Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Bewertung von Mehrkampfleistungen : Entwicklung eines Zählsystems im fächerübergreifenden Unterricht Bewegung & Sport und Mathematik

Diese Diplomarbeit behandelt die historische Entwicklung der Mehrkampfbewertung im Zuge eines Projekts, welches im fächerübergreifenden Unterricht Bewegung & Sport und Mathematik in der 11. Schulstufe durchgeführt wird und gliedert sich in einen theoretischen und praktischen Teil.Im theoretischen Teil der Arbeit wird die historische Entwicklung der Mehrkampfbewertung erläutert. Anschließend wird das Prinzip des fächerübergreifenden bzw. fächerverbindenden Unterrichts, das für die Entwicklung des Projekts relevant ist, thematisiert. Der letzte Teil der Theorie widmet sich einer bestimmten Unterrichtsmethode, nämlich dem Projekt. Auf dieser Methode basiert der nachfolgende praktische Teil.Der praktische Teil beinhaltet die Entwicklung und Bearbeitung des Projekts. Hierbei werden bestimmte Rahmenbedingungen geklärt, die Wahl der Schulstufe begründet, das Arbeitsblatt erläutert, der Projektablauf geschildert und ein abschließendes Resümee verfasst. Im Anhang befinden sich das Arbeitsblatt, das zur Bearbeitung des Projekts von der Lehrperson zur Verfügung gestellt wird und der Evaluationsbogen, der am Ende des Projekts von den Schülern und Schülerinnen anonym und freiwillig auszufüllen ist.This thesis covers the historical development of the assessment of combined event competitions in the course of a project. It is carried out in the eleventh grade in the interdisciplinary lessons physical education and mathematics and is structured in a theoretical and practical part.The theoretical part of this thesis deals with the historical development of the assessment of combined event competitions. Afterwards, the principles of interdisciplinary lessons are explained, because this is an important aspect for the project. A description of the method “project” is given in the last part of the theoretical chapter. This method is relevant for the following practical part. The practical section includes the development and processing of the project. In doing so, specific frameworks are defined, the choice of this specific grade is reasoned, the worksheet is explained, the layout of the project is outlined and a result is composed. The attachment includes the worksheet that the teacher will provide for the students, and the evaluation sheet that the students will fill out voluntarily and anonymously at the end of the project.vorgelegt von Peter SchermannZusammenfassungen in Deutsch und EnglischAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinKarl-Franzens-Universität Graz, Diplomarbeit, 2018(VLID)267995

Alterações estomatognáticas e de fala são comuns entre crianças com incontinência pigmentar

Objetivo Identificar possíveis alterações fonoaudiológicas de crianças com Incontinência Pigmentar (IP), buscando caracterizar o papel da Fonoaudiologia na avaliação e manejo dessa condição genética. Métodos A amostra foi composta por sete crianças do gênero feminino com diagnóstico de IP. Todas foram submetidas aos procedimentos de avaliação nas áreas de motricidade orofacial, deglutição, fala e voz. Resultados Os pacientes que compuseram a amostra tinham média de idade de 6,4 anos. Dentre as principais características clínicas estruturais verificadas, destacaram-se a presença de diastemas não fisiológicos e anormalidades de palato duro, encontradas em 85,7% da amostra, além da agenesia dentária em 71,4% dos casos. Quanto aos achados funcionais, 71,4 % apresentaram alteração de mobilidade da língua e 57,1 %, mastigação inadequada. Em relação às alterações de fala, os principais achados foram alterações fonéticas e/ou fonológicas, verificadas em 85,7% da amostra, sendo mais comum a alteração fonética caracterizada pela distorção na fricativa alveolar [s], presente em 57,1% dos casos. Nenhuma das crianças apresentou alteração de voz e deglutição, de acordo com o protocolo utilizado. Além disso, não se evidenciou anormalidade de audição, de acordo com a queixa familiar ou por meio da observação durante a avaliação. Conclusão Nesta amostra, as alterações fonoaudiológicas mais frequentes entre os pacientes com IP relacionaram-se, principalmente, com as estruturas do sistema estomatognático e com a fala

Prediction uncertainty of environmental change effects on temperate European biodiversity.

FR2116International audienceObserved patterns of species richness at landscape scale (gamma diversity) cannot always be attributed to a specific set of explanatory variables, but rather different alternative explanatory statistical models of similar quality may exist. Therefore predictions of the effects of environmental change (such as in climate or land cover) on biodiversity may differ considerably, depending on the chosen set of explanatory variables. Here we use multimodel prediction to evaluate effects of climate, land-use intensity and landscape structure on species richness in each of seven groups of organisms (plants, birds, spiders, wild bees, ground beetles, true bugs and hoverflies) in temperate Europe. We contrast this approach with traditional best-model predictions, which we show, using cross-validation, to have inferior prediction accuracy. Multimodel inference changed the importance of some environmental variables in comparison with the best model, and accordingly gave deviating predictions for environmental change effects. Overall, prediction uncertainty for the multimodel approach was only slightly higher than that of the best model, and absolute changes in predicted species richness were also comparable. Richness predictions varied generally more for the impact of climate change than for land-use change at the coarse scale of our study. Overall, our study indicates that the uncertainty introduced to environmental change predictions through uncertainty in model selection both qualitatively and quantitatively affects species richness projections

Indicators for biodiversity in agricultural landscapes: a pan-European study.

1DInternational audience1. In many European agricultural landscapes, species richness is declining considerably. Studies performed at a very large spatial scale are helpful in understanding the reasons for this decline and as a basis for guiding policy. In a unique, large-scale study of 25 agricultural landscapes in seven European countries, we investigated relationships between species richness in several taxa, and the links between biodiversity and landscape structure and management. 2. We estimated the total species richness of vascular plants, birds and five arthropod groups in each 16-km 2 landscape, and recorded various measures of both landscape structure and intensity of agricultural land use. We studied correlations between taxonomic groups and the effects of landscape and land-use parameters on the number of species in different taxonomic groups. Our statistical approach also accounted for regional variation in species richness unrelated to landscape or land-use factors. 3. The results reveal strong geographical trends in species richness in all taxonomic groups. No single species group emerged as a good predictor of all other species groups. Species richness of all groups increased with the area of semi-natural habitats in the landscape. Species richness of birds and vascular plants was negatively associated with fertilizer use. 4. Synthesis and applications. We conclude that indicator taxa are unlikely to provide an effective means of predicting biodiversity at a large spatial scale, especially where there is large biogeographical variation in species richness. However, a small list of landscape and land-use parameters can be used in agricultural landscapes to infer large-scale patterns of species richness. Our results suggest that to halt the loss of biodiversity in these landscapes, it is important to preserve and, if possible, increase the area of semi-natural habitat

MALDI-ToF mass spectrometry for studying noncovalent complexes of biomolecules.

International audienceMatrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been demonstrated to be a valuable tool to investigate noncovalent interactions of biomolecules. The direct detection of noncovalent assemblies is often more troublesome than with electrospray ionization. Using dedicated sample preparation techniques and carefully optimized instrumental parameters, a number of biomolecule assemblies were successfully analyzed. For complexes dissociating under MALDI conditions, covalent stabilization with chemical cross-linking is a suitable alternative. Indirect methods allow the detection of noncovalent assemblies by monitoring the fading of binding partners or altered H/D exchange patterns