Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.

Tobacco smoking is a risk factor for various diseases. The underlying cellular mechanisms are not fully characterized, but include oxidative stress, apoptosis, and necrosis. Electronic-cigarettes (e-cigarettes) have emerged as an alternative to and a possible means to reduce harm from tobacco smoking. E-cigarette vapor contains significantly lower levels of toxicants than cigarette smoke, but standardized methods to assess cellular responses to exposure are not well established. We investigated whether an in vitro model of the airway epithelium (human bronchial epithelial cells) and commercially available assays could differentiate cellular stress responses to aqueous aerosol extracts (AqE) generated from cigarette smoke and e-cigarette aerosols. After exposure to AqE concentrations of 0.063-0.500 puffs/mL, we measured the intracellular glutathione ratio (GSH:GSSG), intracellular generation of oxidant species, and activation of the nuclear factor erythroid-related factor 2 (Nrf2)-controlled antioxidant response elements (ARE) to characterize oxidative stress. Apoptotic and necrotic responses were characterized by increases in caspase 3/7 activity and reductions in viable cell protease activities. Concentration-dependent responses indicative of oxidative stress were obtained for all endpoints following exposure to cigarette smoke AqE: intracellular generation of oxidant species increased by up to 83%, GSH:GSSG reduced by 98.6% and transcriptional activation of ARE increased by up to 335%. Caspase 3/7 activity was increased by up to 37% and the viable cell population declined by up to 76%. No cellular stress responses were detected following exposure to e-cigarette AqE. The methods used were suitably sensitive to be employed for comparative studies of tobacco and nicotine products.

Residential universities are increasingly integrating online interaction within courses in the form of synchronous online chats, asynchronous online discussions and access to interactive resources. This article evaluates the educational effectiveness of online chats within a Humanities postgraduate course and a final year Commerce course. We consider the roles of course design, group dynamics, and facilitation style in the successful use of online collaboration within primarily face-to-face courses, as well as the potential for online collaboration within a blended course design to facilitate more inclusive learning conversations than are possible with exclusively face-to-face interaction.

of the Multimedia Education Group (MEG) at the University of Cape Town (UCT), researches online collaboration. Glenda Cox (gcox@ched.uct.ac.za) specialises in the coding and analysis of online and face-to-face learning conversations. Andrea Eden (aeden@ched.uct.ac.za) coordinates connect, MEG's online learning environment. Monique Hanslo (mhanslo@ched.uct.ac.za) is a statistician in the Alternative Admissions Research Project at UCT. AbstractThis article considers the extent and nature of student participation in a trade bargaining simulation from a community of practice perspective. This thirdyear economics module included a blend of online communication (through email, online chats and online discussions) and face-to-face meetings, both in smaller bargaining groups and in whole class plenary meetings. Our method of analysis includes the use of Exchange Structure Analysis of text chats and face-to-face learning conversations, triangulated by observation, survey and interview data. The focus on community of practice enables us to offer a nuanced interpretation of differences in crude participation data derived from the online chats. Superficially, the data may suggest marginalisation of participants, but Wenger's (1988) notion of peripheral participation with a trajectory towards full participation reframes the disparities in terms of an active community of practice. Some members are fully engaged with the practices of trade bargaining from the early stages of the simulation, while others move towards full participation over the duration of the simulation. Our results suggest that the laboratory-based online text chats did provide opportunities for student participation in the simulation, and that male and female students exhibited different patterns of participation in the chats.