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  1. Article ; Online: Novel Drug Screening Assay for

    Haapanen, Susanna / Barker, Harlan / Carta, Fabrizio / Supuran, Claudiu T / Parkkila, Seppo

    Journal of medicinal chemistry

    2023  Volume 67, Issue 1, Page(s) 152–164

    Abstract: Acanthamoeba ... ...

    Abstract Acanthamoeba castellanii
    MeSH term(s) Acanthamoeba castellanii ; Carbonic Anhydrase Inhibitors/pharmacology ; Amoeba ; Drug Evaluation, Preclinical
    Chemical Substances Carbonic Anhydrase Inhibitors
    Language English
    Publishing date 2023-12-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c01020
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  2. Article ; Online: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2.

    Harlan Barker / Seppo Parkkila

    PLoS ONE, Vol 15, Iss 10, p e

    2020  Volume 0240647

    Abstract: The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human ...

    Abstract The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2.

    Barker, Harlan / Parkkila, Seppo

    PloS one

    2020  Volume 15, Issue 10, Page(s) e0240647

    Abstract: The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human ...

    Abstract The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.
    MeSH term(s) Aging/metabolism ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus/physiology ; Binding Sites ; COVID-19 ; Carrier Proteins/biosynthesis ; Carrier Proteins/genetics ; Computational Biology ; Coronavirus Infections/virology ; Female ; Gene Expression Regulation, Enzymologic ; Gene Ontology ; Humans ; Interferons/physiology ; Lung/metabolism ; Male ; Metalloproteases/biosynthesis ; Metalloproteases/genetics ; Neovascularization, Physiologic/physiology ; Organ Specificity ; Pandemics ; Peptidyl-Dipeptidase A/biosynthesis ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/physiology ; Pneumonia, Viral/virology ; Promoter Regions, Genetic ; RNA, Messenger/biosynthesis ; Receptors, Virus/biosynthesis ; Receptors, Virus/genetics ; Receptors, Virus/physiology ; Renin-Angiotensin System/physiology ; SARS-CoV-2 ; Sex Characteristics ; Single-Cell Analysis ; Transcription Factors/metabolism ; Transcription Initiation Site ; Virus Attachment
    Chemical Substances Carrier Proteins ; RNA, Messenger ; Receptors, Virus ; Transcription Factors ; Interferons (9008-11-1) ; Metalloproteases (EC 3.4.-) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-10-28
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0240647
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Author Correction: Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.

    Maldonado, Horacio / Savage, Bryan D / Barker, Harlan R / May, Ulrike / Vähätupa, Maria / Badiani, Rahul K / Wolanska, Katarzyna I / Turner, Craig M J / Pemmari, Toini / Ketomäki, Tuomo / Prince, Stuart / Humphries, Martin J / Ruoslahti, Erkki / Morgan, Mark R / Järvinen, Tero A H

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 234

    Language English
    Publishing date 2024-01-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44574-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

    Barker, Harlan / Parkkila, Seppo

    PLOS ONE

    2020  Volume 15, Issue 10, Page(s) e0240647

    Keywords General Biochemistry, Genetics and Molecular Biology ; General Agricultural and Biological Sciences ; General Medicine ; covid19
    Language English
    Publisher Public Library of Science (PLoS)
    Publishing country us
    Document type Article ; Online
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0240647
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Author Correction

    Horacio Maldonado / Bryan D. Savage / Harlan R. Barker / Ulrike May / Maria Vähätupa / Rahul K. Badiani / Katarzyna I. Wolanska / Craig M. J. Turner / Toini Pemmari / Tuomo Ketomäki / Stuart Prince / Martin J. Humphries / Erkki Ruoslahti / Mark R. Morgan / Tero A. H. Järvinen

    Nature Communications, Vol 15, Iss 1, Pp 1-

    Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function

    2024  Volume 1

    Keywords Science ; Q
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: A reverse vaccinology approach on transmembrane carbonic anhydrases from Plasmodium species as vaccine candidates for malaria prevention.

    Zolfaghari Emameh, Reza / Barker, Harlan R / Turpeinen, Hannu / Parkkila, Seppo / Hytönen, Vesa P

    Malaria journal

    2022  Volume 21, Issue 1, Page(s) 189

    Abstract: Background: Malaria is a significant parasitic infection, and human infection is mediated by mosquito (Anopheles) biting and subsequent transmission of protozoa (Plasmodium) to the blood. Carbonic anhydrases (CAs) are known to be highly expressed in the ...

    Abstract Background: Malaria is a significant parasitic infection, and human infection is mediated by mosquito (Anopheles) biting and subsequent transmission of protozoa (Plasmodium) to the blood. Carbonic anhydrases (CAs) are known to be highly expressed in the midgut and ectoperitrophic space of Anopheles gambiae. Transmembrane CAs (tmCAs) in Plasmodium may be potential vaccine candidates for the control and prevention of malaria.
    Methods: In this study, two groups of transmembrane CAs, including α-CAs and one group of η-CAs were analysed by immunoinformatics and computational biology methods, such as predictions on transmembrane localization of CAs from Plasmodium spp., affinity and stability of different HLA classes, antigenicity of tmCA peptides, epitope and proteasomal cleavage of Plasmodium tmCAs, accessibility of Plasmodium tmCAs MHC-ligands, allergenicity of Plasmodium tmCAs, disulfide-bond of Plasmodium tmCAs, B cell epitopes of Plasmodium tmCAs, and Cell type-specific expression of Plasmodium CAs.
    Results: Two groups of α-CAs and one group of η-CAs in Plasmodium spp. were identified to contain tmCA sequences, having high affinity towards MHCs, high stability, and strong antigenicity. All putative tmCAs were predicted to contain sequences for proteasomal cleavage in antigen presenting cells (APCs).
    Conclusions: The predicted results revealed that tmCAs from Plasmodium spp. can be potential targets for vaccination against malaria.
    MeSH term(s) Animals ; Anopheles/metabolism ; Carbonic Anhydrases/chemistry ; Carbonic Anhydrases/metabolism ; Epitopes, B-Lymphocyte ; Humans ; Malaria/prevention & control ; Plasmodium ; Plasmodium falciparum/metabolism ; Vaccines ; Vaccinology
    Chemical Substances Epitopes, B-Lymphocyte ; Vaccines ; Carbonic Anhydrases (EC 4.2.1.1)
    Language English
    Publishing date 2022-06-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2091229-8
    ISSN 1475-2875 ; 1475-2875
    ISSN (online) 1475-2875
    ISSN 1475-2875
    DOI 10.1186/s12936-022-04186-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Carbonic anhydrases in metazoan model organisms: molecules, mechanisms, and physiology.

    Aspatwar, Ashok / Tolvanen, Martti E E / Barker, Harlan / Syrjänen, Leo / Valanne, Susanna / Purmonen, Sami / Waheed, Abdul / Sly, William S / Parkkila, Seppo

    Physiological reviews

    2022  Volume 102, Issue 3, Page(s) 1327–1383

    Abstract: During the past three decades, mice, zebrafish, fruit flies, ... ...

    Abstract During the past three decades, mice, zebrafish, fruit flies, and
    MeSH term(s) Acid-Base Equilibrium ; Animals ; Carbonic Anhydrases ; Humans ; Mice ; Species Specificity ; Zebrafish
    Chemical Substances Carbonic Anhydrases (EC 4.2.1.1)
    Language English
    Publishing date 2022-02-15
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 209902-0
    ISSN 1522-1210 ; 0031-9333
    ISSN (online) 1522-1210
    ISSN 0031-9333
    DOI 10.1152/physrev.00018.2021
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  9. Article ; Online: A reverse vaccinology approach on transmembrane carbonic anhydrases from Plasmodium species as vaccine candidates for malaria prevention

    Reza Zolfaghari Emameh / Harlan R. Barker / Hannu Turpeinen / Seppo Parkkila / Vesa P. Hytönen

    Malaria Journal, Vol 21, Iss 1, Pp 1-

    2022  Volume 13

    Abstract: Abstract Background Malaria is a significant parasitic infection, and human infection is mediated by mosquito (Anopheles) biting and subsequent transmission of protozoa (Plasmodium) to the blood. Carbonic anhydrases (CAs) are known to be highly expressed ...

    Abstract Abstract Background Malaria is a significant parasitic infection, and human infection is mediated by mosquito (Anopheles) biting and subsequent transmission of protozoa (Plasmodium) to the blood. Carbonic anhydrases (CAs) are known to be highly expressed in the midgut and ectoperitrophic space of Anopheles gambiae. Transmembrane CAs (tmCAs) in Plasmodium may be potential vaccine candidates for the control and prevention of malaria. Methods In this study, two groups of transmembrane CAs, including α-CAs and one group of η-CAs were analysed by immunoinformatics and computational biology methods, such as predictions on transmembrane localization of CAs from Plasmodium spp., affinity and stability of different HLA classes, antigenicity of tmCA peptides, epitope and proteasomal cleavage of Plasmodium tmCAs, accessibility of Plasmodium tmCAs MHC-ligands, allergenicity of Plasmodium tmCAs, disulfide-bond of Plasmodium tmCAs, B cell epitopes of Plasmodium tmCAs, and Cell type-specific expression of Plasmodium CAs. Results Two groups of α-CAs and one group of η-CAs in Plasmodium spp. were identified to contain tmCA sequences, having high affinity towards MHCs, high stability, and strong antigenicity. All putative tmCAs were predicted to contain sequences for proteasomal cleavage in antigen presenting cells (APCs). Conclusions The predicted results revealed that tmCAs from Plasmodium spp. can be potential targets for vaccination against malaria.
    Keywords Reverse vaccinology ; Immunoinformatics ; Vaccine ; Carbonic anhydrase ; Plasmodium spp ; Malaria ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Subject code 629
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

    Barker, Harlan / Parkkila, Seppo

    bioRxiv

    Abstract: The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human ...

    Abstract The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression, putative functions, and transcriptional regulation. The small intestine expressed higher levels of ACE2 than any other organ. The large intestine, kidney and testis showed moderate signals, whereas the signal was weak in the lung specimens. Single cell RNA-Seq data indicated positive signals along the respiratory tract in the key protective cell types including the goblet and ciliary epithelial cells, as well as in the endothelial cells and type I pneumocytes. Gene ontology analysis suggested that, besides its classical role in renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. A novel tool for the prediction of transcription factor binding sites identified several putative sites for determined transcription factors within the ACE2 gene promoter. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.
    Keywords covid19
    Language English
    Publishing date 2020-04-13
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.04.13.038752
    Database COVID19

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