’Tis the Season for Weight Loss!

 

By Robert Thorn

It is that time of year again. 2014 is coming to an end and it is time to think about our past year and make our New Year’s resolutions for 2015. If you are like me (and many others), one of your 2014 resolutions was weight loss, and perhaps you haven’t quite met your goals. A quick search of weight loss supplements on the internet will lead you to a myriad of “miracle” weight loss solutions. Its so simple, just put lemon in your water, drink 5 glasses of ice cold water a day, and/or replace one meal a day with a shake/bar/handful of nuts. Well, now it's time to throw away all those snake oil voodoo weight loss “solutions” because there may be a new molecule in town to help cut the pounds.

 

A paper recently published in Nature Medicine from a group in Germany has shown that there may be a way to trick your body into losing weight by mimicking hormones that normally help regulate the body’s response to food. They aimed to affect three hormones that are known to be important for the regulation of weight in obesity. The three hormones are glucagon-like peptide-1 (GLP-1), glucose-dependent insulin tropic polypeptide (GIP) and glucagon. These three hormones have been studied by themselves to determine if they could have any positive effect in controlling obesity. Scientists have created molecules, called agonists, that are able to activate the receptors that are normally activated by either glucagon, GIP or GLP-1. By themselves these agonists allow a modest benefit to obesity, but also came with negative side effects that would make them unpleasant to use. It has been hypothesized that regulating all three of these hormones at once would allow for greater anti obesity effects with less unpleasant side effects.

 

First, the group decided to test how using three agonists at once, one each for GLP-1, GIP and glucagon, would alter weight loss in a mouse model with an altered diet high in sucrose to induce obesity. The tests showed a synergistic effect by using all three, versus using each one individually in weight lose in this mouse model. Next, they decided to attempt to create a single molecule that would be an agonist to each of the 3 hormones at once (aka a triagonist). Previously, coagonist molecules that affected different combinations of the three pathways had been designed and by using these sequences and structures they were able to rationally design a triagonist to all thee hormones. Once designed and synthesized, the triagonist was tested for activity with the intended receptors (i.e. the receptors for GLP-1, GIP and glucagon) and for non-intended receptors. These tests showed that the triagnoist was effective in activating all 3 intended receptors and when tested against a set of other receptors it showed no cross reactivity, suggesting that the triagonist is a specific triagonist of GLP-1, GIP and glucagon.

 

Once in vitro studies showed that the triagonist interacted with receptors as they were designed to be, the group moved on to testing in mice. They again used the diet induce obesity mouse model to test the triagonist. Both short term and long term exposure to the triagonist showed a decrease in overall body fat in the mice, without any hypoglycemia. Remarkably, this difference was even greater than the difference previously seen with coagonists. In addition to the weight reduction, treatment with the triagonist was also able to slow the progression of type II diabetes in these mice. To further test the triagonist, rat models of both obesity and diabetes were treated with the triagonist. In both of these models the triagonist was able to alleviate the effects of both obesity and diabetes respectively. To date, there have been other triagonists designed and tested by other groups, but none have shown such robots anti-obesity and anti-diabetes effects as this triagonist.

 

This level of weight loss from a single molecule is extremely promising as a way to fight the ever-growing obesity epidemic. Not only does the increased obesity negatively affect individuals who are obese, but it also can act as a burden on public health. This triagonist could serve as a safer, non-invasive alternative to biatric surgery, which is oftentimes the only solution for some cases of obesity. While all this information is very promising, it is important to note that mouse models don’t always translate perfectly to human trials but it is definitely possible that in the next few years we may very well have a “miracle” weight loss solution that actually works!


Communicating science over the airwaves

Science Through the Airwaves:

 

By Robert Thorn

 

Have you ever been curious about the way different organisms seen light, the history behind zoos or how the placebo effect works? Then Radiolab might be the radio show for you! Radiolab is produced by WNYC, which is one of New York’s public radio stations, and can be found in podcast form at radiolab.org. To date Radiolab has released over 70 full length podcasts (about an hour in length), countless “shorts” and a handful of live shows. Radiolab is hosted by Jad Abumrad and Robert Krulwich. Neither Jad nor Robert are scientists per se, but what they do during each segment can only be described as science. Each episode starts with Jad and Robert discussing a topic, they give their thoughts about how a topic may work (a hypothesis if you will) and throughout the hour they discuss the topic and unravel some of the mysteries, leaving each episode with a better understanding of the topic.

 

Throughout each hour Jad and Robert get in contact with experts in the field, many times by phone, to help them build the story. Not only are these people expert scientists, but they will sometimes contact people who were personally involved in events pertaining to the topic and can give eyewitness accounts of revolutionary events in the field, giving the show a wonderful sense of relevance that would be otherwise hard to obtain. Oftentimes Jad will take one point of view and Robert will take another, allowing a full, genuine discussion of topics that may sometimes be controversial. Jad and Robert are supported by a team of producers and writers who will often be heard on the show helping to synthesize the ideas for shows or tracking down story leads around the country and sometimes even further!

 

The team at Radiolab thrives in its ability to discuss subjects in such a way that it is accessible to people of all scientific persuasions. I find as much enjoyment listening to the show, as my non-science friends do. It not only expands my perspectives on familiar topics, but it also allows me to discuss science topics with friends who are new to the topic. The Radiolab podcast is not only about the science though. They interweave sounds and music into the podcast in such a way as to breathe life into the story. Before listening to Radiolab I thought that public radio was solely comprised of boring newscasters speaking in monotone reporting on political events, but Radiolab shattered that perception in a wonderful way. Sound is not only used as a way to liven up the narrative, but it is also used as a tool to help explain scientific concepts.

 

The best example of the use of sound to illustrate a point is in the Radiolab episode titled “Colors” (Season 10 Episode 13). Jad and Robert were discussing how different animals would see a rainbow. As they explored this topic, they enlisted the help of a choir to illustrate what they learned about color vision in animals. Different voice parts of the choir sang different color names. Lower voice groups were the reds of the rainbow and the voice groups became progressively higher until they reached the violet and ultraviolet ranges of the rainbow. As they moved on to different animals with better vision than humans they would play a recap of the voices harmonizing as an analogy to the rainbow that the animal would see. This use of sound is typical of Radiolab’s ingenious ability to illustrate points that are otherwise sight dependent.

 

Overall, the best description of Radiolab comes straight from the about section at radiolab.org, stating, “Radiolab is a show about curiosity. Where sound illuminates ideas, and the boundaries blur between science, philosophy, and human experience.” Whether you are casually interested in science, or work in a scientific field, Radiolab is a podcast that will captivate your interests and have you thinking about science in a new way.


Preparing for the PhD qualifying exam

Surviving Your Qualifying Exam

 

By Robert Thorn

The qualifying exam is a part of graduate school that everybody has to go through, but nobody is really prepared for. The qualifying exam, also called a comprehensive or preliminary exam depending on the program, is generally a test of a student’s knowledge and expertise. Many programs schedule it towards the end of a student’s 2nd year, but the timing varies with each program. Overall this exam aims to determine that a student is prepared to continue on with their PhD training, and usually marks a transition period in their graduate training. Having just finished my own qualifying exam I thought it would be good to pass along some helpful information I learned along the way.

Ask senior graduate students in your program about their qualifying exam experience

Talking to senior students will help to give insight into how the exam will go in terms of expectations and pacing. In addition to giving you logistical advice, they can give you advice on how to deal with the stress associated with the exam.

Know your committee

If you have to submit your exam to a committee of professors in the department, know what they like and do not like. If you choose a committee member with a certain expertise, make sure to talk about their area of expertise. Talking to senior graduate students will help with this as well as they can give you insight into some of the likes and dislikes of the committee in terms of writing and presentation styles.

Take time for yourself!

This may seem like a silly piece of advice, but in this time of extreme stress it will be very easy to lose yourself in studying. Overloading yourself with stress will just add to anxiety over the exam and can be detrimental in the long run so reward yourself! If you spend a few hours studying take an hour off to do something fun or relaxing.

Edit, edit, edit and more editing

If there is a written component to your exam, finish writing it well before the date and spend time editing it. Your written piece will evolve and become better with every edit. Allow time for other people to read it (if that is allowed) to give you a better chance to succeed and to gain alternate perspectives.

Don’t take criticism too personally

If you are writing about your own project you will receive tons of criticism. From your PI, other students who help proofread and especially from the committee in charge of assessing you. They all are trying to help you succeed and their criticisms will help you become a better scientist. This is also good practice for receiving criticism from grant and paper submissions in the future. Take the criticism as a chance to become better, not as a personal attack.

It's OK to pass the second time

Finally, if at first you don’t succeed, try again! I know this is very cliché but many people will not pass their exams the first time around and that’s why many programs allow a 2nd, or 3rd Just keep your head up and try not to become discouraged.


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.


Ancient virus can infected after being defrosted.

Ancient Viruses - New Concerns

 

By Robert Thorn

Recently scientists have discovered a new type of virus in the Siberian permafrost. The virus discovered is about 30,000 years old, and amazingly after all that time the virus was still able to infect cells after being defrosted. Specifically, the scientists who discovered the virus have shown that it can infect amoebas, which are single celled organisms. They also found that this virus poses no risk to humans or animals but the real worry behind this discovery is that there could be more virulent microorganisms lying dormant under the ice.

 

In recent years there has been growing concerns over global warming but much of the focus has been on changing weather patterns, the melting of the polar ice caps and rising sea levels. The scientists who discovered this new virus have raised the concern that more, unidentified viruses could be released with the melting of ice and permafrost around the globe and that these pathogens may pose a risk to humans, plants or animals. Climate change is not the only way that these potentially harmful viruses could be released. Drilling, mining, or anything other human intervention that might disrupt the permafrost could be an avenue for these dormant viruses to be awakened. With increasing pressure on the oil industry to find new stores of fuel to power our modern world, these dormant viruses may add an extra layer of concern to drilling for oil in areas covered by permafrost.

 

With all of the uncertainty that is lying under these sheets of ice and frozen soil, there is a pressing need for a discussion on how to deal with an ever thawing permafrost due to climate change, and increased pressure or taking advantages of untapped resources. The paper mentions that in the 20th century alone there was a 7% decrease in the permafrost. Based on the author’s research this decrease in permafrost has very likely coincided with a revival of dormant organisms that could be altering the ecosystems of the world in unknown ways. It is clear that these findings need to be added to the conversations about global climate change that are being had across the world.

 

While this may all seem scary, there is a silver lining. Despite the potential risk that is posed by these ancient microorganisms, the methods the authors used to revive and analyze this new virus can be used as an inexpensive and safe way to assess the viruses that are dormant in the permafrost. By documenting these pathogens in the permafrost, we can be more prepared to contain the potentially harmful organisms, or to fend them off if they do get reactivated.

 

 


’Til Death Do Us Part - The Science of Love and Attachment

 

By Robert Thorn

As Valentine’s Day approaches, excitement starts to fill the air in anticipation of Cupid’s visit. The key to the potency and strength of love has been a mystery to scientists for some time. It may surprise you to know that the key to unlocking the secrets of love came from studies of common prairie voles. Prairie voles are unique in the fact that when they get together during mating season they generally mate with one partner and this connection lasts for life. This is in stark contrast to the prairie vole’s evolutionary cousin, the montane vole which is a more promiscuous species of vole. By comparing the different between these monogamous and promiscuous voles, scientists were able to get an idea of what hormones and brain regions may be involved in pair bonding, or as we humans call it, relationships!

 

Two hormones that were identified in early studies of the prairie and montane voles are oxytocin and vasopressin. If you have heard of these before, it is probably because they are important hormones in different human systems. Oxytocin is used primarily during childbirth, acting to start muscle contractions during birth, as well as being involved in lactation during breastfeeding. Vasopressin is important for a healthy functioning cardiovascular system, as well as maintaining blood pressure by helping to regulating the amount of water filtered out in the kidney. While both of these hormones seem unrelated to each other, and definitely unrelated to love, they were thought to be important for pair bonding because compared to the montane voles, prairie voles have more oxytocin and vasopressin receptors in their brains.

 

Once two prairie voles mate, vasopressin and oxytocin are released and pair bonding occurs. To show the importance of these two hormones, scientists manipulated the action of one or the other in prairie and montane voles. When the action of either vasopressin or oxytocin was blocked, prairie voles began displaying more promiscuous behaviors, similar to those seen in montane voles. On the other hand, when scientists increase the activity of vasopressin in the brains of montane voles, by increasing the number of vasopressin receptors located in the brain, they began to adopt a more monogamous relationship with their mating partners.

 

To further examine the role of these hormones in pair bonding, the location of their receptors were mapped to different areas of the brain. Oxytocin receptors were seen in areas of the brain that are involved in dopamine reward system (nucleus accumbens) and emotional memory formation (amygdaloid complex). Vasopressin is seen in different areas of the brain that are involved in motivation and the dopamine reward system (ventral palladium). The role of the dopamine reward system in pair bonding was further confirmed by experiments, which showed that blocking dopamine blocks pair bonding, and adding extra dopamine artificially creates pair bonding without mating (i.e. without the release of oxytocin).

 

It is interesting to note that the dopamine reward system has been implicated in the addictive nature of some drugs. Keep this in mind if you get struck by one of Cupid’s arrows this Valentine’s Day - You might just get hooked on love.


5 Do's and Don'ts for Choosing Your Thesis Committee

 

Robert Thorn

As a 2nd year PhD student I know that picking a thesis committee can seem like an overwhelming decision. Having just gone through the process of picking a committee and setting up a committee meeting I’ve compiled some of the tips that I received to help you put together the best possible committee.

Do’s

1)    Pick PIs who have complimentary experiences to your own PI

Throughout your PhD training you will most likely be writing grants as well as papers. If your PI does not have much experience with graduate student training it may be difficult for them to help you in this writing. It is a good idea to have a committee member who can help you write and even co-sponsor you for grants if needed. This will help make sure your training is as successful as possible

2)    Pick a committee with diverse interests

This one goes along with #1. Just like you want a committee with different experiences from your PI, you also want committee members who have a range interests. By having this diversity you will be able to maximize the range of input you receive on project.

3)    Pick PIs you feel comfortable talking to

Remember that you will be stuck with this committee for most of your PhD career and they will be the ones who make the ultimate decision on whether you are qualified to graduate or not. By making sure you have a committee you can talk to, you can keep an open line of communication with your committee members and make sure you are reaching their expectations.

4)    Ask other students about PIs you are considering

If you know of other students who have had PIs on their committee they will be able to let you know. How are they with responding to emails? How open is their schedule? Are they open to talking outside of meetings? All these questions can be answered by your peers who have already gone through the process and help you make the final decision.

5)    Pick PIs who ask thoughtful questions

You want to make sure your committee helps guide you through the process of developing your PhD project. You can get a sense of the types of questions a PI asks by listening to the questions they ask during seminars and classes. Make sure that the questions the PI asks are going to fit with the way you want to receive feedback and so that their feedback can help further your project.

 

Don’ts

1)    Pick PIs who don’t get along

The last thing you want to worry about is whether or not your committee members will get along for a committee meeting. Asking your PI or other students about how different PIs get along with help keep drama out of your committee meetings.

2)    Pick too many busy PIs

It is very tempting to immediately pick a few high profile PIs to have a really high impact committee but this could backfire big time. Picking a time for a committee meeting can be difficult enough to begin with and the busier the PIs are, the more difficult it will be for you to get all your committee members together at one time.

3)    Pick PIs who talk too much about unrelated topics

Make sure the PIs you choose know how to keep their discussion to a limited amount of time. Even though committee meetings only happen once or twice a year, you still probably don’t want to have 3 or 4 hour long committee meetings because your committee members keep talking about tangential or unrelated topics.

4)    Pick selfish PIs

The point of the committee is to help you grow and develop your project. You definitely do not want a PI who will continually want to know how your project will relate back to their research. Make sure the PIs you choose will have your needs in mind during committee meetings.

5)    Make the decision lightly!

Your committee will play an integral role during your PhD, from guidance and advice to letters of recommendations for grants and post-doctoral positions you will rely on your committee for many different aspects of your training. Make sure to talk with your PI, lab mates and peers to get the best possible information you can while putting your committee together.

Have Do's or Don'ts we didn't mention? Share them with us!


Signed, Sealed and Delivered… to the Brain

 

Robert Thorn

The blood brain barrier has been a problem for pharmaceutical companies for some time. The blood brain barrier separates the body’s circulatory system (the blood) from the fluid that surrounds the brain. It allows for transfer of vital nutrients and exchange of gases to make sure the brain properly functions, but not everything can pass through which poses a problem for treating brain diseases with pharmaceuticals. The classic example of the blood brain barrier hindering proper drug delivery is in the case of Parkinson’s disease. Parkinson’s disease is caused by a loss of dopamine neurons in a specific area of the brain, the substantia nigra. The first idea to treat this was to give the patient dopamine, but this was ineffective because dopamine itself could not cross the blood brain barrier. Instead it was discovered that the precursor of dopamine, L-Dopa, could cross the blood brain barrier and treat the disease. Unfortunately, other drugs that may help treat brain disease do not have such an easy method to get around the blood brain barrier.

 

A new paper in the Journal of Molecular Therapy proposes a solution to this problem. The main idea is that by attaching a drug that cannot pass through the blood brain barrier to a protein that can pass through the barrier, you may be able to get the compound you want into the brain. They set out to test this in two ways: First they wanted to prove their concept by delivering a green fluorescent protein (GFP) to the brain to test levels and then they wanted to try delivering myelin basic protein (MBP) to the brain to test for function. The interesting thing about MBP is that it has been shown to be able to reduce the brain plaques associated with Alzheimer’s disease in previous studies. Finding a way to deliver this to the brain of living beings could lead to a new way to treat Alzheimer’s patients.

 

To act as the transfer motif of the construct they chose Cholera Toxin B subunit (CTB), which is able to transcytose through the blood brain barrier. They attached CTB to both GFP and MBP with a linker that will allow enough movement so that neither the structure nor the function of CTB or the linked protein is altered. The researchers did experiments both in vivo using a wild type mouse and a mouse that has Alzheimer’s as well as doing studies ex vivo by using slices of mouse and human brains afflicted with Alzheimer’s disease in culture to test the efficacy of their drug.  They first gave oral doses of CTB-GFP to normal mice and they found that there was an increase in the amount of GFP in the brain versus just giving oral GFP. In addition, when they treated the Alzheimer’s disease mice with oral CTB-MBP they saw a decrease in the amount of plaques in the brain of these mice. These results were recapitulated in the ex vivo studies using brains from humans afflicted with Alzheimer’s Disease, showing that the drug treatment could be effective in humans as well. These results showed that the researchers had developed an interesting way to deliver drugs to the brain while being minimally invasive and bypassing the blood brain barrier.

 

While this research is still a long way from being FDA approved and in the open market, the researchers have developed a promising method to better treat neurological diseases in the future.

 

 


The Gut-Brain Connection

 

Robert Thorn

In my last post, I talked about some interesting developments in the study of the gut microbiome and the effects changes in the gut environment can have on human health and development. As more work is done in the field of gut microbiomes more links are found between human disease and the types of bacteria that are present in the gut. A recent paper in Cell has found a new link between the neurodevelopment disorder, autism spectrum disorder (ASD) and a change in the microbiome. In addition to the cognitive impairments that are associated with ASD, many of those affected by ASD also have gastrointestinal problems. This correlation between ASD and gastrointestinal problems prompted the researchers to see if there was any link between the gut microbiome and ASD.

The researchers decided to focus on one specific type of ASD, called maternal immune activation (MIA)-associated ASD. There is a correlation between activation of a mother’s immune system by an infection at some point during pregnancy and an increased risk of ASD in the child. The researchers in this study take advantage of the ability to mimic MIA-associated ASD using a mouse model where they activate a pregnant mouse’s immune system. They go on to show that the offspring of the immune activated mice show similar gastrointestinal defects to those correlated with human ASD. The researchers investigate the type of bacteria that are colonizing the gut of the MIA offspring and they found that the MIA-associated ASD mice have a similar imbalance in the gut microbiome as those seen in humans with ASD. This result shows that the MIA offspring closely resemble ASD not only neurologically and behaviorally, but also gastrointestinally.

After characterizing this imbalance, they aimed to correct it by introducing good bacteria into the mice. They treated MIA offspring mice with human commensal bacteria, B. Fragilis, to fix the imbalance. They find that the treatment with B. Fragilis was able to rescue much of the gastrointestinal problems. Surprisingly, they also find that many of the ASD associated behaviors were ameliorated by the treatment with B. Fragilis, showing improvements in behaviors associated with anxiety, repetition, and communication. Although the treatment ameliorated some of the behaviors, the mice still show some hallmarks of ASD such as sociability and social preference defects. Upon further investigation, the researchers are able to link this rescue to serum levels of metabolites. They find that increases in serum levels of metabolites from the gut are associated with an increase in anxiety like behavior and that these serum levels are normalized by B. Fragilis treatment. This finding is important in linking the mechanisms of both gastrointestinal problems with some of the autism-related behavioral abnormalities.

With the prevalence of ASD rising to about 1 in every 88 live births in the US, this research is making important steps towards finding ways to alleviate some of the symptoms of ASD. In addition to helping further the treatment of ASD, they were also able to show a link between the gut microbiome, serum metabolites and distinctive behavioral defects.


The Most Scizzling Papers of 2013

 

The Scizzle Team

Bacteriophage/animal symbiosis at mucosal surfaces

The mucosal surfaces of animals, which are the major entry points for pathogenic bacteria, are also known to contain bacteriophages. In this study, Barr et al. characterized the role of these mucus associated phages. Phages were more commonly found on mucosal surfaces than other environments and adhere to mucin glycoproteins via hypervariable immunoglobulin like domains. Bacteriophage pre-treatment of mucus producing cells provided protection from bacterial induced death, but this was not the case for cells that did not produce mucus. These studies show that there may be a symbiotic relationship between bacteriophages and multicellular organisms which provides bacterial prey for the phages and antimicrobial protection for the animals.

[hr]

Interlocking gear system discovered in jumping insects

Champion jumping insects need to move their powerful hind legs in synchrony to prevent spinning. Burrows and Sutton studied the mechanism of high speed jumping in Issus coleoptratus juveniles and found the first ever example in nature of an interlocking gear system. The gears are located on the trochantera (leg segments close to the body’s midline) and ensure both hind legs move together when Issus is preparing and jumping. As the insect matures, the gear system is lost, leaving the adults to rely on friction between trochantera for leg synchronization.

[hr]

HIV-1 capsid hides virus from immune system

Of the two strains of HIV, HIV-1 is the more virulent and can avoid the human immune response, whereas HIV-2 is susceptible. This may be due to the fact that HIV-2 infects dendritic cells, which detect the virus and induce an innate immune response. HIV-1 cannot infect dendritic cells unless it is complexed with the HIV-2 protein Vpx, and even then the immune response isn’t induced until late in the viral life cycle, after integration into the host genome. Lahaye et al. found that only viral cDNA synthesis is required for viral detection by dendritic cells, not genome integration. Mutating the capsid proteins of HIV-1 showed that the capsid prevents sensing of HIV-1 cDNA until after the integration step. This new insight into how HIV-1 escapes immune detection may help HIV vaccine development.

[hr]

Transcription factor binding in exons affects protein evolution

Many amino acids are specified by multiple codons that are not present in equal frequencies in nature. Organisms display biases towards particular codons, and in this study Stamatoyannopoulos et al. reveal one explanation. They find that transcription factors bind within exonic coding sequences, providing a selective pressure determining which codon is used for that particular amino acid. These codons are called duons for their function as both an amino acid code and a transcription factor binding site.

[hr]

Chromosome silencing

Down syndrome is caused by the most common chromosomal abnormality in live-born humans: Trisomy 21. The association of the syndrome with an extra (or partial extra) copy of chromosome 21 was established in 1959. In the subsequent fifty years a number of advances have been made using mouse models, but there are still many unanswered questions about exactly why the presence of this extra chromosome should lead to the observed defects. An ideal experimental strategy would be to turn off the extra chromosome in human trisomy 21 cells and compare the “corrected” version of these cells with the original trisomic cells. This is exactly what a team led by Jeanne Lawrence at the University of Massachusetts Medical School has done. Down syndrome is not the only human trisomy disorder: trisomy 13 (Patau syndrome) and trisomy 18 (Edward’s syndrome), for example, produce even more severe effects, with life expectancy usually under one to two years. Inducible chromosome silencing of cells from affected individuals could therefore also provide insights into the molecular and cellular etiology of these diseases.

[hr]

Grow your own brain

By growing organs in a dish researchers can easily monitor and manipulate the organs' development, gaining valuable insights into how they normally develop and which genes are involved. Now, however, a team of scientists from Vienna and Edinburgh have found a way to grow embryonic “brains” in culture, opening up a whole world of research possibilities. Their technique, published in Nature, has also already provided a new insight into the etiology of microcephaly, a severe brain defect.

[box style="rounded"]Scizzling extra: In general, 2013 was a great year for growing your own kidneyspotentially a limb and liver. What organ will be next? [/box]

[hr]

Sparking metastatic cell growth

A somewhat controversial paper published in Nature Cell Biology this year showed that the perivescular niche regulates breast tumor cells dormancy. The paper showed how disseminated breast tumor cells (DTC) are kept dormant and how they can be activated and aggressively metastasize. Based on the paper, this is due to the interaction of interaction with the microvascularate, where thrombospondin-1 (TSP-1) induces quiescence in DTC and TGF-beta1 and periosstin induces DTC growth. This work opens the door for potential therapeutic against tumor relapse.

[hr]

Fear memories inherited epigenetically

Scientists showed that behavioral experiences can shape mice epigenetically in a way that is transmittable to offspring.  Male mice conditioned to fear an odor showed hypomethylation for the respective odor receptor in their sperm; offspring of these mice showed both increased expression of this receptor, and increased sensitivity to the odor that their fathers had been conditioned on.  Does this suggest that memories can be inherited?

[hr]

Grid cells found in humans

Scientists have long studied rats in a maze, but what about humans?  An exciting paper last August demonstrated that we, like out rodent counterparts, navigate in part using hippocampal grid cells.  Initially identified in the entorhinal cortex of rats back in 2005, grid cells have the interesting activity pattern of firing in a hexagonal grid in the spatial environment and as such are thought to underlie the activity of place cells. Since then grid cells have been found in mice, rats, and monkeys, and fMRI data has suggested grid cells in humans.  This paper used electrophysiological recordings to document grid cell activity in humans.

[hr]

Sleep facilitates metabolic clearance

Sleep is vital to our health, but researchers have never been entirely sure why.  It turns out part of the function of sleep may be washing waste products from the brain, leaving it clean and refreshed for a new day of use.  Exchange of cerebral spinal fluid (CSF), which is the primary means of washing waste products from the brain, was shown to be significantly higher when animals were asleep compared to waking.  This improved flow was traced back to increased interstitial space during sleep, and resulted in much more efficient clearance of waste products.  Thus, sleep may be crucial to flushing metabolites from the brain, leaving it fresh and ready for another day’s work.

[box style = "rounded"] Robert adds: As a college student my friends and I always had discussions about sleep and it was also this mysterious black box of why we actually need to sleep. Studies could show the effects of lack of sleep such as poor cognition and worse memory but this paper linked it to an actual mechanism by which this happens. First of all I found it very impressive that the researchers trained mice to sleep under the microscope. On top of that showing the shrinkage of the neurons and the flow of cerebrospinal fluid which cleans out metabolites finally linked the cognitive aspects of sleep deprivation to the physical brain. [/box]

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Poverty impedes cognitive function

People who are struggling financially often find it difficult to escape poverty, in part due to apparently poor decision making.  Investigators demonstrated that part of this vicious cycle may arise from cognitive impairment as a direct result of financial pressures.  The researchers found that thinking about finances reduced performance on cognitive tasks in participants who were struggling, but not in those who were financially comfortable.  Furthermore, farmers demonstrated poorer cognitive performance before harvest, at a time of relative poverty, compared to after harvest when money was more abundant.

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Gut Behavior

2013 has definitely been the year of the gut microbiome! Studies have shown that diet affects the composition of trillions of microorganisms in the human gut, and there is also a great deal of evidence pointing towards the gut microbiome affecting an individual's susceptibility to a number of diseases. Recently published in Cell, Hsiao and colleagues report that gut microbiota also affect behavior, specifically in autism spectrum disorder (ASD). Using a mouse model displaying ASD behavioral features, the researchers saw that probiotic treatment not only altered microbial composition, but also corrected gastrointestinal epithelial barrier defects and reduced leakage of metabolites, as demonstrated by an altered serum metabolomic profile. Additionally, a number of ASD behaviors were improved, including communication, anxiety, and sensorimotor behaviors. The researchers further showed that a particular metabolite abundant in ASD mice but lowered with probiotic treatment is the cause of certain behavioral abnormalities, indicating that gut bacteria-specific effects on the mammalian metabolome influence host behavior.
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Your skin - their home

A paper published in Nature examined the diversity of the fungal and bacterial communities that call our skin home. The analysis done in this study revealed that the physiologic attributes and topography of skin differentially shape these two microbial communities. The study opens the door for studying how the pathogenic and commensal fungal and bacterial communities interact with each other and how it affects the maintenance of human health.

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Discovery of new male-female interaction can help control malaria

A study published in PLOS Biology provided the first demonstration of an interaction between a male allohormone and a female protein in insects.  The identification of a previously uncharacterized reproductive pathway in A. Gambiae has promise for the development of tools to control malaria-transmitting mosquito populations and interfere with the mating-induced pathway of oogenesis, which may have an effect on the development of Plasmodium malaria parasites.

[box style = "rounded"]Chris adds: "My friend chose this paper to present at journal club one week, because he thought it was well written, interesting etc etc. Unbeknownst to him, one of the paper’s authors was visiting us at the time. We sit down for journal club and one of the PIs comes in, sees the guy and exclaims (with mock exasperation) “you can’t be here!” Me and the presenter look at one another, confused. He presents journal club, and luckily enough, the paper is so well written, that he can’t really criticize it!" [/box]

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Using grapefruit to deliver chemotherapy

Published in Nature Communications, this paper describes how nanoparticles can be made from edible grapefruit lipids and used to deliver different types of therapeutic agents, including medicinal compounds, short interfering RNA, DNA expression vectors, and proteins to different types of cells. Grapefruit-derived nanovectors demonstrated the ability to inhibit tumor growth in two tumor animal models. Moreover, the grapefruit nanoparticles used in this study had no detectable toxic effects, could be manipulated or modified to target specific cells/ tissues, and were economical to create. Grapefruits may have a bad reputation for interfering with drugs, but perhaps in the future we will be using grapefruit products to deliver drugs more effectively!

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Getting CLARITY

In May, a new technique called CLARITY to effectively make tissue transparent through a new fixation technique was published in Nature. This new process has allowed them to clearly see neuron connection networks not possible before because they can now view the networks in thicker tissue sections. This new advancement will help researchers be able to better map the brain, but this new technology can also be to create 3-D images of other tissues such as cancer. This new ability allows us to gain better insight into the macroscopic networks within a specific tissue type.

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Crispier genome-editing

This year, the CRISPR technique was developed as an efficient gene-targeting method. The benefit of this method over the use of TALENS or a zinc-finger knockout is it allows for the rapid generation of mice that have multiple genetic mutations in just one step. The following review gives even more information on this new technique and compares its usefulness to that of TALENS and zinc-finger knockouts. Further, just couple of weeks ago, two back-to-back studies in Cell Stem Cell using the CRISPR-Cas9 system to cure diseases in mice and human stem cells.  In the first study the system was used in mice to correct the Crygc gene that causes cataracts; in the second study the CRSPR-Cas9 system was used to correct the CFTR locus in cultured intestinal stem cells of CF patients. These findings serve as a proof-of-concept that diseases caused by a single mutation can be “fixed” with genome editing using the CRISPR-Cas9 system.

What was your favorite paper this year? Let us know! And of course - use Scizzle to stay on top of your favorite topics and authors.


So What Is It You Do, Exactly?

Tips and anecdotes on how to explain your science over the holiday dinner.

 

The Scizzle Team

 

Pick your project carefully

Chris works on a malaria vector and how it survives by blood-feeding, so he usually just says he's trying to kill all the malaria mosquitoes. After that people rarely have follow up questions, since it’s a goal people can easily get behind!

[box style="rounded"]Scizzle tip: Work on a disease everyone knows[/box]

Be prepared

Stephanie says that everyone should have an elevator pitch ready to pull out of their back pocket at a moment's notice! Start working on your 3 minute miracle as soon as you've picked up a pipette and learned which way to point it.

[box style="rounded"]Scizzle tip: This doubles as a great networking tool![/box]

Try once (and you might never get asked again)

Robert's first lab experience was during a summer internship, and he shares: for the first month I was working there I was commuting from the suburbs to NYC to work. Since my dad was retired at the time he usually drove me in and would pick me up when I was done. When he picked me up he would always ask me about what I had done that day. In the beginning it was simple stuff to explain like sectioning kidneys, doing dissections, etc. One day I had done PCR for the first time and when my dad asked me what I did that day I went on the spiel about PCR. How you have DNA and primers and taq polymerase and dNTPs. I explained it as simply as I could think going one step at a time and slowly and ended with "basically, its like photocopying DNA and we use it to see what genes the mice have". After a pause my dad said to me "I have no idea what you were just talking about." I offered to try to explain again but he politely declined and that was the last time he asked me about what I did in lab.

[box style="rounded"]Scizzle tip: Don't use fancy words[/box]

Tell them what you do

Celine suggests to focus on what she does rather than what she studies: if I tell my people that I work on cortical interneuron circuits their eyes glaze over, but if I say that I use a tiny electrode to listen to neurons and observe their behavior, people are actually quite interested.  A good visual helps a lot too; for a long time I had a picture on my phone from my electrophysiology rig monitor showing neurons and a blood vessel, and even people who don’t care about science at all thought it was pretty neat.

[box style="rounded"]Scizzle tip: Have good visuals! (Just make sure it's not gross)[/box]

What's your model organism?

Thalyana's words of wisdom for those studying model organisms: be careful how you explain what organism you are studying. For example, I study the nematode C. elegans, and I made the mistake of saying "I study worms" at a family get-together. I spent the rest of the party explaining that I do not spend my day digging in the soil for earthworms! Also, if you study yeast, make sure to point out that you are not brewing beer in the lab (...unless you are!).

[box style="rounded"]Scizzle tip: Choose your words! C.Elegans sounds way more sophisticated than worms[/box]

Start with something they know

Joseph tells us the importance of a few key words: I recently tried to explain my research on the evolution of developmental mechanisms in moss, and found myself seeing an increasingly confused face in front of me.  I was then helpfully notified that, while delving into details about making mutant lines and tracking cell divisions, I had left the word “evolution” out of my explanation!  This was a great learning experience; there are words that your mother/father/aunt/cousin has probably heard in the news that relate to what it is you do, so make sure to use them!

[box style="rounded"]Scizzle tip: Use those buzzwords![/box]

Keep it Real

Zach tries to relate his work to human problems and interactions: as a computer scientist, my work often has broad applications, so I look for the human element - an analogy to a common problem or familiar pain often helps people to understand how my work is useful. It helps to anthropomorphize as well - presenting my work as teaching a silly, ignorant computer how to complete a useful task is often easier than trying to convey the set of abstractions and mechanical and electrical processes that are the true nature of my work.

[box style="rounded"]Scizzle tip: Find the human element[/box]

 

Do you have a tip on how to deal with the question or a funny story? Please share!


Don't Touch That! You'll Get Germs

 

Robert Thorn

Everybody can relate to a parent saying “Don’t touch that, you’ll get germs.” For most of our lives we have been told to avoid ‘germs’, an ambiguous mix of all things that might get you sick. The truth is that not all germs are created equal. Scientists have been trying to decode the human “microbiome,” or the bacteria that live within our digestive system, to determine how these bacteria come to inhabit our digestive tract and how they relate to human health and disease. Good bacteria in the intestines can help us digest food and keep out bad bacteria, but bad bacteria in the intestine can have harmful effects such as obesity, allergies, and short-term sicknesses like food poisoning.

A recent paper in Nature suggests a method by which bacteria can initially colonize our digestive system. It is well known that newborns have a weaker immune response to infection but this has generally been attributed to an immature immune system. These researchers suggest a different reason, that newborns have a system to actively suppress the immune system. They have found an enrichment of CD71 positive immune cells in newborn mice compared to adults. In addition they have shown that these CD71 positive immune cells secrete factors that repress immune function, even in mature adult immune cells. Newborn mice that were depleted of these CD71 cells could fight infection better than those that still had an enrichment of the CD71 positive cells. The obvious question is why? The researches went on to answer this question by looking at the effects of bacteria in the intestine and the amount of CD71 cells. They showed that there was a positive correlation between the amount of CD71 cells and the amount of bacteria in the intestine. This means that evolution has made it so that newborns are more susceptible to possibly harmful infections in an attempt to protect the potentially helpful bacteria that colonize the intestines.

In contrast to the shutting down of the immune system by gut bacteria, a new study published in eLife has suggested a role for certain kinds of gut bacteria in rheumatoid arthritis. Rheumatoid arthritis is an autoimmune disorder, meaning it is one in which the immune system attacks the body. In this case, joints are being attacked, and the resulting inflammation causes the arthritis. Based on a screen done of human fecal samples (which shows a representation of gut bacteria) of people with and without rheumatoid arthritis, the researchers correlated a single strain of bacteria, P. copri, to patients newly diagnosed with rheumatoid arthritis. Since rheumatoid arthritis is a multifaceted disease, it is possible that the P. copri bacteria either thrives in an environment that also causes rheumatoid arthritis or that P. copri pushes an already compromised over the edge and is an early factor in rheumatoid arthritis. The researchers also showed that mice infected with P. copri had an increased occurrence of colitis, which is inflammation of the colon. This could show a link between P. copri and general inflammation in the host, strengthening the correlation between P. copri and rheumatoid arthritis.

Whether we are talking about good gut bacteria or bad gut bacteria, new areas of medicine are focused on how to maintain a healthy microbiome. Generally, good bacteria can be maintained by proper diet but upsetting the balance with a bad diet, or by taking too many antibiotics, can give opportunistic bad bacteria a chance to over-colonize the digestive system. In many cases of intestinal disease that result from microbiome imbalance, fecal transplants have been used to treat patients. Fecal transplants involve the use of a fecal sample from an individual with a healthy mix of bacteria and transplanting it into a sick person, generally by enema. This allows a healthy mix of bacteria to recolonize the sick person’s gut. This may seem like a barbaric or gross treatment, but it has been shown to be effective in treating cases of inflammatory intestinal disease. As research on gut microbiomes progresses, we may discover more sophisticated ways to treat these diseases, but currently fecal transplant can be the best option.

As our understanding of the microbiome increases, we may discover a more complicated relationship between human health and gut bacteria. Finding more links will help advance medicine by taking advantage of this relationship to more easily detect and cure diseases.