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  1. Article ; Online: R-Loop-Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin.

    Safari, Maryam / Litman, Thomas / Robey, Robert W / Aguilera, Andrés / Chakraborty, Arup R / Reinhold, William C / Basseville, Agnes / Petrukhin, Lubov / Scotto, Luigi / O'Connor, Owen A / Pommier, Yves / Fojo, Antonio T / Bates, Susan E

    Molecular cancer research : MCR

    2021  Volume 19, Issue 8, Page(s) 1361–1374

    Abstract: ... by which hyperacetylation induces DNA damage. We identified accumulation of DNA-RNA hybrids (R-loops) following romidepsin ... proteins such as PARP will increase dsDNA breaks in this context. These studies establish accumulation of R ... hybrids (R-loops) due to chromatin hyperacetylation that provokes single-stranded DNA damage as a first ...

    Abstract Histone deacetylase inhibitors (HDACi) induce hyperacetylation of histones by blocking HDAC catalytic sites. Despite regulatory approvals in hematological malignancies, limited solid tumor clinical activity has constrained their potential, arguing for better understanding of mechanisms of action (MOA). Multiple activities of HDACis have been demonstrated, dependent on cell context, beyond the canonical induction of gene expression. Here, using a clinically relevant exposure duration, we established DNA damage as the dominant signature using the NCI-60 cell line database and then focused on the mechanism by which hyperacetylation induces DNA damage. We identified accumulation of DNA-RNA hybrids (R-loops) following romidepsin-induced histone hyperacetylation, with single-stranded DNA (ssDNA) breaks detected by single-cell electrophoresis. Our data suggest that transcription-coupled base excision repair (BER) is involved in resolving ssDNA breaks that, when overwhelmed, evolve to lethal dsDNA breaks. We show that inhibition of BER proteins such as PARP will increase dsDNA breaks in this context. These studies establish accumulation of R-loops as a consequence of romidepsin-mediated histone hyperacetylation. We believe that the insights provided will inform design of more effective combination therapy with HDACis for treatment of solid tumors. IMPLICATIONS: Key HDAC inhibitor mechanisms of action remain unknown; we identify accumulation of DNA-RNA hybrids (R-loops) due to chromatin hyperacetylation that provokes single-stranded DNA damage as a first step toward cell death.
    MeSH term(s) Acetylation/drug effects ; Cell Line, Tumor ; DNA Damage/drug effects ; DNA Damage/genetics ; DNA Repair/drug effects ; DNA Repair/genetics ; DNA, Single-Stranded/drug effects ; DNA, Single-Stranded/genetics ; Depsipeptides/pharmacology ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/metabolism ; Humans ; PC-3 Cells ; R-Loop Structures/drug effects ; R-Loop Structures/genetics
    Chemical Substances DNA, Single-Stranded ; Depsipeptides ; Histone Deacetylase Inhibitors ; romidepsin (CX3T89XQBK) ; Histone Deacetylases (EC 3.5.1.98)
    Language English
    Publishing date 2021-05-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2098788-2
    ISSN 1557-3125 ; 1541-7786
    ISSN (online) 1557-3125
    ISSN 1541-7786
    DOI 10.1158/1541-7786.MCR-20-0833
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: OssaNMA: An R package for using information from network meta-analyses to optimize the power and sample allocation of a new two-arm trial.

    Ye, Fangshu / Wang, Chong / O'Connor, Annette M

    PloS one

    2023  Volume 18, Issue 12, Page(s) e0296020

    Abstract: ... of different analysis methods in terms of power. We also implement our proposed method into the R package ... OssaNMA and publish an R Shiny app for the convenience of the application. The goal of the package is ... therefore resource-saving. In the R Shiny app, We also provide the option to include the cost of each treatment ...

    Abstract Randomized clinical trials (RCTs) are designed for measuring the effectiveness of the treatments and testing a hypothesis regarding the relative effect between two or more treatments. Trial designers are often interested in maximizing power when the total sample size is fixed or minimizing the required total sample size to reach a pre-specified power. One approach to maximizing power proposed by previous researchers is to leverage prior evidence using meta-analysis (NMA) to inform the sample size determination of a new trial. For example, researchers may be interested in designing a two-arm trial comparing treatments A and B which are already in the existing trial network but do not have any direct comparison. The researchers' intention is to incorporate the result into an existing network for meta-analysis. Here we develop formulas to address these options and use simulations to validate our formula and evaluate the performance of different analysis methods in terms of power. We also implement our proposed method into the R package OssaNMA and publish an R Shiny app for the convenience of the application. The goal of the package is to enable researchers to readily adopt the proposed approach which can improve the power of an RCT and is therefore resource-saving. In the R Shiny app, We also provide the option to include the cost of each treatment which would enable researchers to compare the total treatment cost associated with each design and analysis approach. Further, we explore the effect of allocation to treatment group on study power when the a priori plan is to incorporate the new trial result into an existing network for meta-analysis.
    MeSH term(s) Network Meta-Analysis ; Sample Size ; Randomized Controlled Trials as Topic
    Language English
    Publishing date 2023-12-21
    Publishing country United States
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0296020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A perspective on improving the R-CHOP regimen: from Mega-CHOP to ROBUST R-CHOP, the PHOENIX is yet to rise.

    Lue, Jennifer K / O'Connor, Owen A

    The Lancet. Haematology

    2020  Volume 7, Issue 11, Page(s) e838–e850

    Abstract: The integration of rituximab (R) into cyclophosphamide, doxorubicin, vincristine, and prednisone ... regimen, which has endured now for almost 20 years. Countless attempts to redefine R-CHOP for patients ... In this Viewpoint, we explore the history of the collective efforts to improve upon R-CHOP, and underscore ...

    Abstract The integration of rituximab (R) into cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) by Coiffier and colleagues was the first, and last, successful modification of this backbone regimen, which has endured now for almost 20 years. Countless attempts to redefine R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL) have migrated from a focus on dose-intense and dose-dense regimens, to the use of maintenance therapies, and most recently the addition of novel agents. To date, none have changed the basic formula. Although there are many reasons for the absence of success, the incredible molecular heterogeneity of DLBCL is likely to be a major complicating factor. It is clear that as the scientific field's understanding of the genetic heterogeneity of DLBCL deepens, a precision medicine approach should be accounted for and might be one of several paths that could lead to improved outcomes. The rapid identification of poor prognostic groups within the evolving diverse molecular landscape of DLBCL will create new opportunities to produce the next generation of studies with targeted agents against specific pathological drivers. It is conceivable that targeting these driver pathways will require more than one agent, and of course, splitting the pool of patients with DLBCL into smaller groups on the basis of molecular characteristics, will reduce the number of eligible patients for clinical trial investigation. The integration of immunological agents might afford new opportunities to develop treatments agnostic to the complex molecular diversity, while adding minimal toxicity to the regimen. With each of these iterations, the hope is to ultimately shift away from a one-size-fits-all chemotherapy mentality to one predicated on an individualised approach, whether that be through the use of a targeted small molecule or a biological drug. In this Viewpoint, we explore the history of the collective efforts to improve upon R-CHOP, and underscore those lessons that might help to reshape our future plans.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Clinical Trials as Topic ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Genetic Heterogeneity ; Humans ; Lenalidomide/administration & dosage ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/pathology ; Precision Medicine ; Prednisone/therapeutic use ; Prognosis ; Rituximab/administration & dosage ; Vincristine/therapeutic use
    Chemical Substances Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Lenalidomide (F0P408N6V4) ; Prednisone (VB0R961HZT)
    Language English
    Publishing date 2020-10-22
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2352-3026
    ISSN (online) 2352-3026
    DOI 10.1016/S2352-3026(20)30222-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Equity360: Gender, Race, and Ethnicity: Heroes, Rep. John R. Lewis, and Orthopaedics.

    O'Connor, Mary I

    Clinical orthopaedics and related research

    2021  Volume 479, Issue 2, Page(s) 233–235

    MeSH term(s) Black or African American/history ; COVID-19/history ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Orthopedics/history ; Pandemics/history ; Politics ; Racism/history ; SARS-CoV-2 ; United States
    Language English
    Publishing date 2021-01-05
    Publishing country United States
    Document type Biography ; Historical Article ; Journal Article
    ZDB-ID 80301-7
    ISSN 1528-1132 ; 0009-921X
    ISSN (online) 1528-1132
    ISSN 0009-921X
    DOI 10.1097/CORR.0000000000001586
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts.

    Buga, Alex / Kackley, Madison L / Crabtree, Christopher D / Bedell, Teryn N / Robinson, Bradley T / Stoner, Justen T / Decker, Drew D / Hyde, Parker N / LaFountain, Rich A / Brownlow, Milene L / O'Connor, Annalouise / Krishnan, Deepa / McElroy, Craig A / Kraemer, William J / Volek, Jeff S

    Clinical nutrition ESPEN

    2023  Volume 54, Page(s) 277–287

    Abstract: ... racemic KS doses (6 g R-BHB + 6 g S-BHB per serving) on 1) daily fasting capillary R-BHB and glucose (R ... low-fat diet (LFD). All meals were provided to subjects. Capillary blood was collected daily to measure R-BHB ... GLU: Results: Mean R-BHB: Conclusions: A hypocaloric KD was effective at reducing diurnal ...

    Abstract Background: Single doses of exogenous ketone salts (KS) transiently increase circulating beta-hydroxybutyrate (BHB) (∼1 mM; 1-2 h) regardless of starting levels of ketosis; however, no studies have explored how sustained use of KS influences measures of ketonemia and glycemia.
    Objectives: To determine the response to a hypocaloric, well-formulated ketogenic diet (KD), with and without the inclusion of two daily racemic KS doses (6 g R-BHB + 6 g S-BHB per serving) on 1) daily fasting capillary R-BHB and glucose (R-BHB/GLU
    Methods: Non-diabetic adults with overweight and obesity were randomized to receive a precisely measured hypocaloric KD (∼75 %en of maintenance) for six weeks, supplemented twice-daily with KS or placebo (PL). A non-randomized comparison group was provided an isonitrogenous/isoenergetic low-fat diet (LFD). All meals were provided to subjects. Capillary blood was collected daily to measure R-BHB/GLU
    Results: Mean R-BHB
    Conclusions: A hypocaloric KD was effective at reducing diurnal glucose compared to a LFD independent of weight loss, but twice-daily racemic KS ingestion during KD augmented ketonemia, both as R- and S-BHB, and decreased mean fasting glucose beyond a KD alone. The hypoglycemic effects of KD in combination with exogenous ketones merit further investigation.
    MeSH term(s) Adult ; Humans ; Diet, Ketogenic ; 3-Hydroxybutyric Acid ; Salts ; Ketone Bodies ; Ketosis ; Ketones ; Glucose ; Insulin ; Fasting
    Chemical Substances 3-Hydroxybutyric Acid (TZP1275679) ; Salts ; Ketone Bodies ; Ketones ; Glucose (IY9XDZ35W2) ; Insulin
    Language English
    Publishing date 2023-02-04
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2405-4577
    ISSN (online) 2405-4577
    DOI 10.1016/j.clnesp.2023.01.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Quantifying rehabilitation risks for surface-strip coal mines using a soil compaction Bayesian network in South Africa and Australia: To demonstrate the R

    Weyer, Vanessa D / de Waal, Alta / Lechner, Alex M / Unger, Corinne J / O'Connor, Tim G / Baumgartl, Thomas / Schulze, Roland / Truter, Wayne F

    Integrated environmental assessment and management

    2019  Volume 15, Issue 2, Page(s) 190–208

    Abstract: ... risk assessment integrated network (R ...

    Abstract Environmental information is acquired and assessed during the environmental impact assessment process for surface-strip coal mine approval. However, integrating these data and quantifying rehabilitation risk using a holistic multidisciplinary approach is seldom undertaken. We present a rehabilitation risk assessment integrated network (R
    MeSH term(s) Australia ; Bayes Theorem ; Coal Mining ; Environmental Restoration and Remediation ; Risk Assessment ; Soil ; South Africa
    Chemical Substances Soil
    Language English
    Publishing date 2019-02-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2234931-5
    ISSN 1551-3793 ; 1551-3777
    ISSN (online) 1551-3793
    ISSN 1551-3777
    DOI 10.1002/ieam.4128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: C3: An R package for cross-species compendium-based cell-type identification.

    Kabir, Md Humayun / Djordjevic, Djordje / O'Connor, Michael D / Ho, Joshua W K

    Computational biology and chemistry

    2018  Volume 77, Page(s) 187–192

    Abstract: ... The framework is implemented as an open source R package called C3. We have evaluated the performance of C3 ...

    Abstract Cell type identification from an unknown sample can often be done by comparing its gene expression profile against a gene expression database containing profiles of a large number of cell-types. This type of compendium-based cell-type identification strategy is particularly successful for human and mouse samples because a large volume of data exists for these organisms. However, such rich data repositories often do not exist for most non-model organisms. This makes transcriptome-based sample classification in these species challenging. We propose to overcome this challenge by performing a cross-species compendium comparison. The key is to utilise a recently published cross-species gene set analysis (XGSA) framework to correct for biases that may arise due to potentially complex homologous gene mapping between two species. The framework is implemented as an open source R package called C3. We have evaluated the performance of C3 using a variety of public data in NCBI Gene Expression Omnibus. We also compared the functionality and performance of C3 against some similar gene expression profile matching tools. Our evaluation shows that C3 is a simple and effective method for cell type identification. C3 is available at https://github.com/VCCRI/C3.
    MeSH term(s) Animals ; Cells/metabolism ; Databases, Genetic ; Gene Expression Profiling ; Humans ; Organ Specificity/genetics ; Software
    Language English
    Publishing date 2018-10-09
    Publishing country England
    Document type Journal Article
    ISSN 1476-928X
    ISSN (online) 1476-928X
    DOI 10.1016/j.compbiolchem.2018.10.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts

    Buga, Alex / Kackley, Madison L. / Crabtree, Christopher D. / Bedell, Teryn N. / Robinson, Bradley T. / Stoner, Justen T. / Decker, Drew D. / Hyde, Parker N. / LaFountain, Rich A. / Brownlow, Milene L. / O'Connor, Annalouise / Krishnan, Deepa / McElroy, Craig A. / Kraemer, William J. / Volek, Jeff S.

    European Society for Clinical Nutrition and Metabolism Clinical Nutrition ESPEN. 2023 Feb. 04,

    2023  

    Abstract: ... 6 g R-BHB + 6 g S-BHB per serving) on 1) daily fasting capillary R-BHB and glucose (R-BHB/GLUfₐₛₜ ... 2) bi-weekly 13 h diurnal BHB and glucose (R-BHB/GLUdᵢᵤᵣ), 3) three-hours post–KS ingestion kinetics ... R-BHBKS), and 4) bi-weekly fasting plasma enantiomer-specific BHB (R/S-BHBₚₗₐₛₘₐ). Non-diabetic ...

    Abstract Single doses of exogenous ketone salts (KS) transiently increase circulating beta-hydroxybutyrate (BHB) (∼1 mM; 1–2 h) regardless of starting levels of ketosis; however, no studies have explored how sustained use of KS influences measures of ketonemia and glycemia. To determine the response to a hypocaloric, well-formulated ketogenic diet (KD), with and without the inclusion of two daily racemic KS doses (6 g R-BHB + 6 g S-BHB per serving) on 1) daily fasting capillary R-BHB and glucose (R-BHB/GLUfₐₛₜ), 2) bi-weekly 13 h diurnal BHB and glucose (R-BHB/GLUdᵢᵤᵣ), 3) three-hours post–KS ingestion kinetics (R-BHBKS), and 4) bi-weekly fasting plasma enantiomer-specific BHB (R/S-BHBₚₗₐₛₘₐ). Non-diabetic adults with overweight and obesity were randomized to receive a precisely measured hypocaloric KD (∼75 %en of maintenance) for six weeks, supplemented twice-daily with KS or placebo (PL). A non-randomized comparison group was provided an isonitrogenous/isoenergetic low-fat diet (LFD). All meals were provided to subjects. Capillary blood was collected daily to measure R-BHB/GLUfₐₛₜ and hourly for R-BHB/GLUdᵢᵤᵣ. Plasma was collected to measure R/S-BHBₚₗₐₛₘₐ, insulin, fasting glucose, and insulin resistance (HOMA-IR). Total AUC was calculated using the trapezoidal method. Mean R-BHBfₐₛₜ increased significantly during KD + PL (1.0 mM BHB), an effect enhanced 26% during KD + KS. GLUfₐₛₜ AUC was −6% lower during KD + KS versus LFD. Mean R-BHBdᵢᵤᵣ increased 40% in KD + KS versus KD + PL, whereas GLUdᵢᵤᵣ decreased 13% during both KDs versus LFD. R-BHBKS peaked (Δ: ∼1 mM) 1 h after the morning KS dose, but not following the afternoon dose. Both R/S-BHBₚₗₐₛₘₐ increased during KD independent of KS inclusion. R-BHBₚₗₐₛₘₐ was 50-times greater compared to S-BHBₚₗₐₛₘₐ, and the KS augmented S-BHBₚₗₐₛₘₐ 50% more than PL. Fasting insulin and HOMA-IR decreased after 14 days independent of diet. A hypocaloric KD was effective at reducing diurnal glucose compared to a LFD independent of weight loss, but twice-daily racemic KS ingestion during KD augmented ketonemia, both as R- and S-BHB, and decreased mean fasting glucose beyond a KD alone. The hypoglycemic effects of KD in combination with exogenous ketones merit further investigation.
    Keywords 3-hydroxybutyric acid ; blood ; blood glucose ; clinical nutrition ; glucose ; ingestion ; insulin ; insulin resistance ; ketogenic diet ; ketonemia ; ketosis ; low fat diet ; obesity ; placebos ; weight loss ; Beta-hydroxybutyrate ; Low-fat diet ; Ketone salts
    Language English
    Dates of publication 2023-0204
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Pre-press version
    ISSN 2405-4577
    DOI 10.1016/j.clnesp.2023.01.030
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: R-Smad competition controls activin receptor output in Drosophila.

    Peterson, Aidan J / Jensen, Philip A / Shimell, MaryJane / Stefancsik, Ray / Wijayatonge, Ranjula / Herder, Rachel / Raftery, Laurel A / O'Connor, Michael B

    PloS one

    2012  Volume 7, Issue 5, Page(s) e36548

    Abstract: ... on relationships between ligands, receptors, and R-Smads. Several previous reports have shown that, in cell culture ... Type I receptor, can phosphorylate Mad, the BMP-specific R-Smad, in addition to its normal substrate ...

    Abstract Animals use TGF-β superfamily signal transduction pathways during development and tissue maintenance. The superfamily has traditionally been divided into TGF-β/Activin and BMP branches based on relationships between ligands, receptors, and R-Smads. Several previous reports have shown that, in cell culture systems, "BMP-specific" Smads can be phosphorylated in response to TGF-β/Activin pathway activation. Using Drosophila cell culture as well as in vivo assays, we find that Baboon, the Drosophila TGF-β/Activin-specific Type I receptor, can phosphorylate Mad, the BMP-specific R-Smad, in addition to its normal substrate, dSmad2. The Baboon-Mad activation appears direct because it occurs in the absence of canonical BMP Type I receptors. Wing phenotypes generated by Baboon gain-of-function require Mad, and are partially suppressed by over-expression of dSmad2. In the larval wing disc, activated Baboon cell-autonomously causes C-terminal Mad phosphorylation, but only when endogenous dSmad2 protein is depleted. The Baboon-Mad relationship is thus controlled by dSmad2 levels. Elevated P-Mad is seen in several tissues of dSmad2 protein-null mutant larvae, and these levels are normalized in dSmad2; baboon double mutants, indicating that the cross-talk reaction and Smad competition occur with endogenous levels of signaling components in vivo. In addition, we find that high levels of Activin signaling cause substantial turnover in dSmad2 protein, providing a potential cross-pathway signal-switching mechanism. We propose that the dual activity of TGF-β/Activin receptors is an ancient feature, and we discuss several ways this activity can modulate TGF-β signaling output.
    MeSH term(s) Activin Receptors/genetics ; Activin Receptors/metabolism ; Animals ; Blotting, Western ; Cell Line ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/cytology ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Female ; Larva/growth & development ; Larva/metabolism ; Mutation ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; RNA Interference ; Receptor Cross-Talk ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Receptors, Transforming Growth Factor beta/genetics ; Receptors, Transforming Growth Factor beta/metabolism ; Signal Transduction ; Smad Proteins, Receptor-Regulated ; Smad2 Protein/genetics ; Smad2 Protein/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism ; Wings, Animal/growth & development ; Wings, Animal/metabolism
    Chemical Substances DNA-Binding Proteins ; Drosophila Proteins ; MAD protein, Drosophila ; Receptors, Cell Surface ; Receptors, Transforming Growth Factor beta ; Smad Proteins, Receptor-Regulated ; Smad2 Protein ; Smox protein, Drosophila ; Transcription Factors ; Transforming Growth Factor beta ; sara protein, Drosophila ; sax protein, Drosophila ; tkv protein, Drosophila (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Activin Receptors (EC 2.7.11.30) ; Babo protein, Drosophila (EC 2.7.11.30)
    Language English
    Publishing date 2012-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0036548
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  10. Article ; Online: Biocatalytic versatility of engineered and wild-type tyrosinase from R. solanacearum for the synthesis of 4-halocatechols.

    Davis, Reeta / Molloy, Susan / Quigley, Blathnaid / Nikodinovic-Runic, Jasmina / Solano, Francisco / O'Connor, Kevin E

    Applied microbiology and biotechnology

    2018  Volume 102, Issue 12, Page(s) 5121–5131

    Abstract: We evaluated the kinetic characteristics of wild type (WT) and three engineered variants (RVC10, RV145, and C10_N322S) of tyrosinase from Ralstonia solanacearum and their potential as biocatalysts to produce halogenated catechols. RV145 exhibited a 3.6- ... ...

    Abstract We evaluated the kinetic characteristics of wild type (WT) and three engineered variants (RVC10, RV145, and C10_N322S) of tyrosinase from Ralstonia solanacearum and their potential as biocatalysts to produce halogenated catechols. RV145 exhibited a 3.6- to 14.5-fold improvement in catalytic efficiency (k
    MeSH term(s) Biocatalysis ; Biotransformation ; Catalysis ; Catechols/analysis ; Catechols/metabolism ; Monophenol Monooxygenase/genetics ; Monophenol Monooxygenase/metabolism ; Mutation ; Organisms, Genetically Modified/enzymology ; Organisms, Genetically Modified/genetics ; Ralstonia solanacearum/enzymology ; Ralstonia solanacearum/genetics
    Chemical Substances Catechols ; Monophenol Monooxygenase (EC 1.14.18.1)
    Language English
    Publishing date 2018-04-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 392453-1
    ISSN 1432-0614 ; 0171-1741 ; 0175-7598
    ISSN (online) 1432-0614
    ISSN 0171-1741 ; 0175-7598
    DOI 10.1007/s00253-018-8994-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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