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Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by deposition of the β-amyloid (Ab) peptide in the brain. Although many Ab-centric therapies have been attempted, they all failed and no efficacious therapy is available yet. Objectives. Main objectives of this study were to investigate the efficacy of multifunctional liposomes (Lip), designed to target the brain, to 1. promote disaggregation of brain Ab assemblies in AD mouse brain, 2. reduce brain Ab burden and 3. restore mouse memory, at a post-symptomatic stage. 4. Arrest pathology progression at a presymptomatic stage. Methods. Functionalized Lip with a peptide derived from apolipoprotein-E receptorbinding domain (mApoE) for blood-brain barrier targeting, and with phosphatidic acid (PA) for Ab binding (mApoE-PA-Lip) were administered (I.P.) for 3 weeks in post- and 4 months in pre-symptomatic APP/PS1 mice subsequently tested in the novel object recognition memory test (NORT). At the end mouse brains were collected and analyzed through histology and biochemistry for Ab deposition. Results. Administration of mApoE-PA-Lip decreased total insoluble brain Ab1-42, total plaque area and Ab oligomers. Plaque reduction was confirmed by PET imaging with [11C]-PIB. The reduction of brain Ab was associated with its increase in liver and spleen. Treatment also restored mouse impaired memory to normal at post-symptomatic ages and prevented its loss when administered at pre-symptomatic ages. Conclusions. These data suggest that bi-functionalized Lip destabilize brain Ab aggregates and promote peptide removal from the brain and its peripheral clearance. This innovative therapeutic approach can be considered as a new candidate for AD treatment.

We report the near full length genome sequence, of an hepatitis C virus isolate from a man originating from Democratic Republic of Congo, whose genotype could not be determined by the routinely used sequence technique.The near-complete genome sequence of this variant BAK1 was obtained by the association of two next generation sequencing technologies.Evolutionary analysis indicates that this isolate BAK1 could be the first reported strain belonging to a new HCV-7b subtype. This new subtype has been incorrectly identified as genotype 2 by Versant HCV Genotype 2.0 assay (LiPA).The requirement of three independent isolates has been filled and a new subtype can be assigned. More examples of HCV-7 are required to better understand its origin, its pathogenicity and its relationship with genotype 2.

This thesis is an account of a curriculum reform initiative that took place in 2005 at the Pathways College of Australia (PCA) [a pseudonym]. It is an investigation of an innovative collaborative educational development project in an Australian higher education pathway institution. The research highlights the neglect of the professional development of casually employed teachers and makes contributions to the literatures of educational development, curriculum and collaboration. It suggests ways to improve quality in the current higher education context through a process of action research enquiry and organisational change In recent times the higher education landscape in Australia has transformed with growing numbers of casual and part-time teachers, many more international students and an increasing focus on quality assurance. This changing context has led to the emergence of a number of private institutions providing an alternative entry pathway to tertiary study for students who do not meet standard university entrance requirements. The story of PCA and its growth during this time comes out of an increasing focus on quality and accountability underpinning the funding changes to, and the internationalisation of, higher education. This study presents a curriculum development framework which engages casually employed teachers and supports curriculum reform. It addresses a need to ensure quality in the teaching and learning at PCA by developing an integrated curriculum. The framework allows for the professional development of casualised teaching staff in a pathways higher education institution and encourages a critical reflection on the process through action research. An exploration of the usefulness of communities of practice theory for examining the workings of this group-based educational development process frames the data analysis. The research contributes to the literature by analysing how the participants engaged in the project cycles and illuminates the different ways in which they were working. Insights into curriculum reform are given through building collaboration under adverse conditions. The discussion adds a new dimension to communities of practice theory as it does not account for the important set of tensions found in the data. It furthers our understanding of its application in an environment with mostly casually employed teachers. The story about this research reveals the complexities in the relationships between the researcher, the participants and PCA and shows a successful collaboration can be achieved under challenging employment conditions.

The role of first-stage β–amyloid aggregation in the development of the Alzheimer disease, is widely accepted but still unclear. Intimate interaction with the cell membrane is invoked. We designed Neutron Reflectometry experiments to reveal the existence and extent of the interaction between β–amyloid (Aβ) peptides and a lone customized biomimetic membrane, and their dependence on the aggregation state of the peptide. The membrane, asymmetrically containing phospholipids, GM1 and cholesterol in biosimilar proportion, is a model for a raft, a putative site for amyloid-cell membrane interaction. We found that the structured-oligomer of Aβ(1-42), its most acknowledged membrane-active state, is embedded as such into the external leaflet of the membrane. Conversely, the Aβ(1-42) unstructured early-oligomers deeply penetrate the membrane, likely mimicking the interaction at neuronal cell surfaces, when the Aβ(1-42) is cleaved from APP protein and the membrane constitutes a template for its further structural evolution. Moreover, the smaller Aβ(1-6) fragment, the N-terminal portion of Aβ, was also used. Aβ N-terminal is usually considered as involved in oligomer stabilization but not in the peptide-membrane interaction. Instead, it was seen to remove lipids from the bilayer, thus suggesting its role, once in the whole peptide, in membrane leakage, favouring peptide recruitment.

J.BIOL.CHEM.

Veri toplama teknolojisinin hızlı gelişimi ve süreçlerin bilgisayarlar aracılığıyla izlenmesi, birden fazla kalite bileşeninin veya süreç değişkeninin eş zamanlı kontrolüne olan ilgiyi arttırmıştır. Çok değişkenli istatistiksel süreç kontrol yöntemleri olarak adlandırılan bu tekniklerin en önemli özellikleri değişkenler arasındaki ilişkileri de göz önünde bulundurarak süreci bir bütün olarak incelemeleridir. Hotelling T2, çok değişkenli süreçlerin incelenmesinde en yaygın olarak kullanılan kontrol diyagramı istatistiklerinden biridir. Çalışmamızda cam takviyeli plastik borular ve bağlantı manşonları üreten bir endüstri işletmesinde sürekli elyaf sarma sürecine çok değişkenli istatistiksel kalite kontrolü uygulanması hedeflenmiştir. Özellikle Hotelling T2 istatistiği üzerine kurduğumuz çalışma QualStat yazılım programı aracılığıyla gerçekleştirilmiştir. İstanbul Ticaret Üniversitesi

We report the cloning of the AOH1 and AOH2 genes, which encode two novel mammalian molybdo-flavoproteins. We have purified the AOH1 protein to homogeneity in its catalytically active form from mouse liver. Twenty tryptic peptides, identified or directly sequenced by mass spectrometry, confirm the primary structure of the polypeptide deduced from the AOH1 gene. The enzyme contains one molecule of FAD, one atom of molybdenum, and four atoms of iron per subunit and shows spectroscopic features similar to those of the prototypic molybdo-flavoprotein xanthine oxidoreductase. The AOH1 and AOH2 genes are 98 and 60 kilobases long, respectively, and consist of 35 coding exons. The AOH1 gene has the potential to transcribe an extra leader non-coding exon, which is located downstream of exon 26, and is transcribed in the opposite orientation relative to all the other exons. AOH1 and AOH2 map to chromosome 1 in close proximity to each other and to the aldehyde oxidase gene, forming a molybdo-flavoenzyme gene cluster. Conservation in the position of exon/intron junctions among the mouse AOH1, AOH2, aldehyde oxidase, and xanthine oxidoreductase loci indicates that these genes are derived from the duplication of an ancestral precursor.