Mutationsanalyse von Kandidatengenen für die neurologische Mutation wobbler der Maus

Fuchs S. Mutationsanalyse von Kandidatengenen für die neurologische Mutation wobbler der Maus. Bielefeld (Germany): Bielefeld University; 2001.Die autosomal rezessive Mutation wobbler (Gensymbol wr, Phänotyp WR) der Maus führt zur Degeneration von Motoneuronen in Hirnstamm und Rückenmark und löst so eine Muskelatrophie aus. WR-Männchen zeigen außerdem einen Spermiogenesedefekt. Die wr-Mutation wurde auf dem proximalen Chromosom 11 in einem Bereich konservierter Syntänie zum humanen Chromosom 2p13-15 lokalisiert. In der Positionsklonierung des wr-Gens wurden physikalische Karten der Regionen bei Maus und Mensch erstellt. Dort konnten die Gene für die cytoplasmatische Malatdehydrogenase Mor2 und das Homöobox-Protein Otx1 kartiert werden. Durch die Übertragung von Genen bzw. Genbruchstücken vom humanen Chromosom 2p13-15 auf die Maus-Karte wurden weitere Kandidatengene identifiziert: die Gene für ein Tumorantigen Hcc8, die Uridin-Diphosphoglukose-Pyrophosphorylase Ugp2, und das Drosophila Pellino-Homolog Peli1 und außerdem die anonymen cDNAs Kiaa0903 und hEST13. Hcc8, Ugp2 und Peli1 wurden als Kandidaten für die wr-Mutation ausgeschlossen. In dieser Arbeit wurde die physikalische Karte der Region verbessert. Es konnten neue Kandidatengene kartiert und gleichzeitig für die wr-Mutation ausgeschlossen werden: die anonymen cDNAs Hspc159 und Murr1, und die Gene für das Endozepine-like peptide Elp, das peroxisomale Protein Pex13 und das Exportin1 Xpo1. Durch die Detektion von Rekombinationen in einem Intron von Murr1 wurde der wr-kritische Bereich um 2,15 cM verkleinert. Für das Otx1-Gen konnte die genomische Sequenz und für die cDNAs Homoloc-13 und Kiaa0903 die cDNA-Sequenz erstellt werden. Die vergleichende Sequenzierung der kodierenden Regionen von Mor2, Otx1, Homoloc-13 und Kiaa0903 ergab keinen Unterschied zwischen WT und WR; auch in der Expression dieser Gene bzw. cDNAs konnte keine Veränderung gefunden werden, so dass sie als Kandidaten für wobbler ausscheiden. Nach der in dieser Arbeit durchgeführten Mutationsanalyse sind keine weiteren Kandidatengene für die wr-Mutation mehr vorhanden, so dass nun Mutationen in nicht-kodierenden Bereichen, die regulatorische Funktion haben könnten, gesucht werden müssen

"Dauerbaustelle" Erzieher:innenausbildung. Strukturen, Ausbildungsformate und Entwicklungen an Fachschulen für Sozialpädagogik

Fachschulen für Sozialpädagogik sind nach wie vor die wichtigsten Ausbildungsinstitutionen für die Frühe Bildung, ihre Kapazitäten haben sich in den vergangenen zehn bis fünfzehn Jahren nahezu verdoppelt. Diese Expansion wurde begleitet von umfassenden Reformen, die zu einer Pluralisierung und Diversifizierung des Ausbildungssystems führten. Welchen konkreten Niederschlag haben diese Reformen in der Fachschullandschaft gefunden? Welche weiteren Entwicklungspotenziale ergeben sich daraus und wo liegen Stolpersteine? Diesen Fragen geht die Studie anhand einer bundesweiten Befragung von Fachschulleitungen nach. (DIPF/Verlag

Pluralisierung und Diversifizierung der Ausbildung zur Erzieherin und zum Erzieher. Vorschlag zu einer Systematisierung

Aufgrund des hohen Fachkräftebedarfs in der Kindertagesbetreuung ist erneut Bewegung in die Ausbildungslandschaft der Frühen Bildung gekommen. Während es um die hochschulische Ausbildung vergleichsweise still geworden ist, agieren die Fachschulen äußerst vital: Hier werden bestehende Ausbildungsmodelle optimiert und neue rasant entwickelt. Diese neuen Formate haben eines gemeinsam: Über eine stärkere Praxisanbindung während der Ausbildung sowie eine Verkürzung der Gesamtausbildungsdauer sollen "arbeitsmarktfähige Fachkräfte" schneller in die Praxis einmünden. Die daraus resultierenden erwünschten und unerwünschten Begleiterscheinungen drohen die bisher erreichten Ausbildungs- und Qualitätsstandards zu unterlaufen. (DIPF/Orig.

Human-Centric Process-Aware Information Systems (HC-PAIS)

Process-Aware Information Systems (PAIS) support organizations in managing and automating their processes. A full automation of processes is in particular industries, such as service-oriented markets, not practicable. The integration of humans in PAIS is necessary to manage and perform processes that require human capabilities, judgments and decisions. A challenge of interdisciplinary PAIS research is to provide concepts and solutions that support human integration in PAIS and human orientation of PAIS in a way that provably increase the PAIS users' satisfaction and motivation with working with the Human-Centric Process Aware Information System (HC-PAIS) and consequently influence users' performance of tasks. This work is an initial step of research that aims at providing a definition of Human-Centric Process Aware Information Systems (HC-PAIS) and future research challenges of HC-PAIS. Results of focus group research are presented.Comment: 8 page

Comparative transcription map of the wobbler critical region on mouse chromosome 11 and the homologous region on human chromosome 2p13-14

BACKGROUND: To support the positional cloning of the mouse mutation wobbler (wr) the corresponding regions on human Chr2p13-14 and mouse Chr11 were analyzed in detail and compared with respect to gene content, order, and orientation. RESULTS: The gene content of the investigated regions was highly conserved between the two species: 20 orthologous genes were identified on our BAC/YAC contig comprising 4.5 Mb between REL/Rel and RAB1A/Rab1a. Exceptions were pseudogenes ELP and PX19 whose mouse counterparts were not located within the analyzed region. Two independently isolated genomic clones indicate an inversion between man and mouse with the inverted segment being identical to the wobbler critical interval. We investigated the wobbler critical region by extensive STS/EST mapping and genomic sequencing. Additionally, the full-length cDNA sequences of four newly mapped genes as well as the previously mapped gene Otx1 were established and subjected to mutation analysis. Our data indicate that all genes in the wr critical region have been identified. CONCLUSION: Unexpectedly, neither mutation analysis of cDNAs nor levels of mRNAs indicated which of the candidate genes might be affected by the wr mutation. The possibility arises that there might be hitherto unknown effects of mutations, in addition to structural changes of the mRNA or regulatory abnormalities

Physician-Specific Symptoms of Burnout Compared to a Non-Physicians Group

Physician burnout is a systemic problem in health care due to its high prevalence and its negative impact on professional functioning and individual well-being. While unique aspects of the physician role contributing to the development burnout have been investigated recently, it is currently unclear whether burnout manifests differently in physicians compared to the non-physician working population. We conducted an individual symptom analysis of burnout symptoms comparing a large sample of physicians with a non-physician group. In this cross-sectional online study, burnout was assessed with the Maslach Burnout Inventory—General Survey. We matched physicians with non-physicians regarding their age, gender, educational level, occupational status, and total burnout level using a “nearest neighbour matching” procedure. We then conducted a series of between-groups comparisons. Data of 3846 (51.0% women) participants including 641 physicians and 3205 non-physicians were analysed. The most pronounced difference was that physicians were more satisfied with their work performance (medium effect size (r = 0.343). Our findings indicate minor yet significant differences in burnout phenomenology between physicians and non-physicians. This demonstrates unique aspects of physician burnout and implies that such differences should be considered in occupational research among physicians, particularly when developing burnout prevention programs for physicians

Deregulated Syk inhibits differentiation and induces growth factor–independent proliferation of pre–B cells

The nonreceptor protein spleen tyrosine kinase (Syk) is a key mediator of signal transduction in a variety of cell types, including B lymphocytes. We show that deregulated Syk activity allows growth factor–independent proliferation and transforms bone marrow–derived pre–B cells that are then able to induce leukemia in mice. Syk-transformed pre–B cells show a characteristic pattern of tyrosine phosphorylation, increased c-Myc expression, and defective differentiation. Treatment of Syk-transformed pre–B cells with a novel Syk-specific inhibitor (R406) reduces tyrosine phosphorylation and c-Myc expression. In addition, R406 treatment removes the developmental block and allows the differentiation of the Syk-transformed pre–B cells into immature B cells. Because R406 treatment also prevents the proliferation of c-Myc–transformed pre–B cells, our data indicate that endogenous Syk kinase activity may be required for the survival of pre–B cells transformed by other oncogenes. Collectively, our data suggest that Syk is a protooncogene involved in the transformation of lymphocytes, thus making Syk a potential target for the treatment of leukemia

Problematizando Experiências de Vítimas de Violências: Indagações e Análises

Título Problematizando experiências de vítimas de violência: indagações e análises. Autor Thiago Sandrini Mansur RESUMO Em geral, as reflexões sobre as pessoas que sofrem algum tipo de violência foram, por muito tempo, negligenciadas pelas sociedades em todo o mundo. Isso se torna ainda mais enfático no que diz respeito aos segmentos menos favorecidos da sociedade, sobretudo com relação àqueles que estão confinados em estabelecimentos de internação. No Brasil, este cenário foi se modificando lentamente ao longo do século XX, ganhando novos contornos por meio das experiências dos movimentos de defesa dos direitos humanos, sobretudo, a partir do período de contestação à ditadura militar. Num período mais recente de nossa história, o surgimento de centros de apoio às vítimas de violência pode ser considerado como uma maneira de colocar em análise as diversas formas de manifestação da violência, embora tais estabelecimentos não sejam os únicos, nem os primeiros a fazer isso. Os centros de apoio se tornaram locais não somente para que as vítimas de violência recebessem atendimento, mas, sobretudo, para que se incitasse a luta pela responsabilização de seus algozes e a criação de novos paradigmas para uma cultura de paz e não-violência. Tendo em vista este cenário, objetivou-se problematizar as experiências de pessoas que foram atingidas pela violência, residentes na Região Metropolitana da Grande Vitória e que buscaram apoio em um desses centros de atendimento. Problematizar uma experiência significa se perguntar como um conjunto de práticas discursivas e não discursivas que antes era aceito em uma sociedade sem questionamentos e tido como familiar e natural se torna um motivo de preocupação, incitando discussões, polemizando debates, suscitando mudanças de comportamento e instigando novos hábitos. Para alcançar tal propósito, foram realizadas atividades em grupo, nas quais se problematizou as experiências de mães que tiveram seus filhos violentados por agentes do Estado, quando em cumprimento de medida sócio-educativa de privação de liberdade. Também foram feitas entrevistas de restituição nas quais as mães puderam avaliar as experiências em grupo, bem como discutir os resultados e as conclusões da pesquisa. O objetivo dessas atividades foi compreender que práticas discursivas e não-discursivas sobre (e de) vítimas de violência se atualizam através de falas, ações, sentimentos e pensamentos. A que supostas verdades remetem? Que relações de saber-poder fazem funcionar? Como a experiência de estar em grupo coloca em questão certos modos de ser das vítimas? Em primeiro lugar, evidenciou-se que as pessoas participantes da pesquisa eram, em sua grande maioria, pobres, afro-descendentes, moradores de periferia e com baixa escolaridade, justamente o perfil típico das pessoas atingidas pela violência. Os resultados e as discussões levaram à conclusão de que muitas das pessoas atingidas pela violência, bem como seus familiares, embora sob esse forte impacto, apostaram e ainda apostam em afirmar a vida, ao invés de se colocarem no lugar de resignação, que muitas vezes é destinado às vítimas. Percebeu-se que conhecer e compartilhar as experiências dessas pessoas pode contribuir para a discussão acadêmica do problema e para a transformação de alguns dos efeitos deletérios da violência. Atualmente, quando falamos em vítimas de violência, imediatamente nos surgem imagens de indivíduos passivos e inertes que padecem na dor pelo resto de suas vidas. Tais imagens estão atreladas a uma visão intimista da realidade (SENNET, 1998), na qual se pensam as experiências como vivências individuais e particulares de cada um. Sendo assim, aquilo que uma pessoa vive diria respeito apenas a ela mesma e a mais ninguém. A existência dos centros de apoio às vítimas de violência delimita a constituição de espaços em que essas experiências podem ser problematizadas em suas verdades instituídas. Entendemos que problematizar uma experiência é evidenciar seu caráter de produção histórica e social. Isto significa dizer que aquilo que denominamos vítima de violência apresenta-se como uma forma circunstancial e provisória, ou seja, não-natural. Palavras-chave: Violência; Vítima; Experiência

Tuning a robust system: N,O Zinc Guanidine Catalysts for the ROP of Lactide

Non-toxic, highly-active and robust complexes are the holy grail as ideal green catalysts for the polymerisation of biobased and biodegrable polylactide. Four new zinc guanidine complexes [ZnCl2(TMG4NMe2asme)], [ZnCl2(TMG5Clasme)], [ZnCl2(TMG5Measme)] and [ZnCl2(TMG5NMe2asme)] with different electron-donating and electron-withdrawing groups on aromatic backbone of the ligand have been synthesised. Ligands are derived from low-cost commercially available compounds and have been converted in a three- or four-step synthesis into the desired ligand in good yields. The compounds have been fully characterised and tested in the ROP of rac-LA in the melt under industrially relevant conditions. The complexes are based on the recently published structure [ZnCl2(TMGasme)] which has shown high activity in the polymerisation of lactide at 150 °C. Different substituents in the para-position to the guanidine moiety significantly increase the polymerisation rate whereas positioning substituents in meta-position causes no change in the reaction rate. With molecular weights over 71 000 g mol-1, the best catalyst produces polymer for several industrial applications and its polymerisation rate approaches the one of Sn(Oct)2. The robust systems are able to polymerise non-purified lactide. The initiation of the polymerisation is suggested to occur by impurities in the monomer

Simple Zn(ii) complexes for the production and degradation of polyesters

Nine new complexes based on thioether appended iminophenolate (ONS) ligands have been prepared and fully characterized in solution by NMR spectroscopy. Solid-state structures were also obtained for seven complexes. In solution, all complexes were monomeric. The complexes were highly active for the polymerization of purified rac-lactide ([M] : [Zn] : [BnOH] = 10 000 : 1 : 30 at 180 °C) reaching TOF values up to 250 000 h−1. The kinetics of the polymerization have been probed by in situ Raman spectroscopy. The rate of reaction was dramatically reduced using technical grade rac-lactide with increased initiator loading. To move towards a circular economy, it is vital that catalysts are developed to facilitate chemical recycling of commodity and emerging polymeric materials. In this vein, the complexes have been assessed for their ability to break down poly(lactic acid) and poly(ethylene terephthalate). The results from both the polymerization and degradation reactions are discussed in terms of ligand functionality