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  1. AU=Harmer Matthew James
  2. AU="Jamaludin, Faridi S"
  3. AU="Sahebalzamani, Afsaneh"
  4. AU="Valverde-Molina, José"
  5. AU="Xiangpeng Yuan"
  6. AU="Rajpoot, Akanksha"
  7. AU="Aragaw, Kassaye"
  8. AU="Nalesso, Giovanna"
  9. AU="Remzi, F"
  10. AU="Lely Solari"
  11. AU="Aldridge, Daniel L"
  12. AU=Gross Lissy Z F AU=Gross Lissy Z F
  13. AU="DeVita, Robert"
  14. AU=Berkenstock Meghan K
  15. AU=Saleh Mohammed
  16. AU="Ganesan, Anuradha"
  17. AU="Ye, Yi-Fan"
  18. AU="Astasov-Frauenhoffer, Monika"
  19. AU="Ferrer-Diaz, Alejandra I"
  20. AU="Iwata, Miko"

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  1. Artikel ; Online: Paediatric trainees' training experiences during the COVID-19 pandemic: a national survey.

    Harmer, Matthew James / Southgate, Genevieve / Raja, Maduri / Alam, Shouja

    Archives of disease in childhood. Education and practice edition

    2021  Band 107, Heft 1, Seite(n) 64–70

    Abstract: This study examines trainees' experiences of paediatric education and training during the COVID-19 pandemic. Paediatric trainees across the UK undertook an online survey. 368 of approximately 4000 trainees responded; quantitative and qualitative data ... ...

    Abstract This study examines trainees' experiences of paediatric education and training during the COVID-19 pandemic. Paediatric trainees across the UK undertook an online survey. 368 of approximately 4000 trainees responded; quantitative and qualitative data were collected. Although the majority of trainees remained in their specialties, there was significant disruption to training events, teaching and learning opportunities. Despite this, for many, novel opportunities presented themselves that may not have otherwise been accessible. Trainees reported increased virtual learning, reflection, leadership and management opportunities. A breadth of trainee-identified web-based paediatric training resources were also highlighted. As the COVID-19 pandemic persists, these trainee experiences inform educators to adopt helpful training practices from other regions, including sharing of virtual learning regionally and acting-up opportunities. Trainees highlighted previously under-recognised areas of concern that can inform quality improvement initiatives, such as enhancing patient safety through tackling trainee fatigue, combating reduced clinical experience or instituting protected supporting professional activity time.
    Mesh-Begriff(e) COVID-19 ; Child ; Humans ; Learning ; Pandemics/prevention & control ; SARS-CoV-2 ; Surveys and Questionnaires
    Sprache Englisch
    Erscheinungsdatum 2021-02-26
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2148818-6
    ISSN 1743-0593 ; 1743-0585
    ISSN (online) 1743-0593
    ISSN 1743-0585
    DOI 10.1136/archdischild-2020-321151
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Biophysical Techniques for Distinguishing Ligand Binding Modes in Cytochrome P450 Monooxygenases.

    Podgorski, Matthew N / Harbort, Joshua S / Coleman, Tom / Stok, Jeanette E / Yorke, Jake A / Wong, Luet-Lok / Bruning, John B / Bernhardt, Paul V / De Voss, James J / Harmer, Jeffrey R / Bell, Stephen G

    Biochemistry

    2020  Band 59, Heft 9, Seite(n) 1038–1050

    Abstract: The cytochrome P450 superfamily of heme monooxygenases catalyzes important chemical reactions across nature. The changes in the optical spectra of these enzymes, induced by the addition of substrates or inhibitors, are critical for assessing how these ... ...

    Abstract The cytochrome P450 superfamily of heme monooxygenases catalyzes important chemical reactions across nature. The changes in the optical spectra of these enzymes, induced by the addition of substrates or inhibitors, are critical for assessing how these molecules bind to the P450, enhancing or inhibiting the catalytic cycle. Here we use the bacterial CYP199A4 enzyme (Uniprot entry Q2IUO2), from
    Mesh-Begriff(e) Bacterial Proteins/chemistry ; Benzoates/metabolism ; Binding Sites ; Cytochrome P-450 Enzyme System/metabolism ; Heme/chemistry ; Kinetics ; Ligands ; Mixed Function Oxygenases/chemistry ; Mixed Function Oxygenases/metabolism ; Models, Molecular ; Protein Binding/physiology ; Rhodopseudomonas/enzymology ; Rhodopseudomonas/metabolism ; Substrate Specificity
    Chemische Substanzen Bacterial Proteins ; Benzoates ; Ligands ; Heme (42VZT0U6YR) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Mixed Function Oxygenases (EC 1.-)
    Sprache Englisch
    Erscheinungsdatum 2020-02-24
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/acs.biochem.0c00027
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

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  3. Artikel: Biophysical Techniques for Distinguishing Ligand Binding Modes in Cytochrome P450 Monooxygenases

    Podgorski, Matthew N / Harbort, Joshua S / Coleman, Tom / Stok, Jeanette E / Yorke, Jake A / Wong, Luet-Lok / Bruning, John B / Bernhardt, Paul V / De Voss, James J / Harmer, Jeffrey R / Bell, Stephen G

    Biochemistry. 2020 Feb. 14, v. 59, no. 9

    2020  

    Abstract: The cytochrome P450 superfamily of heme monooxygenases catalyzes important chemical reactions across nature. The changes in the optical spectra of these enzymes, induced by the addition of substrates or inhibitors, are critical for assessing how these ... ...

    Abstract The cytochrome P450 superfamily of heme monooxygenases catalyzes important chemical reactions across nature. The changes in the optical spectra of these enzymes, induced by the addition of substrates or inhibitors, are critical for assessing how these molecules bind to the P450, enhancing or inhibiting the catalytic cycle. Here we use the bacterial CYP199A4 enzyme (Uniprot entry Q2IUO2), from Rhodopseudomonas palustris HaA2, and a range of substituted benzoic acids to investigate different binding modes. 4-Methoxybenzoic acid elicits an archetypal type I spectral response due to a ≥95% switch from the low- to high-spin state with concomitant dissociation of the sixth aqua ligand. 4-(Pyridin-3-yl)- and 4-(pyridin-2-yl)benzoic acid induced different type II ultraviolet–visible (UV–vis) spectral responses in CYP199A4. The former induced a greater red shift in the Soret wavelength (424 nm vs 422 nm) along with a larger overall absorbance change and other differences in the α-, β-, and δ-bands. There were also variations in the ferrous UV–vis spectra of these two substrate-bound forms with a spectrum indicative of Fe–N bond formation with 4-(pyridin-3-yl)benzoic acid. The crystal structures of CYP199A4, with the pyridinyl compounds bound, revealed that while the nitrogen of 4-(pyridin-3-yl)benzoic acid is coordinated to the heme, with 4-(pyridin-2-yl)benzoic acid an aqua ligand remains. Continuous wave and pulse electron paramagnetic resonance data in frozen solution revealed that the substrates are bound in the active site in a form consistent with the crystal structures. The redox potential of each CYP199A4–substrate combination was measured, allowing correlation among binding modes, spectroscopic properties, and the observed biochemical activity.
    Schlagwörter Rhodopseudomonas palustris ; absorbance ; active sites ; benzoic acid ; catalytic activity ; chemical reactions ; correlation ; crystal structure ; cytochrome P-450 ; dissociation ; electron paramagnetic resonance spectroscopy ; enzymes ; heme ; ligands ; nitrogen ; redox potential ; spectral analysis ; wavelengths
    Sprache Englisch
    Erscheinungsverlauf 2020-0214
    Umfang p. 1038-1050.
    Erscheinungsort American Chemical Society
    Dokumenttyp Artikel
    Anmerkung NAL-light
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/acs.biochem.0c00027
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    Verfügbar in ZB MED Köln/Königswinter

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  4. Artikel ; Online: Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung.

    Harmer, Christopher J / Wynn, Matthew / Pinto, Rachel / Cordwell, Stuart / Rose, Barbara R / Harbour, Colin / Triccas, James A / Manos, Jim

    PloS one

    2015  Band 10, Heft 8, Seite(n) e0134229

    Abstract: Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. ... ...

    Abstract Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. Previously we analysed the transcriptomes of AES-1 grown in Luria broth, nematode growth medium for Caenorhabditis elegans assay (both aerobic) and artificial sputum medium (mainly hypoxic). Transcriptional comparisons included chronic AES-1 strains against PAO1 and acute AES-1 (AES-1R) against its chronic isogen (AES-1M), isolated 10.5 years apart from a CF patient and not eradicated in the meantime. Prominent amongst genes downregulated in AES-1M in all comparisons was homogentisate-1-2-dioxygenase (hmgA); an oxygen-dependent gene known to be mutationally deactivated in many chronic infection strains of P. aeruginosa. To investigate if hmgA downregulation and deactivation gave similar virulence persistence profiles, a hmgA mutant made in UCBPP-PA14 utilising RedS-recombinase and AES-1M were assessed in the C. elegans virulence assay, and the C57BL/6 mouse for pulmonary colonisation and TNF-α response. In C. elegans, hmgA deactivation resulted in significantly increased PA14 virulence while hmgA downregulation reduced AES-1M virulence. AES-1M was significantly more persistent in mouse lung and showed a significant increase in TNF-α (p<0.0001), sustained even with no detectable bacteria. PA14ΔhmgA did not show increased TNF-α. This study suggests that hmgA may have a role in P. aeruginosa persistence in chronic infection and the results provide a starting point for clarifying the role of hmgA in chronic AES-1.
    Mesh-Begriff(e) Animals ; Australia ; Bacterial Proteins/metabolism ; Caenorhabditis elegans/microbiology ; Cystic Fibrosis/microbiology ; Disease Models, Animal ; Down-Regulation/drug effects ; Epidemics ; Female ; Flow Cytometry ; Genotype ; Homogentisate 1,2-Dioxygenase/metabolism ; Immunophenotyping ; Lung/microbiology ; Lung/pathology ; Mice, Inbred C57BL ; Mutation ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Pseudomonas Infections/microbiology ; Pseudomonas aeruginosa/drug effects ; Pseudomonas aeruginosa/enzymology ; Pseudomonas aeruginosa/pathogenicity ; Tumor Necrosis Factor-alpha/pharmacology ; Virulence
    Chemische Substanzen Bacterial Proteins ; Tumor Necrosis Factor-alpha ; Homogentisate 1,2-Dioxygenase (EC 1.13.11.5)
    Sprache Englisch
    Erscheinungsdatum 2015
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0134229
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung.

    Christopher J Harmer / Matthew Wynn / Rachel Pinto / Stuart Cordwell / Barbara R Rose / Colin Harbour / James A Triccas / Jim Manos

    PLoS ONE, Vol 10, Iss 8, p e

    2015  Band 0134229

    Abstract: Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. ... ...

    Abstract Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01) cause persistent chronic infection in cystic fibrosis (CF) patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. Previously we analysed the transcriptomes of AES-1 grown in Luria broth, nematode growth medium for Caenorhabditis elegans assay (both aerobic) and artificial sputum medium (mainly hypoxic). Transcriptional comparisons included chronic AES-1 strains against PAO1 and acute AES-1 (AES-1R) against its chronic isogen (AES-1M), isolated 10.5 years apart from a CF patient and not eradicated in the meantime. Prominent amongst genes downregulated in AES-1M in all comparisons was homogentisate-1-2-dioxygenase (hmgA); an oxygen-dependent gene known to be mutationally deactivated in many chronic infection strains of P. aeruginosa. To investigate if hmgA downregulation and deactivation gave similar virulence persistence profiles, a hmgA mutant made in UCBPP-PA14 utilising RedS-recombinase and AES-1M were assessed in the C. elegans virulence assay, and the C57BL/6 mouse for pulmonary colonisation and TNF-α response. In C. elegans, hmgA deactivation resulted in significantly increased PA14 virulence while hmgA downregulation reduced AES-1M virulence. AES-1M was significantly more persistent in mouse lung and showed a significant increase in TNF-α (p<0.0001), sustained even with no detectable bacteria. PA14ΔhmgA did not show increased TNF-α. This study suggests that hmgA may have a role in P. aeruginosa persistence in chronic infection and the results provide a starting point for clarifying the role of hmgA in chronic AES-1.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 005
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Genomes of ubiquitous marine and hypersaline Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira spp. encode a diversity of mechanisms to sustain chemolithoautotrophy in heterogeneous environments.

    Scott, Kathleen M / Williams, John / Porter, Cody M B / Russel, Sydney / Harmer, Tara L / Paul, John H / Antonen, Kirsten M / Bridges, Megan K / Camper, Gary J / Campla, Christie K / Casella, Leila G / Chase, Eva / Conrad, James W / Cruz, Mercedez C / Dunlap, Darren S / Duran, Laura / Fahsbender, Elizabeth M / Goldsmith, Dawn B / Keeley, Ryan F /
    Kondoff, Matthew R / Kussy, Breanna I / Lane, Marannda K / Lawler, Stephanie / Leigh, Brittany A / Lewis, Courtney / Lostal, Lygia M / Marking, Devon / Mancera, Paola A / McClenthan, Evan C / McIntyre, Emily A / Mine, Jessica A / Modi, Swapnil / Moore, Brittney D / Morgan, William A / Nelson, Kaleigh M / Nguyen, Kimmy N / Ogburn, Nicholas / Parrino, David G / Pedapudi, Anangamanjari D / Pelham, Rebecca P / Preece, Amanda M / Rampersad, Elizabeth A / Richardson, Jason C / Rodgers, Christina M / Schaffer, Brent L / Sheridan, Nancy E / Solone, Michael R / Staley, Zachery R / Tabuchi, Maki / Waide, Ramond J / Wanjugi, Pauline W / Young, Suzanne / Clum, Alicia / Daum, Chris / Huntemann, Marcel / Ivanova, Natalia / Kyrpides, Nikos / Mikhailova, Natalia / Palaniappan, Krishnaveni / Pillay, Manoj / Reddy, T B K / Shapiro, Nicole / Stamatis, Dimitrios / Varghese, Neha / Woyke, Tanja / Boden, Rich / Freyermuth, Sharyn K / Kerfeld, Cheryl A

    Environmental microbiology

    2018  Band 20, Heft 8, Seite(n) 2686–2708

    Abstract: Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome ... ...

    Abstract Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1-3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb
    Mesh-Begriff(e) Chemoautotrophic Growth ; Ecosystem ; Genome, Bacterial ; Hydrogenase/genetics ; Phylogeny ; Piscirickettsiaceae/classification ; Piscirickettsiaceae/enzymology ; Piscirickettsiaceae/genetics ; Piscirickettsiaceae/metabolism ; Sulfur/metabolism
    Chemische Substanzen Sulfur (70FD1KFU70) ; Hydrogenase (EC 1.12.7.2)
    Sprache Englisch
    Erscheinungsdatum 2018-04-06
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2020213-1
    ISSN 1462-2920 ; 1462-2912
    ISSN (online) 1462-2920
    ISSN 1462-2912
    DOI 10.1111/1462-2920.14090
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel: Genomes of ubiquitous marine and hypersaline Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira spp. encode a diversity of mechanisms to sustain chemolithoautotrophy in heterogeneous environments

    Scott, Kathleen M / Antonen, Kirsten M / Boden, Rich / Bridges, Megan K / Camper, Gary J / Campla, Christie K / Casella, Leila G / Chase, Eva / Clum, Alicia / Conrad, James W / Cruz, Mercedez C / Daum, Chris / Dunlap, Darren S / Duran, Laura / Fahsbender, Elizabeth M / Freyermuth, Sharyn K / Goldsmith, Dawn B / Harmer, Tara L / Huntemann, Marcel /
    Ivanova, Natalia / Keeley, Ryan F / Kerfeld, Cheryl A / Kondoff, Matthew R / Kussy, Breanna I / Kyrpides, Nikos / Lane, Marannda K / Lawler, Stephanie / Leigh, Brittany A / Lewis, Courtney / Lostal, Lygia M / Mancera, Paola A / Marking, Devon / McClenthan, Evan C / McIntyre, Emily A / Mikhailova, Natalia / Mine, Jessica A / Modi, Swapnil / Moore, Brittney D / Morgan, William A / Nelson, Kaleigh M / Nguyen, Kimmy N / Ogburn, Nicholas / Palaniappan, Krishnaveni / Parrino, David G / Paul, John H / Pedapudi, Anangamanjari D / Pelham, Rebecca P / Pillay, Manoj / Porter, Cody M. B / Preece, Amanda M / Rampersad, Elizabeth A / Reddy, T.B.K / Richardson, Jason C / Rodgers, Christina M / Russel, Sydney / Schaffer, Brent L / Shapiro, Nicole / Sheridan, Nancy E / Solone, Michael R / Staley, Zachery R / Stamatis, Dimitrios / Tabuchi, Maki / Varghese, Neha / Waide, Ramond J / Wanjugi, Pauline W / Williams, John / Woyke, Tanja / Young, Suzanne

    Environmental microbiology. 2018 Aug., v. 20, no. 8

    2018  

    Abstract: Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome ... ...

    Abstract Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL‐ and GGDEF‐domain proteins and methyl‐accepting chemotaxis proteins) despite their small sizes (2.1–3.1 Mbp). An array of sulfur‐oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2‐6, acquired via horizontal gene transfer. In addition to high‐affinity cbb3 cytochrome c oxidase, some also encode cytochrome bd‐type quinol oxidase or ba3‐type cytochrome c oxidase, which could facilitate growth under different oxygen tensions, or maintain redox balance. Carboxysome operons are present in most, with genes downstream encoding transporters from four evolutionarily distinct families, which may act with the carboxysomes to form CO2 concentrating mechanisms. These adaptations to habitat variability likely contribute to the cosmopolitan distribution of these organisms.
    Schlagwörter bacteria ; carbon dioxide ; chemotaxis ; cytochrome-c oxidase ; habitats ; horizontal gene transfer ; Hydrogenovibrio marinus ; hypersalinity ; marine sediments ; nucleotide sequences ; operon ; oxygen ; salt lakes ; sulfur ; Thiomicrospira ; transporters
    Sprache Englisch
    Erscheinungsverlauf 2018-08
    Umfang p. 2686-2708.
    Erscheinungsort John Wiley & Sons, Ltd
    Dokumenttyp Artikel
    Anmerkung JOURNAL ARTICLE
    ZDB-ID 2020213-1
    ISSN 1462-2920 ; 1462-2912
    ISSN (online) 1462-2920
    ISSN 1462-2912
    DOI 10.1111/1462-2920.14090
    Datenquelle NAL Katalog (AGRICOLA)

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