Allergilised silmahaigused

Allergiline silmahaigus on ülitundlikkusreaktsioon, mis haarab tavaliselt ainult silmi, kuid kaasneda võivad ka muud sümptomid. Klassikalisteks allergilisteks konjunktiviitideks peetakse hooajalist ning aastaringset allergilist konjunktiviiti, atoopilist keratokonjunktiviiti ja vernaalset ehk kevadkeratokonjunktiviiti. Tekkemehhanismid on atoopilisel ja vernaalsel konjunktiviidil aga teised kui hooajalisel ning aastaringsel allergilisel konjunktiviidil. Allergiliste silmahaiguste diagnoosimisel tuleb toetuda täpse anamneesi võtmisele ja haiguse kliinilistele ilmingutele. Nii farmakoloogilise kui ka immuunraviga on võimalik haigestunu sümptomeid leevendada. Patsiendi teadlikkus ning allergeenide vältimine on nende haiguste puhul esmatähtsad.Eesti Arst 2015; 94(9):551–55

Regulation of activation induced deaminase

Activation Induced Deaminase (AID) belongs to the protein family of DNA deaminases, which catalyse the deamination of the cytosine residues in single stranded DNA, resulting in the formation of deoxy-uracils. The enzymatic activity of AID is required for the immunoglobulin gene modifications by class switch recombination (CSR), somatic hypermutation (SHM) and gene conversion (iGC). While being essential for antibody diversification, the activity of AID can be harmful for the organism due to its direct mutagenic activities and induction of genomic instability. This thesis investigates AID regulation both, on the level of gene expression and its interaction partners, and the DNA repair pathways triggered by AIDmediated DNA deamination. Firstly, I have identified estrogen and progesterone as regulators of AID expression. This is achieved via direct binding of estrogen and progesterone receptors to AID promoter. Estrogen leads to an induction of AID expression and increase in AID-mediated downstream pathways – SHM, CSR as well as oncogenic translocations between Ig and c-myc loci. In contrast, progesterone results in a decrease in AID expression and an attenuation of its downstream pathways. Secondly, by generating DT40 cell lines with endogenously tagged AID, we used co-immunoprecipitation and subsequent mass spectrometry for identifying proteins that form a complex with AID in the cytoplasm, nucleoplasm and chromatin. The results of this approach gave us possible insight into the mechanistic process of AID-mediated DNA deamination in vivo, suggesting that chromatin bound AID resides in a complex with elongating RNA polymerase II. Thirdly, by expressing AID in meiotic recombination deficient fission yeast and nematode, we have established that a meiotic cell can process a base mismatch, using the base excision repair machinery, to give rise to meiotic recombination. This suggests that meiotic cells can process lesions other than Spo-11 induced DSBs for recombination

Kardioloogia

Eesti Arst 2016; 95(11):737–74

Toiduallergia

Toiduallergia on immuunvahendatud reaktsioon, mille esinemissagedus on viimase 10 aasta jooksul kahekordistunud. Toiduallergiat esineb lastel sagedamini kui täiskasvanutel: lastest umbes 5–10%-l ja täiskasvanutest hinnanguliselt 5%-l. Põhilised toiduallergia tekitajad on munas, piimas, kalas, sojas, teraviljas, maapähklites, puupähklites, koorikloomades leiduvad valgud. Puu- ja aedviljade allergeensus väljendub rohkem värskelt, toorelt kasutades ning on seotud põhiliselt õietolmu ja toidu ristallergiaga. Reaktsioon võib tekkida nii toidu söömisest kui ka muul viisil allergeeniga kokkupuutumisest. Toiduallergia võib väljenduda nahal, haarata hingamiselundeid, gastrointestinaaltrakti ja kardiovaskulaarsüsteemi. Toiduallergia esmavaliku uuringuteks on nahatorketestid ja seerumi IgE testid, kuid toidu esilekutsutud enteropaatiate diagnoosimiseks võivad osutuda vajalikuks endoskoopilised uuringud koos biopsiaga

Activin/Nodal signalling in stem cells.

Activin/Nodal growth factors control a broad range of biological processes, including early cell fate decisions, organogenesis and adult tissue homeostasis. Here, we provide an overview of the mechanisms by which the Activin/Nodal signalling pathway governs stem cell function in these different stages of development. We describe recent findings that associate Activin/Nodal signalling to pathological conditions, focusing on cancer stem cells in tumorigenesis and its potential as a target for therapies. Moreover, we will discuss future directions and questions that currently remain unanswered on the role of Activin/Nodal signalling in stem cell self-renewal, differentiation and proliferation.S.P. was supported by the EUFP7 grant InnovaLIV and an FEBS long-term fellowship. L.V. was supported by the ERC starting grant Relieve IMDs and the Cambridge Hospitals National Institute for Health Research Biomedical Research Centre.This is the accepted manuscript of a paper published in Development (Pauklin S, Vallier L, Development 2015, 142, 607-619, doi: 10.1242/dev.091769). The final version is available at http://dx.doi.org/10.1242/dev.09176

Kuivnahksus

Kuivnahksus on sagedasemaid dermatoloogilisi probleeme ning kaasnev sümptom paljude naha-, sise- ja neuroloogiliste haiguste korral. Patsientidele põhjustab see tihti erinevaid kaebusi ja elukvaliteedi halvenemist, mistõttu pöördutakse abi saamiseks erinevate spetsialistide poole. Oluline on, et arst mõtleks muu hulgas ka kuiva naha diagnoosi võimalikkusele. Artiklis on antud lugejatele ülevaade kuiva naha põhjustest, patsiendi käsitlusest ja ravivõtetest

Füüsilise koormuse põhjustatud anafülaksia

Artikli eesmärk on lühidalt tutvustada koormuse tekitatud anafülaksiat, mille peamine vallandaja on füüsiline koormus. Diagnoosimise põhitalaks on täpne anamnees. Diagnoosimise kuldstandardiks peetakse topeltpimedat ja platseeboga kontrollitud toidukoormuse-provokatsioonitesti, mida tehakse meditsiiniasutuses, jälgides vererõhku ja kopsufunktsiooni ning tagades anafülaksia korral ravi- ja elustamisvõimekuse. Eestis toidu-koormuse provokatsiooni diagnoosimise otstarbel ei tehta, vaid lähtutakse anamneesist, kliinilisest pildist ja kinnitavatest analüüsidest. Seisundi ravi on sama kui teiste anafülaksiate korral. Artiklis on kirjeldatud ka kahe patsiendi (ühe täiskasvanu ja ühe lapse) haigusjuhtu

Chemically modified neoantigen-based immunotherapy for targeting KRASG12C-driven tumors

The clinical efficacy and durability of KRASG12C-targeted therapies are limited by the development of resistance mechanisms. Here, we provide a review of recent KRASG12C-targeted therapy and immunotherapy-unifying strategies that utilize covalently modified peptide/MHC class I complexes as tumor-specific neoantigens to tag drug-resistant cancer cells for destruction with hapten-based immunotherapeutics

Alkoholivastase kampaania “Palju sina jood?” meediasisendite raamistamine ajakirjanduses

The aim of this bachelor's thesis is to find out how Estonian mainstream media frames the messages of anti-alcohol social campaign "Palju Sina jood?" organized by the National Institute Of Health Development in 2009. The research covers 23 articles from Postimees, Eesti Päevaleht, Eesti Ekspress and Äripäev that appeared between 9.November 2009 and 1.June 2010 in order to analyse message framing during and after the campaign. To determine how newspapers wrote about Estonians' drinking problems and also the campaign (how the messages of the campaign were interpreted, sent to audience) the framing theory was implemented. According to the framing theory of public opinion, journalists and news agencies construct frames that reflect cultural narratives in the whole society. Journalists are fundamental influencers when news' readers interpret the world and social problems around them. To determine the frames that media was using when writing about Estonians' binge drinking and the anti-alcohol campaign, the author used framing analysis according to William A. Gamson's approach - the author read all the articles at least twice and determined frame's signature elements – i.e. framing devices (metaphors, depictions, exemplars, catch-phrases, visual images) and reasoning devices (problem's roots, consequences, principles). Generalizing all the frame's signature elements the author found 4 following frames: "binge drinking as cultural, social and psychological inevitability" (with 3 sub-frames), "alcohol and the state" (with 2 counter-frames), "health risks of abusing alcohol" and "pseudoproblem". The author also determined all the possible solutions for solving Estonia's binge drinking problem that could be found from the articles. When comparing frames detected from the media with messages of the campaign, it appears that media has a negative influence on campaign's key message - the message of Estonians drinking more than they think, consuming 11,9 litres of pure alcohol a year and taking second place in European alcohol consumption rankings. Media frames are therefore trying to marginalize statistical results, blaming Finnish tourists and certain social groups to explain shocking statistics. The frames also try to normalize heavy alcohol consumption when explaining these tendencies with Estonia's regional culture (Estonians have always drunk much), psychological aspects (drinking is a result of boredom, ignorance and habits) and social aspects (certain groups of society e.g. heavy drinkers from small villages are used to drink and that is considered normal). The only message the media frames fully support is "health risks of alcohol consumption" that also influences Estonia's economy and social sphere. When trying to find solutions for Estonians' binge drinking problem, it appears that professionals, anti-alcohol activists, scientists and doctors think the state is fully responsible and should take steps to toughen laws concerning selling, buying and advertising alcohol. While professionals blame the state, journalists, bloggers and writers find that the state shouldn't restrict buying and consuming alcohol as much as it currently does because it is considered to be the reason why Estonians drink at home and stock a home bar with alcohol. The only suitable solution for the state is to get involved in prevention of binge drinking instead of dealing with consequences. The state should also offer more opportunities for the citizens to spend their free time. In conclusion, the research shows that the anti-alcohol campaign should find more positive approach addressing and explaining the problem and should also try to not criticize and shock their target group because of the tendency to block receiving new information which can be actually very useful in order to reduce alcohol consumption. While organizing the following campaigns National Institution Of Health Development should also consider media's tendency to simplify the problem, to have certain biases and attitudes towards alcohol related topics.http://www.ester.ee/record=b4056405~S1*es

Initiation of stem cell differentiation involves cell cycle-dependent regulation of developmental genes by Cyclin D.

Coordination of differentiation and cell cycle progression represents an essential process for embryonic development and adult tissue homeostasis. These mechanisms ultimately determine the quantities of specific cell types that are generated. Despite their importance, the precise molecular interplays between cell cycle machinery and master regulators of cell fate choice remain to be fully uncovered. Here, we demonstrate that cell cycle regulators Cyclin D1-3 control cell fate decisions in human pluripotent stem cells by recruiting transcriptional corepressors and coactivator complexes onto neuroectoderm, mesoderm, and endoderm genes. This activity results in blocking the core transcriptional network necessary for endoderm specification while promoting neuroectoderm factors. The genomic location of Cyclin Ds is determined by their interactions with the transcription factors SP1 and E2Fs, which result in the assembly of cell cycle-controlled transcriptional complexes. These results reveal how the cell cycle orchestrates transcriptional networks and epigenetic modifiers to instruct cell fate decisions.This work was supported by the European Research Council grant Relieve IMDs and the Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V.). A.B. was funded by the British Heart Foundation Ph.D. Studentship. S.P. was funded by a Federation of European Biochemical Societies long-term fellowship and a InnovaLiv EuFP7 grant. S.P. and L.V. conceived the research and wrote the manuscript. S.P. and A.B. performed the experiments. P.M. performed bioinformatic analyses.This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via http://dx.doi.org/10.1101/gad.271452.11