Neuropathic pain is extremely common, affecting up to 5-10% of the population globally, and no cures or effective treatments are currently available. Moreover, chemotherapy-induced pain can be so extreme that it causes some patients with cancer to discontinue treatment and greatly impairs quality of life in survivors.

Prior to this study, researchers were aware that pathological pain is triggered by a biological pathway that is activated by binding of the excitatory transmitter glutamate to receptors called NMDARs. This process then triggers activation of an enzyme neuronal nitric oxide synthase (nNOS) that generates nitric oxide gas that plays a role in aberrant pain sensation. However, experimental drugs designed to block either the NMDAR receptor or the nNOS enzyme can cause intolerable side effects, such as memory impairment and motor dysfunction.

Now, researchers from Indiana University in Bloomington, USA and the Turku Centre for Biotechnology in Finland have demonstrated that an experimental molecule reduces neuropathic pain in rodents resulting from either nerve damage or a common chemotherapy drug.

The team in the University of Turku in Finland was able to design the molecule after discovering that a protein, NOS1AP, that is downstream of nNOS, triggers several biological pathways that are associated with abnormal glutamate signaling, including neuropathic pain.

The Indiana University group demonstrated that an experimental molecule designed by the Turku group to prevent nNOS signalling to NOS1AP reduced two forms of neuropathic pain in rodents. These forms of pain develop as result of either chemotherapeutic agent paclitaxel or nerve damage.

The treatment also disrupted markers of nociceptive signaling in the spinal cord when the test drug was injected at that site into mice. Importantly, the NOS1AP inhibitor did not cause typical motor side effects observed with previous experimental molecules that directly target NMDARs.

– Importantly, the chemical that prevents this signalling did not cause the negative side effects observed in previous experiments. Our studies suggest that the nNOS-NOS1AP interaction site is a previously unrecognized target for pain therapies,” says Professor Andrea Hohmann from the Indiana University in Bloomington.

The results suggest that the protein NOS1AP might be a valuable novel target in the development of more effective medicines to treat neuropathic pain.

“NOS1AP should be studied in more detail to find the best way to prevent this protein from contributing to chronic pain,” said Senior Researcher Michael Courtney from the University of Turku.

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Materials provided by University of Turku. Note: Content may be edited for style and length.

Prof. Peter Physick-Sheard and a team of researchers examined 1,713 cases of racehorse deaths from 2003 to 2015, and found racing was connected to some of the deaths.

“The study reveals parallels between mortality and the intensity of the overall management of the horses, their lifestyle and the type of work they do,” said Physick-Sheard, Department of Population Medicine. “Training and racing at top speed within a short amount of time and space is a health risk for horses, as it would be for any other species, including humans.”

Most racing in North America involves intense exertion over a relatively short distance, he added.

Published recently in the Equine Veterinary Journal, the study is the first of its kind to compare mortality in three racing breeds, and represents the most complete data set on the issue so far.

With the support of Ontario’s racing regulatory body, the Alcohol and Gaming Commission, researchers analyzed race and trial run data from the Ontario horse racing industry. A provincial registry of racehorse mortality requires mandatory reporting of all deaths occurring within 60 days of a race or trial run.

“The industry is committed to using scientific research to mitigate health risks to animals, and this new research definitely holds insights that will help in that effort,” said Physick-Sheard.

His study aimed to characterize and quantify exercise-associated mortality in racehorses and identify breed differences.

Physick-Sheard said breed differences provide deeper insights into strategies that could reduce mortality, improve the welfare of racehorses and reduce the costs of participation in the sport.

He discovered that thoroughbreds had the highest exercise-associated mortality rate and risk. Out of every 1,000 races, 2.27 deaths were exercise-associated. About one per cent of racing thoroughbreds die annually in association with racing or trial runs.

The mortality rate and risk were lowest for standardbreds, at 0.28 deaths per 1,000 race starts, and an annual death rate of 0.23 to 0.24 per cent. This breed is given more extensive training preparation and racing, said Physick-Sheard.

Mortality related to high-intensity exercise in quarter horses was 1.49 deaths per 1,000 race starts, with an annual death rate of 0.60 to 0.69 per cent from the activity.

For all breeds, musculoskeletal injury was the major contributing cause of mortality.

Thoroughbreds and quarter horses also succumbed to dying suddenly and accidents.

“The industry has characteristics revealed by this data that point at mechanisms that could be used to significantly reduce mortality,” said Physick-Sheard. “You can use carefully targeted strategies to reduce risk and increase the safety of the sport, something to which the Ontario and the global racing industries are devoting a lot of time and energy.”

The study revealed that the sex of standardbreds strongly affects mortality risk, with young stallions at higher risk than mares or geldings. Among older horses, geldings have higher risk than males.

Thoroughbred stallions face higher risk than standardbred stallions.

Training strategies could be modified to address the animal welfare and economic implications, said Physick-Sheard.

“It is possible that the very behavioural attributes traditionally seen as conferring a competitive advantage may have an overall negative impact.”

The findings allow the industry to monitor and assess changes in management and racing practices, he said. Structural factors within the horseracing industry can be addressed through rule changes, knowledge and education, Physick-Sheard added. But the characteristics of the individual horse breeds also play a significant role in mortality risks and need to be considered.

“We’re starting to focus more on the things that are potentially inherent to the breeds of horse, as opposed to characteristics of the work they perform,” Physick-Sheard said. “As we get more insight into those horse factors, we become more aware of other influences that are possible causes of increased mortality risk.”

Superconductors are key to a range of exciting potential applications. For example, zero resistivity promises loss-free power transmission and powerful electromagnets. The challenge has been to discover a material that retains this property at higher temperatures, closer to ambient temperatures. Despite focused work and a number of breakthroughs in recent years, the hunt is still on for effective strategies to create new superconducting materials.

One strategy is the use of layered materials with a molecular structure consisting of alternating superconducting layers and “blocking layers” acting as insulating spacers. A team led by Associate Professor Yoshikazu Mizuguchi from the Department of Physics, Tokyo Metropolitan University, has uncovered an important aspect of designing the insulating layer. They were able to combine five different rare earth (RE) elements, lanthanum, cerium, praseodymium, neodymium, and samarium, and create a “high entropy alloy” in the blocking layer. High entropy alloys have attracted considerable attention in recent years for their toughness, resistance to fatigue and ductility, amongst many other notable physical properties.

The team’s new materials, with different proportions of REs (10-30%), exhibited enhanced superconducting properties; in particular, materials with the same period in their molecular structure exhibited a superconducting transition at higher temperatures when the blocking layer contained a high entropy alloy. They believe that the high entropy alloy helps to stabilize the crystal structure of the superconducting layer.

The work’s impact is not limited to the new materials they present. Given the existence of a large number of superconducting layers which are compatible with RE oxides, this innovation opens the way for a broad new strategy for engineering new, revolutionary superconducting materials.

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Materials provided by Tokyo Metropolitan University. Note: Content may be edited for style and length.

As vegetation in and around bodies of water continues to change, with forest cover being lost while global warming causes wetland plants to thrive, the many lakes of the northern hemisphere — already a major source of methane — could almost double their emissions in the next fifty years.

The researchers say that the findings suggest the discovery of yet another “feedback loop” in which environmental disruption and climate change trigger the release of ever more greenhouse gas that further warms the planet, similar to the concerns over the methane released by fast-melting arctic permafrost.

“Methane is a greenhouse gas at least twenty-five times more potent than carbon dioxide. Freshwater ecosystems already contribute as much as 16% of the Earth’s natural methane emissions, compared to just 1% from all the world’s oceans,” said study senior author Dr Andrew Tanentzap from the University of Cambridge’s Department of Plant Sciences.

“We believe we have discovered a new mechanism that has the potential to cause increasingly more greenhouse gases to be produced by freshwater lakes. The warming climates that promote the growth of aquatic plants have the potential to trigger a damaging feedback loop in natural ecosystems.”

The researchers point out that the current methane emissions of freshwater ecosystems alone offsets around a quarter of all the carbon soaked up by land plants and soil: the natural ‘carbon sink’ that drains and stores CO2 from the atmosphere.

Up to 77% of the methane emissions from an individual lake are the result of the organic matter shed primarily by plants that grow in or near the water. This matter gets buried in the sediment found toward the edge of lakes, where it is consumed by communities of microbes. Methane gets generated as a byproduct, which then bubbles up to the surface.

Working with colleagues from Canada and Germany, Tanentzap’s group found that the levels of methane produced in lakes varies enormously depending on the type of plants contributing their organic matter to the lake sediment. The study, funded by the UK’s Natural Environment Research Council, is published today in the journal Nature Communications.

To test how organic matter affects methane emissions, the scientists took lake sediment and added three common types of plant debris: deciduous trees that shed leaves annually, evergreen pine-shedding coniferous trees, and cattails (often known in the UK as ‘bulrushes’) — a common aquatic plant that grows in the shallows of freshwater lakes.

These sediments were incubated in the lab for 150 days, during which time the scientists siphoned off and measured the methane produced. They found that the bulrush sediment produced over 400 times the amount of methane as the coniferous sediment, and almost 2,800 times the methane than that of the deciduous.

Unlike the cattail debris, the chemical makeup of the organic matter from trees appears to trap large quantities of carbon within the lake sediment — carbon that would otherwise combine with hydrogen and get released as methane into the atmosphere.

To confirm their findings, the researchers also “spiked” the three samples with the microbes that produce methane to gauge the chemical reaction. While the forest-derived sediment remained unchanged, the sample containing the bulrush organic matter doubled its methane production.

“The organic matter that runs into lakes from the forest trees acts as a latch that suppresses the production of methane within lake sediment. These forests have long surrounded the millions of lakes in the northern hemisphere, but are now under threat,” said Dr Erik Emilson, first author of the study, who has since left Cambridge to work at Natural Resources Canada.

“At the same time, changing climates are providing favourable conditions for the growth and spread of aquatic plants such as cattails, and the organic matter from these plants promotes the release of even more methane from the freshwater ecosystems of the global north.”

Using species distribution models for the Boreal Shield, an area that covers central and eastern Canada and “houses more forests and lakes than just about anywhere on Earth,” the researchers calculated that the number of lakes colonised by just the common cattail (Typha latifolia) could double in the next fifty years — causing current levels of lake-produced methane to increase by at least 73% in this part of the world alone.

Added Tanentzap: “Accurately predicting methane emissions is vital to the scientific calculations used to try and understand the pace of climate change and the effects of a warmer world. We still have limited understanding of the fluctuations in methane production from plants and freshwater lakes.”