by Kate Wheeling
BU News Service

Sloths are known for their slow-paced lifestyles. Their sedentary habits allow sloths to pick up a wide variety of microscopic passengers that settle down in the cracks that crisscross their coarse, spongy hair.

A vast fungal community thrives in this shaggy, green-algae glazed coat, churning out bioactive compounds that could one day serve as the basis for new drugs, according to a new study published January 15^th in PLoS ONE. The study’s authors identified over 80 distinct fungal species from sloth hair samples, many of which proved to have anti-parasitic, anti-bacterial and even anti-cancer activity.

“The structure of sloth hair itself is ideal,” says Higginbotham. The crazed hairs absorb water like a sponge, creating a warm damp environment where myriad microorganisms cohabitate in a fast-paced community that drives up competition for space and thus the production of bioactive compounds.

“It’s a pretty clever study,” says Nicholas Oberlies, professor of chemistry and biochemistry at the University of North Carolina at Greensboro. It’s a new niche for scientists to explore in their search for new bioactive compounds.

The researchers took hair samples from nine living three-toed sloths living in Soberanía National Park, Panama in February 2011. Higginbotham and her colleagues at the Smithsonian Tropical Research Institute, UC Santa Cruz, and the University of Arizona, chopped up the hair samples, placed them on agar plates and collected anything that would grow—an important step in drug development research; if it doesn’t grow in the lab, it can’t be used to make drugs. They identified 84 fungal species, three of which were previously unidentified.

The authors used concentrated samples of the fungi, to test for bioactivity against parasitic diseases, cancer cells, and pathogenic bacteria. The crude fungal extracts were considered highly bioactive if they inhibited 50% of the growth of the pathogens and cancer cells they were tested against. They found two fungi that were highly bioactive against the malaria parasite, eight active against the parasite that causes Chagas disease, and a full 15 fungal species that produced compounds active against the breast cancer cell line MCF-7. Another 20 fungi had antibacterial properties. At least one killed off Gram-negative bacteria in a way that didn’t match up with any known antibiotics, suggesting a completely new mode of action—a valuable attribute for potential drugs.

This is just the first step towards the identification of bioactive compounds suitable for drug development. Future studies will need to look at purer, more concentrated samples of the bioactive fungi identified, rule out anything with less than 90% inhibition rates, and tweak growing conditions in the lab so that they’re closer to nature. In the lab, under ideal conditions, fungi might quit producing the same bioactive compounds they need to compete out in the wild.

“It’s quite likely that what they produce in the lab is only a snapshot of what they produce in the wild,” says Higginbotham.

Higginbotham and her co-authors demonstrate that there are still plenty of places to look for new antimicrobials, but in order to tap into those resources we have to preserve them. Some species of sloth, like the pygmy three-toed sloth, are critically endangered. Studies like this demonstrate why “it’s more valuable to have that rainforest as a rainforest than it is to turn it into some sort of turpentine plantation,” says Oberlies. “The conservation aspect transcends the science.”

By: Sara Knight
BU News Service

When English poet John Donne claimed that “no man is an island,” he probably did not anticipate how closely his philosophical musings would align with biological theory four centuries later. As genetic research progresses, scientists are realizing that evolution may be more about cooperation among organisms than competition – truly, no organism is an island unto itself.

Biologists increasingly can pinpoint instances of interdependence among species in all kingdoms of life – leading some to believe it is time for traditional Darwinian theory to evolve. Mounting evidence of cooperation among diverse creatures and their respective microbial communities provides tantalizing hints of a more comprehensive view of life – one that challenges the definition of an organism. For decades many microbiologists have believed that no organism evolves alone, but rather as a joint effort with the millions of microscopic creatures teeming with them – fungal, bacterial, and protist. Now, evolutionary biologists are catching on: some think that natural selection acts on “super organisms,” the creature plus its microbes, rather than an organism itself.

Charles Darwin proposed the theory of natural selection in 1859, and it remains a hallmark of evolutionary biology today. Natural selection’s basic tenet is that traits that prove beneficial to an organism will become more common over successive generations. While this basic premise seems almost obvious in its simplicity, many evolutionary puzzles are left unaddressed. For example, the level of organization on which natural selection acts remained an enigma. Do evolutionary pressures act on cells themselves, or whole organisms… or even groups of organisms?

Biologists Eugene Rosenberg and Ilana Zilber-Rosenberg think they have the answer. In 2007 they proposed that organisms adapt to their environments with and because of their microbial communities. They noted that a change in the makeup of species in Mediterranean corals’ microbe population, prompted by changing sea temperatures, enabled the coral to fight off a devastating bleaching virus. The coral, which lacks an adaptive immune system, overcame a viral threat in one generation. The microbial community of the coral successfully fought off the lethal threat, ensuring its survival into another generation. Their observation led the team to develop the hypothesis that natural selection acts not just on one set of genes, but on all of the genes within (and on) an individual, including those of the micro-occupants.

All lifeforms possess robust microbial communities that are linked to physiologic function – humans, for example, rely on hundreds of species within our gut to digest our food and absorb nutrients. Hyenas have unique microbe collections in their anal glands, the distinctive scent of which acts as a badge of pack membership. The mixture of intestinal microbes in the common fruit fly influences with whom they choose to mate. Rosenberg believes these facts justify extending his team’s hypothesis to encompass all life, rather than just this specific Mediterranean coral.

Biologists have long accepted the importance of microbes to the lives of larger creatures – for example, the mitochondria in your own cells originated from a once free-living bacterium that was engulfed by a larger cell – yet many hesitate to agree with Rosenberg’s broad generalization of cooperative evolution in larger creatures.

Roberto Iglesias Prieto of the National Autonomous University of Mexico does not believe Rosenberg and his team proved that the Mediterranean coral was suffering from the viral perpetrator they identified. He, among other marine biologists, calls for a more rigorous examination of Rosenberg’s claim. Iglesias Prieto also cautions that an organism’s fitness might not rely on its entire set of microorganisms, but probably only its beneficial microbes.

Other biologists like John R. Finnerty, director of Boston University’s marine program echo this caveat. Finnerty does not question Rosenberg’s basic claim, but suggests the primary coral research does not support the larger hypothesis that natural selection acts on super-organisms. In some cases, a creature may need a very specific species of microbe to fill a role, while in others the co-occupancy is more of an incidental arrangement between the microbe and host, Finnerty says. The relationship between host and microbe can be very flexible – a fact that Rosenberg’s hypothesis does not address.

Despite these concerns, biologists are becoming more interested in the role our resident microbes fill. In 1998 microbiologist Lynn Margulis wrote that “the full impact of the symbiotic view of evolution has yet to be felt.” Her foresight anticipated Rosenberg’s ambitious, broadened concept of how to define an organism and a concept of evolution that stresses cooperation, rather than competition, as the main catalyst for change. Researchers are currently working toward teasing out the exact roles microbes play in the production of life, but there is a general-consensus that we literally are more than the sum of our parts.

By Matthew Hardcastle
BU News Service

Meet Cymotha exigua, an adorable crustacean of the Cymothoidae family. C. exigua sometimes goes by the common name “tongue-eating louse,” which is a completely unfair mischaracterization: it’s not a louse at all. The tongue-eating part is accurate though.

Cymothoidae contains a number of fish parasites, but none are as charismatic as our C. exigua. This plucky crustacean lives off the western coast of Mexico and Central America. Though its lifecycle is a bit of a mystery, males can be found attached to the gills of at least eight species of fish. When necessary, one of the males will become female, growing larger and making its way to the fish’s tongue, where the real fun begins.

Rather than selfishly sapping the resources of her host and offering nothing in return, C. exigua decides to do her fishy friend a favor by giving it a brand new tongue. Using specially adapted claws, C. exigua draws blood from the boring, regular tongue of her host, until the organ withers away. Then the crustacean makes itself at home by attaching to the muscles on the stub of the amputated tongue.

C. exigua happily begins her new life as a fish tongue, doing all the regular duties of her host’s old organ. All she asks for in return is the occasional sip of blood or nibble of mucus. The fish doesn’t seem to miss its old tongue at all.

You may find yourself wishing for a happy crustacean like C. exigua to come and live in your mouth, but alas they have no effect on humans, apart from a possible love bite if you handle a live one. Snapper with crustaceans for tongues occasionally wind up in fish markets, but C. exigua is not toxic to humans even if you accidentally cook her up.

Truly, C. exigua is one of evolution’s most whimsical and enchanting creations.

By Sara Knight
BU News Service

You eat right, you exercise, you meditate daily. You had an ideal childhood with loving parents and a healthy social life. Cigarettes and alcohol? Never! And yet despite your textbook health precautions and lack of turmoil, you find yourself diagnosed with a serious mood disorder. Why? The answer may lie with the type of childhood one of your grandparents experienced – maybe your maternal grandfather was neglected as a boy and experienced social isolation from his peers. This obviously extreme illustration may be overly simplistic, but current research hints that this story may not be all that ridiculous or fictional. In mice, researchers have found evidence of grandparents’ distress manifest in the genetic code of their grandpups.

Developing a psychiatric illness may not rely so much on the genes you inherit, but rather the accessories that accompany them. Evidence is mounting that chemical changes on genes actually contribute to certain mental illnesses, not the presence or absence of a gene itself. These alterations, called epigenetic markers, influence how lively or inertly a gene acts and result directly from environmental factors. Intriguingly the evidence that these changes are heritable is also mounting, meaning for example your grandfather’s lifestyle could affect your likelihood of suffering schizophrenia. Because the changes are simple chemical reactions they may be also reversible – a fact that excites many doctors frustrated by the trial-and-error style of most psychiatric medications.

The backbone of this research is a fusion of developmental biology and genetics called epigenetics, epi- meaning “above” in Latin. Developmental biologist Conrad Hal Waddington coined the term in the early twentieth century to describe, for example, how a blood cell is able to “know” how to function as an oxygen carrier rather than a liver cell, despite containing the same instruction manual (DNA) as the cells within the liver. ‘Epigenetics’ refers to molecular “light switches” that act on DNA, telling which genes to turn on and which to turn off.

These switches consist of different molecular markers attached to your DNA. Methylation, or the addition of a methyl group to a segment of DNA, effectively tells a gene to stop interacting or to increase its output within a cell. The changes can also tighten or loosen the coil around your DNA – the looser the coil the more likely the DNA will interact with other chemicals, causing increased expression.

Environmental stressors, diet, and exposure to chemicals all affect the changes to your DNA that can lead to altered expression. This means that your environment leaves a physical imprint on your genes and subsequently affects how your DNA is expressed. Epigenetics silences the old nature versus nurture “debate” – our genetic material (nature) is honed by our environment (nurture); there is no actual discrepancy between the two.

Doctors have used epigenetics to examine differences between cancerous cells and their healthy counterparts, but now some epigenetics researchers are setting out to tackle the notoriously complex problems presented by mental illness. Diseases like schizophrenia, depression, and bipolar disorder possess a genetic component – they run in families but there has been no conclusive “smoking gene” to predict who will develop the conditions. Mental illness and childhood trauma correlate; leading researchers to hypothesize early stress may trigger alterations on genes important in mental illness.

Researchers found mice that were traumatized in early life had grandpups with DNA that was more heavily methylated – indicating the trauma’s physical alterations on their genes could be passed down their familial line. In 2010 Isabelle Mansuy, a neurobiologist at the University of Zurich, randomly separated mice pups from their moms for a period of 14 days immediately after their birth. After that stressful period, she raised the pups normally. Mansuy found the pups that suffered early trauma had epigenetic modifications on genes related to emotional regulation and stress response. The genes were more heavily methylated. This reflected in the behavior of the mice – they had a higher incidence of the mousey version of depression and anxiety, namely increased stress and lowered grooming and social behavior.

Most intriguingly Mansuy’s male mice seemingly passed on their early ordeal’s genetic legacy through their sperm – their pups also showed the same methylated DNA despite a lack of early trauma. Dr. Tracy L. Bale of the University of Pennsylvania has found that the genetic effects of early stress can be seen in up to three generations of mice, even if the subsequent two generations are raised without stress or separation. Bale also has isolated key developmental windows in which mice are particularly vulnerable to modification.

Were the mice born with genes “marked” for depression and anxiety, or were they simply born more sensitive to environmental stressors? The research community has not reached a consensus, but Bale found the telltale methylation in the mouse sperm, indicating it is a physical transmission. Not all researchers are convinced though, especially when humans are involved.

These molecular light switches are fused onto our DNA through simple chemical reactions, leading many researchers hopeful about potential treatment options. Medications could potentially reverse these modifications and change how a gene functions, as happens in several cancer medications currently on the market. Understanding the underlying causes of mental illness could lead to an increased ability for doctors to intervene before symptoms hit. “The implications are huge from a social public health standpoint,” says neuroscientist David Dietz of the University of Buffalo. He believes that being able to identify and treat vulnerable populations means the next generation “may not be in such a doomed state.”

Though most of the hard evidence for generational transmission has been found in mice, researchers have collected retrospective data on humans that hints the same may be true for us. Researchers Alan S. Brown and Ezra Susser, both of Columbia University, linked prenatal malnourishment to an increased incidence of schizophrenia in children conceived during the Dutch famine of 1944. Humans, however, have lengthier lifespans and less motivation to faithfully participate in multi-generational studies compared to mice, so researchers have a much harder time gathering convincing data. Most human epigenetic studies concerning mental illness are ongoing and the evidence is anecdotal.

Neuroscientists studying epigenetics are still in the first phase of discovery – techniques need refining before any grand statements can be made. Researchers like Johns Hopkins researcher Zachary Kaminsky is working towards developing cleaner research techniques by cataloguing different kinds of genetic markers that may indicate the sort of genetic changes found in mental illness.

By Matthew Hardcastle
BU News Service

This summer, hundreds of dolphins beached themselves along the coast of New England. The National Oceanic and Atmospheric Administration (NOAA) has tentatively pegged the cause of this particular dolphin die-off as a viral outbreak. Yet even in normal years, dozens of dolphins around the country become stranded in shallow water or beach themselves on shorelines. Are these often sickened or injured animals simply disoriented, or are they making a conscious decision to leave their tightly-knit social groups and die on the beaches? In other words, do dolphins commit suicide?

Quite possibly.

From what we know of dolphin intelligence, they certainly have the capability of choosing to die. According to Lori Marino, a researcher who studies the brains and behaviors of animals, we know that dolphin intelligence has a lot in common with human intelligence. By administering tests to captive dolphins using mirrors, props, and memorized tasks, researchers have proved that the marine mammals are self-aware, remember their past actions, and can even think about their own thoughts.

However, compared to humans a dolphin’s sense of self-identity is more tightly tied up to its social identity. In the wild, this dolphin groupthink can result in one sick leader beaching its entire pod. To swim away from the shore and defy the will of the group would go against their core instincts. If rescuers push healthy dolphins back to sea while their leader remains on shore, the dolphins will usually just re-strand themselves.

Dolphin neurology also differs significantly from humans. The sophisticated echolocation system that dolphins use to hunt also serves as a constant form of communication, transferring personal information at a greater rate than do our sluggish human voices. A dolphin’s limbic system, the part of the brain that controls emotions, is also highly developed. Marino describes dolphins as hyper emotional; when they are hunted by fisherman, simple panic can send dolphins into cardiac or neurological shock.

A dolphin’s mix of intelligence, strong social bonds, and hyper-emotionality can backfire in the form of destructive behavior. Dolphins in captivity, even those born into it, are deprived of social interaction with their own kind, resulting in high levels of stress. Captive dolphins may ram their heads into the sides of their tank or aggressively lash out at other dolphins.

When a stressed dolphin jumps out of its tank, is it making a decision to ends its life? When a sick dolphin beaches itself, is it a selfless act made for the good of its social group? It’s hard to say. A test has not yet been developed to show whether dolphins understand the permanence of death or their own actions.

However, Marino said, dolphins can and do lose the will to live. If two dolphins in captivity become close companions, the removal or death of one will cause the other to spiral into despondency. The abandoned animal will stop eating and spend more and more time floating lethargically at the surface. At that point, it is only a matter of time before the dolphin dies of a broken heart.