Academic literature on the topic 'RNA modifikace'

Samomor je dobro opisan javnozdravstveni problem. Glede na število samomorov se Slovenija že dolgo uvršča v svetovni vrh. Na biološki ravni so bile opravljene številne genetske in biokemijske raziskave živčnih prenašalcev, v zadnjih letih so pogostejše tudi raziskave na področju epigenetike, kamor uvrščamo delovanje nekodirajočih RNA (miRNA), metilacijo DNA in posttranslacijske modifikacije histonov. Mikro RNA so kratke, 19–25 nukleotidov dolge enoverižne molekule RNA, ki se specifično vežejo na mRNA in znižajo izražanje tarčnih genov. Pri žrtvah samomora so zaznali spremembe v izražanju miRNA v povezavi z možganskim nevrotrofnim dejavnikom (BDNF) in njegovim receptorjem (TrkB), transkripcijskimi in rastnimi dejavniki ter poliaminskim sistemom. Metilacija DNA je proces dodajanja metilne skupine na mesto 5C citozina, posledica pa je znižanje prepisovanja genov. S študijami globalnega vzorca metilacije so pri žrtvah samomora prepoznali spremenjene vzorce metilacije promotorskih regij. Številni promotorji so pripadali genom, vpletenim v kognitivne funkcije. Na ravni posameznih genov so spremembe v vzorcu metilacije promotorske regije opazili pri BDNF in genu za receptor TrkB, ribosomski RNA in serotoninskem receptorju tipa 2A. Histoni so osnovni gradniki jedrnega kromatina; predstavljajo proteinsko osnovo, okoli katere se navije DNA. Tako skupaj tvorijo nukleosom. Histone sestavlja globulni centralni del in N-terminalni rep. Dolžina slednjega je lahko različna in na aminokislinskih ostankih repa so lahko prisotne posttranslacijske modifikacije. Med njimi so najpogostejše acetilacija in metilacija lizinov in argininov, fosforilacija serinov in treoninov, ubikvitinacija in sumoilacija lizinov in ADP-ribozilacija. Pri žrtvah samomora so opazili spremembe modifikacij histonov pri TrkB in poliaminskem sistemu. Številne študije tako povezujejo epigenetske mehanizme s samomorilnim vedenjem.

Tanaman kelapa sawit memiliki kandungan polisakarida dan polifenol yang tinggi. Kontaminasi polisakarida dan polifenol menyebabkan sulitnya proses isolasi RNA dari jaringan tanaman kelapa sawit. Penelitian ini dilakukan untuk mengoptimasi beberapa protokol isolasi RNA tanaman kelapa sawit yang efektif dan efisien. Penelitian dilaksanakan selama tiga bulan, pada bulan Oktober-Desember 2018 di Laboratorium Biokimia dan Biologi Molekuler, Pusat Penelitian Bioteknologi dan Bioindustri Indonesia (PPBBI), Jalan Taman Kencana No. 1 Bogor 16128. Penelitian dilakukan dengan melaksanakan teknik isolasi RNA menggunakan tiga protokol, yaitu modifikasi Cetyl Trimethyl Ammonium Bromide (CTAB), kit isolasi RNA RNeasy Plant Mini Kit (Qiagen), dan kit isolasi NucleoSpin RNAPlant (Macherey-Nagel). Sampel yang digunakan adalah daun dan akar tanaman kelapa sawit berumur kurang dari tiga bulan dengan bobot 0,1 gram dan 2,5 gram yang disesuaikan untuk tiap protokol. Variabel yang diamati adalah konsentrasi (ng/µl), kemurnian (rasio A260/A280 dan A260/A230), dan pita RNA pada elektroforesis gel agarosa. Hasil penelitian menunjukkan, RNA total hasil isolasi protokol NucleoSpin RNAPlant (Macherey-Nagel) memiliki kualitas paling tinggi. Konsentrasi RNA total daun dan akar kelapa sawit yang didapatkan melalui protokol NucleoSpin RNAPlant (Macherey-Nagel) sebesar 338 ng/µl dan 184,4 ng/µl dengan rasio A260/A280 RNA total daun dan akar kelapa sawit sebesar 2,13 dan 2,18 serta rasio A260/A230 sebesar 2,09 dan 2,20. Hasil elektroforesis gel agarosa menunjukkan integritas yang bagus dari RNA total hasil isolasi RNeasy Plant Mini Kit (Qiagen) dan NucleoSpin RNAPlant (Macherey-Nagel), namun terdapat kontaminasi dan smear pada RNA total hasil isolasi CTAB modifikasi 1 dan 2. Kata kunci: kelapa sawit, isolasi RNA, spektrofotometer, elektroforesis gel agarosa

Tanaman kelapa sawit memiliki kandungan polisakarida dan polifenol yang tinggi. Kontaminasi polisakarida dan polifenol menyebabkan sulitnya proses isolasi RNA dari jaringan tanaman kelapa sawit. Penelitian ini dilakukan untuk mengoptimasi beberapa protokol isolasi RNA tanaman kelapa sawit yang efektif dan efisien. Penelitian dilaksanakan selama tiga bulan, pada bulan Oktober-Desember 2018 di Laboratorium Biokimia dan Biologi Molekuler, Pusat Penelitian Bioteknologi dan Bioindustri Indonesia (PPBBI), Jalan Taman Kencana No. 1 Bogor 16128. Penelitian dilakukan dengan melaksanakan teknik isolasi RNA menggunakan tiga protokol, yaitu modifikasi Cetyl Trimethyl Ammonium Bromide (CTAB), kit isolasi RNA RNeasy Plant Mini Kit (Qiagen), dan kit isolasi NucleoSpin RNAPlant (Macherey-Nagel). Sampel yang digunakan adalah daun dan akar tanaman kelapa sawit berumur kurang dari tiga bulan dengan bobot 0,1 gram dan 2,5 gram yang disesuaikan untuk tiap protokol. Variabel yang diamati adalah konsentrasi (ng/µl), kemurnian (rasio A260/A280 dan A260/A230), dan pita RNA pada elektroforesis gel agarosa. Hasil penelitian menunjukkan, RNA total hasil isolasi protokol NucleoSpin RNAPlant (Macherey-Nagel) memiliki kualitas paling tinggi. Konsentrasi RNA total daun dan akar kelapa sawit yang didapatkan melalui protokol NucleoSpin RNAPlant (Macherey-Nagel) sebesar 338 ng/µl dan 184,4 ng/µl dengan rasio A260/A280 RNA total daun dan akar kelapa sawit sebesar 2,13 dan 2,18 serta rasio A260/A230 sebesar 2,09 dan 2,20. Hasil elektroforesis gel agarosa menunjukkan integritas yang bagus dari RNA total hasil isolasi RNeasy Plant Mini Kit (Qiagen) dan NucleoSpin RNAPlant (Macherey-Nagel), namun terdapat kontaminasi dan smear pada RNA total hasil isolasi CTAB modifikasi 1 dan 2. Kata kunci: kelapa sawit, isolasi RNA, spektrofotometer, elektroforesis gel agarosa

Senyawa turunan kumarin menunjukkan aktivitas anti koagulasi darah, menghambat kerja enzim, antimikroba, antibiotik, dan anti kanker dengan mengganggu sintesa DNA/RNA. Penelitian ini bertujuan memperoleh hubungan kuantitatif struktur-aktivitas senyawa turunan kumarin terhadap reseptor kanker kolon dengan pendekatan Hansch melalui analisis multilinear, untuk dapat melakukan modifikasi senyawa berdasarkan persamaan HKSA dalam usaha memperbesar potensi dan selektifitas obat. Deskriptor yang terpilih mewakili parameter elektronik,hidrofobik dan sterik. Penambatan molekul dilakukan dengan menggunakan Autodock Vina untuk menganalisa interaksi dari turunan kumarin terhadap enzim Topoisomerase II. Hasil persamaan HKSA yang didapat telah tervalidasi dengan metode LOO (Leave One Out) adalah Log IC50= -4.047+(0.496 x AM1_dipol) + (-0.089 x AM1_HOMO) + (0.899 x logP(o/w)) + (0.903 x logS) + (0.351 x mr). Hasil penelitian menunjukkan IC50 prediksi dari senyawa yang di modifikasi (MOD2) dengan subtituen NO2 mempunyai aktivitas terbaik dengan (ΔGbind) terendah (-8.8 Kcal/mol) dan memiliki IC50 prediksi terkecil yaitu 1.0897 µM dibandingkan IC50 lead compound (C14) yaitu 1.77 µM.

Senyawa turunan kumarin menunjukkan aktivitas anti koagulasi darah, menghambat kerja enzim, antimikroba, antibiotik, dan anti kanker dengan mengganggu sintesa DNA/RNA. Penelitian ini bertujuan memperoleh hubungan kuantitatif struktur-aktivitas senyawa turunan kumarin terhadap reseptor kanker kolon dengan pendekatan Hansch melalui analisis multilinear, untuk dapat melakukan modifikasi senyawa berdasarkan persamaan HKSA dalam usaha memperbesar potensi dan selektifitas obat. Deskriptor yang terpilih mewakili parameter elektronik,hidrofobik dan sterik. Penambatan molekul dilakukan dengan menggunakan Autodock Vina untuk menganalisa interaksi dari turunan kumarin terhadap enzim Topoisomerase II. Hasil persamaan HKSA yang didapat telah tervalidasi dengan metode LOO (Leave One Out) adalah Log IC50= -4.047+(0.496 x AM1_dipol) + (-0.089 x AM1_HOMO) + (0.899 x logP(o/w)) + (0.903 x logS) + (0.351 x mr). Hasil penelitian menunjukkan IC50 prediksi dari senyawa yang di modifikasi (MOD2) dengan subtituen NO2 mempunyai aktivitas terbaik dengan (ΔGbind) terendah (-8.8 Kcal/mol) dan memiliki IC50 prediksi terkecil yaitu 1.0897 µM dibandingkan IC50 lead compound (C14) yaitu 1.77 µM.

Pemindahan produk dari mesin press memiliki resiko yang sangat tinggi terhadap keselamatan operator. Salah satu mesin yang terdapat di PT Mitsuba Indonesia adalah Press Fit Pump Assy yang berfungsi untuk menyatukan lower cup dan upper cup module fuel pump. Permasalahan yang terjadi yaitu kapasitas produksi belum tercapai. Penyebabnya adalah ruang di dalam mesin yang cukup sempit, sehingga gerakan operator kurang leluasa dan perlu waktu pada saat pengambilan produk. Solusi untuk mengatasi masalah tersebut yaitu melakukan modifikasi pada mesin Cup Lower Pump Wire Press dengan menambahkan alat bantu pemindah produk. Tujuan dari penelitian ini mengetahui performansi dari modifikasi mesin Cup Lower Pump Wire Press. Metode penelitian yang digunakan yaitu metode RCA (Root Cause Analysis) yang meliputi identifikasi masalah, penentuan masalah, pemahaman masalah, identifikasi faktor penyebab, tindakan korektif, dan pemantauan system. Pengujian yang dilakukan adalah pengukuran waktu proses mesin Cup Lower Pump Wire Press sebelum dimodifiksi dan setelah dilakukan modifikasi. Hasil dari penelitian ini adalah lama waktu proses mesin Cup Lower Pump Wire Press yang sebelumnya rata-rata 10.10 detik dapat berkurang menjadi 8.99 detik atau berkurang sebesar 10,99%.

Meningkatkan Fungsi CRISPR-Cas9 untuk Terapi Pengeditan GenPengeditan gen menjadi mudah dilakukan sejak ditemukannya clustered regularly interspaced short palindromic repeat (CRISPR) dan CRISPR-associated protein 9 (Cas9) sebagai alat untuk menyunting gen suatu organisme. Sebagian besar penyakit genetik tidak dapat disembuhkan secara kausal dengan terapi yang ada, maka pengeditan gen merupakan suatu cara yang prospektif dalam terapi medis di masa depan. Sayangnya, pengeditan gen dengan Cas9 yang ada saat ini masih memiliki banyak kelemahan, yaitu: 1) kurang spesifik, di mana RNA pemandu dapat berikatan dengan beberapa segmen pada genom manusia, sehingga memungkinkan terjadinya salah target; 2) kurang efisien, karena sekalipun telah berhasil memotong utas ganda DNA, kebanyakan penyambungan kembali akan dilakukan secara non-homology end joining (NHEJ), yang justru meningkatkan peluang terjadinya mutasi; 3) sulit disalurkan ke dalam inti sel karena berbagai sawar fisiologis maupun biokimiawi. Tulisan ini akan membahas perkembangan terkini dalam mengatasi ketiga masalah di atas. Untuk meningkatkan spesifisitas, dapat dilakukan modifikasi RNA pemandu dan struktur Cas9. Efisiensi dapat ditingkatkan dengan meningkatkan peluang terjadinya homology-directed repair dibandingkan NHEJ, sedangkan untuk meningkatkan distribusi ke dalam sel, dapat digunakan berbagai macam vektor, seperti virus dan nanopartikel. CRISPR-Cas9 merupakan area yang aktif diteliti dalam bidang biosains, dan dalam waktu dekat, diharapkan dapat dimanfaatkan dalam bidang klinik.Kata kunci: CRISPR, Cas9, efektivitas, spesifisitas, terapi genABSTRACTGene editing has become reasonably easy since the discovery of clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein 9 (Cas9). Most genetic diseases cannot be treated causally, and currently available therapies are mainly symptom-based. To treat the etiology of genetic diseases, a firm gene editing therapy is necessary to be established. This posits Cas9-facilitated gene editing as a prospective modality to become a clinically approved therapy in the future to treat genetic disorders. However, until recently, Cas9-based genome editing is still facing several hurdles, including low specificity, low effectiveness, and difficult delivery. Currently available Cas9 nucleases are able to bind to non-specific DNA sequence and produce non-specific cleavage. The efficiency has been relatively low due to the preference of non-homologous end-joining (NHEJ) over homology-directed repair (HDR) by the host cell. Furthermore, in order to deliver Cas9 into the nucleus, multiple physiological barriers have to be overcome. This review discussed recent developments in tackling these three hurdles, ranging from designing the guide RNA using multiple bioinformatics tools, modifying Cas9 structure, as well as packaging the nuclease-guide RNA complex into viral vectors and nanoparticles. Considering the active research on this area, it is expected that CRISPR/Cas9 can be utilized as a clinical therapy in the near future.Received: 02 June 2017 Accepted: 07 July 2017 Published: 19 July 2017

ABSTRAKSektor industri kecil dan menengah (IKM) berkontribusi cukup besar dalam perkembangan perekonomian Indonesia. Salah satu IKM yang bergerak di sektor ini adalah usaha circuit breaker. Mereka memiliki permasalahan defect produk. Lean sixsigma dipakai sebagai pendekatan improvement yang bertujuan untuk meningkatkan kualitas dengan cara mengurangi variasi produk. Tiga alternatif solusi, yaitu pelatihan staff, pengadaan fasilitas, dan modifikasi fasilitas. Alternatif perbaikan yang paling optimal untuk setiap proses adalah pelatihan untuk karyawan blanking dan pelatihan untuk karyawan electroplating. Alternatif perbaikan yang dipilih selanjutna diterapkan dengan tujuan meningkatkan sigma level dan mengurangi biaya kualitas. Penerapan alternatif menunjukkan kenaikan nilai sigma untuk proses blanking dari 3.96 sigma menjadi 4.05 sigma. Sedangkan untuk proses electroplating terjadi kenaikan nilai sigma dari 3.20 sigma menjadi 3.51 sigma.Kata kunci: lean, waste, Sixsigma, defect, RCA, FMEA ABSTRACTThe industrial sectors of small and medium enterprises (SMEs) have a considerable contribution to economic development in Indonesia. One SMEs engaged in the business sector is the circuit breaker. The main problem occurs the defected product is quite high and needs improvement, to increase product quality. Lean six sigma is used as improvement approach aimed at improving quality by reducing the variety of products. There are three alternative solutions, namely the training of staff, the purchase of the facility, and modification of the facility. The most optimal alternative for each process is blanking worker training and electroplating worker training. Training in both processes, then applied to increase sigma levels and reduce quality costs. Alternative implementations showed an increasing sigma value for blanking process from 3.96 sigma becomes 4.05 sigma. As for the electroplating process an increasing rate from 3.20 sigma becomes 3.51 sigma. Keywords: lean, waste, Sixsigma, defect, RCA, FMEA

Background : Examination of Calcium scoring in Radiology Departement Telogorejo Hospital Semarang using CINE scan type and recon phase images using a slice thickness of 2.5mm, this affect will be plaque with small size cann’t to calculate. Aim : The Purpose of this study was to determine the variation of parameters of calcium scoring MSCT scan examination right in calculating optimal plaque.Methods : The study was preceded by Pre experiments using a thorax phantom with an added 3-calcium artificial heart is likened to the RCA, LCX, LAD and have determined the weight and volume. Experiments with 10 patient samples by applying the best parameters from the pre experiment. Statistical analysis of the results of research conducted by Paired T-Test, while the assessment of the quality radiographs evaluated by an expert in this specialist radiology by providing anatomical criteria scores with 3 choices of items (not clear = 1, is quite clear = 2 and obvious = 3)Result : The volume of plaque is embedded in the thorax Panthom 900mm3. Results of pre experiments with hellical scan type and pitch of 0.5, 0.9, 1.3 in a score of plaque volume is 104mm3, 67mm3, 60mm3. While the scan type CINE with slice thickness 0.625mm, 1.25mm, 2.5mm produces a score of volume plaque is 880mm3, 878mm3, 867mm3. Further experiments were performed by applying parameters with the best result is CINE scan with variations slice thickness 0,625mm, 1.25mm, 2.5mm. To determine the best parameters assessment of image quality with the results on slice thickness 0.625mm was 2.2 (quite obvious), slice thickness 1,25mm scoring average of 2.7 (quite obvious), and slice thickness 2.5 mm average scoring 2.9 (obviously). While image noise on the slice thickness 0.625mm, 1.25mm, 2.5mm, namely 2.7(very high), 1.6 (low), 1.1 (low).Conclusions : Selected parameters that calculate optimal scoring calcium and low noise image for MSCT scan calcium scoring in Telogorejo Hospital Semarang is Scan type CINE with slice thickness variation 1,25mm

The prevalence of ADHD children increases every year. Some researchers have shown that psychosocial behavior therapy (antecedents-consequences modification) was effective to decrease hyperactivity and increase attention to ADHD children. This study aims to find out the effectiveness of antecedents-consequences modification by parents and teachers to decrease hyperactivity and increase attention to a 6 years old boy with ADHD. The study was a single case experimental design. Psychosocial behavior therapy has been used with antecedents-consequences modification. The antecedents-consequences modification was applied by teacher at school and parents at home. Data were analyzed using Wilcoxon Signed Rank Test. Results showed that there’s a significant decrease of hyperactivity behavior and significant increase of doing his assignment both at school and also at home. Not only about the content of behavior therapy itself, but how to give the therapy is important. Parents and teacher should do the therapy consistently, immediately, specifically and saliency to reach the target of intervention. Keywords: ADHD Children, Antecedents, Consequences, Modification Reference: (APA), A. A. P. (2013). Diagnostic and Manual of Mental Disorder (5th ed.). Arlington: American Psychiatric Association. Amalia, R. (2018). Intervensi terhadap Anak Usia Dini yang Mengalami Gangguan ADHD Melalui Pendekatan Kognitif Perilaku dan Alderian Play Therapy. Jurnal Obsesi : Jurnal Pendidikan Anak Usia Dini, 2(1), 27. https://doi.org/10.31004/obsesi.v2i1.4 Anastopoulos, A.D; Farley, S. . (2003). A Cognitive Behavioural Training Program for Parents of Children with Attention-Deficit/Hyperactivity Disorder. In W. J. Kazdin, Alan E (Ed.), Evidence-based psychotherapies for children and adolescents (pp. 187–203). New York: Guildford Press. Barkley, Russell A; DuPaul, G.L ; McMurray, M. . (1990). 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Evidence-based Psychosocial Treatment for ADHD Children and Adolescents. Retrieved from http://ccf.fiu.edu Davidson, G. C. (2010). Abnormal Psychology. New Jersey: Wiley. DuPaul, George; Stoner, G. (2003). ADHD in the schools. New York: Guildford Press. DuPaul, G., & Weyandt, L. (2006). School-based intervention for children with attention deficit hyperactivity disorder: Effects on academic, social, and behavioural functioning. International Journal of Disability, Development and Education, 53(2), 161–176. https://doi.org/10.1080/10349120600716141 Erinta, D. B. M. S. (2012). Efektivitas penerapan terapi permainan sosialisasi untuk menurunkan perilaku impulsif pada anak dengan attention deficit hyperactive disorder (ADHD). Jurnal Psikologi : Teori & Terapan, 3(1). Evans, Steven W; Owens, Julie; Bunford, M. N. (2014). Evidence-Based Psychosocial Treatments for Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. 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N., Burrows-MacLean, L., Fabiano, G. A., … Pelham, W. E. (2015). Effects of behavioral and pharmacological therapies on peer reinforcement of deviancy in children with ADHD-Only, ADHD and conduct problems, and controls. Journal of Consulting and Clinical Psychology, 83(2), 280–292. https://doi.org/10.1037/a0038505 Hidayati, DM Ria ; Purwandari, E. (2010). Time Out : Alternatif Modifikasi Perilaku Anak ADHD (Attention Deficit/ Hyperacitivity Disorder). Indigenous, Jurnal Ilmiah Berkala Psikologi, 12(2), 101–114. Hinshaw, S. P., Owens, E. B., Wells, K. C., Kraemer, H. C., Abikoff, H. B., Arnold, L. E., … Wigal, T. (2000). Family processes and treatment outcome in the MTA: Negative/ineffective parenting practices in relation to multimodal treatment. Journal of Abnormal Child Psychology, 28(6), 555–568. https://doi.org/10.1023/A:1005183115230 Hinshaw, Stephen P., Owens, E. B., Zalecki, C., Huggins, S. P., Montenegro-Nevado, A. J., Schrodek, E., & Swanson, E. N. (2012). Prospective follow-up of girls with attention-deficit/hyperactivity disorder into early adulthood: Continuing impairment includes elevated risk for suicide attempts and self-injury. Journal of Consulting and Clinical Psychology,80(6), 1041–1051. https://doi.org/10.1037/a0029451 Jackson, N. A. (2003). A Survey of Music Therapy Methods and Their Role in the Treatment of Early Elementary School Children with ADHD. Journal of Music Therapy, 40(4), 302–323. https://doi.org/10.1093/jmt/40.4.302 Johnston, Charlotte; Mash, E. J. (2001). Families of Children With Attention-Deficit/Hyperactivity Disorder : Review and Recommendations for Future Research. Clinical Child and Family Psychology Review, 4(3), 183–207. Jr, W. E. P., Fabiano, G. A., & Pelham, W. E. (2008). Evidence-Based Psychosocial Treatments for Attention- Deficit / Hyperactivity Disorder (Vol. 4416). https://doi.org/10.1080/15374410701818681 Kaiser, N. M., McBurnett, K., & Pfiffner, L. J. (2011). 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New York: Guildford Press. Pfiffner, L. J., Calzada, E., & McBurnett, K. (2000). Interventions to enhance social competence. Child and Adolescent Psychiatric Clinics of North America, 9(3), 689–709. https://doi.org/10.1016/s1056-4993(18)30113-5 Pfiffner, Linda J., Hinshaw, S. P., Owens, E., Zalecki, C., Kaiser, N. M., Villodas, M., & McBurnett, K. (2014). A two-site randomized clinical trial of integrated psychosocial treatment for ADHD-inattentive type. Journal of Consulting and Clinical Psychology, 82(6), 1115–1127. https://doi.org/10.1037/a0036887 Pfiffner, Linda J, & Haack, L. M. (2014). Behavior Management for School - Aged Children with ADHD. 23, 731–746. Pfiffner, Linda J, Hinshaw, S. P., Owens, E., Zalecki, C., Kaiser, N. M., Villodas, M., & Mcburnett, K. (2015). A two-site randomized clinical trial of Integrated Psychosocial Treatment for ADHD-Inattentive Type. Journal of Consulting and Clinical Psychology, 82(6), 1115–1127. https://doi.org/10.1037/a0036887.A Riddle, M. 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Alternative splicing (AS) is involved in expansion of transcriptome and proteome during cell growth, cell death, pluripotency, cell differentiation and development. There is increasing evidence to suggest that splicing decisions are made when the nascent RNA is still associated with chromatin. Here, I studied regulation of AS via chromatin modification with main focus on histone acetylation. First, we demonstrate that activity of histone deacetylases (HDACs) influences splice site selection in 700 genes. We provided evidence that HDAC inhibition induces histone H4 acetylation and increases RNA Polymerase II (RNA Pol II) processivity along an alternatively spliced element. In addition, HDAC inhibition reduces co-transcriptional association of the splicing regulator SRp40 with the target fibronectin exon. Further we showed that histone acetylation reader, Brd2 protein, affect transcription of 1450 genes. Besides, almost 290 genes change their AS pattern upon Brd2 depletion. We study distribution of Brd2 along the target and control genes and find that Brd2 is specifically localized at promoters of target genes only. Surprisingly, Brd2 interaction with chromatin cannot be explained solely by histone acetylation, which suggests that other protein-domains (in addition to bromodomains) are important for...

Mast cells are tissue resident members of the immune system. They have a wide range of functions and receptors including the FcεRI receptor, which gets activated by binding to IgE bound to an antigen. When the cells are activated in this manner, a process termed the LysRS- Ap4A-MITF signalling pathway occurs, resulting in the translocation of the Lys tRNA synthetase into the nucleus and an activation of its moonlighting activity - the production of diadenosine tetraphosphate (Ap4A). Ap4A is a dinucleoside polyphosphate, a type of ubiquitous molecule present in all domains of life. They are made up of two nucleosides joined together by a 5' to 5' phosphodiester bridge of variable lengths. Recently, these molecules have been shown to serve as non-canonical initiating nucleotides during bacterial transcription, where they function as 5' RNA caps, similar to the well-known 7- methylguanosine eukaryotic mRNA cap. In this thesis, I present proof of existence of Ap 4A capped RNA in mast cells, a previously unknown 5' RNA structure in eukaryotic cells, and I attempt to pinpoint its role in the activation of these cells and in the wider context of mast cell mediated immune response. Keywords: mast cells, RNA caps, Dinucleoside polyphosphates, Ap 4A, RNA modification, IgE, FcεRI receptor, Lysine tRNA synthetase

Introduction: The epigenetic modifications can significantly affect and alter the gene activity by regulating their expression, having direct impact on various processes in human body. Epigenetic processes are involved in ethiopathogenesis of many diseases. From this point of view, MHC genes are very important as they were linked to many autoimmune disorders, for example type 1 diabetes mellitus. In general autoimmune diseases appear to be connected to certain MHC class II genes. Aims: The aim of this thesis is to determine the relationship between expression levels and histone modifications present in the promoter area of MHC class II gene, DQA1. Moreover, we also analyze and compare the DQA1 gene mRNA expression depending on the QAP promoter allele. Methods: We isolated both nucleic acids (DNA and RNA) and leukocytes from peripheral blood samples collected from voluntary donors. DNA was utilized for genotypization of individuals. RNA was subjected to reverse transcription and the quantitative PCR was performed in order to determine the level of expression. Leukocytes were used for chromatin immunoprecipitation, which was evaluated using quantitative PCR. Results: The expression level of QAP allele 3.1 was found to be higher than for the rest of the alleles Allele 4.1A showed, on the other hand,...

In this doctoral thesis we study novel analogues based on R06 aptamers and targeting TAR hairpins of the HIV virus by means of surface plasmon resonance biosensor, which allows for sensitive and real-time monitoring of molecular interactions. We investigate seven different modifications placed at nine different positions on the R06 aptamer in order to find out their applicability in the construction of efficient and stable anti-TAR oligonucleotides. We also determine which positions are suitable for substitutions with a modification and interpret the results in the context of the local nucleotide geometries and interactions in the TAR/anti-TAR complex. In this doctoral thesis we further develop a new fluidic system. This fluidic system eliminates sample dispersion and intermixing effects and thus enables accurate monitoring of molecular interactions on the surface of an SPR chip. We also characterize experimental conditions on the surface of an oligonucleotide chip and their relations towards bio-molecular assays. Specifically, we study the shielding effect of monovalent and divalent cations, which are crucial for the interaction of negatively charged oligonucleotides.

This work introduces a database of experimentally verified structures of nucleic acids which were collected from published scientific literature. The database is annotated and the structures are analysed from the perspective of quality and it was found that the experimentally obtained data are not always sufficient - their supporting evidence is often limited and their quality is not convincing. This work also discusses some of the problems, that can be encountered when the structures are experimentally probed. Contents of the database were compared to the RFAM database and despite of its small range it contains 80 new structures. The complete database of 166 structures can be possibly used to optimise software used to predict derived structures of nucleic acids. Furthermore, the work presents several possible ways of improvement of the quality of contained structures.