Knowledge and use of prevention measures for chikungunya virus among visitors to Virgin Islands National Park

By: Helen Beilinson

Reprinted with permission from Open Science DB. Open Science DB is a centralized database of scientific research. It is led by graduate students from Northwestern University and scientists from leading research universities/institutes contribute summaries of research papers to the database. Each summary is reviewed to ensure accuracy and accessibility. 

 

Pretravel health research— not something people typically think about when they’re packing their flip flops and sunscreen for a sunny vacation in the tropics. Unfortunately, mosquitos love the warm temperatures just as much as humans do. Without the knowledge of proper mosquito bite prevention strategies, vacationers are put at risk for catching viruses carried by mosquitos.
 
Chikungunya is caused by Chikungunya Virus that is transmitted to human by mosquitoes. Chikungunya outbreaks have been observed in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans. But Chikungunya spread to Americas in 2013, and by the end of 2014, about 1 million suspected and confirmed cases of Chikungunya were reported across 43 countries in the Americas. Infected people start feeling symptoms about a week after being infected by a Chikungunya-carrying mosquito, the most common of which are a high fever and joint pain. Although most patients start feeling better within a week, many experience prolonged joint pain up to several months. There is no vaccine against Chikungunya, so the best way to prevent infection is making sure that people are educated about the virus and instilling mosquito bite prevention practices. However, there is no information regarding how many travelers are aware of Chikungunya and prevention methods.  
 
To answer this question, the Center for Disease Control and Prevention (CDC) investigated what percentage of travelers to the U.S. Virgin Islands are aware of mosquito-borne diseases (Chikungunya and other viruses) and mosquito bite prevention measures. Visitors to Virgin Islands National Park on St. John were asked to complete a questionnaire addressing knowledge related to mosquito-spread diseases and prevention measures .446 of 783 travelers completed the survey.
 
According to the survey results, more than half of respondents were unaware of Chikungunya virus. Moreover, the majority responded that they had not been wearing clothing treated with an insect repellent or long-sleeve shirts/pants, or using bed nets for the past three days.
 
Overall, this survey showed that most visitors arrive the U.S. Virgin Islands without adequate pre-travel research and knowledge about mosquito safety. As the number of international travelers increases each year, this survey data strongly emphasizes the urgent need for developing creative ways to encourage pre-travel health research among travelers. 

Treating Depression with Drugs

By: Helen Beilinson

[I would like to note that Because Science does not endorse the recreational use of drugs, psychedelic or otherwise. Please see your doctor before taking any new medications or changing your current regiment. All of the drugs mentioned below are illegal in the United States and were tested in experimental settings to ensure the safety of the volunteers.]

Refurbishing drugs fashioned for one therapy to treat another illness has been in practice for years. The anti-nausea drug, Thalidomide, was found to be efficacious in treating leprosy and multiple myeloma, and many therapies originally designed to fight tumors are currently being studied for efficacy against autoimmunity. Although many of these studies go under the media radar, an ever-growing group of studies of reusing drugs has raised a fair amount of controversy because the drugs that are being recycled are illegal, psychedelic drugs. The drugs they explore are felonious and their physiological and psychological effects are highly understudied. That being said, new effective and widely used treatments for depression have not been developed since the 1970’s and these studies hold important information in treating this disorder.

Last week, a group at the Imperial College London published a study in The Lancet Psychiatry exploring the effects psilocybin on depression. Psilocybin is the active, hallucinogenic molecule found in many toadstools, including magic mushrooms. Psilocybin is an alkaloid, a class of nitrogen-containing organic compounds found predominantly in plants. It also also includes morphine, a pain-reliving drug, and atropine, the poison found in deadly nightshade, but active as a muscle relaxant to dilate pupils and increase heart rate in small doses. Psilocybin is metabolized by the body to form psilocybin, which stimulates the serotonin receptor Serotonin works in many ways in many places in the body. It is believed to be critical in mood regulation, appetite, and sleep. Serotonin is a neurotransmitter, which is a molecule used by neurons to communicate with each other, relaying information from one end of the body to another. Many current available antidepressants, and other mood related disorders, act to increase the amount of serotonin, which subsequently increases its consequential signaling, lifting mood. Psilocybin acts kind of like serotonin in that it triggers the same receptor as serotonin, which stimulates the same chemical signaling that serotonin does. The biochemistry of psilocybin provides insight into its strong potential in treating depression.

 Although there is evidence that magic mushrooms have been used for religious, spiritual, and recreational purposes since 9000 BCE, they, as well as other psychedelics, only entered the academic and medical field in the late 1950’s. Backlash against the hippie culture of the 60’s and 70’s, however, halted research of hallucinogens. The last decade has brought back studies of these drugs and their effects on various human ailments, triggering molecular studies to elucidate the molecules responsible for hallucinations and changes in mood. 

In the aforementioned study, twelve clinically depressed patients, who were unresponsive to other treatments, were given two doses of psilocybin. The first was a low dose and the second, administered a week later, was higher dose. The patients were then questioned for the next three months and their mean depression severity scores were noted. Before treatment, all patients had scores reflecting severe depression. After the second dose of psilocybin, scores, on average, dropped to scores of mild depression and staying in that range three months after the treatments. Five of the twelve patients were in complete remission after three months, with all patients seeing a notable improvement. The study also noted that all patients experience side effects (including anxiety, confusion, and headaches), which, in all cases were mild and most symptoms passed within two hours of treatment.

 These results are very exciting for the field, as such success in an initial study, particularly for psychiatric disorders, is rare. Interestingly, this isn’t the first time psychedelic drugs have been used as a basis for depression therapy.

In March of 2015, researchers from Brazil published the first clinical trial exploring the potential therapeutic benefit of ayahuasca. Ayahuasca is a botanical hallucinogen used by indigenous groups of the Amazon for ritual and medicinal purposes. The ayahuasca beverage contains two ingredients. The first is a monoamine oxidase inhibitor (MAOI), which inhibits the breakdown of specific neurotransmittors, molecules used by neurons to communicate with each other, such that their effectiveness is increased. The second is dimethyltryptamine, or DMT, a psychedelic compound. Traditionally, the ayahuascan MAOI is from the bark of Banisteriopsis caapi, a jungle vine, and the DMT is from Psychotria viridis, a shrub common in the northwest of the Amazon. These plants are boiled together and concentrated over several hours. Interestingly, other MAOIs have been used for years in treating depression and Parkinson’s disease. For example, many MAOIs prevent serotonin degradation, increasing its signaling capacity. However, available MAOIs are not routinely used as they have a significant risk in interacting with over-the-counter medications and other prescription medicines and require strict diet restrictions, as they can cause high blood pressure.

In the study, six patient volunteers diagnosed with recurrent major depression were given ayahuasca prepared by members of the Santo Daime community in Brazil. Patients’ moods were analyzed for two weeks prior to drug administration, as well as at multiple intervals after drug administration. Three weeks after drinking the ayahuasca, almost all patients had reduced depressive symptoms. Not all patients saw dramatic decreases and throughout the course of the three weeks, and in some, moods did fluctuate from above the initial scores to below the scores seen at the conclusion of the three weeks. Although some patients experienced vomiting that is known to occur after consumption of ayahuasca, no other adverse side effects were noted. It is important to note that the sample size used in this study was very small, but the results are interesting.

 Magic mushrooms and ayahuasca have only recently entered the medical sphere as potential depression treatments. Ketamine is an anesthetic, used to treat chronic pain and has the potential for addiction and abuse. It also can cause severe confusion or hallucinations. It has long been known that ketamine, a club drug commonly referred to as “special K,” acts as an antidepressant at a surprisingly rapid rate, in comparison to other antidepression treatments. Unlike the current available treatments that require several weeks or months that take effect, ketamine has been found to suppress depressive symptoms after a single dose, occurring within hours of drug administration and lasting about a week. It is not approved by the FDA as a treatment, however, due to its side effects, which include blurred or double vision, jerky movements, including muscle tremors, and vomiting, in addition to its addictiveness. The side effects of ketamine are dangerous, but its beneficial actions have prompted it to be used as a last resort in patients with depression that have not responded to other treatments; it has been used to treat suicidal patients in emergency rooms, and there are ketamine clinics that have begun to appear to administer the drug off-label.

As most molecules, ketamine, scientifically known as N-methyl-D-aspartate receptor antagonist (NMDA) (R,S)-ketamine, is metabolized, or broken down into multiple components, by various enzymes once it has been digested. The components into which ketamine is broken down have different effects on the organism, which partially explains the broad set of reactions one can experience after ketamine consumption. NMDA receptors are found on nerve cells and signaling through these receptors is important for synaptic plasticity, which is the ability for synapses (the structure on a neuron that releases and captures neurotransmitters (electrical or chemicals signals, such as serotonin) allowing for neurons to communicate) to get stronger or weaker, changing the speed at which neurons can communicate. NMDA receptor agonists, such as ketamine, block the signaling through these receptors. This allows for anesthetic effects (as pain is felt through neurons), as well as hallucinogenic effects, due to signaling that is offset from baseline. As the signaling balance is complex, and ketamine can be broken down into so many different components, a study published early this month attempted to elucidate whether there were distinct chemicals in ketamine involved in depression suppression and side effect induction. This study was done to understand whether the molecules involved in the former could be isolated for depression treatment without the negative side effects.

 This paper showed that one of the molecules into which ketamine is degraded, specifically (2S,6S;2R,6R)-hydroxynorketamine (HNK) is responsible for the drug’s antidepressant effects. After doing multiple biochemical assays to study the degradation patterns of ketamine, the group assayed the physical, psychological, and behavioral effects of ketamine treatment as a whole versus treatment with its degraded forms, such as HNK, in mice. They found that although ketamine treatment suppressed depressive symptoms, it additionally induced motor incoordination, hyperactive locomotive activity, and other similar side effects that are seen in humans. In comparison, HNK treatment alone similarly suppressed depressive symptoms, but it did not induce the noted side effects.

This study was conducted in mice, meaning it still needs to undergo multiple rounds of testing before it reaches the potential for human treatment. However, the importance of the study lies in that the antidepression molecule of ketamine was separated from the whole of the drug. This molecule, in portions of the study I did not speak to, elucidated nuances of neuronal signaling that were previously unknown, uncovering potential treatment targets of depression. The study of recreational drugs, particularly with human volunteers, is, indeed, controversial. However, research is a step-wise progression. In order to unravel the mechanism by which these drugs affect mood, and subsequently how we can take advantage of these pathways pharmacologically to treat depression, research must start at the top, proving that these drugs truly have a true effect on mood. From there, detailed biochemical work can be done to chemically tease apart the drugs, eventually leading to the discovery of particular molecules that have beneficially effects without negative side effects, as was done with ketamine. From understanding how, biochemically, recreational drugs effect mood, both in positive and negative ways, scientists can develop novel drugs that target the former without inducing the latter. 

Friends & Foes: Immunology, Neurology, and Schizophrenia

By: Helen Beilinson

At the end of the nineteenth century, Ilya Metchnikoff discovered phagocytes, a subset of cells that ingests and digests foreign particles and cells. This Nobel-winning finding spearheaded the study of immunobiology. The twentieth century brought innumerable basic biological discoveries in how the immune system works— from how it battles and eliminates unwanted invaders to what causes its functions to go awry and induce autoimmunity. The last decade has brought yet another layer into immunology research. Advances in studies of immunology and studies of other organ systems have become integrated to understand how these systems work together and influence each other. Each system is not isolated from the rest of the body; they function in unison, often with overlapping functions, to ensure the health of the whole body.

Phagocytes play a crucial role in immune responses as they work to remove invading pathogens before they are able to harm the host. They are also vital in eliminating debris that is formed during the development and day-to-day maintenance of an organism. Multicellular organisms often have to eliminate unwanted cells, and do so using a type of programmed cell death, termed apoptosis. Swift removal of dying and dead cells, also called apoptotic cells, is necessary for the maintenance of the health and homeostasis of the organism. As opposed to living cells, apoptotic cells display “eat me” signals on their surface as a label for phagocytes to distinguish which cell they should be eliminating. Numerous of these “eat me” signals have been identified and come in many forms, from changes to the sugars attached to surface proteins, to the exposure of new proteins or lipids (also known as fats). The signals can also be derived from the apoptotic cell itself or be attached to the cell after the induction of apoptosis.

One system that plays a notable role is tagging cells for elimination is called complement. The complement system is made up of numerous proteins that have a multitude of functions to strengthen the immune response against pathogens. One of its roles is to deposit specified proteins on bacterial cells to mark them as foreign for their enhanced uptake and elimination by phagocytes. Although complement has been traditionally thought to act in combating infectious agents, there has been an increased appreciation for its role in the removal of apoptotic cells. Throughout the course of apoptosis, the composition of a cell’s outer membrane changes, such that they gain the capacity to bind to complement proteins, marking them for uptake by phagocytes.

For many years, it was believed that certain organs are sites of immune privilege—free of inflammation and immune cells, including phagocytes. Too much uncontrolled inflammation can cause permanent damage to the tissues surrounding the inflamed location. Immune privilege was believed to be an evolutionary adaptation that added an extra layer of protection to critical sites, such as the brain, to prevent organ failure. Recently, the converged studies of neurological and immunological research have brought to light the intricate relationship between these two organ systems, revealing that, in fact, the brain is not a site of immune privilege. In fact, although neuroimmunological research is still in its adolescent stages, it has shown that the immune system plays a heavy role in the development, regulation, and maintenance of the nervous system, particularly of the brain.

Between birth and the onset of puberty, neurons undergo a process called synaptic pruning, or the targeted elimination of the structures that allow neurons to communicate to each other using electrical and chemical signals. Targeted pruning and apoptosis eliminate imperfect neuronal connections and those unnecessary for an adult organism, allowing for the maturation of neuronal circuitry. In complete opposition to the idea that the brain is immune privileged, both of these processes rely on brain-specific phagocytes, called microglia, to eliminate the unwanted synapses and dying cells.

Apoptotic neurons are marked, for the most part, the classic “eat me” signals that are traditionally associated with dying cells, mostly processes that are driven by the cell itself. The “eat me” signals of synapses were a bit more surprising. A finding made nearly a decade ago showed that complement proteins are deposited on synapses during synaptic pruning, targeting them for elimination by the microglia. This finding was unexpected, as it was one of the first papers showing the importance of the complement system in neuronal development. It also emphasized the extent of the complex relationship between the nervous and immune systems. The cells of the immune system provide an invaluable service in the proper maturation of the brain; however, growing research in neuroimmunology has revealed an unfortunate side effect of having immune cells involved heavily in the nervous system.

Scientific and anecdotal evidence has shown for centuries that the immune system loses its strength throughout aging, not only working less effectively, but also working in a less targeted manner, increasing the chance of immunopathology, or damage done to an organism by its own immune system. Immunopathology is caused when the immune cells of an organism begin to attack ‘self’ cells and molecules. Many aging-associated diseases are now believed to be driven, at least to some extent, by the loss of control of the immune system—including neurodegenerative diseases. For example, Alzheimer’s and Parkinson’s diseases have both been linked to increased and mistargeted neuroinflammation. Both have also been associated with elevation of complement proteins and inappropriate loss of mature synapses, as well as the loss of proper function of microglial cells, the phagocytic cells of the brain. Biomedical research has begun to explore how to target neuroinflammation in patients, in an attempt to target the source of the disease, as opposed to current medications, which predominantly work to alleviate symptoms.

Fascinatingly, psychiatric diseases, diagnosed in significantly younger patients than most neurodegenerative diseases, have been increasingly linked to increased neuroinflammation as well. Schizophrenia is a serious psychotic disorder affecting a patient’s cognition, behavior, and perception. Its age of onset is, on average, 18 in men and 25 in women, much younger ages than most neurodegenerative diseases associated with aging. Although there is a strong heritability associated with schizophrenia, the specific genes involved in the disease, and the mechanism by which they do this, has for a long time been only speculative and correlative. In 2011, a Scandinavian study linked complement control-related genes to the heritability of schizophrenia. These genes are involved in regulating the level of complement activity. The study found that schizophrenic patients were more likely to have variants of these genes that were unable to control the level of complement proteins, such that, those patients would have increased levels of complement proteins in their brains. This research, however, was correlative, looking only at the genetics of the patients.

A paper published a few months ago, however, sought to find whether this correlation, and other correlations with similar findings found by other labs, had a biological basis. The authors looked at the presence of complement proteins in human patients with schizophrenia. They first confirmed other groups’ findings that there is a correlation of increased complement activity and schizophrenia. Further, they found that the genetic correlation also manifested in an increase in complement protein expression in the brains of schizophrenic patients. Human complement proteins localized specifically to neuronal synapses and neurons. In mice, they found that the same complement proteins found to be highly elevated in their human patients were responsible for synaptic pruning and neural development. Schizophrenia, as well has other psychiatric diseases, is an incredibly difficult disease to replicate in mice, making it difficult to definitively prove that complement-mediated synaptic pruning and neuron elimination by microglia is the major mechanism driving disease. However, the evidence for this has only been increasing.

Millions of years of evolution have driven our neuronal and immune systems to be dependent on each other. Unfortunately, as regulated as these systems are, imperfections in their regulation can lead to many diseases. Neuroimmunology research is a quickly expanding field working to explore the relationship between these two fields to find new and innovative ways to treat not only neurodegenerative diseases, but also psychiatric diseases, both of which that have been surprisingly linked to a loss of immune regulation. 

A Friendship Threatening Our Honey Supply

By: Helen Beilinson

The Araña Caves in Valencia, Spain are famous for the rock art left by prehistoric people. Aside from more traditional images featuring human figures hunting with bows and knives, there is a portrait of a human gathering honey from a beehive high in a tree, surrounded by a swarm of honeybees. Estimated at 8,000 years old, it is the oldest known depiction of humans consuming honey. Millennia later, we are still eating honey, although our methods for obtaining honey have gotten much simpler and safer. However, the last three decades have been harsh for the apiculture (beekeeping) industry, with our honey supplies diminishing frightfully rapidly. The problem lies in honeybee populations being threatened, but fortunately, research aimed at understanding why honeybee death is at such a high point and how it can be stopped.

Honey is a sweet, thick liquid food made by various species of bees foraging nectar from various species of flowers. Distinct kinds of honey, differing in taste, viscosity, and other properties, arise from varying combinations of bee species feasting on different flowers. After collecting nectar from flowers, honeybees convert it to honey by regurgitating the nectar and allowing the liquid within it to evaporate, while it is stored in wax honeycombs that the bees build within their beehives. Although it is incredibly sweet and delicious for humans and many other animals, its acidity, lack of water (thanks to the evaporation process by which it is made), and low presence of hydrogen peroxide, mean that most microorganisms cannot live in honey. In fact, when burial chambers of Egyptian royals were discovered, the pots of honey they had buried with them (to ensure a sweet transition into the afterlife) were entirely unspoiled, and just as delicious, after thousands of years.

Aside from being a delectable addition to tea, Greek yogurt, and Nutella sandwiches, honey has medicinal applications, thanks again to its biochemical properties. In 220 BCE during the Qin dynasty, a Chinese medicine book was published praising the ability of honey to cure indigestion. Folk healers in Mali use it topically to treat measles, and my dad used to put honey in my nose when I was a kid because according to Russian folk medicine, if you let honey flow through your nose to your mouth, you can get rid of a stuffy nose. I cannot speak to honey’s curative abilities in indigestion and against measles, but I can say that for at least a day after honey being put in my nose, I didn’t need to blow my nose even once.

Since the 1980’s, the honeybee population has been drastically declining, nearly halving in those years. Not only does this pose a threat to the apiculture industry, it also means that any foods pollinated by bees are also facing the prospect of being threatened. According to the United States Department of Agriculture, one in three foods directly or indirectly benefit from honey bee pollination. The loss of honeybees has been linked to various causes, particularly to infection. Bees have very strong and interesting immune systems, but bee populations are often being infected with many new emerging pathogens that lead them to die more quickly. Additionally, Colony Collapse Disorder (CCD) has also been connected to the loss of honeybees. This is a mysterious phenomenon in which worker bees, who physically collect pollen and nectar and make honey, leave their hives and queen bees behind. In essence, this renders the hive nonfunctional. It is not known what exactly causes CCD, but many believe that when worker bees get infected, they will leave their hives to die independently, preventing the risk of getting their queen bee sick.

One of the biggest threats to the beekeeping community is the parasitic mite, Varroa destructor. This mite reproduces in honeybee colonies, sucking the circulating fluids of adult bees for food. If the mite is infected with a microorganism and this microorganism is present in the saliva, this microorganism can spread to the honeybee. Recently, a group of scientists published their discovery of the mechanism by which a virus takes advantage of this means of transmission.

Deformed wing virus (DMV) causes wing and abdominal deformities, as well as affects the cognitive functions, in its bee hosts. Infected bees not only have a drastically reduced lifespan, they are thrown out of their hives in an attempt to prevent the spread of the disease to other individuals. Because of this innate mechanism bees have to eliminate sick bees from their hives, DMV is not an exceptionally good virus at spreading. In fact, only about one in ten colonies are affected by DMV, and those colonies infected tend to eliminate the virus quite readily. Unfortunately, DMV not only can replicate within honeybees, but it can also quite readily expand in the mite, V. destructor. The mite acts as a species in which the viral population can be concentrated and also makes viral spread much faster and more efficient. When mites are also infected with DMV, frequency of the virus in colonies increases from 10 to 100 percent. This relationship is arguably the single greatest inducer of CCD. Although the relationship between DMV and mites was previously known, the details of how these two species work together to aid each other’s replication were not well understood.

It was known that DMV suppresses the immune system of honeybees. To gain an understanding of how the virus affects the bees, the authors of the aforementioned study assessed how the bee larvae respond to different levels of virus infection, without the presence of the dust mite. They found that with increasing levels of virus, the larvae had lower melanization and encapsulation indexes. Melanization is the process by which melanin, the dark pigment in skin, is concentrated, and encapsulation is the process by which the larvae can uptake things, like pathogens to neutralize, from their environment. These processes are linked in that when foreign objects occur in the larva, they are encapsulated and these capsules are subsequently deposited with melanin (melanization) and other toxic molecules to mark them for elimination. The genes responsible for these processes are genes involved in the immune responses of these honeybees, controlled by a factor called NF-κB.

The authors found that in honeybees with more virus particles, there was a greater effect on the expression of their immune genes: the more infected the bees are, the less NF-κB they express. Less NF-κB means less immune genes being expressed, leading to decreased immune responses, such as melanization and encapsulation. The authors observed that these responses are also increasingly dampened with more viral particles.

From the observation that the dampening of the immune response was proportional to virus presence, the authors hypothesized that mites would replicate better on honeybees with more virus and would replicate worse on honeybees with less virus. To test this, the scientists infected the larva first with DMV. After some stages of development, they placed only one mite on each bee. After the honeybees were able to grow independently, they assessed how many mites were on each bee. The proportion of mites on an individual bee correlated with the amount of virus in each bee, such that if a honeybee had lots of virus, the honeybee was covered in tons of mites. Any lucky honeybee to have only a few viruses or none at all had practically no mites living on it.

The close relationship between the Varroa mite and DMV has been a major cause of CCD in honeybees around the world. Many current treatments and prevention techniques against this disease have been targeted at eliminating the mite from bee colonies. However, this study has shown that by reducing the viral load in a bee population, it could directly reduce the mite burden, as well. Studying the basic biology of this complex relationship has shown that the current methods of treating honeybees may not be the best way to tackle the problem, highlighting the importance of basic science. Without the virus suppressing the immune system of the bees, the mites are not as able to feed on their honeybee hosts. Not only will targeting DMV help the honeybees combat the dust mites, but it will also maintain the strength of their immune systems to fight off any other pathogens that enter their colonies and keep honey a staple in many dishes around the world. 

Timing Decomposition with Microbes

By: Helen Beilinson

The last decade has seen many new discoveries that have revolutionized science. Arguably, one of the most influential of these advances has been the appreciation of the impact of microorganisms on human health. In particular, the important roles played by the bacteria, viruses, and other bugs (collectively called the microbiota) that live in or on us, continue to be enumerated. Numerous elegant studies have characterized changes that happen in a person’s microbiota throughout the course of a regular year, during the progression of an infection, or even how a space environment can affect the composition of bacteria in our gut. Recently, a group from the University of California, San Diego explored the changes in bacterial composition during a different phase of life—corpse decomposition.

It might sound a bit gruesome, but the decay of once living things is critical for the cycling of nutrients on earth. The completion of this task requires an extensive arsenal of microbial and biochemical activity. Previous studies had shown that decomposition occurs in a somewhat predictable, stepwise fashion. It was also known that bacteria and other microorganisms are critical for this natural process to occur properly. However, the details of this process were not well understood. The authors of this specific study wanted to know if the environment an organism inhabits dictates the microbial decomposers, whether these microbes come from the host or the environment, and how a decomposed organism changes the environment around it.

To answer these questions, the authors determined the composition of the communities of microorganisms in decaying mice and humans in various environments. Using human cadavers might sound a bit grisly, but it’s important. Mice are good models of various human diseases and are great tools to study many aspects of biology and organismal biochemistry. However, human and mice are still two different organisms, and human subjects were required in this study to verify that their findings in mice matched what occurs in humans. The use of human cadavers is important for the implications and potential applications of this study, as it may be the newest tool in forensic science... but I’m getting ahead of myself.

To identify the families that make up the microbial communities in their samples, the authors utilized a precise technique, 16S rRNA sequencing. This technique takes advantage of the fact that there are some genes that are pretty similar in bacteria that are closely related, and grow more different the less related they are. By sequencing all the microbes, the authors are able to group them into their families and compare how similar or different the microbial populations are between different experimental groups.

An exciting preliminary piece of evidence these authors observed is that the previously described stages of decomposition followed hand in hand with a very precise and dynamic microbial community. The microbes present on day 1 are different from those that emerge on day 4 which again are different from those on day 10. At every stage, between day 1 and day 71, the microbial communities were unique. Perhaps surprisingly, when the authors changed the location of where their mouse specimen was decomposing, there was no effect on the microbial decomposers! A microbial community from a mouse decomposing in a desert environment on day 7 was almost identical to that from a mouse decomposing in a forest on day 7. Seasons also did not significantly impact microbial populations. These same data were obtained using human cadavers.

Based on the latter piece of information, one might expect that if microbial decomposers are more or less the same in different environments, which these decomposers would come from within the host itself. However, the authors found that the soil is the primary source of the microbes, even if the soil type and environment is different. It’s important to note that 16S rRNA sequencing is not the best technique for identifying specific microbes. It is mostly used to identify families of microbes that are closely related. Families of microbes tend to have similar functions, meaning they can carry out similar reactions. These data together imply that because specific microbes carry out specific reactions and that there is a predictable change in microbes over the course of decomposition, one could predict that the biochemical changes carried out by microbes can be tracked in sequential steps during the course of decomposition.

To further explore this question, the authors examined biochemical reactions taking place in the abdomen of the decaying specimen. They found that indeed, throughout the process of decomposition, there are specific reactions that can be detected at each step. The biochemical reactions that take place correlate almost perfectly with the presence of particular microbes that can carry out this process. Interestingly, the authors were also able to show that the soil around decomposing organisms also has such post-death dating properties, in that the products of the biochemical reactions occurring in the organism seep into the soil surround it, changing its chemical properties. The products produced, such as nitrate and ammonium, are used by plants to grow. Although it is a tad ghastly to think about, mammalian decomposition is important for the cycle of life on Earth. The products of decomposition allow for plants to grow which feed the living mammals.

Although now a fairly simple technology, sequencing of the microbiota of an organism has been an incredibly powerful tool in the biomedical sciences. This study has shown that another, perhaps surprising, field that may benefit from this technology is forensic science. Although there are technologies in place to help forensic scientists identify when a person has died, these are often not very precise. This paper’s methods were able to distinguish time of death with a one to two day accuracy based on the microbes found in that body and the biochemical reactions occurring. The microbes around us clearly have a constant influence on our lives: from our birth to our death, microorganisms make us who we are.

Sex > Food for Male C. Elegans

By: Helen Beilinson

Caenorhabditis elegans, or simply C. elegans, are small nematodes (worms) that are one of the most popular organisms used to study animal biology. There are many reasons for this: they replicate quickly and they are easy and inexpensive to care for. But the most fascinating fact is that each individual worm has a set number of cells that each has a specific position and function. Each of the cells can be followed from its conception to its final location. In the 1980’s, Sir John Sultson was one of the first scientists to track each of the worm’s cells throughout development to create one of the first maps of cell lineage. Since then, many researchers have continued to follow up on Sultson’s studies, leading to the belief that C. elegans’ cell lineage map had been completed. So, it came as a big surprise to the field when a group out of London discovered two new neuronal cells in the male worms.

Although C. elegans are sexually dimorphic, like humans, they are not divided into males and females. Instead, they are made up of hermaphrodites that can self-fertilize and males that can only fertilize the hermaphrodites. Males and hermaphrodites have different reproductive behaviors to reflect their reproductive patterns. Male worms need to learn how to optimally locate mating partners, which they accomplish through a process called sexual conditioning. It was previously known that males are attracted to hermaphrodites by sensing their pheromones or by directly sensing them with their tails. A recent study in the journal Nature identified two previously undescribed male-specific neurons that are necessary for sexual maturation.

This finding came as a surprise. Because they are self-perpetuating, hermaphroditic worms are easy to maintain, and are consequently more widely studied than male worms. When studying males, most scientists have focused on physically obvious attributes, such as the worms’ tails, not their brains. However, when these authors looked more closely at male worms’ brains, which had been thought to contain 383 neurons, they found that they contained 385. They called these neurons mystery cells of the male, or MCMs. To identify the function of MCMs, the authors explored other cells that the MCMs interact with. They found that these cells are a component in a loop of interactions between neurons that function in regulating mating experiences by modulating behavior. Specifically, the MCMs are necessary for a male-specific switch in puberty, in which they respond to chemical signals differently after sexual conditioning. This sexual conditioning functions to make the males suppress cues from the environment that indicates presence or absence of food in favor of sex. While hermaphrodites will always migrate towards areas with good food and migrate away from dangerous areas without food, sexual conditioning causes males to go away from areas with good food or go towards areas with bad food if there are potential mates in those locations. In effect, males prioritize sex over food.

To test this hypothesis, the authors set up the following experiment. C. elegans tend to avoid salt-rich environments, because high salt is usually an indication of food scarcity. The authors placed potential mates into a salt-rich environment and placed either hermaphrodites or males outside of this salt-rich location. They found that hermaphrodites, before and after sexual conditioning, will always avoid salt locations. However, the males will avoid the salt location before sexual conditioning, and will enter the salt-rich area after sexual conditioning. If the authors remove the MCMs from sexually conditioned males, they no longer enter the salt-rich area after sexual conditioning. The authors conclude that male C. elegans suppress their knowledge of the risk of no food for the benefit of potentially mating.

This phenomenon makes sense. Hermaphrodites are capable of self-fertilization, so in order to procreate, they need any other worms around and need to prioritize their health to be good parents. Males, on the other hand, absolutely need another partner to reproduce. The health of the male is not as critical in producing viable children as is their partners, the hermaphrodites. Thus, they can risk putting sex before food.

When the authors tried to find the origin of the MCMs during C. elegans’ development, they found that they arise from glial cells. Glia are cells that reside next to neurons and provide structural and functional support to neurons with which they are associated. However, during sexual maturation, some of the worms’ glial cells begin to start expressing neuronal proteins and develop into MCMs. Hermaphrodites do not have the glial precursors of the MCMs, so these cells, from the beginning of the male worms’ lives, are male-specific. This is the first case found in non-vertebrates where neurons develop from glial cells.

The discovery of these new neurons links developmental and anatomical differences between males and hermaphrodites to their sex-specific behaviors. It’s fascinating that the behavioral patterns of these worms is quite literally hard-wired in their minds, as opposed to something they have learned and apply to a situation. These findings are also a testament to how many new discoveries are happenstance and often come from re-observing something that’s right under your own nose. 

Ovararian Transplants in Cancer Patients & Their Implications: Are we challenging nature too much?

By: Helen Beilinson

Cancer results from the accumulation of mutations within normal cells in our bodies that result in their abnormal and uncontrolled growth. These cells replicate very rapidly and amass to form tumors. Two of the most common treatments for cancer, chemotherapy and radiation therapy, function to eliminate cancer cells. Chemotherapy works by delivering chemical substances (such as anti-cancer drugs) into the patient, where they act as cytotoxic agents, killing cells that divide very rapidly. Chemotherapy is unfortunately not specific for cancer cells, just dividing cells, so it kills healthy cells as well. An infamous side effect of chemotherapy is  hair loss, or alopecia, which happens due to the cytotoxic effect of chemotherapy on hair follicles, a rapidly dividing cell type. Radiation therapy uses ionizing radiation, which takes advantage of high-energy rays, to kill cancer cells. Radiation can be targeted to a particular area within the body, as opposed to chemotherapy, which is predominantly administered into the blood stream. However, it still leads to the death of healthy, noncancerous cells, surrounding the tumor location.

Although cancer is predominantly known as a disease associated with age, youth doesn’t protect entirely from cancer. Teenagers and young adults can still be diagnosed with a variety of cancers. An unfortunate side effect in female cancer survivors is that chemotherapy and radiation therapy can often result in infertility, rendering the women unable to have children.

In an article this week in Human Reproduction, authors explored whether they could restore fertility in women who had survived cancer. To do this, before beginning cancer treatment, doctors removed either entire or partial ovaries from these patients who decided they would want to have children after treatment. They then cryopreserved the ovaries, freezing them at subzero temperatures for long-term preservation. After successful treatment of the women’s’ cancer, the surgeons transplanted the cryopreserved ovarian tissues back into their patients.

The doctors found that of the 32 women who chose to try to become pregnant after transplantation, 10 (31%) were able to conceive one or more children. Doctors estimate that women who do not undergo ovary transplants have a maximum of a 5% chance of conceiving after cancer treatments. A 25% increase is not too shabby.

Though it involves two additional surgeries, the treatment is very safe and has provided a lot of comfort to women diagnosed with cancers early in life. As Claus Yding Andersen, a reproductive physiologist who was involved in this study, said in an interview with Capital Public Radio, “Obviously, the thing that interests [patients] the most is to survive the cancers, but immediately after that they would say they are really interested in maintaining their fertility.” This advancement in transplantation medicine has provided cancer survivors with the ability to continue their life plans after the jolting reality of cancer.

This study, however, raises many moral questions. In 1970, the average age of a woman to have her first child was 21.4. Nearly half a century later, today the average age is 25.2. As women are having children later in their lives due to a variety of social, political, and economic reasons, many have considered freezing their eggs as a way for them to retain their fertility until a time when they are ready to have children. In light of the success of cryopreservation of ovaries of cancer patients, physicians have began asking whether it should be available for women who are not cancer patients, giving them the chance to preserve their ovaries until a time when they are ready to have children.

Due to how egg cells develop in women, which I will not go into detail here, eggs that are released from ovaries earlier in life tend to be more healthy and have less potential mutations, compared to those released later in life. It is also believed that the uterus is not as affected by age as other reproductive parts. Thus, in theory, if a woman freezes her eggs and undergoes in vitro fertilization later in life, the woman is very likely to have a healthy pregnancy and a healthier child than if she chose to have children without in vitro fertilization. In theory, this idea is also applicable to transplanted cryopreserved ovaries. However, many other problems deserve consideration. For example, due to decreased estrogen production later in life, the mother will be less able to produce milk to feed her child.

 

Of course, advances in medicine are always incredible—especially when we are able to protect and conserve such a complex system as pregnancy. However, there may be unknown consequences to having children later in life, especially by more medically aided means. Evolution has shaped the way our bodies work for millions of years. Evolution functions not only to advance traits that are helpful in a particular organism, but also to maintain a balance between all systems within that particular organism. Medicine has changed how our bodies interact with the outside world (with treatment of infectious diseases) and how our bodies handle changes within us, such as cancer or pregnancy. Medicine is able to target specific problems or concerns of patients, however, targeting one problem can off set known and unknown factors leading to unforeseen consequences. There is still a lot to be learned about how offsetting the age at which organisms have children can affect the offspring. Although medical advances have been incredibly helpful in some situations, such as allowing women who have lost their fertility do to cancer treatment to mother children, they also raise moral and ethical questions that should be considered before allowing such treatments to be used by everyone.

 

Changing Intrinsic Social Biases While You Sleep

picture by Moyan Brenn on Flickr

picture by Moyan Brenn on Flickr

As we all know, a good night’s sleep is necessary to maintain normal function and to prepare our bodies for the demands of day-to-day life. Without proper sleep, we are more likely to feel groggy or depressed, be more susceptible to becoming sick, and are more likely to develop chronic diseases, such as obesity. Outside of these more disease-preventing functions of sleep, it has also been shown that sleeping promotes learning and recollection of events. In particular, sleep plays an important role in our ability to consolidate our memories. Neuronal traces of memories are reactivated during sleep in order to strengthen these memories and provide them with long-term stability. It’s kind of like our brains replay while we sleep what we saw, smelled, heard, etc. while we were awake in order to instill it in our memory.  

Rapid eye movement (REM) sleep is the most beneficial phase of sleep for memory consolidation; it’s also the phase where you experience the most dreams. During REM sleep, exposure to odors associated with a particular experience can enhance the reactivation and consolidation of specific memories. For example, if you were studying wearing a particular perfume, smelling that perfume during REM sleep reminds your brain of what you were studying that day, as the smell and the facts are associated. After waking up, trying to remember those particular facts becomes easier, particularly if you smell the particular perfume. Scientists have recently shown that a similar phenomenon exists for sounds. One can imagine that by using either olfactory or auditory triggers while we sleep, we can learn new things, or, as a recent paper in the journal Science explored, relearn things in a different way.

Gender biases, particularly the association of women with art and men with science, are a form of memory, as are racial biases that associate people of color with negative words over positive ones. The authors of the aforementioned paper asked whether one’s intrinsic gender and racial biases could be altered using auditory cues during REM sleep. The researchers in this study investigated whether such gender or racial biases could be during sleep.

To do this, pictures of men and women of different racial groups were shown next to either science or art words, as seen in the figure below (from Science). Participants were asked to choose counterbias pairs- men with art terms and women with science terms. When these pairs were seen, participants pressed a button. A correct counterbias association would cause the program to produce a sound. Thus, when they saw a picture of a woman with a science word and reacted in a timely manner, a sound was made. When they saw a picture of a woman with an art word, no sound was made.

After this initial “training”, participants were invited to take a 90-minute nap. Once participants entered REM sleep (which you can distinguish as your eyes make rapid movements during this phase), the authors played the sound that was associated with counterbias pairs to half of the participants. Participants took bias exams both after they woke from their naps and a week after, to see whether they gained or lost social biases. In both cases, participants were more likely to correctly associate counterbias pairs, such that they were more likely to match women with science-related words or those of color with positive words. They only observed this significant change in those participants that were exposed to the sound while sleeping. Those that weren’t exposed didn’t show any changes in their biases.

So what does this all mean? First, it’s pretty cool that sound alone can change how a person thinks. This, of course, has Brave New World caution tape all over it. Manipulation of human thinking is an ethical issue that needs to be taken into account, in research and otherwise. This study also raises the question of whether or not their experiments are truly a test of social bias, or just adept picture/word matching. Many questions remain, but the study does open a lot of new doors. For example, auditory therapy could potentially be used in the treatment of posttraumatic stress disorder (PTSD). The benefits of such therapies could outweigh its costs, but ethical considerations must always be taken into account.

T-Rex’s Weird Looking Vegetarian Cousin

By: Helen Beilinson

Eleven years ago, seven-year-old Diego Suarez found dinosaur bones while hiking with his parents in the Toqui Formation in southern Chile. Fortunately, his parents, Manuel Suarez and Rita de la Cruz, are geologists. They were instantly able to identify these bones as fossils and continued to search of the rest of this beast. Little did the family know, but they had unearthed a previously unknown species—T-Rex’s funny looking, vegetarian cousin. A study published this week in Nature describes this interesting beast, named Chilesaurus diegosuarezi (as the name suggests, this dinosaur was named after the lucky kid who discovered it).

Velociraptors and T-Rexes are some of the best known meat-eating dinosaurs. They both, along with many of their cousins, belong to the group of dinosaurs known as theropods. Theropods are bipeds, meaning they walk on two legs. They first appeared 230 million years ago and although the ‘dinosaurs’ have since gone extinct, common day birds are modern dinosaurs evolved from the theropod family.

For a long time, it was thought that theropods were strictly carnivores. The last decade, however, has brought forth new data showing that a variety of different diets were consumed. Of course, as these organisms are no longer around, it’s difficult to know for sure what they ate, but paleontologists have many tools at their disposal to understand dinosaur diets. First, instead of looking what goes into the dinosaurs, they can study what came out of them by looking at their fossilized poop, called coprolites. Meat-eating dinosaurs tend to have crushed up bones in their poop, whereas coprolites from vegetarian dinosaurs contain more traces of plants. Sometimes, paleontologists are even able to find another animal's bones inside the stomach of a bigger predatory dinosaur! Second, a dinosaur’s teeth give many clues about its diet. Sharp teeth, as you can imagine, are good for killing prey and biting through skin. Large, flat teeth, or leaf teeth, are better for chewing up plants. Skeletons also give scientists an idea of what the animal’s body type was, which gives hints to how it hunted, and thus, what it ate. For example, if you compare the body of an elephant to that of a panther, you might be able to predict which one would be better at chasing after prey. So based on all of these sources of evidence, paleontologists have been able to discern that most theropods are carnivores, except for a few anomalies, likes C. diegosuarezi.

The 3-meter long C. diegosuarezi was found to have flat teeth and a horny beak, characteristic of a vegetarian dinosaur. Although most theropods have sharp teeth characteristic of carnivores, it isn’t entirely surprising that they would have a plant-eating cousin. When in competition with other organisms, it’s good to have something that sets you apart; this make it easier for you to survive. When you are surrounded by meat eaters, if you eat plants, you’ll have less competition for your food source. This leads to many forms of convergent evolution, where you see the same type of feature (such as short, fatter leaf teeth) in different organisms that are unrelated, which can give the appearance they are related. This is why it took so long for this dinosaur to be announced, even though it was discovered over a decade ago—its features were convergently evolved with other vegetarian dinosaurs. Importantly, the discovery of C. diegosuarezi shows that vegetarianism in theropods appeared much earlier than previously thought.

You might be thinking that if only this dinosaur’s teeth were slightly different than other theropods, why did it take so long to classify it? That’s because C. diegosuarezi is special not just because of its teeth, but because it has other non-theropod features, like the leaf teeth.

Like other theropods, C. diegosuarezi ran on its two hind legs with its shorter forearms (about half the size of its hind legs) in the air, much like a raptor. Their hands have two, stump-like fingers with short claws at the end, much like other theropods such as  the T-Rex. Unlike the T-Rex, however, which had a characteristic massive head with a large mouth and thick neck, C. diegosuarezi had a longer neck and a small, rounded head with a small neck. These physical features provide even more evidence that it was a vegetarian.

The femur (a large bone in the leg) of C. diegosuarezi is somewhat different that the classic femurs of theropods, looking a lot more like those of another group dinosaurs called sauropodomorpha. These dinosaurs were long-necked, bipedal herbivores, like C. diegosuarezi, but usually a bit larger. This is another example of convergent evolution contained within C. diegosuarezi’s body. The pelvic girdle, which connects the lower limbs to the spine and upper body, of C. diegosuarezi is also distinct from other theropods.

I can honestly say I’m not a paleontologist, so I cannot give you the details of the new dinosaur with much confidence, but I can say this: it is always fascinating to me when such ‘platypus’ animals come about (as Martín Ezcurra at University of Birmingham calls them). These are animals that at first glance look like they’re made up of different parts of different animals (like the duck-like bill, otter-like body, and beaver-like tail of the platypus), but actually they’re merely very demonstrative examples of convergent evolution. If something works for one animal, proof of how highly adapted it is for a particular function or environment is much stronger if it independently evolves in separate families of organisms. And, hey, they might look slightly different, but if it works, it works.

The Extinction of Tasmanian Devils: Sometimes It's Better to be Different

By: Helen Beilinson

Australia has an incredibly unique list of animal inhabitants. From massive pythons to flying foxes (the largest bat species in the world) to ridiculous spiders and centipedes to some of the largest, smallest, and most poisonous jellyfish, Australians definitely have more interesting backyard fauna than I do here in New Haven (although the black squirrels are pretty cute).

Aside from its slightly more terrifying creatures, Australia is home to a huge amount of marsupials. Marsupials are mammals, meaning they feed their young with milk, like humans do. Unlike humans, however, mother marsupials do not carry their young in their uteri until birth. Instead, after a certain time of developing in utero (meaning, in the uterus), marsupial young will climb into a special pouch on their mothers’ belly to continue developing. These pouches contain the mother’s nipples, to feed the young, and offer protection while the baby marsupials continue growing. Some of the best known marsupials are kangaroos, koalas, and the happiest animal on Earth, quokkas. One marsupial that’s predominantly known more for its cartoon depiction is the Tasmanian Devil, which is currently the largest carnivorous marsupial. Unfortunately, their population is at high risk of extinction. Extinction of species is nothing new; it happens all of the time. Extinction can be caused by high predation, changes in food or climate, high rates of disease or infection, or a slew of others reasons. The pathway to extinction of devils is particularly interesting because their population is threatened by a rare type of disease—a transmissible cancer.

That’s right, the devils are transmitting cancer to each other, like humans can spread a cold.

Before the 1400s, Tasmanian Devils populated the entirety of Australia. However, due to heavy predation by dingoes and indigenous people, the devils were isolated to the Australian island of Tasmania. Since then, major population crashes have continued to affect the devil population. From 1830 to 1930, locals made efforts to exterminate the devils because they preyed on their livestock. In 1909 and 1950, there were smaller epidemics of infectious disease that hurt the devil population. In 1941, however, laws were enacted to protect the devil population because half a decade prior, another carnivorous marsupial, the Tasmanian Tiger, went extinct. These laws aided the devil population drastically, until about half a century later.

In 1996, the first case of Devil Facial Tumor Disease (DFTD) was documented in the Tasmanian Devils. This cancer, as the name suggests, causes large facial tumors on the devils. These facial tumors eventually cause the devils to die of thirst and starvation, as they are unable to eat, drink, or see. The fascinating thing about these tumors, as I previously alluded to, is that they are passed from devil to devil through biting. This transmissibility is incredibly rare in cancer. Usually, cancerous cells develop within one individual and cannot be passed from one person to another. Curiously, the same phenomenon helps to explain why cancer cannot be spread in most species and why it is spread through the devil population.

Each of our cells contains markers (these are basically proteins that cover the exterior of the cell such that other cells can “see” them) on its surface to tell other cells that they are part of the same organism. They mark our cells as “self” as opposed to other cells, that either have “nonself” markers or have no “self” markers. One self marker is the Major Histocompatibility Complex (MHC) molecule. These molecules are critical to our immune responses because they will hold motifs (kind of a protein pattern) that allow other immune cells to recognize what is infecting the body. Because they need to bind to so many different kinds of proteins (they have to be able to display features of all the bacteria, viruses, fungi, etc. that invade our bodies), you can imagine that have different forms is a good thing for your immune system, because you can bind various forms of such proteins, instead of a smaller subset, which would allow you to react to a greater variety of things. Mammalian immune systems have this taken into account. MHC genes are some of the most diverse, or polymorphic, genes out there. This means that there are many, many forms of it throughout the population (don’t worry, they still work great!). Because you have two copies of DNA (one from your mother, one from your father), you get two copies of these MHC genes. This means that the more different your mom and dad’s MHC genes are, the greater variety of foreign proteins you can display on your MHC. This positive aspect of MHC genetic variety can be more greatly appreciated when you see a population where this variety doesn’t exist. This loops us back to the Tasmanian Devils.

Due to the massive population downsizing and isolation of a small population of the devils, they have a very limited variety of these MHC molecules. This observation is one of the major reasons why DFTD is so rampant. As I mentioned before, MHC molecules are self markers. The variety that we see in these molecules allows for a greater system of defining what “self” is compared to nonself. For example, if you have a signal of two letters for variety, there’s only 262 (676) options. So out of the 7.1 billion people on earth, your body will see 10.5 MILLION people’s cells are your cells. If you have a signal for ten letters of variety, there’s 2610 (140,000,000,000,000), so your body will only recognize your body’s cells are your cells.

When rejection occurs after an organ transplant, this is due to the acceptor’s body recognizing the MHC on the donor’s organ, thereby seeing it as nonself and attacking it. Although this isn’t good for a transplant, this keeps a lot of problems at bay. Unfortunately, due to their lack of variety of MHC genes, Tasmanian Devils do not have this ability. The cancer cells of the DFTD can be found on teeth and on lesions on infected devils’ faces. When they bite another devil, these cells are transferred into the wounds of the uninfected devil. If there were enough variety in the MHC genes of the devils, the newly infected devil would recognize the cancerous cells as nonself and would eliminate them, preventing the development of a facial tumor. However, because there is so little variety in the devil’s genes, the newly infected organisms do not recognize the cancerous cells as nonself, and instead see them as self. Self cells are not attacked by the system normally, so the cancerous cells stay, and develop into tumors. This perpetuates the cycle, leading to the cancer spreading throughout the population.

There are currently two other known transmissible cancers. One is a venereal tumor that affects dogs that has been spreading around the world for the past 11,000 years. The second was recently confirmed as a transmissible cancer—it is a soft-shell clam leukemia that has spread throughout the east coast of North America.

The extinction of the Tasmanian Devil is being driven by this transmissible cancer that the devils are unable to eliminate. However, without the initial downsizing of their population due to human predation, its highly probable that the population would have enough diversity of their MHC genes that this cancer would not have been able to even come about.

Some future kids will have three parents to embarrass them

By: Helen Beilinson

In each cell of our bodies, DNA is stored in two places. The nucleus contains nearly all of our genetic material, storing information that ranges from our hair color to how quickly we can break down the food we eat. A few genes are stored in an organelle called the ‘mitochondrion’, known more colloquially as ‘the powerhouse of the cell’. Mitochondria are predominantly in charge of generating their cell’s supply of chemical energy (hence their nickname), but are also involved in a variety of other tasks, such as cell growth and cell death.

Despite being involved in so many functions, mitochondria only have 37 genes (as opposed to the 25,000 in the nucleus). This may sound insignificant, but these genes are critical in ensuring that cells are happy and function properly. Consequently, defects in the function of mitochondria can have major effects on our health, resulting in a set of disorders called mitochondrial diseases. These include Leber’s hereditary optic neuropathy (LHON), which causes loss of vision at early ages and progressive loss of vision due to optic nerve degeneration, and mitochondrial myopathy, a muscle tissue disease. Fifteen percent of mitochondrial diseases are caused by mutations in mitochondrial DNA (the remaining are due to nuclear DNA mutations or other causes).

Mitochondrial diseases are treatable. However, current therapies are predominantly directed toward alleviating symptoms and in order to provide more comfort to the patient. These therapies don’t actually eliminate the cause of the symptoms— particularly mutated mitochondrial DNA. Why is it so hard to target the cause of mitochondrial diseases? Mitochondria are incredibly abundant; nearly half the space inside of heart muscle cells is taken up by mitochondria, and each liver cell contains up to 2000 individual mitochondria. So to target the cause of mitochondrial disease, one would need to eliminate the problem in the original mitochondria that gave rise to the lifetime supply present in all the cells of our bodies. Luckily, scientists have found a trick to do just that.

All of this potentially mutated mitochondrial DNA is inherited from our mothers, because the female egg, unlike sperm, contains all the mitochondria that the offspring will inherit. If a woman’s eggs contain only unhealthy or mutated mitochondria, the egg will usually be killed before it can further develop into a fetus. This is a common protective strategy used to eliminate fertilized eggs with any number of defects that could cause disease in the fetus. There are rare cases where the fetus will continue to birth with such inherited diseases. Luckily, accumulated knowledge about mitochondrial diseases and advancements in cellular biology have led to an invention that helps prevent infertility in women with defective mitochondria and protects their children from inheriting mitochondrial diseases.

This method, called three-parent in vitro fertilization (TPIVF), is essentially a twist on in vitro fertilization, where an egg is mixed with a sperm in a dish, outside of a body, and this fertilized egg is then implanted into a woman’s uterus. Unlike traditional in vitro fertilization, however, fertilized eggs generated through TPIVF contain DNA from three parents (hence the name). In this method, the nucleus from an egg with healthy mitochondria is removed and replaced by the nucleus from an egg with unhealthy mitochondria. This egg, composed of the mitochondrial DNA of parent A and the nuclear DNA of parent B, is then fertilized by sperm of parent C. In this way, a woman whose eggs contain mutated mitochondria is still able to conceive a child whose nuclear DNA is half her own.

At the beginning of February, the United Kingdom became the first country to legalize this method of in vitro fertilization. As early as January of next year, children will be born with three biological parents. As wonderful as this method is at preventing disease and infertility, it raises a lot of ethical issues, which are the predominant reason as to why TPIVF hasn’t been legalized in countries other than the UK.  Allowing for such extreme genetic modification of offspring opens the door to acceptance of “designer babies”. The idea of designer babies is that with advancements in basic cellular biology, people may start wanting to manipulate the genetic make up of their future children to personally select for features such as blue vs. brown eyes, curly vs. straight hair, etc. To my knowledge, in vitro fertilization, be it two or three parent, has thus far only been used to allow couples experiencing infertility or those whose offspring have a high risk of debilitating disease to give birth to healthy children. However, there will always be the question of whether such manipulations will lead to something more extreme.

TPIVF is an incredible advancement that highlights how far cellular, genetic, and developmental biology have come. Nevertheless, with great power comes great responsibility (thanks, Voltaire). It will definitely be interesting to see where our new abilities to genetically modulate offspring will lead.

Sisterhood of the Traveling Genes

By: Helen Beilinson

Unlike humans, bacteria reproduce asexually (yet another reason why I’m happy I’m not a bacterium). This means that one bacterium splits itself into two, giving rise to two daughter cells. The two asexual offspring have the same genome as their one parent. Although keeping the same genome as your parent has a lot of benefits (moms always know best), it can also lead to problems; the lack of new genes sometimes makes it hard for bacteria to adapt to changing environments. Luckily for them, bacteria have found lots of ways of acquiring new genes to survive new environments. One such strategy is getting genes from other bacteria through a process called ‘horizontal gene transfer’ (as opposed to ‘vertical gene transfer’ where parents give genes to their offspring). Horizontal gene transfer doesn’t just occur between bacterial species—it has also happened between bacteria and eukaryotes, which are much more complex organisms. And recently, scientists from the University of Washington found that horizontal gene transfer has brought bacterial genes into animal genomes.

The researchers, led by Joseph D. Moungos, published a study in a recent issue of Nature. They found a bacterial gene called Tae that has repeatedly entered eukaryotic lineages through horizontal gene transfer. Many bacteria have Tae proteins, which function as antimicrobials to kill other bacteria. To do this, Tae breaks down the layer of protection that surrounds the bacteria, called the cell wall. The bacteria that Tae targets actually have two cell walls—an inner wall and outer wall. Tae goes in between the two walls and breaks down a sugar-rich structural protein called peptidoglycan. By targeting peptidoglycan, Tae essentially makes the two cell walls collapse in on each other, killing the bacteria. This group found that at least six times in history, eukaryotes have gotten this gene from bacteria to use as their own. When they looked at the animal versions of the proteins, termed Dae, they discovered that their function in animals is the same as in bacteria; Dae proteins are antimicrobial agents that target peptidoglycan.

The experiments initially showing that Dae has antimicrobial function were performed in a test tube, outside an actual organism. To investigate whether Dae has antimicrobial function within organisms, this study looked at an animal that got Tae from bacteria—the deer tick. Deer ticks can spread the bacteria that cause Lyme disease, which results in fevers, headaches, and rashes, and can lead to more serious symptoms if untreated. Borrelia burgdorferi is one bacterium that can cause Lyme disease in humans. It moves from person to person by living in ticks and transmitted through tick bites. To see if Dae works as an antimicrobial in deer ticks, the scientists removed the Dae protein from the deer ticks and looked for changes in the amount of B. burgdorferi. Turns out that without Dae, deer ticks have more B. burgdorferi. Dae restricts the population size of B. burgdorferi can get in the deer tick by killing the bacteria.

 Collectively, bacteria harbor heaps of antimicrobial peptides. This group looked at one such protein in a defined animal species. If one protein has been transferred to eukaryotic genomes six times in the species that they looked at, this implies that with the thousands of other antimicrobial peptides and thousands of other animals, it is highly probable that many other bacterial genes have been transferred into animals. Who knows, maybe it wouldn’t be so bad being a little bacterial.

The Cold and A Cold: Do they really go hand-in-hand?

By: Helen Beilinson and Zuri Sullivan

Biology is complex—very, very, very, very, very complex—and because of this, simplification is incredibly important. Many experiments are conducted by breaking down a complex system and studying its constituent parts, manipulating specific components (or “variables,” in science slang) to understand how they impact the system as a whole. For example, to understand how viruses replicate within their animal hosts, scientists often study how the virus replicates in animal cells grown in an incubator, instead of the whole organism. As a consequence, scientific knowledge accumulates in tiny increments—each study answers a small, but specific question. When we amass sufficient answers to simple questions, we learn something new about a complex biological system. 

This strategy of deconstruction and reconstruction has led to a number of important scientific discoveries, but it comes at a cost. Findings made in smaller systems can’t always be extrapolated to the larger system. Sometimes, these findings are really exciting, and they tempt us to jump to conclusions because of their potential impact on the larger system. This presents a major challenge to science reporters: keeping a story exciting at its beginning while resisting the temptation for overstatement. Some stories in the media meet this challenge better than others, but like all news, science news should be taken with a grain of salt—a scientist’s interpretation of his or her findings and their potential impact on society can vary widely from the interpretations of reporters.

As a case study for this idea, we investigated a recent high-profile story about the relationship between temperature and catching the common cold. The original study, published last month in the Proceedings of the National Academy of Sciences by a team of investigators headed by the laboratory of Akiko Iwasaki, an investigator of Howard Hughes Medical Institute and Professor of Immunobiology at Yale University, investigated the effect of temperature on protective immune responses to rhinovirus, the predominant causative agent of the common cold.

“It’s been known since the 1960s that the virus replicates better at nasal cavity temperature, which is around 33 to 35 degrees Celsius,” said Dr. Ellen Foxman, a post-doctoral fellow at Yale University who was the primary author of the study. Core body temperature for humans is 37 degrees Celsius (98.6°F), but inhaling cool air brings the temperature in our noses down to about 33-35 degrees Celsius (91.4-95°F)—the temperature at which rhinovirus grows best. By exploring the role of specific immune responses in a cell system, the study found that the temperature difference in viral replication was caused by a temperature-dependent difference in immune responses. Turns out, key immune responses against rhinovirus don’t work as well at 33-35 degrees as they do at core body temperature, so the virus is able to replicate more.

Given the implications of these findings (particularly that we should always listen to our moms and bundle up in cold weather), this study was covered widely by the media, with such headlines as “Common cold ‘prefers cold noses’” and “Common cold really is triggered by cold weather”.

“Some of the headlines went further than we did in our study,” says Ellen. “We didn’t actually study weather at all. Or people going out in the cold.” This was apparent in the original research findings, but many journalists bit into the cold weather/cold virus relationship. “To really make that claim, in terms of a clinical research study, you’d need to have two groups of people, normalize them, put some people in the cold…all that we didn’t do. So some people took it a bit further than we would have.”

This study wasn’t conducted in humans or in animals for that matter. It was done in a system where cells that live on a dish in an incubator in a lab are infected with the virus and are grown at different temperatures. Organisms are a lot more complicated than cells in a dish, making it difficult to extrapolate the findings from the study to a complex organism like a human. The relevance of these studies in humans is not currently known. This was seen as a limitation in other mainstream articles that covered the study, but was never fully discussed. On another note, the study looked at temperatures of 33-35°C compared to 37°C. The temperature of the human nasal cavity during winter could reach far below 33°C. Studies exploring how the immune responses functions below 33°C have not been done. Far from invalidating their results, however, the controlled system in which the experiments were performed is a major strength of the research. It demonstrated that the slight shift in the temperature dampens the immune response to the virus. Because inhaling cold air results in cooling of the nasal cavity temperature, the study implies that the cold weather could lead to more virus replication in human nose.

“After we isolated the primary cells, everything was identical about them, except for a few hours of incubation at different temperatures. So, it’s not the same as studying it in a person…but in a person, there are so many variables that you can’t control, that you can’t analyze. That’s the advantage of doing something in a laboratory. You can control everything except for one variable at a time and see how this variable affects the immune response, and thereby the infection.” This high degree of control is an indispensable component of the scientific method—without it, results are extremely difficult to interpret because outcomes cannot necessarily be attributed to a single variable. In order to show cause and effect, scientists need to ask straightforward questions under tightly controlled conditions. This control allowed for the discovery of what Ellen sees as the most important implication of the study.

The Other Sputnik: The First Known Virophage

By: Helen Beilinson

For every organism on earth, there are a multitude of viruses that can infect it. Every. Single. Organism. There are viruses that infect everything from bacteria to fish to humans, and anything in between. I’m going to tell you about one of my personal favorite viruses, Sputnik.

But first, let me introduce our host, the amoeba. Amoebae are single celled organisms, more closely resembling our cells than those of bacteria. Unlike humans, they don’t have an extensive immune system that protects them from harmful pathogens in their environment. Their main mechanism of protection is ‘eating’ things in their environment and breaking them down, in a process called ‘phagocytosis’. Although this defense works great often enough, there is not much the amoeba can do to protect itself once it’s infected with a virus.

One such virus is the Mamavirus. Mamavirus is a HUGE virus at around 750 nm in diameter. This may seem small, but that’s about half the size of the bacterium E. coli and it’s almost eight times as large as the infamous influenza virus. You can even see it under a regular light microscope, the kind of microscope used in many high school science labs, compared to most other smaller viruses that you need a high powered microscope to see them. It was first found almost seven years ago living inside amoeba in a cooling tower. Mamavirus lives and replicates in the cytoplasm of amoeba, where it sets up a “replication factory” that takes over the cell. This replication factory is where the virus replicates its DNA genome and makes the proteins necessary to build the outer shell in which it keeps its genome. Once Mamavirus replicates to a high degree, the viruses break down the amoeba cell, a process called ‘lysis’, to be released. As I’m sure is clear, this isn’t a great fate for the amoeba who has little defense against the virus once it starts replicating. That’s where Sputnik comes in.

Sputnik is a very small DNA virus, only about 50 nm in size, about fifteen times smaller than Mamavirus. It became fairly famous after its discovery as the first known virophage, a virus that infects viruses. That’s right—Sputnik is a virus that infects viruses. In fact, it infects Mamaviruses. Although Sputnik can infect amoeba on its own, it’s not that great at replicating by itself. However, when the amoeba is also infected with Mamavirus, Sputnik replicates like crazy. It takes over Mamavirus’ replication factory, which is a perfect little nook for the smaller virus to replicate. Although it might sound kind of unpleasant to be infected with two viruses at once, it’s actually a benefit for the amoeba. By hijacking the Mamavirus’ machinery, Sputnik reduces the ability for the big virus to replicate and make proper virions (or virus particles). It can reduce the Mamavirus load up to 70% and decreases amoeba lysis by threefold. Turns out the old proverb “the enemy of my enemy is my friend” really is the case with the amoeba and Sputnik.

Since the discovery of Sputnik, many more virophages have been discovered, which predominantly attack the large viruses that infect amoeba and zooplankton (a marine microorganism). Virophages have increased our knowledge of the deep complexity of the microbial world. As these critters are essentially brand new to our understanding, there is still a lot to learn about how they influence our ecosystems. There has been an ongoing battle amongst scientists about whether or not viruses are living things. Without getting too much into the details of things, the major point of contention is whether we can consider something living if it has to live within another organism’s cells to replicate. Maybe we need to reconsider whether we should classify viruses are living organisms or not. If they can also be infected with viruses, just like us and our pets and the bacteria that live in our guts—why can’t they be alive?

Viral infections and the microbiota

By: Helen Beilinson

Take home points:

1)    The microbiota can influence viral infections—exacerbating disease or preventing disease—so we need to be mindful of how we take antibiotics during viral infection

2)    Antibiotic treatment during flu infection can exacerbate disease

3)    Antibiotic treatment during other viral infections could prevent viruses from taking advantage of immunosuppressive properties of microbiota

 The microbiota—two words that have been splattered across scientific papers, the evening news, and “yogurt for women” packages. The multitude of bacterium that live within and on us constitutes, essentially, another organ that plays a role in many aspects of development and maintenance of the larger organism. It has been long appreciated that the microbiota plays a beneficial role in a host’s metabolism. However, only recently it has been shown that the microbiota is a significant player in the host’s immune system. In fact, it has a huge influence on how we interact with external pathogens and on the pathogenesis (the development of disease) of these pathogens. The predominantly bacterial microbiota live mostly at mucosal surfaces of the host (such as the gastrointestinal tract, genital mucosa, and upper airways), as well as on the skin. Interestingly, viruses are predominantly spread through routes where they would interact with the aforementioned microbiota. Thus, it is highly probable that the microbiota and viral pathogens interact and influence each other in some way. In fact, it has been documented that the microbiota can either obstruct or advance infections of various viral pathogens (or have no effect).

In mouse studies, it has been shown that eliminating the microbiota, either through antibiotics treatment (treatments against bacteria) or by raising mice germ-free (meaning that they have never been colonized with any bacteria), is very detrimental during influenza infection. Mice have more viral particles, higher mortality rates, and more degeneration and death of their lung tissue without their proper bacterial population. The mechanism of microbiota-dependent protection currently is unknown. This trend is incredibly important to study for its implications in human health. Flu infection changes the landscape of our lungs, making it easier for bacteria to infect the lungs. One such bacterium is Streptococcus pneumoniae, a causative agent of pneumonia. The most fatal cases of influenza are due to such secondary bacterial infections. Increases in mortality due to co-infection have been confirmed in mouse models. When patients enter the hospital with bacterial pneumonia, they are placed on antibiotics. This could potentially exacerbate flu disease by eliminating the beneficial bacteria of the patient’s microbiota, leading to death. Unfortunately, there have not yet been studies to show that antibiotic treatment causes patients to fare worse in co-infection situations.

In theory, our immune systems are activated once they sense an invader via certain molecular patterns that are unique to the invaders. For all intents and purposes, however, the molecular patterns decorating pathogenic bacteria are the same as those decorating the bacteria composing our microbiota. Although one of the current mysteries of the microbiota is why our immune system doesn’t eliminate it, it is known that these commensal organisms possess immunosuppressive properties. For example, a molecule that decorates the surface of particular bacteria is called lipopolysaccharide (LPS). There are various forms of LPS, some forms are immunostimulatory, while others, such as those expressed by the microbiota, are immunosuppressive. It has been shown that there are viruses that take advantage of the immunosuppressive properties of commensal LPS to dampen the responses of the host, allowing for active viral replication. Thus, although depletion of a host’s microbiota may be detrimental in flu infection, in cases where the microbiota aids viral replication and disease progression, antibiotics may be a source of treatment.

Studies in mice utilizing two different retroviruses (the family of viruses to which HIV belongs) have shown that these viruses require the presence of the microbiota to be present to flourish. By binding to LPS of the gut bacteria, the viral particles stimulate immunosuppressive pathways, allowing the virus to replicate without the host attempting to eliminate it. These studies were done in mice with murine viruses, so the question remains: Do human viruses interact similarly with LPS? Potentially.

It has been shown that HIV virions can directly bind to LPS molecules. It has also been shown that the presence of LPS during HIV infection (in a series of experiments in cells, not full organisms) decreases the “activated” state of antiviral immune cells, called plasmacytoid dendritic cells, preventing them from potently attacking infected cells. LPS is recognized by Toll-like receptor 4 (TLR4) in our immune system. In an unknown fashion, different LPS variants stimulate TLR4 to produce either a pro- or anti-inflammatory state, which is defined by immune signaling molecules called cytokines. An HIV protein, Tat, has been shown to stimulate the same immunosuppressive pathway as the mouse viruses by interacting with TLR4. This study did not show whether or not LPS was present in the experiments shown (LPS is a pesky molecule that is incredibly difficult to eliminate in a lab setting). Either way, it points to interesting evidence that HIV, as the mouse retroviruses, has possibly evolved the ability to take advantage of the immunosuppressive properties of the microbiota to allow for its replication. Thus, antibiotic treatment could be a potential treatment for HIV replication by decreasing the amount of commensal-expressed LPS that the virus may take advantage of to evade the immune system.

Living predominantly in areas that are directly exposed to the elements and invading pathogens, our microbiota may hold essential information regarding how our body battles infection and either wins or loses. The modulation of our live-in bugs will certainly be a future step in medicine in aiding the treatment of various infections, including those of viral pathogens. So next time you have a viral infection, be sure to ask your doctor whether it is safe for you to take antibiotics—or whether it could possibly help your immune system eliminate the infection.

It is important to note that neither the flu nor the HIV findings have been confirmed in humans, particularly the HIV studies. The intricacies of the microbiota, and particularly the details of how it interacts with intruding viruses, are still very enigmatic. Presented here are very brief summaries of very few papers on this topic, these should not be taken as medical advice.