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  1. Article ; Online: Pulsatile Deformations of a Conformable Descending Thoracic Aortic Endograft in Aneurysm, Dissection, and Blunt Traumatic Aortic Injury Patients.

    Cheng, Christopher P / Suh, Ga-Young / Moainie, Sina L / Stern, Jordan R / Szeto, Wilson Y

    Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists

    2023  , Page(s) 15266028231187741

    Abstract: Purpose: This study presents analytic techniques to quantify cardiac pulsatility-induced deformations of thoracic aortic endografts in patients with thoracic aortic aneurysm (TAA), dissection (TAD), and blunt thoracic aortic injury (BTAI) after thoracic ...

    Abstract Purpose: This study presents analytic techniques to quantify cardiac pulsatility-induced deformations of thoracic aortic endografts in patients with thoracic aortic aneurysm (TAA), dissection (TAD), and blunt thoracic aortic injury (BTAI) after thoracic endovascular aortic repair (TEVAR).
    Technique: We analyzed 19 image data sets from 14 patients treated for TAA, TAD, and BTAI with cardiac-gated post-TEVAR CTs. Systolic and diastolic geometric models were constructed and diametric, axial, and bending deformations were quantified. For patients with cardiac-gated pre-op scans, the damping of pulsatile diametric distension was computed. Maximum localized diametric distension was 2.4±1.0%, 4.2±1.7%, and 5.5±1.6%, and axial deformation was 0.0±0.1%, -0.1±0.3%, and 1.1±0.6% in the endografts of TAA, TAD, and BTAI cohorts, respectively. Diametric distension damping from pre- to post-TEVAR was ~50%. Diametric and bending deformations were localized at certain axial positions on the endograft, and the inner curve bends more than the centerline, especially adjacent to overlapping regions.
    Conclusion: The presented techniques support investigation of multi-axial endograft deformations between disease causes and geometric locations on the device. Discretized quantification of deformation is needed to define device fatigue testing conditions and predict device durability in patients.
    Clinical impact: This study demonstrates analytic techniques to quantify discretized deformation of thoracic endografts. Cardiac-resolved computed tomography is sometimes acquired for surgical planning and follow-up, however, the dynamic data are not typically used to quantify pulsatile deformations. Our analytic techniques extract the centerline and surface geometry of the stented thoracic aorta during the cardiac cycle, which are used to quantify diametric, axial, and bending deformations to provide better understanding of device durability and impact on the native anatomy.
    Language English
    Publishing date 2023-07-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2006618-1
    ISSN 1545-1550 ; 1526-6028
    ISSN (online) 1545-1550
    ISSN 1526-6028
    DOI 10.1177/15266028231187741
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The pockets guide to HLA class I molecules.

    Nguyen, Andrea T / Szeto, Christopher / Gras, Stephanie

    Biochemical Society transactions

    2021  Volume 49, Issue 5, Page(s) 2319–2331

    Abstract: Human leukocyte antigens (HLA) are cell-surface proteins that present peptides to T cells. These peptides are bound within the peptide binding cleft of HLA, and together as a complex, are recognised by T cells using their specialised T cell receptors. ... ...

    Abstract Human leukocyte antigens (HLA) are cell-surface proteins that present peptides to T cells. These peptides are bound within the peptide binding cleft of HLA, and together as a complex, are recognised by T cells using their specialised T cell receptors. Within the cleft, the peptide residue side chains bind into distinct pockets. These pockets ultimately determine the specificity of peptide binding. As HLAs are the most polymorphic molecules in humans, amino acid variants in each binding pocket influences the peptide repertoire that can be presented on the cell surface. Here, we review each of the 6 HLA binding pockets of HLA class I (HLA-I) molecules. The binding specificity of pockets B and F are strong determinants of peptide binding and have been used to classify HLA into supertypes, a useful tool to predict peptide binding to a given HLA. Over the years, peptide binding prediction has also become more reliable by using binding affinity and mass spectrometry data. Crystal structures of peptide-bound HLA molecules provide a means to interrogate the interactions between binding pockets and peptide residue side chains. We find that most of the bound peptides from these structures conform to binding motifs determined from prediction software and examine outliers to learn how these HLAs are stabilised from a structural perspective.
    MeSH term(s) Amino Acid Sequence ; Crystallography, X-Ray ; Histocompatibility Antigens Class I/metabolism ; Humans ; Peptides/chemistry ; Peptides/metabolism ; Protein Binding
    Chemical Substances Histocompatibility Antigens Class I ; Peptides
    Language English
    Publishing date 2021-09-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 184237-7
    ISSN 1470-8752 ; 0300-5127
    ISSN (online) 1470-8752
    ISSN 0300-5127
    DOI 10.1042/BST20210410
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Successful treatment of Kimura disease with benralizumab.

    Szeto, Vivian G / Chin-Yee, Benjamin / Dehghani, Mina / Rizkalla, Kamilia / Licskai, Christopher / Hsia, Cyrus C

    Annals of hematology

    2022  Volume 101, Issue 9, Page(s) 2099–2100

    MeSH term(s) Antibodies, Monoclonal, Humanized/therapeutic use ; Asthma ; Disease Progression ; Double-Blind Method ; Eosinophils ; Humans ; Kimura Disease
    Chemical Substances Antibodies, Monoclonal, Humanized ; benralizumab (71492GE1FX)
    Language English
    Publishing date 2022-05-27
    Publishing country Germany
    Document type Letter
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-022-04873-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Protein purification and crystallization of HLA-A∗02:01 in complex with SARS-CoV-2 peptides.

    Chatzileontiadou, Demetra S M / Szeto, Christopher / Jayasinghe, Dhilshan / Gras, Stephanie

    STAR protocols

    2021  Volume 2, Issue 3, Page(s) 100635

    Abstract: ... execution of this protocol, please refer to Szeto et al. (2021). ...

    Abstract Understanding T-cell responses requires identifying viral peptides presented by human leukocyte antigens (HLAs). X-ray crystallography can be used to visualize their presentation. This protocol describes the expression, purification, and crystallization of HLA-A∗02:01, one of the most frequent HLA in the global population in complex with peptides derived from the SARS-CoV-2 nucleocapsid protein. This protocol can be applied to different HLA class I molecules bound to other peptides. For complete details on the use and execution of this protocol, please refer to Szeto et al. (2021).
    MeSH term(s) COVID-19/immunology ; COVID-19/metabolism ; COVID-19/virology ; Coronavirus Nucleocapsid Proteins/chemistry ; Coronavirus Nucleocapsid Proteins/isolation & purification ; Coronavirus Nucleocapsid Proteins/metabolism ; Crystallography, X-Ray ; Epitopes, T-Lymphocyte/immunology ; HLA-A2 Antigen/chemistry ; HLA-A2 Antigen/metabolism ; Humans ; Peptide Fragments/chemistry ; Peptide Fragments/isolation & purification ; Peptide Fragments/metabolism ; Phosphoproteins/chemistry ; Phosphoproteins/isolation & purification ; Phosphoproteins/metabolism ; SARS-CoV-2/metabolism ; T-Lymphocytes/immunology
    Chemical Substances Coronavirus Nucleocapsid Proteins ; Epitopes, T-Lymphocyte ; HLA-A*02:01 antigen ; HLA-A2 Antigen ; Peptide Fragments ; Phosphoproteins ; nucleocapsid phosphoprotein, SARS-CoV-2
    Language English
    Publishing date 2021-06-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100635
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Protein purification and crystallization of HLA-A∗02:01 in complex with SARS-CoV-2 peptides

    Demetra S.M. Chatzileontiadou / Christopher Szeto / Dhilshan Jayasinghe / Stephanie Gras

    STAR Protocols, Vol 2, Iss 3, Pp 100635- (2021)

    2021  

    Abstract: ... on the use and execution of this protocol, please refer to Szeto et al. (2021). ...

    Abstract Summary: Understanding T-cell responses requires identifying viral peptides presented by human leukocyte antigens (HLAs). X-ray crystallography can be used to visualize their presentation. This protocol describes the expression, purification, and crystallization of HLA-A∗02:01, one of the most frequent HLA in the global population in complex with peptides derived from the SARS-CoV-2 nucleocapsid protein. This protocol can be applied to different HLA class I molecules bound to other peptides.For complete details on the use and execution of this protocol, please refer to Szeto et al. (2021).
    Keywords Immunology ; Protein expression and purification ; X-ray Crystallography ; Science (General) ; Q1-390
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

    Cooper, Lucy / Xu, Hui / Polmear, Jack / Kealy, Liam / Szeto, Christopher / Pang, Ee Shan / Gupta, Mansi / Kirn, Alana / Taylor, Justin J / Jackson, Katherine J L / Broomfield, Benjamin J / Nguyen, Angela / Gago da Graça, Catarina / La Gruta, Nicole / Utzschneider, Daniel T / Groom, Joanna R / Martelotto, Luciano / Parish, Ian A / O'Keeffe, Meredith /
    Scharer, Christopher D / Gras, Stephanie / Good-Jacobson, Kim L

    Immunity

    2024  

    Abstract: Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are ... ...

    Abstract Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet
    Language English
    Publishing date 2024-03-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2024.03.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: TCR Recognition of Peptide-MHC-I: Rule Makers and Breakers.

    Szeto, Christopher / Lobos, Christian A / Nguyen, Andrea T / Gras, Stephanie

    International journal of molecular sciences

    2020  Volume 22, Issue 1

    Abstract: T cells are a critical part of the adaptive immune system that are able to distinguish between healthy and unhealthy cells. Upon recognition of protein fragments (peptides), activated T cells will contribute to the immune response and help clear ... ...

    Abstract T cells are a critical part of the adaptive immune system that are able to distinguish between healthy and unhealthy cells. Upon recognition of protein fragments (peptides), activated T cells will contribute to the immune response and help clear infection. The major histocompatibility complex (MHC) molecules, or human leukocyte antigens (HLA) in humans, bind these peptides to present them to T cells that recognise them with their surface T cell receptors (TCR). This recognition event is the first step that leads to T cell activation, and in turn can dictate disease outcomes. The visualisation of TCR interaction with pMHC using structural biology has been crucial in understanding this key event, unravelling the parameters that drive this interaction and their impact on the immune response. The last five years has been the most productive within the field, wherein half of current unique TCR-pMHC-I structures to date were determined within this time. Here, we review the new insights learned from these recent TCR-pMHC-I structures and their impact on T cell activation.
    MeSH term(s) Animals ; Binding Sites, Antibody ; Cross Reactions ; Histocompatibility Antigens Class I/chemistry ; Histocompatibility Antigens Class I/immunology ; Humans ; Lymphocyte Activation ; Peptides/chemistry ; Peptides/immunology ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/immunology
    Chemical Substances Histocompatibility Antigens Class I ; Peptides ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2020-12-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22010068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Genome-Wide CRISPR Screen Identifies Phospholipid Scramblase 3 as the Biological Target of Mitoprotective Drug SS-31.

    Silvaroli, Josie A / Bisunke, Bijay / Kim, Ji Young / Stayton, Amanda / Jayne, Laura A / Martinez, Shirely A / Nguyen, Christopher / Patel, Prisha S / Vanichapol, Thitinee / Verma, Vivek / Akhter, Juheb / Bolisetty, Subhashini / Madhavan, Sethu M / Kuscu, Cem / Coss, Christopher C / Zepeda-Orozco, Diana / Parikh, Samir V / Satoskar, Anjali A / Davidson, Alan J /
    Eason, James D / Szeto, Hazel H / Pabla, Navjot Singh / Bajwa, Amandeep

    Journal of the American Society of Nephrology : JASN

    2024  

    Abstract: Background: The synthetic tetra-peptide SS-31 shows promise in alleviating mitochondrial dysfunction associated with common diseases. However, the precise pharmacological basis of its mitoprotective effects remains unknown.: Methods: To uncover the ... ...

    Abstract Background: The synthetic tetra-peptide SS-31 shows promise in alleviating mitochondrial dysfunction associated with common diseases. However, the precise pharmacological basis of its mitoprotective effects remains unknown.
    Methods: To uncover the biological targets of SS-31, we performed a genome-scale CRISPR screen in HK-2 cells, a cell culture model where SS-31 mitigates cisplatin-associated cell death and mitochondrial dysfunction. The identified hit candidate gene was functionally validated using knockout cell lines, siRNA mediated downregulation, and tubular epithelial specific conditional knockout mice. Biochemical interaction studies were also performed to examine the interaction of SS-31 with the identified target protein.
    Results: Our primary screen and validation studies in HK-2 and primary murine tubular epithelial cells showed that phospholipid scramblase 3 (PLSCR3), an understudied inner mitochondrial membrane protein, is essential for the protective effects of SS-31. For in vivo validation, we generated tubular epithelial-specific knockout mice and found that Plscr3 gene ablation did not influence kidney function under normal conditions or affect the severity of cisplatin and rhabdomyolysis-associated AKI. However, Plscr3 gene deletion completely abrogated the protective effects of SS-31 during cisplatin and rhabdomyolysis-associated AKI. Biochemical studies showed that SS-31 directly binds to a previously uncharacterized N-terminal domain and stimulates PLSCR3 scramblase activity. Finally, PLSCR3 protein expression was found to be increased in the kidneys of AKI patients.
    Conclusions: PLSCR3 is identified as the essential biological target that facilitates the mitoprotective effects of SS-31 in vitro and in vivo. PLSCR3 agonists can alleviate mitochondrial dysfunction linked to AKI.
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.0000000000000338
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Switching protein metalloporphyrin binding specificity by design from iron to fluorogenic zinc.

    Bowen, Benjamin J / McGarrity, Adam R / Szeto, Jenn-Yeu A / Pudney, Christopher R / Jones, D Dafydd

    Chemical communications (Cambridge, England)

    2020  Volume 56, Issue 31, Page(s) 4308–4311

    Abstract: Metalloporphyrins play important roles in areas ranging from biology to nanoscience. Using computational design, we converted metalloporphyrin specificity of cytochrome ... ...

    Abstract Metalloporphyrins play important roles in areas ranging from biology to nanoscience. Using computational design, we converted metalloporphyrin specificity of cytochrome b
    MeSH term(s) Computer Simulation ; Cytochrome b Group/chemistry ; Cytochrome b Group/genetics ; Cytochrome b Group/radiation effects ; Escherichia coli/chemistry ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/radiation effects ; Light ; Metalloporphyrins/chemistry ; Metalloporphyrins/radiation effects ; Protein Engineering ; Zinc/chemistry ; Zinc/radiation effects
    Chemical Substances Cytochrome b Group ; Escherichia coli Proteins ; Metalloporphyrins ; cytochrome b562, E coli (9064-79-3) ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2020-03-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d0cc00596g
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: STS/AATS-Endorsed Rebuttal to 2023 ACC/AHA Chronic Coronary Disease Guideline: A Missed Opportunity to Present Accurate and Comprehensive Revascularization Recommendations.

    Bakaeen, Faisal G / Ruel, Marc / Calhoon, John H / Girardi, Leonard N / Guyton, Robert / Hui, Dawn / Kelly, Rosemary F / MacGillivray, Thomas E / Malaisrie, S Christopher / Moon, Marc R / Sabik, Joseph F / Smith, Peter K / Svensson, Lars G / Szeto, Wilson Y

    The Annals of thoracic surgery

    2023  Volume 116, Issue 4, Page(s) 675–678

    MeSH term(s) Humans ; United States ; Myocardial Ischemia ; Coronary Artery Disease ; Heart Diseases ; American Heart Association
    Language English
    Publishing date 2023-07-31
    Publishing country Netherlands
    Document type Editorial
    ZDB-ID 211007-6
    ISSN 1552-6259 ; 0003-4975
    ISSN (online) 1552-6259
    ISSN 0003-4975
    DOI 10.1016/j.athoracsur.2023.02.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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