
kaalam (janyuvu)

period (purr) anedi "drosophila melanogaster" yokka x chromosomelo unna janyuvu. prati" transcript mariyu daani sambandhita protein rendinti sthaayilalo dolanalu sumaru 24 gantala vyavadhini kaligi untaayi mariyu grahanam mariyu locomotor karyakalapalalo syrcadian layalanu nadipinche "drosophila" jeeva gadiyaram yokka paramaanu yantraamgamlo kalisi pradhana paatra poeshistaayi. prati janyuvulo utparivartanalu syrcadian laya kaalanni tagginchavachhu ("pers"), podiginchavacchu ("perl"), mariyu raddu cheyavachu ("perr0").
aavishkarana.
period janyuvu mariyu moodu utparivartanaalu ("pers", "perl" mariyu "perr0") 1971loe ronald konopka mariyu seamer benzer dwara oka ms utparivartana terapai vaeru cheyabaddaayi. "pers", "perl" mariyu "perr0" utparivartanalu okadaanikokati puurti cheyaledani kanugonabadindi, kabatti moodu samalakshanhaalu oke janyuvulooni utparivartanala valla anie nirdhaarinchabadindi. grahanam mariyu locomotor karyakalapalalo syrcadian layala vyavadhini marchina utparivartanaseelula aavishkarana ("pers" mariyu "perl") gadiyaramlone prati janyuvu yokka paatranu suuchistumdi, avtput marganni kaadu. eee kaalapu janyuvunu modatisaarigaa 1984loe maikhel rosebash mariyu sahacharulu kramabaddheekarinchaaru. 1998loe, "purr" rendu pratilekhalanu utpatti chestundani kanugonabadindi (anuvaadam cheyani oke intron yokka pratyaamnaaya spliesing dwara matrame bhinnamgaa untundi), ivi rendoo prati proteinnu encode chestaayi.
function.
syrcadian gadiyaram.
drosophilalo", prati "mrna sthaayilu sumaru 24 gantala vyavadhilo oogisalaadataayi, prarambha aatmaasraya raatri samayamlo garishta sthaayiki cherukuntaayi. prati "prati" utpatti kooda daadaapu 24 gantala vyavadhitho oogisalaadutundi, madhya aatmaasraya raatri samayamlo "prati" mrna sthaayila tarvaata aaru gantala tarvaata garishta sthaayiki cherukuntundi. prati sthaayilu periginappudu, "prati" pratilekhana nirodham perugutundi, protein sthaayilanu taggistundi. ayithe, prati protein neerugaa dnatho bandhinchalemu kabatti, idhi daani swantha transcription neerugaa prabhaavitam cheyadu; pratyamnaayamgaa, idhi daani swantha activatorlanu nirodhistundi. prati mrna nundi utpatti cheyabadina tarvaata, idhi kaalaatiita (samayam) thoo dimerise avutundi mariyu complexes kendrakamloki velli "prati" mariyu "samayam", gadiyaram/saikil heterodymer yokka transcription kaarakaalanu nirodhistundi. eee gadiyaram/chakra samudaayam vaari promoterla yokka nirdishta enhancerlaku (ii-baakslu anie pilustaaru) kattubadi "purr" mariyu "time" kosam transcriptional activatorga panichestundi. anduvalla, cluck/saik nirodham "purr" mariyu "time" mrna sthaayilanu taggistundi, idhi prati mariyu time sthaayilanu taggistundi. ippudu, cryptochrome (krai) anedi kaanti samakshamlo samayanni nirodhinche telikapati sunnitamaina protein. time anedi maroka protein, double time ledhaa dbt, phosphorylatesto sanklishtamgaa lenappudu, daanini ksheenata kosam lakshyamgaa chesukuntundi.
ksheeradaalalo, oka saaruupya transcription-translation negative feedback loop gamaninchabadutundi. drosophila-purr yokka moodu ksheeradaala homologla nundi anuvadinchabadina, proteinlaku moodu (purr1, purr2, mariyu purr3) loe okati daani paas domine dwara rendu cryptochrome proteinlalo (krai1 mariyu krai2) okadaanitoe dimerise chesi gadiyaaramlo pratikuula muulakaanni yerparustundi. eee purr/krai complexes ck1-epsilon ("casine kines 1 epsilon") dwara phosphorylation tarvaata kendrakamloki kadulutundi mariyu praathamika helix-loop-helix (bhlh) dna-binding domainla dwara moodu purr mariyu rendu krai promoterla yokka ii-baxulaku kattubadi unde transcription karakam ayina cluck/bimal1 heterodymernu nirodhistundi.
ksheerada kaalam 1 mariyu kaalam 2 janyuvulu syrcadian gadiyaram yokka kaanti penulu kosam photoentrainmentlo keelaka paatralu poeshistaayi. idhi modatisaarigaa 1999loe akiama mariyu itarulu chusinappudu kanipinchindi. kaanti ledhaa glutamate vidudala dwara prerepinchabadina dasha maarpulaku mpr1 avasaramani choopinchindi. rendu samvatsaraala taruvaata, albrecht mariyu itarulu. ardharaatri kaanti pulls (jedti 22) kuu pratispandanagaa mpr1 utparivartanaalu gadiyaranni munduku teesukellalevani mariyu mpr2 utparivartanalu arley nait light pulls (jedti 14) kuu pratispandanagaa gadiyaranni alasyam cheyalevani vaaru kanugonappudu eee phalitaaniki maddatu ichhe janyu aadhaaraalanu kanugonnaru. anduvalla, syrcadian gadiyaranni rojuvaaree saadhaarana paryaavarana kaanti sankethaalaku reset cheyadaaniki mpr1 mariyu mpr2 avasaram.
"purr" mutation mariyu nakout prayogaala dwara samyoga karyakalapalu mariyu aakseekarana ottidi pratispandanato sahaa jeeva gadiyaram yokka aneka avtput prakriyala niyantranalo kooda "purr" chikkukundi.
"drosophila melanogaster" anedi akshaamsha cline venta sambhavinche thurr-gly punaraavruttulaloo sahajamgaa sambhavinche vaividhyaanni kaligi untundi. 17 thurr-gly punaraavruttulu kaligina eegalu dakshina airopalo saadhaaranamgaa kanipistaayi mariyu 20 thurr-gly punaraavruttulu uttara airopalo saadhaaranamgaa kanipistaayi.
syrcadian kaanidi.
daani syrcadian vidhulatho paatu, "purr" kooda vividha rakaala syrcadian kaani prakriyalalo chikkukundi.
ksheerada kaalam 2 janyuvu elukalalo kaniti perugudalalo keelaka paatra poeshistumdi; mpr 2 nakout unna elukalu kaniti abhivruddhilo gananeeyamaina perugudalanu mariyu apoptosislo gananeeyamaina taggudalanu chuuputaayi. idhi saadhaarana kaniti anachiveta mariyu "saiklin dii1", "saiklin eah", "mdm-2" mariyu "gaad45α" vanti kana chakra niyantrana janyuvula mpr2 syrcadian niyantrana tolagimpu, alaage ii-baaks-madhyavartitva praticharyala dwara syrcadian regulatorlache neerugaa niyantrinchabade transcription karakam "sii-mike" valla sambhavistundani bhaavistunnaaru. adanamgaa, mpr2 nakout elukalu gaama radiation mariyu kaniti abhivruddhiki perigina sunnitatvaanni chuuputaayi, dna nashtam-pratispandinche maargaala niyantrana dwara cancer abhivruddhilo mpr2 nuu marinta prabhaavitam chestaayi. anduvalla, kanaala perugudala niyantranalo panichese gadiyara niyantrita janyuvula syrcadian niyantrana mariyu dna nashtam pratispandana cancer "inn vivo" abhivruddhini prabhaavitam cheyavachu.
"" "drosophila melanogaster" "loe deerghakaalika ghnaapakasakti (ell. tii. emm) erpadataaniki purr" "avasaram mariyu saripotundani choopabadindi". "prati" "utparivartanalu ltm nirmaanamloo lopaalanu chuuputaayi, veetini" "prati" "transgene choppinchadam dwara rakshinchavachhu mariyu" "prati" "janyuvu yokka athi vyakteekaranhatho meruguparachavacchu". itara gadiyara janyuvula ("kaalaatiita", "gadiyaram" mariyu "chakram") utparivartanallo eee pratispandana undadu. ell. tii. emm. tirigi pondadaaniki "prati"-vyaktaparichae kanaala dwara synaptic prasaram avasaramani parisoedhanalu suuchistunnaayi.
"purr" kooda fruit fly yokka jeevitakaalaanni podigistundani choopabadindi, idhi vruddhaapyamlo paatranu suuchistumdi. ayithe, eee prayogaalu maroka parisoedhanaa brundam vijayavantamgaa punaraavrutam kaananduna, eee phalitam ippatikee vivadaspadamga undhi.
elukalalo purr2 mariyu ishtapade madyam teesukovadam madhya sambandham undani choopabadindi. madyam viniyogam kooda swechchagaa nadiche vyavadhini tagginchadamtho mudipadi undhi. prati 1 mariyu prati 2 janyuvulapai madyapaanam yokka prabhavam madyamtho sambandham unna niraasatoe paatu madyapaanamloki tirigi vellae vyakti yokka vaikharitho kooda mudipadi undhi.
purr" yokka ksheeradaala homolaglu.
ksheeradaalalo, prati kutumbaaniki telisina moodu janyuvulu unnaih prati 1, prati 2, mariyu prati 3. ksheerada paramaanu gadiyaram "drosophilalo" kanipinche proteinlaku samanamga untundi. gadiyaram yokka homolog maanava gadiyaaramlo adhe paatra poeshistumdi, mariyu saik bmal1 dwara bharti cheyabadutundi. krailo rendu maanava homolaglu unnaayi, krai1 mariyu krai2, veetini edmond a kanugonnaru. griffin, juuniyar., david stockniss mariyu charless zhe. gadiyaram mariyu bii. emm. ell. 1 thoo kaanti-swatantra paraspara charyalanu kaligi undataaniki wheatz. zeane-christophe leloop mariyu albert goldbeater eee proteins mariyu janyuvula madhya paraspara charyala dwara srushtinchabadina feedback loopnu anukarinchadaaniki namuunaa kosam ganana namuunaanu abhivruddhi chesaaru, indulo "prati" janyuvu mariyu prati protein unnaayi.
maanava homolaglu prati drosophilatho kramam mariyu amaino aamlam saaruupyatanu chuuputaayi mariyu prati drosophilaku unde paas domine mariyu nuclear localization kramaanni kooda kaligi untaayi. maanava proteins suprachiasamatic nucleuselo alaage scn velupala unna praantaalalo layabaddhamgaa vyakteekarinchabadataayi. adanamgaa, cytoplasm mariyu nucleus madhya kadalikalaku drosophila ayithe, ksheeradaalu marinta compartmentalise cheyabadataayih mpr1 pradhanamgaa nucleusku mariyu mpr2 cytoplasmku sthaanikeekaristundi.
clinical praamukhyata.
ksheeradaala prati 2 janyuvulo utparivartanaalato anubandhinchabadina kutumba adhunaatana nidra-dasha syndrome. eee rugmatato badhapaduthunna vyaktulu takkuva vyavadhi mariyu adhunaatana dasha kaligi untaaru, ikkada vaaru saayantram praarambhamlo (saayantram 7 gantala samayamlo) nidrapotaru mariyu suuryoedayaaniki mundu (udayam 4 gantala samayamlo) melkontaru. 2006loe, germanyloni oka prayogasaala, phospsto badhapaduthunna vyaktulalo utparivartana chendina purr2 yokka nirdishta phosphorylated avasheshaalanu gurtinchindi. prakaasavantamaina kaanti chakralanu upayoginchi vyakti yokka gadiyaram yokka dasanu marche prayatnamgaa kalakrama chikitsanu konnisaarlu chikitsagaa upayogistaaru.

