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  1. Article ; Online: m

    Martinez De La Cruz, Braulio / Gell, Chris / Markus, Robert / Macdonald, Ian / Fray, Rupert / Knight, Helen Miranda

    Neuropathology and applied neurobiology

    2023  Volume 49, Issue 1, Page(s) e12885

    Abstract: ... profiling of m: Results: In non-diseased tissue, we found that m: Conclusions: These results provide ... evidence for disrupted m ...

    Abstract Aims: N
    Methods: Using microscopy and a machine learning approach, we performed cellular profiling of m
    Results: In non-diseased tissue, we found that m
    Conclusions: These results provide evidence for disrupted m
    MeSH term(s) Humans ; Lewy Body Disease/pathology ; Parkinson Disease/pathology ; Methylation ; Lewy Bodies/pathology ; Proteomics ; Alzheimer Disease/pathology ; Brain/pathology ; RNA/metabolism ; RNA, Messenger/metabolism
    Chemical Substances RNA (63231-63-0) ; RNA, Messenger
    Language English
    Publishing date 2023-01-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80371-6
    ISSN 1365-2990 ; 0305-1846
    ISSN (online) 1365-2990
    ISSN 0305-1846
    DOI 10.1111/nan.12885
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    Zs.A 1241: Show issues Location:
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  2. Article ; Online: The component of the m

    Miranda-Gonçalves, Vera / Lobo, João / Guimarães-Teixeira, Catarina / Barros-Silva, Daniela / Guimarães, Rita / Cantante, Mariana / Braga, Isaac / Maurício, Joaquina / Oing, Christoph / Honecker, Friedemann / Nettersheim, Daniel / Looijenga, Leendert H J / Henrique, Rui / Jerónimo, Carmen

    Journal of experimental & clinical cancer research : CR

    2021  Volume 40, Issue 1, Page(s) 268

    Abstract: ... to investigate the role of N6-methyladenosine (m: Methods: Four cell lines representative of GCTs (three ... its phenotypic effect in vivo.: Results: We demonstrated the differential expression of the various m ... target elements of the m ...

    Abstract Background: Germ cell tumors (GCTs) are developmental cancers, tightly linked to embryogenesis and germ cell development. The recent and expanding field of RNA modifications is being increasingly implicated in such molecular events, as well as in tumor progression and resistance to therapy, but still rarely explored in GCTs. In this work, and as a follow-up of our recent study on this topic in TGCT tissue samples, we aim to investigate the role of N6-methyladenosine (m
    Methods: Four cell lines representative of GCTs (three testicular and one mediastinal), including an isogenic cisplatin resistant subline, were used. CRISPR/Cas9-mediated knockdown of VIRMA was established and the chorioallantoic membrane assay was used to study its phenotypic effect in vivo.
    Results: We demonstrated the differential expression of the various m
    Conclusions: VIRMA has an oncogenic role in GCTs confirming our previous tissue-based study and is further involved in response to cisplatin by interfering with DNA repair. These data contribute to our better understanding of the emergence of cisplatin resistance in GCTs and support recent attempts to therapeutically target elements of the m
    MeSH term(s) Adenosine/analogs & derivatives ; Adenosine/physiology ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cisplatin/therapeutic use ; DNA Damage ; Drug Resistance, Neoplasm/physiology ; Gene Knockdown Techniques ; Humans ; Male ; Methyltransferases/physiology ; Neoplasms, Germ Cell and Embryonal/drug therapy ; Neoplasms, Germ Cell and Embryonal/genetics ; Neoplasms, Germ Cell and Embryonal/pathology ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/physiology
    Chemical Substances Antineoplastic Agents ; RNA-Binding Proteins ; VIRMA protein, human ; N-methyladenosine (CLE6G00625) ; Methyltransferases (EC 2.1.1.-) ; METTL3 protein, human (EC 2.1.1.62) ; Adenosine (K72T3FS567) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2021-08-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-021-02072-9
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    Zs.A 2065: Show issues Location:
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  3. Article ; Online: Modifying the m

    Martinez De La Cruz, Braulio / Markus, Robert / Malla, Sunir / Haig, Maria Isabel / Gell, Chris / Sang, Fei / Bellows, Eleanor / Sherif, Mahmoud Awad / McLean, Denise / Lourdusamy, Anbarasu / Self, Tim / Bodi, Zsuzsanna / Smith, Stuart / Fay, Michael / Macdonald, Ian A / Fray, Rupert / Knight, Helen Miranda

    Molecular psychiatry

    2021  Volume 26, Issue 12, Page(s) 7141–7153

    Abstract: ... methyladenosine (m ...

    Abstract Synaptic plasticity processes, which underlie learning and memory formation, require RNA to be translated local to synapses. The synaptic tagging hypothesis has previously been proposed to explain how mRNAs are available at specific activated synapses. However how RNA is regulated, and which transcripts are silenced or processed as part of the tagging process is still unknown. Modification of RNA by N6-methyladenosine (m
    MeSH term(s) AlkB Homolog 5, RNA Demethylase/genetics ; AlkB Homolog 5, RNA Demethylase/metabolism ; Brain/metabolism ; Demethylation ; Epigenome ; Humans ; Neuronal Plasticity/physiology ; Synapses/metabolism
    Chemical Substances ALKBH5 protein, human (EC 1.14.11.-) ; AlkB Homolog 5, RNA Demethylase (EC 1.14.11.-)
    Language English
    Publishing date 2021-10-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-021-01282-z
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    Zs.A 4812: Show issues Location:
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  4. Article ; Online: Downregulation of m

    Guimarães-Teixeira, Catarina / Lobo, João / Miranda-Gonçalves, Vera / Barros-Silva, Daniela / Martins-Lima, Cláudia / Monteiro-Reis, Sara / Sequeira, José Pedro / Carneiro, Isa / Correia, Margareta P / Henrique, Rui / Jerónimo, Carmen

    Molecular oncology

    2022  Volume 16, Issue 9, Page(s) 1841–1856

    Abstract: N6-methyladenosine (m ...

    Abstract N6-methyladenosine (m
    MeSH term(s) Adenosine/metabolism ; Carcinoma, Transitional Cell ; Down-Regulation ; Female ; Humans ; Male ; Methyltransferases/genetics ; Methyltransferases/metabolism ; Urinary Bladder/metabolism ; Urinary Bladder Neoplasms/genetics
    Chemical Substances METTL14 protein, human (EC 2.1.1.-) ; Methyltransferases (EC 2.1.1.-) ; METTL3 protein, human (EC 2.1.1.62) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2022-03-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13181
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  5. Article ; Online: Differential expression of m

    PerezGrovas-Saltijeral, Adriana / Rajkumar, Anto P / Knight, Helen Miranda

    Molecular neurobiology

    2023  Volume 60, Issue 4, Page(s) 2223–2235

    Abstract: ... mechanisms. 5-Methylcytosine methylations of DNA (5mC) and RNA (m ...

    Abstract Epigenetic processes have become increasingly relevant in understanding disease-modifying mechanisms. 5-Methylcytosine methylations of DNA (5mC) and RNA (m
    MeSH term(s) Humans ; Aged ; Alzheimer Disease/pathology ; RNA/metabolism ; Brain Injuries, Traumatic/pathology ; DNA Methylation ; Methyltransferases/metabolism ; RNA, Messenger/metabolism ; CCAAT-Enhancer-Binding Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism ; tRNA Methyltransferases/genetics ; tRNA Methyltransferases/metabolism
    Chemical Substances RNA (63231-63-0) ; Methyltransferases (EC 2.1.1.-) ; RNA, Messenger ; UHRF1 protein, human (EC 2.3.2.27) ; CCAAT-Enhancer-Binding Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; NSUN6 protein, human (EC 2.1.1.-) ; tRNA Methyltransferases (EC 2.1.1.-)
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-022-03195-6
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  6. Article ; Online: Impact of M Dwarfs Ultraviolet Radiation on Prebiotic Chemistry: The Case of Adenine.

    Armas-Vázquez, M Zulema / González-Espinoza, Cristina E / Segura, Antígona / Heredia, Alejandro / Miranda-Rosete, Arturo

    Astrobiology

    2023  Volume 23, Issue 6, Page(s) 705–722

    Abstract: To date, several exoplanets have been found to orbit within the habitable zone of main sequence M ... stars (M dwarfs). These stars exhibit different levels of chromospheric activity that produces ...

    Abstract To date, several exoplanets have been found to orbit within the habitable zone of main sequence M stars (M dwarfs). These stars exhibit different levels of chromospheric activity that produces ultraviolet (UV) radiation. UV may be harmful to life, but it can also trigger reactions of prebiotic importance on the surface of a potentially habitable planet (PHP). We created a code to obtain the adenine yield for a known adenine synthesis route from diaminomaleonitrile (DAMN). We used computational methods to calculate the reaction coefficient rates (photolysis rate
    MeSH term(s) Ultraviolet Rays ; Extraterrestrial Environment/chemistry ; Exobiology/methods ; Planets ; Atmosphere/chemistry
    Language English
    Publishing date 2023-04-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2047736-3
    ISSN 1557-8070 ; 1531-1074
    ISSN (online) 1557-8070
    ISSN 1531-1074
    DOI 10.1089/ast.2022.0050
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  7. Article: RETRACTED: Sturtz, M.; House, C. Metal Catalysis Acting on Nitriles in Early Earth Hydrothermal Systems.

    Sturtz, Miranda / House, Christopher

    Life (Basel, Switzerland)

    2024  Volume 14, Issue 4

    Abstract: ... ...

    Abstract The
    Language English
    Publishing date 2024-03-26
    Publishing country Switzerland
    Document type Retraction of Publication
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life14040439
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  8. Article ; Online: Differential effects of disulfide bond formation in TEM-1 versus CTX-M-9 β-lactamase.

    Villanueva, Miranda / Vostal, Lauren E / Cohen, Drew N / Biesbrock, Devin / Kuwaye, Elise P / Driver, Sasha G / Hart, Kathryn M

    Protein science : a publication of the Protein Society

    2023  Volume 33, Issue 1, Page(s) e4816

    Abstract: ... of adding or removing a disulfide in two β-lactamase enzymes, TEM-1 and CTX-M-9. The homologs share ... in thermodynamic stability and in the number of states populated at equilibrium: CTX-M-9 is two-state whereas TEM-1 ... bridge from TEM-1 and introduced a disulfide bridge at the same location in CTX-M-9. This modest change ...

    Abstract To investigate how disulfide bonds can impact protein energy landscapes, we surveyed the effects of adding or removing a disulfide in two β-lactamase enzymes, TEM-1 and CTX-M-9. The homologs share a structure and 38% sequence identity, but only TEM-1 contains a native disulfide bond. They also differ in thermodynamic stability and in the number of states populated at equilibrium: CTX-M-9 is two-state whereas TEM-1 has an additional intermediate state. We hypothesized that the disulfide bond is the major underlying determinant for these observed differences in their energy landscapes. To test this, we removed the disulfide bridge from TEM-1 and introduced a disulfide bridge at the same location in CTX-M-9. This modest change to sequence modulates the stabilities-and therefore populations-of TEM-1's equilibrium states and, more surprisingly, creates a novel third state in CTX-M-9. Unlike TEM-1's partially folded intermediate, this third state is a higher-order oligomer with reduced cysteines that retains the native fold and is fully active. Sub-denaturing concentrations of urea shifts the equilibrium to the monomeric form, allowing the disulfide bond to form. Interestingly, comparing the stability of the oxidized monomer with a variant lacking cysteines reveals the disulfide is neither stabilizing nor destabilizing in CTX-M-9, in contrast with the observed stabilization in TEM-1. Thus, we can conclude that engineering disulfide bonds is not always an effective stabilization strategy even when analogous disulfides exist in more stable structural homologs. This study also illustrates how homo-oligomerization can result from a small number of mutations, suggesting complex formation might be easily accessed during a protein family's evolution.
    MeSH term(s) beta-Lactamases/chemistry ; Cysteine ; Disulfides/chemistry ; Escherichia coli Proteins ; Protein Folding
    Chemical Substances beta-Lactamases (EC 3.5.2.6) ; CTX-M-9 protein, E coli (EC 3.5.2.-) ; Cysteine (K848JZ4886) ; Disulfides ; Escherichia coli Proteins ; beta-lactamase TEM-1 (EC 3.5.2.6)
    Language English
    Publishing date 2023-10-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1106283-6
    ISSN 1469-896X ; 0961-8368
    ISSN (online) 1469-896X
    ISSN 0961-8368
    DOI 10.1002/pro.4816
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    Zs.A 3407: Show issues Location:
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  9. Article ; Online: Effects of Training and Taper on Neuromuscular Fatigue Profile on 100-m Swimming Performance.

    Ribeiro, Felipe Alves / de Carvalho, Carlos Dellavechia / Andreossi, Júlia Causin / Miranda, Douglas Rodrigues Messias / Papoti, Marcelo

    International journal of sports medicine

    2022  Volume 44, Issue 5, Page(s) 329–335

    Abstract: ... period on neuromuscular fatigue profile in 100-m front crawl swimming performance. Seventeen competitive ... level young-adult swimmers performed a 100-m swimming performance at baseline and after 6-week specific ... each 100-m maximal effort. Performance improved (p=0.001) 2.24 and 3.06% after specific and taper ...

    Abstract This study aimed to investigate the effects of 6-week specific preparatory period and 2-week taper period on neuromuscular fatigue profile in 100-m front crawl swimming performance. Seventeen competitive-level young-adult swimmers performed a 100-m swimming performance at baseline and after 6-week specific preparatory followed by 2-week taper periods. Neuromuscular fatigue profile was assessed through percutaneous electrical stimuli on the femoral nerve during a maximal voluntary contraction performed before and immediately after each 100-m maximal effort. Performance improved (p=0.001) 2.24 and 3.06% after specific and taper, respectively. Potentiated peak force at post-effort condition decreased (p<0.001) 16.26% at baseline, 11.70% at specific, and 12.86% at taper period. Maximal voluntary contraction force also decreased (p<0.001) at post-effort condition by about 6.77 and 9.33% at baseline and specific period, respectively. Both variables did not present significant differences between times. No condition or time effects were observed to superimposed peak force and voluntary activation, both related to central fatigue. In conclusion, neuromuscular fatigue during 100-m swimming performance was exclusively developed by peripheral mechanisms regardless of the training period, and 2-week taper was able to prevent decreases in maximal voluntary contraction induced by 100-m maximal effort.
    MeSH term(s) Adult ; Humans ; Swimming/physiology ; Muscle Fatigue
    Language English
    Publishing date 2022-05-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 603122-5
    ISSN 1439-3964 ; 0172-4622 ; 0943-917X
    ISSN (online) 1439-3964
    ISSN 0172-4622 ; 0943-917X
    DOI 10.1055/a-1841-3081
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  10. Article ; Online: Mutagenesis and structural analysis reveal the CTX-M β-lactamase active site is optimized for cephalosporin catalysis and drug resistance.

    Lu, Shuo / Montoya, Miranda / Hu, Liya / Neetu, Neetu / Sankaran, Banumathi / Prasad, B V Venkataram / Palzkill, Timothy

    The Journal of biological chemistry

    2023  Volume 299, Issue 5, Page(s) 104630

    Abstract: CTX-M β-lactamases are a widespread source of resistance to β-lactam antibiotics ... such as cefotaxime. To investigate the preference of CTX-M enzymes for cephalosporins, we examined eleven active-site ... residues in the CTX-M-14 β-lactamase model system by alanine mutagenesis to assess the contribution ...

    Abstract CTX-M β-lactamases are a widespread source of resistance to β-lactam antibiotics in Gram-negative bacteria. These enzymes readily hydrolyze penicillins and cephalosporins, including oxyimino-cephalosporins such as cefotaxime. To investigate the preference of CTX-M enzymes for cephalosporins, we examined eleven active-site residues in the CTX-M-14 β-lactamase model system by alanine mutagenesis to assess the contribution of the residues to catalysis and specificity for the hydrolysis of the penicillin, ampicillin, and the cephalosporins cephalothin and cefotaxime. Key active site residues for class A β-lactamases, including Lys73, Ser130, Asn132, Lys234, Thr216, and Thr235, contribute significantly to substrate binding and catalysis of penicillin and cephalosporin substrates in that alanine substitutions decrease both k
    MeSH term(s) Ampicillin/metabolism ; Ampicillin/pharmacology ; beta-Lactamases/chemistry ; beta-Lactamases/metabolism ; Catalysis ; Catalytic Domain/genetics ; Cefotaxime/metabolism ; Cefotaxime/pharmacology ; Cephalosporins/metabolism ; Cephalosporins/pharmacology ; Drug Resistance/genetics ; Escherichia coli/drug effects ; Escherichia coli/metabolism ; Mutagenesis ; Penicillins/metabolism ; Penicillins/pharmacology ; beta-Lactams/metabolism ; Models, Molecular ; Protein Structure, Tertiary
    Chemical Substances Ampicillin (7C782967RD) ; beta-Lactamases (EC 3.5.2.6) ; Cefotaxime (N2GI8B1GK7) ; Cephalosporins ; Penicillins ; beta-Lactams
    Language English
    Publishing date 2023-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.104630
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