Remarks on the fractional Laplacian with Dirichlet boundary conditions and applications

We prove nonlinear lower bounds and commutator estimates for the Dirichlet fractional Laplacian in bounded domains. The applications include bounds for linear drift-diffusion equations with nonlocal dissipation and global existence of weak solutions of critical surface quasi-geostrophic equations

On some electroconvection models

We consider a model of electroconvection motivated by studies of the motion of a two dimensional annular suspended smectic film under the influence of an electric potential maintained at the boundary by two cylindrical electrodes. We prove that this electroconvection model has global in time unique smooth solutions

Province-Wide Survey of the Effects of Quality Assurance Measures on Services for Adults with Intellectual/Developmental Disabilities and Challenging Behaviours

Introduction: In 2008, the Ministry of Community and Social Services in Ontario, Canada passed a developmental services act that includes the Quality Assurance Measures (QAM) for Behaviour Interventions (Part III) and the QAM Policy Directives for adults with intellectual and developmental disabilities (IDD) and challenging behaviour. No research has examined the impact of QAM on IDD services. Methods: Online surveys addressing knowledge, practices and opinions related to QAM Part III and the Policy Directives were distributed to four general groups of Ontario IDD service personnel. Results: Sixty-six direct-care supervisors, 76 direct-care staff, 79 behaviour consultants, and 26 supervisors in behaviour support services participated. Direct-care staff had less knowledge and a poorer opinion of QAM than the other personnel. Primary reported concerns involved inadequate training and resources to meet QAM requirements. Conclusions: Personnel’s overall evaluation of QAM is predominantly favourable. Increasing resources, clarifying requirements, and promoting consistent monitoring related to QAM may help address the identified concerns

Identification and characterization of novel methyltransferases

So far 172 different types of nucleic acid modifications had been identified. However, for many RNA and DNA modifications the function(s) and the modifying enzymes (”writers”) are still not known. In my Ph.D. project, I focused on the identification of novel RNA and DNA methyltransferases. To identify novel enzymes, I systematically screened a collection of potential methyltransferases on the range of substrates in in vitro methyltransferase assay. I found four enzymes that exhibit robust methyltransferases activity towards RNA. Size exclusion chromatography in combination with labelling approaches and mass spectrometry allowed me to narrow down potential substrates and to identify the modified nucleosides for two candidate enzymes. I characterized METTL6 as a tRNA methyltransferases that specifically catalyzes methylation of cytosines at position 3 (m3C). By performing methyltransferase assays as well as sequence-specific purification of individual tRNAs, I identified the specific tRNA isoacceptors that are METTL6 targets and the precise position of the methylated C. RNA-seq and Ribosome profiling of KO mES cell lines revealed global changes in the transcriptome and translatome. In line with these changes, Mettl6 KO cells showed slower proliferation rates. Interestingly, METTL6 depletion resulted in slower hepatocellular tumor growth in in vitro models. In agreement with this, patients with high METTL6 expression levels have a reduced survival rate. I identified, METTL5 as a novel m6A RNA methyltransferase. Mass spectrometry analysis of RNA from Mettl5 KO mES cells revealed a decrease in m6A levels in 18S rRNA. By performing m6A-immunopreciptaion followed by sequencing in wt and Mettl5 KO cells, I mapped the transcript wide distribution of m6A in non-ribosomal RNAs. In addition to this, Mettl5 KO mES cells are less pluripotent and compromised in their ability to differentiate into neuronal precursors cells. In a complementary approach, I wanted to identify the interactome of METTL proteins. For this, I generated stable cells lines expressing tagged METTL family members, purified the complexes, and analysed interaction partners by mass spectrometry. The systematic identification of the complexes in which these potential enzymes act provides a useful resource for the epitranscriptomics community as it helps to understand METTL proteins function(s) and substrate specificities. Overall, in my Ph.D. project, I profiled the enzymatic activities and the interactome of 13 proteins of the METTL family. For two novel RNA methyltransferases, I characterized the substrates and the type of methylation they catalyse, profiled changes in the transcriptome and translatome, and characterized the phenotypes of mES cells upon KO of these two enzymes.Bisher wurden 172 verschiedene Arten von Nukleinsäuremodifikationen identifiziert. Für viele dieser RNA- und DNA-Modifikationen sind die Funktion (en) und die modifizierenden Enzyme ("Writer") jedoch noch nicht bekannt. In meinem Promotionsprojekt beschäftigte ich mich mit der Identifizierung neuartiger RNA- und DNA- Methyltransferasen. Um neue Enzyme zu identifizieren, habe ich systematisch eine Sammlung potenzieller Methyltransferasen in in-vitro-Methyltransferase-Assays auf verschiedenen Substraten untersucht. Ich habe vier Enzyme identifiziert, die robuste Methyltransferaseaktivität gegenüber RNA aufweisen. Größenausschlusschromatographie in Kombination mit Markierungsansätzen und Massenspektrometrie ermöglichten es mir, potenzielle Substrate einzugrenzen und die modifizierten Nukleoside für zwei positive Kandidaten zu identifizieren. Ich charakterisierte METTL6 als tRNA-Methyltransferase, die spezifisch m3C katalysiert. Durch Methyltransferase-Assays sowie sequenzspezifische Aufreinigung einzelner tRNAs identifizierte ich spezifische tRNA-Isoakzeptoren als METTL6-Tagets und die genaue Position des methylierten Cytosins. RNA-seq- und Ribosomen-Profiling von KO-mES-Zelllinien ergab globale Veränderungen im Transkriptom und Translatom. In Übereinstimmung mit diesen Änderungen zeigten Mettl6-KO-Zellen geringere Proliferationsraten. Interessanterweise führte METTL6-Depletion in in vitro-Modellen zu einem langsameren Wachstum hepatozellulärer Tumore. In Übereinstimmung damit haben Patienten mit hoher METTL6 Exoression eine verringerte Überlebensrate. Ich identifizierte METTL5 als eine neue m6A-RNA-Methyltransferase. Die massenspektrometrische Analyse von RNA aus Mettl5 KO mES-Zellen ergab eine Abnahme der Menge an m6A in 18S-rRNA. Durch das Durchführen von m6A- Immunpräzipationen, gefolgt von Sequenzierung in wt- und Mettl5 KO-Zellen, kartierte ich die transkriptweite Verteilung von m6A in nicht-ribosomalen RNAs. Diese METTL5-KO mES-Zellen verlieren Pluripotency und ihre Fähigkeit sich korrekt in neuronale Vorläuferzellen zu differenzieren. In einem komplementären Ansatz wollte ich das „Interaktom“ von METTL-Proteinen identifizieren. Zu diesem Zweck erzeugte ich stabile Zelllinien, die getagte METTL Protein exprimieren, reinigte die Komplexe und analysierte die Interaktionspartner durch Massenspektrometrie. Die systematische Identifizierung von Komplexen, in denen diese potenziellen Enzyme wirken, ist eine nützliche Ressource für das Epitranscriptomics Field, da sie zum Verständnis der Funktionen und Substratspezifitäten von METTL-Proteinen beitragen kann. Insgesamt habe ich in meiner Doktorarbeit die enzymatische Aktivität und das Interaktom von 13 Proteinen der METTL-Familie analysiert. Für zwei neue RNA- Methyltransferasen charakterisierte ich die Substrate und die Art der Methylierung, die sie katalysieren, profilierte Veränderungen im Transkriptom und Translatom und identifizierte die Phänotypen von mES-Zellen auf KO dieser beiden Enzyme

Influence of Gut Microbiota on Behavior and Its Disturbances

Hippocrates statement that “All disease begins in the gut” continues to be up to date more than 2000 years later. Growing number of scientific reports focus on the important role of intestinal microorganisms for modulation of many systems and human behavior. As a key component of the gut brain, gut microbiota influences the development and maturation of the hypothalamic-pituitary-adrenal axis, affects the development and function of the immune system, regulates the blood-brain barrier, modulates the synthesis and recognition of neurotransmitters, regulates neurogenesis, formation of myelination and supports the development and function of the brain. Disruption of gut-brain axis function is associated with alterations in the stress response and might contribute to neuropsychiatric diseases as depression, autistic spectrum disorders, rapid eye movement sleep behavior disorder, Parkinson disease, Alzheimer disease and other mental conditions. Studies in animal models are crucial for guiding research on brain-gut-microbiome axis in humans, as the impact of microbiota on specific brain regions and aspects of animal behavior will help in the selection of tasks for cognitive assessment. Exploring the interaction of gut microbes and human brain will not only allow us to better understand the pathogenesis of neuropsychiatric disorders, but will also provide us new opportunities for the design of novel immuno- or microbe-based therapies

Die Phraseologismen mit dem Tierkomponent als Darstellung des Menschen

One of the aims of the present paper is to present animal idioms in German, analyze whether and to what extent languages share identical animals to express the same quality and which animals are associated with which qualities in the German language

Exopolysaccharides from Bacteria with Novel Application

The physiological role of EPS depends on the ecological niches and the natural environment in which microorganisms have been isolated. In this chapter, data on EPS production and the effect of EPS on corrosion of steel produced by Lactobacillus sp. are presented and discussed. Lactobacillus plantarum Ts was obtained from the Collection of Department of Biology, Shumen University. It was tested for its ability to produce exopolysaccharides when cultivated in a medium containing 10% sucrose. It could be underlined that 10% sucrose in the medium stimulated the process of protection of corrosion. Also, the biofilm in vitro in the combined cultivation of Staphylococcus aureus and the Lactobacillus plantarum Ts probiotic bacterium on the surface of different metal materials for fixed dental prostheses was investigated [unpublished results]. The structure of layer over steel plates was analyzed by scanning electron microscopy (SEM) JSM 5510. In our opinion, more detailed research is needed to be done in the future, and the possibilities should be analyzed for the creation of a thin biofilm from a probiotic bacterium or an exopolysaccharide this bacterium has produced, which would protect the implants against the growth of a pathogenic biofilm