keyword
MENU ▼
Read by QxMD icon Read
search

Site directed mutations

keyword
https://www.readbyqxmd.com/read/29160025/development-of-a-specific-fluorescent-phage-endolysin-for-in%C3%A2-situ-detection-of-clostridium-species-associated-with-cheese-spoilage
#1
Natalia Gómez-Torres, Matthew Dunne, Sonia Garde, Rob Meijers, Arjan Narbad, Marta Ávila, Melinda J Mayer
Late blowing defect (LBD) is a major cause of spoilage in cheeses, caused by the growth of Clostridium spp. in the cheese matrix. We investigated the application of CTP1L, a bacteriophage endolysin active against Clostridium tyrobutyricum, and its enzymatically active and cell wall-binding domains (EAD and CBD) attached to green fluorescent protein (GFP) to detect dairy-related Clostridium species by fluorescence microscopy. GFP-CTP1L and GFP-CBD demonstrated specificity for Clostridium spp. by labelling 15 and 17 of 20 Clostridium strains, respectively, but neither bound to other members of the cheese microbiota...
November 21, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/29156616/a-novel-mutation-in-the-fibrinogen-b%C3%AE-chain-c-490g-a-end-of-exon-3-causes-a-splicing-abnormality-and-ultimately-leads-to-congenital-hypofibrinogenemia
#2
Chiaki Taira, Kazuyuki Matsuda, Shinpei Arai, Mitsutoshi Sugano, Takeshi Uehara, Nobuo Okumura
We found a novel heterozygous mutation in the fibrinogen Bβ chain (c.490G>A) of a 3-year-old girl with congenital hypofibrinogenemia. To clarify the complex genetic mechanism, we made a mini-gene including a FGB c.490G>A mutation region, transfected it into a Chinese Hamster Ovary (CHO) cell line, and analyzed reverse transcription (RT) products. The assembly process and secretion were examined using recombinant mutant fibrinogen. Direct sequencing demonstrated that the mutant RT product was 99 bp longer than the wild-type product, and an extra 99 bases were derived from intron 3...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156593/site-directed-mutagenesis-of-the-fibronectin-domains-in-insulin-receptor-related-receptor
#3
Igor E Deyev, Natalia A Chachina, Egor S Zhevlenev, Alexander G Petrenko
The orphan insulin receptor-related receptor (IRR), in contrast to its close homologs, the insulin receptor (IR) and insulin-like growth factor receptor (IGF-IR) can be activated by mildly alkaline extracellular medium. We have previously demonstrated that IRR activation is defined by its extracellular region, involves multiple domains, and shows positive cooperativity with two synergistic sites. By the analyses of point mutants and chimeras of IRR with IR in, we now address the role of the fibronectin type III (FnIII) repeats in the IRR pH-sensing...
November 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29155107/structural-insights-of-rmxyn10a-a-prebiotic-producing-gh10-xylanase-with-a-non-conserved-aglycone-binding-region
#4
Anna Aronsson, Fatma Güler, Maxim V Petoukhov, Susan J Crennell, Dmitri I Svergun, Javier A Linares-Pastén, Eva Nordberg Karlsson
Hydrolysis of arabinoxylan (AX) by glycoside hydrolase family 10 (GH10) xylanases produces xylo- and arabinoxylo-oligosaccharides ((A)XOS) which have shown prebiotic effects. The thermostable GH10 xylanase RmXyn10A has shown great potential to produce (A)XOS. In this study, the structure of RmXyn10A was investigated, the catalytic module by homology modelling and site-directed mutagenesis and the arrangement of its five domains by small-angle X-ray scattering (SAXS). Substrate specificity was explored in silico by manual docking and molecular dynamic simulations...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29150967/drug-delivery-strategies-for-chemoprevention-of-uvb%C3%A2-induced-skin-cancer-a-review
#5
REVIEW
Arvind Bagde, Arindam Mondal, Mandip Singh
Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed towards improvements in terms of delivery modes, therapeutic agents and site-specificity of therapeutics delivery...
November 18, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/29150433/tyrosine-phosphorylation-of-munc18-1-inhibits-synaptic-transmission-by-preventing-snare%C3%A2-assembly
#6
Marieke Meijer, Bernhard Dörr, Hanna Ca Lammertse, Chrysanthi Blithikioti, Jan Rt van Weering, Ruud Fg Toonen, Thomas H Söllner, Matthijs Verhage
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18-1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho-proteomics abolished the stimulatory effect of Munc18-1 on SNARE complex formation ("SNARE-templating") and membrane fusion in vitro Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18-1-null neurons expressing Munc18-1Y473D Synaptic transmission was temporarily restored by high-frequency stimulation, as well as by a Munc18-1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29149730/divergence-of-insulin-superfamily-ligands-receptors-and-igf-binding-proteins-in-marine-versus-freshwater-stickleback-evidence-of-selection-in-known-and-novel-genes
#7
Tim Pellissier, Hend Al Nafea, Sara V Good
Three-spine stickleback (Gasterosteus aculeatus) is a teleost model for understanding genetic, physiological and morphological changes accompanying freshwater (FW) adaptation. There is growing evidence that the insulin superfamily plays important roles in traits involved in marine and FW adaptation. We performed a candidate gene analysis to look for evidence of selection on 33 insulin superfamily ligand-receptor genes and insulin-like growth factor binding proteins (Igfbp's) in stickleback. Using genotype data from 11 marine and 10 FW populations, we calculated the number of SNPs per site in regulatory and intronic regions, the number of synonymous and nonsynonymous mutations in coding regions, Wright's fixation index (Fst), and performed t-tests to identify SNPs with divergent genotype frequencies between marine/FW versus Atlantic/Pacific populations...
November 10, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/29146558/role-of-his-his-interaction-in-ser-474-his-475-tyr-476-sequence-of-chondroitinase-abc-i-in-the-enzyme-activity-and-stability
#8
Monireh Maleki, Khosro Khajeh, Massoud Amanlou, Abolfazl Golestani
Despite clinical importance of chondroitinase ABC I, its application has been limited due to thermal instability as reported in the literature. There are various approaches to improve thermal stability of enzymes, among them, His-His interactions are believed generally as an effective means. In the present study and for preparing a His-His interaction, various mutations in the sequence of Ser(474)-His(475)-Tyr(476) at catalytic domain of the enzyme were performed using site directed mutagenesis method. The effect of these mutations on activity, stability and structural features of cABC I was assessed...
November 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29145480/engineering-the-gh1-%C3%AE-glucosidase-from-humicola-insolens-insights-on-the-stimulation-of-activity-by-glucose-and-xylose
#9
Luana Parras Meleiro, José Carlos Santos Salgado, Raquel Fonseca Maldonado, Sibeli Carli, Luiz Alberto Beraldo Moraes, Richard John Ward, João Atílio Jorge, Rosa Prazeres Melo Furriel
The activity of the GH1 β-glucosidase from Humicola insolens (Bglhi) against p-nitrophenyl-β-D-glucopyranoside (pNP-Glc) and cellobiose is enhanced 2-fold by glucose and/or xylose. Kinetic and transglycosylation data showed that hydrolysis is preferred in the absence of monosaccharides. Stimulation involves allosteric interactions, increased transglycosylation and competition of the substrate and monosaccharides for the -1 glycone and the +1/+2 aglycone binding sites. Protein directed evolution has been used to generate 6 mutants of Bglhi with altered stimulation patterns...
2017: PloS One
https://www.readbyqxmd.com/read/29143996/long-non-coding-rna-h19-suppresses-retinoblastoma-progression-via-counteracting-mir-17-92-cluster
#10
Aihui Zhang, Weiwei Shang, Qiaoli Nie, Ting Li, Suhui Li
Long non-coding RNAs (lncRNAs) are frequently dysregulated and play important roles in many cancers. lncRNA H19 is one of the earliest discovered lncRNAs which has diverse roles in different cancers. However, the expression, roles, and action mechanisms of H19 in retinoblastoma are still largely unknown. In this study, we found that H19 is downregulated in retinoblastoma tissues and cell lines. Gain-of-function and loss-of-function assays showed that H19 inhibits retinoblastoma cell proliferation, induces retinoblastoma cell cycle arrest and cell apoptosis...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29142066/characterization-of-sgn-cd123a-a-potent-cd123-directed-antibody-drug-conjugate-for-acute-myeloid-leukemia
#11
Fu Li, May Kung Sutherland, Changpu Yu, Roland B Walter, Lori Westendorf, John Valliere-Douglass, Lucy Pan, Ashley Cronkite, Django Sussman, Kerry Klussman, Michelle Ulrich, Martha E Anderson, Ivan J Stone, Weiping Zeng, Mechthild Jonas, Timothy S Lewis, Maitrayee Goswami, Sa A Wang, Peter D Senter, Che-Leung Law, Eric J Feldman, Dennis R Benjamin
Treatment choices for acute myeloid leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. Interleukin-3 receptor alpha (IL-3Rα, or CD123) is expressed on the majority of AML blasts and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate utilizing the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29141987/brachyury-directs-histone-acetylation-to-target-loci-during-mesoderm-development
#12
Arica Beisaw, Pavel Tsaytler, Frederic Koch, Sandra U Schmitz, Maria-Theodora Melissari, Anna D Senft, Lars Wittler, Tracie Pennimpede, Karol Macura, Bernhard G Herrmann, Phillip Grote
T-box transcription factors play essential roles in multiple aspects of vertebrate development. Here, we show that cooperative function of BRACHYURY (T) with histone-modifying enzymes is essential for mouse embryogenesis. A single point mutation (T(Y88A)) results in decreased histone 3 lysine 27 acetylation (H3K27ac) at T target sites, including the T locus, suggesting that T autoregulates the maintenance of its expression and functions by recruiting permissive chromatin modifications to putative enhancers during mesoderm specification...
November 15, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29141921/microrna-574-suppresses-oocyte-maturation-via-targeting-hyaluronan-synthase-2-in-porcine-cumulus-cells
#13
Bo Pan, Derek Toms, Julang Li
MicroRNAs (miRNAs) have been established as important regulators of gene expression in the mammalian ovary. A previous screen of small RNA in the porcine ovary identified the down regulation of miR-574 during oocyte maturation, although its role during this process was not established. Here, we found that miR-574 directly targets the transcript for hyaluron synthase 2 protein (HAS2), a key enzyme in the production of extracellular matrix by the surrounding cumulus cells. Inhibiting this miRNA during in vitro maturation (IVM) increased HAS2 levels along with several markers of oocyte quality...
November 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29141279/efficacy-of-stiripentol-in-dravet-syndrome-with-or-without-scn1a-mutations
#14
Min Jung Cho, Soon Sung Kwon, Ara Ko, Seung Tae Lee, Young Mock Lee, Heung Dong Kim, Hee Jung Chung, Se Hee Kim, Joon Soo Lee, Dae Sung Kim, Hoon Chul Kang
BACKGROUND AND PURPOSE: The aim of this study was to determine the effectiveness of stiripentol (STP) add-on therapy to valproate and clobazam in patients with Dravet syndrome (DS) according to the presence of mutations in the sodium channel alpha-1 subunit gene (SCN1A). METHODS: We performed direct sequencing to analyze SCN1A mutations in 32 patients with clinically confirmed with DS, and classified them into mutation (pathogenic or likely pathogenic) and nonmutation groups based on American College of Medical Genetics and Genomics guidelines...
October 31, 2017: Journal of Clinical Neurology
https://www.readbyqxmd.com/read/29140092/determinants-and-expansion-of-specificity-in-a-trichothecene-udp-glucosyltransferase-from-oryza-sativa
#15
Karl M Wetterhorn, Kaitlyn Gabardi, Herbert Michlmayr, Alexandra Malachova, Mark Busman, Susan Patricia McCormick, Franz Berthiller, Gerhard Adam, Ivan Rayment
Family 1 UDP-glycosyltransferases in plants (UGTs) primarily form glucose conjugates of small molecules and, besides other functions, play a role in detoxification of xenobiotics. Indeed, overexpression of a barley UGT in wheat has been shown to control Fusarium head blight, where this is a plant disease of global significance that leads to reduced crop yields and contamination with trichothecene mycotoxins such as deoxynivalenol (DON), T-2 toxin and many other structural variants. The UGT Os79 from rice has emerged as a promising candidate for inactivation of mycotoxins on account of its ability to glycosylate DON, nivalenol and hydrolyzed T-2 toxin (HT-2)...
November 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29138281/a-conserved-cytoskeletal-signaling-cascade-mediates-neurotoxicity-of-ftdp-17-tau-mutations-in-vivo
#16
Farah H Bardai, Liqun Wang, Yamini Mutreja, Mythili Yenjerla, T Chris Gamblin, Mel B Feany
The microtubule binding protein tau is strongly implicated in multiple neurodegenerative disorders, including frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), which is caused by mutations in tau. In vitro, FTDP-17 mutant versions of tau can reduce microtubule binding and increase aggregation of tau, but the mechanism by which these mutations promote disease in vivo is not clear. Here we take a combined biochemical and in vivo modeling approach to define functional properties of tau driving neurotoxicity in vivo We express wild type human tau and five FTDP-17 mutant forms of tau in Drosophila using a site-directed insertion strategy to ensure equivalent levels of expression...
November 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29137637/molecular-evolution-of-hiv-1-integrase-during-the-20%C3%A2-years-prior-to-the-first-approval-of-integrase-inhibitors
#17
Karolin Meixenberger, Kaveh Pouran Yousef, Maureen Rebecca Smith, Sybille Somogyi, Stefan Fiedler, Barbara Bartmeyer, Osamah Hamouda, Norbert Bannert, Max von Kleist, Claudia Kücherer
BACKGROUND: Detailed knowledge of the evolutionary potential of polymorphic sites in a viral protein is important for understanding the development of drug resistance in the presence of an inhibitor. We therefore set out to analyse the molecular evolution of the HIV-1 subtype B integrase at the inter-patient level in Germany during a 20-year period prior to the first introduction of integrase strand inhibitors (INSTIs). METHODS: We determined 337 HIV-1 integrase subtype B sequences (amino acids 1-278) from stored plasma samples of antiretroviral treatment-naïve individuals newly diagnosed with HIV-1 between 1986 and 2006...
November 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/29137431/mitochondrial-dna-depletion-mitochondrial-mutations-and-high-tfam-expression-in-hepatocellular-carcinoma
#18
Lihua Qiao, Guoqing Ru, Zhuochao Mao, Chenghui Wang, Zhipeng Nie, Qiang Li, Yiyi Huang-Yang, Ling Zhu, Xiaoyang Liang, Jialing Yu, Pingping Jiang
We investigated the role of mitochondrial genetic alterations in hepatocellular carcinoma by directly comparing the mitochondrial genomes of 86 matched pairs of HCC and non-tumor liver samples. Substitutions in 637 mtDNA sites were detected, comprising 89.80% transitions and 6.60% transversions. Forty-six somatic variants, including 15 novel mutations, were identified in 40.70% of tumor tissues. Of those, 21 were located in the non-coding region and 25 in the protein-coding region. Twenty-two somatic nonsynonymous changes were identified as putative pathogenic variants, including 4 truncating mutations produced by three frameshifts (MT-ATP6 8628 insC; MT-ND5 13475 T-del, and MT-CYB 14984 insA) and 1 nonsense mutation in MT-CO3 9253 G>A...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137403/chicken-ccdc152-shares-an-nfyb-regulated-bidirectional-promoter-with-a-growth-hormone-receptor-antisense-transcript-and-inhibits-cells-proliferation-and-migration
#19
Shudai Lin, Wei Luo, Mingya Jiang, Wen Luo, Bahareldin Ali Abdalla, Qinghua Nie, Li Zhang, Xiquan Zhang
The chicken coiled-coil domain-containing protein 152 (CCDC152) recently has been identified as a novel one implicated in cell cycle regulation, cellular proliferation and migration by us. Here we demonstrate that CCDC152 is oriented in a head-to-head configuration with the antisense transcript of growth hormone receptor (GHR) gene. Through serial luciferase reporter assays, we firstly identified a minimal 102 bp intergenic region as a core bidirectional promoter to drive basal transcription in divergent orientations...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136775/high-parathyroid-hormone-concentration-in-tenofovir-treated-patients-are-due-to-inhibition-of-calcium-sensing-receptor-activity
#20
Alessandra Mingione, Katia Maruca, Federica Chiappori, Francesca Pivari, Caterina Brasacchio, Tiziana Quirino, Ivan Merelli, Laura Soldati, Paolo Bonfanti, Stefano Mora
Bone health impairment is a common finding in HIV-infected patients on antiretroviral treatment. High serum parathyroid hormone (PTH) concentration in patients on antiretroviral treatment containing tenofovir disoproxil fumarate (TDF) has been reported. Hyperparathyroidism was not always sustained by a reduction in vitamin D concentration. We thus hypothesized a direct inhibitory effect of TDF on the Calcium-sensing receptor (CaSR), leading to hyperparathyroidism. Human embryonic kidney cells were transfected with CASR wild-type gene or mutated in different sites (N124K, T1051G, C788T, T888M)...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
keyword
keyword
105452
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"