Genomic and functional study on the Tiger Mosquito, Aedes albopictus, in Italy

In few decades Aedes albopictus has spread from its' native range in south-east-Asia all over the world. In Europe this mosquito species has been described in Albania and Italy first and has nowadays expanded to all Mediterranean and east-European countries. Aedes albopictus is also a known vector of Dengue (DENV) and Chikungunya (CHKV) and has been responsible for two CHKV epidemics in Italy, becoming thus an increasing public health concern. Despite this, little knowledge is available on the effectiveness of insecticides commonly used to control adult populations of this species as well as on invasion history of European populations. We here present first evidence of resistance to pyrethroids in Aedes albopictus populations from Italy, which raises alarm on the effectiveness of these control measures in the future. Moreover, we complement this evidence with genomic analysis of 9 Ae. albopictus populations collected across Italy, as well as 1 population from Greece and 1 from Albania, showing occurrence of multiple invasions initiated from large propagules and followed by genetic drift and admixture among different source populations, which created a complex genomic pattern with generally low levels of differentiation and weak signatures of isolation by distance among populations

Synthesis and characterisation of novel antitumour platinum(IV) compounds

Die Verbesserung der Behandlungsmethoden von Krebs ist ein wichtiges Ziel der heutigen Forschung, vor allem wenn man bedenkt, dass diese Krankheit für 13% aller Todesfälle weltweit verantwortlich ist (25% in Österreich). Eine der wichtigsten Behandlungsmethoden ist die Chemotherapie mit Platinverbindungen. Ihre Anfänge liegen in den 1960er Jahren begründet, als Barnett Rosenberg die Antitumoraktivität von Cisplatin entdeckte. Heutzutage sind, neben Cisplatin zwei weitere platinhältige Chemotherapeutika weltweit für die klinische Anwendung zugelassen: Carbo- und Oxaliplatin. Jedoch führt die unzureichende Selektivität dieser Platin(II) Verbindungen dazu, dass nicht nur Krebszellen angegriffen werden. In weiterer Folge führt dies beim Patienten zum Teil schweren Nebenwirkungen. Dieser Umstand führte zu einer Verlagerung der Forschung hin zu Platin(IV)-Verbindungen, da diese eine erhöhte Inertheit aufweisen. Diese Eigenschaften könnten zu einer möglichen oralen Applizierbarkeit und gesteigerten Selektivität führen. Platin(IV)-Verbindungen werden durch Reduktion in die aktive Platin(II) Spezies überführt und agieren daher als Prodrugs. Die axialen Liganden werden während der Reduktion freigesetzt und sind daher für eine zielgerichtete Synthese von Wirkstoffen von besonderem Interesse. Durch Variation dieser Liganden können gewisse Eigenschaften, wie z.B. die Aufnahme in das Gewebe, verbessert werden, ohne die Aktivität der Substanz zu verändern. Darüber hinaus eröffnet sich die Möglichkeit, das Wirkspektrum durch eine Kopplung mit bioaktiven Molekülen zu erweitern. Das Repertoire zur Synthese von Platin(IV)-Verbindungen wurde durch die Umsetzung mit zyklischen Anhydriden enorm erweitert. Bei dieser Reaktion wird eine freie Carboxylgruppe erzeugt, die weitere Derivatisierung mit Aminen oder Alkoholen ermöglicht. Es muss angemerkt werden, dass immer zwei funktionelle Gruppen erhalten werden. Dieser Umstand kann, vor allem beim Umsatz mit Trägermolekülen, zu einigen Nachteilen führen. Diese Diplomarbeit enthält die erfolgreiche Synthese asymmetrischer Platin(IV)-Komplexe. Die Asymmetrisierung erfolgt bei der Carboxylierung von (OC-6-43)-Dichlorido(N,N-dimethylethan-1,2-diamin)dihydroxidoplatinum(IV) mit Bernsteinsäureanhydrid durch sterische Hinderung der zweiten Hydroxylgruppe. Die erhaltene freie Carboxylgruppe wird weiter umgesetzt zum Methylester. Außerdem wurde erstmalig ein Platin(IV) Komplex mit einem sekundären Amin zum entsprechenden Amid umgesetzt. Derzeit werden in vitro Untersuchungen in humanen Tumorzelllinien durchgeführt an drei der synthetisierten Verbindungen.The advancement of cancer treatment is a major aim of modern science, according to the fact that this disease is responsible for 13% of all deaths worldwide (25% in Austria). Chemotherapy based on platinum complexes is a major part in the field of treatment of cancer. Its advent was in the 1960s when Barnett Rosenberg discovered the antitumour activity of cisplatin. Nowadays there are, besides cisplatin, two other platinum-based drugs in worldwide clinical usage: carboplatin and oxaliplatin. Because of the insufficient selectivity of these platinum(II) compounds to attack only cancer cells, patients suffer from a variety of severe side effects. As a result, research turned its focus to the synthesis of platinum(IV) compounds, due to their chemical inertness. These characteristics are expected to raise the possibility for an oral application and increased selectivity. Platinum(IV) compounds have to be activated via reduction to develop their activity against tumours and therefore act as prodrugs. During reduction, the axial ligands are released. Hence, these ligands are of particular interest for target-oriented synthesis, since the features of a drug, like uptake into the tissue, can be improved without abating anti-tumour activity. Another great opportunity is the coupling to bioactive molecules to extend the spectrum of efficacy. The synthesis of platinum(IV) compounds experienced a crucial advance through carboxylation with cyclic anhydrides. The resulting free carboxylic acid besides the coordinated carboxylate allows further derivatisation to yield amides and esters. It has to be mentioned that there are two functional groups available which can be of disadvantage for further reactions with carrier molecules. This diploma thesis presents the successful synthesis of asymmetric platinum(IV) complexes: carboxylation with succinic anhydride of (OC-6-43)-dichlorido(N,N-dimethylethane-1,2-diamine)dihydroxidoplatinum(IV) had led to a monocarboxylation, whereas the second hydroxido group was sterically inhibited. Derivatisation of the carboxylic acid with methanol yielded the corresponding ester. Furthermore, platinum(IV) complex was transformed with a secondary amine to the corresponding amide for the first time. Currently, cytotoxicity studies in human tumour cell lines are being performed with three of the synthesised compounds

Creating a library, museum and citizen service centre for people with dementia. A project on participation and learning through transdisciplinary and interdisciplinary networking in Wiener Neustadt

Im partizipativen Gesundheitsforschungsprojekt "Eine Bibliothek für ALLE. Demenzfreundliche Bibliothek Wiener Neustadt" standen Menschen mit Demenz und betreuende Angehörige im Zentrum. Ziel war es, die Kompetenz der Mitarbeiter*innen in öffentlichen Einrichtungen (Bibliothek, Museum, Bürgerservice) im Umgang mit Menschen mit Vergesslichkeit zu erweitern und die Einrichtungen - im Sinne von Organisationslernen - demenzfreundlicher zu gestalten. Von Anfang an waren betroffene Menschen und ihre Angehörigen in das Projekt eingebunden wie auch soziale Einrichtungen und Selbsthilfegruppen. Erreicht wurde so nicht nur ein individueller Wissenszuwachs über Demenz und den Umgang mit Menschen mit Demenz, sondern die Themen wurden durch die Begegnung mit betroffenen Personen greifbar und erfahrbar. So konnte ein ressourcenorientiertes Bild geschaffen werden, das zur Entstigmatisierung von Menschen mit Demenz beiträgt. Auch für die beteiligten Betroffenen öffneten sich durch das Projekt (wieder) Türen mit neuen Handlungsmöglichkeiten für ihre soziale Teilhabe. Schließlich zeigte das Projekt auf: Es reicht nicht aus, Angebote für Menschen mit Demenz und deren Umfeld über die gewohnten Kanäle zu verbreiten. Vielmehr bedarf es der Vernetzung bzw. Zusammenarbeit mit Organisationen, die mit Menschen mit Demenz in Kontakt sind. (DIPF/Orig.)People with dementia and their caregivers are at the heart of the participatory health research project "A library for EVERYONE. Dementia-friendly Wiener Neustadt library". The goal was to increase the competence of employees of public institutions (library, museum, citizen service centre) in how to deal with people with memory issues and to make the institutions more dementia friendly - in the sense of organizational learning. From the start, people with dementia and their caregivers as well as social institutions and self-help groups were integrated into the project. Not only did individuals increase their knowledge of dementia and how to accommodate people with dementia but they also were able to better understand and experience the topics through encounters with individuals who are affected. This creates a perception of the disease that is oriented to human potential, which helps reduce the stigma of having dementia. For the participating individuals, the project (re)opened doors with new opportunities for social inclusion. The project ultimately demonstrated that it is not enough to communicate opportunities for people with dementia and their caregivers via the usual channels. Instead, it requires networking and cooperation with organizations that have contact with people with dementia. (DIPF/Orig.

Rapid and sensitive single-sample viral metagenomics using Nanopore Flongle sequencing

The ability of viral metagenomic Next-Generation Sequencing (mNGS) to unbiasedly detect nucleic acids in a clinical sample is a powerful tool for advanced diagnosis of viral infections. When clinical symptoms do not provide a clear differential diagnosis, extensive laboratory testing with virus-specific PCR and serology can be replaced by a single viral mNGS analysis. However, widespread diagnostic use of viral mNGS is thus far limited by long sample-to-result times, as most protocols rely on Illumina sequencing, which provides high and accurate sequencing output but is time-consuming and expensive. Here, we describe the development of an mNGS protocol based on the more cost-effective Nanopore Flongle sequencing with decreased turnaround time and lower, yet sufficient sequencing output to provide sensitive virus detection. Sample preparation (6 h) and sequencing (2 h) times are substantially reduced compared to Illumina mNGS and allow detection of DNA/RNA viruses at low input (up to 33-38 cycle threshold of specific qPCR). Although Flongles yield lower sequencing output, direct comparison with Illumina mNGS on diverse clinical samples showed similar results. Collectively, the novel Nanopore mNGS approach is specifically tailored for use in clinical diagnostics and provides a rapid and cost-effective mNGS strategy for individual testing of severe cases

EANM guideline for harmonisation on molar activity or specific activity of radiopharmaceuticals:impact on safety and imaging quality

Abstract This guideline on molar activity (Am) and specific activity (As) focusses on small molecules, peptides and macromolecules radiolabelled for diagnostic and therapeutic applications. In this guideline we describe the definition of Am and As, and how these measurements must be standardised and harmonised. Selected examples highlighting the importance of Am and As in imaging studies of saturable binding sites will be given, and the necessity of using appropriate materials and equipment will be discussed. Furthermore, common Am pitfalls and remedies are described. Finally, some aspects of Am in relation the emergence of a new generation of highly sensitive PET scanners will be discussed

Marked Increase in Avidity of SARS-CoV-2 Antibodies 7-8 Months After Infection Is Not Diminished in Old Age

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, Austria, was studied 0.5-1.5 months (baseline) and 7-8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays

Micro- and Nanoplastics Breach the Blood–Brain Barrier (BBB): Biomolecular Corona’s Role Revealed

Humans are continuously exposed to polymeric materials such as in textiles, car tires and packaging. Unfortunately, their break down products pollute our environment, leading to widespread contamination with micro- and nanoplastics (MNPs). The blood–brain barrier (BBB) is an important biological barrier that protects the brain from harmful substances. In our study we performed short term uptake studies in mice with orally administered polystyrene micro-/nanoparticles (9.55 µm, 1.14 µm, 0.293 µm). We show that nanometer sized particles—but not bigger particles—reach the brain within only 2 h after gavage. To understand the transport mechanism, we performed coarse-grained molecular dynamics simulations on the interaction of DOPC bilayers with a polystyrene nanoparticle in the presence and absence of various coronae. We found that the composition of the biomolecular corona surrounding the plastic particles was critical for passage through the BBB. Cholesterol molecules enhanced the uptake of these contaminants into the membrane of the BBB, whereas the protein model inhibited it. These opposing effects could explain the passive transport of the particles into the brain

Einführung und Optimierung eines praxisorientierten Problem-based-Learning-Moduls im Life-Science-Bereich

Der vorliegende Beitrag soll zur Diskussion rund um effektive Lehrkonzepte unter Anwendung des Problem-based-Learning-Ansatzes beitragen. Anhand eines konkreten Beispiels aus dem Life-Science-Bereich Tissue Engineering werden zunächst Herausforderungen in der Einführungsphase eines PBL-Moduls beleuchtet. Anschließend werden das aktuelle Konzept des Moduls, die vorgenommenen Maßnahmen zur Optimierung während dessen kontinuierlicher Weiterentwicklung sowie deren Wirksamkeit aus Sicht der Studierenden dargestellt. 13.05.2016 | Christine Leeb, Rita Leitner, Verena Pichler, Carina Huber-Gries, Dominik Rünzler & Veronika Jesenberger (Wien

Novel genotyping approaches to easily detect genomic admixture between the major Afrotropical malaria vector species, Anopheles coluzzii and An. gambiae

The two most efficient and most recently radiated Afrotropical vectors of human malaria - Anopheles coluzzii and An.gambiae - are identified by single-locus diagnostic PCR assays based on species-specific markers in a 4Mb region on chromosome-X centromere. Inherently, these diagnostic assays cannot detect interspecific autosomal admixture shown to be extensive at the westernmost and easternmost extremes of the species range. The main aim of this study was to develop novel, easy-to-implement tools for genotyping An.coluzzii and An.gambiae-specific ancestral informative markers (AIMs) identified from the Anopheles gambiae 1000 genomes (Ag1000G) project. First, we took advantage of this large set of data in order to develop a multilocus approach to genotype 26 AIMs on all chromosome arms valid across the species range. Second, we tested the multilocus assay on samples from Guinea Bissau, The Gambia and Senegal, three countries spanning the westernmost hybridization zone, where conventional species diagnostic is problematic due to the putative presence of a novel "hybrid form". The multilocus assay was able to capture patterns of admixture reflecting those revealed by the whole set of AIMs and provided new original data on interspecific admixture in the region. Third, we developed an easy-to-use, cost-effective PCR approach for genotyping two AIMs on chromosome-3 among those included in the multilocus approach, opening the possibility for advanced identification of species and of admixed specimens during routine large scale entomological surveys, particularly, but not exclusively, at the extremes of the range, where WGS data highlighted unexpected autosomal admixture

Spinophilin expression determines cellular growth, cancer stemness and 5-flourouracil resistance in colorectal cancer

The putative tumor suppressor gene spinophilin has been involved in cancer progression in several types of cancer. In this study, we explored the prognostic value of spinophilin expression in 162 colon adenocarcinoma patients. In addition, we generated stably expressing spinophilin-directed shRNA CRC cell lines and studied the influence of spinophilin expression on cellular phenotypes and molecular interactions. We independently confirmed that low spinophilin expression levels are associated with poor prognosis in CRC patients (p = 0.038). A reduction of spinophilin levels in p53 wild-type HCT116 and p53-mutated Caco-2 cells led to increased cellular growth rates and anchorage-independent growth (p<0.05). At molecular level, reduced spinophilin levels increased the expression of the transcription factor E2F-1. In addition, we observed an increased formation of tumor spheres, increased number of CD133 positive cells and an increased resistance to 5-flourouracil (p<0.05). Finally, treatment with the de-methylating agent 5-aza-dC increased spinophilin expression in CRC cells (p<0.05), corroborated by a correlation of spinophilin expression and extent of methylated CpG sites in the gene promoter region (p<0.001). In conclusion, gain of aggressive biological properties of CRC cells including cellular growth, cancer stem cell features and 5-flourouracil resistance partly explains the role of spinophilin in CRC