residual wild type band (Supplementary Fig. 5c) that may be explained by the presence of
|
|
- Eugene Carr
- 6 years ago
- Views:
Transcription
1 doi:1.138/nture9387 Supplementry Text RANK deletion in tumors nd Cre effects. Southern lotting of the tumors tht developed in RANK mm femles showed deletion of RANK, leit we oserved some residul wild type nd (Supplementry Fig. 5c) tht my e explined y the presence of other cell types nd/or escper cells. We did not oserve differences in tumor onset in Cre-negtive control femles nd littermtes expressing the MMTV-Cre trnsgene indicting tht Cre expression per se does not lter tumor incidence in the MPA/DMBA mmmry tumor model (Supplementry Fig. 5d). Gene expression profiling. Gene expression profiling of mmmry crcinoms from control nd RANK mm femles showed distinctive differences in their moleculr signtures s ssessed y gene clustering (Supplementry Fig. 7). Moreover, using gene set enrichment nlyses (GSEA), genes nnotted to TGFβ signling (TOB1 pthwy), oxidtive phosphoryltion, mitochondril ftty cid β-oxidtion, specific trnscriptionl repressor ctivity, PPRG signling, epithelil to mesenchyml trnsition (EMT), nd MMP ctivity were enriched in tumors from control mice (Supplementry Fig. 7). By contrst, mmmry tumors from RANK mm femles showed enrichment for the p53 hypoxi pthwy, glycolysis, glyconeogenesis, poptosis, polrized growth, nd morphogenesis of n epithelium (Supplementry Fig. 7c). 1
2 RESEARCH tmrankl srankl Shm MPA 3d 6d 3d 6d 45kD 19kD TM RANKL1 N TM RANKL2 N- 1 -C 316 -C 287 -ctin RANKL3 N- 1 -C 199 c reltive mrna expression 16 shm Shm MPA d Shm MPA e reltive mrna expression f Shm shm MPA PRL-R KO Shm MPA MPA srankl -ctin Supplementry Figure 1. The progesterone-derivtive MPA triggers RANKL expression. -d, Induction of RANKL expression y the progesterone-derivtive MPA. Nulliprous 2
3 RESEARCH wild type femles were s.c. implnted with slow-relese MPA pellets or treted with surgery shm., Expression of trnsmemrne (tm) nd solule (s) RANKL protein ws ssyed on isolted mmmry glnd epithelil cells y Western lot 3 nd 6 dys fter MPA pellet implnttion or shm surgery. β-ctin is shown s loding control. Recominnt murine srankl nd recominnt humn tmrankl protein re shown for moleculr size comprison in the right pnels. Dt re representtive of 8 nimls tested., Schemtic representtion of the three RANKL isoforms dpted from Iked et l. 1. The trnsmemrne domin of RANKL1 nd RANKL2 is indicted (TM, lck ox, spnning 48-71). RANKL2 is lcking of the intrcellulr domin while RANKL3 is lcking spnning the whole intrcellulr domin s well s the trnsmemrne domin. Numers indicte mino cid residues. c, Expression of totl (t) RANKL, RANKL1, RANKL2, nd RANKL3 mrna in purified mmmry epithelil cells fter three dys MPA tretment. β-ctin mrna ws used for normliztion. d, Representtive grose gel of RT-PCR products s in c. e, mrna expression of vrious proteses known to shed RANKL from the surfce of cells. mrna ws determined in purified mmmry epithelil cells y qrt-pcr three dys fter MPA implnttion. β- ctin mrna ws used for normliztion. Dt re shown s fold chnge compred to shm tretment (+/- sem, n=3 per group). f, Induction of solule RANKL protein ssyed on isolted mmmry glnd epithelil cells from control, ut not in prolctin receptor mutnt (PRL-R KO) femles on dy 3 fter s.c. MPA implnttion. Mmmry glnds from shm operted control littermtes nd PRL-R KO femles re shown s controls. P<.5; P <.5; P <.1 (Student s t-test). 3
4 RESEARCH RANK fl/d, K5-Cre Nulliprous Lcttion L1 fl/+ D c nu/nu Clered wt nu/nu RANK fl/d, K5-Cre nu/nu 5x Supplementry Figure 2. RANK fl/ femles crossed to K5-Cre mice show defective loulo-lveolr development in pregnncy., Whole-mount nlyses of mmmry tissue of nulliprous nd lctting (L1) RANK fl/ 4
5 RESEARCH femles crossed with K5-Cre compred to mmmry glnds of control littermtes. Alveoli in gestting wild-type femles (rrow) form loulo-lveolr structures, wheres this development is rrested t rudimentry lveolr ud (rrow) in K5-Cre RANK fl/ femles., Southern lot of purified mmmry epithelil cells derived from RANK flox/ nd RANK flox/ ; K5-Cre femles. The wild type or floxed RANK llele (fl/+; 9.6 k) nd the deleted RANK llele ( ; 3.9 k) re indicted fter digestion of genomic DNA with PvuII nd SphI. c, Whole-mount nlyses of mmmry glnds from control BALBc nude (nu/nu) femles showing norml loulo-lveolr structures t dy 1 of lcttion (L1), norml loulo-lveolr structures t L1 in clered nu/nu mice trnsplnted with wild type mmmry glnd tissue, nd defective loulo-lveolr development t L1 in clered nu/nu mice trnsplnted with RANK fl/ ; K5-Cre mmmry glnd tissue. Ft pds of nu/nu mice fter surgicl clering re lso shown. All mgnifictions X
6 RESEARCH RANK fl/d, MMTV-Cre Nulliprous Nulliprous RANK fl/d, MMTV-Cre c Lcttion L1 Nulliprous fl/+ D Supplementry Figure 3. Norml formtion of lctting mmmry glnd in pregnnt MMTV-Cre, RANK fl/ femles., H&E nlyses of mmmry tissue of nulliprous littermte control nd RANK fl/ ; MMTV-Cre femles showing norml lveolr/ductl epithelil structures. Mgnifictions X 1 (top) nd X 4 (ottom pnels)., Whole-mount nlyses of mmmry tissue of nulliprous nd lctting (L1) RANK fl/ femles crossed with MMTV-Cre compred to mmmry glnds of control littermtes. MMTV-Cre medited deletion of RANK did not ffect formtion of lctting mmmry glnd. c, Southern lot of purified mmmry epithelil cells derived from RANK flox/ nd RANK flox/ ; MMTV-Cre femles. The wild type or floxed RANK llele (fl/+; 9.6 k) nd the deleted RANK llele ( ; 3.9 k) re indicted fter digestion of genomic DNA with PvuII nd SphI. RANK flox/ ; MMTV-Cre nimls re denoted RANK mm herefter. 6
7 RESEARCH fold chnge Ki67 + cells cini (%) low med high % Ki67 positive cells/cinus c cini (%) low med high % Ki67 positive cells/cinus d RANKL PBS e Ki67 positive cells (%) f Numer of CD24 + CD49 high cells x PBS RANKL Shm MPA Supplementry Figure 4. MPA nd RANKL induce prolifertion of mmmry epithelil cells. -c, Quntifiction of epithelil prolifertion in mmmry glnds of control littermtes nd RANK mm femles 3 dys fter shm tretment nd MPA implnttion s shown in Fig. 1d., Dt re shown s reltive chnges in totl Ki67 + epithelil cells compred to shm-operted femles of the respective genotype. At lest 1 mmmry glnd epithelil cells were counted per mouse. n = 3 mice per genotype. P <.5; P <.1 (Student s t-test)., Quntifiction of in situ Ki67 immunostined cells per cinus from mmmry glnds of control littermte nd RANK mm femles on dy 3 fter MPA 7
8 RESEARCH s.c. implnttion. Wheres in control femles ~ 8% of cini showed signs of medium to high prolifertion, more thn 6% of cini in RANK mm femles exhiited very low prolifertion rtes. c, To control for estrus-dependent ckground prolifertion levels, superovulted nd shm operted control littermte nd RANK mm femles were nlysed. At lest 1 cells were counted per mmmry glnd. n = 3 per genotype. In, nd c, dt re shown s percentge of cini/ducts with low (<2% of epithelil cells re Ki67 + ), medium (2-8% of epithelil cells re Ki67 + ) nd high (>8% of epithelil cells re Ki67 + ) numers of proliferting cells (+/- sem). P <.1; P <.3 (Student s t-test). d, Epithelil prolifertion in mmmry glnds of control littermtes nd RANK mm femles 1 dy fter i.p. injection of PBS or RANKL (1µg). Prolifertion ws determined in situ Ki67 immunostining. Mgnifictions X 4. e, Quntifiction of epithelil prolifertion 1 dy fter i.p. injection of PBS or RANKL (1µg). Men percentges of Ki67 positive cells re shown (+/- sem, n=5). P <.3; (Student s t-test). f, Quntifiction of the MSC-enriched CD24 + CD49f high popultion from mmmry glnds of MPA- or shm-treted virgin RANK mm nd littermte control femles. For ll MSCs experiments mice were treted with MPA for 3 dys (+/- sem, n=4 per group). P <.5; P <.1 (Student s t-test). 8
9 RESEARCH Supplementry Figure 5. Delyed onset nd enhnced survivl of RANK mm femle mice in MPA-driven rest cncer.,, MPA induces RANKL expression in mmmry epithelil cells. Nulliprous wild type femles were treted with orl gvge of DMBA or oil vehicle, s.c. implnted with slow- relese MPA pellets, or treted with shm surgery., RANKL mrna ws determined in purified mmmry epithelil cells y qrt-pcr 3 dys fter implnttion/orl gvges. β- ctin mrna ws used for normliztion. Dt re shown s fold chnge compred to shm tretment (+/- sem, n=3 mice per group)., Expression of solule (s) RANKL protein (19kD) ws ssyed on cell lystes from purified mmmry epithelil cells y c fold chnge RANKL mrna oil DMBA shm MPA RANK fl/+ RANK fl/d MMTV-Cre+ MMTV-Cre+ fl/+ D d tumor-free mice (%) srankl 19kD -ctin Cre + Cre time fter lst DMBA (d) e Survivl (%) p< time fter lst DMBA (d)
10 RESEARCH Western lot 3 dys fter tretment with oil vehicle, DMBA, MPA, or shm surgery. β- ctin is shown s loding control. Of note, only MPA ut not DMBA or the oil vehicle lone induced RANKL mrna nd protein expression. c, Representtive Southern lot of MPA/DMBA-induced mmmry tumors derived from RANK flox/+ ; MMTV-Cre nd RANK flox/ ; MMTV-Cre (RANK mm ) femles. The wild type or floxed RANK llele (fl/+; 9.6 k) nd the deleted RANK llele ( ; 3.9 k) re indicted fter digestion of genomic DNA with PvuII nd SphI. All tumors derived from RANK mm femles showed lmost complete deletion. d, Onset of plple mmmry tumors in RANK mm (n=14) nd ge-mtched littermte control femles with MMTV-Cre (Cre+ control; n=13) or without MMTV-Cre (Cre- control; n=9) treted with MPA pellets nd DMBA s indicted in Fig. 2. Dt re shown s percentge of tumor-free mice fter the lst DMBA chllenge. No significnt difference ws found etween the Cre+ nd the Cre- control groups. Medin tumor onset for Cre+ controls ws 9 dys, for Cre- controls 11 dys, nd for RANK mm femles 3 dys fter the lst DMBA tretment. e, Kpln Myer nlysis for overll survivl of RANK mm (n=9) nd ge-mtched littermte control femles (n=9) fter tretment with MPA /DMBA. Medin survivl ws 48 dys for control nd 93 dys fter the lst DMBA tretment for RANK mm femles. 1
11 RESEARCH 7dys fter DMBA E-Cdherin CK14 H&E H&E 22 dys fter DMBA Supplementry Figure 6. Development of squmous denocrcinoms in RANK mm femles.,, Representtive histologicl sections of mmmry tumors isolted from control littermte nd RANK mm femles 7 () nd 22 () dys fter the lst DMBA tretment. H&E nd E-cdherin stinings re shown indicting typicl fetures of ductl denocrcinoms in tumors from control littermtes nd RANK mm femles. Cytokertin 14 (CK14) expression demonstrtes the sl cell origin in oth controls nd RANK mm femles. However, RANK mm femles tend to show chrcteristics of squmous metplsi. All mgnifictions X
12 RESEARCH Gene Sets enriched in control c Gene Sets enriched in TOB1 pthwy TGFB2 TGFB3 CD28 CD3G INFG Oxidtive phosphoryltion NDUFB8 NDUFA5 NDUFA13 NDUFA4 ATP6VB PPA2 CYC1 NDUFA8 NDUFB11 NDUFS6 NDUFS3 ATP5G2 COX6A1 NDUFB5 UQCRQ COX17 NDUFA6 NDUFB3 COX6C ATP6VA2 NDUFV2 COX7A1 NDUFA1 UQCRB COX7B COX8A,5 Mitochondril ftty cid -oxidtion ACADM ACSL3 EHHADH HADHA ACSL1 ACADS Metlloendopeptidse ctivity MMP3 MMP2 ADAMTS2 MMP16 MMP14 ECE2 MEP1A MMP11 MMP15 PITR p53 Hypoxi pthwy AKT1 NFKBIB CDKN1A HIF1A HSPA1A CSNK1A1 Glycolysis & Glyconeogenesis HK1 Apoptosis PG ADH4 ENO1 PKLR LDHC ALDOB BPGM ALDH3A2 ALDH9A1 ALDH3B1 PGA PK LDHA PGK1 PG PFKP TRAF6 CASP3 BCL2L1 TNFRSF1B NFKBIA TNF NTRK1 TFG FAS BOK CASP8 CASP6 MCL1 CASP1 CD4 CASP4 Morphogenesis of n epithelium BCL1 VANGL2 UPK1B UPK3A Trnscriptionl repressor ctivity NCOA1 HDAC5 EID1 HDAC6 PPRG pthwy NCOA1 EP3 LPL CREBBP Site of polrized growth MAPT APBB1 APBB2 PRKCI ANG Epithelil to mesenchyml trnsition TRI8 TGB2 TGFB3 BMP2 HNRPAB CTNNR1 Supplementry Figure 7. Gene expression profiling of RANK mm mmmry cncers. Gene profiling of lte stge tumors from littermte control nd RANK mm femles., Gene clustering from individul tumors isolted from 5 control littermte nd 5 RANK mm femles. The dendrogrm ws generted using hierrchicl clustering. Levels of expression re represented on scle from lue (lowest expression) to red (highest expression).,c, Gene Set Enrichment Anlysis (GSEA) from the sme tumors s shown in, to determine whether defined sets of genes or pthwys show sttisticlly significnt enrichment in the most ltered genes., Gene Sets enriched in mmmry tumors tht developed in control littermte femles. c, Gene Sets enriched in mmmry tumors tht developed in RANK mm femles. GSEA were performed using the GSEA tool t All dt sets re ville upon requests nd will e pulished online t NCBI. 12
13 RESEARCH c tumor-free mice (%) BAC time fter lst DMBA (dys) thymus hert RANK Mx-Cre Mx-Cre RANK D fl liver spleen MECs fl/+ D spleen hert liver thymus Poly I:C BAC fl D d e tumor-free mice (%) (%) time (d) time (dys) NeuT NeuT RANK control fl/+ D NeuT RANK +/D MMTV-Cre+ NeuT RANK fl/d MMTV-Cre+ Supplementry Figure 8. Mmmry cncer onset in Mx-Cre RANK floxed/ nd NeuT RANK mm mice., Onset of plple mmmry tumors in Mx-Cre rnk floxed/ (n=4) nd ge mtched Mx- Cre rnk +/ littermte control femles (n=6) treted with MPA pellets nd DMBA s 13
14 RESEARCH indicted in Fig. 2. The Mx-driven Cre recominse ws ctivted y four poly I:C injections i.p. over the course of 8 dys (2µg in 2 ml PBS). Dt re shown s percentge of tumor free mice fter the lst DMBA chllenge. No significnt differences were found., Southern lot of the non-deleted RANK floxed llele (fl/+) nd fter induction of deletion ( ) in Mx-Cre rnk floxed/ mice. c, Southern lot of vrious orgns fter induction of deletion ( ) in Mx-Cre rnk floxed/ mice. Note tht while vrious degrees of deletion (5-1%) cn e seen in thymus, hert, liver, nd spleen, deletion of the RANK floxed llele ws not induced in purified mmmry epithelil cells (MECs). d, Onset of plple mmmry tumors in NeuT RANK mm (NeuT, MMTV-Cre rnk floxed/ ) femles (n=18) nd ge mtched NeuT (NeuT MMTV-Cre rnk +/ ) control littermte femles (n=17). No significnt difference ws found. e, Southern lot of tumors derived from NeuT MMTVCre rnk floxed/ nd mmmry cncers from littermte NeuT MMTVCre RANK +/ femles to control for RANK deletion in tumors. 14
15 RESEARCH NeuT+ Cytokertin 5 NeuT+ Cytokertin 14 NeuT- NeuT- c NeuT+ E-cdherin NeuT- d 2 e reltive RANKL mrna expression RANK RANKL -ctin Supplementry Figure 9. Tumor formtion in NeuT RANK mm femles. -c, Representtive histologicl sections with typicl denocrcinoms detected in control 15
16 RESEARCH nd NeuT RANK mm femle mice. Cytokertin 5 (), Cytokertin 14 () nd E-cdherin (c) stinings re shown in mmmry glnds of 6-month old femles. Mmmry glnds from littermte RANK mm femles not expressing NeuT (NeuT-) re shown s controls. d, RANKL mrna expression in mmmry epithelil cells (MECs) isolted from either shm- or MPA-treted virgin mice, in MPA-driven mmmry denocrcinoms, nd primry mmmry tumors derived from NeuT, Pym, Neu, nd Neu/TGFβ trnsgenic mice. RANKL mrna ws determined y qrt-pcr. β-ctin mrna ws used for normliztion. Dt re shown s fold chnge compred to shm tretment (+/- sem, n=3 per group). e, RANKL nd RANK protein expression in vrious tumors isolted from the indicted genetic mouse models nd MPA-driven tumors in control RANK /+ nd RANK mm femles. Recominnt murine srankl protein is shown for moleculr size comprison. β-ctin is shown s loding control. 16
17 RESEARCH RANKL RANKL min P-Akt RANK IKK IkB Akt P-Erk1/2 Id2 Id2 p21 P-NFκB CyclinD1 Erk1/2 P-p38 p38 Supplementry Figure 1. RANKL/RANK downstrem signling in MECs., Schemtic outline of geneticlly confirmed signlling pthwys tht control RANKL/RANK medited formtion of lctting mmmry glnd during pregnncy 2, 3., Western lotting for phosphorylted (P) AKT, totl AKT, phosphorylted (P) ERK1/2, totl ERK1/2, phosphorylted (P) p38-mapk, nd p38-mapk in isolted primry mouse mmmry glnd epithelil cells in response to RANKL stimultion (1µg/ml). Dt re representtive of 4 experiments. 17
18 RESEARCH Shm P-IkB MPA srankl RANK D/+ Shm MPA Shm MPA CyclinD1 RANKL -ctin Supplementry Figure 11. MPA ctivtes the NFκB pthwy nd triggers CyclinD1 expression vi RANKL/RANK.,, Activtion of the NFκB pthwy nd CyclinD1 expression y MPA. Nulliprous RANK mm nd littermte control femles were s.c. implnted with slow-relese MPA pellets or treted with shm surgery., In situ immunostining to detect phosphorylted (P) IκBα in mmmry epithelil cells of RANK mm nd littermte control femles fter 3d MPA tretment., Western lot nlysis of CyclinD1 nd RANKL in isolted mmmry epithelil cells from RANK mm nd littermte control femles fter 3d MPA tretment. Recominnt, murine srankl protein is shown for moleculr size comprison. β-ctin is shown s loding control. 18
19 RESEARCH RANKL min P-p65 NFkB p65 NFkB P-IkB IkB P-Erk1/2 Erk1/2 P-p38 p38 1x1 5 cells RANKL time (dys) c d tumor-free mice (%) NFATc1 Dmm time fter lst DMBA (d) 4 reltive NFATc1 mrna expression 2 1,5 1,5 MECs NFATc1 Dmm MPA tumor Supplementry Figure 12. RANKL/RANK downstrem signling pthwys., Western lotting for phosphorylted (P) p65 NFκB, totl p65 NFκB, phosphorylted (P) IκBα, totl IκBα, phosphorylted (P) ERK1/2, totl ERK1/2, phosphorylted (P) p38-mapk, nd p38-mapk in humn SKBR3 rest cncer cells in response to RANKL stimultion (1µg/ml). Dt re representtive of 3 experiments., Growth curve of SKBR3 rest cncer cells cultured in norml growth medium (control, DMEM supplemented with 1% FCS) or in the presence of RANKL (1µg/ml). Cell numers were determined y counting live cells (trypn lue exclusion) over 3 dys. c, Onset of plple mmmry tumors in NFATc1 mm (n=1) nd ge mtched littermte control (n=16) femles treted with MPA pellets nd DMBA. Dt re shown s percentge of tumor free mice fter the lst DMBA chllenge. No significnt difference ws found. d, Quntifiction of NFATc1 mrna expression in purified mmmry epithelil cells (MECs) nd MPA-driven mmmry tumors from NFATc1 mm nd littermte control femles. mrna ws determined y qrt-pcr. β-ctin mrna ws used for normliztion. Dt re shown s fold chnge compred to control (+/- sem, n=5 per group). P <.5 (Student s t-test). 19
20 RESEARCH MECs hours fter g-irrdition RANKL gh2ax P-Chk1 Chk1 p53 -ctin MECs h 8h MEC 16h 2Gy RANKL.26 24h MECs 24h 2Gry.44 MECs M4 MECs 11h 2GRy M4 M4 M4 g-irrdition counts MECs RANKL MECs 11h 2GRy RANKL.34 SKB3 8h RANKL 1Gry RANKL.25 MECs 24h 2Gry RANKL M M4 M4 M4 g-irrdition + RANKL c SKBR3 h 8h 24h 48h SKB3 24h M g-irrdition counts SKB3 24h R.32 SKB3 8h RANKL 2Gry RANKL F L 2 - A M4 M4 6 g-irrdition + RANKL Suppl. Figure S13 Supplementry Figure 13. RANKL protects primry murine mmmry epithelil cells nd humn SKBR3 rest cncer cells from poptosis in response to γ-irrdition., Western Blot nlysis for γh2ax, phosphorylted (P) Chk1, totl Chk1, p53 nd β- ctin in isolted primry mouse mmmry glnd epithelil cells in response to γ- irrdition (2 Gry) in the presence (1µg/ml) or sence of RANKL stimultion.,c, FACS nlysis of propidium iodide (PI) stined, mmmry epithelil cells nd c, SKBR3 humn rest cncer cells fter γ-irrdition (2 Gry) in the sence or presence (1µg/ml) of RANKL. Dt re representtive of t lest 3 experiments. Apoptotic cells with DNA content < 2n pper in the su-g1 region. Percent of cells in su-g1 (), G1-phse (), S/G2/M-phse () s well s polyploid cells with DNA content > 4n re given for the indicted time points. 2
21 SKB3 24h D.27 SKB3 36h DR test next dy M4 SKB3 36h D test next dy.36 M4 M RESEARCH MECs 24h 36h M 5 SKBR3 24h SKB3 24h h M MECs 24h untreted.15 MECs 36h R.18 SKB3 24h R.26 SKB3 24h R.5 RANKL M RANKL M4 M4 Dox counts MECs 24h D/R.18 MECs 36h D F L 2 - A M Dox counts Dox + RANKL MECs 24h D R nchhltig F L 2 - A MECs 36h D/R M Dox + RANKL 11 SKB3 24h DR M c MECs fold chnge RANKL mrna RANKL 6h g-irrdition fter irrdition 6h g-irrdition fter irrdition +RANKL + RANKL Bim Pum Nox Supplementry Figure 14. RANKL protects primry murine mmmry epithelil cells nd humn SKBR3 rest cncer cells from poptosis in response to doxoruicin.,, FACS nlysis of, mmmry epithelil cells nd, SKBR3 humn rest cncer cells incuted with the genotoxic gent doxoruicin (Dox, 1µΜ) in the presence (1µg/ml) or sence of RANKL. Dt re representtive of t lest 3 experiments. Percent of cells in su-g1 (), G1-phse (), S/G2/M-phse () s well s polyploid cells with DNA content >4n re given for 24 nd 36 hours fter doxoruicin tretment. c, mrna expression of pro-poptotic genes Bim, Pum, nd Nox 6 hours fter γ-irrdition (2 Gry) in the presence (1µg/ml) or sence of RANKL stimultion. β-ctin mrna ws used for normliztion. Dt re shown s fold chnge compred to control (+/- sem, n=3 per group). P <.5; P <.5 (Student s t-test). 21
22 RESEARCH IKK Dmm 5Gy + MPA 5Gy % poptosis 2 1,5 1,5 shm MPA 5Gy 5Gy+MPA IKK Dmm Supplementry Figure 15. IKKα medites MPA-induced protection from rdition-induced epithelil poptosis.,, Reduced induction of mmmry epithelil cell poptosis in response to γ-irrdition in IKKα mm femles. Littermtes control nd IKKα mm femles were either shm operted or implnted with n MPA pellet nd γ-irrdited (5 Gry). MPA pellets were implnted 3 dys efore γ-irrdition. 24 hours fter irrdition, poptosis ws detected y immunostining for ctive Cspse 3., Apoptotic nuclei of epithelil cells (rrows) re shown for representtive mmmry glnd sections. Mgnifictions X 4., Quntifiction of mmmry epithelil poptosis. A minimum of 5 nuclei ws counted for ech mouse. Results shown re men vlues (+/- sem, n = 3 mice per group). P <.5 (Student s t-test). 22
23 RESEARCH Densitometry Suppl. Fig. 1 Suppl. Fig. 1f fold increse srankl d 6d 3d 6d Shm MPA fold increse srankl 8 4 Contorl PRL-R KO Contorl PRL-R KO Shm MPA Fig. 3 Fig. 3 fold increse P-IKK fold increse IKK 2 1 RANK KO IKK KO fold increse P-p fold increse P-p RANK KO IKK KO fold increse P-IkB fold increse IkB RANK KO IKK KO time (min) Supplementry Figure 16. Quntifiction of Western lots. Densitometry ws performed on t lest three independent Western lots per experiment. Dt re shown for Western lots in Supplementry Fig. 1, Supplementry Fig. 1f, Fig. 3, nd Fig. 3. Expression vlues for the indicted proteins were normlized to β-ctin loding controls. For quntifiction of phosphoryltion dt were normlized to the respective totl protein nds. P <.5; P <.1 (Student s t-test). 23
24 RESEARCH Supplementl References 1. Iked, T., Ksi, M., Utsuym, M. & Hirokw, K. Determintion of three isoforms of the receptor ctivtor of nucler fctor-kppb lignd nd their differentil expression in one nd thymus. Endocrinology 142, (21). 2. Co, Y. et l. IKKlph provides n essentil link etween RANK signling nd cyclin D1 expression during mmmry glnd development. Cell 17, (21). 3. Kim, N.S. et l. Receptor ctivtor of NF-kppB lignd regultes the prolifertion of mmmry epithelil cells vi Id2. Mol Cell Biol 26, (26). 24
SUPPLEMENTARY INFORMATION
Prentl doi:.8/nture57 Figure S HPMECs LM Cells Cell lines VEGF (ng/ml) Prentl 7. +/-. LM 7. +/-.99 LM 7. +/-.99 Fold COX induction 5 VEGF: - + + + Bevcizum: - - 5 (µg/ml) Reltive MMP LM mock COX MMP LM+
More informationSupplementary Figure 1
doi: 1.138/nture6188 SUPPLEMENTARY INFORMATION Supplementry Figure 1 c CFU-F colonies per 1 5 stroml cells 14 12 1 8 6 4 2 Mtrigel plug Neg. MCF7/Rs MDA-MB-231 * * MCF7/Rs-Lung MDA-MB-231-Lung MCF7/Rs-Kidney
More informationPDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis
Supplementry Informtion PDGF-BB secreted y preosteoclsts induces ngiogenesis during coupling with osteogenesis Hui Xie, Zhung Cui, Long Wng, Zhuying Xi, Yin Hu, Lingling Xin, Chngjun Li, Ling Xie, Jnet
More informationSUPPLEMENTARY INFORMATION
doi:1.138/nture1794 BR EPFs BRI1? ERECTA TMM BSKs YDA PP2A BSU1 BIN2 pbzr1/2 BZR1/2 MKK4/5/7/9 MPK3/6 SPCH Cell growth Stomtl production Supplementry Figure 1. The model of BR nd stomtl signling pthwys.
More informationSupplementary Figure 1
Roles of endoplsmic reticulum stress-medited poptosis in -polrized mcrophges during mycocteril infections Supplementry informtion Yun-Ji Lim, Min-Hee Yi, Ji-Ae Choi, Jung-hwn Lee, Ji-Ye Hn, Sung-Hee Jo,
More informationDOI: 10.1038/nc2331 PCre;Ros26R 12 h induction 48 h induction Vegfr3 i EC c d ib4 24 h induction VEGFR3 e Fold chnge 1.0 0.5 P < 0.05 Vegfr3 i EC Vegfr3 Figure S1 Cre ctivtion leds to genetic deletion
More informationSupplementary Figure S1
Supplementry Figure S1 d MAP2 GFAP e MAP2 GFAP GFAP c f Clindin GFAP Supplementry Figure S1. Neuronl deth nd ltered strocytes in the rin of n ffected child. Neuron specific MAP2 ntiody stining in the hippocmpus
More informationSupplementary figure 1
Supplementry figure 1 Dy 8 post LCMV infection Vsculr Assoc. Prenchym Dy 3 post LCMV infection 1 5 6.7.29 1 4 1 3 1 2 88.9 4.16 1 2 1 3 1 4 1 5 1 5 1.59 5.97 1 4 1 3 1 2 21.4 71 1 2 1 3 1 4 1 5 1 5.59.22
More informationTNF-α (pg/ml) IL-6 (ng/ml)
Xio, et l., Supplementry Figure 1 IL-6 (ng/ml) TNF-α (pg/ml) 16 12 8 4 1,4 1,2 1, 8 6 4 2 med Cl / Pm3CSK4 zymosn curdln Poly (I:C) LPS flgelin MALP-2 imiquimod R848 CpG TNF-α (pg/ml) IL-6 (ng/ml) 2 1.6
More informationSUPPLEMENTARY INFORMATION
doi:1.138/nture1228 Totl Cell Numer (cells/μl of lood) 12 1 8 6 4 2 d Peripherl Blood 2 4 7 Time (d) fter nti-cd3 i.p. + TCRβ + IL17A + cells (%) 7 6 5 4 3 2 1 Totl Cell Numer (x1 3 ) 8 7 6 5 4 3 2 1 %
More informationAcute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons
nd grdul increses in BDNF concentrtion elicit distinct signling nd functions in neurons Yunyun Ji,, Yun Lu, Feng Yng, Wnhu Shen, Tin Tze-Tsng Tng,, Linyin Feng, Shumin Dun, nd Bi Lu,.. - Grdul (normlized
More informationSUPPLEMENTARY INFORMATION
SUPPEMENTARY INFORMATION DOI: 1.138/ncb956 Norml CIS Invsive crcinom 4 months months b Bldder #1 Bldder # Bldder #3 6 months (Invsive crcinom) Supplementry Figure 1 Mouse model of bldder cncer. () Schemtic
More informationSUPPLEMENTARY INFORMATION
X p -lu c ct ivi ty doi:.8/nture8 S CsA - THA + DAPI Merge FSK THA TUN Supplementry Figure : A. Ad-Xp luc ctivity in primry heptocytes exposed to FSK, THA, or TUN s indicted. Luciferse ctivity normlized
More information% cells forming Neurospheres 81 ± 6 % 0 % 2.6 ± 0.7 % 76 ± 8 % 0 % 3.4 ± 0.6 % 83 ± 5 % 0 % 2.4 ± 0.9 % 89 ± 5 % 3 ± 1.5 % Total 10, ± 6 % 0 %
Bo et l., Suppl. Tle 1 Supplementl Tle 1. Neurosphere formtion nd tumorigencity is enriched within the tumour cell popultions derived from humn primry glioms nd gliom xenogrfts. GBM smples or Gliom xenogrfts
More informationSupplementary Figure S1
Supplementry Figure S Connexin4 TroponinI Merge Plsm memrne Met Intrcellulr Met Supplementry Figure S H9c rt crdiomyolsts cell line. () Immunofluorescence of crdic mrkers: Connexin4 (green) nd TroponinI
More informationSUPPLEMENTARY INFORMATION
doi: 10.1038/nture07679 Emryonic Stem (ES) cell Hemngiolst Flk1 + Blst Colony 3 to 3.5 Dys 3-4 Dys ES differentition Sort of Flk1 + cells Supplementry Figure 1. Chrcteristion of lst colony development.
More informationAlimonti_Supplementary Figure 1. Pten +/- Pten + Pten. Pten hy. β-actin. Pten - wt hy/+ +/- wt hy/+ +/- Pten. Pten. Relative Protein level (% )
Alimonti_Supplementry Figure 1 hy 3 4 5 3 Neo 4 5 5 Proe 5 Proe hy/ hy/ /- - 3 6 Neo β-tin d Reltive Protein level (% ) 15 1 5 hy/ /- Reltive Gene Expr. (% ) 15 1 5 hy/ /- Supplementry Figure 1 Chrteriztion
More informationSupplementary information for: Low bone mass and changes in the osteocyte network in mice lacking autophagy in the osteoblast lineage
Supplementry informtion for: Low one mss nd chnges in the osteocyte network in mice lcking utophgy in the osteolst linege Mrilin Piemontese, Meld Onl, Jinhu Xiong, Li Hn, Jeff D. Thostenson, Mri Almeid,
More informationSUPPLEMENTARY INFORMATION
doi: 1.138/nture862 humn hr. 21q MRPL39 murine Chr.16 Mrpl39 Dyrk1A Runx1 murine Chr. 17 ZNF295 Ets2 Znf295 murine Chr. 1 COL18A1 -/- lot: nti-dscr1 IgG hevy hin DSCR1 DSCR1 expression reltive to hevy
More informationSUPPLEMENTARY INFORMATION
. Norml Physiologicl Conditions. SIRT1 Loss-of-Function S1. Model for the role of SIRT1 in the regultion of memory nd plsticity. () Our findings suggest tht SIRT1 normlly functions in coopertion with YY1,
More informationMolecular Analysis of BRCA1 in Human Breast Cancer. Cells Under Oxidative Stress
Moleculr Anlysis of BRCA1 in Humn Brest Cncer Cells Under Oxidtive Stress Brin L. Gilmore 1, Ynping Ling 1, Crly E. Winton 1,2, Ky Ptel 1, Vsile Krgeorge 1, A. Cmeron Vrno 1,3, Willim Dernley 1, Zhi Sheng
More information* * * * * liver kidney ileum. Supplementary Fig.S1
Supplementry Fig.S1 liver kidney ileum Fig.S1. Orlly delivered Fexrmine is intestinlly-restricted Mice received vehicle or Fexrmine (100mg/kg) vi per os (PO) or intrperitonel (IP) injection for 5 dys (n=3/group).
More informationSUPPLEMENTARY INFORMATION
DOI: 1.138/n358 TLR2 nd MyD88 expression in murine mmmry epithelil supopultions. CD24 min plus MRU Myo-epithelil Luminl progenitor (CD61 pos ) Mture luminl (CD61 neg ) CD49f CD61 Reltive expression Krt5
More informationSUPPLEMENTARY INFORMATION
SUPPLEMENTARY INFORMATION doi:10.1038/nture11225 Numer of OTUs sed on 3% distnce Numer of 16s rrna-sed V2-V4 tg sequences LF MF PUFA Supplementry Figure 1. High-ft diets decrese the richness nd diversity
More informationNappHS. rrna. transcript abundance. NappHS relative con W+W 0.8. nicotine [µg mg -1 FM]
(A) W+OS 3 min 6 min con L S L S RNA loding control NppHS rrna (B) (C) 8 1 k NppHS reltive trnscript undnce 6 4.5 *** *** *** *** 3 k. + + + line 1 line (D) nicotine [µg mg -1 FM] 1..8.4. con W+W Supplementl
More informationSUPPLEMENTARY INFORMATION
DOI: 1.138/nc286 Figure S1 e f Medium DMSO AktVIII PP242 Rp S6K1-I Gr1 + + + + + + Strvtion + + + + + IB: Akt-pT38 IB: Akt K-pT389 K IB: Rptor Gr1 shs6k1-a shs6k1-b shs6k1-c shrictor shrptor Gr1 c IB:
More informationSUPPLEMENTARY INFORMATION
SUPPLEMENTARY INFORMATION doi:1.138/nture1188 1mM CCl 2 (min) 3 4 6 CCl 2 (mm) for 4min.1. 1 (mm) Pro- d WT GdCl 3 R-68 -/- P2x7r -/- -/- Csp1 -/- WT -/- P2x7r -/- -/- Csp1 -/- Csp1 (p2) (p17) Pro-Csp1
More informationD14 D 10 D 7. Untreated CYTOXAN 5-FU
Dipeptidylpeptidse Negtively Regultes Colony Stimulting Fctor Activity nd Stress Hemtopoiesis. Hl E. Broxmeyer, Jonthn Hoggtt, Hether A. O Lery, Chrlie Mntel, Brhmnnd R. Chitteti, Scott Cooper, Steven
More informationUlk λ PPase. 32 P-Ulk1 32 P-GST-TSC2. Ulk1 GST (TSC2) : Ha-Ulk1 : AMPK. WB: Ha (Ulk1) : Glu. h CON - Glu - A.A WB: LC3 AMPK-WT AMPK-DKO
DOI: 10.1038/ncb2152 C.C + - + - : Glu b Ulk1 - - + λ PPse c AMPK + - + + : ATP P-GST-TSC2 WB: Flg (Ulk1) WB Ulk1 WB: H (Ulk1) GST (TSC2) C.C d e WT K46R - + - + : H-Ulk1 : AMPK - + - + + + AMPK H-Ulk1
More informationSUPPLEMENTARY INFORMATION
doi:1.138/nture17 Men tumour dimeter (mm) 2 Rg2-/- 2 1 2 2 1 Control IgG!-CD8!-CD4 1 2 3 1 2 3 c Men tumour dimeter (mm) 2 2 1 d Ifnr1-/- Rg2-/- 2 2 1 Ifngr1-/- d42m1!ic 1 2 3 Dys post trnsplnt 1 2 3 Supplementry
More informationSUPPLEMENTARY INFORMATION
doi:0.08/nture0987 SUPPLEMENTARY FIGURE Structure of rbbit Xist gene. Exons re shown in boxes with romn numbers, introns in thin lines. Arrows indicte the locliztion of primers used for mplifiction. WWW.NATURE.COM/NATURE
More informationSupplementary Information
Supplementry Informtion Cutneous immuno-surveillnce nd regultion of inflmmtion y group 2 innte lymphoid cells Ben Roediger, Ryn Kyle, Kwok Ho Yip, Nitl Sumri, Thoms V. Guy, Brin S. Kim, Andrew J. Mitchell,
More informationSUPPLEMENTARY INFORMATION
SUPPLEMEARY IFORMAIO doi:./nture correction to Supplementry Informtion Adenom-linked rrier defects nd microil products drive IL-/IL-7-medited tumour growth Sergei I. Grivennikov, Kepeng Wng, Dniel Mucid,
More informationSUPPLEMENTARY INFORMATION
Supplementry Figure 1. Genertion of N- nd C-tgged cyclin D1 knock-in mice., N-tgged cyclin D1 gene trgeting construct, cyclin D1 genomic locus, cyclin D1 locus following homologous recomintion (trgeted
More informationHeparanase promotes tumor infiltration and antitumor activity of CAR-redirected T- lymphocytes
Supporting Online Mteril for Heprnse promotes tumor infiltrtion nd ntitumor ctivity of -redirected T- lymphocytes IgnzioCrun, Brr Svoldo, VlentinHoyos, Gerrit Weer, Ho Liu, Eugene S. Kim, Michel M. Ittmnn,
More informationCopy Number ID2 MYCN ID2 MYCN. Copy Number MYCN DDX1 ID2 KIDINS220 MBOAT2 ID2
Copy Numer Copy Numer Copy Numer Copy Numer DIPG38 DIPG49 ID2 MYCN ID2 MYCN c DIPG01 d DIPG29 ID2 MYCN ID2 MYCN e STNG2 f MYCN DIPG01 Chr. 2 DIPG29 Chr. 1 MYCN DDX1 Chr. 2 ID2 KIDINS220 MBOAT2 ID2 Supplementry
More information2018 American Diabetes Association. Published online at
Supplementry Figure S1. Ft-1 mice exhibit reduced diposity when fed n HFHS diet. WT nd ft-1 mice were fed either control or n HFHS diet for 18 weeks. A: Representtive photogrphs for side-by-side comprison
More informationSUPPLEMENTARY INFORMATION
DOI: 10.1038/nc2824 Hcn4 Tx5 Mlc2 c Hcn4- ISH d Tx5- ISH e Mlc2-ISH Hcn4-ISH f e Tx5-ISH f -ISH Figure S1 Section in situ hyridistion nlysis of crescent stge mouse emryos (E7.5). () More nterior section
More information*** *** *** *** T-cells T-ALL. T-cells T-ALL. T-cells T-ALL. T-cells T-ALL. T-cells T-ALL. Relative ATP content. Relative ATP content RLU RLU
RLU Events 1 1 1 Luciferin (μm) T-cells T-ALL 1 1 Time (min) T-cells T-ALL 1 1 1 1 DCF-DA Reltive ATP content....1.1.. T-cells T-ALL RLU 1 1 T-cells T-ALL Luciferin (μm) 1 1 Time (min) c d Control e DCFH-DA
More informationSupplementary Figure 1
Supplementry Figure 1 Ncor1 Expression 2. 1.5 1..5. Muscle Liver Lmi Ppropi Kindey Pncres Lung Testis Bone Mrrow Thymus Spleen Peripherl Lymph nods Smll Intestine Ncor1 Expression 1.5 1..5. DN DP SP CD8
More informationMicrotubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome
Supplementry Informtion Microtuule-driven sptil rrngement of mitochondri promotes ctivtion of the NLRP3 inflmmsome Tkum Misw 1,2, Michihiro Tkhm 1,2, Ttsuy Kozki 1,2, Hnn Lee 1,2, Jin Zou 1,2, Ttsuy Sitoh
More informationSupplemental Information. Lymphocytes Negatively Regulate NK Cell Activity. via Qa-1b following Viral Infection
Cell Reports, Volume 21 Supplementl Informtion Lymphocytes Negtively Regulte NK Cell Activity vi Q-1b following Virl Infection Hifeng C. Xu, Jun Hung, Aleksndr A. Pndyr, Elisbeth Lng, Yun Zhung, Christine
More informationExpression of Three Cell Cycle Inhibitors during Development of Adipose Tissue
Expression of Three Cell Cycle Inhiitors during Development of Adipose Tissue Jiin Zhng Deprtment of Animl Sciences Advisor: Michel E. Dvis Co-dvisor: Kichoon Lee Development of niml dipose tissue Hypertrophy
More informationSUPPLEMENTARY INFORMATION
{ OI: 1.138/n31 Srifie n nlyze APs on week 1 s of iet 1 4 6 High-ft iet BrU High-ft iet BrU 4 High-ft iet BrU 6 High-ft iet BrU Lin - Lin - : C34 + : C9 + 1 1 3 1 4 1 5 C45 1 C34 1 1 1 1 3 1 4 1 5 S-1
More informationSupplemental Materials
Supplementl Mterils Cellulose deficiency of shv3svl1 is enhnced y hyper ccumultion of exogenous sucrose vi the plsm memrne sucrose/h symporter SUC1 Trevor H. Yets, Hgit Sorek, Dvid E. Wemmer, Chris R.
More informationSUPPLEMENTARY INFORMATION
Icos-/ CD3 Icos Y181F OT-2 T cells doi:1.138/nture158 IgD Supplementry Figure 1. is required for folliculr locliztion of ctivted helper T cells. Icos nd Icos-/- OT-2 T cells were retrovirlly trnsduced
More informationSUPPLEMENTARY INFORMATION
% ells with ili (mrke y A-Tu) Reltive Luiferse % ells with ili (mrke y Arl13) % ells with ili DOI: 1.138/n2259 A-Tuulin Hoehst % Cilite Non-ilite -Serum 9% 8% 7% 1 6% % 4% +Serum 1 3% 2% 1% % Serum: -
More informationEFFECTS OF AN ACUTE ENTERIC DISEASE CHALLENGE ON IGF-1 AND IGFBP-3 GENE EXPRESSION IN PORCINE SKELETAL MUSCLE
Swine Dy 22 Contents EFFECTS OF AN ACUTE ENTERIC DISEASE CHALLENGE ON IGF-1 AND IGFBP-3 GENE EXPRESSION IN PORCINE SKELETAL MUSCLE B. J. Johnson, J. P. Kyser, J. D. Dunn, A. T. Wyln, S. S. Dritz 1, J.
More informationSUPPLEMENTARY INFORMATION
SUPPLEMENTARY INFORMATION doi:.8/nture89 4 4 Ilr -/- Ilr -/- Ilr -/- Cspse- -/- As -/- Nlrp -/- Il8 -/- Ilr -/- Supplementl figure. Inresed severity of NASH in inflmmsome-defiient mie, ut not in Ilr-defiient
More informationSUPPLEMENTARY INFORMATION
DOI: 1.13/n7 Reltive Pprg mrna 3 1 1 Time (weeks) Interspulr Inguinl Epididyml Reltive undne..1.5. - 5 5-51 51-1 1-7 7 - - 1 1-1 Lipid droplet size ( m ) 1-3 3 - - - 1 1-1 1-1 1-175 175-3 3-31 31-5 >5
More informationPrimers used for real time qpcr
Supplementry Tble 1. Primers used for rel time qpcr Gene Accession number Forwrd/reverse primers Tgfα Tgfβ1 Hgf Cyclin A2 Cyclin B1 Cyclin D1 Cyclin E1 FoxM1 p21 Lrt Cyp26A1 CrbpI Rrβ Bcmo1 Bcmo2 NM_31199
More informationCheckMate 153: Randomized Results of Continuous vs 1-Year Fixed-Duration Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer
CheckMte 53: Rndomized Results of Continuous vs -Yer Fixed-Durtion Nivolumb in Ptients With Advnced Non-Smll Cell Lung Cncer Abstrct 297O Spigel DR, McCleod M, Hussein MA, Wterhouse DM, Einhorn L, Horn
More informationNdfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4 þ effector T cells
Received 4 Jul 15 Accepted 9 Fe 16 Pulished 18 Apr 16 DOI: 1.138/ncomms116 OPEN Ndfip-medited degrdtion of Jk1 tunes cytokine signlling to limit expnsion of CD4 þ effector T cells Clire E. O Lery 1, Christopher
More informationsupplementary information
DOI: 10.1038/nc2089 H3K4me1 H3K4me1 H3K4me1 H3K4me1 H3K4me1 H3K4me1 5 PN N1-2 PN H3K4me1 H3K4me1 H3K4me1 2-cell stge 2-c st cell ge Figure S1 Pttern of loclistion of H3K4me1 () nd () during zygotic development
More informationSUPPLEMENTARY INFORMATION
doi:10.1038/nture09973 Plsm Memrne Phgosome TLR1/2/4 ROS Mitochondrion ROS OXPHOS Complex I ROS TRAF6 NADPH Oxidse Supplementry Figure 1 Model detiling the roles of mitochondril ROS in mcrophge cteril
More informationSUPPLEMENTARY INFORMATION
DOI:.38/nc393 Nnog DAPI Nnog/DAPI c-jun DAPI c-jun/dapi c e Reltive expression to Gpdh mescs ( Feeder free) mescs ( Feeder) MEFs.5 MEFs ipscs ESCs..5 p=.24 p=.483 p=.22. JunB JunD Fos Fr Fr2 ATF2 ATF3
More informationClinical Study Report Synopsis Drug Substance Naloxegol Study Code D3820C00018 Edition Number 1 Date 01 February 2013 EudraCT Number
EudrCT Number 2012-001531-31 A Phse I, Rndomised, Open-lbel, 3-wy Cross-over Study in Helthy Volunteers to Demonstrte the Bioequivlence of the Nloxegol 25 mg Commercil nd Phse III Formultions nd to Assess
More informationDefective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome
correction notice Nt. Med. 17, 726 731 (2011) Defective Wnt-dependent cereellr midline fusion in mouse model of Jouert syndrome Mdeline A Lncster, Dipik J Gopl, Joon Kim, Shr N Sleem, Jennifer L Silhvy,
More informationSupplementary Information Titles
Supplementry Informtion Titles Journl: Nture Medicine Article Title: Corresponding Author: Modelling colorectl cncer using CRISPR-Cs9-medited engineering of humn intestinl orgnoids Toshiro Sto Supplementry
More informationSUPPLEMENTARY INFORMATION
doi:10.1038/nture09663 Scrmle shnlrp3 shcsp1 IL-1β (p17) IL-1β (pg/ml) 2000 1500 1000 500 Wt Nlrp3-/- Ipf-/- 0 APDC IL-1β (p17) Supplementl Figure 1. Mitochondril ROS cn trigger NLRP3 inflmmsome ctivtion,
More informationSUPPLEMENTARY INFORMATION
doi:0.08/nture078 RNse VifHA VifHA βctin 6 Cell lyste IP: ntiha MG VifHA VifHA β ctin 6 7 Cell lyste IP: ntiha Supplementry Figure. Effect of RNse nd MG tretment on the Vif interction., RNse tretment does
More informationSupplementary Figure 1
Supplementry Figure 1 c d Wistr SHR Wistr AF-353 SHR AF-353 n = 6 n = 6 n = 28 n = 3 n = 12 n = 12 Supplementry Figure 1 Neurophysiologicl properties of petrosl chemoreceptive neurones in Wistr nd SH rts.
More informationSUPPLEMENTARY INFORMATION
TM TM tip link horizontl top connectors 1 leucine-rich (21 %) otoncorin-like 1809 ntigenic peptides B D signl peptide hydrophoic segment proline/threonine-rich (79 %) Supplementry Figure 1. () The outer
More informationSupplementary Information
Supplementry Informtion Non-nonil prevents skeletl ging n inflmmtion y inhiiting NF-κB Bo Yu, Ji Chng, Yunsong Liu, Jiong Li, Kreen Kevork, Khli Al Hezimi, Dn T. Grves, No-Hee Prk, Cun-Yu Wng Supplementry
More informationmir-212 and mir-132 are required for epithelial stromal interactions necessary for mouse mammary gland development
mir-212 nd mir-132 re required for epithelil stroml interctions necessry for mouse mmmry glnd development Ahmet Ucr 1,5, Vid Vfizdeh 2, Huertus Jrry 3, Jn Fiedler 4, Petr A B Klemmt 2, Thoms Thum 4, Bernd
More informationType II monocytes modulate T cell-mediated central nervous system autoimmunity
Type II monocytes modulte T cell-medited centrl nervous system utoimmunity Mrtin S. Weer, Thoms Prod homme, Swsn Youssef, Shnnon E. Dunn, Cynthi D. Rundle, Lind Lee, Jun C. Ptrroyo, Olf Stüve, Rymond A.
More informationSUPPLEMENTARY INFORMATION
doi:.3/nture93 d 5 Rttlesnke DRG (reds) Rttlesnke TG (reds) c 3 TRPV1 other TRPs 1 1 3 Non-pit snke TG (reds) SFig. 1 5 5 3 other TRPs TRPV1 1 1 3 Non-pit snke DRG (reds) 5 Antomy of the pit orgn nd comprison
More informationSUPPLEMENTARY INFORMATION
doi:.38/nture99 Dy Dy Dy 3 Dy 4 Bleed INDO INDO INDO INDO INDO INDO INDO INDO 3 7 CFU-GM/ml lood 6 4 3 Indomethcin Biclein + Indo + Bcln c WBC PMN LYMPH MONO RBC PLT Ctrl 7.4±.9.4±.8.4±.39.37±.6 8.88±.
More informationCritical role of c-kit in beta cell function: increased insulin secretion and protection against diabetes in a mouse model
Dietologi (1) 55:14 5 DOI 1.17/s15-1-5-5 ARTICLE Criticl role of c-kit in et cell function: incresed insulin secretion nd protection ginst dietes in mouse model Z. C. Feng & J. Li & B. A. Turco & M. Riopel
More informationSupplementary Figure S1
Supplementry Figure S1 - UTR m - 3HA - 2-1 hgh - 1 Uiquitin *! *! lk distl promoter m K3R/ K121R-3HA UTR hgh founder lines - HA - - founder lines TG- E1 L A2 B1 F9 G6 H4 H6 B C D2 G1 H3 J2 L - 7 IP: lk
More informationHistone H2AX is integral to hypoxia-driven neovascularization
Histone H2AX is integrl to hypoxi-driven neovsculriztion Mtin Economopoulou 1,5, Hrld F Lnger 1,5, Arkdy Celeste 1, Vleri V Orlov 1, Eun Young Choi 1, Mingcho M 2, Athnssios Vssilopoulos 3, Els Cllen 1,
More informationFoxP3 + regulatory CD4 T cells control the generation of functional CD8 memory
Received Fe Accepted 6 Jul Pulished 7 Aug DOI:.8/ncomms99 FoxP + regultory CD T cells control the genertion of functionl memory M.G. de Goër de Herve,,, S. Jfour,,, M. Vllée, & Y. Toufik, During the primry
More informationSupplementary Materials. Viral delivery of mir-196a ameliorates the SBMA phenotype via the silencing of CELF2
Supplementry Mterils Virl delivery of mir-96 meliortes the SBMA phenotype vi the silencing of CELF2 Yu Miyzki, Hiroki Adchi, Mshis Ktsuno, Mkoto Minmiym, Yue-Mei Jing, Zhe Hung, Hideki Doi, Shinjiro Mtsumoto,
More informationSupplementary information
Supplementry informtion Unsturted liphtic lcohol s nturl lignd for mouse odornt receptor Keiichi Yoshikw, Hiroki Nkgw, Noki Mori, Hidenori Wtne nd Kzushige Touhr* Deprtment of Applied Biologicl Chemistry,
More informationThe effect of dietary α-linolenic acid levels on regulation of omega-3 lipid synthesis in rat
The effect of dietry α-linolenic cid levels on regultion of omeg-3 lipid synthesis in rt Wei-Chun Tu School of Agriculture Food nd Wine The University of Adelide Conversion of PUFA to LCPUFA PUFA LCPUFA
More informationPHYSIOLOGICAL AND PROTEOMIC RESPONSES OF TOBACCO SEEDLINGS EXPOSED TO SILVER NANOPARTICLES
PHYSIOLOGICAL AND PROTEOMIC RESPONSES OF TOBACCO SEEDLINGS EXPOSED TO SILVER NANOPARTICLES Rent Bi Deprtment of Biology, Fculty of Science, University of Zgre INTRODUCTION Nnoprticles (NPs) Silver nnoprticles
More informationA rt i c l e s. a Events (% of max)
Continuous requirement for the TCR in regultory T cell function Andrew G Levine 1,, Aron Arvey 1,,4, Wei Jin 1,,4 & Alexnder Y Rudensky 1 3 14 Nture Americ, Inc. All rights reserved. Foxp3 + regultory
More informationGinsenoside from Panax ginseng Meyer Enhances the Cytotoxic and Apoptotic Effect of Cisplatin in A549 Human Lung Cancer Cells
Ginsenoside from Pnx ginseng Meyer Enhnces the ytotoxic nd Apoptotic Effect of ispltin in A549 Humn Lung ncer ells J. K. PARK, V. ASTRO-AEITUNO, S. AHN, S. Y. SIMU 1, M. H. SIDDIQI 1, D. H. KIM, Y. J.
More informationTLR7 induces anergy in human CD4 + T cells
TLR7 induces nergy in humn CD T cells Mrgrit Dominguez-Villr 1, Anne-Sophie Gutron 1, Mrine de Mrcken 1, Mrl J Keller & Dvid A Hfler 1 The recognition of microil ptterns y Toll-like receptors (TLRs) is
More informationSUPPLEMENTARY INFORMATION
DOI: 1.138/n2977 Numer of ells per field 6 4 2 P =.1 Orthotopi eum Normlized ventrl photon flux 1E7 1E6 1E5 1E4 1E3 1E2 n=8 n=9 1 2 3 4 5 6 Dys Dy54 1.5E5 2.4E7 d Mie with lymph node metstsis (%) 1 8 6
More informationARTICLE. E. Pavlova 1, N. Atanassova 1, C. McKinnell 2, R.M. Sharpe 2 1 Institute of Experimental Morphology, Pathology and Anthropology with Museum,
DOI:.554/5YRTIMB..3 OPPOSITE MODELS OF EXPRESSION OF ANDROGEN RECEPTOR (AR) AND RETINOIC ACID RECEPTOR-α (RAR-α) IN THE ONSET OF MALE GERM CELL DEVELOPMENT IN HORMONALLY MANIPULATED RATS E. Pvlov, N. Atnssov,
More information11/7/2011. Disclosures. Psoriatic Arthritis (PsA) DC-STAMP I II III IV. None
unstimulte stimulte 11/7/11 Ientifiction of Unique Suset + (Denritic Cell-Specific Trnsmemrne Protein) T cells with Th17 Signture in Psoritic rthritis () Ptients Disclosures None Y.H. Chiu, E.M. Schwrz,
More informationEffect of Aqueous Extract of Carica papaya Dry Root Powder on Lactation of Albino Rats
Effect of Aqueous Extrct of Cric ppy Dry Root Powder on Lcttion of Alino Rts G. Tosswnchuntr nd S. Aritjt Deprtment of Biology Fculty of Science Ching Mi University Ching Mi 50200 Thilnd Keywords: mmmry
More informationSupplementary Information. SAMHD1 Restricts HIV-1 Infection in Resting CD4 + T Cells
Supplementry Informtion SAMHD Restricts HIV- Infection in Resting CD T Cells Hnn-Mri Blduf,2,, Xioyu Pn,, Elin Erikson,2, Srh Schmidt, Wqo Dddch 3, Mnj Burggrf, Kristin Schenkov, In Amiel,2, Guido Wnitz
More informationAMPK maintains energy homeostasis and survival in cancer cells via. regulating p38/pgc-1α-mediated mitochondrial biogenesis
SUPPLEMENTARY INFORMATION AMPK mintins energy homeostsis nd survivl in cncer cells vi regulting p38/pgc-1α-medited mitochondril iogenesis Blkrishn Chue 1, Prmnnd Mlvi 1, Shivendr Vikrm Singh 1, Noshd Mohmmd
More informationMERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2
ARTICLE NUMBER: 164 DOI: 1.138/NMICROBIOL.216.4 MERS coronvirus induces poptosis in kidney nd lung y upregulting Smd7 nd FGF2 Mn-Lung Yeung, Ynfeng Yo, Lilong Ji, Jsper F. W. Chn, Kwok-Hung Chn, Kwok-Fn
More informationESM Table 1. Characterisation of the human non-diabetic cohort used for MRIbased assessment of pancreatic fat and insulin secretion via OGTT.
ESM Tle 1. Chrcteristion of the humn non-dietic cohort used for MRIsed ssessment of pncretic ft nd insulin secretion vi OGTT. Trit sex Medin (IQR) 86 femles, 5 mles ge (yers) 4.4 (.5-5.57) BMI (kg/m²).62
More informationThe potential future of targeted radionuclide therapy: implications for occupational exposure? P. Covens
The potentil future of trgeted rdionuclide therpy: implictions for occuptionl exposure? Introduction: Trgeted Rdionuclide Therpy (TRT) Systemic tretment Molecule lbelled with rdionuclide delivers toxic
More informationSUPPLEMENTARY INFORMATION
doi:1.13/nture173 Supplementry Text: Wheel-running ctivity hs secondry effects on ehvior Previous studies utilized wheel-running ctivity to ssy the influence the cycles on circdin rhythms 1, 2. Since wheel
More informationSUPPLEMENTARY INFORMATION
doi:.38/nture73 Glucose SSP THF Methyl- THF Purines 3- PG PHGDH PSAT PSPH Glycine SHMT GSH Lctte Pyruvte ROS TCA Cycle Glucose p53 p Purines 3- PG PHGDH PSAT PSPH Glycine SHMT GSH Lctte Pyruvte ROS TCA
More informationOptimisation of diets for Atlantic cod (Gadus morhua) broodstock: effect of arachidonic acid on egg & larval quality
Optimistion of diets for Atlntic cod (Gdus morhu) roodstock: effect of rchidonic cid on egg & lrvl qulity Dr Gordon Bell, Ms. An Blnco, Dr Bill Roy, Dr Derek Roertson, Dr Jim Henderson nd Mr Richrd Prickett,
More informationTHE EVALUATION OF DEHULLED CANOLA MEAL IN THE DIETS OF GROWING AND FINISHING PIGS
THE EVALUATION OF DEHULLED CANOLA MEAL IN THE DIETS OF GROWING AND FINISHING PIGS THE EVALUATION OF DEHULLED CANOLA MEAL IN THE DIETS OF GROWING AND FINISHING PIGS John F. Ptience nd Doug Gillis SUMMARY
More information% Inhibition of MERS pseudovirus infection. 0 h 0.5 h 1 h 2 h 4 h 6 h Time after virus addition
% Inhiition of MERS pseudovirus infection 1 8 h.5 h 1 h 2 h 4 h 6 h Time fter virus ddition Supplementry Figure S1. Inhiition of on MERS pseudovirus infection t the different intervls postinfection. A
More informationUSE OF SORGHUM-BASED DISTILLERS GRAINS IN DIETS FOR NURSERY AND FINISHING PIGS
Swine Dy 1996 USE OF SORGHUM-BASED DISTILLERS GRAINS IN DIETS FOR NURSERY AND FINISHING PIGS B. W. Senne, J. D. Hncock, I. Mvromichlis, S. L. Johnston, P. S. Sorrell, I. H. Kim, nd R. H. Hines Summry Two
More informationJournal of Hainan Medical University.
132 Journl of Hinn Medicl University 2017; 23(11): 132-136 Journl of Hinn Medicl University http://www.hnykdxxb.com Assessment of the efficcy nd sfety of bronchil rtery perfusion chemotherpy combined with
More informationAxl Promotes Cutaneous Squamous Cell Carcinoma Survival through Negative Regulation of Pro-Apoptotic Bcl-2 Family Members
ORIGINAL ARTICLE Axl Promotes Cutneous Squmous Cell Crcinom Survivl through Negtive Regultion of Pro-Apoptotic Bcl-2 Fmily Memers Emmnouil S. Ppdkis 1, Monik A. Cichoń 1, Jshmin J. Vys 1, Nkul Ptel 1,
More informationIrs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling
Irs-2 coordintes Igf-1 receptor-medited β-cell development nd peripherl insulin signlling Dominic J. Withers 1,2 *, Deorh J. Burks 1 *, Hether H. Towery 1, Shri L. Altmuro 1, Crrie L. Flint 1 & Morris
More informationEFFECTS OF INGREDIENT AND WHOLE DIET IRRADIATION ON NURSERY PIG PERFORMANCE
Swine Dy 21 EFFECTS OF INGREDIENT AND WHOLE DIET IRRADIATION ON NURSERY PIG PERFORMANCE J. M. DeRouchey, M. D. Tokch, J. L. Nelssen, R. D. Goodbnd, S. S. Dritz 1, J. C. Woodworth, M. J. Webster, B. W.
More informationOne of the most important biological mechanisms of
Brief Report Serum Thymidine Kinse 1 Activity in the Prognosis nd Monitoring of Chemotherpy in Lung Cncer Ptients: A Brief Report Benjmin Nismn, PhD,* Hovv Nechushtn, MD, PhD,* Him Birn, MD, Hds Gntz-Sorotsky,
More informationSUPPLEMENTARY INFORMATION
oi:1.138/nture11943 E12.5-CON E12.5-KO b E14.5-CON E14.5-KO Supplementry Figure S1 Loss of Bmpr1 in the Myf5 + linege oes not result in obvious morphologicl chnges prior to E16.5., b, Hemtoxylin & Eosin
More information