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ToxSquad Outreach Blog 
Issues in Environmental Health, Current events, and cutting edge research

The Last Straw

8/22/2018

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Nima Madani
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With the hazards of plastics as such a hot topic in the news today, more companies are trying different methods to reduce the overall usage of single-use plastics. According to an article from the New York Times, 300 million tons of plastic is produced globally each year with only 10% of the waste recycled. Many groups are working together to cut down the plastic waste – including one mega coffee franchise. 
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On July 9, 2018, Starbucks debuted their strawless lids in response to the company pledge to remove all straw use by 2020 (That’s right, our pumpkin spice lattes are about to get even cooler). Though a very innovative idea, critics have complained that the lids use more plastic to make than a straw would normally use. And it’s true, the lids are made of plastic, but unlike straws, they are much more easily recycled. Although eliminating plastic straws will not do much address plastic pollution (since plastic straws make up less than 1 percent of the total plastic waste in the world), supporters of this move see it as a small step to gain more momentum in solving the plastic problem.
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The debate will continue on whether these lids will be beneficial or not to the waste problem. The strawless lids could be a small step to a better solution, or a quick fix to an eventual bigger problem. No matter the outcome, more solutions should be innovated to tackle the waste dilemma – maybe the biggest impact of these strawless lids will to provide inspiration for tackling the problems of tomorrow. 
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Single-Use Plastics: The Real Sea Monsters

7/25/2018

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Devrah Arndt
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Plastics have been around since the early 20th century, but only recently has the problem of plastic pollution started to attract attention. We’ve all seen the unnerving images of marine animals in distress from plastic exposure (just check out this video of a turtle getting a straw removed from its nostril or this article about a dead whale with a stomach full of plastic bags). National Geographic recognized plastic pollution as one of mankind’s most pressing issues to date, and the U. S. and United Kingdom have recently passed laws banning the use of microplastics in certain commercial products. The ubiquitous nature of plastics in our society begs the question: Just what is all the hype about? And if there really is a problem, can we do anything to fix it?
 
As it turns out, plastic pollution does pose a real threat to humans and the environment, but the problem is much more complex than a whale with a stomach full of plastic bags.

What is all the hype about?
​​Gut obstruction and animal confinement. The most well-known problem associated with plastic pollution is gut obstruction in marine animals and birds and the incidental confinement of marine animals by plastic debris. Both can result in death or injury for the animal
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Figure 1: Biofouled plastic bottles
Biofouling and animal transport. In the ocean, organisms like barnacles and algae will stick to the surface of floating plastic debris (Figure 1). These organisms will ride their plastic boat across vast distances that would not normally be possible, resulting in problems with invasive species and ecosystem degradation. This occurrence, called biofouling, also creates a sink-to-float-to-sink cycle of ocean plastic because these organisms will attach and detach from the plastic. This makes plastics available to marine organisms that dwell deeper in the water column (like whales).
Sorption of secondary contaminants. Although plastics are biologically inert, they can grab onto secondary contaminants like a toxic ocean flypaper. These contaminants usually include organic pollutants like pesticides and industrial chemicals. Such organic pollutants are often resistant to environmental degradation, tend to hang out in fatty tissues, and love to accumulate on the surface of plastics. In fact, the concentrations of contaminants stuck on a plastic surface can greatly exceed ambient concentrations in the surrounding waters.
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Figure 2: Smaller objects have a higher surface-area-to-volume ratio, which is why more chemicals stick to the surface of compounds
Bioaccumulation and biomagnification. The sorption of secondary contaminants on the plastic surface is of particular concern for smaller-sized plastics (such as micro- and nano- plastics) because their relative surface area is much greater compared to larger plastics (Figure 2). In addition, these small plastics are consumed by organisms residing in lower trophic levels of the ecosystem (think oysters and plankton), resulting in greater potential for the accumulation and transfer of toxic contaminants to top predators, including humans! 

Yes, it seems that we have a personal stake in the fight against plastic pollution, as well! The plastic problem extends beyond a moral imperative to save the whales.  We need to 
address the plastic problem to ensure our own well-being. 
Now the real question is.....What can we do about this? 
Reduce. Reuse. Recycle. The most effective way to address plastic pollution on a personal level is to replace single-use plastic items with reusable items. Grocery shop with a reusable bag. Avoid using plastic straws at restaurants. Carry a reusable water bottle instead of a crinkly plastic one. These small lifestyle changes will help us turn the tides on the plastic pollution problem, and you might even find that the reusable items work better than the single-use plastic items! When you must use plastic materials, make sure to choose plastic materials that can be recycled - and actually recycle them!

Make your voice heard. The use of plastic microbeads in personal care products was banned in the United States in 2015, but the use of microplastics in other products (cosmetics, sunscreen, glitter, toothpaste, nail polish, abrasives in dish detergent pods) has not been addressed. And although some companies are taking action to reduce single-use plastics in their business design, the problem of single-use plastics has not been formally addressed by state or federal regulations. Be vocal and let your legislature know how you feel about these problems!
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Figure 3: Responsible lifestyle changes to reduce single-use plastics will result in happier marine animals!
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Mercury and Madness: The Case of the Mad Hatter

6/21/2018

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Amanda Buerger
There is often a historical truth behind fictional characters, no matter how absurd it may seem. I was 22 years old, in my first class as a PhD student, when I learned that there was something more to an iconic character from my childhood than I realized. Alice in Wonderland’s Mad Hatter may not have been just this fun, crazy, unpredictable character - he was possibly inspired by real-life hat makers suffering from chronic mercury poisoning.
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Often cited as a classic example in occupational toxicology, Mad Hatter Disease (also known as Erethism) is a neurological condition resulting from daily exposure to mercury fumes. Mercury was used to help hatters manipulate felt into hats. However prolonged (chronic) inhalation exposure to mercury often led to hatters experiencing tremors and various psychological symptoms, including depression, irritability, and even hallucinations. Various reports of this disease and its relationship to hat-making emerged as early as the 1800s; in fact, a cohort of New Jersey hat makers were experiencing these symptoms in 1860, just 5 years prior to the publication of Alice in Wonderland by Lewis Carroll.

Long after the hazards of occupational mercury exposure were first observed, the United States outlawed the use of mercury in the felt industry in 1941. This was not the only time the United States government has acted to protect workers from occupational hazards; for instance, in 1989 the Environmental Protection Agency banned the use of asbestos in building materials after evidence emerged that asbestos exposure results in chronic respiratory problems. As technology continues to advance, we must work to proactively protect workers before they become ill. While the Mad Hatter is an iconic and beloved character, the reality behind his origin is heartbreaking, and is a powerful reminder of the importance of occupational safety procedures and regulations. 
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The Lasting Legacy of Rachel Carson

5/27/2018

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Sara Humes
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​Rachel Louise Carson was born on May 27, 1907 (she would celebrate her 101st birthday today!) in Springdale, Pennsylvania, a small town along the Allegheny River just east of Pittsburgh. She grew up in a poor family, but was awarded a scholarship to attend the Pennsylvania College of Women - today known as Chatham University in Pittsburgh. She originally planned to study English and writing, but realized that years exploring the wilderness around her childhood home had fostered a love for biology and the environment. After receiving a bachelor’s degree in biology, she continued her studies at the oceanographic institute at Woods Hole, Massachusetts and at Johns Hopkins University, where she earned a master’s degree in zoology. Carson then went on to work for the U.S. Bureau of Fisheries where she wrote radio segments about marine life. In her spare time, she wrote freelance pieces for newspapers and magazines on the topics of conservation and nature. She was eventually promoted to Editor-in-Chief of all Fish and Wildlife Service publications. During this time, she also published three acclaimed books about aquatic life, Under the Sea-Wind (1941), The Sea Around Us (1951), and The Edge of the Sea (1955). 
PictureFigure 1: Rachel Carson and her famous book, Silent Spring.
​However, it is her fourth book, called Silent Spring, which makes her a renowned figure in the fields of ecology, toxicology, and environmental health. Published in 1962, Silent Spring outlines the negative impact of pesticide use on the environment, ecosystems, and human health. She wrote specifically about the insecticide DDT (dichlorodiphenyltrichloroethane), which at that time was sprayed aerially throughout the United States to control insect populations. DDT had been linked to the thinning of eagle eggshells, causing them to crack during incubation and ultimately leading to a decline in the eagle population. The book was a bestseller, and launched the environmental justice movement in the United States. Silent Spring and Carson faced substantial backlash from chemical companies, but also made Americans more aware of the fragility of our environment and the need to protect it from irresponsible chemical use. Her book and subsequent appearance before the Senate subcommittee in 1963 would plant the seeds for the founding of the Environmental Protection Agency in 1970, the passage of the Clean Air and Water Acts, the establishment of Earth Day, and the eventual banning of DDT in the United States in 1972. Unfortunately, Carson did not live to see the full impacts of her work, and lost her battle to breast cancer on April 14, 1964. Posthumously awarded the Presidential Medal of Freedom, she left behind a legacy of appreciating and protecting the environment, best illustrated by her quote: 

“The more clearly we can focus our attention on the wonders and realities of the universe about us, the less taste we shall have for destruction.”



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The Indian Vulture Crisis and its Relationship to Sustainable Chemistry

5/3/2018

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This month, the University of Toronto’s Green Chemistry Initiative and the Gainesville ToxSquad teamed up to co-author a post about the Indian Vulture Crisis…

Shira Joudan (Green Chemistry Initiative) and Alexis Wormington (ToxSquad)
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Pharmaceuticals have drastically changed our society, quality of life, and life expectancy. Advances in chemistry are the driving forces behind the optimization of pharmaceuticals and other synthetic chemicals which have shaped the way we live our lives.  Sometimes, a chemical used has undesired side effects, such as non-target toxicity to animals in the environment. A historic example of the consequences of chemical use is the toxicity of the pesticide dichlorodiphenyltrichloroethane (DDT) to eagles, which was profiled in Rachel Carson’s famous book Silent Spring. Although current regulations require extensive toxicity testing for new chemicals, those with a high production volume can still elicit unforeseen environmental effects on the environment.

More recently, there have been unforeseen environmental implications of chemical use in another essential bird population in India, a phenomenon now known as the Indian Vulture Crisis. Between 1993 and 2000, Indian vultures (Gyps bengalensis, Figure 1) began to mysteriously disappear, with the population declining by over 97% in less than 10 years (Figure 2). Researchers worked frantically to identify the cause, and came up with several theories ranging from infectious disease to food shortage to chemical exposure. Scientists began noticing visceral gout on a majority of the dead vultures, which is a sign of kidney failure in birds, and from there it didn’t take long to determine the culprit was a chemical contaminant. In 2004, a paper reported startling amounts of diclofenac (Figure 3) in the tissues of the dead vultures, providing compelling evidence that the non-steroidal anti-inflammatory drug (NSAID) was the cause of the population collapse.3 To figure out how to restore the vulture population, or at least slow down its decline, researchers needed to figure out how the vultures were being exposed to diclofenac, why it was killing them, and if there was a chemical alternative to the deadly pharmaceutical.
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Figure 1: Two G. bengalensis adults with a dead chick.
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Figure 2: Catastrophic decline in Gyps vultures in India over a 10-year period. Results from vulture nest monitoring in Koeladeo National Park from 1985 through 2001.

​So, What Happened?
PictureFigure 3: Chemical structure of diclofenac, the pharmaceutical implicated as the cause of the Indian Vulture Crisis.
​The problem began when diclofenac was approved for veterinary use in India in the early 1990s, where it was widely utilized to treat inflammation in cattle due to its efficacy and affordable cost. As a result, many livestock carcasses in India were contaminated with diclofenac, which brought catastrophic consequences to any vulture that consumed the carcasses. Vultures within the Gyps genus cannot metabolize diclofenac, and are extremely sensitive to the drug, with toxic doses ranging from just 0.1-0.8 mg/kg depending on the species.1 A vulture would receive a lethal dose of diclofenac after consuming a small amount of contaminated tissue, and die of renal failure within 48 hours. Just one contaminated carcass affected several vultures at once due to their group feeding behaviour, and because of this, diclofenac contamination in as little as 1 of every 200 carcasses would have been enough to cause the decline in the vulture population.
Although diclofenac is either banned or not used for veterinary purposes in most countries, it is still legally utilized throughout Europe, which has drawn controversy in those countries where it is approved for use in food animals.

Human Health Impact of the Vulture Crisis
India is a developing country and relies more on natural processes for the removal of dead animals, where scavengers like vultures play a huge role. With the loss of the vultures, less efficient scavengers such as rats and dogs have moved in to replace them, leading to major problems with disease in the affected areas. Unlike vultures, which are terminal hosts for pathogens due to their strong stomach acid, dogs and rats are reservoirs for diseases – and now these animals are the primary scavengers in India. A rise in feral dogs has caused an increase in the number of rabies cases in humans, which has cost India approximately 998-1095 billion Rupees in healthcare costs between 1992 and 2006 (15-16.5 billion USD).

In addition to the economic and health costs associated with a rise in infectious diseases, the disappearance of the vultures has also lead to issues with the prolonged decomposition of carcasses. Vultures play a major role in the decomposition process – a group of them can skeletonize a body within a few hours. But in their absence, bodies take days or months to decompose, which can lead to issues with water or food contamination. This ‘carcass crisis’ has had cultural implications as well, threatening the ancient Parsi burial tradition where bodies are not buried, but disposed of through natural means (i.e. vultures). Without the vultures, the Parsis struggle to continue the two-thousand-year-long practice and are forced to seek alternative methods of body disposal, causing a deep divide within the community.  
Diclofenac and Green Chemistry: Could This Have Been Prevented?
PictureFigure 4: Meloxicam, an NSAID alternative to diclofenac.
The short answer: probably not. For a drug to be approved for human or animal use, toxicity research must be conducted (although these requirements vary by country, read more about how drugs are approved in Canada10 and how drugs are approved in the USA11). Unfortunately, potential ecosystem toxicity (ecotoxicity) is not often at the forefront of the drug-approval process. Even if ecotoxicity studies were performed with diclofenac, it is unlikely that the toxicity to vultures would have been discovered before drug approval, as vultures are not a common test animal used in these types of studies. Only a full chemical assessment with ecosystem modelling and subsequent toxicity tests could have predicted the toxicity to the vultures; but these tests are expensive, time consuming, and not the norm during the current drug-approval process.

In India, farmers cannot afford to lose animals, and rely on affordable NSAIDs such as diclofenac to improve the health and quality of life of their livestock. Since NSAID use cannot be prevented, it is up to green chemists to find a suitable replacement for diclofenac that is efficient, affordable, and less toxic to vultures.

To predict the potential toxicity of a pharmaceutical or chemical to humans and the environment, it is important to consider all interactions that occur once the compound enters the body. Every pharmaceutical has a “therapeutic index” (the difference between an effective and toxic dose),  which can vary between different species or susceptible populations (e.g. infants, elderly). If the concentration of a drug exceeds the toxic level, toxic endpoints such as renal failure or death could be observed. The toxic level of a drug depends on two major processes: drug excretion and metabolism. The sum of these two processes determines how quickly a pharmaceutical is broken down and eliminated from the body. In the case of diclofenac, vultures could not metabolize or eliminate the drug, so it was free to wreak havoc on susceptible organ systems. For an NSAID to be a suitable replacement for diclofenac, vultures should be able to break it down and excrete it safely. 

Currently, meloxicam has replaced diclofenac as an NSAID for livestock in India. Both drugs have a similar mechanism of action in the treatment of inflammation; however, unlike diclofenac, meloxicam is rapidly metabolized and excreted by vultures. In a study where different vulture species were administered meloxicam, researchers observed the production of three metabolites identical to those observed in humans during clinical trials. Vultures have the enzymes required for the metabolism of meloxicam (specifically cytochrome P450s and glucuronide transferase). The formation of metabolites alters the biological activity of meloxicam, increasing its water solubility and allowing for faster renal excretion.
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​Understanding the biological interactions of a drug can also help us eliminate potential replacements for diclofenac. An example of a poor replacement for diclofenac in cattle would be aceclofenac, because it is 
metabolized to form diclofenac via hydrolysis. This particular pharmaceutical would not do anything to improve the vulture population, and should not be selected as a replacement for diclofenac.

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Figure 5: Aceclofenac, an NSAID that would not be suitable as a replacement for diclofenac.

​Current Status and Remaining Challenges
In 2016, the Indian minister of the environment launched the Gyps Vulture Reintroduction Programme with the hope of restoring the vulture population to 40 million individuals within the next decade through breeding programs. Although this effort to restore the Indian vultures is a step in the right direction, there are still many challenges in way of their recovery. Despite the fact that meloxicam is a safer NSAID for use in livestock, diclofenac is still obtained and used illegally among farmers in India due to its affordability. Since the ban of diclofenac for veterinary use in 2006, the decline rate of Gyps has decreased, but vultures are still likely to decline by 18% per year despite the ban. Until the drug is completely removed from the equation, the reintroduction and recovery of the vultures remains a challenge. 
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Post-Modern Science Communication

3/7/2018

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By Danielle Love Cucchiara and Alexis Wormington
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​In the digital age, information is shared across the world with just one click. Facilitated by the world-wide web, ideas are proposed, discussed, and spread globally within seconds; a fact that has introduced a new, unprecedented level of collaboration to human society. However, the unlimited availability of information is a double-edged sword, as the spread of information is not always dependent upon its value or truth, but instead by how it is communicated. And often enough, communicators can manipulate or even falsify information to achieve a purpose. Some of the most valuable information is gathered through scientific discovery; and, unfortunately, this information is often the target of deceptive communication.
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The internet is riddled with ads claiming lavender oil or shark cartilage can cure cancer. There are anti-vaccination parties where parents take their children to the home of a child with chickenpox or measles, intentionally trying to infect them. There are large, vocal groups of people who do not believe in scientifically verified concepts such as climate change and a round earth. Companies are making millions selling “health” products that are unregulated and scientifically unverified. All these ideas are shared and supported through the spread of scientific-sounding information – not all of which is accurate or even true.
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Figure 1: Examples of misleading advertisements claiming to be scientifically based.
There is wealth of misleading or blatantly false information out there posing as science, leading to real-life, substantial consequences.  For example, nutritional and herbal supplements, which are often advertised as “safe” and “natural” even though they are unregulated, are responsible for around 23,000 emergency room visits and 2000 hospitalizations annually. Another example of the harm caused by misleading science is the re-emergence of preventable diseases, such as measles, due to the “supposed” controversy surrounding vaccinations. The vaccines controversy originated from a retracted paper published in 1998 that falsely claimed that the MMR vaccine was associated with autism – a claim based on falsified data and an experiment conducted by a discredited physician with a huge financial conflict of interest. Although the paper’s “findings” are widely disregarded by the scientific and medical communities, all it took was the support of the charismatic, non-scientist celebrity Jenny McCarthy to get the anti-vaccination movement rolling in 2007. Despite the scientific support and success of vaccination programs, physicians are seeing more parents who ignore medical advice and refuse to vaccinate their children – a problem with no easy solution except to continue educating the public and addressing the concerns of parents in a respectful way.

Communicating effectively with a general audience is a learned skill that academics do not always have the time or resources to develop. Researchers tend to take the logical approach to convey a message, reporting only facts and neglecting to consider the emotions, beliefs, and culture of those receiving the information. This has created a disconnect between scientists and those who do not have scientific training. The archetype of the cold, calculating scientist and of the ivory tower elitist exists, and unsurprisingly, many people believe that it’s accurate. With Scott Pruitt (a non-scientist, former lobbyist for big oil companies) running the Environmental Protection Agency, vacant research positions throughout the federal government, cuts to federal research funding, and a decreasing number of scientifically literate legislators in Washington, researchers can’t afford to stay in our towers any longer.  Scientists must become better at communicating the importance and role of their research in the lives of regular people. The question is: How?
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Figure 2: A comic representing the post-truth thought process.
The Oxford Dictionary chose “post-truth” as their 2016 word of the year.  The definition: Relating to or denoting circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief. Attacking people with only data and complicated terminology does not work; in fact, people tend to think of those with opposing views as morally or intellectually inferior, even when those opposing views are factually correct. So, if a full-frontal fact attack doesn’t accomplish an efficient exchange of information, then it’s time to investigate some alternative strategies. During a seminar entitled The Counter Intuitive Nature of Effective Science Communication, Dr. Kevin Folta, a professor and chairman of the horticultural sciences department at the University of Florida, discussed ways to better communicate scientific information to concerned citizens. Rather than pelting them with facts, Dr. Folta suggested listening to the audience, ensuring them that their concerns are important, and trying to relate to them on a more personal level. 
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Something to consider during the exchange of information is the amount of trust and respect between the two parties. 
The truth is, the public has a more negative view of the role science in society than it did ten years ago. It is clear that scientists need to try harder to foster trust and respect with the public, but doing so is easier said than done. Many of the issues facing the country affect people on a personal level, and so it may be effective to connect with people personally when discussing these issues from a scientific perspective. The mother of three listening to a presentation on food safety doesn’t care about p-values or bar graphs, she cares about the health and well-being of herself and her family.  Empathy is the key here – scientists should try to listen to the concerns of the public, understand where they’re coming from, and show them that their concerns matter. Additionally, scientists should try a little harder to break the bubble of academia that metaphorically separates them from regular society, and emphasize the fact that they are just people, just trying to contribute to society world– like everyone else. Scientists, like everyone else, have values and things that they feel passionately about. Express that passion – it makes scientists more approachable when they care, and can communicate that with compassion and enthusiasm.                                     
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Figure 3: Difference in opinion between U.S. adults and scientists over scientific topics.
Another issue faced by the scientific community is that the public and scientists differ widely in their opinions on scientific topics. This issue, while likely influenced by several factors from media coverage to social circles, is not helped by the way that scientists are currently trained to communicate their work. Explaining a complicated topic scientific jargon may be effective for communicating within an academic circle, but is likely not an efficient way to relay information to the public. Dr. Marshall Shepherd, Director of Atmospheric Sciences Program at the University of Georgia, suggests the use of analogy or metaphor in lieu of hard data. Scientists are trained to discuss all of the details, but Dr. Shepherd advises getting straight to the point and to avoid oversharing. His take-home tips are to stick to 3 topics and keep the message memorable, meaningful, and miniature. 

Going forward, it is of the utmost importance to teach young scientists to properly communicate to a layperson audience. A paper published in the Journal of Undergraduate Neuroscience Education in 2013 advocates for the incorporation of formal science communication into university undergraduate and graduate program curricula. Social media is an excellent tool to encourage this sort of communication, and is good way to help introduce researchers to scientific communication. For example, to underscore the importance of learning to communicate our work to the public, Dr. Folta asks his students to present in one publication geared to regular people for every scientific publication they submit.

Scientists have information that is important to everyone, and it is paramount that the general population understands this information so that the members of the public can make informed decisions about their own lives. There is a lot of false or manipulated information out there with the goal of taking advantage of uninformed individuals, influencing policy decisions, or simply pushing an idea. These purveyors of faux-science are appealing to consumers and lawmakers in a different way than scientists do, through the use of emotions and beliefs. If scientists want a voice in this world, and they should, it’s time to move outside of their comfortable boxes of data and facts, reach out to the public, and earn their trust.  
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Bee My Valentine

2/7/2018

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By Amanda Buerger 
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​Everyone knows that St. Valentine is the patron saint of lovers (and the namesake of Valentine’s Day), but did you know that he is also the patron saint of beekeepers? Unfortunately, over the past several decades, there has been a drastic decrease in global honeybee populations. In the United States, nearly half of all honeybee colonies died off from April 2015-April 2016 (Figure 1). You may have even noticed the “B’s” missing from your Burt’s Bee’s lip balm lately in an effort to raise awareness for the disappearance of honeybees.  So, what is happening?
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Figure 1: Honey bee colony loss in the United States over the past decade
Researchers have found a link between the decline in honeybee populations and the broad use of a class of pesticides called neonicotinoids. Several studies have found that neonicotinoids are toxic to honeybees. One study found that honeybees exposed to these pesticides have altered learning abilities and are less efficient at foraging pollen for their colonies, which has negative impacts on colony growth. Another study found that neonicotinoids impair honeybee motor control and their response to light, which are skills honeybees need to find pollen and carry it back to their colony. Both of these possibilities relate to a reduced ability of bees to harvest pollen, which can lead to colony starvation.
So, why do we care about the honeybees? Honey bees pollinate around 75 crops for us, including apples, avocados and even coffee! A decline in bee populations means a decline in pollination, a vital ecosystem service, and therefore fewer crops, which will make their prices surge and may ultimately contribute to food shortages. It is estimated that insects in the United States, including honey bees, create revenue upwards of $30 billion annually for agriculture.
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How can you help? Support your local beekeepers! Instead of buying some flowers for your special someone this Valentine’s Day, get your honey some honey from a local beekeeper! 
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Figure 2: If you’re in Gainesville, we recommend the Cross Creek Honey Company!
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Spotlight Toxicant: Tetrodotoxin

1/24/2018

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By Alexis Wormington
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Ah, the humble pufferfish. Known for its particularly unique defensive strategy, the pufferfish is likely one the world's most comical marine fish, next to the blobfish (yes, it’s a thing, Google it for a giggle). However, this funny little fish packs a deadly punch – it secretes tetrodotoxin, one of the most potent neurotoxins on the planet!  
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Tetrodotoxin, although known colloquially as the pufferfish toxin, is actually produced by a variety of marine and even terrestrial animals – not just the pufferfish! It has been found in certain species of 
octopus, starfish, frogs, and even newts. Although there is some scientific debate regarding the how tetrodotoxin is produced in these species, there is a large amount of new evidence that suggests that these animals accumulate the toxin from gastrointestinal bacteria - the literal definition of a toxic relationship!  
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Figure 1: Some animals that produce the neurotoxin tetrodotoxin. Astropecten scoparius (left), the rough-skinned newt (middle), and the blue-ringed octopus (right).
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Figure 2: The chemical structure of tetrodotoxin.
Tetrodotoxin works by blocking ion channels, which disrupts the function of neurons and causes paralysis. The toxin is extremely potent, meaning that the fatal dose is very small compared to other toxic substances. The oral lethal dose of tetrodotoxin in mice is around 0.000334 grams/kilogram, which is at least 25 times more toxic than cyanide, although some sources claim that it is anywhere from 100 to 2500 times more toxic! Despite decades of research into this topic, there is currently no existing antidote for tetrodotoxin poisoning. ​
Luckily for most of us, it's pretty difficult to be exposed to tetrodotoxin. The animals that produce it tend to mind their own business, so it's an unlikely thing to come across during a casual day at the beach. Most exposures actually occur through the consumption of fugu (pufferfish meat) that has been improperly prepared. However, despite the popularity of fugu in countries like Japan, fugu poisoning is rare and only affects a few people annually. Japanese chefs must be licensed to prepare the dish, and only a handful of restaurants have it on their menu. Additionally, some Japanese companies are raising pufferfish that do not produce the toxin with the hope that more people can consume fugu safely. 
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Figure 3: Fugu, a common delicacy in Japan.
Although tetrodotoxin is obviously dangerous in its undiluted form, its neurological effects make it useful for medicinal and research purposes. At very dilute concentrations, it is potentially therapeutic - showing promise for use in ​​pain relief and thought to reduce drug cravings in heroin addicts. Tetrodotoxin is also used extensively in the research of ion channels and organ function., a valuable tool for the field of neuroscience. Just like botulinum toxin (aka Botox), tetrodotoxin has a place in human society as well, and there is still much to learn from it. 
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Model Organisms in Environmental Health

11/9/2017

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By Amanda Buerger, Sara Humes, and Alexis Wormington
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​One aspect of environmental health revolves around understanding how changes in the environment, whether human or naturally-caused, may impact the health of global populations and ecosystems. Model organisms are non-human species used to understand biological processes in a laboratory setting. Model species should be affordable, easy to keep in a laboratory setting, and an appropriate species to study in the context of the scientific question being asked. In this post we’ll go over three model species that are commonly used in the field of environmental health, why we use them, and their advantages and disadvantages as models.
 
Daphnia
 
Daphnia, commonly known as the “water flea”, are a genus of aquatic crustaceans used very commonly in basic toxicological studies. Daphnia species are favored because they are very inexpensive, low maintenance animals with a short life cycle. Since they are invertebrates, the ethical and legal requirements for their use are minimal compared to more complex models, such as non-human primates and rodents. Daphnia are unique because they typically reproduce asexually, meaning all of their offspring are genetically identical to the mother. They can produce over 100 eggs at a time, and reproduce approximately every two days! Because of their rapid and unique life cycle, these organisms are valuable to use in both reproductive studies and toxicity tests. Daphnia studies often provide the foundation for the basic toxicity of chemicals.
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Like with any model, using Daphnia comes with its disadvantages. Since Daphnia are invertebrates, their application to human health is very limited, as mammals and invertebrates have vastly different molecular, chemical, and physical processes involved in biological function. Additionally, their brief life cycle makes them impossible to use in long-term studies, which restricts the kinds of questions we can ask and answer using Daphnia as models.


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Figure 1: Three commonly used Daphnia models. Daphnia magna (left), Daphnia pulex (middle), and Ceriodaphnia dubia (right).
Zebrafish
 
Alternatives to invertebrate and mammalian models are fish, which are generally smaller, cheaper, and easier to care for than rodents, non-human primates, and other higher level models. There are several species of model fish, from tiny minnows, to predatory trout and bass, to one of the most common fish models - zebrafish. While not as closely related to humans as mammals, fish share several characteristics with humans, including conserved biochemical processes in the brain, gastrointestinal system, and cardiovascular system. In the case of the zebrafish, the gut is similar to that of humans, and therefore these fish are used to study diseases related to the intestinal tract, such as obesity and inflammatory diseases. Due to increased funding of studies using zebrafish, this inexpensive model organism is becoming more commonly used in scientific research.  Because of their prolific use, the genome of the zebrafish has been sequenced, and scientists are able to utilize this knowledge to create zebrafish that are useful for their studies.  Finally, the development of zebrafish is easy to monitor, as the embryos and larvae are transparent.

As with any model, there are limitations to its use. Most fish species experienced a duplication of genes millions of years ago, and therefore generally have two functioning genes for each one human gene. Additionally, there are some other differences between fish and humans, such as the respiratory tract and the presence of two pairs of kidneys in some fish, each with distinct function.  Fish are also housed together in tanks, and there is uncertainty as to whether the whole tank should count as one sample or if each fish in a tank should be considered individually. As we understand more about zebrafish, we will be able to evaluate the use of this organism as a model for different human diseases.

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Figure 2: An adult zebrafish (left) and a larval zebrafish that has been modified to express green fluorescent protein (right).
Rodents
 
The most commonly used and well-established mammalian models in scientific research are the mouse and rat. Compared to other mammalian models, such as non-human primates, livestock, and cats, mouse and rat models are less expensive and easier to house. Some advantages of using mice and rats for toxicological research include their short lifespan, small size (for easier care and housing), short gestation times for large litters, and genetic and biological similarity to humans. Approximately 95% of some 30,000 genes are shared between mice, rats, and humans, resulting in a lot of biological resemblance. This similarity makes rats and mice a good stepping stone between lower models and humans. Additionally, we have fully sequenced the genome of the mouse and rat, making it easier to focus on a particular gene of interest for a research project. Knowing the full genome allows researchers to create genetically engineered rodents that are missing or have an excess of certain genes or proteins to shed light on their function and role in response to toxicological stressors. Research rodents are also bred so that two animals of the same strain are nearly genetically identical, eliminating much of the variability between individual animals.
 
Despite these advantages, there are some disadvantages to using rodent models. Rodents and humans still have some fundamental differences in physiology, limiting their application to humans in certain cases. For example, rodents cannot cough, so study outcomes related to the respiratory system may be different than those observed in humans. Since rodents are mammals, there are also many more regulations, training, financial resources, and ethical considerations required to work with them compared to non-mammalian models. Regardless, rodents are a well-respected, frequently used model in all areas of scientific research, and their use has led to many scientific advancements. 
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Figure 3: Commonly used mouse and rat strains for toxicological research. Top row: BALB/c mouse (left) and C57BL/6 mouse (right). Bottom row: Sprague-Dawley rat (left) and Wistar rat (right).
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