Communicating Science Course 2012 Blogs
Time your meals and stay thin!
By: Pallavi Lamba
Have you ever wondered why your low fat diet or the zumba workout sessions have not helped you lose weight? Well, the secret behind weight loss might lie in the timings of your food intake and not in eating less or exercising more! A recent study conducted at Salk Institute and published in the journal Cell Metabolism suggests that restricting the number of hours of food intake during the day and maintaining a daily rhythm in consumption of food can help prevent obesity and metabolic disorders such as diabetes.
Till now, obesity was a fairly ignored disease, with HIV, Tuberculosis and Cancer still being considered as the most serious life threatening diseases worldwide. Recently, obesity has emerged as a global health issue with about 500 million people being considered obese and nearly 1.4 billion people being considered overweight worldwide. Obesity is a silent but one of the deadliest killers, because of its association with variety of metabolic disorders such as diabetes, cardiovascular diseases and liver diseases.
Lifestyle modification plays a seminal role in the treatment of obesity. Although much emphasis has been placed on reducing the calorie intake and increasing the physical activity, much less is known about the effect of time of eating in the maintenance of body weight. The researchers of this new study claim that restricting the time of food intake without reducing the number of calories can help prevent obesity and it’s associated disorders. Previous research shows that there is extensive crosstalk between the components of body’s biological clock and the molecules regulating the metabolic cycle. And disruption of the circadian clock can result in weight gain and predispose a person to diabetes and other metabolic disorders.
In this new study, Satchidananda Panda and his colleagues at Salk Institute for Biological Studies, CA fed two groups of mice with a high fat diet and a normal healthy diet. One group of mice could eat throughout the day (ad lib) whereas the other group of mice was allowed access to food only for eight hours in a day. Both groups consumed equivalent amount of calories. Their body weight and other metabolic parameters were gauged after three months of initial feeding. The body weight of the mice eating all day long increased by 28%. In addition, these mice had higher blood glucose levels, a risk factor for diabetes. Their lipid metabolism was also completely disrupted with increased synthesis of fatty acid and accumulation of fat deposits in the liver. In the body fats are broken down into molecules called fatty acids. The energy in the body is stored in the form of fats which increases with increased fatty acid synthesis. If fats are not utilized for biological processes or as a source of energy, excess fat is stored in the body leading to weight gain. These mice also had high levels of cholesterol in their blood and were more vulnerable to inflammatory liver diseases.
Conversely, the mice following a time restricted feeding regimen did not show excessive weight gain even from high fat diet, had lower blood glucose levels, lower levels of fatty acid synthesis in the liver and did not show any signs of hepatic or liver inflammatory diseases. Moreover, they also showed increased activity and improved learning capability.
The metabolic cycle of your body is responsible for utilizing nutrients from the food that you eat and provides fuel in the form of energy to run your body. The researchers of this study claim that the metabolic cycle shows a periodic pattern which is synchronized by our internal body clock and the feeding-fasting rhythm. The mice which ate all day long, had a short fasting gap and an elongated feeding period which led to an altered circadian clock and metabolic cycle resulting in an increased production of certain metabolic molecules which drive up levels of glucose in blood and accumulation of fat deposits in the liver.
The liver is the main metabolic organ of your body and doesn’t have a timer of its own. It works according to the time that you eat and fast. Irregular eating patterns at inappropriate times could wreak havoc in your liver by completely blowing your metabolic cycle out of pace.
The findings of this study suggest time restricted eating regimen as a relatively new and non-pharmacological strategy to treat obesity and its associated metabolic disorders. So, don’t be tempted by those wonder weight loss pills flooding in the market. Instead, try adopting these trivial modifications in your lifestyle to stay fit and disease free. Think about how that bowl of ice cream or the bag of chips that you eat after dinner disrupts your metabolic cycle. In the future, with more evidence about the benefits of regular feeding timings the phrase “you are what you eat” may just get replaced by “you are when you eat!!”
Turning a tail into a heart—Progress in regenerative medicine
By: Sara Lewandowski
According to the Centers for Disease Control, heart disease is the leading cause of death in the United States. This means that not only is heart disease common among Americans, but for millions of patients, heart disease is the villain that doctors, with all of their training and arsenal of pills, are unable to defeat.
Scientists around the world have taken on the challenge of studying heart disease and developing the understanding, and ultimately the tools, which will enable doctors to save the lives of these patients. One approach taken by many researchers is not merely to create a pill, but to build a new heart. Sound a bit far-fetched? A group of scientists lead by Kunhua Song and Eric Olson at the University of Texas Southwestern Medical Center suggest that it may one day be possible.
In a recent issue of the journal Nature, the group described how they isolated cells, called fibroblasts, from the tails of mice and transformed them into myocytes, the beating cells that compose the heart. This ability, if perfected, could provide hope for the millions of heart disease patients.
If the heart were an orchestra, myocytes would be the musicians, the functional units that produce rhythms and melodies. As in an orchestra, the myocytes do not function alone. Purkinje fibers are the conductors, keeping the myocytes beating in harmony. Fibroblasts are the support staff, all of the behind-the-scenes workers that ensure that the show runs smoothly.
During a heart attack, the supply lines to a portion of the heart become blocked and the cells in that region stop receiving the oxygen and nutrients that they require to support their demanding jobs. In such grim circumstances, the cells have no escape from imminent death. Myocytes in the affected region of the heart die, leaving patches of the heart lacking functional muscle cells to beat and pump blood.
Returning to the orchestra analogy, a heart attack is like a crisis in which the entire violin section stops receiving paychecks, can no longer afford to continue performing, and subsequently pack up their violins, discard their music, and leave the group. When this happens in the heart, the region of dead myocytes is replaced by fibroblasts in a process known as fibrosis. Fibroblasts, being the support cells of the heart, can fill in the empty space, but are not muscle cells and cannot replace the myocytes in terms of their beating function. This is akin to ushers, janitors, and ticket salesmen standing on stage in the vacant violin section—the space is occupied, but the music of the orchestra remains impaired.
Unfortunately for heart attack patients, the human heart has very little capacity to build new myocytes. Shortly after birth, heart cells reach maturity and stop replicating. There are no music schools training new students to play the violin and the violin factories have shut their doors. For a human, this translates into a weakened heart with patches of scar tissue where heart muscle once was.
In an attempt to address these issues, scientists, including the group at the University of Texas Southwestern, have been intensely studying ways in which they can convince a patient’s non-myocyte cells to produce new myocytes that can replace those destroyed by a heart attack. Researchers have developed clever tools to trick cells into producing certain factors, called proteins, which act as the building blocks of cells and regulate the identity and activities of each cell and organ. Song, Olson, and their colleagues have used these tools, seeking to determine which of the millions of proteins the cells must be instructed to produce in order to transform into myocytes.
They focused on a set of six proteins known to be important in the development of the heart. After testing combinations of these six, the scientists found that four: GATA4, HAND2, MEF2C, and TBX5, had the most success in directing the conversion of mouse tail fibroblasts into myocyte-like cells. Using even more cool science tricks, this group labeled specific types of cells in different colors—first the tail cells, then the myocytes, and so on—and observed the conversion of fibroblasts into cells exhibiting traits of myocytes.
This conversion was not a complete transformation. On average, less than ten percent of fibroblasts expressed myocyte characteristics. Of these converted cells, the majority displayed only some features of myocytes. This is analogous to some of the substitutes in the orchestra having violins, some having musical scores, and a very small fraction having both violins and music. But just having violins and sheets of music does not ensure that the stand-in violinists will play the songs. Indeed, only a small fraction of the converted fibroblasts actually beat like myocytes.
The conversion of fibroblasts into myocytes may not be highly efficient, but it is none-the-less an exciting find. Cells are stubborn and convincing them to change their identities is not a trivial matter. The observations set forth by these scientists provide hope that, with optimization, regeneration of heart cells is possible.
Applying the same techniques used to convert tail cells to heart muscle in a dish, the scientists looked to see whether the fibroblasts that live in the mouse heart could undergo a similar transition. At a detectable level, the team was able to coax the support cells of the heart to become myocytes. Amazingly, these techniques stymied heart deterioration in mice that had experienced heart damage.
The group plans to continue investigating why some fibroblasts become myocyte-like while others stubbornly remain fibroblasts. They are also searching for additional factors that could improve the conversion process and ensure that the cells are fully transformed into myocytes that can function effectively. While these regenerative techniques are not yet ready to try on humans, the potential for creating new heart muscle from a patient’s existing cells is promising. With more work like this, regenerating organs could move from a fantasy into a clinical reality.
A Cup of Coffee Might Help You Live Longer
By: Ana Liso
I’ve learned today something interesting about coffee. Coffee, this smelly black liquid that most of us drink once or more a day. Personally I drink it every morning because it allows me to start my day with energy and somewhat awake.
After petroleum, coffee is the second most traded product in the world. According to some 2008 world wide consumption coffee data, the countries where coffee is most consumed are the Nordic countries of Europe. Finland is ahead of all of them, with a consumption of 12 kg of coffee per person a year! Although USA is not in the top ten countries for coffee consumption by capita it remains the first country of the world in total coffee consumed. All these data and the huge economic volume that coffee can represent explain why there is so much research done on it.
Coffee has more than 1000 compounds in it. The most known is, of course, caffeine but it also contains many others, among them some antioxidants. Since coffee is so popular, we constantly hear a lot of things about it, with of course, differing views. Some claim that it is good for health and some say that it is bad for health. Some maintain that coffee is good for attention, concentration and for some other aspects of your health. Meanwhile others argue that coffee can be bad for the heart and blood pressure. Others say that it does not influence the risk of cancer. With so many different views, whether or not coffee is bad for you is hard to determine. But for those of us who can't go a day without a fix, a new study suggests that coffee may prolong your life.
A recent study published in the prestigious New England Journal of Medicine by Freedman et al shows that if you drink coffee you may live longer. The study was done in sample of 402,260 North American individuals who answered a questionnaire in between 1995 and 1996. These subjects were followed up till December 2008 or their date of death.
When we pay attention to the results there are some not very positive data for us coffee drinkers. The dietary and lifestyle factors extracted from the study give a poor portrait of our profile. Coffee drinkers tend to consume more red meat, more alcoholic drinks and we are more likely to smoke. We also consume fewer fruits and vegetables and we, as a group, seem more lazy and less educated. In brief, it doesn’t look that coffee drinkers have a very healthy lifestyle. If we only consider data like this it doesn’t look like coffee drinkers will live longer. However, after the researchers further analyzed the data and removed some confounding factors that were biasing the results, such as smoking, they saw good things happening.
After a lot of statistical corrections and analyses they conclude that if you drink 6 or more cups of coffee per day and you are a man, you have a 10% less risk of death. If you are a woman and you drink 6 cups of coffee a day you have a 15% less chance of dying from one of the common causes (like stroke or diabetes). Keep in mind the results are only valid if you have never smoked or you are a former smoker. If you like coffee with a little cigarette you are actually at a higher risk of death. In the study they also conclude that it doesn’t matter if you drink coffee with or without caffeine.
The more coffee you drink the less chance you have of dying from the most common causes like stroke, diabetes. and even from accidents and injuries. The only exception for the most common cause of death is cancer; they haven’t found any relation either positive or negative with coffee. But as usual things cannot be as good as they appear and there are some little hiccups with these results.
For example even if it is a really big sample, presenting a self reported questionnaire is one of the problems. Participants say what they want to say and at a specific time point, so that can be true now but maybe not in the next six months, or even in the next 13 years. You can make a lot of changes to your lifestyle in 13 years! Another point is about the coffee itself: was it espresso or American coffee? How big was the cup? A ristretto or a “Dunkin Donuts” coffee is not the same size. Also, coffees are not prepared the same way everywhere; for example coffee habits in Europe and in the USA are quite different, based on my own experience. Is it important for this study? Probably yes.
As the authors pointed out, this study is observational so we cannot conclude that there is a cause-effect. We can say that we see a connection but we cannot conclude that because you drink coffee that you will live longer. Even if that is true, among the 1000 compounds of the coffee which one can be responsible?
But even with all of that, don’t forget, we can be satisfied with ourselves and drink our coffee thinking that we may live longer!!!
Freedman et al. 2012. Association of Coffee Drinking with Total and Cause-Specific Mortality. The New England Journal of Medicine. 366:1891-904
Cheaper, better, faster, stronger vaccines from new technique
By: Zachary Maben
Remember those shots that traumatized you as a kid? You may not know it, but those needles represent the most effective medical treatments we humans have. They’re the reason you don’t know anyone suffering from smallpox or polio. Vaccines against these diseases and many others have protected billions of people. These two examples are viruses, which are very small germs with only a few different parts. This made their vaccine production relatively simple. As scientists try to make new vaccines against more complex germs, however, the procedures used have gotten complicated and expensive. Michael Valentino unveiled a simpler way to produce vaccines in 2011 with his paper titled “Identification of T-cell epitopes in Francisella tularensis using an ordered protein array of serological targets.” To get an idea of the importance of this improvement, we first need to talk about how vaccines work.
Vaccines keep us from getting sick by training our immune system to recognize germs. Like when police send out an alert, the immune system looks for several small but distinctive details to find, identify, and eventually remove invading germs. These small pieces are called “epitopes”. Scientists find these pieces that the immune system can recognize and make a mixture of them, which is the vaccine. The injection gives advance notice to the body to be on alert for those pieces, and when the real germs try to attack, the immune system is ready.
Previously, research groups found epitopes by making as many pieces as they could, and then seeing if any of them activate the immune system. This lengthy and expensive procedure requires custom-making tens of thousands of chemicals. Michael’s research is more like making a police sketch of a criminal using a witness’s testimony.
The lab used mice which had been infected with bacteria named Francisella tularensis. This germ can make humans very sick if they aren’t given antibiotics quickly. Also, some versions have been made antibiotic resistant by the USA and the USSR during the Cold War. The infected mice were given time and antibiotics to help them recover. The lab then took out immune cells that the mice had made, and tested what epitopes they saw. These scientists learned from the immune systems of mice that already fought off this germ, just like having a witness of a crime point out details of the criminals.
In this particular germ, the lab group found three new epitopes that might be suitable for vaccines. One epitope is a piece of a large protein named IglB. This protein is unique to Francisella tularensis. Its job in the germ isn’t completely known, but it is very important when the germ wants to infect someone. This makes it a great target, because germs sometimes try to disguise themselves by getting rid of some epitopes. If this germ tries that trick with the epitope in IglB, it won’t be able to infect anymore! This sort of medicinal catch-22 is perfect for therapeutics. The other two epitopes are equally indispensable, but for a different reason. These epitopes come from proteins called GroEL and DnaK. These have been studied extensively and are important for the bacteria to survive in any condition. This means that the bacteria also can’t get rid of these epitopes to avoid immune detection.
One other difference between the old approach to making vaccines and this new method is the applicability. With the old way, an epitope can be found to work in the lab, but doesn’t help with fighting disease in the real world. This means that all the extra time and money required might not even pay off in the end. The new procedure uses information from immune systems that won the battle against the germ, so the epitopes they use have proven to be protective. Michael shows this when he made a prototype vaccine using these epitopes and saw immune cells respond! This result shows the practicality of this technique.
By using this same method, it might be possible someday to make vaccines against many more difficult pathogens, like HIV. These germs often use decoy epitopes to distract the immune system while the germs spread happily. These decoy attempts highlight how crucial it is to identify heavy-hitting, indispensable epitopes against germs of all sorts. Once our scientists find their weak spots, our immune systems have no trouble fighting off these diseases. Now if only they could do it without the needles…
Artificial Stem Cells: Stem cells without the Moral Dilemma
By: Sean McCauley
No topic in modern biology has received as much public and political attention as stem cell research. Nowadays, most people have some opinion on the situation, and for good reason. Stem cells have the capability to multiply and convert into any other kind of cell in the body. That means stem cells, when properly motivated, could be used to treat an enormous variety of ailments. For example, a heart attack leaves a person with scaring in their heart that does not beat. An especially severe one can leave the heart critically damaged. In theory, stem cells could be used to regrow the heart back to its original condition or even rebuild a new one. This advantage applies to all kinds of include physical trauma, degenerative conditions, and genetic diseases.
Stem cells come in several varieties, the most common of which are embryonic stem cells. These are the most versatile, but are also the most controversial due to the nature of their origin; embryonic stem cells are collected from an early embryo, which requires its termination. This brings complex ethical questions to the table that are not to be taken lightly. Many believe that the termination of an embryo violates the sanctity of life and view it as tantamount to murder. While it does not appear that these moral issues are going to be resolved anytime soon, less controversial alternatives to embryonic stem cells are possible.
In 2006, Kazutoshi Takahashi and Shinya Yamanaka of Kyoto University wrote a landmark paper based on their research that changed stem cell technology forever. Their discovery arose from work that aimed to determine what made embryonic stem cells so unique. Specifically, what made stem cells different from normal cells? They found that several genetic factors worked together to give stem cells their inherent flexibility. This gave them the idea that perhaps the “stem cell state” was not as complex as previously thought. If stem cells can differentiate into any other kind of cell, conceivably the process could be reversed.
Takahashi and Yamanaka first began by infecting normal skin cells with specially made viruses. However, instead of making the cells sick, the viruses contained DNA that activated the same factors that were found in stem cells. The infected cells began to construct the stem cell factors and, over a period of several weeks, the skin cells began to look like embryonic stem cells. After a great deal of trial and error, they narrowed a pool of 24 original candidates to four specific factors, Oct3/4, Sox2, c-Myc, and Klf4, required to convert skin cells into stem cells. The new stem cells were dubbed induced pluripotent stem cells, or iPS cells for short.
Further experimenting confirmed their expectations. From the skin tissue samples, they were able to create numerous batches of iPS cells. The new iPS cells could replicate indefinitely in a dish, something skin cells cannot do. Even more importantly, they were capable of growing into the three main tissue groups in the body. To the naïve onlooker, the cells could not be distinguished from bona fide embryonic stem cells.
Unlike embryonic stem cells, induced pluripotent stem cells are converted from fully matured, normal cells, which we each have more than enough of. As such, there is no need to destroy embryos. The previously mentioned ethical quandaries are therefore circumvented.
Just as significantly, nearly any type of body cell can undergo the transformation. This means that iPS cells can be made from the spare cells of a person who needs more of a specific type. In effect this would allow the donor cells to be genetically identical to the recipient.
Normally, our immune system can sense when cells are not from our own body and will attack them. When a donated organ is received, the patient requires powerful drugs that stop their immune system from attacking and rejecting the foreign cells. Because iPS cells can be made from a donors own skin, there is no risk of immune rejection. The artificially created organ could be implanted and the body would treat it as its own.
It is well known that stem cells represent a great hope for bringing medical science a great step forward in clinical care and treatment. iPS cells provide a solution that eliminates ethical complications while maintaining the benefits of embryonic stem cells. The hope at this point is so great that multiple researchers are jumping on board to push the science further and faster. It would not be out of the realm of possibility that stem cell treatments could become commonplace in the near future. Perhaps in a few years, replacement tissues and organs made from our own cells will bring hope to the millions of families struggling with “incurable” diseases.
Mental Retardation may soon be a thing of the past
By: Rhonda McClure
Did you know that the most common form of mental retardation affects 1 out of every 1,250 males? This hereditary disease called Fragile X Syndrome has puzzled scientist for centuries. Dr. Liu recently published a scientific breakthrough that identified the root cause of this syndrome and a possible way to reverse it.
Fragile X patients have learning disabilities, speech impairments, and various physical abnormalities. Imagine having dementia at the age of seven, or experiencing severe panic attacks with every social interaction. No known treatment of Fragile X syndrome exists, and currently patients receive treatment for each individual symptom. Children may end up on several different types of medications their entire lives. Understanding the root cause of the syndrome can lead to the discovery of one treatment for all of these symptoms.
Fragile X Syndrome is caused by a mutation in a single gene called the Fragile X Mental Retardation gene (FMR-1). Our body contains about 25,000 different genes that serve as blueprints for making particular proteins. Fragile X syndrome inhibits the creation of the Fragile X Mental Retardation Protein (FMRP). FMRP functions to lower the amount of various other proteins in the brain. The loss of FMRP causes the level of the proteins in the brain to rise.
At its root, mental retardation results from memory dysfunction. With every memory or piece of information learned, the brain makes changes at the connections between brain cells. Without these changes, you would not remember how to tie your shoe or learn why 2+2=4. When you learn how to tie your shoe certain connections between certain brain cells get activated. In order to remember how to tie your shoe your body has to make that connection unique so it can be the “tie your shoe” connection. Your body tags this connection by making new proteins right at that connection. These new proteins make this connection different from all the other connections in the brain. FMRP normally lowers the proteins involved in this tagging process.
Scientists study Fragile X Syndrome in the lab using mice with the same mutation in the FMR-1 gene as humans with the syndrome. These mice show similar symptoms as humans. Different drugs are tried out on these mice to test if the mice return to normal. Until recently scientist hadn’t identified a single, cure-all treatment that could make these mice completely normal.
Dr. Liu is a leader in the field for discovering treatments for Fragile X Syndrome. In a previous study Dr. Liu gave mice with Fragile X Syndrome lithium over a long period of time, and actually saw that the mice returned to normal! How can lithium, a salt, reverse so many symptoms in such a complicated syndrome? It must affect the root cause of the syndrome.
Dr. Liu’s latest findings identify the root cause for the Fragile X Syndrome. This is a breakthrough for finding a cure for over 100,000 males in the United States alone. Dr. Liu’s findings are based on previous Fragile X research that show Fragile X mice have the same increase in protein levels in the brain as humans with Fragile X syndrome. They don’t experience an increase in protein all over the brain but in particular regions important for learning and memory. Dr. Liu’s breakthrough research shows that too many proteins in particular regions of the brain are the root cause of Fragile X Syndrome.
He proved that too many proteins were the problem by looking at the protein levels in the brain before and after Lithium. Lithium did not change the protein levels in normal mice. In Fragile X mice, long term lithium returned protein levels to normal in areas that usually see an increase in protein. This further supported the idea that the problem causing this syndrome was just a matter of too many proteins, and by returning the protein levels to normal you can actually reverse the disease!
Next Dr. Liu focused on how lithium actually changed the protein levels so drastically. What could a salt possibly be doing to the brain? Dr Liu started thinking maybe lithium affected the machinery involved in making the proteins. Many different types of machinery exist to make all of these new proteins in the brain. More of this machinery is active in Fragile X mice. This increase in active machinery is important to make all the extra proteins seen in these mice. Dr. Liu checked if lithium decreased the amount of active protein making machinery in the brain. He tested two different types of machinery and found no difference between mice that received lithium and mice that didn’t! Both groups of mice had increased levels of active protein making machinery.
Dr. Liu remains puzzled on how lithium affects the protein levels. However, this study shows the root cause of Fragile X syndrome is too many proteins in the brain; leading to the idea that in the brain, balance is everything. With this information doctors can began to target the extra proteins in the brain to address the whole syndrome and not just each symptom. If other forms of Mental Retardation share the root cause of having too many proteins, Dr. Liu may have stumbled onto the road to curing all forms of mental retardation.
Liu et al. Neurobiology of Disease 45, 1145–1152 (2012)
Illegal emigration of RNAs, a natural mechanism
By: Mihir Metkar
A process called transcription decodes the information in deoxyribonucleic acid (DNA) and its end product is ribonucleic acids (RNA). In eukaryotes (organisms whose cells have a nucleus), the produced RNAs are transported out of the nucleus, into the cytoplasm where the information in RNA is converted into other biomolecules called proteins, which carry out most functions in the cell. Thus, RNA act as an intermediate, a messenger, for translating the information encoded in DNA to a functional form called proteins. This is the central dogma of biology.
However, it is unfair to simplify the process to such an extent that it starts sounding bland and insipid. To give you an example of how to make cell biology interesting if you look at it closely, I wish to discuss a new mechanism of RNA transport that was recently discovered by Speese et al (1).
But before we go into the new mechanism, I would like to briefly explain the known mechanism of this messenger RNA transport.
Imagine a cell as made up of two countries- the central, inner spherical nucleus and the surrounding cytoplasm. These two countries are separated by a fatty (lipid) membrane and a mesh-like structure called lamina, formed by the protein lamin, on the nuclear side. For molecules like RNAs and proteins to travel between these countries, there are special structures called nuclear pores. However, all molecules that travel between the countries of the nucleus and cytoplasm need a visa, specific proteins called importins and exportins. Importins import molecules from the cytoplasm to the nucleus, and exportins export molecules from the nucleus to the cytoplasm. Thus, newly synthesized RNA is coated by a lot of different proteins, including the export proteins (exportins), which allow emigration of RNAs from the nucleus to the cytoplasm.
In a recently published article, Speese et al. show that RNAs can travel out of the nucleus independent of nuclear pores. The scientists showed that special proteins signal the muscle cells of flies to release another protein called Frizzled. This Frizzled protein then interacts with the lamina and by unknown mechanisms separated RNAs into big granules with proteins. Another specialized protein (PKC) breaks open the mesh-like wall of lamina and helps the granules to emigrate out of the nucleus. These granules are easily 3-4 times bigger than the diameter of the nuclear pore, so they cannot be transported through the pores. Initially scientists thought that the granules were formed in the cytoplasm after exporting single RNAs through the nuclear pore. But this new mechanism gives a whole new perspective for transporting RNAs from the nucleus to the cytoplasm.
Doesn’t this mechanism uncannily resemble the illegal emigration of groups of people? I imagined this process to be like trafficking RNAs without a valid visa. RNAs with a valid visa move from the nucleus into the cytoplasm without a problem through the nuclear pore. However, the RNAs inside granules may not be able to pass through the nuclear pore without a visa. Hence, they seem to have devised a mechanism similar to illegal emigration wherein they move into the other country in the wee hours of the night, without a visa. They have an insider, the Frizzled protein, which works with certain other unknown accomplices to help in this trafficking. Late into the night when no one is watching, these RNAs and their associated proteins gather in a busload in the areas marked by Frizzled. These marked areas are logically away from the nuclear pores so as to avoid risk of detection by the border patrol. Once they have gathered, another friend of Frizzled, the PKC proteins, locally disrupts the lamin wall to allow the group (the large granule with RNA and proteins) to pass into the membrane and then into the cytoplasm, without anyone noticing.
This study is also important from a disease point of view. This mechanism was discovered in developing fly muscle, and the process of muscle development does not change much from flies to humans. Speese et al. showed that this type of RNA-protein granule emigration from cell nuclei was important for the proper development of muscle cells. Hence, alteration in this mechanism might play an important role in the development of diseases such as some types of muscular dystrophy and Gilford progeria that show lamin mutations and start with improper development of muscle cells. Dystonia, a sustained muscle-contraction disorder, shows a similar disruption of this new mechanism of transport of RNAs.
Biology is not as bland as it is sometimes made to sound. It has a lot of new and interesting stories. As this paper shows, even the simplest of things like transporting RNAs out of the nucleus can have very interesting mechanisms. Most of the things that happen inside the cell have analogies to what happens in society. Such analogies make it even more interesting and fun to learn about biology. Something that we regularly see outside our bodies also happens inside us.
Sean D. Speese et al., “Nuclear Envelope Budding Enables Large Ribonucleoprotein Particle Export during Synaptic Wnt Signaling”, Cell 149, 832–846, May 11, 2012
On a diet or doing liposuction? Why we gain the fats back
By: So Yun Min
Have you ever wished if fats on your belly go away without arduous exercises and sweating? More and more people care about their appearance as well as better health. One of the important issues on the quality of people’s lives and health closely relate to their weight. It is noteworthy that obesity causes most of the chronic diseases, including cardiovascular disease, diabetes, and cancer, which threat number of lives in our society.
All we know that we should eat less and move more to stay slim and healthy. So do we follow the rules to keep ourselves healthier? It is not always easy to follow what we had better to. Also, many people suffer from malfunctioned metabolism and genetically inherited obesity. These reasons led obese people to go on an extreme diet or to do liposuction. Unfortunately, in most of the cases, their bodies get back to their original status even after successful reduction of body weight. Why do we have to struggle with removing fats? How does the body re-build up fats and go back to the original shape even if a whole tissue chunk is removed? Furthermore, we do not clearly know the difference between the lean people who do not gain weight much even when they eat much and the obese people who get fatter easily.
These issues are ultimately linked to the big question of how our body develop, maintain and monitor adipocytes (fat cells). Our body stores fats in existing adipocytes and keeps making new adipocytes because each adipocyte has the capacity to reservoir fats, maintaining the structure of fat tissues. If we know which population of cells are precursors (parent cells) of adipocytes, we can expect to find a way to suppress or expedite the formation of adipocytes, depending on the cases. This might eventually not only help the morbidly obese but also the patients who want better shape of their body. Therefore, defining the precursors and inducing factors of increase of the number of adipocyte became an interesting topic in the field and numbers of intensive studies have identified the specific markers (characteristic marks on or in each cell) of precursor cells for adipocytes. The most recent and conclusive study from Cell (Rodeheffer et al., 2008) characterized a set of stem cell markers to identify adipocyte precursors in mice. Also, Tang and his colleagues (Science 322, 583-586, 2008) showed that adipocyte precursors located the narrow blood vessels of adipocyte tissue. These clues provided a strong foundation and stimulated the research area.
Recently, Khanh-Van Tran and her colleagues (Cell Metabolism 15, 222-229, 2012) suggested that a part of vascular endothelial cells (lining cells around blood vessels) develop into adipocytes, meaning that the cells forming our vasculature can give rise to fat cells in various tissues. Of course not any vascular endothelial cell turned into adipocytes. To trace which portion of the vascular endothelium forms the adipocytes, the authors marked endothelial cells with a marker for endothelial cells in mice. When they traced the expression of the endothelial marker in fat tissues, they could find that fat tissues expressed the endothelial marker, which represents that the cells having characteristics of endothelial cells developed into fat tissues. Moreover, the authors found that human adipose tissue which formed endothelial-like sprouts also expressed a marker of adipocyte precursors. This supports the author’s argument that endothelial cells in blood vessels of adipose tissue can develop into adipocytes in human as well as in mice although not all the adipocytes are derived from them. Together, while multiple populations of precursors develop into adipocytes and form fat tissues, endothelial cell in blood vessels of adipose tissue is one of the populations which can become fat cells.
The fact that endothelial cells in blood vessels of fat tissues can develop into fat cells implies that we need to reconsider the way we treat obesity, especially physical removal of fats from the body. That is, because fat fills up the space again as vasculature grows back in the adipose tissue, we cannot ultimately overcome obesity with merely removing fat tissues. We would need to find other ways to monitor adipocyte precursors to ultimately cure obesity in addition to better diet and exercise. This might be bad news for the people who depend on liposuction without active efforts, but the research shed light on the ultimate solution for obesity.
**Paper: The Vascular Endothelium of the Adipose Tissue Gives Rise to Both White and Brown Fat Cells, Cell Metabolism, Volume 15, Issue 2, 222-229, 8 February 2012
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