Boldly Going Where No One Has Gone Before

 

By Knicole Colon, PhD

Launched more than a decade ago, the European Space Agency’s Rosetta spacecraft  has finally reached its destination. For the first time, humans have maneuvered a spacecraft through the vastness of space to meet up with a comet and, believe it or not, that spacecraft will soon enter in orbit around that comet. Rosetta will then travel along with the comet for over a year and provide us with never-before-seen access to the life of a comet.

This now famous comet is known as Comet 67P/Churyumov-Gerasimernko. Comets are generally named for their discoverers, hence the lengthy surnames. This comet (which we will call 67P for short) is also the 67th periodic comet discovered, and it was discovered in 1969. The periodic part refers to the orbit of the comet. Periodic comets will continue to orbit the Sun as long as they aren’t burned alive (like Comet ISON was in late 2013) or don’t collide with other objects in the Solar System (like Comet Shoemaker-Levy 9 did when it collided with Jupiter in 1994). For those comets that have highly elliptical orbits and survive dangerously close encounters to the Sun, the comet’s proximity to the Sun is what results in the evaporation of cometary material. This effectively creates a temporary atmosphere around the comet, which can form the cometary tails that we all know and love.

Besides having exciting deaths and awesome-looking tails, comets are quite interesting objects since they contain complex organic compounds made up of carbon, hydrogen, oxygen, and nitrogen. It has been hypothesized that the building blocks of life on Earth came from comets that deposited organic molecules and water on Earth. If this is the case, then we need to understand how exactly this happened. Given the high interest in the composition of comets, they have been heavily studied for years. For example, there have been a number of spacecraft that had flybys of different comets in the past. However, this is the first time that a spacecraft will enter in orbit and travel along with a comet for a significant amount of time. We will be able to see firsthand how a frozen comet (that potentially contains original material from the formation of the Solar System) is affected over time by the Sun. On top of that, the Rosetta spacecraft is home to a little lander called Philae which will in fact land on the nucleus of Comet 67P this November. Prior to landing, data from Rosetta will help astronomers determine an optimal and safe landing site for Philae. This may be a bit more difficult than anticipated, given that as Rosetta approached Comet 67P, it discovered that the comet has a double nucleus with very variable terrain (as shown here  and here).

Once Philae has landed and secured itself to the comet’s surface with harpoons (necessary due to the extremely low surface gravity, estimated to be about one ten-thousandth of Earth’s surface gravity), it will send back to Earth an incredible amount of information. Philae has ten instruments installed to do this (not to mention the numerous instruments installed on Rosetta). Some of these will take close-up pictures and run tests to determine the chemical composition of the comet’s surface. A drill system will obtain soil samples at different depths and a mass spectrometer will analyze those samples. A radar will be used to determine the internal structure of the comet. Needless to say, these little spacecrafts are going to tell us a great deal about this comet.

Currently, the Rosetta spacecraft is less than 62 miles from the comet’s surface. By mid-September it will be just 19 miles from the surface, and then it will be maneuvered to officially enter orbit around the comet at that time. Philae’s landing on the surface is currently scheduled for November 2014, so keep an eye out for news on that. Just like landing men on the Moon and rovers on Mars, this landing will be one for the record books. Beyond that, stay tuned for when Comet 67P has its closest approach to the Sun in August 2015, with Rosetta in tow.

A new HIV Model Could Help Shed Light on Mechanisms of Viral Host Tropism

 

By Asu Erden

 

To better understand the epidemiology of human diseases, we must identify the immunological mechanisms that govern their transmission and enable their jumping from one reservoir to the next. In this regard, animal models have proven useful. Yet the pathogenic mechanisms enabling the interspecies transmission of many diseases remain elusive. This is the case for the Human Immunodeficiency Virus (HIV). Primate and humanized mouse models have helped shed light on the viral mechanisms of HIV. As far as primate models go, pigtailed macaques have been particularly useful since they present the advantage of better mimicking the pathogenesis of AIDS as seen in humans. However, these macaques are not susceptible to HIV-1 since the virus does not normally cause AIDS in this host species. But Hatziioannou et al. recently provided a new stepping-stone to the field when they published their findings of an HIV-1 infection leading to AIDS in pigtailed macaques in the journal Science.

The team of researchers used a modified HIV-1 that encodes Simian Immunodeficiency Virus (SIV) Vif. The latter protein prevents the action of host-specific antiviral enzymes. By passaging this virus and taking advantage of the lack of key antiviral proteins (e.g. TRIM5) in pigtailed macaques, Hatziioannou and her colleagues were able to successfully infect these animals. In one of them, the virus replicated to reach stable high titers. The team decided to deplete this animal of circulating CD8+ T cells to alleviate immune pressure and allow for higher viral titers, since these cells are believed to contribute to the initial control of viremia. By the fourth passage (P4) of this virus in CD8-depleted macaques, AIDS-like pathogenesis became apparent (e.g. sustained high viremia, immune activation in the gut) and eventually animals fully developed the disease (stark loss of CD4+ T cells).

Hatziioannou et al. confirmed that they had obtained a virus capable of causing AIDS in pigtailed macaques by isolating it from P4 animals and inoculating new CD8-depleted animals. The infected macaques developed AIDS confirming that the researchers had developed a virus capable of triggering a pathogenesis similar to what is seen in humans. Moreover, the key time period for CD8+ T cell-depletion was identified to be the acute phase of infection since depletion at the chronic stage did not yield AIDS-like symptoms.

Several signature mutations in the passaged virus’ genome also reflected that Hatziioannou et al. had successfully adapted the virus to acquire characteristics seen in human HIV-1 infection. Single viral genome sequencing revealed that envelope mutations were essential for the aforementioned adaptation in pigtailed macaques. Of specific interest was a deletion in one of the loops of the envelope protein, which is typical of human lentiviral infections but much more rarely observed in non-human primates. Additionally, an insertion mutation in the transmembrane domain of the HIV-1 Vpu immune evasion protein enabled it to immunologically outcompete macaque tetherin, which normally prevents virions from budding from the host cells.

HIV-1 causes AIDS in humans and chimpanzees. The fact that Hatziioannou et al. were able to develop a model of HIV-1-induced AIDS in pigtailed macaques promises to shed light on the key immunological factors at play in the epidemiology of HIV. Their protocol also reinforces the idea that CD8+ T cells play an essential role in the early stages of the pathogenesis, since macaques had to be depleted of this cell subtype during the acute phase of infection to progress to AIDS. Overall, these results highlight the importance of the arms race between the virus and the host. In four passages, Hatziioannou et al.’s modified HIV-1 virus developed the ability to counteract macaque tetherin. Such evolution is required for the virus to spread to new hosts. In the future, studies of HIV-1 in this pigtail macaque model have the potential to provide insight about new prophylactic vaccines and therapeutic drugs against the virus.

Is Fido Jealous?

 

By Robert Thorn

If you were to ask a dog owner if their canine companion was ever jealous the answer would most likely be a resounding “Yes!” Every dog owner has anecdotes about their dog whining, pushing and pawing to receive more attention when they were not receiving adequate attention. As any good scientist knows, anecdotal evidence is not enough to prove a theory, so a group at the University of California San Diego set out to obtain concrete evidence on whether or not dogs become jealous.

 

At first glance it may seem like a silly undertaking to test whether dogs become jealous, but the study will allow a better understanding of the basic nature of jealousy. Most of the research regarding jealousy has focused on jealousy that is felt within romances when one partner feels that the relationship may be in danger. This kind of jealousy is deemed as “complex jealousy” as it involves complex cognitive abilities and the jealousy can be altered by the context of the relationship. Researchers have also theorized that there may also be a “primordial jealousy” which is much more basic and does not involve complex cognitive abilities. This form of jealousy has been supported by research involving the jealousy that infants feel when they are not receiving sufficient attention from their parent.

 

The experimental set up used to test if dogs become jealous involved the use of three objects: a stuffed dog, a jack-o-lantern bucket and a book. The stuffed dog was the jealousy inducing object that should act as a proxy to the owner giving attention to another dog. The bucket was a control object that when treated the same way as the stuffed dog should not pose a threat to the dog’s relationship with the owner and therefore not induce jealousy. Finally, the book was used as a control that would take the owner’s attention away from the dog, but not on to another object, testing whether the reactions observed stemmed from lack of attention or from attention being given to another object. The experimenters videotaped 35 sets of dogs and owners in situations with the various objects. The owners were instructed to show affection to the stuffed dog or the bucket (e.g. petting, sweet talking, etc.) or to read the book out loud and the dog’s reactions were scored.

Unsurprisingly, based on anecdotal evidence, the dogs seemed to show some level of jealousy in these experiments. More dogs exhibited behaviors that are indicative of jealousy such as snapping, getting between the owner and object, pushing the owner or object and whining, when the attention was given to the stuff dogged compared to the bucket or the book. In addition the researchers grouped the dogs who had snapped and compared the “snapping” group’s metrics and the “nonsnapping” groups to see if there was some predisposition to jealousy. The snapping group had an even more striking indications of jealousy, but the nonsnapping group still showed jealousy-related behaviors. The researchers suggest that these individual differences may indicate that different dogs displaying jealousy in different ways.

 

The fact that dogs show these jealous behaviors will give better insight into the evolution of jealousy. This “primordial jealousy” may have originated as a way for animals who have large litters to compete for resources, as a way for animals to cooperate better in packs or this jealousy could be unique to dogs, which have been domesticated by and have become dependent on humans for survival. This domestication has been shown to give humans and dogs a unique relationship and dogs have been shown to mimic some human behaviors. Determining which of these options is most probable will fuel research on jealousy and give scientists a much better understanding of the evolutionary advantage of jealousy.

Why Panic Can Accelerate the Therapies Discovery

 

Jesica Levingston Mac leod, PhD

 

In March, the Center of Disease Control (CDC) reported an outbreak of a “more virulent” Ebola virus infection in Guinea and Sierra Leone .Now, the disease has been spread to Liberia and Nigeria, among other West Africa countries. The final count is more than 1600 confirmed cases of Ebola hemorrhagic fever, with almost 900 deaths caused for this syndrome. Some of these cases included health-care workers. Indeed, two medical doctors were taken back to US to be treated with a new cocktail in the Emory University Hospital facilities in Atlanta, GA. Some Americans began to panic, for example Jon Stewart said in his show that “They are importing Ebola”.

Last week, two patients with Ebola like symptoms were all over the news. One of these cases happened in the New York City Mount Sinai Hospital, and the patient was isolated and tested right away. The hospital sent an email to all the employees updating them about the situation, and the press took over it. The bright side of the situation, in addition to the negative test result for Ebola virus, was the fast reply. The dark side was the paranoia and the lack of information and knowledge about this virus from the Manhattan community. It was alarming to read that some neighbors did not want to go to the emergency room in the hospital for fear to get infected. Well, you can’t get infected just for seating next to a sick person, or talk, or shake your hands: it is not an airborne transmitted virus.

The other problem is that the symptoms are pretty similar to other more “common” diseases: Fever, rash, severe abdominal pain, vomiting, and bleeding, both internally and externally. The difference is that the fatality rate is more than 60%. The transmission of the virus mostly occurs by contact with infected blood, secretions or organs of either bats, nonhuman primates or humans. This is why you should not eat bats or monkeys if you visit any of the affected areas, or hang around any cemeteries. Not surprisingly, Ebola was named as the most frightening disease in the world. It was documented for the first time in 1976 in the Republic of Congo; one of the sources came from the Ebola River.

 

In 2012 an outbreak in Uganda found us in a similar medical emptiness: the research of two of the vaccines that were “apparently” going great had been canceled by the department of defense, due to funding constraints. Therefore, so far we do not have any vaccine or effective treatment available.

In 2009, Dr. Feldmann, by then working in Canada (now in Montana, US), developed a vaccine that was used years after in Germany when a researcher accidentally pricked her finger with a syringe containing Ebola The Feldmann’s vaccine consists in a recombinant vesicular stomatitis virus expressing the Ebola glycoprotein which protects macaques from Ebola virus infections; although this method is not licensed for human use and the government founding has been random. A similar vaccine has been produce by Profectus BioSciences in Tarrytown, New York, but they are also short in the monetary founding that will push the research to the human trials.

The famous ZMapp serum, the treatment that the 2 Americans are receiving, is a cocktail of humanized, three-monoclonal- antibodies. This “cure” was the result of the collaboration of 25 laboratories among seven countries. The project, funded by the National Institute of Allergy and Infectious Diseases (NIAID), has a total budget of $28 millions. The scientific leader is the Dr. Erica Ollmann-Shapire, whom claimed that she would take the cocktail without doubts if she would be infected. Also the company Mapp Biopharmaceutical, based in California, is the principal producer of these antibodies. The initial trials in macaques were very successful, but the approval for the use in human trial is pending until 2015.

A lot of laboratories along the world are working towards the better understanding of the Ebola virus and the possible vaccines and cures. Most of these researches are founded by the US Department of Defense. But, why does the US Department of Defense care about an African virus? The answer is pretty obvious: it can be used as a bio hazard weapon. On the other hand, no leading pharmaceutical is going to invest in a “very expensive and time consuming” vaccine development to be used in countries that can’t afford even a basic level of health care. Some compounds are showing a promising antiviral effect in vitro and/or an inhibition of a variety of viral proteins activities. Sadly, all of them are in an early stage of drug development. On the other hand,the actual need for a therapy and a vaccine to stop this outbreak is speeding the drug development process.

 

Before freaking out, the best prevention method against this scaring virus is knowledge, so check out the updates in the CDC website.

You Can Be a Guardian of the Galaxy!

 

By Knicole Colon, PhD

Scientists want you to help save the galaxy!

Well, not exactly…

What I am really referring to is known as “citizen science.” Scientists are constantly collecting data, and sometimes there are simply not enough scientists in the world to analyze all the data. In some cases computer algorithms provide a relatively simple solution, as a computer can be used to analyze gigabytes of data in a reasonable amount of time. However, there are some cases where human intervention is needed. Nature constantly surprises us, from revealing new species on Earth or unexpected properties of galaxies. Since we don’t know what we don’t know, it can help to have a human visually extract information from data. The Zooniverse was created for this very purpose.

The Zooniverse is home to a collection of various projects, relating to astronomy, the humanities, biology, and more. A user can sign up for free and participate in any project that interests them. This can range from identifying different types of galaxies to searching for near-Earth asteroids to reading historic ship weather logs to classifying different animals seen in the Serengeti to studying genetics by spotting worms laying eggs. This is science that is both fun and accessible to anyone, regardless of your field of expertise.

The details of each project are a bit different. For instance, Planet Hunters allows you to search for planets that transit (pass in front of) their host star by visually checking the light curves (i.e. the brightness over time) of these stars, using archived data from the Kepler space mission. If you identify a signal as a potential planet, and the Planet Hunters team ends up confirming the planetary nature of that signal, then you get to be acknowledged in the publication of those results. To date, over 60 new candidate planets have been found through the Planet Hunters project, including the confirmation of two new planets (now known as PH1 b and PH2 b). According to the Planet Hunters team, this is a result of the efforts of over 280,000 volunteers who searched through more than 21 million Kepler light curves since December 2010. This is equivalent to a cumulative total of 200 years of work.

Clearly, the Zooniverse is an amazingly successful platform that has allowed scientists and non-scientists alike to participate in different research projects. I highly recommend checking out the site, as it is quite fun and gives you a break from your daily research routine. Plus, by participating, you get to help “save” science (and the galaxy!) by helping scientists analyze the plethora of data they have gathered. New projects continue to be added, and who knows, maybe you are working on a project right now that could benefit from being added to the Zooniverse! The opportunities are endless, and it excites me to see how much citizen science continues to grow.

Predicting Suicide

 

By Jesica Levingston Mac leod, PhD

 

The play “suicide is forbidden in spring”. written by Alejandro Casona, describes an organization that helps potential suicide patients to end their lives, but the truth is that the doctors really want to avoid the sad end, and… they actually save the patients. They work with the “leitmotiv” that if you really want to finish your life, you will just do it, but the search for help is an indicator or alert signal of some survival and seek for attention behavior.

As reported by the Health Research found worldwide, 1 million suicides are committed by year. This means 1 death every 40 seconds. According to the CDC, In United States the percentage of suicidal is around 0.012%, where is the 10th leading cause of death. North America has 1 suicide every 13 minutes.The suicidal capital of the world is Greenland with a 108.1 suicide rate, followed by South Korea with 31.7. China is in the seventh place, it accounts for almost one third of all the suicides, and differently than the other countries it is the only one where women have a higher suicidal rate than men. Indeed, 3 years ago the terrible news about how in some factories, like Foxconn, making sought-after Apple iPads and iPhones were forcing staff to sign pledges not to commit suicide. Among 2013 at least 14 workers at Foxconn factories have taken the decision of terminating the horrendous working and housing conditions, ending their lives.

 

This initiative to attempt against your own life was been related to mental illness (almost in 50% of the cases) and metabolic disorders. The most implemented way of killing themselves is firearms, followed by suffocation/hanging and falls. The alarming fact is that rates of suicide have increased by 60% in the last 30 years, especially in developed countries. Also, you must consider that for every suicide that results in death there are between 10 to 40 attempted suicides. But what does bring a human been to the edge… and push him to jump?

New research has found that the answer would be the lack of the correct expression of one gene. Yes, only the downregulation of SKA2, the guilty gene, could be a biomarker for detecting suicidal behaviors. SKA2 stands for spindle and kinetochore associated complex subunit 2. The protein encoded by this gene is part of a microtubule biding complex that is essential for proper chromosomal segregation.

When they examined the postmortem brain samples from 3 independent cohorts (around 29 from suicide assesd humans and 29 controls per each group) they found that SKA2 had lower expression levels in the suicide cases than in the control, and its expression was negatively associated with DNA methylation. The chemical addition of a methyl group can activate or negatively modulate a gene, as it is considered an epigenetic modification.

I guess you are thinking: these are “Frankenstein” samples, how can this gene be related to really live human beings? Well, apparently the Johns Hopkins researchers also made the same question. In order to answer it they collected blood samples from other 3 independent cohorts with suicidal ideation and controls (with a number of subjects of 22, 51 and 327 each). In these study, the expression of the SKA2 gene was significantly reduced in suicide decedents. Furthermore, they analyzed levels of salivary cortisol. Cortisol is implicated in the glucocorticoid receptor transactivation and stress response. The results suggested that SKA2 epigenetic and genetic variation may modulate cortisol expression. The most important discovery was that the model that they generated based on these data allowed them to predict the suicidal ideation of subjects just using blood samples. They analyzed the methylated status of the SKA2 gene, which correlated with the suicidal attempts.

The great thinker Albert Camus ones recalled the attention in this issue when he said: There is but one truly serious philosophical problem and that is suicide.”  For some in risk groups, like the soldiers who are coming back home with traumas after the war, the possibility of attempts against their lives is a ghost that has taken a lot of lives. This simple blood test can point out which individuals could be in risk and therefore they may get a correct follow up and treatment that might end preventing the catastrophe. Some high pressure jobs can also implement this analysis to avoid the lost of lives, giving correct care to people who tested positive. And even closer to all: would you like to know if you have this tendency printed on your DNA? Or your partner? Or your kids?

While you think about this, let me leave you with a relief quote: “If I had no sense of humor, I would long ago have committed suicide.” Perhaps, you would be surprise to know that the wise man who said this was the Dr. Mahatma Gandhi, whom almost killed himself in a starving protest trying to obtain the independence of the Indian Republic.

 

5 Tips for Applying to Postdoc Positions

 

By Tara Burke, PhD

 

As you’re rounding home base in your graduate career you have more than a few things on your plate: wrapping up your research and publications, finishing your dissertation, scheduling your defense, and nailing down your next job. More than likely, the last thing on your mind is your next step. If you know that you would like to continue with bench research and pursue a postdoctoral fellowship after graduation, it’s best to get an early start in the application process. Since many labs interview candidates months to even a year before they may need a postdoc, the earlier you start applying the better. Applying to postdoc jobs can be a daunting and lengthy process, especially for graduate students, who have spent several years out of the job market. Fear not! The tips listed below will provide you with some helpful guidelines to get you organized, prepared and make you an attractive postdoc candidate.

 

1)   Make a list of potential labs

Hopefully in the last few years of graduate school you have taken the time to think about what type of research you’d like to pursue, the research environment you prefer as well as where, geographically, you’d like to be located. Ideally, you have a list of labs that interest you or, even better, that you have networked with already. Since funding these days is somewhat volatile, you want to make sure this list is pretty long. Also, you want to have an extensive list because even though you are very interested in the science, it is very difficult to know if a lab is good fit until you visit in person. Although many investigators advertise their open positions, many do not, so take the time to go through the websites of all labs that seem interesting and do not discount them because you do not see that they are currently advertising an open position. I recommend rating the list and apply to the ones that interest you the most first.

 

2)   Perfect your CV

Since there is little structure to how a CV (curriculum vitae) should be constructed, it can be confusing to know what to include and what not to include in your CV. Science Careers has a great post about creating a successful CV with basic dos and don’t along with tips on structuring and styling your CV. Once you have a good draft, it is crucial that you have other people proofread and edit your CV. They will catch mistakes that you miss. Ask to see a colleague’s or your mentor’s CV. Having examples of great CVs on hand will help you create a great one yourself. Seek out the career resources at your university. They have professionals that will be vital in helping you create a CV that is error-free, aesthetically pleasing, and that presents you and your qualifications in the best light. Once you have a great master CV you can use this template to create a CV that is tailored to the postdoc to which you are applying. For example, you may want to highlight a specific method that may be beneficial to the lab you are applying to by placing at the top of a subheading. Also, if you are applying to lab that is not in the same field as your graduate lab, you may need to simplify the scientific language used on your CV for that particular application.

 

 

3)   Master the cover letter

The key to a good cover letter is that it is tailored specifically to the position you are applying. A good cover letter should not be a regurgitation of your CV; it should highlight your accomplishments and emphasize how your expertise would work well in that prospective lab. I cannot stress enough that making one general cover letter for a myriad of different labs is not a good idea. A good outline for academic cover letters is to construct a letter of three short paragraphs. In the first paragraph you should introduce yourself, state your current position including your current department/university name as well as the name of your Principal Investigator. If you haven’t yet completed your Ph.D. you need to mention your predicted or scheduled defense date. You will also want to mention how you came to know about the position. The second paragraph is the most important paragraph and the meat of your letter. Here, you will talk about what interests you about the research of this particular lab and why you think you are a good candidate. You want to accentuate the skills and expertise you have that you can bring to the lab. It also helps to mention specific papers or research talks that compelled you to apply to this lab. In the third paragraph you should state what additional documents you are sending with this cover letter. Also, include a thank-you and how it is best to reach you. Science Careers has an excellent article on cover letters that I highly recommend using a guide.

 

4)   Obtain and ask for recommendations

On your CV you should list three references. Before you list these individuals as references you need to ask them first. You want to make sure that these individuals will provide you will positive reviews. If one of your references seems hesitant to give you a review, it is probably a good idea not to pursue it. Also, don’t choose a reference because they are big name in place of a younger faculty member who knows you well. Let your references know the time frame of when you will start applying and talk to them about your process. They may even know some of the labs on your list and can help you get a personalized introduction. Once this entire process is over, don’t forget to thank all your references for their help and time as you may need them to serve as a reference for you in the future!

 

5)   Proofread one last time!

You’ve constructed your email. You have a stellar cover letter and a pristine CV. You are ready to send your application. Wait! Save your email. Walk away from the computer and take a break. Walk your dog that has been patiently sleeping at your feet while you finish this application, or go for a run to clear your mind. Then, after you have taken a mental break from the computer drain, go back to your application and give it one last, slow read. You’d be surprised what you missed. You will be able to find errors that you didn’t see before. This will allow you to confidently send a great application.

 

Good Luck!