By Aditya Nair
The Nobel Prize in Medicine or Physiology is awarded annually to the scientist or scientists that perform the most influential research contributing to science’s understanding of medicine or physiology. This year, the award went to James E. Rothman (Yale, and formerly Columbia), Randy W. Schekman (University of California at Berkeley), and Dr. Thomas C. Südhof (Stanford). Each played his part in helping to further understand one of the mysteries of biology: How a cell knows where to send its products.
It helps to think of cells as little factories. Each factory has a production line of sorts, and makes some kind of specific product that is needed somewhere else – sometimes somewhere very far away. In order to do this, the factory packages the product in a convenient and safe shipping container, and sticks a label on it that determines the final location of the box. While this process may seem simple and easy in the human world, in the molecular factories of cells, the process is much more intricate and complicated. Unlike factory shipping, cells aren’t directly controlled by sentient beings who have devised a specific and efficient postal system to get products delivered to exactly where they need to go.
But, as the Nobel Prize-winning researchers discovered, they have come pretty close.
Schekman first worked on figuring out the biomechanics behind this cellular packaging process in the 1970’s. He knew that in order to transport products, cells wrap the products inside a sphere called a vesicle. He studied defective yeast cells, where the transportation process wasn’t working properly. Much like the traffic jams in our world, he found areas where “backed-up” vesicles were piling together and getting stuck. It turns out that a particular set of genes was malfunctioning in the yeast cells affected, meaning that it was those genes that provided the blueprint for this cellular postal system.
Building upon this discovery, Rothman in the 1980’s focused on the action of the proteins that those genes coded for. A protein complex on the vesicles interacts with a protein complex on the receptor site and “locks” the vesicle to the destination cell. Different combinations of proteins code for different destination sites and thus allows for cell-specific targeting. Then, like a zipper, the vesicle unravels and dumps its contents into the destination cell. I’d analogize this to a “ZIP code,” but there are so many brilliant puns possible that I just can’t decide upon one.
Although this research was completed in yeast cells, it was later discovered that some of the genes that Schekman discovered encode for the proteins that Rothman described in humans, suggesting a common evolutionary mechanism for vesicle delivery across species.
Südhof extended this discovery to nerve cells, where vesicles containing neurotransmitters empty their contents into the synaptic cleft (the space between the ends of two neurons), initiating communication with the next neuron. These vesicles can only do this when the nerve cell intends to signal its neighbor. Südhof discovered the way that the vesicles time the release. He found that vesicles are sensitive to calcium ions, which are released by other parts of neurons during neuronal firing, which is how the vesicles know precisely when to empty.
Not only are these discoveries extremely interesting – these three discoveries taken together open up possibilities for hyper-specific drug delivery and, eventually, potential cures for neurological disorders.
By Alexander Bernstein
A great biological benefit of a nation located in a temperate climate, as is the case with the majority of the United States, is that tropical diseases such as typhoid fever and malaria are typically non-issues. Yet, a recent dengue fever outbreak in Florida seems to indicate that perhaps the changing climate, in tandem with certain additional factors, has ended those days of security against such medical problems.
On a worldwide basis, some 300 million people are affected by the disease, which, although rarely fatal, accounts for some 25,000 deaths. A mosquito-borne infection caused by a family of four viral species (DEN-1, DEN-2, DEN-3, and DEN4), dengue yields severe flu-like symptoms with a characteristic combination of very high (>40°C) fever, pain behind the eyes, and general rash. Although there aren’t any specific treatments or vaccines, medical care administered in cases of severe dengue decreases mortality rates from 20% to 1%.
While the past century has seen virtually no locally-acquired cases of dengue in the United States, with any documented infections coming from people crossing the Texas-Mexico border or from immigrants, the recent outbreak in Florida has given researchers serious reason to believe that the virus-carrying mosquitoes have finally gained a foothold on U.S. soil.
Currently, much of the situation is plagued by uncertainty. One phenomenon that is baffling researchers is that while reasonably large populations of dengue-carrying mosquitoes have been found both in Florida and Arizona, only Florida has experienced a chain of confirmed cases of dengue while no documented cases have come from Arizona. Mary Hayden, a researcher at the National Center for Atmospheric Research in Boulder, has so far published the leading theory, in which she suggests that the answer may lie in the length of the virus cycle in the mosquitoes. According to Hayden, Florida’s warm and humid climate appears to allow the infected mosquitoes to live long enough (4-9 days) to transmit the disease to humans. If this theory proves accurate, then it will have serious geographic and climate repercussions as scientists will be able to predict the areas where dengue fever may hit based on the mosquito life expectancy that the area’s climate supports.
With that said, however, Hayden warns that much of her research is still in its infancy as she explains, “We have just finished our first season of collecting mosquitoes but they are still being processed in the lab.” Further, Hayden and colleagues are quick to point out that while cases of patients with dengue fever are documented, little work has been done to track the populations of mosquitoes that carry the virus. Thus, further research is required before the true scope of the situation can be understood and quantitatively evaluated.
With the lack of availability of any true remedies against dengue fever, a better comprehension of why it appears to affect some areas but not others would prove quite the valuable discovery.
By Kellie Lu
After Edward Snowden’s grand alert about the National Security Agency’s (NSA) secret data mining program PRISM, Americans (and the entire world) have woken up to issues of privacy and cyber security. Quantum computing, a better form of cyber security, is evolving as the next standard for semiconductor-based computing (right now, we use silicon and gallium arsenide in transistors). Just as computers evolved from shelves of vacuum tubes piled against walls to 2.5 billion transistors packed into Intel’s 10-core Xeon processor, quantum computers represent the next level of evolution of computing power.
Quantum’s computing’s power, if harnessed fully, has the potential to completely revise our current standards of cyber security. The most prevalent current form of cryptography on the web that protects private information, online banking and shopping, and other modes of sensitive information transfer is a form of public key encryption known as RSA encryption (with RSA standing for the founder’s names). This current form of encryption relies upon extremely large prime numbers that modern day transistor-based computing devices cannot decrypt in a plausible amount of time, allowing secure transfer. However, the power of quantum computing will be able to break down these large prime numbers easily. These qubits, or units of quantum information, that the quantum computers harness are used to solve complex problems. The computers find an elusive solution out of many by solving numerous equations simultaneously from a property called superposition. Schrodinger’s cat is a famous example of this paradox, but here’s another way to think about superposition:
Pretend you’re in a room with a Quidditch snitch, and you have your eyes closed. You don’t know whether the snitch is to your right or to your left until you open your eyes or make a measurement. While your eyes are closed and you haven’t made a measurement, quantum mechanics would dictate that the snitch is both to your right and to your left. More precisely, the snitch is omnipresent, populating all positions in the room at once, (super-) positioned everywhere at any time. However, the moment your eyes flicker open and make a measurement by judging the location of the snitch, you affect the location of the snitch by making this measurement.
Currently, the first commercial quantum computing company, called D-Wave Systems in Canada has produced a 512-qubit computer, able to perform optimization algorithms thousands of times faster than transistor-based computers. We can expect the development of qubits to parallel the development of transistors in Moore’s Law, which is Intel founder Gordon Moore’s perception that the number of transistors on a computer chip doubles every two years, increasing general processing ability of a computer. In fact, since D-wave’s first quantum computer launch in 2010, D-Wave has actually managed to double the number of qubits in the processors of quantum computers each year so far – an astounding rate of development. We’ll have to see if exponential growth can continue in the upcoming years. But in the meantime, the field of quantum computing is enjoying growing sponsorship and interest; NASA, Google, and the Universities Space Research Association have all reportedly signed on contracts with D-Wave. Google has even created a free, downloadable quantum computing packet for the popular video game Minecraft.
However, at this very moment in time, quantum computing is still a ripe discipline; researchers have yet to wholly comprehend and exploit the power of the qubit. Nevertheless, within the next decade or two, the current transistor digital age will almost certainly undergo the transformation into a quantum digital age as quantum computing shifts from being a theoretical concept to a reality. The reality is close: for instance, researchers from the London Centre for Nanotechnology and University of British Columbia recently discovered an element whose electrons possess the capability to adopt superpositioned states. This blue pigment, copper phthalocyanine (CuPc), could potentially be the next material inside a CPU (Central Processing Unit) of the next generation of computers. And right now, who knows what quantum computer scientists may discover next? One conviction is for sure: these developments highlight the growing practicality of quantum computing, one of the most revolutionary computing technologies in the near future.
By Alexandra DeCandia
You can tell by the way she uses her walk that there’s something wrong. Tail outstretched and wings akimbo, the killdeer (Charadrius vociferous) cries aloud, limping along the rocky shore as if unable to fly. She appears injured, pained, and consequently, an easy target for any predators in the vicinity. Walk, squawk, falter. Enemies follow every movement of this pathetic scuttle and trail closely behind. Walk, squawk, falter. They near her position. Walk, squawk, falter. They open their mouths. Walk, squawk – the killdeer flies away. She circles the beach and, once her deceived predators have vanished, returns to her eggs hidden in the rocks.
This distraction display of a devoted plover mother is one example of an anti-predator adaptation in the animal kingdom. Driven by the urge to stay alive and filtered through the finely toothed comb of natural selection, numerous strategies have evolved to protect prey species from voracious foes. While some have adopted fairly common tactics, such as hiding in herds (“dilution of risk”) or mimicking poisonous species (“Batesian mimicry”), others have erred on the side of unique innovation. Cuttlefish, horned lizards, and common potoos all fall into this latter category, and like the thespian killdeer, possess sublimely bizarre means of protection.
Cuttlefish (Sepia officinalis) are masters of visual crypsis. Lacking structures for self-defense (other than a deployable ink sack), these protein-rich invertebrates had to devise means of evading predators without being seen. Their strategy: camouflage. Unlike other organisms that bounce light off their scales (“reflective silvering”) or cover themselves with surrounding corals (“self-decoration”), cuttlefish have evolved the ability to alter their skin color to match any background. Manipulating the muscles surrounding roughly 20 million pigmented chromatophores and corresponding reflective cells, cuttlefish can change their color and pattern faster than any other organism on the planet. Therefore, at the first sight of a predator, cuttlefish immediately vanish, rendering their attackers dumbfounded and hungry.
North American horned lizards (Phrynosoma hernandesi) have a similar effect on their predators. However, their method of evasion is drastically different (and, in my opinion, horrifically traumatizing). When threatened by a potential attacker, these colloquial “horny toads” engage in deimatic displays in an attempt to intimidate their rivals. Puffing out their bodies for increased size, horned lizards resort to autohaemorrhaging if the predator doesn’t back down. A stream of red, noxious hemolymph propels from the corners of their eyes onto the face of their attackers. Stunned, the predator ceases its attack, thereby allotting the horny toad a hasty, albeit bloody, escape.
A far cry from the blood-infused-attack-of-strange employed by the horned lizard, the last anti-predator adaptation is one of peace, tranquility, and arboreal inspiration. Its innovator, the common potoo (Nyctibius griseus), is the elusive singer of the Central and South American night. With its characteristically bugged-out eyes and speckled gray feathers, the potoo is a nocturnal insectivore most at risk of predation during the day. Rather than seeking cover for these resting hours, though, the potoo boldly perches on the conspicuous remains of dead trees. Predators are rampant, but this seemingly easy prey eludes all captors by artfully employing mimesis. Head aloft, eyes closed, every muscle stilled, the potoo spends his day posing as the tree. He does not call, he does not move; he is the master of disguise, and he lives another day.
As is apparent from the above examples, anti-predator adaptations take a variety of forms. Whether an individual hides among a herd, or more dramatically feigns injury, matches its surroundings, ejects blood from its eye sockets, or steadfastly adheres to a tree, it is acting to stay alive. If the adaptation is a success, the animal will pass its genes to the next generation. If it is a failure, the adaptation will disappear. It may seem harsh, but through this process, natural selection produces the incredible diversity of behavior, morphology, and ultimate speciation that makes the study of non-human animals so fascinating, absurd, and, in the case of these prey species and their anti-predator defenses, delightfully bizarre.
By Aditya Nair
You don’t need to be a board-certified physician to diagnose the nation with zombie fever. The Walking Dead. Left for Dead. Dead Set. Shaun of the Dead. Zombieland. Countless zombie Halloween outfits. There’s no denying it: our nation is obsessed with zombies.
The concept of the possessed, brainless, half-living deformed creatures roaming the earth may seem to be purely a product of human imagination, yet this may not be too far from the reality of the natural world.
Meet the Cordyceps fungus, a genus of fungus that has evolved one extremely special trait: mind control. One species closely related to this genus is Ophiocordyceps unilateralis. Upon infecting an ant, the fungus heads straight for the ant’s brain and compels the ant to break from the rest of its colony. It directs the ant, in an astoundingly intricate and specific manner, to travel to the underside of a leaf that is facing north-northwest at around solar noon. The “zombie ant” then clamps down on the leaf with its powerful mandibles, a sort of rigor mortis before the ant is even dead. It will never again move from this position.
Now that the fungus has reached its destination, where temperature and humidity conditions are ideal, a stalk emerges from the dead ant’s head, a deadly skyscraper towering into the jungle air. Then, as if this wasn’t weird enough, the tip of the stalk eventually ruptures and spews clusters of fungus spores into the air from its high-altitude position. These clusters then explode mid-flight, showering the jungle floor (and unsuspecting, innocent ants) with more fungus spores. If an ant is unlucky enough to be “rained on” in this way, the spore will attach itself to the exoskeleton of the ant and slowly build up enough pressure to rupture the exoskeleton, perpetuating the cycle.
However, evolution isn’t done yet: the ants have their own ways of fighting back. If an uninfected colony ant notices the telltale weird behavior of an infected ant, the healthy ant and some friends will carry the stricken ant as far away from the colony as it can and dump the zombie somewhere where it can no longer hurt the colony.
To top it all off, scientists have recently discovered another unidentified fungus that infects Ophiocordyceps unilateralis. That’s right – this unknown fungus’ evolutionary role is to infect another fungus (fungus-ception?). Upon infection, only 6-7% of the spores of unilateralis are viable, checking its potential spread and protecting ant colonies from excessive destruction.
From fossil evidence, scientists think that zombie fungi such as these have been around for 48 million years. Here we have a testament to the power and creativity of evolution that can capture our own imaginations. In fact, in the hit video game The Last of Us, humankind is afflicted with a mutated form of this fungus.
Once again, nature’s imagination has proven to be much more elegant, beautiful, and complex than our own.
By Erik Schiferle
As midterm season at Columbia is nearing an end, surely some students are suffering from the blues. Short periods of the blues are not out of the ordinary, especially for people in high stress environments. However, if an individual lacks a sense of well-being for extended periods of time or with an intensity great enough to create a loss of interest in daily activity, the individual may be suffering from a mood disorder.
According to the National Institute of Mental Health, approximately 11 percent of adolescents suffer from a depressive disorder by age 18 and approximately 9.5 percent of the U.S. population age 18 or older in a given year has a mood disorder. For many, psychological counseling and the use of psychiatric medication ease mood disorder symptoms. However, for some, standard treatments are not enough. Individuals that do not respond to standard treatments may have treatment-resistant depression or refractory depression. Unfortunately, there are no proven treatment options for individuals with treatment-resistant depression.
However, in a preliminary study of treatment-resistant depression, Helen S. Mayberg of Emory University and her colleagues observed that an area of the brain known as Brodmann area 25, or the subgenual cingulate, is extremely rich in serotonin transporters. The researchers also observed that Brodmann area 25 is metabolically overactive in individuals with treatment-resistant depression. They believed that the elevated levels of activity could be linked to the inability to treat the resistant form of depression. Using an experimental procedure known as Deep Brain Stimulation Surgery, the researchers performed a study in an attempt to reduce the elevated brain activity.
Deep Brain Stimulation Surgery involves implanting two metal electrodes into white matter tissue of the brain adjacent to Broadmann area 25, denoted “Cg25” in the photo. The electrodes are attached to an external power source that provides a high frequency impulse of electricity. The electrodes remain in the brain for an indefinite period of time to provide continuous stimulation. The six subjects upon whom the stimulation surgery was performed remained conscious during the procedure so that Mayberg and her colleagues could observe their mood changes. According to Mayberg in a publication released in 2005, “all patients reported acute effects including ‘sudden calmness or lightness,’ ‘disappearance of the void,’ a sense of heightened awareness, increased interest, ‘connectedness,’ and sudden brightening of the room.”
Mayberg and her colleagues concluded that continual stimulation of Broadmann area 25 resulted in remission of depression in four of the six patients. She reported that the electrical stimulation of the “subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.” However, A.L. Malizia of North Bristol NHS Trust and his colleagues reported earlier this year that Deep Brain Stimulation may not result in lasting benefits for patients with treatment-resistant depression. In their study of eight patients, only two patients achieved response/partial response, three patients had a temporary response, while the remaining three patients had no response. Malizia stated that a significantly larger group should be studied to confirm or refute his findings.
There is still much work to be done to develop treatments for people with treatment-resistant depression. However, in many cases, depression is treatable. Each year, depression claims the lives of many people that could have had successful treatment. Many of these deaths are preventable, but they continue to occur because of the stigmas associated with seeking help to battle the disease. Not only must great strides be made to develop alternative treatments for the disease, but also in the ability to convince people that there is nothing wrong with seeking help.
By Alexandra DeCandia
The situation may be worse than we anticipated for the little brown bat (Myotis lucifugus). In a harrowing new study published by University of Illinois researchers earlier this week, it appears that the fungus Pseudogymnoascus (Geomyces) destructans (the cause of White-Nose Syndrome or WNS in bats) is even more resilient than previously thought. Able to colonize any complex carbon source found within the confines of a cave environment, the fungus can persist on a plethora of organisms and at a variety of pH levels. For the little brown bat, this implies that any attempt at the fungus’ eradication from known hibernacula proves futile. The fungus will merely lay in wait on another organism until its preferred host reappears en masse each fall.
The North American strain of Pseudogymnoascus destructans(Gd) examined in this study first appeared in 2006. Infecting only a few hibernacula in upstate New York, the fungus has since spread to over two-dozen states and migrated as far northward as Canada. Highly transmissible, highly persistent, and incredibly lethal, Gd has already claimed the lives of over 5.7 million North American bats with no perceivable end to its destructive reign yet in sight.
Gd infects bats while they hibernate, passing from one individual to the next in the cramped conditions of a M. lucifugus colony. The fungus grows on the cold cutaneous tissues of their muzzles and wings and specifically degrades their epidermal keratin. Resultant lesions form and increase the bat’s vulnerability to other pathogens and parasites lurking within the caves.
Of even greater concern, though, is the fungus’ effect on the patterning of torpor and consciousness during hibernation. As an order, chiropterans possess incredibly efficient metabolisms. Flying or even heating their bodies above ambient temperature can deplete their energy stores to the point of emaciation within days. Therefore, remaining in a state of torpor (i.e. decreased body temperature, lowered metabolic rate, etc.) proves crucial when ambient temperature and food availability decrease in winter. Bats infected with Gd cannot remain in hibernation undisturbed, due either to fungal itch or rapid dehydration. With increasing frequency, they arouse until ultimately perishing from starvation.
Intrinsic value of the species aside, the loss of so many little brown bats at the hands of Gd-induced starvation poses a serious economic risk to North Americans. Through insect predation, consequential reduction in pesticide utilization, and natural agricultural pollination, bats provide ecosystem services worth an estimated $3.7 to $53 billion USD per annum (Boyles et al., 2011). Should WNS eradicate certain chiropterans from the continent as it seems poised to do (at least as far as M. lucifugus is concerned), thousands of metric tons of insects will pour into our fields and lead to a cascade of negative ecological, economic, and human health implications.
Combatting Gd and WNS has proven difficult thus far, to say the least. Indeed, studies have concluded that even if little brown bats manage to evolve means of surviving infection (as their European cousins have done), their populations will still decrease to fewer than 1% of their initial numbers within 20 years (Frick et al., 2010). Such estimates combined with the newfound resilience of Gd paint a grim depiction of the future for M. lucifugus, but they by no means necessitate surrender. Scientists continue to seek physical, chemical, and biological means of impeding the fungus, and some have even developed artificial hibernacula devoid of spores for bats to roost in unaffected. While neither management strategy has yet proven to drastically mitigate the spread of WNS, they represent steps in the right direction towards preserving an often overlooked but economically and intrinsically significant species, North America’s little brown bat.