niehs spotlight science notebook · 2020-01-11 · niehs spotlight science notebook niehs partners...

NIEHS Spotlight Science Notebook

January 2013

Birnbaum gives keynote at environmental health meeting in IndiaNIEHS/NTP Director Linda Birnbaum, Ph.D., traveled to New Delhi, India Dec. 6 to present the keynote address at an international symposium on occupational health.

Resnick elected AAAS FellowThe American Association for the Advancement of Science has announced the election of lead researcher Michael Resnick, Ph.D., as a new fellow.

Suk honored for leadership by Society of ToxicologyThe Society of Toxicology has selected NIEHS Superfund Research Program Director Bill Suk, Ph.D., to receive its 2013 Founders Award.

Grassroots well water testing initiative reveals high levels of arsenic and radonA recent push to test well water revealed high levels of arsenic and radon in homes throughout the Tuftonboro, N.H., community.

NTP board gives go ahead for PAH research and systematic reviewThe Board of Scientific Counselors endorsed the NTP multi-year PAH research concept with some minor tweaks, and accepted a working group report on systematic review.

Environmental health atlas provides interactive portal to promote awarenessLongtime grantee Bruce Lanphear, MD., gave an audience at NIEHS a sneak peek at the Canadian Environmental Health Atlas website he and his colleagues are developing.

Climate impacts of kerosene lamps used in developing countriesA new study, funded in part by NIEHS, suggests that replacing kerosene lamps with more efficient sources of artificial light would have a major impact in slowing the earth’s warming trend.

ASU appoints Halden to lead new Center for Environmental SecuritySuperfund grantee Rolf Halden, Ph.D., is the new director of the Center for Environmental Security at Arizona State University.

Audio

Video

Video

Video

2012 papers of the yearFrom the nearly 2,500 NIEHS-funded studies published in 2012, leaders of the Institute’s three research divisions selected 30 for special recognition as Papers of the Year.

NIEHS Spotlight Science Notebook

NIEHS Partners gather in Friendship HeightsThe annual NIEHS Partners meeting Dec. 14 in Friendship Heights, Md., featured the lively discussion participants have come to expect in this casual roundtable venue.

Faculty position takes postdoc to remote Arctic communityNIEHS postdoc Anshul Pandya, Ph.D., leaves this month for a tenure-track faculty position at the University of Alaska, Fairbanks Chukchi Campus.

Uranium exposure linked to increased lupus ratePeople living near a former uranium ore processing facility in Ohio are experiencing a higher than average rate of lupus, according a new NIEHS-funded study.

NICEATM holds workshop on new safety tests for pertussis vaccinesNIEHS and FDA scientists joined other experts from around the world at a workshop on improved methods and approaches for safety testing of whooping cough vaccines.

Former NIEHS fellow pursues a career in mentoring postdocsAs the new director of the Office of Postdoctoral Affairs at NCSU, Nisha Cavanaugh, Ph.D., is now in the best position to realize her ambition.

Environmental Polymorphisms Registry gets new leaderThe NIEHS Clinical Research Unit welcomed its newest member, Shepherd Schurman, M.D., to the fold as new director of the Environmental Polymorphisms Registry.

Basic metabolism studies lead to a treatment for laminitis in horsesA compound developed through NIEHS-funded Superfund research shows promise in treating a severe inflammatory disorder.

Casey meets with international experts to assess endocrine disruptor testingNTP scientist Warren Casey, Ph.D., participated in expert meetings Nov. 28-30 about in vitro methods for detecting substances that might interfere with normal hormone function.

NIEHS employees recognized by NIH ODTen NIEHS employees were among those recognized Dec. 19 at the 2012 NIH Office of the Director Honor Award ceremony in Bethesda, Md.

Stokes honored by U.S. Public Health ServiceNTP center director Rear Adm. William Stokes, D.V.M., received the Distinguished Service Medal Dec. 19, during his flag officer retirement ceremony at NIEHS.

Video

Papers explore chemical risk assessment in light of climate changeThe seven publications detail the ways climate change might affect how chemicals are transported and cause toxicity to ecosystems and humans.

Inside the Institute

NIEHS celebrates diversity and generosity on International DayNIEHS offered employees and contractors sustenance for the body and the soul during this year’s International Day celebration Dec. 12.

Extramural Research

Extramural papers of the month• Mechanism for melanoma risk in people with red

hair and fair skin

• Early exposures to air pollution linked with autism

• Flame retardant Firemaster 550 confirmed as endocrine disruptor

• Prenatal mercury and ADHD

Intramural Research

Intramural papers of the month• Chloride channel regulation may lead to

improvements in vascular disease

• Mechanisms of anticancer drug resistance

• New insights into lung dendritic cell migration in adaptive immune responses

• Tobacco smoke exposure in utero increases adult cardiovascular disease risk

Science Notebook

Upcoming data integration workshopAn innovative NIEHS-sponsored program continues its workshop series with an exploration of Integrating Environmental Health Data to Advance Discovery Jan. 10-11.

Rose to give distinguished lectureThe first 2013 NIEHS distinguished lecture, “Myocarditis: an environmentally initiated autoimmune disease,” will be presented Jan. 8 by Noel Rose, M.D., Ph.D.

Video

This month in EHPEnvironmental Health Perspectives goes paperless in January with its first entirely electronic issue featuring a cover article on cooler-by-design architecture and engineering.

Audio

Calendar of Upcoming Events

• Jan. 4, in Rodbell C, 11:00 a.m.-12:00 p.m. — Laboratory of Reproductive and Developmental Toxicology Seminar Series presentation on “Regulation of Cytochrome P450 Enzyme Proteolysis by Reactive Nitrogen Species,” by Edward Morgan, Ph.D.

• Jan. 8, in Rodbell Auditorium, 11:00 a.m.-12:00 p.m. — Distinguished Lecture Series featuring Noel Rose, M.D., Ph.D., speaking on “Myocarditis: An Environmentally Initiated Autoimmune Disease”

• Jan. 9-11, in Rodbell Auditorium, 8:30 a.m.-4:30 p.m. — Nano Exposure Workshop, followed by Nano Characterization Workshop

• Jan. 10-11 (offsite event), at the Keck Center in Washington, D.C., and online — Emerging Science Workshop on Integrating Environmental Health Data to Advance Discovery, register

• Jan. 16-17 (offsite event), at the California Environmental Protection Agency in Sacramento and online — Cumulative Impacts and Children’s Environmental Health

• Jan 17, in Rodbell Auditorium, 10:00-11:00 a.m. — Office of the Director Seminar with Story Landis, Ph.D.

• Jan. 23 (offsite event), at Louisiana State University in Baton Rouge and online — Superfund Research Program Symposium on Response, Recovery, and Resilience to Oil Spills and Environmental Disasters: Engaging Experts and Communities, registration required

• Jan. 25, in Rodbell Auditorium, 10:30-11:30 a.m. — Martin Luther King Jr. Observance by Griffin Rodgers, M.D.

• Jan. 28-30, in Rodbell Auditorium, 8:30 a.m.-4:30 p.m. — BPA Grantee Research and Women’s Reproductive Health Meeting

• View More Events: NIEHS Public Calendar

http://www.surveygizmo.com/s3/1087258/January-Data-Meeting-On-Site-Registration

http://circle.berkeley.edu/Events2013Symposiumr.html

http://circle.berkeley.edu/Events2013Symposiumr.html

http://srp.lsu.edu/ResourcesfortheCommunity/item50452.html

http://tools.niehs.nih.gov/pubevents/

1

NIEHS SpotlightBirnbaum gives keynote at environmental health meeting in India By Eddy Ball

NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,traveledtoNewDelhi,India,Dec.6topresentthekeynoteaddressataninternationalsymposiumonoccupationalhealth.OrganizedbytheCentreforOccupationalandEnvironmentalHealth(COEH)atMaulanaAzadMedicalCollege(MAMC),thegatheringofspecialistsDec.6-8wastitled“AnInternationalMeetonClimate,theWorkplace,andtheLungs.”

TheCOEHisgovernedbytheIndraprastha(Delhi)SocietyforOccupationalandEnvironmentalHealth,aresearchandgovernmentadvisorygroupdedicatedtopreventingwork-relatedinjuryandillhealth,aswellasenvironmentalillness,througheducation,training,clinicalaction,andmonitoringregulatorycompliance.AcentralgoaloftheCOEHisdevelopingthespecialtyofoccupationalandenvironmentalmedicineinIndia.

Birnbaum,theonlyU.S.federalscientistpresentingatthemeeting,joinedenvironmentalandoccupationalhealthexpertsfromNorthAmerica,Europe,India,andotherAsiannationsinawide-rangingexplorationofexistingandemergingenvironmentalhealthissuesinIndia.

Primer on environmental health focuses on IndiaBirnbaumsetthetoneforhertalkon“NIEHSandtheFutureofEnvironmentalHealth”bydescribingwhatmakesNIEHSstandoutamongitssisterinstitutesandcentersatNIH.“NIEHSisuniqueattheNIH,becausewearetheonlyonewhoseresearchhasaprimaryfocusonpreventingdisease,ratherthandiagnosingandtreatingit,”shetoldheraudience.“Thismeansthatwehaveacommitmenttoconductingoutreach,education,training,andsupportingcommunitypartnerships,inadditiontothehighestquality,mostrigorouslaboratory-basedscience.”

ShethenmovedintoabroaddiscussionofenvironmentalhealthresearchsupportedbyNIEHSwithspecialrelevancetohealthconcernsinIndia.Theseareasofresearchincludepersistentissues,suchasarsenicindrinkingwaterandindoorairpollutionfromcookstoves,andemergingproblemsrelatedtodevelopment,suchasobesity,airpollution,electronicwaste,climatechange,andasbestos.

Birnbaum also discussed the new NIEHS strategic plan, which includes a statement of the Institute’s strong commitment to global environmental public health. Her talk featured a number of references to the extensive research and preventive efforts NIEHS has funded in developing nations. (Photo courtesy of Steve McCaw)

Linked video:Watch an Australian Broadcasting Corporation report on asbestos in India (03:10)

(Launches in new window)

Download Media Player: Flash

http://www.coeh.delhigovt.nic.in/rti.asp

http://www.mamc.ac.in/

http://www.youtube.com/watch?v=cO3LOo6mlfw




http://get.adobe.com/flashplayer/

2

AsBirnbaumnotedthroughoutherpresentation,NIEHS-supportedresearchonproblemsthatNorthAmericanshaveconfrontedcanhelpbuildthefoundationforadvancingawareness,research,andpreventiveeffortstopromoteoccupationalandenvironmentalhealthinIndiaandotherdevelopingnations.“TheenvironmentalhealthissuesthatwefaceintheU.S.arenotuniquetoourcountry,”sheexplained.“IndiaissufferingfromsomeofthesameenvironmentalhealtheffectsthataffecttheU.S.”

The world’s premier environmental health sciences research institutionBirnbaum’skeynoteaddressinNewDelhiisbutthelatestexampleoftheemergenceofNIEHSasamodelforenvironmentalhealthsciencesresearchworldwide.Amongitsmanysuchinitiativesinthepasttwoyearsalone,theInstitutehaspartneredwithothergovernmentagenciesintheinternationalGlobalAllianceforCleanCookstoves;workedwiththeWorldHealthOrganization(WHO)andPanAmericanHealthOrganizationtobringenvironmentalhealthtotheforefrontoftheinternationaldebateonclimatechangeandeconomicdevelopment;spearheadedasymposiumwiththeEuropeanCommissiononlowdoseeffectsofendocrinedisruptors;hostedavisitbyrepresentativesoftheFrenchhealthresearchorganizationInserm;andplayedamajorroleatinternationaldioxinsymposiainBelgiumandAustralia.

Naturallyenough,whenT.K.Joshi,directoroftheOccupationalandEnvironmentalHealthProgrammeatCOEH,beganputtingtogethertheconferenceprogram,heturnedforAmericanexpertisetoBirnbaum,aswellasenvironmentallungdiseaseexpertArthurFrank,M.D.,Ph.D.,oftheDrexelUniversitySchoolofPublicHealth.TheyjoinedrepresentativesofWHO,theOccupationalHealthClinicsforOntarioWorkers,theUnitedNationsEnvironmentProgramme,severalIndianorganizationsandgovernmentagencies,andotherspecialiststhroughouttheworld.

Return to Table of Contents

Birnbaum let headlines tell part of the story, as she underscored the health issues that India and the U.S. both experience. (Slide courtesy of Linda Birnbaum)

With this slide as a backdrop, Birnbaum pointed to NIEHS-funded research drawing attention to, and documenting, the impact of exposure to mixed metals from unregulated recycling and disposal of electronic waste. (Slide courtesy of Linda Birnbaum)

http://publichealth.drexel.edu/Faculty/Faculty-Member/5034/facultyid--39/

3

Resnick elected AAAS Fellow By Eddy Ball

IntheNov.30,2012issueofScience,theAmericanAssociationfortheAdvancementofScience(AAAS)announcedtheelectionofleadresearcherMichaelResnick,Ph.D.,asanewfellow.ResnickisheadoftheChromosomeStabilityGroupintheNIEHSLaboratoryofMolecularGenetics.

TheorganizationwillpresentResnickwithacertificateandgoldrosetteFeb.16inBostonduringtheAAASFellowsForum,whichispartofthe2013AAASannualmeeting,honoringhimforseminalcontributionsinunderstandingthemolecularbasisofDNArepairbyhomologousrecombination.

“ThisisanhonorMikerichlydeserves,”saidNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,whenshelearnedoftheaward.“Hisworkisanexcellentexampleofthewaybasicresearchcanbroadenunderstandingofenvironmentalhealthandinformclinicalresearch,especiallywithhisgroup’scross-divisionalcollaborationwithourClinicalResearchUnitphysiciansontheroleofthemasterregulatorp53,anearlyrespondertoDNAdamage,ininflammatoryresponses.”

Resnickandhisgroupareinterestedingeneticandstructure-functionrelationshipsbetweenrepair,replication,mutationavoidance,andsignalingresponses;sourcesofDNAdamage,especiallydouble-strandbreaks,mechanismsofrepair,andgeneticconsequences;andenvironmentalagentsandconditionsthatimpactgenomestability.Thefindingsareintegratedintohisstudiesontheorganizationandevolutionofthehumanp53tumorsuppressormasterregulatorynetworkandconsequencesofcancer-associatedmutations.

ResnickjoinedNIEHSin1979followingpostdoctoralfellowshipswiththeMedicalResearchCouncilinLondonandOakRidgeNationalLaboratoryinTennessee,andpositionsattheUniversityofRochesterinNewYorkandtheMRCNationalInstituteforMedicalResearchinLondon.HewastheNIEHSScientistoftheYearin2008.HisgrouphasbeenawardedthreeNIEHSBestPaperoftheYearAwardsandauthorednumerousDivisionofIntramuralResearchpapersofthemonth.

AAAS – 164 years of advancing scientific excellenceFoundedin1848,AAASservessome262affiliatedsocietiesandacademiesofscience,representingmorethan10millionindividuals.TheAAASjournalSciencehasthelargestpaidcirculationofanypeer-reviewedgeneralsciencejournalintheworld,withanestimatedtotalreadershipofonemillion.

AAASbeganelectingfellowsin1874,anhonorbestoweduponmembersbytheirpeers.Fellownominationsmaybemadebythesteeringgroupsoftheassociation’s24sections,bythechiefexecutiveofficer,orbyanythreefellowswhoarecurrentAAASmembers,solongastwoofthethreesponsorsarenotaffiliatedwiththenominee’sinstitution.Eachnomineemustreceivetheapprovalofamajorityofthesteeringgroupmembers.

Listen as Resnick discusses his research into p53 and the innate immune system (03:15)

Read Transcript

Newly elected AAAS fellow Mike Resnick holds seven patents for research conducted in his lab and has published more than 160 peer-reviewed studies indexed by PubMed. (Photo courtesy of Steve McCaw)

http://www.niehs.nih.gov/research/atniehs/labs/lmg/cs/index.cfm

http://www.aaas.org/meetings/future_mtgs/

http://ocplmedia.od.nih.gov/nihradio/20110426niehstlr.mp3

http://ocplmedia.od.nih.gov/nihradio/20110426niehstlr.mp3

http://www.nih.gov/news/radio/apr2011/20110426niehstlr.htm

4


Suk honored for leadership by Society of Toxicology By Eddy Ball

TheSocietyofToxicology(SOT)hasselectedNIEHSSuperfundResearchProgram(SRP)DirectorBillSuk,Ph.D.,toreceiveits2013FoundersAward.SOTwillpresentSukwithaplaqueandastipendataceremonyMarch10duringits52ndannualmeetinginSanAntonio.

InherannouncementofSuk’saward,SOTAwardsCommitteeChairMaryAnnSmith,Ph.D.,describedtheawardasawell-deservedhonor.“TheFoundersAwardisawardedtoafullmemberofthesocietywhohasdemonstratedoutstandingleadershipinfosteringtheroleoftoxicologicalsciencesinsafetydecision-making,throughdevelopmentand/orapplicationofstate-of-the-artapproachesthatelucidate,withahighdegreeofconfidence,thedistinctionsforhumansbetweensafeandunsafelevelsofexposurestochemicalandphysicalagents,”shewrote.

Superfund’s 25 years of leadership in toxicologySukhasservedasSRPdirectorsincetheprogram’sinceptionin1987.Hehasledthedevelopmentofcomprehensiveresearch,remediation,education,translation,andoutreachefforts,toprevent

In good companyResnickjoinsaselectgroupofNIEHSscientistselectedasAAASfellowsinpreviousyears:

• JoelAbramowitz,Ph.D.,specialassistanttothescientificdirector

• MarianJohnson-Thompson,Ph.D.,formerdirectorofEducationandBiomedicalResearchDevelopment

• JamesMason,Ph.D.,researcherintheDrosophilaChromosomeStructureGroupintheLaboratoryofMolecularGenetics

• JamesPutney,Ph.D.headoftheCalciumRegulationGroupintheLaboratoryofSignalTransduction

• AnneSassaman,Ph.D.,directoremeritusoftheDivisionofExtramuralResearchandTraining

• BarbaraShane,Ph.D.,formerNTPstaffscientistandexecutivesecretaryoftheNTPBoardofScientificCounselors

• SamuelWilson,M.D.,headoftheDNARepairandNucleicAcidEnzymologyGroupintheLaboratoryofStructuralBiology

• JerrelYakel,Ph.D.,headoftheIonChannelPhysiologyGroupintheLaboratoryofNeurobiology

2013 Founders Award winner Suk (Photo courtesy of Steve McCaw)

http://www.toxicology.org/ai/csot/specific_funds.asp#founders

http://www.toxicology.org/AI/MEET/AM2013/

5

diseaseandillnessrelatedtoexposuretotoxicsubstancesgeneratedatthemorethan15,000federallymanagedhazardouswastesitesintheU.S.TheprogramhasnurturedproductiverelationshipswiththeU.S.EnvironmentalProtectionAgency,whichoverseeshazardouswastecleanupatSuperfundsites,andtheAgencyforToxicSubstancesandDiseaseRegistry,whichsharestheSRPpublichealthmission.

Inrecognitionofitsmilestoneanniversary,SRPproducedacommemorativebookletonitsaccomplishmentsintheU.S.andabroadforitsannualmeetingOct.22-24,2012inRaleigh,N.C.(seestory).Atthemeeting,grantees,trainees,andfriendsoftheprogramlookedaheadtothefuturedirectionsofSRPasamodelforglobalhealthinterventionsindevelopingcountrieswhereatleast20percentofdeathsaredirectlyattributabletopreventableenvironmentalexposures.

Honoring a pioneer in applying toxicology to public health SukreceivedhisPh.D.inmicrobiologyfromtheGeorgeWashingtonUniversityandhisMastersinPublicHealthinhealthpolicyfromtheUniversityofNorthCarolinaatChapelHill.HehasalsobeenaNationalScienceFoundationfellow.

Affiliatedwithanumberoforganizationsandcommitteesconcernedwithtoxicexposuresandpublichealth,SukisamemberoftheRoundtableonEnvironmentalHealthSciences,Research,andMedicineattheInstituteofMedicineoftheNationalAcademies;InternationalAdvisoryBoardoftheChulabhornResearchInstituteinBangkok;andWorldHealthOrganizationConsultationonScientificPrinciplesandMethodologiesforAssessingHealthRisksinChildrenAssociatedwithChemicalExposures.Healsoservesonanumberoftrans-NIHcommittees.

Heisamemberoftheeditorialboardsofanumberofinternationaljournals,includingEnvironmentalHealth,ToxicologicalandEnvironmentalChemistry,InternationalJournalofOccupationalMedicineandEnvironmentalHealth,andtheCentralEuropeanJournalofPublicHealth.

InadditiontohisrecognitionbySOT,SukhasreceivedNIHhonorsforhismanyefforts,aswellastheU.S.DepartmentofHealthandHumanServicesSecretary’sAwardforDistinguishedService.HeisarecipientoftheRoyE.AlbertMemorialAwardforTranslationalResearchinEnvironmentalHealthfromtheUniversityofCincinnati;theChildHealthAdvocateAwardfromtheChildren’sEnvironmentalHealthNetwork;theJohnP.WyattLectureAwardinEnvironmentalHealthandDiseasefromtheUniversityofKentucky;andtheAdelF.SarofimAwardforExcellenceinCombustionResearch.HeisafellowoftheCollegiumRamazzini.


Grassroots well water testing initiative reveals high levels of arsenic and radon By Sara Mishamandani

ArecentpushtotestwellwaterrevealedhighlevelsofarsenicandradoninhomesthroughouttheTuftonboro,N.H.,community.FollowingapresentationinJune2012bytheDartmouthCollegeSuperfundResearchProgram(SRP)CommunityEngagementCore(CEC)totheTownofTuftonboroBoardofSelectmenabouttheimportanceofregularwelltesting,theTuftonboroConservationCommission(TCC)ledanefforttoincreasewelltestingratesintheregion.

http://www.niehs.nih.gov/news/newsletter/2012/11/spotlight-srp/file154739.pdf

http://www.niehs.nih.gov/news/newsletter/2012/11/spotlight-srp/index.htm

http://www.tuftonboro.org/Pages/TuftonboroNH_boards/concom/Index

6

InNewHampshire,oneineveryfivewellshasmorethan10partsperbillionofarsenic,whichisabovetheU.S.EnvironmentalProtectionAgencystandardforsafety.AnewreportreleasedDec.4,2012,bytheU.S.GeologicalSurvey(USGS)showsthatlowlevelsofarsenicindrinkingwaterismuchmorewidespread.Theresearchersfoundthatnearly40percentofNewHampshire’sgroundwaterlikelycontainsatleastlowlevelsofnaturallyoccurringarsenic.

The well testing initiative in TuftonboroInpartnershipwiththeDartmouthCECandtheN.H.DepartmentofEnvironmentalServices(DES),thecommissionmadeiteasierforresidentstotesttheirwater,byprovidingadrop-offlocationandthendeliveringsamplestothestatelab.Topublicizethewellwatertestingopportunity,theywrotearticlesforthetownnewsletterandlocalnewspapers,andplacednoticesinthetownpostoffices,withinformationaboutthehealthrisksassociatedwithelementscommonlyfoundinN.H.wells.

Aftertesting,resultsweresentdirectlytotheresidents.InOctober2012,theDartmouthCECpresentedthecollectiveresults,whichshowedthat34percentofsamplesexceededtheU.S.EnvironmentalProtectionAgency’smaximumcontaminantlevelforarsenic,and25percentofthesampleswereabovetheadvisorylevelforradon.

Duetothesehighlevels,DEShostedaforumNov.13toallowresidentstoaskquestionsabouttheirtestresultsandremediationoptions.TheDartmouthCECcontinuestoworkwiththeresidentsinthecommunity,informingthemoftheimportanceofregularwelltestingandprovidingthemwithoptionstoreduceexposuretoarsenicandradonfromwellwater.

“Mostlocalresidentsaren’tinformedaboutthehealtheffectsandtheneedtotestforarsenicwhentheirwateristested,”saidSteveWingate,amemberoftheTCCandalocalresident.“Dartmouthhashelpeduswithtechnicalinformation,andcan‘talkthetalk’wherewestrugglewithinformingresidents.”

Linked video:Watch the Dartmouth SRP video, which reaches out to the general public to encourage testing private wells for arsenic contamination (10:00)



Steve Wingate, left, and Nancy Piper, of the TCC, worked with Dartmouth SRP to raise awareness of the need for well testing. (Photo courtesy of Steve Wingate)

Christine Bowman, right, a DES employee who works in the Municipal Water group, helped a homeowner understand options for reducing exposure, at the well water forum in November 2012. (Photo courtesy of Steve Wingate)

http://www.usgs.gov/newsroom/article.asp?ID=3474#.UL94lKyCn6I

http://www.youtube.com/watch?v=hi5DfRy01vE






7

Reaching out to othersDartmouthSRPresearcherBruceStanton,Ph.D.,wasfeaturedinapublicradioreportafterthenewstudyfromtheUSGSwaspublished.Stantonexplainedthattheselevelscouldbeaffectingpeople’shealth.

“Somepreliminarystudiesshowthattheseverylowarsenicexposurescouldbemakingpeoplemoresusceptibletolunginfections,”saidStanton.“Thebottomlineisthere’snotalotofresearchattheselowlevels,we’rebeginningtodoresearch,andwearefindingsignificanteffects.”

Intheradioreport,Stantonaddedthatthesafestthingtodo,forpeopleconcernedaboutwaterquality,istogettheirwellstested.

DartmouthSRPhascreatedaten-minutevideoabouttherisksassociatedwithexposuretopotentiallyharmfulamountsofarsenicinprivatewellwater.Thevideoincludesinformationabouthowarsenicmovesintogroundwater,howitisdetected,andwhatcanbedonetoremoveit.

(SaraMishamandaniisaresearchandcommunicationspecialistforMDBInc.,acontractorfortheNIEHSSuperfundResearchProgram,WorkerEducationandTrainingProgram,andDivisionofExtramuralResearchandTraining.)


ASU appoints Halden to lead new Center for Environmental Security By Sara Mishamandani

RolfHalden,Ph.D.,anArizonaStateUniversity(ASU)environmentalengineeringprofessorandNIEHSSuperfundResearchProgram(SRP)grantee,isthenewdirectoroftheCenterforEnvironmentalSecurity(CES)atASU,aninnovativeinitiativetomanageenvironmentalstresstoprotecthumanhealthandcriticalecosystems.

HaldenseesCESasawaytoaddresstheneedtoworkonaregional,national,andglobalscaletoprotectenvironmentalqualityandhumanhealth,usingbothtraditionalandinnovativepublichealthstrategies.

“ThegoalofCESistoprotecthumanpopulationsandourplanetbydetecting,minimizing,andultimatelyeliminatingharmfulchemicalandbiologicalagentsthroughengineeringinterventions,”saidHalden.“Wewillbeutilizingaproactiveapproachtoexaminechemicalandbiologicalthreatsintheenvironmentlocallyandglobally,totrackhumandiseasesofenvironmentaletiology,andtodevelopinterventionstrategiessuitableformitigatingthesethreats.”

In addition to leading CES, Halden formed In Situ Well Technologies, a spinout company that focuses on remediation for contaminated water resources and aquifers. (Photo courtesy of ASU)

http://www.nhpr.org/post/usgs-low-levels-arsenic-40-percent-nh-groundwater

http://www.biodesign.asu.edu/research/research-centers/environmental-security

https://webapp4.asu.edu/directory/person/1114611

8

Uniting public health engineering and global securityThecenterwillbethefirstof11researchcentersatASU’sBiodesignInstitute,whichwillpartnertoleverageexpertiseandresourcesfromASU’sSecurityandDefenseSystemsInitiative(SDSI).Byusingenvironmentalengineeringtoanticipatethreatsandpreventavoidablediseases,Halden’scenterwillfocusonnationalandglobalsecurity,throughatransdisciplinaryapproach,tohelpanswernumerouspresent-daysustainabilitychallengesandtoofferanotablereturnoninvestment.

“Publichealthengineeringsaveslivesandmoney,”Haldenexplained.“Morethanhalfofhumanity’shealthproblemsaredependent,eitherdirectlyorindirectly,onenvironmentalfactors.Peoplegetexposedtopotentiallyharmfulagentsthroughfood,air,water,andsoil.Wearelookingatallrelevantexposurerouteswiththegoaltointerveneearly.”

ThemajorresearchthemesofCESincludeenvironmentalmonitoringasameansofthreatdetection;environmentalepidemiologyforhealthimpactassessment;publichealthpreparednessforbioterrorismprevention;innovativeenvironmentaldiagnosticsandmanagementstrategiesusingmicrocosmarraysandpolicyinterventions;andfoodsafetyandsecuritythroughmicrobialdrug-resistancetracking.

Thecenterwasestablishedinlate2012,withfundingfromthePiperCharitableTrust,aswellastheASUSDSI,FultonSchoolsofEngineering,andOfficeofKnowledgeEnterpriseDevelopment.CESalsohassupportfromtheDepartmentofDefensefortwoprojects.

A focus on Superfund researchHalden’spastandcurrentNIEHS-fundedresearchconcentratesonthedevelopmentofanin situmicrocosmarray(ISMA)remedialdesigndeviceandasamplingtoolforassessingbioavailabilityandtoxicityofsediments.BothprojectsaddressthepressingneedofSuperfundstakeholderstodetermine,inaconvenientandreliableway,bothhumanhealthrisksfromcontaminatedsedimentsandtheeffectivenessofimplementedremediationstrategies.

HisteamattheASUBiodesignInstituterecentlyreachedanarrangementwithGeosyntecConsultants,aninternationalenvironmentalremediationfirm,tojointlydeveloptheNIEHS-fundedISMAtechnologyforcommercialization.

HaldenhasreceivedSRPfundingsince2006,resultinginover35peer-reviewedpublications,multiplepatentapplications,andthreeSRPResearchBriefs(169,180,and199).Halden’sresearchhasalsosparkedtwostartupcompanies.

(SaraMishamandaniisaresearchandcommunicationspecialistforMDBInc.,acontractorfortheNIEHSSuperfundResearchProgramandDivisionofExtramuralResearchandTraining.)


NIEHS Partners gather in Friendship Heights By Eddy Ball

TheannualNIEHSPartnersmeetingDec.14,2012,inFriendshipHeights,Md.,featuredthelivelydiscussionparticipantshavecometoexpectinthiscasualroundtablevenue.AlongwiththewelcomeopportunitytotalkpersonallywithNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,thisyear’sgatheringalsofeaturedaninformalsymposiumonOne-NIEHSendocrinedisruptionresearch,byrepresentativesoftheInstitute’sthreeresearchdivisions.

http://tools.niehs.nih.gov/srp/researchbriefs/view.cfm?Brief_ID=169&searchTerm=Halden



9

ThepurposeofthesemeetingswiththeNIEHSPartnersistoseekinputandimprovecommunicationwithcommunitiesandorganizationsdirectlyaffectedbythemissionandresearchofNIEHS.Themembershiprepresentsdiversegroups,includingdisease,disability,andenvironmentaleducationandadvocacyorganizations.ThegrouplendsgrassrootsperspectivestotheresearchagendaofNIEHS,whileservingasakeycontributortothetranslationofresearchfindingstothepublic,policymakers,andprivatefoundations.

Research divisions collaborate on endocrine researchBirnbaum,whoobviouslyenjoysthecamaraderieofthePartners,openedthemeetingwithasincereexpressionofherappreciationoftheirinput.“Youallareareallyterrificgroup,”shetoldthe15attendees,asparticipantspreparedtointroducethemselvesandenjoy21/2hoursofopendiscussionoverlunch.ThefinaltwohoursofthemeetingweredevotedtopresentationsbyleadresearcherKenKorach,Ph.D.,oftheDivisionofIntramuralResearch;leadresearcherSueFenton,Ph.D.,oftheDivisionoftheNationalToxicologyProgram;andhealthscientistThaddeusSchug,Ph.D.,oftheDivisionofExtramuralResearchandTraining.

AlongwithBirnbaum,whoseinterestinendocrinedisruption,andtheatypicaldose-responsepatternstohormone-likechemicals,hasinspiredseveralofherrecenttalks,Korach,Fenton,andSchugdescribedtheInstitute’sintegratedresearchstrategytobetterunderstandthepublichealthimpactofexposure.

Asthespeakersexplained,endocrine-disruptingcompoundscanaffecthumanhealthfrompreconceptiontooldage,withespeciallysignificantimpactsduringdevelopmentalwindowsofsusceptibility.Recentresearchsuggeststhatexposuresmayhaveeffectsongeneexpressionthatcanmanifestyearsanddecadeslater,triggeringarangeofdiseaseanddysfunctionthatmayevenaffectoffspringinsubsequentgenerations.

Keeping a finger on the pulse of environmental healthNIEHSreachesouttothePartnersinseveralways,includingsuchgatheringsastheinformalmeetinginFriendshipHeights,monthlyconferencecalls,collectionsofnewNIEHS-supportedscientificstudies,andparticipationbyrepresentativesatmeetingsoftheNationalAdvisoryEnvironmentalHealthSciencesCouncil.Alongwithrepresentativesoftheresearchdivisions,staffmembersfromtheNIEHSBethesda,Md.,office

Partner Nsedu Obot Witherspoon, right, took advantage of the informal setting, to air concerns about the effects of environmental exposures on children’s development. Witherspoon is a former NIEHS council member and the executive director of the Children’s Environmental Health Network. (Photo courtesy of John Schelp)

Birnbaum, right, made a point that low-dose exposures to hormone-like chemicals, at certain stages of development, can potentially be very harmful. Schug, left, spoke about NIEHS grants for endocrine-disruption research. (Photo courtesy of John Schelp)

http://www.niehs.nih.gov/about/community/publicinterest/index.cfm

http://www.niehs.nih.gov/about/boards/naehsc/index.cfm

10

interactwiththePartners.Atthisyear’smeeting,NIEHSLegislativeLiaisonMaryGantandSpecialAdvisorforPublicHealthJohnBalbus,M.D.,wereonhandtoofferupdatesaswell.

“Wedidn’thavepreparedspeechesorPowerPoints.Justanopenconversationaroundabigtable,”saidSpecialAssistantforCommunityEngagementandOutreachJohnSchelpoftheOfficeofScienceEducationandDiversity,whichorganizestheevents.

ThiskindoffluidagendastrikesapositivechordwiththePartners.“Eachyear,theNIEHSsharesadvancesincuttingedgeresearchwiththePartners,sowecanhelpourpublicunderstandtherolethatenvironmentmaybeplayinginthedisabilityorhealthconditioneachgrouprepresents,”saidBettyMekdeci,Partnersco-chairanddirectorofBirthDefectResearchforChildren.“WearealsoprivilegedtobeabletoaskDr.Birnbaumanyquestionthatwillfurtherourunderstandingofthescience.”

Partnerco-chairKarenMiller,founderandpresidentoftheHuntingtonBreastCancerActionCoalition,agreedandaddedherownappreciationoftheInstitute’scross-disciplinaryapproachtoenvironmentalhealthscience.“NIEHSreallybringseverythingtogether...dynamic...energizing...oppositeofsilos.Thisisthemodeltoemulate,becauseeverysinglethingisconnected,”shesaid.


Faculty position takes postdoc to remote Arctic community By Eddy Ball

FortunatelyforNIEHSpostdocAnshulPandya,Ph.D.,andhiswife,thecoupleknowswhattoexpectwhentheymovetothesublimelandscapeofruralnorthwesternAlaskathismonth—bone-chillingwintercoldwithhighsmostdaysstayingwellbelowzero,followedbyabrief,butglorious,Alaskansummertheybelieveiswellworththewait.

PandyaisagraduateoftheUniversityofAlaskaFairbanks(UAF),wherehewillreturntoassumeatenure-trackfacultypositionattheUAFChukchiCampusinthestate’sNorthwestArcticBorough.HiswifelivedinNome

The Partners joined NIEHS representatives for a photo opportunity, at the conclusion of the program. (Photo courtesy of John Schelp)

http://www.niehs.nih.gov/about/od/deputy/osed/index.cfm

http://www.uaf.edu/chukchi/About/

11

beforetheymovedtotheTriangletogether.AfterPandyacompletedhisdoctoratein2009,andpriortojoiningNIEHSforhispostdoctoraltraininglaterthatsummer,hewasanadjunctprofessorintheRuralAlaskaHonorsInstitute(RAHI),whichservedaminoritypopulationverysimilartothepeopleinthenorthwesternInupiathubwherehe’llbeteachingandconductingresearch.

“It’slikegoinghome,”Pandyasaid.“I’mreallylookingforwardtomovingouttoAlaska,livinginthewilderness,andbeingoutdoorsinthesummers.”

Training at the bench and beyondForthepast31/2years,PandyahasworkedintheLaboratoryofNeurobiologyIonChannelPhysiologyGroupheadedbyJerrelYakel,Ph.D.InhisworkwithYakel’sgroup,Pandyabroughthisperspective,asapharmacologist,toresearchthatfocusedonthenicotinicacetylcholinereceptorchannelsandtheirroleinneurologicaldisorders.Hewasfirstauthoroftwopapersonallostericmodulatorsofthosereceptors,andaco-authororcontributoronseveralotherpapersfromthegroup.

Butateacher/researcherisnotmerelyasourceofknowledge,asPandyarecognizedearlyinhisfellowshipatNIEHS.So,Pandyasoonbeganlookingforadditionalmentorsandcareerdevelopmentopportunities.

In2011,hebeganwritingDivisionofIntramuralResearchpaperofthemonthsummaries,workingwithScienceEditorRobinArnette,Ph.D.,aswellasotherarticlesfortheEnvironmentalFactor.Laterthatyear,hejumpedatthechancetoworkwiththeNIEHSOfficeofScienceEducationandDiversity(OSED),

“I’ve had a good experience here,” Pandya said of his time as a trainee. “I’ve enjoyed working at NIEHS, and Jerry [Yakel] gave me a lot of freedom to explore career development opportunities, as well as take higher-risk approaches to my research.” (Photo courtesy of Steve McCaw)

Blending academics with communityInhisnewposition,PandyawillbeapartoftheUAFeducationaloutreachmissionandliveinaverysmallcommunityofnativeAlaskansinthetownofKotzebue,whichhasabout4,000residentsandishometotheChukchiCampus.Hewillprobablyteachafewcoursesatsatellitelocationsinsomeofthetensmallervillagesintheregion,wheresome3,000morepeopleliveinthe38,000squaremileNANAregion,whichwasnamedforitsprecursor,theNorthwestAlaskaNativeAssociation,andisroughlythesizeofIndiana.

Becauseofthevastness,remoteness,andsusceptibilitytopermafrostfreezingandmelting,theNANAregiondoesnothavehighwayaccesstoitsvillages.WhenUAFChukchiCampusfacultymemberscommute,theyflyinandoutinsmallaircraft.BargesdeliverheatingoilwhentheChukchiSeaoftheArcticOceanisnavigable.

Ashighlytrainedscientistswholivewheretheywork,PandyaandhisUAFcolleaguesserveasrolemodelsforyoungpeople.Theyarealsoanintegralpartofaclose-knitcommunitywherepeopleoftendependonothers.“Peoplewhocanflyintolargertownsandcitiesoftenbringbacksuppliestohelpothersthroughthewinters,”hesaid.“Peoplearereallyfriendlythere,andthefeelingisthatcooperation[ratherthancompetition]bringsyouabetterfuture.”

http://www.uaf.edu/rahi/

http://www.niehs.nih.gov/research/atniehs/labs/ln/icp/staff/index.cfm

http://www.niehs.nih.gov/about/od/deputy/osed/index.cfm

http://www.nana.com/regional

12

headedbyErickaReid,Ph.D.,inspiredinpartbyhisearlyexperiencesaspartofRAHI.HealsoservedasamentorforNIHSummerInternProgramparticipantsinhislabgroup.

Theseoff-benchtrainingexperiencesprovedtobehelpfulinlandinghisnewjobatUAF,wherehewillbeteachingandmentoringnativeAlaskanfreshmanandsophomorestudentsinlifesciencecourses.Writingaboutscienceoutsidehisfieldgavehimexperienceincommunicatingarangeoftopicstoamoregeneralaudience.

AttendingtheannualconferencesoftheSocietyforAdvancementofChicanosandNativeAmericansinScienceandtheAnnualBiomedicalResearchConferenceforMinorityStudentsin2011and2012asarepresentativeofOSED,Pandyahadanopportunitytonetwork,aswellaslearnhowtoexplainNIEHSandNIHtrainingandemploymentopportunitiestoyoungscientistsfromunderrepresentedpopulations.

PandyaalsotookadvantageofopportunitiestolearnfromoutsidespeakershehostedatNIEHS.“WetalkedaboutwhatIshoulddowhenItransitionmycareerfromapostdoc,whatprecautionstotake,howtonegotiateapackage,andwhattolookoutforduringmyjobsearch,”hesaid.

Thatcombination,plusproactiveeffortstoestablishpersonalcontactwithsearchcommitteemembersattheinstitutionswhereheapplied,ledtofourinterviewsduringPandya’ssix-monthsearchfortherightposition.


Shown in red, the sparsely populated NANA region borders the Arctic Slope, not far from Russia. (Map courtesy of the NANA Corporation)

13

Former NIEHS fellow pursues a career in mentoring postdocs By Sheila Yong

DuringhertimeasapostdoctoralfellowatNIEHS,NishaCavanaugh,Ph.D.,discoveredherpassioninadvocatingforpostdoctoralfellowsandhelpingthemseekoutthebestopportunitiesavailabletothem.EquippedwithherpreviousleadershipexperienceasthechairoftheNIEHSTraineesAssembly(NTA),shewantedtocontinueherquesttoassistpostdoctoralfellowsinexploringpotentialcareerpathsandhelpthemacquiretheskillstheyneedtoachievetheirgoals.

AsthenewdirectoroftheOfficeofPostdoctoralAffairs(OPA)atNorthCarolinaStateUniversity(NCSU),apositionsheassumedinDecember2012,Cavanaughisnowinthebestpositiontorealizeherambition.

Preparing for a career away from the benchWhileservingastheNTAchairin2010-2011,CavanaughworkedcloselywithDianeKlotz,Ph.D.,theformerdirectoroftheOfficeofFellows’CareerDevelopment(OFCD).Usingherowncareerexperienceasanexample,KlotzwasinstrumentalinadvisingCavanaughregardingcareersawayfromthebench.

“MypostdoctoralexperienceatNIEHSandmyinteractionwithDr.Klotzallowedmetobetterunderstandthevariouschallengespostdoctoralfellowsoftenfacebothinandoutsidethelab,anditputmeinapositiontohelpfuturepostdocsovercomethesechallenges,”Cavanaughcommented.ShebelievesthatthesequalitieswillenablehertocarryoutherdutiesmoreeffectivelyastheOPAdirector.HerresponsibilitiesatOPAincludeoverseeingthedevelopmentofprogramsandservicesforpostdoctoralscholarsthatwillenhancetheirexperienceatNCSU,facilitatingnetworkingopportunitiesforthemintheResearchTriangleParkarea,andcreatinganetworkamongpastandpresentNCSUpostdocs.

Cavanaughisalsogratefultoherformersupervisor,SamuelWilson,M.D.,whoheadstheDNARepairandNucleicAcidEnzymologyGroupatNIEHS.WilsonwasverysupportiveofCavanaugh’sinvolvementwithNTAandOFCDactivities,whichenabledhertodevelopcommunicationandleadershipskillsthatarecrucialtohercurrentposition.

“Dr.Wilsonregularlyadviseshispostdoctoralfellowsonmattersthatwillhelpthembecomeindependentresearchers,”Cavanaughsaid.“AlthoughIdidnotpursueacareerinbenchscience,IappreciatethetraininghegavemeandtheanalyticalskillsIamabletoapplyatmynewposition.”

Along with her work with NTA and OFCD, Cavanaugh also was a contributing writer for the Environmental Factor during the final months of her fellowship at NIEHS. (Photo courtesy of Steve McCaw)

Wilson, who was Cavanaugh’s science mentor and supervisor, supported her in career development experiences away from the bench. (Photo courtesy of Steve McCaw)

http://www.ncsu.edu/grad/postdoctoral-affairs/index.php

http://www.niehs.nih.gov/research/atniehs/labs/lsb/dnarna/staff/index.cfm

http://www.niehs.nih.gov/research/atniehs/labs/lsb/dnarna/staff/index.cfm

14

The importance of professional networkingCavanaughcreditsherlandingtheOPAdirectorpositiontothestrongprofessionalnetworkshebuiltwhileatNIEHS.“Severalpeopleinmynetworkinformedmeofthejobopportunityandintroducedmetopeoplewhowerealsoontheinterviewcommittee,”sheexplained.Herprofessionalnetworkcontinuedtobehersourceofsupportandadvicethroughoutthelongjobapplicationprocess.

CavanaughurgescurrentpostdoctoralfellowstoactivelyparticipateinvariouscareerdevelopmenteventsatNIEHS,andtofamiliarizethemselveswiththeinstituteanditspolicies.“BothNTAandOFCDprovideinvaluableleadershipandnetworkingopportunities,andbeinginvolvedisanexcellentwaytoenhanceyourcommunicationandtransferableskills,”sheconcluded.

(SheilaYong,Ph.D.,isavisitingfellowintheNIEHSLaboratoryofSignalTransduction.)


Environmental Polymorphisms Registry gets new leader By Robin Arnette

Sinceitsopeningin2009,theNIEHSClinicalResearchUnit(CRU)hassteadilyexpandedthenumberofresearchprojectsandnumbersofstaffwhohelpfacilitatethework.InearlyOctober2012,theCRUwelcomeditsnewestmember,ShepherdSchurman,M.D.,tothefold.SchurmancomestoNIEHSfromtheNationalInstituteonAging(NIA)andnowservesastheCRU’sstaffclinicianandheadoftheEnvironmentalPolymorphismsRegistry(EPR).

Fromthetimehewas4yearsold,Schurmansaidheknewhewantedtobecomeaphysician-scientist.Bothofhisparentswerefascinatedwithscienceandhadrelativeswhowerephysicians,sotheyfosteredhisinterestinmedicineandgenetics.Aftercompletingmedicalschoolandaresidencyininternalmedicine,hejoinedtheNationalHumanGenomeResearchInstitute(NHGRI)asaresearchfellow,studyinggenetherapyandimmunedeficiencydisorders.AftermovingtoNIA,hestartedworkingwithDNArepairandpolymorphisms,orgenedifferences,associatedwithage-relateddiseases.

“Whenthepositionofstaffcliniciancameopenhere,Ithoughtitwasagreatopportunity,”Schurmansaid.“Ibelieveditwouldbeaprettygoodfit,givenmybackgroundingenetics,clinicaltrials,andpolymorphismsresearch.”

DarrylZeldin,M.D.,theNIEHSScientificDirector,hiredSchurmanforthejob.Hesaid,“IamconfidentthatDr.SchurmanwillexceedouralreadyhighexpectationsinleadingthenextphaseoftheEPR.”

Schurman is a native of Chicago, Ill., and takes over the position of EPR director from Patricia Chulada, Ph.D. (Photo courtesy of Steve McCaw)

http://www.niehs.nih.gov/research/clinical/join/durham/index.cfm

http://dnaregistry.niehs.nih.gov/

15

Heading the EPRTheCRUisa14,000squarefootfacilityontheNIEHScampusthatconductsstudiestodeterminehowenvironmentalexposuresinfluencedisease.TheEPR,whichisoneofseveralongoingstudiesattheCRU,providesaccesstoDNAfrommorethan17,000individualsfromtheNorthCarolinaTriangleregion.Participantswithpolymorphismsofinterestmaybeinvitedtojoinfollow-upstudiesthatallowresearcherstoperformbasiclaboratoryexperiments,suchascellphenotypingfromdonatedblood,orbeaskedtoparticipateinmorecomprehensiveclinical-basedresearch.WiththeadditionoftheEPR’shealthandexposuresurvey,anindividual’ssusceptibilitytocommonconditions,suchasasthma,diabetes,cardiovasculardisease,cancer,andotherillnessescanbeassociatedwithinvestigatedpolymorphisms.

AccordingtoSchurman,theEPRfitsnicelywithintheframeworkofthenewNIEHSstrategicplan,becauseofitsfocusontranslationalresearch.Asexamples,hementionedEPR’sadherencetogoal1,whichseekstoidentifymechanismsbehindcomplexdisease,andgoal2,whichaimstounderstandindividualsusceptibilitytodiseaseresultingfromenvironmentalfactors.Healsopointedoutthatthethirdthemeinthestrategicplan,translationalscience,describesperfectlyjustwhattheEPRisdoing.

“Thekeypassagefromthatsectionis‘Environmentalhealthtranslationalresearchcanintroduce,intomedicaldecision-making,anewlevelofinformationaboutgene-environmentinteractionaffectingdrugs,biologics,infections,andotherenvironmentalfactorsinhealthanddisease,’”hesaid.“TheEPRcanbeavaluableresourcetobothintramuralandextramuralresearchers.”

AsmedicaldirectoroftheCRU,StavrosGarantziotis,M.D.,knowsthattheonlywayfortheEPRtomaximizeitspotentialistogetmanymoreresearcherstoinitiatestudiesusingitsDNA.RecruitingscientiststominetheEPR’sgeneticinformationwillbeachallengeGarantziotisfeelsSchurmanisreadytomeet.

“Dr.Schurmanisverywellqualifiedforthisrole,havingworkedformanyyearsattheNIAwiththeBaltimoreLongitudinalStudyofAging,aswellashavingcollaboratedintheearliestgenetreatmenttrialsattheNHGRI,”Garantziotissaid.“HethusbringsagreatamalgamofskillsandexperiencesthatwillenablehimtoleadtheEPRtoanewphase,andhelpusgainnewinsightsintotheinteractionofgenesandtheenvironmentinthedevelopmentofdisease.”


NIEHS employees recognized by NIH OD By Eddy Ball

TenNIEHSemployeeswereamongthoserecognizedDec.19atthe2012NIHOfficeoftheDirector(OD)HonorAwardceremonyintheNatcherAuditoriumontheNIHcampusinBethesda,Md.

OnhandtopresenttheawardswereNIHDirectorFrancisCollins,M.D.,Ph.D.,andPrincipalDeputyDirectorLawrenceTabak,D.D.S.,Ph.D.,whowerejoinedonstagebydeputydirectorsoftherespectiveareasinwhichrecipientemployeeswerehonored.

Linked video:People with NIH system access can view an archived video of the ceremony (01:55:00)



http://videocast.nih.gov/summary.asp?live=12264





16

“TheODHonorAwardrecognizesexceptionalcontributionsbyemployeestotheNIHmission,”saidNIHODSeniorProgramAdvisorJanieKuhn,whoorganizedtheprogram.TheHonorAwardrankswiththeNIHMeritAward,whichcanbeawardedbydirectorsofinstitutesandcenters,andisoftenpresentedinrecognitionofoutstandingperformancebyemployeesinvolvedintrans-NIH,U.S.DepartmentofHealthandHumanServices(DHHS),andotherfederalinitiatives.

Awardees from NIEHS included the following:• OfficeofManagementProgramCoordinatorMonya BraceandOfficeofClinicalResearchClinicalLaboratoryManagerAnnette Rice—2011FedsFeedFamiliesTeam—InrecognitionofexemplaryeffortsinpromotingtheFed’sFeedFamiliesCampaignattheNationalInstitutesofHealthandthroughouttheUnitedStates.

• OfficeofAcquisitionsContractSpecialistAntoinette Bridges, D.M.,OfficeofAcquisitionsBranchChiefCharles Conrad,andAdministrativeServicesandAnalysisBranchEmployeeServicesProgramSpecialistCynthia Radford—AppropriationsLawTrainingandLeadershipGroup—Foroutstandingachievementinprovidingalternativeofferings,essentialcommunications,tracking,andproblemresolutiontoensurefullcompliancewiththeDHHSAppropriationsLawRequirement.

• OfficeofTechnologyTransferDirectorElizabeth Denholm, Ph.D.—NIHBiospecimenWorkingGroup—Fordedicationanddiligent,persistentefforts,whichhaveresultedinamajoroverhaulinthereportingofbiospecimensatNIH.

Monya Brace (Photo courtesy of Steve McCaw)

Charles Conrad (Photo courtesy of Steve McCaw)

Jane Lambert (Photo courtesy of Steve McCaw)

Janice Allen (Photo courtesy of Steve McCaw)

Antoinette Bridges (Photo courtesy of Steve McCaw)

Elizabeth Denholm (Photo courtesy of Steve McCaw)

17

• ClinicalResearchProgramInstitutionalReviewBoardAdministratorJane Lambert—NIHClinicalResearchProtocolApplicationTaskforce—Forpersistent,outstandingeffortstocreateandharmonizethecontentsoftheNIHclinicalresearchprotocoltemplate.

• GrantsManagementBranchGrantsManagementSpecialistMolly Puente, Ph.D.—ResearchPerformanceProgressReportGroup—InrecognitionofexceptionalleadershipandoutstandingeffortsinNIH’simplementationoftheFederal-wideResearchPerformanceProgressReport.

• ScientificReviewBranchHealthScientistAdministratorJanice Allen, Ph.D.—ReviewPolicyCommitteeScientificReviewOfficerTechnicalCompetenciesTeam—Inrecognitionofexceptionalvision,teamwork,andcollaborationinidentifyingScientificReviewOfficerCoreTechnicalCompetencies.

• LaboratoryofMolecularCarcinogenesisStaffScientistJohn Roberts, Ph.D.—TeamforImplementingtheAnimalCareandUseGuideatNIH—ForassuringafuturenationalandinternationalleadershiproleoftheNIHAnimalCareandUseProgramwiththe8theditionoftheirguide.


Stokes honored by U.S. Public Health Service By Eddy Ball

NTPcenterdirectorRearAdm.WilliamStokes,D.V.M.,receivedtheDistinguishedServiceMedalfromtheU.S.PublicHealthService(USPHS)Dec.19,2012,duringhisflagofficerretirementceremonyatNIEHS.TheeventfilledRodbellauditoriumwithwell-wishers,includingmembersofhisfamily,manyofhisco-workersinNTP,andmorethan70fellowUSPHSofficersindressuniform.

Cynthia Radford (Photo courtesy of Steve McCaw)

John Roberts (Photo courtesy of Steve McCaw)

Molly Puente (Photo courtesy of Steve McCaw)

Annette Rice (Photo courtesy of Steve McCaw)

http://niehs.nih.gov/news/newsletter/2013/1/spotlight_stokes/file202364.pdf

18

TheDistinguishedServiceMedalisthehighestawardpresentedbyUSPHS,andtheflagofficerretirementceremonyisatime-honoredtraditionoftheUSPHS,basedonthecenturies-oldpompandcircumstanceofmaritimechanging-of-commandformalities.OnhandtosupportthecarefullychoreographedeventweretheU.S.SurgeonGeneral’sHonorCadre,USPHSChoralEnsemble,andU.S.ArmyForcesCommandBrassQuintet.

Stokes’retirementasarearadmiralandassistantU.S.SurgeonGeneral,withnearly34yearsofactivedutyserviceasacommissionedofficer,wasmandatedbyUSPHSregulations.

High praise for a stellar careerOnstagewithStokesduringthe21/2-houreventwereNIEHS/NTPDirectorLindaBirnbaum,Ph.D.;NTPAssociateDirectorJohnBucher,Ph.D.;DeputyU.S.SurgeonGeneralBorisLushniak,M.D.;andfellowofficerswhohadservedwithStokesduringthecourseofhiscareerasaUSPHScommissionedofficer.

MasterofCeremonyUSPHSCommanderGeorgeDurgin,ResilienceDivisionchiefattheDefenseCentersofExcellenceintroducedtheprogramofninespeakerswhodeliveredthehighestpraisefortheirretiringcolleague.CaptainTerriClark,D.V.M.,thetenthchiefveterinaryofficerforUSPHSanddirectoroftheNIHOfficeofAnimalCareandUse,setthetoneforthosewhofollowedher.“Billisjustasteadfastvisionaryleader,”shesaidofhermentorandlongtimecomrade.

OtherspraisedStokesforhisworkindisasterdeployments,includingthe2005aftermathofHurricaneKatrina;hisimportantcontributionsduringthetransformationofUSPHStoamoreconsistentlymilitary-likeuniformedservice;andhisselflesseffortstospurthecareerdevelopmentofsubordinatesandcolleagues.TheceremonyincludedthereadingoflettersfromtheassistantsecretaryoftheU.S.DepartmentofHealthandHumanServices,formerU.S.SurgeonGeneralRichardCarmona,M.D.,membersoftheNorthCarolinacongressionaldelegation,andanumberofcolleagueswhowereunabletoattend.

Lushniakofferedtheultimatepraisefromacommandingofficer,whenhesaidofStokes,“Ifyouwantajobdonetherightway,putBillincharge.”

Emotionsrunhighatthisimportantpointinanofficer’scareer,anditwashardlysurprisingthatStokeshadtopauseseveraltimeswhenhisturncametospeak.Facingtheseaofblueuniforms,Stokesrecalledfondlythemanyrolemodelswho,duringhislife,helpedtobuildhisstrongworkethicandinstill,earlyon,thecorevaluesofUSPHS—integrity,excellence,leadership,andservicetoothers.

Stokes, above, and the other uniformed speakers saluted briskly as they received military honors and entered the auditorium to make their way to the stage. (Photo courtesy of Steve McCaw)

The U.S. Surgeon General’s Honor Cadre presented the colors, as well as performed the symbolic retirement of Stokes’ Assistant Surgeon General flag and the Old Glory tribute. (Photo courtesy of Steve McCaw)

19

StokesreceivedUSPHSandU.S.flags,assymbolsofhisdedicatedservice,aswellasgiftsfromcolleagues.Inanespeciallytouchingpartoftheceremony,LushniakpresentedStokes’wife,Nancy,withacitationandflowersinappreciationofhersupportduringwhatLushniakdescribedasStokes’marathonofservicetothenation’spublichealth.

Stokes’ legacy at NIHPriortohisofficialseparationDec.31,2012,StokesservedasdirectoroftheNationalToxicologyProgramInteragencyCenterfortheEvaluationofAlternativeToxicologicalMethods(NICEATM)andexecutivedirectoroftheInteragencyCoordinatingCommitteeontheValidationofAlternativeMethods(ICCVAM).NICEATMandICCVAMprovidescientificsupportandcoordinateinteragencyinitiativesforadvancingnewandalternativesafetytestingmethods,includingthosedesignedtoreplace,reduce,andrefinetheuseofanimalsintoxicitytesting.

Stokeshas33yearsofexperienceinbiomedicalandtoxicologicalresearch,26yearsofthatwithNIH,andhasservedtheNTPsince1992.Heservedhiscountryinthreeofthesevenuniformedservices,foratotalof42yearsofactivedutyandreserveservice.HealsoheldpositionsastheanimalprogramdirectoratNIEHSandtheTheEuniceKennedyShriverNationalInstituteofChildHealthandHumanDevelopment,andastheeighthchiefveterinaryofficerforUSPHS.

As master of ceremony, Durgin set the tone for the event with his gravitas and defined the military cadence of the ceremony with the staccato emphasis of his delivery. (Photo courtesy of Steve McCaw)

Lushniak was energetic, humorous, and candid, as he described the changes officers face as they move from active duty as health warriors on call virtually 24 hours a day to officers at ease awaiting orders that may not come. Turning to face Stokes, Lushniak said, “This ain’t gonna be easy for you.” (Photo courtesy of Steve McCaw)

Stokes’ family members enjoyed a place of honor on the front row of the audience. His wife, Nancy, right, was also honored for her support of her husband’s career, especially during the times he was deployed and absent from the home. (Photo courtesy of Steve McCaw)

20

In one of his final acts as NIEHS chief of staff, Captain Paul Jung, M.D., read letters of congratulations from the North Carolina congressional delegation. Jung assumed the position of deputy director of the newly formed headquarters for the USPHS Commissioned Corps in Rockville, Md., Jan. 1. (Photo courtesy of Steve McCaw)

In a moving tribute to Old Glory and the long history of selfless sacrifice to country on the part of uniformed officers, Stokes received his retirement national ensign that had flown at several of his duty stations, including NIEHS. (Photo courtesy of Steve McCaw)

Following their own tributes to their colleague, Bucher, left, and Birnbaum had an opportunity to enjoy the comic relief Stokes’ uniformed colleagues and friends added to this generally solemn ceremony. (Photo courtesy of Steve McCaw)

Warren Casey, Ph.D., who assumes the role of acting director of NICEATM with Stokes’ transition, was among the many NTP colleagues on hand to congratulate and thank him for his long service to the cause of alternative testing. Casey joined NICEATM as deputy director in 2010. (Photo courtesy of Steve McCaw)

The ceremony concluded with the speakers and the audiences standing in respect as Stokes received his symbolic permission to go ashore. Following the benediction, attendees gathered for a reception in the NIEHS cafeteria. (Photo courtesy of Steve McCaw)Return to Table of Contents

21

Science Notebook

2012 papers of the yearFromthenearly2,500NIEHS-fundedstudiespublishedin2012,leadersoftheInstitute’sthreeresearchdivisionsselected30forspecialrecognitionasPapersoftheYear.

Research funded by grants (click title for abstract)• Non-coding DNA variants may link early exposures with later health problems

• Reversible epigenetic changes associated with bee behavior

• Triclosan impairs heart and skeletal muscle contractility

• Whole genome sequencing reveals genetic basis for diversity and evolution

• Gene variants linked with faster Parkinson’s disease progression

• Cardiovascular effects of Beijing Olympics air pollution reduction

• Environmental exposures influence behavior of later generations

• Autism risk linked to maternal diabetes and obesity

• Health implications of temperature variability

• Air pollution linked to cognitive decline

• The cost of asthma from traffic-related air pollution

• Menthol lessens irritation from cigarette smoke

• Perfluorinated compounds and immune response in children

• Rice consumption and arsenic exposure in pregnant women

• Consuming canned soup linked to higher BPA levels

In-house research (click title for abstract)• EET research may help in the fight against cancer

• Calcium influx is a critical component of embryonic development

• Pol II pausing modulates basal gene expression in signal transduction cascades

• Clustered mutations attributed to body’s natural defenses

• Fertility drugs and young-onset breast cancer

• Cerium dioxide nanoparticles may lead to human immune cell death

22

• New treatment allows medicines to cross blood-brain barrier

• Glucocorticoid signaling could lead to better therapeutics

• Bacteria in house dust worsens asthma


National Toxicology Program research (click title for abstract)• Arsenic-transformed malignant prostate epithelia can convert noncontiguous normal stem cells into an

oncogenic phenotype

• Testing an aflatoxin B1 gene signature in rat archival tissues

• Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two-years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways

• An ethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents

• The genome architecture of the Collaborative Cross mouse genetic reference population

Research funded by grants

Non-coding DNA variants may link early exposures with later health problemsResearchers,supportedinpartbyNIEHS,reportthatgeneticdifferenceslinkedtoavarietyofdiseasesareactivatedduringfetaldevelopment.Thesefindingscouldhelpexplainwhysomeearlyenvironmentalexposuresincreasediseaseriskyearsorevendecadeslater.

TheresearchersinvestigatedwhethervariantsinnoncodingregionsofDNAregulategeneexpression,bylookingatthousandsofthesevariantsidentifiedingenome-wideassociationstudies(GWAS).TheresearchersalsoidentifiedthegenesregulatedbyhundredsofGWASvariants,includinggenesassociatedwithseveraldiseases.Almost80percentofGWASvariantsinregulatoryDNAwereconnectedtogenesthatwerenottheclosestonestothevariant,whichisprobablywhypreviousattemptstolinkGWASvariantswithtargetgeneshavebeensodifficult.

Citation:MauranoMT,HumbertR,RynesE,ThurmanRE,HaugenE,WangH,ReynoldsAP,SandstromR,QuH,BrodyJ,ShaferA,NeriF,LeeK,KutyavinT,Stehling-SunS,JohnsonAK,CanfieldTK,GisteE,DiegelM,BatesD,HansenRS,NephS,SaboPJ,HeimfeldS,RaubitschekA,ZieglerS,CotsapasC,SotoodehniaN,GlassI,SunyaevSR,KaulR,StamatoyannopoulosJA.2012.Systematiclocalizationofcommondisease-associatedvariationinregulatoryDNA.Science337(6099):1190-1195.

[synopsis]

Return to Table of Contents | Return to Papers of the Year

http://www.ncbi.nlm.nih.gov/pubmed/22955828




http://www.niehs.nih.gov/news/newsletter/2012/11/dert/#a1

23

Reversible epigenetic changes associated with bee behaviorResearchersstudyinghoneybeesreportwhatcouldbethefirstevidenceofreversibleepigeneticchangesassociatedwithbehavior.Theresearchmayshedlightonproblemsthatpeoplehavewithlearning,memory,stressresponse,andmooddisorders,whichallinvolveinteractionsbetweengeneticandepigeneticcomponents.TheworkwassupportedbyanNIHDirector’sPioneerAward.

TheresearchersfoundnodifferencesinDNAmethylationbetweenworkerandqueenbees,rolesthatareirreversible.However,theysawsubstantialdifferencesbetweennursesandforagerbees.Revertingforagersbacktonursesreestablishedmethylationlevelsforamajorityofgenes,providingevidenceofreversibleepigeneticchangesthatareassociatedwithbehavior.

Citation:HerbBR,WolschinF,HansenKD,AryeeMJ,LangmeadB,IrizarryR,AmdamGV,FeinbergAP.2012.Reversibleswitchingbetweenepigeneticstatesinhoneybeebehavioralsubcastes.NatNeurosci15(10):1371-1373.

[synopsis]


Triclosan impairs heart and skeletal muscle contractilityNIEHSgranteesreportthattriclosanhindersmusclecontractionsatacellularlevelandalsocausesmuscleproblemsinfishandmice.Triclosanisanantibacterialagentwidelyusedinpersonal-careproductssuchashandsoapandtoothpaste,andithasbeendetectedinwaterwaysandfish.Thisnewstudyprovidesevidenceofthechemical’spotentiallynegativeeffectsonhumanandenvironmentalhealthandalsorevealsamechanismfortheseeffects.

Micegivenasingledoseoftriclosanshowedan18-percentreductioningripstrengthforupto60minutes.Minnowsexposedtotriclosaninthewaterforsevendaysshowedsignificantlyreducedswimmingactivitycomparedtocontrols.

Citation:CherednichenkoG,ZhangR,BannisterRA,TimofeyevV,LiN,FritschEB,FengW,BarrientosGC,SchebbNH,HammockBD,BeamKG,ChiamvimonvatN,PessahIN.2012.Triclosanimpairsexcitation-contractioncouplingandCa2+dynamicsinstriatedmuscle.ProcNatlAcadSciUSA109(35):14158-14163.

[synopsis]


Whole genome sequencing reveals genetic basis for diversity and evolutionInoneofthefirstpopulationgenomicsstudiestousehigh-coveragewhole-genomesequencing,NIEHS-supportedresearchersanalyzedthegenomesof15Africansfromthreedifferenthunter-gatherergroups.






24

Theworkrevealsnewinsightintohumandiversityandevolutionandalsoshowsthepotentialofnewgenomesequencingtechnologyforuncoveringthegeneticbasisofnormalvariationsinhumansandforidentifyingthegeneticbasisofdiseaserisk.

Theresultsfromthegenomeanalysisprovideevidencethatthedirectancestorsofmodernhumansmighthaveinterbredwithmembersofanunknownancestralgroupofhomininsandthatdifferentgroupsevolveddistinctly.TheworkalsoidentifiesnewcandidategenesthatarelikelyinvolvedinmakingPygmiesshortinstature.

Citation:LachanceJ,VernotB,ElbersCC,FerwerdaB,FromentA,BodoJM,LemaG,FuW,NyamboTB,RebbeckTR,ZhangK,AkeyJM,TishkoffSA.2012.Evolutionaryhistoryandadaptationfromhigh-coveragewhole-genomesequencesofdiverseAfricanhunter-gatherers.Cell150(3):457-469.

[synopsis]


Gene variants linked with faster Parkinson’s disease progressionNIEHSgranteesreportthatParkinson’sdiseasepatientswithtwospecificvariantsofthealpha-synucleingeneprogressedtowardmotordeclinesignificantlyfasterthanpatientswithoutthesevariants.Thisworkcouldleadtonewtherapiesandhelpidentifythosewhowouldbenefitmostfromearlyintervention.

Althoughthefindingsneedreplicationinotherwell-characterizedParkinson’sdiseasepopulations,theresearcherssaythattheirworkshowsthatthesegenevariantscouldbeusedtoidentifypatientswhowilllikelyexperiencefasterdiseaseprogression.Theworkalsopointstothealpha-synucleinpathwayasapromisingpotentialtherapeutictarget.

Citation:RitzB,RhodesSL,BordelonY,BronsteinJ.2012.Alpha-synucleingeneticvariantspredictfastermotorsymptomprogressioninidiopathicParkinsondisease.PLoSOne7(5):e36199.

[synopsis]


Cardiovascular effects of Beijing Olympics air pollution reductionTheChinesegovernmentshutdownfactoriesandlimitedautomobiletrafficduringtheBeijingOlympics,tolessenairpollution.Thesetemporarychangesinairpollutionlevelswereassociatedwithacutechangesincardiovascularbiomarkersinhealthyyoungpeople,accordingtoastudyfromNIEHSgrantees.Theresearchaddsevidencethathigherlevelsofairpollutionarelinkedwithanincreasedriskofcardiovascularproblems.

DuringtheOlympics,thestudyparticipantsshowedsignificantreductionsinvonWillebrandfactorandsolubleCD62Plevels,whicharebothassociatedwithbloodcoagulation.SolubleCD62PandsystolicbloodpressurelevelsincreasedsignificantlyoncethepollutioncontrolswereliftedaftertheOlympics.






25

Citation:RichDQ,KipenHM,HuangW,WangG,WangY,ZhuP,Ohman-StricklandP,HuM,PhilippC,DiehlSR,LuSE,TongJ,GongJ,ThomasD,ZhuT,ZhangJJ.2012.AssociationbetweenchangesinairpollutionlevelsduringtheBeijingOlympicsandbiomarkersofinflammationandthrombosisinhealthyyoungadults.JAMA307(19):2068-2078.

[synopsis][story]


Environmental exposures influence behavior of later generationsAnewNIEHS-fundedstudyshowsthatanimalswhoseancestorswereexposedtoafungicidehaveamoreprofoundreactiontostressthantheoffspringofunexposedanimals.Theworkdemonstratesthatanancestor’sexposurecaninfluencethestressresponseoffuturegenerations.

Theauthorsofthestudyusedasystemsbiologyapproachbyexamininggeneticandmolecularchangesinthebrainaswellasbehavior.Theyexposedgestatingfemaleratstothefungicidevinclozolinandlaterperformedtestingonthethirdgenerationofoffspring.Whenexposedtostressduringadolescence,theoffspringofexposedratshadgreateranxiety,sensitivitytostress,andmoreactivityinstress-relatedregionsofthebrain.

Citation:CrewsD,GilletteR,ScarpinoSV,ManikkamM,SavenkovaMI,SkinnerMK.2012.Epigenetictransgenerationalinheritanceofalteredstressresponses.ProcNatlAcadSciUSA109(23):9143-9148.

[synopsis]


Autism risk linked to maternal diabetes and obesityFindingsfromtheNIEHS-fundedChildhoodAutismRisksfromGeneticsandtheEnvironment(CHARGE)studyprovideevidencethatmaternalmetabolicconditionscanincreasetheriskforautism,aswellasdevelopmentaldelaywithoutautisticsymptoms.Thefindingssuggestthatfetalexposuretoelevatedlevelsofglucoseandmaternalinflammationadverselyaffectfetaldevelopment.

Themetabolicconditionsstudiedincludedobesityorhypertensionatthestartofpregnancy,ordiabetesduringpregnancy,whichwerelinkedwithsignificantlyincreasedriskforhavingachildwithautismorotherdevelopmentaldisorders.Inaddition,childrenwithautismspectrumdisorderanddiabeticmothershadgreaterdeficitsinadaptivecommunication,languagecomprehension,andlanguageproductionthanchildrenwithautismspectrumdisorderborntohealthymothers.

Citation:KrakowiakP,WalkerCK,BremerAA,BakerAS,OzonoffS,HansenRL,Hertz-PicciottoI.2012.Maternalmetabolicconditionsandriskforautismandotherneurodevelopmentaldisorders.Pediatrics129(5):e1121-1128.

[synopsis]





http://www.niehs.nih.gov/news/newsletter/2012/6/science-cvd/





26

Health implications of temperature variabilityClimatechangeisexpectedtobringincreasingvariabilityinsummertemperatures,whichcouldshortenlifeexpectancyforolderpeoplewithchronicmedicalconditions,accordingtoanNIEHS-fundedstudy.Althoughotherstudieshavelookedattheshort-termeffectsofheatwaves,thisstudyexaminedthelong-termeffectsofclimatechangeonlifeexpectancy.

TheresearchersusedMedicaredatafrom1985to2006tofollowthehealthof3.7millionchronicallyillpeopleoverage65.Theystudiedwhethermortalityrelatedtovariabilityinsummertemperaturein125citiesandtookintoaccountotherfactors,suchaswintertemperaturevariance,ozonelevels,andindividualriskfactors.Theycompiledresultsfor125individualcitiesandthenpooledtheresults.

Citation:ZanobettiA,O’NeillMS,GronlundCJ,SchwartzJD.2012.Summertemperaturevariabilityandlong-termsurvivalamongelderlypeoplewithchronicdisease.ProcNatlAcadSciUSA109(17):6608-6613.

[synopsis][story]


Air pollution linked to cognitive declineInoneofthefirststudiesofitskind,NIEHSgranteesreportthatasignificantlyfasterdeclineinthecognitivefunctionofolderwomenisassociatedwithlong-termexposuretoparticulatematter(PM)airpollutionatlevelstypicalofmanyareasoftheU.S.

Theresearchersestimatethata10-microgrampercubicmeterincreaseinlong-termPMexposurewascognitivelyequivalenttoagingbyapproximatelytwoyears.Ifthefindingsareconfirmedinotherstudies,reducingairpollutioncouldofferawaytolessenage-relatedcognitivedeclineand,becausecognitivedeclineoftenprecedesthedevelopmentofdementia,awaytoreducethefuturepopulationburdenofdementia.

Citation:WeuveJ,PuettRC,SchwartzJ,YanoskyJD,LadenF,GrodsteinF.2012.Exposuretoparticulateairpollutionandcognitivedeclineinolderwomen.ArchInternMed172(3):219-227.

[synopsis]


The cost of asthma from traffic-related air pollutionNIEHS-fundedresearchershaveestimatedthatchildhoodasthmaassociatedwithairpollutioninLongBeachandRiverside,Calif.,costs$18millioneachyear.

Usinganewmethodthatresearcherssaymoreaccuratelyestimatestheoverallburdenofasthmaandthecostsassociatedwithairpollution,theycalculatedthetotalannualcostforatypicalasthmacasetobe$3,819inLongBeachand$4,063inRiverside.Thelargestportionofthiscostcamefromasthma-relatedschoolabsences,whichoftenrequirethatparentsorcaregiversmisswork.Theinvestigatorssaythattheirnewmethodtakesintoaccountthefullimpactoftraffic-relatedpollutionandcanbeappliedtootherurbanareas.



http://www.niehs.nih.gov/news/newsletter/2012/5/science-temperature/index.htm



27

Citation:BrandtSJ,PerezL,KünzliN,LurmannF,McConnellR.2012.Costsofchildhoodasthmaduetotraffic-relatedpollutionintwoCaliforniacommunities.EurRespirJ40(2):363-70.

[synopsis][story]


Menthol lessens irritation from cigarette smokeAnNIEHS-supportedstudyhasshownthatmenthol,thecoolingagentinpeppermint,counteractstheirritatingeffectsofcigarettesmokeconstituents.Theresearchersstudiedacrolein,aceticacid,andcyclohexanone,whichareirritatingcomponentsofcigarettesmokethatvarywidelyintheirchemicalstructureandbiologicalproperties.Theexperimentsdemonstratedthatmenthol’scounterirritanteffectsresultedfromactivationofthechemicalreceptorTRPM8.

Bysuppressingreactionssuchascoughing,mentholcouldincreasetheamountofsmokeinhaledandthuspromoteaddictiontonicotine.The2009FamilySmokingPreventionandTobaccoControlActbannedflavoredtobaccoadditivesbutexemptedmentholwhiletheU.S.FoodandDrugAdministrationevaluatedscientificdata.

Citation:WillisDN,LiuB,HaMA,JordtSE,MorrisJB.2011.Mentholattenuatesrespiratoryirritationresponsestomultiplecigarettesmokeirritants.FASEBJ25(12):4434-4444.

[synopsis][story]


Perfluorinated compounds and immune response in childrenResearchfundedbyNIEHShasshownthatelevatedexposuretoperfluorinatedcompoundswasassociatedwithreducedimmuneresponsesinchildren.

Theprospectivestudyfoundthatchildrenwithelevatedexposuretoperfluorinatedcompoundshadlowerantibodyresponsestochildhoodimmunizations.Theantibodyresponsetochildhoodimmunizationreflectshowwelltheimmunesystemisfunctioning.Theresearchersreportthatthisstudyisoneofthefirsttolinkchildhoodexposuretoperfluorinatedcompoundswithimmunesystemdeficiency.Theresultspointtotheimportanceofassessingtheimmunotoxicpotentialofthesecompounds,whicharehighlypersistentandcancontaminatedrinkingwater,aswellasfood.

Citation:GrandjeanP,AndersonEW,Budtz-JorgensenE,NielsenF,MolbakK,WeiheP,HeilmannC.2012.Serumvaccineantibodyconcentrationsinchildrenexposedtoperfluorinatedcompounds.JAMA307(4):391-397.

[synopsis][story]




http://www.niehs.nih.gov/news/newsletter/2012/3/science-traffic-pollution/index.htm


http://www.niehs.nih.gov/news/newsletter/2012/2/extramural/#a3

http://www.niehs.nih.gov/news/newsletter/2011/october/science-menthol/index.cfm


http://www.niehs.nih.gov/news/newsletter/2012/2/extramural/#a2

http://www.niehs.nih.gov/news/newsletter/2012/4/science-vaccine/

28

Rice consumption and arsenic exposure in pregnant womenNIEHSgranteesreportthaturinaryarsenicconcentrationswerehigherforpregnantwomenwhohadrecentlyconsumedricethanforthosewhohadnot.Thefindingshighlighttheneedtomonitorarseniclevelsinfood.

Theresearcherstestedforarsenicintheurineof229pregnantwomeninNewHampshire,73ofwhomreportedeatingriceduringthetwodaysbeforeurinecollection.Thearsenicconcentrationofthetapwaterinthewomen’shomeswasalsotestedtoidentifyanyexposurefromdrinkingwater.Thewomenwhoreportedeatingriceduringthetwodayspriortourinecollectionhadamediantotalurinaryarsenicconcentrationof5.27microgramsperliter,whichwassignificantlydifferentfromthe3.38microgramsperlitermedianconcentrationforthosewhodidnotconsumerice.

Theresearchersnotetheneedformoreresearchtodetermineanyhealthimpactsofthissourceofexposure.Anyidentifiedhealthriskswillalsoneedtobeweighedagainstthenutritionalbenefitsofeatingrice.

Citation:Gilbert-DiamondD,CottinghamKL,GruberJF,PunshonT,SayarathV,GandolfiAJ,BakerER,JacksonBP,FoltCL,KaragasMR.2011.RiceconsumptioncontributestoarsenicexposureinUSwomen.ProcNatlAcadSciUSA108(51):20656-20660.

[synopsis][story]


Consuming canned soup linked to higher BPA levelsResearchersfundedbyNIEHSfoundthatagroupofvolunteerswhoconsumedaservingofcannedsoupeverydayforfivedayshadmorethana1,000percentincreaseinurinarybisphenolA(BPA)concentrationsthanwhenthesameindividualsconsumedfreshsoupdailyforfivedays.

Eatingaservingofcannedsoupdailywasassociatedwitha1,221percentincreaseinBPAconcentrationcomparedtolevelsinurinecollectedafterconsumptionoffreshsoup.EventhoughtheelevationinurinaryBPAconcentrationsmightbetemporary,theresearcherscommentthattheirfindingscouldbeimportant,especiallyasmoreandimprovedalternativestoepoxyliningsaredeveloped.

Citation:CarwileJL,YeX,ZhouX,CalafatAM,MichelsKB.2011.CannedsoupconsumptionandurinarybisphenolA:arandomizedcrossovertrial.JAMA306(20):2218-2220.

[synopsis]





http://www.niehs.nih.gov/news/newsletter/2012/3/science-arsenic/


http://www.niehs.nih.gov/news/newsletter/2012/1/dert/index.htm#a2

29

In-house research

EET research may help in the fight against cancerAcollaborativeteamofNIEHS-fundedscientistshasfoundthattheremovalofsmallmoleculesproducedinthebodycalledepoxyeicosatrienoicacids(EETs)maypreventtheformationofbloodvesselsthatfeedtumorcells.

HighlevelsofEETsarebeneficialinpatientswithdiseases,suchashypertension,heartattack,andstroke,becausethemoleculescausebloodvesselstodilate.However,theteamdeterminedforthefirsttimethatEETsinthehealthytissuesurroundingthetumorsalsoworkwithaproteinknowntoinducebloodvesselgrowth,calledvascularendothelialgrowthfactor,toactivatebloodvesselformationthatfeedstumors.MiceintheexperimentswithhigherEETsproducedmoremetastatictumorsthanmicewithlowerEETs.

Citation:PanigrahyD,EdinML,LeeCR,HuangS,BielenbergDR,ButterfieldCE,BarnésCM,MammotoA,MammotoT,LuriaA,BennyO,ChaponisDM,DudleyAC,GreeneER,VergilioJA,PietramaggioriG,Scherer-PietramaggioriSS,ShortSM,SethM,LihFB,TomerKB,YangJ,SchwendenerRA,HammockBD,FalckJR,ManthatiVL,IngberDE,KaipainenA,D’AmorePA,KieranMW,ZeldinDC.2012.Epoxyeicosanoidsstimulatemultiorganmetastasisandtumordormancyescapeinmice.JClinInvest122(1):178-191.[synopsis][story]


Calcium influx is a critical component of embryonic developmentUponfertilizationbythesperm,repetitivecalciumoscillationsoccurasaresultofthemovementofcalciumfromeggstorageoroutsidethecell,intotheeggcytoplasm,andthenbackintostorageoroutoftheegg.Thesecalciumoscillationsareessentialformammalianeggactivationandtheearlystagesofembryonicdevelopment.

NIEHSscientistsdeterminedthatsomeofthesignalingpathwaysinducedbycalciummovementstakeplacedirectlyundertheegg’splasmamembrane,ratherthanentirelyinsideoftheegg.Theresearchhasfar-reachingimplicationsforclinicallyassistedreproductionandfertilitypreservationtechnologies,sincedefectsincalciumsignalingatfertilizationcanresultinafailureoftheembryotoimplantordeveloptoterm.

Citation:MiaoYL,SteinP,JeffersonWN,Padilla-BanksE,WilliamsCJ.2012.Calciuminflux-mediatedsignalingisrequiredforcompletemouseeggactivation.ProcNatlAcadSciUSA109(11):4169-4174.[synopsis][story]


Pol II pausing modulates basal gene expression in signal transduction cascadesNIEHSscientistshaverevealedthatRNApolymeraseII(PolII)pausingdoesnotnecessarilyleadtohighergeneexpressionuponinductionofstimulus-responsivenetworks.Rather,itisimportantinmodulatingbasalgeneexpression.TheresearchoffersanewmodelforunderstandinghowpausedPolIIimpactsgeneexpressioninrestingcells.





http://www.niehs.nih.gov/news/newsletter/2012/3/dir/#a2

http://www.niehs.nih.gov/news/newsletter/2012/1/science-cancer/index.htm



http://www.niehs.nih.gov/news/newsletter/2012/4/science-calcium/

30

Theresearchersfoundthatmanydownstreamtargetgeneswererapidlyinduced,despitenotharboringpausedPolIIattheirpromoterspriortopathogenicchallenge.Theirfindingsindicatethat,althoughtheregulatorycomponentsaremoremodestlyexpressedinresponsetoimmunechallenge,theirbasalexpressioninrestingcellsismoretightlyregulatedsothatthesecellsarebetterpoisedtorapidlyinitiatetheimmuneresponsecascadeasneeded.

Citation:GilchristDA,FrommG,dosSantosG,PhamLN,McDanielIE,BurkholderA,FargoDC,AdelmanK.2012.Regulatingtheregulators:thepervasiveeffectsofPolIIpausingonstimulus-responsivegenenetworks.GenesDev26(9):933-944.

[synopsis]


Clustered mutations attributed to body’s natural defensesAteamofNIEHS-fundedscientistshasidentifiedDNAregionswithahighnumberofnonrandommutationsinyeastandsomehumancancers.Contrarytothetraditionallyheldviewthatmutationsoccurrandomly,thesemutationswerenotcausedbyenvironmentaldamage,butbyaspecificsetofproteinsknownasAPOBECcytosine-deaminases,whicharepartofthehumanimmunesystem’sresponsetovirusesthatenterthebody.

Theresearchteamdevelopedbioinformaticstoolstodetermineifhumancancerscontainedsimilarmutationclusterssimilartothosefoundinyeastand,surprisingly,nearlyhalfofthemdid.Theresultsofthisstudysuggestthatseveralantiviraldrugs,capableofstimulatingAPOBECgenes,shouldbeconsideredpotentialmutagens.

Citation:RobertsSA,SterlingJ,ThompsonC,HarrisS,MavD,ShahR,KlimczakLJ,KryukovGV,MalcE,MieczkowskiPA,ResnickMA,GordeninDA.2012.Clusteredmutationsinyeastandinhumancancerscanarisefromdamagedlongsingle-strandDNAregions.MolCell46(4):424-435.

[synopsis][story]


Fertility drugs and young-onset breast cancerAmongparticipantsintheNIEHSTwoSisterStudy,fundedinpartbySusanG.KomenfortheCure,womenwhohadusedovary-stimulatingfertilitydrugs,clomiphenecitrateorfollicle-stimulatinghormone,withoutgettingpregnant,hadreducedriskofyoung-onsetbreastcancer.

Participantswerepairsofsisters,oneofwhomhadbeendiagnosedwithbreastcancerbeforetheageof50.Theywerecategorizedbasedonwhethertheyhadusedovulation-stimulatingfertilitydrugsandwhetherpregnancyhadresulted.Unlikepreviousstudies,theTwoSisterStudydistinguishedbetweenfertilitytreatmentsthatproducedpregnancyversusthosethatdidnot.Moreover,useofsisterswhoarewell-matchedformanyfactorsallowsforafaircomparison.

Citation:FeiC,DeRooLA,SandlerDP,WeinbergCR.2012.Fertilitydrugsandyoung-onsetbreastcancer:ResultsfromtheTwoSisterStudy.JNatlCancerInst104(13):1021-1027.

[synopsis]







http://www.niehs.nih.gov/news/newsletter/2012/6/science-celldamage/index.htm



31

Cerium dioxide nanoparticles may lead to human immune cell deathAnewstudybyNIEHSresearchersusinghumanperipheralbloodmonocytesfromhealthydonorsshowsthatceriumdioxide(CeO2)nanoparticlesatenvironmentallyrelevantexposurelevelscausescelldeathviaapoptosisandautophagy.ItisthefirstreportontheeffectsofCeO2nanoparticlesinprimaryhumancells.GiventhefactthatCeO2emissionsfromdieselfuelareestimatedtoreach22millionpoundsperyearinEurope,itisvitaltounderstandtheirpotentialimpactonhumanhealth.

Theapoptoticmechanismwasindependentofcaspaseactivation,butdependentonmitochondrialdamageandinductionofapoptosis-inducingfactor.Celldeathwasalsomediatedthroughautophagy,whichincreasedifthep53tumorsuppressorproteinwasinhibited.

Citation:HussainS,Al-NsourF,RiceAB,MarshburnJ,YinglingB,JiZ,ZinkJI,WalkerNJ,GarantziotisS.2012.Ceriumdioxidenanoparticlesinduceapoptosisandautophagyinhumanperipheralbloodmonocytes.ACSNano6(7):5820-5829.

[synopsis]


New treatment allows medicines to cross blood-brain barrierAstudybyNIEHSresearchersidentifiedasignalingpathwaythatreducesthetransportactivityofP-glycoprotein,anATP-drivendrugeffluxpumpinratbraincapillariesknowntobeamajorobstacletodeliveringmedicinestothebrain.Theworkmayleadtonewtreatmentsforbrainandspinalcordinjury,braincancer,andepilepsyinhumans.

Theresearchteamusedaconfocalmicroscopy-basedassaytoidentifyasignalingpathwaythatabolishedP-glycoproteintransportactivitywithoutchangingtransporterproteinexpression.ThesefindingswerevalidatedinvivoandledtheresearcherstoconcludethatreducingP-glycoproteinactivitycanallowsmallmoleculepharmaceuticalstosafelycrosstheblood-brainbarrier.

Citation:CannonRE,PeartJC,HawkinsBT,CamposCR,MillerDS.2012.Targetingblood-brainbarriersphingolipidsignalingreducesbasalP-glycoproteinactivityandimprovesdrugdeliverytothebrain.ProcNatlAcadSciUSA109(39):15930-15935.

[synopsis][story]


Glucocorticoid signaling could lead to better therapeuticsNIEHSscientistshavedeterminedthatglucocorticoidsmodulatethesignalingprofileofGprotein-coupledreceptors(GPCRs)throughalterationsinarrestingeneexpression.SinceGPCRsaretargetedbynearlyhalfofallprescriptiondrugs,theworkcouldresultinthedevelopmentofspecifictreatmentsthatwillreducesideeffectsandboostefficacy.





http://www.niehs.nih.gov/news/newsletter/2012/11/science-signaling/

32

TheactivityofGPCRsisgovernedbyagroupofadaptorproteinscalledarrestins.Usingseveraldifferentcelltypes,theresearchteamdiscoveredthatglucocorticoidsdirectlyregulatearrestingeneexpression.ThefluctuationinarrestinexpressioncanmodifytheeffectGPCRscanhaveonhumancellsbybiasingtheirsignalingprofiletofavorGprotein-dependentorbeta-arrestin-dependentresponses.

Citation:OakleyRH,RevolloJ,CidlowskiJA.2012.GlucocorticoidsregulatearrestingeneexpressionandredirectthesignalingprofileofGprotein-coupledreceptors.ProcNatlAcadSciUSA109(43):17591-17596.

[synopsis][story]


Bacteria in house dust worsens asthmaNIEHSscientistsfoundthatflagellin(FLA),abacterialproteinfoundinhousedust,exacerbatesasthmabyinducingallergicresponsestoallergens.Thefindings,whichwereconfirmedinahumanstudy,reinforcetheconnectionbetweenasthmaandtheenvironment.

InhalationofFLAorhousedustextractscontainingFLAtogetherwithchickenovalbumin(OVA)causedmiceinthestudytodevelopallergicpulmonaryinflammationfollowingOVAchallenge.TheresearchteamalsofoundthatthemammalianreceptorforFLA,toll-likereceptor5(TLR5),wasrequiredforprimingofstrongallergicresponsesinmicebysomehousedustextracts.ThestudyconcludedthathouseholdFLApromotesthedevelopmentofallergicasthmabyTLR5-dependentpriming.

Citation:WilsonRH,MaruokaS,WhiteheadGS,FoleyJF,FlakeGP,SeverML,ZeldinDC,KraftM,GarantziotisS,NakanoH,CookDN.2012.TheToll-likereceptor5ligandflagellinpromotesasthmabyprimingallergicresponsestoindoorallergens.NatMed18(11):1705-1710.

[synopsis][story]


Mechanisms of anticancer drug resistanceNIEHSscientistsdescribedthemolecularmechanismsbywhichtopoisomeraseII(topoII)-DNAadductsarerepairedbythemammaliantyrosyl-DNAphosphodiesterase2(Tdp2)enzyme.SincesomeofthemostsuccessfulcancerchemotherapeuticsworkbyinducingtopoII-DNAadductsthatpromotecancercelldeath,thisstudydetermineshowTdp2,inturn,contributestoanticancerdrugresistancethroughitstopoII-DNAadductrepairfunctions.

Bydefiningtheprotein-DNAconjugateprocessingmechanismattheatomiclevel,theteamdeterminedthatTdp2dictatesarepairpathwaybyrecognizingandremovingthesetopoII-DNAadducts.ThesefindingshavefutureimplicationsindevisingstrategiestopreventanticancerdrugresistancebytargetingTdp2anddevelopingTdp2inhibitors.



http://www.niehs.nih.gov/news/newsletter/2012/11/science-signaling/




http://www.niehs.nih.gov/news/newsletter/2012/11/science-bacterial/

33

Citation:SchellenbergMJ,AppelCD,AdhikariS,RobertsonPD,RamsdenDA,WilliamsRS.2012.Mechanismofrepairof5’-topoisomeraseII-DNAadductsbymammaliantyrosyl-DNAphosphodiesterase2.NatStructMolBiol19(12):1363-1371.

[synopsis][story]


National Toxicology Program research

Arsenic-transformed malignant prostate epithelia can convert noncontiguous normal stem cells into an oncogenic phenotypeResearchersexploredthehypothesisthattherepeateddemonstrationsofarsenic-inducedcancerstemcell(CSC)overabundanceintumorsandmultiplicityofprimarytumorsmaybeexplainedbyanabilityofarsenictransformedcellstorecruitnormalstemcells(NSCs)intoCSCs.

Thescientistsplacedarsenic-inducedmalignantepithelialcells(MECs)innoncontactco-culturebyusinginsertswithnormalstemcells(NSC)andassessedtheNSCsformalignanttransformation.TheNSCsrapidlyacquiredphysical(invasion,colonyformation,MMPsecretion)andmolecularcharacteristicsofCSCs.Theresultsshowedarsenic-transformedMECsrecruitedNSCsintoCSCsatasignificantdistance(50-100cellwide)andhadanimpactoncancergrowth,dissemination,andfieldcanceration.

Citation:XuY,TokarEJ,SunY,WaalkesMP.2012.Arsenic-TransformedMalignantProstateEpitheliaCanConvertNoncontiguousNormalStemCellsintoanOncogenicPhenotype.EnvironHealthPerspect20(6):865-871.

[story]


Testing an aflatoxin B1 gene signature in rat archival tissuesFormalin-fixedandparaffin-embedded(FFPE)tissuesfromtoxicologystudiesareavaluableresourceforlinkinghistopathologicaldiagnosistogeneexpressionprofilesforinsightsintomolecularmechanismsofchemicalpathologiesanddisease.

Fourteengenesthatrepresentcellcycleprogression,responsetoDNAdamage,xenosensoranddetoxicationsystemswereevaluatedbyquantitativePCRinFFPEtissuesandcorrespondingfreshfrozenliversamplesfrommaleratstreatedfor90dayswithaflatoxinB1,alivercarcinogen,andconcurrentcontrolanimals.Theresultingdatademonstratethatitisnowpossibletoconductretrospectiveevaluationsofgenesignaturesinarchivaltissues.Archivaltoxicogenomicswillreduceanimalusebyallowingforpriortoxicologystudiestobeinterrogatedforcriticalmoleculareventsinchemicallyinduceddisease.


http://www.niehs.nih.gov/news/newsletter/2012/11/science-anticancer/index.htm


http://www.niehs.nih.gov/news/newsletter/2012/5/science-arsenicstem/

34

Citation:MerrickBA,AuerbachSS,StocktonPS,FoleyJF,MalarkeyDE,SillsRC,IrwinRD,TiceRR.2012.TestinganaflatoxinB1genesignatureinratarchivaltissues.ChemResToxicol25(5):1132-1144.


Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two-years differ from spontaneous liver tumors in cancer gene mutations and genomic pathwaysThisstudyprovidesamolecularcontextforthegeneticchangesassociatedwithhepatocarcinogenesisinGinkgo bilobaleafextract(GBE)-exposedmiceandillustratesthemarkeddifferencesbetweenthesetumorsandthosearisingspontaneouslyintheB6C3F1mouse.

Themolecularchangesobservedinhepatocellularcarcinoma(HCC)fromGBE-treatedanimalsmaybeofrelevancetothoseseeninhumanHCCandothertypesofcancer.AlthoughasignificantamountofdataispresentinthescientificliteraturepertainingtothereportedhealthbenefitsofGBEuse,thesefindingssuggestthatwithlongtermuseofhighdosesofGBEtheremaybepotentialhealthrisks,anditisthereforeimportantthatthehealthstatusofindividualsonchronicGBEtherapyismonitored.

Citation:HoenerhoffMJ,PandiriAR,SnyderSA,HongHH,TonT-V,PeddadaS,ShockleyKR,WittK,ChanP,RiderC,KooistraL,NyskaA,SillsRC.2012.HepatocellularcarcinomasinB6C3F1micetreatedwithGinkgobilobaextractfortwo-yearsdifferfromspontaneouslivertumorsincancergenemutationsandgenomicpathways.ToxicolPathol;doi:10.1177/0192623312467520[Online21December2012].


An ethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodentsBlackcohoshextract(BCE)isusedasaremedyforpainandgynecologicalailments,andmodernpreparationsarecommonlysoldasethanolicextractsavailableasdietarysupplements.Inthisfirststudyofitskind,researchersusedrodentmodelstocharacterizethegeneraltoxicityofBCEandaddresssuspectedestrogenicandanti-estrogenicactivity.

BCEinduceddose-dependenthematologicalchangesconsistentwithanon-regenerativemacrocyticanemiaandincreasedfrequenciesofperipheralmicronucleatedredbloodcells.Effectsweremoresevereinmice—seenatallexposuredoselevels—thanrats.Dose-dependentthymusandlivertoxicitywasalsoobservedinrats.Apparenteffectsonpubertywereobserved,butwerenotassociatedwithalterationinestrogenicandanti-estrogenicactivity.

Citation:Mercado-FelicianoM,CoraMC,WittKL,GranvilleCA,HejtmancikMR,FombyL,KnostmanKA,RyanMJ,NewboldR,SmithC,FosterPM,VallantMK,StoutMD.2012.Anethanolicextractofblackcohoshcauseshematologicalchangesbutnotestrogeniceffectsinfemalerodents.ToxicolApplPharmacol263(2):138-147.







35

The genome architecture of the Collaborative Cross mouse genetic reference populationTheCollaborativeCrossConsortium,whichincludesNTPscientistJefFrench,Ph.D.,reportsonthedevelopmentofauniquegeneticresourcepopulation,theCollaborativeCross(CC),amultiparentalrecombinantinbredpanelderivedfromeightlaboratorymouseinbredstrainsusingmicefromTheJacksonLaboratory,involvedtheUniversityofNorthCarolina,TelAvivUniversity,andGeniadinAustralia.

ThereportincludesinformationonaccesstotheCCpopulationandtotheassociatedrawdatadescribingthegeneticstructureofindividuallines.IntegrationofrichphenotypicandgenomicdataovertimeandacrossawidevarietyoffieldswillbevitaltodeliveringononeofthekeyattributesoftheCC,acommongeneticreferenceplatformforidentifyingcausativevariantsandgeneticnetworksdeterminingtraitsinmammals.

Citation:CollaborativeCrossConsortium.2012.ThegenomearchitectureoftheCollaborativeCrossmousegeneticreferencepopulation.Genetics190(2):389-401.

(ThecontributingwriterforExtramuralsummarieswasNancyD.LamontagneasciencewriterwithMDB,Inc.,acontractorfortheNIEHSDivisionofExtramuralResearchandTraining,SuperfundResearchProgram,andWorkerEducationandTrainingProgram.

IntramuralsummarieswerewrittenbyMamtaBehl,Ph.D.,acontractneurotoxicologistintheNTPToxicologyBranch;NishaCavanaugh,Ph.D.,aformerIntramuralResearchTrainingAward(IRTA)postdoctoralfellowintheNIEHSLaboratoryofStructuralBiologyDNARepairandNucleicAcidEnzymologyGroup;RalucaDumitru,M.D.,Ph.D.,aformerIntramuralResearchTrainingAwardfellowintheNIEHSLaboratoryofMolecularCarcinogenesisStemCellBiologyGroup;BrantHamelPh.D.,aformerIRTAfellowintheNIEHSLaboratoryofSignalTransductionMolecularEndocrinologyGroup;MelissaKerr,achemistrystudentatNorthCarolinaCentralUniversityandinternintheNIEHSOfficeofCommunicationsandPublicLiaison;AnshulPandya,Ph.D.,aformerIRTAfellowintheLaboratoryofNeurobiologyIonChannelPhysiologyGroup;SonikaPatial,D.V.M.,Ph.D.,avisitingfellowintheLaboratoryofSignalTransductionPolypeptideHormoneActionGroup;BhargaviRao,Ph.D.,anIRTAfellowintheNIEHSLaboratoryofMolecularCarcinogenesisChromatinandGeneExpressionGroup;JeffreyStumpf,Ph.D.,aformerIRTAFellowintheNIEHSLaboratoryofMolecularGeneticsMitochondrialDNAReplicationGroup;SheetalThakur,Ph.D.,anIRTAfellowintheNIEHS/NTPToxicologyBranch;IanThomas,apublicaffairsspecialistwiththeNIEHSOfficeofCommunicationsandPublicLiaison,andaregularcontributortotheEnvironmentalFactor;DarshiniTrivedi,Ph.D.,anIRTAfellowintheNIEHLaboratoryofToxicologyandPharmacologyMetabolismandMolecularMechanismsGroup;SheilaYong,Ph.D.,avisitingfellowintheNIEHSLaboratoryofSignalTransductionInositolSignalingGroup;andEmilyZhou,Ph.D.,aformerresearchfellowintheNIEHSLaboratoryofSignalTransductionInositolSignalingGroup.

AuthorsoftheNTPPapersoftheYearcontributedtheirsummaries,whichweresubmittedbytheirNTPbranchchiefs.)



36

NTP board gives go ahead for PAH research and systematic review By Robin Mackar

WhentheNTPBoardofScientificCounselors(BSC)metonDec.11,2012,twomainagendaitemstookcenterstage—polycyclicaromatichydrocarbons(PAHs)andsystematicreview.TheboardendorsedNTP’smulti-yearPAHresearchconceptwithsomeminortweaks,andacceptedaworkinggroupreportonsystematicreview.

Polycyclic aromatic hydrocarbonsScottMasten,Ph.D.,whoheadstheNTPOfficeofNominationsandSelection,providedabriefintroductiontotheresearchconceptonPAHs.MastenexplainedthatanNTPconceptrepresentsahigh-levellookatthescope,approach,strategy,anddirectionthatNTPwouldtakeinanareaofinterest,butisnottobethoughtofasastudydesign.

NTPtoxicologistCynthiaRider,Ph.D.,leadforthePAHresearcheffort,provideddetailsaboutPAHsandtheNTPapproachtostudyingthem.ShesaidthatPAHsarealargeclassofcompoundsfoundvirtuallyeverywhereinourenvironment.Theyoccurnaturallyinpetroleumandcoal,orarecreatedandreleasedintotheenvironmentthroughnaturalevents,suchasforestfiresandvolcanoes.Ridernotedthatthe2010DeepwaterHorizonoilspillalsoreignitedpublicconcernoverthehumanandecologicalhealthhazardsofPAHs.

A flexible iterative process“PAHsalwaysoccurincomplexmixtures.Thereareatleast1,500differentPAHs,andtherearenumerouswaysthathumanscanbeexposed,includingthroughfood,inhalation,orthroughtheskin,”Riderexplained.NTPplanstolookatavarietyofhealtheffects,usingabatteryoftoxicitytests,includingexperimentalanimalsandcellculturesystems.

RiderdiscussedtheprosandconsoftwodifferentapproachesforassessingcumulativeeffectsofPAHs—thecomponent-based,orrelativepotencyfactorapproach,andthewholemixtureapproach.ShesaidtheNTPproposalwouldcontributedatatobothapproaches,andthattheywouldbeflexibleanditerative.“Thetestingprogramwillbebuiltinunits,witheachroundoftestinginformingthenext,”Riderexplained.

Left to right, Birnbaum, Bucher, Eastmond, and Mary Wolfe, Ph.D., director of the NTP Office of Liaison Policy and Review, listened carefully to public comments and board discussions on high profile topics. (Photo courtesy of Steve McCaw)

Masten, who oversees the nomination and selection process for NTP studies, shared information about how the PAH research concept came to fruition. (Photo courtesy of Steve McCaw)

http://ntp.niehs.nih.gov/NTP/About_NTP/BSC/2012/December/PAHResearchConcept_508BE.pdf

37

Using PAHs to move mixtures research forwardNTPplanstotestbothindividualPAHsandcomplexenvironmentalmixtures.Understandinghowcombinedenvironmentalexposuresaffectdiseasepathogenesis,ordevelopment,isahighpriorityforNIEHSandNTP.ItisidentifiedasGoal4intheNIEHSstrategicplanandwasthesubjectofaworkshopin2011.

Boardmembersprovidedsuggestionsformovingtheresearchforward,toensureNTPlooksatthebreadthofendpointsorhealtheffectsPAHsmaybecausing,includingendpointsrelevanttoknownhumaneffects.

“TheboardissupportiveoftheNTP’seffortstohelpusbetterunderstandthehealtheffectsfromPAHs.Thiseffortwillalsohelpmovethewholefieldofmixturescienceforward,”saidBSCchairDavidEastmond,Ph.D.,oftheUniversityofCalifornia,Berkeley.

BoardmemberRobertChapin,Ph.D.,ofPfizer,whole-heartedlyagreed.“TheNTPneedstobedoingthis.Itneedstotakeonmixturescienceandwrestleittotheground,”hesaid.

Systematic review processMostoftheafternoonwasspentdiscussingtheNTPapproachforsystematicreviewthatisbeingledbytheNTPOfficeofHealthAssessmentandTranslation(OHAT).SystematicreviewallowsformoretransparencyofhowNTPhealthassessmentconclusionsaredetermined(seestory).

Theboardmemberslistenedtothreepubliccommentsbyphoneandreceivedallwrittenpubliccomments.

BothNTPAssociateDirectorJohnBucher,Ph.D.,andEastmondremindedtheboardthatitschargewastoacceptorrejecttheNTPBSCdraftworkinggroupreportontheapproachtosystematicreview.Theboardunanimouslyacceptedthereport(seetextbox).

AndrewRooney,Ph.D.,andKrisThayer,Ph.D.,ofOHATtookturnswalkingtheboardthroughthedraftapproach,answeringquestions,andtalkingaboutnextsteps,includingdevelopingseveralcasestudiestoshowhowtheprocessworks.

Evaluating NTP’s approach to reaching conclusions for literature-

based evidence assessmentsLynnGoldman,M.D.,ofGeorgeWashingtonUniversity,servedastheNTPBSCworkinggroupchair,andsummarizedthedraftreporttotheboard.

ThereportonevaluatingNTP’sapproachforreachingconclusionsforliterature-basedevidenceassessmentswasdevelopedbytenscientistsrepresentingacademia,industry,andgovernment.Thedraftprovidescommentsandrecommendationsoneachofthesevenstepsproposedforconductingtheliterature-basedassessments.

“Overall,wefelttheNTP’sproposedapproachforreachingconclusionsforliterature-basedassessmentswasveryproactiveinincreasingtransparency,”Goldmansaid.

InresponsetoGoldman’scomment,NIEHS/NTPDirectorLindaBirnbaum,Ph.D.,underscoredNTP’sinterestingettingpublicinput.“Therewillbeatleastsixopportunitiesforthepublictocomment,asweareconductingasystematicreview,”shesaid.“Wewanttobetransparentandwewanttohavestakeholdersinvolved.”

Rider, who is relatively new to NTP, shared her extensive knowledge about PAHs with the board. (Photo courtesy of Steve McCaw)

http://www.niehs.nih.gov/about/strategicplan/

http://www.niehs.nih.gov/news/newsletter/2011/november/science-workshop/index.cfm

http://ntp.niehs.nih.gov/NTP/OHAT/EvaluationProcess/RevisedDraftNTPApproach_508.pdf

http://www.niehs.nih.gov/research/atniehs/dntp/ohat/index.cfm

http://www.niehs.nih.gov/news/newsletter/2012/7/science-ntp/

http://ntp.niehs.nih.gov/go/38173

http://ntp.niehs.nih.gov/NTP/About_NTP/BSC/2012/December/DraftReport_LiteratureBasedEvi.pdf

http://ntp.niehs.nih.gov/NTP/About_NTP/BSC/2012/December/DraftReport_LiteratureBasedEvi.pdf

38

(RobinMackaristhenewsdirectorintheNIEHSOfficeofCommunicationsandPublicLiaison,andafrequentcontributortotheEnvironmentalFactor.)


BSC Working Group Chair Goldman summarized the draft report on evaluating NTP’s approach for reaching conclusions for literature-based evidence assessments. (Photo courtesy of Steve McCaw)

Birnbaum and Zelikoff share a smile, after Birnbaum presented her with a certificate of appreciation. (Photo courtesy of Steve McCaw)

OHAT Deputy Rooney, left, and OHAT Director Thayer, reviewed their slides on the systematic review process, before presenting to board members. (Photo courtesy of Steve McCaw)

Birnbaum, left, took a few minutes during a busy BSC meeting to show appreciation to board members whose appointments ended on December 27, 2012. Birnbaum thanked Eastmond, above, for his service, especially his role as chair. Eastmond, Judith Zelikoff, Ph.D., of New York University Langone Medical Center, Elaine Faustman, Ph.D., of the University of Washington, and Dana Loomis, Ph.D., from the University of Nebraska Medical Center, all completed their appointments in December. Faustman and Loomis were unable to attend the meeting in person. (Photo courtesy of Steve McCaw)

39

Environmental health atlas provides interactive portal to promote awareness By Ashley Godfrey

LongtimegranteeBruceLanphear,M.D.,gaveanaudienceatNIEHSasneakpeekattheCanadianEnvironmentalHealthAtlaswebsiteheandhiscolleaguesaredeveloping.

InthepresentationDec10,2012,hostedbyNIEHS/NTPDirectorLindaBirnbaum,Ph.D.,Lanpheardescribedhowhisinteractivedocumentaimstoraiseawarenessoftheenvironmentinhealthpromotionanddiseaseprevention,bymakingiteasiertoaccessthevastamountsofenvironmentalhealthdatatheatlasintegratesthroughitsportal.Hedescribedthewebsiteasaworkinprogress,andsoughtbothadviceandinputaboutitfromtheNIEHScommunity.

LanphearisaprofessorattheChildandFamilyResearchInstituteinVancouver,BritishColumbia.Lanphear,whoiswellknownforhisresearchonleadexposureandchildren’shealth,saidhehopestheatlaswillattractabroaderaudienceandraiseawarenessthattheenvironmentisanessentialpartofanyefforttopromotehumanhealth.“Whoisouttheresellingenvironmentalhealth?”askedLanphear,ashepointedtotherelativelysmallnumberofrelevant,user-friendlyresourcescurrentlyavailable.“Notenoughpeopleknowthattheenvironmentiskey[topublichealth].”

Bringing life to a flat conceptLanphearexplainedhowtheideafortheatlasemergedfromanadvisorypanelandbeganasapaperbook,butevolvedintothecurrentwebsite.Heandhisteamenvisionthewebsiteworkingasaportalormoderatedwikipage,whereknowledgecanbeeasilyaccessedandtranslatedforageneralaudience.

Watch the short video created by Lanphear’s team to explain the concept of shifting the curve with the cumulative effects of multiple environmental exposures. Videos like this one will be part of the website and help translate complex ideas into information easily understood by a broader audience (04:12)

(Launches in new window)Download Media Player: Flash

Following his talk, Lanphear also made time to meet with Epidemiology Branch fellows. He told them about his struggle to make the scientific community realize that small amounts of lead exposure can have health effects, as small amounts were originally thought to be safe. (Photo courtesy of Steve McCaw)

Members of the Epidemiology Branch and NTP enjoyed Lanphear’s lighthearted description of some of the struggles he encountered while creating the atlas. Shown, left to right, are Hazel Nichols, Ph.D., Dale Sandler, Ph.D., Mary Wolfe, Ph.D., and Abee Boyles, Ph.D. (Photo courtesy of Steve McCaw)

http://www.cfri.ca/our_research/researchers/search_researchers/researcher_detail.asp?ID=302

http://www.ehatlas.ca/

http://www.youtube.com/watch?v=jOQFYOR8tgk









40

Bycreatingaccuratebutsimpletextsandgraphics,Lanphear’sgoalisfortheatlastobecomeanactive,livingdocument.Heandhiscollaboratorshaveworkedtocreateawebsitethatisabout50percenttext,withseveralinteractivemapsandothergraphics.Plansaretoincorporateinfographics,bycreatingrepresentationsthatdisplaycomplexinformationandencouragereaderstointeractastheynavigate.Tohelpexplainkeyconcepts,theteamplanstousevideostobreakdowntheseconceptsintosimpleexamplesthatcanbeeasilyunderstood.

Narrativeandcasestudieswillalsobeapartoftheatlas,Lanphearsaid,inresponsetoasuggestionfromNIEHSepidemiologistAllenWilcox,Ph.D.Lanphearagreedthatpeoplerespondtoastory,andnotedthatthekeytoasuccessfulwebsiteistousegraphicsandvideosthatmakecomplexdataandconceptseasytofollow.

“Thechallengeistomakingitdataaccessibletoabroaderaudience,withoutjeopardizingaccuracy,”statedLanphear.

Future goalsThewebsitewillbeopentothepublicin2013,butLanphear’splansextendbeyondthelaunchoftheCanadianhealthatlas.Hewantstoexpandthisconceptintoaworldatlasofenvironmentalhealth,providingaccesstocollectivedatafromallaroundtheworld.Bydoingthis,Lanphearexpectstoseeadditionalpatternsemerging,graphically,tounderscoretheroleresearchplaysinlinkingtheenvironmentwithpublichealth.

Therearealsoplanstoexpandthecurrentversionoftheatlastoincludeembeddedanalyticsoftware,givinguserstheabilitytobothaccessandanalyzepubliclyavailabledatasets.Lanphearsaidhewouldliketocontractwithsciencewriterstohelpfillinsomeofthegaps.Currently,sectionsoftheatlasonasbestosandleadexposurearenearlycomplete,butLanphearhopestoprovidemoredata,byaddingmanyotherchemicalsandexposures.

Oneofthemostimportantgoalsfortheatlasistohelppeoplelinkevidenceofenvironmentalexposureswithdiseaseor,conversely,linkaspecificdiseasewithevidencethatmayexistforpotentialenvironmentalinfluences.Notonlywillthistypeofdatabeusefulforthepublicaudience,butitalsospeakstoresearchersandtraineesworkingattheintersectionoftheenvironmentandhumanhealth.LanphearpointedoutthathismodelcouldbeappliedtoseveralofthegoalsinthenewNIEHSstrategicplan,byfillingthenicheoftranslationalknowledgethroughdataaccessibility.

Members of the NIEHS intramural and extramural community, as well as staff from the NIEHS journal Environmental Health Perspectives, were on hand to hear about Lanphear’s exciting concept. Shown, right to left, are Martha Dimes, Ph.D., Jane Hoppin, Sc.D., Dan Shaughnessy, Ph.D., and Kimberley McAllister, Ph.D. (Photo courtesy of Steve McCaw)

Living every presenter’s worst nightmare, Lanphear was unable to navigate through the website during his presentation as he had planned. Staying quite calm and collected throughout, he reached out to his brother, who is part of his team working to complete the site, to ask for assistance, hoping he might be able to restore functionality. (Photo courtesy of Steve McCaw)

41

(AshleyGodfrey,Ph.D.,isapostdoctoralfellowintheMolecularandGeneticEpidemiologyGroupintheNIEHSLaboratoryofMolecularCarcinogenesis.)


Climate impacts of kerosene lamps used in developing countries By Jeffrey Stumpf

Whilepolicymakersfocusoncarbondioxideemissionswhenconsideringeffortstoreduceclimatechange,anewstudy,fundedinpartbyNIEHS,suggeststhatreplacingthetypeofkerosenewicklampsusedwidelyindevelopingcountrieswouldhaveamajorimpactinslowingtheearth’swarmingtrend.

Thereport,presentedbyamultinationalresearchcoalitionandpublishedinthejournalEnvironmentalScienceandTechnology,addsthereplacementofinefficientkerosenelampstoalistofpracticalchangesthatcouldhelplimittemperatureincreasesoverthenext50years,whilealsodramaticallyimprovingindoorairquality.

Lightproducedbykerosenelampsisextremelyimportantforthetwentypercentoftheworld’spopulationthatlacksaccesstoelectricity.Infact,previousreportsestimatethat77billionlitersofliquidfuel,mostlykerosene,areusedannuallytolighthouseswithoutelectricity.However,incompletecombustionofthelampfueloftenyieldsblackcarbonthatabsorbslight,therebyheatingtheatmosphere.

The atlas webpage gives a color-coded snapshot of Canadian environmental exposures and disease occurrences. The interactive site will be easy to navigate, with redundancy built in, along with separate sections on different exposures. (Screen shot courtesy of Bruce Lanphear)


42

Emission of significant amounts of black carbonThestudypresentsnewlaboratoryandfieldmeasurementsshowingthat7−9percentofkeroseneconsumedbythistypeofwicklampisconvertedtocarbonaceousparticulatematterthatisnearlypureblackcarbon.Incontrast,lessthanhalfof1percentofemissionsfromwoodcombustionisblackcarbon.Theauthorsnotethat3percentofglobalblackcarbonemissionscomefromtheseinefficientkerosenelamps.

Oneoftheauthors,KirkR.Smith,Ph.D.,isexcitedaboutsimpleopportunitiestoradicallyreducetheglobalfootprintofhumanactivities.“Therearenomagicbulletsthatwillsolveallofourgreenhousegasproblems,butreplacingkerosenelampsislow-hangingfruit,”saidSmith,anNIEHSgranteeanddirectoroftheGlobalHealthandEnvironmentProgramattheUniversityofCalifornia(UC),Berkeley,inaNov.28,2012pressrelease.“Wedon’thavemanyexamplesofthatintheclimateworld.”

“There’salotofinterestrightnowinreducingblackcarbonasaquickwaytoreduceclimatewarming—awaytoreducewarmingintheimmediatefuture,althoughnotafullsolutiontolong-termclimatechange,”explainedseniorstudyauthorTamiBond,Ph.D.,aprofessorofcivilandenvironmentalengineeringattheUniversityofIllinoisatUrbanaChampaign.

Thereportcitedseveralexamplesofviablealternativestokerosenelampsinadditiontoprovidingreliableandaffordableelectricitytohouseholds.Optionsincludecheaplight-emittingdiodelampsorevensimplymoreefficientkerosene-fueledlamps.

“Therearemanyinexpensive,cleaneralternativestokerosenelampsthatareavailablenow,andfewifanybarrierstoswitchingtothem,”Smithremarked.

Burning kerosene as an environmental health hazardInpoorhouseholdsindevelopingcountries,peoplelivewithandinhalethesmokegeneratedfromcookingandheatingfires.Themostrecentestimates,whicharepartoftheGlobalBurdenofDiseaseStudy2010publishedDec.13,2012,indicatethatapproximatelyfourmillionpeopledieprematurelyeachyearfromillnessattributabletohouseholdairpollutionduetobiomassandcoalcookingfuelsalone.

WorkfundedbyNIEHSandothers,however,isstartingtoshowthatkerosenesmokewhetherfromstovesorlampsisanadditionalimportantcauseofillhealthinthesepoorhouseholds.NIEHShasalsofundedalargenewstudybySmithandcolleaguesjuststartinginNepaltoexaminethetuberculosisrisksofkerosenesmokeinmuchmoredetail.

In addition to research on indoor air pollution and emissions associated with household energy in developing countries, Lam has worked on development of field respirators for wild land firefighters and investigations into the effects of ambient air pollution on lead paint degradation as a source of lead exposure in children. (Photo courtesy of Ajay Pillarisetti)

As a champion for reducing global climate change and promoting environmental health, Smith shared the 2007 Nobel Peace Prize and earned the 2009 Heinz Prize and 2012 Tyler Prize for achievements in environmental research. Smith has conducted pioneering studies of the health effects of indoor air pollution in homes that use inefficient cookstoves. (Photo courtesy of UC Berkeley)

http://ehs.sph.berkeley.edu/people/smithk.htm

http://newscenter.berkeley.edu/2012/11/28/kerosene-lamps-black-carbon/

http://cee.illinois.edu/research/bondresearch

http://www.thelancet.com/themed/global-burden-of-disease


43

Replacingkerosenelampsisthusimportantnotonlyforreducingglobalclimatechangebutalsodecreasingtheriskofadversehealthoutcomes.

“Gettingridofkerosenelampsmayseemlikeasmallinconsequentialsteptotake,butwhenconsideringthecollectiveimpactofhundredsofmillionsofhouseholds,it’sasimplemovethataffectstheplanet,”saidfirstauthorandUCBerkeleygraduatestudentNicholasLam.

Citations:LamNL,ChenY,WeyantC,VenkataramanC,SadavarteP,JohnsonMA,SmithKR,BremBT,ArineitweJ,EllisJE,BondTC.2012.Householdlightmakesglobalheat:highblackcarbonemissionsfromkerosenewicklamps.EnvironSciTechnol46(24):13531-13538.

PokhrelAK,BatesMN,VermaSC,JoshiHS,SreeramareddyCT,SmithKR.2010.TuberculosisandindoorbiomassandkeroseneuseinNepal:acase-controlstudy.EnvironHealthPerspect118(4):558-564.

(JeffreyStumpf,Ph.D.,isaresearchfellowintheNIEHSLaboratoryofMolecularGeneticsMitochondrialDNAReplicationGroup.)


Papers explore chemical risk assessment in light of climate change By Ed Kang

Anewseriesofpapers,byleadingexpertsinecology,toxicology,andpublichealth,explorestheissuessurroundingchemicalriskassessmentandmanagement,inlightofachangingglobalclimate.PublishedonlineDec.18,2012,thepapersappearintheJanuary2013issueofthejournalEnvironmentalToxicologyandChemistry(ET&C).Thesevenpublicationsdetailthewaysclimatechangemightaffecthowchemicalsaretransportedandcausetoxicitytoecosystemsandhumans,andconsequentlyhowchemicalriskassessmentandmanagementpracticesmayhavetobeadapted.

“Riskassessorsandpublichealthpractitionersneedtounderstandhowclimatechangemayalterchemicalriskstopeopleinthefuture,”saidoneofthepapers’leadauthorsJohnBalbus,M.D.,whoisleadingtheNIEHSGlobalEnvironmentalHealthandSustainableDevelopmentprojects.“Existingdatasourcesandassumptionsusedinexposureandriskassessmentmaynotapply.Environmentalhealthresearchersandriskassessorswillneedtoconsiderinteractionsbetweenclimate-relatedstressorsandchemicalstressorsandotherwaysthatfuturerisksmaybechanging,”headded.

Smoke emitted by simple wick lamps, similar to the one shown here, was found to be a significant but previously overlooked source of global black carbon. These lamps are used by hundreds of millions of households, and can be replaced by cleaner, affordable alternatives. (Photo courtesy of Ajay Pillarisetti)






http://onlinelibrary.wiley.com/doi/10.1002/etc.v32.1/issuetoc


44

Intheirreport,Balbusandhisco-authorsdetailfourbroadgroupsofchemicals—naturaltoxins,pesticides,airpollutants,andlegacycontaminants,suchasdioxins,PCBs,andmercury—toillustratetheimpactofclimatechangeonthelikelihoodandseverityofchemicalinsultstohumanhealth.

Theauthorscallforresearchtoinformhowchemicalusemaychangeinthefuture;improveddatasetsandmodelstodeterminehumanexposure;focusonunderstandinghowclimate,weather,andhumansensitivityinteract;andrefinementofregulatorymodelstoutilizeupdatedriskassessmentandchemicalmanagementprograms.Theyunderscorethatfutureprojectionsofchemicalriskswillalsoneedtoexplorehowfactors,includingheatstress,psychosocialfactors,urbanization,demographicshifts,andtechnologydevelopment,canpotentiallyimpactexposure,humansusceptibility,andrisk.

Theauthorsconclude,“Thepotentialcumulativeimpactsofmultipleinfluencescouldsignificantlyalterriskstohumanhealth.Thesealterationsinriskshaveimplicationsfornationalandinternationaldecision-makersinvolvedintheregulationandauthorizationofchemicalproducts.”

Balbus has taken the lead in NIEHS global health initiatives, including participation in the Global Alliance for Clean Cookstoves. (Photo courtesy of Steve McCaw)

The following publications in this series can be located on the ET&C website:

BalbusJM,BoxallAB,FenskeRA,McKoneTE,ZeiseL.2013.ImplicationsofGlobalClimateChangefortheAssessmentandManagementofHumanHealthRisksofChemicalsintheNaturalEnvironment.EnvironToxicolChem32(1):62-78.

GouinT,ArmitageJM,CousinsIT,MuirDC,NgCA,ReidL,TaoS.2013.InfluenceofGlobalClimateChangeonChemicalFateandBioaccumulation:TheRoleofMultimediaModels.EnvironToxicolChem32(1):20-31.

HooperMJ,AnkleyGT,CristolDA,MaryoungLA,NoyesPD,PinkertonKE.2013.InteractionsBetweenChemicalandClimateStressors:ARoleforMechanisticToxicologyinAssessingClimateChangeRisks.EnvironToxicolChem32(1):32-48.

LandisWG,DurdaJL,BrooksML,ChapmanPM,MenzieCA,StahlRG,StauberJL.2013.EcologicalRiskAssessmentintheContextofGlobalClimateChange.EnvironToxicolChem32(1):79-92.

MoeSJ,DeSchamphelaereK,ClementsWH,SorensenMT,VandenBrinkPJ,LiessM.2013.CombinedandInteractiveEffectsofGlobalClimateChangeandToxicantsonPopulationsandCommunities.EnvironToxicolChem32(1):49-61.

RohrJR,JohnsonP,HickeyCW,HelmRC,FritzA,BrasfieldS.2013.ImplicationsofGlobalClimateChangeforNaturalResourceDamageAssessment,Restoration,andRehabilitation.EnvironToxicolChem32(1):93-101.

StahlRG,HooperMJ,BalbusJM,ClementsW,FritzA,GouinT,HelmR,HickeyC,LandisW,MoeSJ.2013.TheInfluenceofGlobalClimateChangeontheScientificFoundationsandApplicationsofEnvironmentalToxicologyandChemistry:IntroductiontoaSETACInternationalWorkshop.EnvironToxicolChem32(1):13-19.


http://onlinelibrary.wiley.com/doi/10.1002/etc.2046/abstract







45

TheseriesofsevenpapersstemsfromaSocietyofEnvironmentalToxicologyandChemistry(SETAC)internationalworkshopheldinJuly2011andsponsoredbyNIEHSandtheNIEHSSuperfundResearchProgram.Inaneditorialaccompanyingthereleaseofthepublications,ET&CEditor-in-ChiefAllenBurton,Ph.D.,notes,“Thiscollectionofpeer-reviewedpapersrepresentstheconsensusofexpertparticipantsfromacrossacademia,government,andbusiness.”

“Thepaperstackletheimpactsofglobalclimatechangeonchemicalcontaminants,organismacclimation,andvulnerablecommunities,asimportantconsiderationsforfutureassessmentsofhumanandecologicalrisk,”theeditorialstates.

(EdKangisapublicaffairsspecialistintheNIEHSOfficeofCommunicationsandPublicLiaison,andafrequentcontributortotheEnvironmentalFactor.)


Basic metabolism studies lead to a treatment for laminitis in horses By Sara Mishamandani

Hulahalla,a4-year-oldthoroughbredhorse,waslameandadayawayfrombeingeuthanizedwhenUniversityofCalifornia(UC),DavisveterinarianAlonsoGuedes,D.V.M.,Ph.D.,madeacalltoUCDavisresearcherBruceHammock,Ph.D.GuedeswasinterestedinacompoundthathadbeendevelopedthroughNIEHS-fundedSuperfundResearchProgram(SRP)basicresearch.Testinginanimalstudieshaddemonstratedthesafetyofthecompound,aswellasitspotentialforinhibitinginflammation.

WithinhoursafterGuedesadministeredtheexperimentaldrug,Hulahallawasbackonherfeet,thefirstsignshewasrecoveringfromlaminitis,anagonizinglypainfulandusuallyterminalfootdiseaseoftenseeninhorses.

Today,oneyearaftertreatment,Hulahallaremainsanactiveandhealthycompanionanimal,andherexampleisinspiringcontinuingeffortstoimproveoutcomesforotheranimalswithlaminitis.

ResearchersattheUCDavisSRP,ledbyHammock,hadoriginallydevelopedthecompoundtostudybasiccatalyticmechanismsofanenzymeinthebodyand,intheprocess,foundthatthecompoundalsorelievedneuropathicpainandinflammation(seetextbox).

Making the call for treatmentTheopportunityfortheHammockgrouptotesttheanti-inflammatorydrugonlargeranimalspresenteditselfthroughGuedes,whohadbeencollaboratingwiththeHammocklabforseveralyears.Laminitisisinitiatedbyinflammation,progressesintosevereinflammatorypain,andthenintoachronicorneuropathicpainconditionthatleadstotissuedestructionandoftencausesseverehighbloodpressure.

Guedes, pictured with Hulahalla, is a veterinarian at UC Davis with a research focus in pain biology and analgesic pharmacology. (Photo courtesy of UC Davis)

http://www.setac.org/

46

“IntheUnitedStates,itisestimatedthatlaminitiswillstrike15percentofhorsesduringtheirlifetimes,and75percentofhorseswithlaminitiswilllosetheirlives,”saidGuedes.

Hulahalladevelopedacutelaminitisinbothfrontfeet.VeterinariansatUCDavistreatedherwiththestandardofcareforseveraldays,butherconditiondeterioratedandsherefusedtostand.GuedesmadeanemergencycalltoHammock,afterobtainingcompassionatepermissiontousethesolubleepoxidehydrolases(sEH)inhibitortheyhaddeveloped—theonlyoptionleft,asidefromeuthanasia,torelievetheextremepainandsuffering.

WithinthreehoursaftercliniciansadministeredthedrugtoHulahalla,shewasabletostand.Herpainlevelandbloodpressuredecreasedprogressivelyand,afterthreedays,shecouldwalkalmostnormallyandhersystolicbloodpressuredroppedsignificantly,from200to110.Afterfivedays,HulahallawasdoingverywellandnolongerneededthesEHinhibitor.Therehasbeennoreoccurrenceoflaminitisorsignofadversedrugeffects.

BoraInceoglu,Ph.D.,acollaboratorofGuedesandHammock,isworkingtomovethecompoundstotheclinicforhumandiabeticandotherneuropathicpain.“Itisoftenhardtoextrapolatefromtreatmentofrodentmodelsofpaintoman,”saidInceogluThismarewassufferingfromarealdisease.NotonlyisitgratifyingtosavethelifeofHulahalla,butsheandotherhorsesprovidestrongevidencethatoursuccesswithtreatingneuropathicpaininrodentscanbeextrapolatedtoman.”

Moving the treatment forwardSincetestingthecompoundwithHulahallain2011,fouradditionalhorsessufferingfromlaminitishavebeentreatedunderacompassionateuseprotocolapprovedby

Starting from basic NIEHS researchSinceitsinception25yearsago,SRPhassupportedtheHammocklabtostudytheroleofepoxidehydrolases,enzymesthatcatalyzetheopeningofepoxiderings,todetoxifyavarietyofenvironmentalchemicals.

Someepoxidesareveryreactivechemicalcompoundsthatforminsidethebodyduringthemetabolismofdrugsandenvironmentalcontaminants.Becauseoftheirreactivity,suchepoxidescanbepotentmutagens,toxins,andcarcinogens.Thusepoxidehydrolasesoffersignificantprotectionagainstcellularinjury,bytransformingtheseharmfulepoxidesintolesstoxicandmorewatersolublecompounds.

NIEHS-fundedresearchersledbyHammockdiscoveredanothersolubleepoxidehydrolase(sEH),anewformoftheenzymethatexistsinthecellcytosolanddegradeschemicallystablefattyacidepoxides.Toinvestigatethebiologicalroleofthisenzyme,theycreatedpotentinhibitors.Inhibitorsarecommonlyusedtodeterminethelocationoftheenzyme’sactivesiteandtostudyfactorsthatcontrolenzymeactivity.

HammockandhisteamdiscoveredthatsEHisverygoodatconvertingfattyacidepoxidesintodiols,eliminatingtheepoxidesfromthebody.However,somefattyacidepoxidesofomega-3andomega-6canbeverybeneficialandhavebeenfoundtoreduceinflammation,inflammatorypainand,surprisingly,evenchronicorneuropathicpain.TheyfoundthatthepotentinhibitorsthattheycreatedtostudysEHcouldbeusedinmouseandratmodelsasadrugtoreduceinflammationandinflammatorypainmoreeffectivelythannon-steroidalanti-inflammatorydrugs(NSAIDs).Theyalsobeganstudyingtheuseofthedrugwithhorseenzymes,buthadnotyetusedthedruginahorseoranyothercompanionanimal.

“Itisveryhardtotellwheresciencewilllead,”saysHammock.“WearehopingthatthefundamentalworksupportedbyNIEHSonforeigncompoundmetabolismwillresultinatreatmentfordevastatingpainandinflammationindogsandcats,aswellashorses.”

Aclinicaltrialtoassessthedrug’ssafetyandestablishatolerabledoseforthecompoundisexpectedtobegininthespring.Furtherclinicaltrialswouldbeneededtoestablishthedrug’seffectivenessasalaminitistreatment.

47

theUCDavisInstitutionalAnimalCareandUseCommittee.Thatprotocolallowsanimalstobetreatedwithanexperimentaldrugifnoapprovedalternativetreatmentexists.Hulahallaexperiencedacompleteremissionthathaslastedformorethanayear,andthreeothershaveshownsomeimprovement.

“Thesolubleepoxidehydrolaseinhibitorsarefarmoreeffectivethananyothercommercialcompoundwehavetriedwithpainmodels,”saidformerSRPgraduatestudentKarenWarren,Ph.D.

“Thisisanunusualstepforustoannouncethissofarinadvance,butbecauseeuthanasiaisoftentheonlywaytoalleviatepaininseverelaminitis,wefeltthatitwasimportanttolettheveterinariansandhorseownersknowthatthiscompoundhasshownpotentialasatreatment,”saidGuedes.

(SaraMishamandaniisaresearchandcommunicationspecialistforMDBInc.,acontractorfortheNIEHSSuperfundResearchProgramandDivisionofExtramuralResearchandTraining.)


Hammock’s research interests range across omics platform development, pest control, and drug development. He has been honored for his teaching and mentoring, as well as for his groundbreaking scientific research. (Photo courtesy of Bruce Hammock)

Hulahalla a year later, showing the effects of the treatment were dramatic. (Photo courtesy of Robert Warren)

Laminitis made it too painful for Hulahalla to stand. In this 2011 photo, she is wearing a pair of equine gel orthotic comfort boots on her front hooves, a common veterinary treatment to help ease pain in cases of wounds, drains, casts, and other special conditions. (Photo courtesy of Robert Warren)

48

Uranium exposure linked to increased lupus rate By Amanda Harper

PeoplelivingnearaformeruraniumoreprocessingfacilityinOhioareexperiencingahigherthanaveragerateoflupus,accordingtoanewNIEHS-fundedstudyconductedbyscientistsattheUniversityofCincinnati(UC)andCincinnatiChildren’sHospitalMedicalCenter.

Systemiclupuserythematosus,orlupus,isachronicinflammatorydiseasethatcanaffecttheskin,joints,kidneys,lungs,nervoussystem,andotherorgansofthebody.Theunderlyingcausesoflupusareunknown,butitismuchmorecommoninwomen.

Forthisnewstudy,acollaborativeteamofUCandCincinnatiChildren’sresearcherscomparedlupusratesinpeoplewhowereexposedtouraniumtoratesinthosewhowerenot,inanefforttoexplainthehighnumberoflupuscasesreportedinasuburbanCincinnaticommunity.

Environmental exposures from a former uranium processing plantIntheirextensivereviewofmedicalrecordsandserumantibodyanalysis,toverifythecases,theresearchersfoundthatpeoplewhowereexposedtohigherlevelsofuranium,basedontheirlivingincloseproximitytoaformeruraniumoreprocessingplant,hadlupusratesfourtimeshigherthantheaveragepopulation.

“Formerstudieshavesuggestedthatpeoplewithlupusmaybemoresensitivetoradiation,andthatbothgeneticsandenvironmentalexposuresplayaroleindiseasedevelopment,”saidPai-YueLu,M.D.,apediatricrheumatologyfellowatCincinnatiChildren’sandleadresearcherforthestudy.“Ourstudyshowsastrongcorrelationbetweenexposuretouranium,aradioactivesubstance,andanincreasedlupusratethatmeritsfurtherinvestigation.”

“Withmoreresearchinthisarea,wemaygainadditionalinsightonthetypesofenvironmentalfactorsthatcontributetolupusdevelopmentandthemechanismsbywhichtheywork,”Luadded.“Therecouldbeothereffectsofuraniumandrelatedexposuresthatcouldcontributetoorhelpexplainourfindings.”

LupresentedthisfindinganditspotentialimplicationsinNovember2012attheAmericanCollegeofRheumatologyannualmeetinginWashington,D.C.Shecompletedtheprojectaspartofhermaster’sdegreesinclinicalandtranslationalresearchtrainingatUC.

Lead researcher Lu is shown outside Cincinnati Children’s Hospital Medical Center (CCHMC). (Photo courtesy of CCHMC)

Senior author Pinney also serves as a member of the Fernald Medical Monitoring Program staff. (Photo courtesy of CCHMC)

http://www.eh.uc.edu/Clinicalresearch/

http://intmed.uc.edu/fmmp/global_tpl.cfm?SecId=Staff%20Information&SubId=Staff%20Information

49

TheCincinnati-basedteam’sresearchisbasedonnearlytwodecadesofdatacollectedthroughtheFernaldMedicalMonitoringProgram,thefirstandlargestlegallymandatedcomprehensivemedicalmonitoringprogramintheU.S.Theprogramwasestablishedin1990,afterafederalinvestigationrevealedthatNationalLeadofOhio’sFeedMaterialsProductionCenterintheHamiltonCounty,Ohio,communityofFernald,wasemittingdangerouslevelsofuraniumdustandgasesintosurroundingcommunities.

“Theavailabilityofthiscohort,andcarefullycollecteddataandbiospecimens,providesagreatsettingtoaskresearchquestions,”saidSusanPinney,Ph.D.,UCprofessorofenvironmentalhealthandprincipalinvestigatorontheFernaldstudy.

Almost10,000communityresidentsenrolledintheFernaldMedicalMonitoringProgram.Communityresidentswereclassifiedintoseveralexposuregroups—highexposure,moderateexposure,lowexposure,andnoexposure.Uraniumplantworkerswerenotpartofthisstudy,sincethefocusofthestudywasenvironmentalratherthanoccupationalexposure.

“TypicalU.S.incidenceratesforlupusare1.8to7.6casesper100,000.Amongthe25confirmedlupuscasesweidentifiedthroughtheFernaldcommunitycohort,12wereinthehighexposuregroup,eightexperiencedmoderateexposure,andfivewereinthelowexposuregroup,”Luexplained.

ResearchwassupportedbyapilotgrantfromtheCenterforEnvironmentalGenetics(CEG),anNIEHS-fundedprogramtosupportcorefacilitiesandtechnologiesneededtoconductinnovativeresearchthatfocusesonhowenvironmentalagentsinteractwithgeneticandepigeneticfactorstoinfluencediseaseriskandoutcome.Shuk-meiHo,Ph.D.,theJacobA.SchmidlappEndowedChairandprofessorintheUCDepartmentofEnvironmentalHealth,servesasdirectoroftheCEG.

Citation:LuP-Y,KottyanLC,PinneySM,JamesJA,XieC,BuckholzJM,HarleyJB.2012.IdentifyingaLinkBetweenUraniumExposureandSystemicLupusErythematosusinaCommunityLivingnearaUraniumPlant.ArthritisRheum64:(10Suppl):S686.

(AmandaHarperisapublicinformationofficerintheOfficeofPublicRelationsandCommunicationsattheUCAcademicHealthCenter.Formoreinformationaboutthisstudy,contactHarperbyphoneat513-558-4657orbyemailatamanda.harper@uc.edu)


This map shows the one-mile increments that defined uranium exposure levels for subjects in the study of residents of Fernald, located just outside Cincinnati. (Map courtesy of the Fernald Environmental Management Project)

http://intmed.uc.edu/fmmp/global_tpl.cfm?SecId=Overview&SubId=Overview

http://www.eh.uc.edu/dir_individual_details.asp?qcontactid=81

http://www.eh.uc.edu/ceg/project_overview.asp

http://www.eh.uc.edu/dir_individual_details.asp?qcontactid=702

http://www.rheumatology.org/education/annual/2012_Abstract_Supplement.pdf#toolbar=1

mailto:[email protected]

50

NICEATM holds workshop on new safety tests for pertussis vaccines By Debbie McCarley and Cathy Sprankle

NIEHSandU.S.FoodandDrugAdministration(FDA)scientistsjoinedotherexpertsfromaroundtheworldataworkshoptoconsiderimprovedmethodsandapproachesforsafetytestingofvaccinesthatprotectagainstpertussis.The“InternationalWorkshoponAlternativestotheMurineHistamineSensitizationTest(HIST)forAcellularPertussisVaccines:StateoftheScienceandthePathForward”washeldNov.28-29,2012,attheWilliamH.NatcherConferenceCenterontheNIHcampusinBethesda,Md.

Theworkshopprovidedaforumforparticipantstoreviewprotocolsandavailabledatafromanongoinginternationalstudyofin vitroalternativesforsafetytestingofpertussisvaccines.Theworkshopparticipantsalsoconsideredthenextstepstoachievevalidation,globalacceptance,andimplementationofthesetestmethods.

TheNTPInteragencyCenterfortheEvaluationofAlternativeToxicologicalMethods(NICEATM)organizedtheworkshopincollaborationwiththeInteragencyCoordinatingCommitteeontheValidationofAlternativeMethods(ICCVAM)andpartnerorganizationsoftheInternationalCooperationonAlternativeTestMethods.

Pertussis is an important public health concernPertussis,alsoknownaswhoopingcough,isahighlycontagiousbacterialdiseasethatwasonceamajorcauseofchildhoodmortality.Whilewidespreadvaccinationhassubstantiallydecreasedtheincidenceofpertussis,recentoutbreakshaveledpublichealthofficialstorecommendrenewedandexpandedvaccinationefforts.

TheHISTisakeysafetytestperformedonpertussisvaccines,topreventadverseeffectsfromresidualpertussistoxinthathasnotbeencompletelyinactivated.However,thetestingusesalargenumberofanimals,andmanyoftheanimalsexperiencepainanddistress.Therefore,NICEATMandICCVAMidentifiedtheHISTasapriorityforfutureresearch,development,andvalidationofalternativetestmethodsthatcouldreduce,refine,orreplaceanimaluseforpertussisvaccinesafetytesting.

GiventheneedforalternativestotheHIST,aninternationalcommitteeofregulatoryandindustryexpertswasestablishedtoevaluateanimalreplacementmethodsthatcouldalsoprovidegreateraccuracy,precision,andefficiency.Thecommitteeinitiatedaninternationalcollaborativestudyonin vitroalternativestotheHIST.Inthisstudy,referencepertussistoxinandsevenacellularpertussisvaccinesfromthreemanufacturersweredistributedto12internationallaboratoriesfortesting.Dataweregeneratedonthedetectionofpertussistoxinintoxin-spikedvaccinesusingconventionalhigh-performanceliquidchromatographyandenzyme-linkedimmunosorbentassayplatforms,aswellasadvancedcell-basedandgenomicstechnologies.

Workshopparticipantsrevieweddatafromthisstudy.Basedonthefindings,attendeesselectedtwoofthecell-basedmethodsforfurtherdevelopmentandoptimizationinthenextinternationalcollaborativestudyplannedforlaterthisyear.

“Bothvaccinemanufacturersandregulatorsareactivelyworkingtodevelopandvalidateimprovedalternativesthatcanachieveacceptanceanduse,”notedWilliamStokes,D.V.M.,whoparticipatedintheworkshopinhisroleasdirectorofNICEATM.“Thisisanimportantopportunitytoreduceanimaluseandimprovesafetytestingwithatestthathasaclearimpactonpublichealth.”

AmoredetailedsummaryoftheworkshopandspeakerpresentationsareavailableontheICCVAMwebsite.AreportontheworkshopwillbeappearlaterthisyearinthejournalBiologicals.

http://iccvam.niehs.nih.gov/meetings/HISTWksp-2012/HISTWksp.htm

http://iccvam.niehs.nih.gov/about/about_NICEATM.htm

http://iccvam.niehs.nih.gov/about/about_ICCVAM.htm

http://iccvam.niehs.nih.gov/about/icatm.htm

http://iccvam.niehs.nih.gov/meetings/HISTWksp-2012/HISTWksp.htm

51

(DebbieMcCarleyisaspecialassistanttoStokes.CathySprankleisacommunicationsspecialistwithILSInc.,supportcontractorforNICEATM.)


Casey meets with international experts to assess endocrine disruptor testing By Debbie McCarley and Cathy Sprankle

NTPscientistWarrenCasey,Ph.D.,participatedintwoexpertmeetingsinNovember2012thatconsideredin vitromethodsfordetectingsubstancesthatmightinterferewithnormalhormonefunction.CaseyisactingdirectoroftheNationalToxicologyProgram(NTP)InteragencyCenterfortheEvaluationofAlternativeToxicologicalMethods(NICEATM).

Stokes, front right, joined more than 40 scientists from 11 countries representing vaccine manufacturers and government regulatory agencies at the November 2012 workshop.(Photo courtesy of NICEATM)

http://iccvam.niehs.nih.gov/

52

CaseyattendedtheannualmeetingoftheValidationManagementGroupforNon-animalTesting(VMG-NA)Nov.29-30.HealsoattendedthefirstmeetingoftheThyroidScopingEffortExpertGroup(TSEEG)Nov.28.BothmeetingsweresponsoredbytheOrganisationforEconomicCo-operationandDevelopment(OECD)andtookplaceatOECDHeadquartersinParis.

NICEATMiscommittedtobuildingglobalpartnershipstoadvancealternativestoanimaltesting.ParticipationineventssuchastherecentOECDmeetingsisanimportantpartofdevelopingthosepartnerships.

Concerns about endocrine disruptors spur test method developmentEndocrinedisruptorsaresubstancesthatinterferewiththenormalfunctionofhormonesintheendocrinesystem.Studieshaveshownthatanimalsexposedtothesesubstancesexhibitreproductiveanddevelopmentalabnormalities.Thesestudieshaveraisedconcernsthatsuchsubstancesmighthavesimilareffectsinhumans,andagrowingbodyofresearchsupportsthishypothesis.Thus,testmethodsareneededthatcanprovideaccurateandtimelyidentificationofpotentialendocrinedisruptors.

NICEATMcoordinatedaninternationalvalidationstudyoftheBG1Lucestrogenreceptor(ER)transactivation(TA)assays,whichidentifysubstanceswiththepotentialtoinduceorinhibitactivityoftheestrogenreceptor.TheBG1LucERTAtestmethodsgainedinternationalacceptancewhentheOECDadoptedatestguidelinedescribingtheminOctober2012.

TheNovemberVMG-NAmeetingconsideredadditionalmethodscurrentlyunderevaluationforthispurposebytheU.S.EnvironmentalProtectionAgency(EPA)andgroupsinEuropeandJapan.Caseyservesonthestudymanagementteamsfortheseprojects.Hecommentedontheirprogressandaddressedquestionsaboutselectionofreferencechemicalsandevaluationmethods.

AnothertopicconsideredattheNovembermeetingwasthedevelopmentofmediumandhighthroughputscreeningmethodsforendocrinedisruptors.CaseypresentedrecentworkperformedbytheTox21consortiumontheadaptationoftheBG1LucERTAmethodstoahighthroughputplatform,whichwasoneofseveralcasestudiesdiscussedatthemeeting.

Group established to evaluate status of thyroid assaysParticipantsofthenewlyestablishedTSEEGgatheredinanefforttoidentifyavailableassaysforthedetectionofpotentialthyroiddisruptorsandassesstheirsuitabilityforregulatoryuseorpotentialfuturetestguidelinedevelopment.

Thethyroidglandregulatesenergyuseinthebodyandaffectsthebody’sresponsetootherhormones.Itisanotherpotentialtargetofendocrinedisruptors.Inthepast,thethyroidsystemhasreceivedlessattentionthantheestrogensystem,inregardtothedevelopmentoftestmethods.EstablishmentoftheTSEEGwasrecommendedbytheVMG-NAtoaddressthisimportantneed.TheexpertgroupischairedbyKevinCrofton,Ph.D.,oftheEPANationalCenterforComputationalToxicology.

Casey is one of several scientists from NIEHS research divisions who are striving for a better understanding of endocrine disruption. (Photo courtesy of Steve McCaw)

http://www.oecd.org/about/

http://www.niehs.nih.gov/health/assets/docs_p_z/tox21_transforming_environmental_health_508.pdf

53

RecommendationsfromthismeetingwillbesubmittedtothenationalcoordinatorsoftheOECDTestGuidelinesProgramme,whowillconsideritattheirmeetinglaterthisspring.Approvaloftherecommendationswillprovidedirectionforfuturedevelopmentoftestmethodstoidentifypotentialthyroiddisruptors.

(DebbieMcCarleyisaspecialassistanttoWilliamStokes,D.V.M.CathySprankleisacommunicationsspecialistwithILSInc.,supportcontractorforNICEATM.)


This month in EHPEnvironmentalHealthPerspectives(EHP)goespaperlessinJanuarywithitsfirstentirelyelectronicissuefeaturingacoverarticleoncooler-by-designarchitectureandengineering.

Alternatives to Air Conditioning for a Warm World

Thedevelopingworldishometomostoftheglobe’shottestandfastest-growingcitiesaswellasarapidlyexpandingmiddleclassthatcannowaffordtheamenitiesthatcitizensinthedevelopedworldhavelongtakenforgranted.Highonthatlististheairconditioner.Althoughair-conditioningusewillcertainlycontinuetoincreasegloballywithnoseriousregulatoryframeworksinsight,someobserversbelieveawarenessofitsenvironmentalimpactisbeginningtochangethewaysinwhicharchitectsandengineers,atleast,areapproachingthechallengeofkeepingpeoplecool.

Beyond Uncertainty Factors: Protecting the Tails of the Bell Curve

Fordecades,environmentalriskassessorshavetriedtoaddressinterindividualvariationbysettingexposurelimitslowenoughtoprotectthemostsensitivesubgroupsinthepopulation.Nowtheyarelookingformoretargetedwaystoaddresstheunderlyingfactorsthatgovernindividualsusceptibility.

Podcast: The Secret Life of Fat Tissue, with Michele La Merrill

Yourbulgesarebusierthanyoumaythink.Manypeopleseeadiposetissue—fat—asnothingmorethanlumpyextrabaggage.Butfatservesseveralimportantfunctionsinthebody.Ithelpsusstoreenergyandendocrinehormonesthatcanaffectbehavior,energyregulation,immunity,andvascularfunction—tonameafew.Italsoprotectsagainsttoxiceffectsofpersistentorganicpollutants,orPOPs.Inthispodcast,MicheleLaMerrill,Ph.D.,talkswithhostAshleyAhearnaboutthediversewaysthatfatinteractswiththesechemicalsasbothamodulatorandatargetofPOPtoxicity.

http://twitter.com/ehponline

http://ehp.niehs.nih.gov/

http://ehp.niehs.nih.gov/category/podcasts/

http://twitter.com/ehponline

54

Featuredcommentaries,reviews,andresearchthismonthinclude:

• GeneticModificationoftheAssociationBetweenPeripubertalDioxinExposureandPubertalOnsetinaCohortofRussianBoys

• PossiblePositiveSelectionforanArsenic-ProtectiveHaplotypeinHumans

• CoplanarPolychlorinatedBiphenylsImpairGlucoseHomeostasisinLeanC57BL/6MiceandMitigateBeneficialEffectsofWeightLossonGlucoseHomeostasisinObeseMice

• ClimateChangeandOlderAmericans:StateoftheScience


Rose to give distinguished lecture By Sheetal Thakur

Thefirst2013NIEHSdistinguishedlecture,“Myocarditis:anenvironmentallyinitiatedautoimmunedisease,”willbepresentedbyNoelRose,M.D.,Ph.D.,Jan.8at11a.m.inRodbellAuditorium.Rose’svisittoNIEHSwillbehostedbyDoriGermolec,Ph.D.,whoistheSystemsToxicologyGroupleaderintheNTPToxicologyBranch.

Roseisaprofessorofpathology,molecularmicrobiology,andimmunology,aswellasthedirectoroftheAutoimmuneDiseaseResearchCenteratJohnsHopkinsUniversity(JHU).Heisapioneerandinternationallyrenownedexpertinthefieldofautoimmunediseases,andhasservedasthechairoftheAutoimmuneDiseasesCoordinatingCommitteeoftheNationalInstitutesofHealth.Inhisearlycareerduringthe1950’s,Rosedemonstrated,forthefirsttime,thatimmunizinganimalsexperimentallywiththeirownthyroglobulininducesautoimmunethyroiditis.Thisfindingrevolutionizedtheoutlookoftheentireresearchcommunityonautoimmunediseases.

TheRoselaboratoryatJHUcontinuestoinvestigatethetriggers,mechanisms,andpathologyofautoimmunediseases,inbothclinicalandlaboratoryanimalsettings.Hisgroup’sresearchhasunraveledthecomplexinterplaybetweengeneticandenvironmentalfactorsthatinfluencethedevelopmentofautoimmunediseases.SomeoftherecentfindingsfromRose’sgrouphighlightthesignificanceofautoantibodiesinthehumanpopulationandtheirprediagnosticvalueintheearlydetectionofautoimmunethyroiddisease.

Rose made his first seminal discovery about Hashimoto’s thyroiditis in 1956 — the beginning of a long series of important contributions toward the understanding of autoimmune diseases and the gene-environment interactions responsible for them. (Photo courtesy of Johns Hopkins University)

Linked video:Watch as Rose presents an “Introduction to Autoimmunity” at an October 2012 conference (50:52)



http://autoimmune.pathology.jhmi.edu/aboutcenter.cfm

http://www.youtube.com/watch?v=bjTBZObWuPY





55

Inhiscareerof50-plusyears,Rosehaspublishedmorethan200papers,edited17books,andgivennumerouslecturesatconferencesworldwide.Hismanyawardsincludethe2005AmericanSocietyforMicrobiologyFoundersDistinguishedServiceAward,2006KeystoneLifetimeAchievementAward,andthe2009NicolausCopernicusMedalfromthePolishAcademyofSciences.Rosehasdedicatedhiscareertounderstandingthemechanismsandpathogenesisofautoimmunediseasesandhisresearchcontinuestoenrichthefieldandsuggesttherapeuticstrategiesforthesedebilitatingdiseases.

(SheetalThakur,Ph.D.,isanIntramuralResearchTrainingAwardfellowintheNTPToxicologyBranch.)


Upcoming data integration workshop By Eddy Ball

AninnovativeNIEHS-sponsoredprogramcontinuesitsworkshopserieswithanexplorationof“IntegratingEnvironmentalHealthDatatoAdvanceDiscovery”Jan.10-11attheKeckCenterinWashington,D.C.

Theworkshop,whichispartoftheNationalAcademiesEmergingScienceforEnvironmentalHealthDecisionsseries,isfreeandopentothepublic.Registrationsforon-siteattendanceandwebcastaccessarenowbeingaccepted.

Integrating increasing volumes of dataResearchinbiomedicalscienceshasundergoneadramatictransformationinthepasttwodecades.Scienceisincreasinglydataintensive,computational,interdisciplinary,andcollaborative—atrendthatispervasivethroughoutscience,andimposingnewchallengesforbiomedicalresearch.

Whilesignificantprogresshasbeenmadeinthedevelopmentofdigitaltechnologies,community-wideprinciples,andresourcemanagementforsomelargeandrapidlyexpandingdatatypes,suchasgenomicsequences,theintegrationofexistingheterogeneousdatasetshaslagged.Thislagpresentsparticularchallengesforenvironmentalhealthscience,whichisuniquelyandinherentlycross-disciplinary.

Thismeetingaimstofosterdiscussionabouttheneedforenhanceddataintegrationinenvironmentalhealthsciencesandevaluatethelessonsthatcanbelearnedfromintegrativeinitiativesinotherscientificdomains.Italsooffersparticipantsaforumforstrategizingaboutwaysthecommunitycantakemajorstepstowardimprovingdatacoordinationandaccesstoadvanceunderstandingaboutenvironmentaleffectsonhumanhealth.

An ongoing series of workshopsSponsoredbyNIEHS,theprogramholdsthreeworkshopsperyearontheuseofnewdiscoveries,tools,andapproachesforguidingenvironmentalhealthdecisions.Theworkshopsprovideapublicvenueforcommunicationamonggovernment,industry,environmentalgroups,andtheacademiccommunity.

http://nas-sites.org/emergingscience/meetings/data-meeting/



http://www.surveygizmo.com/s3/1087258/January-Data-Meeting-On-Site-Registration

56

Thedataintegrationworkshopisthethirteenthintheseries,whichbeganinJuly2009withaworkshoponthe“UseofEmergingScienceandTechnologiestoExploreEpigeneticMechanismsUnderlyingtheDevelopmentalBasisforDisease.”Pastpresentationsarearchivedonline,andvideosareavailableforseveralrecentworkshops.


Extramural papers of the month By Nancy Lamontagne

• Mechanism for melanoma risk in people with red hair and fair skin

• Early exposures to air pollution linked with autism

• Flame retardant Firemaster 550 confirmed as endocrine disruptor

• Prenatal mercury and ADHD

Mechanism for melanoma risk in people with red hair and fair skinAstudysupportedbytheNIEHSidentifiesanewmechanismthathelpsexplainriskformelanoma,themostdangeroustypeofskincancer,andprovidesinformationthatmightaidinprotectingpeoplewiththehighestmelanomarisk.

Pheomelanin,thepredominantskinpigmentforpeoplewithredhairandfairskin,islessprotectiveagainstultraviolet(UV)radiationdamagethantheeumelaninfoundinpeoplewithdarkskinandhair.However,studiesindicatethatreducedUVprotectionmaynotfullyexplainwhyindividualswithredhairandfrecklesaremoreatriskformelanoma,sotheresearchersconductedastudyinvolvingdark-coloredmicewiththetypicalgenevariantforapredominanceofeumelaninandmicewiththevariantthatproducesredhairandfairskininhumans.

EvenwithoutUVexposure,theredhair/fairskinmicehadagreaternumberofinvasivemelanomas,suggestingthatthepheomelaninpigmentitselfwasinvolvedinmelanoma.Theresearchersthentestedmicewithnoskinpigment(albino),andthesemicedevelopedfewermelanomasthantheredhair/fairskinmice.Inaddition,theredhair/fairskinmicehadsignificantlygreateroxidativeDNAandlipiddamagethanthealbinomice.ThestudyfindingssuggestthatintheabsenceofUVexposure,thepheomelaninpigmentcontributestomelanomaviaoxidativedamage.Theresearcherssayprotectionfromultravioletradiationremainsimportant,butadditionalstrategiesmaybeneededtoachievethebestmelanomaprevention.

Citation:MitraD,LuoX,MorganA,WangJ,HoangMP,LoJ,GuerreroCR,LennerzJK,MihmMC,WargoJA,RobinsonKC,DeviSP,VanoverJC,D’OrazioJA,McMahonM,BosenbergMW,HaigisKM,HaberDA,WangY,FisherDE.2012.Anultraviolet-radiation-independentpathwaytomelanomacarcinogenesisintheredhair/fairskinbackground.Nature491(7424):449-453.


ReadthecurrentSuperfundResearchProgramResearchBrief.NewissuesarepublishedonthefirstWednesdayofeachmonth.

http://dels-old.nas.edu/envirohealth/workshops.shtml




http://tools.niehs.nih.gov/srp/researchbriefs/currentissue.cfm

57

Early exposures to air pollution linked with autismNIEHSgranteesreportthatexposuretolocaltraffic-relatedairpollutionandregionalairpollutioninthewombandduringthefirstyearoflifeisassociatedwithincreasedriskforautism.Thestudybuildsonpreviousresearchinwhichthegranteesfoundthatchildrenborntomotherswholivewithin309metersoffreewayshadanincreasedriskofdevelopingautism.

Inthenewstudy,theresearchersexamineddatafromchildrenenrolledintheChildhoodAutismRisksfromGeneticsandtheEnvironmentstudy,including279childrenwithautismand245controlchildrenwithnormaldevelopment.Theyestimatedtraffic-relatedpollutionexposuresusingthemother’saddressandusedU.S.EnvironmentalProtectionAgency’sAirQualitySystemmeasurementsofregionalpollution.

Thechildrenwithautismweremorelikelythanthecontrolchildrentoliveinhomeswiththehighestexposuretotraffic-relatedairpollutionduringgestation(adjustedoddsratio[AOR]1.98[95percentconfidenceinterval(CI)1.20-3.31])andthefirstyearoflife(AOR,3.10[95percentCI,1.76-5.57]).Duringgestation,exposuretoregionalnitrogendioxideandparticulatematterlessthan2.5and10micronsindiameterwasalsoassociatedwithautism.Theresearcherssaythatadditionalpopulationandtoxicologicalstudiesoflikelybiologicalpathwaysareneededtodetermineiftheairpollutionexposurecausestheincreaseinautismrisk.

Citation:VolkHE,LurmannF,PenfoldB,Hertz-PicciottoI,McConnellR.2012.Traffic-RelatedAirPollution,ParticulateMatter,andAutism.ArchGenPsychiatry;doi:10.1001/jamapsychiatry.2013.266[Online26November2012].


Flame retardant Firemaster 550 confirmed as endocrine disruptorTheflame-retardantmixtureFiremaster550iscommonlyfoundinhouseholddust,butthephysiologicaleffectsofitscomponentsatrelevantexposurelevelsaren’tknown.AnanimalstudyconductedbyNIEHSgranteesshowsthatperinatalexposuretotheflame-retardantmixtureisassociatedwithendocrinedisruptingeffects.Theresearchersobservedweightgain,earlyonsetofpuberty,andcardiovascularhealtheffectsatlevelsthatarerelevanttohumanexposureandlowerthanthenoobservableadverseeffectslevelreportedbythemanufacturer.

TheresearchersevaluatedtheeffectsofFM550inratsexposedto100or1000microgramsoftheflame-retardantperdayduringgestationandlactation.TheyfoundthatthecomponentsofFiremaster550accumulatedintissuesofexposedmiceaswellastheiroffspringandinducedmetabolicsyndromecharacteristicsintheoffspring.Theyobservedhigherlevelsofthethyroxinethyroidhormoneandreducedhepaticcarboxylestereaseactivityintheexposedmice.Theoffspringexhibitedadvancedfemalepuberty,weightgain,malecardiachypertrophy,andproblemswithexploratorybehaviors.Theresearcherssaythattheirfindingsrevealthattheflameretardantmayaffectgrowthandneurodevelopmentandsupporttheneedformoreresearchintothemechanismsinvolvedandhumanexposurelevels.

Citation:PatisaulHB,RobertsSC,MabreyN,McCaffreyKA,GearRB,BraunJ,BelcherSM,StapletonHM.2012.AccumulationandEndocrineDisruptingEffectsoftheFlameRetardantMixtureFiremaster(®)550inRats:AnExploratoryAssessment.JBiochemMolToxicol;doi:10.1002/jbt.21439[Online8November2012].


http://archpsyc.jamanetwork.com/article.aspx?articleid=1393589


58

Prenatal mercury and ADHDAnewpaperfromNIEHS-fundedresearchersfoundanassociationbetweenlow-levelprenatalmercuryexposureandincreasedriskofattention-deficit/hyperactivitydisorder(ADHD)-relatedbehaviorsinchildren.However,consumingmorethantwoservingoffishperweekwaslinkedwithalowerriskforADHD-relatedbehaviors.

TheresearchersstudiedchildrenborninNewBedford,Mass.Theyconductedneuropsychologicalassessmentsforchildrenatage8whohadperipartummaternalhairmercurymeasures(421children)ormaternalreportingoffishconsumptionduringpregnancy(515children).Themothers’medianhairmercurylevelwas0.45microgramspergram(µg/g)(range=0.03to5.14µg/g),and52percentofthemconsumedmorethantwoservingsoffishaweek.Multivariableregressionmodelsshowedthatmercuryexposurewasassociatedwithinattentionandimpulsivity/hyperactivity.Associationsbetweenmercuryandbehaviorweredetectedprimarilyforboys.However,whenthemothersconsumedmorethantwoservingsoffishperweek,therewasaprotectiveeffectforADHD-relatedbehaviors,particularlyimpulsive/hyperactivebehaviors(relativerisk=0.4;95percentCI0.2-0.6).

Theauthorofarelatededitorialsaidthatthestudy’sfindingspointtotheneedforanationalscientificadvisorypaneltoevaluateenvironmentalinfluencesofADHDandthatnewevidencelinkingenvironmentalcontaminantswithADHDreinforcestheurgencyofrevisingtheregulatoryframeworkforenvironmentalcontaminantsandtoxicants.

Citation:SagivSK,ThurstonSW,BellingerDC,AmarasiriwardenaC,KorrickSA.2012.PrenatalExposuretoMercuryandFishConsumptionDuringPregnancyandAttention-Deficit/HyperactivityDisorder–RelatedBehaviorinChildren.ArchPediatrAdolescMed166(12):1123-1131.

Related Editorial:LanphearBP.2012.Attention-Deficit/HyperactivityDisorder:APreventableEpidemic?ArchPediatrAdolescMed166(12):1182-1184.

(NancyLamontagneisasciencewriterwithMDB,Inc.,acontractorfortheNIEHSDivisionofExtramuralResearchandTraining,SuperfundResearchProgram,andWorkerEducationandTrainingProgram.)


Intramural papers of the month By Sonika Patial, Bhargavi Rao, Darshini Trivedi, and Sheila Yong

• Chloride channel regulation may lead to improvements in vascular disease


• New insights into lung dendritic cell migration in adaptive immune responses

• Tobacco smoke exposure in utero increases adult cardiovascular disease risk



59

Chloride channel regulation may lead to improvements in vascular diseaseArecentNIEHS-fundedstudydeterminedthatthemigrationofvascularsmoothmusclecells(VSMCs)isregulatedbychlorideionfluxthroughchloridechannelClC-3.TheteamisthefirsttoshowthatthechloridecurrentdramaticallydecreasesinVSMCslackingtheClC-3proteinandthatcalmodulin-dependentproteinkinaseII(CaMKII),amediatorofcalciumsignaling,actsthroughClC-3tostimulatethechloridecurrentinVSMCs.SinceVSMCmigrationcauseshealthconditionssuchashighbloodpressure(hypertension),arteryhardening(atherosclerosis),andarteryre-narrowingfollowingcorrectivesurgery(restenosis),understandingthesecellularsignalsmayaidthedevelopmentofmedicinesthatwillinhibitvascularremodeling.

ThroughelectrophysiologicalrecordingsofaorticVSMCsfromwild-typemiceandmicewithouttheClC-3gene,theresearchersfoundthatthechloridecurrentoftheClC-3-knockoutVSMCswasabouthalfthatofthewild-typecells.Thesefindingsindicatethattherearetwocomponentstothechloridecurrent—aClC-3-dependentandClC-3-independent.Additionally,thechloridechannelblockerniflumicacidinhibitedmigrationofwild-typeVSMCsbuthasnofurthereffectontheknockoutcells,suggestingthattheClC-3-dependentcomponentwasmoreimportantinVSMCmigration.

Thescientistsalsodemonstratedthatinositol-3,4,5,6-tetrakisphosphate(IP4)reducedClC-3-mediatedVSMCmigrationwithoutalteringCaMKIIactivity;IP4maybealeadcompoundfordevelopingtherapeuticdrugstospecificallytargetClC-3.(SY)

Citation:GanapathiSB,WeiSG,ZarembaA,LambFS,ShearsSB.2012.FunctionalregulationofCIC-3inthemigrationofvascularsmoothmusclecells.Hypertension61(1):174-179.


Mechanisms of anticancer drug resistanceAnewstudypublishedbyNIEHSscientistsdescribesthemolecularmechanismsbywhichtopoisomeraseII(topoII)-DNAadductsarerepairedbythemammaliantyrosyl-DNAphosphodiesterase2(Tdp2)enzyme.SincesomeofthemostsuccessfulcancerchemotherapeuticsworkbyinducingtopoII-DNAadductsthatpromotecancercelldeath,thisstudydetermineshowTdp2,inturn,contributestoanticancerdrugresistancethroughitstopoII-DNAadductrepairfunctions.

VisitingfellowMatthewSchellenberg.Ph.D.,andbiologistDeniseAppelemployedX-raycrystallographyandbiochemicalanalysestodeterminehowTdp2dictatesarepairpathwaythatiscriticalforcellsdealingwithbulkytopoII-DNAadducts.TopoisomerasesplaycriticalrolesinenablingcellularDNAreplicationandtranscription.However,stressorsincludingenvironmentaltoxicantscaninterruptthetopo2DNAprocessingreaction,therebygeneratingtopoII-DNAadductsthatcanblockthereplicationandtranscriptionmachinery.Tdp2dictatesarepairpathwaybyrecognizingandremovingthesetopoII-DNAadducts.TheresearcherstrappedTdp2inanumberofconformationsboundtoDNAthatenabledthemtodefinetheprotein-DNAconjugateprocessingmechanismattheatomiclevel.

ThisstudyhasfutureimplicationsindevisingstrategiestopreventanticancerdrugresistancebytargetingTdp2anddevelopingTdp2inhibitors.(SP)


60

Citation:SchellenbergMJ,AppelCD,AdhikariS,RobertsonPD,RamsdenDA,WilliamsRS.2012.Mechanismofrepairof5’-topoisomeraseII-DNAadductsbymammaliantyrosyl-DNAphosphodiesterase2.NatStructMolBiol19(12):1363-1371.Story


New insights into lung dendritic cell migration in adaptive immune responsesArecentreportbyNIEHSinvestigatorsfoundthatthechemokinereceptorCCR7,whichisimportantinthemigrationofdendriticcells(DCs)todraininglymphnodes(LNs),isexpressedinCD103+DCsandasmallpopulationofCD11b-hiDCs.BothofthesecelltypesaresubsetsofclassicalDCs(cDCs)anddisplaymigratorypotential.Incontrast,theteamfoundthatmonocyte-derivedDCs(moDCs)donotexpressCCR7andarenon-migratory.ThedatafurtherstheunderstandingofthemigratorypotentialofDCsandprovidesimportantimplicationsfortherapeuticinterventionforpulmonarydiseases.

PulmonaryDCsareimmunecells,whichprimarilyfunctiontoprocessinhaledantigensandmigratetoLNsforpresentationtonaïveTcells,therebyinitiatinganadaptiveimmuneresponse.DCmigrationisacrucialeventbecausenaïveTcellsarenotabundantinperipheraltissues,butrathercirculatebetweenthebloodandlymphoidtissuessuchaslymphnodes.Untilthisstudy,itwasunknownwhetherallDCsubsetspossessedmigratoryproperties.

Usingmicedeficientinthefms-liketyrosinekinase3ligand(FLT3L),aglycoproteinknowntoregulatethedevelopmentofsomeDCs,theinvestigatorsfoundthatallofthemigratoryDCsinthelungareinfactFLT3L-dependentcDCs.Thus,theyconcludedthatthemigratorypropertiesofpulmonaryDCsaredependentontheirdevelopmentallineage.(DT)

Citation:NakanoH,BurgentsJE,NakanoK,WhiteheadGS,CheongC,BortnerCD,CookDN.2012.Migratorypropertiesofpulmonarydendriticcellsaredeterminedbytheirdevelopmentallineage.MucosalImmunol;doi:10.1038/mi.2012.106[Online21November2012].


Tobacco smoke exposure in utero increases adult cardiovascular disease riskInanewstudy,NIEHSEpidemiologyBranchscientistsreportedthatexposuretotobaccosmokein uteroledtoincreasedlevelsoftriglyceridesandlowerlevelsofhigh-densitylipoproteincholesterol(HDL),alsoknownasgoodcholesterol,inadulthood,18-44yearsafterexposure.

Thestudyincluded479pregnantwomenfromtheNorwegianMotherandChildCohortStudy(MoBa).Theresearchersalsofoundthatafteradjustingforage,physicalactivity,education,personalsmoking,andbodymassindex(BMI),therewasnosignificanteffectonlow-densitylipoproteincholesterol(LDL),totalcholesterol,apolipoproteinB,andC-reactiveprotein.


http://www.niehs.nih.gov/news/newsletter/2012/11/science-anticancer/index.htm


61

Atstudyenrollment,womenwereaskedabouttheirmother’ssmokingwhilepregnantwiththem;thisinformationwasusedtoassignin uteroexposure.Standardclinicaltestsonnonfastingbloodspecimensfollowedbyrigorousstatisticalanalysisledthemtoconcludethatwomenexposedtotobaccosmokein uteroweretwiceaslikelytohaveelevatedtriglyceridesorlowHDL.

Thisstudyhassignificantimplicationsinunderstandinghowexposuretotobaccosmokein uterorelatestotherisksofdevelopingmetabolicalterationsandcardiovasculardiseaseyearsafterexposure.Studiesinthepasthaveonlylookedateffectsinearlychildhood.(BR)

Citation:Cupul-UicabLA,SkjaervenR,HaugK,TravlosGS,WilsonRE,EggesboM,HoppinJA,WhitworthKW,LongneckerMP.2012.Exposuretotobaccosmokeinuteroandsubsequentplasmalipids,apoB,andCRPamongadultwomenintheMoBAcohort.EnvironHealthPerspect120(11):1532-1537.

(SonikaPatial,D.V.M.,Ph.D.,isavisitingfellowintheNIEHSLaboratoryofSignalTransduction.BhargaviRao,Ph.D.,isanIntramuralResearchTrainingAward(IRTA)fellowintheNIEHSLaboratoryofMolecularCarcinogenesis.DarshiniTrivedi,Ph.D.,isanIRTAfellowintheNIEHSLaboratoryofToxicologyandPharmacology.SheilaYong,Ph.D.,isavisitingfellowintheNIEHSLaboratoryofSignalTransduction.)


http://ehp.niehs.nih.gov/2012/11/1104563/

http://ehp.niehs.nih.gov/2012/11/1104563/

62

Inside the InstituteNIEHS celebrates diversity and generosity on International Day By Eddy Ball

NIEHSofferedemployeesandcontractorssustenanceforthebodyandthesoul,duringthisyear’sInternationalDaycelebrationDec.12,2012.TheeventsetitselfapartfrompreviouscelebrationswithtwofirstsfromtheNIEHSDiversityCouncil—aninternationalbestchefcompetitionandtheGivingTree,aseasonaldrivetocollectgiftsforunderprivilegedchildren,supportedbytheSalvationArmyofWakeCounty.OnlyorganizationsthatareapprovedcharitieswithintheCombinedFederalCampaignareallowedtoreceivegiftscollectedinaGivingTreedrive.

Fellowship and fine fareInternationalDayopenedwithaheartywelcomefromNIEHSDeputyDirectorRickWoychik,Ph.D.,whoofferedcelebrantsbestwishesonbehalfofhimselfandDirectorLindaBirnbaum,Ph.D.,whowasunabletoattend.“ThisisthedaywereallycelebratetherichculturaldiversitythatexistshereatNIEHS.Aspartoftheprogram,wehavesometraditionsfromyesteryear,butwehaveacoupleofotherfeaturesthatarenewtoInternationalDaythisyear.”

WhatfollowedwereupbeatmusicalselectionsbytheNIEHSband,opportunitiesforfood,fellowship,andnewfriendships,andpodiumbanterfromNTPscientistandemceeNigelWalker,Ph.D.,asjudgessystematicallysampledentriesandcarefullyponderedtheirvotesforthebestchefentréeanddessertawards.

ThejudgesincludedWoychik;ScientificDirectorDarrylZeldin,M.D.;EmployeeServicesManagerDonaMcNeill;BioinformaticsScientistDavidFargo,Ph.D.;ScientificReviewOfficerRoseAnneMcGee;andNTPCellularandMolecularPathologyBranchChiefRobertSills,D.V.M.,Ph.D.Whentheyreachedtheirdifficult,andnodoubtagonizingdecision,thewinnerswerepostdoctoralfellowBhargaviRao,Ph.D.,forbestentree,andbiologistLisaPadilla-Banks,forbestdessert.OtherculinarycontestantswereMaileHenson,Ph.D.,IreneLee,EllenMoul,andBillQuattlebaum.

Woychik set the tone for the tasty and exotic fare partygoers enjoyed on International Day. “I’m looking forward to the wonderful music and great food,” he said before turning the podium back to Walker. (Photo courtesy of Steve McCaw)

Ramen Saha, Ph.D., left, was among the first to queue up for refreshments, as the line of hungry people grew longer and stragglers arrived to sample the fare. Saha, who describes himself as a foodie, said afterwards, “I wish I knew who cooked what so that I could ask for recipes or leftovers.” (Photo courtesy of Steve McCaw)

63

The spirit of the seasonAspeopleateandmingled,othersgatheredattheGivingTree,whichwasdecoratedwithstarsmadebychildrenattheNIEHSdaycarefacility,FirstEnvironments,andsurroundedbygiftswithangeltags,donatedbyemployeesandcontractors.TheDiversityCouncil’sdriveispartofanefforttoprovideholidaytoysandclothestonearly8,700disadvantagedchildrenthroughSalvationArmy’sAngelTreeprogram.

ThedrivecontinuedthroughDec.14,2012,whenDiversityCouncilmemberstook120taggedpackagesandmorethan20bagsoftoystotheSalvationArmywarehouseinRaleigh,N.C.

Media and glassware contractor Mike Watkins, left, and cafeteria contractor Lamont Alexander took a well-deserved break to enjoy the hospitality made possible by the Diversity Council. (Photo courtesy of Steve McCaw)

While the band played holiday — and some not so seasonal — tunes, the judges prepared for the rigor of their tasty task. Seated around the table, left to right, are Zeldin, Woychik, Sills, Fargo, McNeill, and McGee. (Photo courtesy of Steve McCaw)

Organizers paid attention to the details of presentation, as well as to the quality of the food, including Rao’s prize-winning entrée, rear, and Padilla-Bank’s prize-winning dessert, front. (Photo courtesy of Steve McCaw)

Performing was a labor of love for the NIEHS band. Shown, left to right in the front row, are Roger Callahan, Mike Humble, Ph.D., Andrea Moon, Miranda Bernhardt, Ph.D., and Dick Sloane. Standing in the back to help keep rhythm is Alyson Scoltock. (Photo courtesy of Steve McCaw)

http://www.keepthebellringing.org/

64


The e-Factor, which is produced by the Office of Communications and Public Liaison, is the staff newsletter at the National Institute of Environmental Health Sciences. It is published as a communication service to NIEHS employees. We welcome your comments and suggestions. The content is not copyrighted. It can be downloaded and reprinted without permission. If you are an editor who wishes to use our material in your publication, we ask that you send us a copy for our records.• Director of Communications: Christine Bruske• Writer-Editor: Eddy Ball• Science Editor: Robin Arnette

The Giving Tree was as beautiful as it was an emblem of the generosity of people at NIEHS. Thanks to the gift drive, many children in the Raleigh area, who were facing a bleak holiday, will wake up to gifts. (Photo courtesy of Steve McCaw)

Winners Padilla-Banks, left, and Rao received aprons and certificates for their winning efforts, as well as the thanks from grateful NIEHS staff for their quality cooking. (Photo courtesy of Steve McCaw)

In his opening remarks, Woychik recognized the members of the Diversity Council. Shown, left to right, are Molly Vallant, Jenn Evans, Cynthia Radford, Eli Ney, Chair Brad Collins, Quattlebaum, Walker, and Veronica Godfrey Robinson. (Photo courtesy of Steve McCaw)




niehs spotlight science notebook · 2020-01-11 · niehs spotlight science notebook niehs partners...

Documents