Effects of SIDT2 on the miR-25/NOX4/HuR axis and SIRT3 mRNA stability lead to ROS-mediated TNF-α expression in hydroquinone-treated leukemia cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-03-18

AUTHORS

Liang-Jun Wang, Yuan-Chin Lee, Jing-Ting Chiou, Ying-Jung Chen, Long-Sen Chang

ABSTRACT

Our previous studies indicated that the benzene metabolite hydroquinone (HQ) evokes the ROS/p38 MAPK/protein phosphatase 2A/tristetraprolin axis, leading to increased TNF-α expression in human acute myeloid leukemia cell lines U937 and HL-60. In this study, we aimed to identify the upstream pathway involved in ROS-mediated TNF-α expression. HQ treatment increased SIDT2 expression, which subsequently decreased miR-25 and SIRT3 expression in U937 cells. Notably, miR-25 downregulation promoted SIDT2 expression in HQ-treated U937 cells. SIDT2 induced lysosomal degradation of SIRT3 mRNA, but inhibited miR-25 expression through a lysosome-independent pathway. MiR-25 inhibition reduced NOX4 mRNA turnover, resulting in increased NOX4 protein levels. NOX4 induces mitochondrial ROS production and HuR downregulation. Restoration of HuR expression increased SIRT3 expression, suggesting that NOX4-mediated HuR downregulation promotes SIDT2-mediated degradation of SIRT3 mRNA. Inhibition of NOX4 or SIRT3 overexpression abolished HQ-induced ROS production, thereby abolishing TNF-α upregulation. Overall, these results indicate that SIDT2 regulates the miR-25/NOX4/HuR axis and SIRT3 mRNA destabilization, leading to ROS-mediated TNF-α upregulation in HQ-treated U937 cells. HQ-induced increase in TNF-α expression in HL-60 cells was also mediated through a similar pathway.Graphical abstract More... »

PAGES

1-19

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10565-022-09705-5

DOI

http://dx.doi.org/10.1007/s10565-022-09705-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1146343519

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35302183


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/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan", 
          "id": "http://www.grid.ac/institutes/grid.412036.2", 
          "name": [
            "Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Liang-Jun", 
        "id": "sg:person.016133500567.97", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016133500567.97"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan", 
          "id": "http://www.grid.ac/institutes/grid.412036.2", 
          "name": [
            "Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lee", 
        "givenName": "Yuan-Chin", 
        "id": "sg:person.01043111067.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01043111067.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan", 
          "id": "http://www.grid.ac/institutes/grid.412036.2", 
          "name": [
            "Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chiou", 
        "givenName": "Jing-Ting", 
        "id": "sg:person.014205745163.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014205745163.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, 807, Kaohsiung, Taiwan", 
          "id": "http://www.grid.ac/institutes/grid.412019.f", 
          "name": [
            "Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, 807, Kaohsiung, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Ying-Jung", 
        "id": "sg:person.0726732663.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0726732663.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biotechnology, Kaohsiung Medical University, 807, Kaohsiung, Taiwan", 
          "id": "http://www.grid.ac/institutes/grid.412019.f", 
          "name": [
            "Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan", 
            "Department of Biotechnology, Kaohsiung Medical University, 807, Kaohsiung, Taiwan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chang", 
        "givenName": "Long-Sen", 
        "id": "sg:person.0770353614.14", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0770353614.14"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/leu.2015.234", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015707672", 
          "https://doi.org/10.1038/leu.2015.234"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41467-017-01106-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092170309", 
          "https://doi.org/10.1038/s41467-017-01106-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep46144", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084538188", 
          "https://doi.org/10.1038/srep46144"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00204-016-1753-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002979310", 
          "https://doi.org/10.1007/s00204-016-1753-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10565-019-09495-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1123812573", 
          "https://doi.org/10.1007/s10565-019-09495-3"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00204-019-02443-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1113378443", 
          "https://doi.org/10.1007/s00204-019-02443-4"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2022-03-18", 
    "datePublishedReg": "2022-03-18", 
    "description": "Our previous studies indicated that the benzene metabolite hydroquinone (HQ) evokes the ROS/p38 MAPK/protein phosphatase 2A/tristetraprolin axis, leading to increased TNF-\u03b1 expression in human acute myeloid leukemia cell lines U937 and HL-60. In this study, we aimed to identify the upstream pathway involved in ROS-mediated TNF-\u03b1 expression. HQ treatment increased SIDT2 expression, which subsequently decreased miR-25 and SIRT3 expression in U937 cells. Notably, miR-25 downregulation promoted SIDT2 expression in HQ-treated U937 cells. SIDT2 induced lysosomal degradation of SIRT3 mRNA, but inhibited miR-25 expression through a lysosome-independent pathway. MiR-25 inhibition reduced NOX4 mRNA turnover, resulting in increased NOX4 protein levels. NOX4 induces mitochondrial ROS production and HuR downregulation. Restoration of HuR expression increased SIRT3 expression, suggesting that NOX4-mediated HuR downregulation promotes SIDT2-mediated degradation of SIRT3 mRNA. Inhibition of NOX4 or SIRT3 overexpression abolished HQ-induced ROS production, thereby abolishing TNF-\u03b1 upregulation. Overall, these results indicate that SIDT2 regulates the miR-25/NOX4/HuR axis and SIRT3 mRNA destabilization, leading to ROS-mediated TNF-\u03b1 upregulation in HQ-treated U937 cells. HQ-induced increase in TNF-\u03b1 expression in HL-60 cells was also mediated through a similar pathway.Graphical abstract", 
    "genre": "article", 
    "id": "sg:pub.10.1007/s10565-022-09705-5", 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1095523", 
        "issn": [
          "0742-2091", 
          "1573-6822"
        ], 
        "name": "Cell Biology and Toxicology", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }
    ], 
    "keywords": [
      "TNF-\u03b1 expression", 
      "TNF-\u03b1 upregulation", 
      "SIRT3 expression", 
      "SIRT3 mRNA", 
      "U937 cells", 
      "miR-25 downregulation", 
      "miR-25 inhibition", 
      "acute myeloid leukemia cell line U937", 
      "inhibition of Nox4", 
      "miR-25 expression", 
      "ROS production", 
      "Nox4 protein levels", 
      "lysosome-independent pathway", 
      "benzene metabolite hydroquinone", 
      "cell line U937", 
      "SIRT3 overexpression", 
      "miR-25", 
      "leukemia cell line U937", 
      "mitochondrial ROS production", 
      "Nox4", 
      "HuR expression", 
      "HL-60 cells", 
      "leukemia cells", 
      "metabolite hydroquinone", 
      "protein levels", 
      "HQ treatment", 
      "downregulation", 
      "SIDT2", 
      "upstream pathways", 
      "upregulation", 
      "HL-60", 
      "cells", 
      "expression", 
      "ROS", 
      "inhibition", 
      "lysosomal degradation", 
      "pathway", 
      "similar pathways", 
      "mRNA", 
      "previous studies", 
      "treatment", 
      "U937", 
      "study", 
      "overexpression", 
      "mRNA destabilization", 
      "axis", 
      "levels", 
      "restoration", 
      "Abstract Effects", 
      "increase", 
      "effect", 
      "turnover", 
      "production", 
      "stability lead", 
      "hydroquinone", 
      "lead", 
      "results", 
      "destabilization", 
      "degradation", 
      "mRNA turnover"
    ], 
    "name": "Effects of SIDT2 on the miR-25/NOX4/HuR axis and SIRT3 mRNA stability lead to ROS-mediated TNF-\u03b1 expression in hydroquinone-treated leukemia cells", 
    "pagination": "1-19", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1146343519"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s10565-022-09705-5"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "35302183"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s10565-022-09705-5", 
      "https://app.dimensions.ai/details/publication/pub.1146343519"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-08-04T17:12", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220804/entities/gbq_results/article/article_942.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1007/s10565-022-09705-5"
  }
]
 

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.10.1007/s10565-022-09705-5'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10565-022-09705-5'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10565-022-09705-5'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10565-022-09705-5'


 

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

173 TRIPLES      21 PREDICATES      89 URIs      75 LITERALS      5 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s10565-022-09705-5 schema:about anzsrc-for:06
2 anzsrc-for:0601
3 schema:author N56bcb37719074b328e041c15c8d47060
4 schema:citation sg:pub.10.1007/s00204-016-1753-4
5 sg:pub.10.1007/s00204-019-02443-4
6 sg:pub.10.1007/s10565-019-09495-3
7 sg:pub.10.1038/leu.2015.234
8 sg:pub.10.1038/s41467-017-01106-1
9 sg:pub.10.1038/srep46144
10 schema:datePublished 2022-03-18
11 schema:datePublishedReg 2022-03-18
12 schema:description Our previous studies indicated that the benzene metabolite hydroquinone (HQ) evokes the ROS/p38 MAPK/protein phosphatase 2A/tristetraprolin axis, leading to increased TNF-α expression in human acute myeloid leukemia cell lines U937 and HL-60. In this study, we aimed to identify the upstream pathway involved in ROS-mediated TNF-α expression. HQ treatment increased SIDT2 expression, which subsequently decreased miR-25 and SIRT3 expression in U937 cells. Notably, miR-25 downregulation promoted SIDT2 expression in HQ-treated U937 cells. SIDT2 induced lysosomal degradation of SIRT3 mRNA, but inhibited miR-25 expression through a lysosome-independent pathway. MiR-25 inhibition reduced NOX4 mRNA turnover, resulting in increased NOX4 protein levels. NOX4 induces mitochondrial ROS production and HuR downregulation. Restoration of HuR expression increased SIRT3 expression, suggesting that NOX4-mediated HuR downregulation promotes SIDT2-mediated degradation of SIRT3 mRNA. Inhibition of NOX4 or SIRT3 overexpression abolished HQ-induced ROS production, thereby abolishing TNF-α upregulation. Overall, these results indicate that SIDT2 regulates the miR-25/NOX4/HuR axis and SIRT3 mRNA destabilization, leading to ROS-mediated TNF-α upregulation in HQ-treated U937 cells. HQ-induced increase in TNF-α expression in HL-60 cells was also mediated through a similar pathway.Graphical abstract
13 schema:genre article
14 schema:isAccessibleForFree false
15 schema:isPartOf sg:journal.1095523
16 schema:keywords Abstract Effects
17 HL-60
18 HL-60 cells
19 HQ treatment
20 HuR expression
21 Nox4
22 Nox4 protein levels
23 ROS
24 ROS production
25 SIDT2
26 SIRT3 expression
27 SIRT3 mRNA
28 SIRT3 overexpression
29 TNF-α expression
30 TNF-α upregulation
31 U937
32 U937 cells
33 acute myeloid leukemia cell line U937
34 axis
35 benzene metabolite hydroquinone
36 cell line U937
37 cells
38 degradation
39 destabilization
40 downregulation
41 effect
42 expression
43 hydroquinone
44 increase
45 inhibition
46 inhibition of Nox4
47 lead
48 leukemia cell line U937
49 leukemia cells
50 levels
51 lysosomal degradation
52 lysosome-independent pathway
53 mRNA
54 mRNA destabilization
55 mRNA turnover
56 metabolite hydroquinone
57 miR-25
58 miR-25 downregulation
59 miR-25 expression
60 miR-25 inhibition
61 mitochondrial ROS production
62 overexpression
63 pathway
64 previous studies
65 production
66 protein levels
67 restoration
68 results
69 similar pathways
70 stability lead
71 study
72 treatment
73 turnover
74 upregulation
75 upstream pathways
76 schema:name Effects of SIDT2 on the miR-25/NOX4/HuR axis and SIRT3 mRNA stability lead to ROS-mediated TNF-α expression in hydroquinone-treated leukemia cells
77 schema:pagination 1-19
78 schema:productId N07cd3ce8a55f45f18593d0a0b6e30d7c
79 N5c41caec907f43e59f627f906f718c50
80 N97d05f05f09445aaa129dab2aa01c4fa
81 schema:sameAs https://app.dimensions.ai/details/publication/pub.1146343519
82 https://doi.org/10.1007/s10565-022-09705-5
83 schema:sdDatePublished 2022-08-04T17:12
84 schema:sdLicense https://scigraph.springernature.com/explorer/license/
85 schema:sdPublisher Nb61c2f8e78f840ceb3ff48c4bf5ebec5
86 schema:url https://doi.org/10.1007/s10565-022-09705-5
87 sgo:license sg:explorer/license/
88 sgo:sdDataset articles
89 rdf:type schema:ScholarlyArticle
90 N0643b163d7e64868a436775e703b105f rdf:first sg:person.01043111067.02
91 rdf:rest Na774ec04eb9a48638ff73f318ba2b99f
92 N07cd3ce8a55f45f18593d0a0b6e30d7c schema:name pubmed_id
93 schema:value 35302183
94 rdf:type schema:PropertyValue
95 N56bcb37719074b328e041c15c8d47060 rdf:first sg:person.016133500567.97
96 rdf:rest N0643b163d7e64868a436775e703b105f
97 N5c41caec907f43e59f627f906f718c50 schema:name dimensions_id
98 schema:value pub.1146343519
99 rdf:type schema:PropertyValue
100 N97d05f05f09445aaa129dab2aa01c4fa schema:name doi
101 schema:value 10.1007/s10565-022-09705-5
102 rdf:type schema:PropertyValue
103 N983407e1ea8a48109588e220482f1fcd rdf:first sg:person.0726732663.35
104 rdf:rest Ncff2738e0da84459bbb6de69fd00a676
105 Na774ec04eb9a48638ff73f318ba2b99f rdf:first sg:person.014205745163.41
106 rdf:rest N983407e1ea8a48109588e220482f1fcd
107 Nb61c2f8e78f840ceb3ff48c4bf5ebec5 schema:name Springer Nature - SN SciGraph project
108 rdf:type schema:Organization
109 Ncff2738e0da84459bbb6de69fd00a676 rdf:first sg:person.0770353614.14
110 rdf:rest rdf:nil
111 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
112 schema:name Biological Sciences
113 rdf:type schema:DefinedTerm
114 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
115 schema:name Biochemistry and Cell Biology
116 rdf:type schema:DefinedTerm
117 sg:journal.1095523 schema:issn 0742-2091
118 1573-6822
119 schema:name Cell Biology and Toxicology
120 schema:publisher Springer Nature
121 rdf:type schema:Periodical
122 sg:person.01043111067.02 schema:affiliation grid-institutes:grid.412036.2
123 schema:familyName Lee
124 schema:givenName Yuan-Chin
125 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01043111067.02
126 rdf:type schema:Person
127 sg:person.014205745163.41 schema:affiliation grid-institutes:grid.412036.2
128 schema:familyName Chiou
129 schema:givenName Jing-Ting
130 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014205745163.41
131 rdf:type schema:Person
132 sg:person.016133500567.97 schema:affiliation grid-institutes:grid.412036.2
133 schema:familyName Wang
134 schema:givenName Liang-Jun
135 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016133500567.97
136 rdf:type schema:Person
137 sg:person.0726732663.35 schema:affiliation grid-institutes:grid.412019.f
138 schema:familyName Chen
139 schema:givenName Ying-Jung
140 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0726732663.35
141 rdf:type schema:Person
142 sg:person.0770353614.14 schema:affiliation grid-institutes:grid.412019.f
143 schema:familyName Chang
144 schema:givenName Long-Sen
145 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0770353614.14
146 rdf:type schema:Person
147 sg:pub.10.1007/s00204-016-1753-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002979310
148 https://doi.org/10.1007/s00204-016-1753-4
149 rdf:type schema:CreativeWork
150 sg:pub.10.1007/s00204-019-02443-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1113378443
151 https://doi.org/10.1007/s00204-019-02443-4
152 rdf:type schema:CreativeWork
153 sg:pub.10.1007/s10565-019-09495-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1123812573
154 https://doi.org/10.1007/s10565-019-09495-3
155 rdf:type schema:CreativeWork
156 sg:pub.10.1038/leu.2015.234 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015707672
157 https://doi.org/10.1038/leu.2015.234
158 rdf:type schema:CreativeWork
159 sg:pub.10.1038/s41467-017-01106-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092170309
160 https://doi.org/10.1038/s41467-017-01106-1
161 rdf:type schema:CreativeWork
162 sg:pub.10.1038/srep46144 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084538188
163 https://doi.org/10.1038/srep46144
164 rdf:type schema:CreativeWork
165 grid-institutes:grid.412019.f schema:alternateName Department of Biotechnology, Kaohsiung Medical University, 807, Kaohsiung, Taiwan
166 Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, 807, Kaohsiung, Taiwan
167 schema:name Department of Biotechnology, Kaohsiung Medical University, 807, Kaohsiung, Taiwan
168 Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, 807, Kaohsiung, Taiwan
169 Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan
170 rdf:type schema:Organization
171 grid-institutes:grid.412036.2 schema:alternateName Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan
172 schema:name Institute of Biomedical Sciences, National Sun Yat-Sen University, 804, Kaohsiung, Taiwan
173 rdf:type schema:Organization
 




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


...