Search

Spermatogeneza je složen proces reguliran velikim brojem gena. Identifikacija specifičnih proteina u tkivu testisa ključna je za razumijevanje pravilnog razvoja zametnih stanica. U ovoj studiji istražili smo mijenja li se ekspresija proteina koji imaju ulogu u spermatogenezi i popravku DNA s obzirom na poremećaj funkcije proteina Spartan. Protein Spartan (kodiran SPRTN genom) uklanja DNA lezije koje mogu zaustaviti replikaciju i dovesti do nastanka dvolančanih lomova i genomske nestabilnosti. Mutacije u genu SPRTN uzrokuju nastanak hepatocelularnog karcinoma te sindroma preuranjenog starenja nazvanog Ruijs-Aalfs, poznatog i kao Spartan sindrom. U ranijim studijama je dokazana veća ekspresija SPRTN gena u testisima u odnosu na ostala tkiva što ukazuje na njegovu važnu ulogu u tkivu testisa. U našoj studiji testirali smo promjene izražaja odabranih proteina uključenih u održavanje stabilnosti DNA i replikaciju. Imunohistokemijskom metodom pokazali smo da postoji promijenjena ekspresija pojedinih proteina u tkivu testisa miševa s homozigotnom mutacijom u genu SPRTN. Spermatogenesis is a complex process regulated by a large number of genes. Identification of specific proteins in testicular tissue is important for development of germ cells. In this study, we investigated whether the expression of proteins that play a role in spermatogenesis and DNA repair changes with dysfunction of Spartan protein. The Spartan protein (encoded by the SPRTN gen) removes DNA lesions that can stop replication and lead to double-stranded breaks and genomic instability. Mutations in the SPRTN gene cause hepatocellular carcinoma and a syndrome of premature aging called Ruijs-Aalfs, also known as Spartan syndrome. Previous studies have shown greater expression of the SPRTN gene in the testes compared to other tissues indicating its important role in testicular tissue. By immunohistochemical method, we showed that there is an altered expression of certain proteins in testis tissue of mice with a homozygous mutation in the SPRTN gene.

Infekcija HCMV-om, pripadnikom porodice β herpesvirusa, široko je rasprostranjena u ljudskoj populaciji. Kod imunokompetentnih pojedinaca infekcija uzrokuje blaže ili nikakve simptome, dok kod osoba sa oslabljenim ili nezrelim imunološkim sustavom može biti životno ugrožavajuća. Kao najčešći uzročnik kongenitalnih virusnih infekcija, HCMV uzrokuje teška strukturalna i funkcionalna oštećenja CNS-a. Trenutno ne postoji cjepivo za citomegalovirus, a dostupni terapijski postupci pokazuju ograničenu učinkovitost, stoga su istraživanja temeljnih mehanizama nastanka bolesti od izuzetne važnosti. Skoro sva dostupna istraživanja infekcije neurona CMV-om provedena su u in vitro uvjetima i pokazuju oprečne rezultate o sklonosti CMV-a prema neuronima. Svrha ovog rada bila je provesti in vivo istraživanje na mišjem modelu s reporterskim MCMV virusom kako bi se otkrilo mogu li neuroni biti produktivno inficirani. Rezultati su pokazali da u mozgu miševa dolazi do in vivo konverzije reporterskog virusa 14. dan nakon infekcije. Ovi rezultati ukazuju da inficirani neuroni produciraju virus, ali zbog niskog titra reporterskog virusa u mozgu korištenih miševa nismo saznali koliki postotak neurona ima sposobnost produkcije virusnih čestica. Stoga, ovo istraživanje služi kao preliminarno za daljnja in vivo istraživanja citomegalovirusne infekcije neurona., Infection with HCMV, a member of the β herpesvirus family, is widely distributed within the human population. In immunocompetent individuals the infection causes mild or none symptoms. On the other hand, it can be a life-threatening infection in people with weakened or immature immune system. As the most common cause of congenital viral infections, HCMV leads to severe structural and functional abnormalities of the CNS. At the moment there is no vaccine to prevent cytomegalovirus infection. Also, the available therapeutic procedures show limited efficacy. Therefore, the research on basic mechanisms of CMV infection are of great importance. Almost all the available research on CMV infection of neurons have been conducted in vitro and suggest conflicting results on CMV preference for neurons. The purpose of this paper was to conduct an in vivo research using mouse model with reporter MCMV virus to determine whether neurons can be productively infected. The results have demonstrated that in vivo conversion of the reporter virus occurs in the brain of mice 14 days after the infection. These results indicate that infected neurons can produce the virus. However, due to the low titer of reporter virus in the brain of mice, we haven't found out the exact percentage of neurons that has the ability to produce the virus. In conclusion, this paper serves as a preliminary research for necessary further in vivo research on CMV infection of neurons.