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▁be ▁killed ▁like ▁other ▁terror ists ." ▁In ▁September ▁ 2 0 1 8 , ▁the ▁United ▁Kingdom ▁granted ▁as yl um ▁to ▁about ▁ 1 0 0 ▁White ▁Hel met ▁staff ▁and ▁relatives ▁that ▁had ▁been ▁ev acu ated ▁to ▁Jordan . ▁ ▁The ▁co - found er ▁of ▁the ▁White ▁Hel m ets , ▁James ▁Le ▁Mes ur ier , ▁was ▁found ▁dead ▁in ▁Ist an bul ▁on ▁ 9 ▁November ▁ 2 0 1 9 . ▁ ▁Oper ations ▁ ▁S CD ' s ▁stated ▁mission ▁is ▁" to ▁save ▁the ▁greatest ▁number ▁of ▁lives ▁in ▁the ▁short est ▁possible ▁time ▁and ▁to ▁minim ize ▁further ▁injury ▁to ▁people ▁and ▁damage ▁to ▁property ." ▁Their ▁work ▁covers ▁the ▁ 1 5 ▁civil ▁defence ▁tasks ▁as ▁laid ▁out ▁in ▁international ▁human itar ian ▁law ▁( I HL ); ▁the ▁bulk ▁of ▁their ▁activity ▁in ▁Sy ria ▁consists ▁of ▁urban ▁search ▁and ▁rescue ▁in ▁response ▁to ▁bomb ing , ▁medical ▁ev acu ation , ▁ev acu ation ▁of ▁civ ili ans ▁from ▁danger ▁areas , ▁and ▁essential ▁service ▁delivery . ▁ ▁The ▁most ▁prominent ▁role ▁of ▁S CD ▁was ▁res cu ing ▁civ ili ans ▁from ▁a irst rik es ▁with ▁bar rel ▁bomb s , ▁impro vised ▁explos ive ▁devices ▁dropped ▁by ▁SA AF ▁hel ic op ters . ▁Following ▁a ▁request ▁from ▁Bash ar ▁al - Ass ad ▁for ▁support , ▁Russia ▁interven ed ▁in ▁the ▁Sy rian ▁Civil ▁War ▁on ▁ 3 0 ▁September ▁ 2 0 1 5 |
. ▁Much ▁of ▁the ▁work ▁of ▁S CD ▁has ▁been ▁in ▁response ▁to ▁aer ial ▁bomb ard ments ▁by ▁the ▁Russian ▁Air ▁Force ▁attack ▁aircraft . ▁ ▁As ▁well ▁as ▁providing ▁rescue ▁services , ▁S CD ▁undert akes ▁repair ▁works ▁such ▁as ▁se cur ing ▁dam aged ▁buildings ▁and ▁re connect ing ▁elect rical ▁and ▁water ▁services , ▁clear ing ▁roads , ▁teaching ▁children ▁about ▁ha z ards ▁from ▁un expl oded ▁ord n ance , ▁as ▁well ▁as ▁fire f ight ing ▁and ▁winter ▁storm ▁relief . ▁Sometimes ▁described ▁as ▁the ▁most ▁dangerous ▁job ▁in ▁the ▁world , ▁S CD ▁operations ▁involve ▁risk ▁from ▁being ▁active ▁in ▁a ▁war - zone . ▁By ▁late ▁ 2 0 1 6 , ▁ 1 5 9 ▁White ▁Hel m ets ▁had ▁been ▁killed ▁since ▁the ▁organisation ' s ▁in ception . ▁ ▁S CD ▁is ▁not ▁affili ated ▁with ▁the ▁International ▁Civil ▁Def ence ▁Organisation ▁( IC DO ), ▁nor ▁is ▁it ▁connected ▁to ▁the ▁Dam asc us ' s ▁Sy rian ▁Civil ▁Def ence ▁Forces ▁( SC DF ), ▁an ▁IC DO - member ▁since ▁ 1 9 7 2 . ▁But , ▁since ▁the ▁SC DF ▁operate ▁in ▁government - h eld ▁areas ▁and ▁since ▁civil ian ▁cas ual ties ▁in ▁Sy ria ▁over wh el ming ly ▁result ▁from ▁government ▁forces ' ▁bomb ard ments ▁against ▁targets ▁in ▁opposition - h eld ▁areas , ▁the ▁una ff ili ated ▁S CD ▁eng ages ▁in ▁civil ▁defence ▁tasks ▁in ▁said ▁re bel |
- h eld ▁areas . ▁ ▁In ▁ 2 0 1 5 , ▁the ▁S CD ▁un success fully ▁lo bb ied ▁the ▁European ▁Union ▁( E U ) ▁and ▁govern ments ▁to ▁imp ose ▁a ▁no ▁fly ▁zone ▁over ▁certain ▁parts ▁of ▁Sy ria ▁to ▁protect ▁civ ili ans ▁from ▁a irst rik es . ▁The ▁White ▁Hel m ets ▁have ▁un success fully ▁called ▁upon ▁govern ments ▁such ▁as ▁France ▁to ▁act ▁to ▁effect ▁a ▁ce ase fire ▁and ▁protect ▁lives ▁in ▁subsequent ▁years . ▁ ▁As ▁of ▁ 2 0 1 5 , ▁S CD ▁had ▁an ▁annual ▁budget ▁of ▁$ 3 0 ▁million ▁provided ▁by ▁a ▁mix ▁of ▁state ▁don ors ▁and ▁public ▁fund ra ising . ▁Vol unte ers ▁who ▁work ▁full - time ▁receive ▁a ▁$ 1 5 0 ▁month ly ▁st ip end . ▁ ▁It ▁has ▁a ▁co - ord ination ▁office ▁on ▁the ▁Turkish - S y rian ▁border ▁in ▁Gaz iante p ▁and ▁a ▁training ▁centre ▁in ▁Turkey . ▁ ▁As ▁of ▁April ▁ 2 0 1 7 , ▁there ▁were ▁about ▁ 3 , 0 0 0 ▁White ▁Hel met ▁members , ▁about ▁ 1 0 0 ▁of ▁which ▁were ▁women . ▁As ▁of ▁March ▁ 2 0 1 8 , ▁a ▁British ▁government ▁programme ▁review ▁recorded ▁that ▁st ip ends ▁were ▁being ▁paid ▁for ▁ 4 , 0 1 1 ▁volunte ers ▁in ▁ 1 7 9 ▁cent res ▁to ▁provide ▁search ▁and ▁rescue ▁and ▁other ▁services , ▁and ▁that ▁ |
1 1 4 , 5 0 7 ▁civ ili ans ▁had ▁been ▁reported ▁res cu ed ▁or ▁a ided . ▁ ▁In ▁October ▁ 2 0 1 8 , ▁the ▁Jordan ian ▁Foreign ▁Ministry ▁announced ▁that ▁at ▁least ▁ 3 0 0 ▁White ▁Hel m ets ▁members ▁who ▁had ▁fled ▁Sy ria ▁into ▁Jordan ▁are ▁now ▁res ett led ▁in ▁several ▁Western ▁countries , ▁one ▁of ▁which ▁is ▁Canada . ▁ ▁Part ners hips ▁and ▁fund ing ▁S CD ▁is ▁officially ▁an ▁im partial ▁human itar ian ▁N GO , ▁with ▁no ▁affili ation ▁to ▁any ▁political ▁or ▁military ▁actor ▁and ▁a ▁commit ment ▁to ▁render ▁services ▁to ▁anyone ▁in ▁need . ▁Like ▁all ▁N GO s ▁operating ▁in ▁opposition - control led ▁areas , ▁S CD ▁negoti ates ▁human itar ian ▁access ▁with ▁organis ations ▁such ▁as ▁local ▁coun c ils , ▁provincial ▁coun c ils , ▁and ▁armed ▁groups , ▁with ▁relationships ▁varying ▁widely ▁from ▁governor ate ▁to ▁governor ate . ▁ ▁S CD ▁work ▁in ▁close ▁partners hip ▁with ▁the ▁Netherlands - based ▁N GO ▁May day ▁Res cue ▁Foundation . ▁May day ▁Res cue ' s ▁Program ▁Manager ▁for ▁Sy ria ▁is ▁Far ou q ▁Hab ib , ▁who ▁has ▁also ▁been ▁described ▁as ▁the ▁White ▁Hel m ets ' ▁Head ▁of ▁International ▁Rel ations . ▁ ▁The ▁White ▁Hel m ets ▁receives ▁char itable ▁fund ing ▁from ▁the ▁United ▁States , ▁the ▁United ▁Kingdom , ▁and ▁other ▁western ▁govern ments . ▁Initial ly ▁the ▁United ▁Kingdom ▁Foreign ▁and |
▁Commonwealth ▁Office ▁was ▁the ▁largest ▁single ▁source ▁of ▁fund ing ▁through ▁May day ▁Res cue ▁Foundation . ▁U . S . ▁government ▁funds ▁are ▁directed ▁to ▁S CD ▁through ▁Ch emon ics , ▁a ▁U . S . ▁based ▁private ▁international ▁development ▁company . ▁Fund ers ▁now ▁include ▁the ▁Canadian ▁government ▁Peace ▁and ▁St abil ization ▁Oper ations ▁Program , ▁the ▁Dan ish ▁government , ▁the ▁German ▁government , ▁the ▁Japan ▁International ▁Co operation ▁Agency , ▁the ▁Netherlands ▁Ministry ▁of ▁Foreign ▁Affairs . ▁the ▁New ▁Zealand ▁Ministry ▁of ▁Foreign ▁Affairs , ▁the ▁United ▁States ▁Agency ▁for ▁International ▁Development ▁( USA ID ) ▁and ▁the ▁United ▁Kingdom ▁Conf lict , ▁St ability ▁and ▁Security ▁Fund ▁( CSS F ). ▁USA ID ▁have ▁contributed ▁at ▁least ▁$ 2 3 ▁million ▁from ▁ 2 0 1 3 ▁to ▁March ▁ 2 0 1 6 . ▁The ▁British ▁government ▁had ▁provided ▁£ 1 5 ▁million ▁of ▁fund ing ▁between ▁ 2 0 1 2 ▁and ▁November ▁ 2 0 1 5 , ▁increased ▁to ▁£ 3 2 ▁million ▁by ▁October ▁ 2 0 1 6 . ▁As ▁of ▁ 3 1 ▁March ▁ 2 0 1 8 , ▁the ▁British ▁government ▁had ▁provided ▁£ 3 8 . 4 m ▁in ▁aid ▁to ▁the ▁White ▁Hel m ets . ▁The ▁S CD ▁has ▁also ▁received ▁individual ▁don ations ▁online ▁to ▁their ▁Hero ▁Fund , ▁which ▁provides ▁treatment ▁for ▁wounded ▁volunte ers ▁and ▁supports ▁their ▁families . ▁ ▁In ▁March ▁ 2 0 1 7 , ▁the ▁organization ▁was |
▁reported ▁to ▁be ▁operating ▁on ▁an ▁annual ▁budget ▁of ▁about ▁$ 2 6 ▁million . ▁May day ▁Res cue ▁reports ▁that ▁between ▁ 2 0 1 4 ▁and ▁ 2 0 1 8 ▁the ▁White ▁Hel m ets ▁received ▁fund ing ▁of ▁$ 1 2 7 ▁million , ▁$ 1 9 ▁million ▁of ▁which ▁came ▁from ▁non - g overn ment ▁sources ; ▁it ▁is ▁not ▁clear ▁if ▁this ▁included ▁U . S . ▁government ▁fund ing ▁which ▁went ▁through ▁Ch emon ics ▁rather ▁than ▁May day ▁Res cue . ▁In ▁ 2 0 1 8 , ▁the ▁White ▁Hel m ets ' ▁vice ▁president ▁reported ▁that ▁the ▁group ’ s ▁finan cing ▁for ▁ 2 0 1 8 ▁from ▁foreign ▁govern ments ▁had ▁fallen ▁to ▁$ 1 2 ▁million ▁from ▁$ 1 8 ▁million ▁the ▁previous ▁year . ▁ ▁In ▁April ▁ 2 0 1 8 , ▁the ▁Trump ▁administration ▁susp ended ▁the ▁fund ing ▁of ▁the ▁White ▁Hel m ets ▁as ▁part ▁of ▁a ▁wider ▁susp ension ▁of ▁the ▁fund ing ▁of ▁stabil ization ▁projects ▁in ▁Sy ria ▁while ▁the ▁U . S . ▁re ass esses ▁its ▁role ▁in ▁Sy ria . ▁The ▁U . S . ▁had ▁provided ▁more ▁than ▁$ 3 3 ▁million ▁to ▁support ▁the ▁group ▁since ▁ 2 0 1 3 . ▁On ▁ 1 4 ▁June ▁ 2 0 1 8 , ▁the ▁Trump ▁administration ▁author ised ▁USA ID ▁and ▁the ▁United ▁States ▁Department ▁of ▁State ▁to ▁release ▁approximately ▁$ 6 . 6 ▁million ▁in |
▁aid ▁to ▁be ▁shared ▁between ▁the ▁group ▁and ▁the ▁UN ' s ▁International , ▁Imp art ial ▁and ▁Independent ▁Mechan ism ▁in ▁Sy ria . ▁ ▁The ▁Netherlands ▁announced ▁that ▁it ▁would ▁end ▁its ▁fund ing ▁of ▁several ▁aid ▁projects ▁in ▁opposition ▁strong holds ▁in ▁Sy ria , ▁including ▁the ▁White ▁Hel m ets , ▁by ▁December ▁ 2 0 1 8 . ▁This ▁announ cement ▁followed ▁a ▁Ministry ▁of ▁Foreign ▁Affairs ▁report ▁according ▁to ▁which ▁the ▁super vision ▁over ▁the ▁activity ▁of ▁White ▁Hel m ets ▁is ▁in ade qu ate ▁and ▁there ▁is ▁a ▁risk ▁that ▁funds ▁meant ▁for ▁the ▁rescue ▁workers ▁would ▁end ▁up ▁in ▁the ▁hands ▁of ▁armed ▁groups ▁instead . ▁ ▁Public ity ▁and ▁recognition ▁ ▁S CD ▁is ▁widely ▁c ited , ▁quoted , ▁or ▁dep icted ▁in ▁regional ▁and ▁international ▁media ▁coverage ▁of ▁the ▁conflict ▁in ▁Sy ria . ▁Ra ed ▁Al ▁S ale h , ▁the ▁Director ▁of ▁S CD , ▁has ▁been ▁an ▁out sp oken ▁advoc ate ▁against ▁bomb ard ment ▁of ▁civ ili ans , ▁address ing ▁the ▁United ▁Nations ▁Security ▁Council ▁and ▁other ▁international ▁bodies ▁on ▁a ▁number ▁of ▁occasions . ▁ ▁S CD ▁has ▁been ▁the ▁subject ▁of ▁two ▁films . ▁The ▁streaming ▁service ▁Net fli x ▁released ▁a ▁document ary ▁film ▁entitled ▁The ▁White ▁Hel m ets ▁on ▁ 1 6 ▁September ▁ 2 0 1 6 ▁by ▁British ▁director ▁Or lando ▁von ▁Eins ied el ▁and ▁producer ▁Jo anna ▁Nat as eg ara . ▁The ▁film ▁won ▁the |
▁Best ▁Document ary ▁( Short ▁Sub ject ) ▁at ▁the ▁ 8 9 th ▁Academy ▁Awards . ▁S CD ▁head ▁Ra ed ▁S ale h ▁was ▁unable ▁to ▁attend ▁the ▁O sc ars ▁ceremony ▁due ▁to ▁es cal ation ▁of ▁the ▁conflict , ▁despite ▁having ▁a ▁valid ▁vis a . ▁Kh aled ▁Kh ate eb , ▁cinemat ograph er ▁of ▁the ▁film , ▁was ▁unable ▁to ▁attend ▁due ▁to ▁a ▁vis a ▁problem . ▁The ▁Associ ated ▁Press ▁reported ▁that ▁the ▁United ▁States ▁Department ▁of ▁Hom eland ▁Security ▁under ▁President ▁Trump ▁decided ▁to ▁block ▁Kh aled ▁Kh ate eb ▁at ▁the ▁ 1 1 th ▁hour . ▁Re leased ▁in ▁ 2 0 1 7 , ▁Last ▁Men ▁in ▁Ale ppo ▁was ▁directed ▁by ▁Sy rian ▁director ▁Fer as ▁F ay y ad ▁in ▁collaboration ▁with ▁Dan ish ▁film - maker ▁Steven ▁Johann essen ▁and ▁the ▁Ale ppo ▁Media ▁Centre ; ▁it ▁was ▁the ▁W inner ▁of ▁the ▁Grand ▁J ury ▁Document ary ▁prize ▁at ▁the ▁Sund ance ▁Film ▁Festival ▁in ▁ 2 0 1 7 . ▁ ▁S CD ▁was ▁nominated ▁for ▁the ▁ 2 0 1 6 ▁Nobel ▁Peace ▁Prize ▁and ▁was ▁a ▁recip ient ▁of ▁the ▁ 2 0 1 6 ▁Right ▁Liv elihood ▁Award , ▁the ▁" Al tern ative ▁Nobel ▁Prize ". ▁ ▁In ▁ 2 0 1 7 , ▁it ▁was ▁awarded ▁the ▁Mc Call - P ier pa oli ▁Human itar ian ▁Award ▁by ▁Ref uge es ▁International ▁and ▁its ▁women ▁volunte ers ▁were ▁awarded ▁the |
▁Their world ▁Hope ▁award ▁by ▁Sarah ▁Jane ▁Brown ' s ▁children ' s ▁char ity ▁Their world . ▁Fem ale ▁S CD ▁volunte er ▁Man al ▁Ab az eed , ▁who ▁accepted ▁these ▁awards , ▁was ▁listed ▁by ▁Fort une ▁magazine ▁as ▁being ▁among ▁the ▁" World ' s ▁Most ▁Power ful ▁Women " ▁of ▁ 2 0 1 7 . ▁ ▁In ▁ 2 0 1 7 , ▁Polit ico ▁listed ▁Kh aled ▁O mar ▁Har rah , ▁a ▁leading ▁member ▁in ▁Ale ppo , ▁known ▁as ▁the ▁' child ▁res c uer ', ▁as ▁one ▁of ▁the ▁ 2 8 ▁people ▁" sh aping , ▁sh aking ▁and ▁stir ring ▁Europe ". ▁He ▁was ▁killed ▁in ▁Ale ppo ▁in ▁an ▁a irst rike ▁in ▁August ▁ 2 0 1 6 . ▁Har rah ▁is ▁the ▁main ▁character ▁in ▁Last ▁Men ▁in ▁Ale ppo , ▁which ▁was ▁dedicated ▁to ▁him ▁after ▁his ▁death . ▁ ▁Another ▁prominent ▁member ▁is ▁Moh ammed ▁Ab u ▁K if ah , ▁a ▁civil ▁defence ▁team ▁member ▁who ▁res cu ed ▁another ▁child ▁from ▁beneath ▁the ▁rub ble ▁in ▁Id lib .< ref ▁name =" Se ven ▁members "> R af ▁San chez ▁Seven ▁members ▁of ▁Sy ria ' s ▁White ▁Hel m ets ▁shot ▁dead ▁by ▁unknown ▁gun men , ▁' Te legraph , ▁ 1 2 ▁August ▁ 2 0 1 7 </ ref > ▁Following ▁his ▁death ▁in ▁an ▁apparent ▁assass ination ▁on ▁ 1 2 ▁August ▁ 2 0 1 7 , ▁aged |
▁ 2 5 ▁years ▁old , ▁K if ah ' s ▁life ▁was ▁comm emor ated ▁on ▁BBC ▁Radio ▁ 4 ' s ▁Last ▁Word . ▁▁ ▁Cont ro vers ies ▁ ▁According ▁to ▁investig ative ▁journal ists ▁and ▁anal yst s , ▁S CD ▁became ▁a ▁target ▁of ▁a ▁system atic ▁information ▁war fare ▁campaign ▁by ▁the ▁Russian ▁government , ▁the ▁Sy rian ▁government , ▁alt - right ▁personal ities , ▁and ▁their ▁supp or ters , ▁who ▁have ▁accused ▁the ▁organisation ▁of ▁taking ▁sides ▁in ▁the ▁Sy rian ▁Civil ▁War , ▁carrying ▁arms ▁and ▁supporting ▁" ter ror ist " ▁groups . ▁Cla ims ▁by ▁contrib utors ▁to ▁the ▁English ▁language ▁Russian - fund ed ▁R T ▁television ▁network ▁and ▁S put nik ▁news ▁ag ency ▁have ▁come ▁under ▁critical ▁scr ut iny . ▁Multiple ▁journal ists ▁have ▁raised ▁serious ▁questions ▁as ▁to ▁the ▁cred ibility ▁and ▁government ▁t ies ▁of ▁individuals ▁making ▁accus ations ▁against ▁S CD . ▁According ▁to ▁The ▁New ▁York ▁Times ' ', ▁Ass ad ' s ▁claim ▁that ▁the ▁White ▁Hel m ets ▁are ▁" Al - Q a eda ▁members " ▁was ▁" without ▁evidence ". ▁Cla ims ▁made ▁by ▁R T ▁contrib utor ▁Eva ▁Bart lett ▁that ▁the ▁White ▁Hel m ets ▁stage ▁res c ues ▁and ▁" re cycle " ▁children ▁in ▁its ▁videos ▁were ▁reported ▁as ▁false ▁" be yond ▁a ▁reasonable ▁doubt ". ▁ ▁In ▁November ▁ 2 0 1 6 , ▁the ▁Revolution aries ▁of ▁Sy ria ▁Media ▁Office , |
▁an ▁opposition ▁media ▁organisation , ▁published ▁a ▁video ▁showing ▁two ▁S CD ▁volunte ers ▁performing ▁a ▁st aged ▁rescue ▁operation ▁for ▁the ▁Man ne quin ▁Challenge ▁m eme . ▁The ▁White ▁Hel m ets ▁apolog ised ▁for ▁their ▁volunte ers ' ▁error ▁of ▁jud g ement ▁and ▁said ▁it ▁had ▁not ▁shared ▁the ▁recording ▁on ▁their ▁official ▁channels . ▁ ▁In ▁June ▁ 2 0 1 7 , ▁a ▁member ▁of ▁the ▁White ▁Hel m ets ▁was ▁susp ended ▁in def initely ▁after ▁he ▁was ▁discovered ▁to ▁have ▁assist ed ▁armed ▁milit ants ▁in ▁the ▁bur ial ▁of ▁m util ated ▁corps es ▁of ▁soldiers ▁belonging ▁to ▁pro - g overn ment ▁forces . ▁ ▁Foot age ▁showing ▁White ▁Hel m ets ▁members ▁removing ▁a ▁man ' s ▁body ▁following ▁his ▁execution ▁by ▁re bel ▁milit ants ▁has ▁caused ▁critics ▁to ▁acc use ▁the ▁group ▁of ▁" ass isting " ▁in ▁execution s . ▁The ▁leader ▁of ▁the ▁White ▁Hel m ets ▁has ▁remarked ▁that ▁these ▁are ▁" is ol ated ▁inc idents " ▁and ▁are ▁not ▁representative ▁of ▁the ▁leadership ▁of ▁the ▁organisation . ▁ ▁In ▁ 2 0 1 8 , ▁Ang lic an ▁vic ar ▁Andrew ▁Ash down , ▁along ▁with ▁Church ▁of ▁England ▁and ▁House ▁of ▁L ords ▁figures ▁such ▁as ▁Lord ▁Care y ▁of ▁Cl if ton ▁and ▁Michael ▁Naz ir - A li , ▁visited ▁Sy ria ▁and ▁met ▁with ▁Ass ad ; ▁Ash down ▁accused ▁the ▁White ▁Hel m ets ▁of ▁being ▁milit ants , ▁and |
▁accused ▁the ▁group ▁of ▁" keep ing ▁an ▁injured ▁Sy rian ▁child ▁un tre ated ▁and ▁covered ▁in ▁dust ▁and ▁blood " ▁for ▁propag anda ▁purposes . ▁A ▁UK ▁Foreign ▁Office ▁memor and um ▁critic ized ▁the ▁trip , ▁warning ▁that ▁it ▁would ▁be ▁explo ited ▁by ▁Ass ad . ▁ ▁The ▁White ▁Hel m ets ▁have ▁had ▁a ▁difficult ▁relationship ▁with ▁the ▁majority - K urd ish ▁Sy rian ▁Democratic ▁Forces ▁( S DF ). ▁The ▁group ▁operated ▁in ▁Afr in ▁until ▁the ▁local ▁Kur d ish ▁administration ▁b anned ▁it ▁in ▁December ▁ 2 0 1 5 . ▁It ▁returned ▁following ▁the ▁capture ▁of ▁the ▁city ▁by ▁the ▁Turkish ▁Army ▁and ▁Sy rian ▁reb els ▁in ▁the ▁Turkish - led ▁Operation ▁O live ▁Branch ▁in ▁ 2 0 1 8 . ▁In ▁June ▁ 2 0 1 9 , ▁after ▁fires ▁set ▁to ▁c rop ▁fields ▁by ▁the ▁Islam ic ▁State ▁of ▁Ira q ▁and ▁the ▁Lev ant ▁threatened ▁the ▁food ▁supply ▁of ▁Sy ri ans ▁living ▁in ▁S DF - control led ▁areas , ▁the ▁White ▁Hel m ets ▁offered ▁to ▁enter ▁S DF ▁territory ▁and ▁help ▁fight ▁the ▁fires , ▁but ▁permission ▁was ▁denied . ▁Nicholas ▁A . ▁Her as , ▁a ▁Fellow ▁at ▁the ▁Center ▁for ▁a ▁New ▁American ▁Security , ▁stated ▁that ▁the ▁White ▁Hel m ets , ▁as ▁an ▁organization , ▁referred ▁to ▁Turkey ’ s ▁operation ▁in ▁Afr in ▁as ▁the ▁" li ber ation " ▁of ▁Afr in , ▁and ▁maintained ▁that ▁there ▁was |
▁" cred ible ▁evidence " ▁that ▁the ▁White ▁Hel m ets ▁assist ed ▁Turkish ▁soldiers ▁and ▁reb els ▁by ▁providing ▁de - min ing ▁assistance . ▁The ▁White ▁Hel m ets ▁denied ▁that ▁they ▁supported ▁the ▁campaign . ▁ ▁References ▁ ▁External ▁links ▁ ▁Sy ria ▁Civil ▁Def ense ▁( o fficial ▁website ) ▁ ▁The ▁White ▁Hel m ets ▁( fund ra ising ▁website ) ▁ ▁May day ▁Res cue ▁( register ed ▁foundation ▁in ▁the ▁Netherlands ) ▁ ▁Inter im ▁Articles ▁of ▁Association ▁– ▁Sy ria ▁Civil ▁Def ence ▁ ▁Category : E mer gency ▁services ▁in ▁Sy ria ▁Category : Vol unte er ▁organizations ▁Category : Right ▁Liv elihood ▁Award ▁la ure ates ▁Category : 2 0 1 4 ▁establish ments ▁in ▁Sy ria <0x0A> </s> ▁Ch oe ▁Se jin ▁( 최 세 진 , ▁[ t ͡ ɕ ʰ we <0xCC> <0x9E> ▁s ʰ ed ͡ ʑ in ]; ▁ 1 4 6 5 ▁– ▁February ▁ 1 0 , ▁ 1 5 4 2 ) ▁was ▁a ▁Korean ▁lingu ist , ▁and ▁a ▁transl ator ▁and ▁interpreter ▁of ▁the ▁Chinese ▁language ▁during ▁the ▁Jose on ▁D ynast y . ▁He ▁is ▁of ▁the ▁Go es an ▁Ch oe ▁cl an ▁and ▁his ▁cour tes y ▁name ▁was ▁G ong se o ▁( 공 서 ; ▁ 公 <0xE7> <0x91> <0x9E> ). ▁He ▁is ▁widely ▁known ▁for ▁his ▁research ▁with ▁the ▁Korean ▁hang ul ▁letters , ▁and ▁compar ative ▁studies ▁with ▁Chinese ▁and ▁Korean , ▁which ▁further ▁led ▁to |
▁the ▁propag ation ▁of ▁hang ul ▁during ▁a ▁time ▁period ▁when ▁Chinese ▁characters ▁were ▁used ▁as ▁the ▁main ▁system ▁of ▁writing . ▁Ch oe ▁was ▁recognized ▁by ▁many ▁for ▁his ▁tal ents ▁as ▁an ▁official ▁interpreter ▁in ▁the ▁Korean ▁Emb ass ies ▁in ▁Be ij ing ▁and ▁in ▁his ▁works ▁in ▁hang ul ▁research . ▁However , ▁he ▁lived ▁a ▁tum ult uous ▁life ▁due ▁to ▁this ▁middle ▁class ▁status , ▁which ▁led ▁him ▁to ▁be ▁the ▁target ▁of ▁many ▁en vious ▁arist ocr ats ▁of ▁his ▁era . ▁ ▁Ch oe ▁de vised ▁the ▁modern ▁South ▁Korean ▁order ▁of ▁the ▁hang ul ▁characters , ▁and ▁assigned ▁names ▁to ▁the ▁letters . ▁ ▁His ▁most ▁famous ▁book ▁on ▁hang ul ▁is ▁the ▁Hun m ong ▁Jah oe ▁( ; ▁ ▁" Collection ▁of ▁Char acters ▁for ▁Training ▁the ▁Un en light ened ", ▁ 1 5 2 7 ). ▁Over ▁the ▁course ▁of ▁ 4 0 ▁years , ▁he ▁composed ▁ 7 ▁original ▁works , ▁and ▁published ▁ 1 0 ▁transl ations ▁and ▁research ▁works . ▁ ▁Ch oe ▁Se jin ' s ▁Life ▁ ▁Ch oe ▁Se jin ▁was ▁born ▁into ▁a ▁middle ▁class ▁family ▁in ▁Se oul . ▁His ▁father ▁was ▁Ch oe ▁Jung bal , ▁who ▁was ▁also ▁a ▁transl ator ▁and ▁interpreter ▁of ▁the ▁government . ▁Ch oe ▁Se jin ' s ▁birth ▁year ▁is ▁not ▁found ▁in ▁any ▁records , ▁but ▁given ▁the ▁record ▁found ▁in ▁" J ung j ong ▁of ▁Jose on ▁Chron icles ", ▁his |
▁birth ▁year ▁is ▁estimated ▁as ▁ 1 4 6 5 . ▁However , ▁there ▁are ▁also ▁other ▁claims ▁that ▁he ▁was ▁born ▁in ▁ 1 4 7 3 . ▁When ▁he ▁was ▁ 2 1 , ▁he ▁passed ▁the ▁" Trans l ating ▁and ▁Inter pre ting ▁Government ▁Ex am " ▁and ▁when ▁he ▁was ▁ 3 8 , ▁he ▁placed ▁second ▁in ▁another ▁exam , ▁the ▁" B ong ▁Se ▁Ja ▁By ul ▁Sh i " ▁Ex am , ▁an ▁exam ▁conducted ▁to ▁celebr ate ▁the ▁crow ning ▁of ▁the ▁Prince . ▁ ▁Ch oe ▁was ▁known ▁as ▁very ▁sk illed ▁as ▁a ▁transl ator ▁and ▁interpreter . ▁However , ▁during ▁a ▁time ▁period ▁when ▁society ▁was ▁strictly ▁strat ified , ▁his ▁middle ▁class ▁status ▁restricted ▁his ▁career ▁and ▁even ▁led ▁him ▁to ▁many ▁difficulties ▁and ▁hard ships . ▁The ▁noble ▁class ▁organized ▁society ▁in ▁a ▁way ▁that ▁they ▁controlled ▁and ▁possessed ▁a ▁majority ▁of ▁the ▁wealth ▁and ▁property ▁of ▁the ▁country , ▁and ▁it ▁was ▁common ▁for ▁the ▁nob ility ▁to ▁be ▁je alous ▁over ▁highly ▁tal ented ▁middle ▁class ▁government ▁officials ▁who ▁might ▁successfully ▁become ▁promoted , ▁and ▁sur pass ▁nobles ▁in ▁rank , ▁although ▁this ▁was ▁very ▁rare . ▁Ch oe ▁Se jin ▁was ▁a ▁target ▁for ▁the ▁nobles ' ▁je alous y , ▁and ▁he ▁was ▁sacrific ed ▁in ▁the ▁fa ction al ▁str ife ▁and ▁tum ult uous ▁political ▁climate ▁at ▁the ▁time . ▁For ▁example , ▁two ▁months ▁after ▁he ▁passed ▁the ▁" B ong ▁Se |
▁Ja ▁By ul ▁Sh i " ▁Ex am , ▁his ▁accept ance ▁became ▁null ified ▁because ▁of ▁an ▁invol vement ▁in ▁a ▁trial ▁for ▁the ▁murder ▁of ▁the ▁de posed ▁Queen , ▁Y oon . ▁Even ▁though ▁he ▁was ▁not ▁directly ▁involved , ▁the ▁Minister ▁of ▁Culture ▁and ▁Education , ▁Lee ▁Se j wa , ▁who ▁conducted ▁the ▁exam ▁and ▁personally ▁recommended ▁Ch oe ▁was ▁involved ▁in ▁the ▁trial , ▁and ▁as ▁a ▁result , ▁all ▁accept ances ▁were ▁null ified . ▁Some ▁were ▁able ▁to ▁retain ▁their ▁accept ance ▁due ▁to ▁famil ial ▁t ies , ▁however , ▁Ch oe ▁was ▁not ▁one ▁of ▁them . ▁Even ▁after ▁ 3 ▁years ▁of ▁waiting , ▁he ▁was ▁accused ▁of ▁writing ▁the ▁anonymous ▁letter ▁critic izing ▁the ▁National ▁Court ▁in ▁ 1 5 0 7 ▁and ▁was ▁subject ▁to ▁a ▁severe ▁sentence . ▁He ▁was ▁saved ▁from ▁this ▁accus ation ▁after ▁more ▁investigation , ▁but ▁this ▁highlight s ▁the ▁kind ▁of ▁difficulties ▁he ▁faced ▁due ▁to ▁his ▁social ▁class . ▁ ▁Two ▁months ▁after ▁the ▁accus ations ▁proved ▁false , ▁he ▁encountered ▁a ▁golden ▁opportunity ▁that ▁allowed ▁him ▁to ▁receive ▁his ▁government ▁rank ▁back . ▁An ▁en voy ▁from ▁China ▁was ▁visit ing ▁the ▁King ▁of ▁Jose on , ▁but ▁there ▁was ▁no ▁one ▁appropriate ▁and ▁qualified ▁to ▁serve ▁as ▁the ▁interpreter ▁during ▁the ▁visit . ▁Ch oe ▁Se jin ▁was ▁chosen ▁as ▁the ▁interpreter ▁rel uct antly , ▁but ▁he ▁successfully ▁completed ▁the ▁task ▁and ▁was ▁recognized ▁for ▁his ▁tal ents . ▁The |
▁King ▁recognized ▁his ▁works , ▁and ▁he ▁was ▁able ▁to ▁further ▁his ▁career . ▁ ▁Upon ▁his ▁death , ▁a ▁scholar ▁named ▁Kim ▁An ▁G ook ▁dedicated ▁a ▁poem ▁to ▁Ch oe . ▁The ▁poem ▁is ▁called ▁" Cho i ▁D ong ▁Ji ▁Se ▁Jin ▁Man " ▁( <0xE5> <0xB4> <0x94> 同 知 世 <0xE7> <0x8F> <0x8D> <0xE6> <0x8C> <0xBD> ) ▁and ▁is ▁widely ▁known ▁because ▁of ▁the ▁information ▁it ▁holds ▁about ▁Ch oe ▁Se jin . ▁Because ▁there ▁are ▁few ▁records ▁left ▁about ▁Ch oe , ▁this ▁poem ▁provides ▁one ▁of ▁the ▁best ▁sources ▁of ▁details ▁about ▁Ch oe ' s ▁life ▁through ▁the ▁eyes ▁of ▁his ▁friend , ▁Kim . ▁ ▁Hun m ong ▁Jah oe ▁( 훈 몽 자 회 ) ▁and ▁his ▁works ▁with ▁hang ul ▁▁ ▁Ch oe ▁Se jin ▁is ▁mostly ▁known ▁for ▁his ▁ 1 5 2 7 ▁work , ▁Hun m ong ▁Jah oe ▁( 훈 몽 자 회 ). ▁It ▁is ▁a ▁text book ▁for ▁children ▁to ▁learn ▁the ▁Chinese ▁characters , ▁and ▁is ▁known ▁to ▁be ▁very ▁practical ▁in ▁its ▁teach ings . ▁During ▁the ▁Jose on ▁Era , ▁liter acy ▁in ▁Chinese ▁was ▁an ▁essential ▁skill ▁for ▁adv ancement ▁in ▁society . ▁Chinese ▁was ▁the ▁dominant ▁language ▁of ▁literature ▁at ▁this ▁time , ▁and ▁children ▁were ▁taught ▁Chinese ▁from ▁an ▁early ▁age ▁to ▁prepare ▁for ▁the ▁future . ▁Although ▁hang ul , ▁the ▁Korean ▁orth ography , ▁existed ▁by ▁this ▁time , ▁it ▁was ▁not ▁widely ▁used ▁in ▁the ▁country . ▁Ch |
oe ▁wanted ▁to ▁promote ▁the ▁usage ▁of ▁hang ul ▁through ▁his ▁work ▁Hun m ong ▁Jah oe . ▁As ▁a ▁text book ▁for ▁children ▁to ▁learn ▁Chinese , ▁Hun m ong ▁Jah oe ▁incorpor ated ▁hang ul ▁in ▁the ▁text book ▁to ▁promote ▁both ▁the ▁learning ▁of ▁Chinese ▁characters , ▁as ▁well ▁as ▁hang ul . ▁The ▁Chinese ▁characters ▁were ▁annot ated ▁in ▁hang ul , ▁and ▁in ▁order ▁for ▁one ▁to ▁understand ▁and ▁learn ▁the ▁Chinese ▁characters , ▁one ▁must ▁have ▁a ▁full ▁grasp ▁of ▁hang ul ▁first ▁to ▁compreh end ▁the ▁annotations . ▁Ch oe ▁wanted ▁people ▁to ▁use ▁hang ul ▁more ▁extens ively , ▁and ▁he ▁thought ▁that ▁this ▁would ▁encou rage ▁people ▁to ▁take ▁some ▁time ▁to ▁fully ▁learn ▁hang ul , ▁before ▁starting ▁to ▁learn ▁Chinese . ▁He ▁wrote ▁that ▁" it ▁would ▁take ▁[ only ▁a ▁single ▁day ] ▁to ▁learn ▁H ang ul ", ▁comment ing ▁on ▁the ▁simplicity ▁of ▁hang ul , ▁and ▁afterwards , ▁one ▁would ▁be ▁able ▁to ▁learn ▁Chinese ▁on ▁their ▁own ▁without ▁an ▁instruct or ▁if ▁one ▁knew ▁hang ul ▁and ▁util ized ▁his ▁text book . ▁ ▁This ▁book ▁was ▁known ▁at ▁the ▁time ▁for ▁being ▁revolution ary ▁for ▁its ▁practical ity ▁and ▁cre ativity . ▁The ▁two ▁widely - used ▁works ▁for ▁learning ▁Chinese ▁characters ▁during ▁his ▁time ▁were ▁called ▁" Th ous and ▁Character ▁Classic " ▁and ▁" Y oo ▁H ap ". ▁The ▁" Th ous and ▁Character ▁Classic " ▁was ▁considered ▁very ▁ted ious ▁and ▁contained |
▁words ▁that ▁were ▁concept ual ▁and ▁not ▁suitable ▁for ▁daily ▁use , ▁while ▁the ▁other ▁text ▁" Y oo ▁H ap " ▁was ▁thought ▁to ▁be ▁not ▁suitable ▁for ▁daily ▁instruction . ▁Hun m ong ▁Jah oe ▁attempted ▁to ▁supp lement ▁these ▁weak ness es , ▁while ▁combining ▁their ▁strength s ▁in ▁the ▁bread th ▁of ▁content . ▁The ▁" Th ous and ▁Character ▁Classic " ▁contained ▁ 1 , 0 0 0 ▁characters , ▁while ▁Hun m ong ▁Jah oe ▁contained ▁ 3 , 3 6 0 ▁characters . ▁It ▁also ▁ordered ▁the ▁Chinese ▁characters ▁with ▁relation ▁to ▁its ▁mean ings : ▁Chinese ▁characters ▁with ▁similar ▁mean ings ▁were ▁grouped ▁together ▁to ▁ease ▁the ▁process ▁of ▁learning . ▁ ▁As ▁one ▁of ▁the ▁ph on et icians ▁in ▁the ▁history ▁of ▁the ▁Jose on ▁D ynast y , ▁he ▁compiled ▁the ▁order ▁of ▁the ▁Korean ▁letters ▁in ▁Hun m ong ▁Jah oe . ▁The ▁first ▁eight ▁characters ▁in ▁the ▁order ▁that ▁is ▁presented ▁in ▁this ▁work ▁are ▁character ized ▁as ▁sounds ▁that ▁are ▁" used ▁for ▁both ▁the ▁initial ▁and ▁the ▁final ▁sounds ". ▁The ▁next ▁eight ▁set ▁of ▁characters ▁are ▁described ▁as ▁" th ose ▁used ▁only ▁for ▁the ▁initial ▁sounds ". ▁These ▁eight ▁characters ▁that ▁occur ▁initially ▁are ▁ordered ▁as ▁the ▁following : ▁" M olar ▁[ kh ], ▁the ▁T ong ue ▁[ th ], ▁the ▁Lip ▁[ ph ], ▁the ▁To oth ▁[ c ▁ch ], ▁the ▁Half ▁To oth ▁[ z ], ▁and ▁the ▁Th ro at |
▁[ 0 ] ". ▁Only ▁the ▁order ▁of ▁these ▁eight ▁characters ▁have ▁been ▁retained ▁until ▁the ▁present ▁and ▁the ▁order ▁of ▁the ▁other ▁characters ▁as ▁proposed ▁by ▁Ch oe ▁have ▁been ▁alter ed . ▁The ▁reason ▁for ▁the ▁change ▁of ▁the ▁order ▁of ▁the ▁other ▁characters ▁are ▁un ident ifiable . ▁Ch oe ▁also ▁ordered ▁the ▁v ow els ▁in ▁H ang ul . ▁He ▁ordered ▁them ▁according ▁to ▁sequence ▁in ▁which ▁we ▁open ▁our ▁mouth ▁to ▁art ic ulate ▁these ▁v ow els . ▁His ▁ordering ▁of ▁the ▁v ow els ▁is ▁the ▁order ▁that ▁is ▁currently ▁used ▁in ▁present ▁day ▁Korea . ▁ ▁Hun m ong ▁Jah oe ▁has ▁been ▁repub lished ▁ 1 0 ▁times ▁over ▁the ▁time ▁period ▁of ▁ 4 0 0 ▁years . ▁It ▁was ▁the ▁most ▁reprodu ced ▁Chinese ▁text book ▁of ▁the ▁Jose on ▁Era , ▁and ▁it ▁was ▁also ▁widely ▁used ▁in ▁Japan . ▁ ▁Career ▁and ▁legacy ▁ ▁Despite ▁Ch oe ' s ▁social ▁class ▁and ▁the ▁difficulties ▁he ▁faced ▁during ▁his ▁lifetime , ▁the ▁records ▁we ▁have ▁of ▁him ▁indicate ▁his ▁significance ▁and ▁influence ▁on ▁Korean ▁hang ul , ▁the ▁education ▁of ▁Chinese ▁characters , ▁and ▁the ▁field ▁of ▁lingu istics . ▁Sch ol ars ▁that ▁belong ▁to ▁the ▁middle ▁class ▁rarely ▁get ▁recognized ▁for ▁their ▁works , ▁and ▁no ▁historical ▁records ▁are ▁ever ▁kept ▁of ▁middle - class ▁citizens . ▁The ▁available ▁records ▁of ▁Ch oe ▁are ▁very ▁scar ce , ▁however , ▁the ▁sole ▁presence ▁of ▁even ▁a ▁min usc |
ule ▁historical ▁record ▁indicates ▁that ▁he ▁was ▁an ▁influ ential ▁figure ▁in ▁the ▁history ▁of ▁the ▁Korean ▁language . ▁ ▁When ▁his ▁reputation ▁was ▁restored ▁after ▁he ▁served ▁as ▁a ▁transl ator ▁to ▁the ▁king ▁during ▁a ▁visit ▁by ▁the ▁Chinese ▁en voy ▁, ▁Ch oe ▁successfully ▁built ▁his ▁career ▁as ▁a ▁transl ator , ▁interpreter ▁and ▁lingu ist . ▁His ▁lingu istic ▁talent ▁is ▁even ▁recorded ▁in ▁the ▁Jung j ong ▁of ▁Jose on ▁Chron icles , ▁which ▁is ▁a ▁chron ological ▁record ▁of ▁King ▁Jung j ong ' s ▁historical ▁reign s ▁from ▁ 1 5 0 6 ▁to ▁ 1 5 4 4 . ▁Y oo ▁So on , ▁a ▁prime ▁minister ▁of ▁the ▁Jose on ▁D ynast y , ▁wrote ▁that ▁Ch oe ▁was ▁" the ▁best ▁in ▁the ▁nation ▁when ▁it ▁comes ▁to ▁Chinese ▁writing ▁and ▁pron unci ation " ▁and ▁that ▁he ▁was ▁wor ried ▁that ▁there ▁was ▁no ▁one ▁to ▁succeed ▁him ▁to ▁translate ▁and ▁respond ▁to ▁documents ▁sent ▁from ▁China . ▁Thus , ▁Y oo ▁So on ▁wrote ▁a ▁pet ition ▁to ▁the ▁King , ▁asking ▁him ▁to ▁pick ▁approximately ▁six ▁tal ented ▁individuals ▁to ▁be ▁instruct ed ▁by ▁Ch oe ▁Se jin , ▁in ▁order ▁to ▁make ▁sure ▁that ▁Ch oe ' s ▁legacy ▁was ▁maintained . ▁The ▁King ▁also ▁wrote ▁about ▁his ▁wor ries ▁that ▁Ch oe ▁might ▁be ▁the ▁only ▁person ▁capable ▁of ▁handling ▁proper ▁relations ▁with ▁China . ▁ ▁In ▁addition ▁to ▁his ▁skills ▁as ▁a ▁transl ator ▁and ▁interpreter , |
▁his ▁works ▁also ▁contain ▁his ▁legacy . ▁He ▁published ▁a ▁lot ▁in ▁the ▁field ▁of ▁lingu istics , ▁especially ▁in ▁the ▁real m ▁of ▁Chinese ▁lingu istics ▁directed ▁towards ▁a ▁Korean ▁audience . ▁He ▁translated ▁numerous ▁works ▁such ▁as ▁" B ak ▁T ong sa ", ▁Inter pre ter ▁Park , ▁which ▁was ▁a ▁Chinese ▁text book , ▁and ▁elabor ated ▁on ▁its ▁research ▁through ▁his ▁own ▁work ▁" S as ung ▁T ong ha e ", ▁Exp la ining ▁the ▁Four ▁S ounds . ▁ ▁Comment ary ▁on ▁Ch oe ▁Se jin ▁and ▁his ▁works ▁ ▁There ▁are ▁very ▁scar ce ▁resources ▁available ▁to ▁shed ▁light ▁onto ▁Ch oe ▁Se jin ' s ▁life . ▁One ▁work ▁that ▁reve als ▁a ▁lot ▁about ▁Ch oe ' s ▁character ▁and ▁his ▁influence ▁during ▁his ▁time ▁is ▁a ▁poem ▁written ▁as ▁a ▁e ul ogy ▁by ▁one ▁of ▁his ▁friends , ▁Kim ▁An k ook . ▁The ▁poem ▁was ▁written ▁in ▁ 1 5 4 2 ▁after ▁Ch oe ' s ▁death , ▁and ▁is ▁titled ▁" Cho e ▁D ong ▁Ji ▁Se ▁Jin ▁Man " ▁( 최 동 지 세 진 만 , ▁ <0xE5> <0xB4> <0x94> 同 知 世 <0xE7> <0x8F> <0x8D> <0xE6> <0x8C> <0xBD> ). ▁ ▁This ▁is ▁a ▁poem ▁that ▁reflect s ▁Kim ▁An k ook ' s ▁sorrow ▁upon ▁his ▁friend ▁Ch oe ' s ▁death . ▁This ▁is ▁a ▁poem ▁that ▁is ▁one ▁of ▁the ▁most ▁known ▁among ▁Korean ▁lingu istics , ▁because ▁there ▁is ▁a ▁lot ▁of |
▁information ▁about ▁Ch oe ▁pack ed ▁into ▁a ▁single ▁poem . ▁According ▁to ▁Kim , ▁it ▁can ▁be ▁known ▁that ▁Ch oe ▁went ▁through ▁a ▁lot ▁of ▁hard ships ▁during ▁the ▁ 4 0 ▁years ▁he ▁served ▁as ▁a ▁government ▁official , ▁and ▁eventually ▁lived ▁a ▁long ▁life , ▁" h aving ▁seen ▁the ▁death ▁of ▁many ▁of ▁his ▁loved ▁ones ". ▁Another ▁line ▁of ▁the ▁poem , ▁" who ▁will ▁I ▁discuss ▁and ▁debate ▁with ▁when ▁compos ing ▁diplom at ▁documents ? ", ▁indicates ▁that ▁he ▁was ▁an ▁important ▁figure ▁in ▁international ▁diplom acy , ▁especially ▁with ▁respect ▁to ▁translation ▁and ▁interpretation . ▁Last ly , ▁Kim ▁notes ▁that ▁his ▁accomplish ments ▁will ▁last ▁far ▁into ▁the ▁future , ▁since ▁his ▁works ▁are ▁considered ▁as ▁" a ▁great ▁service ▁to ▁the ▁future ". ▁This ▁highlight s ▁Ch oe ' s ▁influence ▁in ▁the ▁field ▁of ▁Korean ▁lingu istics . ▁ ▁Other ▁Notable ▁Works ▁ ▁In ▁addition ▁to ▁Hun m ong ▁Jah oe , ▁Ch oe ▁also ▁composed ▁ 1 7 ▁research ▁publications ▁over ▁the ▁course ▁of ▁ 4 0 ▁years ▁in ▁total . ▁A ▁few ▁of ▁his ▁most ▁notable ▁works ▁are : ▁▁ ▁S as ung ▁T ong ha e ▁( 사 성 통 해 ) ▁( 1 5 1 7 ) ▁marks ▁the ▁in ton ations , ▁and ▁the ▁correct ▁pron unci ations ▁of ▁Chinese ▁characters ▁in ▁hang ul . ▁It ▁also ▁includes ▁records ▁of ▁ 4 5 0 ▁Korean ▁words ▁in ▁hang ul , ▁and ▁is ▁an ▁important ▁source ▁for |
▁the ▁research ▁on ▁the ▁history ▁of ▁the ▁Korean ▁language . ▁ ▁So h ak ▁Py un m ong ▁( 소 학 편 몽 ) ▁( 1 5 3 7 ) ▁is ▁a ▁text book ▁for ▁Chinese ▁language ▁learn ers , ▁dedicated ▁to ▁the ▁King . ▁ ▁Un ho e ▁Ok py un ▁( 운 회 옥 편 ) ▁( 1 5 3 7 ) ▁is ▁a ▁supp lement ary ▁material ▁published ▁to ▁add ▁on ▁to ▁the ▁works ▁in ▁S as ung ▁T ong ha e . ▁ ▁Ye oh yo ▁Ky ung ▁( 여 효 경 ) ▁( 1 5 4 1 ) ▁was ▁one ▁of ▁his ▁last ▁works , ▁written ▁when ▁he ▁was ▁ 7 6 . ▁ ▁Ky ungs ung ▁Ji ▁( 경 성 지 ) ▁( 1 5 4 1 ), ▁a ▁work ▁about ▁the ▁Nan j ing ▁city ▁in ▁China , ▁was ▁one ▁of ▁his ▁last ▁works ▁before ▁he ▁died ▁at ▁the ▁age ▁of ▁ 7 7 . ▁ ▁See ▁also ▁▁ ▁List ▁of ▁Korea - related ▁topics ▁ ▁History ▁of ▁Korea ▁ ▁Jose on ▁D ynast y ▁ ▁References ▁▁ ▁Category : 1 4 7 3 ▁birth s ▁Category : 1 5 4 2 ▁death s ▁Category : Jose on ▁D ynast y ▁people ▁Category : L ingu ists ▁from ▁Korea ▁Category : Cho e ▁cl an ▁of ▁Go es an <0x0A> </s> ▁Mag nes ium ▁trans por ters ▁are ▁prote ins ▁that ▁transport ▁mag nes ium ▁across ▁the ▁cell ▁memb rane . ▁All ▁forms ▁of ▁life ▁require |
▁mag nes ium , ▁yet ▁the ▁mole cular ▁mechan isms ▁of ▁M g 2 + ▁u pt ake ▁from ▁the ▁environment ▁and ▁the ▁distribution ▁of ▁this ▁vital ▁element ▁within ▁the ▁organ ism ▁are ▁only ▁slowly ▁being ▁el uc id ated . ▁ ▁The ▁ATP ase ▁function ▁of ▁M gt A ▁is ▁highly ▁card i ol ip in ▁dependent ▁and ▁has ▁been ▁shown ▁to ▁detect ▁free ▁mag nes ium ▁in ▁the ▁ μ M ▁range ▁▁ ▁In ▁b acter ia , ▁M g 2 + ▁is ▁probably ▁mainly ▁supplied ▁by ▁the ▁Cor A ▁protein ▁and , ▁where ▁the ▁Cor A ▁protein ▁is ▁absent , ▁by ▁the ▁M gt E ▁protein . ▁In ▁ye ast ▁the ▁initial ▁u pt ake ▁is ▁via ▁the ▁Al r 1 p ▁and ▁Al r 2 p ▁prote ins , ▁but ▁at ▁this ▁stage ▁the ▁only ▁internal ▁M g 2 + ▁distrib uting ▁protein ▁identified ▁is ▁Mrs 2 p . ▁Within ▁the ▁proto zo a ▁only ▁one ▁M g 2 + ▁trans porter ▁( X nt Ap ) ▁has ▁been ▁identified . ▁In ▁met az oa , ▁Mrs 2 p ▁and ▁M gt E ▁hom olog ues ▁have ▁been ▁identified , ▁along ▁with ▁two ▁novel ▁M g 2 + ▁transport ▁systems ▁TR PM 6 / TR PM 7 ▁and ▁P CL N - 1 . ▁Finally , ▁in ▁plants , ▁a ▁family ▁of ▁Mrs 2 p ▁hom olog ues ▁has ▁been ▁identified ▁along ▁with ▁another ▁novel ▁protein , ▁At M H X . ▁ ▁E volution ▁▁ ▁The ▁evolution ▁of |
▁M g 2 + ▁transport ▁appears ▁to ▁have ▁been ▁rather ▁complicated . ▁Prote ins ▁apparently ▁based ▁on ▁M gt E ▁are ▁present ▁in ▁b acter ia ▁and ▁met az oa , ▁but ▁are ▁missing ▁in ▁fung i ▁and ▁plants , ▁whilst ▁prote ins ▁apparently ▁related ▁to ▁Cor A ▁are ▁present ▁in ▁all ▁of ▁these ▁groups . ▁The ▁two ▁active ▁transport ▁trans por ters ▁present ▁in ▁b acter ia , ▁M gt A ▁and ▁M gt B , ▁do ▁not ▁appear ▁to ▁have ▁any ▁hom ologies ▁in ▁higher ▁organ isms . ▁There ▁are ▁also ▁M g 2 + ▁transport ▁systems ▁that ▁are ▁found ▁only ▁in ▁the ▁higher ▁organ isms . ▁ ▁Types ▁▁ ▁There ▁are ▁a ▁large ▁number ▁of ▁prote ins ▁yet ▁to ▁be ▁identified ▁that ▁transport ▁M g 2 + . ▁Even ▁in ▁the ▁best ▁studied ▁e uk ary ote , ▁ye ast , ▁Bor rel ly ▁has ▁reported ▁a ▁M g 2 + / H + ▁ex ch anger ▁without ▁an ▁associated ▁protein , ▁which ▁is ▁probably ▁local ised ▁to ▁the ▁Gol gi . ▁At ▁least ▁one ▁other ▁major ▁M g 2 + ▁trans porter ▁in ▁ye ast ▁is ▁still ▁un account ed ▁for , ▁the ▁one ▁affect ing ▁M g 2 + ▁transport ▁in ▁and ▁out ▁of ▁the ▁ye ast ▁vac u ole . ▁In ▁higher , ▁mult ic ell ular ▁organ isms , ▁it ▁seems ▁that ▁many ▁M g 2 + ▁transport ing ▁prote ins ▁await ▁discovery . ▁ ▁The ▁Cor A - domain - cont aining ▁M g 2 |
+ ▁trans por ters ▁( Cor A , ▁Al r - like ▁and ▁Mrs 2 - like ) ▁have ▁a ▁similar ▁but ▁not ▁identical ▁array ▁of ▁aff in ities ▁for ▁div al ent ▁c ations . ▁In ▁fact , ▁this ▁observation ▁can ▁be ▁extended ▁to ▁all ▁of ▁the ▁M g 2 + ▁trans por ters ▁identified ▁so ▁far . ▁This ▁similarity ▁suggests ▁that ▁the ▁basic ▁properties ▁of ▁M g 2 + ▁strongly ▁influence ▁the ▁possible ▁mechan isms ▁of ▁recognition ▁and ▁transport . ▁However , ▁this ▁observation ▁also ▁suggests ▁that ▁using ▁other ▁metal ▁ ions ▁as ▁trac ers ▁for ▁M g 2 + ▁u pt ake ▁will ▁not ▁necessarily ▁produce ▁results ▁compar able ▁to ▁the ▁trans porter ' s ▁ability ▁to ▁transport ▁M g 2 + . ▁Ide ally , ▁M g 2 + ▁should ▁be ▁measured ▁directly . ▁ ▁Since ▁ 2 8 M g 2 + ▁is ▁pract ically ▁un ob tain able , ▁much ▁of ▁the ▁old ▁data ▁will ▁need ▁to ▁be ▁re inter pre ted ▁with ▁new ▁tools ▁for ▁meas uring ▁M g 2 + ▁transport , ▁if ▁different ▁trans por ters ▁are ▁to ▁be ▁compared ▁directly . ▁The ▁pione ering ▁work ▁of ▁Kol ise k ▁and ▁Fro sch auer ▁using ▁mag - f ura ▁ 2 ▁has ▁shown ▁that ▁free ▁M g 2 + ▁can ▁be ▁reli ably ▁measured ▁in ▁v ivo ▁in ▁some ▁systems . ▁By ▁returning ▁to ▁the ▁analysis ▁of ▁Cor A ▁with ▁this ▁new ▁tool , ▁we ▁have ▁gained ▁an ▁important ▁bas eline ▁for ▁the ▁analysis |
▁of ▁new ▁M g 2 + ▁transport ▁systems ▁as ▁they ▁are ▁discovered . ▁However , ▁it ▁is ▁important ▁that ▁the ▁amount ▁of ▁trans porter ▁present ▁in ▁the ▁memb rane ▁is ▁accur ately ▁determined ▁if ▁compar isons ▁of ▁transport ▁cap ability ▁are ▁to ▁be ▁made . ▁This ▁b acter ial ▁system ▁might ▁also ▁be ▁able ▁to ▁provide ▁some ▁utility ▁for ▁the ▁analysis ▁of ▁e uk ary otic ▁M g 2 + ▁transport ▁prote ins , ▁but ▁differences ▁in ▁bi ological ▁systems ▁of ▁pro k ary otes ▁and ▁e uk ary otes ▁will ▁have ▁to ▁be ▁considered ▁in ▁any ▁experiment . ▁ ▁Function ▁▁ ▁Compar ing ▁the ▁functions ▁of ▁the ▁character ised ▁M g 2 + ▁transport ▁prote ins ▁is ▁currently ▁almost ▁impossible , ▁even ▁though ▁the ▁prote ins ▁have ▁been ▁investig ated ▁in ▁different ▁bi ological ▁systems ▁using ▁different ▁method ologies ▁and ▁techn ologies . ▁F inding ▁a ▁system ▁where ▁all ▁the ▁prote ins ▁can ▁be ▁compared ▁directly ▁would ▁be ▁a ▁major ▁advance . ▁If ▁the ▁prote ins ▁could ▁be ▁shown ▁to ▁be ▁functional ▁in ▁b acter ia ▁( S . ▁ty ph im ur ium ), ▁then ▁a ▁combination ▁of ▁the ▁techniques ▁of ▁mag - f ura ▁ 2 , ▁quant ification ▁of ▁protein ▁in ▁the ▁en velope ▁memb rane , ▁and ▁structure ▁of ▁the ▁prote ins ▁( X - ray ▁cry stal ▁or ▁cry o - TE M ) ▁might ▁allow ▁the ▁determ ination ▁of ▁the ▁basic ▁mechan isms ▁involved ▁in ▁the ▁recognition ▁and ▁transport ▁of ▁the ▁M g 2 + ▁ion |
. ▁However , ▁perhaps ▁the ▁best ▁advance ▁would ▁be ▁the ▁development ▁of ▁methods ▁allowing ▁the ▁measurement ▁of ▁the ▁protein ' s ▁function ▁in ▁the ▁patch - cl amp ▁system ▁using ▁artificial ▁memb ran es . ▁ ▁B acter ia ▁ ▁Early ▁research ▁In ▁ 1 9 6 8 , ▁L usk ▁described ▁the ▁limitation ▁of ▁b acter ial ▁( E scher ich ia ▁col i ) ▁growth ▁on ▁M g 2 + - po or ▁media , ▁suggesting ▁that ▁b acter ia ▁required ▁M g 2 + ▁and ▁were ▁likely ▁to ▁act ively ▁take ▁this ▁ion ▁from ▁the ▁environment . ▁The ▁following ▁year , ▁the ▁same ▁group ▁and ▁another ▁group , ▁Silver , ▁independently ▁described ▁the ▁u pt ake ▁and ▁eff l ux ▁of ▁M g 2 + ▁in ▁met abol ically ▁active ▁E . ▁col i ▁cells ▁using ▁ 2 8 M g 2 + . ▁By ▁the ▁end ▁of ▁ 1 9 7 1 , ▁two ▁papers ▁had ▁been ▁published ▁describing ▁the ▁inter ference ▁of ▁Co 2 + , ▁Ni 2 + ▁and ▁M n 2 + ▁on ▁the ▁transport ▁of ▁M g 2 + ▁in ▁E . ▁col i ▁and ▁in ▁Aer ob acter ▁aer ogen es ▁and ▁Bac ill us ▁meg ater ium . ▁In ▁the ▁last ▁major ▁development ▁before ▁the ▁cl oning ▁of ▁the ▁gen es ▁encoding ▁the ▁trans por ters , ▁it ▁was ▁discovered ▁that ▁there ▁was ▁a ▁second ▁M g 2 + ▁u pt ake ▁system ▁that ▁showed ▁similar ▁aff inity ▁and ▁transport ▁k inet ics |
▁to ▁the ▁first ▁system , ▁but ▁had ▁a ▁different ▁range ▁of ▁sens it iv ities ▁to ▁inter fer ing ▁c ations . ▁This ▁system ▁was ▁also ▁repr ess ible ▁by ▁high ▁ext rac ell ular ▁concentr ations ▁of ▁M g 2 + ▁. ▁ ▁Cor A ▁ ▁The ▁Cor A ▁gene ▁and ▁its ▁corresponding ▁protein ▁are ▁the ▁most ▁exhaust ively ▁studied ▁M g 2 + ▁transport ▁system ▁in ▁any ▁organ ism . ▁Most ▁of ▁the ▁published ▁literature ▁on ▁the ▁Cor A ▁gene ▁comes ▁from ▁the ▁labor atory ▁of ▁M . ▁E . ▁Mag u ire . ▁Rec ently ▁the ▁group ▁of ▁R . ▁J . ▁Schwe yen ▁made ▁a ▁significant ▁impact ▁on ▁the ▁understanding ▁of ▁M g 2 + ▁transport ▁by ▁Cor A . ▁The ▁gene ▁was ▁originally ▁named ▁after ▁the ▁c ob alt - res istant ▁phen ot ype ▁in ▁E . ▁col i ▁that ▁was ▁caused ▁by ▁the ▁gene ' s ▁in activ ation . ▁ ▁The ▁gene ▁was ▁gen et ically ▁identified ▁in ▁E . ▁col i ▁by ▁Park ▁et ▁al ., ▁but ▁wasn ' t ▁cl oned ▁until ▁H m iel ▁et ▁al . ▁isolated ▁the ▁Sal mon ella ▁enter ica ▁ser ov ar ▁Ty ph im ur ium ▁( S . ▁ty ph im ur ium ) ▁hom olog ue . ▁Later ▁it ▁would ▁be ▁shown ▁by ▁Smith ▁and ▁Mag u ire ▁that ▁the ▁Cor A ▁gene ▁was ▁present ▁in ▁ 1 7 gram - negative ▁b acter ia . ▁With ▁the ▁large ▁number ▁of ▁complete ▁gen |
ome ▁sequences ▁now ▁available ▁for ▁pro k ary otes , ▁Cor A ▁has ▁been ▁shown ▁to ▁be ▁virt ually ▁u bi quit ous ▁among ▁the ▁E ub acter ia , ▁as ▁well ▁as ▁being ▁widely ▁distributed ▁among ▁the ▁Arch ae a . ▁The ▁Cor A ▁loc us ▁in ▁E . ▁col i ▁contains ▁a ▁single ▁open ▁reading ▁frame ▁of ▁ 9 4 8 ▁nucle ot ides , ▁producing ▁a ▁protein ▁of ▁ 3 1 6 ▁am ino ▁ac ids . ▁This ▁protein ▁is ▁well ▁conser ved ▁amongst ▁the ▁E ub acter ia ▁and ▁Arch ae a . ▁Between ▁E . ▁col i ▁and ▁S . ▁ty ph im ur ium , ▁the ▁prote ins ▁are ▁ 9 8 % ▁identical , ▁but ▁in ▁more ▁dist antly ▁related ▁species , ▁the ▁similarity ▁falls ▁to ▁between ▁ 1 5 ▁and ▁ 2 0 %. ▁In ▁the ▁more ▁dist antly ▁related ▁gen es , ▁the ▁similarity ▁is ▁often ▁restricted ▁to ▁the ▁C - term inal ▁part ▁of ▁the ▁protein , ▁and ▁a ▁short ▁am ino ▁acid ▁mot if ▁G M N ▁within ▁this ▁region ▁is ▁very ▁highly ▁conser ved . ▁The ▁Cor A ▁domain , ▁also ▁known ▁as ▁P F 0 1 5 4 4 ▁in ▁the ▁p FA M ▁conser ved ▁protein ▁domain ▁database ▁( http :// web archive . loc . gov / all / 2 0 1 1 0 5 0 6 0 3 0 9 5 7 / http % 3 A // pf am . s anger . ac . uk |
/), ▁is ▁addition ally ▁present ▁in ▁a ▁wide ▁range ▁of ▁higher ▁organ isms , ▁and ▁these ▁trans por ters ▁will ▁be ▁review ed ▁below . ▁ ▁The ▁Cor A ▁gene ▁is ▁const itut ively ▁expressed ▁in ▁S . ▁ty ph im ur ium ▁under ▁a ▁wide ▁range ▁of ▁external ▁M g 2 + ▁concentr ations . ▁However , ▁recent ▁evidence ▁suggests ▁that ▁the ▁activity ▁of ▁the ▁protein ▁may ▁be ▁reg ulated ▁by ▁the ▁Pho P Q ▁two - component ▁regul atory ▁system . ▁This ▁sensor ▁respond s ▁to ▁low ▁external ▁M g 2 + ▁concentr ations ▁during ▁the ▁in fection ▁process ▁of ▁S . ▁ty ph im ur ium ▁in ▁humans . ▁In ▁low ▁external ▁M g 2 + ▁conditions , ▁the ▁Pho P Q ▁system ▁was ▁reported ▁to ▁suppress ▁the ▁function ▁of ▁Cor A ▁and ▁it ▁has ▁been ▁previously ▁shown ▁that ▁the ▁trans cription ▁of ▁the ▁alternative ▁M g 2 + ▁trans por ters ▁M gt A ▁and ▁M gt B ▁is ▁activ ated ▁in ▁these ▁conditions . ▁Cham n ong pol ▁and ▁Gro is man ▁suggest ▁that ▁this ▁allows ▁the ▁b acter ia ▁to ▁escape ▁metal ▁ion ▁to x icity ▁caused ▁by ▁the ▁transport ▁of ▁other ▁ ions , ▁particularly ▁Fe ( II ), ▁by ▁Cor A ▁in ▁the ▁absence ▁of ▁M g 2 + . ▁P app ▁and ▁Mag u ire ▁offer ▁a ▁conflic ting ▁report ▁on ▁the ▁source ▁of ▁the ▁to x icity . ▁ ▁The ▁figure ▁( not ▁to ▁scale ) ▁shows ▁the ▁originally ▁published ▁transm emb rane |
▁( TM ) ▁domain ▁topology ▁of ▁the ▁S . ▁ty ph im ur ium ▁Cor A ▁protein , ▁which ▁was ▁said ▁to ▁have ▁three ▁memb rane - sp anning ▁regions ▁in ▁the ▁C - term inal ▁part ▁of ▁the ▁protein ▁( sh own ▁in ▁blue ), ▁as ▁determined ▁by ▁Smith ▁et ▁al .. ▁Ev idence ▁for ▁Cor A ▁acting ▁as ▁a ▁hom ot et ram er ▁was ▁published ▁by ▁Warren ▁et ▁al . ▁in ▁ 2 0 0 4 . ▁In ▁December ▁ 2 0 0 5 ▁the ▁cry stal ▁structure ▁of ▁the ▁Cor A ▁channel ▁was ▁posted ▁to ▁the ▁R SC B ▁protein ▁structure ▁database . ▁The ▁results ▁showed ▁that ▁the ▁protein ▁has ▁two ▁T M ▁domains ▁and ▁exists ▁as ▁a ▁hom op ent amer , ▁in ▁direct ▁conflict ▁with ▁the ▁earlier ▁reports . ▁Follow ▁this ▁link ▁to ▁see ▁the ▁structure ▁in ▁ 3 D . ▁The ▁sol ub le ▁int rac ell ular ▁parts ▁of ▁the ▁protein ▁are ▁highly ▁charged , ▁containing ▁ 3 1 ▁posit ively ▁charged ▁and ▁ 5 3 ▁neg atively ▁charged ▁resid ues . ▁Con vers ely , ▁the ▁T M ▁domains ▁contain ▁only ▁one ▁charged ▁am ino ▁acid , ▁which ▁has ▁been ▁shown ▁to ▁be ▁un important ▁in ▁the ▁activity ▁of ▁the ▁trans porter . ▁From ▁mut agen esis ▁experiments , ▁it ▁appears ▁that ▁the ▁chem istry ▁of ▁the ▁M g 2 + ▁transport ▁re lies ▁on ▁the ▁hydro x yl ▁groups ▁l ining ▁the ▁inside ▁of ▁the ▁transport ▁p ore ; ▁there ▁is ▁also ▁an |
▁absolute ▁requirement ▁for ▁the ▁G M N ▁mot if ▁( sh own ▁in ▁red ). ▁ ▁Before ▁the ▁activity ▁of ▁Cor A ▁could ▁be ▁studied ▁in ▁v ivo , ▁any ▁other ▁M g 2 + ▁transport ▁systems ▁in ▁the ▁b acter ial ▁host ▁had ▁to ▁be ▁identified ▁and ▁in activ ated ▁or ▁deleted ▁( see ▁below ). ▁A ▁stra in ▁of ▁S . ▁ty ph im ur ium ▁containing ▁a ▁functional ▁Cor A ▁gene ▁but ▁lack ing ▁M gt A ▁and ▁M gt B ▁was ▁constructed ( also ▁see ▁below ), ▁and ▁the ▁u pt ake ▁k inet ics ▁of ▁the ▁trans porter ▁were ▁anal ys ed . ▁This ▁stra in ▁showed ▁nearly ▁normal ▁growth ▁rates ▁on ▁standard ▁media ▁( 5 0 ▁ μ M ▁M g 2 + ), ▁but ▁the ▁removal ▁of ▁all ▁three ▁gen es ▁created ▁a ▁b acter ial ▁stra in ▁requiring ▁ 1 0 0 ▁m M ▁external ▁M g 2 + ▁for ▁normal ▁growth . ▁ ▁M g 2 + ▁is ▁transport ed ▁into ▁cells ▁containing ▁only ▁the ▁Cor A ▁transport ▁system ▁with ▁similar ▁k inet ics ▁and ▁c ation ▁sens it iv ities ▁as ▁the ▁M g 2 + ▁u pt ake ▁described ▁in ▁the ▁earlier ▁papers , ▁and ▁has ▁addition ally ▁been ▁quant ified ( see ▁table ). ▁The ▁u pt ake ▁of ▁M g 2 + ▁was ▁seen ▁to ▁plate au ▁as ▁in ▁earlier ▁studies , ▁and ▁although ▁no ▁actual ▁mechanism ▁for ▁the ▁decrease ▁in ▁transport ▁has ▁been ▁determined , ▁so ▁it ▁has ▁been |
▁assumed ▁that ▁the ▁protein ▁is ▁in activ ated . ▁Co 2 + ▁and ▁Ni 2 + ▁are ▁to xic ▁to ▁S . ▁ty ph im ur ium ▁cells ▁containing ▁a ▁functional ▁Cor A ▁protein ▁and ▁this ▁to x icity ▁st ems ▁from ▁the ▁blocking ▁of ▁M g 2 + ▁u pt ake ▁( comp et itive ▁in hib ition ) ▁and ▁the ▁accum ulation ▁of ▁these ▁ ions ▁inside ▁the ▁cell . ▁Co 2 + ▁and ▁Ni 2 + ▁have ▁been ▁shown ▁to ▁be ▁transport ed ▁by ▁Cor A ▁by ▁using ▁radio active ▁trac er ▁analysis , ▁although ▁with ▁lower ▁aff in ities ▁( km ) ▁and ▁veloc ities ▁( V max ) ▁than ▁for ▁M g 2 + ▁( see ▁table ). ▁The ▁km ▁values ▁for ▁Co 2 + ▁and ▁Ni 2 + ▁are ▁significantly ▁above ▁those ▁expected ▁to ▁be ▁encountered ▁by ▁the ▁cells ▁in ▁their ▁normal ▁environment , ▁so ▁it ▁is ▁unlikely ▁that ▁the ▁Cor A ▁transport ▁system ▁medi ates ▁the ▁u pt ake ▁of ▁these ▁ ions ▁under ▁natural ▁conditions . ▁To ▁date , ▁the ▁evidence ▁for ▁M n 2 + ▁transport ▁by ▁Cor A ▁is ▁limited ▁to ▁E . ▁col i . ▁ ▁The ▁table ▁lists ▁the ▁transport ▁k inet ics ▁of ▁the ▁Cor A ▁M g 2 + ▁transport ▁system . ▁This ▁table ▁has ▁been ▁compiled ▁from ▁the ▁publications ▁of ▁S nav ely ▁et ▁al . ▁( 1 9 8 9 b ), ▁Gib son ▁et ▁al . ▁( 1 9 9 1 ) ▁and ▁Smith ▁et ▁al |
. ▁( 1 9 9 8 a ) ▁and ▁summar ises ▁the ▁kin etic ▁data ▁for ▁the ▁Cor A ▁transport ▁protein ▁expressed ▁from ▁the ▁wild ▁type ▁prom oter ▁in ▁b acter ia ▁lack ing ▁M gt A ▁and ▁M gt B . ▁km ▁and ▁V max ▁were ▁determined ▁at ▁ 2 0 ° C ▁as ▁the ▁u pt ake ▁of ▁M g 2 + ▁at ▁ 3 7 ° C ▁was ▁too ▁rapid ▁to ▁measure ▁accur ately . ▁ ▁Rec ently ▁the ▁M g 2 + - dependent ▁flu ores c ence ▁of ▁mag - f ura ▁ 2 ▁was ▁used ▁to ▁measure ▁the ▁free ▁M g 2 + ▁content ▁of ▁S . ▁ty ph im ur ium ▁cells ▁in ▁response ▁to ▁external ▁M g 2 + , ▁which ▁showed ▁that ▁Cor A ▁is ▁the ▁major ▁u pt ake ▁system ▁for ▁M g 2 + ▁in ▁b acter ia . ▁The ▁authors ▁also ▁showed ▁for ▁the ▁first ▁time ▁that ▁the ▁changes ▁in ▁the ▁electric ▁potential ▁( Δ Ψ ) ▁across ▁the ▁pl asma ▁memb rane ▁of ▁the ▁cell ▁affected ▁both ▁the ▁rate ▁of ▁M g 2 + ▁u pt ake ▁and ▁the ▁free ▁M g 2 + ▁content ▁of ▁the ▁cell ; ▁dep olar isation ▁suppress ed ▁transport , ▁while ▁hyper pol ar isation ▁increased ▁transport . ▁The ▁k inet ics ▁of ▁transport ▁were ▁defined ▁only ▁by ▁the ▁rate ▁of ▁change ▁of ▁free ▁M g 2 + ▁inside ▁the ▁cells ▁( 2 5 0 ▁ μ M ▁s − 1 ). |
▁Because ▁no ▁quant ification ▁of ▁the ▁amount ▁of ▁Cor A ▁protein ▁in ▁the ▁memb rane ▁was ▁made , ▁this ▁value ▁is ▁cannot ▁be ▁compared ▁with ▁other ▁experiments ▁on ▁M g 2 + ▁trans por ters . ▁ ▁The ▁eff l ux ▁of ▁M g 2 + ▁from ▁b acter ial ▁cells ▁was ▁first ▁observed ▁by ▁L usk ▁and ▁Kennedy ▁( 1 9 6 9 ) ▁and ▁is ▁medi ated ▁by ▁the ▁Cor A ▁M g 2 + ▁transport ▁system ▁in ▁the ▁presence ▁of ▁high ▁ext rac ell ular ▁concentr ations ▁of ▁M g 2 + . ▁The ▁eff l ux ▁can ▁also ▁be ▁triggered ▁by ▁Co 2 + , ▁M n 2 + ▁and ▁Ni 2 + , ▁although ▁not ▁to ▁the ▁same ▁degree ▁as ▁M g 2 + . ▁No ▁Co 2 + ▁eff l ux ▁through ▁the ▁Cor A ▁transport ▁system ▁was ▁observed . ▁The ▁process ▁of ▁M g 2 + ▁eff l ux ▁addition ally ▁requires ▁one ▁of ▁the ▁Cor B , ▁Cor C ▁or ▁Cor D ▁gen es . ▁The ▁mut ation ▁of ▁any ▁single ▁one ▁of ▁these ▁gen es ▁leads ▁to ▁a ▁Co 2 + ▁resistance ▁a ▁little ▁less ▁than ▁half ▁of ▁that ▁provided ▁by ▁a ▁Cor A ▁mut ant . ▁This ▁effect ▁may ▁be ▁due ▁to ▁the ▁in hib ition ▁of ▁M g 2 + ▁loss ▁that ▁would ▁otherwise ▁occur ▁in ▁the ▁presence ▁of ▁high ▁levels ▁of ▁Co 2 + . ▁It ▁is ▁currently ▁unknown ▁whether ▁M g 2 + ▁is ▁more ▁to xic ▁when ▁the ▁Cor |
BC D ▁gen es ▁are ▁deleted . ▁ ▁It ▁has ▁been ▁spec ulated ▁that ▁the ▁M g 2 + ▁ion ▁will ▁initially ▁interact ▁with ▁any ▁transport ▁protein ▁through ▁its ▁hyd r ation ▁shell . ▁Cob alt ▁( III ) ▁hex a amm ine , ▁Co ( III ) H ex , ▁is ▁a ▁c oval ently ▁bound ▁( non - lab ile ) ▁analog ▁for ▁the ▁first ▁shell ▁of ▁hyd r ation ▁for ▁several ▁div al ent ▁c ations , ▁including ▁M g 2 + . ▁The ▁radius ▁of ▁the ▁Co ( III ) H ex ▁mole c ule ▁is ▁ 2 4 4 ▁pm , ▁very ▁similar ▁to ▁the ▁ 2 5 0 ▁pm ▁radius ▁of ▁the ▁first ▁hyd r ation ▁shell ▁of ▁M g 2 + . ▁This ▁analog ▁is ▁a ▁pot ent ▁in hib itor ▁of ▁the ▁Cor A ▁transport ▁system , ▁more ▁so ▁than ▁M g 2 + , ▁Co 2 + ▁or ▁Ni 2 + . ▁The ▁additional ▁strength ▁of ▁the ▁Co ( III ) H ex ▁in hib ition ▁might ▁come ▁from ▁the ▁blocking ▁of ▁the ▁transport ▁p ore ▁due ▁to ▁the ▁in ability ▁of ▁the ▁protein ▁to ▁‘ de h yd rate ’ ▁the ▁substr ate . ▁It ▁was ▁also ▁shown ▁that ▁Co ( III ) H ex ▁was ▁not ▁transport ed ▁into ▁the ▁cells , ▁suggesting ▁that ▁at ▁least ▁partial ▁de h yd r ation ▁would ▁be ▁required ▁for ▁the ▁transport ▁of ▁the ▁normal ▁substr ate ▁( M g 2 + ). ▁Nick el ▁( |
II ) ▁hex a amm ine , ▁with ▁a ▁radius ▁of ▁ 2 5 5 ▁pm , ▁did ▁not ▁in hib it ▁the ▁Cor A ▁transport ▁system , ▁suggesting ▁a ▁maximum ▁size ▁limit ▁exists ▁for ▁the ▁binding ▁of ▁the ▁Cor A ▁substr ate ▁ion . ▁These ▁results ▁suggest ▁that ▁the ▁important ▁property ▁involved ▁in ▁the ▁recognition ▁of ▁M g 2 + ▁by ▁Cor A ▁is ▁the ▁size ▁of ▁the ▁ion ▁with ▁its ▁first ▁shell ▁of ▁hyd r ation . ▁Hence , ▁the ▁volume ▁change ▁generally ▁quoted ▁for ▁the ▁bare ▁to ▁hyd r ated ▁M g 2 + ▁ion ▁of ▁greater ▁than ▁ 5 0 0 - fold , ▁including ▁the ▁second ▁sphere ▁of ▁hyd r ation , ▁may ▁not ▁be ▁bi olog ically ▁relevant , ▁and ▁may ▁be ▁a ▁reason ▁for ▁the ▁first ▁sphere ▁volume ▁change ▁of ▁ 5 6 - fold ▁to ▁be ▁more ▁commonly ▁used . ▁ ▁M gt A ▁and ▁M gt B ▁The ▁presence ▁of ▁these ▁two ▁gen es ▁was ▁first ▁sus pected ▁when ▁Nelson ▁and ▁Kennedy ▁( 1 9 7 2 ) ▁showed ▁that ▁there ▁were ▁M g 2 + - re press ible ▁and ▁non - re press ible ▁M g 2 + ▁u pt ake ▁systems ▁in ▁E . ▁col i . ▁The ▁non - re press ible ▁u pt ake ▁of ▁M g 2 + ▁is ▁medi ated ▁by ▁the ▁Cor A ▁protein . ▁In ▁S . ▁ty ph im ur ium ▁the ▁repr ess ible ▁M g 2 + ▁u pt ake ▁was ▁eventually |
▁shown ▁to ▁be ▁via ▁the ▁M gt A ▁and ▁M gt B ▁prote ins . ▁ ▁Both ▁M gt A ▁and ▁M gt B ▁are ▁reg ulated ▁by ▁the ▁Pho P Q ▁system ▁and ▁are ▁act ively ▁trans cribed ▁during ▁the ▁process ▁of ▁in fection ▁of ▁human ▁patients ▁by ▁S . ▁ty ph im ur ium . ▁Although ▁neither ▁gene ▁is ▁required ▁for ▁path ogen icity , ▁the ▁M gt B ▁protein ▁does ▁enh ance ▁the ▁long - term ▁surv ival ▁of ▁the ▁path ogen ▁in ▁the ▁cell . ▁The ▁gen es ▁are ▁also ▁up reg ulated ▁in ▁vit ro ▁when ▁the ▁M g 2 + ▁concentration ▁falls ▁below ▁ 5 0 ▁ μ M ▁( S nav ely ▁et ▁al ., ▁ 1 9 9 1 a ). ▁Although ▁the ▁prote ins ▁have ▁km ▁values ▁similar ▁to ▁Cor A ▁and ▁transport ▁rates ▁approximately ▁ 1 0 ▁times ▁less , ▁the ▁gen es ▁may ▁be ▁part ▁of ▁a ▁M g 2 + ▁sc av eng ing ▁system . ▁Cham n ong pol ▁and ▁Gro is man ▁( 2 0 0 2 ) ▁presents ▁evidence ▁that ▁the ▁role ▁of ▁these ▁prote ins ▁may ▁be ▁to ▁compens ate ▁for ▁the ▁in activ ation ▁of ▁the ▁Cor A ▁protein ▁by ▁the ▁Pho P Q ▁regul on . ▁The ▁authors ▁suggest ▁that ▁the ▁Cor A ▁protein ▁is ▁in activ ated ▁to ▁allow ▁the ▁avoid ance ▁of ▁metal ▁to x icity ▁via ▁the ▁protein ▁in ▁the ▁low ▁M g 2 + ▁environments ▁S . ▁ty ph im ur |
ium ▁is ▁subject ed ▁to ▁by ▁cells ▁after ▁in fection . ▁ ▁The ▁prote ins ▁are ▁both ▁P - type ▁ATP ases ▁ ▁and ▁neither ▁gene ▁shows ▁any ▁similarity ▁to ▁Cor A . ▁The ▁M gt A ▁and ▁M gt B ▁prote ins ▁are ▁ 7 5 % ▁similar ▁( 5 0 % ▁identical ), ▁although ▁it ▁seems ▁that ▁M gt B ▁may ▁have ▁been ▁acquired ▁by ▁horizontal ▁gene ▁transfer ▁as ▁part ▁of ▁Sal mon ella ▁Path ogen icity ▁Island ▁ 3 . ▁The ▁T M ▁topology ▁of ▁the ▁M gt B ▁protein ▁has ▁been ▁experiment ally ▁determined , ▁showing ▁that ▁the ▁protein ▁has ▁ten ▁T M - sp anning ▁hel ices ▁with ▁the ▁term ini ▁of ▁the ▁protein ▁in ▁the ▁cy top las m ▁( see ▁figure ▁). ▁M gt A ▁is ▁present ▁in ▁widely ▁diver gent ▁b acter ia , ▁but ▁is ▁not ▁nearly ▁as ▁common ▁as ▁Cor A , ▁while ▁M gt B ▁appears ▁to ▁have ▁a ▁quite ▁restricted ▁distribution . ▁No ▁hypoth eses ▁for ▁the ▁unusual ▁distribution ▁have ▁been ▁suggested . ▁ ▁The ▁figure , ▁adapted ▁from ▁Smith ▁et ▁al . ▁( 1 9 9 3 b ), ▁shows ▁the ▁experiment ally ▁determined ▁memb rane ▁topology ▁of ▁the ▁M gt B ▁protein ▁in ▁S . ▁ty ph im ur ium . ▁The ▁T M ▁domains ▁are ▁shown ▁in ▁light ▁blue ▁and ▁the ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - ▁and ▁C - termin i ▁are ▁indicated . ▁The ▁figure ▁is ▁not ▁drawn ▁to ▁scale |
. ▁ ▁While ▁the ▁M gt A ▁and ▁M gt B ▁prote ins ▁are ▁very ▁similar , ▁they ▁do ▁show ▁some ▁minor ▁differences ▁in ▁activity . ▁M gt B ▁is ▁very ▁sensitive ▁to ▁temperature , ▁losing ▁all ▁activity ▁( with ▁regard ▁to ▁M g 2 + ▁transport ) ▁at ▁a ▁temperature ▁of ▁ 2 0 ° C . ▁Additionally , ▁M gt B ▁and ▁M gt A ▁are ▁in hib ited ▁by ▁different ▁ranges ▁of ▁c ations ▁( Table ▁A 1 0 . 1 ). ▁ ▁The ▁table ▁lists ▁c ation ▁transport ▁characteristics ▁of ▁the ▁M gt A ▁and ▁M gt B ▁prote ins ▁in ▁S . ▁ty ph im ur ium ▁as ▁well ▁as ▁the ▁kin etic ▁data ▁for ▁the ▁M gt A ▁and ▁M gt B ▁transport ▁prote ins ▁at ▁ 3 7 ° C . ▁The ▁V max ▁numbers ▁listed ▁in ▁parentheses ▁are ▁those ▁for ▁u pt ake ▁at ▁ 2 0 ° C . ▁The ▁in hib ition ▁of ▁M g 2 + ▁transport ▁by ▁M n 2 + ▁via ▁M gt A ▁showed ▁unusual ▁k inet ics ▁( see ▁Figure ▁ 1 ▁of ▁S nav ely ▁et ▁al ., ▁ 1 9 8 9 b ) ▁ ▁The ▁M gt A ▁and ▁M gt B ▁prote ins ▁are ▁ATP ases , ▁using ▁one ▁mole c ule ▁of ▁ATP ▁per ▁transport ▁cycle , ▁whereas ▁the ▁M g 2 + ▁u pt ake ▁via ▁Cor A ▁is ▁simply ▁electro chem ically ▁fav ou rable . ▁Cham n |
ong pol ▁and ▁Gro is man ▁( 2 0 0 2 ) ▁have ▁suggested ▁that ▁the ▁M gt A ▁and ▁M gt B ▁prote ins ▁form ▁part ▁of ▁a ▁metal ▁to x icity ▁avoid ance ▁system . ▁Alternatively , ▁as ▁most ▁P - type ▁ATP ases ▁function ▁as ▁eff l ux ▁medi ating ▁trans por ters , ▁it ▁has ▁been ▁suggested ▁that ▁the ▁M gt A ▁and ▁M gt B ▁prote ins ▁act ▁as ▁eff l ux ▁prote ins ▁for ▁a ▁currently ▁un ident ified ▁c ation , ▁and ▁M g 2 + ▁transport ▁is ▁either ▁non - specific ▁or ▁ex changed ▁to ▁maintain ▁the ▁electro - neut ral ity ▁of ▁the ▁transport ▁process . ▁Further ▁experiments ▁will ▁be ▁required ▁to ▁define ▁the ▁phys i ological ▁function ▁of ▁these ▁prote ins . ▁ ▁M gt E ▁ ▁Two ▁papers ▁describe ▁M gt E , ▁a ▁fourth ▁M g 2 + ▁u pt ake ▁protein ▁in ▁b acter ia ▁un related ▁to ▁M gt A / B ▁or ▁Cor A . ▁This ▁gene ▁has ▁been ▁sequ enced ▁and ▁the ▁protein , ▁ 3 1 2 ▁am ino ▁ac ids ▁in ▁size , ▁is ▁predicted ▁to ▁contain ▁either ▁four ▁or ▁five ▁T M ▁sp anning ▁domains ▁that ▁are ▁closely ▁arranged ▁in ▁the ▁C - term inal ▁part ▁of ▁the ▁protein ▁( see ▁figure ). ▁This ▁region ▁of ▁the ▁protein ▁has ▁been ▁identified ▁in ▁the ▁Pf am ▁database ▁as ▁a ▁conser ved ▁protein ▁domain ▁( PF 0 1 7 6 9 ) ▁and ▁species ▁containing ▁prote |
ins ▁that ▁have ▁this ▁protein ▁domain ▁are ▁roughly ▁equally ▁distributed ▁throughout ▁the ▁E ub acter ia ▁and ▁Arch ae a , ▁although ▁it ▁is ▁quite ▁rare ▁in ▁comparison ▁with ▁the ▁distribution ▁of ▁Cor A . ▁However , ▁the ▁divers ity ▁of ▁the ▁prote ins ▁containing ▁the ▁domain ▁is ▁significantly ▁larger ▁than ▁that ▁of ▁the ▁Cor A ▁domain . ▁The ▁Pf am ▁database ▁lists ▁seven ▁distinct ▁groups ▁of ▁M gt E ▁domain ▁containing ▁prote ins , ▁of ▁which ▁six ▁contain ▁an ▁arch a ic ▁or ▁e ub acter ial ▁member . ▁The ▁expression ▁of ▁M gt E ▁is ▁frequently ▁controlled ▁by ▁a ▁conser ved ▁R NA ▁structure , ▁Y ko K ▁leader ▁or ▁M - box . ▁ ▁The ▁figure ▁( right ), ▁adapted ▁from ▁Smith ▁et ▁al . ▁( 1 9 9 5 ) ▁and ▁the ▁P FA M ▁database ▁entry , ▁shows ▁the ▁computer - pred icted ▁memb rane ▁topology ▁of ▁the ▁M gt E ▁protein ▁in ▁Bac ill us ▁firm us ▁OF 4 . ▁The ▁T M ▁domains ▁are ▁shown ▁in ▁light ▁blue . ▁The ▁CBS ▁domains , ▁named ▁for ▁the ▁protein ▁they ▁were ▁identified ▁in , ▁c yst ath ion ine - beta ▁synth ase , ▁shown ▁in ▁orange , ▁are ▁identified ▁in ▁the ▁Pf am ▁database ▁as ▁regul atory ▁domains , ▁but ▁the ▁mechanism ▁of ▁action ▁has ▁not ▁yet ▁been ▁described . ▁They ▁are ▁found ▁in ▁several ▁voltage - g ated ▁ch lor ide ▁channels . ▁The ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - |
▁and ▁C - termin i ▁are ▁indicated . ▁This ▁figure ▁is ▁not ▁drawn ▁to ▁scale . ▁This ▁trans porter ▁has ▁recently ▁had ▁its ▁structure ▁solved ▁by ▁x - ray ▁cry stal log raph y . ▁ ▁The ▁M gt E ▁gene ▁was ▁first ▁identified ▁by ▁Smith ▁et ▁al . ▁( 1 9 9 5 ) ▁during ▁a ▁screen ▁for ▁Cor A - like ▁prote ins ▁in ▁b acter ia ▁and ▁comple ments ▁the ▁M g 2 + - upt ake - def ic ient ▁S . ▁ty ph im ur ium ▁stra in ▁MM 2 8 1 ▁( cor A ▁m gt A ▁m gt B ), ▁rest oring ▁wild ▁type ▁growth ▁on ▁standard ▁media . ▁The ▁k inet ics ▁of ▁M g 2 + ▁transport ▁for ▁the ▁protein ▁were ▁not ▁determined , ▁as ▁ 2 8 M g 2 + ▁was ▁un available . ▁As ▁a ▁substitute , ▁the ▁u pt ake ▁of ▁ 5 7 Co 2 + ▁was ▁measured ▁and ▁was ▁shown ▁to ▁have ▁a ▁km ▁of ▁ 8 2 ▁ μ M ▁and ▁a ▁V max ▁of ▁ 3 5 4 ▁pm ol ▁min − 1 ▁ 1 0 8 ▁cells − 1 . ▁M g 2 + ▁was ▁a ▁compet itive ▁in hib itor ▁with ▁a ▁Ki ▁of ▁ 5 0 ▁ μ M — the ▁Ki ▁of ▁M g 2 + ▁in hib ition ▁of ▁ 6 0 Co 2 + ▁u pt ake ▁via ▁Cor A ▁is ▁ 1 0 ▁ μ M . ▁A ▁comparison |
▁of ▁the ▁available ▁kin etic ▁data ▁for ▁M gt A ▁and ▁Cor A ▁is ▁shown ▁in ▁the ▁table . ▁Clear ly , ▁M gt E ▁does ▁not ▁transport ▁Co 2 + ▁to ▁the ▁same ▁degree ▁as ▁Cor A , ▁and ▁the ▁in hib ition ▁of ▁transport ▁by ▁M g 2 + ▁is ▁also ▁less ▁efficient , ▁which ▁suggests ▁that ▁the ▁aff inity ▁of ▁M gt E ▁for ▁M g 2 + ▁is ▁lower ▁than ▁that ▁of ▁Cor A . ▁The ▁strong est ▁in hib itor ▁of ▁Co 2 + ▁u pt ake ▁was ▁Z n 2 + , ▁with ▁a ▁Ki ▁of ▁ 2 0 ▁ μ M . ▁The ▁transport ▁of ▁Z n 2 + ▁by ▁this ▁protein ▁may ▁be ▁as ▁important ▁as ▁that ▁of ▁M g 2 + . ▁ ▁The ▁table ▁shows ▁a ▁comparison ▁of ▁the ▁transport ▁k inet ics ▁of ▁M gt E ▁and ▁Cor A , ▁and ▁key ▁kin etic ▁parameter ▁values ▁for ▁them ▁are ▁listed . ▁As ▁shown , ▁the ▁data ▁has ▁been ▁generated ▁at ▁differ ing ▁inc ub ation ▁temper atures . ▁km ▁and ▁Ki ▁are ▁not ▁significantly ▁alter ed ▁by ▁the ▁differ ing ▁inc ub ation ▁temperature . ▁Con vers ely , ▁V max ▁shows ▁a ▁strong ▁positive ▁correlation ▁with ▁temperature , ▁hence ▁the ▁value ▁of ▁Co 2 + ▁V max ▁for ▁M gt E ▁is ▁not ▁directly ▁compar able ▁with ▁the ▁values ▁for ▁Cor A . ▁ ▁Ye ast ▁ ▁Early ▁research ▁The ▁earliest ▁research ▁showing ▁that ▁ye ast ▁takes ▁up ▁M g 2 |
+ ▁appears ▁to ▁be ▁done ▁by ▁Schmidt ▁et ▁al . ▁( 1 9 4 9 ). ▁However , ▁these ▁authors ▁only ▁showed ▁alter ed ▁ye ast ▁M g 2 + ▁content ▁in ▁a ▁table ▁within ▁the ▁paper , ▁and ▁the ▁report ' s ▁conclus ions ▁de alt ▁entirely ▁with ▁the ▁met abol ism ▁of ▁ph osph ate . ▁A ▁series ▁of ▁experiments ▁by ▁Roth stein ▁shift ed ▁the ▁focus ▁more ▁towards ▁the ▁u pt ake ▁of ▁the ▁metal ▁c ations , ▁showing ▁that ▁ye ast ▁take ▁up ▁c ations ▁with ▁the ▁following ▁aff inity ▁series ; ▁M g 2 + , ▁Co 2 + , ▁Z n 2 + ▁> ▁M n 2 + ▁> ▁Ni 2 + ▁> ▁Ca 2 + ▁> ▁Sr 2 + . ▁Additionally , ▁it ▁was ▁suggested ▁that ▁the ▁transport ▁of ▁the ▁different ▁c ations ▁is ▁medi ated ▁by ▁the ▁same ▁transport ▁system ▁— ▁a ▁situation ▁very ▁much ▁like ▁that ▁in ▁b acter ia . ▁ ▁In ▁ 1 9 9 8 , ▁Mac Di arm id ▁and ▁Gard ner ▁finally ▁identified ▁the ▁prote ins ▁responsible ▁for ▁the ▁observed ▁c ation ▁transport ▁phen ot ype ▁in ▁Sac char omy ces ▁c ere vis iae . ▁The ▁gen es ▁involved ▁in ▁this ▁system ▁and ▁a ▁second ▁mit och ond rial ▁M g 2 + ▁transport ▁system , ▁function ally ▁identified ▁significantly ▁after ▁the ▁gene ▁was ▁cl oned , ▁are ▁described ▁in ▁the ▁sections ▁below . ▁ ▁AL R 1 ▁and ▁AL R 2 ▁Two ▁gen es , ▁AL R |
1 ▁and ▁AL R 2 , ▁were ▁isolated ▁in ▁a ▁screen ▁for ▁Al 3 + ▁toler ance ▁( res istance ) ▁in ▁ye ast . ▁Over - expression ▁construct s ▁containing ▁ye ast ▁genom ic ▁DNA ▁were ▁introduced ▁into ▁wild ▁type ▁ye ast ▁and ▁the ▁transform ants ▁were ▁screen ed ▁for ▁growth ▁on ▁to xic ▁levels ▁of ▁Al 3 + . ▁AL R 1 ▁and ▁AL R 2 ▁containing ▁pl asm ids ▁allowed ▁the ▁growth ▁of ▁ye ast ▁in ▁these ▁conditions . ▁ ▁The ▁Al r 1 p ▁and ▁Al r 2 p ▁prote ins ▁consist ▁of ▁ 8 5 9 ▁and ▁ 8 5 8 ▁am ino ▁ac ids ▁respectively ▁and ▁are ▁ 7 0 % ▁identical . ▁In ▁a ▁region ▁in ▁the ▁C - term inal , ▁half ▁of ▁these ▁prote ins ▁are ▁weak ly ▁similar ▁to ▁the ▁full ▁Cor A ▁protein . ▁The ▁computer - pred icted ▁T M ▁topology ▁of ▁Al r 1 p ▁is ▁shown ▁in ▁the ▁figure . ▁The ▁presence ▁of ▁a ▁third ▁T M ▁domain ▁was ▁suggested ▁by ▁Mac Di arm id ▁and ▁Gard ner ▁( 1 9 9 8 ), ▁on ▁the ▁strength ▁on ▁sequence ▁hom ology , ▁and ▁more ▁recently ▁by ▁Lee ▁and ▁Gard ner ▁( 2 0 0 6 ), ▁on ▁the ▁strength ▁of ▁mut agen esis ▁studies , ▁making ▁the ▁T M ▁topology ▁of ▁these ▁prote ins ▁more ▁like ▁that ▁of ▁Cor A ▁( see ▁figure ). ▁Also , ▁Al r 1 p ▁contains ▁the ▁conser ved ▁G M N ▁mot if |
▁at ▁the ▁outside ▁end ▁of ▁T M ▁ 2 ▁( TM ▁ 2 ') ▁and ▁the ▁mut ation ▁of ▁the ▁m eth ion ine ▁( M ) ▁in ▁this ▁mot if ▁to ▁a ▁le uc ine ▁( L ) ▁led ▁to ▁the ▁loss ▁of ▁transport ▁cap ability . ▁ ▁The ▁figure ▁shows ▁the ▁two ▁possible ▁T M ▁top ologies ▁of ▁Al r 1 p . ▁Part ▁A ▁of ▁the ▁figure ▁shows ▁the ▁computer - pred icted ▁memb rane ▁topology ▁of ▁the ▁Al r 1 p ▁protein ▁in ▁ye ast ▁and ▁part ▁B ▁shows ▁the ▁topology ▁of ▁Al r 1 p ▁based ▁on ▁the ▁experimental ▁results ▁of ▁Lee ▁and ▁Gard ner ▁( 2 0 0 6 ). ▁The ▁G M N ▁mot if ▁location ▁is ▁indicated ▁in ▁red ▁and ▁the ▁T M ▁domains ▁in ▁light ▁blue . ▁The ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - ▁and ▁C - termin i ▁are ▁indicated , ▁the ▁various ▁sizes ▁of ▁the ▁sol ub le ▁domains ▁are ▁given ▁in ▁am ino ▁ac ids ▁( AA ), ▁and ▁T M ▁domains ▁are ▁number ed ▁by ▁their ▁similarity ▁to ▁Cor A . ▁Where ▁any ▁T M ▁domain ▁is ▁missing , ▁the ▁remaining ▁domains ▁are ▁number ed ▁with ▁pr imes . ▁The ▁figure ▁is ▁not ▁drawn ▁to ▁scale . ▁A ▁third ▁AL R - like ▁gene ▁is ▁present ▁in ▁S . ▁c ere vis iae ▁and ▁there ▁are ▁two ▁hom olog ous ▁gen es ▁in ▁both ▁Sch iz os ac char omy ces ▁pom be ▁and |
▁Ne uro sp ora ▁cr assa . ▁These ▁prote ins ▁contain ▁a ▁G M N ▁mot if ▁like ▁that ▁of ▁Cor A , ▁with ▁the ▁exception ▁of ▁the ▁second ▁N . ▁cr assa ▁gene . ▁No ▁AL R - like ▁gen es ▁have ▁been ▁identified ▁in ▁species ▁outside ▁of ▁the ▁fung i . ▁ ▁M emb rane ▁fraction ation ▁and ▁green ▁flu ores cent ▁protein ▁( G FP ) ▁fusion ▁studies ▁established ▁that ▁Al r 1 p ▁is ▁local ised ▁to ▁the ▁pl asma ▁memb rane . ▁The ▁local isation ▁of ▁the ▁Al r 1 p ▁was ▁observed ▁to ▁be ▁internal ised ▁and ▁de grad ed ▁in ▁the ▁vac u ole ▁in ▁response ▁to ▁ext rac ell ular ▁c ations . ▁M g 2 + , ▁at ▁very ▁low ▁ext rac ell ular ▁concentr ations ▁( 1 0 0 ▁ μ M ; ▁< ▁ 1 0 % ▁of ▁the ▁standard ▁media ▁M g 2 + ▁content ), ▁and ▁Co 2 + ▁and ▁M n 2 + ▁at ▁relatively ▁high ▁concentr ations ▁( > ▁ 2 0 × ▁standard ▁media ), ▁induced ▁the ▁change ▁in ▁Al r 1 p ▁protein ▁local isation , ▁and ▁the ▁effect ▁was ▁dependent ▁on ▁functional ▁u bi quit ination , ▁end oc yt osis ▁and ▁vac u olar ▁de grad ation . ▁This ▁mechanism ▁was ▁proposed ▁to ▁allow ▁the ▁reg ulation ▁of ▁M g 2 + ▁u pt ake ▁by ▁ye ast . ▁ ▁However , ▁a ▁recent ▁report ▁ ▁indicates ▁that ▁several ▁of ▁the ▁observations ▁made ▁by |
▁Stad ler ▁et ▁al . ▁were ▁not ▁reprodu cible . ▁For ▁example , ▁reg ulation ▁of ▁AL R 1 ▁m R NA ▁accum ulation ▁by ▁M g 2 + ▁supply ▁was ▁not ▁observed , ▁and ▁the ▁stability ▁of ▁the ▁Al r 1 ▁protein ▁was ▁not ▁reduced ▁by ▁expos ure ▁to ▁excess ▁M g 2 + . ▁The ▁original ▁observation ▁of ▁M g - dependent ▁accum ulation ▁of ▁the ▁Al r 1 ▁protein ▁under ▁steady - state ▁low - M g ▁conditions ▁was ▁rep licated , ▁but ▁this ▁effect ▁was ▁shown ▁to ▁be ▁an ▁artifact ▁caused ▁by ▁the ▁addition ▁of ▁a ▁small ▁pe pt ide ▁( ep ito pe ) ▁to ▁the ▁protein ▁to ▁allow ▁its ▁detection . ▁Despite ▁these ▁problems , ▁Al r 1 ▁activity ▁was ▁demonstrated ▁to ▁respond ▁to ▁M g ▁supply , ▁suggesting ▁that ▁the ▁activity ▁of ▁the ▁protein ▁is ▁reg ulated ▁directly , ▁as ▁was ▁observed ▁for ▁some ▁b acter ial ▁Cor A ▁prote ins . ▁ ▁A ▁functional ▁Al r 1 p ▁( w ild ▁type ) ▁or ▁Al r 2 p ▁( over ex pressed ) ▁is ▁required ▁for ▁S . ▁c ere vis iae ▁growth ▁in ▁standard ▁conditions ▁( 4 ▁m M ▁M g 2 + ), ▁and ▁Al r 1 p ▁can ▁support ▁normal ▁growth ▁at ▁M g 2 + ▁concentr ations ▁as ▁low ▁as ▁ 3 0 ▁ μ M . ▁ 5 7 Co 2 + ▁is ▁taken ▁up ▁into ▁ye ast ▁via ▁the ▁Al r 1 p ▁protein ▁with ▁a ▁km ▁of ▁ |
7 7 ▁– ▁ 1 0 5 ▁ μ M ▁( ; ▁C . ▁Mac Di arm id ▁and ▁R . ▁C . ▁Gard ner , ▁un pub lished ▁data ), ▁but ▁the ▁Ki ▁for ▁M g 2 + ▁in hib ition ▁of ▁this ▁transport ▁is ▁currently ▁unknown . ▁The ▁transport ▁of ▁other ▁c ations ▁by ▁the ▁Al r 1 p ▁protein ▁was ▁ass ay ed ▁by ▁the ▁in hib ition ▁of ▁ye ast ▁growth . ▁The ▁over expression ▁of ▁Al r 1 p ▁led ▁to ▁increased ▁sens itivity ▁to ▁Ca 2 + , ▁Co 2 + , ▁Cu 2 + , ▁La 3 + , ▁M n 2 + , ▁Ni 2 + ▁and ▁Z n 2 + , ▁an ▁array ▁of ▁c ations ▁similar ▁to ▁those ▁shown ▁to ▁be ▁transport ed ▁into ▁ye ast ▁by ▁a ▁Cor A - like ▁transport ▁system . ▁The ▁increased ▁to x icity ▁of ▁the ▁c ations ▁in ▁the ▁presence ▁of ▁the ▁trans porter ▁is ▁assumed ▁to ▁be ▁due ▁to ▁the ▁increased ▁accum ulation ▁of ▁the ▁c ation ▁inside ▁the ▁cell . ▁ ▁The ▁evidence ▁that ▁Al r 1 p ▁is ▁primarily ▁a ▁M g 2 + ▁trans porter ▁is ▁that ▁the ▁loss ▁of ▁Al r 1 p ▁leads ▁to ▁a ▁decre ased ▁total ▁cell ▁content ▁of ▁M g 2 + , ▁but ▁not ▁of ▁other ▁c ations . ▁Additionally , ▁two ▁electro phys i ological ▁studies ▁where ▁Al r 1 p ▁was ▁produced ▁in ▁ye ast ▁or ▁X en opus ▁o ocy tes ▁showed ▁a |
▁M g 2 + - dependent ▁current ▁in ▁the ▁presence ▁of ▁the ▁protein ; ▁S ali h ▁et ▁al ., ▁in ▁prep . ▁ ▁The ▁k inet ics ▁of ▁M g 2 + ▁u pt ake ▁by ▁Al r 1 p ▁have ▁been ▁investig ated ▁by ▁electro phys i ology ▁techniques ▁on ▁whole ▁ye ast ▁cells . ▁The ▁results ▁suggested ▁that ▁Al r 1 p ▁is ▁very ▁likely ▁to ▁act ▁as ▁an ▁ion - select ive ▁channel . ▁In ▁the ▁same ▁paper , ▁the ▁authors ▁reported ▁that ▁M g 2 + ▁transport ▁by ▁Al r 1 p ▁varied ▁from ▁ 2 0 0 ▁p A ▁to ▁ 1 5 0 0 ▁p A , ▁with ▁a ▁mean ▁current ▁of ▁ 2 6 4 ▁p A . ▁No ▁quant ification ▁of ▁the ▁amount ▁of ▁protein ▁producing ▁the ▁current ▁was ▁presented , ▁so ▁the ▁results ▁lack ▁compar ability ▁with ▁the ▁b acter ial ▁M g 2 + ▁transport ▁prote ins . ▁ ▁The ▁alternative ▁techniques ▁of ▁ 2 8 M g 2 + ▁radi ot rac er ▁analysis ▁and ▁mag - f ura ▁ 2 ▁to ▁measure ▁M g 2 + ▁u pt ake ▁have ▁not ▁yet ▁been ▁used ▁with ▁Al r 1 p . ▁ 2 8 M g 2 + ▁is ▁currently ▁not ▁available ▁and ▁the ▁mag - f ura ▁ 2 ▁system ▁is ▁unlikely ▁to ▁provide ▁simple ▁u pt ake ▁data ▁in ▁ye ast . ▁The ▁ye ast ▁cell ▁maintain s ▁a ▁heter ogeneous ▁distribution ▁of ▁M g 2 + ▁suggesting ▁that |
▁multiple ▁systems ▁inside ▁the ▁ye ast ▁are ▁transport ing ▁M g 2 + ▁into ▁storage ▁compart ments . ▁This ▁internal ▁transport ▁will ▁very ▁likely ▁mask ▁the ▁u pt ake ▁process . ▁The ▁expression ▁of ▁AL R 1 ▁in ▁S . ▁ty ph im ur ium ▁without ▁M g 2 + ▁u pt ake ▁gen es ▁may ▁be ▁an ▁alternative , ▁but , ▁as ▁stated ▁earlier , ▁the ▁effects ▁of ▁a ▁heter olog ous ▁expression ▁system ▁would ▁need ▁to ▁be ▁taken ▁into ▁account . ▁ ▁M NR 2 ▁The ▁M NR 2 ▁gene ▁enc odes ▁a ▁protein ▁closely ▁related ▁to ▁the ▁Al r ▁prote ins , ▁but ▁includes ▁conser ved ▁features ▁that ▁define ▁a ▁distinct ▁subgroup ▁of ▁Cor A ▁prote ins ▁in ▁fung al ▁genom es , ▁suggesting ▁a ▁distinct ▁role ▁in ▁M g 2 + ▁home ost asis . ▁Like ▁an ▁al r 1 ▁mut ant , ▁growth ▁of ▁an ▁m nr 2 ▁mut ant ▁was ▁sensitive ▁to ▁M g 2 + - def ic ient ▁conditions , ▁but ▁the ▁m nr 2 ▁mut ant ▁was ▁observed ▁to ▁accum ulate ▁more ▁M g 2 + ▁than ▁a ▁wild - type ▁stra in ▁under ▁these ▁conditions . ▁These ▁phen ot ypes ▁suggested ▁that ▁M nr 2 ▁may ▁reg ulate ▁M g 2 + ▁storage ▁within ▁an ▁int rac ell ular ▁compart ment . ▁Cons istent ▁with ▁this ▁interpretation , ▁the ▁M nr 2 ▁protein ▁was ▁local ized ▁to ▁the ▁memb rane ▁of ▁the ▁vac u ole , ▁an ▁internal ▁compart ment ▁imp licated ▁in |
▁the ▁storage ▁of ▁excess ▁min eral ▁nut ri ents ▁by ▁ye ast . ▁A ▁direct ▁role ▁of ▁M nr 2 ▁in ▁M g 2 + ▁transport ▁was ▁suggested ▁by ▁the ▁observation ▁that ▁increased ▁M nr 2 ▁expression , ▁which ▁redirect ed ▁some ▁M nr 2 ▁protein ▁to ▁the ▁cell ▁surface , ▁also ▁suppress ed ▁the ▁M g 2 + - require ment ▁of ▁an ▁al r 1 ▁al r 2 ▁double ▁mut ant ▁stra in . ▁The ▁m nr 2 ▁mut ation ▁also ▁alter ed ▁accum ulation ▁of ▁other ▁div al ent ▁c ations , ▁suggesting ▁this ▁mut ation ▁may ▁increase ▁Al r ▁gene ▁expression ▁or ▁protein ▁activity . ▁Rec ent ▁work ▁ ▁supported ▁this ▁model , ▁by ▁showing ▁that ▁Al r 1 ▁activity ▁was ▁increased ▁in ▁an ▁m nr 2 ▁mut ant ▁stra in , ▁and ▁that ▁the ▁mut ation ▁was ▁associated ▁with ▁induction ▁of ▁Al r 1 ▁activity ▁at ▁a ▁higher ▁external ▁M g ▁concentration ▁than ▁was ▁observed ▁for ▁an ▁M nr 2 ▁wild - type ▁stra in . ▁These ▁effects ▁were ▁observed ▁without ▁any ▁change ▁in ▁Al r 1 ▁protein ▁accum ulation , ▁again ▁indicating ▁that ▁Al r 1 ▁activity ▁may ▁be ▁reg ulated ▁directly ▁by ▁the ▁M g ▁concentration ▁within ▁the ▁cell . ▁ ▁M RS 2 ▁and ▁L pe 1 0 ▁Like ▁the ▁AL R ▁gen es , ▁the ▁M RS 2 ▁gene ▁was ▁cl oned ▁and ▁sequ enced ▁before ▁it ▁was ▁identified ▁as ▁a ▁M g 2 + ▁trans porter . ▁The ▁M RS 2 ▁gene ▁was |
▁identified ▁in ▁the ▁nuclear ▁gen ome ▁of ▁ye ast ▁in ▁a ▁screen ▁for ▁suppress ors ▁of ▁a ▁mit och ond rial ▁gene ▁R NA ▁sp lic ing ▁mut ation , ▁and ▁was ▁cl oned ▁and ▁sequ enced ▁by ▁W iesen berger ▁et ▁al . ▁( 1 9 9 2 ). ▁Mrs 2 p ▁was ▁not ▁identified ▁as ▁a ▁put ative ▁M g 2 + ▁trans porter ▁until ▁B ui ▁et ▁al . ▁( 1 9 9 9 ). ▁Greg an ▁et ▁al . ▁( 2 0 0 1 a ) ▁identified ▁L PE 1 0 ▁by ▁hom ology ▁to ▁M RS 2 ▁and ▁showed ▁that ▁both ▁L PE 1 0 ▁and ▁M RS 2 ▁mut ants ▁alter ed ▁the ▁M g 2 + ▁content ▁of ▁ye ast ▁mit och ond ria ▁and ▁affected ▁R NA ▁sp lic ing ▁activity ▁in ▁the ▁organ elle . ▁M g 2 + ▁transport ▁has ▁been ▁shown ▁to ▁be ▁directly ▁medi ated ▁by ▁Mrs 2 p , ▁but ▁not ▁for ▁L pe 1 0 p . ▁ ▁The ▁Mrs 2 p ▁and ▁L pe 1 0 p ▁prote ins ▁are ▁ 4 7 0 ▁and ▁ 4 1 3 ▁am ino ▁acid ▁resid ues ▁in ▁size , ▁respectively , ▁and ▁a ▁ 2 5 0 – 3 0 0 ▁am ino ▁acid ▁region ▁in ▁the ▁middle ▁of ▁the ▁prote ins ▁shows ▁a ▁weak ▁similarity ▁to ▁the ▁full ▁Cor A ▁protein . ▁The ▁T M ▁top ologies ▁of ▁the ▁Mrs 2 p ▁and ▁L pe 1 0 p ▁prote |
ins ▁have ▁been ▁ass essed ▁using ▁a ▁prote ase ▁protection ▁ass ay ▁and ▁are ▁shown ▁in ▁the ▁figure . ▁T M ▁ 1 ▁and ▁ 2 ▁correspond ▁to ▁T M ▁ 2 ▁and ▁ 3 ▁in ▁the ▁Cor A ▁protein . ▁The ▁conser ved ▁G M N ▁mot if ▁is ▁at ▁the ▁outside ▁end ▁of ▁the ▁first ▁T M ▁domain , ▁and ▁when ▁the ▁g ly c ine ▁( G ) ▁in ▁this ▁mot if ▁was ▁mut ated ▁to ▁a ▁c yst e ine ▁( C ) ▁in ▁Mrs 2 p , ▁M g 2 + ▁transport ▁was ▁strongly ▁reduced . ▁ ▁The ▁figure ▁shows ▁the ▁experiment ally ▁determined ▁topology ▁of ▁Mrs 2 p ▁and ▁L pe 1 0 p ▁as ▁adapted ▁from ▁B ui ▁et ▁al . ▁( 1 9 9 9 ) ▁and ▁Greg an ▁et ▁al . ▁( 2 0 0 1 a ). ▁The ▁G M N ▁mot if ▁location ▁is ▁indicated ▁in ▁red ▁and ▁the ▁T M ▁domains ▁in ▁light ▁blue . ▁The ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - ▁and ▁C - termin i ▁are ▁indicated . ▁The ▁various ▁sizes ▁of ▁the ▁sol ub le ▁domains ▁are ▁given ▁in ▁am ino ▁ac ids ▁( AA ), ▁T M ▁domains ▁are ▁number ed , ▁and ▁the ▁figure ▁is ▁not ▁drawn ▁to ▁scale . ▁ ▁Mrs 2 p ▁has ▁been ▁local ised ▁to ▁the ▁mit och ond rial ▁inner ▁memb rane ▁by ▁sub cell ular ▁fraction ation ▁and ▁imm un od ete ction ▁and |
▁L pe 1 0 p ▁to ▁the ▁mit och ond ria . ▁M ito ch ond ria ▁lack ing ▁Mrs 2 p ▁do ▁not ▁show ▁a ▁fast ▁M g 2 + ▁u pt ake , ▁only ▁a ▁slow ▁‘ le ak ’ , ▁and ▁over acc um ulation ▁of ▁Mrs 2 p ▁leads ▁to ▁an ▁increase ▁in ▁the ▁initial ▁rate ▁of ▁u pt ake . ▁Additionally , ▁Cor A , ▁when ▁f used ▁to ▁the ▁mit och ond rial ▁leader ▁sequence ▁of ▁Mrs 2 p , ▁can ▁partially ▁complement ▁the ▁mit och ond rial ▁defect ▁con ferred ▁by ▁the ▁loss ▁of ▁either ▁Mrs 2 p ▁or ▁L pe 1 0 p . ▁Hence , ▁Mrs 2 p ▁and / or ▁L pe 1 0 p ▁may ▁be ▁the ▁major ▁M g 2 + ▁u pt ake ▁system ▁for ▁mit och ond ria . ▁A ▁possibility ▁is ▁that ▁the ▁prote ins ▁form ▁heter od im ers , ▁as ▁neither ▁protein ▁( when ▁over ex pressed ) ▁can ▁fully ▁complement ▁the ▁loss ▁of ▁the ▁other . ▁ ▁The ▁characteristics ▁of ▁M g 2 + ▁u pt ake ▁in ▁isolated ▁mit och ond ria ▁by ▁Mrs 2 p ▁were ▁quant ified ▁using ▁mag - f ura ▁ 2 . ▁The ▁u pt ake ▁of ▁M g 2 + ▁by ▁Mrs 2 p ▁shared ▁a ▁number ▁of ▁attributes ▁with ▁Cor A . ▁First , ▁M g 2 + ▁u pt ake ▁was ▁directly ▁dependent ▁on ▁the ▁electric ▁potential ▁( Δ Ψ ) ▁across ▁the ▁boundary ▁memb rane |
. ▁Second , ▁the ▁u pt ake ▁is ▁s atur ated ▁far ▁below ▁that ▁which ▁the ▁ Δ Ψ ▁theoret ically ▁perm its , ▁so ▁the ▁transport ▁of ▁M g 2 + ▁by ▁Mrs 2 p ▁is ▁likely ▁to ▁be ▁reg ulated ▁in ▁a ▁similar ▁manner ▁to ▁Cor A , ▁possibly ▁by ▁the ▁in activ ation ▁of ▁the ▁protein . ▁Third , ▁M g 2 + ▁eff l ux ▁was ▁observed ▁via ▁Mrs 2 p ▁upon ▁the ▁artificial ▁dep olar isation ▁of ▁the ▁mit och ond rial ▁memb rane ▁by ▁val in om yc in . ▁Finally , ▁the ▁M g 2 + ▁flux es ▁through ▁Mrs 2 p ▁are ▁in hib ited ▁by ▁c ob alt ▁( III ) ▁hex a amm ine . ▁ ▁The ▁k inet ics ▁of ▁M g 2 + ▁u pt ake ▁by ▁Mrs 2 p ▁were ▁determined ▁in ▁the ▁Fro sch auer ▁et ▁al . ▁( 2 0 0 4 ) ▁paper ▁on ▁Cor A ▁in ▁b acter ia . ▁The ▁initial ▁change ▁in ▁free ▁M g 2 + ▁concentration ▁was ▁ 1 5 0 ▁ μ M ▁s - 1 ▁for ▁wild ▁type ▁and ▁ 7 5 0 ▁ μ M ▁s - 1 ▁for ▁mit och ond ria ▁from ▁ye ast ▁over express ing ▁M RS 2 . ▁No ▁attempt ▁was ▁made ▁to ▁scale ▁the ▁observed ▁transport ▁to ▁the ▁amount ▁of ▁trans porter ▁present . ▁ ▁Pro to zo an ▁( Par ame ci um ) ▁The ▁transport ▁of ▁M g 2 + ▁into |
▁Par ame ci um ▁has ▁been ▁character ised ▁largely ▁by ▁R . ▁R . ▁Pr eston ▁and ▁his ▁cow ork ers . ▁Elect ro phys i ological ▁techniques ▁on ▁whole ▁Par ame ci um ▁were ▁used ▁to ▁identify ▁and ▁character ise ▁M g 2 + ▁curr ents ▁in ▁a ▁series ▁of ▁papers ▁before ▁the ▁gene ▁was ▁cl oned ▁by ▁Hay nes ▁et ▁al . ▁( 2 0 0 2 ). ▁ ▁The ▁open ▁reading ▁frame ▁for ▁the ▁X N TA ▁gene ▁is ▁ 1 7 0 7 ▁b p ▁in ▁size , ▁contains ▁two ▁intr ons ▁and ▁produces ▁a ▁predicted ▁protein ▁of ▁ 5 5 0 ▁am ino ▁ac ids . ▁The ▁protein ▁has ▁been ▁predicted ▁to ▁contain ▁ 1 1 ▁T M ▁domains ▁and ▁also ▁contains ▁the ▁α 1 ▁and ▁α 2 ▁mot ifs ▁( see ▁figure ) ▁of ▁the ▁S LC 8 ▁( Na + / Ca 2 + ▁ex ch anger ) ▁and ▁S LC 2 4 ▁( K + ▁dependent ▁Na + / Ca 2 + ▁ex ch anger ) ▁human ▁sol ute ▁transport ▁prote ins . ▁The ▁X nt Ap ▁is ▁equally ▁similar ▁to ▁the ▁S LC 8 ▁and ▁S LC 2 4 ▁protein ▁families ▁by ▁am ino ▁acid ▁sequence , ▁but ▁the ▁predicted ▁T M ▁topology ▁is ▁more ▁like ▁that ▁of ▁S LC 2 4 , ▁but ▁the ▁similarity ▁is ▁at ▁best ▁weak ▁and ▁the ▁relationship ▁is ▁very ▁distant . ▁The ▁At M H X ▁protein ▁from ▁plants ▁also ▁shares ▁a ▁distant ▁relationship ▁with ▁the ▁S LC |
8 ▁prote ins . ▁ ▁The ▁figure ▁shows ▁the ▁predicted ▁T M ▁topology ▁of ▁X nt Ap . ▁Ada pt ed ▁from ▁Hay nes ▁et ▁al . ▁( 2 0 0 2 ), ▁this ▁figure ▁shows ▁the ▁computer ▁predicted ▁memb rane ▁topology ▁of ▁X nt Ap ▁in ▁Par ame ci um . ▁The ▁orientation ▁in ▁the ▁memb rane ▁was ▁determined ▁using ▁H MM T OP . ▁The ▁T M ▁domains ▁are ▁shown ▁in ▁light ▁blue , ▁the ▁α 1 ▁and ▁α 2 ▁domains ▁are ▁shown ▁in ▁green . ▁The ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - ▁and ▁C - termin i ▁are ▁indicated ▁and ▁the ▁figure ▁is ▁not ▁drawn ▁to ▁scale . ▁ ▁The ▁M g 2 + - dependent ▁curr ents ▁carried ▁by ▁X nt Ap ▁are ▁k inet ically ▁like ▁that ▁of ▁a ▁channel ▁protein ▁and ▁have ▁an ▁ion ▁select ivity ▁order ▁of ▁M g 2 + ▁> ▁Co 2 + , ▁M n 2 + ▁> ▁Ca 2 + ▁— ▁a ▁series ▁again ▁very ▁similar ▁to ▁that ▁of ▁Cor A . ▁Un like ▁the ▁other ▁transport ▁prote ins ▁reported ▁so ▁far , ▁X nt Ap ▁is ▁dependent ▁on ▁int rac ell ular ▁Ca 2 + . ▁The ▁transport ▁is ▁also ▁dependent ▁on ▁ Δ Ψ , ▁but ▁again ▁M g 2 + ▁is ▁not ▁transport ed ▁to ▁equilibrium , ▁being ▁limited ▁to ▁approximately ▁ 0 . 4 ▁m M ▁free ▁M g 2 + ▁in ▁the ▁cy top las m . ▁The ▁existence ▁of ▁an |
▁int rac ell ular ▁compart ment ▁with ▁a ▁much ▁higher ▁free ▁concentration ▁of ▁M g 2 + ▁( 8 ▁m M ) ▁was ▁supported ▁by ▁the ▁results . ▁ ▁Anim als ▁The ▁investigation ▁of ▁M g 2 + ▁in ▁animals , ▁including ▁humans , ▁has ▁lag ged ▁behind ▁that ▁in ▁b acter ia ▁and ▁ye ast . ▁This ▁is ▁largely ▁because ▁of ▁the ▁complexity ▁of ▁the ▁systems ▁involved , ▁but ▁also ▁because ▁of ▁the ▁impression ▁within ▁the ▁field ▁that ▁M g 2 + ▁was ▁maintained ▁at ▁high ▁levels ▁in ▁all ▁cells ▁and ▁was ▁un changed ▁by ▁external ▁influ ences . ▁Only ▁in ▁the ▁last ▁ 2 5 ▁years ▁has ▁a ▁series ▁of ▁reports ▁begun ▁to ▁challenge ▁this ▁view , ▁with ▁new ▁method ologies ▁finding ▁that ▁free ▁M g 2 + ▁content ▁is ▁maintained ▁at ▁levels ▁where ▁changes ▁might ▁influence ▁cell ular ▁met abol ism . ▁ ▁M RS 2 ▁A ▁bio in form atic ▁search ▁of ▁the ▁sequence ▁databases ▁identified ▁one ▁hom olog ue ▁of ▁the ▁M RS 2 ▁gene ▁of ▁ye ast ▁in ▁a ▁range ▁of ▁met az o ans . ▁The ▁protein ▁has ▁a ▁very ▁similar ▁sequence ▁and ▁predicted ▁T M ▁topology ▁to ▁the ▁ye ast ▁protein , ▁and ▁the ▁G M N ▁mot if ▁is ▁int act ▁at ▁the ▁end ▁of ▁the ▁first ▁T M ▁domain . ▁The ▁human ▁protein , ▁h sa M rs 2 p , ▁has ▁been ▁local ised ▁to ▁the ▁mit och ond rial ▁memb rane ▁in ▁mouse ▁cells ▁using ▁a ▁G FP ▁fusion ▁protein . |
▁ ▁Very ▁little ▁is ▁known ▁about ▁the ▁M g 2 + ▁transport ▁characteristics ▁of ▁the ▁protein ▁in ▁m amm als , ▁but ▁Z sur ka ▁et ▁al . ▁( 2 0 0 1 ) ▁has ▁shown ▁that ▁the ▁human ▁Mrs 2 p ▁comple ments ▁the ▁m rs 2 ▁mut ants ▁in ▁the ▁ye ast ▁mit och ond rial ▁M g 2 + ▁u pt ake ▁system . ▁ ▁S LC 4 1 ▁( M gt E ) ▁The ▁identification ▁of ▁this ▁gene ▁family ▁in ▁the ▁met az oa ▁began ▁with ▁a ▁signal ▁sequence ▁trap ▁method ▁for ▁isol ating ▁secret ed ▁and ▁memb rane ▁prote ins . ▁Much ▁of ▁the ▁identification ▁has ▁come ▁from ▁bio in form atic ▁anal ys es . ▁Three ▁gen es ▁were ▁eventually ▁identified ▁in ▁humans , ▁another ▁three ▁in ▁mouse ▁and ▁three ▁in ▁Ca en or hab d itis ▁eleg ans , ▁with ▁a ▁single ▁gene ▁in ▁An oph eles ▁g amb iae . ▁The ▁p FA M ▁database ▁lists ▁the ▁M gt E ▁domain ▁as ▁p FA M 0 1 7 6 9 ▁and ▁addition ally ▁ident ifies ▁a ▁M gt E ▁domain - cont aining ▁protein ▁in ▁D ros oph ila ▁mel an og aster . ▁The ▁prote ins ▁containing ▁the ▁M gt E ▁domain ▁can ▁be ▁divided ▁into ▁seven ▁classes , ▁as ▁defined ▁by ▁p FA M ▁using ▁the ▁type ▁and ▁organisation ▁of ▁the ▁ident ifiable ▁domains ▁in ▁each ▁protein . ▁Met az o an ▁prote ins ▁are ▁present ▁in ▁three ▁of ▁the ▁seven ▁groups . |
▁All ▁of ▁the ▁met az oa ▁prote ins ▁contain ▁two ▁M gt E ▁domains , ▁but ▁some ▁of ▁these ▁have ▁been ▁predicted ▁only ▁by ▁context ▁recognition ▁( Co in , ▁Bat eman ▁and ▁Dur bin , ▁un pub lished . ▁See ▁the ▁p FA M ▁website ▁for ▁further ▁details ). ▁ ▁The ▁human ▁S LC 4 1 A 1 ▁protein ▁contains ▁two ▁M gt E ▁domains ▁with ▁ 5 2 % ▁and ▁ 4 6 % ▁respective ▁similarity ▁to ▁the ▁P F 0 1 7 6 9 ▁cons ensus ▁sequence ▁and ▁is ▁predicted ▁to ▁contain ▁ten ▁T M ▁domains , ▁five ▁in ▁each ▁M gt E ▁domain ▁( see ▁figure ), ▁which ▁suggests ▁that ▁the ▁M gt E ▁protein ▁of ▁b acter ia ▁may ▁work ▁as ▁a ▁dim er . ▁ ▁Ada pt ed ▁from ▁W ab ak ken ▁et ▁al . ▁( 2 0 0 3 ) ▁and ▁the ▁p FA M ▁database , ▁the ▁figure ▁shows ▁the ▁computer ▁predicted ▁memb rane ▁topology ▁of ▁M gt E ▁in ▁H . ▁s api ens . ▁The ▁T M ▁domains ▁are ▁shown ▁in ▁light ▁blue , ▁the ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - ▁and ▁C - termin i ▁are ▁indicated , ▁and ▁the ▁figure ▁is ▁not ▁drawn ▁to ▁scale . ▁ ▁W ab ak ken ▁et ▁al . ▁( 2 0 0 3 ) ▁found ▁that ▁the ▁trans cript ▁of ▁the ▁S LC 4 1 A 1 ▁gene ▁was ▁expressed ▁in ▁all ▁human ▁t issues ▁tested , ▁but |
▁at ▁varying ▁levels , ▁with ▁the ▁heart ▁and ▁test is ▁having ▁the ▁highest ▁expression ▁of ▁the ▁gene . ▁No ▁explanation ▁of ▁the ▁expression ▁pattern ▁has ▁been ▁suggested ▁with ▁regard ▁to ▁M g 2 + - related ▁phys i ology . ▁ ▁It ▁has ▁not ▁been ▁shown ▁whether ▁the ▁S LC 4 1 ▁prote ins ▁transport ▁M g 2 + ▁or ▁complement ▁a ▁M g 2 + ▁transport ▁mut ation ▁in ▁any ▁experimental ▁system . ▁However , ▁it ▁has ▁been ▁suggested ▁that ▁as ▁M gt E ▁prote ins ▁have ▁no ▁other ▁known ▁function , ▁they ▁are ▁likely ▁to ▁be ▁M g 2 + ▁trans por ters ▁in ▁the ▁met az oa ▁as ▁they ▁are ▁in ▁the ▁b acter ia . ▁This ▁will ▁need ▁to ▁be ▁verified ▁using ▁one ▁of ▁the ▁now ▁standard ▁experiment ▁systems ▁for ▁exam ining ▁M g 2 + ▁transport . ▁ ▁TR PM 6 / ▁TR PM 7 ▁The ▁investigation ▁of ▁the ▁TR PM ▁gen es ▁and ▁prote ins ▁in ▁human ▁cells ▁is ▁an ▁area ▁of ▁inten se ▁recent ▁study ▁and , ▁at ▁times , ▁debate . ▁Mont ell ▁et ▁al . ▁( 2 0 0 2 ) ▁have ▁review ed ▁the ▁research ▁into ▁the ▁TR P ▁gen es , ▁and ▁a ▁second ▁review ▁by ▁Mont ell ▁( 2 0 0 3 ) ▁has ▁review ed ▁the ▁research ▁into ▁the ▁TR PM ▁gen es . ▁ ▁The ▁TR PM ▁family ▁of ▁ion ▁channels ▁has ▁members ▁throughout ▁the ▁met az oa . ▁The ▁TR PM 6 ▁and ▁TR PM 7 ▁prote ins |
▁are ▁highly ▁unusual , ▁containing ▁both ▁an ▁ion ▁channel ▁domain ▁and ▁a ▁kin ase ▁domain ▁( Fig ure ▁ 1 . 7 ), ▁the ▁role ▁of ▁which ▁brings ▁about ▁the ▁most ▁he ated ▁debate . ▁ ▁The ▁activity ▁of ▁these ▁two ▁prote ins ▁has ▁been ▁very ▁difficult ▁to ▁quant ify . ▁TR PM 7 ▁by ▁itself ▁appears ▁to ▁be ▁a ▁Ca 2 + ▁channel ▁but ▁in ▁the ▁presence ▁of ▁TR PM 6 ▁the ▁aff inity ▁series ▁of ▁transport ed ▁c ations ▁places ▁M g 2 + ▁above ▁Ca 2 + . ▁The ▁differences ▁in ▁reported ▁conduct ance ▁were ▁caused ▁by ▁the ▁expression ▁patterns ▁of ▁these ▁gen es . ▁TR PM 7 ▁is ▁expressed ▁in ▁all ▁cell ▁types ▁tested ▁so ▁far , ▁while ▁TR PM 6 ▁shows ▁a ▁more ▁restricted ▁pattern ▁of ▁expression . ▁An ▁un fortun ate ▁choice ▁of ▁experimental ▁system ▁by ▁Vo ets ▁et ▁al ., ▁( 2 0 0 4 ) ▁led ▁to ▁the ▁conclusion ▁that ▁TR PM 6 ▁is ▁a ▁functional ▁M g 2 + ▁trans porter . ▁However , ▁later ▁work ▁by ▁Ch ub an ov ▁et ▁al . ▁( 2 0 0 4 ) ▁clearly ▁showed ▁that ▁TR PM 7 ▁is ▁required ▁for ▁TR PM 6 ▁activity ▁and ▁that ▁the ▁results ▁of ▁Vo ets ▁et ▁al . ▁are ▁explained ▁by ▁the ▁expression ▁of ▁TR PM 7 ▁in ▁the ▁experimental ▁cell ▁line ▁used ▁by ▁Vo ets ▁et ▁al . ▁in ▁their ▁experiments . ▁Whether ▁TR PM 6 ▁is ▁functional ▁by ▁itself ▁is ▁yet ▁to ▁be ▁determined . ▁ ▁The |
▁predicted ▁T M ▁topology ▁of ▁the ▁T PR M 6 ▁and ▁TR PM 7 ▁prote ins ▁has ▁been ▁adapted ▁from ▁Nad ler ▁et ▁al . ▁( 2 0 0 1 ), ▁R unn els ▁et ▁al . ▁( 2 0 0 1 ) ▁and ▁Mont ell ▁et ▁al . ▁( 2 0 0 2 ), ▁this ▁figure ▁shows ▁the ▁computer ▁predicted ▁memb rane ▁topology ▁of ▁the ▁TR PM 6 ▁and ▁TR PM 7 ▁prote ins ▁in ▁H omo ▁s api ens . ▁At ▁this ▁time , ▁the ▁topology ▁shown ▁should ▁be ▁considered ▁a ▁tent ative ▁hypothesis . ▁The ▁T M ▁domains ▁are ▁shown ▁in ▁light ▁blue , ▁the ▁p ore ▁loop ▁in ▁pur ple , ▁the ▁TR P ▁mot if ▁in ▁red ▁and ▁the ▁kin ase ▁domain ▁in ▁green . ▁The ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - ▁and ▁C - termin i ▁are ▁indicated ▁and ▁the ▁figure ▁is ▁not ▁drawn ▁to ▁scale . ▁ ▁The ▁conclus ions ▁of ▁the ▁Vo ets ▁et ▁al . ▁( 2 0 0 4 ) ▁paper ▁are ▁probably ▁incorrect ▁in ▁att rib uting ▁the ▁M g 2 + ▁dependent ▁curr ents ▁to ▁TR PM 7 ▁alone , ▁and ▁their ▁kin etic ▁data ▁are ▁likely ▁to ▁reflect ▁the ▁combined ▁TR PM 7 / ▁TR PM 6 ▁channel . ▁The ▁report ▁presents ▁a ▁robust ▁collection ▁of ▁data ▁consistent ▁with ▁a ▁channel - like ▁activity ▁passing ▁M g 2 + , ▁based ▁on ▁both ▁electro phys i ological ▁techniques ▁and ▁also ▁mag - f ura |
▁ 2 ▁to ▁determine ▁changes ▁in ▁cy top las mic ▁free ▁M g 2 + . ▁ ▁Par ac ell ular ▁transport ▁Claud ins ▁allow ▁for ▁M g 2 + ▁transport ▁via ▁the ▁par ac ell ular ▁path way ; ▁that ▁is , ▁it ▁medi ates ▁the ▁transport ▁of ▁the ▁ion ▁through ▁the ▁tight ▁j unction s ▁between ▁cells ▁that ▁form ▁an ▁ep ith el ial ▁cell ▁layer . ▁In ▁particular , ▁Claud in - 1 6 ▁allows ▁the ▁select ive ▁re upt ake ▁of ▁M g 2 + ▁in ▁the ▁human ▁kid ney . ▁Some ▁patients ▁with ▁mut ations ▁in ▁the ▁C LD N 1 9 ▁gene ▁also ▁have ▁alter ed ▁mag nes ium ▁transport . ▁ ▁The ▁gene ▁Claud in - 1 6 ▁was ▁cl oned ▁by ▁Simon ▁et ▁al . ▁( 1 9 9 9 ), ▁but ▁only ▁after ▁a ▁series ▁of ▁reports ▁described ▁the ▁M g 2 + ▁flux ▁itself ▁with ▁no ▁gene ▁or ▁protein . ▁The ▁expression ▁pattern ▁of ▁the ▁gene ▁was ▁determined ▁by ▁R T - PC R , ▁and ▁was ▁shown ▁to ▁be ▁very ▁tight ly ▁conf ined ▁to ▁a ▁continuous ▁region ▁of ▁the ▁kid ney ▁tub ule ▁running ▁from ▁the ▁med ull ary ▁thick ▁desc ending ▁lim b ▁to ▁the ▁dist al ▁con vol uted ▁tub ule . ▁This ▁local isation ▁was ▁consistent ▁with ▁the ▁earlier ▁reports ▁for ▁the ▁location ▁of ▁M g 2 + ▁re - upt ake ▁by ▁the ▁kid ney . ▁Following ▁the ▁cl oning , ▁mut ations ▁in ▁the ▁gene ▁were |
▁identified ▁in ▁patients ▁with ▁famil ial ▁hyp om agn esa emia ▁with ▁hyper cal ci uria ▁and ▁ne ph ro calc inos is , ▁strength ening ▁the ▁links ▁between ▁the ▁gene ▁and ▁the ▁u pt ake ▁of ▁M g 2 + . ▁ ▁Pl ants ▁The ▁current ▁knowledge ▁of ▁the ▁mole cular ▁mechan isms ▁for ▁M g 2 + ▁transport ▁in ▁plants ▁is ▁very ▁limited , ▁with ▁only ▁three ▁publications ▁reporting ▁a ▁mole cular ▁basis ▁for ▁M g 2 + ▁transport ▁in ▁plants . ▁However , ▁the ▁importance ▁of ▁M g 2 + ▁to ▁plants ▁has ▁been ▁well ▁described , ▁and ▁phys i ological ▁and ▁ec oph ys i ological ▁studies ▁about ▁the ▁effects ▁of ▁M g 2 + ▁are ▁numerous . ▁This ▁section ▁will ▁summar ise ▁the ▁knowledge ▁of ▁a ▁gene ▁family ▁identified ▁in ▁plants ▁that ▁is ▁dist antly ▁related ▁to ▁Cor A . ▁Another ▁gene , ▁a ▁M g 2 + / H + ▁ex ch anger ▁( At M H X ), ▁un related ▁to ▁this ▁gene ▁family ▁and ▁to ▁Cor A ▁has ▁also ▁been ▁identified , ▁is ▁local ised ▁to ▁the ▁vac u olar ▁memb rane , ▁and ▁will ▁be ▁described ▁last . ▁ ▁The ▁At M RS 2 ▁gene ▁family ▁Sch ock ▁et ▁al . ▁( 2 0 0 0 ) ▁identified ▁and ▁named ▁the ▁family ▁At M RS 2 ▁based ▁on ▁the ▁similarity ▁of ▁the ▁gen es ▁to ▁the ▁M RS 2 ▁gene ▁of ▁ye ast . ▁The ▁authors ▁also ▁showed ▁that ▁the ▁At M RS 2 |
- 1 ▁gene ▁could ▁complement ▁a ▁ Δ m rs 2 ▁ye ast ▁mut ant ▁phen ot ype . ▁Independ ently , ▁Li ▁et ▁al . ▁( 2 0 0 1 ) ▁published ▁a ▁report ▁ident ifying ▁the ▁family ▁and ▁showing ▁that ▁two ▁additional ▁members ▁could ▁complement ▁M g 2 + ▁transport ▁def ic ient ▁mut ants , ▁one ▁in ▁S . ▁ty ph im ur ium ▁and ▁the ▁other ▁in ▁S . ▁c ere vis iae . ▁ ▁The ▁three ▁gen es ▁that ▁have ▁been ▁shown ▁to ▁transport ▁M g 2 + ▁are ▁At M RS 2 - 1 , ▁At M RS 2 - 1 0 ▁and ▁At M RS 2 - 1 1 , ▁and ▁these ▁gen es ▁produce ▁prote ins ▁ 4 4 2 , ▁ 4 4 3 ▁and ▁ 4 5 9 ▁am ino ▁ac ids ▁in ▁size , ▁respectively . ▁Each ▁of ▁the ▁prote ins ▁shows ▁significant ▁similarity ▁to ▁Mrs 2 p ▁of ▁ye ast ▁and ▁a ▁weak ▁similarity ▁to ▁Cor A ▁of ▁b acter ia , ▁contains ▁the ▁conser ved ▁G M N ▁am ino ▁acid ▁mot if ▁at ▁the ▁outside ▁end ▁of ▁the ▁first ▁T M ▁domain , ▁and ▁is ▁predicted ▁to ▁have ▁two ▁T M ▁domains . ▁ ▁The ▁At M RS 2 - 1 ▁gene , ▁when ▁expressed ▁in ▁ye ast ▁from ▁the ▁M RS 2 ▁prom oter ▁and ▁being ▁f used ▁C - termin ally ▁to ▁the ▁first ▁ 9 5 ▁am ino ▁ac ids ▁of ▁the ▁Mrs 2 p ▁protein |
, ▁was ▁directed ▁to ▁the ▁mit och ond ria , ▁where ▁it ▁complement ed ▁a ▁ Δ m rs 2 ▁mut ant ▁both ▁phen ot yp ically ▁( m ito ch ond rial ▁R NA ▁sp lic ing ▁was ▁restored ) ▁and ▁with ▁respect ▁to ▁the ▁M g 2 + ▁content ▁of ▁the ▁organ elle . ▁No ▁data ▁on ▁the ▁k inet ics ▁of ▁the ▁transport ▁was ▁presented . ▁The ▁At M RS 2 - 1 1 ▁gene ▁was ▁anal ys ed ▁in ▁ye ast ▁( in ▁the ▁al r 1 ▁al r 2 ▁stra in ), ▁where ▁it ▁was ▁shown ▁that ▁expression ▁of ▁the ▁gene ▁significantly ▁increased ▁the ▁rate ▁of ▁M g 2 + ▁u pt ake ▁into ▁star ved ▁cells ▁over ▁the ▁control , ▁as ▁measured ▁using ▁fl ame ▁atomic ▁absor ption ▁spect ro sc opy ▁of ▁total ▁cell ular ▁M g 2 + ▁content . ▁However , ▁Al r 1 p ▁was ▁shown ▁to ▁be ▁significantly ▁more ▁effective ▁at ▁transport ing ▁M g 2 + ▁at ▁low ▁ext rac ell ular ▁concentr ations , ▁suggesting ▁that ▁the ▁aff inity ▁of ▁At M RS 2 - 1 1 ▁for ▁M g 2 + ▁is ▁lower ▁than ▁that ▁of ▁Al r 1 p . ▁An ▁electro phys i ological ▁( vol t age ▁cl amp ) ▁analysis ▁of ▁the ▁At M RS 2 - 1 1 ▁protein ▁in ▁X en opus ▁o ocy tes ▁also ▁showed ▁a ▁M g 2 + - dependent ▁current ▁at ▁memb rane ▁potential s ▁( Δ Ψ |
) ▁of ▁– 1 0 0 ▁– ▁– 1 5 0 ▁m V ▁inside . ▁These ▁values ▁are ▁phys i olog ically ▁significant , ▁as ▁several ▁memb ran es ▁in ▁plants ▁maintain ▁ Δ Ψ ▁in ▁this ▁range . ▁However , ▁the ▁author ▁had ▁difficulty ▁reprodu cing ▁these ▁results ▁due ▁to ▁an ▁apparent ▁" de ath " ▁of ▁o ocy tes ▁containing ▁the ▁At M RS 2 - 1 1 ▁protein , ▁and ▁therefore ▁these ▁results ▁should ▁be ▁viewed ▁with ▁ca ution . ▁ ▁The ▁At M RS 2 - 1 0 ▁trans porter ▁has ▁been ▁anal ys ed ▁using ▁radio active ▁trac er ▁u pt ake ▁analysis . ▁ 6 3 N i 2 + ▁was ▁used ▁as ▁the ▁substitute ▁ion ▁and ▁M g 2 + ▁was ▁shown ▁to ▁in hib it ▁the ▁u pt ake ▁of ▁ 6 3 N i 2 + ▁with ▁a ▁Ki ▁of ▁ 2 0 ▁ μ M . ▁U pt ake ▁was ▁also ▁in hib ited ▁by ▁Co ( III ) H ex ▁and ▁by ▁other ▁div al ent ▁c ations . ▁Only ▁Co 2 + ▁and ▁Cu 2 + ▁in hib ited ▁transport ▁with ▁Ki ▁values ▁less ▁than ▁ 1 ▁m M . ▁ ▁The ▁At M RS 2 - 1 0 ▁protein ▁was ▁f used ▁to ▁G FP , ▁and ▁was ▁shown ▁to ▁be ▁local ised ▁to ▁the ▁pl asma ▁memb rane . ▁A ▁similar ▁experiment ▁was ▁attempted ▁in ▁the ▁Sch ock ▁et ▁al . ▁( 2 0 0 0 ) ▁paper , |
▁but ▁the ▁observed ▁local isation ▁was ▁not ▁significantly ▁different ▁from ▁that ▁seen ▁with ▁unf used ▁G FP . ▁The ▁most ▁likely ▁reason ▁for ▁the ▁lack ▁of ▁a ▁definit ive ▁local isation ▁of ▁At M RS 2 - 1 ▁in ▁the ▁Sch ock ▁et ▁al . ▁paper ▁is ▁that ▁the ▁authors ▁removed ▁the ▁T M ▁domains ▁from ▁the ▁protein , ▁thereby ▁pre cluding ▁its ▁insert ion ▁into ▁a ▁memb rane . ▁ ▁The ▁exact ▁phys i ological ▁significance ▁of ▁the ▁At M RS 2 - 1 ▁and ▁At M RS 2 - 1 0 ▁prote ins ▁in ▁plants ▁has ▁yet ▁to ▁be ▁clar ified . ▁The ▁At M RS 2 - 1 1 ▁gene ▁has ▁been ▁over ex pressed ▁( from ▁the ▁Ca M V ▁ 3 5 S ▁prom oter ) ▁in ▁A . ▁th al iana . ▁The ▁trans gen ic ▁line ▁has ▁been ▁shown ▁to ▁accum ulate ▁high ▁levels ▁of ▁the ▁At M RS 2 - 1 1 ▁trans cript . ▁A ▁strong ▁M g 2 + ▁def ic iency ▁phen ot ype ▁( ne c rot ic ▁sp ots ▁on ▁the ▁leaves , ▁see ▁Chapter ▁ 1 . 5 ▁below ) ▁was ▁recorded ▁during ▁the ▁screen ing ▁process ▁( in ▁both ▁the ▁T 1 ▁and ▁T 2 ▁gener ations ) ▁for ▁a ▁hom o zy g ote ▁line , ▁but ▁this ▁phen ot ype ▁was ▁lost ▁in ▁the ▁T 3 ▁generation ▁and ▁could ▁not ▁be ▁reprodu ced ▁when ▁the ▁earlier ▁gener ations ▁were ▁screen ed ▁a ▁second ▁time . ▁The |
▁author ▁suggested ▁that ▁environmental ▁effects ▁were ▁the ▁most ▁likely ▁cause ▁of ▁the ▁incons istent ▁phen ot ype . ▁ ▁At M H X ▁The ▁first ▁mag nes ium ▁trans porter ▁isolated ▁in ▁any ▁mult ic ell ular ▁organ ism , ▁At M H X ▁shows ▁no ▁similarity ▁to ▁any ▁previously ▁isolated ▁M g 2 + ▁transport ▁protein . ▁The ▁gene ▁was ▁initially ▁identified ▁in ▁the ▁A . ▁th al iana ▁genom ic ▁DNA ▁sequence ▁database , ▁by ▁its ▁similarity ▁to ▁the ▁S LC 8 ▁family ▁of ▁Na + / Ca 2 + ▁ex ch anger ▁gen es ▁in ▁humans . ▁ ▁The ▁c D NA ▁sequence ▁of ▁ 1 9 9 0 ▁b p ▁is ▁predicted ▁to ▁produce ▁a ▁ 5 3 9 - am ino ▁acid ▁protein . ▁At M H X ▁is ▁quite ▁closely ▁related ▁to ▁the ▁S LC 8 ▁family ▁at ▁the ▁am ino ▁acid ▁level ▁and ▁shares ▁a ▁topology ▁with ▁eleven ▁predicted ▁T M ▁domains ▁( Fig ure ▁A 1 0 . 5 ). ▁There ▁is ▁one ▁major ▁difference ▁in ▁the ▁sequence , ▁in ▁that ▁the ▁long ▁non - m emb ran al ▁loop ▁( see ▁Figure ▁A 1 0 . 5 ) ▁is ▁ 1 4 8 ▁am ino ▁ac ids ▁in ▁the ▁At M H X ▁protein ▁but ▁ 5 0 0 ▁am ino ▁ac ids ▁in ▁the ▁S LC 8 ▁prote ins . ▁However , ▁this ▁loop ▁is ▁not ▁well ▁conser ved ▁and ▁is ▁not ▁required ▁for ▁transport ▁function ▁in ▁the ▁S LC 8 ▁family . |
▁ ▁The ▁At M H X ▁gene ▁is ▁expressed ▁throughout ▁the ▁plant ▁but ▁most ▁strongly ▁in ▁the ▁v asc ular ▁t issue . ▁The ▁authors ▁suggest ▁that ▁the ▁phys i ological ▁role ▁of ▁the ▁protein ▁is ▁to ▁store ▁M g 2 + ▁in ▁these ▁t issues ▁for ▁later ▁release ▁when ▁needed . ▁The ▁protein ▁local isation ▁to ▁the ▁vac u olar ▁memb rane ▁supports ▁this ▁suggestion ▁( see ▁also ▁Chapter ▁ 1 . 5 ). ▁ ▁The ▁protein ▁trans ports ▁M g 2 + ▁into ▁the ▁vac u olar ▁space ▁and ▁H + ▁out , ▁as ▁demonstrated ▁by ▁electro phys i ological ▁techniques . ▁The ▁transport ▁is ▁driven ▁by ▁the ▁ Δ p H ▁maintained ▁between ▁the ▁vac u olar ▁space ▁( p H ▁ 4 . 5 ▁– ▁ 5 . 9 ) ▁and ▁the ▁cy top las m ▁( p H ▁ 7 . 3 ▁– ▁ 7 . 6 ) ▁by ▁an ▁H + - AT P ase . ▁How ▁the ▁transport ▁of ▁M g 2 + ▁by ▁the ▁protein ▁is ▁reg ulated ▁was ▁not ▁determined . ▁C urr ents ▁were ▁observed ▁to ▁pass ▁through ▁the ▁protein ▁in ▁both ▁directions , ▁but ▁the ▁M g 2 + ▁out ▁current ▁required ▁a ▁‘ cy top las mic ’ ▁p H ▁of ▁ 5 . 5 , ▁a ▁condition ▁not ▁found ▁in ▁plant ▁cells ▁under ▁normal ▁circumstances . ▁In ▁addition ▁to ▁the ▁transport ▁of ▁M g 2 + , ▁Sh a ul ▁et ▁al . ▁( 1 9 9 9 ) ▁also |
▁showed ▁that ▁the ▁protein ▁could ▁transport ▁Z n 2 + ▁and ▁Fe 2 + , ▁but ▁did ▁not ▁report ▁on ▁the ▁capacity ▁of ▁the ▁protein ▁to ▁transport ▁other ▁div al ent ▁c ations ▁( e . g . ▁Co 2 + ▁and ▁Ni 2 +) ▁or ▁its ▁sus cept ibility ▁to ▁in hib ition ▁by ▁c ob alt ▁( III ) ▁hex a amm ine . ▁ ▁The ▁detailed ▁k inet ics ▁of ▁M g 2 + ▁transport ▁have ▁not ▁been ▁determined ▁for ▁At M H X . ▁However , ▁phys i ological ▁effects ▁have ▁been ▁demonstrated . ▁When ▁A . ▁th al iana ▁plants ▁were ▁transformed ▁with ▁over expression ▁construct s ▁of ▁the ▁At M H X ▁gene ▁driven ▁by ▁the ▁Ca M V ▁ 3 5 S ▁prom oter , ▁the ▁plants ▁over - acc um ulated ▁the ▁protein ▁and ▁showed ▁a ▁phen ot ype ▁of ▁ne c rot ic ▁les ions ▁in ▁the ▁leaves , ▁which ▁the ▁authors ▁suggest ▁is ▁caused ▁by ▁a ▁dis ruption ▁in ▁the ▁normal ▁function ▁of ▁the ▁vac u ole , ▁given ▁their ▁observation ▁that ▁the ▁total ▁M g 2 + ▁( or ▁Z n 2 +) ▁content ▁of ▁the ▁plants ▁was ▁not ▁alter ed ▁in ▁the ▁trans gen ic ▁plants . ▁▁ ▁The ▁image ▁has ▁been ▁adapted ▁from ▁Sh a ul ▁et ▁al . ▁( 1 9 9 9 ) ▁and ▁Qu ed n au ▁et ▁al . ▁( 2 0 0 4 ), ▁and ▁combined ▁with ▁an ▁analysis ▁using ▁H MM T OP , |
▁this ▁figure ▁shows ▁the ▁computer ▁predicted ▁memb rane ▁topology ▁of ▁the ▁At M H X ▁protein ▁in ▁Arab id opsis ▁th al iana . ▁At ▁this ▁time ▁the ▁topology ▁shown ▁should ▁be ▁considered ▁a ▁tent ative ▁hypothesis . ▁The ▁T M ▁domains ▁are ▁shown ▁in ▁light ▁blue , ▁the ▁orientation ▁in ▁the ▁memb rane ▁and ▁the ▁positions ▁of ▁the ▁N - ▁and ▁C - termin i ▁are ▁indicated , ▁and ▁the ▁figure ▁is ▁not ▁drawn ▁to ▁scale . ▁The ▁α 1 ▁and ▁α 2 ▁domains , ▁shown ▁in ▁green , ▁are ▁both ▁quite ▁hydro ph ob ic ▁and ▁may ▁both ▁be ▁inserted ▁into ▁the ▁memb rane . ▁ ▁References ▁▁ ▁Category : Bi ology ▁and ▁ph arm ac ology ▁of ▁chemical ▁elements ▁Category : I on ▁channels ▁Category : Phys i ology ▁Category : M agn es ium ▁Category : M emb rane ▁bi ology <0x0A> </s> ▁The ▁N inth ▁AR MM ▁Regional ▁Legisl ative ▁Assembly ▁was ▁the ▁last ▁meeting ▁of ▁the ▁un ic amer al ▁regional ▁legisl ature ▁of ▁the ▁Aut onom ous ▁Region ▁in ▁Muslim ▁Mind ana o ▁( AR MM ). ▁Due ▁to ▁the ▁rat ification ▁of ▁the ▁Bang sam oro ▁Organ ic ▁Law ▁creating ▁the ▁Bang sam oro ▁Aut onom ous ▁Region ▁which ▁replaced ▁the ▁AR MM , ▁the ▁election ▁of ▁legisl ators ▁for ▁a ▁t enth ▁meeting ▁of ▁the ▁assembly ▁was ▁cancel led . ▁ ▁Ron nie ▁S ins u at ▁was ▁the ▁last ▁speaker ▁of ▁the ▁last ▁meeting ▁of ▁the ▁assembly . ▁ ▁M embers ▁ ▁See |
▁also ▁Aut onom ous ▁Region ▁of ▁Muslim ▁Mind ana o ▁AR MM ▁Regional ▁Legisl ative ▁Assembly ▁ ▁References ▁ ▁Category : AR MM ▁Regional ▁Legisl ative ▁Assembly ▁by ▁legisl ative ▁period <0x0A> </s> ▁H unt ▁Hill ▁is ▁a ▁mountain ▁located ▁in ▁the ▁Cat sk ill ▁Mountains ▁of ▁New ▁York ▁south ▁of ▁And es . ▁Hem lock ▁Kn oll ▁is ▁located ▁north , ▁and ▁Mary ▁Smith ▁Hill ▁is ▁located ▁south west ▁of ▁H unt ▁Hill . ▁ ▁References ▁ ▁Category : Mount ains ▁of ▁Del aware ▁County , ▁New ▁York ▁Category : Mount ains ▁of ▁New ▁York ▁( state ) <0x0A> </s> ▁Ash ets co lex ▁is ▁a ▁genus ▁of ▁lower ▁Ord ov ician ▁p ala e os cole cid . ▁ ▁References ▁▁ ▁Category : Pre histor ic ▁proto st ome ▁gener a ▁Category : P ale os cole c ids <0x0A> </s> ▁Jo el ▁E lias ▁Pay amps ▁( born ▁April ▁ 7 , ▁ 1 9 9 4 ) ▁is ▁a ▁Domin ican ▁professional ▁baseball ▁pitch er ▁for ▁the ▁Arizona ▁Diam ond back s ▁of ▁Major ▁League ▁baseball ▁( ML B ). ▁ ▁Career ▁ ▁Colorado ▁Rock ies ▁Pay amps ▁signed ▁with ▁the ▁Colorado ▁Rock ies ▁as ▁an ▁international ▁free ▁agent ▁on ▁May ▁ 1 , ▁ 2 0 1 1 . ▁He ▁spent ▁his ▁first ▁two ▁seasons ▁with ▁the ▁D SL ▁Rock ies , ▁going ▁ 1 – 3 ▁with ▁a ▁ 3 . 2 9 ▁E RA ▁in ▁ 3 8 ▁inn ings ▁in ▁ 2 0 1 1 |
▁and ▁going ▁ 1 – 2 ▁with ▁a ▁ 3 . 0 2 ▁E RA ▁in ▁ 5 9 . 2 ▁inn ings ▁in ▁ 2 0 1 2 . ▁He ▁spent ▁ 2 0 1 3 ▁with ▁the ▁Grand ▁J unction ▁Rock ies , ▁going ▁ 4 – 7 ▁with ▁a ▁ 6 . 0 6 ▁E RA ▁in ▁ 6 8 ▁inn ings . ▁He ▁played ▁for ▁the ▁Tri - City ▁D ust ▁Dev ils ▁in ▁ 2 0 1 4 , ▁going ▁ 0 – 2 ▁with ▁a ▁ 6 . 1 0 ▁E RA ▁in ▁ 2 0 . 2 ▁inn ings . ▁▁ ▁He ▁did ▁not ▁appear ▁in ▁a ▁game ▁in ▁ 2 0 1 5 ▁after ▁being ▁released ▁by ▁the ▁Rock ies ▁on ▁May ▁ 6 . ▁ ▁Arizona ▁Diam ond back s ▁He ▁signed ▁a ▁minor ▁league ▁contract ▁with ▁the ▁Arizona ▁Diam ond back s ▁on ▁November ▁ 3 0 , ▁ 2 0 1 5 . ▁He ▁returned ▁in ▁ 2 0 1 6 ▁and ▁split ▁the ▁season ▁between ▁the ▁K ane ▁County ▁C oug ars ▁and ▁the ▁Vis alia ▁Ra wh ide , ▁going ▁a ▁combined ▁ 1 0 – 8 ▁with ▁a ▁ 3 . 8 6 ▁E RA ▁in ▁ 1 3 2 . 1 ▁inn ings . ▁His ▁ 2 0 1 7 ▁season ▁was ▁split ▁between ▁Vis alia , ▁the ▁Jackson ▁Gener als , ▁and ▁the ▁Ren o ▁A ces , ▁going ▁a ▁combined ▁ 1 1 – 7 ▁with |
▁a ▁ 4 . 3 0 ▁E RA ▁in ▁ 1 5 0 . 2 ▁inn ings . ▁He ▁split ▁the ▁ 2 0 1 8 ▁season ▁between ▁Jackson ▁and ▁Ren o , ▁going ▁a ▁combined ▁ 9 – 8 ▁with ▁a ▁ 3 . 8 7 ▁E RA ▁in ▁ 1 1 6 ▁inn ings . ▁▁ ▁The ▁Diam ond back s ▁added ▁him ▁to ▁their ▁ 4 0 - man ▁ro ster ▁after ▁the ▁ 2 0 1 8 ▁season . ▁ ▁He ▁opened ▁the ▁ 2 0 1 9 ▁season ▁back ▁with ▁Ren o . ▁He ▁suffered ▁a ▁broken ▁foot ▁on ▁April ▁ 6 ▁when ▁he ▁was ▁hit ▁by ▁a ▁batt ed ▁ball . ▁He ▁finished ▁the ▁ 2 0 1 9 ▁minor ▁league ▁season ▁after ▁posting ▁a ▁combined ▁ 5 – 6 ▁record ▁with ▁a ▁ 3 . 8 9 ▁E RA ▁in ▁ 7 8 . 2 ▁inn ings ▁between ▁Jackson ▁and ▁Ren o . ▁ ▁On ▁August ▁ 1 7 , ▁ 2 0 1 9 , ▁the ▁Diam ond back s ▁promoted ▁Pay amps ▁to ▁the ▁major ▁le agues . ▁He ▁made ▁his ▁major ▁league ▁debut ▁on ▁August ▁ 2 1 ▁versus ▁the ▁Colorado ▁Rock ies , ▁allowing ▁two ▁runs ▁over ▁three ▁inn ings ▁pitch ed . ▁ ▁References ▁ ▁External ▁links ▁ ▁Category : 1 9 9 4 ▁birth s ▁Category : L iving ▁people ▁Category : Pe ople ▁from ▁Santiago ▁de ▁los ▁Cab all eros ▁Category : D omin ican ▁Republic ▁exp atri ate |
▁baseball ▁players ▁in ▁the ▁United ▁States ▁Category : M aj or ▁League ▁Baseball ▁players ▁from ▁the ▁Domin ican ▁Republic ▁Category : M aj or ▁League ▁Baseball ▁pitch ers ▁Category : A rizona ▁Diam ond back s ▁players ▁Category : D omin ican ▁Summer ▁League ▁Rock ies ▁players ▁Category : Gr and ▁J unction ▁Rock ies ▁players ▁Category : Tri - City ▁D ust ▁Dev ils ▁players ▁Category : K ane ▁County ▁C oug ars ▁players ▁Category : Vis alia ▁Ra wh ide ▁players ▁Category : Jack son ▁Gener als ▁( S ou thern ▁League ) ▁players ▁Category : R eno ▁A ces ▁players ▁Category : Est rell as ▁Orient ales ▁players ▁Category : 2 0 1 5 ▁W B SC ▁Premier 1 2 ▁players <0x0A> </s> ▁This ▁list ▁of ▁University ▁of ▁She ff ield ▁people ▁is ▁a ▁selected ▁list ▁of ▁notable ▁past ▁staff ▁and ▁students ▁of ▁the ▁University ▁of ▁She ff ield . ▁ ▁Notable ▁al umn i ▁ ▁Academ ics ▁ ▁Fred a ▁Brig gs , ▁Emer it us ▁Professor , ▁University ▁of ▁South ▁Australia , ▁child ▁protection ▁expert ▁ ▁Thom ▁Bro oks , ▁Dean , ▁Dur ham ▁Law ▁School ▁& ▁Professor ▁of ▁Law ▁and ▁Government ▁Dur ham ▁University ▁( Ph D ▁Philosoph y ▁ 2 0 0 4 ) ▁ ▁Sir ▁Paul ▁Cur ran , ▁President , ▁City , ▁University ▁of ▁London ▁( B Sc ▁Geography ▁ 1 9 7 6 ) ▁ ▁P addy ▁N ixon , ▁Vice - Ch an cell or ▁& ▁President , ▁Ul ster ▁University ▁( |
Ph D ▁ 1 9 9 4 ) ▁ ▁Stuart ▁Pal mer ▁F RE ng , ▁Deput y ▁Vice - Ch an cell or , ▁University ▁of ▁War wick ▁ ▁Michael ▁Ster ling , ▁Vice - Ch an cell or , ▁University ▁of ▁B irmingham ▁( B Eng ▁Electron ic ▁and ▁Elect rical ▁Engineering ▁ 1 9 6 7 , ▁Ph D ▁ 1 9 7 1 ) ▁ ▁George ▁Martin ▁Stephen , ▁High ▁Master , ▁St ▁Paul ' s ▁School ▁( Ph D ) ▁ ▁John ▁S utton , ▁Sir ▁John ▁H icks ▁Professor ▁of ▁Econom ics , ▁London ▁School ▁of ▁Econom ics ▁ ▁Richard ▁Wild ing ▁O BE , ▁Professor ▁of ▁Supp ly ▁Ch ain ▁Str ategy , ▁C ran field ▁University ▁and ▁Chair man ▁of ▁the ▁Char tered ▁Institute ▁of ▁Log istics ▁& ▁Transport ▁( B Sc ▁( T ech ) ▁Material ▁Science ▁ 1 9 8 7 ) ▁ ▁Business ▁people ▁ ▁Richard ▁C ous ins , ▁CE O ▁of ▁Com pass ▁Group ▁world ' s ▁largest ▁food service ▁company ▁ ▁H uss ain ▁Da wood , ▁Chair man ▁of ▁Da wood ▁Her cules ▁Corporation ▁Limited , ▁Eng ro ▁Corporation ▁Limited ▁ ▁John ▁De van ey , ▁Chair man , ▁Mar con i ▁P LC ▁ ▁Jer emy ▁Gran th am , ▁Co - found er ▁of ▁G MO ▁asset ▁management ▁Param ▁Singh , ▁Property ▁Develop er , ▁Entre pr ene ur ▁ ▁Pen ny ▁Hugh es , ▁former ▁president ▁of ▁C oca - Col a ▁Enter pr ises |
▁( UK ) ▁( B Sc ▁( H ons ) ▁Chem istry ) ▁ ▁Sir ▁Peter ▁Middle ton , ▁Cam el ot ▁Bar cl ays ▁Chair man ▁ ▁Edward ▁H ▁N tal ami , ▁Chief ▁Executive , ▁Capital ▁Mark ets ▁Author ity , ▁Ken ya ▁ ▁Jim ▁O ' Ne ill , ▁Head ▁of ▁global ▁economic ▁research , ▁Gold man ▁Sach s ▁and ▁co ined ▁the ▁th esis ▁of ▁BR IC ▁countries ▁ ▁Richard ▁Sim m ons , ▁CE O ▁Commission ▁for ▁Architecture ▁and ▁the ▁Bu ilt ▁Environment ▁( C AB E ) ▁Wei ▁Yang , ▁Found er ▁of ▁Wei ▁Yang ▁& ▁Part ner , ▁Town ▁Pl anner ▁and ▁Urban ▁Design er ▁( MS c ▁ 2 0 0 1 , ▁Ph D ▁ 2 0 0 5 ) ▁ ▁Law y ers ▁ ▁David ▁Child s , ▁former ▁Man aging ▁Part ner ▁of ▁Cl iff ord ▁Ch ance ▁ ▁Moh amm ad ▁Q as im ▁Hash im za i , ▁Deput y ▁Minister ▁of ▁Justice , ▁Afghan istan ▁ ▁M d . ▁M uz amm el ▁H oss ain , ▁Chief ▁Justice ▁of ▁Bang l adesh ▁ ▁Henry ▁M . ▁J oko - Sm art , ▁former ▁Sierra ▁Le one an ▁Supreme ▁Court ▁Justice ▁ ▁Sir ▁Maurice ▁Kay ▁Lord ▁Justice ▁of ▁App e al ▁ ▁Sir ▁Paul ▁Kennedy , ▁Lord ▁Justice ▁of ▁App e al , ▁Inter ception ▁of ▁Communic ations ▁Commission er ▁ ▁Sir ▁N ig el ▁Know les , ▁CE O ▁of ▁the ▁Ang lo - American ▁law ▁firm ▁D |
LA ▁Pi per ▁ ▁D ame ▁Julia ▁Mac ur , ▁Lord ▁Justice ▁of ▁App e al ▁ ▁Sir ▁Al ist air ▁Mac D uff , ▁High ▁Court ▁of ▁Justice ▁of ▁England ▁and ▁Wales ▁ ▁D ame ▁Anne ▁Raf fer ty , ▁Lord ▁Justice ▁of ▁App e al ▁ ▁Tommy ▁S ih ot ang , ▁Indones ian ▁Law yer ▁ ▁Ar if in ▁Zak aria , ▁Chief ▁Justice ▁of ▁Malays ia ▁ ▁In ▁November ▁ 2 0 1 3 , ▁for ▁the ▁first ▁time ▁in ▁history , ▁the ▁Court ▁of ▁App e al ▁had ▁an ▁all - She ff ield ▁al umn i ▁ben ch . ▁The ▁jud ges ▁sitting ▁were ▁Lord ▁Justice ▁Maurice ▁Kay ▁( LL B ▁Law , ▁ 1 9 6 4 ; ▁Ph D ▁Law , ▁ 1 9 7 1 ▁and ▁Hon ▁L LD , ▁ 2 0 0 3 ), ▁Lady ▁Justice ▁Anne ▁Raf fer ty ▁( LL B ▁Law , ▁ 1 9 7 1 ▁and ▁Hon ▁L LD , ▁ 2 0 0 5 ) ▁and ▁Lady ▁Justice ▁Julia ▁Mac ur ▁( LL B ▁Law , ▁ 1 9 7 8 ). ▁This ▁event ▁was ▁also ▁extremely ▁significant ▁because ▁outside ▁Oxford ▁and ▁Cambridge , ▁She ff ield ▁now ▁has ▁the ▁record ▁for ▁the ▁highest ▁number ▁of ▁gradu ates ▁appointed ▁to ▁the ▁ben ch ▁above ▁any ▁other ▁UK ▁University . ▁ ▁Auth ors ▁▁ ▁L inds ay ▁Ash ford , ▁author ▁ ▁Lee ▁Child , ▁novel ist ▁( LL B ) ▁ ▁Soph ie ▁De en , |
▁children ’ s ▁book ▁author ▁ ▁Nic ci ▁G err ard , ▁author ▁ ▁Jo anne ▁Harris , ▁author ▁( l ater ▁became ▁fac ulty ) ▁ ▁Bro oke ▁Magn anti ▁a . k . a . ▁" B elle ▁de ▁J our ", ▁author ▁ ▁Hil ary ▁Mant el ▁author ▁( LL B ), ▁two ▁times ▁Book er ▁Prize ▁winner ▁ ▁Jack ▁Ros ent hal , ▁play w right ▁ ▁John ▁Thompson ▁( po et ) ▁( 1 9 3 8 – 1 9 7 6 ), ▁Canadian ▁poet ▁ ▁Rock y ▁Fl int stone , ▁author ▁ ▁Media ▁and ▁artists ▁ ▁Carol ▁Bar nes , ▁IT N ▁News reader ▁ ▁Douglas ▁B ost ock , ▁conduct or ▁ ▁Luc ie ▁C ave , ▁journalist , ▁editor ▁of ▁He at ▁magazine ▁ ▁Peter ▁Che es eman , ▁theatre ▁director , ▁leading ▁pione er ▁of ▁theatre - in - the - round ▁and ▁document ary ▁drama ▁ ▁Stephen ▁D ald ry , ▁stage ▁and ▁film ▁director ▁ ▁Chris ▁F aw kes , ▁BBC ▁We ather ▁forec aster ▁ ▁Martin ▁F ry , ▁lead ▁singer ▁of ▁ABC ▁ ▁Brian ▁Glo ver , ▁actor ▁ ▁Ian ▁Hall ard , ▁actor ▁ ▁Edd ie ▁I zz ard , ▁com ed ian ▁ ▁Tim ▁Key , ▁com ed ian , ▁poet , ▁recip ient ▁of ▁the ▁Edinburgh ▁Com edy ▁Award ▁ 2 0 0 9 ▁ ▁Gl enn ▁Moore , ▁com ed ian ▁ ▁Sid ▁L owe , ▁The ▁Guardian , ▁journalist ▁ ▁Paul ▁Mason , ▁BBC |
▁News night ▁ ▁John ▁O ' Le ary , ▁Times ▁High er ▁Education ▁Supp lement ▁editor ▁ ▁Rach el ▁Sh elle y , ▁actress ▁( BA ▁( H ons ) ▁English ▁and ▁D rama ) ▁ ▁L inda ▁Smith , ▁com ed ian ▁and ▁head ▁of ▁the ▁British ▁Human ist ▁Association ▁ ▁Dan ▁Walker , ▁sports ▁journalist ▁ ▁Andrew ▁Wilson , ▁Sky ▁News ▁News ▁Pres enter ▁and ▁former ▁foreign ▁correspond ent ▁ ▁Frank ▁Wor r all , ▁The ▁Sun , ▁author ▁and ▁journalist ▁Sel ina ▁Thompson , ▁performance ▁artist ▁and ▁play w right ▁ ▁P ione ers ▁ ▁Amy ▁Johnson , ▁pilot ▁( BA ▁( H ons ) ▁Econom ics , ▁ 1 9 2 6 ) ▁ ▁Roy ▁Ko erner , ▁Pol ar ▁Explorer ▁ ▁Helen ▁Sh ar man , ▁first ▁British ▁astr onaut ▁( B Sc ▁( H ons ) ▁Chem istry , ▁ 1 9 8 4 ) ▁ ▁Eric ▁M ox ey , ▁bomb ▁dispos al ▁expert ▁and ▁invent or ▁of ▁the ▁Fu ze ▁Ext ractor ▁ ▁Polit icians ▁▁ ▁Nicholas ▁Liverpool , ▁ 6 th ▁President ▁of ▁Domin ica ▁ ▁N ure tt in ▁Can ik li , ▁Inc umb ent ▁First ▁Deput y ▁Prime ▁Minister ▁of ▁Turkey ▁in ▁B inal i ▁Y ald rim ' s ▁Cab inet , ▁former ▁Minister ▁for ▁Custom s ▁and ▁Trade , ▁Turkey ▁ ▁Jean - Paul ▁Adam , ▁Minister ▁for ▁Foreign ▁Affairs ▁( S ey ch elles ) ▁ ▁Peter ▁Adams , ▁Canadian ▁politician ▁ ▁Jonathan ▁Ar not t , ▁UK |
▁Independ ence ▁Party ▁M EP ▁ ▁Kevin ▁Bar ron , ▁Labour ▁MP ▁ ▁Ger ry ▁B erm ingham , ▁Labour ▁MP ▁ ▁J ake ▁Ber ry , ▁Conserv ative ▁MP ▁ ▁Oliv ia ▁Bla ke , ▁Labour ▁MP ▁for ▁She ff ield ▁Hall am ▁ ▁David ▁Bl unk ett , ▁MP ▁for ▁She ff ield ▁Bright side ▁and ▁former ▁Home ▁Secretary ▁ ▁Sarah ▁Champion ▁Labour ▁MP ▁ ▁David ▁Clark , ▁Baron ▁Clark ▁of ▁Wind erm ere , ▁Labour ▁peer ▁ ▁Serge ▁Jo yal , ▁Canadian ▁Senator ▁ ▁Jud ith ▁Kir ton - D ar ling , ▁Labour ▁Member ▁of ▁the ▁European ▁Parliament ▁ ▁Anne ▁Main , ▁Conserv ative ▁MP ▁for ▁St ▁Alb ans ▁ ▁Brian ▁Mill ard , ▁leader ▁of ▁Stock port ▁Metropolitan ▁Bor ough ▁Council ▁from ▁ 2 0 0 5 ▁to ▁ 2 0 0 7 ▁ ▁Fen ella ▁M uk ang ara , ▁Minister ▁of ▁Information , ▁Culture ▁and ▁Sports , ▁T anz ania ▁ ▁Hugo ▁Antonio ▁L avi ada ▁Mol ina , ▁Mexican ▁politician ▁ ▁Philip ▁N orton , ▁Baron ▁N orton ▁of ▁L outh , ▁Conserv ative ▁peer ▁& ▁academic ▁ ▁Steve ▁Re ed , ▁Labour ▁MP ▁ ▁On kar ▁Sah ota , ▁Labour ▁London ▁Assembly ▁Member ▁for ▁E aling ▁and ▁H illing don ▁ ▁K adi ▁Ses ay , ▁Minister ▁of ▁Trade ▁and ▁Indust ry , ▁S ierre ▁Le one ▁ ▁Graham ▁String er , ▁Labour ▁MP ▁ ▁Y b ▁D ato ' ▁R ash id ▁bin ▁Has non , De put y ▁Chief ▁Minister ▁of ▁Pen |
ang , Mal ays ia ▁PK R ▁M LA ▁ ▁Sir ▁Ch ung ▁S ze - y uen , ▁former ▁Con ven or ▁of ▁the ▁Executive ▁Council ▁of ▁Hong ▁Kong ▁ ▁Ann ▁Taylor , ▁Baron ess ▁Taylor ▁of ▁Bol ton , ▁Labour ▁MP ▁for ▁Bol ton ▁West ▁and ▁D ew s bury , ▁subsequently ▁a ▁life ▁peer ▁and ▁former ▁minister ▁at ▁the ▁Ministry ▁of ▁Def ence ▁ ▁Mont fort ▁T ad ier , ▁Jersey ▁Polit ician ▁ ▁Nick ▁Tim othy , ▁Down ing ▁Street ▁Chief ▁of ▁Staff ▁ ▁Eric ▁Graham ▁Var ley , ▁former ▁Labour ▁Cab inet ▁minister ▁ ▁Caroline ▁Vo aden , ▁Liberal ▁Dem ocrat ▁M EP ▁ ▁Sir ▁Frederick ▁Arch ib ald ▁Warner , ▁diplom at ▁& ▁Member ▁of ▁the ▁European ▁Parliament ▁ ▁Public ▁servants ▁▁ ▁K hal id ▁S . ▁Al - Age el , ▁General ▁Secretary ▁of ▁the ▁High ▁Commission ▁for ▁Indust rial ▁Security , ▁Sa udi ▁Arab ia ▁ ▁Mag gie ▁At kin son , ▁Children ' s ▁Commission er ▁for ▁England ▁ ▁Sir ▁Michael ▁Carl is le , ▁Senior ▁Civil ▁Serv ant ▁ ▁Lim ▁Ne o ▁Ch ian , ▁former ▁Chief ▁of ▁Singapore ▁Army ▁ ▁Major - General ▁Andrew ▁Far qu har , ▁British ▁Army ▁ ▁Sir ▁Vincent ▁Fe an , ▁British ▁diplom at ▁ ▁Andy ▁H ald ane , ▁Chief ▁Econom ist ▁at ▁the ▁Bank ▁of ▁England ▁ ▁Sir ▁Bernard ▁Hog an - H owe , ▁Commission er , ▁London ' s ▁Metropolitan ▁Police ▁Service ▁ ▁Sir ▁Ken ▁Jones , ▁Deput y ▁Commission er ▁of ▁Victoria |
▁Police , ▁Chief ▁Const able , ▁Sus sex ▁Police ▁ ▁Van essa ▁Lawrence , ▁Or dn ance ▁Survey ▁Director - General ▁ ▁Vice - Ad mir al ▁Sir ▁Charles ▁Mont gom ery , ▁Director ▁General , ▁UK ▁Border ▁Force ▁ ▁Air ▁Chief ▁Marsh al ▁Sir ▁Stuart ▁Pe ach , ▁Chief ▁of ▁the ▁Def ence ▁Staff , ▁UK ▁ ▁Cris p ian ▁Stra chan , ▁Chief ▁Const able ▁of ▁North umb ria ▁Police ▁ ▁Phil ▁Whe at ley , ▁Director - General ▁H M ▁Pr ison ▁Service ▁ ▁C ler gy ▁ ▁Wes ley ▁Car r , ▁Dean ▁of ▁West min ster ▁Ab bey ▁John ▁Che w , ▁Bishop ▁of ▁Singapore ▁Gl enn ▁Dav ies , ▁Arch bishop ▁of ▁Sydney ▁Jan ▁Mc F ar lane , ▁Bishop ▁of ▁Re pton ▁Tony ▁Nich ols , ▁Bishop ▁of ▁North ▁West ▁Australia ▁John ▁Park es , ▁Bishop ▁of ▁Wang ar atta ▁Mart yn ▁Per cy , ▁Dean ▁of ▁Christ ▁Church , ▁Oxford ▁Henry ▁William ▁S cri ven , ▁Bishop ▁of ▁Pitts burgh ▁Stephen ▁S my th , ▁General ▁Secretary ▁of ▁Action ▁of ▁Church es ▁T ogether ▁in ▁Scotland ▁( 2 0 0 7 – 2 0 1 4 ) ▁Mart yn ▁Snow , ▁Bishop ▁of ▁Le ic ester ▁Alan ▁W inton , ▁Bishop ▁of ▁Th et ford ▁ ▁Scient ists ▁ ▁Sir ▁Donald ▁Ba iley , ▁civil ▁engineer ▁and ▁invent or ▁of ▁the ▁Ba iley ▁bridge ▁ ▁Sir ▁Harold ▁K ro to , ▁Nobel ▁Prize - win ning ▁chem ist ▁( B Sc ▁( H ons ) |
▁Chem istry , ▁ 1 9 6 1 ; ▁Ph D , ▁ 1 9 6 1 – 1 9 6 4 ) ▁ ▁Sir ▁Hans ▁K orn berg , ▁bio chem ist , ▁Master ▁of ▁Christ ' s ▁College ▁Cambridge ▁ ▁Sir ▁Richard ▁Roberts , ▁Nobel ▁Prize - win ning ▁gen etic ist ▁( B Sc ▁( H ons ) ▁Chem istry , ▁ 1 9 6 5 ; ▁Ph D , ▁ 1 9 6 8 ) ▁ ▁O live ▁Scott , ▁pa ed iat ric ▁card i ologist ▁( MB BS ▁ 1 9 4 8 ; ▁MD ▁ 1 9 5 7 ) ▁ ▁Sports ▁people ▁▁ ▁Nick ▁Be ight on , ▁Par al ym pic ▁Bron ze ▁Med all ist ▁ 2 0 1 6 , ▁Men ' s ▁K L 2 ▁can oe ▁s print ▁ ▁Z ara ▁D amp ney , ▁ ▁beach ▁vol ley ball ▁player ▁ ▁David ▁Dav ies , ▁The ▁Football ▁Association ▁Chief ▁Executive ▁ ▁Jess ica ▁En nis , ▁Olympic ▁Gold ▁Medal ist , ▁he pt ath lete ▁ ▁Catherine ▁F aux , ▁tri ath lete ▁ ▁Tony ▁Mil es , ▁the ▁United ▁Kingdom ' s ▁first ▁ch ess ▁grand ▁master ▁ ▁Bry ony ▁Page , ▁Olympic ▁Silver ▁Med all ist ▁ 2 0 1 6 , ▁tr amp ol ining ▁ ▁C ▁R ▁Roberts , ▁ath lete ▁ ▁Tim ▁Robinson , ▁England ▁International ▁Cr ick eter ▁ ▁H oll ie ▁Web b , ▁Olympic ▁Gold ▁Med all ist ▁ 2 0 |
1 6 , ▁women ' s ▁hockey ▁ ▁David ▁W ether all , ▁footballer ▁ ▁David ▁W ether ill , ▁Par al ym pic ▁table ▁tennis ▁player ▁ ▁Krist ian ▁Jones ▁and ▁Jam ie ▁Stevens on , ▁or iente ers ▁with ▁med als ▁at ▁world ▁champion ships ▁ ▁Notable ▁academ ics ▁ ▁Francis ▁Ber ry , ▁poet ▁and ▁literary ▁critic ▁ ▁Norman ▁Bla ke , ▁Middle ▁English ▁and ▁Early ▁Modern ▁English ▁language ▁and ▁literature ▁scholar ▁ ▁Peter ▁Bl und ell ▁Jones , ▁Professor ▁in ▁Architecture ▁ ▁Sir ▁Anthony ▁B ottom s , ▁Professor ▁of ▁C rimin ology ▁ ▁Ang ela ▁Carter , ▁author ▁( 1 9 7 6 – 1 9 7 8 ) ▁ ▁Henry ▁Cow ard , ▁conduct or ▁ ▁D anny ▁Dor ling , ▁former ▁professor ▁of ▁Geography ▁ ▁Sir ▁Bernard ▁Cr ick , ▁former ▁Professor ▁of ▁Polit ics ▁ ▁Sir ▁Gra eme ▁Dav ies , ▁Vice - Ch an cell or ▁University ▁of ▁London ▁ ▁Charles ▁Eli ot , ▁diplom at , ▁Vice - Ch an cell or ▁ ▁Sir ▁William ▁Em pson , ▁poet ▁( The ▁School ▁of ▁English ▁names ▁its ▁facilities ▁after ▁him ) ▁ ▁L ilian ▁Edwards , ▁Professor ▁of ▁Internet ▁Law ▁ ▁Howard ▁Fl ore y , ▁Nobel ▁Prize ▁winner , ▁Joseph ▁Hunter ▁Professor ▁of ▁Path ology ▁ ▁Andrew ▁Gam ble , ▁political ▁econom ist , ▁Professor ▁of ▁Polit ics ▁ ▁Jo anne ▁Harris , ▁author ▁( 2 0 0 0 ; ▁was ▁also ▁a ▁student ) ▁ ▁Peter ▁Hill , ▁well - known ▁pian |
ist ▁and ▁expert ▁on ▁the ▁works ▁of ▁Oliv ier ▁Mess ia en ▁ ▁Sir ▁Robert ▁H oney com be , ▁met all urg ist ▁ ▁R . ▁J . ▁Ho pper , ▁Professor ▁of ▁An cient ▁History ▁ ▁David ▁Hugh es , ▁astronom er , ▁Ast ero id ▁ 4 2 0 5 ▁is ▁named ▁in ▁his ▁honour . ▁ ▁D ame ▁Betty ▁K ers h aw , ▁Dean ▁of ▁the ▁School ▁of ▁N urs ing ▁ ▁Sir ▁Ian ▁K ers h aw , ▁historian ▁ ▁Sir ▁Hans ▁Adolf ▁Kre bs , ▁Nobel ▁Prize - win ning ▁bio chem ist ▁( 1 9 3 5 – 1 9 5 4 ) ▁ ▁Stephen ▁Laur ence , ▁phil os opher ▁and ▁cogn itive ▁scient ist ▁ ▁Sir ▁Col in ▁Lucas , ▁historian , ▁chair ▁of ▁the ▁board ▁of ▁the ▁British ▁Library ▁ ▁Peter ▁M ait lis ▁F RS , ▁Professor ▁of ▁In organ ic ▁Chem istry ▁ ▁David ▁Mar qu and , ▁politician ▁ ▁Edward ▁M ellan by , ▁Professor ▁of ▁Ph arm ac ology , ▁discover er ▁of ▁Vit amin ▁D ▁ ▁Brian ▁Robert ▁Morris , ▁Professor ▁of ▁English ▁ ▁Douglas ▁North c ott ▁F RS , ▁Professor ▁of ▁Mathemat ics ▁ ▁George ▁Por ter , ▁Nobel ▁Prize - win ning ▁chem ist ▁( 1 9 5 5 – 1 9 6 6 ) ▁ ▁Sir ▁David ▁Read , ▁Emer it us ▁Professor ▁of ▁Plant ▁Science ▁ ▁Col in ▁Ren f rew , ▁arch ae ologist ▁ ▁Sir ▁G are th ▁Roberts , |
▁Vice - Ch an cell or ▁ ▁P iers ▁Robinson , ▁professor ▁of ▁politics , ▁society ▁and ▁political ▁journal ism ▁ ▁William ▁Sar je ant , ▁ge ologist ▁ ▁Jo anna ▁Sh ap land , ▁Edward ▁Br am ley ▁Professor ▁of ▁C riminal ▁Justice ▁ ▁No el ▁Sh ar key , ▁broad c aster , ▁Professor ▁of ▁Art ific ial ▁Int elligence ▁and ▁Rob ot ics , ▁Professor ▁of ▁Public ▁Eng agement ▁ ▁Susan ▁Sh err att , ▁arch ae ologist ▁of ▁Bron ze ▁Age ▁Greece , ▁Cy pr us , ▁and ▁the ▁Eastern ▁Mediter rane an ▁ ▁Sir ▁F ras er ▁St od dart , ▁chem ist ▁ ▁Stephen ▁St ich , ▁Honor ary ▁Professor ▁of ▁Philosoph y ▁ ▁Charles ▁St ir ling ▁F RS , ▁Professor ▁of ▁Chem istry ▁ ▁Gren ville ▁Turner ▁F RS , ▁Professor ▁of ▁Physics ▁ ▁W ▁E ▁S ▁Turner ▁( 1 8 8 1 – 1 9 6 3 ), ▁Professor ▁of ▁G lass ▁Technology ▁and ▁founder ▁of ▁the ▁museum ▁which ▁be ars ▁his ▁name ▁ ▁Sir ▁James ▁Under wood , ▁Joseph ▁Hunter ▁Professor ▁of ▁Path ology ▁and ▁Dean ▁of ▁the ▁Fac ulty ▁of ▁Medicine ▁ ▁Y or ick ▁Wil ks , ▁Professor ▁of ▁Art ific ial ▁Int elligence ▁ ▁Peter ▁Wille tt , ▁Professor ▁of ▁Information ▁Science ▁ ▁Sir ▁Michael ▁Wood ru ff , ▁trans plant ▁sur geon ▁ ▁References ▁▁▁ ▁She ff ield ▁Category : She ff ield - related ▁lists <0x0A> </s> ▁Ma ure en ▁N is ima ▁( born ▁July ▁ 3 |
0 , ▁ 1 9 8 1 ▁in ▁Bond y , ▁Seine - Saint - D enis ) ▁is ▁a ▁French ▁ép ée ▁fen cer , ▁who ▁won ▁the ▁bronze ▁medal ▁at ▁the ▁ 2 0 0 4 ▁Summer ▁Olympics ▁alongside ▁Laura ▁F less el - Col ov ic , ▁H aj nal ka ▁Kir aly ▁Pic ot ▁and ▁Sarah ▁Dan int he . ▁ ▁She ▁also ▁won ▁the ▁silver ▁medal ▁in ▁the ▁ép ée ▁team ▁event ▁at ▁the ▁ 2 0 0 6 ▁World ▁F encing ▁Championships ▁after ▁losing ▁to ▁China ▁in ▁the ▁final . ▁She ▁accomplished ▁this ▁with ▁her ▁team m ates ▁Mary sa ▁Bar ad ji - D uch ene , ▁H aj nal ka ▁Kir aly ▁Pic ot ▁and ▁Laura ▁F less el - Col ov ic . ▁ ▁Other ▁achiev ements ▁▁ 2 0 0 6 ▁European ▁Sen iors ▁F encing ▁Championship , ▁ép ée ▁ ▁References ▁ ▁Category : 1 9 8 1 ▁birth s ▁Category : L iving ▁people ▁Category : S ports people ▁from ▁Bond y ▁Category : F rench ▁people ▁of ▁Mart ini qu ais ▁descent ▁Category : F rench ▁female ▁f enc ers ▁Category : F rench ▁ép ée ▁f enc ers ▁Category : F enc ers ▁at ▁the ▁ 2 0 0 4 ▁Summer ▁Olympics ▁Category : O lymp ic ▁f enc ers ▁of ▁France ▁Category : O lymp ic ▁bronze ▁medal ists ▁for ▁France ▁Category : O lymp ic ▁medal ists ▁in ▁f encing ▁Category : Med al ists ▁at ▁the |
▁ 2 0 0 4 ▁Summer ▁Olympics <0x0A> </s> ▁De ▁Th es aur is ▁in ▁Peru ▁is ▁a ▁treat ise ▁by ▁Spanish ▁Domin ican ▁priest ▁and ▁reform er ▁Bart ol om é ▁de ▁las ▁Cas as ▁( 1 4 8 4 ▁– ▁July ▁ 1 7 , ▁ 1 5 6 6 ), ▁who ▁was ▁the ▁first ▁resident ▁Bishop ▁of ▁Ch ia pas . ▁In ▁it , ▁one ▁of ▁his ▁last ▁works ▁before ▁his ▁death , ▁he ▁vig or ously ▁def ended ▁the ▁rights ▁of ▁the ▁native ▁pe op les ▁of ▁Peru ▁against ▁the ▁sla very ▁im posed ▁by ▁the ▁early ▁Spanish ▁Con quest . ▁The ▁work ▁also ▁question ed ▁Spain ' s ▁right ▁to ▁take ▁the ▁gold ▁and ▁silver ▁acquired ▁from ▁the ▁r ans om ▁paid ▁to ▁free ▁At ah ual pa , ▁the ▁In ca ▁so ver eign ▁em peror , ▁as ▁well ▁as ▁valu ables ▁lo oted ▁from ▁the ▁bur ial ▁sites ▁of ▁the ▁ind igen ous ▁population . ▁ ▁As ▁a ▁sett ler ▁in ▁the ▁New ▁World , ▁he ▁was ▁app alled ▁by ▁the ▁behaviour ▁of ▁the ▁conquist adors ▁towards ▁the ▁Native ▁Americans . ▁In ▁De ▁th es aur is ▁in ▁Peru , ▁which ▁was ▁dedicated ▁to ▁King ▁Philip ▁II ▁of ▁Spain , ▁Las ▁Cas as ▁wrote ▁that ▁when ▁he ▁had ▁first ▁reached ▁the ▁New ▁World ▁he ▁had ▁supported ▁the ▁at roc ities , ▁but ▁had ▁soon ▁become ▁sure ▁that ▁these ▁acts ▁would ▁lead ▁to ▁the ▁collapse ▁of ▁Spain ▁itself ▁in ▁an ▁act ▁of ▁Div ine ▁ret ribution . |
▁According ▁to ▁Las ▁Cas as , ▁it ▁was ▁the ▁duty ▁of ▁the ▁Spanish ▁to ▁convert ▁the ▁Indians , ▁who ▁would ▁then ▁be ▁loyal ▁subjects ▁of ▁Spain , ▁rather ▁than ▁to ▁kill ▁them . ▁To ▁remove ▁the ▁bur den ▁of ▁sla very ▁from ▁them , ▁Las ▁Cas as ▁suggested ▁that ▁Afr icans ▁should ▁be ▁brought ▁to ▁America ▁instead , ▁although ▁he ▁later ▁decided ▁against ▁this ▁when ▁he ▁saw ▁how ▁Afr icans ▁were ▁affected ▁by ▁sla very . ▁ ▁See ▁also ▁ ▁Bart ol om é ▁de ▁las ▁Cas as ▁ ▁New ▁La ws ▁ ▁External ▁links ▁ ▁Bart ol om é ▁de ▁Las ▁Cas as ▁and ▁the ▁Trad ition ▁of ▁Med ieval ▁Law ▁ ▁Category : Span ish ▁colon ization ▁of ▁the ▁Amer icas ▁Category : Span ish ▁literature <0x0A> </s> ▁The ▁ 2 0 0 4 ▁San ▁Diego ▁City ▁Att orney ▁election ▁occurred ▁on ▁T ues day , ▁November ▁ 2 , ▁ 2 0 0 4 . ▁The ▁primary ▁election ▁was ▁held ▁on ▁T ues day , ▁June ▁ 2 , ▁ 2 0 0 4 . ▁ ▁Municipal ▁elections ▁in ▁California ▁are ▁officially ▁non - part isan , ▁although ▁most ▁members ▁do ▁identify ▁a ▁party ▁preference . ▁A ▁two - round ▁system ▁was ▁used ▁for ▁the ▁election , ▁starting ▁with ▁a ▁primary ▁in ▁June ▁followed ▁by ▁a ▁run off ▁in ▁November ▁between ▁the ▁top - two ▁candidates . ▁ ▁Results ▁ ▁References ▁▁ ▁San ▁Diego ▁City ▁Att orney ▁Category : San ▁Diego ▁City ▁Att orney ▁elections <0x0A> </s> ▁Fem in ist |
▁empir ic ism ▁is ▁a ▁perspective ▁within ▁femin ist ▁research ▁that ▁comb ines ▁the ▁object ives ▁and ▁observations ▁of ▁femin ism ▁with ▁the ▁research ▁methods ▁and ▁empir ic ism . ▁Fem in ist ▁empir ic ism ▁is ▁typically ▁connected ▁to ▁main stream ▁not ions ▁of ▁posit iv ism . ▁Fem in ist ▁empir ic ism ▁propos es ▁that ▁femin ist ▁theories ▁can ▁be ▁object ively ▁proven ▁through ▁evidence . ▁ ▁Fem in ist ▁empir ic ism ▁crit iques ▁what ▁it ▁perce ives ▁to ▁be ▁in ade qua cies ▁and ▁bi ases ▁within ▁main stream ▁research ▁methods , ▁including ▁posit iv ism . ▁ ▁Fem in ist ▁empir ic ism ▁is ▁one ▁of ▁three ▁main ▁femin ist ▁ep ist em ological ▁pers pect ives . ▁The ▁other ▁two ▁are ▁stand point ▁femin ism ▁and ▁post - struct ural / post mod ern ▁femin ism . ▁ ▁Example ▁ ▁In ▁international ▁relations ▁rational ist ▁femin ism ▁emp lo ys ▁femin ist ▁empir ic ism ▁to ▁explain ▁the ▁political ▁landscape . ▁R ational ist ▁femin ism ▁exam ines ▁state , ▁trans n ational ▁and ▁institution al ▁actors , ▁and ▁specifically ▁looks ▁at ▁caus al ▁relationships ▁between ▁these ▁actors ▁and ▁gender ▁issues . ▁Quant itative ▁data ▁is ▁used ▁to ▁relate ▁gender ▁to ▁these ▁phen omena . ▁This ▁may ▁be ▁done ▁by ▁directly ▁correl ating ▁gender ▁data ▁to ▁specific ▁state ▁behav iors , ▁or ▁indirect ly ▁by ▁exam ining ▁a ▁" gender ▁gap " ▁through ▁indirect ▁caus al ▁relationships . ▁Popular ▁pers pect ives ▁linked ▁to ▁rational ist |
▁femin ism ▁within ▁international ▁relations ▁include ▁conventional ▁construct iv ism ▁and ▁quant itative ▁peace ▁research . ▁ ▁Ep ist em ological ▁Pers pect ives ▁ ▁Stand point ▁femin ism ▁Among ▁other ▁critic isms , ▁stand point ▁femin ism ▁or ▁also ▁known ▁anti - r ational , ▁arg ues ▁that ▁femin ist ▁empir ic ism ▁cannot ▁explain ▁the ▁way ▁the ▁political ▁world ▁works ▁because ▁the ▁found ations ▁on ▁which ▁it ▁is ▁built ▁are ▁based ▁on ▁the ▁same ▁gender ed ▁assumptions ▁that ▁all ▁main stream ▁scientific ▁in qui ries ▁face . ▁Fem in ist ▁empir ic ism ▁arg ues ▁that ▁its ▁ep ist em ological ▁out look , ▁lets ▁it ▁tack le ▁this ▁gender ▁bias . ▁ ▁Post - mod ern ▁femin ism ▁Post - struct ural / post - mod ern ▁femin ist ▁ep ist em ology ▁is ▁entirely ▁disc ursive , ▁seeking ▁to ▁develop ▁understanding ▁through ▁social ▁analysis ; ▁to ▁interpret ▁rather ▁than ▁explain ▁femin ist ▁theories ▁in ▁the ▁political ▁world . ▁▁ ▁Fem in ist ▁empir ic ism ▁is ▁more ▁likely ▁to ▁favor ▁qual itative ▁data . ▁Object ive ▁measurements ▁are ▁seen ▁as ▁important ▁to ▁elimin ating ▁the ▁gender ▁bias ▁that ▁exists . ▁Post - struct ural ism ▁is ▁inher ently ▁opposed ▁to ▁the ▁idea ▁of ▁an ▁objective ▁truth ▁in ▁the ▁social ▁sciences . ▁The ▁belief ▁is ▁that ▁those ▁who ▁study ▁within ▁the ▁human ▁sciences ▁are ▁ens n ared ▁by ▁the ▁same ▁structures ▁that ▁affect ▁the ▁society ▁in ▁which ▁they ▁study . ▁Post - struct ural ▁femin ism ▁crit iques ▁the ▁belief |
▁that ▁any ▁view point ▁is ▁im partial ; ▁knowledge ▁is ▁not ▁found ▁but ▁constructed . ▁A ▁specific ▁result ▁of ▁this ▁disag re ement ▁is ▁the ▁way ▁in ▁which ▁the ▁two ▁theories ▁view ▁gender : ▁femin ist ▁empir ic ism ▁claims ▁that ▁gender ▁variables ▁are ▁based ▁on ▁bi ological ▁sex , ▁while ▁post - struct ural / post - mod ern ▁femin ism ▁sees ▁gender ▁as ▁a ▁soci ally ▁constit uted ▁entity . ▁ ▁See ▁also ▁ ▁Fem in ism ▁Post mod ern ▁femin ism ▁Stand point ▁femin ism ▁ ▁References ▁ ▁Category : F em in ist ▁movements ▁and ▁ide ologies ▁Category : F em in ist ▁theory ▁Category : F em in ism ▁and ▁society ▁Category : F em in ism ▁and ▁social ▁class ▁Category : F em in ism ▁and ▁history <0x0A> </s> ▁Hill ▁End ▁is ▁a ▁village ▁in ▁County ▁Dur ham , ▁England . ▁It ▁is ▁situated ▁on ▁the ▁south ▁side ▁of ▁We ard ale , ▁near ▁Fro ster ley . ▁ ▁References ▁ ▁External ▁links ▁ ▁Category : V ill ages ▁in ▁County ▁Dur ham ▁Category : St an ho pe , ▁County ▁Dur ham <0x0A> </s> ▁Bad ▁Or b ▁(" Th er ma e ▁on ▁the ▁Or b ▁River ") ▁is ▁a ▁sp a ▁town ▁in ▁the ▁Main - K in zig - K re is ▁district ▁of ▁H esse , ▁Germany . ▁It ▁is ▁situated ▁ ▁east ▁of ▁Han au ▁between ▁the ▁for ested ▁hills ▁of ▁the ▁Sp ess art . ▁Bad ▁Or b ▁has ▁a ▁population |
▁of ▁over ▁ 9 0 0 0 . ▁Its ▁economy ▁is ▁domin ated ▁by ▁the ▁health ▁and ▁tour ism ▁se ctors . ▁ ▁Geography ▁ ▁Location ▁ ▁Bad ▁Or b ▁is ▁located ▁in ▁the ▁valley ▁of ▁the ▁Or b , ▁a ▁trib ut ary ▁of ▁the ▁Kin zig . ▁The ▁town ▁is ▁surrounded ▁by ▁the ▁wood ed ▁hills ▁of ▁the ▁Sp ess art , ▁including ▁the ▁Winter s berg . ▁The ▁closest ▁larger ▁cities ▁are ▁Han au , ▁A sch affen burg ▁and ▁Frankfurt ▁to ▁the ▁south west ▁and ▁Ful da ▁to ▁the ▁n ortheast . ▁ ▁Ne igh bor ing ▁communities ▁From ▁the ▁north , ▁clock wise , ▁Bad ▁Or b ▁borders ▁on ▁W äch ters bach , ▁Bad ▁S oden - S alm ün ster , ▁the ▁un in cor por ated ▁area ▁G uts bez irk ▁Sp ess art , ▁J oss grund ▁and ▁ ▁B ie berg em ünd . ▁ ▁History ▁The ▁region ▁was ▁inhab ited ▁by ▁Cel ts ▁by ▁c . ▁ 6 5 0 ▁BC , ▁but ▁it ▁is ▁not ▁known ▁whether ▁they ▁were ▁aware ▁of ▁the ▁local ▁salt ▁depos its . ▁▁ ▁In ▁ 1 0 5 4 ▁Henry ▁IV , ▁Holy ▁Roman ▁Emperor ▁gift ed ▁the ▁area ▁around ▁Or b ▁( Or b aha ) ▁to ▁the ▁St ift ▁St . ▁Stefan ▁at ▁Main z , ▁it ▁thus ▁came ▁under ▁the ▁control ▁of ▁the ▁Elect or ate ▁of ▁Main z , ▁a ▁part ▁of ▁which ▁it ▁remained ▁until ▁ 1 8 0 3 . |
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