-in-the-vitamin-d-receptor-collagen-type-1-and-low-density-lipoprotein-receptor-related-peptide-5-genes
#20
Maria P Yavropoulou, Panagoulia Kollia, Dimitris Chatzidimitriou, Stavroula Samara, Lemonia Skoura, John G Yovos
: Osteoporosis is a common disease with a strong genetic component. Several studies have reported the vitamin D receptor (VDR), collagen type I (COL1A1), and LDL receptor-related protein 5 (LRP5) genes as the most likely candidates. However, most of the studies have been carried out in postmenopausal women and older men and show inconsistent results. CASE PRESENTATION: We report a case of a 26-year old male who presented with severe back pain of acute onset, unrelated to any kind of trauma, and diffuse myalgia...
October 2016: Hormones: International Journal of Endocrinology and Metabolism
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