Histonų potransliacinės modifikacijos sąlygoja chromatino struktūros pakitimus, lemiančius genų, atsakingų už ląstelėje vykstančių įvairių procesų, tokių kaip proliferacija, diferenciacija, apoptozė reguliavimą. Šiame darbe įvertinome chromatino baltymų, histonų H3 ir H4, modifikacijų dinamiką HL-60 ląstelėse, indukuotose granuliocitinei diferenciacijai su retinoine rūgštimi (RA) ir histonų deacetilazių slopikliais, fenilo butiratu (PB) ir vitaminu B3 (vitB3) bei jų kombinacijomis. Aktyvaus chromatino baltymų kompleksai proliferuojančiose ir diferenciacijai indukuotose ląstelėse buvo analizuojami chromatino imunoišsodinimo metodu, naudojant antikūnus prieš histonus - hiperacetilintą H4 ir trimetil-Lys4 H3, esančius aktyvaus chromatino vietose mononukleosomų frakcijoje. Atlikta baltymų, esančių komplekse su modifikuotais histonais H3 ir H4 proteominė analizė vienmatėje (SDS/PAGE) ir dvimatėje (2DE) elektroforezės sistemose. Nustatyti baltymai, sąveikaujantys su hiperacetilintu H4 ir trimetil-Lys4 H3. Tai baltymai, dalyvaujantys genų raiškos iniciavime bei chromatino modifikacijose, t.y. transkripcijos faktorius Sp1, metionino acetiltransferazė, DNR metiltransferazė ir kt. Taip pat patodyta, kad HL-60 ląstelėse p21 WAF1/CIP geno raiška priklauso nuo pasirinkto induktoriaus. Apibendrinant manome, kad poveikio variantas - 3mM PB su 5mM vit.B3 6 val., nuplovus tolesnis poveikis su 1μM RA ir 5mM vit.B3 24 val., galėtų būti tinkamas leukeminių ląstelių diferenciacinei terapijai... [toliau žr. visą tekstą] / Recently, a novel strategy for the treatment of leukemia’s through the modulation of chromatin structure is applicable. In this study, we conducted a detailed analysis of anti-leukemia effects of histone deacetylase (HDAC) inhibitors and their combinations with retinoic acid using human promyelocytic leukemia cell line HL-60. We have shown that HDAC inhibitors - phenyl butyrate and vitamin B3, cause rapid histone H3 and H4 modifications. Further we examined how HDACI and retinoic acid (RA) can modulate gene expression via acetylation and other modifications of histones associated with targeted genes. We performed Chip assay to identify proteins associated with hyperacetylated histone H4. Immunoprecipitated proteins were fractionated by SDS/PAGE and 2DE. Proteomic analysis was performed by using mass spectrometry (MALDI TOF and ESI MS/MS). We identified Sp1 transcriptional activation, DNA methyltransferase, methionine acetyltransferase and other proteins that were associated with modified histones H3 and H4. To evaluate the changes ofp21 gene expression affected by hyperacetylation of histone H4 during HL-60 cell granulocytic differentiation we performed PGR of active chromatin immunoprecipitated with hyperacetylated H4 by using different primers of p21 gene. In this study we have shown that p21 gene expression changes during granulocytic differentiation and depends on inducer. Our results suggest that the chromatin remodeling caused by HDAC inhibitors could be a promising... [to full text]

SANTRAUKA PAUKŠČIUOSE APTINKAMŲ NEAPIBŪDINTŲ SARCOCYSTIS GENTIES RŪŠIŲ FILOGENETINIŲ RYŠIŲ TYRIMAS NAUDOJANT DALINES 18S IR 28S rRNR GENŲ SEKAS Petras Prakas Vilniaus Universiteto Ekologijos Institutas, Populiacinės Genetikos Laboratorija, Vilnius, Lietuva. Pagal cistų morfologiją, baltakaktėje žąsyje (Anser albifrons) aptiktos I tipo sarkocistos, didžiojoje antyje (Anas platyrhynchos) rastos II tipo sarkocistos, dviejose baltakaktėse žąsyse ir pilkojoje žąsyje (Anser anser) nustatytos III tipo sarkocistos, varnoje (Corvus cornix) identifikuotos V tipo sarkocistos. Iš paukščių, kaip tarpinių šeimininkų išskirtos sarkosporidijos aprašomos pirmą kartą bei yra neįvardintos rūšys. Baltakaktėje bei pilkojoje žąsyse išskirtos III tipo sarkocistos gali būti tos pačios sarkocistų rūšies parazitavimo skirtingų rūšių tarpiniuose šeimininkuose atvejis. Nustatytos 18S ir 28S rDNR fragmentų sekos pasižymėjo didžiausia homologija Sarcocystis bei Frenkelia gentims. Filogenetinių ryšių medyje sugrupuojamos šiame darbe tiriamos rūšys su Frenkelia microti, Frenkelia glareoli, Sarcocystis muris, Sarcocystis neurona. Rezultatai atskleidė Sarcocystis genties rūšių koevoliuciją su jų galutiniais šeimininkais. Remiantis tyrimo duomenimis, galima teigti, kad Sarcocystidae šeimos filogenetinius ryšius apsprendžia sarkosporidijų gyvybinio ciklo ypatybės, šeimininkų spektras bei parazitų specifiškumas šeimininkui. 18S ir 28S rRNR genų dalinių sekų analizė atskleidžia tirtų Sarcocystis sp. rūšių... [toliau žr. visą tekstą] / SUMMARY INVESTIGATION OF THE PHYLOGENETIC RELATIONSHIPS OF SARCOCYSTIS SPP. FOUND IN BIRDS USING 18S AND 28S rRNA GENE PARTIAL SEQENCES Petras Prakas Institute of Ecology of Vilnius University, Laboratory of Population Genetics, Vilnius, Lithuania Based on cyst morphology, Sarcocystis cysts type I were found in white-fronted goose (Anser albifrons), cysts type II in mallard (Anas platyrhynchos), cyst type III in one grey-lag goose (Anser anser) and two white-fronted geese, cyst type V in hooded crow (Corvus cornix). The sarcocysts isolated from the infected birds as intermediate host have not been previously described and are unnamed. Type III sarcocysts detected in white-fronted and greylag geese may illustrate the case of polyhostal nature of sarcocysts when the same-species parasites infesting intermediate hosts of different species. The obtained 18S and 28S ribosomal RNA partial gene sequences showed the highest homology for the genera Sarcocystis and Frenkelia. In the tree of phylogenetic relationships, the species involved in this study were grouped with Frenkelia microti, Frenkelia glareoli, Sarcocystis muris and Sarcocystis neurona. Results show co-evolution of Sarcocystis spp. with the final host. Based on data obtained it could be stated that phylogenetic relationships of Sarcocystidae family are influenced by peculiarity of life cycle, hosts spectrum and host specificity. Analysis of the partial sequences of 18S and 28S ribosomal RNA revealed the phylogenetic and... [to full text]

Krūties vėžys yra dažniausia Lietuvos ir viso pasaulio moterų onkologinė liga. Ši liga pasižyminti nevienoda eiga, todėl molekulinė vėžio analizė yra labai svarbi. Šiuo metu ligos eiga prognozuojama, remiantis riboto informatyvumo klinikinių žymenų sistema, o gydymui tik pavieniais atvejais skiriami atrankūs vaistai, nukreipti į ligą sukėlusį genetinį pakitimą. Naviko molekulinė analizė padeda aptikti pažaidas vėžio genuose ar jų raiškos pakitimus ir informuoja apie ligos išsivystymo priežastis, padeda prognozuoti ligos progresavimo tikimybę, atskleidžia taikinius naujos kartos gydymo priemonėms. Siekiant įvertinti krūties vėžio epigenetinių biožymenų efektyvumą mes tyrėme reguliacinių genų, dalyvaujančių ląstelės ciklo kontrolėje, signalų perdavime, apoptozėje ir DNR reparacijoje, promotoriaus sekų hipermetilinimą. Tyrimui buvo atrinktos 76 pirminės ankstyvos stadijos (pT1-2) krūties karcinomos. Metilinimo pakitimai promotoriaus sekoje buvo tiriami septyniuose naviką slopinančiuose genuose (p14, p16, RARβ, RASSF1A, DAPK, GSTP1 ir MGMT), taikant metilinimui jautrią PGR. „Tikro laiko“ PGR metodas buvo įdiegtas epigenetinių pakitimų tyrimams cirkuliuojančioje vėžio DNR, išskirtoje iš ligonių kraujo plazmos. Didžioji dalis ankstyvos stadijos krūties karcinomų (63/76) turėjo bent vieno tirto geno hipermetilinimą. Bendras epigenetinių žymenų informatyvumas – 83%. Dažniausiai hipermetilinimas krūties karcinomose nustatytas gene RASSF1A (56/76). Statistinė analizė parodė... [toliau žr. visą tekstą] / Breast cancer is the most prevalent malignancy of women in Lithuania and word-wide. The course of disease differ markedly among patients, therefore molecular characterisation of tumour is very important. However, current prognostic markers are mainly based on clinical parameters and do not enable a reliable selection of the patients with high risk of disease progression. Molecular characterisation of tumour through detection of changes in cancer-related genes can help to estimate the risk of cancer progression, detect the molecular targets for modern treatment strategies. In order to evaluate the suitability of epigenetic biomarkers for molecular characterisation of breast cancer we analysed promoter hypermethylation in a wide panel of regulatory genes involved in cell cycle control, signalling, apoptosis and DNA repair. 76 primary breast carcinomas of early stage (pT1-2) were selected for the study. Aberrant methylation in promoter regions of seven tumour suppressor genes (p16, p14, RARβ, RASSF1A, DAPK, GSTP1 and MGMT) was analysed by means of methylation-specific PCR. The “Real Time” PCR method was adapted for detection of epigenetic changes in circulating tumour DNA from plasma of cancer patients. Most of the early-stage breast tumours (63/76) exhibited hypermethylation in at least one gene involved in analysis. The overall sensitivity of the epigenetic biomarkers was 83%. Gene RASSF1A was the most frequently (56 of 76 cases) hypermethylated gene in breast tumours... [to full text]

Glioblastoma (GBM) is the most common primary brain tumor in adults. This study attempted to identify the genes potentially regulated by promoter methylation in GBM. Therefore, we analyzed the expression of COX7A1, SPINT1, AREG, NPTX2, and KRT81 in glioblastomas and human brain tissue and investigated if there were any associations between the expression and methylation of these genes. Moreover, we aimed to determine the methylation frequency of 11 genes (AREG, CASP8, CD81, DcR1, DR4, GATA4, GATA6, hMLH1, NPTX2, TES, and TFPI2) promoters in 100 patients with glioblastoma multiforme and to evaluate the associations between patients’ clinical characteristics and prognostic value. The methylation status of the following 4 gene promoters was significantly related to patients’ survival after surgery: AREG, CASP8, GATA6 and TFPI2. Identification of the methylation status of these genes could be one of the objective criteria in the prognosis of disease course in patients with glioblastoma and could supplement the list of already known epigenetic markers. The methylation status of a combination of 6 genes (AREG, CASP8, DR4, GATA4, GATA6, and TFPI2) was found to be a more accurate independent prognostic factor associated with patients’ survival after surgery when compared with the methylation status of individual genes. The molecular classification of GBM according to the methylation profile of a combination of these 6 genes could help clinicians tailor an appropriate treatment... [to full text] / Glioblastoma (GBM) yra vienas labiausiai paplitusių ir agresyviausių pirminių galvos smegenų auglių. Siekiant nustatyti molekulinius žymenis, susijusius su GBM vystymusi, diagnoze ir prognoze, buvo atlikta 14 genų (AREG, CASP8, CD81, COX7A1, DcR1, DR4, GATA4, GATA6, hMLH1, KRT81, NPTX2, SPINT1, TES ir TFPI2) promotorių metilinimo analizė. Buvo nustatyti naviką slopinančių genų promotorių metilinimo dažniai, ryšiai su klinikinėmis sergančiųjų GBM charakteristikomis ir prognozinė vertė. Disertacinio darbo metu nustatyta, kad AREG ir NTPX2 genų raiška susijusi su šių genų promotorių metilinimu, tuo tarpu COX7A1, KRT81 ir SPINT1 genų raiškos skirtumai nėra susiję su šių genų promotorių metilinimu. Naujų epigenetinių žymenų tyrimai 100 GBM pavyzdžių parodė navikų epigenetinį heterogeniškumą ir įvairų tirtų genų promotorių metilinimo dažnį. Nustatyta, kad AREG, CASP8, GATA6 ir TFPI2 genų promotorių metilinimas statistiškai patikimai susijęs su išgyvenimo trukme po operacijos. Šių genų promotoriaus metilinimo nustatymas gali būti vienas iš objektyvių kriterijų prognozuojant pacientų ligos eigą ir papildyti jau nustatytų epigenetinių žymenų sąrašą. Buvo sudarytas, suminis šešių genų (AREG, CASP8, DR4, GATA4, GATA6 ir TFPI2) derinys, kuris yra tikslesnis nepriklausomas prognozinis veiksnys, susijęs su išgyvenimo trukme po operacijos lyginant su atskirų genų promotorių metilinimu. GBM molekulinis tipavimas pagal šių šešių genų derinį galėtų padėti parenkant gydymo strategiją.

Our study investigates the possibility of integrating ChatGPT, an AI text generative tool, as a didactic supporting tool within the Swedish upper-secondary school curricula. Particularly, it takes interest in the English foreign language teaching context and examines eight peer reviewed articles on the matter. The questions it aims to answer are: In light of existing research, 1) what are some of the implications of integrating ChatGPT as a didactic supporting tool in Sweden’s English as a Foreign Language (EFL) upper-secondary classroom and 2) how could this tool be incorporated successfully into the teaching process? In the results, the synthesis identifies ethical concerns, teacher beliefs and perspectives, and pros and cons of integration as the three primary themes and shows how 75% of the articles are concerned with the ethical implications of ChatGPT, hence requesting ethical frameworks and guidelines. Additionally, it identifies teachers' beliefs and attitudes on integration of AI as the biggest influencing factor on the integration of ChatGPT and that the dominant benefits of integration of ChatGPT are in student accessibility and reduced workload for teachers. Conversely, the concerns include those of unethical nature such as cheating, plagiarizing, and information security and accuracy. The discussion suggests that ChatGPT, as a didactic tool, is supported by the Swedish upper-secondary curricula. However, additional efforts are needed to ensure its safe and effective integration. The study concludes that ChatGPT, and other AI generative tools, could be implemented in the curricula, but before this is accomplished we require policies, guidelines, and ethical frameworks to ensure it can be done safely and effectively.

The rise of Artificial Intelligence (AI), with its potential to be either highly beneficial or detrimental to humanity, is driving the rapid evolution of digital technologies, significantly impacting the business world and fostering new entrepreneurial opportunities. AI, characterized by its ability to learn, adapt, and make decisions, optimizes crucial elements such as time and resources, which are essential for entrepreneurial success. Generative AI (GenAI), a subset of AI, has gained unprecedented traction, exemplified by the rapid adoption of tools like ChatGPT, which democratize access to advanced technology previously limited to large corporations. The proliferation of GenAI across various business functions is ushering in a new era of entrepreneurship, where leveraging AI's efficiencies can determine a venture's success and longevity. This thesis examines GenAI's role in entrepreneurship by addressing the lack of empirical evidence through an explorative approach using interview data. It develops a framework to understand GenAI's role in different stages of the venture creation process (VCP) and offers a practical guide for entrepreneurs to leverage GenAI technologies effectively. Focusing on German tech entrepreneurs, the research uses the External Enabler (EE) framework to provide empirical evidence of GenAI's benefits in the VCP. This thesis employs an exploratory research design with semi-structured interviews to gather qualitative data. A purposive and snowball sampling strategy was used to select 5 experts and 9 entrepreneurs of the software industry with relevant experience, ensuring a comprehensive understanding of GenAI's application in the VCP. Data was analyzed using qualitative content analysis, combining deductive and inductive methods to develop a robust category system. Triangulation of data sources enhanced the credibility of the findings, validating insights through referencing and consistency checks. This thesis identifies key enabling mechanisms of GenAI in the VCP. Additionally, it highlights inhibiting factors such as technical knowledge, trust, data security, and ethics of GenAI. The findings bridge the gap between theoretical models and practical applications, offering valuable insights for entrepreneurs, policymakers, and other stakeholders. The research underscores the importance of empirical evidence and the transformative potential of GenAI in enhancing operational efficiencies and achieving competitive advantages.

The marketing process has undergone significant changes over the years, due to new technologies. Among these advancements, artificial intelligence (AI) has been increasingly used to generate advertising messages and images. This study examines consumers' perceptions of AI-generated advertisements, with a focus on the influence of age. Participants were divided into two groups, with one group believing the ads were human-created and the other assuming they were AI-generated. Results indicated that perceived ad falsity led to more negative perceptions. However, younger individuals exhibited more favorable attitudes toward AI-generated ads compared to older individuals. Despite an overall negative bias towards AI-generated ads, one AI-generated ad was received as most positively across all age groups, supporting prior research that AI-generated content can be well-received. A theoretical model was built and tested to explore the relationship between age and ad perception, suggesting that prior experience with AI, attitudes towards AI, and AI credibility sequentially mediate this relationship. While the effect of machine heuristics was found to be nonsignificant, it did influence AI credibility, indicating potential avenues for future research.

Artificial Intelligence (AI) is ever increasingly becoming more and more widespread, and is available, for the most part freely to anyone. While AI can be used for both good and bad, the potential for misuse exists. This study focuses on the intersection of AI and cybersecurity, with a focus on AI-generated phishing emails. In this study a mixed-method approach was applied and, an experiment, interviews, and a survey were conducted. Experiments and interviews were conducted with 9 participants with various backgrounds, but novices in phishing. In the experiment, phishing emails were created in three distinct ways: Human-Crafted, Internet-aided, and AI-generated. Emails were evaluated during semi-structured interviews, and each participant reviewed six emails in total, where two of these, were real phishing emails. The results from the interviews indicate that AI-generated phishing emails are as persuasive as those created in the Human-Crafted task. On the contrary, in the survey, participants ranked the AI-generated phishing email as the most persuasive, followed by Human-Crafted. The survey was answered by 100 participants. Familiarity plays a crucial part in both persuasiveness and also willingness to go along with the requests in the phishing emails, this was highlighted during interviews and the survey. Urgency was seen as very negative by both the respondents and interviewees. The results from the study highlight the potential for misuse, specifically with the creation of AI-generated phishing emails, research into protection measures should not be overlooked. Adversaries have the potential to use AI, as it is right now, to their advantage.