pre-miRNA Information | |
---|---|
pre-miRNA | hsa-mir-2115 |
Genomic Coordinates | chr3: 48316360 - 48316459 |
Description | Homo sapiens miR-2115 stem-loop |
Comment | None |
RNA Secondary Structure | ![]() |
Mature miRNA Information | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Mature miRNA | hsa-miR-2115-3p | |||||||||
Sequence | 58| CAUCAGAAUUCAUGGAGGCUAG |79 | |||||||||
Evidence | Experimental | |||||||||
Experiments | 454 | DRVs in miRNA |
|
|||||||
SNPs in miRNA |
|
|||||||||
Putative Targets |
miRNA Expression profile | |
---|---|
miRNAs in Extracellular Vesicles |
|
Circulating MicroRNA Expression Profiling |
Gene Information | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Gene Symbol | KCNJ3 | ||||||||||||||||||||
Synonyms | GIRK1, KGA, KIR3.1 | ||||||||||||||||||||
Description | potassium voltage-gated channel subfamily J member 3 | ||||||||||||||||||||
Transcript | NM_002239 | ||||||||||||||||||||
Expression | |||||||||||||||||||||
Putative miRNA Targets on KCNJ3 | |||||||||||||||||||||
3'UTR of KCNJ3 (miRNA target sites are highlighted) |
>KCNJ3|NM_002239|3'UTR 1 CAAAGCACTCCCTTAGGCATTATTTAATGTTTGATTTAGTAATAGTCCAATATTTGGCGATGAGGTAATTCTCCCTAAGG 81 AATCTGAAAGTATATTTTCCTCCCAGTTCTACAAGCATATTTGAGAACCCTTCCTTTCCCAAGTATTGCGAATGTGCAGA 161 AAGCAACAGTTACGGAGGGAGGACATCATAAGGAAGTTATTAACGGGCATGTATTATCACATCAAGCATGCAATAATGTG 241 CAAATTTTGCATTTAGTTTTATGGCATGATTTATATATGGCATATTTATATTGTATATTCTGGAAAAAAAATATATATAT 321 ATATTTAAAGGGGAGATACTCTCCCTGACATTTCTAACATATGTATTAAGCCAAACATGAGTGAATAGCTTTCAGGGCGA 401 TAAAACTAAATATATGTCTGTGTGTGTGTGTGTATGTATACACACATATACATATATATATACACATACATACACATACA 481 TACATACATACATATATATCTGATAAAATTGTGATGTTTTGTTCAAAGTTGTAGTTCTTGTGCATGTTTACTTTATTAGA 561 GTAGGAAGGCTACTGGCATTAATTATTAATACCAAATATTTTAGCCTTAAATTTTTGTCATTTTAAAATCTGATTTAATG 641 TTTTCTGCTGTTTAAGGTCTTGGGAGGCTTTCAATTGTATTTTATATGAGAGAATCACACAAGTTTGTGCTATCTATGGC 721 CCTGCAAAAATATAACCATTACATGTTTAAATTGTAAATTTTAGAGCATACCAGTACTCAGTATAGCATTGAACATTTCT 801 TATGATTTTTAAAAGTTGCTAGTACTGGGGAGAAATAATTGTTGATTAATTTGAGAATTATTCCTTTCCTAGACTAATTA 881 AAATCTGGAAATCTGTTTTGTATATGATCTAATACAAAGATGAGCTCTGAACAAACACTGAATCATGTTAATAGACAGTA 961 GCCAAGTTATATTGAATATATCAGAATCTGTGTGAAGTTACACAATTAATTGTCCCTGTTTCAAACTGAGTAAATTGGAA 1041 ACATTTTCTTTCTTTTTCTGGAAATTTTGTCCATTTTAAAAACCAATCATTTTAAGAAGACATGACAATGCAATGAAACA 1121 GATGATAAATATTTATGCTTAAAATATGTATGTCTAATTGAGTCTCTTTTTTATTCTGTTTTCTTGTTTATGGCATTTGT 1201 TGTAACAGGATAGACTTTTTCCTCACCTAGGAAACCTATCCCATGCCTGTCACTTATAGTTCAGGAGGAAGTTTTTGCAC 1281 AGACCAGAGAGAAATTAAAATTAGATGATAAATTGAAGATATCTTACACACAGTTTTTTGGTGAACACTGATTTTATTGG 1361 TGTCTTAGATCCCTAGTCTACCCAAATAATTTTAACAGTACTGTTTTTTCTAATCCTGAAGTCTGATATTTATGACTCAT 1441 TAGCAGGAATCAAAACTAGTGATCAGTAGAACACTTTCAAAATAAAAATTTGGAATGCAGACTTTTATGAAAATTTAAAA 1521 GTGCTCCTTAACAGAATATCATGGGTTTTCCTATAAAACTTCTTTAAGTATTGTAATTCCAGTCTGCCCCAACTTTAAAA 1601 AAAATTCTTATTAATATGTCAGTCATTAATTGCTAGTTTGGGCTCTCATTATTTCCTGTTTTTTAACAATTTTGTGATAA 1681 TTTTATTATTGGCAAATTAATACATCAACACTTAAATCATTGACTATAATAATACCTTCTGGCTACCTCTGTATCAACCA 1761 AATTCTGTAGGTGCAAACATATACCAGGGAATTCTTACTGGCAAAATGATCAATCTGGAGTGTGCATCCACTGTGAATGG 1841 AGCAAATTGCCCTATACCCATTGATAACCTAGCTTTCTTAGTTTGTAGATGTAGGAAACAAAATAGTGACAGAGAGAGAA 1921 GGGGGTCCACAGGGCATGGTATATTTATCAGCAGTGGAAAAAAAGTGCATAGATCATTTAGTCCAAGAACTTAAAACTAA 2001 ATAGAGCCATAATTTACTTTGGAGAGTCATTTTAATTTGTCTTTGGTACCAAGGAGAAGACGGAACCAAAAACAAACTCT 2081 CCAAGTATATTCACACATTCAACAAAATTTTTGCATGCCTTCTATGTCGTAGGCATTTTTAGTTCCTGGGGATTTGGACA 2161 TGGCTAAGTCAGAGAAGGCCATTGCTCACCATGAACACTGTATACCAGAAGGAGAGTGGGGAGGAGACAAAAAACAAATA 2241 AGACCACTTCAGACAATCAAAGTATCAGTTAAGAGAATGAAAACAGGCCTGACTCAGTGGCTCACGCCTGTAATCCCAGT 2321 ACTTTGGGAGGCGGAGGTTGGGGGATCACCTGAGGTCAGGAGATCGAGACCAGCCTGGACAACATGGTGAAAACCCGTCT 2401 CTACTAAAAATACAAAAATTAACTGGGCATGGTGGCAGGCACCTGTAATCCCAGCTACTGGGGAAGCTGAGGCAGGAGAA 2481 TCGTTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCCAAGATTCTGCCACTGCACTCCAGCCTGGGTGACAGTGCGAGACT 2561 CCATCTCAACATCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGAATAAAAACAGGGTAACATAATGCA 2641 AAGTAACTGTGTGGAATAAAAATTGATTATTTTAGAAAATGTGACTGGCTTAGGACGGGGATAATATGTGAACAGAAATC 2721 TATCTCATGAGAAAGTGCTACTGTTGTCAAAATTACCTTATCTGAGTGAATGGTATTTTTTTTATCTTTTCCACACATGC 2801 GTGGGAAAGGTATGATTTCTGCATGTAATTGCAGTTTAACCCTTATTTCTAGGTTGATCATAGGTCCCAGTTTACCCAGG 2881 AAAATTCCAGTTTATACCTGTTGTACCTGTGTAATTATTGGTAGCACTCCCTTTCACTCTTACAATGTCTTGGTTTGGAT 2961 GATATATGGTGAAGTTTTTGTTGAAACTAAATTATGAAGTCTGATATATTTGGATAAAAATAAAGAATTGCTTTTCTTC Target sites
Provided by authors
Predicted by miRanda
DRVs
SNPs
DRVs & SNPs
|
||||||||||||||||||||
miRNA-target interactions (Predicted by miRanda) |
|
||||||||||||||||||||
DRVs in gene 3'UTRs | |||||||||||||||||||||
SNPs in gene 3'UTRs |
Experimental Support 1 for Functional miRNA-Target Interaction | |
---|---|
miRNA:Target | ---- |
Validation Method |
|
Conditions | HEK293 |
Disease | 3760.0 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in GSM714644. RNA binding protein: AGO2. Condition:completeT1
... - Kishore S; Jaskiewicz L; Burger L; Hausser et al., 2011, Nature methods. |
Article |
- Kishore S; Jaskiewicz L; Burger L; Hausser et al. - Nature methods, 2011
Cross-linking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins. We developed a method for CLIP data analysis, and applied it to compare CLIP with photoactivatable ribonucleoside-enhanced CLIP (PAR-CLIP) and to uncover how differences in cross-linking and ribonuclease digestion affect the identified sites. We found only small differences in accuracies of these methods in identifying binding sites of HuR, which binds low-complexity sequences, and Argonaute 2, which has a complex binding specificity. We found that cross-link-induced mutations led to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect their binding sites sufficiently under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific RNases strongly biases the recovered binding sites. This bias can be substantially reduced by milder nuclease digestion conditions.
LinkOut: [PMID: 21572407]
|
Experimental Support 2 for Functional miRNA-Target Interaction | |
---|---|
miRNA:Target | ---- |
Validation Method |
|
Conditions | HEK293 |
Disease | 3760.0 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in GSM1065667. RNA binding protein: AGO1. Condition:4-thiouridine
... - Memczak S; Jens M; Elefsinioti A; Torti F; et al., 2013, Nature. |
Article |
- Memczak S; Jens M; Elefsinioti A; Torti F; et al. - Nature, 2013
Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.
LinkOut: [PMID: 23446348]
|
CLIP-seq Support 1 for dataset GSM714644 | |
---|---|
Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | HEK293 / completeT1, repA |
Location of target site | ENST00000295101.2 | 3UTR | AUGUAUACACACAUAUACAUAUAUAUAUACACAUACAUACACAUACAUACAUACAUACAUAUAUAUC |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21572407 / GSE28865 |
CLIP-seq Viewer | Link |
CLIP-seq Support 2 for dataset GSM1065667 | |
---|---|
Method / RBP | PAR-CLIP / AGO1 |
Cell line / Condition | HEK293 / 4-thiouridine, ML_MM_6 |
Location of target site | ENST00000295101.2 | 3UTR | UAUACACACAUAUACAUAUAUAUAUACACAUACAUACACAUACAUACAUACAUACAUAUAUAUCUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 23446348 / GSE43573 |
CLIP-seq Viewer | Link |
MiRNA-Target Expression Profile | |||||||
---|---|---|---|---|---|---|---|
|
MiRNA-Target Expression Profile (TCGA) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
80 hsa-miR-2115-3p Target Genes:
Functional analysis:
ID![]() |
Target | Description | Validation methods |
![]() |
![]() |
|||||||
Strong evidence | Less strong evidence | |||||||||||
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
|||||
MIRT057089 | DDIT4 | DNA damage inducible transcript 4 | ![]() |
![]() |
2 | 2 | ||||||
MIRT071216 | FCF1 | FCF1, rRNA-processing protein | ![]() |
![]() |
2 | 2 | ||||||
MIRT226901 | RAD23B | RAD23 homolog B, nucleotide excision repair protein | ![]() |
![]() |
2 | 2 | ||||||
MIRT235961 | BACH1 | BTB domain and CNC homolog 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT294569 | ZNF460 | zinc finger protein 460 | ![]() |
![]() |
2 | 4 | ||||||
MIRT321046 | RAC1 | Rac family small GTPase 1 | ![]() |
![]() |
2 | 4 | ||||||
MIRT359666 | NUS1 | NUS1 dehydrodolichyl diphosphate synthase subunit | ![]() |
![]() |
2 | 8 | ||||||
MIRT366451 | KLHL15 | kelch like family member 15 | ![]() |
![]() |
2 | 2 | ||||||
MIRT405375 | ZBTB18 | zinc finger and BTB domain containing 18 | ![]() |
![]() |
2 | 2 | ||||||
MIRT441794 | TCEAL5 | transcription elongation factor A like 5 | ![]() |
![]() |
2 | 2 | ||||||
MIRT443295 | TCEAL3 | transcription elongation factor A like 3 | ![]() |
![]() |
2 | 2 | ||||||
MIRT455275 | DDX39B | DExD-box helicase 39B | ![]() |
![]() |
2 | 2 | ||||||
MIRT458523 | C5orf22 | chromosome 5 open reading frame 22 | ![]() |
![]() |
2 | 2 | ||||||
MIRT464960 | TWIST1 | twist family bHLH transcription factor 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT466848 | STX6 | syntaxin 6 | ![]() |
![]() |
2 | 2 | ||||||
MIRT469252 | RHOB | ras homolog family member B | ![]() |
![]() |
2 | 2 | ||||||
MIRT469825 | RAB14 | RAB14, member RAS oncogene family | ![]() |
![]() |
2 | 4 | ||||||
MIRT470047 | PTGFRN | prostaglandin F2 receptor inhibitor | ![]() |
![]() |
2 | 2 | ||||||
MIRT471420 | PDP2 | pyruvate dehyrogenase phosphatase catalytic subunit 2 | ![]() |
![]() |
2 | 2 | ||||||
MIRT472024 | NPM1 | nucleophosmin 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT484156 | CENPN | centromere protein N | ![]() |
![]() |
2 | 2 | ||||||
MIRT485490 | HMGN2 | high mobility group nucleosomal binding domain 2 | ![]() |
![]() |
2 | 2 | ||||||
MIRT490462 | PROSER2 | proline and serine rich 2 | ![]() |
![]() |
2 | 2 | ||||||
MIRT493069 | MTCH1 | mitochondrial carrier 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT493573 | HSP90AA1 | heat shock protein 90 alpha family class A member 1 | ![]() |
![]() |
2 | 8 | ||||||
MIRT494919 | NDUFC2-KCTD14 | NDUFC2-KCTD14 readthrough | ![]() |
![]() |
2 | 2 | ||||||
MIRT500439 | ZMAT3 | zinc finger matrin-type 3 | ![]() |
![]() |
2 | 2 | ||||||
MIRT500931 | SRPR | SRP receptor alpha subunit | ![]() |
![]() |
2 | 4 | ||||||
MIRT501551 | POC1B-GALNT4 | POC1B-GALNT4 readthrough | ![]() |
![]() |
2 | 2 | ||||||
MIRT501809 | NEURL1B | neuralized E3 ubiquitin protein ligase 1B | ![]() |
![]() |
2 | 2 | ||||||
MIRT502415 | GALNT4 | polypeptide N-acetylgalactosaminyltransferase 4 | ![]() |
![]() |
2 | 2 | ||||||
MIRT506504 | MSANTD4 | Myb/SANT DNA binding domain containing 4 with coiled-coils | ![]() |
![]() |
2 | 2 | ||||||
MIRT507861 | CCNE2 | cyclin E2 | ![]() |
![]() |
2 | 2 | ||||||
MIRT510511 | YOD1 | YOD1 deubiquitinase | ![]() |
![]() |
2 | 6 | ||||||
MIRT516073 | RAB42 | RAB42, member RAS oncogene family | ![]() |
![]() |
2 | 2 | ||||||
MIRT519030 | KYNU | kynureninase | ![]() |
![]() |
2 | 6 | ||||||
MIRT521762 | PPIL1 | peptidylprolyl isomerase like 1 | ![]() |
![]() |
2 | 4 | ||||||
MIRT522898 | KCNJ3 | potassium voltage-gated channel subfamily J member 3 | ![]() |
![]() |
2 | 4 | ||||||
MIRT527370 | MGARP | mitochondria localized glutamic acid rich protein | ![]() |
![]() |
2 | 2 | ||||||
MIRT530691 | C8orf46 | chromosome 8 open reading frame 46 | ![]() |
![]() |
2 | 2 | ||||||
MIRT530867 | TRUB1 | TruB pseudouridine synthase family member 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT531832 | MTPAP | mitochondrial poly(A) polymerase | ![]() |
![]() |
2 | 4 | ||||||
MIRT533035 | ZBTB5 | zinc finger and BTB domain containing 5 | ![]() |
![]() |
2 | 2 | ||||||
MIRT533165 | WIPF2 | WAS/WASL interacting protein family member 2 | ![]() |
![]() |
2 | 2 | ||||||
MIRT533464 | TRIM71 | tripartite motif containing 71 | ![]() |
![]() |
2 | 2 | ||||||
MIRT534331 | SHCBP1 | SHC binding and spindle associated 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT539372 | ADSS | adenylosuccinate synthase | ![]() |
![]() |
2 | 6 | ||||||
MIRT545951 | ZBTB10 | zinc finger and BTB domain containing 10 | ![]() |
![]() |
2 | 2 | ||||||
MIRT553283 | TSR1 | TSR1, ribosome maturation factor | ![]() |
![]() |
2 | 2 | ||||||
MIRT553532 | TMEM185B | transmembrane protein 185B | ![]() |
![]() |
2 | 4 | ||||||
MIRT556480 | LIPA | lipase A, lysosomal acid type | ![]() |
![]() |
2 | 2 | ||||||
MIRT556975 | HSPA4L | heat shock protein family A (Hsp70) member 4 like | ![]() |
![]() |
2 | 2 | ||||||
MIRT557697 | GATA6 | GATA binding protein 6 | ![]() |
![]() |
2 | 2 | ||||||
MIRT558901 | CCDC58 | coiled-coil domain containing 58 | ![]() |
![]() |
2 | 2 | ||||||
MIRT559224 | BLMH | bleomycin hydrolase | ![]() |
![]() |
2 | 2 | ||||||
MIRT559827 | SLPI | secretory leukocyte peptidase inhibitor | ![]() |
![]() |
2 | 2 | ||||||
MIRT563435 | SLC3A2 | solute carrier family 3 member 2 | ![]() |
![]() |
2 | 2 | ||||||
MIRT569270 | PCDH11X | protocadherin 11 X-linked | ![]() |
![]() |
2 | 2 | ||||||
MIRT571386 | JKAMP | JNK1/MAPK8-associated membrane protein | ![]() |
![]() |
2 | 2 | ||||||
MIRT572567 | AFF1 | AF4/FMR2 family member 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT610400 | AR | androgen receptor | ![]() |
![]() |
2 | 2 | ||||||
MIRT611058 | ZNF621 | zinc finger protein 621 | ![]() |
![]() |
2 | 2 | ||||||
MIRT635118 | TMEM233 | transmembrane protein 233 | ![]() |
![]() |
2 | 2 | ||||||
MIRT641617 | DEFB118 | defensin beta 118 | ![]() |
![]() |
2 | 2 | ||||||
MIRT642146 | CHORDC1 | cysteine and histidine rich domain containing 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT647295 | C8orf33 | chromosome 8 open reading frame 33 | ![]() |
![]() |
2 | 2 | ||||||
MIRT648155 | MPLKIP | M-phase specific PLK1 interacting protein | ![]() |
![]() |
2 | 2 | ||||||
MIRT652780 | TENM3 | teneurin transmembrane protein 3 | ![]() |
![]() |
2 | 2 | ||||||
MIRT657356 | HNRNPA2B1 | heterogeneous nuclear ribonucleoprotein A2/B1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT658718 | ELN | elastin | ![]() |
![]() |
2 | 2 | ||||||
MIRT662441 | RALGAPA1 | Ral GTPase activating protein catalytic alpha subunit 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT665302 | ZBTB38 | zinc finger and BTB domain containing 38 | ![]() |
![]() |
2 | 2 | ||||||
MIRT699898 | RUNX1 | runt related transcription factor 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT700921 | PDS5A | PDS5 cohesin associated factor A | ![]() |
![]() |
2 | 2 | ||||||
MIRT700992 | PDE3A | phosphodiesterase 3A | ![]() |
![]() |
2 | 2 | ||||||
MIRT707397 | DCAF4L1 | DDB1 and CUL4 associated factor 4 like 1 | ![]() |
![]() |
2 | 2 | ||||||
MIRT711895 | INSIG2 | insulin induced gene 2 | ![]() |
![]() |
2 | 2 | ||||||
MIRT712072 | XRCC5 | X-ray repair cross complementing 5 | ![]() |
![]() |
2 | 2 | ||||||
MIRT716121 | PTPLAD2 | 3-hydroxyacyl-CoA dehydratase 4 | ![]() |
1 | 1 | |||||||
MIRT724470 | SMAD2 | SMAD family member 2 | ![]() |
![]() |
2 | 2 |
miRNA-Drug Resistance Associations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|