;PMID: 10820437 ;source_file_1910.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..40] = [t:0..40] ;1)sentence:[e:46..156] = [t:46..156] ;2)section:[e:160..215] = [t:160..215] ;3)section:[e:219..295] = [t:219..295] ;4)sentence:[e:299..377] = [t:299..377] ;5)sentence:[e:379..596] = [t:379..596] ;6)sentence:[e:597..765] = [t:597..765] ;7)sentence:[e:767..1069] = [t:767..1069] ;8)sentence:[e:1070..1221] = [t:1070..1221] ;9)sentence:[e:1222..1453] = [t:1222..1453] ;10)sentence:[e:1454..1653] = [t:1454..1653] ;11)sentence:[e:1654..1756] = [t:1654..1756] ;12)sentence:[e:1757..1901] = [t:1757..1901] ;13)sentence:[e:1902..2137] = [t:1902..2137] ;14)sentence:[e:2138..2395] = [t:2138..2395] ;15)sentence:[e:2396..2644] = [t:2396..2644] ;16)section:[e:2645..2676] = [t:2645..2676] ;17)section:[e:2680..2725] = [t:2680..2725] ;section 0 Span:0..40 ;J Neurosci Res. 2000 Jun 1;60(5):656-65. (SEC (FRAG (NNP:[0..1] J) (NNP:[2..10] Neurosci) (NNP:[11..14] Res) (.:[14..15] .) (CD:[16..20] 2000) (JJ:[21..24] Jun) (CD:[25..29] 1;60) (-LRB-:[29..30] -LRB-) (CD:[30..31] 5) (-RRB-:[31..32] -RRB-) (CD:[32..39] :656-65) (.:[39..40] .))) ;sentence 1 Span:46..156 ;Human neuroblastoma SH-SY5Y cell line: neurosteroid-producing cell line ;relying on cytoskeletal organization. ;[85..97]:substance:"neurosteroid" (SENT (NP-HLN (NP (JJ:[46..51] Human) (NN:[52..65] neuroblastoma) (NN:[66..73] SH-SY5Y) (NN:[74..78] cell) (NN:[79..83] line)) (::[83..84] :) (NP (NP (ADJP (NN:[85..97] neurosteroid) (HYPH:[97..98] -) (VBG:[98..107] producing)) (NN:[108..112] cell) (NN:[113..117] line)) (VP (VBG:[118..125] relying) (PP-CLR (IN:[127..129] on) (NP (JJ:[130..142] cytoskeletal) (NN:[143..155] organization))))) (.:[155..156] .))) ;section 2 Span:160..215 ;Guarneri P, Cascio C, Piccoli T, Piccoli F, Guarneri R. (SEC (FRAG (NNP:[160..168] Guarneri) (NNP:[169..171] P,) (NNP:[172..178] Cascio) (NNP:[179..180] C) (,:[180..181] ,) (NNP:[182..189] Piccoli) (NNP:[190..191] T) (,:[191..192] ,) (NNP:[193..200] Piccoli) (NNP:[201..202] F) (,:[202..203] ,) (NNP:[204..212] Guarneri) (NNP:[213..215] R.))) ;section 3 Span:219..295 ;Istituto di Biologia dello Sviluppo, Palermo, Italy. pguarneri@ibs.pa.cnr.it (SEC (FRAG (NNP:[219..227] Istituto) (NNP:[228..230] di) (NNP:[231..239] Biologia) (NNP:[240..245] dello) (NNP:[246..254] Sviluppo) (,:[254..255] ,) (NNP:[256..263] Palermo) (,:[263..264] ,) (NNP:[265..270] Italy) (.:[270..271] .) ('':[272..285] pguarneri@ibs) (VBD:[285..288] .pa) (``:[288..292] .cnr) (NN:[292..295] .it))) ;sentence 4 Span:299..377 ;Pregnenolone, the precursor of all steroids, is synthesized by CNS ;structures. ;[299..311]:substance:"Pregnenolone" ;[317..326]:substance:"precursor" ;[334..342]:substance:"steroids" (SENT (S (NP-SBJ-1 (NP (NN:[299..311] Pregnenolone)) (,:[311..312] ,) (NP (NP (DT:[313..316] the) (NN:[317..326] precursor)) (PP (IN:[327..329] of) (NP (DT:[330..333] all) (NNS:[334..342] steroids))))) (,:[342..343] ,) (VP (VBZ:[344..346] is) (VP (VBN:[347..358] synthesized) (NP-1 (-NONE-:[358..358] *)) (PP (IN:[359..361] by) (NP-LGS (NN:[362..365] CNS) (NNS:[366..376] structures))))) (.:[376..377] .))) ;sentence 5 Span:379..596 ;The synthesis requires an obligatory step involving cholesterol transport to ;mitochondrial cytochrome P450-cholesterol side chain cleavage (cytP450scc), ;although the underlying mechanism(s) are still mostly unknown. ;[431..442]:substance:"cholesterol" ;[471..518]:cyp450:"cytochrome P450-cholesterol side chain cleavage" ;[520..530]:cyp450:"cytP450scc" (SENT (S (NP-SBJ (DT:[379..382] The) (NN:[383..392] synthesis)) (VP (VBZ:[393..401] requires) (NP (NP (DT:[402..404] an) (JJ:[405..415] obligatory) (NN:[416..420] step)) (VP (VBG:[421..430] involving) (NP (NP (NN:[431..442] cholesterol) (NN:[443..452] transport)) (PP (TO:[453..455] to) (NP (NP (JJ:[457..470] mitochondrial) (NML (NML (NN:[471..481] cytochrome) (NN:[482..486] P450)) (HYPH:[486..487] -) (NML (NN:[487..498] cholesterol) (NN:[499..503] side) (NN:[504..509] chain))) (NN:[510..518] cleavage)) (NP (-LRB-:[519..520] -LRB-) (NN:[520..530] cytP450scc) (-RRB-:[530..531] -RRB-))))))) (,:[531..532] ,) (SBAR-ADV (IN:[534..542] although) (S (NP-SBJ (DT:[543..546] the) (VBG:[547..557] underlying) (NNS:[558..570] mechanism-LRB-s-RRB-)) (VP (VBP:[571..574] are) (ADVP (RB:[575..580] still)) (ADJP-PRD (RB:[581..587] mostly) (JJ:[588..595] unknown)))))) (.:[595..596] .))) ;sentence 6 Span:597..765 ;We used the human neuroblastoma SH-SY5Y cell line to investigate cytP450scc ;expression and activity and to establish a role of cytoskeleton in ;pregnenolone synthesis. ;[663..673]:cyp450:"cytP450scc" ;[742..754]:substance:"pregnenolone" (SENT (S (NP-SBJ (PRP:[597..599] We)) (VP (VBD:[600..604] used) (NP (DT:[605..608] the) (JJ:[609..614] human) (NN:[616..629] neuroblastoma) (NN:[630..637] SH-SY5Y) (NN:[638..642] cell) (NN:[643..647] line)) (S-PRP (NP-SBJ (-NONE-:[647..647] *)) (VP (VP (TO:[648..650] to) (VP (VB:[651..662] investigate) (NP (NP (NML-1 (NN:[663..673] cytP450scc)) (NN:[674..684] expression)) (CC:[685..688] and) (NP (NML-1 (-NONE-:[688..688] *P*)) (NN:[690..698] activity))))) (CC:[699..702] and) (VP (TO:[703..705] to) (VP (VB:[706..715] establish) (NP (NP (DT:[716..717] a) (NN:[718..722] role)) (PP (IN:[723..725] of) (NP (NN:[726..738] cytoskeleton)))) (PP-LOC (IN:[739..741] in) (NP (NN:[742..754] pregnenolone) (NN:[755..764] synthesis)))))))) (.:[764..765] .))) ;sentence 7 Span:767..1069 ;Immunocytochemical and biochemical approaches revealed that undifferentiated ;as well as differentiated cells either by retinoic acid (RA) or phorbol ;ester 12-O-tetradecanoylphorbol-13-acetate (TPA), possess cytP450scc and ;rapidly synthesize pregnenolone in the presence of a NADPH-generating ;system. ;[887..900]:substance:"retinoic acid" ;[902..904]:substance:"RA" ;[909..922]:substance:"phorbol ester" ;[924..960]:substance:"12-O-tetradecanoylphorbol-13-acetate" ;[962..965]:substance:"TPA" ;[976..986]:cyp450:"cytP450scc" ;[1011..1023]:substance:"pregnenolone" ;[1045..1050]:substance:"NADPH" (SENT (S (NP-SBJ (NP (JJ:[767..785] Immunocytochemical) (NML-2 (-NONE-:[785..785] *P*))) (CC:[786..789] and) (NP (JJ:[790..801] biochemical) (NML-2 (NNS:[802..812] approaches)))) (VP (VBD:[813..821] revealed) (SBAR (IN:[822..826] that) (S (NP-SBJ (NP (JJ:[827..843] undifferentiated) (NML-1 (-NONE-:[843..843] *P*))) (CONJP (RB:[844..846] as) (RB:[848..852] well) (IN:[853..855] as)) (NP (NP (VBN:[856..870] differentiated) (NML-1 (NNS:[871..876] cells))) (PP (CC:[877..883] either) (IN:[884..886] by) (NP (NP (NP (JJ:[887..895] retinoic) (NN:[896..900] acid)) (NP (-LRB-:[901..902] -LRB-) (NN:[902..904] RA) (-RRB-:[904..905] -RRB-))) (CC:[906..908] or) (NP (NP (NN:[909..916] phorbol) (NN:[917..922] ester) (NN:[924..960] 12-O-tetradecanoylphorbol-13-acetate)) (NP (-LRB-:[961..962] -LRB-) (NN:[962..965] TPA) (-RRB-:[965..966] -RRB-))))))) (,:[966..967] ,) (VP (VP (VBP:[968..975] possess) (NP (NN:[976..986] cytP450scc))) (CC:[987..990] and) (VP (ADVP (RB:[991..998] rapidly)) (VBP:[1000..1010] synthesize) (NP (NN:[1011..1023] pregnenolone)) (PP (IN:[1024..1026] in) (NP (NP (DT:[1027..1030] the) (NN:[1031..1039] presence)) (PP (IN:[1040..1042] of) (NP (DT:[1043..1044] a) (ADJP (NN:[1045..1050] NADPH) (HYPH:[1050..1051] -) (VBG:[1051..1061] generating)) (NN:[1062..1068] system)))))))))) (.:[1068..1069] .))) ;sentence 8 Span:1070..1221 ;The newly neurosteroid formation by SH-SY5Y cells was increased by ;22R-hydroxycholesterol and blocked by the cytP450scc inhibitor, ;aminoglutethimide. ;[1081..1093]:substance:"neurosteroid" ;[1138..1160]:substance:"22R-hydroxycholesterol" ;[1181..1191]:cyp450:"cytP450scc" ;[1192..1201]:substance:"inhibitor" ;[1203..1220]:substance:"aminoglutethimide" (SENT (S (NP-SBJ-1 (NP (DT:[1070..1073] The) (ADJP (RB:[1074..1079] newly) (JJ:[1081..1093] neurosteroid)) (NN:[1094..1103] formation)) (PP (IN:[1104..1106] by) (NP (NN:[1107..1114] SH-SY5Y) (NNS:[1115..1120] cells)))) (VP (VBD:[1121..1124] was) (VP (VP (VBN:[1125..1134] increased) (NP-1 (-NONE-:[1134..1134] *)) (PP (IN:[1135..1137] by) (NP-LGS (NN:[1138..1160] 22R-hydroxycholesterol)))) (CC:[1162..1165] and) (VP (VBN:[1166..1173] blocked) (PP (IN:[1174..1176] by) (NP-LGS (NP (DT:[1177..1180] the) (NN:[1181..1191] cytP450scc) (NN:[1192..1201] inhibitor)) (,:[1201..1202] ,) (NP (NN:[1203..1220] aminoglutethimide))))))) (.:[1220..1221] .))) ;sentence 9 Span:1222..1453 ;When trilostane was used to inhibit 3beta-hydroxysteroid dehydrogenase ;catalyzing pregnenolone conversion into progesterone, a higher pregnenolone ;accumulation occurred in TPA-differentiated cells than in RA-differentiated ;ones. ;[1227..1237]:substance:"trilostane" ;[1259..1293]:substance:"3beta-hydroxysteroid dehydrogenase" ;[1305..1317]:substance:"pregnenolone" ;[1335..1347]:substance:"progesterone" ;[1358..1370]:substance:"pregnenolone" ;[1397..1400]:substance:"TPA" ;[1430..1432]:substance:"RA" (SENT (S (SBAR-ADV (WHADVP-2 (WRB:[1222..1226] When)) (S (NP-SBJ (NN:[1227..1237] trilostane)) (VP (VBD:[1238..1241] was) (VP (VBN:[1243..1247] used) (S-PRP (NP-SBJ (-NONE-:[1247..1247] *)) (VP (TO:[1248..1250] to) (VP (VB:[1251..1258] inhibit) (S (NP-SBJ (NN:[1259..1279] 3beta-hydroxysteroid) (NN:[1280..1293] dehydrogenase)) (VP (VBG:[1294..1304] catalyzing) (NP (NN:[1305..1317] pregnenolone) (NN:[1319..1329] conversion)) (PP (IN:[1330..1334] into) (NP (NN:[1335..1347] progesterone)))))))) (ADVP-TMP-2 (-NONE-:[1347..1347] *T*)))))) (,:[1347..1348] ,) (NP-SBJ (NP (DT:[1349..1350] a) (JJR:[1351..1357] higher) (NN:[1358..1370] pregnenolone) (NN:[1371..1383] accumulation)) (PP-1 (-NONE-:[1383..1383] *ICH*))) (VP (VBD:[1384..1392] occurred) (PP-LOC (IN:[1393..1395] in) (NP (ADJP (NN:[1397..1400] TPA) (HYPH:[1400..1401] -) (VBN:[1401..1415] differentiated)) (NNS:[1416..1421] cells))) (PP-1 (IN:[1422..1426] than) (PP-LOC (IN:[1427..1429] in) (NP (ADJP (NN:[1430..1432] RA) (HYPH:[1432..1433] -) (VBN:[1433..1447] differentiated)) (NNS:[1448..1452] ones))))) (.:[1452..1453] .))) ;sentence 10 Span:1454..1653 ;Although SU 10603, a blocker of 17alpha-hydroxylase/c17,20-lyase enzyme ;involved in DHEA formation from pregnenolone, gave rise to an elevated ;neurosteroid content only in RA-differentiated cells. ;[1463..1471]:substance:"SU 10603" ;[1476..1483]:substance:"blocker" ;[1487..1506]:substance:"17alpha-hydroxylase" ;[1507..1526]:substance:"c17,20-lyase enzyme" ;[1539..1543]:substance:"DHEA" ;[1560..1572]:substance:"pregnenolone" ;[1599..1611]:substance:"neurosteroid" ;[1629..1631]:substance:"RA" (SENT (S (ADVP (IN:[1454..1462] Although)) (NP-SBJ (NP (NN:[1463..1465] SU) (CD:[1466..1471] 10603)) (,:[1471..1472] ,) (NP (NP (NP (DT:[1473..1474] a) (NN:[1476..1483] blocker)) (PP (IN:[1484..1486] of) (NP (NML (NN:[1487..1506] 17alpha-hydroxylase) (SYM:[1506..1507] /) (NN:[1507..1519] c17,20-lyase)) (NN:[1520..1526] enzyme)))) (VP (VBN:[1527..1535] involved) (NP (-NONE-:[1535..1535] *)) (PP-CLR (IN:[1536..1538] in) (NP (NP (NN:[1539..1543] DHEA) (NN:[1544..1553] formation)) (PP (IN:[1555..1559] from) (NP (NN:[1560..1572] pregnenolone)))))))) (,:[1572..1573] ,) (VP (VBD:[1574..1578] gave) (NP-CLR (NN:[1579..1583] rise)) (PP-CLR (TO:[1584..1586] to) (NP (DT:[1587..1589] an) (VBN:[1590..1598] elevated) (JJ:[1599..1611] neurosteroid) (NN:[1612..1619] content))) (PP-LOC (RB:[1620..1624] only) (IN:[1625..1627] in) (NP (ADJP (NN:[1629..1631] RA) (HYPH:[1631..1632] -) (VBN:[1632..1646] differentiated)) (NNS:[1647..1652] cells)))) (.:[1652..1653] .))) ;sentence 11 Span:1654..1756 ;No difference in pregnenolone levels was found in undifferentiated cells ;treated with each inhibitor. ;[1671..1683]:substance:"pregnenolone" ;[1746..1755]:substance:"inhibitor" (SENT (S (NP-SBJ-1 (NP (DT:[1654..1656] No) (NN:[1657..1667] difference)) (PP (IN:[1668..1670] in) (NP (NN:[1671..1683] pregnenolone) (NNS:[1684..1690] levels)))) (VP (VBD:[1691..1694] was) (VP (VBN:[1695..1700] found) (NP-1 (-NONE-:[1700..1700] *)) (PP-LOC (IN:[1701..1703] in) (NP (NP (JJ:[1705..1721] undifferentiated) (NNS:[1722..1727] cells)) (VP (VBN:[1728..1735] treated) (NP (-NONE-:[1735..1735] *)) (PP (IN:[1736..1740] with) (NP (DT:[1741..1745] each) (NN:[1746..1755] inhibitor)))))))) (.:[1755..1756] .))) ;sentence 12 Span:1757..1901 ;Thus, differentiation seems to promote pregnenolone-metabolizing enzyme ;activities that may vary upon phenotypic changes induced by RA or TPA. ;[1797..1829]:substance:"pregnenolone-metabolizing enzyme" ;[1891..1893]:substance:"RA" ;[1897..1900]:substance:"TPA" (SENT (S (ADVP (RB:[1757..1761] Thus)) (,:[1761..1762] ,) (NP-SBJ-2 (NN:[1763..1778] differentiation)) (VP (VBZ:[1779..1784] seems) (S (NP-SBJ-2 (-NONE-:[1784..1784] *)) (VP (TO:[1786..1788] to) (VP (VB:[1789..1796] promote) (NP (NP (ADJP (NN:[1797..1809] pregnenolone) (HYPH:[1809..1810] -) (VBG:[1810..1822] metabolizing)) (NN:[1823..1829] enzyme) (NNS:[1830..1840] activities)) (SBAR (WHNP-1 (WDT:[1841..1845] that)) (S (NP-SBJ-1 (-NONE-:[1845..1845] *T*)) (VP (MD:[1846..1849] may) (VP (VB:[1850..1854] vary) (PP (IN:[1855..1859] upon) (NP (NP (JJ:[1861..1871] phenotypic) (NNS:[1872..1879] changes)) (VP (VBN:[1880..1887] induced) (NP (-NONE-:[1887..1887] *)) (PP (IN:[1888..1890] by) (NP-LGS (NN:[1891..1893] RA) (CC:[1894..1896] or) (NN:[1897..1900] TPA))))))))))))))) (.:[1900..1901] .))) ;sentence 13 Span:1902..2137 ;Treatments of differentiated cells with the microtubule-depolymerizing drug ;colchicine and the actin microfilament-altering agent cytochalasin D ;decreased pregnenolone synthesis without affecting cell viability or ;cytP450scc amount. ;[1974..1978]:substance:"drug" ;[1979..1989]:substance:"colchicine" ;[1998..2033]:substance:"actin microfilament-altering agent" ;[2034..2048]:substance:"cytochalasin D" ;[2059..2071]:substance:"pregnenolone" ;[2119..2129]:cyp450:"cytP450scc" (SENT (S (NP-SBJ (NP (NNS:[1902..1912] Treatments)) (PP (IN:[1913..1915] of) (NP (VBN:[1916..1930] differentiated) (NNS:[1931..1936] cells))) (PP (IN:[1937..1941] with) (NP (NP (NP (DT:[1943..1946] the) (ADJP (NN:[1947..1958] microtubule) (HYPH:[1958..1959] -) (VBG:[1959..1973] depolymerizing)) (NN:[1974..1978] drug)) (NP (NN:[1979..1989] colchicine))) (CC:[1990..1993] and) (NP (NP (DT:[1994..1997] the) (ADJP (NML (NN:[1998..2003] actin) (NN:[2005..2018] microfilament)) (HYPH:[2018..2019] -) (VBG:[2019..2027] altering)) (NN:[2028..2033] agent)) (NP (NN:[2034..2046] cytochalasin) (NN:[2047..2048] D)))))) (VP (VBD:[2049..2058] decreased) (NP (NN:[2059..2071] pregnenolone) (NN:[2072..2081] synthesis)) (PP-MNR (IN:[2083..2090] without) (S-NOM (NP-SBJ (-NONE-:[2090..2090] *)) (VP (VBG:[2091..2100] affecting) (NP (NP (NN:[2101..2105] cell) (NN:[2106..2115] viability)) (CC:[2116..2118] or) (NP (NN:[2119..2129] cytP450scc) (NN:[2130..2136] amount))))))) (.:[2136..2137] .))) ;sentence 14 Span:2138..2395 ;Addition of the cell-permeant cholesterol analogue 22R-hydroxycholesterol ;known to elude cholesterol transport systems induced pregnenolone synthesis, ;however, indicating that perturbations in cytoskeleton likely affect ;endogenous cholesterol transport. ;[2169..2189]:substance:"cholesterol analogue" ;[2190..2212]:substance:"22R-hydroxycholesterol" ;[2229..2240]:substance:"cholesterol" ;[2267..2279]:substance:"pregnenolone" ;[2373..2384]:substance:"cholesterol" (SENT (S (NP-SBJ (NP (NN:[2138..2146] Addition)) (PP (IN:[2147..2149] of) (NP (NP (NP (DT:[2150..2153] the) (ADJP (NN:[2155..2159] cell) (HYPH:[2159..2160] -) (JJ:[2160..2168] permeant)) (NN:[2169..2180] cholesterol) (NN:[2181..2189] analogue)) (NP (NN:[2190..2212] 22R-hydroxycholesterol))) (VP (VBN:[2213..2218] known) (S (NP-SBJ (-NONE-:[2218..2218] *)) (VP (TO:[2219..2221] to) (VP (VB:[2222..2227] elude) (NP (NN:[2229..2240] cholesterol) (NN:[2241..2250] transport) (NNS:[2251..2258] systems))))))))) (VP (VBD:[2259..2266] induced) (NP (NN:[2267..2279] pregnenolone) (NN:[2280..2289] synthesis)) (,:[2289..2290] ,) (ADVP (RB:[2291..2298] however)) (,:[2298..2299] ,) (S-MNR (NP-SBJ (-NONE-:[2299..2299] *)) (VP (VBG:[2301..2311] indicating) (S (IN:[2312..2316] that) (S (NP-SBJ (NP (NNS:[2317..2330] perturbations)) (PP-LOC (IN:[2331..2333] in) (NP (NN:[2334..2346] cytoskeleton)))) (ADVP (RB:[2347..2353] likely)) (VP (VBP:[2354..2360] affect) (NP (JJ:[2361..2371] endogenous) (NN:[2373..2384] cholesterol) (NN:[2385..2394] transport)))))))) (.:[2394..2395] .))) ;sentence 15 Span:2396..2644 ;The relevance of this finding may rest on the observed involvement of ;cytoskeletal organization in such events as neuronal plasticity, cognitive ;function and also neurodegenerative disorders in which neurosteroids have ;been shown to have a part. ;[2598..2611]:substance:"neurosteroids" (SENT (S (NP-SBJ (NP (DT:[2396..2399] The) (NN:[2400..2409] relevance)) (PP (IN:[2410..2412] of) (NP (DT:[2413..2417] this) (NN:[2418..2425] finding)))) (VP (MD:[2426..2429] may) (VP (VB:[2430..2434] rest) (PP (IN:[2435..2437] on) (NP (NP (DT:[2438..2441] the) (VBN:[2442..2450] observed) (NN:[2452..2463] involvement)) (PP (IN:[2464..2466] of) (NP (JJ:[2467..2479] cytoskeletal) (NN:[2480..2492] organization))) (PP-LOC (IN:[2493..2495] in) (NP (NP (JJ:[2496..2500] such) (NNS:[2501..2507] events)) (PP (IN:[2508..2510] as) (NP (NP (JJ:[2511..2519] neuronal) (NN:[2520..2530] plasticity)) (,:[2530..2531] ,) (NP (JJ:[2533..2542] cognitive) (NN:[2543..2551] function)) (CC:[2552..2555] and) (RB:[2556..2560] also) (NP (JJ:[2561..2578] neurodegenerative) (NNS:[2579..2588] disorders)))) (SBAR (WHPP-2 (IN:[2589..2591] in) (WHNP (WDT:[2592..2597] which))) (S (NP-SBJ-1 (NNS:[2598..2611] neurosteroids)) (VP (VBP:[2613..2617] have) (VP (VBN:[2618..2622] been) (VP (VBN:[2623..2628] shown) (S (NP-SBJ-1 (-NONE-:[2628..2628] *)) (VP (TO:[2629..2631] to) (VP (VB:[2632..2636] have) (NP (DT:[2637..2638] a) (NN:[2639..2643] part)) (PP-2 (-NONE-:[2643..2643] *T*)))))))))))))))) (.:[2643..2644] .))) ;section 16 Span:2645..2676 ;Copyright 2000 Wiley-Liss, Inc. (SEC (FRAG (NN:[2645..2654] Copyright) (CD:[2655..2659] 2000) (NNP:[2660..2665] Wiley) (HYPH:[2665..2666] -) (NNP:[2666..2670] Liss) (,:[2670..2671] ,) (NNP:[2672..2676] Inc.))) ;section 17 Span:2680..2725 ;PMID: 10820437 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2680..2684] PMID) (::[2684..2685] :) (CD:[2686..2694] 10820437) (NN:[2695..2696] -LSB-) (NNP:[2696..2702] PubMed) (::[2703..2704] -) (NN:[2705..2712] indexed) (IN:[2713..2716] for) (NNP:[2717..2725] MEDLINE-RSB-)))