Messung und Bewertung der Wirkung von umweltbedingten Partikelexpositionen (PM10 und PM2.5) auf die Lungenfunktion und Befindlichkeit von Kindern

In der vorliegenden umweltepidemiologischen Longitudinalstudie sollte geklärt werden, ob die im Raum München auftretenden Partikelkonzentrationen (PM10, PM2.5, UF)Auswirkungen auf die Lungenfunktion und das subjektive Befinden von Kindern haben- falls ja, ob einzelne Größenfraktionen von Bedeutung sind und eine Wirkschwelle festgelegt werden kann.Die Studie wurde an einer staatlichen Grundschule in Neuperlach durchgeführt. Das Untersuchungskollektiv bestand aus 50 Kindern im Alter zwischen sechs und zehn Jahren. Einziges Ausschlusskriterium war Tabakrauchexposition im häuslichen Umfeld. Es wurden bei jedem Probanden im Mittel 27 Untersuchungen durchgeführt, insgesamt 1234 Lungenfunktionsuntersuchungen und 1354 Befragungen. Die Ergebnisse zeigen, dass die Partikelkonzentrationen im Raum München keinen Einfluss auf das subjektive Befinden und die Lungenfunktion von Kindern besitzen

On Using Expansions to the Base of -2

This short note investigates the effects of using expansions to the base of -2. The main applications we have in mind are cryptographic protocols, where the crucial operation is computation of scalar multiples. For the recently proposed groups arising from Picard curves this leads to a saving of at least 7% for the computation of an m-fold. For more general non-hyperelliptic genus 3 curves we expect a larger speed-up.Comment: 5 page

Perspectives of Swiss Paediatric Health Care Professionals on Factors Influencing Physical Activity Participation in Children with Disabilities

Aim: Investigation of the perspectives of paediatric health care professionals (PHCPs) in Switzerland regarding factors that influence participation in physical activity programs for children and adolescents with disabilities or chronic conditions (CADCCs). Evaluation of self-reported exercise counselling behavior of those professionals. Method: A cross-sectional survey was used to collect the opinions of 171 PHCPs working with CADCCs using a structured questionnaire. The information obtained was evaluated by performing a combined quantitative and qualitative statistical analysis. Results: PHCPs in Switzerland think that CADCC do not get enough physical activity and see the underlying reasons in lacking information/knowledge and organizational factors. We found that the level of knowledge about disability sports opportunities among PHCPs has a positive influence on their exercise counselling behaviour. Conclusions: We propose three approaches to increase the level of physical activity in CADCC: Establishing personalized exercise counseling, intensifying information about disability sports pro-grammes towards PHCPs, and improving inclusion and integration in PE lessons or regular sports club

Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Calcitonin Gene-Related Peptide (CGRP)-I and Procalcitonin (Pro-CT) Production in Human Adipocytes

Context: Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet. Objective: The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients. Design and Participants: Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed. Results: Treatment with 1 nm GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P > 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P > 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P > 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P > 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P > 0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients. Conclusion: GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations

A very mild phenotype in six individuals of a three-generation family with the novel HRAS variant c.176C > G p.(Ala59Gly): Emergence of a new HRAS-related RASopathy distinct from Costello syndrome

Costello syndrome is a clinically recognizable, severe neurodevelopmental disorder caused by heterozygous activating variants in HRAS. The vast majority of affected patients share recurring variants affecting HRAS codons 12 and 13 and a relatively uniform phenotype. Here, we report the unique and attenuated phenotype of six individuals of an extended family affected by the HRAS variant c.176C>T p.(Ala59Gly), which, to our knowledge, has never been reported as a germline variant in patients so far. HRAS Alanine 59 has been previously functionally investigated as an oncogenic hotspot and the p.Ala59Gly substitution was shown to impair intrinsic GTP hydrolysis. All six individuals we report share a phenotype of ectodermal anomalies and mild features suggestive of a RASopathy, reminiscent of patients with Noonan syndrome-like disorder with loose anagen hair. All six are of normal intelligence, none have a history of failure to thrive or malignancy, and they have no known cardiac or neurologic pathologies. Our report adds to the previous reports of patients with rare variants affecting amino acids located in the SWITCH II/G3 region of HRAS and suggests a consistent, attenuated phenotype distinct from classical Costello syndrome. We propose the definition of a new distinct HRAS-related RASopathy for patients carrying HRAS variants affecting codons 58, 59, 60

Personalentwicklung für Wissenschaftler/innen - Professionalisierung von Selbst-, Führungs- und Lehrkompetenzen

Die zunehmende Professionalisierung des Wissenschaftsbetriebes wirkt sich auch auf die Anforderungen an Wissenschaftlerinnen und Wissenschaftler aus. Um multiplen und wachsenden Rollenanforderungen gerecht werden zu können, wird eine Erweiterung und Professionalisierung der eigenen Kompetenzen notwendig. Am Beispiel des LMU Center for Leadership and People Management soll aufgezeigt werden, wie mit Hilfe professioneller Personalentwicklungsmaßnahmen dabei sowohl die wissenschaftliche Exzellenz an Hochschulen gezielt gefördert als auch ein wichtiger Beitrag zu Innovation und Organisationsentwicklung geleistet werden kann. Ziel des Beitrages ist es, ein Bewusstsein für die Notwendigkeit von Personalentwicklung an Hochschulen zu schaffen und zugleich anderen Universitäten Hilfestellung bei der Implementierung ähnlicher Maßnahmen zu bieten. 02.11.2011 | Silke Weisweiler, Tanja Peter, Claudia Peus & Dieter Frey (München

Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing

Pancreatic ductal adenocarcinoma (PDA) is an inherently immune cell deprived tumor, characterized by desmoplastic stroma and suppressive immune cells. Here we systematically dissect PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening, and identify Vps4b and Rnf31 as essential factors required for escaping CD8+ T cell killing. For Vps4b we find that inactivation impairs autophagy, resulting in increased accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis. For Rnf31 we demonstrate that it protects tumor cells from TNF-mediated caspase 8 cleavage and subsequent apoptosis induction, a mechanism that is conserved in human PDA organoids. Orthotopic transplantation of Vps4b- or Rnf31 deficient pancreatic tumors into immune competent mice, moreover, reveals increased CD8+ T cell infiltration and effector function, and markedly reduced tumor growth. Our work uncovers vulnerabilities in PDA that might be exploited to render these tumors more susceptible to the immune system

Phylogeography and population structure of the biologically invasive phytopathogen Erwinia amylovora inferred using minisatellites

Summary Erwinia amylovora causes a major disease of pome fruit trees worldwide, and is regulated as a quarantine organism in many countries. While some diversity of isolates has been observed, molecular epidemiology of this bacterium is hindered by a lack of simple molecular typing techniques with sufficiently high resolution. We report a molecular typing system of E. amylovora based on variable number of tandem repeats (VNTR) analysis. Repeats in the E. amylovora genome were identified with comparative genomic tools, and VNTR markers were developed and validated. A Multiple-Locus VNTR Analysis (MLVA) was applied to E. amylovora isolates from bacterial collections representing global and regional distribution of the pathogen. Based on six repeats, MLVA allowed the distinction of 227 haplotypes among a collection of 833 isolates of worldwide origin. Three geographically separated groups were recognized among global isolates using Bayesian clustering methods. Analysis of regional outbreaks confirmed presence of diverse haplotypes but also high representation of certain haplotypes during outbreaks. MLVA analysis is a practical method for epidemiological studies of E. amylovora, identifying previously unresolved population structure within outbreaks. Knowledge of such structure can increase our understanding on how plant diseases emerge and spread over a given geographical region