A review of the “metallome” within neurons and glia, as revealed by elemental mapping of brain tissue

It is now well established that transition metals, such as Iron (Fe), Copper (Cu), and Zinc (Zn) are necessary for healthy brain function. Although Fe, Cu, and Zn are essential to the brain, imbalances in the amount, distribution, or chemical form (“metallome”) of these metals is linked to the pathology of numerous brain diseases or disorders. Despite the known importance of metal ions for both brain health and disease, the metallome that exists within specific types of brain cells is yet to be fully characterised. The aim of this mini-review is to present an overview of the current knowledge of the metallome found within specific brain cells (oligodendrocytes, astrocytes, microglia, and neurons), as revealed by direct elemental mapping techniques. It is hoped this review will foster continued research using direct elemental mapping techniques to fully characterise the brain cell metallome

Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks

Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits. © 2021, The Author(s). *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Andrew Lavender” is provided in this record*

Light as a chronobiologic countermeasure for long-duration space operations

Long-duration space missions require adaptation to work-rest schedules which are substantially shifted with respect to earth. Astronauts are expected to work in two-shift operations and the environmental synchronizers (zeitgebers) in a spacecraft differ significantly from those on earth. A study on circadian rhythms, sleep, and performance was conducted by exposing four subjects to 6 deg head-down tilt bedrest (to simulate the effects of the weightless condition) and imposing a 12-h shift (6 h delay per day for two days). Bright light was tested in a cross-over design as a countermeasure for achieving faster resynchronization and regaining stable conditions for sleep and circadian rhythmicity. Data collection included objective sleep recording, temperature, heart rate, and excretion of hormones and electrolytes as well as performance and responses to questionnaires. Even without a shift in the sleep-wake cycle, the sleep quantity, circadian amplitudes and 24 h means decreased in many functions under bedrest conditions. During the shift days, sleepiness and fatigue increased, and alertness decreased. However, sleep quantity was regained, and resynchronization was completed within seven days after the shift for almost all functions, irrespective of whether light was administered during day-time or night-time hours. The time of day of light exposure surprisingly appeared not to have a discriminatory effect on the resynchronization speed under shift and bedrest conditions. The results indicate that simulated weightlessness alters circadian rhythms and sleep, and that schedule changes induce additional physiological disruption with decreased subjective alertness and increased fatigue. Because of their operational implications, these phenomena deserve additional investigation

Synchrotron Macro ATR-FTIR Microspectroscopy for High Resolution Chemical Mapping of Single Cells

Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy has been used widely for probing the molecular properties of materials. Coupling a synchrotron infrared (IR) beam to an ATR element using a high numerical aperture (NA) microscope objective enhances the spatial resolution, relative to transmission or transflectance microspectroscopy, by a factor proportional to the refractive index (n) of the ATR element. This work presents the development of the synchrotron macro ATR-FTIR microspectroscopy at Australian Synchrotron Infrared Microspectroscopy (IRM) Beamline, and demonstrates that high quality FTIR chemical maps of single cells and tissues can be achieved at an enhanced spatial resolution. The so-called “hybrid” macro ATR-FTIR device was developed by modifying the cantilever arm of a standard Bruker macro ATR-FTIR unit to accept germanium (Ge) ATR elements with different facet sizes (i.e. 1 mm, 250 μm and 100 μm in diameter) suitable for different types of sample surfaces. We demonstrated the capability of the technique for high-resolution single cell analysis of malaria-infected red blood cells, individual neurons in a brain tissue and cellular structures of a Eucalyptus leaf. The ability to measure a range of samples from soft membranes to hard cell wall structures demonstrates the potential of the technique for high-resolution chemical mapping across a broad range of applications in biology, medicine and environmental science

Risky Business: The Issue of Timing, Entry and Performance in the Asia-Pacific LNG Market

Canada’s federal government has championed the prospect of exporting liquefied natural gas (LNG) to overseas markets. The government of British Columbia is aggressively planning to turn itself into a global LNG-export hub, and the prospect for Canadian LNG exports is positive. However, there are market and political uncertainties that must be overcome in a relatively short period of time if Canada is to become a natural gas exporter to a country other than the United States. This report assesses the feasibility of Canadian exports and examines the policy challenges involved in making the opportunity a reality. Demand for natural gas in the Asia-Pacific region is forecast to grow over 60 per cent by 2025. LNG trade is expected to make up nearly two-thirds of global natural gas trade by 2035. Supply in the Asia-Pacific region is limited, requiring significant LNG imports with corresponding infrastructure investment. This results in substantial price differentials between North America and the Asia-Pacific countries, creating a potentially lucrative opportunity for Canada. The lower North American prices are a reflection of the fact that there is a surplus of gas on this continent. Canada’s shipments to its sole export market, the United States, are shrinking in the face of vast increases in American production of shale and tight gas. Canada has a surplus of natural gas and there is growing demand in the Asia-Pacific region. Proponents argue that all Canada needs to do is build and supply facilities to liquefy gas and ship it across the Pacific; the reality is not so simple. Timing is one of the key challenges Canada faces. Producers around the world — including in the newly gas-rich U.S. — are racing to lock up market-share in the Asia-Pacific region, in many cases much more aggressively than Canada. While this market is robust and growing, the nature of the contracts for delivery will favour actors that are earliest in the queue; margins for those arriving late will be slimmer and less certain over time. As supply grows, so too does the likelihood of falling gas prices in the Asia-Pacific region, making later projects less lucrative. LNG projects are feasible only on the basis of long-term contracts; once a piece of market share is acquired, it could be decades before it becomes available again. Currently, there are more proposed LNG-export projects around the world than will be required to meet projected demand for the foreseeable future. Delays beyond 2024 risk complete competitive loss of market entry for Canadian companies. B.C. is behind schedule on the government’s goal of having a single terminal operational by 2015. Of equal concern is the lack of policy and regulatory co-ordination, with disagreements between governments over standards, process and compensation for those stakeholders involved in the potential LNG industry. Issues as basic as taxing and royalty charges for gas shipments between provinces and locating facilities and marine-safety standards remain unsettled in Canada. The B.C. government has announced plans to levy special taxes on LNG, a policy that could render many current proposals uncompetitive. The LNG market is much more complicated than current discussions suggest; this report delves into every aspect relevant for Canada as a potential exporter. The prospect for Canada expanding into the Asia-Pacific market is entirely viable. Canada has almost everything going for it: political stability, free-market principles, immense resources, extensive infrastructure and industry experience. Everything, that is, except a co-ordinated regulatory and policy regime. Without that, Canada could be shut out, stuck relying on a single U.S. gas-export market that, increasingly, does not need us

Objectively assessed physical activity, adiposity, and inflammatory markers in people with type 2 diabetes.

OBJECTIVE: Inflammatory processes may play an important role in the development of acute coronary syndromes in people with type 2 diabetes; thus, strategies to control inflammation are of clinical importance. We examined the cross-sectional association between objectively assessed physical activity and inflammatory markers in a sample of people with type 2 diabetes. METHODS: Participants were 71 men and 41 women (mean age=63.9±7 years), without a history of cardiovascular disease, drawn from primary care clinics. Physical activity was objectively measured using waist-worn accelerometers (Actigraph GT3X) during waking hours for seven consecutive days. RESULTS: We observed inverse associations between moderate-to-vigorous physical activity (per 10 min) with plasma interleukin-6 (B=-0.035, 95% CI -0.056 to -0.015), interleukin-1ra (B=-0.033, 95% CI -0.051 to -0.015), and monocyte chemotactic protein-1 (B=-0.011, 95% CI -0.021 to 0.000). These associations largely persisted in multivariable adjusted models, although body mass index considerably attenuated the effect estimate. CONCLUSIONS: These data demonstrate an inverse association between physical activity and inflammatory markers in people with type 2 diabetes

Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes.

Psychological stress may contribute to type 2 diabetes but mechanisms are still poorly understood. In this study, we examined whether stress responsiveness is associated with glucocorticoid and mineralocorticoid sensitivity in a controlled experimental comparison of people with type 2 diabetes and non-diabetic participants. Thirty-seven diabetes patients and 37 healthy controls underwent psychophysiological stress testing. Glucocorticoid (GR) and mineralocorticoid sensitivity (MR) sensitivity were measured by dexamethasone- and prednisolone-inhibition of lipopolysaccharide (LPS)-induced interleukin (IL) 6 levels, respectively. Blood pressure (BP) and heart rate were monitored continuously, and we periodically assessed salivary cortisol, plasma IL-6 and monocyte chemotactic protein (MCP-1). Following stress, both glucocorticoid and mineralocorticoid sensitivity decreased among healthy controls, but did not change in people with diabetes. There was a main effect of group on dexamethasone (F(1,74)=6.852, p=0.013) and prednisolone (F(1,74)=7.295, p=0.010) sensitivity following stress at 45 min after tasks. People with diabetes showed blunted stress responsivity in systolic BP, diastolic BP, heart rate, IL-6, MCP-1, and impaired post-stress recovery in heart rate. People with Diabetes had higher cortisol levels as measured by the total amount excreted over the day and increased glucocorticoid sensitivity at baseline. Our study suggests that impaired stress responsivity in type-2 diabetes is in part due to a lack of stress-induced changes in mineralocorticoid and glucocorticoid sensitivity

Distribution of selenium in zebrafish larvae after exposure to organic and inorganic selenium forms

Selenium is an essential micronutrient for many organisms, and in vertebrates has a variety of roles associated with protection from reactive oxygen species. Over the past two decades there have been conflicting reports upon human health benefits and detriments arising from consumption of selenium dietary supplements. Thus, early studies report a decrease in the incidence of certain types of cancer, whereas subsequent studies did not observe any anti-cancer effect, and adverse effects such as increased risks for type 2 diabetes have been reported. A possible contributing factor may be that different chemical forms of selenium were used in different studies. Using larval stage zebrafish (Danio rerio) as a model organism, we report a comparison of the toxicities and tissue selenium distributions of four different chemical forms of selenium. We find that the organic forms of selenium tested (Se-methyl-l-selenocysteine and l-selenomethionine) show considerably more toxicity than inorganic forms (selenite and selenate), and that this appears to be correlated with the level of bioaccumulation. Despite differences in concentrations, the tissue specific pattern of selenium accumulation was similar for the chemical forms tested; selenium was found to be highly concentrated in pigment (melanin) containing tissues especially for the organic selenium treatments, with lower concentrations in eye lens, yolk sac and heart. These results suggest that pigmented tissues might serve as a storage reservoir for selenium. © 2016 The Royal Society of Chemistry

Antioxidants and dementia risk: Consideration through a cerebrovascular perspective

A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects on cognition and dementia are still unclear. An emerging body of evidence suggests that the integrity of the cerebrovascular blood-brain barrier (BBB) is centrally involved in the onset and progression of cognitive impairment and dementia. While recent studies revealed that some anti-oxidative agents appear to be protective against the disruption of BBB integrity and structure, few studies considered the neuroprotective effects of antioxidants in the context of cerebrovascular integrity. Therefore, in this review, we examine the mechanistic insights of antioxidants as a pleiotropic agent for cognitive impairment and dementia through a cerebrovascular axis by primarily focusing on the current available data from physiological studies. Conclusively, there is a compelling body of evidence that suggest antioxidants may prevent cognitive decline and dementia by protecting the integrity and function of BBB and, indeed, further studies are needed to directly examine these effects in addition to underlying molecular mechanisms