Random Moment Problems under Constraints

We investigate moment sequences of probability measures on $E\subset\mathbb{R}$ under constraints of certain moments being fixed. This corresponds to studying sections of $n$-th moment spaces, i.e. the spaces of moment sequences of order $n$. By equipping these sections with the uniform or more general probability distributions, we manage to give for large $n$ precise results on the (probabilistic) barycenters of moment space sections and the fluctuations of random moments around these barycenters. The measures associated to the barycenters belong to the Bernstein-Szeg\H{o} class and show strong universal behavior. We prove Gaussian fluctuations and moderate and large deviations principles. Furthermore, we demonstrate how fixing moments by a constraint leads to breaking the connection between random moments and random matrices.Comment: 43 page

Cytoplasmic RNA decay pathways - enzymes and mechanisms

RNA decay plays a crucial role in post-transcriptional regulation of gene expression. Work conducted over the last decades has defined the major mRNA decay pathways, as well as enzymes and their cofactors responsible for these processes. In contrast, our knowledge of the mechanisms of degradation of non-protein coding RNA species is more fragmentary. This review is focused on the cytoplasmic pathways of mRNA and ncRNA degradation in eukaryotes. The major 3’ to 5’ and 5’ to 3’ mRNA decay pathways are described with emphasis on the mechanisms of their activation by the deprotection of RNA ends. More recently discovered 3’-end modifications such as uridylation, and their relevance to cytoplasmic mRNA decay in various model organisms, are also discussed. Finally, we provide up-to-date findings concerning various pathways of non-coding RNA decay in the cytoplasm

Perlman syndrome nuclease DIS3L2 controls cytoplasmic non-coding RNAs and provides surveillance pathway for maturing snRNAs

The exosome-independent exoribonuclease DIS3L2 is mutated in Perlman syndrome. Here, we used extensive global transcriptomic and targeted biochemical analyses to identify novel DIS3L2 substrates in human cells. We show that DIS3L2 regulates pol II transcripts, comprising selected canonical and histone-coding mRNAs, and a novel FTL short RNA from the ferritin mRNA 5� UTR. Importantly, DIS3L2 contributes to surveillance of maturing snRNAs during their cytoplasmic processing. Among pol III transcripts, DIS3L2 particularly targets vault and Y RNAs and an Alu-like element BC200 RNA, but not Alu repeats, which are removed by exosome-associated DIS3. Using 3� RACE-Seq, we demonstrate that all novel DIS3L2 substrates are uridylated in vivo by TUT4/TUT7 poly(U) polymerases. Uridylationdependent DIS3L2-mediated decay can be recapitulated in vitro, thus reinforcing the tight cooperation between DIS3L2 and TUTases. Together these results indicate that catalytically inactive DIS3L2, characteristic of Perlman syndrome, can lead to deregulation of its target RNAs to disturb transcriptome homeostasis

A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans.

The exosome complex is a major eukaryotic exoribonuclease that requires the SKI complex for its activity in the cytoplasm. In yeast, the Ski7 protein links both complexes, whereas a functional equivalent of the Ski7 has remained unknown in the human genome.Proteomic analysis revealed that a previously uncharacterized short splicing isoform of HBS1L (HBS1LV3) is the long-sought factor linking the exosome and SKI complexes in humans. In contrast, the canonical HBS1L variant, HBS1LV1, which acts as a ribosome dissociation factor, does not associate with the exosome and instead interacts with the mRNA surveillance factor PELOTA. Interestingly, both HBS1LV1 and HBS1LV3 interact with the SKI complex and HBS1LV1 seems to antagonize SKI/exosome supercomplex formation. HBS1LV3 contains a unique C-terminal region of unknown structure, with a conserved RxxxFxxxL motif responsible for exosome binding and may interact with the exosome core subunit RRP43 in a way that resembles the association between Rrp6 RNase and Rrp43 in yeast. HBS1LV3 or the SKI complex helicase (SKI2W) depletion similarly affected the transcriptome, deregulating multiple genes. Furthermore, half-lives of representative upregulated mRNAs were increased, supporting the involvement of HBS1LV3 and SKI2W in the same mRNA degradation pathway, essential for transcriptome homeostasis in the cytoplasm

Maude Essig World War I Diary

The World War I Diary of Maude Essig depicts her experiences as a nurse in Base Hospital #32 overseas in Contrexeville, France. Maude saw patients from many countries in all conditions while there, some having sustained mustard gas burns, gun shot wounds, and shrapnel lodging. She depicts life in and out of the hospital and gives major insight into the life of a nurse during war.https://digitalcommons.iwu.edu/nursing_documents/1011/thumbnail.jp

Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated recombination system

Deciphering a function of a given protein requires investigating various biological aspects. Usually, the protein of interest is expressed with a fusion tag that aids or allows subsequent analyses. Additionally, downregulation or inactivation of the studied gene enables functional studies. Development of the CRISPR/Cas9 methodology opened many possibilities but in many cases it is restricted to non-essential genes. Recombinase-dependent gene integration methods, like the Flp-In system, are very good alternatives. The system is widely used in different research areas, which calls for the existence of compatible vectors and efficient protocols that ensure straightforward DNA cloning and generation of stable cell lines. We have created and validated a robust series of 52 vectors for streamlined generation of stable mammalian cell lines using the FLP recombinase-based methodology. Using the sequence-independent DNA cloning method all constructs for a given coding-sequence can be made with just three universal PCR primers. Our collection allows tetracycline-inducible expression of proteins with various tags suitable for protein localization, FRET, bimolecular fluorescence complementation (BiFC), protein dynamics studies (FRAP), co-immunoprecipitation, the RNA tethering assay and cell sorting. Some of the vectors contain a bidirectional promoter for concomitant expression of miRNA and mRNA, so that a gene can be silenced and its product replaced by a mutated miRNA-insensitive version. Our toolkit and protocols have allowed us to create more than 500 constructs with ease. We demonstrate the efficacy of our vectors by creating stable cell lines with various tagged proteins (numatrin, fibrillarin, coilin, centrin, THOC5, PCNA). We have analysed transgene expression over time to provide a guideline for future experiments and compared the effectiveness of commonly used inducers for tetracycline-responsive promoters. As proof of concept we examined the role of the exoribonuclease XRN2 in transcription termination by RNAseq

Wpływ kształtowania treści tez dowodowych na szacowanie wartości szkód w związku z ustanowieniem obszaru ograniczonego użytkowania

This paper discusses the issues related to the functioning of the areas of limited usufruct in Poland in connection with the judicial decisions. The author has reviewed selected judgments that concern undertaken subject. The study concentrates on the problem of the formulating theses in connection with the establishment of the limited usufruct for Airport Katowice-Pyrzowice, Airport Poznań-Ławica and Airport Gdańsk.Niniejszy artykuł poświęcony jest tematyce formułowania tez dowodowych w postępowaniach odszkodowawczych toczących się w związku z ustanowieniem obszarów ograniczonego użytkowania dla Portu Lotniczego Katowice-Pyrzowice, Portu Lotniczego Poznań-Ławica oraz Portu Lotniczego im. L. Wałęsy w Gdańsku. Celem artykułu jest identyfikacja błędów popełnianych w związku z formułowaniem zakresu opinii biegłych sądowych w sprawach o odszkodowania za szkody powstałe w związku z utworzeniem OOU i oceny ich wpływu na szacowanie wartości szkód. Przedmiotem badań objęto postanowienia o dopuszczeniu dowodu z opinii biegłego wydawane przez Sądy Okręgowe w Katowicach, Poznaniu i Gdańsku