Ó¹½ŰŦŢȵȻǭɈʯɄɺʔ ,&"
7V,# °©¿Õhm *EC<=6=G=B ƞĨ
ƍê˕ʶ ˒Ǜ ʭ˒ʌɚ ÜȀ̌ƒ ʦʟƪ ȮǶ˯̑
_ m
ÛʠɉÖÕ§ÚŐɄƵ· Ö¨½Ƙk˙osɺʔ]ʯâ ŰŦŢȵɼʉǐŞs
̲½ɺʔd^o ɺʔ]ɺʔʳ̙ #; 7 ִɶÚ#AAHBC;@C6H@=BɾǠıȮĿżý
Ő #; ǁýɾŅsĿżýDŽ{~e^#; 7 ִɶÚǑɡ̟ŴŞq]â #; ̦ʾŒƭ Ŀżýd 7V,# ]#; ïq~ǁĸÖÕ«ØɾŅso]ɺʔȘƭı°©¿Õɇąs^
o °©¿Õɇą] 7V,# ÷Ņ̕ʘsĞųʍ˙ȨsĞų̄ɏéĀȺjƨ̛d^o ɏ éĀȺɱŽÕÚ½jd]ɺʔʛiɺʔĘ ļƩʵʊ°©¿Õj̖ƋƗŧƑp~ø˯p^
o ɾǰ]˙Įqxɺʔ̜ɰ ǎĝȧɅƭ® ½¥ Ø ȹȸefè| ɺʔƩɪjˋ˙p^o
fŰŦŢȵÙ̲½ɺʔ °©¿Õø˯ˈɺˀǯq]Ģƣso]ȸý˭ħļƩdÖÕ
§ÚɅȱ ¬Ø½×ÚÕƨ̛d^
Ƽ_]ÖÕ§Úˋ˙s 7V,# ˙Ȩs]ĠǦ°©¿ÕƜƻ ˈɺÏ¥À³Îˀǜsx
]ŰŦŢȵɺʔǴȺexÛ˩ ˀǯʰ{x^ˢƓ]o Ğ˼ ɗɤ̂˜ ˪Ȇ˫n~e^q xj{~]Ƽ_]Ȱɗɤ ǾɉĠǦ°©¿ÕƜƻ Ťdɺʔʛˢčɿ{x^ɺʔʛ ,5:G Ő°©¿ÕĞų̓Ņ Ťjd^Ƽ_],5:G ̓Ņˀ̕s¶ØÃ¨˗̓âɉˀǯsƿȓ
d̉Ÿ°©¿ÕÉ×»¤ÚÎˀǯʰ{x^o ɾǰ]ŰŦŢȵ °©¿Õø˯˙Ȩ ,5:G ȼĞ
DEC<=6=G=BôÞ *" Ⱦ˄ʻeyqx^*" ]Ǚɖ ¶ØÃ¨˗dj]ŰŦŢȵ 7V,# °
©¿ÕhmƞĨǜip~ee^ǩɗɤ]Ƽ_ *" j°©¿ÕĢƣ̅às
i]x̅àss fÏ¥À³Îïs iˀǜqfˇx^
ǩẒ́Ó¹½ŰŦŢȵƭɈʯɄɺʔǴE5G65FCD<=@=7@9H?9A=579@@@=B9,&"Ⱥex^*"
ȁʕˀǯq~]Ƽ_]t]o ɺʔǴi *"¶ØÃ¨˗Ȃůpu]Ȃůùfɺʔȁʕ Ūı
ʾɺʔȌˠˀǯso]*" ǩǭ ȁʕʏſqfɗɤƽȾ{x^o fȰŸ Ǿɉ
¶ØÃ¨˗Ȃůpuƿȓ Û|jÁ¹¨·¡Ø%ȓd^Ƽ_],&" ɺʔ *" % q]ȅ Ɛɺʔ̨1.J=@8GLD9̩Ȍˠqx^,&" ɺʔ]˦Ɛ`ǁĸ#;a ģȤ]ĶǞŠ ļƩq
~]ÖÕ§ÚˋƂȯ˗İŊqx̜ɰǎĝs^o]sɺʔĘʪgx̜ɰǎĝs
]ʘ̜ɰļƩŐ^x],&" ɺʔ]`ǁĸ#;a ģȤ°©¿Õø˯ ɾǰ]ʘ̜
ɰġɽ˝]ȰŸ® ½¥ ضØÃ¨˗ ɇȴjˋƂp^ÖÕ§ÚƭȧɅƘk˙os® ½
¥ Ø Û|d .( S.HACEB97ECF=F:57GCESȹȸjv óʳd^Ƽ_]*"% {~ʘ
̜ɰ .( Sj fŪısiˎx^Ẓ́ ɾǰ]ʞŏȜeo]*"% ɺʔ 1. Ȍ
~ʘ̜ɰļƩ ë˪sÛǗ]ģȤˋƂp .( Sȹȸ˽üÞqx^
*" ]ŰŦŢȵ ʘ̜ɰ® ½¥ Øȹȸ˥ Ɲ̚àgojǜi{xx]v
Ƙk˙osɺʔʰ©¿Õø˯ȁǼ ˀǜˇx^o ˀǯ]ÔØ˹ı°©¿ÕˀǯƽʱȺex^
sz]ǁĸģȤơ ɺʔĘˋƂpɡ_ °©¿Õ¶ØÃ¨˗ ¸×°ØÔØ˹ıÃ¶ÚØ Ūı
|e~ ˀǯd^t] 7V,Z ģȤùf]1. *"% ɺʔĘ ʄ¶ØÃ¨˗ ¸×°ØÔØ˹ı Ã¶ÚØȌˠˀǯqx^o ɾǰ]1. ǁĸģȤùe¸×°ØÔØ˹ıjˋƂpĞų˽ɴ ?5 Ğų ÔØ˹ı亢進j % ]Ėlǹĝpi{x^o f¸×°ØÔØ˹ıÃ¶ÚØ˰ejʻ
xo] 7V,Z ɎÞŴŞq]°©¿Õ ̃ű˻ʺp~e -E7:5A=@LGLECF=B9?=B5F9 - % Û|d &LB Șƭ 1. % Ȍˠqx^ 7V,Z °©¿Õ &LB j] 7V,Z °©¿Õø˯
ÝșŢ˗ ¸×°ØȉŢÔØ˹ısoj˻ʺdo]sǜi{~e^o
j]1. % &LB ÔØ˹ıÃ¶ÚØ]ƌɀˊi{x^qxj{~]*" &LB ô̈ °©
¿ÕĀȺȨDŽz]v Ǿɉ Û|j]Ē ɴ ?5 ¶ØÃ¨˗dʏgx^ȃ] 7V,Z
°©¿Õ Þșûʊs '*?=B5F9 ÔØ˹ı 1. % Ȍˠqx^'*?=B5F9ŐǑɡ Ô Ø˹ı˸ɸ]˞ĚŘų Ģƣ]ɺʔ ĞıÙȘƭıÙŧȊĢƣq~eojɖ~e^,%]
D]$(% Üɡ '*?=B5F9]1. he~ǁĸģȤÔØ˹ıjˋƂpx^ÛǗ]% et
ÔØ˹ıˋƂpi{x^
ôÝ ɾǰĵɶʄŅs]*"]°©¿Õ²½ÔÚÎ &LB ô̈]ȴǞȨȅýßǜ ?5 ¶ØÃ¨˗Ǿɉq~e~]v Þș '*?=B5F9 Șƭıjdʏg^o õˍŢ}m]
*"% .( Sȹȸj̇Żpxojˍǜĝǭ^qiq]łʕƭɡ_dƫ]Ȱʘ̜ɰjë
˪qxʓǟdĞųÏ¥À³Î|e~]îơÛƇ ˀǯjƨʺd^
îŗ]ǩɗɤ *" ]ŰŦŢȵjÖÕ§ÚƘk˙os̏˻ʺĎksĞųdojǜ
i{x^*" 7V,Z °©¿Õø˯ȁǼĢƣ ˈɺÏ¥À³ÎˀǜǧyßijĞdj]î ơ ˈɺɗɤ]*" ǾɉqxǖxǁÖÕ§Úʫ ĩʫ˔ȲsojǦƠp^
l \
ȴŞ]ƼjŜhe~]ÖÕ§ÚɃưǥsưʐ]Ŝȍ hv ˁ~h]
ɑ˭ĝǭeɛ÷ŕ̝{~e^Ĕɂŵɉɡ_ ÖÕ§ÚjŴŞsj]â # ŠÖÕ
§Ú]#; ǁý{~Ƙk˙opĶǞŠÖÕ§Úd]ʣɯɅ]ŖƮ]½ÆÚƭɋʚȧe {x¨¤Ô»Ú¤ÈÓ Ç+)&bíȸhmȸȘ ˗cŭkƝ̚Ļs i]¿ÇÓ
¦°Ú°Ò¹¨ fȸőʗis˻ɮɅĂʝŬǽʜƕďŌq~e^ǣɻʳȴŠ]Ŭ ǽdj]o ǩ˗ɉɺʔÖÊÕ ÖÕ§ÚɇɅ˙Ȩ]ņÛĞųÏ¥À³ÎȻǭs^v Ï¥À³Î]ôÞ ˦d^# ŠÖÕ§Ú ĸŘɺʔd̲½ɺʔ]ŰŦŢȵ ʳ̙]
̦ʾŒƭ #; Ŀżýd 7V,# jɇȴq~e^o 7V,# #; jɾŅq]pǁĸÖÕ«
Øj #; 7V,# ʹŅýĞųÖÊÕDZȀso{~ɺʔʰ©¿ÕjƲ˙p]IJ¶ÍØ
ȧɅˋŘƭȯ˗Ŋ̜ɰ ǎĝʘ̜ɰ]ȧɅƭ® ½¥ Ø ȹȸj˙o]ÖÕ§ÚɅ ȱjƘk˙op ^o 7V,# °©¿Õ ɇąş j]ɺʔʛ ,5:G d ^ 7V,# ¶ ØÂ¨˗]ǁĸʴǡĤ]ɺʔʛÝǐŞs^vq~]#; jɾŅqxȱƵ 7V,# ¶ØÃ¨˗j ,5:G
̓ɢsvo̓Ņqx LB&LBi -L? efșȘƭıj˙o]ôÞ]Ś əsf
ș]ʘ̜ɰ89;E5BH@5G=CBȧɅ¶ØÃ¨˗ɇȴ x ˞ĚGE5BF7E=DG=CBjˋƂp^Ś
#ŠÖÕ§Ú ɗɤ]̂Ɠ]̲½ɺʔȫȨjƛ~~kxj]ˢƓ]̲½ɺʔņrl 7V,#
DŽ|ɺʔq~]ŰŦŢȵjȕɍp~e^ôĤ]ŰŦŢȵ]ɺʔǑɉ]ǨǷɈʯȵ fzɠ Ɩqieɺʔd]̲½ɺʔ̟ú ȁʕDŽ| ]d˻ʺƭ eʯțƤȷŠ Ì²½ɺ ʔʏg~ex^qiq]ˢƓ]ŰŦŢȵÖÕ§ÚļƩ˻ʺ® ½¥ Ød#& ã ʺȹȸɺʔo ]#;ăŴƭ ƷƭÖÕ§ÚȧɅƘk˙osojţōp~h]
ÖÕ§ÚȧɅhmŰŦŢȵ ƞĨ|e~]ǣˢ̘Ɛȕɍp~e^îŗẒ́Ⱥexɺʔ
Ó¹½ŰŦŢȵɈʯɄɺʔ̨,&"̩d ^o ɺʔ]ĹŽˁgŰŦŢȵdj] 7V,#
°©¿Õɗɤhe~]̲½ɺʔ мÕq~Ẓ́ƔlȺe~kx ^ǣˢ]ŰŦŢȵ
̲½ɺʔ #; 7Ŀżý °©¿Õø˯ ǻʺ|e~]ņɨd]ˋƂpx˞ĚŘų Ș ƭıô̈ƌjȸr]ĔɂɳĖý ƞĨĞǂjd eiʏg~e^qxj{~]̲½ɺ ʔ°©¿Õø˯ ˀǯºÚÕq~Ⱥe~kx,&"]ĠǦ°©¿Õ|e~̲½ɺʔņǽ]
Q
Q ( <;?B5H rhp
ǁĸģȤ 7V,#j,5:GÔ¨ÕÚ½p]&LB{~ÔØ˹ıĿm^ÔØ˹ıqx 7V,#-L?jÔ¨
ÕÚ½p]&.ÔØ˹ıs^ÔØ˹ı&.÷Ņqx*&Uj-L?Șƭıq]ƃʔýi 5șĕ]*%
ȘƭıƘk˙oq]ʘ̜ɰˋɇs^ÛǗ]ÔØ˹ı&.÷ŅsĞų],5:ïq~D]$(%]E?Ŋ
'*%Șƭıq]°©¿ÕÞș ˞ĚŘųȘƭıq]® ½¥ ØȹȸƘk˙os^x] 7V,# ÔØ˹ı
{~ LBjȘƭısɽ˝]*#%?Gɽ˝ ȘƭıƘk˙os^
˳øųɇȴ|e~]î ɀʻǗjƨʺdʏg^ǩɗɤ]#; 7Ŀżý ĠǦ
°©¿Õˀǯqx^
Ƽ_],&" 7V,#ģȤ]ɺʔʛÝ ,5:G ƅŞjŪıs¶ØÃ¨˗°©¿ÕÉ×»¤
ÚÎˀǯ ƿȓƩȺq~LJɹqxɾǰ],5:G ƅŞjģȤ˩Įq~ŧīsÛ˩ ¶ØÃ¨˗ ĉʷ
ʻeyqx^v â |j*"d{x^
*"]ƓjɺʔǴ"9&5ɺʔȅƐʅʃʤɺʔ ŧȊǀĢs¶ØÃ¨˗q~ţōpx16)^ o ţō˙Ȩq]*"|e~Ŭl ɗɤɞţōp~e^o ţōǘe~]*"]ɡ˛g
~̦ƖĄŴp~e¶ØÃ¨˗dojǜi{~e^ĞųĘ*EC<=6=G=B8CA5=BŐ
ȰƦɉǼ˨ǥq~e^đǭ]*"]v ŇjəsfɺʔŧȊÉ×ÄŹ½]ŧȊ̇Żǂf Řųq~őŇpx^
*"]ƛĠ]ͽ¬Ø¾ÔƅŞjţōpxx]ͽ¬Ø¾ÔÌÚ¥Úq~]ÛǞ]ǥŇd{
x^Ź̏]*"jͽ¬Ø¾ÔƅŞq~eefţōŬe17, 18)^x]ͽ¬Ø¾ÔŬlŴŞq]
˽ڰ²̅àssţōd^qiq]*" ɺʔĘƅŞ|e~]Ź̏]ɗɤĠǦȋ
̎ʀÛɉʻˀƢ~ei{x^åjɺʔ]FGEC;9BE979DGCE5,5ǵĘɾŅq]
v °©¿ÕǀĢɉĢƣsefţō]ǵĘ ˞ĚǀĢŘųq~Ďlefţōd^p
]ɺʔĘ̜ɰâŴŞq~eefţōd21)^o f]*"j]ɺʔĘƅŞssţō
ġɺʔʛÝƅŞsţōŬǑd^Ýɋɺʔ]Ýɋƻ̂ŘųĿżý! ,°©¿Õhe
~7,5:ɏéĀȺq],% ȘƭıĢƣso]ɺʔŧȊ ǀĢˋƂsţōp~e ^ oīg]*"jĽ.ɺʔɈʯȵɺʔǴ$HE?5Gɺʔhe~ɺʔʛÝ ,5:GŴŞq~h].ɺʔǁĸ Ŀżý., °©¿Õø˯̅{~eefţō24)]Ì¡²̤̥Ȼǭĵǵɺʔ''he~ǁĸģ Ȥɺʔʛɟʰq],5:Gɟʰsefţōd24)^o f]ȇŃɉ]*"ɗɤ ĠǦȋ̎
]*" ƅŞsŤ|e~ȝäjʂe~ex^ǣˢ{~]ŬǑ ɗɤʐ ʻˀ]ɾƅet
ȅqeţōd]ɺʔ{~]xv ɺʔ Șƭıȋ̎{~*" ƾŞɀfyp~
e^vq~]o f]ɺʔĘ *"ƅŞŬǽƭ|e~]*"Ğų Ć̡j˻ʺdojţō p~e^*"¾Ï ØĘ °²» ØȉŢ ÃÕͽ Õıjɺʔʛhm,5:G ˡˤƨʺd
o]ȿɍ ÍÁ˹d°²» Øjɺʔʛ ɟʰ̅{~eojǜi{~e
25)^Ƽ_,&"ɺʔhe~]*"j 7V,#°©¿ÕŐƩq~,5:G ƅŞıso]°©¿ÕĢ ƣ˻ʺƳŏDŽ|ʏg~e^etu],&"ɺʔȺe~] 7V,#ˢč °©¿Õ ̅à
ˎxţōe^Ƽ_ôĤ ɗɤ],&"he~]*"ɺʔʛ,5:Ghe~ ǹĝp
osǜiq~e^
ǩɗɤ] 7V,# °©¿Õhm *" ȁʕˀǜɍDžq]v ƿȋq~]ÔËÇ¢¨°ÒØȓ
ȺexÁ¹¨·¡Øȓײ¤ÈÇØ¨°ÒØˀǯhĔɂȑ̈ȓ÷ҶØÃ¨˗ ǹ ɹˀǯho{x^
]Z2[`
ɺʔšşhˇʫ
ɺʔ]Ó¹½ŰŦŢȵƭɈʯɄɺʔǴ ,&"Ǯì˶ɜɽɞŵʄŅɗɤƾɕćʥ̍ĺçɗɤœ
ƯàȺex^,&" š̢šşq~],*'#15?C*HE9<9A=75@#B8HFGE=9F &G8 )-%
$*( ôÞ 15?C Ⱦ˄ 9G5@CI=B9-9EHA(#"#,##)-#(#B7 .)%3) $*(]' '9E75DGC9G<5BC@15?C]A;A&!9BG5A=7=BFC@HG=CB̨-=;A5@8E=7<#B7 -G&CJ=F ') /- ôÞ -=;A5 Ⱦ˄̩ BG=6=CG=7BG=AL7CG=7-C@HG=CB HB=GFD9B=7=@@=B A;FGE9DGCAL7=B 5B8W;5AD<CG9E=7=BD9EA& ˷Ņ -=;A5īgx Ⱥex^ɺʔ Y]) ǬöÞ
š̢qx^š̢ ,&" ɺʔ ĥ̕].ELDF=B.!#) #BI=GEC;9B5E@F658 /-
Ⱥe] Ğ̄]Y ) ئÑÊÚ¶ÚĘīȡsoʰ{x^*- ˎʸ]s~ 15?C ȰɷˇʫȺex^
#; ĿżýƴĀ]BG=8=B=GECD<9BL@(*ACHF9ACBC7@CB5@#;-*-=;A5Ⱥex^-*
ƴĀqx ,&" ɺʔ ģȤ](*"--=;A5Ⱥex^
¡£²¶ØÈ×¹½ȓȰŸ¶ØÃ¨˗ ǹĝ]ôÞ ǁýȺex^x]ǁý āȺȦƖ
]Ȟñ¥¶×© Džəqxj{~Ǝ˺qx^BG=*EC<=6=G=B5BG=6C8L5675A]BG=*<CFD<CGLECF=B9 7@CB9!P =CG=BCB>H;5G9'9E?'=@@=DCE9 ' /-]&LBE566=GDC@L7@CB5@#;!-5BG5 EHM =CG97<BC@C;L /- ] !C5G BG=,566=G#;!",* #BI=GEC;9B CEDCE5G=CB (3 /- ô Þ
#BI=GEC;9B Ⱦ˄]"=;<-9BF=G=I=GL-GE9DG5I=8=B",*.<9EAC =F<9E-7=9BG=:=7%% ' /-]
D<CFD<C&LB.LEBG=6C8L@CG75G-9@@-=;B5@=B;.97<BC@C;L #BG' /-]
BG=D<CFD<CGLECF=B9ACHF9ACBC7@CB5@#;!6? 7@CB9! @CG75G/DFG5G9
=CG97<BC@C;L #B7 #& /-]D'*%=B5F9BG=6C8L@CG75G9@@-=;B5@=B;
.97<BC@C;L #BG' /- ôÞ 9@@-=;B5@=B; Ⱦ˄]D<CFD<CD'*%=B5F9.<E.LE BG=6C8L@CG 75G-9@@-=;B5@=B;]D'*%=B5F9BG=6C8L@CG75G 9@@-=;B5@=B;]D<CFD<CD'*%=B5F9.<E.LEBG=6C8L@CG75G- 9@@-=;B5@=B;]-*%$(%BG=6C8L@CG75G9@@-=;B5@=B;]D<CFD<C-*%$(%
.<E.LEBG=6C8L@CG75G9@@-=;B5@=B;] #.CB>H;5G98BG=ACHF9 7V,#
@CB9',@CG75G9=CF7=9B79 -5B=9;C /-] !C5G BG=,566=G#;!"&<=;<@L7ECFF56FCE698@CG75GW&=CG=HA #B7
"5LJ5E8 /-
9@@@LF5G9 ˎʸ
,&" #;(* ģȤơ]*-0 ȗȚq].( īg~ Ğ̄ȎÝłȣıq]9@@@LF5G9
qx^9@@@LF5G9 &59AA@=F5AD@96H::9E=C,58&56CE5GCE=9F #B7 /- ôÞ =C,58 Ⱦ
˄ ̬ ȝŅq~ Y Ğ̄īȭq]¶ØÃ¨˗Ūƭpux^
---*! Ļ 19FG9EB6@CG
--*! ÍÀÉ×»Ø\=C,58Ⱥe~ʰe]ËÔ¨ÔÕ;«ÕāȺqx^
ȖĮơ]«Õ 6@CGG=B;6H::9EA'.E=F]A'©Ô°Ø]϶ÁÚÕII]D"
Ğ̄ƒʲıq]ÍÀÉ×»Ø\¡¢²¶ØÈ×¹½Ð±ÑÚÕ°²»Î=C,58Ⱥe~]¶Ø è˗ B=GEC79@@H@CF9A9A6E5B9=C,58 0] Ğ̄ Ǭö GE5BF:9E qx^.E5BF:9E ơ ÏØÈÖØ]--=;A5X.- Y]CI9EB=;<G6@C7?=B; qx^@C7?=B; ơ]ÏØÈÖØ
..- ŗ].- ŗȗȚq]Ûȃǁý CI9EB=;<G ļƩpux^ļƩơ]ÏØÈÖØ ..- ŗ]
.- ŗȗȚq]èȃǁý Y Ǟ̄ļƩpu]ÏØÈÖØ ..- ŗ].- ŗȗȚq]&
ɇʢ¦¹½!"95@G<75E9 &=GG@9<5@:CBG /%Ĝȶqxơ] /$#'#&2,3 #&',2/ /$# #&' CEDCE5G=CB .)%3) $*(Ý̗ēpux^
CH6@9FGE5B8,(8F,( Ƃĕ
ɺʔš̢Ⱥ 7A8=F< â]A& )DG=''P#,98H798-9EHA'98=HA#BI=GEC;9Bâ *"8F,(
DAC@]&=DC:97G5A=B9.',(='2,95;9BG#BI=GEC;9BW& īg~ɣiȝŅq]źȡ РئÑÊÚ½qx^,&" ],*'# -]'A9E75DGC9G<5BC@ īgx A98=HĄôÞ ,(= Ⱥ A98=HA s̩ R79@@A&A98=HA fˎʸq 8F,( ĕ{x 8=F< īg~
ɣiȝŅqxơ]Y]) ǬöÞ Ǟ̄ ئÑÊÚ½qx^8F,( Ƃĕqxɺʔ
Ǟ̄ôĘô̈ Ẓ́Ⱥex^x 8F,( Ƃĕqxɺʔ Ġŗ ʁó ,(= Ⱥ A98=HA Ⱥe]v ơǁȸȯ˗Ŋyš̢šşȺe~š̢qx^
7V,# ģȤ
®ØÉÕñk R ɺʔƁq~]ǣɻȦƖ B;A& -* īg]Y]) CI9EB=;<G ƴĀqx^-* ]Ì¡²ǁ (*ǁýd]ǁý ¨Ó² #; d^Ì¡²hÓ
¹½ 7V,# ʡlɾŅsoi] 7V,# °©¿Õ ˀǯƔlȺe~eÐÁ¨×Ú¿Õǁý
d^-* ȞīȪȞīńɺʔ ئÑÊÚ½qx^o njĀ]#; ɺʔʳ̙ 7V,#
ǁĸɾŅ˵ûūČ˷qxȱƵ] 7V,# S̀ɾŅsŚ ^o ȱƵ`ƴĀaŐ^ƴ Āơ]ɺʔ -=E5;5B=5B6H::9EZ ŗȗȚq]-* Ȱɀǁĸd (* ǣɻȦƖ B;A&
(*@6HA=B q~īg]ɸ˧lš̢ÝȟNjǃsoģȤqx^
7V,# ɇȴ˽ ȢŸ
,&" ɺʔʳ̙ɇȴs 7V,# ɇȴ˽|e~]1. *"% ƌɀjeoôÞ Ǘȓ
ɘˊqx^vw ɺʔģȤȪqde]#;(* ģȤơ]*-0 ȗȚqx^ȗȚơ]ńɺ ʔȦƖęˎǒqR79@@FGH69] CEA5@89<L8915?C Ğ̄ȎÝ~śŸqx^˱
ƧơÝȟľ̋k]*- ŗȗȚơ],&" W;A@ #. 7V,#*-FC@HG=CB âƺȥq]
Ǟ̄ȎÝ~ #.CB>H;5G98BG=ACHF9 7V,#ôÞ #. 7V,# sDzʢqx^*-
ŗȗȚơ] #. ʬēƚƖ @CJ7LGCA9G9E -5BGC.'[6=CF7=9B79FȺe~ȢŸqx^Ȣ ŸǬö˅mx«Ú½Ę ɺʔǑj 7CHBG qx^ˀǯÉÔªÚ°ÒØ]1=B'# Ⱥex^
T<9KCF5A=B=85F9E9@95F95FF5L
J9@@ ÌÕ¸ÉÖÚ½97GCB =7?=BFCB5B8CAD5BL E5B?@=B&5?9F ($ /- ôÞ Ⱦ˄
,&"R79@@FJ9@@ʩk]#;B;A& CI9EB=;<G ƴĀqx^Ýȟ̋k]W&
-=E5;5B=5B6H::9E#A'(5@ A'%@ A'';@ A'*#*- (5)" ~ D" ˎǒ
ɺʔ ŗȗȚơ]-=E5;5B=5B6H::9E[-=E5;5B=5B6H::9E# A';@H7CF9 A'5@ -
ȞīW& īg]Y]) ǬöÞ Ğ̄ ئÑÊÚ½qx^v ơ]-=E5;5B=5B6H::9E [~Ǝ˺qx (*"-B;A& Ⱥe~]ɺʔ Ğ̄ģȤqx^ģȤơ]Ýȟ W& ½ÔÉÖ
¹½ J9@@ ÌÕ¸ÉÖÚ½ɟqx^x]ɺʔ W& ̫.( ȣˀq]Ýȟņǽ]W&
t|½ÔÉÖ¹½ J9@@ ÌÕ¸ÉÖÚ½ɟqx^o W& FH6FGE5G9FC@HG=CBA' DB=GECD<9BL@579G5A=8C89CKLT;@H7CDLE5BCF=89 15?C'FC8=HA7=GE5G96H::9E D"
īg]Y]) ǬöÞ Ǟ̄ ئÑÊÚ½qx^ ئÑÊÚ½ơ]W& -GCD FC@HG=CB'(5)(5") D"īg~ļƩċȄpux^ńǣɻ®ØÉÕ ŋēƖ]BA
hmŋēÉÖÚ½ÔÚ· =@G9E'5K 'C@97H@5E9I=79F -HBBLI5@9 /-ȢŸqx^ɺ ʔ T<9KCF5A=B=85F9 E9@95F9 ] ô Þ Ɨ ȏ x ^ T<9KCF5A=B=85F9 E9@95F9 FHD9EB5G5BGFHD9EB5G5BG79@@@LF5G9R
.( S ȹȸ˽ȢŸ
¡¢ÕÌÕ¸ÉÖÚ½ ,&"R79@@FJ9@@ʩk]#;B;A& CI9EB=;<G ƴĀqx^v ơ](*"-B;A& vw ɺʔ Ǟ̄ģȤqxơ]Y~ʔěɾpux^
ěɾʮˀqx®ØÉÕɺʔȣˀțâ .( S &#- ȓ~ȢŸqx^&#- ȓ ,3-.!),5G .( S9=CF7=9B79Ⱥex^¦¹½ȞñˣƗqxjeļƩċȄơÉÖÚ½ÔÚ· =@G9E'5K
Ⱥe~]®ØÉÕ ŋēƖ BA ȢŸqx^
i ^
Z*"%,&" ǿɥ
7V,# °©¿Õhm *" ȁʕˀǯsx]*" A,( Ǿɉq~˅˂qx 8F,( ,&" Ƃĕq]*" % ʰ{x^Ẓ́Ⱥex 8F,( ŦŢ˷ğŚ əs^o 8F,( ÔË Ç¢¨°ÒØȓ ,&" Ƃĕqx^|e]19FG9EB6@CG ȓ]¶ØÃ¨˗ÖÊÕ *"
ɇȴɘˊqx^[email protected]. % ¶ØÃ¨˗ɇȴ˽ ƌȌˠqxɾǰŚ əs^Śəs
f]% ]*" ¶ØÃ¨˗ÖÊÕ ǜiɇȴüÞjʻx^ȼďˀǯ ɾǰ]*" ɇȴüÞ
]1. Ȍ~ɴ d{xŚ ©ÓÇ^x]*" ɇȴ˽ȠƄɺʔƜƵ Ūıˎx^
Q
Q gdJF- 5 ' $"# !
# XL4G+8Vv
1. x %,&"R79@@FA& #;B;A&
CI9EB=;<G ƴĀqx^Ýȟ̋k](*"-B;A&
Ğ̄ģȤqx^ģȤơ]ÝȟŗĽq]ǎĝpx T<9KCF5A=B=85F9T<9K˽ȢŸqx^x]ɺʔĘ T<9K ˽]ÝȟŗĽơ ɺʔ .( łȣıqȢŸ qx^T<9KCF5A=B=85F9E9@95F9 ]ǪǔǗȓə qxɬĝƗŢ}e~˂ɬqx^̪D
ûɏƌ̞ƥ́ɺʔď ʿſʰ{xɾǰ]% ùfƜƵŭkpŪıʿſpi{xŚ ^ p]% njĀĦĭǰq~]°©¿Õ ˙Ȩd 7V,# ɇȴ˽Ɲ̚j~eeoɘ ˊqx^% 1. vwǁ 7V,# #. Dzʢq]ȢŸqxɾǰ]z ɺʔņ˽ 7V,# jɇ ȴq~eoɘˊqx^Ś ^
Z*" % jʘ̜ɰĻsƝ̚
*" ɇȴ˽üÞj ,&" ʘ̜ɰ fƝ̚àgiˎȩ]T<9KCF5A=B=85F9FF5L T<9KFF5Lʰ{x^o FF5L ȓ]̜ɰŊǥ˸ɸd T<9K ǎĝ˽jʘ̜ɰ˽ȌĂso
ŢɌqx d^T<9K ǎĝ˽o ˸ɸ Ţ˗īg~]˸ɸļƩŢ}lŌʢŋēƖ˂
{~ȢŸsǗȓd]̲½ɺʔ ʘ̜ɰļƩ DžǾq~ƔlȺe~eŚ ^ ǁ(*#; CI9EB=;<G ƴĀqx ,&" (*"-ǩẒ́ ǁĸģȤq~ʘ̜ɰļƩˋ˙q x^v ơ]Ýȟâǎĝpx T<9K ȢŸqxŚ ^Ś ©ÓÇəqxh]*" % q x ,&" he~]ǁĸģȤˋƂpʘ̜ɰļƩj 1. Ȍ~ǥƳë˪sojǜi{
x^x]o Ǟ]vw ɺʔĘŊǥpxʄ T<9K ˽ŭkŪıʻi{x^
Z
*" % j .( S ȹȸĻsƝ̚
Count
FITC C
negative control KD(-) KD(+) WT WT
KD WTWTWTWTWWTWTWTWTWTWTWTWTWTWTWTWTWTWTWTWTWTWTTTTTTTTTTTTTT phase contrast
50.0μm 50.0μm
5ʼ-AAGCAAGCCCUCAAUUUUUdTdT-3ʼ 3ʼ-dTdTUUCGUUCGGGAGUUAAAAA-5ʼ
WT KD
PHB actin A
B
C
D
Q
Q # 5TK478 5 g
gdJF2/94I* ( gduRN
*"8F,( ŦŢ˷ğəqx^
ǪǔǗȓəqxƿȓ *" % qxɺʔ
1=@8GLD9 ɺʔłȣıq 19FG9EB6@CG ȓ
~ˀǯqx^ÂØ¾ Ȧp (#"=A5;9 ɬĝ q~©ÓÇıqx^ʇ˟ 1. hm *"
57G=B ƁsɏƁƚƖ q~ %F5AD@9
hm *" ĨŅ?BC7?8CJBE5G9əs^
%BC7?8CJBE5G9)DG=75@89BF=GLC:G<9*"
CDG=75@89BF=GLC:G<957G=BR ,&" Y]) CI9EB=;<G ئ
Ñ Ê Ú ½ q ] ɺ ʔ Ɯ Ƶ =CM9EC 4
%3(~NJƝqx^
1. Ļ *"% ɺʔ #;B;A& ƴĀq]
(*"-B;A& Ǟ̄ģȤqx^ŗĽqx ɺʔ 7V,# #. Dzʢơ]Ç×Ú® ½Ï Ú¶ÚȢŸʰ{x^
WT KD
120 100 80 60 40 20 0 rate of TNF-α production
A * *p<0.05
̲½ɺʔĻŰŦŢȵiǎĝp .( S ]ɺʧƴDzǞ ȸý̆ƣ˻ʺƞĨǰxq]Ö Õ§ÚƭȧɅļƩ Ƙk˾ ^vo]*" % j ,&" .( S ȹȸ fƝ̚
ĻsiˎxŚ ^Ǹ©ÓÇəqxh]ǁĸģȤˋɇp .( S ȹȸ]1. Ȍ
~ % he~ɴ ȠƄjˊx^
[*" % jɺʔʸװØÔØ˹ı°©¿ÕĻsƝ̚
*" ĀȺȨLJˀǯˇx^ɧ ]ǁĸģȤ{~ɺʔĘˋƂpʄ¶ØÃ¨˗ ¸×°
ØÔØ˹ı°©¿Õɓɍqx^o °©¿Õˀǯʰfx]ʄ¶ØÃ¨˗ ¸×°ØÔØ˹ıÃ¶Ú Ø 19FG9EB6@CG ȓǹĝqxŚ ^ɧ ] 7V,# ɎÞûʊqŚ ĺȬ]°©¿Õ ̃űȁ Ǽ˻ʺƞĨDŽ|ojţōp~e - % Û|d &LB?=B5F9&LB ¸×°ØÔØ˹ıȱƵ
ˎxŚ ^
Ś əqxf]*"% ]˦Ɛ 1. ǁĸģȤùeˋƂpɴ ?5 Ğų˽ûʊs
¶ØÃ¨˗ ¸×°ØÔØ˹ıÂØ¾jˊi{x^
ÛǗ]ǁĸģȤ°©¿Õ{~ˋƂp &LB B9;5G=I9E9;H@5GCELF=G9.LE ÔØ˹ı ȠƄ]ǁĸģȤ Ğ ǞȨ 1. *"% áǗhe~ņɠƖdçjʿſpxŚ ^x]o Ź ̣ Ǭ ö h e ~ ] Ź ̣ Ⱥ e x ń ® Ø É Õ &LB ¶ Ø Ã ¨ ˽ ƌ ɀ ʻ i { x ^
Q
Q 5gdJF- 5 & fe 4G+8Vv
1. x %ɺʔ #;B;A& CI9EB=;<G ƴĀq]
(*"-B;A& Ǟ̄ģȤqx^ɺʔš̢țė
ěɾʮˀq]˱Ƨơ]Ýȟ®ØÉÕq~]ooŊ
.( S ]&#- ȓȺe~ȢŸqx^ʇ˟ģȤ
.( S ȹȸ ŧī ĨŅÞ˄ Ɨ˂ɬq]1. ® ØÉÕ ŧī ĨŅ q~©ÓÇəq~e^
,5G9 C:.( SDEC8H7G=CB
̨FG=AH@5G=CBBCBFG=AH@5G=CB̩R
h]ȪģȤǞ .( Sȹȸ˽ 1.]% ėǹĝ̉Ƚô Þd{x^̪D
Q
Q WOMb4I * 2 5j=D@: o>C<DAD tN@=ED 5s)
1. x % ɺʔ B;A@ ǁ(*#;
-*ƴĀqx^ƴĀɺʔ B;A@
(*"- Ğ̄ģȤ]xȪģȤȱƵ]
.E=GCB2.( łȣıq]79@@@LF5G9 qx^9@@@LF5G9 ]--*!]19FG9EB6@CG ȓ { ~ Ï Ø È Ö Ø ˞ Ě q ] 5BG=D3 5BG=6C8L7@CB9!Ⱥe~¸×°ØȉŢ ÔØ˹ıpx¶ØÃ¨˗ ǹĝqx^
[*" ɇȴüÞj '*?=B5F9 °©¿ÕĻsƝ̚
7V,# ˙Ȩs°©¿Õø˯Ýș¸×°ØÔØ˹ı]âș¥Õ°¡Î°©¿Õ]vq~Þș
]'*?=B5F9 °©¿ÕjŴŞs^o °©¿ÕÞșňifqxj{~ʹ̔ĞƉq~ʰ l^¥Õ°¡Î°©¿Õ pÞșʘ̜ɰļƩ]'*?=B5F9 °©¿Õ pÞș® ½¥ Øȹ ȸ]ɺʔŧȊɨe{xʳȴŠjˋƂp^Ƽ_]ȃ '*?=B5F9 °©¿ÕƁs *" ȁʕˀǯ
ʰ{x^*" % qx ,&" 1. ǁĸģȤơ '*?=B5F9 ÔØ˹ı|e~ Ȍˠˀǯʰ{
xŚ ^
1. he~],%]D]$(% ń '*% ƁȌq~ʿſs]ʑɒǥƳ¸×°ØÔØ˹ı ؾ ŧƚjˊŚ 1.^oƁq~ % ]ń '*% et]ÔØ˹ıjˋƂ peoj]ɘˊpx^Ś əqx¡£²¶ØÈ×¹½ ÂØ¾]ÔØ˹ıÃ¶ÚØ Ȍˠ
ȅɘĝǭe ]Ś ]ńÖÚØș~evw '*% ¶ØÃ¨˗Ɓq~ʷȅim
~ǑĊıqxÔØ˹ı ë˪ȳɏƁɉÔØ˹ı˽əqx^Ś əqxh]1. ɬĝqxɏƁɉ ÔØ˹ı˽ Ǹ©ÓÇ % ],%]D]vq~ $(% et '*?=B5F9 he~] ̧
ˢeǑĊəq~h]ȪģȤȱƵȌ~ Ĉ ÔØ˹ıjˋƂpx^ÛǗ]% ]Ś əs
h],%]D]vq~ $(% et ÃڴؽˢeĊəq~e^osz]ģȤĤ
A B
*
(%)
relative percent
KD
ERK1/2
Q 5gdaU- ! # <;?B4G +8Vv
1. x % ɺʔ 5BG=(*#;-*īg~ƴĀqx^ƴĀɺʔ B;A@ (*"- Ğ̄ģȤơ
łȣıqx^9@@@LF5G9 ]--*!]J9FG9EB6@CG ȓ{~]Ȱɀǁýǹĝʰ{x^,% D h
$(% ǁýǹĝqxÂØ¾]vw ¶ØÃ¨˗ ʄ˽əs^x]D,% DD h D$(% ǁý
ǹĝqxÂØ¾]vw ¶ØÃ¨˗ ÔØ˹ı˵ûȰɀǁýd]ÔØ˹ı˽əq~e^
Ẓ́ƢxÂØ¾ȼďˀǯq~ǑĊıqx©ÓÇ əqx^ʇ˟ģȤ '*?=B5F9 ÔØ
˹ı ŧƚĨŅôÞ Ɨ˂ɬq~əqx^
E9@5G=I9D9E79BGN(*D'*%'*%ON(*D'*%'*%OR Q
Q WOMb4I * % !! # 5>C<
DADtN@ =ED6 4Vv.9 3,10
Ś ņǽ 1. % ɺʔ F5AD@9 ˎʸq 5BG=&LB5BG=6C8LGCG5@ &LB ǹĝ]
5BG=D&LB.LE5BG=6C8L ȿɍ ¸×°
ØȉŢjÔØ˹ıpx &LB ǹĝǹĝqx^
ơ ÔØ˹ıÃ¶ÚØŪıji{xefɾǰļǝq~e^% ,% ÔØ˹ı]q
̧üeĊəqxj]1. ÔØ˹ıë˪Ȍ~tiŪĮd]Ẓ́ˌƌ ɭřd^
k S
Ƽ_] 7V,# °©¿Õø˯ȁǼ ˈɺˀǜ]oŢɌqxÖÕ§ÚĢƣɍDžq~e^
v Ûȷq~ 7V,# ģȤ{~ ,5:G ƅŞjŧīs¶ØÃ¨˗q~] Ɠ *" ņŸq x^îŗ] 7V,# °©¿Õhm *" ƞĨȰŸsx]Á¹¨·¡Øȓ *" ɇȴü Þpu]v ɾǰiȸrɺʔȁʕŪı]*" ǩǭ ƞĨƏɵqfˇx^
Ƽ_]o ,&"]*"j,5:GȼĞŴŞsotȸıŵɉƿȓɘˊqx^x]îŗ ţōĒʰsẒ́ėȫȨÖÚ¯Ú˘dz̞ƥ́Ⱥe~]*" ƅŞɘˊqx^o ɾǰ]
,&"he~,5:GƅŞs*" ďʿſqx¼Ú¶əq~ee^,5:G]²ÇØʖ˗¬
Ö²»×ÚÕžɺʔʛÝ ¾Ï Ød]°©¿Õø˯ ɇąşq~˻ʺŤƜƻsojǜ
i{~e ^ÛǗ]o fȼď ÏÚ±ɀ,5:GˀǯŁliʰ~e^ȸı ŵɉ],5:G9G9E;9BGE9F=FG5BGA9A6E5B9F,'FŐ]°ÒɲŽƖį˷˚˱ƧȓȺe~Ğȼ sojĝǭ ^ 7V,#ǁĸģȤ{~,5:GÔ¨ÕÚ½pojţōp~h],5:G
ɟĮqx 7V,#&LB - %ÔØ˹ıĿm~-L?Ô¨ÕÚ½s^ȃeȘƭıqx-L?]
&.(.&ÔØ˹ıq]vo̓ɢs˸ɸjÔØ˹ıʖ˗ óːŗ˞¥Õ°¡Î°©¿Õ ŧœˁ{
xô̈ ÖÕ§Ú°©¿Õøg~ʰl^o fŭi°©¿Õ ș|e~]Śəqx^
o °©¿Õø˯ ŚƗ|e~]sŬl ţōjd33, 34, 35. 36, 37)^qiq]Ƽ_j,&" ,5:G
ƅŞsoɇʻqx*" ƞĨ|e~]ǧyßǜȨjŬe^
Ƽ_]*" 8F,( ÔËÇ¢¨°ÒØȓ % njĀ]¶ØÃ¨˗ÖÊÕ ɇȴ˽ɴ Ƞ ƄpuoƻĪqxŚ ^o njĀ *" ɇȴüÞ]ǹˆqx̉ ɺʔ ŭkpÙƜƵ]
vq~ŧȊƝ̚ˊi{xŚ ŧȊ¼Ú¶əq~ee^o ɾǰ]*"% jɺʔŧȊ
ŊɺʔŎǦ̅°©¿Õɳ Ɲ̚qi{xoəs^
% ɺʔȺe~]*" ɇȴüÞj ,&" ʘ̜ɰļƩàgƝ̚ǹ˃qxɾǰ]% ɺʔhe
~ǁĸģȤʘ̜ɰǎĝ˽jë˪qxŚ ^o ɾǰ]*" ,&" 7V,# °©¿Õhm
ʘ̜ɰļƩƁq~ǀĢɉĎloəŔq~e^ÛǗ]*" ɇȴüÞj ,&" .( S ȹȸ
àgƝ̚ǹ˃qxɾǰ]% ɺʔǁĸģȤhm .( S ȹȸˋƂjǀĢpxŚ ^qxj {~]*" ʘ̜ɰǀĢȁʕɀ 7V,# °©¿ÕˋƂp .( S ȹȸ|e~ǩǭ]ĀĮɉ
ƞĨǂ{~eʏg^ŰŦŢȵ ȹȸs® ½¥ Øq~].( S yml]#&]
#& jɖ~e ^îơ]o ® ½¥ Ø *" ̅ǹ˃q~ʰlƨʺj d^
îˣxɾǰjəsf]Ŀżýi °©¿Õȅ˓ áǗĢƣs°©¿Õ˙Ȩ Ğų
q~]®Ú¨ÇÍÔÚ¦¿Úµ- % ̅àjɁ^Ăg]̭ɺʔ]- % ɇs°©¿
Õïq~]ɺʔȈxɺʔŧȊe{xɏɀɾǰjˋƂpj]oņÛ°©¿Õɦɇ s°©¿Õj]ÞșĞƉs°©¿Õ{~ǣɻɉ˳øųɇȴjɀxdojţōp
~e^*" 7V,# °©¿Õø˯ȁǼhmĀȺȨ ˀǯˇɧÛȋ̎q~] 7V,# ģȤ
ˋƂpɺʔʸװØÔØ˹ı°©¿Õj *" % {~Ɲ̚piʼniǹ˃qx^*"
% qx ,&" ]ǁĸģȤùeˋƂp ?5 ñˢ ¶ØÃ¨˗ ¸×°ØÔØ˹ıjˋƂ pi{xŚ ^ǏɞǢɉ]̲½ɺʔŰŦŢȵ 7V,# ģȤ{~]ɺʔjȘƭıp
̏]ĿżýɎÞ]t]- % Șƭıj˙o^,&" ]v - %q~ &LB?=B5F9&LB jȘƭıp ^v˙Ȩq]ǽ_°©¿ÕĞų ÔØ˹ıïq~ɺʔʰ©¿Õj ø˯p]ɾǰ]ɺʔʶØÃ¨˗ ¸×°ØÔØ˹ı ŧƚjˊojɖ~e ^ɺ ʔʶØÃ¨˗ ¸×°ØÔØ˹ıʂe~]*" j &LB ȘƭıàgƝ̚ˎx^&LB Șƭı DžǾq~] ǨɦŴŞs B9;5G=I9E9;H@5GCELF=G9.LE ¸×°ØÔØ˹ıˎxŚ ^ ßȘƭȱƵ &LB .LE jÔØ˹ıp~h]˸ɸȘƭ˵ûj̐xǼ˨{~ej] ɨ ʘÔØ˹ı˸ɸ{~ .LE ÔØ˹jʘÔØ˹ıpȘƭıȱƵ]°©¿ÕĞųÔØ˹
ıq~Þș°©¿Õø˯kfojɖ~e ^Ś 1. *"% áɺʔ
he~]ǁĸģȤơ Ğ &LB .LE ÔØ˹ı Ƞƙjǹĝpx^oģȤ]&LB jȅƐ
Șƭıpxoəq~e^o ɾǰ *" ǾɉĞųj &LB ÞșŴŞq]v Ǿɉ Û|j *"% ùeÔØ˹ıjˋƂpl{x ?5 ¶ØÃ¨˗dłʕƭəq~e^oo
efǾɉƔʎ Ƴŏd]ĹŽ ?5 ¶ØÃ¨˗ ÔØ˹ı̅ÔØ˹ı˸ɸj]
ɎLj Ǿɉdłʕƭd^etq~]o ?5 ¶ØÃ¨˗jþdiȐŸsçƬ je^
ŰŦŢȵ̲½ɺʔ 7V,# °©¿Õø˯ Ģƣ˻ʺp~e - % q~]&LB ð LB j ɖ~h ]̲½ɺʔ 7V,# °©¿Õø˯he~ &LB q LB j˻ʺd
sţōŴŞs^qiq],&" ] LB ɇȴq~ee ]ǩɗɤƢxɾǰj] LB
Ï ØȘȺsɺʔ˯ņǽ ɾǰjƢiʼni|e~]ǹ˃ ÿşjd^
7V,# °©¿Õhm *" ĀȺȨj]&LB ô̈ °©¿ÕdojəŔpxx]pÞ ș °©¿Õd '*?=B5F9 ÔØ˹ı|e~ǹ˃qx^'*?=B5F9 °©¿Õ̲½ɺʔ ʘ̜ɰ ļƩ Ģƣ® ½¥ ØÙªÐ¥ Ø˳øų ˞ĚȘƭı]ȸŴÙŧȊ̅às°©¿Õq~ɖ
~h]#; ïqxǁĸģȤ{~Șƭıjhoojɖ~e ^
Ś əqxf]*" % qx ,&" ]ǁĸģȤơ Ğ ǞȨhe~ 1. ˊ ,%]
D]$(% ÔØ˹ı ë˪jˊi{x^o ɾǰ *" jĒ *" ǾɉĞųɍp ?5
¶ØÃ¨˗°©¿Õ șj˲ǕpʏgƼ_ ²½ÚÔÚɔɐqe^*" % qx "9&5 ɺʔȺexɗɤ]% ɺʔ]! ĿżýģȤˋƂp ,% ÔØ˹ıjȠƙsojţō p~e ^o ţō],% ÝșŴŞs '*%%% d 7,5: ɏéĀȺso
{~]*" j ! ĿżýģȤˋƂp ,5F,5:'%,% ɽ˝Ģƣq~eˣ~e^ǩɗɤ
ʿſpx ,&" ȺexƼ_ ¼Ú¶]1. ǁĸģȤˋƂp ,% ÔØ˹ı j *"
% ˋƂpeefɾǰ]Ɵ ţō̟úq~e^o oi]Ƽ_ Ẓ́ɳ 7,5: j
*" Ǿɉ{~ełʕƭjʏg^o Ȩ|e~ÛƇ ˀǯjƨʺdf^ÛǗ]D
$(% Șƭı̅q~],5F,5:'%,% ɽ˝ɀɽ˝jĢƣsojɖ~h ]'*
%=B5F9 °©¿Õhm *" ĀȺȨjʹǑŴŞsłʕƭ|e~ʽ˼ĕxɗɤjƨʺd^
îŗooəqx ,&" Ẓ́]*" ŰŦŢȵ #; Ö´É¶Ú °©¿Õø˯Ɲ̚Ļ
sçjəpx^o Ï¥À³Î]*"% #; ִɶÚģȤ¸×°ØÔØ˹ı ˋƂj
ˊi{x ?5 Ğųj°©¿ÕĢƣ ˿łʕƭjəŔpx^o ?5 Ğų]
¸×°ØÔØ˹ıjˋƂpi{x l]¶ØÃ¨˗v ɇȴjüÞqxłʕƭd^
qiq]½Ú¶Õ¶ØÃ¨˗ ȖĮDzʢÃ¶ÚØƝ̚ji{xo¼Ú¶əq~ee^vq~]
Ƽ_ņrl *" % ̲½ɺʔʰ{x©ÕÚÉj]Ś əqxf°©¿Õ¶ØÃ¨˗ Ȫģ ȤȱƵ ɇȴƁsƝ̚ˊ~eeoi]v łʕƭüeiqe^x]o ?5 ôū °©¿ÕĢƣ]ǁĸģȤˋƂp ,&" ɺʔʸװØÔØ˹ı°©¿Õ Ļ ,%]D]$(% ÔØ˹ıƝ̚sġÕÚ½ŴŞsłʕƭ|e~]yŬl Ẓ́jƨʺ
d^etu]îŗ Ẓ́ɾǰ]ǽ_łʕƭ â]o ?5 Ğųj *" ɎLjx̄
Lj Ǎ˷Þd{~]°©¿Õø˯̅łʕƭəŔq~eƫ^îŗo ¶ØÃ¨˗
ŹýȰŸʝi{xj]ŭʝƬo Ğų Źýˀǜso]*" Ģƣsîɖ~
eeÖÕ§ÚĢƣ ˮɩjæƱp^
ǩɗɤ˫ʰâɇʳpxˏǓhe~]%%=A ]Ì¡² ̲½ɺʔhe~]*" -L??5jɏéĀȺsţōqx^Ɵ]*" j] 7V,# &LB h -L? ʹŅýŶŸıq]
,5:G hm˜Ť¶ØÃ¨q~ȁʕsɾˏq~e21)^Ƽ_ Ẓ́]?5 ¶ØÃ¨ ÔØ˹
ıƌɀˊi{xj]Ɵ Ẓ́ɾǰ]*"% ùe ?5 -L? ¸×°ØÔØ˹ıj ŷĖǀĢp~ex^%=A ]Ì¡²̤̥Ȼǭ̲½ɺʔẒ́Ǫǔq~h]Ƽ_ ŰŦŢȵɺʔ Ǵ Ẓ́ɾǰĵɶȌˠĝǭe^qiq]îơƼ_]?5 ¶ØÃ¨˗ ?5 -L? ɀņ
ÔØ˹ıÃ¶ÚØƶ˻Ȍˠǹ˃sƨʺjd^qiq]et ɗɤɾǰhe~îɖ
~ei{x 7V,# °©¿Õ *" ĢƣȁǼjŴŞsɾǰjəpxo˻ʺd^îơ]
*" ɗɤ pɖʻj] 7V,# °©¿Õø˯ȁǼ ˈɺˀǜʈjç̄˰eeyf^îơ ɗɤƻǰjÖÕ§ÚˋɇȁǼˀǜq]ǁÖÕ§Úǖʫ ĩʫ˔ȲsoǦƠqxe^
nq
ǩɗɤ ˫ʰƛx]ǩŵIJŵ˵ĔɂŵǏź ǫŀɮǏdžņǏź ɊǽŵʱÙȯ˖ á̙Ŭl ƣljĬexykqx^ɊǽƧiƴːexqs^
ཧ⪃ᩥ⊩
1. ࣐ࣜ࢘ࢳ࣭ࣞࣝࢠ࣮ᑐ⟇ጤဨሗ࿌᭩, ᖹᡂ23ᖺ8᭶,ཌ⏕⛉Ꮫᑂ㆟ᑐ⟇㒊.
2. MacGlashan DW Jr. IgE-dependent signaling as a therapeutic target for allergies. Trends Pharmacol Sci. 2012;33(9):502-9.
3. Kawakami T, Galli SJ. Regulation of mast-cell and basophil function and survival by IgE. Nat Rev Immunol. 2002;2(10):773-86.
4. Gilfillan AM, Tkaczyk C. Integrated signalling pathways for mast-cell activation. Nat Rev Immunol. 2006;6(3):218-30.
5. Dráber P, Dráberová L. Lipid Rafts in mast cell signaling. Mol Immunol. 2002;38(16-18):1247-52.
6. Brown DA, London E. Functions of lipid Rafts in biological membranes. Annu Rev Cell Dev Biol. 1998;14:111-36.
7. Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T. Nonredundant roles of basophils in immunity. Annu Rev Immunol.
2011;29:45-69.
8. Sokol CL, Barton GM, Farr AG, Medzhitov R. A mechanism for the initiation of allergen-induced T helper type 2 responses.
Nat Immunol. 2008;9(3):310-8.
9. Sawaguchi M, Tanaka S, Nakatani Y, Harada Y, Mukai K, Matsunaga Y, Ishiwata K, Oboki K, Kambayashi T, Watanabe N, Karasuyama H, Nakae S, Inoue H, Kubo M. Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness. J Immunol. 2012;188(4):1809-18.
10. Obata K, Mukai K, Tsujimura Y, Ishiwata K, Kawano Y, Minegishi Y, Watanabe N, Karasuyama H. Basophils are essential initiators of a novel type of chronic allergic inflammation. Blood. 2007;110(3):913-20.
11. Segal DM, Sharrow SO, Jones JF, Siraganian RP. Fc (IgG) receptors on rat basophilic leukemia cells. J Immunol. 1981 Jan;126(1):138-45.
12. Morita Y, Siraganian RP. Inhibition of IgE-mediated histamine release from rat basophilic leukemia cells and rat mast cells by inhibitors of transmethylation. J Immunol. 1981 Oct;127(4):1339-44.
13. McGivney A, Crews FT, Hirata F, Axelrod J, Siraganian RP. Rat basophilic leukemia cell lines defective in phospholipid methyltransferase enzymes, Ca2+ influx, and histamine release: reconstitution by hybridization. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6176-80.
14. Peng Z, Beaven MA. An essential role for phospholipase D in the activation of protein kinase C and degranulation in mast cells.
Journal of Immunology. 2005;174 (9):5201-8. 16) Beaven MA, Baumgartner RA. Downstream signals initiated in mast cells by Fc epsilon RI and other receptors. Curr Opin Immunol. 1996 Dec;8(6):766-72
15. ᒣ㔝㐟ዲሷᇶ⌫/LSLG5DIWᒁᅾࡍࡿ᪂つࣞࣝࢠ࣮ࢩࢢࢼࣝ㛵㐃ศᏊࡢ᥈⣴ᐩᒣᏛᏛ㝔ಟኈㄽᩥ
16. Nuell MJ, Stewart DA, Walker L, Friedman V, Wood CM, Owens GA, Smith JR, Schneider EL, Dell' Orco R, Lumpkin CK, et al. Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells.
Mol Cell Biol. 1991 Mar;11(3):1372-81.
17. Nijtmans LG, Artal SM, Grivell LA, Coates PJ. The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease. Cell Mol Life Sci. 2002 Jan;59(1):143-55.
18. Merkwirth C, Langer T. Prohibitin function within mitochondria: essential roles for cell proliferation and cristae morphogenesis.
Biochim Biophys Acta. 2009 Jan;1793(1):27-32. doi: 10.1016/j.bbamcr.2008.05.013. Epub 2008 Jun 17.
19. Osman C, Merkwirth C, Langer T. Prohibitins and the functional compartmentalization of mitochondrial membranes. J Cell Sci. 2009 Nov 1;122(Pt 21):3823-30.
20. He B, Feng Q, Mukherjee A, Lonard DM, Demayo FJ, Katzenellenbogen BS, Lydon JP, O'malley BW. A Repressive Role for Prohibitin in Estrogen Signaling. Mol Endocrinol. 2008 Feb;22(2):344-60. Epub 2007 Oct 11.
21. D. K. Kim, H. S. Kim, A.-R. Kim, G. H. Jang, H. W. Kim, Y. H. Park, B. Kim, Y. M. Park, M. A. Beaven, Y. M. Kim, W. S.
Choi, The scaffold protein prohibitinis required for antigen-stimulated signaling in mast cells. Sci. Signal.2013; 6, ra80.
22. Rajalingam K, Wunder C, Brinkmann V, Churin Y, Hekman M, Sievers C, Rapp UR, Rudel T. Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration. Nature Cell Biology. 2005;7 (8): 837-43.
23. Rajalingam K, Rudel T. Ras-Raf signaling needs prohibitin. Cell Cycle. 2005;4 (11): 1503-5.
24. H. Yurugi, S. Tanida, A. Ishida, K. Akita, M. Toda, M. Inoue, H. Nakada, Expression of prohibitins on the surface of activated T cells. Biochem. Biophys. Res. Commun. 2012;420, 275–280.
25. I. C. Morrow, S. Rea, S. Martin, I. A. Prior, R. Prohaska, J. F. Hancock, D. E. James, R. G. Parton, Flotillin-1/reggie-2 traffics to surface Raft domains via a novel golgi-independent pathway: Identification of a novel membrane targeting domain and a role for palmitoylation. J. Biol. Chem. 2002;277, 48834–48841.
26. ⚽Ἠ⅖ᛶᝈ㛵ࢃࡿ⭘⒆ቯṚᅉᏊ㸦71)㸧ࡢ⏘⏕yᨺฟ᪥ᮏ⸆⌮Ꮫ㞧ㄅVol. 121 (2003) No. 3 P 163-173 27. Abraham SN, Arock M. Mast cells and basophils in innate immunity. Semin Immunol. 1998;10(5):373-81.
28. Lock JG, Strömblad S. Systems microscopy: an emerging strategy for the life sciences. Exp Cell Res. 2010 May 1;316(8):1438-44.
29. Owen DM, Magenau A, Williamson D, Gaus K. The lipid raft hypothesis revisited--new insights on raft composition and function from super-resolution fluorescence microscopy. Bioessays. 2012 Sep;34(9):739-47.
30. van der Goot FG, Harder T. Raft membrane domains: from a liquid-ordered membrane phase to a site of pathogen attack.Semin Immunol. 2001;13(2):89-97.
31. Radeva G, Sharom FJ. Biochem J. Isolation and characterization of lipid Rafts with different properties from RBL-2H3 (rat basophilic leukaemia) cells. Biochem J. 2004;380(Pt 1):219-30.
32. Quinn PJ. A lipid matrix model of membrane Raft structure. Prog Lipid Res. 2010;49(4):390-406.
33. Holowka D, Gosse JA, Hammond AT, Han X, Sengupta P, Smith NL, Wagenknecht-Wiesner A, Wu M, Young RM, Baird B.Lipid segregation and IgE receptor signaling: a decade of progress. Biochim Biophys Acta. 2005;1746(3):252-9.
34. Peng Z, Beaven MA. An essential role for phospholipase D in the activation of protein kinase C and degranulation in mast cells.
Journal of Immunology. 2005;174 (9):5201-8.
35. Bugajev V, Bambousková M, Dráberová L, Dráber P. What precedes the initial tyrosine phosphorylation of the high affinity IgE receptor in antigen-activated mast cell? FEBS Lett. 2010;584(24):4949-55.
36. Heneberg P, Dráberová L, Bambousková M, Pompach P, Dráber P. Down-regulation of protein-tyrosine phosphatases activates an immune receptor in the absence of its translocation into lipid Rafts. J Biol Chem. 2010;285(17):12787-802.
37. Sanderson MP, Wex E, Kono T, Uto K, Schnapp A. Syk and Lyn mediate distinct Syk phosphorylation events in FcܭRI-signal transduction:implications for regulation of IgE-mediated degranulation. Mol Immunol.2010;48(1-3):171-8.
38. Min B, Brown MA, Legros G. Understanding the roles of basophils: breaking dawn. Immunology. 2012;135(3):192-7.
39. Wakahara K, Van VQ, Baba N, Bégin P, Rubio M, Delespesse G, Sarfati M. Basophils are recruited to inflamed lungs and exacerbate memory Th2 responses in mice and humans. Allergy. 2012.
40. Volná P, Lebduska P, Dráberová L, Símová S, Heneberg P, Boubelík M, Bugajev V, Malissen B, Wilson BS, Horejsí V, Malissen M, Dráber P. Negative regulation of mast cell signaling and function by the adaptor LAB/NTAL. Journal of Experimental Medicine. 2004;200 (8): 1001-13.
41.㇂࣐᪼࢘ࢫ㦵㧊⏤᮶࣐ࢫࢺ⣽⬊ࡢᶞ❧ࡇࢀࢆ⏝࠸ࡓ࣐ࢫࢺ⣽⬊ࢩࢢࢼࣝࡢゎᯒᐩᒣᏛ⸆Ꮫ㒊༞ᴗㄽᩥ
42. Shrivastava P, Katagiri T, Ogimoto M, Mizuno K, Yakura H. Dynamic regulation of Src-family kinases by CD45 in B cells.
Blood. 2004;103 (4): 1425-32.
43.Hermiston ML, Tan AL, Gupta VA, Majeti R, Weiss A. The juxtamembrane wedge negatively regulates CD45 function in B cells.
Immunity. 2005;23 (6): 635-47.
44. Parravicini V, Gadina M, Kovarova M, Odom S, Gonzalez-Espinosa C, Furumoto Y, Saitoh S, Samelson LE, O'Shea JJ, Rivera J.
Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nature Immunology. 2002;3 (8):
741-8.
45. Chan JH, Liao W, Lau HY, Wong WS. Gab2 antisense oligonucleotide blocks rat basophilic leukemic cell functions.
International Immunopharmacology 2007;7 (7): 937-44.
46. ᓥᏊᚋ㣤ሯ࣐ࢫࢺ⣽⬊ࡢάᛶ㛵ࡍࡿࢲࣉࢱ࣮ศᏊࣞࣝࢠ࣮⛉ 㸸 47. Xiao W, Nishimoto H, Hong H, Kitaura J, Nunomura S, Maeda-Yamamoto M, Kawakami Y, Lowell CA, Ra C, Kawakami T.
Positive and negative regulation of mast cell activation by Lyn via the FcepsilonRI. Journal of Immunology. 2005;175(10):
6885-92.
48. Blank U, Rivera J. The ins and outs of IgE-dependent mast-cell exocytosis. Trends Immunology 2004;25 (5): 266-73. Review.
49. ᒣᮏ㞞 Ἴ᠇ኴ㑻⦅ࢩࢢࢼࣝఏ㐩㞟୰࣐ࢫࢱ࣮⨺ᅵ♫
50. Fukao T, Yamada T, Tanabe M, Terauchi Y, Ota T, Takayama T, Asano T, Takeuchi T, Kadowaki T, Hata Ji J, Koyasu S.
Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Nature Immunology. 2002;3(3):
295-304.
ᕷ㈗⿱
ᐩᒣᏛ་Ꮫ⸆Ꮫᩍ⫱㒊 ⸆࣭⏕≀Ꮫ◊✲ᐊ
㇂ ᪼
ᐩᒣᏛ་Ꮫ⸆Ꮫᩍ⫱㒊 ⸆࣭⏕≀Ꮫ◊✲ᐊ
⻏㇂⨾♩
ᐩᒣᏛ་Ꮫ⸆Ꮫᩍ⫱㒊 ⸆࣭⏕≀Ꮫ◊✲ᐊ
୕ᶫ㝧ᖹ
ᐩᒣᏛ་Ꮫ⸆Ꮫᩍ⫱㒊 ⸆࣭⏕≀Ꮫ◊✲ᐊ
Ⲩ⯓ᛅ
ᐩᒣᏛᏛ㝔་Ꮫ⸆Ꮫ◊✲㒊 ་࣭⏕≀Ꮫᩍᐊ
∦᱒㐩㞝
ᐩᒣᏛᏛ㝔་Ꮫ⸆Ꮫ◊✲㒊 ⸆࣭⏕≀Ꮫ◊✲ᐊ