Statistical methods were not used to predetermine the sample size. The experiments were not randomized. Data are presented as the mean ± SEM or mean + SEM. All tests were performed with Sigma Plot (Systat software Inc.) or BellCurve for Excel (Social Survey Research Information Co.). For the comparison between two groups, we used two-tailed Student’s t-test, MannWhitney U-test, Wilcoxon signed-rank test or KolomogorovSmirnov test unless stated otherwise. For the comparison among several groups, analyses of variance (ANOVA) or KruskalWallis test, followed by the post-hoc tests, was used. p < 0.05 was considered statistically significant.
Figure 1 Click here to download Figure Kakegawa et al. Fig. 1 (1.5 column).tif
Figure 2 Click here to download Figure Kakegawa et al. Fig. 2 (2 columns).tif
Figure 3 Click here to download Figure Kakegawa et al. Fig. 3 (1.5 column).tif
Figure 4 Click here to download Figure Kakegawa et al. Fig. 4 (2 columns).tif
Figure 5
Click here to download Figure Kakegawa et al. Fig. 5 (2 columns
Figure 6 Click here to download Figure Kakegawa et al. Fig. 6 (1.5 column).tif
Figure 7
Click here to download Figure Kakegawa et al. Fig. 7 (1.5 colum
Figure 8 Click here to download Figure Kakegawa et al. Fig. 8 (1.5 column).tif
6XSSOHPHQWDO,QIRUPDWLRQ
2SWRJHQHWLF&RQWURORI6\QDSWLF$03$5HFHSWRU(QGRF\WRVLV
5HYHDOV5ROHVRI/7'LQ0RWRU/HDUQLQJ
:DWDUX.DNHJDZD$NLUD.DWRK6DNDH1DUXPL(ULNR0LXUD-XQNR0RWRKDVKL$NL\R 7DNDKDVKL.D]XKLVD.RKGD<XJR)XND]DZD0LFKLVXNH<X]DNLDQG6KLQML0DWVXGD
)LJXUH65HODWHGWR)LJXUH3KRWRQ6$%(55HJXODWHV(QGRVRPDOS+LQ+HWHURORJRXV &HOOV
$ ,PPXQRF\WRFKHPLFDO DQDO\VHV RI +(. FHOOV H[SUHVVLQJ )/$*WDJJHG 3KRWRQ6$%(5 DQGUHGDQG*)3WDJJHG5DEVJUHHQWRS5DEPLGGOH5DEERWWRP5DEVKRZHGWKDW 3KRWRQ6$%(5 ZDV PRVWO\ ORFDOL]HG DW WKH 5DESRVLWLYH HDUO\ HQGRVRPHV DQG ZDV SDUWLDOO\ ORFDOL]HG DW WKH 5DESRVLWLYH ODWH HQGRVRPHV 6FDOH EDU PP 7KH ULJKW OLQHVFDQ JUDSKV LQGLFDWHWKHIOXRUHVFHQWLQWHQVLWLHVRI3KRWRQ6$%(5DQG5DE*)3DORQJWKHOLQHVKRZQLQWKH OHIWSDQHOV$UURZVDQGDUURZVZLWKODEHOV$'LQGLFDWH3KRWRQ6$%(5FRORFDOL]HGZLWK5DE *)3V
% 7KH OLJKWLQGXFHG DOWHUQDWLRQ RI HQGRVRPDO S+ +(. FHOOV H[SUHVVLQJ 6(3WDJJHG 3KRWRQ6$%(5 ZHUH LQFXEDWHG ZLWK GH[WUDQFRQMXJDWHG S+URGH 7KH JUDSK LQGLFDWHV WKH IOXRUHVFHQFHUDWLRRI6(3WRS+URGHLQHQGRVRPHVLQGDUN>/6@DQGOLJKW>/6@FRQGLWLRQV 7KHIOXRUHVFHQFHUDWLRVLQWKHS+FDOLEUDWLRQEXIIHUVFRQWDLQLQJ+LRQRSKRUHDUHDOVRVKRZQ
7KHDYHUDJHYDOXHDWS+ ZDVHVWDEOLVKHGDVQ FHOOV
& (IIHFW RI FRQWLQXRXV DQG WUDQVLHQW LOOXPLQDWLRQ RQ HQGRVRPDO S+ 7LPHODSVH LPDJLQJ SHUIRUPHGLQ&26FHOOVH[SUHVVLQJ3KRWRQ6$%(5XQGHUPLQRIFRQWLQXRXVUHGFLUFOHVRU PLQRILOOXPLQDWLRQIROORZHGE\GDUNQHVVEOXHGLDPRQGVQ HQGRVRPHVIRUHDFKWLPH SRLQW S SQVQRWVLJQLILFDQWWZRWDLOHG6WXGHQW¶VWWHVWLQ%DQGRQHZD\$129$ IROORZHGE\)LVKHU¶V/6'SRVWKRFWHVWLQ&'DWDDUHSUHVHQWHGDVPHDQ6(0
)LJXUH 6 5HODWHG WR )LJXUH 3KRWRQ6$%(5 ,QKLELWV WKH (QGRF\WRVLV RI 'H[WUDQ LQ +(.&HOOV
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
UHJLRQXQGHUGDUNFRQGLWLRQVZHUHHVWDEOLVKHGDVQ FHOOVIURPH[SHULPHQWV S WZRWDLOHG6WXGHQW¶VWWHVW
&4XDQWLWDWLYHDQDO\VLVRIGH[WUDQWUDQVSRUWWRWKHODWHHQGRVRPHVDWYDULRXVOLJKWLQWHQVLWLHV 7KH DYHUDJHG GH[WUDQ LQWHQVLWLHV LQ WKH 5DESRVLWLYH UHJLRQ XQGHU /6 FRQGLWLRQV ZHUH HVWDEOLVKHGDV
'DWDDUHSUHVHQWHGDVPHDQ6(0LQ%RU6(0LQ&
)LJXUH 6 5HODWHG WR )LJXUH 3KRWRQ6$%(5 ,QKLELWV 10'$,QGXFHG $03$5 7UDIILFNLQJWR(DUO\(QGRVRPHVLQ+LSSRFDPSDO1HXURQV
$3KRWRQ6$%(5GRHVQRWDIIHFWWKHEDVDOODWHHQGRVRPDOWUDIILFNLQJRI$03$5VZLWKRXWOLJKW VWLPXODWLRQ /6 +LSSRFDPSDO QHXURQV H[SUHVVLQJ 3KRWRQ6$%(5 DQG +$*OX$ ZHUH FR LPPXQRVWDLQHG IRU +$ JUHHQ D ODWH HQGRVRPDO PDUNHU 035 UHG DQG D GHQGULWH PDUNHU 0$3 EOXH ZLWKRXW /6 7KH JUDSK UHSUHVHQWV WKH TXDQWLILHG *OX$ LPPXQRUHDFWLYLW\ FRORFDOL]HGZLWK035SRVLWLYHHQGRVRPHV7KHUDWLRLQ3KRWRQ6$%(5H[SUHVVLQJQHXURQVZDV GHILQHGDVQ 3KRWRQ6$%(5DQGQ 3KRWRQ6$%(5FHOOV
%(IIHFWVRI3KRWRQ6$%(5RQFKHPLFDO/7'LQKLSSRFDPSDOQHXURQV&XOWXUHGKLSSRFDPSDO QHXURQVH[SUHVVLQJ+$*OX$DQG3KRWRQ6$%(5)/$*ZHUHWUHDWHGZLWKP010'$IRU PLQ &HOOV ZHUH LPPXQRVWDLQHG IRU VXUIDFH UHG WRWDO EOXH RU JUD\ +$*OX$ DQG 3KRWRQ6$%(5JUHHQ7KHUHJLRQVPDUNHGE\VTXDUHVDUHPDJQLILHGLQWKHULJKWSDQHOV7KH UDWLRRIWKHVXUIDFHWRWRWDO*OX$IOXRUHVFHQFHLQWHQVLWLHVLVVKRZQLQWKHKHDWPDSV
&4XDQWLILFDWLRQRI10'$LQGXFHGFKDQJHVLQWKHUDWLRRIVXUIDFHWRWRWDO*OX$IOXRUHVFHQFH LQWHQVLWLHVZLWK>/6@RUZLWKRXW>/6±@OLJKWVWLPXODWLRQ7KHUDWLRLQWKHFRQWUROQHXURQVZDV GHILQHGDVQ FHOOVHDFK
' ( 3KRWRQ6$%(5 LQKLELWV WKH FRORFDOL]DWLRQ RI$03$5 ZLWK 5DESRVLWLYH HQGRVRPHV 10'$P0ZDVDSSOLHGWRFXOWXUHGKLSSRFDPSDOQHXURQVH[SUHVVLQJ+$*OX$5DE*)3 DQG 3KRWRQ6$%(5 WR LQGXFH FKHPLFDO /7' ,PPXQRF\WRFKHPLFDO DQDO\VLV PLQ DIWHU WKH WUHDWPHQW UHYHDOHG +$*OX$ FRORFDOL]DWLRQ ZLWK 5DESRVLWLYH HDUO\ HQGRVRPHV LQ /6± FRQGLWLRQXSSHUSDQHOV7KHFRORFDOL]DWLRQZDVUHGXFHGE\/6ORZHUSDQHOV7KHULJKWJUDSK ( LQGLFDWHV WKH TXDQWLWDWLYH DQDO\VLV RI *OX$ IOXRUHVFHQFH LQWHQVLW\ RQ WKH 5DESRVLWLYH UHJLRQ7KHDYHUDJHYDOXHIURPWKHGDUNFRQGLWLRQZDVHVWDEOLVKHGDVQ /6DQG /6±FHOOVIURPLQGHSHQGHQWH[SHULPHQWV
) * $Q DQWLERG\ IHHGLQJ DVVD\ VKRZLQJ WKH LQKLELWLRQ RI $03$5 LQWHUQDOL]DWLRQ E\ 3KRWRQ6$%(5/LYLQJQHXURQVH[SUHVVLQJ+$*OX$DQG3KRWRQ6$%(5ZHUHODEHOHGZLWKDQ DQWL+$ DQWLERG\ DQG WUHDWHG ZLWK 10'$ IRU PLQ ZLWK >/6@ RU ZLWKRXW >/6±@ OLJKW VWLPXODWLRQ 6XUIDFH UHG DQG LQWHUQDOL]HG JUHHQ +$ DQWLERGLHV DQG 3KRWRQ6$%(5 EOXH RU
JUD\ZHUHYLVXDOL]HGE\LPPXQRVWDLQLQJ10'$WUHDWPHQWLQGXFHGWKHLQWHUQDOL]DWLRQRI+$ *OX$LQ/6±FRQGLWLRQXSSHUSDQHOV7KHHIILFLHQF\RIWKHLQWHUQDOL]DWLRQZDVUHGXFHGE\/6 ORZHU SDQHO 7KH ULJKW JUDSK * LQGLFDWHV WKH UDWLR RI LQWHUQDOL]HG WR VXUIDFH +$*OX$ IOXRUHVFHQFHLQWHQVLWLHV7KHDYHUDJHYDOXHIURP/6±FRQGLWLRQZDVHVWDEOLVKHGDVQ /6DQG/6±FHOOVIURPLQGHSHQGHQWH[SHULPHQWV
6FDOHEDUPP S SQVQRWVLJQLILFDQWWZRWDLOHG6WXGHQW¶VWWHVW'DWDDUH SUHVHQWHGPHDQ6(0
)LJXUH 6 5HODWHG WR )LJXUH ,OOXPLQDWLRQ &RQGLWLRQV 1HFHVVDU\ WR 5HJXODWH$03$5 (QGRF\WRVLVLQ+LSSRFDPSDO1HXURQV
$7KHZDYHOHQJWKRIOLJKW9DULRXVZDYHOHQJWKVRIOLJKWZHUHDSSOLHGIRUPLQWKURXJKEDQG SDVV ILOWHUV &\DQ QP IRU SHDNKDOI ZLGWK *UHHQ QP <HOORZ QP ,QIUDUHGQPWRFXOWXUHGKLSSRFDPSDOQHXURQVH[SUHVVLQJ+$*OX$DQG3KRWRQ6$%(5 7KHLU HIIHFWV RQ WKH 10'$LQGXFHG FKDQJHV LQ WKH UDWLR RI WKH VXUIDFH WR WRWDO *OX$ IOXRUHVFHQFHLQWHQVLWLHVZHUHTXDQWLILHG7KHUDWLRLQWKH10'$XQWUHDWHGQHXURQVZDVGHILQHG DVQ FHOOVHDFK SWZRWDLOHG6WXGHQW¶VWWHVW'DWDUHSUHVHQWPHDQ6(0 %4XDQWLWDWLYHDQDO\VLVRIWKH10'$LQGXFHGFKDQJHVLQWKHUDWLRRIWKHVXUIDFHWRWRWDO*OX$ IOXRUHVFHQFHLQWHQVLWLHVDWYDULRXVOLJKWLQWHQVLWLHV7KHUDWLRLQWKH10'$XQWUHDWHGQHXURQVZDV GHILQHGDVQ FHOOVHDFK
)LJXUH 6 5HODWHG WR )LJXUH )RFDO /LJKW 6WLPXODWLRQ 'RHV 1RW ,QKLELW /7' LQ +LSSRFDPSDO1HXURQV([SUHVVLQJ3KRWRQ6$%(5 $5HSUHVHQWDWLYHLPDJHVVKRZLQJIRFDOOLJKWVWLPXODWLRQ/6DSSOLHGWRSDUWRIWKHGHQGULWHV LQGLFDWHGE\\HOORZER[HVRIKLSSRFDPSDOQHXURQVH[SUHVVLQJ+$*OX$DQG3KRWRQ6$%(5 ,OOXPLQDWHGLQGLFDWHGE\ZKLWHER[HVUHJLRQRILQWHUHVW>52,@DQG52,DQGXQLOOXPLQDWHG LQGLFDWHGE\UHGER[HV52,DQG52,GHQGULWHVZHUHDQDO\]HGLQ%WRH[DPLQHWKHHIIHFWRI IRFDO/6
%5HSUHVHQWDWLYHLPPXQRF\WRFKHPLFDOVWDLQLQJRIFHOOVXUIDFHUHGDQGWRWDO*OX$EOXHLQ LOOXPLQDWHG>XSSHUSDQHOVIRFDO/6@DQGXQLOOXPLQDWHG>ERWWRPSDQHOVIRFDO/6±@GHQGULWHV DIWHU10'$RUFRQWUROWUHDWPHQWV7KHULJKWJUDSKVLQGLFDWHWKHTXDQWLWDWLYHDQDO\VLVRI10'$ LQGXFHGFKDQJHVLQWKHUDWLRRIWKHVXUIDFHWRWRWDO*OX$IOXRUHVFHQFHLQWHQVLWLHVLQIRFDO/6 DQG/6GHQGULWHV7KHUDWLRLQWKH10'$XQWUHDWHGQHXURQVZDVGHILQHGDVQ FHOOV HDFKIRUIRFDO/6DQGQ FHOOVIRUIRFDO/6 SWZRWDLOHG6WXGHQW¶VWWHVW 'DWDUHSUHVHQWPHDQ6(0
)LJXUH65HODWHGWR)LJXUH1RUPDO(OHFWURSK\VLRORJLFDO3URSHUWLHVRI3XUNLQMHFHOOVLQ $FXWH6OLFHVIURP3&3KRWRQ6$%(50LFH $6SRQWDQHRXVVSLNHVUHFRUGHGIURP3XUNLQMHFHOOVLQDFHOODWWDFKHGYROWDJHFODPSPRGH7KH ULJKWJUDSKVKRZVWKHTXDQWLILFDWLRQRIVSLNHIUHTXHQFLHVLQPhotonSABER-LSLFRQWURODQG3& 3KRWRQ6$%(53XUNLQMHFHOOV
% 3DVVLYH PHPEUDQH SURSHUWLHV RI 3XUNLQMH FHOOV 1R GLIIHUHQFHV LQ PHPEUDQH UHVLVWDQFH RU FDSDFLWDQFHZHUHREVHUYHGEHWZHHQFRQWURODQG3&3KRWRQ6$%(53XUNLQMHFHOOV
& P(36&V UHFRUGHG IURP 3XUNLQMH FHOOV 5HSUHVHQWDWLYH WUDFHV DUH VKRZQ RQ WKH WRS 7KH ERWWRPJUDSKVVKRZWKHTXDQWLWDWLYHDQDO\VHVRIWKHDPSOLWXGHOHIWDQGWKHIUHTXHQF\ULJKWRI P(36&VLQFRQWURODQG3&3KRWRQ6$%(5PLFH
)LJXUH65HODWHGWR)LJXUH$PELHQW5RRP/LJKW'RHV1RW$IIHFWWKH,QGXFWLRQRI/7'
$ 7KH HIIHFW RI DPELHQW URRP OLJKW RQ /7' LQGXFWLRQ &RQMXQFWLYH VWLPXODWLRQV &-VWLP LQGXFHG/7'LQVOLFHVIURP3&3KRWRQ6$%(5PLFHXQGHUDPELHQWURRPOLJKWOX[7KH WUDFHV LQGLFDWH UHSUHVHQWDWLYH 3)(36&V PLQ OHIW DQG PLQ UHG ULJKW DIWHU &-VWLP 6XSHULPSRVHG WUDFHV DUH DOVR SUHVHQWHG LQ WKH ULJKW SDQHOV 7KH ORZHU JUDSK LQGLFDWHV WKH TXDQWLWDWLYHDQDO\VLVRIWKH3)(36&DPSOLWXGHXQGHUDPELHQWURRPOLJKWRSHQFLUFOHVWRJHWKHU ZLWK WKRVH LQ WKH GDUN FRQGLWLRQV ILOOHG FLUFOHV WDNHQ IURP )LJXUH & 7KH DPSOLWXGHV DUH QRUPDOL]HGWRWKHDYHUDJH(36&DPSOLWXGHVEHIRUH&-VWLPQ FHOOVIURPVOLFHVIURPPLFH %6FDWWHUSORWRIWKH3)(36&VDPSOLWXGHPLQDIWHU&-VWLPXQGHUDPELHQWURRPOLJKWRSHQ FLUFOHV DQG LQ WKH GDUN FRQGLWLRQ ILOOHG FLUFOHV WDNHQ IURP )LJXUH & QV QRW VLJQLILFDQW 0DQQ:KLWQH\8WHVW