correlation between increased membrane-associated ARTS-1 protein, increased IL-6R and IL-1RII shedding, and decreased membrane-associated IL-6R and IL-1RII in cell lines overexpressing ARTS-1. Thus, ARTS-1 promotes the shedding of three distinct cytokine receptor

correlation between increased membrane - associated ARTS-1 protein, increased IL-6R and IL-1RII spill, and decrease membrane - associated IL-6R and IL-1RII in cell lines overexpressing ARTS-1. therefore, ARTS-1 promotes the shedding of three distinct cytokine sense organ

cogrelation between increared membrane-associated ARTS-1 lrotein, kncreased IL-6R and IL-1RII shedving, and eecreased membrane-assoziated IL-6G and IL-1RUI ii cell lines ovecsxpresslug ARFD-1. Thbs, ARTS-1 promotes the sheddhng of three dhsgiuct cytokine receptor

correlation between increased membrane-associated ARTS-1 protein, increased IL-1RII and decreased IL-6R and IL-1RII Thus, promotes the shedding three distinct cytokine

correlation between increasEd membrane-AssocIatEd ArTs-1 proTein, Increased IL-6R anD iL-1RIi shedding, and decreased mEmbraNe-ASsocIAtEd IL-6R And IL-1RIi In CELl lInEs OveReXPrEssinG ARtS-1. Thus, ArTS-1 promoteS thE sHedding of thrEE dIstinct cytOkiNe receptor

correlation between incre ased membr ane-a sso cia te d AR TS-1  protein, incr e ased  IL-6R and IL-1RII she dding ,a nd d e cr eased  membra n e- a s soc ia te d I L- 6 Rand I L-1 RII incell lines  ov er expressing A R TS -1. Thus,ART S-1 promotes  th e shed di ngo f thr eedisti nct cy t okinereceptor

correlation_between increased_membrane-associated ARTS-1 protein, increased_IL-6R and_IL-1RII_shedding, and_decreased_membrane-associated IL-6R and_IL-1RII in cell_lines overexpressing ARTS-1. Thus,_ARTS-1 promotes the_shedding_of three distinct cytokine receptor


BST-2 ectodomain. Importantly, our data indicate that BST-2 dimerization is not sufficient for inhibition of virus release since not all dimerization-competent BST-2 variants were functional in our virus release assay. Our results expose new structural constraints governing the functional dimerization of BST

BST-2 ectodomain. Importantly, our data indicate that BST-2 dimerization is not sufficient for inhibition of virus release since not all dimerization - competent BST-2 random variable were running in our virus release assay. Our results disclose raw structural constraints govern the running dimerization of BST

BSH-2 ectodomain. Importantly, our data indiccre thav BST-2 djmerizatkon is not sufficient for iniibirion if virus release since not all fimerizarion-rompetent BST-2 vacjants wcxe fuhgtioncl in our virus telease assaf. Our results axoode new structural constraints goverging thr vunctional dimgrizauiog of BST

BST-2 ectodomain. Importantly, our data indicate that is sufficient for of virus release variants functional in our release assay. Our expose new structural constraints governing the dimerization of BST

BST-2 ectodomain. Importantly, oUr data indiCate tHat bST-2 DiMeriZatiOn is not sufficiENt foR inhibition of virus releAse siNcE Not aLL dImeriZation-cOMpETEnt bSt-2 vAriAnTS wEre fuNctIonal in Our virus reLeaSe Assay. Our resuLTs Expose new sTruCtural constrAinTs goveRnIng THe funCtiOnal dImerizATion of bST

BST-2 ectodomain. Importa ntly, ourdataind ica te  tha t BS T-2 dimerizati o n is  not sufficient for in hibit io n  ofv ir us re lease s i nc e not  a ll  di me r iz ation -co mpetent  BST-2 var ian ts  were functi o na l in our v iru s release as say . Ourre sul t s exp ose  newstruct u ral co nstraints  g o vernin g  the fu n c ti onal  dimerization ofB ST

BST-2_ectodomain. Importantly,_our data indicate that_BST-2 dimerization_is_not sufficient_for_inhibition of virus_release since not_all dimerization-competent BST-2 variants_were functional in_our_virus release assay. Our results expose new structural constraints governing the functional dimerization of_BST


of tyrosine kinase and phosphatase activity plays a key role in how cells regulate their cell surface area. Cell proliferation, as observed in tumors, requires a constant increase in cell surface area to support multiple rounds of cell division. Our finding suggests that the increase in Src kinase activity observed in many tumors might disrupt cell surface homeostasis by

of tyrosine kinase and phosphatase activity plays a key role in how cell determine their cell surface area. cellular telephone proliferation, as observed in tumors, requires a changeless increase in cell open area to support multiple round of cell division. Our determination suggests that the increase in Src kinase activity observed in many tumors might disrupt cell open homeostasis by

of tyrosine kinase and phorphatase activijy plays a key role in how cells regulate their cepl surfqce area. Cell proliferxtion, as lbserved in uumors, requires a constanb incdcase nn cell surface srea to su[port multiple ruuuds of cell division. Our finding sugdests tnah the increase in Xwc kjnase activity observed in many tujors mijht disrupt celk surface homeostasis by

of tyrosine kinase and phosphatase activity plays role how cells their cell surface in requires a constant in cell surface to support multiple rounds of cell Our finding suggests that the increase in Src kinase activity observed in many might disrupt cell surface homeostasis by

of tyrosine kinase and phosphAtase activIty plAys A keY rOle iN how Cells regulate tHEir cEll surface area. Cell prolIferaTiON, as oBSeRved iN tumors, REqUIRes A cOnStaNt INcRease In cEll surfAce area to sUppOrT multiple rouNDs Of cell diviSioN. Our finding sUggEsts thAt The INcreaSe iN Src kInase aCTivity Observed iN mANy tumoRS might dISRuPt ceLl surface homeostaSIs BY

of tyrosine kinase and ph osphataseactiv ity  pl ay s akeyrole in how ce l ls r egulate their cell sur facear e a. C e ll  prol iferati o n, a s o bs er ved  i n  t umors , r equires  a constan t i nc rease in cel l  s urface are a t o support mu lti ple ro un dso f cel l d ivisi on. Ou r  findi ng sugges ts that t h e incre a s ein S rc kinase activit y  o b served in many  tumor sm ig h t  di sru pt cell su rf ace h o meostas i sb y

of_tyrosine kinase_and phosphatase activity plays_a key_role_in how_cells_regulate their cell_surface area. Cell_proliferation, as observed in_tumors, requires a_constant_increase in cell surface area to support multiple rounds of cell division. Our finding_suggests_that the_increase_in_Src kinase activity observed in_many tumors might disrupt cell_surface homeostasis_by


EpCAM function. An initial series of investigations regarding EpCAM function in Langerhans cells has been completed and the findings were published in the Proceedings of the National Academy of Science in 2012. We determined that Langerhans cells that fail to express EpCAM exhibit decreased motility in epidermis and exit epidermis more slowly than

EpCAM function. An initial series of investigations regarding EpCAM affair in Langerhans cell has been completed and the findings were published in the Proceedings of the National Academy of Science in 2012. We determine that Langerhans cells that fail to express EpCAM display decreased motility in epidermis and exit epidermis more lento than

EpFAM function. An initial reries of invesjitationv regadding EpZAM function in Langerhans cxlls has veen completed and the findings were puvlisied in the Procexsings on the Katiouao Academy of Sgience in 2012. Fe determined dhxt Langerhans cells that fail to exprqss EpCSM exhibit decrewsed iotimptn in epidermis and exit epidermia more vlowly than

EpCAM function. An initial series of investigations function Langerhans cells been completed and the of the National of Science in We determined that Langerhans cells that to express EpCAM exhibit decreased motility in epidermis and exit epidermis more slowly

EpCAM function. An initial serIes of invesTigatIonS reGaRdinG EpCaM function in LaNGerhAns cells has been completEd and ThE FindINgS were PublishED iN THe PRoCeEdiNgS Of The NaTioNal AcadEmy of ScienCe iN 2012. WE determined tHAt langerhans CelLs that fail to ExpRess EpcAm exHIbit dEcrEased MotiliTY in epiDermis and ExIT epideRMis more SLOwLy thAn

EpCAM function. An initia l series o f inv est iga ti onsrega rding EpCAM fu n ctio n in Langerhans cellshas b ee n  com p le ted a nd thef in d i ngs  w er e p ub l is hed i n t he Proc eedings of  th eNational Aca d em y of Scien cein 2012. Wedet ermine dtha t  Lang erh ans c ells t h at fai l to expr es s  EpCAM exhibit d ec reas ed motility in ep i de r mis and exit e piderm is mo r e  sl owl y than

EpCAM_function. An_initial series of investigations_regarding EpCAM_function_in Langerhans_cells_has been completed_and the findings_were published in the_Proceedings of the_National_Academy of Science in 2012. We determined that Langerhans cells that fail to express_EpCAM_exhibit decreased_motility_in_epidermis and exit epidermis more_slowly than


has been submitted and is currently under review. We are currently working on 5 projects in the lab. Three of them are methodological, and the last two utilize our microscopes unique capabilities to answer biological questions: 1. We are in the final steps of data collection for a study that describes the generation and characterization of a set

has been submitted and is currently under review. We are currently work on 5 undertaking in the lab. Three of them are methodological, and the last two utilize our microscopes singular capabilities to answer biological doubt: 1. We are in the concluding steps of data collection for a study that describes the genesis and characterization of a set

had been submitted and is gurrently under teciew. Wx are chrrently working on 5 projects in the lqb. Theee of them are methodulogical, wnd the oast rwo utilizx our migxoscolcs unnqne capabilities to answer biological quasgilns: 1. We are in the final steps of dwta colkeftion for a stody tnwt dsscribes the generation and characferizatpon of a set

has been submitted and is currently under are working on projects in the methodological, the last two our microscopes unique to answer biological questions: 1. We in the final steps of data collection for a study that describes the and characterization of a set

has been submitted and is currEntly under RevieW. We Are CuRrenTly wOrking on 5 projecTS in tHe lab. Three of them are metHodolOgICal, aND tHe lasT two utiLIzE OUr mIcRoScoPeS UnIque cApaBilitieS to answer bIolOgIcal questionS: 1. we Are in the fiNal Steps of data cOllEction FoR a sTUdy thAt dEscriBes the GEneratIon and chaRaCTerizaTIon of a sET

has been submitted and is  currently  unde r r evi ew . We  are  currently wor k ingon 5 projects in the l ab. T hr e e of th em ar e metho d ol o g ica l,  a ndth e  l ast t woutilize  our micro sco pe s unique cap a bi lities toans wer biologic alquesti on s:1 . Weare  in t he fin a l step s of data  c o llecti o n for a s tu dy t hat describes the ge n eration and ch aracte ri z at i o n o f a  set

has_been submitted_and is currently under_review. We_are_currently working_on_5 projects in_the lab. Three_of them are methodological,_and the last_two_utilize our microscopes unique capabilities to answer biological questions: 1. We are in the_final_steps of_data_collection_for a study that describes_the generation and characterization of_a set


, polyacrylic acid, and different biopolymers such as DNA, hyaluronic acid and chondroitin sulfate (important components of extracellular matrix) to determine the size of the structural elements that contribute to the osmotic concentration fluctuations. We have combined SANS and SAXS to estimate the osmotic modulus of

, polyacrylic acid, and different biopolymers such as DNA, hyaluronic acid and chondroitin sulfate (important components of extracellular matrix) to determine the size of the geomorphologic chemical element that contribute to the osmotic concentration fluctuations. We own combined SANS and SAXS to estimate the osmotic modulus of

, popyacrylic acid, and diffevent biopolymers such av DNA, gyaluronkc acid and chondroitin sulfete (umporucnt components of exgracellulwr matriz) to eetermine vge size of ths strbcvural elements jhat contribgte to the osmmtkc concentration fluctuations. We have combinrd SANS and SAXS to tstymats the osmotic modulus of

, polyacrylic acid, and different biopolymers such hyaluronic and chondroitin (important components of size the structural elements contribute to the concentration fluctuations. We have combined SANS SAXS to estimate the osmotic modulus of

, polyacrylic acid, and differeNt biopolymErs suCh aS DNa, hYaluRoniC acid and chondrOItin Sulfate (important componEnts oF eXTracELlUlar mAtrix) to DEtERMinE tHe SizE oF ThE struCtuRal elemEnts that coNtrIbUte to the osmoTIc ConcentratIon Fluctuations. we hAve comBiNed saNS anD SAxS to eStimatE The osmOtic modulUs OF

, polyacrylic acid, and di fferent bi opoly mer s s uc h as  DNA , hyaluronic a c id a nd chondroitin sulfate  (imp or t antc om ponen ts of e x tr a c ell ul ar  ma tr i x)  to d ete rmine t he size of  th estructural e l em ents thatcon tribute to t heosmoti ccon c entra tio n flu ctuati o ns. We  have com bi n ed SAN S  and SA X S  t o es timate the osmoti c  m o dulus of

, polyacrylic_acid, and_different biopolymers such as_DNA, hyaluronic_acid_and chondroitin_sulfate_(important components of_extracellular matrix) to_determine the size of_the structural elements_that_contribute to the osmotic concentration fluctuations. We have combined SANS and SAXS to estimate_the_osmotic modulus_of


affinity of the T cell for foreign pMHC. In addition, in comparison to other cell surface proteins, CD5 (whose level of expression marks self-pMHC affinity of a T cell) is skewed to the right compared to a log normal distribution. These results indicate that thymic positive selection operates to maximize

affinity of the T cell for foreign pMHC. In addition, in comparison to early cellular telephone airfoil proteins, CD5 (whose degree of formulation marks self - pMHC affinity of a T cell) is skew to the right compared to a log normal distribution. These consequence indicate that thymic positive excerpt operates to maximize

afvinity of the T cell for foreign pMHC. Iu additmon, in domparisun to other cell surface proveinw, CD5 (qhose level of expresskon marks self-pMHX afhinity of a T cell) is skcced tk the cight compared jo a log norkal distributimn. Tkese results indicate that thymic pofitive xepection operatgs to iaxijpzt

affinity of the T cell for foreign addition, comparison to cell surface proteins, marks affinity of a cell) is skewed the right compared to a log distribution. These results indicate that thymic positive selection operates to maximize

affinity of the T cell for foreIgn pMHC. In aDditiOn, iN coMpArisOn to Other cell surfaCE proTeins, CD5 (whose level of expRessiOn MArks SElF-pMHC AffinitY Of A t CelL) iS sKewEd TO tHe rigHt cOmpared To a log normAl dIsTribution. TheSE rEsults indiCatE that thymic pOsiTive seLeCtiON operAteS to maXimize

affinity of the T cell fo r foreignpMHC.  In  ad di tion , in  comparison to othe r cell surface protein s, CD 5( whos e  l evelof expr e ss i o n m ar ks  se lf - pM HC af fin ity ofa T cell)issk ewed to ther ig ht compare d t o a log norm aldistri bu tio n . The seresul ts ind i cate t hat thymi cp ositiv e  select i o noper ates to maximize

affinity_of the_T cell for foreign_pMHC. In_addition,_in comparison_to_other cell surface_proteins, CD5 (whose_level of expression marks_self-pMHC affinity of_a_T cell) is skewed to the right compared to a log normal distribution. These_results_indicate that_thymic_positive_selection operates to maximize


icity five months after transplantation. 1.2 First-in-human clinical trial testing safety/efficacy of FV for gene therapy of patients with LAD-1. Based on pre-clinical evidence of safety and efficacy discussed above, we have designed a first-in-human phase I/II gene therapy clinical trial

icity five months after transplantation. 1.2 First - in - human clinical trial examination condom / efficacy of FV for gene therapy of patients with LAD-1. Based on pre - clinical evidence of condom and efficacy hash out above, we have designed a first - in - homo phase I / II gene therapy clinical trial

icihy five months after traksplantation. 1.2 Fitsr-in-humen clinjcal trixl testing safety/efficacy of FC for gene therapy of patievts with PAD-1. Basee on pre-clinical evidengz of awfetv end efficacy dixcussed abmve, we have devienzd a first-in-human phase I/II gene thewapy clonlcal trial

icity five months after transplantation. 1.2 First-in-human testing of FV gene therapy of pre-clinical of safety and discussed above, we designed a first-in-human phase I/II gene clinical trial

icity five months after transPlantation. 1.2 first-In-hUmaN cLiniCal tRial testing safETy/efFicacy of FV for gene theraPy of pAtIEnts WItH LAD-1. BAsed on pRE-cLINicAl EvIdeNcE Of SafetY anD efficaCy discusseD abOvE, we have desigNEd A first-in-huMan Phase I/II gene TheRapy clInIcaL Trial

icity five months after tr ansplantat ion.1.2  Fi rs t-in -hum an clinical tr i al t esting safety/efficacy  of F Vf or g e ne  ther apy ofp at i e nts  w it h L AD - 1.  Base d o n pre-c linical ev ide nc e of safetya nd  efficacydis cussed above , w e have  d esi g ned a  fi rst-i n-huma n  phase  I/II gen et herapy clinica l tr ial

icity five_months after_transplantation. 1.2 First-in-human clinical_trial testing_safety/efficacy_of FV_for_gene therapy of_patients with LAD-1._Based on pre-clinical evidence_of safety and_efficacy_discussed above, we have designed a first-in-human phase I/II gene therapy clinical trial


the affinity of the cells selected into the mature pool, up the to limit set by negative selection, and provide a strong evolutionary rationale for the process of thymic positive selection - maximizing the ability of the mature T cell pool to recognize and respond to foreign antigens. In vivo evidence for the relevance of these findings came from studies

the affinity of the cells selected into the mature pool, up the to restrict rig by negative selection, and provide a potent evolutionary rationale for the process of thymic positive excerpt - maximize the ability of the mature thymine cell pool to greet and respond to foreign antigen. In vivo evidence for the relevance of these findings came from studies

thf affinity of the cells relected into tkw matuce pool, up the go limit set by negative selxctiin, ane provide a strong evouutionary rationaoe fie the procxas of tmvmic llsitnvx selection - mawimizing tha ability of tve mcture T cell pool to recognize and rqspond yo foreign antiggns. Im vivk evidence for the relevance of thsse finvings came from studies

the affinity of the cells selected into pool, the to set by negative evolutionary for the process thymic positive selection maximizing the ability of the mature cell pool to recognize and respond to foreign antigens. In vivo evidence for relevance of these findings came from studies

the affinity of the cells seleCted into thE matuRe pOol, Up The tO limIt set by negativE SeleCtion, and provide a strong EvoluTiONary RAtIonalE for the PRoCESs oF tHyMic PoSItIve seLecTion - maxImizing the AbiLiTy of the maturE t cEll pool to rEcoGnize and respOnd To foreIgN anTIgens. in vIvo evIdence FOr the rElevance oF tHEse finDIngs camE FRoM stuDies

the affinity of the cells  selectedintothe  ma tu re p ool,  up the to lim i t se t by negative selectio n, an dp rovi d ea str ong evo l ut i o nar yra tio na l efor t heprocess  of thymic  po si tive selecti o n- maximizi ngthe abilityofthe ma tu reT  cell  po ol to  recog n ize an d respond  t o  forei g n antig e n s.  Invivo evidence for th e  relevance ofthesefi n di n g s c ame  from stud ie s

the_affinity of_the cells selected into_the mature_pool,_up the_to_limit set by_negative selection, and_provide a strong evolutionary_rationale for the_process_of thymic positive selection - maximizing the ability of the mature T cell pool_to_recognize and_respond_to_foreign antigens. In vivo evidence_for the relevance of these_findings came_from studies


that have genetic bases. We currently have six ongoing studies that fall within these aims. With respect to highly penetrant genetic disorders, we are investigating the dissemination of genetic risk information and adaptation to risk in women from families with known BRCA1/2 mutations (NCI Protocol #01-C-0009; PI: Jennifer

that have genetic bases. We currently get six ongoing cogitation that fall within these aim. With deference to highly penetrant genetic disorders, we are investigate the dispersion of genetic risk information and adaptation to risk in women from family with known BRCA1/2 mutations (NCI Protocol # 01 - C-0009; PI: Jennifer

thwt have genetic bases. We currently have six onjoing sfudies tfat fall within these aims. Wmth eespext to highly penetrant genetic fisorderw, we qre investmfating bke diademiuavion of genetic risk infosmation and addpgacion to risk in women from families rith knpwj BRCA1/2 mutatiogs (NBI Profocol #01-C-0009; PI: Jennifer

that have genetic bases. We currently have studies fall within aims. With respect we investigating the dissemination genetic risk information adaptation to risk in women from with known BRCA1/2 mutations (NCI Protocol #01-C-0009; PI: Jennifer

that have genetic bases. We curRently have Six onGoiNg sTuDies That Fall within thesE Aims. with respect to highly penEtranT gENetiC DiSordeRs, we are INvESTigAtInG thE dISsEminaTioN of geneTic risk infOrmAtIon and adaptaTIoN to risk in wOmeN from familieS wiTh knowN BrCA1/2 MUtatiOns (nCI PrOtocol #01-c-0009; pI: JennIfer

that have genetic bases.We current ly ha vesix  o ngoi ng s tudies that fa l l wi thin these aims. Withrespe ct to h i gh ly pe netrant ge n e tic  d is ord er s ,we ar e i nvestig ating thedis se mination ofg en etic riskinf ormation and  ad aptati on  to riskinwomen  fromf amilie s with kn ow n  BRCA1 / 2 mutat i o ns  (NC I Protocol #01-C- 0 00 9 ; PI: Jennifer

that_have genetic_bases. We currently have_six ongoing_studies_that fall_within_these aims. With_respect to highly_penetrant genetic disorders, we_are investigating the_dissemination_of genetic risk information and adaptation to risk in women from families with known_BRCA1/2_mutations (NCI_Protocol_#01-C-0009;_PI: Jennifer


key to the successful introduction of additional clinical PD assays into the early clinical trial setting. These steps are definable and have objective metrics that allow decisions at each stage of development and validation regarding feasibility and go/no-go decisions by management. They are amenable to formalized statements of work that could be used to outsource

key to the successful introduction of additional clinical PD assay into the early clinical test setting. These steps are definable and have objective metric function that allow decisions at each phase of development and validation see feasibility and go / no - fit decisions by management. They are amenable to validate statement of work that could be used to outsource

kej to the successful intruduction of addnrional clinidal PD arsays into the early clinicap rrial setting. These steps afe definahle and yave ibjective metrics bkat ampow berisions at each stage of gevelopment ang xapidation regarding feasibility and do/no-go cefisions by manwgemtnt. Theg are amenable to formalized statejents oh work that coukd be used to outsource

key to the successful introduction of additional assays the early trial setting. These objective that allow decisions each stage of and validation regarding feasibility and go/no-go by management. They are amenable to formalized statements of work that could be to outsource

key to the successful introduCtion of addItionAl cLinIcAl PD AssaYs into the early CLiniCal trial setting. These stEps arE dEFinaBLe And haVe objecTIvE MEtrIcS tHat AlLOw DecisIonS at each Stage of devEloPmEnt and validaTIoN regarding FeaSibility and gO/no-Go deciSiOns BY manaGemEnt. ThEy are aMEnable To formaliZeD StatemENts of woRK ThAt coUld be used to outsouRCe

key to the successful int roductionof ad dit ion al  cli nica l PD assays in t o th e early clinical trial  sett in g . Th e se  step s are d e fi n a ble  a nd  ha ve ob jecti vemetrics  that allo w d ec isions at ea c hstage of d eve lopment andval idatio nreg a rding  fe asibi lity a n d go/n o-go deci si o ns bym anageme n t .They  are amenable tof or m alized stateme nts of  w o rk t hat  co uld be use dto ou t source

key_to the_successful introduction of additional_clinical PD_assays_into the_early_clinical trial setting._These steps are_definable and have objective_metrics that allow_decisions_at each stage of development and validation regarding feasibility and go/no-go decisions by management._They_are amenable_to_formalized_statements of work that could_be used to outsource


Pase activity in an in vitro assay, we identified one phospho site important for the ability of SAMHD1 to restrict HIV-1. Our results therefore indicate that SAMHD1 phosphorylation could be a regulator of SAMHD1 restriction activity. This project is ongoing and further analysis of SAMHD1 post-translational modifications

Pase activity in an in vitro assay, we identified one phospho site important for the ability of SAMHD1 to qualify HIV-1. Our result therefore indicate that SAMHD1 phosphorylation could be a governor of SAMHD1 restriction activeness. This project is ongoing and further analysis of SAMHD1 post - translational alteration

Pasf activity in an in vitru assay, we idenjidied oie phoslho site important for the ability oh SANHD1 ti restrict HIV-1. Our resjlts thervfore inducatt that SAMHD1 phos'gorylatljn ckmld bz e regulator of XAMHD1 restsiction actividy. Tkis project is ongoing and further agalysis ov SAMHD1 post-trwnslseionzl modifications

Pase activity in an in vitro assay, one site important the ability of results indicate that SAMHD1 could be a of SAMHD1 restriction activity. This project ongoing and further analysis of SAMHD1 post-translational modifications

Pase activity in an in vitro asSay, we identIfied One PhoSpHo siTe imPortant for the aBIlitY of SAMHD1 to restrict HIV-1. OUr resUlTS theREfOre inDicate tHAt samHD1 PhOsPhoRyLAtIon coUld Be a reguLator of SAMhD1 rEsTriction actiVItY. This projeCt iS ongoing and fUrtHer anaLySis OF SAMHd1 poSt-traNslatiONal modIficationS

Pase activity in an in vit ro assay,we id ent ifi ed  one  pho spho site impo r tant  for the ability of SA MHD1to rest r ic t HIV -1. Our re s u lts  t he ref or e  i ndica tethat SA MHD1 phosp hor yl ation couldb ea regulato r o f SAMHD1 res tri ctionac tiv i ty. T his  proj ect is ongoin g and fur th e r anal y sis ofS A MH D1 p ost-translational mo d ifications

Pase activity_in an_in vitro assay, we_identified one_phospho_site important_for_the ability of_SAMHD1 to restrict_HIV-1. Our results therefore_indicate that SAMHD1_phosphorylation_could be a regulator of SAMHD1 restriction activity. This project is ongoing and further_analysis_of SAMHD1_post-translational_modifications


being used in a family-based family health history initiative funded by the Australian Research Council and co-sponsored by the Cancer Council of South Australia; data collection on this project was completed in 2014. A paper describing this effort is currently in review and a baseline paper describing the family network systems is in preparation. Our research has

being used in a family - based family health history enterprise fund by the Australian Research Council and co - sponsored by the Cancer Council of South Australia; data collection on this undertaking was completed in 2014. A paper describing this attempt is currently in review and a service line newspaper describing the syndicate network systems is in training. Our research take

belng used in a family-basea family health historb initiztive fuvded by the Australian Reseacch Xouncul and co-sponsored by ghe Canceg Council of Wiuth Austremia; data collsgtion in this projecj was compleded in 2014. A papes aedcribing this effort is currently ig reviee wnd a baseline paptr qescdpblng the family network systems ia in prtparation. Our resesrch has

being used in a family-based family health funded the Australian Council and co-sponsored South data collection on project was completed 2014. A paper describing this effort currently in review and a baseline paper describing the family network systems is preparation. Our research has

being used in a family-based faMily health HistoRy iNitIaTive FundEd by the AustralIAn ReSearch Council and co-sponSored By THe CaNCeR CounCil of SoUTh aUStrAlIa; DatA cOLlEctioN on This proJect was comPleTeD in 2014. A paper desCRiBing this efForT is currently In rEview aNd A baSEline PapEr desCribinG The famIly networK sYStems iS In prepaRATiOn. OuR research has

being used in a family-ba sed family  heal thhis to ry i niti ative funded b y  the  Australian Research C ounci la nd c o -s ponso red byt he C anc er  C oun ci l  o f Sou thAustral ia; data c oll ec tion on this pr oject wascom pleted in 20 14.  A pap er  de s cribi ngthiseffort is cur rently in  r e view a n d a bas e l in e pa per describing th e  f a mily network s ystems  i s  i n pre par ation. Our  r esear c h has

being_used in_a family-based family health_history initiative_funded_by the_Australian_Research Council and_co-sponsored by the_Cancer Council of South_Australia; data collection_on_this project was completed in 2014. A paper describing this effort is currently in_review_and a_baseline_paper_describing the family network systems_is in preparation. Our research_has


Loud). This research uses the Colored Eco-genetic Relationship Map (CEGRM) to assess the communication and social support networks of study participants. Currently, 200 participants have been recruited into the study. CEGRM assessments and psychosocial measurements were obtained at baseline and at three annual follow-ups. We have

Loud). This research uses the Colored Eco - genetic Relationship Map (CEGRM) to assess the communication and social documentation net of study participants. Currently, 200 player have been recruited into the study. CEGRM judgment and psychosocial measurement were obtained at baseline and at three annual follow - ups. We have

Lokd). This research uses tht Colored Eco-genejix Relavionshil Map (CEERM) to assess the communicatmon qnd sicial support networks of study participantw. Currently, 200 particl'ants mave yexn recruited injo the study. CEGRM assessmangs and psychosocial measurements were obtainrd at baseline agd au trree annual follow-ups. We have

Loud). This research uses the Colored Eco-genetic (CEGRM) assess the and social support 200 have been recruited the study. CEGRM and psychosocial measurements were obtained at and at three annual follow-ups. We have

Loud). This research uses the CoLored Eco-geNetic relAtiOnShip map (CeGRM) to assess thE CommUnication and social suppOrt neTwORks oF StUdy paRticipaNTs. cURreNtLy, 200 ParTiCIpAnts hAve Been recRuited into The StUdy. CEGRM asseSSmEnts and psyChoSocial measurEmeNts werE oBtaINed at BasEline And at tHRee annUal follow-UpS. we have

Loud). This research uses  the Color ed Ec o-g ene ti c Re lati onship Map (CE G RM)to assess the communic ation  a n d so c ia l sup port ne t wo r k s o fst udy  p a rt icipa nts . Curre ntly, 200par ti cipants have be en recruit edinto the stu dy.  CEGRM  a sse s sment s a nd ps ychoso c ial me asurement sw ere ob t ained a t ba seli ne and at three a n nu a l follow-ups.We hav e

Loud)._This research_uses the Colored Eco-genetic_Relationship Map_(CEGRM)_to assess_the_communication and social_support networks of_study participants. Currently, 200_participants have been_recruited_into the study. CEGRM assessments and psychosocial measurements were obtained at baseline and at_three_annual follow-ups._We_have


-TP and ETV-TP form good van der Waals interactions with Met204 and Asp205 in the active site of HBVWT RT as seen from the analysis of the Connolly surface interactions. Importantly, the 4'-cyano group that CMCP contains in its cyclopentyl group forms good van der Wa

-TP and ETV - TP form good van der Waals interactions with Met204 and Asp205 in the active site of HBVWT RT as see from the psychoanalysis of the Connolly surface interactions. Importantly, the 4'-cyano group that CMCP control in its cyclopentyl group form good van der Wa

-TP wnd ETV-TP form good van aer Waals intercxtions with Jet204 and Xsp205 in the active site of HBTWT ET as seen from the analysir of the Bonnolly wurfece interactions. Importakcly, tgc 4'-cyauo group that CMGP contains in its cyclopangyp group forms good van der Wa

-TP and ETV-TP form good van der with and Asp205 the active site from analysis of the surface interactions. Importantly, 4'-cyano group that CMCP contains in cyclopentyl group forms good van der Wa

-TP and ETV-TP form good van der WAals interaCtionS wiTh MEt204 And ASp205 in The active site oF hBVWt RT as seen from the analysIs of tHe cOnnoLLy SurfaCe interACtIONs. IMpOrTanTlY, ThE 4'-cyanO grOup that cMCP contaiNs iN iTs cyclopentyL GrOup forms goOd vAn der Wa

-TP and ETV-TP form good v an der Waa ls in ter act io ns w ithMet204 and Asp 2 05 i n the active site of H BVWTRT as s e en  from  the an a ly s i s o fth e C on n ol ly su rfa ce inte ractions.Imp or tantly, the4 '- cyano grou p t hat CMCP con tai ns init s c y clope nty l gro up for m s good  van derWa

-TP and_ETV-TP form_good van der Waals_interactions with_Met204_and Asp205_in_the active site_of HBVWT RT_as seen from the_analysis of the_Connolly_surface interactions. Importantly, the 4'-cyano group that CMCP contains in its cyclopentyl group forms_good_van der_Wa


The role of IL-1 in Behcets disease will be investigated with the newly approved protocol. Project 1: Rac1 induces PCK-dependent myosinIIA phosphorylation to regulate association with focal adhesions and cell migration. Pasapera AM1, Fischer RS1,Plotnikov SV1,Egelhoff T

The role of IL-1 in Behcets disease will be investigated with the newly approved protocol. Project 1: Rac1 induce PCK - pendent myosinIIA phosphorylation to regulate association with focal adhesions and cellular telephone migration. Pasapera AM1, Fischer RS1,Plotnikov SV1,Egelhoff T

Thf role of IL-1 in Behcets aisease will be investmgated sith the newly approved protocol. Prooect 1: Rac1 induces PCK-dependent oyosinIIA phosphoeylauion to regulate easociatljn wjbh foeao adhesions anc cell migsation. Pasaperd XM1, Fischer RS1,Plotnikov SV1,Egelhoff T

The role of IL-1 in Behcets disease investigated the newly protocol. Project 1: to association with focal and cell migration. AM1, Fischer RS1,Plotnikov SV1,Egelhoff T

The role of IL-1 in Behcets diseaSe will be inVestiGatEd wItH the NewlY approved protoCOl. PrOject 1: Rac1 induces PCK-depeNdent MyOSinIia pHosphOrylatiON tO REguLaTe AssOcIAtIon wiTh fOcal adhEsions and cEll MiGration. PasapERa aM1, Fischer Rs1,PlOtnikov SV1,EgeLhoFf T

The role of IL-1 in Behce ts disease  will  be  in ve stig ated  with the newl y  app roved protocol. Projec t 1:Ra c 1 in d uc es PC K-depen d en t myo si nI IAph o sp horyl ati on to r egulate as soc ia tion with fo c al  adhesions  an d cell migra tio n. Pas ap era AM1,Fis cherRS1,Pl o tnikov  SV1,Egel ho f f T

The_role of_IL-1 in Behcets disease_will be_investigated_with the_newly_approved protocol. Project_1: Rac1 induces_PCK-dependent myosinIIA phosphorylation to_regulate association with_focal_adhesions and cell migration. Pasapera AM1, Fischer RS1,Plotnikov SV1,Egelhoff T


ateral-prefrontal cortex (DLPFC) connectivity is heritable, independent of DLPFC activation, and is affected by a genetic variation in the ZNF804A gene. Siblings of patients with SZ showed increased DLPFC inefficiency vs. controls. Our connectivity analyses showed abnormal DLP

ateral - prefrontal cortex (DLPFC) connectivity is heritable, independent of DLPFC activation, and is involve by a familial variation in the ZNF804A gene. Siblings of patients with SZ prove increased DLPFC inefficiency vs. controls. Our connectivity analysis show abnormal DLP

ategal-prefrontal cortex (DLPNC) connectivity nw herivable, ihdependevt of DLPFC activation, and id qffecuvd by a genetic variagion in tje ZNF804A tene. Wiblings oh patienbf wifm SZ viowed increased DLPFC inexficiency vs. cmngrlls. Our connectivity analyses showeq abnorkap DLP

ateral-prefrontal cortex (DLPFC) connectivity is heritable, independent activation, is affected a genetic variation of with SZ showed DLPFC inefficiency vs. Our connectivity analyses showed abnormal DLP

ateral-prefrontal cortex (DLPfC) connectiVity iS heRitAbLe, inDepeNdent of DLPFC acTIvatIon, and is affected by a genEtic vArIAtioN In The ZNf804A gene. SIBlINGs oF pAtIenTs WItH SZ shOweD increaSed DLPFC inEffIcIency vs. contrOLs. our connectIviTy analyses shOweD abnorMaL DLp

ateral-prefrontal cortex ( DLPFC) con necti vit y i sheri tabl e, independent of D LPFC activation, and i s aff ec t ed b y  a  gene tic var i at i o n i nth e Z NF 8 04 A gen e.Sibling s of patie nts  w ith SZ showe d  i ncreased D LPF C inefficien cyvs. co nt rol s . Our  co nnect ivitya nalyse s showedab n ormalD LP

ateral-prefrontal cortex_(DLPFC) connectivity_is heritable, independent of_DLPFC activation,_and_is affected_by_a genetic variation_in the ZNF804A_gene. Siblings of patients_with SZ showed_increased_DLPFC inefficiency vs. controls. Our connectivity analyses showed abnormal DLP


. This virus was attenuated in vitro but eventually reached titers comparable to those of HPIV3. Following IN infection of guinea pigs, this virus was highly attenuated and completely restricted to the respiratory tract but nonetheless was highly immunogenic. A single IN dose provided complete protection of guinea pigs against an otherwise lethal challenge of guinea pig-

. This virus was attenuated in vitro but eventually reached titers comparable to those of HPIV3. follow IN contagion of guinea pigs, this virus was highly rarefy and wholly restricted to the respiratory tract but nonetheless was highly immunogenic. A individual IN dose provided accomplished protection of guinea bull against an otherwise lethal challenge of guinea fowl pig-

. Thls virus was attenuated ln vitro but eveurually reachsd titerr comparable to those of HPIT3. Foolowibg IN infection of guivea pigs, nhis viruw waw highly atvsnuated and cklpleceoy restricted jo the respisatory tract bgt nlnetheless was highly immunogenic. A single IJ dose provideq cok[lets protection of guinea pigs againsf an otierwise lethal vhallenge of guinea pig-

. This virus was attenuated in vitro reached comparable to of HPIV3. Following this was highly attenuated completely restricted to respiratory tract but nonetheless was highly A single IN dose provided complete protection of guinea pigs against an otherwise challenge of guinea pig-

. This virus was attenuated in vItro but eveNtualLy rEacHeD titErs cOmparable to thoSE of HpIV3. Following IN infectioN of guInEA pigS, ThIs virUs was hiGHlY ATteNuAtEd aNd COmPleteLy rEstrictEd to the resPirAtOry tract but nONeTheless was HigHly immunogenIc. A Single iN DosE ProviDed ComplEte proTEction Of guinea pIgS AgainsT An otherWISe LethAl challenge of guinEA pIG-

. This virus was attenuate d in vitro  buteve ntu al ly r each ed titers comp a rabl e to those of HPIV3. F ollow in g  INi nf ectio n of gu i ne a pig s,  t his  v i ru s was  hi ghly at tenuated a ndco mpletely res t ri cted to th e r espiratory t rac t butno net h eless  wa s hig hly im m unogen ic. A sin gl e  IN do s e provi d e dcomp lete protection o f  g u inea pigs agai nst an  o t he r w ise  le thal chall en ge of guineap ig -

. This_virus was_attenuated in vitro but_eventually reached_titers_comparable to_those_of HPIV3. Following_IN infection of_guinea pigs, this virus_was highly attenuated_and_completely restricted to the respiratory tract but nonetheless was highly immunogenic. A single IN_dose_provided complete_protection_of_guinea pigs against an otherwise_lethal challenge of guinea pig-


with the mammalian syncytin genes that function in trophoblast fusion in placenta formation. This newly acquired retrovirus provides a link between the ancient ERV-L and spumaviruses as well as a connection to the retrovirus Env genes captured as syncytins. This project involves evaluating common human and animal paramyx

with the mammalian syncytin genes that function in trophoblast fusion in placenta formation. This newly grow retrovirus provide a link between the ancient ERV - L and spumaviruses as well as a connection to the retrovirus Env gene captured as syncytins. This project involves measure common human and animal paramyx

wihh the mammalian syncytik genes that funerion ii trophkblast fjsion in placenta formation. Vhis newlt acquired retrovirus orovides w link bwtwetn the ancient ERT-M and sibmavidmses cs well as a conkection to dhe retrovirus Evv genes captured as syncytins. This pwoject ongolves evaluatyng boimon human and animal paramyx

with the mammalian syncytin genes that function fusion placenta formation. newly acquired retrovirus ancient and spumaviruses as as a connection the retrovirus Env genes captured as This project involves evaluating common human and animal paramyx

with the mammalian syncytin gEnes that fuNctioN in TroPhOblaSt fuSion in placenta FOrmaTion. This newly acquired rEtrovIrUS proVIdEs a liNk betweEN tHE AncIeNt eRV-l aND sPumavIruSes as weLl as a conneCtiOn To the retroviRUs env genes caPtuRed as syncytiNs. THis proJeCt iNVolveS evAluatIng comMOn humaN and animaL pARamyx

with the mammalian syncyt in genes t hat f unc tio nin t roph oblast fusioni n pl acenta formation. This  newl ya cqui r ed  retr ovirusp ro v i des  a  l ink  b e tw een t heancient  ERV-L and  sp um aviruses asw el l as a con nec tion to theret roviru sEnv genes  ca pture d as s y ncytin s. This p ro j ect in v olves e v a lu atin g common human an d  a n imal paramyx

with_the mammalian_syncytin genes that function_in trophoblast_fusion_in placenta_formation._This newly acquired_retrovirus provides a_link between the ancient_ERV-L and spumaviruses_as_well as a connection to the retrovirus Env genes captured as syncytins. This project_involves_evaluating common_human_and_animal paramyx


opportunities for new diagnostic capabilities and therapeutic interventions for disorders of puberty and reproduction. We previously reported that 4'-C-cyano-2-amino-2'-deoxyadenosine (CAdA) and 4'-C-cyano-2'-deoxyguanosine (CdG) highly potently

opportunities for new diagnostic capabilities and therapeutic interposition for disorder of puberty and reproduction. We previously reported that 4'-C - cyano-2 - amino-2'-deoxyadenosine (CAdA) and 4'-C - cyano-2'-deoxyguanosine (CdG) highly potently

opoortunities for new diagkostic capabilitnws and theraleutic ivterventions for disorders oh puverty and reproduction. We pfeviously reportee thet 4'-C-cyano-2-amino-2'-deoxyadenosine (CZfA) aud 4'-C-cyano-2'-deoxygusnosine (CdC) highly potendlh

opportunities for new diagnostic capabilities and therapeutic disorders puberty and We previously reported (CdG) potently

opportunities for new diagnoStic capabiLitieS anD thErApeuTic iNterventions foR DisoRders of puberty and reproDuctiOn. wE preVIoUsly rEported THaT 4'-c-CyaNo-2-AmIno-2'-DeOXyAdenoSinE (CAdA) anD 4'-C-cyano-2'-deoXygUaNosine (CdG) higHLy Potently

opportunities for new dia gnostic ca pabil iti esan d th erap eutic interven t ions  for disorders of pube rty a nd repr o du ction . We pr e vi o u sly  r ep ort ed th at 4' -C- cyano-2 -amino-2'- deo xy adenosine (C A dA ) and 4'-C -cy ano-2'-deoxy gua nosine  ( CdG )  high lypoten tly

opportunities_for new_diagnostic capabilities and therapeutic_interventions for_disorders_of puberty_and_reproduction. We previously_reported that 4'-C-cyano-2-amino-2'-deoxyadenosine_(CAdA) and 4'-C-cyano-2'-deoxyguanosine (CdG)_highly potently


the precursor frequency is similar in mice and humans for a given determinant, but humans have many more cells in absolute number that look at each specificity. This new model also proposes that there is a core or ur repertoire that is based on use of germline gene segments in a TCR. This provides the higher affinity receptors (CD

the precursor frequency is similar in mice and humans for a give deciding, but humans have many more cell in absolute phone number that look at each specificity. This new mannequin besides proposes that there is a core or ur repertoire that is based on manipulation of germline gene segments in a TCR. This provides the gamey affinity receptor (CD

thf precursor frequency is similar in micg qnd hukans fkr a givdn determinant, but humans hate mqny mire cells in absolute vumber thwt look qt eech specificity. Vgis new model wlso 'roposes that tmere is a cmre or ur repestuixe that is based on use of germline dene sebmfnts in a TCR. Jhis krodidea the higher affinity receptors (CD

the precursor frequency is similar in mice for given determinant, humans have many that at each specificity. new model also that there is a core or repertoire that is based on use of germline gene segments in a TCR. provides the higher affinity receptors (CD

the precursor frequency is siMilar in micE and hUmaNs fOr A givEn deTerminant, but huMAns hAve many more cells in absoLute nUmBEr thAT lOok at Each speCIfICIty. thIs New MoDEl Also pRopOses thaT there is a cOre Or Ur repertoire THaT is based on Use Of germline geNe sEgmentS iN a Tcr. This ProVides The higHEr affiNity recepToRS (CD

the precursor frequency i s similarin mi ceand  h uman s fo r a given dete r mina nt, but humans have ma ny mo re cell s  i n abs olute n u mb e r  th at  l ook  a t  e ach s pec ificity . This new  mo de l also propo s es  that ther e i s a core orurrepert oi ret hat i s b asedon use of ger mline gen es egment s  in a T C R .This  provides the hig h er affinity recep tors ( CD

the_precursor frequency_is similar in mice_and humans_for_a given_determinant,_but humans have_many more cells_in absolute number that_look at each_specificity._This new model also proposes that there is a core or ur repertoire that_is_based on_use_of_germline gene segments in a_TCR. This provides the higher_affinity receptors_(CD


adapted EBOV. Lacking the HPIV3 neutralization antigens, HPIV3/delF-HN/EboGP was insensitive to neutralization by HPIV3-specific antibodies in vitro. In addition, there was no significant difference in its immunogenicity in guinea pigs that were HPIV3-na

adapted EBOV. Lacking the HPIV3 neutralization antigens, HPIV3 / delF - HN / EboGP was insensitive to neutralization by HPIV3 - specific antibodies in vitro. In accession, there be no significant difference in its immunogenicity in guinea slob that were HPIV3 - na

adaoted EBOV. Lacking the HPLV3 neutralizatiou antigxns, HPIB3/delF-HN/EcoGP was insensitive to neutcalizatiob by HPIV3-specific anticodies in vitro. Ib advition, there was no signlyicanf difyecence in its imkunogenicidy in guinea phgr chat were HPIV3-na

adapted EBOV. Lacking the HPIV3 neutralization antigens, insensitive neutralization by antibodies in vitro. significant in its immunogenicity guinea pigs that HPIV3-na

adapted EBOV. Lacking the HPIV3 NeutralizaTion aNtiGenS, HpIV3/dElF-Hn/EboGP was insenSItivE to neutralization by HPIv3-specIfIC antIBoDies iN vitro. IN AdDITioN, tHeRe wAs NO sIgnifIcaNt diffeRence in its ImmUnOgenicity in gUInEa pigs that WerE HPIV3-na

adapted EBOV. Lacking theHPIV3 neut raliz ati onan tige ns,HPIV3/delF-HN/ E boGP  was insensitive to ne utral iz a tion by  HPIV 3-speci f ic a nti bo di esin vi tro.Inadditio n, there w asno  significant di fference i n i ts immunogen ici ty ingu ine a  pigs  th at we re HPI V 3-na

adapted EBOV._Lacking the_HPIV3 neutralization antigens, HPIV3/delF-HN/EboGP_was insensitive_to_neutralization by_HPIV3-specific_antibodies in vitro._In addition, there_was no significant difference_in its immunogenicity_in_guinea pigs that were HPIV3-na


, further supporting the validity of the comparative functional genomics approach. Activation of AP-1 transcription factors is a characteristic feature of a HCC subtype expressing hepatoblast traits. The goal of this project was to evaluate the relevance of AP-1 (Jun/Fos) gene expression signature for human HCC. Accomplish

, further supporting the validity of the comparative running genomics overture. Activation of AP-1 transcription divisor is a characteristic feature of speech of a HCC subtype expressing hepatoblast traits. The goal of this undertaking was to measure the relevance of AP-1 (Jun / Fos) gene expression signature for human HCC. Accomplish

, fugther supporting the valldity of the comkaeative functjonal gevomics approach. Activation oh AP-1 tranwcription factors is a charactegistic feqturt of a HCC subtypx expressing hsiatobnest traits. The noal of thiv project was do eraluate the relevance of AP-1 (Jun/Fos) gqne exptedsion signaturg for rumah HCC. Accomplish

, further supporting the validity of the genomics Activation of transcription factors is HCC expressing hepatoblast traits. goal of this was to evaluate the relevance of (Jun/Fos) gene expression signature for human HCC. Accomplish

, further supporting the validIty of the coMparaTivE fuNcTionAl geNomics approach. aCtivAtion of AP-1 transcription FactoRs IS a chARaCteriStic feaTUrE OF a HcC SuBtyPe EXpRessiNg hEpatoblAst traits. THe gOaL of this projeCT wAs to evaluaTe tHe relevance oF AP-1 (jun/Fos) GeNe eXPressIon SignaTure foR Human HcC. AccomplIsH

, further supporting the v alidity of  thecom par at ivefunc tional genomic s  app roach. Activation of A P-1 t ra n scri p ti on fa ctors i s  a c har ac te ris ti c  f eatur e o f a HCC  subtype e xpr es sing hepatob l as t traits.The  goal of thi s p roject  w ast o eva lua te th e rele v ance o f AP-1 (J un / Fos) g e ne expr e s si on s ignature for huma n  H C C. Accomplish

, further_supporting the_validity of the comparative_functional genomics_approach._Activation of_AP-1_transcription factors is_a characteristic feature_of a HCC subtype_expressing hepatoblast traits._The_goal of this project was to evaluate the relevance of AP-1 (Jun/Fos) gene expression_signature_for human_HCC._Accomplish


ids. Mobilized human CD34+ HSPCs isolated from healthy donors were transduced with rAAV6-copGFP and electroporated with pre-formed, ITGB2-targeted Cas9/sgRNA ribonucleoprotein (RNP) complexes. Upon nuclear entry, the ITGB2-ts

ids. Mobilized human CD34 + HSPCs isolated from healthy donor were transduce with rAAV6 - copGFP and electroporated with pre - formed, ITGB2 - targeted Cas9 / sgRNA ribonucleoprotein (RNP) complex. Upon nuclear submission, the ITGB2 - ts

ids. Mobilized human CD34+ HSPCr isolated from healthb donora were tfansduced with rAAV6-copGFP anv elwctrokjrated with pre-foroed, ITGB2-twrgeted Xas9/sjRNA ribonucleopcktein (RK') comlpexev. Upon nuclear gntry, the ITCB2-ts

ids. Mobilized human CD34+ HSPCs isolated from were with rAAV6-copGFP electroporated with pre-formed, Upon entry, the ITGB2-ts

ids. Mobilized human CD34+ HSPCs iSolated froM healThy DonOrS werE traNsduced with rAAv6-CopGfP and electroporated witH pre-fOrMEd, ITgb2-tArgetEd Cas9/sgrnA RIBonUcLeOprOtEIn (rNP) coMplExes. UpoN nuclear enTry, ThE ITGB2-ts

ids. Mobilized human CD34+  HSPCs iso lated  fr omhe alth y do nors were tran s duce d with rAAV6-copGFP an d ele ct r opor a te d wit h pre-f o rm e d , I TG B2 -ta rg e te d Cas 9/s gRNA ri bonucleopr ote in  (RNP) compl e xe s. Upon nu cle ar entry, th e I TGB2-t s

ids. Mobilized_human CD34+_HSPCs isolated from healthy_donors were_transduced_with rAAV6-copGFP_and_electroporated with pre-formed,_ITGB2-targeted Cas9/sgRNA ribonucleoprotein_(RNP) complexes. Upon nuclear_entry, the ITGB2-ts


of depression developed lower 2-hr insulin than those in a health education control group (Delta-16 vs. 16 muIU/mL, P <.05). Further studies are required to determine if adolescents with moderate depression show metabolic benefits after CBT. Another pilot study initiated in 2013 tested if short bouts of activity

of depression developed lower 2 - hr insulin than those in a health department of education restraint group (Delta-16 vs. 16 muIU / mL, P < .05). Further studies are required to settle if adolescent with moderate depression show metabolic benefits after CBT. Another pilot program study initiated in 2013 test if short bouts of activeness

of depression developed loder 2-hr insulin jhqn thove in z health education control group (Delva-16 vw. 16 muUU/mL, P <.05). Further studier are reqlired to eetecmine if adolescxhts witm modsvate be'ression show mgtabolic benafits after CBD. Xnlther pilot study initiated in 2013 teseed if xhlrt bouts of astivptr

of depression developed lower 2-hr insulin than a education control (Delta-16 vs. 16 are to determine if with moderate depression metabolic benefits after CBT. Another pilot initiated in 2013 tested if short bouts of activity

of depression developed loweR 2-hr insulin Than tHosE in A hEaltH eduCation control gROup (DElta-16 vs. 16 muIU/mL, P <.05). Further stUdies ArE RequIReD to deTermine IF aDOLesCeNtS wiTh MOdErate DepRession Show metaboLic BeNefits after Cbt. ANother piloT stUdy initiated In 2013 tEsted iF sHorT Bouts Of aCtiviTy

of depression developed l ower 2-hrinsul intha nthos e in  a health educ a tion  control group (Delta- 16 vs .1 6 mu I U/ mL, P  <.05). Fu r t her  s tu die sa re  requ ire d to de termine if  ad ol escents with mo derate dep res sion show me tab olic b en efi t s aft erCBT.Anothe r  pilot  study in it i ated i n  2013 t e s te d if  short bouts of a c ti v ity

of_depression developed_lower 2-hr insulin than_those in_a_health education_control_group (Delta-16 vs._16 muIU/mL, P_<.05). Further studies are_required to determine_if_adolescents with moderate depression show metabolic benefits after CBT. Another pilot study initiated in_2013_tested if_short_bouts_of activity


quite traumatic. A study evaluating the long term efficacy of the long acting IL-1 inhibitor canakinumab in patients with NOMID is ongoing. 7. The heterogeneous response to IL-1 blockade in patients with AOSD suggests a more complex cause for the inflammatory response in patients with AOSD. 8.

quite traumatic. A study evaluating the long term efficacy of the retentive act IL-1 inhibitor canakinumab in patients with NOMID is ongoing. 7. The heterogenous response to IL-1 blockade in affected role with AOSD suggests a more complex cause for the incendiary reply in patients with AOSD. 8.

qulte traumatic. A study evxluating the lout term efficzcy of tfe long acting IL-1 inhibitor ranajinumqb in patients with NOOID is onhoing. 7. Tye htterogeneous response to LJ-1 blkgkade mn patients witm AOSD suggasts a more cokpuer cause for the inflammatory responsq in payifnts with AOSD. 8.

quite traumatic. A study evaluating the long of long acting inhibitor canakinumab in 7. heterogeneous response to blockade in patients AOSD suggests a more complex cause the inflammatory response in patients with AOSD. 8.

quite traumatic. A study evaluAting the loNg terM efFicAcY of tHe loNg acting IL-1 inhiBItor Canakinumab in patients wIth NOmId Is onGOiNg. 7. The HeterogENeOUS reSpOnSe tO Il-1 BlOckadE in PatientS with AOSD sUggEsTs a more complEX cAuse for the InfLammatory resPonSe in paTiEntS With AoSD. 8.

quite traumatic. A studyevaluating  thelon g t er m ef fica cy of the long acti ng IL-1 inhibitor cana kinum ab in p a ti entswith NO M ID i s o ng oi ng.  7 .  T he he ter ogeneou s response  to  I L-1 blockade in  patientswit h AOSD sugge sts  a mor ecom p lex c aus e for  the i n flamma tory resp on s e in p a tientsw i th  AOS D. 8.

quite_traumatic. A_study evaluating the long_term efficacy_of_the long_acting_IL-1 inhibitor canakinumab_in patients with_NOMID is ongoing. 7._The heterogeneous response_to_IL-1 blockade in patients with AOSD suggests a more complex cause for the inflammatory_response_in patients_with_AOSD._8.


Faroe Islands study were about 3-4 times higher than in most other studies, and c) the exposure levels in the two recent U.S. studies were about one third of those in the four earlier U.S. studies or recent Dutch, German, and Northern Quebec studies. Our results will facilitate a direct

Faroe Islands study were about 3 - 4 times higher than in most early cogitation, and c) the exposure degree in the two late U.S. studies were about one third of those in the four early U.S. studies or recent Dutch, German, and Northern Quebec study. Our results will facilitate a lineal

Fagoe Islands study were anout 3-4 times highgr than mn most other sgudies, and c) the exposure letels in tye two recent U.S. studids were ahout one thicd of those in tis four ccrlied U.S. vvudies or recenj Dutch, Germdn, and Northert Duzbec studies. Our results will facilieate a cigect

Faroe Islands study were about 3-4 times in other studies, c) the exposure U.S. were about one of those in four earlier U.S. studies or recent German, and Northern Quebec studies. Our results will facilitate a direct

Faroe Islands study were abouT 3-4 times highEr thaN in MosT oTher StudIes, and c) the expoSUre lEvels in the two recent U.S. sTudieS wERe abOUt One thIrd of thOSe IN The FoUr EarLiER U.s. studIes Or recenT Dutch, GermAn, aNd northern QuebEC sTudies. Our rEsuLts will facilItaTe a dirEcT

Faroe Islands study wereabout 3-4times  hi ghe rthan  inmost other stu d ies,  and c) the exposure l evels  i n  the tw o rec ent U.S .  s t u die swe reab o ut  onethi rd of t hose in th e f ou r earlier U. S .studies or  re cent Dutch,Ger man, a nd  No r thern  Qu ebecstudie s . Ourresults w il l  facil i tate ad i re ct

Faroe_Islands study_were about 3-4 times_higher than_in_most other_studies,_and c) the_exposure levels in_the two recent U.S._studies were about_one_third of those in the four earlier U.S. studies or recent Dutch, German, and_Northern_Quebec studies._Our_results_will facilitate a direct


spheroids and are we assessing EpCAM-function in the these model system. We have observed a dramatic phenotype that can be reversed to large extent by treatment with a single pharmacologic inhibitor. The mechanism(s) that are responsible for this effect are under investigation, but our studies clearly argue for an important role in

spheroids and are we assessing EpCAM - function in the these model arrangement. We have observe a dramatic phenotype that can be reversed to big extent by discussion with a single pharmacologic inhibitor. The mechanism(s) that are responsible for this consequence are under investigation, but our studies intelligibly argue for an important role in

spjeroids and are we assesring EpCAM-functnin in vhe theae model system. We have observed a dcamaric pyenotype that can be rdversed tl large wxteit by treatment xjth a slugle lmarmaeooogic inhibitot. The mechanhsm(s) that are serplnsible for this effect are under igvestigstlon, but our stodies sleadly argue for an important role in

spheroids and are we assessing EpCAM-function in model We have a dramatic phenotype large by treatment with single pharmacologic inhibitor. mechanism(s) that are responsible for this are under investigation, but our studies clearly argue for an important role in

spheroids and are we assessinG EpCAM-funcTion iN thE thEsE modEl syStem. We have obseRVed a Dramatic phenotype that cAn be rEvERsed TO lArge eXtent by TReATMenT wItH a sInGLe PharmAcoLogic inHibitor. The MecHaNism(s) that are REsPonsible foR thIs effect are uNdeR invesTiGatIOn, but Our StudiEs cleaRLy arguE for an impOrTAnt rolE In

spheroids and are we asse ssing EpCA M-fun cti onin  the  the se model syste m . We  have observed a drama tic p he n otyp e  t hat c an be r e ve r s edto  l arg ee xt ent b y t reatmen t with a s ing le  pharmacolog i cinhibitor.  Th e mechanism( s)that a re  re s ponsi ble  forthis e f fect a re underin v estiga t ion, bu t ou r st udies clearly arg u ef or an importan t role  i n

spheroids_and are_we assessing EpCAM-function in_the these_model_system. We_have_observed a dramatic_phenotype that can_be reversed to large_extent by treatment_with_a single pharmacologic inhibitor. The mechanism(s) that are responsible for this effect are under_investigation,_but our_studies_clearly_argue for an important role_in


ain contains three cysteine residues, each of which can contribute to the formation of cysteine-linked dimers. In FY13 we started to determine the importance of the positioning of the cysteine bridge for BST-2 function. Starting with a cysteine-free monomeric form of BST-2, individual cysteine residues were re

ain contains three cysteine residues, each of which can contribute to the formation of cysteine - connect dimer. In FY13 we started to determine the importance of the placement of the cysteine bridge for BST-2 function. start with a cysteine - free monomeric form of BST-2, individual cysteine residue were re

ain contains three cysteine residues, each of whici can ckntributd to the formation of cysteiie-libked eimers. In FY13 we startea to detegmine the impietance of vge posibnoninf of chx cysteine bridne for BST-2 xunction. Starthne cith a cysteine-free monomeric form os BST-2, imdlvidual cysteige rtsiques were re

ain contains three cysteine residues, each of contribute the formation cysteine-linked dimers. In the of the positioning the cysteine bridge BST-2 function. Starting with a cysteine-free form of BST-2, individual cysteine residues were re

ain contains three cysteine rEsidues, eacH of whIch Can CoNtriBute To the formation OF cysTeine-linked dimers. In FY13 wE starTeD To deTErMine tHe imporTAnCE Of tHe PoSitIoNInG of thE cySteine bRidge for BSt-2 fuNcTion. Starting WItH a cysteine-FreE monomeric foRm oF BST-2, inDiVidUAl cysTeiNe resIdues wERe re

ain contains three cystein e residues , eac h o f w hi ch c an c ontribute to t h e fo rmation of cysteine-li nkeddi m ers. In  FY13  we sta r te d tode te rmi ne th e imp ort ance of  the posit ion in g of the cys t ei ne bridgefor  BST-2 funct ion . Star ti ngw ith a  cy stein e-free monome ric formof BST-2, individ u a lcyst eine residues wer e  r e

ain contains_three cysteine_residues, each of which_can contribute_to_the formation_of_cysteine-linked dimers. In_FY13 we started_to determine the importance_of the positioning_of_the cysteine bridge for BST-2 function. Starting with a cysteine-free monomeric form of BST-2,_individual_cysteine residues_were_re


induced only a slight reduction of CXCR4 at the cell surface, the residual receptor was profoundly impaired for chemotaxis and ligand mediated receptor internalization. The chemotactic defect resulted from inhibition of early signaling steps such as dissociation of G-protein subunits, intracellular Ca++ flux, polarized accumulation of pAKT, F-actin polymers

induced only a slight reduction of CXCR4 at the cellular telephone open, the residual receptor was profoundly impaired for chemotaxis and ligand intercede sense organ internalization. The chemotactic defect resulted from inhibition of early signaling step such as dissociation of G - protein subunits, intracellular Ca++ flux, polarize accumulation of pAKT, F - actin polymers

infuced only a slight redugtion of CXCR4 at the cenl surrace, the residual receptor was profonndlt impqired for chemotaxis avd ligand mediatee rereptor internalivztion. Tmz chejltaccir defect resultgd from inhitition of earlf riynaling steps such as dissociation os G-protrij subunits, inttacelktlar Ba++ flux, polarized accumulation kf pAKT, F-actin polymrrs

induced only a slight reduction of CXCR4 cell the residual was profoundly impaired receptor The chemotactic defect from inhibition of signaling steps such as dissociation of subunits, intracellular Ca++ flux, polarized accumulation of pAKT, F-actin polymers

induced only a slight reductiOn of CXCR4 at The ceLl sUrfAcE, the ResiDual receptor waS ProfOundly impaired for chemoTaxis AnD LigaND mEdiatEd recepTOr INTerNaLiZatIoN. thE chemOtaCtic defEct resulteD frOm Inhibition of EArLy signalinG stEps such as disSocIation Of g-prOTein sUbuNits, iNtraceLLular CA++ flux, polaRiZEd accuMUlation OF PAkT, F-aCtin polymers

induced only a slight red uction ofCXCR4  at  th ecell  sur face, the resi d ualreceptor was profoundl y imp ai r ed f o rchemo taxis a n dl i gan dme dia te d  r ecept orinterna lization.The  c hemotactic d e fe ct resulte d f rom inhibiti onof ear ly  si g nalin g s tepssuch a s  disso ciation o fG -prote i n subun i t s,  int racellular Ca++ f l ux ,  polarized acc umulat io n  o f pAK T,F-actin po ly mers

induced_only a_slight reduction of CXCR4_at the_cell_surface, the_residual_receptor was profoundly_impaired for chemotaxis_and ligand mediated receptor_internalization. The chemotactic_defect_resulted from inhibition of early signaling steps such as dissociation of G-protein subunits, intracellular_Ca++_flux, polarized_accumulation_of_pAKT, F-actin polymers


. To determine how FA protein composition is globally modulated by myosinII contraction, we developed a proteomics approach to isolate native FAs, identify their protein composition, and compare specific protein abundance in FAs from cells with and without myosinII inhibition. We reproducibly identified 905 FA-associated proteins, half (402)

. To determine how FA protein composition is globally modulated by myosinII contraction, we develop a proteomics overture to isolate native FAs, identify their protein musical composition, and compare specific protein abundance in FAs from cells with and without myosinII prohibition. We reproducibly identified 905 FA - associated proteins, one-half (402 )

. To determine how FA proteik composition is globalny modhlated bh myosinII contraction, we deteloped a proteomics approach tu isolate native DAs, mdentify their pcktein composiflon, aud compare specinic protein abundance in XAr yrom cells with and without myosinII inhibiyiln. We reproducybly ydenfpfled 905 FA-associated proteins, half (402)

. To determine how FA protein composition modulated myosinII contraction, developed a proteomics identify protein composition, and specific protein abundance FAs from cells with and without inhibition. We reproducibly identified 905 FA-associated proteins, half (402)

. To determine how FA protein coMposition iS globAllY moDuLateD by mYosinII contracTIon, wE developed a proteomics aPproaCh TO isoLAtE natiVe FAs, idENtIFY thEiR pRotEiN CoMposiTioN, and comPare specifIc pRoTein abundancE In fAs from celLs wIth and withouT myOsinII InHibITion. WE reProduCibly iDEntifiEd 905 FA-assocIaTEd protEIns, half (402)

. To determine how FA prot ein compos ition  is  gl ob ally  mod ulated by myos i nIIcontraction, we develo ped a  p r oteo m ic s app roach t o  i s o lat ena tiv eF As , ide nti fy thei r proteincom po sition, andc om pare speci fic  protein abu nda nce in  F Asf rom c ell s wit h andw ithout  myosinII  i n hibiti o n. We r e p ro duci bly identified 90 5  F A -associated pr oteins ,h al f (40 2)

. To_determine how_FA protein composition is_globally modulated_by_myosinII contraction,_we_developed a proteomics_approach to isolate_native FAs, identify their_protein composition, and_compare_specific protein abundance in FAs from cells with and without myosinII inhibition. We reproducibly_identified_905 FA-associated_proteins,_half_(402)


the organ- specific immune responses downstream of IL-1 and may shed light on processes that determine specific organ manifestations. 6. The development of long acting IL-1 inhibitors may allow for better disease control in those patients who are not in complete remission and offer more convenient treatment options particularly in children in whom daily injections can be

the organ- specific immune responses downstream of IL-1 and may shed light on processes that settle specific electric organ manifestations. 6. The development of long act IL-1 inhibitors may allow for good disease control in those patients who are not in accomplished remission and offer more commodious treatment options particularly in children in whom casual injections can be

thf organ- specific immune vesponses downstteqm of ML-1 and jay shed light on processes that detxrmibe sptbific organ manifestagions. 6. Thv developnent if long acvjng IL-1 luhibiflrs key allow for bejter disease control in thmsd 'atients who are not in complete remyssion snf offer more cjnvemyent nrtatment options particularly in cgildren in whom dailu injections can be

the organ- specific immune responses downstream of may light on that determine specific of acting IL-1 inhibitors allow for better control in those patients who are in complete remission and offer more convenient treatment options particularly in children in daily injections can be

the organ- specific immune resPonses downStreaM of iL-1 aNd May sHed lIght on processeS That Determine specific organ ManifEsTAtioNS. 6. THe devElopmenT Of LONg aCtInG IL-1 InHIbItors May Allow foR better disEasE cOntrol in thosE PaTients who aRe nOt in complete RemIssion AnD ofFEr morE coNveniEnt treATment oPtions parTiCUlarly IN childrEN In Whom Daily injections caN Be

the organ- specific immun e response s dow nst rea mof I L-1and may shed l i ghton processes that dete rmine  s p ecif i corgan  manife s ta t i ons .6.  Th ed ev elopm ent  of lon g acting I L-1  i nhibitors ma y  a llow for b ett er disease c ont rol in  t hos e  pati ent s who  are n o t in c omplete r em i ssiona nd offe r mo re c onvenient treatme n to ptions particu larlyin ch i l dre n i n whom dai ly  inje c tions c a nb e

the_organ- specific_immune responses downstream of_IL-1 and_may_shed light_on_processes that determine_specific organ manifestations._6. The development of_long acting IL-1_inhibitors_may allow for better disease control in those patients who are not in complete_remission_and offer_more_convenient_treatment options particularly in children_in whom daily injections can_be


in individual response to training, including such factors as low cognitive function, cardiovascular status, engagement, and ApoE genotype. 4) To estimate and project the effects of ACTIVE training to the general population of older adults by linking the measures and outcomes of ACTIVE to the Health and Retirement Study. This application aff

in individual response to training, including such factors as depleted cognitive affair, cardiovascular status, engagement, and ApoE genotype. 4) To estimate and project the impression of ACTIVE training to the general population of old adults by linking the measure and outcomes of ACTIVE to the Health and Retirement Study. This application aff

in individual response to uraining, includiny such hactors as low zognitive function, cardiovasrulae stauls, engagement, and ApoD genotypv. 4) To estumatt and project the effects of ACFLVE txamning to the gekeral populdtion of older aaupts by linking the measures and outsomes og WCTIVE to the Realuh wnd Dvtlrement Study. This application arf

in individual response to training, including such low function, cardiovascular engagement, and ApoE project effects of ACTIVE to the general of older adults by linking the and outcomes of ACTIVE to the Health and Retirement Study. This application aff

in individual response to traIning, incluDing sUch FacToRs as Low cOgnitive functiON, carDiovascular status, engagEment, AnD apoE GEnOtype. 4) to estimATe AND prOjEcT thE eFFeCts of aCTiVE traiNing to the gEneRaL population oF OlDer adults bY liNking the measUreS and ouTcOmeS Of ACTiVE To the health ANd RetiRement StuDy. tHis appLIcation AFF

in individual response to  training,  incl udi ngsu ch f acto rs as low cogn i tive  function, cardiovascu lar s ta t us,e ng ageme nt, and Ap o E  ge no ty pe.  4 )  T o est ima te andproject th e e ff ects of ACTI V Etraining t o t he general p opu lation  o f o l der a dul ts by  linki n g themeasuresan d  outco m es of A C T IV E to  the Health and R e ti r ement Study. T his ap pl i ca t i onaff

in_individual response_to training, including such_factors as_low_cognitive function,_cardiovascular_status, engagement, and_ApoE genotype. 4)_To estimate and project_the effects of_ACTIVE_training to the general population of older adults by linking the measures and outcomes_of_ACTIVE to_the_Health_and Retirement Study. This application_aff


-2. We expect to complete this project in FY14. SAMHD1/Vpx: In FY12 we initiated a new project involving the functional characterization of SAMHD1 is a dNTPase that presumably reduces the cellular dNTP levels to levels too low for retroviral reverse transcription to occur. However

-2. We expect to complete this project in FY14. SAMHD1 / Vpx: In FY12 we initiated a newfangled undertaking involving the functional word picture of SAMHD1 is a dNTPase that presumably reduce the cellular dNTP levels to levels besides broken for retroviral reverse arrangement to occur. However

-2. We expect to complete this project in FY14. SAMHD1/Vpe: In FY12 we initkated a new project involvinj thw funxtional characterizatiun of SAMJD1 is a eNTPese that presumaumy redugzs ths celnnlar dNTP levelx to levelv too low for segrlviral reverse transcription to occtr. Howefeg

-2. We expect to complete this project SAMHD1/Vpx: FY12 we a new project SAMHD1 a dNTPase that reduces the cellular levels to levels too low for reverse transcription to occur. However

-2. We expect to complete this proJect in FY14. SAmHD1/VpX: In fY12 wE iNitiAted A new project invOLvinG the functional characteRizatIoN Of SAmhD1 Is a dNtPase thAT pRESumAbLy RedUcES tHe celLulAr dNTP lEvels to levEls ToO low for retroVIrAl reverse tRanScription to oCcuR. HowevEr

-2. We expect to completethis proje ct in  FY 14.  S AMHD 1/Vp x: In FY12 wei niti ated a new project inv olvin gt he f u nc tiona l chara c te r i zat io nofSA M HD 1 isa d NTPasethat presu mab ly  reduces the ce llular dNT P l evels to lev els  too l ow  fo r  retr ovi ral r everse transc ription t oo ccur.H owever

-2. We_expect to_complete this project in_FY14. SAMHD1/Vpx:_In_FY12 we_initiated_a new project_involving the functional_characterization of SAMHD1 is_a dNTPase that_presumably_reduces the cellular dNTP levels to levels too low for retroviral reverse transcription to_occur._However


arial infections are studded with filarial antigen and express markers associated with alternative activation of macrophages (MΦ). To explore the role of filaria-derived parasite antigen in differentiation of human monocytes, cells were exposed to microfilariae (mf) of Brugia malayi, and their phenotypic

arial infections are studded with filarial antigen and express markers consociate with alternate activation of macrophages (M&#934 ;). To research the role of filaria - derive parasite antigen in specialization of human monocytes, cells were exposed to microfilariae (mf) of Brugia malayi, and their phenotypic

ariwl infections are studdea with filarial antigei and espress mxrkers associated with alteriatice acupvation of macrophager (MΦ). To exilore the rolt of filaria-derivxs paraslce anflgen nn differentiatipn of humat monocytes, cenlr cere exposed to microfilariae (mf) of Frugia kapayi, and their phemjtypjb

arial infections are studded with filarial antigen markers with alternative of macrophages (MΦ). filaria-derived antigen in differentiation human monocytes, cells exposed to microfilariae (mf) of Brugia and their phenotypic

arial infections are studded With filariAl antIgeN anD eXpreSs maRkers associateD With Alternative activation oF macrOpHAges (mΦ). to ExploRe the roLE oF FIlaRiA-dEriVeD PaRasitE anTigen in DifferentiAtiOn Of human monocYTeS, cells were ExpOsed to microfIlaRiae (mf) Of bruGIa malAyi, And thEir pheNOtypic

arial infections are studd ed with fi laria l a nti ge n an d ex press markersa ssoc iated with alternative  acti va t iono fmacro phages( M& # 9 34; ).  T o e xp l or e the  ro le of f ilaria-der ive dparasite ant i ge n in diffe ren tiation of h uma n mono cy tes ,  cell s w ere e xposed to mic rofilaria e( mf) of Brugiam a la yi,and their phenoty p ic

arial infections_are studded_with filarial antigen and_express markers_associated_with alternative_activation_of macrophages (MΦ)._To explore the_role of filaria-derived parasite_antigen in differentiation_of_human monocytes, cells were exposed to microfilariae (mf) of Brugia malayi, and their phenotypic


5 years. 3. Chronic inflammation leads to growth retardation, osteoporosis. We showed that bone mineral density increases above the age-expected increase which correlate with a change in bone markers suggesting an increase in bone production and catch-up height and weight gains are seen in treated patients. 4. An ongoing study in patients with N

5 years. 3. Chronic inflammation leads to growth slowdown, osteoporosis. We usher that bone mineral density increases above the age - ask increase which correlate with a change in bone marker suggesting an increase in bone product and catch - up height and weight unit gains are seen in regale patient. 4. An ongoing study in patients with N

5 yfars. 3. Chronic inflammatiun leads to grocrh reterdatioh, osteopurosis. We showed that bone mmnerql debsity increases above ghe age-exiected inxreaww which cocdelate with a ghangz mn bone markers suggestinc an increase hn blne production and catch-up height agd weignt gains are seeg in ereafvd patients. 4. An ongoing study ih patieits with N

5 years. 3. Chronic inflammation leads to osteoporosis. showed that mineral density increases correlate a change in markers suggesting an in bone production and catch-up height weight gains are seen in treated patients. 4. An ongoing study in patients N

5 years. 3. Chronic inflammation lEads to growTh retArdAtiOn, OsteOporOsis. We showed thAT bonE mineral density increasEs aboVe THe agE-ExPecteD increaSE wHICh cOrReLatE wITh A chanGe iN bone maRkers suggeStiNg An increase in BOnE productioN anD catch-up heigHt aNd weigHt GaiNS are sEen In treAted paTIents. 4. AN ongoing sTuDY in patIEnts witH n

5 years. 3. Chronic infla mmation le ads t o g row th  ret arda tion, osteopor o sis.  We showed that bone m inera ld ensi t yincre ases ab o ve t heag e- exp ec t ed  incr eas e which  correlate  wi th  a change in bo ne markers  su ggesting aninc reasein  bo n e pro duc tionand ca t ch-upheight an dw eightg ains ar e se en i n treated patient s .4 . An ongoing s tudy i np at i e nts  wi th N

5_years. 3._Chronic inflammation leads to_growth retardation,_osteoporosis._We showed_that_bone mineral density_increases above the_age-expected increase which correlate_with a change_in_bone markers suggesting an increase in bone production and catch-up height and weight gains_are_seen in_treated_patients._4. An ongoing study in_patients with N


ive versus HPIV3-immune. Thus, HPIV3/delF-HN/EboGP provides an alternative to HPIV3/EboGP that is very highly attenuated, is insensitive to HPIV3-neutralizing antibodies, and nonetheless is nearly as immunogenic. We also are investigating the use

i ve versus HPIV3 - immune. Thus, HPIV3 / delF - HN / EboGP provides an alternative to HPIV3 / EboGP that is very highly attenuated, is insensitive to HPIV3 - counteract antibody, and nonetheless is nearly equally immunogenic. We also are investigate the use

ive versus HPIV3-immune. Thus, MPIV3/delF-HN/EboGP krivides an alfernativd to HPIV3/EboGP that is very iighoy atuvnuated, is insensitivd to HPIV3-jeutralizing qntibodies, and noncchelead is iearly as immunpgenic. We dlso are invesdieacing the use

ive versus HPIV3-immune. Thus, HPIV3/delF-HN/EboGP provides an HPIV3/EboGP is very attenuated, is insensitive is as immunogenic. We are investigating the

ive versus HPIV3-immune. Thus, HPiV3/delF-HN/EbOGP prOviDes An AlteRnatIve to HPIV3/EboGP THat iS very highly attenuated, iS inseNsITive TO HpIV3-neUtralizINg ANTibOdIeS, anD nONeTheleSs iS nearly As immunogeNic. we Also are invesTIgAting the usE

ive versus HPIV3-immune. T hus, HPIV3 /delF -HN /Eb oG P pr ovid es an alternat i ve t o HPIV3/EboGP that isveryhi g hlya tt enuat ed, isi ns e n sit iv etoHP I V3 -neut ral izing a ntibodies,  an dnonethelessi snearly asimm unogenic. We  al so are  i nve s tigat ing  theuse

ive versus_HPIV3-immune. Thus,_HPIV3/delF-HN/EboGP provides an alternative_to HPIV3/EboGP_that_is very_highly_attenuated, is insensitive_to HPIV3-neutralizing antibodies,_and nonetheless is nearly_as immunogenic. We_also_are investigating the use


at a dose of 1 mg/kg/day, showed essentially no reduction in the HBVETV-RL180M/S202G/M204V viremia levels. By contrast, CMCP at the same dose of 1 mg/kg/day, brought about a significant level of viremia reduction

at a dose of 1 mg / kg / day, showed essentially no decrease in the HBVETV - RL180M / S202G / M204V viremia degree. By contrast, CMCP at the same venereal disease of 1 mg / kg / sidereal day, brought about a significant level of viremia decrease

at a dose of 1 mg/kg/day, showtd essentially no reductmon in fhe HBVEGV-RL180M/S202G/M204V viremia levels. By ronteast, XMCP at the same dose uf 1 mg/kg/dwy, brougyt auout a significaif level of vidcmia xevuction

at a dose of 1 mg/kg/day, showed reduction the HBVETV-RL180M/S202G/M204V levels. By contrast, of mg/kg/day, brought about significant level of reduction

at a dose of 1 mg/kg/day, showed essEntially no ReducTioN in ThE HBVeTV-Rl180M/S202G/M204V viremia lEVels. by contrast, CMCP at the samE dose Of 1 MG/kg/dAY, bRoughT about a SIgNIFicAnT lEveL oF ViRemia RedUction

at a dose of 1 mg/kg/day,  showed es senti all y n oredu ctio n in the HBVET V -RL1 80M/S202G/M204V viremi a lev el s . By co ntras t, CMCP at t hesa me  do se of  1 mg /kg /day, b rought abo utasignificantl ev el of vire mia  reduction

at_a dose_of 1 mg/kg/day, showed_essentially no_reduction_in the_HBVETV-RL180M/S202G/M204V_viremia levels. By_contrast, CMCP at_the same dose of_1 mg/kg/day, brought_about_a significant level of viremia reduction


A, we have begun to develop a family health history assessment tool called Families SHARE (Sharing Health Assessments and Risk Evaluation). It is anticipated that this tool will be used by a family genomics health educator to disseminate family risk information to their first and second degree relatives and encourage risk reducing behaviors.

A, we have begun to develop a family health history appraisal cock called Families SHARE (Sharing Health assessment and Risk Evaluation). It is anticipated that this tool will be use by a kin genomics health educator to disseminate family risk information to their beginning and second degree relatives and promote risk reducing behaviors.

A, wf have begun to develop x family health historb assesament toul called Families SHARE (Shacing Healuk Assessments and Rirk Evaluanion). It iw anuicipated that thma tool will bs useb uy a family genpmics healdh educator to dksdeminate family risk information to their gigst and second deggeq rematives and encourage risk reducinf behavpors.

A, we have begun to develop a history tool called SHARE (Sharing Health is that this tool be used by family genomics health educator to disseminate risk information to their first and second degree relatives and encourage risk reducing

A, we have begun to develop a famIly health hIstorY asSesSmEnt tOol cAlled Families ShaRE (SHaring Health AssessmentS and RIsK evalUAtIon). It Is anticIPaTED thAt ThIs tOoL WiLl be uSed By a famiLy genomics HeaLtH educator to dISsEminate famIly Risk informatIon To theiR fIrsT And seConD degrEe relaTIves anD encouragE rISk reduCIng behaVIOrS.

A, we have begun to develo p a family  heal thhis to ry a sses sment tool cal l ed F amilies SHARE (Sharing  Heal th Asse s sm entsand Ris k  E v a lua ti on ).It is  anti cip ated th at this to olwi ll be used b y  a  family ge nom ics health e duc ator t odis s emina tefamil y risk inform ation toth e ir fir s t and s e c on d de gree relatives an d  e n courage risk r educin gb eh a v ior s.

A, we_have begun_to develop a family_health history_assessment_tool called_Families_SHARE (Sharing Health_Assessments and Risk_Evaluation). It is anticipated_that this tool_will_be used by a family genomics health educator to disseminate family risk information to_their_first and_second_degree_relatives and encourage risk reducing_behaviors.


and Met-deficient primary mouse hepatocytes. Novel transcriptional targets of Met pathway were identified that included genes involved in the regulation of oxidative stress responses as well as cell motility, cytoskeletal organization, and angiogenesis. To assess the importance of Met-regulated gene expression signature, a comparative functional genomics approach was applied to 242 human HCC

and Met - deficient primary mouse hepatocytes. Novel transcriptional target of Met nerve pathway were identified that included gene involved in the rule of oxidative stress responses equally well as cell motility, cytoskeletal organization, and angiogenesis. To measure the importance of Met - regulated gene expression key signature, a comparative functional genomics approach path was practice to 242 human HCC

anf Met-deficient primary muuse hepatocytes. Novel transdriptionxl targets of Met pathway wece ieentidied that included gends involvvd in the regnlation of oxidavjve strcfs rsdponvxs as well as cgll motility, cytoskeletal mreauization, and angiogenesis. To assess ehe impprhance of Met-redulaued gens expression signature, a comparatibe funcuional genomics aplroach was applied to 242 humwn HFC

and Met-deficient primary mouse hepatocytes. Novel transcriptional Met were identified included genes involved stress as well as motility, cytoskeletal organization, angiogenesis. To assess the importance of gene expression signature, a comparative functional genomics approach was applied to 242 human

and Met-deficient primary mouSe hepatocyTes. NoVel TraNsCripTionAl targets of Met PAthwAy were identified that inCludeD gENes iNVoLved iN the regULaTIOn oF oXiDatIvE StRess rEspOnses as Well as cell MotIlIty, cytoskeleTAl OrganizatiOn, aNd angiogenesIs. TO assesS tHe iMPortaNce Of Met-RegulaTEd gene ExpressioN sIGnaturE, A comparATIvE funCtional genomics apPRoACh was applied to 242 Human HcC

and Met-deficient primary  mouse hep atocy tes . N ov el t rans criptional tar g etsof Met pathway were id entif ie d  tha t  i nclud ed gene s  i n v olv ed  i n t he re gulat ion  of oxi dative str ess  r esponses asw el l as cellmot ility, cytos kel etal o rg ani z ation , a nd an giogen e sis. T o assessth e  impor t ance of M et -reg ulated gene expre s si o n signature, a  compa ra t iv e fun cti onal genom ic s app r oach wa s  a p p l ied to 242 humanHCC

and_Met-deficient primary_mouse hepatocytes. Novel transcriptional_targets of_Met_pathway were_identified_that included genes_involved in the_regulation of oxidative stress_responses as well_as_cell motility, cytoskeletal organization, and angiogenesis. To assess the importance of Met-regulated gene expression_signature,_a comparative_functional_genomics_approach was applied to 242_human HCC


published in the Journal of Investigative Dermatology. Our interpretation of the our seeming disparate results using mice whose Langerhans cells lack EpCAM is that the role that EpCAM plays in the regulation of Langerhans cells is context dependent. We have also explored mechanisms by which EpCAM regulates intercellular

published in the Journal of Investigative Dermatology. Our interpretation of the our seeming disparate results use mouse whose Langerhans cells lack EpCAM is that the role that EpCAM play in the regulation of Langerhans cells is context subject. We have besides explored mechanisms by which EpCAM regulates intercellular

puhlished in the Journal on Investigative Bwrmatonogy. Ohr interoretation of the our seeming dusparqte results using mice whose Lajgerhans celow lack EpCEJ is that the vole chet EpCAM plays ln the regunation of Langarfaus cells is context dependent. We havq also rxolored mechanifms nr whjbh EpCAM regulates intercellulad

published in the Journal of Investigative Dermatology. of our seeming results using mice is the role that plays in the of Langerhans cells is context dependent. have also explored mechanisms by which EpCAM regulates intercellular

published in the Journal of InVestigativE DermAtoLogY. OUr inTerpRetation of the oUR seeMing disparate results usIng miCe WHose lAnGerhaNs cells LAcK ePCAm iS tHat ThE RoLe thaT EpcAM playS in the reguLatIoN of LangerhanS CeLls is conteXt dEpendent. We haVe aLso expLoRed MEchanIsmS by whIch EpCam regulAtes interCeLLular

published in the Journalof Investi gativ e D erm at olog y. O ur interpretat i on o f the our seeming disp arate  r e sult s  u singmice wh o se L ang er ha nsce l ls  lack  Ep CAM isthat the r ole  t hat EpCAM pl a ys  in the re gul ation of Lan ger hans c el lsi s con tex t dep endent .  We ha ve also e xp l ored m e chanism s by  whi ch EpCAM regulate s  i n tercellular

published_in the_Journal of Investigative Dermatology._Our interpretation_of_the our_seeming_disparate results using_mice whose Langerhans_cells lack EpCAM is_that the role_that_EpCAM plays in the regulation of Langerhans cells is context dependent. We have also_explored_mechanisms by_which_EpCAM_regulates intercellular


completed coding the annual follow-up CEGRMs for future analyses. We continue to consider how families communicate about, experience, and cope with inherited conditions. We have established an Umbrella Protocol that allows us to examine these processes in ongoing studies (NHGRI Protocol #12-HG-N149; PI:

completed coding the annual follow - up CEGRMs for future analyses. We stay to think how families communicate about, experience, and cope with inherited condition. We have established an Umbrella Protocol that allows us to analyze these processes in ongoing studies (NHGRI Protocol # 12 - HG - N149; PI:

colpleted coding the annuau follow-up CEGRMs for huture znalyses. We continue to consider how fqmilitf communicate aboug, experiejce, and xope qith inhermfed conditiona. We kate established sn Umbrelld Protocol thad xlpows us to examine these processes yn ongoonh studies (NHGRY Prpeocom #12-HG-N149; PI:

completed coding the annual follow-up CEGRMs for We to consider families communicate about, conditions. have established an Protocol that allows to examine these processes in ongoing (NHGRI Protocol #12-HG-N149; PI:

completed coding the annual fOllow-up CEGrMs foR fuTurE aNalySes. WE continue to conSIder How families communicate About, ExPErieNCe, And coPe with iNHeRITed CoNdItiOnS. we Have eStaBlished An Umbrella proToCol that allowS Us To examine tHesE processes in OngOing stUdIes (nhGRI PRotOcol #12-Hg-N149; PI:

completed coding the annu al follow- up CE GRM s f or  fut ureanalyses. We c o ntin ue to consider how fam ilies  c o mmun i ca te ab out, ex p er i e nce ,an d c op e  w ith i nhe rited c onditions.  We  h ave establis h ed  an Umbrel laProtocol tha t a llowsus  to exami nethese  proce s ses in  ongoingst u dies ( N HGRI Pr o t oc ol # 12-HG-N149; PI:

completed_coding the_annual follow-up CEGRMs for_future analyses._We_continue to_consider_how families communicate_about, experience, and_cope with inherited conditions._We have established_an_Umbrella Protocol that allows us to examine these processes in ongoing studies (NHGRI Protocol_#12-HG-N149;_PI:


filarial-infected patients. These data provide clues to the pathways induced by infection and those systemic alterations seen in chronic helminth infection. A longstanding issue in environmental health is the need to understand the role the environment plays in human brain development. The brain of the neonate is particularly susceptible to disruption of the sensory

filarial - infected patients. These data provide hint to the nerve pathway induced by infection and those systemic alterations understand in chronic helminth infection. A longstanding issue in environmental health is the indigence to sympathize the role the environment plays in human brain development. The brain of the neonate is peculiarly susceptible to disruption of the sensory

fiparial-infected patients. Uhese data providg xlues vo the lathways induced by infection and thlsw sysuvmic alterations seen in chronpc helminrh iifection. A longsvznding lfsue ln enriconmental healtm is the nead to understatd tke role the environment plays in humwn braim fevelopment. Thg brapn of fhe neonate is particularly suscepfible tm disruption pf the sensory

filarial-infected patients. These data provide clues to induced infection and systemic alterations seen longstanding in environmental health the need to the role the environment plays in brain development. The brain of the neonate is particularly susceptible to disruption of sensory

filarial-infected patients. THese data prOvide CluEs tO tHe paThwaYs induced by infECtioN and those systemic alterAtionS sEEn in CHrOnic hElminth INfECTioN. A LoNgsTaNDiNg issUe iN enviroNmental heaLth Is The need to undERsTand the rolE thE environment PlaYs in huMaN brAIn devEloPment. the braIN of the Neonate is PaRTiculaRLy suscePTIbLe to Disruption of the seNSoRY

filarial-infected patient s. These d ata p rov ide  c lues  tothe pathways i n duce d by infection and tho se sy st e mica lt erati ons see n  i n chr on ic  he lm i nt h inf ect ion. Alongstandi ngis sue in envir o nm ental heal this the needtounders ta ndt he ro lethe e nviron m ent pl ays in hu ma n  brain develop m e nt . Th e brain of the ne o na t e is particula rly su sc e pt i b letodisruption  o f the sensory

filarial-infected_patients. These_data provide clues to_the pathways_induced_by infection_and_those systemic alterations_seen in chronic_helminth infection. A longstanding_issue in environmental_health_is the need to understand the role the environment plays in human brain development._The_brain of_the_neonate_is particularly susceptible to disruption_of the sensory


found that broad neural expression rescued the anesthesia phenotypes but none of 20 drivers that produced restricted expression gave reliable rescue (promising results with the tim-GAL4 driver using the postural assay now appear to be due to a non-specific sensitization to stressors). Happily, a new survey of restricted GAL4 lines

found that broad neural expression rescue the anesthesia phenotype but none of 20 drivers that produced restricted formula yield reliable rescue (promising resultant role with the tim - GAL4 driver use the postural assay now look to be ascribable to a non - specific sensitization to stressors). Happily, a modern survey of restricted GAL4 lines

foknd that broad neural exkression rescued jhw anesvhesia lhenotypds but none of 20 drivers that peoductb restricted expresskon gave geliable eescne (promising resnmts witm the bim-GAN4 driver using jhe postural assay now appaaf co be due to a non-specific sensitizaeion to shressors). Happijy, a gew alryey of restricted GAL4 lines

found that broad neural expression rescued the but of 20 that produced restricted results the tim-GAL4 driver the postural assay appear to be due to a sensitization to stressors). Happily, a new survey of restricted GAL4 lines

found that broad neural expreSsion rescuEd the AneSthEsIa phEnotYpes but none of 20 dRIverS that produced restricteD exprEsSIon gAVe ReliaBle rescUE (pROMisInG rEsuLtS WiTh the Tim-gAL4 drivEr using the PosTuRal assay now aPPeAr to be due tO a nOn-specific seNsiTizatiOn To sTRessoRs). HAppilY, a new sURvey of RestricteD Gal4 lines

found that broad neural e xpressionrescu edthe  a nest hesi a phenotypes b u t no ne of 20 drivers thatprodu ce d  res t ri ctedexpress i on g ave  r el iab le re scue(pr omising  results w ith  t he tim-GAL4d ri ver usingthe  postural as say  now a pp ear to be  du e toa non- s pecifi c sensiti za t ion to stresso r s ).  Hap pily, a new surve y  o f  restricted GA L4 lin es

found_that broad_neural expression rescued the_anesthesia phenotypes_but_none of_20_drivers that produced_restricted expression gave_reliable rescue (promising results_with the tim-GAL4_driver_using the postural assay now appear to be due to a non-specific sensitization to_stressors)._Happily, a_new_survey_of restricted GAL4 lines


was the case in our preliminary study of 14 IGD-related genes, this would provide further evidence that heterozygous variants in these genes may confer an increased susceptibility to developing HA in the setting of physiologic stressors, such as nutritional deficiency, extreme exercise, or psychological stress. At the other extreme of pubertal development are

was the case in our preliminary study of 14 IGD - related genes, this would leave further evidence that heterozygous random variable in these genes may confer an increased susceptibility to developing hour angle in the setting of physiologic stressors, such as nutritional deficiency, extreme use, or psychological tension. At the other extreme of pubertal development are

wad the case in our prelimlnary study of 14 NTD-relaved genss, this dould provide further evidenre tyat htnerozygous variants iv these gvnes may xonftr an increased snaceptibljity bo dereooping HA in tme setting mf physiologic sgrzssors, such as nutritional deficiencr, extreke exercise, or pfychpjogidal stress. At the other extreme of pubertel development sre

was the case in our preliminary study IGD-related this would further evidence that may an increased susceptibility developing HA in setting of physiologic stressors, such as deficiency, extreme exercise, or psychological stress. At the other extreme of pubertal development

was the case in our preliminarY study of 14 IGd-relaTed GenEs, This WoulD provide furtheR EvidEnce that heterozygous vaRiantS iN ThesE GeNes maY confer AN iNCReaSeD sUscEpTIbIlity To dEvelopiNg HA in the sEttInG of physiologIC sTressors, suCh aS nutritional DefIciencY, eXtrEMe exeRciSe, or pSycholOGical sTress. At thE oTHer extREme of puBERtAl deVelopment are

was the case in our preli minary stu dy of  14  IG D- rela tedgenes, this wo u ld p rovide further evidenc e tha th eter o zy gousvariant s  i n the se  g ene sm ay  conf eran incr eased susc ept ib ility to dev e lo ping HA in  th e setting of  ph ysiolo gi c s t resso rs,  such  as nu t rition al defici en c y, ext r eme exe r c is e, o r psychological s t re s s. At the othe r extr em e  o f pub ert al develop me nt ar e

was_the case_in our preliminary study_of 14_IGD-related_genes, this_would_provide further evidence_that heterozygous variants_in these genes may_confer an increased_susceptibility_to developing HA in the setting of physiologic stressors, such as nutritional deficiency, extreme_exercise,_or psychological_stress._At_the other extreme of pubertal_development are