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  1. Article ; Online: N-acetylcysteine: a novel approach to methaemoglobinaemia in normothermic liver machine perfusion.

    Clarke, George / Mao, Jingwen / Fan, Yiyu / Hann, Angus / Gupta, Amita / Nutu, Anisa / Buckel, Erwin / Kayani, Kayani / Murphy, Nicholas / Bangash, Mansoor N / Casey, Anna L / Wootton, Isla / Lawson, Alexander J / Dasari, Bobby V M / Perera, M Thamara P R / Mergental, Hynek / Afford, Simon C

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 19022

    Abstract: ... N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor ...

    Abstract Extended duration of normothermic machine perfusion (NMP) provides opportunities to resuscitate suboptimal donor livers. This intervention requires adequate oxygen delivery typically provided by a blood-based perfusion solution. Methaemoglobin (MetHb) results from the oxidation of iron within haemoglobin and represents a serious problem in perfusions lasting > 24 h. We explored the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor livers declined for transplantation: three were perfused without NAC (no-NAC group), and six organs perfused with an initial NAC bolus, followed by continuous infusion (NAC group), with hourly methaemoglobin perfusate measurements. In-vitro experiments examined the impact of NAC (3 mg) on red cells (30 ml) in the absence of liver tissue. The no-NAC group sustained perfusions for an average of 96 (range 87-102) h, universally developing methaemoglobinaemia (≥ 2%) observed after an average of 45 h, with subsequent steep rise. The NAC group was perfused for an average of 148 (range 90-184) h. Only 2 livers developed methaemoglobinaemia (peak MetHb of 6%), with an average onset of 116.5 h. Addition of NAC efficiently limits formation and accumulation of methaemoglobin during NMP, and allows the significant extension of perfusion duration.
    MeSH term(s) Humans ; Liver Transplantation/methods ; Methemoglobinemia ; Acetylcysteine/pharmacology ; Organ Preservation/methods ; Methemoglobin ; Liver ; Perfusion/methods
    Chemical Substances Acetylcysteine (WYQ7N0BPYC) ; Methemoglobin (9008-37-1)
    Language English
    Publishing date 2023-11-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-45206-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: N-acetylcysteine

    George Clarke / Jingwen Mao / Yiyu Fan / Angus Hann / Amita Gupta / Anisa Nutu / Erwin Buckel / Kayani Kayani / Nicholas Murphy / Mansoor N. Bangash / Anna L. Casey / Isla Wootton / Alexander J. Lawson / Bobby V. M. Dasari / M. Thamara P. R. Perera / Hynek Mergental / Simon C. Afford

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    a novel approach to methaemoglobinaemia in normothermic liver machine perfusion

    2023  Volume 8

    Abstract: ... the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human ...

    Abstract Abstract Extended duration of normothermic machine perfusion (NMP) provides opportunities to resuscitate suboptimal donor livers. This intervention requires adequate oxygen delivery typically provided by a blood-based perfusion solution. Methaemoglobin (MetHb) results from the oxidation of iron within haemoglobin and represents a serious problem in perfusions lasting > 24 h. We explored the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor livers declined for transplantation: three were perfused without NAC (no-NAC group), and six organs perfused with an initial NAC bolus, followed by continuous infusion (NAC group), with hourly methaemoglobin perfusate measurements. In-vitro experiments examined the impact of NAC (3 mg) on red cells (30 ml) in the absence of liver tissue. The no-NAC group sustained perfusions for an average of 96 (range 87–102) h, universally developing methaemoglobinaemia (≥ 2%) observed after an average of 45 h, with subsequent steep rise. The NAC group was perfused for an average of 148 (range 90–184) h. Only 2 livers developed methaemoglobinaemia (peak MetHb of 6%), with an average onset of 116.5 h. Addition of NAC efficiently limits formation and accumulation of methaemoglobin during NMP, and allows the significant extension of perfusion duration.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Targeting branched N-glycans and fucosylation sensitizes ovarian tumors to immune checkpoint blockade.

    Nie, Hao / Saini, Pratima / Miyamoto, Taito / Liao, Liping / Zielinski, Rafal J / Liu, Heng / Zhou, Wei / Wang, Chen / Murphy, Brennah / Towers, Martina / Yang, Tyler / Qi, Yuan / Kannan, Toshitha / Kossenkov, Andrew / Tateno, Hiroaki / Claiborne, Daniel T / Zhang, Nan / Abdel-Mohsen, Mohamed / Zhang, Rugang

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2853

    Abstract: ... therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient ... an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 ... transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans ...

    Abstract Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their resistance to anti-PD-L1 by enhancing its binding with PD-1 on CD8
    MeSH term(s) Humans ; Female ; Animals ; Mice ; BRCA1 Protein/metabolism ; Immune Checkpoint Inhibitors/therapeutic use ; CD8-Positive T-Lymphocytes/metabolism ; Glycosylation ; BRCA2 Protein/metabolism ; Ovarian Neoplasms/pathology ; Carcinoma, Ovarian Epithelial/drug therapy ; B7-H1 Antigen/metabolism
    Chemical Substances BRCA1 protein, human ; BRCA1 Protein ; Immune Checkpoint Inhibitors ; BRCA2 protein, human ; BRCA2 Protein ; B7-H1 Antigen
    Language English
    Publishing date 2024-04-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47069-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Synthesis and Reactivity of an Aluminium N-heterocyclic Aminal.

    Wilde, Taylor / Murphy, Fáinché / Smylie, Cooper R T / Kennedy, Alan R / Weetman, Catherine E

    Chemistry, an Asian journal

    2024  Volume 19, Issue 5, Page(s) e202301058

    Abstract: Tethered N-heterocyclic carbenes (NHCs) are an emerging class of ligand, as they feature ... in the unexpected formation of a bicyclic N-heterocyclic aminal (1). Compound 1 behaves as a metal hydride, capable ...

    Abstract Tethered N-heterocyclic carbenes (NHCs) are an emerging class of ligand, as they feature all the desirable aspects of NHCs (ease of synthesis, high tunabilty) but also enable metal-ligand cooperativity when combined with Lewis acidic metal centres due to the donor-acceptor nature of the complexes formed. Herein we report a simple ethoxy-tethered NHC for the stabilisation of Al(III) hydrides, resulting in the unexpected formation of a bicyclic N-heterocyclic aminal (1). Compound 1 behaves as a metal hydride, capable of reducing benzophenone and carbodiimide to yield compounds 2 and 3, respectively. Furthermore, we show that 1 behaves as an efficient catalyst in the dehydrocoupling of amine-boranes due to the hemi-labile nature of the supporting ligand.
    Language English
    Publishing date 2024-02-16
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2233006-9
    ISSN 1861-471X ; 1861-4728
    ISSN (online) 1861-471X
    ISSN 1861-4728
    DOI 10.1002/asia.202301058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications.

    Chelban, Viorica / Aksnes, Henriette / Maroofian, Reza / LaMonica, Lauren C / Seabra, Luis / Siggervåg, Anette / Devic, Perrine / Shamseldin, Hanan E / Vandrovcova, Jana / Murphy, David / Richard, Anne-Claire / Quenez, Olivier / Bonnevalle, Antoine / Zanetti, M Natalia / Kaiyrzhanov, Rauan / Salpietro, Vincenzo / Efthymiou, Stephanie / Schottlaender, Lucia V / Morsy, Heba /
    Scardamaglia, Annarita / Tariq, Ambreen / Pagnamenta, Alistair T / Pennavaria, Ajia / Krogstad, Liv S / Bekkelund, Åse K / Caiella, Alessia / Glomnes, Nina / Brønstad, Kirsten M / Tury, Sandrine / Moreno De Luca, Andrés / Boland-Auge, Anne / Olaso, Robert / Deleuze, Jean-François / Anheim, Mathieu / Cretin, Benjamin / Vona, Barbara / Alajlan, Fahad / Abdulwahab, Firdous / Battini, Jean-Luc / İpek, Rojan / Bauer, Peter / Zifarelli, Giovanni / Gungor, Serdal / Kurul, Semra Hiz / Lochmuller, Hanns / Da'as, Sahar I / Fakhro, Khalid A / Gómez-Pascual, Alicia / Botía, Juan A / Wood, Nicholas W / Horvath, Rita / Ernst, Andreas M / Rothman, James E / McEntagart, Meriel / Crow, Yanick J / Alkuraya, Fowzan S / Nicolas, Gaël / Arnesen, Thomas / Houlden, Henry

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2269

    Abstract: ... recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation ...

    Abstract Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.
    MeSH term(s) Humans ; Acetylation ; Brain/diagnostic imaging ; Brain/metabolism ; Brain Diseases/genetics ; Inheritance Patterns ; Mutation ; Phosphates/metabolism ; Sodium-Phosphate Cotransporter Proteins, Type III/metabolism
    Chemical Substances Phosphates ; SLC20A2 protein, human ; Sodium-Phosphate Cotransporter Proteins, Type III ; NAA60 protein, human
    Language English
    Publishing date 2024-03-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46354-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: N-acetylcysteine for acetaminophen poisoning: translating poison center protocols to the bedside.

    Austin, Emily / Wolfe, Caitlin E / Murphy, Nancy G

    CJEM

    2024  Volume 26, Issue 3, Page(s) 141–142

    MeSH term(s) Humans ; Acetylcysteine/therapeutic use ; Acetaminophen/therapeutic use ; Poisons/therapeutic use ; Drug Overdose/drug therapy ; Administration, Oral ; Poisoning/drug therapy
    Chemical Substances Acetylcysteine (WYQ7N0BPYC) ; Acetaminophen (362O9ITL9D) ; Poisons
    Language English
    Publishing date 2024-02-15
    Publishing country England
    Document type Editorial
    ISSN 1481-8043
    ISSN (online) 1481-8043
    DOI 10.1007/s43678-024-00660-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Source partitioning using N

    Bracken, Conor J / Lanigan, Gary J / Richards, Karl G / Müller, Christoph / Tracy, Saoirse R / Grant, James / Krol, Dominika J / Sheridan, Helen / Lynch, Mary Bridget / Grace, Cornelia / Fritch, Rochelle / Murphy, Paul N C

    The Science of the total environment

    2021  Volume 781, Page(s) 146515

    Abstract: Nitrous oxide (N ...

    Abstract Nitrous oxide (N
    Language English
    Publishing date 2021-03-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2021.146515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Hepatic glutamine synthetase controls N

    Villar, Victor H / Allega, Maria Francesca / Deshmukh, Ruhi / Ackermann, Tobias / Nakasone, Mark A / Vande Voorde, Johan / Drake, Thomas M / Oetjen, Janina / Bloom, Algernon / Nixon, Colin / Müller, Miryam / May, Stephanie / Tan, Ee Hong / Vereecke, Lars / Jans, Maude / Blancke, Gillian / Murphy, Daniel J / Huang, Danny T / Lewis, David Y /
    Bird, Thomas G / Sansom, Owen J / Blyth, Karen / Sumpton, David / Tardito, Saverio

    Nature chemical biology

    2022  Volume 19, Issue 3, Page(s) 292–300

    Abstract: ... analog, N ...

    Abstract Glutamine synthetase (GS) activity is conserved from prokaryotes to humans, where the ATP-dependent production of glutamine from glutamate and ammonia is essential for neurotransmission and ammonia detoxification. Here, we show that mammalian GS uses glutamate and methylamine to produce a methylated glutamine analog, N
    MeSH term(s) Humans ; Mice ; Animals ; Glutamine/metabolism ; Glutamate-Ammonia Ligase/genetics ; Glutamate-Ammonia Ligase/metabolism ; Ammonia ; Glutamic Acid/metabolism ; Liver/metabolism ; Neoplasms/metabolism ; Homeostasis ; Mammals
    Chemical Substances Glutamine (0RH81L854J) ; Glutamate-Ammonia Ligase (EC 6.3.1.2) ; Ammonia (7664-41-7) ; Glutamic Acid (3KX376GY7L)
    Language English
    Publishing date 2022-10-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2202962-X
    ISSN 1552-4469 ; 1552-4450
    ISSN (online) 1552-4469
    ISSN 1552-4450
    DOI 10.1038/s41589-022-01154-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Chemical Kinetic Method for Active-Site Quantification in Fe-N-C Catalysts and Correlation with Molecular Probe and Spectroscopic Site-Counting Methods.

    Bates, Jason S / Martinez, Jesse J / Hall, Melissa N / Al-Omari, Abdulhadi A / Murphy, Eamonn / Zeng, Yachao / Luo, Fang / Primbs, Mathias / Menga, Davide / Bibent, Nicolas / Sougrati, Moulay Tahar / Wagner, Friedrich E / Atanassov, Plamen / Wu, Gang / Strasser, Peter / Fellinger, Tim-Patrick / Jaouen, Frédéric / Root, Thatcher W / Stahl, Shannon S

    Journal of the American Chemical Society

    2023  Volume 145, Issue 48, Page(s) 26222–26237

    Abstract: Mononuclear Fe ions ligated by nitrogen ( ... ...

    Abstract Mononuclear Fe ions ligated by nitrogen (FeN
    Language English
    Publishing date 2023-11-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.3c08790
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Revealing the transfer pathways of cyanobacterial-fixed N into the boreal forest through the feather-moss microbiome.

    Arróniz-Crespo, María / Bougoure, Jeremy / Murphy, Daniel V / Cutler, Nick A / Souza-Egipsy, Virginia / Chaput, Dominique L / Jones, Davey L / Ostle, Nicholas / Wade, Stephen C / Clode, Peta L / DeLuca, Thomas H

    Frontiers in plant science

    2022  Volume 13, Page(s) 1036258

    Abstract: Introduction: Biological N: Methods: Herein, we combined : Results: NanoSIMS images reveal ... that newly fixed N: Discussion: These images demonstrate that previous assumptions that newly fixed N ...

    Abstract Introduction: Biological N
    Methods: Herein, we combined
    Results: NanoSIMS images reveal that newly fixed N
    Discussion: These images demonstrate that previous assumptions that newly fixed N
    Language English
    Publishing date 2022-12-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2613694-6
    ISSN 1664-462X
    ISSN 1664-462X
    DOI 10.3389/fpls.2022.1036258
    Database MEDical Literature Analysis and Retrieval System OnLINE

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