Engaging casually employed teachers in collaborative curriculum and professional development : change through an action research enquiry in a higher education 'pathways' institution

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

Carrageenan-induced acute inflammation in the mouse air pouch synovial model. Role of tumour necrosis factor

We used the mouse air pouch model of inflammation to study the interaction between cytokines, prostaglandin E2 (PGE2) and cell migration during the various phases of acute local inflammation induced by carrageenan. In serum, the levels of interleukin 1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor (TNF), serum amiloid-A (SAA) and Fe++ were never different from controls, indicating that no systemic inflammatory changes were induced. Locally the exudate volume and the number of leukocytes recruited into the pouch increased progressively until 7 days after carrageenan. The same was true for PGE2 production. We could not measure IL-1 but the production of IL-6 and TNF reached a maximum after 5-24 h then quickly decreased. Anti-TNF antibodies inhibited cell migration by 50% 24 h after treatment. Pretreatment with interleukin 10 (IL-10) inhibited TNF production almost completely and cell migration by 60%. Carrageenan-induced inflammation was modulated by anti-inflammatory drugs. Pretreatment with dexamethasone (DEX) or indomethacin (INDO) inhibited cell migration and reduced the concentration of TNF in the exudate. Production of PGE2 or vascular permeability did not correlate with the number of cells in the pouch. Local TNF seems to play an important role in this model, particularly for leukocyte migration in the first phase of the inflammatory process. In conclusion, the air pouch seems to be a good model for studying the regulation of the early events of local inflammation, particularly the role of cytokines and cell migration

The Stimulation of Inducible Nitric-oxide Synthase by the Prion Protein Fragment 106–126 in Human Microglia Is Tumor Necrosis Factor-α-dependent and Involves p38 Mitogen-activated Protein Kinase

A synthetic peptide consisting of amino acid residues 106-126 of the human prion protein (PrP-(106--126)) has been previously demonstrated to be neurotoxic and to induce microglial activation. The present study investigated the expression of the inducible form of the nitric-oxide synthase (NOS-II) in human microglial cells treated with PrP-(106--126). Using reverse transcriptase-polymerase chain reaction, we found that PrP-(106--126) induces NOS-II gene expression after 24 h of treatment and that this effect is accompanied by a peak of nuclear factor kappa B (NF-kappa B) binding at 30 min as evaluated by electrophoretic mobility shift assay. Since our previous data demonstrated tumor necrosis factor-alpha (TNF-alpha) to be a potent inducer of NOS-II in these cells, we analyzed the expression of this cytokine in PrP-(106--126)-treated microglia. PrP-(106--126) caused the release of TNF-alpha as detected by enzyme-linked immunosorbent assay, and a blocking antibody, anti-TNF-alpha, abolished NOS-II induction elicited by this peptide. Moreover, PrP-(106-126) activates p38 mitogen-activated protein kinase, and the inhibition of this pathway determines the ablation of NF-kappa B binding induced by this fragment peptide

C. elegans expressing human β2-microglobulin: a novel model for studying the relationship between the molecular assembly and the toxic phenotype.

Availability of living organisms to mimic key step of amyloidogenesis of human protein has become an indispensable tool for our translation approach aiming at filling the deep gap existing between the biophysical and biochemical data obtained in vitro and the pathological features observed in patients. Human β(2)-microglobulin (β(2)-m) causes systemic amyloidosis in haemodialysed patients. The structure, misfolding propensity, kinetics of fibrillogenesis and cytotoxicity of this protein, in vitro, have been studied more extensively than for any other globular protein. However, no suitable animal model for β(2)-m amyloidosis has been so far reported. We have now established and characterized three new transgenic C. elegans strains expressing wild type human β(2)-m and two highly amyloidogenic isoforms: P32G variant and the truncated form ΔN6 lacking of the 6 N-terminal residues. The expression of human β(2)-m affects the larval growth of C. elegans and the severity of the damage correlates with the intrinsic propensity to self-aggregate that has been reported in previous in vitro studies. We have no evidence of the formation of amyloid deposits in the body-wall muscles of worms. However, we discovered a strict correlation between the pathological phenotype and the presence of oligomeric species recognized by the A11 antibody. The strains expressing human β(2)-m exhibit a locomotory defect quantified with the body bends assay. Here we show that tetracyclines can correct this abnormality confirming that these compounds are able to protect a living organism from the proteotoxicity of human β(2)-m

c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo.

Altered synaptic function is considered one of the first features of Alzheimer disease (AD). Currently, no treatment is available to prevent the dysfunction of excitatory synapses in AD. Identification of the key modulators of synaptopathy is of particular significance in the treatment of AD. We here characterized the pathways leading to synaptopathy in TgCRND8 mice and showed that c-Jun N-terminal kinase (JNK) is activated at the spine prior to the onset of cognitive impairment. The specific inhibition of JNK, with its specific inhibiting peptide D-JNKI1, prevented synaptic dysfunction in TgCRND8 mice. D-JNKI1 avoided both the loss of postsynaptic proteins and glutamate receptors from the postsynaptic density and the reduction in size of excitatory synapses, reverting their dysfunction. This set of data reveals that JNK is a key signaling pathway in AD synaptic injury and that its specific inhibition offers an innovative therapeutic strategy to prevent spine degeneration in AD

The value of the spineless monkey orange tree (Strychnos madagascariensis) for conservation of northern sportive lemurs (Lepilemur milanoii and L. ankaranensis)

Tree hollows provide shelters for a large number of forest-dependent vertebrate species worldwide. In  Madagascar, where high historical and ongoing rates of deforestation and forest degradation are  responsible for a major environmental crisis, reduced availability of tree hollows may lead to declines in hollow-dwelling species such as sportive lemurs, one of the most species-rich groups of lemurs. The identification of native tree species used by hollow-dwelling lemurs may facilitate targeted management interventions to maintain or improve habitat quality for these lemurs. During an extensive survey of sportive lemurs in northern Madagascar, we identified one tree species, Strychnos madagascariensis (Loganiaceae), the spineless monkey orange tree, as a principal sleeping site of two species of northern sportive lemurs, Lepilemur ankaranensis and L. milanoii (Lepilemuridae). This tree species represented 32.5% (n=150) of the 458 sleeping sites recorded. This result suggests that S. madagascariensis may be valuable for the conservation of hollow-dwelling lemurs. De nombreux vertébrés forestiers à travers le monde trouvent refuge dans des cavités et des trous  d’arbres. À Madagascar, les taux de déforestation historiques et actuels sont responsables d’une crise environnementale majeure. Dans ce contexte, une disponibilité réduite d’arbres pourvus de cavités  pourrait entrainer le déclin des espèces dépendant de ces abris comme par exemple les lépilemurs, un des groupes de lémuriens les plus riches en espèces. L’identification des espèces d’arbres indigènes creusés de trous et utilisés par les lémuriens pourrait faciliter la mise en place d’actions de conservation ayant pour but de maintenir ou améliorer l’habitat de ces lémuriens. Au cours d’une étude réalisée dans le Nord de Madagascar, nous avons observé que Strychnos madagascariensis  (Loganiaceae) était   fréquemment utilisé comme site dortoir par les deux espèces de lépilemurs présentes, Lepilemur   ankaranensis and L. milanoii (Lepilemuridae). Cette espèce d’arbre concernait 32,5% (n = 150) des 458  sites dortoirs enregistrés. Ce résultat suggère que S. madagascariensis pourrait être important pour la  conservation des lémuriens dépendant de sites dortoirs

Pathogenic Aβ A2V versus protective Aβ A2T mutation : early stage aggregation and membrane interaction

We investigated the effects of punctual A-to-V and A-to-T mutations in the amyloid precursor protein APP, corresponding to position 2 of A\u3b21\u201342. Those mutations had opposite effects on the onset and progression of Alzheimer disease, the former inducing early AD pathology and the latter protecting against the onset of the disease. We applied Static and Dynamic Light Scattering and Circular Dichroism, to study the different mutants in the early stages of the aggregation process, essential for the disease. Comparative results showed that the aggregation pathways differ in the kinetics and extent of the process, in the size of the aggregates and in the evolution of the secondary structure, resulting in fibrils of different morphology, as seen by AFM. Mutated peptides had comparable toxic effects on N2a cells. Moreover, as assessed by X-ray scattering, all of them displayed disordering effects on the internal structure of mixed phospholipids-gangliosides model membranes

The Molecular Assembly of Amyloid A beta Controls Its Neurotoxicity and Binding to Cellular Proteins

Accumulation of beta-sheet-rich peptide (A beta) is strongly associated with Alzheimer's disease, characterized by reduction in synapse density, structural alterations of dendritic spines, modification of synaptic protein expression, loss of long-term potentiation and neuronal cell death. A beta species are potent neurotoxins, however the molecular mechanism responsible for A beta toxicity is still unknown. Numerous mechanisms of toxicity were proposed, although there is no agreement about their relative importance in disease pathogenesis. Here, the toxicity of A beta 1-40 and A beta 1-42 monomers, oligomers or fibrils, was evaluated using the N2a cell line. A structure-function relationship between peptide aggregation state and toxic properties was established. Moreover, we demonstrated that A beta toxic species cross the plasma membrane, accumulate in cells and bind to a variety of internal proteins, especially on the cytoskeleton and in the endoplasmatic reticulum (ER). Based on these data we suggest that numerous proteins act as A beta receptors in N2a cells, triggering a multi factorial toxicity

On spontaneous scalarization

We study in the physical frame the phenomenon of spontaneous scalarization that occurs in scalar-tensor theories of gravity for compact objects. We discuss the fact that the phenomenon occurs exactly in the regime where the Newtonian analysis indicates it should not. Finally we discuss the way the phenomenon depends on the equation of state used to describe the nuclear matter.Comment: 41 pages, RevTex, 10 ps figures, submitted to Phys. Rev.