Tech

Tiny thermometer measures how mitochondria heat up the cell by unleashing proton energy

image: Illinois researchers developed a tiny thermometer probe, left, that can quickly take temperatures inside of a cell, outlined with a dotted line for better visibility.

Image: 
Manjunath Rajagopal

CHAMPAIGN, Ill. -- Armed with a tiny new thermometer probe that can quickly measure temperature inside of a cell, University of Illinois researchers have illuminated a mysterious aspect of metabolism: heat generation.

Mitochondria, the cell's power stations, release quick bursts of heat by unleashing the power stored in an internal proton "battery," the researchers found. Better understanding of this process could point to new targets for treating obesity and cancer, they say.

Led by mechanical science and engineering professor Sanjiv Sinha, they published their findings in the Nature journal Communications Biology.

"Producing heat is part of the mitochondria's role in the center of metabolism activity," Sinha said. "It needs to produce the energy currency that's used for the activities in the cell, and heat is one of the byproducts, in most cases. But there is a mechanism that can ramp this process up to produce more heat when the body needs it. That's what fat cells do when they're in need of heat when the body's temperature goes down."

To better understand this ramping up of heat output, the researchers developed a tiny, fast-read thermometer probe to internally measure temperature inside of living cells. The mechanical design proved challenging: It had to be long enough to reach a cell under a microscope, but small enough in diameter not to harm the cell or disrupt its internal processes.

"Think about how we take temperature with a probe under our tongue. We are essentially doing the same, but inside a single cell," Sinha said. "And we wanted to be very fast to measure what's happening. Things happen inside the cell very quickly. It's like, if you're taking a young child's temperature, you need to do it very quickly, or they will move and it won't be accurate."

Sinha's group collaborated with researchers from the lab of Rhanor Gillette, a professor emeritus of molecular and integrative physiology at Illinois, to test the probe in a mitochondria-rich strain of neurons. They induced the mitochondria to produce heat using methods established by previous work, but they were startled by the very fast changes in temperature that the probe was able to measure.

"We found some results that were completely different from what has been published before," said Manjunath Rajagopal, a graduate student and first author of the study. "We saw a sharp temperature spike that is significantly large and short-lived - around 5 degrees Celsius and less than one second. The gold standard for measuring has been with fluorescence, but it is too slow to see this short, high burst of heat. Just with a simple probe measuring at high speed, we have demonstrated that we can find things that other methods have missed."

Researchers previously assumed that increased heat output from the mitochondria came from increased breaking down of glucose, but the heat spikes that Sinha's group measured were too high.

"It cannot be releasing that kind of energy from metabolizing stored glucose. It just didn't make sense," Sinha said. "Where is it coming from? There has to be a source of that energy."

The researchers determined that the energy spike was consistent with the discharging of a cellular battery powered by protons. They verified this by inducing similar temperature spikes with special molecules that open up protein channels in the mitochondria's membrane.

"In the mitochondria, one part of the glucose metabolism reaction stores some of the energy as a proton battery. It pushes all the protons to one side of a membrane, which creates an energy store," Rajagopal said. "We basically short-circuited the stored energy."

The researchers plan to use the temperature probe to study the mitochondria short-circuiting process in other cell lines, with the aim of identifying therapeutic targets. For example, fat cells have naturally occurring proteins that open the proton gates to unleash stored proton energy. Sinha's group would like to collaborate with biologists to study how the process naturally occurs in fat cells when heat is needed - when the body's temperature drops, for example - and whether the proton-unleashing proteins can be targeted as a treatment for obesity.

"Cancer would be another application," Rajagopal said. "Cancer cells have a variety of reprogrammed metabolic pathways that are often driven to extremes. This probe provides us a tool to study thermal activity associated with different metabolic pathways."

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

Flathead Bio Station researcher helps uncover ocean iron level mystery

image: Matthew Church, a researcher with the University of Montana's Flathead Lake Biological Station, helped discover why phosphorus and iron levels fluctuate in part of the Pacific Ocean.

Image: 
UM photo

POLSON, MONTANA - The middle of the Earth's oceans are filled with vast systems of rotating currents known as subtropical gyres. These regions occupy 40% of the Earth's surface and have long been considered remarkably stable biological deserts, with little variation in chemical makeup or the nutrients needed to sustain life.

However, there exists a strange anomaly in the North Pacific Subtropical Gyre ecosystem that has puzzled scientists for years. In this region that occupies the Pacific Ocean between China and the United States, the chemistry changes periodically. There's a particularly notable fluctuation in the levels of phosphorus and iron, which affects the overall nutrient composition and ultimately impacts biological productivity.

In a new study published in the Proceedings of the National Academy of Sciences, a group of researchers uncovered the reason behind these variations in the North Pacific Subtropical Gyre ecosystem. The group includes Matthew Church, a microbial ecologist with the University of Montana's Flathead Lake Biological Station, as well as Oregon State University's Ricardo Letelier and the University of Hawaii's David Karl, among others.

"Variations in ocean climate appear to regulate iron supply, altering the types of plankton growing in these waters, which ultimately controls ocean nutrient concentrations," Church said. "My laboratory has worked on questions related to the role of plankton in controlling ocean nutrient availability for many years, and this study places much of that work in context. As a result of sustained, long-term observations, our work confirms how tightly coupled plankton biology is to the supply of nutrients, specifically iron, delivered from the atmosphere."

Using three decades of observational data from Station ALOHA, a six-mile area in the Pacific Ocean north of Hawaii dedicated to oceanographic research, the team discovered that the periodic shift in iron levels result from iron input from Asian dust, accounting for the chemical variances and providing varying amounts of nutrients to sustain life.

The key to the variance is the Pacific Decadal Oscillation, an ocean-atmosphere relationship that varies between weak and strong phases of atmospheric pressure in the northeast Pacific Ocean.

In years when the low pressure weakens in the northeast Pacific, winds from Asia become stronger and move in a more southern direction. This brings more dust from the Asian continent, "fertilizing" the ocean surrounding Station ALOHA. When the pressure strengthens, the opposite occurs.

The supply of nutrients is a fundamental regulator of ocean productivity, and phosphorous and iron are key components for life. Typically, the ocean's upper water column is fertilized by nutrient-rich water mixing up from the deep. This is a difficult process in the North Pacific Subtropical Gyre ecosystem because the waters are very stratified and little mixing actually takes place.

When strong Asian winds bring in significant amounts of iron, organisms are allowed to grow and use phosphorus in the upper layers of the ocean. When Asian winds weaken and iron input is reduced, organisms are forced to return to a deep-water-mixing nutrient delivery system. This creates the periodic ebb and flow of iron and phosphorus levels in the North Pacific Gyre.

Church said the findings from this study emphasize the critical need to include both atmospheric and ocean circulation variability when forecasting how climate change might impact ocean ecosystems.

"It reaffirms the need to think about how tightly connected plankton biology is to changes in climate and ultimately also to changes in land use, which can directly impact dust supply to the sea," he said.

As Earth's temperature continues to warm, researchers expect to see long-term changes in wind patterns across the North Pacific. The evolution of land use and pollution driven by human activity in Asia also will affect the sources and magnitude of iron and other nutrients carried by wind across the ocean.

Further research is needed to better understand how these changes ultimately will impact ecosystems in this ocean region, as well as others around the world.

Credit: 
The University of Montana

Blue Brain finds how neurons in the mouse neocortex form billions of synaptic connections

video: Researchers at EPFL's Blue Brain Project, a Swiss brain research Initiative have combined two high profile, large-scale datasets to produce something completely new - a first draft model of the rules guiding neuron-to-neuron connectivity of a whole mouse neocortex.

Image: 
Blue Brain Project / EPFL

** Identifying the connections across all neurons in every region of the neocortex **

The structure of synaptic connections between neurons shapes their activity and function. Measuring a comprehensive snapshot of this so-called connectome has so far only been accomplished within tiny volumes, smaller than the head of a pin. For larger volumes, the long-range connectivity, formed by bundles of extremely thin but long fibers, has only been studied for small numbers of individual neurons, which is far from a complete picture. Alternatively, it has been studied at the macro-scale, a 'zoomed-out' view of average features that does not provide single-cell resolution.

In a paper published in Nature Communications, the Blue Brain researchers have shown that the trick lies in combining these two views. By integrating data from two recent datasets - the Allen Mouse Brain Connectivity Atlas and Janelia MouseLight - the researchers identified some of the key rules that dictate which individual neurons can form connections over large distances within the neocortex. This was possible because the two datasets complemented each other in terms of entirety of the neocortex and the cellular resolution provided.

** Emergence of a surprisingly complex structure at single-cell resolution **

Building on their previous work in modelling local brain circuits, the researchers were then able to parameterize these principles of neocortical connectivity and generate statistical connectome instances compatible with them. When they studied the resulting structure, they found something fascinating; at cellular resolution, a surprisingly complex structure that had so far only been seen between neighboring neurons now also tied together neurons in different regions and at opposite ends of the brain. This was comparable to a rule of self-similarity that has been previously found in the human brain (MRI data) and predicts that it extends all the way down to the level of individual neurons.

"This made me re-think how I think about these long-range connections", reveals lead researcher Michael Reimann. "They have been depicted as these blunt cables, connecting or synchronizing whole brain regions. But maybe there is more to them, more specific targeting of individual neurons. And this is what we learned from just a few, relatively course-grained principles. I expect that with improved methods we will find more in the future."

** Openly accessible connectome can serve as a powerful null model to compare experimental findings **

"We have completed such a first-draft connectome of mouse neocortex by using an improved version of our previously published circuit building pipeline (Markram et al., 2015)," explains Michael Reimann. "It has been improved to place neurons in brain-atlas defined 3d spaces instead of hexagonal prisms, taking into account the geometry and cellular composition of individual brain regions. The composition was based on data from the open source Blue Brain Cell Atlas. Further constraints were derived from other openly accessible datasets. Additional constraints that are so far unknown are likely to limit long-range connectivity even more. To start a process of iterative refinement, we made the model and data available to the public. The parameterized constraints on projection strength, mapping, layer profiles and individual axon targeting (i.e. the projection recipe), as well as stochastic instantiations of whole-neocortex micro-connectomes can be found under https://portal.bluebrain.epfl.ch/resources/models/mouse-projections".

This openly accessible connectome can serve as a powerful null model to compare experimental findings to and as a substrate for whole-brain simulations of detailed neural networks. Sparse connection matrices of several instances of the predicted null model of neocortical long-range connectivity have also been publicly available as this result actively demonstrates the power of making datasets available to the public.

** Further advancing the case for Simulation **

The simulation (in-silico) method allowed the scientists to target volumes several orders of magnitude smaller, than would be possible with experimental methods (G?m?nut et al., 2018), right down to the innervation of individual neurons with sub-cellular resolution. Going forward, this will allow the simulation of the electrical activity of individual neurons, entire regions or of the entire neocortex.

"This paper builds upon Blue Brain's earlier work on evaluating morphological constraints on connectivity, 'Morphological Diversity Strongly Constrains Synaptic Connectivity and Plasticity', (Cerebral Cortex, 2017) and 'Reconstruction and Simulation of Neocortical Microcircuitry' (Cell 2015) explains Blue Brain Founder and Director Prof. Henry Markram. "The findings enable us continue our simulation experiments at an exponentially increasing rate meaning, we can now build biologically accurate brain models of bigger and bigger brain regions and at a higher and higher resolution thereby further advancing the case for simulation".

Credit: 
Ecole Polytechnique Fédérale de Lausanne

Biochar: A better start to rain forest restoration

image: Picture of the Early successional species (Guazuma crinita Mart) before transplant, as received by the tree nursery.

Image: 
David Lefebvr

An indigenous farming technique that's been around for thousands of years provides the basis for restoring rain forests stripped clear of trees by gold mining and other threats.

A carbon-based soil amendment called biochar is a cheap and effective way to support tree seedling survival during reforestation efforts in the Amazon rain forest, according to new research from Wake Forest University's Center for Amazonian Scientific Innovation (CINCIA).

Restoring and recovering rain forests has become increasingly important for combatting climate change, since these wide swaths of trees can absorb billions of tons of carbon dioxide each year. The problem is particularly acute in areas mined for alluvial gold deposits, which devastate not only rain forest trees but also soils. High costs can be a huge barrier to replanting, fertilizing and nurturing trees to replace those lost in the rain forest.

The scientists found that using biochar combined with fertilizer significantly improved height and diameter growth of tree seedlings while also increasing the number of leaves the seedlings developed. The experiment, based in a Peruvian Amazon region called Madre de Dios, the heart of illegal gold mining trade in that country, used two tropical tree species: the fast-growing Guazuma crinita and Terminalia amazonia, a late successional tree often used as timber.

"The most difficult period in a tree seedling's life is the first few months after transplanting," said Miles Silman, CINCIA associate director of science and Wake Forest's Andrew Sabin Presidential Chair of Conservation Biology. "But just a little bit of biochar does wonderful things to the soil, and it really shines when you add organic fertilizer."

The CINCIA scientists make biochar out of Brazil nut husks discarded by large-scale processors in Peru. They burn the husks slowly in 55-gallon barrels, a low-tech, inexpensive and easily scalable method for producing biochar.

The study, "Biochar effects on two native tropical tree species and its potential as a tool for reforestation," appears online this month in the peer-reviewed journal Forests. Until this study, little was known about whether biochar could benefit tree growth in tropical tree seedlings.

"We show that while both biochar and fertilizer can improve tree seedling growth, combining them makes seedlings thrive beyond either amendment alone," said Silman.

The native peoples of the Amazon created "dark earths" using biochar thousands of years ago, and those soils are still productive today.

Biochar's benefits are many:

It improves the soil's ability to hold water and makes it less acidic.

It provides a welcoming habitat for microbes, which support plant growth.

It holds onto fertilizer and releases it over time, decreasing the need for repeat applications of fertilizer, which cuts labor and supply costs.

The scientists used soils recovered from the San Jacinto native community, where gold mining has ravaged the land. Silman explained that the dirt that comes from the mining sluice is devoid of the organic matter and microbes that supports plant life.

"These are the kinds of landscapes we have to recover, and we are still trying to determine how to grow plants in them," he said. "This soil is extremely limiting for natural regrowth, but treating them with biochar turns it into something that plants can grow in. That's good for biodiversity and good for the people that have to make a living from the land."

Credit: 
Wake Forest University

How visceral leishmaniasis spread through central-Southern Brazil

image: Dog with visceral leishmaniasis collected at the Teresina Zoonoses Control Center, State of Piauí, Northeast Brazil, where the disease is endemic.

Image: 
Photo taken by Veterinarian Fernando Oliveira (CC BY 4.0)

The protozoan disease visceral leishmaniasis (VL) has recently expanded to places where it had not previously been reported and has expanded its geographic distribution within countries where it was already endemic. Now, researchers writing in PLOS Neglected Tropical Diseases describe three dispersion routes that have moved Leishmania infantum into and through central-Southern Brazil, helping shed light on the overall mechanisms of VL dispersal.

Currently, 1.69 billion people are estimated to be living in VL transmission areas worldwide and 90% of VL cases occurred in six countries, including Brazil. Between 1920 and 1980, VL was restricted to rural areas in Northeast Brazil, however the disease then spread to urban areas in other regions of the country. The dispersal of the protozoan is poorly understood, and in 2012, the parasite was reported in the western region (Foz do Iguaçu) of Paraná state, far from the epidemic regions. Foz do Iguaçu is one of the main touristic destinations in Brazil.

In the new work, Vanete Thomaz-Soccol, of Universidade Federal do Paraná (UFPR), and colleagues genetically analyzed 132 isolates from dogs, humans and sand flies collected in central-Southern Brazil. In addition, historical records of VL cases in central-Southern Brazil were collected by searching publically available literature databases for relevant publications.

The researchers describe three dispersion routes that have likely carried VL into central-Southern Brazil--dispersion from Bolivia via the Bolivia-Brazil gas pipeline from 1998 to 2005, dispersion from Paraguay after 2012, and emergence of a new cluster in western Santa Catarina State in 2013 and its dispersion to southern Paraná State. The routes help highlight risk factors for the dispersion of L. infantum, including the lack of joint policies with countries bordering Brazil.

"Understanding how VL has dispersed is vital to the development of control measures for this disease and to avoid future dispersion events," the researchers say. "Our results highlight the need for the development of plans that efficiently avoid the dispersion of VL in the central-southern Brazil that includes monitoring of this diseases and joint policies with countries bordering this Brazilian region."

Credit: 
PLOS

Maleness-on-the-Y: A novel male sex determiner in major fruit fly pests

Becoming a male Mediterranean fruit fly relies on the newly identified Y-chromosome linked gene - Maleness-on-the-Y (MoY) - which encodes the small protein required to signal male sex determination during development, a new study shows. According to the report, the Y-linked master gene is conserved in several other major fruit fly pests, such as the olive fruit fly and the invasive oriental fruit fly, suggesting it could serve as an important genetic target in efforts to develop more effective gene drive-based pest controls. The globally distributed Mediterranean fruit fly (Ceratitis capitate, or medfly) is widely considered to be one of the most destructive agricultural pests worldwide. While genetic control strategies are useful in suppressing wild medfly populations, a lack of understanding concerning sex determination of the species at the genetic level has limited the effectiveness of similar control strategies in other important Tephritidae pests. Angela Meccariello and colleagues report the discovery of the Y-linked M factor, responsible for activating male sex determination in the medfly. Meccariello et al. show that silencing or disrupting the MoY function in male XY embryos led to the development of fertile females, whilst overexpression of the gene produced fertile males from female XX embryos. What's more, crosses of transformed XY females and transformed XX males yielded offspring, and of both sexes. This indicates that a masculinizing Y chromosome can be transmitted through female meiosis to produce fertile progeny. According to the results, the MoY gene is functionally conserved in other Tephritidae species, which demonstrate similar sex-transformations upon genetic manipulation of the M factor. The discovery of MoY is an important step towards developing strategies to control the destructive members of this particular fly family.

Credit: 
American Association for the Advancement of Science (AAAS)

NASA tracks Tropical Storm Podul's landfall approach to Vietnam

image: On Aug. 29, 2019 at 2 a.m. EDT (0600 UTC), the MODIS instrument aboard NASA's Aqua satellite provided a visible image of Podul in the South China Sea. Podul had already started its landfall in central Vietnam and appeared somewhat elongated.

Image: 
NASA/NRL

NASA's Aqua satellite passed over the South China Sea and provided forecasters with a visible image of Tropical Storm Podul as it moved closer to the coast of north and central Vietnam where it is expected to make landfall on August 29.

On Aug. 29, 2019 at 2 a.m. EDT (0600 UTC), the Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Aqua satellite provided a visible image of Podul in the South China Sea. Podul had already started its landfall in central Vietnam and appeared somewhat elongated because northerly winds outside the storm are pushing clouds south of the center.

At 5 a.m. EDT (0900 UTC) on Aug. 29, Tropical storm Podul was centered near 17.8 degrees north latitude and 108.3 degrees east longitude, about 108 nautical miles north of Da Nang, Vietnam. Podul continued moving west and had maximum sustained winds 35 knots (40 mph/65 kph).

The Vietnam National Centre for Hydro-Meteorological Forecasting (NCHMF) is a governmental organization belonging Vietnam Meteorological Hydrological Administration (VMHA) with authority to issue forecasting/warning information for weather, climate, hydrology, water resource, marine weather (i.e. hydrometeorology) and provide hydro-meteorology services. NHCMF has issued a Tropical Storm Warning for central Vietnam with the approach of Podul.

Credit: 
NASA/Goddard Space Flight Center

NASA sees a transitioned, merging Extra-Tropical Storm Erin off US east coast

image: On Aug. 29, 2019 at 2:30 a.m. EDT (630 UTC), the MODIS instrument that flies aboard NASA's Aqua satellite found Erin's strongest thunderstorms (yellow circle) confined to a small area around the center. Cloud top temperatures were as cold as minus 50 degrees Fahrenheit (minus 45.5 degrees Celsius). Storms with colder cloud top temperatures were located far to the north of Erin's center and are associated with the frontal system of which Erin is merging. Those storms had cloud top temperatures as cold as minus 70F degrees (minus 56.6C). Cloud top temperatures that cold indicate strong storms with the potential to generate heavy rainfall.

Image: 
NASA/NRL

Former tropical depression Erin has made the transition into an extra-tropical system off the eastern coast of the U.S. Infrared imagery from NASA's Aqua satellite provided temperature data on storms associated with Erin and the weather system it is merging with.

On Aug. 29 at 2:30 a.m. EDT (630 UTC), the Moderate Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Aqua satellite used infrared light and found strongest thunderstorms associated with Erin where confined to a small area around the center. There, cloud top temperatures were as cold as minus 50 degrees Fahrenheit (minus 45.5 degrees Celsius). Infrared data provides temperature information, and the strongest thunderstorms that reach high into the atmosphere have the coldest cloud top temperatures.

Storms with colder cloud top temperatures were located far to the north of Erin's center and are associated with the frontal system of which Erin is merging. Those storms had cloud top temperatures as cold as minus 70 degrees Fahrenheit (minus 56.6 Celsius). Cloud top temperatures that cold indicate strong storms with the potential to generate heavy rainfall.

Satellite imagery and scatterometer (wind) data indicate that Erin is merging with a frontal system and is now an extratropical low pressure area. On Aug. 30, Erin is expected to be absorbed by a larger extratropical low pressure area over eastern Canada.

When a storm becomes extra-tropical, it means that a tropical cyclone has lost its "tropical" characteristics. The National Hurricane Center defines "extra-tropical" as a transition that implies both poleward displacement (meaning it moves toward the north or south pole) of the cyclone and the conversion of the cyclone's primary energy source from the release of latent heat of condensation to baroclinic (the temperature contrast between warm and cold air masses) processes. It is important to note that cyclones can become extratropical and still retain winds of hurricane or tropical storm force.

At 5 a.m. EDT (0900 UTC), NHC noted that the center of Post-Tropical Cyclone Erin was located near latitude 36.1 degrees north and longitude 71.6 degrees west. That puts the center of Erin about 225 miles (365 km) east-northeast of Cape Hatteras, North Carolina. The post-tropical cyclone is moving toward the north-northeast near 15 mph (24 kph). A turn toward the northeast and a faster forward motion are expected later today, with this motion continuing through Friday. Maximum sustained winds are near 35 mph (55 kph) with higher gusts.

The post-tropical cyclone is expected to strengthen a little on Friday, Aug. 30, before it is absorbed by a larger extratropical low over eastern Canada Friday night.

Credit: 
NASA/Goddard Space Flight Center

Researchers demonstrate first all-metamaterial optical gas sensor

image: The miniature all-metamaterial optical gas sensor (golden capsule) next to a one-cent coin.

Image: 
Alexander Lochbaum, ETH Zurich

WASHINGTON -- Researchers have developed the first fully-integrated, non-dispersive infrared (NDIR) gas sensor enabled by specially engineered synthetic materials known as metamaterials. The sensor has no moving parts, requires little energy to operate and is among the smallest NDIR sensors ever created.

The sensor is ideal for new Internet of Things and smart home devices designed to detect and respond to changes in the environment. It also could find use in future medical diagnostics and monitoring equipment.

A paper explaining these results will be presented at the Frontiers in Optics + Laser Science (FIO + LS) conference, held 15-19 September in Washington, D.C., U.S.A.

"Our sensor design unites simplicity, robustness, and efficiency. Using metamaterials, we can omit one of the main cost drivers in NDIR gas sensors, the dielectric filter, and simultaneously reduce the size and energy consumption of the device," said Alexander Lochbaum from the Institute of Electromagnetic Fields of ETH Zurich, Switzerland, and lead author on the paper. "This makes the sensors viable for high-volume, low-cost markets such as automotive and consumer electronics."

NDIR sensors are among the commercially most relevant types of optical gas sensors, used to assess vehicle exhaust, measure air quality, detect gas leaks and support a variety of medical, industrial and research applications. The new sensor's small size, potentially low cost, and reduced energy requirements open new opportunities for these and other types of applications.

Shrinking the optical pathway

Conventional NDIR sensors work by shining infrared light through air in a chamber until it reaches a detector. An optical filter positioned in front of the detector eliminates all light except the wavelength that is absorbed by a particular gas molecule so that the amount of light entering the detector indicates the concentration of that gas in the air. Though most NDIR sensors measure carbon dioxide, different optical filters can be used to measure a wide range of other gases.

In recent years, engineers have replaced the conventional infrared light source and detector with microelectromechanical systems (MEMS) technology, miniscule components that bridge between mechanical and electrical signals. In the new work, researchers integrate metamaterials onto a MEMS platform to further miniaturize the NDIR sensor and dramatically enhance the optical path length.

Key to the design is a type of metamaterial known as a metamaterial perfect absorber (MPA) made from a complex layered arrangement of copper and aluminum oxide. Because of its structure, MPA can absorb light coming from any angle. To take advantage of this, the researchers designed a multi-reflective cell that "folds" the infrared light by reflecting it many times over. This design allowed a light absorption path about 50 millimeters long to be squeezed into a space measuring only 5.7 × 5.7 × 4.5 millimeters.

Whereas conventional NDIR sensors require light to pass through a chamber a few centimeters long to detect gas at very low concentrations, the new design optimizes light reflection to accomplish the same level of sensitivity in a cavity that is just over half a centimeter long.

A simple, robust, and low-cost sensor

By using metamaterials for efficient filtering and absorption, the new design is both simpler and more robust than existing sensor designs. Its main parts are a metamaterial thermal emitter, an absorption cell, and a metamaterial thermopile detector. A microcontroller periodically heats up the hotplate, causing the metamaterial thermal emitter to generate infrared light. The light travels through the absorption cell and is detected by the thermopile. The microcontroller then collects the electronic signal from the thermopile, and streams the data to a computer.

The primary energy requirement comes from the power needed to heat the thermal emitter. Thanks to the high efficiency of the metamaterial used in the thermal emitter, the system works at much lower temperatures than previous designs, so less energy is needed for each measurement.

The researchers tested the device's sensitivity by using it to measure varying concentrations of carbon dioxide in a controlled atmosphere. They demonstrated it can detect carbon dioxide concentrations with a noise-limited resolution of 23.3 parts per million, a level on par with commercially available systems. However, to do this the sensor required only 58.6 millijoules of energy per measurement, about a five-fold reduction compared to commercially available low-power thermal NDIR carbon dioxide sensors.

"For the first time, we realize an integrated NDIR sensor that relies exclusively on metamaterials for spectral filtering. Applying metamaterial technology for NDIR gas sensing allows us to rethink the optical design of our sensor radically, leading to a more compact and robust device," said Lochbaum.

Credit: 
Optica

Crouching lion, hidden giraffe

image: Groups of giraffes in Tanzania

Image: 
Wild Nature Institute

The behavior of giraffe groups with calves is influenced more strongly by the risk of predators than is the behavior of all-adult groups, which is mostly determined by the availability of food. An international team of researchers from Penn State and the University of Zürich studied giraffe behavior in a 2,000 square kilometer region of Africa and pinpointed some of the special requirements needed by mother giraffes to keep their babies safe. A paper describing the research, which can help land managers to protect the habitats most important for giraffes, appears online in the journal Oecologia.

"Like all herbivores, giraffes need to find quality food to survive, but also need to avoid lions, or at least see them coming," said Monica Bond, PhD candidate from the University of Zürich and lead author of the paper. "Giraffes in our huge, unfenced study area can choose from among many different places to spend their time--places with different kinds of trees and bushes, places deep inside protected parks, or places closer to farming towns or ranchlands where people live. There are lots of options in this landscape, including fewer lions outside the parks versus inside. So, we wondered how do these options influence giraffe grouping behavior?"

The study found that groups composed of only adult giraffes were food-focused and not affected by predation risk. These adult groups formed the largest groups--up to 66 individuals--in the rainy season when food is plentiful, but formed smaller groups during the dry season when food is harder to find. In contrast, predation risk was a very important factor influencing groups of giraffes with calves.

"Giraffe calves are vulnerable to being killed by lions and other carnivores, while adults are typically large enough to escape predation," said senior author Barbara König, professor at the University of Zürich. "We were testing hypotheses about mother and calf behavior to see if their strategy was for calves to hide in thick bushes to avoid predators, be in the open to see predators coming, or be in large groups for many eyes and lower individual risk."

The researchers showed that in areas with the most lions, groups with calves were found more often in dense bushes than in open grasslands, and that those groups were smaller in size. This observation supports the idea that giraffe mothers and calves have a strategy of hiding in dense bushes, rather than staying in open areas to better see lions or gathering in large groups to dilute the predation risk. Dense bushlands are therefore important habitat for giraffe calves that the researchers suggest should be protected. Some cattle ranchers promote shrub removal to encourage grass for their livestock, but this thinning of brush could be detrimental to giraffes and other animals that share the rangelands.

The study also explored the influence of humans on giraffe grouping behaviors.

"Outside the parks, the human population has been rapidly expanding in recent years," said Derek Lee, associate research professor of biology at Penn State and co-author of the study. "Therefore, we felt it was important to understand how human presence affected grouping behavior, as natural giraffe habitat is ever-more dominated by people."

Interestingly, adult females with calves were more likely to be found closer to traditional pastoralist compounds called bomas, made by livestock-keeping, non-farming people.

"We suspect this is because the pastoralists may disrupt predator behaviors to protect their livestock and this benefits the giraffe calves," said Lee.

Conversely, groups with calves avoided areas close to the larger towns of farming people, suggesting a difference between traditional bomas versus more densely populated human settlements for giraffe mothers seeking food and safety for themselves and their calves.

"We were happy to find that traditional human settlements by ranchers appear to be compatible with the persistence of giraffe populations," said Bond. "But on the other hand, disturbances around towns likely represent a threat and should be limited in areas favored by giraffes. Masai giraffes are the world's tallest herbivores and are beloved by people around the globe, but they were recently classified as an endangered species by the International Union for Conservation of Nature (IUCN). The data in this study can help us know what places are most important for these magnificent animals."

Credit: 
Penn State

Immortalised blood cell lines enable new studies of malaria invasion

Researchers[1] at the University of Bristol and Imperial College London have established a new model system that uses red blood cells grown in the laboratory to study how malaria parasites invade red blood cells.

The work, which was funded by the National Institute for Health Research and NHS Blood and Transplant and is published in Nature Communications, provides a powerful new research tool for the identification of key host proteins and their domains that are involved in parasite infection. It will facilitate attempts to understand and disrupt the mechanism of red blood cell invasion by malaria parasites.

The scientists used a cell line recently developed in Bristol which can produce unlimited numbers of immature 'progenitor cells' that can be pushed to produce new red blood cells (reticulocytes) in the laboratory. Using these cells, they were able to show that red blood cells generated using this technique can support both invasion by and intracellular development of Plasmodium falciparum, the malaria parasite that is responsible for around 200 million new infections and half a million deaths per year worldwide.

By using CRISPR-Cas9 to edit the genome of the immature cells, the team were also able to remove a protein called basigin that is important for invasion and normally present on the surface of red blood cells and show that the reticulocytes generated from this edited line were completely resistant to invasion. Reintroducing the basigin gene into the edited cells restored invasion to normal levels. This important work shows that these cells can be used to remove and replace different red blood cell proteins and assess how their absence or alteration affects the ability of the parasite to successfully invade.

Dr Tim Satchwell, lead author of the study at the University of Bristol said:

"The ability to alter protein expression in the red blood cell and study the effect that these changes have on parasite invasion or development is hugely exciting. This system has opened up many new potential avenues of research that should allow us to better understand the mechanism by which the malaria parasite is able to successfully invade the red blood cell, and the specific roles that host cell proteins play in this process."

Dr Ashley Toye - one of the senior authors on the study and Director of the NIHR Blood and Transplant Research Unit said:

"This work has shown that it is now possible to manipulate the red blood cell surface to better understand the process of malaria invasion. It also shows that our reticulocytes produced from the cell line are recognised by the parasite just the same as reticulocytes produced in the body. This is important as it provides further evidence that the cells are manufactured correctly in the laboratory."

Dr Nick Watkins, Assistant Director - Research and Development at NHS Blood and Transplant, said:

"This demonstration of reticulocytes derived from cell lines supporting malaria invasion will provide an important new tool to better understand how the malaria parasite invades red blood cells. Ultimately, we hope that this work will lead to the development of new therapeutic strategies for malaria."

Credit: 
University of Bristol

Changes in ice volume control seabed methane emissions

image: The manipulator arm of the ROV Ægir 6000 samples seep carbonates from the seabed at 1200 m water depth, off western Svalbard.

Image: 
NORCRUST

Ice sheet dynamics of the past likely caused fault movements in the Earth's crust, resulting in seabed methane release in ~1200 m water depth offshore Svalbard, an archipelago in the Norwegian Arctic.

- Our results show similar patterns over the last two ice ages, from 160,000 years ago through today. The new data suggest a link between changing continental ice volumes and deep-sea methane emission in the Arctic, says Tobias Himmler, researcher at the Geological Survey of Norway (NGU) and principle author of the study.

Seabed and sub-seabed samples reveal the past

Researchers from NGU and the Center for Arctic Gas Hydrate, Environment and Climate (CAGE) at UiT The Arctic University of Norway in Tromsø; participated in two research expeditions connected to this project in the summer of 2016.

During the first expedition aboard research vessel G.O. Sars, samples were collected from the seabed at the Vestnesa Ridge off western Svalbard at ~1200 meter water depth using the remotely operated vehicle (ROV) Æegir 6000.

A second expedition to the same location took place some weeks later aboard research vessel Maria S. Merian, bringing with it the MARUM-MeBo70 deep sea drilling rig. This time, researchers were able to obtain several 10+ m long sediment cores for further study.

Seep carbonates were collected from the seabed with the help of the ROV, while more were also found within the MeBo core samples drawn from below the seabed.

The seep carbonates resulted from the sediment cementation that occurred when methane migrated up from deep below and became oxidized by methane-consuming microbes near the seabed.

- Seep carbonates serve as geological archives of past seabed methane emissions, says Himmler.

Multiple episodes of methane emission revealed

After measuring the amounts of radioactive isotopes uranium and thorium found in the seep carbonates, scientists at the British Geological Survey were able to calculate the ages of the carbonate pieces. This data reveals three separate 10,000- to 20,000-year long methane emission episodes over the last 160,000 years. Methane was released when thick ice sheets moved in to cover Svalbard and the Barents Sea area, and later after the ice diminished.

- During ice sheet growth, the extra weight of the ice presses the Earth's crust downward. Following the melting of the ice, the crust rises again. Our data indicate that methane off western Svalbard emanated from the seabed primarily when ice sheet movements activated faults. How much methane was emitted, however, we don't know, explains Himmler.

Previous research has shown that methane emissions have occurred consistently since the last ice age, beginning about 23,000 years ago. Scientists from NGU and CAGE have now managed to -literally- drill further back in time using the MARUM's MeBo70 sea floor drill rig. The drilled seep carbonate samples reveal that there have been at least two older methane emission episodes in the past, between about 160,000 to 133,000 years and 50,000 to 40,000 years ago.

- Ice sheet dynamics is a new factor when considering the natural drivers of deep-sea methane release in the Arctic, says Tobias Himmler.

The research project "Norwegian margin fluid systems and methane-derived carbonate crusts" (NORCRUST) is funded by the Norwegian Research Council through the Petromaks2 program. NORCRUST is led by NGU in collaboration with CAGE, the MARUM-Center for Marine Environmental Science, and the British Geological Survey.

Credit: 
UiT The Arctic University of Norway

Scientists explore aged paint in microscopic detail to inform preservation efforts

image: An X-ray microtomography scan of a paint sample (left) shows a random distribution of components in a paint sample, and a zoomed-in view by a technique known as photothermal induced resonance (right) reveals that zinc carboxylates, known as soaps, are not evenly distributed but are intermixed with aluminum stearate (yellow). One type of zinc soap, called zinc stearate, is also shown to form in clusters of nanoparticles (red) near the aluminum stearate cluster. The scale bars are in microns, or millionths of a meter.

Image: 
NIST, Berkeley Lab

Watching paint dry may seem like a boring hobby, but understanding what happens after the paint dries can be key in preserving precious works of art.

The formation of metal soaps in artwork composed with oil paints can cause "art acne" - including pimpling and more severe deterioration - which poses a pressing challenge for art conservation around the globe.

It is affecting the works of Georgia O'Keefe, Vincent Van Gogh, Francisco de Goya, and Jackson Pollock, among many others, and researchers haven't yet found a good solution to stop its effects.

To learn more about the chemical processes involved in aging oil paints in microscopic and nanoscale detail, an international team led by researchers at the National Gallery of Art and the National Institute of Standards and Technology (NIST) conducted a range of studies that included 3D X-ray imaging of a paint sample at the Advanced Light Source (ALS), a synchrotron at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) .

"An estimated 70 percent of oil paintings might already have or will have these metal-soap problems," said Xiao Ma, Charles E. Culpeper Fellow at the National Gallery of Art who was the lead author of the team's study, published in the journal Angewandte Chemie International Edition.

"In our collections we see soaps in the paintings - I would say it's not uncommon," he noted. "They might not already show at the surface, but exist at the 'ground,' or priming layers."

The same damaging chemistry, which previous studies have traced to the mixing of fatty acids with metal ions present in paint pigments including lead, zinc, copper, cadmium, and manganese, has been found occurring in some organic coatings, too, such as those used for bronze sculptures and in industry, Ma noted.

The latest study focused on one paint called "Soft Titanium White" that was painted on a canvas in 1995 by a paint manufacturer. In addition to titanium dioxide (TiO2), it contains zinc oxide (ZnO), which is known to form soaps. Paints like it have been in use since around 1930, Ma said. The aged sample hasn't been treated in any way and has remained in a controlled environment.

The study found that clusters of a compound called aluminum stearate are distributed randomly in the paint, and that zinc carboxylates, known as soaps, are intermixed within them. The high spatial resolution analysis showed that one sort of zinc soap, zinc stearate, aggregates in proximity to these clusters.

And while the paint sample didn't yet show physical deterioration, researchers found signs that paint fragmentation and chipping (spalling) could eventually occur if zinc soaps become more concentrated and localized within the paint over time.

"We're trying to get a handle on the very beginning processes to understand where the soaps might be forming and where they might be moving - if they're moving," said Barbara Berrie, who leads the Scientific Research Department at the National Gallery of Art and served as a co-leader of the study. "We want to make sure we understand what's going on in more contemporary paintings so that these works are here for the future."

The study could have broader implications for developing better methods for conservation based around the observed chemistry in oil paints, she said. "I can see this maybe being applied generally to issues of preservation and treatments for all kinds of works of art," she said.

Dula Parkinson, a staff scientist at the ALS who participated in the study, said the X-rays revealed the size, shape, and distribution of tiny spots resembling bubbles in a paint sample that measured just a couple of millimeters across.

"They wanted to understand the basic chemistry and basic processes of what was going on," he said. "These structures that they see are really common in lots of paintings, and so they're trying to see why these structures are here." The imaging, using a technique called X-ray microtomography, mapped varied thicknesses in the paint and revealed some microscopic cracking.

Microtomography at the ALS has also been used to provide microscopic views of a wide range of samples, from plant stems to spacecraft heat shields.

Besides the X-ray exploration of a paint sample at the microscale, the team also used a technique known as photothermal induced resonance (PTIR) that exceeded the magnification limits of conventional light-based microscopes. PTIR couples infrared (IR) lasers with an atomic force microscope to provide a nanoscale window into the paint's chemistry at a scale much smaller than is achievable with conventional IR microscopes.

Another technique, called Fourier transform infrared (FTIR) micro spectroscopy, provided a broader view of the chemical composition across varying layers of paint samples.

Andrea Centrone, a project leader for the Nanoscale Spectroscopy Group at NIST who co-led the study with Berrie, noted that the PTIR technique provides chemical mapping with resolution similar to that of atomic-force microscopy - which offers a scan of the sample via a process that is similar to a record player's needle moving over a surface and mapping it.

While the tip scans over the sample, infrared pulses are absorbed locally and the sample heats up and expands rapidly. This "kicks" the tip like a struck tuning fork and provides chemically specific information about the sample.

The paint sample had a very rough, sticky surface that was difficult to chemically map, so Centrone worked with collaborators at NIST to adapt the technique so that the scanning tip oscillated above the sample surface, touching it gently instead of dragging across it, allowing the capture of high-resolution data.

"We are able to capture very small details down to 10 or 20 nanometers," or billionths of a meter, Centrone said. "We were able to detect which kind of metal soap had formed in the paint samples."

The study notes that the same techniques that were used in combination to explore the paint chemistry could be applied more broadly in other fields where the samples are challenging because their chemistry isn't uniform, and detailed knowledge of chemistry over different scales is required, such as in biomedicine and energy storage.

Berrie said she looks forward to future studies that apply the same techniques to explore different types and layers of paint and other issues for preservation of works of art.

"We hope that we will be able to do some comparing and contrasting of different combinations of oil-pigment interactions," she said. "We will be able to explore some of the underlying chemistry of paintings that we still don't know much about," to provide insight for art preservation, too. "And, we are trying to help inform the range of choices that art conservators have."

Credit: 
DOE/Lawrence Berkeley National Laboratory

Marathoners, take your marks...and fluid and salt!

image: A study of marathon runners led by Johns Hopkins Medicine and Yale University suggests that fluid volume and sweat sodium losses, rather than a rise in core body temperature, are the key contributors to post-race acute kidney injury.

Image: 
Image of runner courtesy of the US Air Force; image of kidneys courtesy of MedicalGraphics via Creative Commons

Legend states that after the Greek army defeated the invading Persian forces near the city of Marathon in 490 B.C.E., the courier Pheidippides ran to Athens to report the victory and then immediately dropped dead. The story — and the distance Pheidippides covered — inspired the modern marathon, a grueling 26.2-mile contest that attracts some 1.3 million runners annually to compete in the more than 800 races held worldwide.

While Pheidippides’ demise was more likely brought about by a 300-mile run he reportedly made just prior to his “marathon,” today’s long-distance runners face a mostly short-term but still serious physical threat known as acute kidney injury, or AKI. Now, results of a new study of marathon runners led by researchers at Johns Hopkins Medicine and Yale University suggest that sweat (fluid) volume and sweat sodium losses, rather than a rise in core body temperature, are the key contributors to post-race AKI.

“We knew from a previous study that a large number of marathoners developed short-term AKI following a race, so we wanted more specifically to pin down the causes,” says Chirag Parikh, Ph.D., director of the Division of Nephrology at the Johns Hopkins University School of Medicine and senior author of the new paper. “Our findings suggest that managing fluid volume and salt losses with a personalized regimen during the time period surrounding a marathon may help reduce the number or lessen the severity of AKI incidences afterward.”

The researchers say they also found that runners with AKI following a marathon had increased levels of a blood serum protein known as copeptin. If the connection is confirmed with future studies, they say, copeptin could be valuable as a biomarker during training for predicting post-marathon susceptibility to AKI.

AKI, as described by the National Kidney Foundation, is a “sudden episode of kidney failure or kidney damage that happens within a few hours or a few days.” It causes waste products to build up in the blood, making it hard for kidneys to maintain the correct balance of fluids in the body. Symptoms of AKI differ depending on the cause and may include: too little urine leaving the body; swelling in legs, ankles and around the eyes; fatigue; shortness of breath; confusion; nausea; chest pain; and in severe cases, seizures or coma. The disorder is most commonly seen in hospitalized patients whose kidneys are affected by medical and surgical stress and complications.

Similarly, a marathon subjects a runner to sustained physical stress, reduced blood flow to the kidneys and significant increases in the metabolic rate. Together, these events severely challenge the body’s ability to keep fluid volume, electrolytes and temperature levels — along with the regulatory responses to changes in all three — in balance. The result, as seen in 82% of the runners evaluated by the same researchers in a 2017 Yale University study, was AKI that averaged two days in duration.

For the latest study, the goal was to better define the risk factors and mechanism for the problem by examining 23 runners, ages 22–63, who competed in the 2017 Hartford Marathon in Connecticut.

Participants were volunteers recruited through local running clubs and the marathon’s registration process. Divided nearly equally between men and women, they were all experienced runners with a body mass index ranging between 18.5–24.9, and had completed at least four races longer than 20 kilometers (12.4 miles) within the previous three years.

Urine and blood samples were collected from the participants at three time points: 24 hours prior to the marathon, within 30 minutes of completing the race and 24 hours after. The researchers evaluated the samples for sodium levels; key biomolecules such as creatine phosphokinase, hemoglobin, urine protein and copeptin; and biomarkers associated with kidney injury such as interleukin-18 and kidney injury molecule-1.

Sweat collection patches were placed on the runners prior to the marathon and recovered at the 5-mile mark (because they became too saturated further in the race). Blood pressure, heart rate and weight were measured at all three time points, while a bioharness worn during the marathon continually recorded body temperature.

Twelve of the 23 runners (55%) developed AKI after the race, while 17 (74%) tested positive for markers indicating some injury to the renal tubules, the tiny portals in the kidneys where blood is filtered.

In the runners with post-race AKI, the researchers observed distinct sodium and fluid volume losses. The median salt loss was 2.3 grams, with some losing as much as 7 grams.

Fluid volume loss via sweat had a midpoint level of 2.5 liters (5.2 pints), up to a maximum of 6.8 liters (14.4 pints). For comparison, a 155-pound (70-kilogram) body contains about 42 liters (85 pints) of fluid.

Core body temperature, while significantly elevated throughout a marathon, was basically the same for all runners and therefore, was not considered a causal factor for AKI. However, the researchers say that the combination of high-body temperature along with fluid and salt losses may add to the development of kidney injury.

“Putting the sodium and fluid volume loss numbers into perspective, the median salt loss for the AKI runners was about 1 1/4 teaspoons, or the entire daily amount recommended by the American Heart Association,” Parikh says. “Their median fluid volume loss was equivalent to sweating out slightly more than a 2-liter soda bottle. Beyond that, we had evidence that runners weren’t adequately keeping up with those depletions.”

In turn, Parikh says, that failure to balance the sodium and fluid losses during a marathon may account for the new study’s other relevant finding: the higher levels of copeptin seen in runners with post-race AKI.

Copeptin is a precursor to the release of vasopressin, a hormone secreted by the pituitary gland in response to reduced blood volume. It tells our kidneys and blood vessels to hold on to water, preventing a sudden drop in blood pressure and physical collapse.

“In the runners who developed AKI, we found copeptin levels as much as 20 times higher than those who did not,” Parikh says. “This is biological evidence that the AKI sufferers were severely volume down.”

Because vasopressin reduces blood flow to the kidneys, and decreases renal filtration and urine output, he adds, it also may induce inflammation and injury to the kidney tissues if secreted for an extended period of time. This may explain why a large number of marathon runners get AKI while those competing at shorter distances do not.

Parikh says future studies, using larger samples, will need to evaluate whether optimizing fluid and salt volumes in marathon runners lowers rates or reduces the severity of post-race AKI. Additionally, he says, the researchers would like to follow runners who participate in multiple marathons to look for any cumulative kidney damage.

“The long-term goal will be to document an individual runner’s metabolic and sweat profile to develop a fluid and salt replacement regimen just for him or her,” he says. “Then, runners could consume this personalized drink during the race to better maintain fluid and salt balance.”

Credit: 
Johns Hopkins Medicine

University of Alberta researchers discover new biomarker for rare autoimmune disease

image: U of A researchers Zaeem Siddiqi (left) and Derrick Blackmore pinpointed 12 metabolic byproducts that only appear in people with myasthenia gravis -- a biological marker that will improve diagnosis and allow for personalized treatments for the rare autoimmune disease.

Image: 
Ryan O'Byrne

University of Alberta researchers have identified a unique biological marker that can be used to identify the presence of the rare autoimmune disease myasthenia gravis, predict the course of the disease and identify new, personalized treatments.

In a study published in the journal Metabolomics, neurologist Zaeem Siddiqi, graduate student Derrick Blackmore and their team used metabolic analysis of serum (blood with all cells removed) to find a unique pattern of metabolites--products of the body's metabolic processes such as amino acids, vitamins or antioxidants--that is specific to myasthenia gravis.

Siddiqi and his team first compared the serum of patients with myasthenia gravis to a healthy control group. They then performed a comparison of serum from myasthenia patients to serum from rheumatoid arthritis, another autoimmune disease. After identifying more than 10,000 compounds in the serum samples, they found a unique pattern of 12 metabolites exclusive to patients with myasthenia gravis.

"This is really important because now we have a way to easily separate a patient with myasthenia gravis from someone with rheumatoid arthritis or another autoimmune disease," said Siddiqi, a member of the U of A's Women's and Children's Health Research Institute and the Neuroscience and Mental Health Institute.

"What's more, now we're able to explore how those 12 metabolites change in mild, moderate or severe cases so we can make this biomarker more robust and more effective for predicting the course of the disease and developing treatment plans."

The rare autoimmune disease affects approximately one in 5,000 people, most often women under age 40 or men over 60. Typically, the disease affects the voluntary muscles in the face, head and neck and may affect torso and limb muscles as well. Patients can experience eyelid drooping and double vision, difficulty speaking and chewing, and weakness in the limbs. In severe cases, the disease can affect breathing and swallowing muscles, which can be fatal.

The results highlight the potential metabolomic profiling has in identifying disease biomarkers.

"Right now we don't have the ability to manage myasthenia gravis in a more specific way; we treat all patients the same," said Siddiqi.

"Now we have a unique fingerprint or map of metabolites that can easily separate healthy individuals from those with myasthenia gravis, and a path to the discovery of more accurate and specific treatments."

Biomarkers are useful in managing diseases because they not only help in early diagnosis of a disease, but can also help outline its severity, predict the course and expected outcomes, and indicate what treatments would be the most effective.

"Biomarker discovery is an important step in individualized medicine," said Siddiqi.

According to Siddiqi, current methods for diagnosing myasthenia gravis only tell physicians whether or not a patient has the disease. There are no other biomarkers that can reliably predict the course of myasthenia gravis in a patient, or the best therapeutic response. Although there is no known cure, there are treatments for the disease that can manage the symptoms throughout the rest of the patient's life. Even so, because myasthenia gravis is so rare, treatments can be extremely expensive, hard to find and not tailored to the patient, Siddiqi said.

"Finding the antibodies is good for diagnosis, but they do not tell us how the patient will react to a specific drug or which drug will be most effective," Siddiqi said. "What we're trying to do with this biomarker discovery is develop treatments specific to the needs of the patient, to have more precise management and to be able to more accurately predict the effects of the treatments."

Siddiqi is hoping to soon expand the team's research by examining patients at different stages of the disease to get a more precise picture of how each stage affects the metabolites, and make their biomarker more robust.

Credit: 
University of Alberta Faculty of Medicine & Dentistry