Do Blood Sugar Levels Affect the Development of Sleeping Sickness?

You have probably never met anyone suffering from sleeping sickness, a potentially fatal condition. This is because the disease, also called African Trypanosomiasis, is only present in certain regions of sub-Saharan Africa. While the number of human cases has dropped to less than 3,000 in 2015, Trypanosoma parasites can also cause disease in cattle, greatly affecting economic development in these rural areas.

Sleeping sickness is transmitted by tsetse flies that carry the parasite Trypanosoma brucei. A recent study published by scientists from Clemson University aimed to better understand the switch between different life stages of T. brucei. While inside the fly, the parasite grows rapidly. Following a fly bite, many T. brucei cells are transferred to the bloodstream of a mammalian host. There, the parasite remains ‘dormant’ and no longer replicates. The research group, led by Dr. James C. Morris, was interested in characterizing the mechanisms T. brucei uses to decide when to grow and when to remain dormant.

Life cycle of T. brucei

Because the parasite lives in two very distinct hosts, flies and mammals, it must be able to adapt and use cues from its environment to ensure proper development and survival. Trypanosomes use the sugar glucose as a critical source of carbon – one of the building blocks for biological molecules. While the levels of glucose are quite high in the blood of mammals, they decrease rapidly after a blood meal by the tsetse fly. This prompted the Dr. Morris’ lab to investigate glucose as a possible signal that controls the switch between the form of T. brucei in flies (dividing) and mammals (non-dividing).

Structure of glucose

Interestingly, Dr. Morris and his group found that if they grew T. brucei in laboratory media without any glucose, the parasite was able to survive, but it changed into a form adapted for survival in the fly. When this fly-adapted form was injected into mammals (mice), it was rapidly cleared by the immune system. This suggested that to avoid immune clearance, the parasite must sense its environment, including glucose levels, and change into a form infectious to mammals prior to or during transmission. Therefore, this sugar-induced switch could potentially be exploited for development of new therapeutics, which would mimic glucose depletion and should lead to improved clearance of the parasite by the immune system.

It is currently unclear how the parasite senses changes in sugar levels. There are several possibilities, including a glucose-responsive receptor on the cell surface and the involvement of glucose metabolism. The authors found that a glucose-resembling molecule, which could not be metabolized by the parasite, elicited similar results to glucose itself. This suggests involvement of a glucose-responsive receptor. Nevertheless, further study is needed to establish the precise mechanism.

While sleeping sickness is fatal if left untreated, the last major epidemic ended in the late 1990s. Moreover, the World Health Organization aims to eliminate sleeping sickness as a public health threat by 2020. However, this study will not only inform the development of vaccines or treatments for humans, but also of protective agents for cattle still often affected by African Trypanosomiasis.

Peer edited by Joanna Warren and Jack Sundberg.

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Science Fail Monday: How a dead salmon taught us about statistics

Any scientist knows the importance of a good negative control. A negative control in an experiment is a group of samples or subjects in which no response is expected to an experimental treatment. The experimental group can then be compared to the control group. Such negative controls are gold standards in science and are supposed to provide confidence in experimental results. However, occasionally, a negative control gives unexpected and hilarious results worth of an Ig-Nobel Prize, the highest honor for scientists who publish the silliest research. Such was the case in an experiment involving fMRI, human emotions, and an Atlantic salmon.

An example of an fMRI scan in a human. The red spots have higher brain activity when subjects are performing a memory task.

fMRI stands for functional magnetic resonance imaging. If you’ve ever had a knee injury or a concussion, you have likely experienced a normal MRI scan, which uses radio waves and a magnet to take a structural picture of the organ of interest. The “functional” in fMRI means that researchers can use MRI images to measure brain activity and take a snapshot of changes over time. When a strong magnet is turned on over the brain, the hydrogen atoms in all of the water molecules in the blood point in the same direction, like a compass needle next to a refrigerator magnet. When the magnet is turned off, the hydrogen atoms relax back to their original positions, which releases a signal. This signal changes based on how much oxygen is in the blood, so the end result is a picture of the brain with information about which regions have more oxygenated blood. Regions needing more oxygen are generally assumed to be more active. Researchers can even have study participants perform a task during an fMRI scan, such as viewing particular images or listening to music, and use the fMRI data to determine which areas of the brain are active during the task. These types of studies can tell us a lot about which brain regions are involved in everything from social situations to processing fear.

In the Ig-Nobel Prize-worthy experiment, researchers wanted to use fMRI to determine which parts of the brain were active in response to seeing human faces displaying different emotions. However, they needed a negative control for their human subjects just to make sure that any brain activity they saw in response to the faces wasn’t just due to chance. The ideal candidate for such a negative control? A four-pound Atlantic salmon, purchased by one of the researchers at the local fish market.

The authors of the IgNobel prize study used an Atlantic salmon like this one as their negative control.

The researchers put the dead salmon in their fMRI scanner and, for the sake of science, asked it what emotions it thought the humans were displaying in pictures flashed up on the screen in the scanner. The authors do not comment on the salmon’s responses, but it can be assumed that the salmon was not a model experimental participant and did not comply with the study directions. Expecting to see nothing, the authors analyzed the fMRI signal in the salmon’s brain before and after the salmon “saw” the photos of the faces. Imagine the shock in the room when a few spots in the salmon’s itty-bitty brain lit up like a Christmas tree, suggesting that it was thinking about the faces it saw. Duh duh duuuuuhh….zombie salmon?

Obviously, the salmon was not alive, nor was it thinking about the emotional state of humans. Luckily for the field of fMRI, instead of publishing a paper telling everyone they should use dead salmon to study human response to the emotions of others, the authors of this study delved deeper into why they were seeing “brain activity” in this very dead fish. In their original data, the researchers failed to correct for multiple comparisons: basically, because you are comparing so many brain regions to so many other brain regions, you’re much more likely to find a spot with significant activity in fMRI purely by chance (for more info on multiple comparisons, click here). The authors applied the appropriate statistical corrections to their data, and voila, no more zombie salmon. And then, because scientists have a funny sense of humor, they wrote up and published these results as a lesson to all on the importance of having a good statistician.

Peer edited by Claire Gyorke.

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Forest Fire Flames and Smoke: Double the Trouble

As of Friday November 16, 2018, California was home to the three most polluted cities in the world. These three cities – San Francisco, Stockton, and Sacramento – topped the world’s chart of polluted cities as a result of the infiltrating smoke produced from the nearby, devastating Camp Fire. To date, the Camp Fire is the deadliest fire in California history and has burned over 170,000 acres of land, roughly the size of New York City. Over its rampage it has destroyed immense areas of California’s wildlife and burned down over 17,000 man-made structures. Unfortunately, the Camp Fire’s destruction isn’t limited to the destruction inflicted by its flames. This mass burning of a variety of natural and man-made sources has resulted in smoke containing a myriad of small particles that can be hazardous when inhaled. Thus, the smoke produced from the Camp Fire, which is spreading over 150 miles away from the fire and polluting the air of California, is a matter of great health importance.

Rim Fire Yosemite National Forest 2013

The link between adverse health effects due to smoke produced from forest fires and those due to emissions produced from other sources such as diesel engines and industrial factories has long been established. Specifically, exposure to these air pollutants is linked with the onset of respiratory effects such as bronchitis, increased asthma attacks, elevated blood pressure, atherosclerosis, and, for more susceptible individuals, heart attack or stroke.

Alveolar sac lined with capillary bed. Anatomical view of Air Blood Barrier (ABB).

These adverse health effects are largely driven from the small, ~1µm – 10µm in diameter, solid and liquid particles (PM) contained in smoke or emitted from a specific source. Due to these particle’s small size, they are able to travel throughout the lung after inhalation and negatively affect both the conducting and gas exchange regions of the lung. Once the particles have “landed” in a region of the lung, they can persist for days and begin to elicit a pro-inflammatory and oxidative stress response which can exacerbate asthma symptoms and damage integral components of the lung, leading to various respiratory effects.How these particles cause adverse cardiovascular effects is an active area of research. There are three proposed mechanisms: 1) particles smaller than 2.5µm in diameter travel through the lung, pass the alveolar blood barrier (ABB), and enter the bloodstream leading to direct vascular damage, 2) particles that reach the ABB, but do not pass, can induce oxidative stress in the underlying vasculature indirectly, and 3) particles can interfere with the autonomic and central nervous system leading to irregular signaling and irregular heart rate.

Overall, while some of the mechanisms leading to the variety of adverse health effects induced by PM exposure are still unknown, it is clear that PM exposure can be detrimental. When forest fires are near it is extremely important to listen to the local official’s recommendations for staying safe – even if the flames are 100+ miles away! Thus, as the incidence of forest fires continues to rise, likely due to factors such as climate change, we need to be mindful of both the destruction the flames create and the hazardous air the fires can produce.

Peer Edited by Rita Meganck and Jacob Pawlik.

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