This HTML5 document contains 954 embedded RDF statements represented using HTML+Microdata notation.

The embedded RDF content will be recognized by any processor of HTML5 Microdata.

Namespace Prefixes

PrefixIRI
rdfshttp://www.w3.org/2000/01/rdf-schema#
bibohttp://purl.org/ontology/bibo/
n9http://pubannotation.org/docs/sourcedb/PMC/sourceid/
n8http://togows.dbcls.jp/entry/pubmed/
xsdhhttp://www.w3.org/2001/XMLSchema#
n3http://purl.jp/bio/10/colil/id/
n11http://dx.doi.org/
n2http://purl.jp/bio/10/colil/ontology/201303#
n10http://www.ncbi.nlm.nih.gov/pmc/articles/
n4http://purl.org/spar/doco/
dchttp://purl.org/dc/elements/1.1/
rdfhttp://www.w3.org/1999/02/22-rdf-syntax-ns#

Statements

Subject Item
n3:20037648
rdf:type
n2:CitationPaper n2:RelevantPaper n2:ReferencePaper
rdfs:seeAlso
n8:20037648 n9:0 n10:0 n11:10.1371%2Fjournal.pone.0008427
bibo:cites
n3:16923388 n3:15633123 n3:19160484 n3:16288479 n3:9391082 n3:19527669 n3:17936423 n3:17618273 n3:19435897 n3:9508771 n3:8380636 n3:12637748 n3:15083532 n3:12778124 n3:14695306 n3:16554034 n3:10753915 n3:16247023 n3:12149446 n3:17094935 n3:10232591 n3:2116421 n3:12835669 n3:12496086 n3:18495866 n3:16500961 n3:11785963 n3:18045965 n3:15674479 n3:15669099 n3:11746774 n3:18096687 n3:16204049 n3:7983147 n3:18200567 n3:18192374 n3:18362906 n3:11832345 n3:11832346 n3:14657486 n3:17974913 n3:9533763 n3:14757754 n3:17896341 n3:18765526
n2:cocitationWith
n3:16923388 n3:22659352 n3:12697889 n3:18687124 n3:15633123 n3:11739652 n3:15094120 n3:17376432 n3:17712357 n3:9391082 n3:23557398 n3:8017863 n3:22294205 n3:11716069 n3:19160484 n3:10866943 n3:18632979 n3:26312134 n3:19969329 n3:12113106 n3:19672209 n3:21740400 n3:19435897 n3:3005320 n3:20610469 n3:18772396 n3:15516961 n3:21078666 n3:19010882 n3:9508771 n3:13298683 n3:10656685 n3:11170299 n3:15083532 n3:20227367 n3:14695306 n3:9426685 n3:16793885 n3:22118458 n3:19908100 n3:14581339 n3:11390353 n3:15849239 n3:22325265 n3:9857077 n3:19167326 n3:23132927 n3:21736894 n3:16169468 n3:10896208 n3:17040992 n3:23292359 n3:20647762 n3:11904754 n3:2393868 n3:20156433 n3:2116421 n3:18772890 n3:19617536 n3:12231534 n3:15959903 n3:21085685 n3:16141784 n3:25296750 n3:23817592 n3:12388552 n3:18495866 n3:15925768 n3:21447562 n3:23508546 n3:20197409 n3:10571411 n3:16557279 n3:19920151 n3:12297042 n3:25082799 n3:18045965 n3:24627985 n3:19497285 n3:18981465 n3:15549107 n3:17805551 n3:17873890 n3:15674479 n3:22887464 n3:19931152 n3:18215660 n3:10433259 n3:28797528 n3:1339456 n3:15380385 n3:16204054 n3:15269225 n3:16982728 n3:15122314 n3:23963648 n3:26493995 n3:16541395 n3:17898132 n3:17925230 n3:26045979 n3:16293750 n3:25047810 n3:19270154 n3:15459390 n3:21446047 n3:24574362 n3:15466194 n3:24946761 n3:22908231 n3:3555767 n3:25174308 n3:22205943 n3:15695406 n3:19151661 n3:11832345 n3:23470260 n3:18362906 n3:22348389 n3:17971532 n3:19357957 n3:19596356 n3:24962319 n3:9046311 n3:17992095 n3:24068827 n3:15048094 n3:18765526 n3:21474972 n3:19460998 n3:14871821 n3:23899839
n2:hasRelevantBibliographicResourceOf
_:vb421799300 _:vb421799301 _:vb421799302 _:vb421799303 _:vb421799296 _:vb421799297 _:vb421799298 _:vb421799299 _:vb421799308 _:vb421799309 _:vb421799310 _:vb421799311 _:vb421799304 _:vb421799305 _:vb421799306 _:vb421799307 _:vb421799316 _:vb421799317 _:vb421799318 _:vb421799319 _:vb421799312 _:vb421799313 _:vb421799314 _:vb421799315 _:vb421799324 _:vb421799325 _:vb421799326 _:vb421799327 _:vb421799320 _:vb421799321 _:vb421799322 _:vb421799323 _:vb421799332 _:vb421799333 _:vb421799334 _:vb421799335 _:vb421799328 _:vb421799329 _:vb421799330 _:vb421799331 _:vb421799340 _:vb421799341 _:vb421799342 _:vb421799343 _:vb421799336 _:vb421799337 _:vb421799338 _:vb421799339 _:vb421799348 _:vb421799349 _:vb421799350 _:vb421799351 _:vb421799344 _:vb421799345 _:vb421799346 _:vb421799347 _:vb421799356 _:vb421799357 _:vb421799358 _:vb421799359 _:vb421799352 _:vb421799353 _:vb421799354 _:vb421799355 _:vb421799236 _:vb421799237 _:vb421799238 _:vb421799239 _:vb421799232 _:vb421799233 _:vb421799234 _:vb421799235 _:vb421799244 _:vb421799245 _:vb421799246 _:vb421799247 _:vb421799240 _:vb421799241 _:vb421799242 _:vb421799243 _:vb421799252 _:vb421799253 _:vb421799254 _:vb421799255 _:vb421799248 _:vb421799249 _:vb421799250 _:vb421799251 _:vb421799260 _:vb421799261 _:vb421799262 _:vb421799263 _:vb421799256 _:vb421799257 _:vb421799258 _:vb421799259 _:vb421799268 _:vb421799269 _:vb421799270 _:vb421799271 _:vb421799264 _:vb421799265 _:vb421799266 _:vb421799267 _:vb421799276 _:vb421799277 _:vb421799278 _:vb421799279 _:vb421799272 _:vb421799273 _:vb421799274 _:vb421799275 _:vb421799284 _:vb421799285 _:vb421799286 _:vb421799287 _:vb421799280 _:vb421799281 _:vb421799282 _:vb421799283 _:vb421799292 _:vb421799293 _:vb421799294 _:vb421799295 _:vb421799288 _:vb421799289 _:vb421799290 _:vb421799291 _:vb421799230 _:vb421799231 _:vb421799360 _:vb421799361
n2:pmcid
PMC0
bibo:doi
10.1371%2Fjournal.pone.0008427
n4:contains
_:vb6699712 _:vb6699668 _:vb6699687 _:vb6699695
Subject Item
_:vb6699668
rdf:type
n4:Section
dc:title
introduction
n4:contains
_:vb6699684 _:vb6699685 _:vb6699686 _:vb6699680 _:vb6699681 _:vb6699682 _:vb6699683 _:vb6699669 _:vb6699670 _:vb6699671 _:vb6699676 _:vb6699677 _:vb6699678 _:vb6699679 _:vb6699672 _:vb6699673 _:vb6699674 _:vb6699675
Subject Item
_:vb6699669
rdf:type
n2:Context
rdf:value
Glioblastoma Multiforme (GBM) is a high-grade astrocytoma characterized by aggressive invasion of individual tumor cells into the brain parenchyma [>>1<<]. The diffuse infiltration of GBM tumors along vasculature and white matter tracts in the central nervous system makes complete resection virtually impossible, giving rise to a mean survival time from diagnosis of only 1–2 years, even with
n2:mentions
n3:17974913
Subject Item
_:vb6699670
rdf:type
n2:Context
rdf:value
The remarkable invasiveness of GBM tumors is attributed in part to the capacity of the constituent tumor cells to remodel the extracellular matrix (ECM), which is made possible by integrin upregulation [>>2<<], matrix metalloprotease (MMP)-mediated proteolysis [3], and de novo secretion of ECM proteins [4].
n2:mentions
n3:9533763
Subject Item
_:vb6699671
rdf:type
n2:Context
rdf:value
of GBM tumors is attributed in part to the capacity of the constituent tumor cells to remodel the extracellular matrix (ECM), which is made possible by integrin upregulation [2], matrix metalloprotease (MMP)-mediated proteolysis [>>3<<], and de novo secretion of ECM proteins [4].
n2:mentions
n3:12835669
Subject Item
_:vb6699672
rdf:type
n2:Context
rdf:value
to the capacity of the constituent tumor cells to remodel the extracellular matrix (ECM), which is made possible by integrin upregulation [2], matrix metalloprotease (MMP)-mediated proteolysis [3], and de novo secretion of ECM proteins [>>4<<]. This remodeling also depends on the ability of the tumor cells to generate actomyosin-based contractile forces, which have been observed in other systems to facilitate ECM fibril remodeling during migration, thereby providing contact
n2:mentions
n3:15674479
Subject Item
_:vb6699673
rdf:type
n2:Context
rdf:value
the ability of the tumor cells to generate actomyosin-based contractile forces, which have been observed in other systems to facilitate ECM fibril remodeling during migration, thereby providing contact guidance cues to invasive cells [>>5<<]. The importance of non-muscle myosin II (NMMII) in glioma invasiveness has been demonstrated by studies where inhibition of myosin light chain kinase (MLCK) completely abrogated glioma motility [6].
n2:mentions
n3:17618273
Subject Item
_:vb6699674
rdf:type
n2:Context
rdf:value
The importance of non-muscle myosin II (NMMII) in glioma invasiveness has been demonstrated by studies where inhibition of myosin light chain kinase (MLCK) completely abrogated glioma motility [>>6<<].
n2:mentions
n3:10232591
Subject Item
_:vb6699675
rdf:type
n2:Context
rdf:value
potential connections between ECM-encoded signals, cellular contractility, and tumor progression, we recently investigated the role of ECM rigidity (stiffness) in controlling behaviors of glioma cells relevant to growth and spread [>>7<<]. We demonstrated that the adhesion and cytoarchitecture of a variety of glioma cell culture models are indeed sensitive to ECM stiffness, and that this microenvironmental parameter can profoundly influence cell motility and proliferation.
n2:mentions
n3:19435897
Subject Item
_:vb6699676
rdf:type
n2:Context
rdf:value
the case of GBM specifically, a comparative study of in vitro migration and invasion across ten human GBM cell lines revealed that levels of the FA and actin-binding protein α-actinin correlates directly with biological aggressiveness [>>9<<]. The field's understanding of α-actinin function in this context has been complicated by the relatively recent discovery that four distinct isoforms exist in humans:
n2:mentions
n3:11746774
Subject Item
_:vb6699677
rdf:type
n2:Context
rdf:value
While both α-actinin-1 and α-actinin-4 have been reported to localize along stress fibers [>>10<<], α-actinin-1 also localizes to FAs and cell-cell contacts [11], and α-actinin-4 is also enriched at the leading edges of invading cells [12].
n2:mentions
n3:10753915
Subject Item
_:vb6699678
rdf:type
n2:Context
rdf:value
While both α-actinin-1 and α-actinin-4 have been reported to localize along stress fibers [10], α-actinin-1 also localizes to FAs and cell-cell contacts [>>11<<], and α-actinin-4 is also enriched at the leading edges of invading cells [12].
n2:mentions
n3:2116421
Subject Item
_:vb6699679
rdf:type
n2:Context
rdf:value
While both α-actinin-1 and α-actinin-4 have been reported to localize along stress fibers [10], α-actinin-1 also localizes to FAs and cell-cell contacts [11], and α-actinin-4 is also enriched at the leading edges of invading cells [>>12<<]. Further, immunohistochemical analysis of human tumors demonstrates that the cytoplasmic localization of α-actinin-4 accurately predicts an infiltrative phenotype and poor clinical prognosis [13], [14], [15].
n2:mentions
n3:9508771
Subject Item
_:vb6699680
rdf:type
n2:Context
rdf:value
Further, immunohistochemical analysis of human tumors demonstrates that the cytoplasmic localization of α-actinin-4 accurately predicts an infiltrative phenotype and poor clinical prognosis [>>13<<], [14], [15].
n2:mentions
n3:18362906
Subject Item
_:vb6699681
rdf:type
n2:Context
rdf:value
Further, immunohistochemical analysis of human tumors demonstrates that the cytoplasmic localization of α-actinin-4 accurately predicts an infiltrative phenotype and poor clinical prognosis [13], [>>14<<], [15].
n2:mentions
n3:15633123
Subject Item
_:vb6699682
rdf:type
n2:Context
rdf:value
Further, immunohistochemical analysis of human tumors demonstrates that the cytoplasmic localization of α-actinin-4 accurately predicts an infiltrative phenotype and poor clinical prognosis [13], [14], [>>15<<].
n2:mentions
n3:18765526
Subject Item
_:vb6699683
rdf:type
n2:Context
rdf:value
For example, siRNA-mediated knockdown of α-actinin-1 increases motility and tumorigenicity of fibroblasts, consistent with a role in stabilizing cell-ECM adhesive contacts [>>16<<], [17]. In intestinal epithelial cells, suppression of α-actinin-1, but not α-actinin-4, inhibits deformation-induced ERK phosphorylation and proliferation [18], reflecting the role of α-actinin-1 in linking the cytoskeleton to the
n2:mentions
n3:7983147
Subject Item
_:vb6699684
rdf:type
n2:Context
rdf:value
For example, siRNA-mediated knockdown of α-actinin-1 increases motility and tumorigenicity of fibroblasts, consistent with a role in stabilizing cell-ECM adhesive contacts [16], [>>17<<]. In intestinal epithelial cells, suppression of α-actinin-1, but not α-actinin-4, inhibits deformation-induced ERK phosphorylation and proliferation [18], reflecting the role of α-actinin-1 in linking the cytoskeleton to the extracellular
n2:mentions
n3:8380636
Subject Item
_:vb6699685
rdf:type
n2:Context
rdf:value
In intestinal epithelial cells, suppression of α-actinin-1, but not α-actinin-4, inhibits deformation-induced ERK phosphorylation and proliferation [>>18<<], reflecting the role of α-actinin-1 in linking the cytoskeleton to the extracellular matrix (ECM).
n2:mentions
n3:17936423
Subject Item
_:vb6699686
rdf:type
n2:Context
rdf:value
In ovarian carcinoma cells, α-actinin-4 knockdown leads to reduced motility and invasion [>>13<<], whereas mice genetically deficient in α-actinin-4 exhibit increased lymphocyte chemotaxis [19].
n2:mentions
n3:18362906
Subject Item
_:vb6699687
rdf:type
n4:Section
dc:title
materials and methods
n4:contains
_:vb6699688 _:vb6699689 _:vb6699690 _:vb6699691 _:vb6699692 _:vb6699693 _:vb6699694
Subject Item
_:vb6699688
rdf:type
n2:Context
rdf:value
U373-MG human glioma cells were obtained and cultured as previously described [>>7<<]. Cells were plated either on glass coverslips or tissue culture polystyrene coated with bovine collagen I (Inamed Biosciences) or on collagen-coated polyacrylamide (PA) hydrogels attached to glass coverslips (see below).
n2:mentions
n3:19435897
Subject Item
_:vb6699689
rdf:type
n2:Context
rdf:value
Immunofluorescence [>>7<<], [20] utilized previously validated primary (mouse anti-α-actinin-1 (1∶200, Santa Cruz); mouse anti-α-actinin-4 (1∶250, Abcam); mouse anti-vinculin (1∶200, Sigma)) and secondary antibodies (Alexa Fluor 543 goat anti-mouse IgG; Alexa Fluor
n2:mentions
n3:19435897
Subject Item
_:vb6699690
rdf:type
n2:Context
rdf:value
Polyacrylamide ECMs of defined stiffness were synthesized by polymerizing and crosslinking predetermined ratios of acrylamide and bisacrylamide [>>7<<], [21]. For TFM experiments [22], [23], Texas red-labeled microspheres (1 µm diameter, Invitrogen) were included in the acrylamide/bisacrylamide solution prior to polymerization.
n2:mentions
n3:19435897
Subject Item
_:vb6699691
rdf:type
n2:Context
rdf:value
Polyacrylamide ECMs of defined stiffness were synthesized by polymerizing and crosslinking predetermined ratios of acrylamide and bisacrylamide [7], [>>21<<]. For TFM experiments [22], [23], Texas red-labeled microspheres (1 µm diameter, Invitrogen) were included in the acrylamide/bisacrylamide solution prior to polymerization.
n2:mentions
n3:9391082
Subject Item
_:vb6699692
rdf:type
n2:Context
rdf:value
For TFM experiments [>>22<<], [23], Texas red-labeled microspheres (1 µm diameter, Invitrogen) were included in the acrylamide/bisacrylamide solution prior to polymerization.
n2:mentions
n3:11832345
Subject Item
_:vb6699693
rdf:type
n2:Context
rdf:value
For TFM experiments [22], [>>23<<], Texas red-labeled microspheres (1 µm diameter, Invitrogen) were included in the acrylamide/bisacrylamide solution prior to polymerization.
n2:mentions
n3:16500961
Subject Item
_:vb6699694
rdf:type
n2:Context
rdf:value
For TFM, maps of substrate displacement and strain were computed from bead positions before and after cell detachment using Fourier transform traction cytometry [>>22<<].
n2:mentions
n3:11832345
Subject Item
_:vb6699695
rdf:type
n4:Section
dc:title
results
n4:contains
_:vb6699704 _:vb6699705 _:vb6699706 _:vb6699707 _:vb6699708 _:vb6699709 _:vb6699710 _:vb6699711 _:vb6699696 _:vb6699697 _:vb6699698 _:vb6699699 _:vb6699700 _:vb6699701 _:vb6699702 _:vb6699703
Subject Item
_:vb6699696
rdf:type
n2:Context
rdf:value
To establish baseline expression and localization of α-actinin isoforms in a human glioma cell line we had previously demonstrated to be mechanosensitive [>>7<<], we cultured U-373 MG human glioma cells on collagen I-coated glass coverslips and examined isoform distributions by immunofluorescence.
n2:mentions
n3:19435897
Subject Item
_:vb6699697
rdf:type
n2:Context
rdf:value
and transfection conditions were optimized to obtain ∼55% depletion of α-actinin-1 and ∼60% depletion of α-actinin-4 by immunoblot, comparable to levels of suppression achieved in previous studies with minimal off-target effects [>>18<<]. Consistent with this incomplete knockdown, α-actinin-1 and α-actinin-4- depleted cells still stained weakly positive for α-actinin-1 and α-actinin-4 respectively (Figure 1C, Figure S1).
n2:mentions
n3:17936423
Subject Item
_:vb6699698
rdf:type
n2:Context
rdf:value
Similar to other cell systems [>>21<<], [24], [25], control cells spread poorly on relatively compliant ECMs (<5 kPa), more extensively on stiffer ECMs (8–20 kPa), and to a maximal area above a threshold ECM stiffness (>20 kPa).
n2:mentions
n3:9391082
Subject Item
_:vb6699699
rdf:type
n2:Context
rdf:value
Similar to other cell systems [21], [>>24<<], [25], control cells spread poorly on relatively compliant ECMs (<5 kPa), more extensively on stiffer ECMs (8–20 kPa), and to a maximal area above a threshold ECM stiffness (>20 kPa).
n2:mentions
n3:14695306
Subject Item
_:vb6699700
rdf:type
n2:Context
rdf:value
Similar to other cell systems [21], [24], [>>25<<], control cells spread poorly on relatively compliant ECMs (<5 kPa), more extensively on stiffer ECMs (8–20 kPa), and to a maximal area above a threshold ECM stiffness (>20 kPa).
n2:mentions
n3:15669099
Subject Item
_:vb6699701
rdf:type
n2:Context
rdf:value
This adaptation of cortical stiffness to ECM stiffness has been observed previously in both cultured fibroblasts [>>26<<] and mesenchymal stem cells [27].
n2:mentions
n3:18045965
Subject Item
_:vb6699702
rdf:type
n2:Context
rdf:value
This adaptation of cortical stiffness to ECM stiffness has been observed previously in both cultured fibroblasts [26] and mesenchymal stem cells [>>27<<]. Knockdown of either α-actinin isoform blunted this stiffness adaptation and significantly reduced cortical stiffness for all ECM stiffnesses. On the most compliant (2 kPa) ECMs, the stiffnesses of α-actinin-1 and α-actinin-4 depleted
n2:mentions
n3:16923388
Subject Item
_:vb6699703
rdf:type
n2:Context
rdf:value
The localization of many mechanosensory FA proteins has been shown to specifically depend on activation of myosin motors, which in turn governs cytoskeletal contractility or prestress [>>28<<], [29]. To determine if this also holds true for α-actinin-1 and -4, we tracked the localization of these two isoforms in the presence of pharmacologic inhibitors of MLCK, ROCK, and NMMII, all key components of the myosin-based
n2:mentions
n3:16288479
Subject Item
_:vb6699704
rdf:type
n2:Context
rdf:value
The localization of many mechanosensory FA proteins has been shown to specifically depend on activation of myosin motors, which in turn governs cytoskeletal contractility or prestress [28], [>>29<<]. To determine if this also holds true for α-actinin-1 and -4, we tracked the localization of these two isoforms in the presence of pharmacologic inhibitors of MLCK, ROCK, and NMMII, all key components of the myosin-based contractility
n2:mentions
n3:16247023
Subject Item
_:vb6699705
rdf:type
n2:Context
rdf:value
if this also holds true for α-actinin-1 and -4, we tracked the localization of these two isoforms in the presence of pharmacologic inhibitors of MLCK, ROCK, and NMMII, all key components of the myosin-based contractility pathway [>>30<<], [31], [32].
n2:mentions
n3:18096687
Subject Item
_:vb6699706
rdf:type
n2:Context
rdf:value
if this also holds true for α-actinin-1 and -4, we tracked the localization of these two isoforms in the presence of pharmacologic inhibitors of MLCK, ROCK, and NMMII, all key components of the myosin-based contractility pathway [30], [>>31<<], [32]. As expected, Western Blots revealed that treatment of U-373 MG cells with ROCK and MLCK inhibitors markedly reduced levels of MLC phosphorylation relative to either untreated controls or cells in which NMMII ATPase was directly
n2:mentions
n3:12778124
Subject Item
_:vb6699707
rdf:type
n2:Context
rdf:value
also holds true for α-actinin-1 and -4, we tracked the localization of these two isoforms in the presence of pharmacologic inhibitors of MLCK, ROCK, and NMMII, all key components of the myosin-based contractility pathway [30], [31], [>>32<<]. As expected, Western Blots revealed that treatment of U-373 MG cells with ROCK and MLCK inhibitors markedly reduced levels of MLC phosphorylation relative to either untreated controls or cells in which NMMII ATPase was directly inhibited
n2:mentions
n3:12637748
Subject Item
_:vb6699708
rdf:type
n2:Context
rdf:value
with cells exhibiting active membrane ruffles at their leading edges and extending long membrane processes at their trailing edges, consistent with previous observations in other cell systems, including glioma cells (Movie S5) [>>33<<], [34].
n2:mentions
n3:16554034
Subject Item
_:vb6699709
rdf:type
n2:Context
rdf:value
with cells exhibiting active membrane ruffles at their leading edges and extending long membrane processes at their trailing edges, consistent with previous observations in other cell systems, including glioma cells (Movie S5) [33], [>>34<<].
n2:mentions
n3:12149446
Subject Item
_:vb6699710
rdf:type
n2:Context
rdf:value
The above results suggest a close association between α-actinin isoforms and NMMII, whose activation is classically associated with increased contractility, increased stiffness, and generation of traction forces [>>35<<], [36], [37].
n2:mentions
n3:17094935
Subject Item
_:vb6699711
rdf:type
n2:Context
rdf:value
The above results suggest a close association between α-actinin isoforms and NMMII, whose activation is classically associated with increased contractility, increased stiffness, and generation of traction forces [35], [36], [>>37<<]. To test whether our observed α-actinin-dependent changes in cellular motility and mechanics were secondary to changes in myosin activity, we compared the levels of NMMII expression and phosphorylation in control and α-actinin-depleted
n2:mentions
n3:11832346
Subject Item
_:vb6699712
rdf:type
n4:Section
dc:title
discussion
n4:contains
_:vb6699716 _:vb6699717 _:vb6699718 _:vb6699719 _:vb6699713 _:vb6699714 _:vb6699715 _:vb6699724 _:vb6699725 _:vb6699726 _:vb6699727 _:vb6699720 _:vb6699721 _:vb6699722 _:vb6699723 _:vb6699728
Subject Item
_:vb6699713
rdf:type
n2:Context
rdf:value
The direct role of NMMII in GBM invasiveness was first demonstrated by studies in which treatment with MLCK inhibitors completely abrogated glioma motility [>>6<<]. Three isoforms of NMMII are known to exist (NMMIIA, B, C); NMMIIA is upregulated in human glioma xenografts, and both NMMIIA and NMMIIB are required to squeeze through pores smaller than the size of nuclei [38]. Our studies reveal a
n2:mentions
n3:10232591
Subject Item
_:vb6699714
rdf:type
n2:Context
rdf:value
Three isoforms of NMMII are known to exist (NMMIIA, B, C); NMMIIA is upregulated in human glioma xenografts, and both NMMIIA and NMMIIB are required to squeeze through pores smaller than the size of nuclei [>>38<<]. Our studies reveal a causal connection between α-actinin and NMMII in which depletion of either α-actinin isoform reduces NMMII expression. This close interplay between α-actinin and NMMII in modulating contractility is consistent with
n2:mentions
n3:18495866
Subject Item
_:vb6699715
rdf:type
n2:Context
rdf:value
and NMMII in modulating contractility is consistent with biophysical studies of gels composed of F-actin, NMMII and α-actinin, which have found that bulk contractility of the gel occurs only above a threshold α-actinin concentration [>>39<<]. The actin-crosslinking activity of NMMII in the initial stages of adhesion has been demonstrated in recent studies where overexpression of wild-type NMMII in α-actinin-depleted CHO cells was able to restore adhesion maturation [40].
n2:mentions
n3:18192374
Subject Item
_:vb6699716
rdf:type
n2:Context
rdf:value
The actin-crosslinking activity of NMMII in the initial stages of adhesion has been demonstrated in recent studies where overexpression of wild-type NMMII in α-actinin-depleted CHO cells was able to restore adhesion maturation [>>40<<]. In human aortic endothelial cells, the increase in cell prestress obtained with knockdown of α-actinin-1 suggests that α-actinin depletion increases actomyosin interactions and raises the possibility that α-actinin and NMMII compete for
n2:mentions
n3:19160484
Subject Item
_:vb6699717
rdf:type
n2:Context
rdf:value
in cell prestress obtained with knockdown of α-actinin-1 suggests that α-actinin depletion increases actomyosin interactions and raises the possibility that α-actinin and NMMII compete for common binding sites in crosslinking F-actin [>>41<<]. The cell softening observed in our studies upon α-actinin knockdown is also consistent with a published report in which microinjection of α-actinin not only increased the stiffness of 3T3 fibroblasts but also the degree of mechanical
n2:mentions
n3:18200567
Subject Item
_:vb6699718
rdf:type
n2:Context
rdf:value
with a published report in which microinjection of α-actinin not only increased the stiffness of 3T3 fibroblasts but also the degree of mechanical heterogeneity of the cytoplasm, as measured by particle tracking microrheology [>>42<<].
n2:mentions
n3:12496086
Subject Item
_:vb6699719
rdf:type
n2:Context
rdf:value
Cell migration requires the coordinated extension of membrane protrusions, formation of transient adhesions along the membrane extensions, and NMMII-dependent detachment of the cell rear [>>43<<]. The activity of NMMII is controlled by MLC phosphorylation, and recent efforts to elucidate regional variations in MLC phosphoregulation have suggested that MLCK preferentially regulates dynamic adhesions at the cell periphery and that
n2:mentions
n3:14657486
Subject Item
_:vb6699720
rdf:type
n2:Context
rdf:value
and recent efforts to elucidate regional variations in MLC phosphoregulation have suggested that MLCK preferentially regulates dynamic adhesions at the cell periphery and that ROCK regulates more stable FAs at the cell center [>>44<<], [45]. We find that motility is reduced most dramatically by suppressing those isoforms and inhibiting MLCK.
n2:mentions
n3:17896341
Subject Item
_:vb6699721
rdf:type
n2:Context
rdf:value
and recent efforts to elucidate regional variations in MLC phosphoregulation have suggested that MLCK preferentially regulates dynamic adhesions at the cell periphery and that ROCK regulates more stable FAs at the cell center [44], [>>45<<]. We find that motility is reduced most dramatically by suppressing those isoforms and inhibiting MLCK.
n2:mentions
n3:14757754
Subject Item
_:vb6699722
rdf:type
n2:Context
rdf:value
Potential mechanisms for this effect might include increased interaction between α-actinin-4 and pMLC, which translocates to membrane protrusions in a Rac-dependent manner [>>46<<].
n2:mentions
n3:16204049
Subject Item
_:vb6699723
rdf:type
n2:Context
rdf:value
to changes in ECM stiffness observed here is reminiscent of the finding that cultured fibroblasts match their stiffness to the underlying ECM substrate for ECM stiffnesses up to 5 kPa and reach a maximal stiffness on ECM substrates [>>26<<]. The failure of α-actinin-depleted cells to exhibit this stiffness adaptation may be due to the requirement for α-actinin to crosslink cortical actin and stabilize connections between F-actin and β integrin subunits in adhesions, which
n2:mentions
n3:18045965
Subject Item
_:vb6699724
rdf:type
n2:Context
rdf:value
to crosslink cortical actin and stabilize connections between F-actin and β integrin subunits in adhesions, which would be expected to require strongest reinforcement on high-rigidity ECMs, which support large traction forces [>>47<<]. Conversely, both α-actinin isoforms contribute most strongly to spreading area at low ECM rigidity.
n2:mentions
n3:15083532
Subject Item
_:vb6699725
rdf:type
n2:Context
rdf:value
This concept is supported by previous studies in which vinculin suppression reduced spreading, stress fiber formation, FA formation, and lamellipodial extension [>>48<<]. This compensatory effect may itself depend on ECM rigidity, such that α-actinin-depleted cells cultured on compliant ECMs are much less capable of recruiting additional vinculin to FAs than their counterparts on rigid ECMs. As a result,
n2:mentions
n3:11785963
Subject Item
_:vb6699726
rdf:type
n2:Context
rdf:value
of α-actinin may switch GBM tumor cells from a strongly adhesive and low-motility phenotype to a highly contractile and invasive phenotype, and the possibility that invading glioma cells may stiffen the brain parenchyma as they invade [>>7<<] suggests a complex interplay between ECM rigidity, α-actinin, and vinculin.
n2:mentions
n3:19435897
Subject Item
_:vb6699727
rdf:type
n2:Context
rdf:value
For example, Janmey and coworkers recently reported that under some conditions, filamin A-null cells increase their spreading in response to increasing ECM stiffness while maintaining a relatively constant cell stiffness [>>49<<], indicating that stiffness and spreading are not strictly coupled.
n2:mentions
n3:19527669
Subject Item
_:vb6699728
rdf:type
n2:Context
rdf:value
Similarly, we recently showed that when U-373 MG cells cultured on highly compliant ECMs are treated with ROCK or NMMII inhibitors, which presumably reduce contractility, they paradoxically begin to spread and migrate [>>7<<]. These and other studies suggest the possibility that specific actin crosslinking proteins may modulate the degree of coupling between cell spreading and cellular contractility.
n2:mentions
n3:19435897
Subject Item
_:vb421799230
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
8
n2:hasRelevantPaperId
n3:9508771
Subject Item
_:vb421799231
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
8
n2:hasRelevantPaperId
n3:20156433
Subject Item
_:vb421799232
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
7
n2:hasRelevantPaperId
n3:18495866
Subject Item
_:vb421799233
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
7
n2:hasRelevantPaperId
n3:15633123
Subject Item
_:vb421799234
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
6
n2:hasRelevantPaperId
n3:18632979
Subject Item
_:vb421799235
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
6
n2:hasRelevantPaperId
n3:19435897
Subject Item
_:vb421799236
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
5
n2:hasRelevantPaperId
n3:18765526
Subject Item
_:vb421799237
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
4
n2:hasRelevantPaperId
n3:19151661
Subject Item
_:vb421799238
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
4
n2:hasRelevantPaperId
n3:18362906
Subject Item
_:vb421799239
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
4
n2:hasRelevantPaperId
n3:10571411
Subject Item
_:vb421799240
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
4
n2:hasRelevantPaperId
n3:20227367
Subject Item
_:vb421799241
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
4
n2:hasRelevantPaperId
n3:22118458
Subject Item
_:vb421799242
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
4
n2:hasRelevantPaperId
n3:16541395
Subject Item
_:vb421799243
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:10433259
Subject Item
_:vb421799244
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:17971532
Subject Item
_:vb421799245
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:23817592
Subject Item
_:vb421799246
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:16923388
Subject Item
_:vb421799247
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:17805551
Subject Item
_:vb421799248
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:17040992
Subject Item
_:vb421799249
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:18772890
Subject Item
_:vb421799250
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:19460998
Subject Item
_:vb421799251
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:15269225
Subject Item
_:vb421799252
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:16293750
Subject Item
_:vb421799253
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:19010882
Subject Item
_:vb421799254
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:19920151
Subject Item
_:vb421799255
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:22205943
Subject Item
_:vb421799256
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:20647762
Subject Item
_:vb421799257
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:12113106
Subject Item
_:vb421799258
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:19167326
Subject Item
_:vb421799259
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:19596356
Subject Item
_:vb421799260
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:16982728
Subject Item
_:vb421799261
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:13298683
Subject Item
_:vb421799262
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:16204054
Subject Item
_:vb421799263
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:21078666
Subject Item
_:vb421799264
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:17712357
Subject Item
_:vb421799265
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:19617536
Subject Item
_:vb421799266
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:19969329
Subject Item
_:vb421799267
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:23557398
Subject Item
_:vb421799268
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:22659352
Subject Item
_:vb421799269
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:15959903
Subject Item
_:vb421799270
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:3005320
Subject Item
_:vb421799271
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:2393868
Subject Item
_:vb421799272
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:16557279
Subject Item
_:vb421799273
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:17898132
Subject Item
_:vb421799274
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
3
n2:hasRelevantPaperId
n3:21736894
Subject Item
_:vb421799275
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:18981465
Subject Item
_:vb421799276
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:12697889
Subject Item
_:vb421799277
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15380385
Subject Item
_:vb421799278
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:23470260
Subject Item
_:vb421799279
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:23963648
Subject Item
_:vb421799280
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:9391082
Subject Item
_:vb421799281
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:12231534
Subject Item
_:vb421799282
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:16141784
Subject Item
_:vb421799283
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:18772396
Subject Item
_:vb421799284
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:21474972
Subject Item
_:vb421799285
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:21740400
Subject Item
_:vb421799286
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:24068827
Subject Item
_:vb421799287
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:19908100
Subject Item
_:vb421799288
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:22294205
Subject Item
_:vb421799289
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:14695306
Subject Item
_:vb421799290
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15459390
Subject Item
_:vb421799291
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:22887464
Subject Item
_:vb421799292
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:24574362
Subject Item
_:vb421799293
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15048094
Subject Item
_:vb421799294
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:16169468
Subject Item
_:vb421799295
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:20197409
Subject Item
_:vb421799296
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:20610469
Subject Item
_:vb421799297
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:11904754
Subject Item
_:vb421799298
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:14581339
Subject Item
_:vb421799299
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15849239
Subject Item
_:vb421799300
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:19270154
Subject Item
_:vb421799301
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:24946761
Subject Item
_:vb421799302
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15466194
Subject Item
_:vb421799303
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:22908231
Subject Item
_:vb421799304
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:26312134
Subject Item
_:vb421799305
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:12297042
Subject Item
_:vb421799306
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15083532
Subject Item
_:vb421799307
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:23132927
Subject Item
_:vb421799308
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:26493995
Subject Item
_:vb421799309
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:3555767
Subject Item
_:vb421799310
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:17992095
Subject Item
_:vb421799311
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:24962319
Subject Item
_:vb421799312
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:26045979
Subject Item
_:vb421799313
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:17376432
Subject Item
_:vb421799314
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:19160484
Subject Item
_:vb421799315
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:23508546
Subject Item
_:vb421799316
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:11716069
Subject Item
_:vb421799317
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15674479
Subject Item
_:vb421799318
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:16793885
Subject Item
_:vb421799319
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:22325265
Subject Item
_:vb421799320
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:9426685
Subject Item
_:vb421799321
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:12388552
Subject Item
_:vb421799322
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15094120
Subject Item
_:vb421799323
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:1339456
Subject Item
_:vb421799324
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:18045965
Subject Item
_:vb421799325
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:19931152
Subject Item
_:vb421799326
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:18687124
Subject Item
_:vb421799327
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:19672209
Subject Item
_:vb421799328
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:24627985
Subject Item
_:vb421799329
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:25174308
Subject Item
_:vb421799330
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:11739652
Subject Item
_:vb421799331
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15695406
Subject Item
_:vb421799332
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:17925230
Subject Item
_:vb421799333
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15925768
Subject Item
_:vb421799334
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:23899839
Subject Item
_:vb421799335
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15516961
Subject Item
_:vb421799336
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:17873890
Subject Item
_:vb421799337
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15122314
Subject Item
_:vb421799338
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:19497285
Subject Item
_:vb421799339
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:19357957
Subject Item
_:vb421799340
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:22348389
Subject Item
_:vb421799341
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:9046311
Subject Item
_:vb421799342
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:11170299
Subject Item
_:vb421799343
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:25047810
Subject Item
_:vb421799344
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:2116421
Subject Item
_:vb421799345
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:10656685
Subject Item
_:vb421799346
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:14871821
Subject Item
_:vb421799347
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:21085685
Subject Item
_:vb421799348
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:21446047
Subject Item
_:vb421799349
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:10866943
Subject Item
_:vb421799350
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:11832345
Subject Item
_:vb421799351
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:23292359
Subject Item
_:vb421799352
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:28797528
Subject Item
_:vb421799353
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:11390353
Subject Item
_:vb421799354
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:21447562
Subject Item
_:vb421799355
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:18215660
Subject Item
_:vb421799356
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:25082799
Subject Item
_:vb421799357
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:15549107
Subject Item
_:vb421799358
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:25296750
Subject Item
_:vb421799359
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:8017863
Subject Item
_:vb421799360
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:9857077
Subject Item
_:vb421799361
rdf:type
n2:RelevantBibliographicResource
n2:RelevantScore
2
n2:hasRelevantPaperId
n3:10896208