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Rotenone and elevated extracellular potassium concentration induce cell-specific fibrillation of α-synuclein in axons of cholinergic enteric neurons in the guinea-pig ileum.
Get PDFUnder embargo until 7 Nov 2017, as per publisher policy.Background: Parkinson’s disease is a progressive neurodegenerative disorder that results in the widespread loss of select classes of neurons throughout the nervous system. The pathological hallmarks of Parkinson’s disease are Lewy bodies and neurites, of which α-synuclein fibrils are the major component. α-Synuclein aggregation has been reported in the gut of Parkinson’s disease patients, even up to a decade before motor symptoms, and similar observations have been made in animal models of disease. However, unlike the central nervous system, the nature of α-synuclein species that form these aggregates and the classes of neurons affected in the gut are unclear. We have previously reported selective expression of α-synuclein in cholinergic neurons in the gut (1), suggesting they may be particularly vulnerable to degeneration in Parkinson’s disease.
Methods: In this study, we used immunohistochemistry to detect α-synuclein oligomers and fibrils via conformation-specific antibodies after rotenone treatment or prolonged exposure to high [K+] in ex vivo segments of guinea-pig ileum maintained in organotypic culture.
Key Results: Rotenone and prolonged raising of [K+] caused accumulation of α-synuclein fibrils in the axons of cholinergic enteric neurons. This took place in a time- and, in the case of rotenone, concentration-dependent manner. Rotenone also caused selective necrosis, indicated by increased cellular autofluorescence, of cholinergic enteric neurons, labeled by ChAT-immunoreactivity, also in a concentration-dependent manner.
Conclusions & Inferences: To our knowledge, this is the first report of rotenone causing selective loss of a neurochemical class in the enteric nervous system. Cholinergic enteric neurons may be particularly susceptible to Lewy pathology and degeneration in Parkinson’s disease
Sensory innervation of the guinea pig colon and rectum compared using retrograde tracing and immunohistochemistry.
No full textEmbargoed until 2 April 2017 as per publisher's policy
Predicting the Activation States of the Muscles Governing Upper Esophageal Sphincter Relaxation and Opening
No full textCopyright © 2016 the American Physiological SocietyThe swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation and deactivation of neural inputs to these muscles, including the intrinsic cricopharyngeus (CP) and extrinsic submental (SM) muscles, results in their mechanical activation or deactivation, which changes the diameter of the lumen, alters the intraluminal pressure, and ultimately reduces or promotes flow of content. By measuring the changes in diameter, using intraluminal impedance, and the concurrent changes in intraluminal pressure, it is possible to determine when the muscles are passively or actively relaxing or contracting. From these “mechanical states” of the muscle, the neural inputs driving the specific motor behaviors of the UES can be inferred. In this study we compared predictions of UES mechanical states directly with the activity measured by electromyography (EMG). In eight subjects, pharyngeal pressure and impedance were recorded in parallel with CP- and SM-EMG activity. UES pressure and impedance swallow profiles correlated with the CP-EMG and SM-EMG recordings, respectively. Eight UES muscle states were determined by using the gradient of pressure and impedance with respect to time. Guided by the level and gradient change of EMG activity, mechanical states successfully predicted the activity of the CP muscle and SM muscle independently. Mechanical state predictions revealed patterns consistent with the known neural inputs activating the different muscles during swallowing. Derivation of “activation state” maps may allow better physiological and pathophysiological interpretations of UES function
Corruption and public value
Get PDF“This is an Accepted Manuscript of an article published by Taylor & Francis in Public Integrity on 7 June 2016, available online: http://www.tandfonline.com/10.1080/10999922.2016.1184518.” This author accepted manuscript is made available following 18 month embargo from date of publication (7 June 2016) in accordance with publisher's copyright policy
Switching on the remote: a new perspective on accessibility in remote Australia
No full textLearning Communities: International Journal of Learning in Social Contexts by https://www.cdu.edu.au/northern-institute/lcj is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.In remote Australia, access to people, goods, services, information and places is difficult because of extreme distances and climates, sparse population, remoteness from markets, and complex economic and socio-cultural dynamics. Most of remote Australia remains disconnected from both the digital revolution and the national transport network due to a lack of adequate infrastructure, affordable and reliable services, and, for most, poor digital literacy. This impedes service delivery including education and health services, economic development and wellbeing of remote residents; contributing to inequalities between remote and non-remote Australians. Whilst the concept of accessibility in transport and telecommunication goods and services is relatively well defined in an urban context and can be measured accordingly, the way accessibility is currently measured fails to capture the complexity of the remote Australian context. The article discusses some of the current knowledge gaps associated with studying accessibility levels in remote Australia with a particular focus on Central Australia. The article presents indicators and tools which could be used to evaluate access issues with practical applications for remote Australia. Developing an accessibility index for remote areas would enable the reconsideration of minimal requirements for sustainable livelihoods in remote areas and the development of effective and appropriate regional development policies and initiatives
Don’t fear the reaper? The zombie university and eating braaaains
No full textAll authors and readers have the right to download, copy, distribute, modify, create derivative works and display publicly the articles in electronic, digital, or print form, provided that the post-print version of the articles are not sold for a profit and the first Publication by KOME, with a URL link and complete bibliographic details, is referenced.This article explores the role and function of neoliberalism in higher education, particularly in its manifestations after the Global Financial Crisis. Theories of managerialism are overlaid not only with questions about the purpose and role of higher education in the economy, but also the renegotiation of power and identity after 2008. Ulrich Beck’s zombie concept is reactivated and applied to the university. The paper moves through a discussion of the zombie and Beck’s zombie categories and concepts, and then concludes with a section applying these ideas to higher education
Novel application of X-ray fluorescence microscopy (XFM) for the non-destructive micro-elemental analysis of natural mineral pigments on Aboriginal Australian objects
No full textOpen Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.This manuscript presents the first non-destructive synchrotron micro-X-ray fluorescence study of natural mineral pigments on Aboriginal Australian objects. Our results demonstrate the advantage of XFM (X-ray fluorescence microscopy) of Aboriginal Australian objects for optimum sensitivity, elemental analysis, micron-resolution mapping of pigment areas and the method also has the advantage of being non-destructive to the cultural heritage objects. Estimates of pigment thickness can be calculated. In addition, based on the elemental maps of the pigments, further conclusions can be drawn on the composition and mixtures and uses of natural mineral pigments and whether the objects were made using traditional or modern methods and materials. This manuscript highlights the results of this first application of XFM to investigate complex mineral pigments used on Aboriginal Australian objects
Early cave art and ancient DNA record the origin of European bison
No full textThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/The two living species of bison (European and American) are among the few terrestrial megafauna to have survived the late Pleistocene extinctions. Despite the extensive bovid fossil record in Eurasia, the evolutionary history of the European bison (or wisent, Bison bonasus) before the Holocene (<11.7 thousand years ago (kya)) remains a mystery. We use complete ancient mitochondrial genomes and genome-wide nuclear DNA surveys to reveal that the wisent is the product of hybridization between the extinct steppe bison (Bison priscus) and ancestors of modern cattle (aurochs, Bos primigenius) before 120 kya, and contains up to 10% aurochs genomic ancestry. Although undetected within the fossil record, ancestors of the wisent have alternated ecological dominance with steppe bison in association with major environmental shifts since at least 55 kya. Early cave artists recorded distinct morphological forms consistent with these replacement events, around the Last Glacial Maximum (LGM, ∼21–18 kya)
Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness
Get PDFThis is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Introduction Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses.
Methods and analysis A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0–100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained.
Ethics and dissemination Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences.
Trial registration number ACTRN12610000464066
Public Infrastructure and Private Sector Productivity, Tasmania 1990-2015
Get PDFThis is an abstract of a paper delivered to the 45th Australian Economics Conference, held at Flinders University 11-13 July 2016The study utilises the recent advances in development of capital stock data at subnational level for Australian states and applies the series for analysis of the effect of the public infrastructure on the private sector productivity in Tasmania. The study employs a version of an aggregate production function to estimate the elasticity of private capital productivity with respect to the public infrastructure. The results of analysis indicate that, in the long run, contrary to the expectations, the public infrastructure contributes negatively to the private sector productivity in Tasmania. There is also some evidence that Tasmanian government is engaged in countercyclical public investment activities