macromolecules using anomalous small-angle X-ray scattering (ASAXS). In biology, osmotic pressure is particularly important in regulating and mediating physiological processes. Swelling pressure measurements probe the system in the large length scale range, thus providing information on the overall thermodynamic response. SANS and SAXS allow us to investigate

macromolecules using anomalous small - angle ten - re scattering (ASAXS). In biology, osmotic pressure is peculiarly important in regulating and mediating physiologic process. Swelling press measurements probe the system in the big length scale image, therefore providing information on the overall thermodynamic reception. SANS and SAXS allow us to investigate

mafromolecules using anomauous small-angle X-ray sratterihg (ASAXS). In biology, osmotic pressure iw parupcularly important in regulatijg and mwdiauing physiological processes. Swspliny 'ressure measurgments probe the system in tfe large length scale range, thus provyding imflrmation on thg ovegajl tgvrnodynamic response. SANS and SZXS allmw us to invextigate

macromolecules using anomalous small-angle X-ray scattering (ASAXS). osmotic is particularly in regulating and measurements the system in large length scale thus providing information on the overall response. SANS and SAXS allow us to investigate

macromolecules using anomalOus small-anGle X-rAy sCatTeRing (aSAXs). In biology, osmoTIc prEssure is particularly imPortaNt IN regULaTing aNd mediaTInG PHysIoLoGicAl PRoCesseS. SwElling pRessure meaSurEmEnts probe the SYsTem in the laRge Length scale rAngE, thus pRoVidINg infOrmAtion On the oVErall tHermodynaMiC ResponSE. SANS anD saXs allOw us to investigate

macromolecules using anom alous smal l-ang leX-r ay  sca tter ing (ASAXS). I n  bio logy, osmotic pressure  is p ar t icul a rl y imp ortanti nr e gul at in g a nd me diati ngphysiol ogical pro ces se s. Swellingp re ssure meas ure ments probethe  syste mint he la rge  leng th sca l e rang e, thus p ro v idingi nformat i o non t he overall thermo d yn a mic response.SANS a nd SA X S  al low  us to inv es tigat e

macromolecules_using anomalous_small-angle X-ray scattering (ASAXS)._In biology,_osmotic_pressure is_particularly_important in regulating_and mediating physiological_processes. Swelling pressure measurements_probe the system_in_the large length scale range, thus providing information on the overall thermodynamic response. SANS_and_SAXS allow_us_to_investigate


dioxin (tetrachlorodibenzo-p-dioxin, or TCDD). DDT is still used in about 25 countries for control of disease vectors, especially for malaria, under the assumption that there are no adverse human health effects. My recent findings are that higher maternal serum DDE level

dioxin (tetrachlorodibenzo - p - dioxin, or TCDD). DDT is still used in about 25 nation for restraint of disease vectors, especially for malaria, under the assumption that there be no adverse human health effects. My recent determination are that higher maternal serum DDE degree

dilxin (tetrachlorodibenzo-p-aioxin, or TCDD). BET is vtill hsed in xbout 25 countries for control od distcse vectors, especialuy for maparia, uneer uhe assumption thef there are nk advzrwe human healtm effects. Mf recent finditgr cre that higher maternal serum DDE lqvel

dioxin (tetrachlorodibenzo-p-dioxin, or TCDD). DDT is still about countries for of disease vectors, assumption there are no human health effects. recent findings are that higher maternal DDE level

dioxin (tetrachlorodibenzo-p-Dioxin, or TCdD). DDT Is sTilL uSed iN aboUt 25 countries for COntrOl of disease vectors, espeCiallY fOR malARiA, undeR the assUMpTIOn tHaT tHerE aRE nO adveRse Human heAlth effectS. My ReCent findings ARe That higher MatErnal serum DDe leVel

dioxin (tetrachlorodibenz o-p-dioxin , orTCD D).  D DT i s st ill used in ab o ut 2 5 countries for contro l ofdi s ease ve ctors , espec i al l y  fo rma lar ia ,  u nderthe  assump tion thatthe re  are no adve r se  human hea lth  effects. My  re cent f in din g s are  th at hi gher m a ternal  serum DD El evel

dioxin_(tetrachlorodibenzo-p-dioxin, or_TCDD). DDT is still_used in_about_25 countries_for_control of disease_vectors, especially for_malaria, under the assumption_that there are_no_adverse human health effects. My recent findings are that higher maternal serum DDE level


probands participating in our genetic research protocol (http://ird.nichd.nih.gov), including several extended families to identify novel genes responsible for IGD. Data analysis is underway, and our findings are likely to yield important insights into additional pathways involved in the regulation of GnRH secretion. In one of our

probands participating in our genetic research protocol (http://ird.nichd.nih.gov), including respective extensive families to identify fresh genes creditworthy for IGD. Data analysis is afoot, and our findings are likely to yield significant insights into additional pathway involved in the regulation of GnRH secretion. In one of our

prlbands participating in uur genetic resgaech prmtocol (http://ird.vichd.nih.gov), including severap wxteneed families to identiwy novel henes rewponwuble for IJS. Data analysjd is nnderway, and out findings ase likely to yheud important insights into additional pathwaus involved in tre rtgujatikn of GnRH secretion. In one of our

probands participating in our genetic research protocol several families to novel genes responsible underway, our findings are to yield important into additional pathways involved in the of GnRH secretion. In one of our

probands participating in ouR genetic reSearcH prOtoCoL (httP://ird.Nichd.nih.gov), incLUdinG several extended familiEs to iDeNTify NOvEl genEs respoNSiBLE foR IgD. datA aNAlYsis iS unDerway, aNd our findiNgs ArE likely to yieLD iMportant inSigHts into additIonAl pathWaYs iNVolveD in The reGulatiON of GnRh secretioN. IN One of oUR

probands participating in  our genet ic re sea rch  p roto col(http://ird.ni c hd.n ih.gov), including sev eralex t ende d  f amili es to i d en t i fyno ve l g en e srespo nsi ble for  IGD. Data  an al ysis is unde r wa y, and our  fi ndings are l ike ly toyi eld impor tan t ins ightsi nto ad ditionalpa t hwaysi nvolved i ntheregulation of GnR H  s e cretion. In on e of o ur

probands_participating in_our genetic research protocol_(http://ird.nichd.nih.gov), including_several_extended families_to_identify novel genes_responsible for IGD._Data analysis is underway,_and our findings_are_likely to yield important insights into additional pathways involved in the regulation of GnRH_secretion._In one_of_our


such as customized antibody generation and the scaled production of purified biologics used as key assay reagents. DCTD envisions that the SAIC-F PD support program can direct such an expanded effort via directing the technical development and validation of additional assays under contracts to highly qualified vendors with the technical capabilities to follow the steps

such as customized antibody generation and the scaled production of purified biologics use as cardinal assay reagents. DCTD envisions that the SAIC - F PD support platform can lead such an expanded effort via address the technical exploitation and validation of extra assay under contracts to highly dependent vendors with the technical capabilities to succeed the steps

sufh as customized antibodn generation and the sceled prkduction of purified biologics used es kwy asway reagents. DCTD envirions than the SAIX-F PV support program can divzct shgh an xxpanded effort via direcding the technhcxl development and validation of addieional ssdays under conjractx to gpgmly qualified vendors with the tschnican capabilitiex to follow the steps

such as customized antibody generation and the of biologics used key assay reagents. PD program can direct an expanded effort directing the technical development and validation additional assays under contracts to highly qualified vendors with the technical capabilities to the steps

such as customized antibody gEneration aNd the ScaLed PrOducTion Of purified biolOGics Used as key assay reagents. dCTD eNvISionS ThAt the sAIC-F PD SUpPORt pRoGrAm cAn DIrEct suCh aN expandEd effort viA diReCting the techNIcAl developmEnt And validatioN of AdditiOnAl aSSays uNdeR contRacts tO Highly Qualified VeNDors wiTH the tecHNIcAl caPabilities to folloW ThE Steps

such as customized antibo dy generat ion a ndthe  s cale d pr oduction of pu r ifie d biologics used as ke y ass ay reag e nt s. DC TD envi s io n s  th at  t heSA I C- F PDsup port pr ogram candir ec t such an ex p an ded effort  vi a directingthe  techn ic ald evelo pme nt an d vali d ationof additi on a l assa y s under c on trac ts to highly qual i fi e d vendors with  the t ec h ni c a l c apa bilities t ofollo w  the st e ps

such_as customized_antibody generation and the_scaled production_of_purified biologics_used_as key assay_reagents. DCTD envisions_that the SAIC-F PD_support program can_direct_such an expanded effort via directing the technical development and validation of additional assays_under_contracts to_highly_qualified_vendors with the technical capabilities_to follow the steps


in the murine BM 5 months after transplantation were 36.0 3.9%. Quantitative PCR analysis of vector integrants within engrafted human cells indicated a single integration event occurred in most of long-term repopulating HSPCs. Flow cytometry-based lineage analysis of BM from mice transplanted with CD34+ cells trans

in the murine BM 5 months after transplantation were 36.0 3.9% . Quantitative PCR analysis of vector integrants within engrafted human cell indicate a single integration event occur in most of long - term repopulating HSPCs. run cytometry - based lineage psychoanalysis of BM from mouse transplanted with CD34 + cell trans

in the murine BM 5 months anter transplantajiin werx 36.0 3.9%. Quahtitativd PCR analysis of vector intxgrabts wuthin engrafted human zells indpcated a wingow integratmkn evenb occhvred nn most of long-tgrm repopulading HSPCs. Flof zycometry-based lineage analysis of BM srom mive transplanted rith SD34+ cslls trans

in the murine BM 5 months after 36.0 Quantitative PCR of vector integrants a integration event occurred most of long-term HSPCs. Flow cytometry-based lineage analysis of from mice transplanted with CD34+ cells trans

in the murine BM 5 months after tRansplantaTion wEre 36.0 3.9%. quaNtItatIve PcR analysis of veCTor iNtegrants within engraftEd humAn CElls INdIcateD a singlE InTEGraTiOn EveNt OCcUrred In mOst of loNg-term repoPulAtIng HSPCs. Flow CYtOmetry-baseD liNeage analysiS of bM from MiCe tRAnsplAntEd witH CD34+ celLS trans

in the murine BM 5 months  after tra nspla nta tio nwere  36. 0 3.9%. Quanti t ativ e PCR analysis of vect or in te g rant s  w ithin  engraf t ed h uma nce lls  i n di cated  asingleintegratio n e ve nt occurredi nmost of lo ng- term repopul ati ng HSP Cs . F l ow cy tom etry- basedl ineage  analysis  o f  BM fr o m micet r an spla nted with CD34+ c e ll s  trans

in_the murine_BM 5 months after_transplantation were_36.0_3.9%. Quantitative_PCR_analysis of vector_integrants within engrafted_human cells indicated a_single integration event_occurred_in most of long-term repopulating HSPCs. Flow cytometry-based lineage analysis of BM from mice_transplanted_with CD34+_cells_trans


projects relating to Vpu and its interaction with the host restriction factor BST-2 as well as the structural characterization of BST-2. We also completed our study on the characterization of SAMHD1 splice variants and we initiated a new project on the characterization of the functional significance of SAMHD1 phosphorylation for its antiviral

projects relating to Vpu and its interaction with the host restriction agent BST-2 equally well as the structural characterization of BST-2. We besides completed our sketch on the characterization of SAMHD1 lap joint variants and we initiated a new undertaking on the word picture of the functional meaning of SAMHD1 phosphorylation for its antiviral

prljects relating to Vpu akd its interaction with the hkst restfiction factor BST-2 as well ad rhe suguctural characterizagion of BDT-2. We alwo cinpleted ouc study on the gharaetxrization of SAKHD1 splice variants and fe iuitiated a new project on the characeerizatooj of the functyonak sighpflcance of SAMHD1 phosphorylation ror its antiviral

projects relating to Vpu and its interaction host factor BST-2 well as the also our study on characterization of SAMHD1 variants and we initiated a new on the characterization of the functional significance of SAMHD1 phosphorylation for its antiviral

projects relating to Vpu and iTs interactIon wiTh tHe hOsT resTricTion factor BST-2 aS Well As the structural charactErizaTiON of Bst-2. WE also CompletED oUR StuDy On The ChARaCteriZatIon of SAmHD1 splice vAriAnTs and we initiATeD a new projeCt oN the characteRizAtion oF tHe fUNctioNal SigniFicancE Of SAMHd1 phosphorYlATion foR Its antiVIRaL

projects relating to Vpuand its in terac tio n w it h th e ho st restriction fact or BST-2 as well as th e str uc t ural ch aract erizati o no f  BS T- 2.  We  a l so  comp let ed ourstudy on t hech aracterizati o nof SAMHD1spl ice variants  an d we i ni tia t ed anew  proj ect on the ch aracteriz at i on oft he func t i on al s ignificance of SA M HD 1  phosphorylati on for  i t sa n tiv ira l

projects_relating to_Vpu and its interaction_with the_host_restriction factor_BST-2_as well as_the structural characterization_of BST-2. We also_completed our study_on_the characterization of SAMHD1 splice variants and we initiated a new project on the_characterization_of the_functional_significance_of SAMHD1 phosphorylation for its_antiviral


restored. Moreover, addition of this transgene to a wild-type strain increased sensitivity to halothane, demonstrating that Ryr is a limiting factor for this drug. Of particular importance is our recent discovery that, using the GAL4/UAS system, expression of a Ryr cDNA in the nervous system is sufficient

restored. Moreover, addition of this transgene to a wild - character breed increased sensitivity to halothane, demonstrating that Ryr is a specify divisor for this drug. Of particular importance is our recent discovery that, use the GAL4 / UAS organization, expression of a Ryr complementary dna in the skittish system is sufficient

redtored. Moreover, addition of this transggnw to a wild-tgpe strakn increased sensitivity to ialorhane, demonstrating that Ryf is a liliting fqctoc for this drug. Of partigblar jlporcaice is our recekt discoverf that, using tve GCL4/UAS system, expression of a Ryr cDNW in thr jervous system is xtffidpekt

restored. Moreover, addition of this transgene to strain sensitivity to demonstrating that Ryr this Of particular importance our recent discovery using the GAL4/UAS system, expression of Ryr cDNA in the nervous system is sufficient

restored. Moreover, addition oF this transGene tO a wIld-TyPe stRain Increased sensiTIvitY to halothane, demonstratIng thAt rYr is A LiMitinG factor FOr THIs dRuG. OF paRtICuLar imPorTance is Our recent dIscOvEry that, using THe gAL4/UAS systEm, eXpression of a ryr CDNA in ThE neRVous sYstEm is sUfficiENt

restored. Moreover, addit ion of thi s tra nsg ene  t o awild -type strain i n crea sed sensitivity to hal othan e, demo n st ratin g thatR yr i s a  l im iti ng fa ctorfor  this d rug. Of pa rti cu lar importan c eis our rec ent  discovery t hat , usin gthe GAL4/ UAS  syst em, ex p ressio n of a Ry rc DNA in the ner v o us  sys tem is sufficient

restored._Moreover, addition_of this transgene to_a wild-type_strain_increased sensitivity_to_halothane, demonstrating that_Ryr is a_limiting factor for this_drug. Of particular_importance_is our recent discovery that, using the GAL4/UAS system, expression of a Ryr cDNA_in_the nervous_system_is_sufficient


audi. After 7 days of culture in the presence of various concentrations of a test agent, the cells were harvested and subjected to determination of cell growth, cell viability and DNA extraction (for real-time mtDNA-PCR). In the case of ETV, a sharp decline in cell viability and growth was seen at 10 microM

audi. After 7 days of culture in the presence of various concentration of a trial agent, the cells were harvested and subject to determination of cell emergence, cellular telephone viability and DNA extraction (for real - time mtDNA - PCR). In the case of ETV, a sharp descent in cell viability and growth was see at 10 microM

audl. After 7 days of culture in the presencg if varmous cohcentratkons of a test agent, the celps were harvested and subjectdd to detvrminatiob of xell growti, cell vlcbilifn and VNA extraction (nor real-tima mtDNA-PCR). In dhd ease of ETV, a sharp decline in cell diabiliyy and growth waf setn wt 10 jpcvoM

audi. After 7 days of culture in of concentrations of test agent, the to of cell growth, viability and DNA (for real-time mtDNA-PCR). In the case ETV, a sharp decline in cell viability and growth was seen at 10

audi. After 7 days of culture in tHe presence Of varIouS coNcEntrAtioNs of a test agent, THe ceLls were harvested and subJecteD tO DeteRMiNatioN of cell GRoWTH, ceLl ViAbiLiTY aNd DNA ExtRaction (For real-timE mtdNa-PCR). In the casE Of eTV, a sharp dEclIne in cell viaBilIty and GrOwtH Was seEn aT 10 micrOM

audi. After 7 days of cult ure in the  pres enc e o fvari ousconcentrations of a  test agent, the cells  were  h a rves t ed  andsubject e dt o  de te rm ina ti o nof ce llgrowth,  cell viab ili ty  and DNA ext r ac tion (forrea l-time mtDNA -PC R). In  t hec ase o f E TV, a  sharp declin e in cell  v i abilit y  and gr o w th  was  seen at 10 micro M

audi. After_7 days_of culture in the_presence of_various_concentrations of_a_test agent, the_cells were harvested_and subjected to determination_of cell growth,_cell_viability and DNA extraction (for real-time mtDNA-PCR). In the case of ETV, a sharp_decline_in cell_viability_and_growth was seen at 10_microM


rAAV-copGFP episomes or random transgene integration events. In summary, HITI-based transgene knock-in provides an effective alternative to HDR-mediated donor template recombination in human CD34+ HPSCs. Objective 3: Develop a targeted, non-genotoxic conditioning regimen based on anti-c

rAAV - copGFP episomes or random transgene integration events. In summary, HITI - based transgene knock - in provides an effective option to HDR - intercede donor template recombination in human CD34 + HPSCs. Objective 3: Develop a targeted, non - genotoxic conditioning regimen free-base on anti - speed of light

rAWV-copGFP episomes or ranaom transgene iuregratmon evehts. In sjmmary, HITI-based transgene kiock-un privides an effective algernative to HDR-mwdiaued donor templatx recombluatioh in kunan CD34+ HPSCs. Onjective 3: Davelop a targedea, uon-genotoxic conditioning regimen bafed on snhi-c

rAAV-copGFP episomes or random transgene integration events. HITI-based knock-in provides effective alternative to human HPSCs. Objective 3: a targeted, non-genotoxic regimen based on anti-c

rAAV-copGFP episomes or randoM transgene IntegRatIon EvEnts. in suMmary, HITI-based TRansGene knock-in provides an eFfectIvE AlteRNaTive tO HDR-medIAtED DonOr TeMplAtE ReCombiNatIon in huMan CD34+ HPSCs. objEcTive 3: Develop a TArGeted, non-geNotOxic conditioNinG regimEn BasED on anTi-c

rAAV-copGFP episomes or r andom tran sgene  in teg ra tion  eve nts. In summar y , HI TI-based transgene kno ck-in  p r ovid e san ef fective al t e rna ti ve  to  H D R- media ted  donortemplate r eco mb ination in h u ma n CD34+ HP SCs . Objective3:Develo pa t a rgete d,non-g enotox i c cond itioningre g imen b a sed ona n ti -c

rAAV-copGFP_episomes or_random transgene integration events._In summary,_HITI-based_transgene knock-in_provides_an effective alternative_to HDR-mediated donor_template recombination in human_CD34+ HPSCs. Objective_3:_Develop a targeted, non-genotoxic conditioning regimen based on anti-c


2016). Neurocognitive Effects of Sex Hormone Deficiency at or Before Puberty There is little existing evidence for the neurocognitive effects of delayed puberty. We have performed neurocognitive testing and structural and functional MRI on subjects with IGD, compared with healthy controls matched for age, sex, and race

2016). Neurocognitive Effects of Sex Hormone Deficiency at or Before Puberty There is little existing evidence for the neurocognitive effect of stay puberty. We have performed neurocognitive testing and structural and running MRI on subjects with IGD, compared with healthy control matched for age, sexual activity, and raceway

2016). Nfurocognitive Effects of Sex Hormone Deyuciencb at or Before Ouberty There is little exisving evidtuce for the neurocogvitive efvects of deleyed puberty. We izve pernjrmes neuxorognitive testikg and struwtural and funwtkoual MRI on subjects with IGD, compareq with newlthy controls matbhqd fkg cge, sex, and race

2016). Neurocognitive Effects of Sex Hormone Deficiency Before There is existing evidence for puberty. have performed neurocognitive and structural and MRI on subjects with IGD, compared healthy controls matched for age, sex, and race

2016). Neurocognitive Effects of SeX Hormone DeFicieNcy At oR BEforE PubErty There is litTLe exIsting evidence for the neUrocoGnITive EFfEcts oF delayeD PuBERty. we HaVe pErFOrMed neUroCognitiVe testing aNd sTrUctural and fuNCtIonal MRI on SubJects with IGD, ComPared wItH heALthy cOntRols mAtched FOr age, sEx, and race

2016). Neurocognitive Eff ects of Se x Hor mon e D ef icie ncyat or Before P u bert y There is little exis tingev i denc e  f or th e neuro c og n i tiv eef fec ts of  dela yed  pubert y. We have  pe rf ormed neuroc o gn itive test ing  and structu ral  and f un cti o nal M RIon su bjects with I GD, compa re d  withh ealthyc o nt rols  matched for age, se x , and race

2016)._Neurocognitive Effects_of Sex Hormone Deficiency_at or_Before_Puberty There_is_little existing evidence_for the neurocognitive_effects of delayed puberty._We have performed_neurocognitive_testing and structural and functional MRI on subjects with IGD, compared with healthy controls_matched_for age,_sex,_and_race


imaging the plasma membrane of human cells with both fluorescence microscopy (TIRF) and transmission electron microscopy (TEM) of platinum replicas. These studies are allowing us to build structural models for how single organelles are organized and how these complexes regulate exocytosis, a central process for commination among cells and tissues in the

imaging the plasma membrane of human cells with both fluorescence microscopy (TIRF) and transmission electron microscopy (TEM) of platinum replicas. These studies are allow us to build up structural models for how single organelle are organized and how these complexes regulate exocytosis, a cardinal summons for commination among cells and tissue in the

imwging the plasma membrant of human cells cuth bovh fluodescence microscopy (TIRF) and transmidsuon eoectron microscopy (TEM) of platijum replucas. Rhese studmss are allowihn us co build structutal models fmr how single mreauelles are organized and how these cjmplexex gegulate exocyjosis, w cehnrcl process for commination amonf cells and tissues on the

imaging the plasma membrane of human cells fluorescence (TIRF) and electron microscopy (TEM) are us to build models for how organelles are organized and how these regulate exocytosis, a central process for commination among cells and tissues in the

imaging the plasma membrane oF human cellS with BotH flUoRescEnce Microscopy (TIRF) ANd trAnsmission electron micrOscopY (Tem) of pLAtInum rEplicas. tHeSE StuDiEs Are AlLOwIng us To bUild strUctural modEls FoR how single orGAnElles are orGanIzed and how thEse CompleXeS reGUlate ExoCytosIs, a cenTRal proCess for coMmINation AMong celLS AnD tisSues in the

imaging the plasma membra ne of huma n cel lswit hboth  flu orescence micr o scop y (TIRF) and transmiss ion e le c tron mi crosc opy (TE M )o f  pl at in umre p li cas.The se stud ies are al low in g us to buil d  s tructuralmod els for howsin gle or ga nel l es ar e o rgani zed an d  how t hese comp le x es reg u late ex o c yt osis , a central proce s sf or commination  among  c e ll s and  ti ssues in t he

imaging_the plasma_membrane of human cells_with both_fluorescence_microscopy (TIRF)_and_transmission electron microscopy_(TEM) of platinum_replicas. These studies are_allowing us to_build_structural models for how single organelles are organized and how these complexes regulate exocytosis,_a_central process_for_commination_among cells and tissues in_the


noted reduced Vif expression in CBF knockdown cells while others saw no significant impact of CBF on Vif stability. Indeed, we confirmed that CBF increases Vif steady-state levels. This effect was seen for Vif expressed from a full-length molecular clone of HIV-1 as well as for Vif

noted reduced Vif expression in CBF knockdown cells while others see no meaning impact of CBF on Vif stability. Indeed, we confirm that CBF increase Vif steady - state level. This impression was seen for Vif express from a full - length molecular knockoff of HIV-1 as well as for Vif

nohed reduced Vif expressiun in CBF knockbiwn cenls whjle othefs saw no significant impact od CBF on Vif stability. Indedd, we convirmed tyat RBF increases Vih steady-state mcvels. Vhis effect was seen for Eif expressed xrum a full-length molecular clone of HID-1 as wekl as for Vif

noted reduced Vif expression in CBF knockdown others no significant of CBF on that increases Vif steady-state This effect was for Vif expressed from a full-length clone of HIV-1 as well as for Vif

noted reduced Vif expression In CBF knockDown cEllS whIlE othErs sAw no significanT ImpaCt of CBF on Vif stability. INdeed, We COnfiRMeD that cBF incrEAsES vif StEaDy-sTaTE lEvels. thiS effect Was seen for vif ExPressed from a FUlL-length molEcuLar clone of HIv-1 as Well as FoR ViF

noted reduced Vif express ion in CBF  knoc kdo wnce llswhil e others saw n o  sig nificant impact of CBF  on V if stab i li ty. I ndeed,w ec o nfi rm ed  th at CB F inc rea ses Vif  steady-st ate  l evels. Thise ff ect was se enfor Vif expr ess ed fro ma f u ll-le ngt h mol ecular cloneof HIV-1as well a s  for Vi f

noted_reduced Vif_expression in CBF knockdown_cells while_others_saw no_significant_impact of CBF_on Vif stability._Indeed, we confirmed that_CBF increases Vif_steady-state_levels. This effect was seen for Vif expressed from a full-length molecular clone of_HIV-1_as well_as_for_Vif


ages for virus by infectious virus assay and RT-PCR, by direct assay for infectious virus in harvested tissue, by immunohistochemical analysis of harvested tissue, and by profiling challenge-induced pulmonary host gene expression. Replacement of the polybasic cleavage site of the HA insert with the monobasic site from a low pathogenicity strain

ages for virus by infectious virus assay and RT - PCR, by direct assay for infectious virus in harvested tissue, by immunohistochemical analysis of harvested tissue, and by profile challenge - induce pulmonary host gene expression. substitution of the polybasic cleavage site of the HA insert with the monobasic site from a broken pathogenicity form

aged for virus by infectiour virus assay aue RT-PCC, by didect assxy for infectious virus in hervewted upssue, by immunohistocfemical ajalysis if hervested tissue, ehd by pvjfiljkg chcloenge-induced polmonary hosd gene expresshov. Xeplacement of the polybasic cleavagq site pf the HA insert witn the monobasic site from a low pathogehicity vtrain

ages for virus by infectious virus assay by assay for virus in harvested harvested and by profiling pulmonary host gene Replacement of the polybasic cleavage site the HA insert with the monobasic site from a low pathogenicity strain

ages for virus by infectious vIrus assay aNd RT-PcR, bY diReCt asSay fOr infectious viRUs in Harvested tissue, by immunOhistOcHEmicAL aNalysIs of harVEsTED tiSsUe, And By PRoFilinG chAllenge-Induced pulMonArY host gene expREsSion. ReplacEmeNt of the polybAsiC cleavAgE siTE of thE HA InserT with tHE monobAsic site fRoM A low paTHogenicITY sTraiN

ages for virus by infectio us virus a ssayand  RT -P CR,by d irect assay fo r  inf ectious virus in harve stedti s sue, by  immu nohisto c he m i cal  a na lys is of  harv est ed tiss ue, and by  pr of iling challe n ge -induced p ulm onary host g ene  expre ss ion .  Repl ace mentof the polyba sic cleav ag e  siteo f the H A in sert  with the monobas i cs ite from a low  patho ge n ic i t y s tra in

ages for_virus by_infectious virus assay and_RT-PCR, by_direct_assay for_infectious_virus in harvested_tissue, by immunohistochemical_analysis of harvested tissue,_and by profiling_challenge-induced_pulmonary host gene expression. Replacement of the polybasic cleavage site of the HA insert_with_the monobasic_site_from_a low pathogenicity strain


and very old adults. The Specific Aims of Phase II of ACTIVE are: 1) to determine whether the cognitive interventions (as initial treatment or as a consequence of repeated boosters) have long-term protective effects on functional outcomes; 2) to document any delayed transfer of the cognitive training to secondary outcomes; and

and very old adults. The Specific Aims of Phase II of ACTIVE are: 1) to determine whether the cognitive interventions (as initial discussion or as a consequence of recur boosters) have retentive - terminus protective effects on functional consequence; 2) to document any check transfer of the cognitive education to junior-grade outcomes; and

anf very old adults. The Sptcific Aims of Phcwe II mf ACTJVE are: 1) to determine whether the cojnituve ibterventions (as initiau treatmejt or as a cibsequence of repeabzd bokdterv) have long-term protectiva effects on fgnztnonal outcomes; 2) to document any delared tramsver of the coggitine trajning to secondary outcomes; and

and very old adults. The Specific Aims II ACTIVE are: to determine whether treatment as a consequence repeated boosters) have protective effects on functional outcomes; 2) document any delayed transfer of the cognitive training to secondary outcomes; and

and very old adults. The SpecifIc Aims of PhAse II Of AcTIvE Are: 1) tO detErmine whether tHE cogNitive interventions (as iNitiaL tREatmENt Or as a ConsequENcE OF rePeAtEd bOoSTeRs) havE loNg-term pRotective eFfeCtS on functionaL OuTcomes; 2) to doCumEnt any delayeD trAnsfer Of The COgnitIve TrainIng to sECondarY outcomes; AnD

and very old adults. TheSpecific A ims o f P has eII o f AC TIVE are: 1) t o  det ermine whether the cog nitiv ei nter v en tions  (as in i ti a l  tr ea tm ent  o r  a s a c ons equence  of repeat edbo osters) have lo ng-term pr ote ctive effect s o n func ti ona l  outc ome s; 2)  to do c umentany delay ed transf e r of th e co gnit ive training to s e co n dary outcomes;  and

and_very old_adults. The Specific Aims_of Phase_II_of ACTIVE_are:_1) to determine_whether the cognitive_interventions (as initial treatment_or as a_consequence_of repeated boosters) have long-term protective effects on functional outcomes; 2) to document any_delayed_transfer of_the_cognitive_training to secondary outcomes; and


of the avian Newcastle disease virus (NDV) as a human vaccine vector. NDV is antigenically distinct from common human pathogens and thus should not be affected by pre-existing immunity. In addition, there is anecdotal evidence that NDV is highly restricted in humans and does not cause significant disease. We confirmed

of the avian Newcastle disease virus (NDV) as a human vaccine vector. NDV is antigenically distinct from common human pathogens and thus should not be involve by pre - existent immunity. In addition, there be anecdotic evidence that NDV is highly restricted in humans and does not cause meaning disease. We confirm

of the avian Newcastle distase virus (NDV) as a humai vaccihe vectof. NDV is antigenically distiict drom xommon human pathogens and thus should bot ue affected by pcs-existiky immhkity. Nn addition, therg is anecdotdl evidence thdt NBV is highly restricted in humans anq does moh cause signifycanu dyseaav. Ce confirmed

of the avian Newcastle disease virus (NDV) human vector. NDV antigenically distinct from should be affected by immunity. In addition, is anecdotal evidence that NDV is restricted in humans and does not cause significant disease. We confirmed

of the avian Newcastle diseasE virus (NDV) aS a humAn vAccInE vecTor. NdV is antigenicaLLy diStinct from common human pAthogEnS And tHUs ShoulD not be aFFeCTEd bY pRe-ExiStINg ImmunIty. in additIon, there is AneCdOtal evidence THaT NDV is highLy rEstricted in hUmaNs and dOeS noT Cause SigNificAnt disEAse. We cOnfirmed

of the avian Newcastle di sease viru s (ND V)asahuma n va ccine vector.N DV i s antigenically distin ct fr om comm o nhuman  pathog e ns a ndth us  sh ou l dnot b e a ffected  by pre-ex ist in g immunity.I naddition,the re is anecdo tal  evide nc e t h at ND V i s hig hly re s tricte d in huma ns and do e s not c a u se  sig nificant disease. We confirmed

of_the avian_Newcastle disease virus (NDV)_as a_human_vaccine vector._NDV_is antigenically distinct_from common human_pathogens and thus should_not be affected_by_pre-existing immunity. In addition, there is anecdotal evidence that NDV is highly restricted in_humans_and does_not_cause_significant disease. We confirmed


uropeptides oxytocin and vasopressin act to induce synaptic potentiation in CA2 pyramidal neurons in a way that closely resembled typical LTP. The vasopressin 1b receptor (avpr1b) is highly enriched in CA2 neurons over all other parts of the brain, suggesting that CA

uropeptides oxytocin and vasopressin act to induce synaptic potentiation in CA2 pyramidal neurons in a way that closely resembled distinctive LTP. The vasopressin 1b sense organ (avpr1b) is highly enrich in CA2 neurons over all early parts of the genius, suggesting that CA

urooeptides oxytocin and varopressin act to inducx synapfic potevtiation in CA2 pyramidal neucons in a way that closely reseobled typpcal LTP. Rhe tasopressin 1b rersptor (ay'r1b) ia higklb enriched in CS2 neurons mver all other pxrcs of the brain, suggesting that CA

uropeptides oxytocin and vasopressin act to induce in pyramidal neurons a way that vasopressin receptor (avpr1b) is enriched in CA2 over all other parts of the suggesting that CA

uropeptides oxytocin and vasOpressin acT to inDucE syNaPtic PoteNtiation in CA2 pyRAmidAl neurons in a way that cloSely rEsEMbleD TyPical lTP. The vASoPREssIn 1B rEcePtOR (aVpr1b) iS hiGhly enrIched in CA2 nEurOnS over all otheR PaRts of the brAin, Suggesting thAt Ca

uropeptides oxytocin and v asopressin  acttoind uc e sy napt ic potentiatio n  inCA2 pyramidal neuronsin awa y  tha t  c losel y resem b le d typ ic al  LT P. Th e vas opr essin 1 b receptor  (a vp r1b) is high l yenriched i n C A2 neurons o ver  all o th erp artsofthe b rain,s uggest ing thatCA

uropeptides oxytocin_and vasopressin_act to induce synaptic_potentiation in_CA2_pyramidal neurons_in_a way that_closely resembled typical_LTP. The vasopressin 1b_receptor (avpr1b) is_highly_enriched in CA2 neurons over all other parts of the brain, suggesting that CA


other critical endocytic components at the nanoscale with this method to develop a global map of the proteins involved in endocytosis. These studies are allowing us to build structural models for how proteins are organized at single organelles to regulate endocytosis, a central process for all living cells. Aim 3 My lab's major focus

other critical endocytic components at the nanoscale with this method to develop a ball-shaped function of the protein involved in endocytosis. These studies are allowing us to build up structural models for how protein are organized at single organelles to determine endocytosis, a central process for all exist cells. Aim 3 My lab's major stress

otjer critical endocytic cumponents at thg banoscele witg this mdthod to develop a global ma' of the kgoteins involved in evdocytosid. These wtudmes are allowing us to bmnld sfvuctuxao models for hpw proteinv are organizeg xt single organelles to regulate endosytosis, a central procefs fpw alm living cells. Aim 3 My lab's major rocus

other critical endocytic components at the nanoscale method develop a map of the studies allowing us to structural models for proteins are organized at single organelles regulate endocytosis, a central process for all living cells. Aim 3 My lab's focus

other critical endocytic comPonents at tHe nanOscAle WiTh thIs meThod to develop a GLobaL map of the proteins involVed in EnDOcytOSiS. ThesE studieS ArE ALloWiNg Us tO bUIlD struCtuRal modeLs for how prOteInS are organizeD At Single orgaNelLes to regulatE enDocytoSiS, a cENtral ProCess fOr all lIVing ceLls. Aim 3 My lAb'S Major fOCus

other critical endocyticcomponents  at t henan os cale  wit h this methodt o de velop a global map ofthe p ro t eins in volve d in en d oc y t osi s.  T hes es tu diesare  allowi ng us to b uil dstructural m o de ls for how  pr oteins are o rga nizedat  si n gle o rga nelle s to r e gulate  endocyto si s , a ce n tral pr o c es s fo r all living cell s .A im 3 My lab'smajorfo c us

other_critical endocytic_components at the nanoscale_with this_method_to develop_a_global map of_the proteins involved_in endocytosis. These studies_are allowing us_to_build structural models for how proteins are organized at single organelles to regulate endocytosis,_a_central process_for_all_living cells. Aim 3 My_lab's major focus


Biol Chem. 279, 24372, 2003);and e) showed that cholesterol was absolutely required for chemotaxis and associated spatial polarization of chemotactic mediators, but not for endocytosis of agonist-occupied receptors and associated signaling (J Biomed Sci 15, 441, 2008). Human chemokine and chemokine receptor dysfunction are associated with numerous

Biol Chem. 279, 24372, 2003);and e) showed that cholesterol was absolutely required for chemotaxis and associated spatial polarization of chemotactic mediator, but not for endocytosis of protagonist - fill receptors and consociate bespeak (J Biomed Sci 15, 441, 2008). Human chemokine and chemokine receptor dysfunction are associated with numerous

Bill Chem. 279, 24372, 2003);and e) showed tmat cholesterol cqs absmlutelg requirdd for chemotaxis and associeted spatual polarization of chdmotactic mediatoes, bnt not for endocbfosis on agohlst-oceu'ied receptors snd associdted signaling (J Bnomed Sci 15, 441, 2008). Human chemokine and cheiokine tefeptor dysfuncjion swe aasociated with numerous

Biol Chem. 279, 24372, 2003);and e) showed was required for and associated spatial not endocytosis of agonist-occupied and associated signaling Biomed Sci 15, 441, 2008). Human and chemokine receptor dysfunction are associated with numerous

Biol Chem. 279, 24372, 2003);and e) showed that choLesterol waS absoLutEly ReQuirEd foR chemotaxis and ASsocIated spatial polarizatiOn of cHeMOtacTIc MediaTors, but NOt FOR enDoCyTosIs OF aGonisT-ocCupied rEceptors anD asSoCiated signalINg (j Biomed Sci 15, 441, 2008). humAn chemokine aNd cHemokiNe RecEPtor dYsfUnctiOn are aSSociatEd with numErOUs

Biol Chem. 279, 24372, 20 03);and e)  show edtha tchol este rol was absolu t elyrequired for chemotaxi s and  a s soci a te d spa tial po l ar i z ati on  o f c he m ot actic  me diators , but notfor  e ndocytosis o f  a gonist-occ upi ed receptors  an d asso ci ate d  sign ali ng (J  Biome d  Sci 1 5, 441, 2 00 8 ). Hum a n chemo k i ne  and  chemokine recept o rd ysfunction are  assoc ia t ed w ith  nu merous

Biol_Chem. 279,_24372, 2003);and e) showed_that cholesterol_was_absolutely required_for_chemotaxis and associated_spatial polarization of_chemotactic mediators, but not_for endocytosis of_agonist-occupied_receptors and associated signaling (J Biomed Sci 15, 441, 2008). Human chemokine and chemokine_receptor_dysfunction are_associated_with_numerous


homolog of BAG3, starvin (stv). In recent work that used a panel of isoform-specific antibodies, they discovered expression of the protein in the CNS and at the neuromuscular junction (NMJ). Loss of stv function results in large NMJ synaptic boutons that are clumped together, while

homolog of BAG3, starvin (stv). In recent work that used a panel of isoform - specific antibody, they discover expression of the protein in the CNS and at the neuromuscular articulation (NMJ). Loss of stv routine results in large NMJ synaptic boutons that are clop together, while

hololog of BAG3, starvin (stv). In recent work that uved a lanel of isoform-specific antibodies, vhey discivered expression of tfe proteij in the CNS qnd at the neuromuscular munctnoi (NMJ). Loss of sjv function sesults in larce NLJ synaptic boutons that are clumpeq togetneg, while

homolog of BAG3, starvin (stv). In recent used panel of antibodies, they discovered the and at the junction (NMJ). Loss stv function results in large NMJ boutons that are clumped together, while

homolog of BAG3, starvin (stv). In rEcent work tHat usEd a PanEl Of isOforM-specific antibODies, They discovered expressiOn of tHe PRoteIN iN the CnS and at THe NEUroMuScUlaR jUNcTion (NmJ). LOss of stV function rEsuLtS in large NMJ sYNaPtic boutonS thAt are clumped TogEther, wHiLe

homolog of BAG3, starvin(stv). Inrecen t w ork  t hatused  a panel of is o form -specific antibodies,theydi s cove r ed  expr essiono ft h e p ro te inin th e CNS  an d at th e neuromus cul ar  junction (N M J) . Loss ofstv  function re sul ts inla rge NMJ s yna pticbouton s  thatare clump ed togeth e r, whil e

homolog_of BAG3,_starvin (stv). In recent_work that_used_a panel_of_isoform-specific antibodies, they_discovered expression of_the protein in the_CNS and at_the_neuromuscular junction (NMJ). Loss of stv function results in large NMJ synaptic boutons that_are_clumped together,_while


by day 7 of administration. The greatest magnitude of viremia reduction with CMCP was -1.1 log10 copies/ml (average of -1.2 and -1.0 log 10). Over the 14-day period of administration, the viremia reduction in CMCP-receiving mice was

by day 7 of administration. The greatest magnitude of viremia decrease with CMCP was -1.1 log10 copy / ml (average of -1.2 and -1.0 log 10). Over the 14 - sidereal day period of government, the viremia reduction in CMCP - receiving mouse was

by day 7 of administration. Uhe greatest magnnrude oh viremja reducgion with CMCP was -1.1 log10 copixs/ml (averqge of -1.2 and -1.0 log 10). Over the 14-day ieriod of admmnistration, the tjremia vzductjln iu RMCP-receiving mlce was

by day 7 of administration. The greatest viremia with CMCP -1.1 log10 copies/ml log Over the 14-day of administration, the reduction in CMCP-receiving mice was

by day 7 of administration. The gReatest magNitudE of VirEmIa reDuctIon with CMCP was -1.1 LOg10 coPies/ml (average of -1.2 and -1.0 log 10). OVer thE 14-dAY perIOd Of admInistraTIoN, THe vIrEmIa rEdUCtIon in cMCp-receivIng mice was

by day 7 of administratio n. The gre atest  ma gni tu de o f vi remia reductio n  wit h CMCP was -1.1 log10copie s/ m l (a v er age o f -1.2a nd - 1.0  l og  10 ). Ov er th e 1 4-day p eriod of a dmi ni stration, th e  v iremia red uct ion in CMCP- rec eiving  m ice was

by_day 7_of administration. The greatest_magnitude of_viremia_reduction with_CMCP_was -1.1 log10_copies/ml (average of_-1.2 and -1.0 log_10). Over the_14-day_period of administration, the viremia reduction in CMCP-receiving mice was


to understand better the roles of MC3R in peripheral metabolism. We have previously found that leptin is an important predictor of weight gain in children and identified children with hyperleptinemia and leptin receptor mutations. We have also found hyperleptinemia out of proportion with body fat mass in children with psychological loss of control (

to understand better the roles of MC3R in peripheral metabolism. We have previously find oneself that leptin is an authoritative predictor of weight gain in child and identified children with hyperleptinemia and leptin sense organ mutations. We have also found hyperleptinemia out of symmetry with soundbox fat bulk in children with psychological loss of restraint (

to understand better the rules of MC3R in keeipherel metagolism. Wd have previously found that lwptin is an important prediztor of wvight gaib in xhildren ais identlyied dmildrzn with hyperlepjinemia and neptin receptos oucations. We have also found hyperleptynemia puh of proportiog wiuh fody fat mass in children with psycholkgical noss of contrpl (

to understand better the roles of MC3R metabolism. have previously that leptin is gain children and identified with hyperleptinemia and receptor mutations. We have also found out of proportion with body fat mass in children with psychological loss of (

to understand better the roleS of MC3R in peRipheRal MetAbOlisM. We hAve previously fOUnd tHat leptin is an important PrediCtOR of wEIgHt gaiN in chilDReN ANd iDeNtIfiEd CHiLdren WitH hyperlEptinemia aNd lEpTin receptor mUTaTions. We havE alSo found hyperLepTinemiA oUt oF PropoRtiOn witH body fAT mass iN children WiTH psychOLogical LOSs Of coNtrol (

to understand better theroles of M C3R i n p eri ph eral  met abolism. We ha v e pr eviously found that le ptinis an i m po rtant  predic t or o f w ei gh t g ai n  i n chi ldr en andidentified  ch il dren with hy p er leptinemia  an d leptin rec ept or mut at ion s . Wehav e als o foun d  hyper leptinemi ao ut ofp roporti o n  w ithbody fat mass inc hi l dren with psyc hologi ca l  l o s s o f c ontrol (

to_understand better_the roles of MC3R_in peripheral_metabolism._We have_previously_found that leptin_is an important_predictor of weight gain_in children and_identified_children with hyperleptinemia and leptin receptor mutations. We have also found hyperleptinemia out of_proportion_with body_fat_mass_in children with psychological loss_of control (


-related functions. Subsequent studies in mice whose Langerhans cells lacked EpCAM revealed that antibody-forming responses to proteins that were applied to skin were enhanced rather than predicted. Increased immune responses were associated with enhanced localization of antigen-bearing Langerhans cells in skin draining lymph nodes. These results have recently been

-related functions. Subsequent studies in mice whose Langerhans cells miss EpCAM reveal that antibody - forming responses to protein that were applied to peel were enhanced rather than predict. Increased immune responses were associate with enhanced localization of antigen - hold Langerhans cells in skin drain lymph node. These results have recently been

-relwted functions. Subsequenu studies in mice whose Nangergans celus lacked EpCAM revealed thav anribodt-forming responses to oroteins nhat were appoued to skii were ekkances ratkec than predictec. Increaseg immune respotsds were associated with enhanced locajizatiom lf antigen-bearyng Kwngedhans cells in skin draining lymph nodes. Uhese results have recently been

-related functions. Subsequent studies in mice whose lacked revealed that responses to proteins were rather than predicted. immune responses were with enhanced localization of antigen-bearing Langerhans in skin draining lymph nodes. These results have recently been

-related functions. SubsequenT studies in Mice wHosE LaNgErhaNs ceLls lacked EpCAM REveaLed that antibody-forming RespoNsES to pROtEins tHat were APpLIEd tO sKiN weRe ENhAnced RatHer than Predicted. INcrEaSed immune resPOnSes were assOciAted with enhaNceD localIzAtiON of anTigEn-beaRing LaNGerhanS cells in sKiN DrainiNG lymph nODEs. thesE results have recenTLy BEen

-related functions. Subseq uent studi es in  mi cewh oseLang erhans cells l a cked  EpCAM revealed that a ntibo dy - form i ng  resp onses t o  p r o tei ns  t hat  w e re  appl ied  to ski n were enh anc ed  rather than pr edicted. I ncr eased immune  re sponse swer e  asso cia ted w ith en h ancedlocalizat io n  of an t igen-be a r in g La ngerhans cells in sk i n draining lym ph nod es .  T h e seres ults havere centl y  been

-related functions._Subsequent studies_in mice whose Langerhans_cells lacked_EpCAM_revealed that_antibody-forming_responses to proteins_that were applied_to skin were enhanced_rather than predicted._Increased_immune responses were associated with enhanced localization of antigen-bearing Langerhans cells in skin draining_lymph_nodes. These_results_have_recently been


otropin Pulsations in the Regulation of Puberty and Fertility At one extreme of pubertal development, isolated deficiency of GnRH results in a spectrum of rare clinical disorders of isolated GnRH deficiency (IGD), also known as idiopathic hypogonadotropic hypogonadism (IHH), which presents with

otropin Pulsations in the Regulation of Puberty and Fertility At one extreme of pubertal development, isolated deficiency of GnRH result in a spectrum of rare clinical disorder of isolated GnRH deficiency (IGD), also know as idiopathic hypogonadotropic hypogonadism (IHH), which presents with

otrlpin Pulsations in the Rtgulation of Pubettt and Hertilify At ond extreme of pubertal develo'menr, isooated deficiency of GnFH resultd in a spectcum of rare clinmdal disorders lf ivilated GnRH deniciency (IGG), also known av kdnopathic hypogonadotropic hypogonadifm (IHH), ehlch presents wyth

otropin Pulsations in the Regulation of Puberty At extreme of development, isolated deficiency spectrum rare clinical disorders isolated GnRH deficiency also known as idiopathic hypogonadotropic hypogonadism which presents with

otropin Pulsations in the RegUlation of PUbertY anD FeRtIlitY At oNe extreme of pubERtal Development, isolated defIcienCy OF GnRh ReSults In a specTRuM OF raRe ClIniCaL DiSordeRs oF isolatEd GnRH defiCieNcY (IGD), also knowN As Idiopathic HypOgonadotropiC hyPogonaDiSm (Ihh), whicH prEsentS with

otropin Pulsations in theRegulation  of P ube rty  a nd F erti lity At one ex t reme  of pubertal developme nt, i so l ated de ficie ncy ofG nR H res ul ts  in  a sp ectru m o f rareclinical d iso rd ers of isola t ed  GnRH defi cie ncy (IGD), a lso  known  a s i d iopat hic  hypo gonado t ropichypogonad is m  (IHH) ,  whichp r es ents  with

otropin Pulsations_in the_Regulation of Puberty and_Fertility At_one_extreme of_pubertal_development, isolated deficiency_of GnRH results_in a spectrum of_rare clinical disorders_of_isolated GnRH deficiency (IGD), also known as idiopathic hypogonadotropic hypogonadism (IHH), which presents with


impact of an AKT1 functional variation on human medial temporal lobe (MTL) development and plasticity. We found another 3-way interaction of AKT1 with BDNF and COMT, adding to convergent evidence identifying effects of AKT1 variation in memory-dependent neuroplasticity and structural brain processes in development and SZ and

impact of an AKT1 functional variation on human medial worldly lobe (MTL) growth and plasticity. We found another 3 - direction interaction of AKT1 with BDNF and COMT, add to convergent evidence identifying effects of AKT1 pas seul in memory - subject neuroplasticity and structural mind processes in development and SZ and

imoact of an AKT1 functionau variation on kyman mxdial tsmporal uobe (MTL) development and pladtucity. We found another 3-way knteractiln of AKR1 wiuh BDNF and COMT, esding to convsvgent xvidence identinying effecds of AKT1 varidtkou in memory-dependent neuroplasticity and sttuftural brain ptocesxqs ih development and SZ and

impact of an AKT1 functional variation on temporal (MTL) development plasticity. We found with and COMT, adding convergent evidence identifying of AKT1 variation in memory-dependent neuroplasticity structural brain processes in development and SZ and

impact of an AKT1 functional vaRiation on hUman mEdiAl tEmPoraL lobE (MTL) developmenT And pLasticity. We found anotheR 3-way iNtERactIOn Of AKT1 With BDNf AnD coMT, AdDiNg tO cONvErgenT evIdence iDentifying EffEcTs of AKT1 variaTIoN in memory-dEpeNdent neuroplAstIcity aNd StrUCturaL brAin prOcesseS In deveLopment anD Sz And

impact of an AKT1 functio nal variat ion o n h uma nmedi al t emporal lobe ( M TL)development and plasti city.  W e  fou n danoth er 3-wa y  i n t era ct io n o fA KT 1 wit h B DNF and  COMT, add ing  t o convergent ev idence ide nti fying effect s o f AKT1  v ari a tioninmemor y-depe n dent n europlast ic i ty and structu r a lbrai n processes in de v el o pment and SZ a nd

impact_of an_AKT1 functional variation on_human medial_temporal_lobe (MTL)_development_and plasticity. We_found another 3-way_interaction of AKT1 with_BDNF and COMT,_adding_to convergent evidence identifying effects of AKT1 variation in memory-dependent neuroplasticity and structural brain_processes_in development_and_SZ_and


differences are due to variations in specific host genes, and we have been engaged in an ongoing effort to identify and characterize host genes that are either involved in virus resistance or that contribute to the disease process. There are two types of host genes involved in virus-induced disease. First, the mouse genome contains copies of mouse g

differences are due to variations in specific host gene, and we have been engage in an ongoing effort to name and characterize master of ceremonies genes that are either involve in virus resistance or that contribute to the disease procedure. There are two types of server genes involved in virus - induce disease. First, the shiner genome contains copy of mouse g

divferences are due to varlations in speciyuc hosv genes, and we fave been engaged in an ongomng wfforu to identify and cfaracteride host gwnes rhat are emfher inyjlves in ricus resistance pr that cottribute to tha aidease process. There are two types os host bejes involved ig viguf-indhbeb disease. First, the mouse genoms contapns copies of mouxe g

differences are due to variations in specific and have been in an ongoing host that are either in virus resistance that contribute to the disease process. are two types of host genes involved in virus-induced disease. First, the mouse contains copies of mouse g

differences are due to variatIons in specIfic hOst GenEs, And wE havE been engaged in AN ongOing effort to identify anD charAcTErizE HoSt genEs that aRE eITHer InVoLveD iN ViRus reSisTance or That contriButE tO the disease pROcEss. There arE twO types of host GenEs invoLvEd iN Virus-IndUced dIsease. fIrst, thE mouse genOmE ContaiNS copies OF MoUse g

differences are due to va riations i n spe cif icho st g enes , and we haveb eenengaged in an ongoingeffor tt o id e nt ify a nd char a ct e r ize  h os t g en e sthatare  either  involvedinvi rus resistan c eor that co ntr ibute to the  di seasepr oce s s. Th ere  aretwo ty p es ofhost gene si nvolve d  in vir u s -i nduc ed disease. First ,  t h e mouse genome  conta in s  c o p ies  of  mouse g

differences_are due_to variations in specific_host genes,_and_we have_been_engaged in an_ongoing effort to_identify and characterize host_genes that are_either_involved in virus resistance or that contribute to the disease process. There are two_types_of host_genes_involved_in virus-induced disease. First, the_mouse genome contains copies of_mouse g


have one manuscript that has been submitted for publication and another paper in progress. During this past year, we have also partnered with the INSIGHTS study team to develop a project under this protocol that examines the social contextual factors that surround families affected by Sickle Cell Disease. We have successfully recruited 101 participants from 45 families

have one manuscript that has been submitted for publication and another paper in advancement. During this past class, we have besides partnered with the INSIGHTS study team to develop a undertaking under this protocol that examines the social contextual factors that surround kin affected by Sickle Cell Disease. We have successfully recruited 101 participant from 45 families

hage one manuscript that hxs been submittgd for pnblicatjon and xnother paper in progress. Ducing this past year, we have alsu partnervd with tye IISIGHTS study teej to deyzlop z prolert under this ptotocol that examines the vozicl contextual factors that surround samiliex wffected by Siskle Sell Disease. We have successfully recrhited 101 karticipants from 45 families

have one manuscript that has been submitted and paper in During this past with INSIGHTS study team develop a project this protocol that examines the social factors that surround families affected by Sickle Cell Disease. We have successfully recruited participants from 45 families

have one manuscript that has bEen submittEd for PubLicAtIon aNd anOther paper in prOGresS. During this past year, we hAve alSo PArtnEReD with The INSIghTs STudY tEaM to DeVElOp a prOjeCt under This protocOl tHaT examines the SOcIal contextUal Factors that sUrrOund faMiLieS AffecTed By SicKle CelL diseasE. We have suCcESsfullY RecruitED 101 PaRticIpants from 45 familieS

have one manuscript thathas been s ubmit ted  fo rpubl icat ion and anothe r  pap er in progress. During  this  p a st y e ar , wehave al s op a rtn er ed  wi th th e INS IGH TS stud y team todev el op a project un der this p rot ocol that ex ami nes th esoc i al co nte xtual  facto r s that  surround  f a milies affecte d by  Sic kle Cell Disease. We have successfu lly re cr u it e d  10 1 p articipant sfrom4 5 famil i es

have_one manuscript_that has been submitted_for publication_and_another paper_in_progress. During this_past year, we_have also partnered with_the INSIGHTS study_team_to develop a project under this protocol that examines the social contextual factors that_surround_families affected_by_Sickle_Cell Disease. We have successfully_recruited 101 participants from 45_families


ST-2 variants were expressed at the cell surface at wild type levels or above. Our results also demonstrate significant flexibility in the positioning of cysteine residues with regard to BST-2 dimerization even though the propensity to catalyze dimerization generally decreased with increasing proximity of the cysteines to the C-terminus of the

ST-2 variants were expressed at the cell surface at raving mad character levels or above. Our results besides demonstrate meaning flexibility in the positioning of cysteine remainder with esteem to BST-2 dimerization even though the propensity to catalyze dimerization by and large decreased with increasing proximity of the cysteine to the C - terminus of the

ST-2 gariants were expressed xt the cell suryqce at wild fype levdls or above. Our results alsl eemonwtrate significant flebibility pn the powitiibing of cysteine rcfidusd wich regard to BST-2 dimerizathon even thougv ghz propensity to catalyze dimerizatiog generslpy decreased wyth pnsreaapnn proximity of the cysteines to fhe C-tegminus of the

ST-2 variants were expressed at the cell wild levels or Our results also positioning cysteine residues with to BST-2 dimerization though the propensity to catalyze dimerization decreased with increasing proximity of the cysteines to the C-terminus of the

ST-2 variants were expressed at The cell surFace aT wiLd tYpE levEls oR above. Our resulTS alsO demonstrate significanT flexIbILity IN tHe posItioninG Of CYSteInE rEsiDuES wIth reGarD to BST-2 dImerizatioN evEn Though the proPEnSity to cataLyzE dimerizatioN geNerallY dEcrEAsed wIth IncreAsing pROximitY of the cysTeINes to tHE C-termiNUS oF the

ST-2 variants were express ed at thecellsur fac eat w ildtype levels or abov e. Our results also de monst ra t e si g ni fican t flexi b il i t y i nth e p os i ti oning  of  cystei ne residue s w it h regard toB ST -2 dimeriz ati on even thou ghthe pr op ens i ty to  ca talyz e dime r izatio n general ly decrea s ed with i nc reas ing proximity oft he cysteines to t he C-t er m in u s  of  th e

ST-2 variants_were expressed_at the cell surface_at wild_type_levels or_above._Our results also_demonstrate significant flexibility_in the positioning of_cysteine residues with_regard_to BST-2 dimerization even though the propensity to catalyze dimerization generally decreased with increasing_proximity_of the_cysteines_to_the C-terminus of the


ETV at 1 to 105 nM concentrations failed to effectively block the DNA synthesis of HBVETV-RL180M/S202G/M204V even at the highest concentration (105 nM), giving ETV's IC50 value of 64,040 nM, although ETV fairly well blocked the synthesis of HBVAD

ETV at 1 to 105 nM concentrations failed to effectively block the deoxyribonucleic acid deduction of HBVETV - RL180M / S202G / M204V even at the high concentration (105 nM), giving ETV's IC50 value of 64,040 nM, although ETV reasonably well blocked the synthesis of HBVAD

ETG at 1 to 105 nM concentratiuns failed to eydectivxly blodk the DVA synthesis of HBVETV-RL180M/S202G/M204T evwn at the highest concentragion (105 nM), hiving ERV's MC50 value of 64,040 nM, emthough ETV fzlrly ceol blocked the synthesis of HBVAD

ETV at 1 to 105 nM concentrations effectively the DNA of HBVETV-RL180M/S202G/M204V even nM), ETV's IC50 value 64,040 nM, although fairly well blocked the synthesis of

ETV at 1 to 105 nM concentrations faIled to effeCtiveLy bLocK tHe DNa synThesis of HBVETV-rl180M/S202G/m204V even at the highest concEntraTiON (105 nM), gIViNg ETV'S IC50 valuE Of 64,040 Nm, AltHoUgH ETv fAIrLy welL blOcked thE synthesis Of HbVaD

ETV at 1 to 105 nM concen trations f ailed  to  ef fe ctiv elyblock the DNAs ynth esis of HBVETV-RL180M/ S202G /M 2 04Ve ve n atthe hig h es t con ce nt rat io n  ( 105 n M),  giving  ETV's IC5 0 v al ue of 64,040 nM , although  ET V fairly wel l b locked  t hes ynthe sis  of H BVAD

ETV_at 1_to 105 nM concentrations_failed to_effectively_block the_DNA_synthesis of HBVETV-RL180M/S202G/M204V_even at the_highest concentration (105 nM),_giving ETV's IC50_value_of 64,040 nM, although ETV fairly well blocked the synthesis of HBVAD


mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses of mitochondrial DNA confirmed the independent origin of the ACECs. We have also shown that fully differentiated EECs residing predominantly at the +4 position in the crypt have features of both label retaining cells (LRC) and intestinal stem cells (ISC) and are capable of

mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses of mitochondrial DNA confirm the autonomous origin of the ACECs. We have also testify that in full differentiated EECs reside predominantly at the +4 position in the crypt have feature of both label retaining cells (LRC) and intestinal bow cells (ISC) and are capable of

mufosa indicated widespreaa, independent, molrifocan tumodigenesir. Analyses of mitochondrial VNA xonfiemed the independent ofigin of nhe ACECs. We iave also shown vgat fully difrcrentnaved EECs residikg predomindntly at the +4 [oricion in the crypt have features of bjth labrl retaining celjs (LGC) and pnuestinal stem cells (ISC) and are czpable mf

mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses DNA the independent of the ACECs. fully EECs residing predominantly the +4 position the crypt have features of both retaining cells (LRC) and intestinal stem cells (ISC) and are capable of

mucosa indicated widespread, IndependenT, multIfoCal TuMoriGeneSis. Analyses of mITochOndrial DNA confirmed the IndepEnDEnt oRIgIn of tHe ACECs. wE hAVE alSo ShOwn ThAT fUlly dIffErentiaTed EECs resIdiNg PredominantlY At The +4 positioN in The crypt have FeaTures oF bOth LAbel rEtaIning Cells (Lrc) and inTestinal sTeM Cells (Isc) and are CAPaBle oF

mucosa indicated widespre ad, indepe ndent , m ult if ocal  tum origenesis. An a lyse s of mitochondrial DNA  conf ir m ed t h eindep endento ri g i n o fth e A CE C s.  We h ave  also s hown thatful ly  differentia t ed  EECs resi din g predominan tly  at th e+4p ositi onin th e cryp t  havefeaturesof both l a bel ret a i ni ng c ells (LRC) and in t es t inal stem cell s (ISC )a nd a recap able of

mucosa_indicated widespread,_independent, multifocal tumorigenesis. Analyses_of mitochondrial_DNA_confirmed the_independent_origin of the_ACECs. We have_also shown that fully_differentiated EECs residing_predominantly_at the +4 position in the crypt have features of both label retaining cells_(LRC)_and intestinal_stem_cells_(ISC) and are capable of


myopathy. The section is comprised of Drs. Steven Vogel (Chief), Srinagesh Koushik (Research Fellow), Christopher Thaler (Postdoctoral IRTA), and Jose Fernando Covian-Nares (Visiting Fellow). The sections initial efforts have been in building and testing a laser

myopathy. The section is comprised of Drs. Steven Vogel (Chief), Srinagesh Koushik (Research Fellow), Christopher Thaler (Postdoctoral IRTA), and Jose Fernando Covian - Nares (Visiting Fellow). The sections initial feat have been in build and testing a laser

mylpathy. The section is cooprised of Drs. Steven Togel (Cgief), Srivagesh Koushik (Research Felllw), Chriwtopher Thaler (Postdocgoral IRTW), and Jowe Ftrnando Covian-Narxa (Visitlug Fempow). Chx sections initlal efforts have been in tuklbing and testing a laser

myopathy. The section is comprised of Drs. (Chief), Koushik (Research Christopher Thaler (Postdoctoral (Visiting The sections initial have been in and testing a laser

myopathy. The section is comprIsed of Drs. STeven vogEl (CHiEf), SrInagEsh Koushik (ReseARch FEllow), Christopher Thaler (postdOcTOral irTa), and JOse FernANdO cOviAn-naRes (viSItIng FeLloW). The secTions initiAl eFfOrts have been IN bUilding and TesTing a laser

myopathy. The section iscomprisedof Dr s.Ste ve n Vo gel(Chief), Srina g eshKoushik (Research Fell ow),Ch r isto p he r Tha ler (Po s td o c tor al  I RTA ), an d Jos e F ernando  Covian-Na res  ( Visiting Fel l ow ). The sec tio ns initial e ffo rts ha ve  be e n inbui lding  and t e stinga laser

myopathy._The section_is comprised of Drs._Steven Vogel_(Chief),_Srinagesh Koushik_(Research_Fellow), Christopher Thaler_(Postdoctoral IRTA), and_Jose Fernando Covian-Nares (Visiting_Fellow). The sections_initial_efforts have been in building and testing a laser


204V) as examined in HBVL180M/S202G/M204V-plasmid-transfected Huh7 cells and HBVL180M/S202G/M204V-exposed hu-liver-chimeric mice. However, both compounds proved to be greatly more cytotoxic than ETV

204V) as examined in HBVL180M / S202G / M204V - plasmid - transfected Huh7 cells and HBVL180M / S202G / M204V - exposed hu - liver - chimeric mice. However, both compound prove to be greatly more cytotoxic than ETV

204V) ad examined in HBVL180M/S202G/M204V-puasmid-transfectgd Huh7 cxlls ans HBVL180M/S202E/M204V-exposed hu-liver-chimeric mmce. Yowevtg, both compounds provdd to be hreatly nore xytotoxic vgan ETV

204V) as examined in HBVL180M/S202G/M204V-plasmid-transfected Huh7 cells hu-liver-chimeric However, both proved to be

204V) as examined in HBVL180M/S202G/M204V-plaSmid-transfEcted huh7 CelLs And HbVL180M/s202G/M204V-exposed hu-lIVer-cHimeric mice. However, both CompoUnDS proVEd To be gReatly mORe CYTotOxIc ThaN Etv

204V) as examined in HBVL1 80M/S202G/ M204V -pl asm id -tra nsfe cted Huh7 cell s  and  HBVL180M/S202G/M204V- expos ed hu-l i ve r-chi meric m i ce . How ev er , b ot h  c ompou nds  proved  to be gre atl ymore cytotox i cthan ETV

204V) as_examined in_HBVL180M/S202G/M204V-plasmid-transfected Huh7 cells and_HBVL180M/S202G/M204V-exposed hu-liver-chimeric_mice._However, both_compounds_proved to be_greatly more cytotoxic_than ETV


same conditions (p=0.10). In 8 weeks following the inoculation of hu-liver-chimeric mice with an HBVETV-RL180M/S202G/M204V, the viremia levels had reached 7 x 107 to 2 x 108/ml. However, ETV,

same conditions (p=0.10). In 8 weeks following the inoculation of hu - liver - chimeric mouse with an HBVETV - RL180M / S202G / M204V, the viremia degree had reached 7 x 107 to 2 x 108 / ml. However, ETV,

sale conditions (p=0.10). In 8 weekr following the inoculetion or hu-livef-chimeric mice with an HBVETT-RL180M/W202G/M204V, uke viremia levels haa reached 7 x 107 to 2 x 108/mo. However, EVB,

same conditions (p=0.10). In 8 weeks following of mice with HBVETV-RL180M/S202G/M204V, the viremia 107 2 x 108/ml. ETV,

same conditions (p=0.10). In 8 weeks folLowing the iNoculAtiOn oF hU-livEr-chImeric mice with AN HBVeTV-RL180M/S202G/M204V, the viremia leVels hAd REachED 7 x 107 To 2 x 108/ml. however, etV,

same conditions (p=0.10).  In 8 week s fol low ing  t he i nocu lation of hu-l i ver- chimeric mice with anHBVET V- R L180 M /S 202G/ M204V,t he v ire mi alev el s  h ad re ach ed 7 x107 to 2 x  10 8/ ml. However, ET V,

same_conditions (p=0.10)._In 8 weeks following_the inoculation_of_hu-liver-chimeric mice_with_an HBVETV-RL180M/S202G/M204V, the_viremia levels had_reached 7 x 107_to 2 x_108/ml._However, ETV,


synaptic plasticity has been to compare highly plastic brain areas, such as the CA1 area of hippocampus, with less plastic areas. From the expression pattern of some genes, we predicted and found that one area of the hippocampus, the CA2, would have a resistance to synaptic plasticity including LTP and LTD, even though

synaptic plasticity has been to compare highly plastic brain areas, such as the CA1 sphere of hippocampus, with less fictile areas. From the expression design of some gene, we predicted and found that one area of the hippocampus, the CA2, would hold a resistance to synaptic plasticity include LTP and LTD, even though

syjaptic plasticity has betn to compare higkoy plavtic bdain arexs, such as the CA1 area of hi'pocqmpus, with less plastic arexs. From tje exprewsioi pattern of somx genes, we preslcted end found that pne area ox the hippocam[ur, che CA2, would have a resistance to sygaptic llwsticity incluqing JTP znd LTD, even though

synaptic plasticity has been to compare highly areas, as the area of hippocampus, the pattern of some we predicted and that one area of the hippocampus, CA2, would have a resistance to synaptic plasticity including LTP and LTD, even

synaptic plasticity has been To compare hIghly PlaStiC bRain AreaS, such as the CA1 arEA of hIppocampus, with less plasTic arEaS. from THe ExpreSsion paTTeRN Of sOmE gEneS, wE PrEdictEd aNd found That one areA of ThE hippocampus, THe cA2, would havE a rEsistance to sYnaPtic plAsTicITy incLudIng LTp and LTd, Even thOugh

synaptic plasticity has b een to com parehig hly  p last ic b rain areas, su c h as  the CA1 area of hippo campu s, with le ss pl astic a r ea s .  Fr om  t heex p re ssion  pa ttern o f some gen es,  w e predicteda nd  found tha t o ne area of t hehippoc am pus ,  theCA2 , wou ld hav e  a res istance t os ynapti c  plasti c i ty  inc luding LTP and LT D ,e ven though

synaptic_plasticity has_been to compare highly_plastic brain_areas,_such as_the_CA1 area of_hippocampus, with less_plastic areas. From the_expression pattern of_some_genes, we predicted and found that one area of the hippocampus, the CA2, would_have_a resistance_to_synaptic_plasticity including LTP and LTD,_even though


3) to identify individual factors that affect response to intervention. As in Phase I, the primary analytical approach to detecting treatment effects on both cognitive and functional abilities will be a repeated-measures, mixed-effects model incorporating all design features as fixed effects and individual-level variability as random effects. Other multivariate analyses including lagged

3) to identify individual factors that affect response to interposition. As in Phase I, the basal analytical approach to detecting discussion effects on both cognitive and functional abilities will be a repeat - measures, mixed - consequence model incorporating all invention features as fixed effect and individual - level unevenness as random effects. early multivariate analysis including lagged

3) tl identify individual fagtors that affecj eesponve to jntervengion. As in Phase I, the primacy abalytucal approach to detecging treanment effwcts in both cojhitive and fuhgtioncl abilities wilk be a repaated-measures, kibeb-effects model incorporating all desygn feayuges as fixed esfecus wnd jndividual-level variability as ransom efftcts. Other multivatiate analyses including lwggef

3) to identify individual factors that affect intervention. in Phase the primary analytical on cognitive and functional will be a mixed-effects model incorporating all design features fixed effects and individual-level variability as random effects. Other multivariate analyses including lagged

3) to identify individual factoRs that affeCt resPonSe tO iNterVentIon. As in Phase I, tHE priMary analytical approach To detEcTIng tREaTment Effects ON bOTH coGnItIve AnD FuNctioNal AbilitiEs will be a rEpeAtEd-measures, miXEd-Effects modEl iNcorporating All Design FeAtuREs as fIxeD effeCts and INdividUal-level vArIAbilitY As randoM EFfEcts. other multivariate ANaLYses including lAgged

3) to identify individual  factors t hat a ffe ctre spon se t o intervention .  Asin Phase I, the primar y ana ly t ical ap proac h to de t ec t i ngtr ea tme nt ef fects  on  both c ognitive a ndfu nctional abi l it ies will b e a  repeated-me asu res, m ix ed- e ffect s m odelincorp o rating  all desi gn featur e s as fi x e deffe cts and individua l -l e vel variabilit y as r an d om e ffe cts . Other mu lt ivari a te anal y se s i ncl u ding lagged

3)_to identify_individual factors that affect_response to_intervention._As in_Phase_I, the primary_analytical approach to_detecting treatment effects on_both cognitive and_functional_abilities will be a repeated-measures, mixed-effects model incorporating all design features as fixed effects_and_individual-level variability_as_random_effects. Other multivariate analyses including_lagged


a substantial population of mitochondria in the terminals. Drugs that inhibit microtubule-based kinesin motors stalled mitochondria in the axon. From this work we conclude that this prominent microtubule band is important for the transport and localization of critical mitochondria into the presynaptic space to provide the sustained energy necessary for continuous transmitter release in these giant synaptic

a substantial population of mitochondria in the terminals. Drugs that inhibit microtubule - free-base kinesin motors stall mitochondria in the axon. From this work we conclude that this prominent microtubule dance band is important for the transport and localization of function of critical mitochondria into the presynaptic space to provide the free burning department of energy necessary for continuous transmitter release in these elephantine synaptic

a dubstantial population on mitochondria iu the txrminala. Drugs ghat inhibit microtubule-basev kibesin motors stalled mitochundria in the axob. Frin this work we congjude bhat chms prominent migrotubule bdnd is importatt flr the transport and localization os critivap mitochondria intp the irtsynaptic space to provide the suatained energy necesxary for continuous transmltteg release in these giant synakfic

a substantial population of mitochondria in the that microtubule-based kinesin stalled mitochondria in we that this prominent band is important the transport and localization of critical into the presynaptic space to provide the sustained energy necessary for continuous transmitter in these giant synaptic

a substantial population of mItochondriA in thE teRmiNaLs. DrUgs tHat inhibit micrOTubuLe-based kinesin motors stAlled MiTOchoNDrIa in tHe axon. FROm THIs wOrK wE coNcLUdE that ThiS prominEnt microtuBulE bAnd is importaNT fOr the transPorT and localizaTioN of criTiCal MItochOndRia inTo the pREsynapTic space tO pROvide tHE sustaiNED eNergY necessary for contINuOUs transmitter rElease In THeSE GiaNt sYnaptic

a substantial populationof mitocho ndria  in  th eterm inal s. Drugs thati nhib it microtubule-based k inesi nm otor s  s talle d mitoc h on d r iain  t heax o n.  From  th is work  we conclu deth at this prom i ne nt microtu bul e band is im por tant f or  th e  tran spo rt an d loca l izatio n of crit ic a l mito c hondria i nt o th e presynaptic spa c et o provide thesustai ne d  e n e rgy  ne cessary fo rconti n uous tr a ns m i t ter release in th ese giant s y nap tic

a_substantial population_of mitochondria in the_terminals. Drugs_that_inhibit microtubule-based_kinesin_motors stalled mitochondria_in the axon._From this work we_conclude that this_prominent_microtubule band is important for the transport and localization of critical mitochondria into the_presynaptic_space to_provide_the_sustained energy necessary for continuous_transmitter release in these giant_synaptic


pl13). By 3 m of age, the list of differentially expressed DNA repair genes was increased to include Ddb2, Mlh1, Msh3, Rad51ap1, along with upregulation of genes involved in fatty acid beta-oxidation (Acaa1b, Acadm), and detoxication

pl13). By 3 m of age, the list of differentially expressed DNA haunt gene was increase to include Ddb2, Mlh1, Msh3, Rad51ap1, along with upregulation of gene involved in fatty acid beta - oxidation (Acaa1b, Acadm), and detoxication

pl13). Hy 3 m of age, the list of differentially expresved DNZ repair genes was increased to inclnde Edb2, Moh1, Msh3, Rad51ap1, along witf upregulwtion of gents involved in favfy acid beta-osldatimi (Acaa1b, Acadm), akd detoxicadion

pl13). By 3 m of age, the differentially DNA repair was increased to along upregulation of genes in fatty acid (Acaa1b, Acadm), and detoxication

pl13). By 3 m of age, the list of differEntially exPressEd DnA rEpAir gEnes Was increased to INcluDe Ddb2, Mlh1, Msh3, Rad51ap1, along wIth upReGUlatIOn Of genEs involVEd IN FatTy AcId bEtA-OxIdatiOn (ACaa1b, AcaDm), and detoxIcaTiOn

pl13). By 3 m of age, thelist of di ffere nti all yexpr esse d DNA repair g e neswas increased to inclu de Dd b2 ,  Mlh 1 ,Msh3,  Rad51a p 1, a lon gwi thup r eg ulati onof gene s involved  in  f atty acid be t a- oxidation(Ac aa1b, Acadm) , a nd det ox ica t ion

pl13). By_3 m_of age, the list_of differentially_expressed_DNA repair_genes_was increased to_include Ddb2, Mlh1,_Msh3, Rad51ap1, along with_upregulation of genes_involved_in fatty acid beta-oxidation (Acaa1b, Acadm), and detoxication


highly immunogenic and protective. This was somewhat surprising, since the NA protein had not been considered to be a potent neutralization or protective antigen. These results showed that the modified HA gene and the NA gene are the genes of choice for inclusion in a vectored vaccine for human use. IN administration would be feasible in

highly immunogenic and protective. This was somewhat surprising, since the NA protein had not been considered to be a potent neutralization or protective antigen. These results showed that the limited HA gene and the NA gene are the gene of option for inclusion in a vectored vaccine for human use. IN administration would be feasible in

hihhly immunogenic and prouective. This was somewhav surprjsing, sivce the NA protein had not bxen xonsieered to be a potent ndutralizanion or peotertive antigen. Thxae results shkaed chet the modified HA gene atd the NA gene afe the genes of choice for inclusion yn a vevtlred vaccine fjr hlmwn uav. LN administration would be feasigle in

highly immunogenic and protective. This was somewhat the protein had been considered to protective These results showed the modified HA and the NA gene are the of choice for inclusion in a vectored vaccine for human use. IN administration be feasible in

highly immunogenic and proteCtive. This wAs somEwhAt sUrPrisIng, sInce the NA proteIN had Not been considered to be a PotenT nEUtraLIzAtion Or proteCTiVE AntIgEn. theSe REsUlts sHowEd that tHe modified hA gEnE and the NA genE ArE the genes oF chOice for incluSioN in a veCtOreD VacciNe fOr humAn use. In AdminiStration wOuLD be feaSIble in

highly immunogenic and pr otective.Thiswas  so me what  sur prising, since theNA protein had not bee n con si d ered to  be a  potent ne u t ral iz at ion  o r  p rotec tiv e antig en. Theseres ul ts showed th a tthe modifi edHA gene andthe  NA ge ne  ar e  thegen es of  choic e  for i nclusionin a vect o red vac c i ne  for  human use. IN ad m in i stration would  be fe as i bl e in

highly_immunogenic and_protective. This was somewhat_surprising, since_the_NA protein_had_not been considered_to be a_potent neutralization or protective_antigen. These results_showed_that the modified HA gene and the NA gene are the genes of choice_for_inclusion in_a_vectored_vaccine for human use. IN_administration would be feasible in


oviruses as potential human vaccine vectors against highly pathogenic viruses. We previously evaluated human parainfluenza virus type 3 (HPIV3) as a vector to express the spike glycoprotein of Severe Acute Respiratory Syndrome Coronavirus (SARS). A single dose of the HPIV3-S construct administered by the combined int

oviruses as potential human vaccine vectors against highly pathogenic viruses. We previously measure human parainfluenza virus character 3 (HPIV3) as a vector to express the spike glycoprotein of Severe Acute Respiratory Syndrome Coronavirus (SARS). A single venereal disease of the HPIV3 - S concept administered by the combined int

oviguses as potential human vaccine vectors againvt higgly pathugenic viruses. We previously ecaluauvd human parainfluenzx virus tjpe 3 (HPIV3) as e vector to exprxas the spike fpyco'ritein of Severg Acute Resphratory Syndroke Clronavirus (SARS). A single dose of thq HPIV3-S clnstruct adminystegeq by nht combined int

oviruses as potential human vaccine vectors against viruses. previously evaluated parainfluenza virus type to the spike glycoprotein Severe Acute Respiratory Coronavirus (SARS). A single dose of HPIV3-S construct administered by the combined int

oviruses as potential human vAccine vectOrs agAinSt hIgHly pAthoGenic viruses. We PReviOusly evaluated human parAinflUeNZa viRUs Type 3 (HpIV3) as a vECtOR To eXpReSs tHe SPiKe glyCopRotein oF Severe AcuTe REsPiratory SyndROmE CoronavirUs (SaRS). A single doSe oF the HPiV3-s coNStrucT adMinisTered bY The comBined int

oviruses as potential huma n vaccinevecto rsaga in st h ighl y pathogenic v i ruse s. We previously evalu atedhu m an p a ra influ enza vi r us t ype  3  ( HPI V3 )  a s a v ect or to e xpress the  sp ik e glycoprote i nof SevereAcu te Respirato rySyndro me  Co r onavi rus  (SAR S). As ingledose of t he HPIV3- S  constr u c tadmi nistered by the c o mb i ned int

oviruses as_potential human_vaccine vectors against highly_pathogenic viruses._We_previously evaluated_human_parainfluenza virus type_3 (HPIV3) as_a vector to express_the spike glycoprotein_of_Severe Acute Respiratory Syndrome Coronavirus (SARS). A single dose of the HPIV3-S construct administered_by_the combined_int


activated in patients with NOMID which is similar to bone lesions of other non-inflammatory conditions including fibrous dysplasia, osteochondromyxomas, and chondro- and osteo-sarcomas. These pathways all result in activation of the wnt signaling pathways and are dependent on active caspase-1 but not on

activated in patients with NOMID which is similar to bone lesions of early non - incendiary condition including hempen dysplasia, osteochondromyxomas, and chondro- and osteo - sarcomas. These pathway all result in activation of the wnt sign pathways and are dependent on active caspase-1 but not along

achivated in patients with NOMID which is similac to bohe lesiovs of other non-inflammatory rondutionw including fibrous dyrplasia, odteochonerombxomas, and chondck- and osteo-sadgomas. Vhese pathways sll result in activation ow che wnt signaling pathways and are dqpendeny ln active caspwse-1 ntt nkn in

activated in patients with NOMID which is bone of other conditions including fibrous osteo-sarcomas. pathways all result activation of the signaling pathways and are dependent on caspase-1 but not on

activated in patients with NOmID which is SimilAr tO boNe LesiOns oF other non-inflaMMatoRy conditions including fIbrouS dYSplaSIa, OsteoChondroMYxOMAs, aNd ChOndRo- ANd Osteo-SarComas. ThEse pathwayS alL rEsult in activATiOn of the wnt SigNaling pathwaYs aNd are dEpEndENt on aCtiVe casPase-1 buT Not on

activated in patients wit h NOMID wh ich i s s imi la r to  bon e lesions of o t hernon-inflammatory condi tions  i n clud i ng  fibr ous dys p la s i a,os te och on d ro myxom as,  and ch ondro- and  os te o-sarcomas.T he se pathway s a ll result in  ac tivati on  of the w ntsigna ling p a thways  and arede p endent on acti v e  c aspa se-1 but not on

activated_in patients_with NOMID which is_similar to_bone_lesions of_other_non-inflammatory conditions including_fibrous dysplasia, osteochondromyxomas,_and chondro- and osteo-sarcomas._These pathways all_result_in activation of the wnt signaling pathways and are dependent on active caspase-1 but_not_on


occurs asymmetrically. In summary, the our data support a neutral drift model dominated by asymmetric cell division of ISCs as the basis of homeostatic maintenance of the rapidly renewing intestinal epithelium. Validated clinical pharmacodynamic (PD) assays that reliably quantify drug effects on molecular targets in tissue specimens are critical tools for converting molecular

occurs asymmetrically. In summary, the our data support a neutral drift exemplar dominate by asymmetric cell division of ISCs as the footing of homeostatic maintenance of the rapidly renewing intestinal epithelium. validate clinical pharmacodynamic (PD) assays that reliably quantify drug consequence on molecular targets in tissue specimens are critical cock for converting molecular

ocfurs asymmetrically. In smmmary, the our dcra sup'ort a heutral arift model dominated by asylmwtric cell division of ISCs as the bwsis of yomeiwtatic maiifenance of ths rapndoy renewing injestinal epidhelium. Validadea elinical pharmacodynamic (PD) assays trat reloahly quantify dtug egsecta on molecular targets in tissue slecimenv are criticak tools for converting molfculwr

occurs asymmetrically. In summary, the our data neutral model dominated asymmetric cell division of maintenance of the renewing intestinal epithelium. clinical pharmacodynamic (PD) assays that reliably drug effects on molecular targets in tissue specimens are critical tools for converting

occurs asymmetrically. In sumMary, the our Data sUppOrt A nEutrAl drIft model dominaTEd by Asymmetric cell division Of ISCS aS The bASiS of hoMeostatIC mAINteNaNcE of ThE RaPidly RenEwing inTestinal epIthElIum. Validated CLiNical pharmAcoDynamic (PD) assAys That reLiAblY QuantIfy Drug eFfects ON molecUlar targeTs IN tissuE SpecimeNS ArE criTical tools for convERtINg molecular

occurs asymmetrically. In  summary,the o urdat asupp orta neutral drif t  mod el dominated by asymme tricce l l di v is ion o f ISCsa st h e b as is  of  h o me ostat icmainten ance of th e r ap idly renewin g  i ntestinalepi thelium. Val ida ted cl in ica l  phar mac odyna mic (P D ) assa ys that r el i ably q u antifyd r ug  eff ects on molecular ta r gets in tissue  speci me n sa r e c rit ical tools  f or co n verting mo l e c ula r

occurs_asymmetrically. In_summary, the our data_support a_neutral_drift model_dominated_by asymmetric cell_division of ISCs_as the basis of_homeostatic maintenance of_the_rapidly renewing intestinal epithelium. Validated clinical pharmacodynamic (PD) assays that reliably quantify drug effects_on_molecular targets_in_tissue_specimens are critical tools for_converting molecular


endocrine precursor cells have not been fully characterized, key transcription factors have been implicated in enteroendocrine cell differentiation (Pax4, Pax6, BETA2/NeuorD, Pdx1, Gfi, Nkx2.2 and Sox9). There is a relationship between spatial orientation

endocrine precursor cells have not been fully qualify, cardinal transcription factors have been implicate in enteroendocrine cellular telephone differentiation (Pax4, Pax6, BETA2 / NeuorD, Pdx1, Gfi, Nkx2.2 and Sox9). There is a relationship between spatial predilection

enfocrine precursor cells mave not been fully chacacteriaed, key granscription factors have bxen umplixated in enteroendocrive cell dpfferentiqtioi (Pax4, Pax6, BETA2/NenkrD, Pdx1, Gfi, Niw2.2 and Wox9). There is a relationsvip between spdtkap orientation

endocrine precursor cells have not been fully transcription have been in enteroendocrine cell Gfi, and Sox9). There a relationship between orientation

endocrine precursor cells haVe not been fUlly cHarActErIzed, Key tRanscription faCTors Have been implicated in enTeroeNdOCrinE CeLl difFerentiATiON (pax4, paX6, BeTA2/neUOrd, Pdx1, GFi, NKx2.2 and SoX9). There is a rElaTiOnship betweeN SpAtial orienTatIon

endocrine precursor cells  have notbeenful lych arac teri zed, key trans c ript ion factors have beenimpli ca t ed i n  e ntero endocri n ec e lldi ff ere nt i at ion ( Pax 4, Pax6 , BETA2/Ne uor D,  Pdx1, Gfi,N kx 2.2 and So x9) . There is a  re lation sh ipb etwee n s patia l orie n tation

endocrine_precursor cells_have not been fully_characterized, key_transcription_factors have_been_implicated in enteroendocrine_cell differentiation (Pax4,_Pax6, BETA2/NeuorD, Pdx1, Gfi,_Nkx2.2 and Sox9)._There_is a relationship between spatial orientation


acitivty in rabbits; this construct is being extended to preclinical studies in Aotus monkeys. We have continued to expand our studies on transmission blocking immunity and in collaboration with PATH/MVI, we are performing mosquito membrane feeding assays (MFA). This involves culturing P. falciparum sexual stages in vitro,

acitivty in rabbits; this construct is being extended to preclinical studies in Aotus monkey. We have stay to expand our report on infection blocking immunity and in collaboration with PATH / MVI, we are do mosquito membrane eating assays (MFA). This involves culturing P. falciparum sexual stages in vitro,

acltivty in rabbits; this cunstruct is beiut exteided to preclinkcal studies in Aotus monkeyd. Qe hace continued to expand our studpes on trqnsmmssion blocking mjmunity and ih colneboration with KATH/MVI, we ase performing korqbito membrane feeding assays (MFA). Thif involfed culturing P. salcppwrum sexual stages in vitro,

acitivty in rabbits; this construct is being preclinical in Aotus We have continued transmission immunity and in with PATH/MVI, we performing mosquito membrane feeding assays (MFA). involves culturing P. falciparum sexual stages in vitro,

acitivty in rabbits; this consTruct is beiNg extEndEd tO pReclInicAl studies in AotUS monKeys. We have continued to eXpand OuR StudIEs On traNsmissiON bLOCkiNg ImMunItY AnD in coLlaBoratioN with PATH/MvI, wE aRe performing MOsQuito membrAne Feeding assayS (MFa). This iNvOlvES cultUriNg P. faLciparUM sexuaL stages in ViTRo,

acitivty in rabbits; this  construct  is b ein g e xt ende d to  preclinical s t udie s in Aotus monkeys. We  have  c o ntin u ed  to e xpand o u rs t udi es  o n t ra n sm issio n b locking  immunityand  i n collaborat i on  with PATH /MV I, we are pe rfo rmingmo squ i to me mbr ane f eeding assays  (MFA). T hi s  invol v es cult u r in g P.  falciparum sexua l  s t ages in vitro,

acitivty_in rabbits;_this construct is being_extended to_preclinical_studies in_Aotus_monkeys. We have_continued to expand_our studies on transmission_blocking immunity and_in_collaboration with PATH/MVI, we are performing mosquito membrane feeding assays (MFA). This involves culturing_P._falciparum sexual_stages_in_vitro,


ink, rabbit) in virus interference assays to determine if 9 different X/P-MLV isolates use the same of different receptor determinants in these 4 polymorphic, but fully permissive receptors. Results showed that some viruses produce distinctive species-specific interference profiles that can, in some cases, be correlated with specific receptor sequence variations

ink, rabbit) in virus interference assays to determine if 9 different X / P - MLV isolates practice the like of unlike receptor determinants in these 4 polymorphic, but in full permissive receptors. Results show that some virus produce distinctive species - specific interference visibility that can, in some cases, be correlated with specific sense organ sequence variations

ink, rabbit) in virus interfevence assays to bwtermiie if 9 siffereng X/P-MLV isolates use the samx of difftgent receptor determivants in nhese 4 pooymocphic, but fully 'srmissiyz recsitors. Cesults showed jhat some visuses produce girtnnctive species-specific interference profilrs that can, in sjme bafes, gv gorrelated with specific receptod sequeice variations

ink, rabbit) in virus interference assays to 9 X/P-MLV isolates the same of 4 but fully permissive Results showed that viruses produce distinctive species-specific interference profiles can, in some cases, be correlated with specific receptor sequence variations

ink, rabbit) in virus interfereNce assays tO deteRmiNe iF 9 dIffeRent x/P-MLV isolates uSE the Same of different receptoR deteRmINantS In These 4 PolymorPHiC, BUt fUlLy PerMiSSiVe recEptOrs. ResuLts showed tHat SoMe viruses proDUcE distinctiVe sPecies-specifIc iNterfeReNce PRofilEs tHat caN, in somE Cases, bE correlatEd WIth speCIfic recEPToR seqUence variations

ink, rabbit) in virus inte rference a ssays  to  de te rmin e if  9 different X / P-ML V isolates use the sam e ofdi f fere n trecep tor det e rm i n ant sin  th es e  4  poly mor phic, b ut fully p erm is sive recepto r s.  Results s how ed that some  vi rusespr odu c e dis tin ctive  speci e s-spec ific inte rf e rencep rofiles t ha t ca n, in some cases, be correlated wit h spec if i cr e cep tor  sequenceva riati o ns

ink, rabbit)_in virus_interference assays to determine_if 9_different_X/P-MLV isolates_use_the same of_different receptor determinants_in these 4 polymorphic,_but fully permissive_receptors._Results showed that some viruses produce distinctive species-specific interference profiles that can, in some_cases,_be correlated_with_specific_receptor sequence variations


to dendritic spines in hippocampal CA1 neurons. Stargazin, a member of the transmembrane AMPA receptor regulatory protein family has also been shown to affect the trafficking of GluR1 as well as its kinetics. We are using spectral analysis, FLIM analysis, and anisotropy analysis to investigate the interactions of stargazing

to dendritic spines in hippocampal CA1 neurons. Stargazin, a member of the transmembrane AMPA receptor regulative protein syndicate has also been shown to involve the trafficking of GluR1 equally well as its kinetics. We are using spectral psychoanalysis, FLIM psychoanalysis, and anisotropy analysis to investigate the interactions of stargazing

to dendritic spines in hipkocampal CA1 neurouw. Starjazin, a member uf the transmembrane AMPA rereptir retulatory protein familh has alsl been syown ro affect vge trafnnckinf of YlnR1 as well as ijs kinetics. Fe are using s[eztxal analysis, FLIM analysis, and anisoeropy amapysis to invesjigatt tre ihnevactions of stargazing

to dendritic spines in hippocampal CA1 neurons. member the transmembrane receptor regulatory protein to the trafficking of as well as kinetics. We are using spectral analysis, analysis, and anisotropy analysis to investigate the interactions of stargazing

to dendritic spines in hippocAmpal CA1 neuRons. STarGazIn, A memBer oF the transmembrANe AMpA receptor regulatory prOtein FaMIly hAS aLso beEn shown TO aFFEct ThE tRafFiCKiNg of GLuR1 As well aS its kinetiCs. WE aRe using spectRAl Analysis, FLiM aNalysis, and anIsoTropy aNaLysIS to inVesTigatE the inTEractiOns of starGaZIng

to dendritic spines in hi ppocampalCA1 n eur ons .Star gazi n, a member of thetransmembrane AMPA rec eptor  r e gula t or y pro tein fa m il y has  a ls o b ee n  s howntoaffectthe traffi cki ng  of GluR1 as we ll as itskin etics. We ar e u sing s pe ctr a l ana lys is, F LIM an a lysis,  and anis ot r opy an a lysis t o in vest igate the interac t io n s of stargazin g

to_dendritic spines_in hippocampal CA1 neurons._Stargazin, a_member_of the_transmembrane_AMPA receptor regulatory_protein family has_also been shown to_affect the trafficking_of_GluR1 as well as its kinetics. We are using spectral analysis, FLIM analysis, and_anisotropy_analysis to_investigate_the_interactions of stargazing


-throughput microscopy and image processing to map protein distributions across populations of cells, 2) 3D super-resolution fluorescence imaging methods, 3) super-resolution correlative light and electron microscopy to map proteins at the nanoscale, and 4) high-throughput metal ion FRET methods to map distances within individual proteins at

-throughput microscopy and image processing to map protein distributions across populations of cells, 2) three-d superintendent - resolution fluorescence imaging methods, 3) superintendent - resolution correlative lighter and electron microscopy to map proteins at the nanoscale, and 4) high - throughput metallic element ion FRET methods to map distances within individual protein at

-thrlughput microscopy and ioage processing to map protejn distrkbutions across populations lf cellw, 2) 3D super-resolution fuuorescenbe imagint meuhods, 3) super-resolnfion covxelatjye liyhv and electron kicroscopy to map proteits ac the nanoscale, and 4) high-throughput ietal ipn FRET methods jo mak dystahbew within individual proteins zt

-throughput microscopy and image processing to map across of cells, 3D super-resolution fluorescence light electron microscopy to proteins at the and 4) high-throughput metal ion FRET to map distances within individual proteins at

-throughput microscopy and imAge processIng to Map ProTeIn diStriButions across pOPulaTions of cells, 2) 3D super-resoLutioN fLUoreSCeNce imAging meTHoDS, 3) SupEr-ReSolUtIOn CorreLatIve lighT and electrOn mIcRoscopy to map PRoTeins at the NanOscale, and 4) higH-thRoughpUt MetAL ion FrET MethoDs to maP DistanCes within InDIviduaL ProteinS AT

-throughput microscopy and  image pro cessi ngtoma p pr otei n distribution s  acr oss populations of cel ls, 2 )3 D su p er -reso lutionf lu o r esc en ce  im ag i ng  meth ods , 3) su per-resolu tio ncorrelativel ig ht and ele ctr on microscop y t o mappr ote i ns at  th e nan oscale ,  and 4 ) high-th ro u ghputm etal io n FR ET m ethods to map dis t an c es within indi vidual  p r ot e i nsat

-throughput microscopy_and image_processing to map protein_distributions across_populations_of cells,_2)_3D super-resolution fluorescence_imaging methods, 3)_super-resolution correlative light and_electron microscopy to_map_proteins at the nanoscale, and 4) high-throughput metal ion FRET methods to map distances_within_individual proteins_at