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  1. Article ; Online: Transcription factor defects causing platelet disorders.

    Daly, Martina E

    Blood reviews

    2016  Volume 31, Issue 1, Page(s) 1–10

    Abstract: Recent years have seen increasing recognition of a subgroup of inherited platelet function disorders which are due to defects in transcription factors that are required to regulate megakaryopoiesis and platelet production. Thus, germline mutations in the ...

    Abstract Recent years have seen increasing recognition of a subgroup of inherited platelet function disorders which are due to defects in transcription factors that are required to regulate megakaryopoiesis and platelet production. Thus, germline mutations in the genes encoding the haematopoietic transcription factors RUNX1, GATA-1, FLI1, GFI1b and ETV6 have been associated with both quantitative and qualitative platelet abnormalities, and variable bleeding symptoms in the affected patients. Some of the transcription factor defects are also associated with an increased predisposition to haematologic malignancies (RUNX1, ETV6), abnormal erythropoiesis (GATA-1, GFI1b, ETV6) and immune dysfunction (FLI1). The persistence of MYH10 expression in platelets is a surrogate marker for FLI1 and RUNX1 defects. Characterisation of the transcription factor defects that give rise to platelet function disorders, and of the genes that are differentially regulated as a result, are yielding insights into the roles of these genes in platelet formation and function.
    MeSH term(s) Blood Platelet Disorders/blood ; Blood Platelet Disorders/etiology ; Blood Platelet Disorders/metabolism ; Blood Platelets/metabolism ; Disease Susceptibility ; Gene Expression Regulation ; Germ-Line Mutation ; Hemostasis ; Humans ; Structure-Activity Relationship ; Thrombopoiesis/genetics ; Transcription Factors/chemistry ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2016-07-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 639015-8
    ISSN 1532-1681 ; 0268-960X
    ISSN (online) 1532-1681
    ISSN 0268-960X
    DOI 10.1016/j.blre.2016.07.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Gene of the issue: RUNX1 mutations and inherited bleeding.

    Morgan, Neil V / Daly, Martina E

    Platelets

    2017  Volume 28, Issue 2, Page(s) 208–210

    MeSH term(s) Blood Coagulation Disorders, Inherited/genetics ; Blood Coagulation Disorders, Inherited/pathology ; Blood Platelet Disorders/genetics ; Blood Platelet Disorders/pathology ; Blood Platelets/metabolism ; Blood Platelets/pathology ; Chromosomes, Human, Pair 21/chemistry ; Core Binding Factor Alpha 2 Subunit/genetics ; Gene Expression ; Genes, Dominant ; Hemorrhage/congenital ; Hemorrhage/genetics ; Hemorrhage/physiopathology ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Mutation ; Platelet Count ; Protein Domains ; RNA, Messenger/genetics
    Chemical Substances Core Binding Factor Alpha 2 Subunit ; RNA, Messenger ; RUNX1 protein, human
    Language English
    Publishing date 2017-02-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2017.1280151
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Determinants of platelet count in humans.

    Daly, Martina E

    Haematologica

    2010  Volume 96, Issue 1, Page(s) 10–13

    MeSH term(s) Blood Platelets/physiology ; Humans ; Platelet Count ; Risk Factors ; Thrombocytosis/blood
    Language English
    Publishing date 2010-12-29
    Publishing country Italy
    Document type Comment ; Editorial
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2010.035287
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  4. Article ; Online: Sorting nexin 24 is required for α-granule biogenesis and cargo delivery in megakaryocytes.

    Lacey, Joanne / Webster, Simon J / Heath, Paul R / Hill, Chris J / Nicholson-Goult, Lucinda / Wagner, Bart E / Khan, Abdullah O / Morgan, Neil V / Makris, Michael / Daly, Martina E

    Haematologica

    2022  Volume 107, Issue 8, Page(s) 1902–1913

    Abstract: Germline defects affecting the DNA-binding domain of the transcription factor FLI1 are associated with a bleeding disorder that is characterized by the presence of large, fused α-granules in platelets. We investigated whether the genes showing abnormal ... ...

    Abstract Germline defects affecting the DNA-binding domain of the transcription factor FLI1 are associated with a bleeding disorder that is characterized by the presence of large, fused α-granules in platelets. We investigated whether the genes showing abnormal expression in FLI1-deficient platelets could be involved in platelet α-granule biogenesis by undertaking transcriptome analysis of control platelets and platelets harboring a DNA-binding variant of FLI1. Our analysis identified 2,276 transcripts that were differentially expressed in FLI1-deficient platelets. Functional annotation clustering of the coding transcripts revealed significant enrichment for gene annotations relating to protein transport, and identified Sorting nexin 24 (SNX24) as a candidate for further investigation. Using an induced pluripotent stem cell-derived megakaryocyte model, SNX24 expression was found to be increased during the early stages of megakaryocyte differentiation and downregulated during proplatelet formation, indicating tight regulatory control during megakaryopoiesis. CRISPR-Cas9 mediated knockout (KO) of SNX24 led to decreased expression of immature megakaryocyte markers, CD41 and CD61, and increased expression of the mature megakaryocyte marker CD42b (P=0.0001), without affecting megakaryocyte polyploidisation, or proplatelet formation. Electron microscopic analysis revealed an increase in empty membrane-bound organelles in SNX24 KO megakaryocytes, a reduction in α-granules and an absence of immature and mature multivesicular bodies, consistent with a defect in the intermediate stage of α-granule maturation. Co-localization studies showed that SNX24 associates with each compartment of α-granule maturation. Reduced expression of CD62P and VWF was observed in SNX24 KO megakaryocytes. We conclude that SNX24 is required for α-granule biogenesis and intracellular trafficking of α-granule cargo within megakaryocytes.
    MeSH term(s) Blood Platelets/metabolism ; Cytoplasmic Granules/metabolism ; DNA ; Humans ; Megakaryocytes/metabolism ; Protein Transport ; Sorting Nexins/genetics ; Sorting Nexins/metabolism
    Chemical Substances Sorting Nexins ; DNA (9007-49-2)
    Language English
    Publishing date 2022-08-01
    Publishing country Italy
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2021.279636
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  5. Article: Transient inherited antithrombin deficiency: a real phenomenon?

    Daly, Martina E / Cooper, Peter C / Hickey, Kieron P / Jennings, Ian / Makris, Mike

    Thrombosis and haemostasis

    2017  Volume 117, Issue 3, Page(s) 642–643

    Language English
    Publishing date 2017-02-28
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 518294-3
    ISSN 0340-6245
    ISSN 0340-6245
    DOI 10.1160/TH16-10-0791
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  6. Article: Imidazo[2,1-i]purin-5-ones and related tricyclic water-soluble purine derivatives: potent A(2A)- and A(3)-adenosine receptor antagonists.

    Müller, Christa E / Thorand, Mark / Qurishi, Ramatullah / Diekmann, Martina / Jacobson, Kenneth A / Padgett, William L / Daly, John W

    Journal of medicinal chemistry

    2019  Volume 45, Issue 16, Page(s) 3440–3450

    Abstract: A series of tricyclic imidazo[2,1-i]purinones and ring-enlarged analogues derived from xanthine derivatives have been prepared as adenosine receptor (AR) antagonists. In comparison with xanthines, the tricyclic compounds exhibit increased water ... ...

    Abstract A series of tricyclic imidazo[2,1-i]purinones and ring-enlarged analogues derived from xanthine derivatives have been prepared as adenosine receptor (AR) antagonists. In comparison with xanthines, the tricyclic compounds exhibit increased water solubility due to a basic nitrogen atom, which can be protonated under physiological conditions. Substituents were introduced that confer high affinity for A(2A) or A(3) ARs, respectively. A new capillary electrophoresis method was developed for the determination of the enantiomeric purity of selected chiral products using native and modified beta-cyclodextrins as chiral discriminators. The compounds were investigated in radioligand binding assays at rat brain A(1) and A(2A) ARs. Selected compounds were additionally investigated in radioligand binding assays at human recombinant A(3) ARs and in functional studies (adenylate cyclase assays) at A(1) ARs of rat fat cell membranes, A(2A) ARs of rat PC 12 cell membranes, and mouse A(2B) ARs of NIH 3T3 cell membranes. Structure-activity relationships were similar to those of corresponding xanthine derivatives. The 2-styrylimidazopurinones were less potent at A(2A) ARs as compared to 8-styrylxanthine derivatives. The most potent compound at A(2A) ARs was (S)-1,4-dimethyl-8-ethyl-2-styryl-imidazo[2,1-i]purinone (S-25) exhibiting a K(i) value of 424 nM at rat A(2A) ARs. The compound was highly selective for A(2A) receptors vs A(1) and A(3) ARs. Selectivity vs A(2B) ARs, however, was low. Among the 1-unsubstituted 2-phenyl-imidazo[2,1-i]purin-5-one derivatives, very potent and highly selective antagonists for human A(3) ARs were identified. The most potent A(3) antagonist of the present series was (R)-4-methyl-8-ethyl-2-phenyl-imidazo[2,1-i]purin-5-one (R-24) exhibiting a K(i) value of 2.3 nM and high selectivity for A(3) receptors vs all other AR subtypes.
    MeSH term(s) 3T3 Cells ; Adenylyl Cyclase Inhibitors ; Adenylyl Cyclases/biosynthesis ; Animals ; Brain/drug effects ; Brain/metabolism ; Electrophoresis, Capillary ; Heterocyclic Compounds, 3-Ring/chemical synthesis ; Heterocyclic Compounds, 3-Ring/chemistry ; Heterocyclic Compounds, 3-Ring/pharmacology ; Humans ; Imidazoles/chemical synthesis ; Imidazoles/chemistry ; Imidazoles/pharmacology ; In Vitro Techniques ; Membranes ; Mice ; PC12 Cells ; Purinergic P1 Receptor Antagonists ; Purines/chemical synthesis ; Purines/chemistry ; Purines/pharmacology ; Purinones/chemical synthesis ; Purinones/chemistry ; Purinones/pharmacology ; Radioligand Assay ; Rats ; Receptor, Adenosine A2A ; Receptor, Adenosine A2B ; Receptor, Adenosine A3 ; Solubility ; Stereoisomerism ; Structure-Activity Relationship ; Water
    Chemical Substances 1,4-dimethyl-8-ethyl-2-styrylimidazo(2,1-i)purinone ; 4-methyl-8-ethyl-2-phenylimidazo(2,1-i)purin-5-one ; Adenylyl Cyclase Inhibitors ; Heterocyclic Compounds, 3-Ring ; Imidazoles ; Purinergic P1 Receptor Antagonists ; Purines ; Purinones ; Receptor, Adenosine A2A ; Receptor, Adenosine A2B ; Receptor, Adenosine A3 ; Water (059QF0KO0R) ; Adenylyl Cyclases (EC 4.6.1.1)
    Language English
    Publishing date 2019-03-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm011093d
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  7. Article ; Online: BMI, Weight Discrimination, and Psychological, Behavioral, and Interpersonal Responses to the Coronavirus Pandemic.

    Sutin, Angelina R / Robinson, Eric / Daly, Michael / Gerend, Mary A / Stephan, Yannick / Luchetti, Martina / Aschwanden, Damaris / Strickhouser, Jason E / Lee, Ji Hyun / Sesker, Amanda A / Terracciano, Antonio

    Obesity (Silver Spring, Md.)

    2020  Volume 28, Issue 9, Page(s) 1590–1594

    Abstract: Objective: This study aimed to examine whether BMI and weight discrimination are associated with psychological, behavioral, and interpersonal responses to the coronavirus pandemic.: Methods: Using a prospective design, participants (N = 2,094) were ... ...

    Abstract Objective: This study aimed to examine whether BMI and weight discrimination are associated with psychological, behavioral, and interpersonal responses to the coronavirus pandemic.
    Methods: Using a prospective design, participants (N = 2,094) were first assessed in early February 2020 before the coronavirus crisis in the United States and again in mid-March 2020 during the President's "15 Days to Slow the Spread" guidelines. Weight, height, and weight discrimination were assessed in the February survey. Psychological, behavioral, and interpersonal responses to the coronavirus were assessed in the March survey.
    Results: Prepandemic experiences with weight discrimination were associated with greater concerns about the virus, engaging in more preventive behaviors, less trust in people and institutions to manage the outbreak, and greater perceived declines in connection to one's community. BMI tended to be unrelated to these responses.
    Conclusions: Despite the risks of complications of coronavirus disease associated with obesity, individuals with higher BMI were neither more concerned about the virus nor taking more behavioral precautions than individuals in other weight categories. Weight discrimination, in contrast, may heighten vigilance to threat, which may have contributed to both positive (greater concern, more precautionary behavior) and negative (less trust, declines community connection) responses to the pandemic.
    MeSH term(s) Adult ; Aged ; Behavior ; Betacoronavirus ; Body Mass Index ; Body Weight ; COVID-19 ; Coronavirus Infections/epidemiology ; Female ; Humans ; Interpersonal Relations ; Male ; Middle Aged ; Obesity/epidemiology ; Obesity/psychology ; Pandemics ; Pneumonia, Viral/epidemiology ; Prospective Studies ; SARS-CoV-2 ; Surveys and Questionnaires ; United States
    Keywords covid19
    Language English
    Publishing date 2020-07-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2230457-5
    ISSN 1930-739X ; 1071-7323 ; 1930-7381
    ISSN (online) 1930-739X
    ISSN 1071-7323 ; 1930-7381
    DOI 10.1002/oby.22914
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  8. Article: Transient inherited antithrombin deficiency: a real phenomenon?

    Daly, Martina E. / Cooper, Peter C. / Hickey, Kieron P. / Jennings, Ian / Makris, Mike

    Thrombosis and Haemostasis

    2017  Volume 117, Issue 03, Page(s) 642–643

    Language English
    Publishing date 2017-01-01
    Publisher Schattauer GmbH
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 518294-3
    ISSN 2567-689X ; 0340-6245
    ISSN (online) 2567-689X
    ISSN 0340-6245
    DOI 10.1160/TH16-10-0791
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  9. Article ; Online: ISTH Advanced Training Course on platelet bleeding disorders: How should they be investigated?

    Watson, Steve P / Daly, Martina E / Harrison, Paul / Lowe, Gillian C / Paterson, Andrew / Rivera, Jose / Warner, Tim D / Morgan, Neil V

    Platelets

    2016  Volume 27, Issue 8, Page(s) 719–721

    Language English
    Publishing date 2016
    Publishing country England
    Document type Journal Article
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2016.1256726
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  10. Article ; Online: Validation and comparison of two new scoring systems for the prediction of complicated versus uncomplicated appendicitis.

    Clifford, Siobhan / McGuire, Andrew / Dhannoon, Amenah / Daly, Gordon / Tong, Emma / O'Grady, Sorcha / Abdulhadi, Abdulaziz / Sorensen, Jan / Morrin, Martina / Hill, Arnold

    Irish journal of medical science

    2023  

    Abstract: Objectives: To validate the Atema and APSI scoring systems in the diagnosis of complicated vs uncomplicated appendicitis. To compare these scoring systems with computed tomography (CT) imaging alone to establish which method provides most accurate ... ...

    Abstract Objectives: To validate the Atema and APSI scoring systems in the diagnosis of complicated vs uncomplicated appendicitis. To compare these scoring systems with computed tomography (CT) imaging alone to establish which method provides most accurate prediction of complicated vs uncomplicated appendicitis.
    Methods: This was a retrospective review of a sample of 160 patients that underwent appendicectomy and CT imaging for suspected appendicitis between 2018 and 2021 in a tertiary university teaching hospital. Each scoring system was applied to all patients and results analysed and compared with the effectiveness of CT imaging, RESULTS: 32.5% (n = 52) were found to have complicated appendicitis and 67.5% (n = 108) uncomplicated appendicitis. Application of the Atema score to our cohort of patients resulted in a sensitivity 76.9% [CI (64.2, 87.5), specificity 58.7% [CI (48.9, 68.1)], PPV 47.1% [CI (40.5, 53.8) and NPV 84.2% [CI (76.0, 89.9)]. By comparison, the APSI yielded a sensitivity 50.9% [CI (36.6, 65.4)], specificity 76.1% [CI (67.0, 87.8)], PPV 50% [CI (39.2, 60.6)] and NPV 76% [CI (71.1, 81.7)]. Radiology prediction of complicated vs uncomplicated appendicitis with CT imaging showed sensitivity 46% [CI (32.2, 60.5)], specificity 79%; [CI (69.8, 86)], PPV 51% [CI (39.6, 62.5)] and NPV 75% [CI (69.8, 79.9)].
    Conclusion: By comparing the APSI and Atema et al. scoring systems with CT reporting in our hospital, it appears that the Atema may confer some benefit in stratifying patient risk of complicated versus uncomplicated appendicitis. Further larger scale prospective studies are required.
    Language English
    Publishing date 2023-12-21
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 390895-1
    ISSN 1863-4362 ; 0021-1265
    ISSN (online) 1863-4362
    ISSN 0021-1265
    DOI 10.1007/s11845-023-03594-1
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