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7th World Congress on Mummy Studies University of San Diego San ...

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CHERyL L. JORCyK*. (Department. <strong>of</strong>. Biological. Sciences,.<br />

Boise. State.<strong>University</strong>,. 1910. <strong>University</strong>.Drive,. Boise,. ID. 83725;.<br />

cjorcyk@boisestate.edu).<br />

Oncostatin.M.(OSM).is.an.interleukin-6.(IL-6)-family.cytokine.that.has.been.implicated<br />

. in.a.number.<strong>of</strong>.biological.processes.<br />

including. the. inducti<strong>on</strong> . <strong>of</strong>. inflammati<strong>on</strong>. and. modulati<strong>on</strong>. <strong>of</strong>. the.<br />

extracellular.matrix..OSM.was.initially.shown.to.inhibit.the.proliferati<strong>on</strong>.<strong>of</strong>.breast.cancer.cell.lines.in<br />

vitro.and.has.been.evaluated.as.<br />

a.potential.cancer.therapy..However,.evidence.in.the.literature.and.<br />

our.data.suggest.that.OSM.may.actually.promote.tumor.invasi<strong>on</strong>.<br />

and.metastasis..Using.the.orthotopic.4T1.2.mouse.mammary.model.<br />

<strong>of</strong>.metastasis,.we.have.investigated.the.ability.<strong>of</strong>.OSM.to.enhance.<br />

the.formati<strong>on</strong>.<strong>of</strong>.metastases.in.organs.such.as.lung.and.b<strong>on</strong>e.in vivo..<br />

OSM.expressi<strong>on</strong>.was.knocked.down.using.shRNA.in.4T1.2.cells,.<br />

which. endogenously. express. both. OSM. and. its. receptor.. These.<br />

4T1.2-OSM.cells.were.orthotopically.injected.into.Balb/c.mice.and.<br />

resulted.in.a.decrease.in.metastasis.to.b<strong>on</strong>e.and.lung.compared.to.<br />

that.<strong>of</strong>.4T1.2-Lac.Z.c<strong>on</strong>trol.cells..Metastases.were.quantified.using.<br />

qPCR.to.detect.the.vector.neomycin.resistance.gene.in.post-mortem.<br />

organ.samples..We.are.currently.investigating.the.specific.cellular.<br />

mechanisms.that.might.be.important.for.tumor.cell-derived.OSM.<br />

promoti<strong>on</strong>.<strong>of</strong>.metastasis.to.b<strong>on</strong>e,.such.as.hypoxia-inducible.factor.1.<br />

alpha.(HIF1α).and.vascular.endothelial.growth.factor.(VEGF)..Our.<br />

results.suggest.that.OSM.might.be.an.important.therapeutic.target.<br />

in.the.preventi<strong>on</strong>.<strong>of</strong>.metastatic.breast.cancer.invasi<strong>on</strong>.<strong>of</strong>.b<strong>on</strong>e.<br />

Funded. by. ACS. RSG-09-276-01-CSM,. Susan. G. Komen. for. the. Cure.<br />

KG100513,.and.NIH/NCRR.P20RR016454.<br />

302 MicroRNA Signatures in Small Molecule Induced Cardiac<br />

and Neural Lineage-Specificati<strong>on</strong> Direct from Pluripotent Human<br />

Embry<strong>on</strong>ic Stem Cells, XUEJUN H. PARSONS (<strong>San</strong>. <strong>Diego</strong>.<br />

Regenerative.Medicine.Institute,.<strong>San</strong>.<strong>Diego</strong>,.CA.92121.and.Xcelthera,.<strong>San</strong>.<strong>Diego</strong>,.CA.92121;.pars<strong>on</strong>s@SDRMI.org).<br />

Human.embry<strong>on</strong>ic.stem.cells.(hESCs).are.genetically.stable.<br />

with.unlimited.expansi<strong>on</strong>.ability.and.unrestricted.plasticity,.pr<strong>of</strong>fering.a.pluripotent.reservoir.for.in.vitro.derivati<strong>on</strong>.<strong>of</strong>.a.large.supply.<strong>of</strong>.disease-targeted.human.somatic.cells.that.are.restricted.to.the.lineage.in.need.<strong>of</strong>.repair..One.<strong>of</strong>.the.major.challenges.for.both.developmental.studies.and.clinical.translati<strong>on</strong>.has.been.how.to.channel.<br />

the.broad.differentiati<strong>on</strong>.potential.<strong>of</strong>.pluripotent.cells.to.a.desired.<br />

phenotype. efficiently. and. predictably.. C<strong>on</strong>venti<strong>on</strong>al. approaches.<br />

rely.<strong>on</strong>.multi-lineage.inclinati<strong>on</strong>.<strong>of</strong>.pluripotent.cells.through.sp<strong>on</strong>taneous.germ.layer.differentiati<strong>on</strong>,.resulting.in.inefficient.and.unc<strong>on</strong>trollable.lineage-commitment.that.is.<strong>of</strong>ten.followed.by.phenotypic.<br />

heterogeneity.and.instability,.hence,.a.high.risk.<strong>of</strong>.tumorigenicity..<br />

To.overcome.these.obstacles,.we.resolved.the.elements.<strong>of</strong>.a.defined.<br />

culture.system.necessary.and.sufficient.for.sustaining.the.epiblast.<br />

pluripotence.<strong>of</strong>.hESCs,.serving.as.a.platform.for.de.novo.derivati<strong>on</strong>.<br />

<strong>of</strong>. therapeutically-suitable. hESCs. and. effectively. directing. such.<br />

hESCs.uniformly.towards.clinically-relevant.lineages..Employing.<br />

the.defined.platform,.we.found.that.nicotinamide.(NAM).and.retinoic.acid.(RA).induced.respective.cardiac-.and.neural-lineage.commitment.direct.from.pluripotent.hESCs.that.further.progressed.to.<br />

beating.cardiomyocytes.and.ventral.neur<strong>on</strong>s.with.drastic.increases.<br />

in.efficiency..To.uncover.key.regulators,.genome-scale.microRNA.<br />

(miRNA).pr<strong>of</strong>iling.was.used.to.identify.novel.sets.<strong>of</strong>.developmentinitiating.miRNAs..A.unique.set.<strong>of</strong>.pluripotence-associated.miR-<br />

NAs.was.down-regulated,.while.novel.sets.<strong>of</strong>.distinct.cardiac-.and.<br />

neural-driving.miRNAs.were.up-regulated.up<strong>on</strong>.lineage.inducti<strong>on</strong>..<br />

Our.study.opens.new.dimensi<strong>on</strong>s.<strong>of</strong>.direct.c<strong>on</strong>trol.and.modulati<strong>on</strong>.<br />

ABSTRACTS.–.C<strong>on</strong>tributed.Oral.Papers<br />

<strong>of</strong>.hESC.fate.when.deriving.clinically-relevant.lineages.from.pluripotent.cells.for.regenerative.therapies.<br />

AAASPD<br />

HISTORY and PHILOSOPHY OF SCIENCE SECTION<br />

Tuesday, starting at 8:20 a.m. in KIPJ Room G<br />

303 The First Pacific C<strong>on</strong>chologist: Eusebio Kino SJ, Abal<strong>on</strong>es<br />

and California’s Insularity,. HANS BERTSCH. (Universidad.<br />

Autónoma.de.Baja.California.Sur,.192.Imperial.Beach.Blvd..#A,.<br />

Imperial.Beach,.CA.91932;.hansmarvida@sbcglobal.net).<br />

<strong>Studies</strong>.<strong>on</strong>.molluscan.biogeography.are.dependent.up<strong>on</strong>.good.<br />

mapping.and.correct.identificati<strong>on</strong>.<strong>of</strong>.localities..Prior.to.the.works.<br />

<strong>of</strong>. Linnaeus,. Martyn. and. Eschscholtz,. Father. Eusebio. Francisco.<br />

Kino.made.the.first.collecti<strong>on</strong>.<strong>of</strong>.American.west.coast.shells..Interestingly,.this.missi<strong>on</strong>ary’s.proper.documentati<strong>on</strong>.<strong>of</strong>.a.mollusc’s.distributi<strong>on</strong>.changed.the.maps.<br />

Kino.recognized.that.blue.shells.given.him.by.the.indigenous.<br />

peoples.<strong>of</strong>.modern.Ariz<strong>on</strong>a.and.northwest.S<strong>on</strong>ora.were.the.same.as.<br />

he.had.seen.14.years.earlier.<strong>on</strong>.the.Pacific.coast.<strong>of</strong>.Lower.California,.but.were.not.present.in.the.Gulf.<strong>of</strong>.California..In.the.1600s.the.<br />

comm<strong>on</strong>ly.held.(and.mapped).European.belief.was.that.California.<br />

was.an.island..Could.their.presence.by.trade.<strong>on</strong>.mainland.Mexico.<br />

indicate.that.California.was.really.a.peninsula?.If.so,.he.could.supply.the.California.missi<strong>on</strong>s.by.an.overland.route.He.c<strong>on</strong>vened.the.First.Internati<strong>on</strong>al.C<strong>on</strong>ference.<strong>on</strong>.the.Zoogeography.<strong>of</strong>.Northeast.Pacific.Abal<strong>on</strong>es.at.<strong>San</strong>.Xavier.del.Bac.(≈32º.<br />

06’.20”.N;.111º.00’.30”.W).<strong>on</strong>.30.April–1.May.1700,.discussing.with.<br />

members.<strong>of</strong>.various.nati<strong>on</strong>s.the.origin.<strong>of</strong>.the.blue.shells.obtained.in.<br />

trade.from.the.Colorado.River.peoples..All.asserted.the.shells.came.<br />

from.the.opposite.coast.<strong>of</strong>.California,.a.ten.or.twelve.days’.walk..<br />

After.further.expediti<strong>on</strong>s,.and.crossing.the.Colorado.River.<strong>on</strong>.a.raft,.<br />

he.was.c<strong>on</strong>vinced.<strong>of</strong>.the.peninsularity.<strong>of</strong>.Lower.California.<br />

In.late.1701,.he.redrew.his.earlier.“insular”.map..After.it.was.<br />

printed.in.1705,.it.was.never.again.in.doubt.that.Lower.California.<br />

was.a.peninsula.<br />

304 Tracing the Birth <strong>of</strong> New Science in the Literature <strong>of</strong> the 17 th<br />

and 18 th Centuries,.FAyE MANKOWSKE.(Department.<strong>of</strong>.English,.<strong>University</strong>.<strong>of</strong>.<strong>San</strong>.<strong>Diego</strong>,.Founders.Hall.173,.5998.Alcalá.Park,.<br />

<strong>San</strong>.<strong>Diego</strong>,.CA.92110;.fayem@sandiego.edu).<br />

The. seventeenth. century. saw. the. birth. <strong>of</strong>. the. Royal. Society.<br />

<strong>of</strong>. L<strong>on</strong>d<strong>on</strong>,. the. activities. <strong>of</strong>. which. were. to. prompt. a. fundamental.<br />

shift. in. the. study. <strong>of</strong>. Natural. Philosophy,. towards. a. paradigm.<br />

initially. known. as. “New. Science.”. Paradigm. shifts. are. generally.<br />

accompanied. by. uncertainty,. experimentati<strong>on</strong>,. failures. and. intellectual.c<strong>on</strong>troversy,.and.the.movement.towards.New.Science.was.<br />

rife.with.these.elements..The.epistemological.shift.occurring.during.<br />

the. Renaissance. c<strong>on</strong>tributed. added. c<strong>on</strong>troversy. to. the. movement.<br />

towards.modern.science.<br />

This.paper.is.c<strong>on</strong>cerned.with.investigati<strong>on</strong>s.<strong>of</strong>.the.evoluti<strong>on</strong>.<br />

<strong>of</strong>.Natural.Philosophy.into.the.New.Science.in.the.c<strong>on</strong>text.<strong>of</strong>.the.<br />

seventeenth. century,. and. specifically. in. tracing. manifestati<strong>on</strong>s. <strong>of</strong>.<br />

this.evoluti<strong>on</strong>ary.shift.in.the.literature.<strong>of</strong>.the.seventeenth.and.eighteenth.centuries..The.ability.<strong>of</strong>.literature.to.provide.a.view.into.both.<br />

the. historical. realities. and. intellectual. c<strong>on</strong>troversies. surrounding.<br />

the.development.<strong>of</strong>.New.Science.allows.a.richer.knowledge.<strong>of</strong>.this.<br />

fundamental.movement,.and.<strong>of</strong>.the.philosophical,.ethical.and.pragmatic.questi<strong>on</strong>s.that.accompanied.its.evoluti<strong>on</strong>.<br />

131

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