Translační iniciační faktory proteinové rodiny 4E a jejich vliv na regulaci genové exprese

The translation represents one of the most crucial processes in the cell. That is why it is often targeted by various regulations. Its initiation phase has a particularly important role in regulatory processes. Initiation of translation usually starts by recognition and binding of canonical eukaryotic initiation factor 4E1 (eIF4E1) to the methylguanosine cap present on the 5' end of the majority of eukaryotic mRNA. The family of 4E translation initiation factors contains two more members - eIF4E2 and eIF4E3. Those two proteins can bind cap structure as well which predetermines it to function in the regulation of translation. Protein eIF4E2 is well known for being a translational repressor in development processes and it takes part in specific miRNA-dependent silencing. It was proven to be able to initiate translation in hypoxia which is consistent with its proposed role in hypoxic tumor cells. The biological roles of the protein eIF4E3 are much less understood. This thesis propounds the picture of the overall functions of all discussed translation initiation factors using cell lines with their overexpression or deletion. Experimental data confirmed the role of the eIF4E2 in the regulation of developmental processes. Cell lines with deleted eIF4E2 and eIF4E3 were characterized based on the influence...Translácia predstavuje jeden z najdôležitejších procesov odohrávajúcich sa v bunke. To je dôvodom, prečo je častým terčom rôznych regulácií. Obzvlášť dôležitú úlohu pre regulačné procesy je jej iniciačná fáza. Ku iniciácii translácie dochádza väčšinou po rozpoznaní a špecifickej väzbe kanonického eukaryotického iniciačného faktoru 4E1 (eIF4E1) na metylguanozínovú čiapočku prítomnú na 5' konci väčšiny eukaryotických mRNA. Rodina translačných iniciačných faktorov 4E však obsahuje ďalších dvoch členov - eIF4E2 a eIF4E3. Tieto dva proteíny tiež disponujú funkčnou schopnosťou viazať čiapočku mRNA, čo ich predurčuje k regulačným funkciám v súvislosti s transláciou. Proteín eIF4E2 je známy ako translačný represor vo vývojových procesoch a podieľa sa aj na umlčovaní génov sprostredkovanom miRNA. Existujú dôkazy o tom, že je schopný iniciovať transláciu v hypoxických podmienkach, čo je v zhode s jeho dokladovanými funkciami v hypoxických nádorových bunkách. Biologické úlohy proteínu eIF4E3 sú podstatne menej preskúmané. Táto práca podáva obraz o fungovaní všetkých troch translačných iniciačných faktorov s využitím bunkových línií s ich nadprodukciou alebo naopak deléciou. Experimentálne dáta potvrdili úlohu eIF4E2 v regulácii vývojových procesov. Bunkové línie s deléciou eIF4E2 a eIF4E3 boli...Department of Genetics and MicrobiologyKatedra genetiky a mikrobiologieFaculty of SciencePřírodovědecká fakult

Interaktom translačního iniciačního faktoru eIF4E2

Regulation of gene expression at the level of translation is one of the most prominent processes when it comes to maintaining cellular vital functions in physiolgical norm. Initiation phase plays an especially important role in translational regulation. Majority of eukaryotic mRNAs possess methylguanosine cap on its 5' end. Binding of initiation factor eIF4E1 to cap is substantial part of canonical mechanism of translational initiation. eIF4E1 is component of bigger complex termed eIF4F, whose association with cap mRNA is essential for initiation of translation. Due to cap-binding ability of noncanonical initiation factors and their interaction partners, that are distinct from those of eIF4E1, there can occur specific regulation of translational initiation. One of these noncanonical factors is eIF4E2. In regulatory processes it mostly acts as a translational repressor. Binding of eIF4E2 to cap impedes association of eIF4F complex with mRNA, and therefore inhibits translation. However, eIF4E2 is also able to promote cap-dependent initiation of translation using an alternative mechanism in hypoxic conditions. This thesis represents the first complex analysis of protein-protein interactions and physiological functions of factor eIF4E2 and its homologs in several model organisms. Key words:...Regulácia expresie génov na úrovni translácie je jedným z najvýznamnejších procesov pre udržanie životných funkcií buniek vo fyziologickej norme. Obzvlášť dôležitú úlohu v regulácii translácie hrá jej iniciačná fáza. Väčšina eukaryotických mRNA obsahuje na svojom 5' konci metylguanozínovú čiapočku. Naviazanie iniciačného faktoru eIF4E1 na čiapočku je podstatnou súčasťou kanonického mechanizmu iniciácie translácie. eIF4E1 je zložkou väčšieho komplexu nazvaného eIF4F, ktorého asociácia s čiapočkou mRNA je nevyhnutná pre kanonickú iniciáciu translácie. Vďaka schopnosti nekanonických iniciačných faktorov viazať čiapočku a súčasne interagovať s proteínmi odlišujúcimi sa od interakčných partnerov eIF4E1, môže dochádzať ku špecifickej regulácii translačnej iniciácie. Jedným z týchto nekanonických faktorov je eIF4E2. V regulačných procesoch vystupuje predovšetkým ako translačný represor. Naviazanie eIF4E2 na čiapočku zabráni asociácii komplexu eIF4F s mRNA a inhibuje tak transláciu. Avšak, eIF4E2 je taktiež schopný sprostredkovať iniciáciu translácie závislej na čiapočke alternatívnym mechanizmom v hypoxických podmienkach. Táto práca predstavuje prvú komplexnú analýzu proteín-proteínových interakcií a fyziologických funkcií faktoru eIF4E2 a jeho homológov u niekoľkých modelových organizmov. Kľúčové slová:...Department of Genetics and MicrobiologyKatedra genetiky a mikrobiologieFaculty of SciencePřírodovědecká fakult

Vectors and transfers in hexagonal quasigroup

Hexagonal quasigroup is idempotent, medial and semisymmetric quasigroup. In this article we define and study vectors, sum of vectors and transfers. The main result is the theorem on isomorphism between the group of vectors, group of transfers and the Abelian group from the characterization theorem of the hexagonal quasigroups

The Effect of Fertilization on Biomass and Metabolism in North Carolina Salt Marshes: Modulated by Location-Specific Factors

The resilience of salt marshes to sea level rise depends on vertical accretion through belowground biomass production and sediment deposition to maintain elevation above sea level. Increased nitrogen (N) availability from anthropogenic sources may stimulate aboveground biomass production and sediment deposition and, thus, accretion; however, increased N may also negatively impact marsh accretion by decreasing belowground biomass and increasing net CO2 emissions. A study was conducted in Spartina alterniflora‐dominated salt marshes in North Carolina, USA, to determine how responses to fertilization vary across locations with different physical and chemical characteristics. Pore water residence time, inundation time, and proximity to tidal creeks drove spatial differences in pore water sulfide, ammonium, and dissolved carbon concentrations. Although annual respiration and gross primary production were greater at the creek edge than interior marsh sites, net ecosystem CO2 exchange (NEE) was nearly balanced at all the sites. Fertilization decreased belowground biomass in the interior sites but not on the creek edge. Aboveground biomass, respiration, gross primary production, and net CO2 emissions increased in response to fertilization, but responses were diminished in interior marsh locations with high pore water sulfide. Hourly NEE measured by chambers were similar to hourly NEE observed by a nearby eddy covariance tower, but correcting for inundation depth relative to plant height was critical for accurate extrapolation to annual fluxes. The impact of fertilization on biomass and NEE, and thus marsh resilience, varied across marsh locations depending upon location‐specific pore water sulfide concentrations

Projecting marine mammal distribution in a changing climate

Climate-related shifts in marine mammal range and distribution have been observed in some populations; however, the nature and magnitude of future responses are uncertain in novel environments projected under climate change. This poses a challenge for agencies charged with management and conservation of these species. Specialized diets, restricted ranges, or reliance on specific substrates or sites (e.g., for pupping) make many marine mammal populations particularly vulnerable to climate change. High-latitude, predominantly ice-obligate, species have experienced some of the largest changes in habitat and distribution and these are expected to continue. Efforts to predict and project marine mammal distributions to date have emphasized data-driven statistical habitat models. These have proven successful for short time-scale (e.g., seasonal) management activities, but confidence that such relationships will hold for multi-decade projections and novel environments is limited. Recent advances in mechanistic modeling of marine mammals (i.e., models that rely on robust physiological and ecological principles expected to hold under climate change) may address this limitation. The success of such approaches rests on continued advances in marine mammal ecology, behavior, and physiology together with improved regional climate projections. The broad scope of this challenge suggests initial priorities be placed on vulnerable species or populations (those already experiencing declines or projected to undergo ecological shifts resulting from climate changes that are consistent across climate projections) and species or populations for which ample data already exist (with the hope that these may inform climate change sensitivities in less well observed species or populations elsewhere). The sustained monitoring networks, novel observations, and modeling advances required to more confidently project marine mammal distributions in a changing climate will ultimately benefit management decisions across time-scales, further promoting the resilience of marine mammal populations

Long- and short-range correlations and their event-scale dependence in high-multiplicity pp collisions at 1as = 13 TeV

Two-particle angular correlations are measured in high-multiplicity proton-proton collisions at s = 13 TeV by the ALICE Collaboration. The yields of particle pairs at short-( 06\u3b7 3c 0) and long-range (1.6 < | 06\u3b7| < 1.8) in pseudorapidity are extracted on the near-side ( 06\u3c6 3c 0). They are reported as a function of transverse momentum (pT) in the range 1 < pT< 4 GeV/c. Furthermore, the event-scale dependence is studied for the first time by requiring the presence of high-pT leading particles or jets for varying pT thresholds. The results demonstrate that the long-range \u201cridge\u201d yield, possibly related to the collective behavior of the system, is present in events with high-pT processes as well. The magnitudes of the short- and long-range yields are found to grow with the event scale. The results are compared to EPOS LHC and PYTHIA 8 calculations, with and without string-shoving interactions. It is found that while both models describe the qualitative trends in the data, calculations from EPOS LHC show a better quantitative agreement for the pT dependency, while overestimating the event-scale dependency. [Figure not available: see fulltext.

Global baryon number conservation encoded in net-proton fluctuations measured in Pb–Pb collisions at √sNN = 2.76 TeV

Experimental results are presented on event-by-event net-proton fluctuation measurements in Pb–Pb collisions at √SNN=2.76 TeV, recorded by the ALICE detector at the CERN LHC. These measurements have as their ultimate goal an experimental test of Lattice QCD (LQCD) predictions on second and higher order cumulants of net-baryon distributions to search for critical behavior near the QCD phase boundary. Before confronting them with LQCD predictions, account has to be taken of correlations stemming from baryon number conservation as well as fluctuations of participating nucleons. Both effects influence the experimental measurements and are usually not considered in theoretical calculations. For the first time, it is shown that event-by-event baryon number conservation leads to subtle long-range correlations arising from very early interactions in the collisions.publishedVersio