Kinetic Analysis of Transcytosis of Epidermal Growth Factor in Madin-Darby Canine Kidney Epithelial Cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-09

AUTHORS

Akiko Kozu, Yukio Kato, Yoshihisa Shitara, Manabu Hanano, Yuichi Sugiyama

ABSTRACT

Purpose. The aim of this study is to clarify the intracellular fate and a rate limiting step in transcytosis of epidermal growth factor (EGF) in Madin-Darby Canine Kidney (MDCK) epithelial cells.Methods. The kinetics of transcytosis of 125I-EGF was investigated. To examine the fate of EGF molecules bound to its receptor on the cell surface, 125I-EGF was prebound to the basal surface at 4°C, followed by extensive washing and subsequent incubation at 37°C in EGF-free medium.Results. Saturable transport of 125I-EGF through the cell monolayer could only be observed from the basal to apical side. Most (~90%) of the EGF molecules bound to the surface receptor are internalized with a half-life of 1−3 min, followed by intracellular degradation with a half-life of 20−50 min. The exocytosis of internalized EGF into the apical medium is much slower with a half-life of 130−250 min. Even when 125I-EGF was incubated with MDCK cells at 37°C and washed with acid to remove cell-surface 125I-EGF, intact 125I-EGF appeared in the basal medium with a half life of 160−170 min.Conclusions. The exocytosis of internalized EGF into the apical medium is a rate limiting step in EGF transcytosis. At least a small amount of internalized EGF is recycled. More... »

PAGES

1228-1235

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1012167126364

DOI

http://dx.doi.org/10.1023/a:1012167126364

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051013913

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9327453


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1115", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Pharmacology and Pharmaceutical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cells, Cultured", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Dogs", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Epidermal Growth Factor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Epithelium", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Exocytosis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Kidney", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Kinetics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Radioligand Assay", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Rats", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kozu", 
        "givenName": "Akiko", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kato", 
        "givenName": "Yukio", 
        "id": "sg:person.0713513601.18", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0713513601.18"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shitara", 
        "givenName": "Yoshihisa", 
        "id": "sg:person.0607677165.24", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0607677165.24"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Faculty of Pharmaceutical Sciences, Nihon University, 274, Narashinodai, Funabashi-shi, Chiba, Japan", 
          "id": "http://www.grid.ac/institutes/grid.260969.2", 
          "name": [
            "Faculty of Pharmaceutical Sciences, Nihon University, 274, Narashinodai, Funabashi-shi, Chiba, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hanano", 
        "givenName": "Manabu", 
        "id": "sg:person.01217670277.65", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01217670277.65"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sugiyama", 
        "givenName": "Yuichi", 
        "id": "sg:person.01334724471.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01334724471.19"
        ], 
        "type": "Person"
      }
    ], 
    "datePublished": "1997-09", 
    "datePublishedReg": "1997-09-01", 
    "description": "Purpose. The aim of this study is to clarify the intracellular fate and a rate limiting step in transcytosis of epidermal growth factor (EGF) in Madin-Darby Canine Kidney (MDCK) epithelial cells.Methods. The kinetics of transcytosis of 125I-EGF was investigated. To examine the fate of EGF molecules bound to its receptor on the cell surface, 125I-EGF was prebound to the basal surface at 4\u00b0C, followed by extensive washing and subsequent incubation at 37\u00b0C in EGF-free medium.Results. Saturable transport of 125I-EGF through the cell monolayer could only be observed from the basal to apical side. Most (~90%) of the EGF molecules bound to the surface receptor are internalized with a half-life of 1\u22123 min, followed by intracellular degradation with a half-life of 20\u221250 min. The exocytosis of internalized EGF into the apical medium is much slower with a half-life of 130\u2212250 min. Even when 125I-EGF was incubated with MDCK cells at 37\u00b0C and washed with acid to remove cell-surface 125I-EGF, intact 125I-EGF appeared in the basal medium with a half life of 160\u2212170 min.Conclusions. The exocytosis of internalized EGF into the apical medium is a rate limiting step in EGF transcytosis. At least a small amount of internalized EGF is recycled.", 
    "genre": "article", 
    "id": "sg:pub.10.1023/a:1012167126364", 
    "inLanguage": "en", 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1094644", 
        "issn": [
          "0724-8741", 
          "1573-904X"
        ], 
        "name": "Pharmaceutical Research", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "9", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "14"
      }
    ], 
    "keywords": [
      "internalized epidermal growth factor", 
      "Madin-Darby canine kidney epithelial cells", 
      "epidermal growth factor", 
      "canine kidney epithelial cells", 
      "kidney epithelial cells", 
      "EGF molecules", 
      "epithelial cells", 
      "growth factor", 
      "apical medium", 
      "EGF-free medium", 
      "MDCK cells", 
      "cell surface", 
      "surface receptors", 
      "intracellular fate", 
      "intracellular degradation", 
      "exocytosis", 
      "apical side", 
      "basal medium", 
      "transcytosis", 
      "cell monolayers", 
      "cells", 
      "fate", 
      "subsequent incubation", 
      "basal surface", 
      "kinetic analysis", 
      "receptors", 
      "saturable transport", 
      "intact 125I-EGF", 
      "molecules", 
      "extensive washing", 
      "degradation", 
      "medium", 
      "acid", 
      "incubation", 
      "half life", 
      "factors", 
      "transport", 
      "step", 
      "basal", 
      "small amount", 
      "analysis", 
      "monolayers", 
      "rate", 
      "kinetics", 
      "amount", 
      "study", 
      "surface", 
      "min", 
      "washing", 
      "side", 
      "life", 
      "aim"
    ], 
    "name": "Kinetic Analysis of Transcytosis of Epidermal Growth Factor in Madin-Darby Canine Kidney Epithelial Cells", 
    "pagination": "1228-1235", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1051013913"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1023/a:1012167126364"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "9327453"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1023/a:1012167126364", 
      "https://app.dimensions.ai/details/publication/pub.1051013913"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-06-01T22:02", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220601/entities/gbq_results/article/article_284.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1023/a:1012167126364"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1023/a:1012167126364'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1023/a:1012167126364'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1023/a:1012167126364'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1023/a:1012167126364'


 

This table displays all metadata directly associated to this object as RDF triples.

188 TRIPLES      21 PREDICATES      90 URIs      82 LITERALS      18 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1023/a:1012167126364 schema:about N065636ba32e649608a2326d895752b0c
2 N20daf6ae7abe46a9892ac91d2dbeda5e
3 N2195fafb989e4e6bae5fa4cb14013dd6
4 N44c8b44c136c4b579e764acda79a6641
5 N69b84f1b159942dfb16816fecf5747da
6 N81929f8e586d40eaa4982acbc4c1f59e
7 N8ac5cfc0641d4b7fae09a8e8a3fccdbb
8 Na6d92379eac344ddb3f980dff6d961c1
9 Nba7d8167d47c470984e00752d682a5e7
10 Nce6c56f64eb34cc18ddbecfb0c041ee2
11 Nef2cecafb00747c9996c77fa7e591e94
12 anzsrc-for:11
13 anzsrc-for:1115
14 schema:author N6d842433872f4a82a77f6b4ae3093fea
15 schema:datePublished 1997-09
16 schema:datePublishedReg 1997-09-01
17 schema:description Purpose. The aim of this study is to clarify the intracellular fate and a rate limiting step in transcytosis of epidermal growth factor (EGF) in Madin-Darby Canine Kidney (MDCK) epithelial cells.Methods. The kinetics of transcytosis of 125I-EGF was investigated. To examine the fate of EGF molecules bound to its receptor on the cell surface, 125I-EGF was prebound to the basal surface at 4°C, followed by extensive washing and subsequent incubation at 37°C in EGF-free medium.Results. Saturable transport of 125I-EGF through the cell monolayer could only be observed from the basal to apical side. Most (~90%) of the EGF molecules bound to the surface receptor are internalized with a half-life of 1−3 min, followed by intracellular degradation with a half-life of 20−50 min. The exocytosis of internalized EGF into the apical medium is much slower with a half-life of 130−250 min. Even when 125I-EGF was incubated with MDCK cells at 37°C and washed with acid to remove cell-surface 125I-EGF, intact 125I-EGF appeared in the basal medium with a half life of 160−170 min.Conclusions. The exocytosis of internalized EGF into the apical medium is a rate limiting step in EGF transcytosis. At least a small amount of internalized EGF is recycled.
18 schema:genre article
19 schema:inLanguage en
20 schema:isAccessibleForFree false
21 schema:isPartOf N19d3ea8bee8849479b2ae51c596e960e
22 Nf76d53cd245141f295f8d34558dda87c
23 sg:journal.1094644
24 schema:keywords EGF molecules
25 EGF-free medium
26 MDCK cells
27 Madin-Darby canine kidney epithelial cells
28 acid
29 aim
30 amount
31 analysis
32 apical medium
33 apical side
34 basal
35 basal medium
36 basal surface
37 canine kidney epithelial cells
38 cell monolayers
39 cell surface
40 cells
41 degradation
42 epidermal growth factor
43 epithelial cells
44 exocytosis
45 extensive washing
46 factors
47 fate
48 growth factor
49 half life
50 incubation
51 intact 125I-EGF
52 internalized epidermal growth factor
53 intracellular degradation
54 intracellular fate
55 kidney epithelial cells
56 kinetic analysis
57 kinetics
58 life
59 medium
60 min
61 molecules
62 monolayers
63 rate
64 receptors
65 saturable transport
66 side
67 small amount
68 step
69 study
70 subsequent incubation
71 surface
72 surface receptors
73 transcytosis
74 transport
75 washing
76 schema:name Kinetic Analysis of Transcytosis of Epidermal Growth Factor in Madin-Darby Canine Kidney Epithelial Cells
77 schema:pagination 1228-1235
78 schema:productId N595140a4e104465b97ec335f40da350e
79 N6ab4e22b9146443fb69a5b077b43e640
80 Ndb24b8010e0d4fcfb6c7951390f8487b
81 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051013913
82 https://doi.org/10.1023/a:1012167126364
83 schema:sdDatePublished 2022-06-01T22:02
84 schema:sdLicense https://scigraph.springernature.com/explorer/license/
85 schema:sdPublisher N0d0ecca6648c4fd3a8b42f8e6629b0ee
86 schema:url https://doi.org/10.1023/a:1012167126364
87 sgo:license sg:explorer/license/
88 sgo:sdDataset articles
89 rdf:type schema:ScholarlyArticle
90 N065636ba32e649608a2326d895752b0c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
91 schema:name Kidney
92 rdf:type schema:DefinedTerm
93 N0d0ecca6648c4fd3a8b42f8e6629b0ee schema:name Springer Nature - SN SciGraph project
94 rdf:type schema:Organization
95 N19d3ea8bee8849479b2ae51c596e960e schema:volumeNumber 14
96 rdf:type schema:PublicationVolume
97 N1a1a422719774500810a2d1b501d6295 rdf:first sg:person.0713513601.18
98 rdf:rest N79118f36fad04105ad45e5a69974f913
99 N20daf6ae7abe46a9892ac91d2dbeda5e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
100 schema:name Radioligand Assay
101 rdf:type schema:DefinedTerm
102 N2195fafb989e4e6bae5fa4cb14013dd6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
103 schema:name Epithelium
104 rdf:type schema:DefinedTerm
105 N44c8b44c136c4b579e764acda79a6641 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
106 schema:name Exocytosis
107 rdf:type schema:DefinedTerm
108 N595140a4e104465b97ec335f40da350e schema:name doi
109 schema:value 10.1023/a:1012167126364
110 rdf:type schema:PropertyValue
111 N66d4c78bc7404cc49edf7da6fc3101d9 rdf:first sg:person.01217670277.65
112 rdf:rest N953484359f2d4538bdbf90e06472393a
113 N69b84f1b159942dfb16816fecf5747da schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
114 schema:name Humans
115 rdf:type schema:DefinedTerm
116 N6ab4e22b9146443fb69a5b077b43e640 schema:name pubmed_id
117 schema:value 9327453
118 rdf:type schema:PropertyValue
119 N6d842433872f4a82a77f6b4ae3093fea rdf:first Nbef059289ff444bba733b418bd48affc
120 rdf:rest N1a1a422719774500810a2d1b501d6295
121 N79118f36fad04105ad45e5a69974f913 rdf:first sg:person.0607677165.24
122 rdf:rest N66d4c78bc7404cc49edf7da6fc3101d9
123 N81929f8e586d40eaa4982acbc4c1f59e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
124 schema:name Animals
125 rdf:type schema:DefinedTerm
126 N8ac5cfc0641d4b7fae09a8e8a3fccdbb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name Cells, Cultured
128 rdf:type schema:DefinedTerm
129 N953484359f2d4538bdbf90e06472393a rdf:first sg:person.01334724471.19
130 rdf:rest rdf:nil
131 Na6d92379eac344ddb3f980dff6d961c1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Rats
133 rdf:type schema:DefinedTerm
134 Nba7d8167d47c470984e00752d682a5e7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Dogs
136 rdf:type schema:DefinedTerm
137 Nbef059289ff444bba733b418bd48affc schema:affiliation grid-institutes:grid.26999.3d
138 schema:familyName Kozu
139 schema:givenName Akiko
140 rdf:type schema:Person
141 Nce6c56f64eb34cc18ddbecfb0c041ee2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
142 schema:name Kinetics
143 rdf:type schema:DefinedTerm
144 Ndb24b8010e0d4fcfb6c7951390f8487b schema:name dimensions_id
145 schema:value pub.1051013913
146 rdf:type schema:PropertyValue
147 Nef2cecafb00747c9996c77fa7e591e94 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Epidermal Growth Factor
149 rdf:type schema:DefinedTerm
150 Nf76d53cd245141f295f8d34558dda87c schema:issueNumber 9
151 rdf:type schema:PublicationIssue
152 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
153 schema:name Medical and Health Sciences
154 rdf:type schema:DefinedTerm
155 anzsrc-for:1115 schema:inDefinedTermSet anzsrc-for:
156 schema:name Pharmacology and Pharmaceutical Sciences
157 rdf:type schema:DefinedTerm
158 sg:journal.1094644 schema:issn 0724-8741
159 1573-904X
160 schema:name Pharmaceutical Research
161 schema:publisher Springer Nature
162 rdf:type schema:Periodical
163 sg:person.01217670277.65 schema:affiliation grid-institutes:grid.260969.2
164 schema:familyName Hanano
165 schema:givenName Manabu
166 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01217670277.65
167 rdf:type schema:Person
168 sg:person.01334724471.19 schema:affiliation grid-institutes:grid.26999.3d
169 schema:familyName Sugiyama
170 schema:givenName Yuichi
171 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01334724471.19
172 rdf:type schema:Person
173 sg:person.0607677165.24 schema:affiliation grid-institutes:grid.26999.3d
174 schema:familyName Shitara
175 schema:givenName Yoshihisa
176 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0607677165.24
177 rdf:type schema:Person
178 sg:person.0713513601.18 schema:affiliation grid-institutes:grid.26999.3d
179 schema:familyName Kato
180 schema:givenName Yukio
181 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0713513601.18
182 rdf:type schema:Person
183 grid-institutes:grid.260969.2 schema:alternateName Faculty of Pharmaceutical Sciences, Nihon University, 274, Narashinodai, Funabashi-shi, Chiba, Japan
184 schema:name Faculty of Pharmaceutical Sciences, Nihon University, 274, Narashinodai, Funabashi-shi, Chiba, Japan
185 rdf:type schema:Organization
186 grid-institutes:grid.26999.3d schema:alternateName Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan
187 schema:name Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan
188 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...