Ubundlobongela, iziyobisi kunye nobutyebi: Indlela i-Brain Controls Ekhuthazwa ngayo izakhono (2011)

Physiol Behav. Author manuscript; available in PMC 2012 Jul 25.

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PMCID: PMC3107928

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Inguqulelo yokugqibela yomhleli yeli nqaku iyafumaneka apha Physiol Behav

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Abstract

U-Bart Hoebel wenze umbono wokuba uthungelwano oluhlanganisiweyo lwe-neural oluyalela phakathi imbuyekezo yendalo kunye nokusetyenziswa kweziyobisi. Uvulele ukuba kusetyenziswe i-microdialysis, kwaye wasebenzisa ngokufanelekileyo ukukhuthaza umbane, izilonda, ii-microinjections, kunye ne-immunohistochemistry. Wafumanisa ukuba ukondla, ukulawula iziyobisi, kunye nokukhuthaza kombane kwi-hypothalamus (LH) eyonyukayo yonke ukukhutshwa kwe-dopamine (DA) kwi-nucleus accumbens (NAc). Nangona kunjalo, ngelixa iDA kwi-NAc iphuculwe inkuthazo, iDA kwi-LH inqabile ekuziphatheni okuzinzileyo. I-Hull lab ilandele ezinye zezo zimvo. Sicebise ukuba i-serotonin (5-HT) kwi-pervivicalLH inhibit yokuziphatha ngokwesondo ngokuthintela i-orexin / hypocretin neurons (OX / HCRT), eya kuthi ngenye indlela ixhase ii-neurons kwiphecana le-mesocorticolimbic DA. Sibonisile ukuba ukukhutshwa kwe-DA kwindawo ye-medial preoptic (MPOA) kubaluleke kakhulu ekuziphatheni ngokwesini kwamadoda, kwaye ukuba i-testosterone, glutamate, nitric oxide (NO) kunye namava ezesondo angaphambili akhuthaza ukukhutshwa kwe-MPOA DA nokukhula komtshato. Uphando lwexesha elizayo kufuneka lulandele ugxininiso lukaBart Hoebel kwiinkqubo ze-neural kunye nokusebenzisana phakathi kweendawo zengqondo kunye ne-neurotransmitters.

Internet: I-Dopamine, i-Serotonin, indawo ye-Medic preoptic, indawo ye-Mesocorticolimbic, iTestosterone, i-Nitric oxide, i-Orexin / hypocretin, i-Glutamate, uKopisho.

1. Uphando lukaBart Hoebel

U-Bart Hoebel ngumntu omkhulu phakathi kwe-neuroscientologists. Uye wangenela ubuchwephesha obutsha kwaye wavelisa ukuqonda okungaphaya kokusebenza kwengqondo. Ukusetyenziswa kwakhe kwe-micodialysis kunye nokusebenza okuphezulu kwe-chromatography ye-fluid (HPLC) ukuqokelela kunye nokuhlalutya ii-neurotransmitters kwiindawo ezahlukeneyo zobuchopho zibonelela ngengqondo ebalulekileyo malunga nokusebenzisana phakathi kwe-hypothalamus kunye nenkqubo ye-mesocorticolimbic dopamine (DA). Umsebenzi wam omninzi ukwiindlela awazisekayo.

Inqaku lakhe lokuqala, lipapashwe ngaphakathi inzululwazi, ingxelo yokuba ukusetyenziswa kokutya kuthintele, kungekuko ukondla kuphela, kodwa nokuzivuselela ngokwasemva, kunye nokuba i-ventromedial hypothalamus iphakathi1]. Okwesibini inzululwazi Inqaku longeze isifundo sakhe malunga neendlela zokuziphatha ezibandakanyiweyo ukubandakanya ukupopolwa. Yachaza ukuba ukhuthazo lombane lwe-hypothalamus yangemva yonyusa ukukhuthaza kunye nokukhuthaza umvuzo wokulinganisa [2]. Usafunda ukubophela, waba nomdla kwindima ye-serotonin (5-HT) kummiselo wayo. Inaliti eyenzekileyo ye-p-chloroamphetamine (PCA) inhibosis yababhinqileyo bengamakhosi ngenxa yokukhutshwa kwe5-HT. Nangona kunjalo, i-PCA engapheliyo iququzelele i-Lordosis, ngenxa ye-5-HT depletion [3]. Ke ngoko, i-5-HT yayinefuthe ekuziphatheni ngokwesini kwabasetyhini.

U-Bart Hoebel kamva waba nobuchule kwi-microdialysis, kunye ne-dopamine (DA), i-serotonin (5-HT), kunye ne-acetylcholine (ACh) eza ngaphambili. Ukutya, i-cocaine, kunye nokuzilawula okwenzeka emva kwexesha, konke ukunyusa kwe-DA kwiphecana ye-mesocorticolimbic ye-DA [4, 5, 6]. Ngaphaya koko, bekukho ukungqubana okungalindelekanga phakathi kweendawo zobuchopho. Umzekelo, bekukho ubudlelwane obungenanto phakathi kweziphumo ze-DA kwi-lateral hypothalamus (LH) vs the NAc [7]. I-DA kwi-LH yayingemnandi kwaye ibathintele ekuziphatheni okuqinisekileyo, kodwa iDA kwi-NAc yayinembuyekezo kwaye ikhuthaza isimilo esichazayo.

2. Uphando lweelebhu

Ilebhu yam ilandelele ezinye zezi mbono. Sisebenzise i-microdialysis, i-microinjection, kunye ne-immunohistochemistry, kunye novavanyo lokuziphatha, ukuphanda ukujikeleza okuphakathi kokuziphatha kwendoda yesini.

2.1. Iziphumo ze-5-HT kwi-LH engaphandle

Umfundi wam wangaphambili uDan Lorrain wasebenzisa i-Microdialysis ukubonisa ukuba i-5-HT ikhutshwa kwi-LH engaphandle ngexesha le-ejaculation [8] (jonga Ikhiwane. 1), kanye njengokuba uBart Hoebel wayexele ukukhutshwa kwe5-HT apho ngokondla [9]. Ngaphaya koko, i-microinjection ye-anhibitake inhibitor ekhethiweyo ye-5-HT kwi-LH engqinelwanga, efana ne-post-ejaculatory quiescence kunye neziphumo ebezingalindelekanga zesondo ezichasene ne-SSRI ezisetyenziselwa ukunyanga uxinzelelo. Ke, ilebhu yeHoebel ibonise ukuba ukwanda okucwangcisiweyo kwi-5-HT engalunganga yokuziphatha kwezesondo kwabasetyhini [10], kunye ne-Hull lab ebekwe kwindawo enye yobuchopho, i-anterior LH, apho i-5-HT yendawo inyusa indlela yokuziphatha yesini yowesilisa [8]. Kwinqaku emva kwexesha, sixele ukuba ukuphinda-dialysis kwe-5-HT kwi-anterior (pericileical) LH kunciphise ukukhutshwa kwe-DA kwi-NAc [11]. Ke ngoko, ukukhutshwa kwe-5-HT kwi-LH ngexesha le-ejaculation kunganegalelo kwi-post-ejaculatory quiescence, ubuncinci ngenxalenye, ngokuthintela indlela ye-mesocorticolimbic ye-DA.

Ikhiwane. 1 

Temporal changes in extracellular serotonin (5-HT) collected from the lateral hypothalamus of male rats before and during copulation. Each data point is the mean (±SEM) for 6-min dialysate samples collected during baseline (B), in the presence ...

2.2. I-OX / HCRT kwi-hyperalamus yangaphandle

Kutshanje sinikeze ngokulandelelana kwebali le-hypothalamic 5-HT. Iqela le-neurons kwi-LH livelisa i-peptide orexin (OX, ekwabizwa ngokuba yi-hypocretin, HCRT). Ngaphaya koko, i-5-HT ngaphambili yayixelwe ukuba ibangela ezo ntsholongwane (12). I-OX / HCRT iyaziwa ngokukhuthaza indlela yokuziphatha13,14] nokulawulwa kwemijikelezo yokuvuka kokulala [15, 16]. I-OX / HCRT-equlathe ii-neurons ibikade ixelwe kwi-projekti ukuya kwindawo yecandelo le-ventral tegmental (VTA) [17], umthombo we-mesocorticolimibc DA iphecana. Ngapha koko, kwaxelwa ukuba i-Intra-VTA yolawulo lwe-OX / HCRT inyusa ukukhutshwa kwe-DA kwi-NAc [18]. Umfundi wam wangaphambili uJohn Muschamp wathi hypotalamic neurons eyayithintelwe yi-post-ejaculatory 5-HT inokuba ziiseli ezi-OX / HCRT. Sibonisile ukuba ukonyusa ukukhula kwe-c-Fos-immunoreactivity kwi-OX / HCRT-cell cell [19]. Ukongeza, ukusasazeka kwehlile inani le-OX / HCRT-immunoreactive neurons, ezazibuyiselwa kakhulu ngenaliti ye-estradiol. I-OX / HCRT ichaphazela indlela yokuziphatha, njengolawulo lwenkqubo ye-OX / HCRT19]. Ukongeza, i-microinjection ye-OX / HCRT kwi-VTA yavelisa iziphumo ezixhomekeke kumthamo wokudubula kweseli dopaminergic. Iidosi ezimbini ezisezantsi zonyuse ukudubula kweseli kunye neempendulo zabemi, nangona eyona dosi iphezuluyo yakhokelela ekubethelelweni kwe-VTA dopaminergic neurons, ethe yatshintshwa ngokuvuselela ii-autoreceptors ze-DA nge-apomistphine ye-DA. Okokugqibela, ukuphinda-phinda kabini i-immunohistochemistry kutyhila ukuba ukuvuthwa kukonyusa i-c-Fosimmunoreactivity kwi-dopaminergic neurons kwi-VTA eyayifakwe kwi-OX / HCRT fibers. Ke, ii-neurons ze-OX / HCRT zibonakala zisebenza ngendlela exhomekeke kwi-steroid ukuvula indlela ye-mesocorticolimbic ye-DA, ngaloo ndlela ikhuthaza indlela yokuziphatha ngokwesondo kunye neminye imbuyekezo yendalo kunye neziyobisi.

2.3. Ukukhutshwa kwe-DA kwindawo ye-medial preoptic (MPOA)

Ukongeza kwi-LH kunye ne-mesocorticolimbic ye-DA inkqubo, ilebhu yam iye yaphanda indima ye-MPOA, kwindawo engaphandle yengqondo ye-hypothalamus, kulawulo lokuziphatha ngokwesondo kwamadoda. Izilonda ze-MPOA ziphazamisa ukusebenza ngokwesondo kwamadoda kuzo zonke iintlobo zezilwanyana ezifundileyo (ezihlaziyiweyo kwi- [20]). Ukunyuswa kombane okanye kweekhemikhali ze-MPOA kuphucula ukwenziwa kunye ex ikopi Iimpawu zesini zesini. I-neurons yengingqi ye-A14 ejikeleze i-neurons ye-DA yangaphakathi kwi-MPOA, njengoko kwenza i-neurons ze-DA ezivela kwezinye iisayithi [21].

Kukho unxibelelwano olusondeleyo phakathi kwendlela yokuziphatha kwamadoda esini kunye nenqanaba le-DA yangaphandle kwi-MPOA. I-DA ikhutshwa kwi-MPOA yeempuku zamadoda ukuphendula kumfazi ophakathi kunye nangexesha lokukhutshwa [22] (jonga Ikhiwane. 2). Ubukho bamva nje be testosterone bebuyimfuneko kokubini ukukhutshwa kwe-DA kunye nokuprintwa. Amadoda anomdla, i-testosterone-yanyangwa i-castrate, kunye ne-castrate eziphathwe ngeoyile ezakhutshelweyo zibonisa ukwanda kwangaphambili kwe-DA, eyayigcinwa okanye yanda ngakumbi ngexesha lokuzala [22, 23]. Ii-castrate eziphathwe ioyile ezingakhange zikopele zingabonisanga nyuso. Kwakukho zombini isimilo sokuziphatha kunye nokungaqondakali kwimpendulo ye-DA. Ngapha koko, isibakala sokuba i-DA inyuke ngaphambi kokuqala kokuzala ibonisa ukuba ukunyuka akubangelwa kukukhuphela, kodwa kusenokwenzeka ukuba kuyayanyaniswa nezizathu zesondo. Iibini, ezintlanu-, kunye neerejimeni zentsuku ezilishumi zokunyangwa kwe-testosterone ye-castrate zikhokelela ekukhuliseni amandla okuprinta okuhambelana kakhulu nokubuyiselwa kokukhutshwa kwe-DA [24]. Unyango lwe-testosterone yeentsuku ezimbini alubuyanga mating okanye impendulo ye-DA. Uninzi lweentsuku ezintlanu ze-testosterone eziphathwe nge-testosterone zazikwazi ukukopa kwaye zibonisa impendulo ye-DA, ngesiqingatha sazo sikwazi ukujikisa. Zonke i-castrate ziphathwe nge testosterone yeentsuku ze-10 zidityaniswe kwi-ejaculation, kwaye zonke zabonisa impendulo ye-DA. Kwakukho ukunxibelelana okuninzi phakathi kwamanyathelo okukhusa kunye namanqanaba e-DA. Ke ngoko, zombini ukuphulukana kweprotocol kulandela ukuthunyelwa kunye nokubuyiselwa kwayo nge-testosterone kunxulunyaniswa ngokusondeleyo nempendulo ye-MPOA ye-DA kumfazi oguqukayo.

Ikhiwane. 2 

Testosterone-mediated enhancement of sexual activity may occur in part through increased DA release in the MPOA. Gonadally intact male rats showed an increase in extracellular DA during precopulatory exposure to an inaccessible estrous female, and all ...

I-metabolites zeTestosterone zazisebenza ngokwahlukileyo ekubuyiseleni ukukhutshwa kwe-DA kwii-castrate zexesha elide [25]. I-Estradiol ibuyisele amanqanaba e-basal aqhelekileyo e-DA, kodwa hayi ukwanda kokuphendula kumfazi. I-Estradiol iphathwe i-castrate engenileyo, kodwa akukho namnye owabonisa iphethini yokuziphatha ye-ejuko. Nokuba i-dihydrotestosterone okanye imoto yeoyile egcinwe ikopi okanye isiseko okanye ukukhutshwa kwe-DA kukhuthazo. Nangona kunjalo, xa i-dihydrotestosterone yayilawulwa nge-estradiol, indibaniselwano ibuyise konke ukukopishwa kunye nokusisiseko kunye nokukhutshwa kwe-DA kukhuthazayo [25].

Nangona amanqanaba e-extracellular e-MPOA DA ephantsi kwiindawo ezinobunkunkqele kunokuba kunjalo kumadoda angamadoda amnyama, amanqanaba entracellular aphakamileyo kunamadoda angasebenziyo [26]. Ewe, bekukho unxibelelwano olubi phakathi kwezicubu (ezigciniweyo) zamanqanaba e-DA kunye nokukwazi ukulingisa [27]. Izilwanyana ezingahambisaniyo (i-dihydrotestosterone- kunye ne-castrate ephathwe ioyile) zazinamanqanaba aphezulu e-DA kunamaqela enza ikopi (i-estradiol−, i-estradiol + dihydrotestosterone-, kunye ne-testosterone yanyangwa i-castrate. Ke ngoko, ukugcinwa nokugcinwa kwe-DA kwi-MPOA kubalasele kakhulu kwiindawo ezinobunkunkqele njengoko kunjalo kumadoda amileyo; Ukunqongophala kweendawo zokuhlala akubikho kumgangatho wokuyila nokugcina i-DA, kodwa kubuchule babo bokukhulula iivenkile zabo ezininzi.

2.4. Indima ye-NO kwi-MPOA DA ukukhutshwa

Izifundo ngaphambili zazichaze ukuba ukukhutshwa kwe-DA kwi-striatum kwenziwa lula yi-NO [28, 29]. Ke ngoko, sivavanye ukuba HAYI ingaba nemiphumela efanayo kwi-MPOA. Ewe, umanduleli we-NO, i-L-arginine, ukwanda kwe-basal MPOA DA, kunye NO-synthase (NOS) umchasi weL-NMMA kunciphise ukukhutshwa [30]. Isithinteli esahlukileyo se-NOS, i-L-NAME, sithintele ukukhutshwa okwenziwe kwi-DA [31], isiphumo esasinxibelelaniswe yi-cGMP [32]. Ngapha koko, ukugonywa kwe-neuronal NOS (nNOS) kuncitshisiwe emva kokuphoswa kwaye kwavuselelwa ukulawulwa kwe-testosterone [33]. Ke ngoko, enye yeendlela apho i-testosterone incedisa ukopisho kukonyusa i-NNOS kwi-MPOA, ethi yona ikonyuse ukukhutshwa kwe-basal kunye nokukhuthaza kwabasetyhini ukukhutshwa kwe-DA kumadoda angasebenziyo kunye ne-testosterone yanyangwa.

2.5. Iziphumo zamava ezesondo

Ilebhu yethu iphinde yaphanda ngeziphumo zamava ezesondo. Amadoda anamava aphumelela “ngokusebenza ngakumbi.” Banamacala amafutshane okunyusa, ukungqengqa, kunye nokufakelwa kwaye bayakwazi ukukhenkceza ngamanani amancinci kunye nokuphazamiseka (kuhlaziywa kwi [20]). Ukuchaza nje i-rat yamadoda ephindaphindiweyo kwibhinqa elingaphantsi komfazi kuyanele ukuphucula amandla akhe okunyanzela kunye nokwandisa ukugonyelwa kwe-c-Fos kwi-MPOA ephakanyiswe yi-ejaculation enye [34]. AKUKHO namnye onokuguqula ezinye zeziphumo zeselula kumava. I-NOS inhibitor L-NAME, encinci kwi-MPOA, yathintela ukukhuselwa kwisini se-naïve yamadoda kwaye yanciphisa inani le-intromissions kunye ne-ejaculations kumadoda anamava ngokwesondo [35]. Xa yayilawulwa kwi-MPOA ngaphambi kokuchazwa kwento nganye kwesixhenxe kumfazi otyhidiweyo, yathintela iziphumo zokubonakalisa. Ngaphaya koko, ukugonyelwa kwe-NNOS kwi-MPOA kukonyuswa ngamava angokwesondo angaphambili [36]. Ke ngoko, ukunyuka kokungabikho kwemveliso kwi-MPOA, kunye nokunyuka kweziphumo zokukhutshwa kwe-DA, kunokunika ezinye zeziphumo eziluncedo kumava ezesondo.

2.6. Igalelo elisuka kwi-amygdala ye-medial ukuya kwi-MPOA

Okona kuphakamisa impendulo ye-MPOA ye-DA kumfazi kukufakelwa kwe-medial amygdala (MeA). UJuan Dominguez wenza izilonda ezinkulu ze-amygdala, eyaphelisa ikopi kwirhasi yamadoda [37]. Nangona kunjalo, i-microinjections ye-apomist ye-agonist ye-DA kwi-MPOA ibuyisele ngokupheleleyo ukukopishwa kuloo malume. Izilonda ezincinci ze-radiofreqency ye-MeA yalimala, kodwa ayitshitshisanga ikopi. Amanqanaba e-Basal MPOA DA awachaphazelekanga, kodwa ukunyuka kwe-DA ekuphenduleni kwabasetyhini kwavalwa.37] (jonga Umzobo 3). Ke ngoko, njengokubuyiselwa kwe-estradiol yokushicilela kwi-castrate [25], amanqanaba asezantsi e-MPOA e-DA ayanele ukukhula ngendlela engafakwanga, kodwa ke ukonyuka okunyuselwe kwinqanaba labasetyhini kwakufuneka ukukhutshwa ngokugqibeleleyo. Kwizilwanyana ezingafakwanga i-anesthetised, ukuvuselelwa kweekhemikhali kweMeA, isebenzisa ubudlakudla kunye ne-glutamate reuptake inhibitor, ukunyusa amanqanaba e-DA angaphandle kwi-MPOA, ukulinganisa isiphumo sokukhuphela [38] (jonga Ikhiwane. 4). Ke ngoko, enye indlela i-MeA ekhuthaza ukukopishwa kukonyusa ukukhutshwa kwe-DA kwi-MPOA.

Ikhiwane. 3 

Lesions of the medial amygdala inhibit the release of DA in the MPOA resulting from exposure to an estrous female and copulation. Levels represent % changes from baseline (BL) in response to precopulatory exposure to an estrous female (PRE), during copulation ...
Ikhiwane. 4 

Levels of DA in dialysate from the MPOA of animals receiving MeA stimulation or vehicle microinjection. Levels represent % change from baseline (BL) in response to MeA-stimulation or vehicle microinjection; samples collected after microinjections into ...

2.7. Ukugcwala kwi-MPOA

Umlamli omnye wokukhutshwa kwe-DA kwi-MPOA glutamate [39]. Ikhutshwe kwi-MPOA ngexesha lokukhuphela, kwaye inyuka malunga ne-300% ngexesha le-ejaculation [40]. Reverse dialysis of glutamate reuptake inhibitors increased extracellular glutamate, as expected, and also facilitated copulation. However, reverse-dialysis of serotonin (5-HT) into the MPOA impaired both copulation and ejaculation-induced glutamate release [41]. Ke ngoko, indawo yesibini apho i-5-HT inokuthi ithintele ukukhula kwayo yi-MPOA, apho inokunciphisa ukukhutshwa kwe-glutamate.

A possible explanation for glutamate’s facilitative effect on DA involves NO. The nNOS inhibitor L-NAME, when reverse-dialyzed into the MPOA, decreased baseline DA and blocked the glutamate-evoked DA release. The inactive isomer D-NAME had no effect. Glutamate binds to NMDA receptors to promote calcium influx, which activates calmodulin, which in turn activates nNOS. NO may inhibit DA uptake in neighboring terminals, prolonging its effects, and may also promote vesicular leakage, increasing DA release directly (reviewed in [42]). Therefore, glutamate, through its stimulation of nNOS, increases DA release in the MPOA, which in turn facilitates copulation. MPOA glutamate may also help to elicit ejaculation.

3. isishwankathelo

Ngamafutshane, uBart Hoebel udale "umfanekiso omkhulu" weendawo zobuchopho eziphembelela imbuyekezo yendalo kunye neziyobisi zokuxhatshazwa. Ngokusebenzisa amandla ombane, izilonda, i-microinjection, i-Microphicalism, kunye ne-immunohistochemistry, kunye nokujonga ngononophelo nangokucwangcisiweyo kokuziphatha, wabeka imephu kwindawo zobuchopho kunye nee-neurotransmitters ezilawula ukondla, ukukhula, ubundlongondlongo, ukuthatha iziyobisi, kunye nomvuzo. I-Hull lab ilandelele ezinye zezo zimvo, kubandakanya ukusebenzisana phakathi kwe-LH kunye nenkqubo ye-mesocorticolimbic ye-DA. Sicebise ukuba i-5-HT kwi-LV ifunekayo inokuthi ithintele indlela yokuziphatha ngokwesondo ngokuthintela i-neurons ye-OX / HCRT, eya kuthi ngenye indlela icenge ii-neurons ze-DA kwiVTA. Sifunde ikakhulu indlela yokuziphatha ngokwesondo yamadoda, ukubonisa ukuba ama-testosterone kunye namava ezesondo anyusa i-NNOS kwi-MPOA, kwaye ukuba isiphumo sokunyuka kwe-NO yemveliso sinokunyusa ukukhutshwa kwe-basal kunye nokuvuselelwa kwabasetyhini. Ngaphaya koko, glutamate nayo ikhutshwa kwi-MPOA ngexesha lokukhwelana, ngakumbi ngexesha lokukhupha, kunye nokuzonwabisa, ukubamba ngee-receptors ze-NMDA kunye nokungena kwe-calcium, kunokunyusa i-NO, kwaye ke ukukhutshwa kwe-DA. Sityala kakhulu lempumelelo yethu, ingekuko kuphela ukuba nguBart Hoebel onguvulindlela osebenzisa ubuchwephetsha bokuchwetheza nezinye iindlela, kodwa nasekugxininiseni kwakhe kwinkqubo ye-neural kunye nokuhlangana kweendawo zobuchopho kunye nee-neurotransmitters.

Okokugqibela, kufanelekile ukuba uBart Hoebel aphumelele intshatsheli yemozulu efudumeleyo, exhasayo, eyoyikisayo, edibeneyo, neyonwabisayo kwisayensi nakwimpilo yakhe. Kuluyolo olukhulu ukwazi, ukunxibelelana naye, nokufunda kuye.

Imibulelo

Uphando olwenziweyo apha luxhaswe yi-NIH isibonelelo se-MH040826 kwi-EM Hull.

Imihlathi

Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.

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