The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

EdU, a new thymidine analogue for labelling proliferating cells in the nervous system

The standard method of labelling proliferating cells uses the thymidine analogue, bromodeoxyuridine (BrdU), which incorporates into the DNA during S-phase of the cell cycle. A disadvantage of this method is that the immunochemical processing requires pre-treatment of the cells and tissue with heat or acid to reveal the antigen. This pre-treatment reduces reliability of the method and degrades the specimen, reducing the ability for multiple immuno-fluorescence labelling at high resolution. We report here the utility of a novel thymidine analogue, ethynyl deoxyuridine (EdU), detected with a fluorescent azide via the “click” chemistry reaction (the Huisgen 1,3-dipolar cycloaddition reaction of an organic azide to a terminal acetylene). The detection of EdU requires no heat or acid treatment and the incorporated EdU is covalently conjugated to fluorescent probe. The reaction is quick and compatible with fluorescence immunochemistry and other fluorescent probes. We show here that EdU is non-toxic in vitro and in vivo and can be used in place of BrdU to label cells during neurogenesis and the progeny identified at least 30 days later. The fluorescent labelling of EdU, markedly improves the detection of proliferating cells and allows concurrent high resolution fluorescence immunochemistry.

The role of the research system in 'Learning Economies'

This paper provides a framework for analysing the role of Australia’s research system in promoting national economic development. The paper is in two parts. Part One focuses on knowledge diffusion and technological development and emphasises the systemic nature of innovation processes within the emerging context of ‘learning economies’. The key understandings relevant to a nation’s research system are drawn out from contemporary developments in the international literature on ‘learning economies’. Some of the implications for Australia are discussed. The aim is to provide readers with some indications of what to look for in considering options for the future of Australia’s research system. More detailed information on relevant aspects of Australia’s industrial and trade structure, the extent of the R&D effort in industry and on issues such as management capability can be obtained from (Marceau et al 1997). In the second part, broad elements of the Australian research system are reviewed in the light of findings from the literature. The central role of universities in the innovation and research systems is described. Actions that can be taken by both universities and governments are suggested, particularly regarding the need to build and maintain efficient information flows at local, national and international levels. The paper briefly points to the nature of a research system capable of contributing effectively to the wealth of the nation and indicates some possible directions for enabling Australia to meet the demands of, and profit from, a knowledge-based economy.

A general approach to tune the vibration properties of the mounting system in the high-speed and heavy-duty engine

Majority of the current research on the mounting system has emphasised on the low/medium power engine, rare work has been reported for the high-speed and heavy-duty engine, the vibration characteristics of which exhibits significantly increased complexity and uncertainty. In this work, a general dynamics model was firstly established to describe the dynamic properties of a mounting system with various numbers of mounts. Then, this model was employed for the optimization of the mounting system. A modified Powell conjugate direction method was developed to improve the optimization efficiency. Basing on the optimization results obtained from the theoretical model, a mounting system was constructed for a V6 diesel engine. The experimental measurement of the vibration intensity of the mounting systems shows excellent agreement with the theoretical calculations, indicating the validity of the model. This dynamics model opens a new avenue in assessing and designing the mounting system for a high-speed and heavy-duty engine. On the other hand, the delineated dynamics model, and the optimization algorithm should find wide applications for other mounting systems, such as the power transmission system which usually has various uncertain mounts.

Foreign-currency and monetary geopolitics of United States and its effects on the future of the international system

The US dollar is still considered as the main strategic deposit among the currencies of different countries of the world and the policies of the World Bank and the International Financial Organizations have been and will always be influenced by the US economy. Despite the economic crises and commercial balance deficits in the United States, dollar has maintained its high position in and its domination over foreign exchanges and foreign-currency deposits of the countries. The novelty of the present research relies on its consideration of the political properties of the governments and the geopolitical effects of these countries on the position of their monetary and foreign-currency policies and consequently, on the international financial organizations such as the International Monetary Fund and the World Bank, which can determine the future of international economy and the political relations among countries. Our research proves that the political development of the United States and its geopolitical situation have been of the effective factors on dollar growth; and unless the competitors acquire such a relative advantage, they will not be able to seriously challenge the currency of dollar and the monetary policies of the United States, at least in a short time

Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system

During development of the primary olfactory system, axon targeting is inaccurate and axons inappropriately project within the target layer or overproject into the deeper layers of the olfactory bulb. As a consequence there is considerable apoptosis of primary olfactory neurons during embryonic and postnatal development and axons of the degraded neurons need to be removed. Olfactory ensheathing cells (OECs) are the glia of the primary olfactory nerve and are known to phagocytose axon debris in the adult and postnatal animal. However, it is unclear when phagocytosis by OECs first commences. We investigated the onset of phagocytosis by OECs in the developing mouse olfactory system by utilizing two transgenic reporter lines: OMP-ZsGreen mice which express bright green fluorescent protein in primary olfactory neurons, and S100β-DsRed mice which express red fluorescent protein in OECs. In crosses of these mice, the fate of the degraded axon debris is easily visualized. We found evidence of axon degradation at embryonic day (E)13.5. Phagocytosis of the primary olfactory axon debris by OECs was first detected at E14.5. Phagocytosis of axon debris continued into the postnatal animal during the period when there was extensive mistargeting of olfactory axons. Macrophages were often present in close proximity to OECs but they contributed only a minor role to clearing the axon debris, even after widespread degeneration of olfactory neurons by unilateral bulbectomy and methimazole treatment. These results demonstrate that from early in embryonic development OECs are the primary phagocytic cells of the primary olfactory nerve.