CLCN5

CLCN5
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2J9L, 2JA3

Identifikatori
AliasiCLCN5
Vanjski ID-jeviOMIM: 300008 MGI: 99486 HomoloGene: 73872 GeneCards: CLCN5
Lokacija gena (čovjek)
Hromosom X
Hrom.Hromosom X[1]
Hromosom X
Genomska lokacija za CLCN5
Genomska lokacija za CLCN5
BendXp11.23Početak49,922,596 bp[1]
Kraj50,099,235 bp[1]
Lokacija gena (miš)
Hromosom X (miš)
Hrom.Hromosom X (miš)[2]
Hromosom X (miš)
Genomska lokacija za CLCN5
Genomska lokacija za CLCN5
BendX A1.1|X 3.21 cMPočetak7,020,049 bp[2]
Kraj7,185,597 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija nucleotide binding
ion channel activity
ATP binding
chloride channel activity
antiporter activity
voltage-gated chloride channel activity
vezivanje identičnih proteina
GO:0001948, GO:0016582 vezivanje za proteine
solute:proton antiporter activity
chloride ion binding
Ćelijska komponenta integral component of membrane
membrana
Golđijeva membrana
apical part of cell
integral component of plasma membrane
lysosomal membrane
endosome membrane
endozom
Golđijev aparat
citosol
ćelijska membrana
early endosome
Biološki proces izlučivanje
ion transport
ion transmembrane transport
regulation of anion transmembrane transport
chloride transport
chloride transmembrane transport
transmembrane transport
GO:0015915 transport
proton transmembrane transport
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_000084
NM_001127898
NM_001127899
NM_001272102
NM_001282163

NM_001243762
NM_016691

RefSeq (bjelančevina)

NP_000075
NP_001121370
NP_001121371
NP_001259031
NP_001269092

NP_001230691
NP_057900

Lokacija (UCSC)Chr X: 49.92 – 50.1 MbChr X: 7.02 – 7.19 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Gen CLCN5 kod ljudi, nalazi se na hromosomu X. Kodira hloridni kanal Cl-/H+ izmjenjivač ClC-5. ClC-5 koji se uglavnom eksprimira u bubregu, posebno u proksimalnim tubulama, gdje učestvuje u preuzimanju albumina i proteina niske molekulse težine, što je jedan od glavnih fiziološka uloga ćelija proksimalnih tubula. Mutacije u genu CLCN5 uzrokuju X-vezano recesivnu nefropatiju pod nazivom Dentova bolest (Dentova bolest 1 MIM#300009) okarakterizirana prekomjernim gubitkom proteina niske molekulske težine i kalcijem u urinu (hiperkalciurija), nefrokalcinoza (prisustvo agregata kalcij-fosfata u tubulskom lumenu i/ili intersticiju) i nefrolitijaza]ma urinarnom traktom. (kamen u bubregu).

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 746 aminokiselina, a molekulska težina 83.147 Da.

1020304050
MDFLEEPIPGVGTYDDFNTIDWVREKSRDRDRHREITNKSKESTWALIHS
VSDAFSGWLLMLLIGLLSGSLAGLIDISAHWMTDLKEGICTGGFWFNHEH
CCWNSEHVTFEERDKCPEWNSWSQLIISTDEGAFAYIVNYFMYVLWALLF
AFLAVSLVKVFAPYACGSGIPEIKTILSGFIIRGYLGKWTLVIKTITLVL
AVSSGLSLGKEGPLVHVACCCGNILCHCFNKYRKNEAKRREVLSAAAAAG
VSVAFGAPIGGVLFSLEEVSYYFPLKTLWRSFFAALVAAFTLRSINPFGN
SRLVLFYVEFHTPWHLFELVPFILLGIFGGLWGALFIRTNIAWCRKRKTT
QLGKYPVIEVLVVTAITAILAFPNEYTRMSTSELISELFNDCGLLDSSKL
CDYENRFNTSKGGELPDRPAGVGVYSAMWQLALTLILKIVITIFTFGMKI
PSGLFIPSMAVGAIAGRLLGVGMEQLAYYHQEWTVFNSWCSQGADCITPG
LYAMVGAAACLGGVTRMTVSLVVIMFELTGGLEYIVPLMAAAMTSKWVAD
ALGREGIYDAHIRLNGYPFLEAKEEFAHKTLAMDVMKPRRNDPLLTVLTQ
DSMTVEDVETIISETTYSGFPVVVSRESQRLVGFVLRRDLIISIENARKK
QDGVVSTSIIYFTEHSPPLPPYTPPTLKLRNILDLSPFTVTDLTPMEIVV
DIFRKLGLRQCLVTHNGRLLGIITKKDVLKHIAQMANQDPDSILFN

Struktura

Ljudski CLCN5 gen (MIM#300008, referentna sekvenca NG_007159.2) je lokalizovan u pericentromernom regionu na hromosoma X, sekvenca Xp11.23. Proteže se na oko 170 Kb genomske DNK, ima kodirajuću regiju od 2,238 bp i sastoji se od 17 egzona, uključujući 11 egzona (od 2 do 12).[5][6][7][8] Gen CLCN5 ima 8 paraloga (CLCN1, CLCN2, CLCN3, CLCN4, CLCN6, CLCN7, CLCNKA, CLCNKB) i 201 ortologa među viličastim kičmenjacima (Gnathostomata).

Otkriveno je pet različitih CLCN5 genskih transkripata, od kojih dvije (varijante transkripta 3 [NM_000084.5] i 4 [NM_001282163.1]) kodiraju kanonski 746-aminokiselinski protein, dvije (varijante transkripta 1 [NM_001127899.3] i 2 [NM_001127898.3]) NH2-terminalni prošireni protein od 816 aminokiselina[9] a jedna ne kodira nijedan protein (varijanta transkripta 5, [NM_001272102.2]). Pet prim neprevedena regija (5'UTR) CLCN5-a je složena struktura i nije u potpunosti razjašnjena. Predviđeno je da će dva jaka i jedan slabi promotor biti prisutni u genu CLCN5.[10][11] Several different 5’ alternatively used exons have been recognized in the human kidney.[9][10][11][12] Tri promotora pokreću sa različitim stepenom efikasnosti 11 različitih iRNK, pri čemu transkripcija počinje sa najmanje tri različita početna mesta.[10]

Lokalizacija i funkcija

ClC-5 pripada porodici hloridnih kanala koji su regulatori ekscitabilnosti membrane, transepitelnog transporta i volumena ćelija u različitim tkivima). Na osnovu homologija sekvenci, devet ClC proteina sisara može se grupisati u tri klase, od kojih se prva (ClC-1, ClC-2, ClC-Ka i ClC-Kb) prvenstveno eksprimira u plazmamembranama, dok su druga dva (ClC-3, ClC-4 i ClC-5 i ClC-6 i ClC-7) prvenstveno eksprimirana u organelskim membranama.[13]

ClC-5 je eksprimiran u malim do umjerenim razinama u mozgu, mišićima, crijevima, ali visoko u bubrezima, prvenstveno u ćelijama proksimalnih tubula segmenta S3, u alfa interkaliranim ćelijama korteksa sabirnih kanala i u korteksmom i medulskom debelom uzlaznom nastavku Henleove petlje.[14][15][16][17][18][19]

Ćelije proksimalnih tubula (PTC) su glavno mjesto ekspresije ClC-5. Pomoću procesa receptorom posredovane endocitoze, preuzimaju albumin i proteine niske molekulske težine koji slobodno prolaze kroz glomerulski filter. ClC-5 se nalazi u ranim endosomima PTC-a, gdje se kolokalizira s elektrogenom vakuolskom H+‐ATPazom (V‐ATPaze). ClC-5 u ovom odjeljku doprinosi održavanju intraendosomske kiselosti pH. Zakiseljavanje okoline je neophodno za disocijaciju liganda od njegovog receptora. Receptor se zatim reciklira u apikalnu membranu, dok se ligand transportuje do kasnog endosoma i lizosoma, gdje se razgrađuje. ClC-5 podržava efikasnu acidifikaciju endosoma, bilo obezbjeđivanjem Cl provodljivosti kako bi se uravnotežila akumulacija pozitivno nabijenog H+ upumpanog V-ATPazom, ili direktnim zakiseljavanjem endosoma u paralelno sa V-ATPazom.[20]

Eksperimentalni dokazi potvrđuju da endosomna koncentracija Cl, koju ClC-5 podiže u zamjenu za protone akumulirane od strane V-ATPaze, može igrati ulogu u endocitozama, neovisno o endosomnoj acidifikaciji, ukazujući tako na drugi mogući mehanizam kojim disfunkcija ClC-5 može poremetiti endocitozu.[21]

ClC-5 se takođe nalazi na površini ćelije PTC-a, gdje vjerovatno ima ulogu u formiranju/funkcionisanju endocitnog kompleksa koji također uključuje megalin i kubilin/amnionske receptore , natrij-vodik antiporter 3 (NHE3) i V-ATPaza.[22][23] Pokazano je da se na C-terminalu ClC-5 vezuje za aktin-depolimerizirajući protein kofilin. Kada se formira endosom u nastajanju, regrutovanje kofilina od strane ClC-5 je preduslov za lokalizovano rastvaranje aktinskog citoskeleta, čime se dozvoljava endosomu da prođe u citoplazmu. Moguće je da na površini ćelije veliki unutarćelijski C-kraj ClC-5 ima ključnu funkciju u posredovanju u sklapanju, stabilizaciji i rastavljanju endocitnog kompleksa, putem interakcija protein-protein. Stoga, ClC-5 može ostvariti dvije uloge u endocitozi posredovanoj receptorima: 1) vezikulska acidifikacija i reciklaža receptora; 2) učešće u neselektivnom unosu proteina male molekulske težine bez megalina-kubilina-amniona na apikalnoj membrani.

Klinički značaj

Dentova bolest je uglavnom uzrokovana gubitkom funkcije, mutacijama u "CLCN5" genu (Dent disease 1; MIM#300009).[24] Dentova bolest 1 pokazuje izraženu alelnu heterogenost. Do danas je opisano 265 različitih patogenih varijanti "CLCN5". Mali broj patogenih varijanti pronađen je u više od jedne porodice.[25] Oko 48% su skraćene mutacije (nonsensne, okvirne ili složene), 37% neskraćene (misensne ili unutar okvira insercije/delecije), 10% mutacija na mjestu prerade i 5% drugih tipova (velike delecije, Alu inseercije ili 5'UTR mutacije). Funkcionalna istraživanja u oocitima Xenopus laevis (afrička kandžasta žaba) i ćelijama sisara.[21][26][27][28] enabled these CLCN5 mutations to be classified according to their functional consequences.[8][25][29][30][31] Najčešće mutacije dovode do defektnog sklapanja proteina i obrađivanja, što rezultira sa endoplazmatskkoretikulumskim zadržavanjem mutantnog proteina za dalju degradaciju putem proteasoma.


Klinička dijagnoza Dentove bolesti može se potvrditi molekulskim genetičkim testiranjem koje može otkriti mutacije u specifičnim genima za koje je poznato da uzrokuju Dentovu bolest. Međutim, oko 20-25% pacijenata sa Dentovom bolešću ostaje genetički neriješeno.

Genetičko testiranje je korisno za određivanje statusa zdravog nositelja kod majke oboljelog muškarca. U stvari, budući da je Dentova bolest X-vezano recesivno oboljenje, muškarci su češće pogođeni nego žene, a žene mogu biti heterozigotne zdrave nositeljice. Zbog X-inaktivacije, žene nositeljice mogu imati neke blage simptome Dentove bolesti, kao što su niske molekulske težine (proteinurija ili hiperkalciurija). Nositeljice će prenijeti bolest na polovinu svojih sinova, dok će polovina njihovih kćeri biti nositeljice. Oboljeli muškarci ne prenose bolest na svoje sinove jer na muškarce prenose hromosom Y, ali sve njihove kćeri će naslijediti mutirani hromosom X. Preimplantacijsko i preneonatusno genetičko testiranje se ne preporučuju za Dentovu bolest 1, jer je prognoza za većinu pacijenata dobra i nedostaje jasna je korelacija između genotipa i fenotipa.[32]

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Reference

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000171365 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004317 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Scheinman SJ, Pook MA, Wooding C, Pang JT, Frymoyer PA, Thakker RV (juni 1993). "Mapping the gene causing X-linked recessive nephrolithiasis to Xp11.22 by linkage studies". The Journal of Clinical Investigation. 91 (6): 2351–7. doi:10.1172/JCI116467. PMC 443292. PMID 8099916.
  6. ^ Fisher SE, Black GC, Lloyd SE, Hatchwell E, Wrong O, Thakker RV, Craig IW (novembar 1994). "Isolation and partial characterization of a chloride channel gene which is expressed in kidney and is a candidate for Dent's disease (an X-linked hereditary nephrolithiasis)". Human Molecular Genetics. 3 (11): 2053–9. PMID 7874126.
  7. ^ Fisher SE, van Bakel I, Lloyd SE, Pearce SH, Thakker RV, Craig IW (oktobar 1995). "Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis)". Genomics. 29 (3): 598–606. doi:10.1006/geno.1995.9960. hdl:11858/00-001M-0000-0012-CC06-6. PMID 8575751.
  8. ^ a b Scheel O, Zdebik AA, Lourdel S, Jentsch TJ (juli 2005). "Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins". Nature. 436 (7049): 424–7. Bibcode:2005Natur.436..424S. doi:10.1038/nature03860. PMID 16034422. S2CID 4412965.
  9. ^ a b Ludwig M, Waldegger S, Nuutinen M, Bökenkamp A, Reissinger A, Steckelbroeck S, Utsch B (2003). "Four additional CLCN5 exons encode a widely expressed novel long CLC-5 isoform but fail to explain Dent's phenotype in patients without mutations in the short variant". Kidney & Blood Pressure Research. 26 (3): 176–84. doi:10.1159/000071883. PMID 12886045. S2CID 41532860.
  10. ^ a b c Hayama, Atsushi; Uchida, Shinichi; Sasaki, Sei; Marumo, Fumiaki (2000). "Isolation and characterization of the human CLC-5 chloride channel gene promoter". Gene (jezik: engleski). 261 (2): 355–364. doi:10.1016/S0378-1119(00)00493-5. PMID 11167024.
  11. ^ a b Tosetto E, Casarin A, Salviati L, Familiari A, Lieske JC, Anglani F (juli 2014). "Complexity of the 5'UTR region of the CLCN5 gene: eleven 5'UTR ends are differentially expressed in the human kidney". BMC Medical Genomics. 7 (1): 41. doi:10.1186/1755-8794-7-41. PMC 4105828. PMID 25001568.
  12. ^ Forino M, Graziotto R, Tosetto E, Gambaro G, D'Angelo A, Anglani F (2004). "Identification of a novel splice site mutation of CLCN5 gene and characterization of a new alternative 5' UTR end of ClC-5 mRNA in human renal tissue and leukocytes". Journal of Human Genetics. 49 (1): 53–60. doi:10.1007/s10038-003-0108-1. PMID 14673707.
  13. ^ Stölting G, Fischer M, Fahlke C (7. 10. 2014). "CLC channel function and dysfunction in health and disease". Frontiers in Physiology. 5: 378. doi:10.3389/fphys.2014.00378. PMC 4188032. PMID 25339907.
  14. ^ Obermüller N, Gretz N, Kriz W, Reilly RF, Witzgall R (februar 1998). "The swelling-activated chloride channel ClC-2, the chloride channel ClC-3, and ClC-5, a chloride channel mutated in kidney stone disease, are expressed in distinct subpopulations of renal epithelial cells". The Journal of Clinical Investigation. 101 (3): 635–42. doi:10.1172/JCI1496. PMC 508607. PMID 9449697.
  15. ^ Günther W, Lüchow A, Cluzeaud F, Vandewalle A, Jentsch TJ (juli 1998). "ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 8075–80. Bibcode:1998PNAS...95.8075G. doi:10.1073/pnas.95.14.8075. PMC 20931. PMID 9653142.
  16. ^ Luyckx VA, Goda FO, Mount DB, Nishio T, Hall A, Hebert SC, et al. (novembar 1998). "Intrarenal and subcellular localization of rat CLC5". The American Journal of Physiology. 275 (5): F761-9. doi:10.1152/ajprenal.1998.275.5.F761. PMID 9815133.
  17. ^ Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (mart 1999). "Expression of CLCN voltage-gated chloride channel genes in human blood vessels". Journal of Molecular and Cellular Cardiology. 31 (3): 657–66. doi:10.1006/jmcc.1998.0901. PMID 10198195.
  18. ^ von Weikersthal SF, Barrand MA, Hladky SB (april 1999). "Functional and molecular characterization of a volume-sensitive chloride current in rat brain endothelial cells". The Journal of Physiology. 516 ( Pt 1): 75–84. doi:10.1111/j.1469-7793.1999.075aa.x. PMC 2269222. PMID 10066924.
  19. ^ Devuyst O, Christie PT, Courtoy PJ, Beauwens R, Thakker RV (februar 1999). "Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent's disease". Human Molecular Genetics. 8 (2): 247–57. doi:10.1093/hmg/8.2.247. PMID 9931332.
  20. ^ Smith AJ, Lippiat JD (juni 2010). "Direct endosomal acidification by the outwardly rectifying CLC-5 Cl(-)/H(+) exchanger". The Journal of Physiology. 588 (Pt 12): 2033–45. doi:10.1113/jphysiol.2010.188540. PMC 2911210. PMID 20421284.
  21. ^ a b Novarino G, Weinert S, Rickheit G, Jentsch TJ (juni 2010). "Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis". Science. 328 (5984): 1398–401. Bibcode:2010Sci...328.1398N. doi:10.1126/science.1188070. PMID 20430975. S2CID 206525928.
  22. ^ Hryciw DH, Wang Y, Devuyst O, Pollock CA, Poronnik P, Guggino WB (oktobar 2003). "Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines". The Journal of Biological Chemistry. 278 (41): 40169–76. doi:10.1074/jbc.M307890200. PMID 12904289.
  23. ^ Wang Y, Cai H, Cebotaru L, Hryciw DH, Weinman EJ, Donowitz M, et al. (oktobar 2005). "ClC-5: role in endocytosis in the proximal tubule" (PDF). American Journal of Physiology. Renal Physiology. 289 (4): F850-62. doi:10.1152/ajprenal.00011.2005. PMID 15942052.
  24. ^ Lloyd SE, Pearce SH, Fisher SE, Steinmeyer K, Schwappach B, Scheinman SJ, et al. (februar 1996). "A common molecular basis for three inherited kidney stone diseases". Nature. 379 (6564): 445–9. Bibcode:1996Natur.379..445L. doi:10.1038/379445a0. hdl:11858/00-001M-0000-0012-CBFE-2. PMID 8559248. S2CID 4364656.
  25. ^ a b Lieske, John C.; Milliner, Dawn S.; Beara-Lasic, Lada; Harris, Peter; Cogal, Andrea; Abrash, Elizabeth (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (ured.), "Dent Disease", GeneReviews®, University of Washington, Seattle, PMID 22876375, pristupljeno 28. 2. 2020
  26. ^ Lloyd SE, Gunther W, Pearce SH, Thomson A, Bianchi ML, Bosio M, et al. (august 1997). "Characterisation of renal chloride channel, CLCN5, mutations in hypercalciuric nephrolithiasis (kidney stones) disorders". Human Molecular Genetics. 6 (8): 1233–9. doi:10.1093/hmg/6.8.1233. PMID 9259268.
  27. ^ Grand T, L'Hoste S, Mordasini D, Defontaine N, Keck M, Pennaforte T, et al. (april 2011). "Heterogeneity in the processing of CLCN5 mutants related to Dent disease" (PDF). Human Mutation. 32 (4): 476–83. doi:10.1002/humu.21467. PMID 21305656. S2CID 25637790.
  28. ^ Gorvin CM, Wilmer MJ, Piret SE, Harding B, van den Heuvel LP, Wrong O, et al. (april 2013). "Receptor-mediated endocytosis and endosomal acidification is impaired in proximal tubule epithelial cells of Dent disease patients". Proceedings of the National Academy of Sciences of the United States of America. 110 (17): 7014–9. Bibcode:2013PNAS..110.7014G. doi:10.1073/pnas.1302063110. PMC 3637698. PMID 23572577.
  29. ^ D'Antonio C, Molinski S, Ahmadi S, Huan LJ, Wellhauser L, Bear CE (juni 2013). "Conformational defects underlie proteasomal degradation of Dent's disease-causing mutants of ClC-5". The Biochemical Journal. 452 (3): 391–400. doi:10.1042/BJ20121848. PMID 23566014.
  30. ^ Smith AJ, Reed AA, Loh NY, Thakker RV, Lippiat JD (februar 2009). "Characterization of Dent's disease mutations of CLC-5 reveals a correlation between functional and cell biological consequences and protein structure". American Journal of Physiology. Renal Physiology. 296 (2): F390-7. doi:10.1152/ajprenal.90526.2008. PMC 2643861. PMID 19019917.
  31. ^ Ludwig M, Doroszewicz J, Seyberth HW, Bökenkamp A, Balluch B, Nuutinen M, et al. (juli 2005). "Functional evaluation of Dent's disease-causing mutations: implications for ClC-5 channel trafficking and internalization". Human Genetics. 117 (2–3): 228–37. doi:10.1007/s00439-005-1303-2. PMID 15895257. S2CID 34623611.
  32. ^ Devuyst O, Thakker RV (oktobar 2010). "Udubljenja disease". Orphanet Journal of Rare Diseases. 5 (1): 28. doi:10.1186/1750-1172-5-28. PMC 2964617. PMID 20946626.

Dopunska literatura

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

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جوزيف فون هامر-برجشتال (بالألمانية: Joseph Freiherr von Hammer-Purgstall)‏    معلومات شخصية اسم الولادة (بالألمانية: Joseph Freiherr von Hammer)‏  الميلاد 9 يونيو 1774(1774-06-09)غراتس[1][2]  الوفاة 23 نوفمبر 1856 (82 سنة) [3][4][5]  فيينا[1][2]  مواطنة النمسا  عضو في الأكاديمي...

 

Pestilence, 2018 Pestilence adalah kelompok death / thrash metal dari Enschede (Belanda) yang didirikan pada 1986. Anggota Patrick Mameli - Lead guitars, vocals Patrick Uterwijk - Lead guitars Jeroen Paul Thesseling - Bass guitar Marco Foddis - Drums Mantan Martin van Drunen - Vocals, Bass guitar Tony Choy - Bass guitar Ken Smith - Keyboards Randy Meinhart - Guitar Jack Dodd - Bass guitar Diskografi Dysentery (Demo, 1987) Penance (Demo, 1988) Malleus Maleficarum (1988) Consuming Impulse (1989...

Mohandas Gandhi's list of negative qualities Seven Social Sins is a list by Frederick Lewis Donaldson that Mohandas Karamchand Gandhi published in his weekly newspaper Young India on October 22, 1925.[1] Later he gave this same list to his grandson, Arun Gandhi, written on a piece of paper on their final day together shortly before his assassination.[2] The Seven Sins are: Wealth without work. Pleasure without conscience. Knowledge without character. Commerce without morality....

 

Ludwig (Gerhard Gustav) Simon (auch bekannt als Simon von Trier; * 20. Februar 1819 in Saarlouis; † 2. Februar 1872 in Montreux, Schweiz) war ein Revolutionär 1848/49 und Mitglied der Frankfurter Nationalversammlung. Inhaltsverzeichnis 1 Leben 2 Werke 3 Literatur 4 Weblinks 5 Einzelnachweise Leben Ludwig Simon Ludwig Simon, Abgeordneter der Frankfurter Nationalversammlung. Foto Jacob Seib, 1848 Ludwig Simon war der Sohn von Thomas Simon und Susanna Auguste Walther. 1836 erwarb er sein Abit...

 

Sufi ceremony performed as part of the meditation and prayer For other uses, see Sama (disambiguation). Sema redirects here. For other uses, see Sema (disambiguation). Mevlevi Sema CeremonyUNESCO Intangible Cultural HeritageWhirling Dervishes in Istanbul, TurkeyCountryTurkeyReference100RegionEurope and AsiaInscription historyInscription2008 (3rd session) Sama (Turkish: Sema; Persian, Urdu and Arabic: سَمَاع, romanized: samā‘un) is a Sufi ceremony performed as part of the meditat...

Untuk film pada masa berikutnya, lihat Fighting Through (film 1934). Fighting ThroughSutradara Christy Cabanne Produser Christy Cabanne Ditulis oleh Christy Cabanne Pemeran E. K. Lincoln Spottiswoode Aitken Millicent Fisher SinematograferSam LandersPerusahaanproduksiWilliam Christy Cabanne Producing Co.Distributor Pathé Exchange W. W. Hodkinson Corporation Tanggal rilis 27 Januari 1919 (1919-01-27) (Amerika Serikat)[1] Durasi6 rolNegara Amerika Serikat Bahasa Bisu intertitel...

 

American journalist (born 1972) For other people with similar names, see Kevin Williamson (disambiguation). Kevin D. WilliamsonKevin D. Williamson hosting a FreedomFest panel in 2016BornKevin Daniel Williamson (1972-09-18) September 18, 1972 (age 51)Amarillo, Texas, U.S.Alma materYale UniversityOccupationRoving correspondentEmployerThe DispatchPolitical partyRepublican (before 2008)[1] Kevin Daniel Williamson (born September 18, 1972) is an American conservative political co...

 

Canadian reality show CNTM redirects here. For other uses, see CNTM (disambiguation). This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Canada's Next Top Model – news · newspapers · books · scholar · JSTOR (May 2016) (Learn how and when to remove this template message) Canada's Next Top ModelCanada's Next Top ...

Rabbi Moshe Feinstein. Yahudi Ortodoks adalah cabang dari agama Yudaisme yang saklek. Penganutnya dikenal sangat kaku dalam mentaati seluruh hukum Taurat yang berjumlah 613 mitzvot/peraturan. Misalnya, mereka memilih berjalan kaki menuju Sinagoge, karena tidak boleh ada transaksi uang pada hari Sabat. Demikian pula tidak boleh ada seorang wanita yang boleh jadi Rabini, hanya pria yang boleh dan semua yang disebut Rabi. Mereka bisa dibilang jauh dari kehidupan duniawi. Pendekatan agama Yudaism...

 

У этого термина существуют и другие значения, см. Come Together (значения). Come Together Сингл The Beatlesс альбома Abbey Road Сторона «А» «Something» Сторона «Б» «Come Together» Дата выпуска 6 октября 1969 года 31 октября 1969 года Формат 7” Дата записи 21 июля — 30 июля 1969 Место записи студия «Эбби-Роуд» Жанр бл...

 

Bài này viết về sân nhà hiện tại của S.L. Benfica. Đối với sân vận động trước đây, xem Sân vận động Ánh sáng (Lisbon, 1954). Đối với sân nhà của Sunderland A.F.C., xem Sân vận động Ánh sáng (Sunderland). Sân vận động Ánh sángA CatedralO Inferno da LuzUEFA Tên đầy đủSân vận động Thể thao Lisboa và Benfica (Estádio do Sport Lisboa e Benfica)Vị tríLisbon, Bồ Đào NhaTọa độ38°45′10″B 9°11′05″T...

R.31 Тип ближний разведчик и самолёт связи Разработчик Renard Производитель Renard, ЭверSABCA, Брюссель Главный конструктор Альфред Ренар Первый полёт 16 октября 1932 года Начало эксплуатации конец 1934 года Конец эксплуатации май 1940 года Статус снят с эксплуатации Эксплуатанты ВВ�...

 

Business terms Push and pull redirects here. For other uses, see Push and pull (disambiguation). The original meaning of push and pull, as used in operations management, logistics and supply chain management. In the pull system production orders begin upon inventory reaching a certain level, while on the push system production begins based on demand (forecasted or actual demand). The CONWIP is a hybrid between a pure push and pure pull system. The image shows a technology push, mainly driven ...

 

American tennis player Harry LikasFull nameHenry Edward Likas Jr.Country (sports) United StatesBorn(1924-02-27)February 27, 1924San Francisco, CaliforniaDiedMarch 2, 2017(2017-03-02) (aged 93)[1]CollegeUniversity of San FranciscoSinglesGrand Slam singles resultsWimbledon3R (1952)US OpenQF (1948)DoublesGrand Slam doubles resultsWimbledon1R (1952) Henry Harry Edward Likas Jr. of San Francisco, and later Belvedere-Tiburon, California, was an Intercollegiate Tennis Ass...

1942 American animated Disney drama film directed by David Hand This article is about the 1942 Disney animated film. For the original novel, see Bambi, a Life in the Woods. For other uses, see Bambi (disambiguation). BambiTheatrical release posterDirected bySupervising directorDavid HandSequence directorsJames AlgarSamuel ArmstrongGraham HeidBill RobertsPaul SatterfieldNorman WrightStory byStory directionPerce PearceStory adaptationLarry MoreyStory developmentVernon StallingsMelvin ShawCarl F...

 

Bagian dari seriGereja Katolik menurut negara Afrika Afrika Selatan Afrika Tengah Aljazair Angola Benin Botswana Burkina Faso Burundi Chad Eritrea Eswatini Etiopia Gabon Gambia Ghana Guinea Guinea-Bissau Guinea Khatulistiwa Jibuti Kamerun Kenya Komoro Lesotho Liberia Libya Madagaskar Malawi Mali Maroko Mauritania Mauritius Mesir Mozambik Namibia Niger Nigeria Pantai Gading Republik Demokratik Kongo Republik Kongo Rwanda Sao Tome dan Principe Senegal Seychelles Sierra Leone Somalia Somaliland ...

 

Strategi Solo vs Squad di Free Fire: Cara Menang Mudah!