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A Closer Look at the Blood-Brain Barrier

Nov 28, 2014

3050

In order to cure illnesses relating to the brain, various kind of simulators are placed deep inside the human brain. Sometimes, things like tubes, catheters, etc., are penetrated deep into the brain ventricles for delivering analgesic, chemotherapy, or to drain out excess cerebral liquids. Take the example of the Ommaya reservoir which is frequently used � it is simply thrust into the brain without caring about the brain tissues that come in its path. The need of the moment is that we should design delicate instruments for the brain, which works with the brain's natural barriers rather than against it. For that we must have the knowledge of membranes of the brain that balances the fluid's constitution, the way it seals the brain blood vessels, etc.

It is interesting to note that pathogens like the viruses, bacteria, fungi, etc., have their own tricks to invade the brain by bypassing its natural barriers. They find a way to enter if the infection persists long enough. Researchers are now wondering if they could apply the same Brain Blood Barrier (BBB) busting skills of the microbes to artificial devices for the brain. Typically, we do not insert a recording or stimulating electrode in the brain through the vasculature, however it could in fact be the most least invasive methods that could help us in enabling future technologies like the smart-dust, optogenetics, etc.

In order to be able to see the mysterious BBB, researchers used superparamagnetic iron oxide nanoparticles (SPION) encapsulated with inert hydrophilic polyethylene glycol (PEG) and obtained the MRI images of the BBB. MRI images of the BBB when it dynamically responds to assault were also recorded. These carefully-engineered nanoparticles are called PEGylated SPIONs by the researchers. These SPIONs did a great job at enhancing T2-weighted images of the permeabilized BBB.

The researchers also were able to analyze the SPION level in the brain parenchyma itself. For the brain, “Parenchyma� generally means the neurons and glial cells. It is estimated that there are over 100,000 miles of astrocytic endfeet-lined capillary tubing in its fractal coastline. In fact, the BBB and other membranous ventricular linings might be considered an organ itself.

The T2-weighted scans can give greater detail in imaging various brain pathologies. �It will be useful to know about the history of BBB to under the work better. A century ago, BBB was discovered by scientists when they were trying to find a way to insert drugs in to a brain for treatment of African trypanosomiasis (sleeping sickness). Scientist Paul Ehrlich was the first person who successfully developed a treatment against the African trypanosomes that caused the disease. He was the man who coined the terms “chemotherapy” and “magic bullet” after the trypan dyes which could kill the parasite’s cells while sparing the healthy cells.

It was then noted that when the trypan dyes are injected into the bloodstream, it would not label the brain. That meant that there was some kind of border. One thing that emerged from that research of trypanosomes is endocytosis – a core principle in cell biology and neuroscience. One of the key events in infection is that the pathogens gain passage through membrane boundaries by budding in through in vesicles. The BBB is lined by the endothelial cells – similar to those found in any other organs yet are held to a slightly higher standard. The junctions they make are tighter, and subject to more points of control.

Doctors today have a few crude tricks they can use to manipulate the BBB. However, those techniques are not very high tech. It is important to have a way for non-invasive measurements of flow and pressure as it will be essential to understand what is happening inside the brain when it has been altered by natural or by artificial means.

References

https://medicalxpress.com/news/2014-10-closer-blood-brain-barrier.html

https://nuzzel.com/story/10072014/medicalxpress/a_closer_look_at_the_bloodbrain_barrier

A New Way to Extract Bone Making Cells from Fat Tissue

Nov 28, 2014

3147

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Bones

The fat cells in our body consist of a variety of cells, that has the potential to become bone, cartilage, or more fat if properly prompted. So, in theory the adipose tissue is a reservoir in the body that can be used in various regenerative therapies like bone healing, etc. The crucial thing here is to be able to get enough of those cells and compel them to produce bone.

In this new study by scientists at the Brown University demonstrated a new method via which a variety of potential bone-producing cells could be extracted from human fat. The study was published in the journal Stem Cell Research & Therapy. They developed a fluorescent tag that has the ability to find and identify cells that expresses a gene called ALPL. The expression of this gene is an indicator of the bone making capability of the cell.

RNA is produced when this gene is expressed. If the tag finds RNA, it latches on and glows. Once that happens, a machine that detects the fluorescent light separates the ALPL expressing cells.� In the study that was published, the scientists have reported that their method have yield as many as twice of the potential bone-makers� than the previous method. That method which was thought to be the best method known sorted the cells based on the surface protein. The method developed in this study found potential bone makers as much as 9% while the previous method yield was just 4%.

In the next three weeks, subsequent cultivation of the similar-sized population of adipose tissues was carried out. It was observed that the ALPL expressing cells produced on average more than twice as much as the bone matrix and four times more bone matrix than cells that don’t express ALPL. It was also seen that ALPL-expressing cells were also better at making cartilage or fat.

There are a couple of other research groups who have sorted stem cells based on gene expression. However, they did not do it so specifically with the aim to enrich cell population for a specific tissue. Brown University has also filed an application for obtaining a patent on the method of gene expression tagging for producing a tissue

Hetal Marble, lead author and Brown graduate student said that the approach of sorting cells based on gene expression rather than surface protein is a �paradigm shift' in the following sense Gene expression gives a way of targeting any cell based on if it can produce another tissue. On the other hand targeting surface proteins is limiting as researchers have to harvest cells that fit a presumed definition of being a stem cell. The new approach, she said, is more practical for the purpose.

The approach that has been discovered in this study allows the researchers to isolate all the cells that are capable of doing what they want. It doesn't matter if they fit the archetype of what a stem cell is or not. The paradigm shift that is being talked about is about isolating populations that are able to achieve an end result without fitting into strictly defined cells.

One drawback of the experiment is that there is a four day delay; it takes that long for the maximum number of cells to express ALPL when cells are chemically primed to do so. To avoid this, the team has thought that they will like to target a gene expressed much earlier in the differentiation process to see if they can avoid a priming period. If they can apply the method based on a gene that’s expressible within a matter of hours it could do wonders for those who need bone healing and other such treatments.

References

https://news.brown.edu/articles/2014/10/sorting

https://economictimes.indiatimes.com/news/science/new-way-to-extract-bone-making-cells-from-fat-tissue/articleshow/44503661.cms

Kidney stone eradication system

Nov 27, 2014

3172

Even the thought of a kidney pain gives you a stomach ache, imagine a stone like structure present inside your organ that is playing such a vital role of filtering all your body waste, being loaded with a wall of stones and you have no option except to lie down on the ground and groan in pain every time it shows prominence.

A lot of people fall prey to kidney stone attacks every year and the first thing that comes to their mind is surgery. But won't you jump with joy if you ever get to know that there have been about 8000 people who flushed the kidney stones out of their system without even getting into the hospital beds or by following any kind of diets?

Kidney Stone

Usually to avoid these kinds of stones, one tends to drink a lot of water, but in case the attack has already happened, nothing can remove the stones from your body.� Even after a surgery, the stones have a tendency to come back, leaving you in a never ending cycle of pain and misery. You wait for the doctor to get the pain out of your body only to find yourself in more pain and a bagful of more medicines to curb the post surgical pain. You are bound to spend as hefty as $2000 to $6000 only to find yourself back in the same bed again after a few months.

But today all you need to do is simply act and not think because we bring you a final path to the culmination of your excruciating pain and a decision that you would not regret taking.� The treatment that is going to be with you now can give you the most peaceful six years of your life relieving you of any pain.

The kidneys have always been functioning since the time immemorial to clean up your system but then certain chemicals get deposited with time from the food and water we drink and they form stones. About 85% of the patients of kidney stones suffer from this problem because of over consumption of Vitamin D and Calcium.� Then there are Uric stones made when there is a regular intake of animal proteins. But no matter what the reason may be, we have a solution.

The best part about this treatment is that it is just a two step program that is going to give you a permanent freedom from stones. This manual is priced very nominally and will cost you just $47. What better can it get!

You will get to learn how to flush your stones without experiencing any pain. You would not need any surgery and thus no going under the doctor's knife or making holes in your pocket for any kind of surgery.

You get to read a thousand other testimonials of people along with their numbers who actually used the manual and have been benefitted a lot.

Lelia Abraham is one of those fortunate people who got rid of stone in the left kidney within hours and this is not less than a miracle.

The thing is even if you have to go and get a surgery one, you are definitely going to wait for the surgery to start and thus you do not have an immediate solution to your kidney problem. But this kidney stone eradication system is going to relieve your pain by not suppressing the cause but by totally removing it to give you a permanent relief.

The funnier part is that even the Doctors have started recommending it after knowing its genuinety. So, why to wait even for a second, when you already have the tool in your hands.

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Teenage Girls Are Exposed To More Stressors That Increase Depression Risk

Nov 27, 2014

2850

Teenage Girls Depression

Adolescence is the time when a lot of changes are happening in a person's life. However, a recent study has suggested that this phase of life is more turbulent for girls. It is also said that in girls this phase is marked by a high rate of depressive symptoms. The study says that it is likely that the gender difference could be a result of high stress events in a girl's life which makes them more immune to ruminate and that contributes to their risk of depression.

The findings of this study were published in the Clinical Psychological Science Journal by Association for Psychological Science.

Jessica Hamilton psychology researcher of Temple University and the lead author on the study opined that the finding dwell on the importance of stress as a potential reason that leads to the development of vulnerabilities to depression, especially in girls. It could greatly influence the way the risk of adolescent depression is treated. She added that there is a range of vulnerabilities that is responsible for the higher rates of depression among adolescent girls; however the study highlights an important malleable pathway that explains girls’ greater risk of depression.

The research pinpoints that certain cognitive vulnerabilities associated with depression, like negative cognitive style and rumination, emerge during adolescence. Those teens who have the habit of interpreting events in negative ways � which is negative cognitive style, and those who tend to focus on their depressed mood following such events � also known as rumination, are at greater risk of suffering from adolescent depression.

It was hypothesized by Hamilton, a doctoral student in the Mood and Cognition Laboratory of Lauren Alloy at Temple University that not only life stressors, those linked to the adolescents' interpersonal relationships but also the adolescent themselves are contributors in facilitating such vulnerabilities. That is the reason why there is an increase in teen's risk of depression.

For this research, data from 382 participating Caucasian and African American adolescent were examined. The adolescents were asked to complete self-report measures which evaluated cognitive vulnerabilities and depressive symptoms at an initial assessment. They were then made to complete three follow-up assessments, each of them were spaced about 7 months apart. As previously hypothesized, teens who had shown higher levels of interpersonal dependent stress reported higher levels of negative cognitive style and rumination at later assessments. The researchers also took initial levels of the cognitive vulnerabilities, depressive symptoms, and sex into account.

The data revealed that girls tended to show more depressive symptoms at follow-up assessments than the boys. Interestingly, it was also noted that the boys’ symptoms seemed to decline from the initial assessment to follow-up. However, the opposite was true for girls. The reason for that was that the girls were exposed to a greater number of interpersonal dependent stressors during that time. The researchers concluded that this exposure to stressors was responsible for higher levels of rumination and stress in girls which ultimately lead to depression.

Another important thing to note here is that the researchers emphasized that the girls were not more reactive to stress as compared to boys. In other words, if the boys and girls had been exposed to the same number of stressors, it is likely that both would have developed rumination and negative cognitive styles.

Hamilton remarks that parents, educators, and clinicians should keep in mind that girls have a greater exposure to interpersonal stressors which makes at high risk for depression.� The next step in this study will be to find out why girls are exposed to more interpersonal stressors. It need to be figured out if it is something specific to adolescent female relationships or if it is it the societal expectations for young adolescent girls.

References

https://www.psychologicalscience.org/index.php/news/releases/teenage-girls-are-exposed-to-more-stressors-that-increase-depression-risk.html

https://www.sciencedaily.com/releases/2014/10/141008122100.htm

Researchers Reveal Lung Cancer Can Stay Hidden For Over 20 Years

Nov 27, 2014

3234

A study published in the journal Science today said that scientists at the Cancer Research UK have discovered that it is possible for lung cancers to lie dormant for over 20 years. It may turn aggressive due to additional faults.

For this research, the team studied lung cancers from seven patients which included smokers, ex-smokers and never smokers. In their study, they discovered that even after the first genetic mistake has happened due to which the cancer is caused, it can exist undetected for many years. Only when new additional faults happen, it will trigger rapid growth of the disease.

This research is jointed funded by Cancer Research UK and the Rosetrees Trust. Its aim is to highlight the need for devising better ways to detect the onset of the disease earlier. Today, as high as two-thirds of patients are diagnosed with advanced forms of the disease. Unfortunately, at such a stage the treatments are most likely to be unsuccessful.

When the lung cancer expands rapidly, there is a surge of different genetic faults which appears in separate areas of the tumor. Studies have shown that each distinct section of the tumor evolves down different paths which mean that every part of the tumor is genetically unique.

The hard truth about the survival rates of lung cancer is that it is devastatingly low. There are many new targeted treatments, but they are making a limited impact on the disease. By understanding how it develops we know how the disease evolves. This knowledge will hopefully help us in predicting its next steps.

Smoking plays a big role in the development of lung cancer as the genetic faults are caused due to smoking. However, as the disease evolves it becomes less important as the majority of faults are then caused by a new process which generates mutations within the tumor. This process is controlled by a protein called APOBEC.

Since, there are a wide variety of faults; targeted treatment doesn't work as it is not effective against all part of the tumor.

Every year over 40,000 people are diagnosed with lung cancer. Even though there have been some positive breakthroughs against the diseases, we are still a long way to finding an effective way of treating it. For the last year, the survival rate of lung cancer is a mere 10% post diagnosis.

It is a priority for the recently established Cancer Research UK Lung Cancer Centre of Excellence at Manchester and UCL to build on this report. The Centre is an important part of Cancer Research UK’s renewed focus that aims to beat lung cancer; bringing together a unique range of internationally renowned scientists and clinicians to create an environment that catalyzes imaginative and innovative lung cancer research. To build on this work, Cancer Research UK is funding a study called TRACERx which will study 100s of patient’s lung cancers while they evolve over time to find out exactly how lung cancers mutate, adapt and become resistant to treatments.

“This fascinating research highlights the need to find better ways to detect lung cancer earlier when it’s still following just one evolutionary path. If we can nip the disease in the bud and treat it before it has started travelling down different evolutionary routes we could make a real difference in helping more people survive the disease.� said Professor Nic Jones, Cancer Research UK’s chief scientist.

References

https://www.sciencedaily.com/releases/2014/10/141009154007.htm

https://www.sciencenewsline.com/summary/2014100919120007.html

Drug Treats Inherited Form of Intellectual Disability in Mice

Nov 26, 2014

2912

A recent study at the Johns Hopkins University School of medicine have shown evidence that inherited form of intellectual disability may not be always irreversible. The researchers studied mice that had a genetic change similar to what is found in Kabuki syndrome � a form of intellectual disability in humans. Then then used an anticancer drug to “open up” DNA which resulted in the improvement of mental functions.

Not only the study suggest a potential treatment for reversing the symptoms seen in Kabuki syndrome, the study also suggest a new way of treating a category of genetically inherited disease known as the Mendelian disorder. This category of disorder is characterized by mutation which errors in the way proteins and chemicals bind to DNA. This in turn affects the rate at which proteins is made by DNA. In their experiment on the mice which had Kabuki syndrome-like condition, the researchers noticed that those errors lead to a decrease in new cell growth in one part of the brain. �The decrease the say is however treatable.

The report on this research appeared online on October 1^st in the journal Science Translational Medicine. The study was led by Bjornsson along with Harry “Hal” Dietz, M.D., the Victor A. McKusick Professor of Medicine and Genetics and director of the William S. Smilow Center for Marfan Syndrome Research.

In the Mendelian disorders of the epigenetic machinery the cell's ability to ‘package’ and use DNA is affected. Hence they tend to have complicated and far-reaching effects remarked Hans Bjornsson, M.D., Ph.D., an assistant professor of pediatrics and genetics in the Johns Hopkins University School of Medicine’s and McKusick-Nathans Institute of Genetic Medicine. �He further said that this finding that a drug could ease some of the symptoms in this group of disorders suggest that other such could be treated in a similar manner.

Bjornsson research focuses on Kabuki syndrome. This disorder is caused when there are mutations in one of two genes that govern proteins that DNA wrap around. The DNA is wound around the packaging proteins called chromatin. The formation of chromatin is necessary to fit in several feet of DNA inside the tiny centers from where commands are send to each cell. For a cell to be able to read the DNA and use it for making new proteins of its own, the chromatin must temporarily open up. Special enzymes are responsible for the opening and closing of the chromatin.

Based on some other recent studies, Bjornsson and his collaborators speculated that conditions like Kabuki syndrome might be due to an imbalance between chromatin’s open and closed states. Bjornsson added that if that assumption is proved to be true, it would mean that the disorders of the histone machinery could be treated by regulating balance between open and closed states.

To test the assumption, Joel Benjamin, a graduate student in Bjornsson's lab, experimented on mice.

The model mice had a mutation in one of the Kabuki syndrome genes and exhibited symptoms that are similar to Kabuki syndrome.

In their young adult phase, the mice were treated with AR-42, a drug developed for cancers of the blood that is known to open up compacted chromatin. Two weeks after the treatment, the mice were put through a drill called the Morris water maze, which tests their ability to form memories in the hippocampus region of the brain. The results showed that the treated mice performed better than the untreated mice almost at par with healthy mice.

Upon studying the brains of the treated mice, the researchers found that compared to untreated peers, they showed some formed neurons in a part of the hippocampus called the dentate gyrus, which is important for memory formation. The researchers came to the conclusion that when DNA’s chromatin opens up, the cells are able to ‘turn up’ one or more genes needed for that new growth.

Bjornsson remarked that now we know that new brain cells continue to form throughout our lives. So, stimulating neuron growth may be an effective strategy for treating intellectual disability.

References

https://www.hopkinsmedicine.org/news/media/releases/drug_treats_inherited_form_of_intellectual_disability_in_mice

https://www.sciencedaily.com/releases/2014/10/141001155556.htm

Newly Discovered Brain Cells Explain a Prosocial Effect of Oxytocin

Nov 25, 2014

3132

Brain Cell

A new research at Rockefeller University has discovered a mechanism by which the Oxytocin hormone has some crucial effect on interactions between the sexes – at least in certain situations. The key is in fact a newly discovered class of brain cells. The findings have been published in the journal Cell on October 9^th.

Oxytocin is the body's natural love�potion. It is what makes couples fall in love; it is responsible for the bond between mothers and babies. Nathaniel Heintz, James and Marilyn Simons Professor and head of the Laboratory of Molecular Biology said that by identifying a new population of neurons that is activated by oxytocin, they have discovered a way through which this chemical influences interactions between male and female mice.

The study was prompted by the search for a new type of interneuron which is a specialized neuron that relays messages to other neurons across relatively short distances. �For this, Miho Nakajima started creating profiles of the genes expressed in interneurons using a technique known as translating ribosome affinity purification (TRAP). This was a part of her doctoral thesis. The technique TRAP was developed by the Heintz lab and Paul Greengard’s Laboratory of Molecular and Cellular Neuroscience at Rockefeller. �In some of the profiles of genes that were collected from the cortex, she noticed an intriguing protein. It was a receptor that responded to oxytocin.

That was what raised the question what this scattered population of interneurons doing in response to this important signal, oxytocin remarked Nakajima. Since, it is known that oxytocin is most involved in social behaviors of females; it was decided to focus on females for the experiment.

In order to find out how these neurons affected behavior when activated by oxytocin, Nakajima silenced only this class of interneurons and, in separate experiments, blocked the receptor’s ability to detect oxytocin in some females. �Post this social behavior test was conducted on them.

The mice were given the choice between exploring a room with a male mouse or a room with an inanimate object like a plastic Lego block. Typically, Legos just aren’t that interesting to rodents. However, Nakajima’s results showed that sometimes the mice with the silenced OxtrINs showed an abnormally high interest in the Lego, and at other times they behaved normally. This confusing behavior led her to suspect the influence of the female reproductive cycle. In the next round of experiment, she also took into account if the female mice were in estrus which is the sexually receptive phase, or diestrus, a period of sexual inactivity. It was found that Estrus was of prime importance.

Those female mice in this sexually active phase showed a lack of interest in the males when their receptor was inactivated. However, there was no effect on mice is diestrus, and there was no effect if the male love interest was replaced with a female. Nakajima then tried the same alteration in males, and found that there was no effect.

Andreas Görlich, a postdoc in the lab, said that typically OxtrINs appear to sit silently when not exposed to oxytocin. The interesting thing to note here is that when exposed to oxytocin these neurons fire more frequently in female mice than they do in male mice. Nakajima remarked that it is not yet understood how oxytocin prompts mice in estrus to become interested in investigating their potential mates but surely it does. The results are an indication that the social computation going on in a female mouse’s brain differs depending on the stage of her reproductive cycle.

We know that Oxytocin has similar effects for humans as for mice. But, it is not yet clear if the hormone influences the human version of this mouse interaction. Further studies are needed for that.

References

https://newswire.rockefeller.edu/2014/10/09/newly-discovered-brain-cells-explain-a-prosocial-effect-of-oxytocin/

https://esciencenews.com/sources/the.rockefeller.university/2014/10/09/newly.discovered.brain.cells.explain.a.prosocial.effect.oxytocin

Ringworm cure

Nov 25, 2014

6792

Ring Worm

So, you have been affected by Ringworm infection? And you are tired of seeing those scaly patches and blisters on your skin? There is nothing more you want in the world than to treat this infection permanently and that too in a matter of days, right?

If yes, then how would you like to get rid of this horrible infection and that too in JUST THREE DAYS? Yes! THREE DAYS!

Can't believe it, right?

Well, here is the solution to your problem.

For those of you who don't know, Ringworm is NOT caused by a worm, it's, in fact, caused by a fungus. The most common places that get affected by ringworm is groin, hands and skin of any part of the body.

If a person has ringworm, they must treat it immediately because ringworm is contagious. It spreads when a person has skin � to � skin contact with another person or animal. It can also spread when things like clothing, towel, etc. are shared.

In most of the cases, you wouldn't even need to go and see a doctor. Sometimes, you can treat the Ringworm infection on your own:

Wash the affected part of the skin with cold or lukewarm water. Use soap or any anti bacterial solution with it too. Once the affected area has been cleaned, dry it thoroughly. If there are blisters, use compresses like the ones made with Burrow's Solution (You can get this solution without having to worry about prescriptions) to soothe and dry out the blisters.
Apply any anti fungal cream around the affected area. Don't apply it to the area, apply it beyond the edge of the rash. Anti fungal creams can also be obtained without prescriptions.
If you see your rashes fading, this means that this treatment is working. However, don't stop using the medicine even if the symptoms go away. Continue using it for two to four weeks to be absolutely certain that the infection doesn't come back.

The above treatment is when the rash is a minor one. However, if the rash doesn't vanish or the skin doesn't start showing signs of improvement in a day or two, this means that the infection is dangerous and needs to be treated immediately. Don't worry because, like we mentioned at the very start, we have the perfect solution for your skin. Our solution guarantees that you would get rid of Ringworm infection in just THREE DAYS. If you want, you can also skip the steps mentioned above and use our product as soon as you see signs of Ringworm infection.

Symptoms and Causes:

If you have got ringworm infection, initial symptoms are red, itchy patches of skin on the body. The affected area would have a rash or blisters on it and would have a circle around it. As the infection gets worse, more parts of the skin start getting affected and itchiness also becomes unbearable.

As mentioned earlier, ringworm is a contagious infection, which is caused by a mold � like parasite. This parasite lives in the cells in the outer layer of the skin. You can either get the infection by physically coming in contact with an already affected person or animal. You can also get it by touching objects or surfaces that an infected person or animal may have touched. The last cause of ringworm infection can be soil. Yes! Soil. In some cases the soil gets infected too, so if you stay in an affected soil for a very long period of time, there is a good chance that you can get Ringworm infection.

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Scientists Question Fundamental Theory about Education of Immune Police

Nov 24, 2014

3217

A new study reveals that the fundamental theory that has long been believed in about how the thymus gland of our body educates our immune police seems to be wrong.

It has been long known that the stem cells emerge from the bone marrow and travel to the thymus gland that is situated behind the breastbone in order to learn to become one of two CD4T cell types. One of them leads an attack and the other one keeps the peace.

Dr. Leszek Ignatowicz, immunologist at the Medical College of Georgia at Georgia Regents University remarked that the widely held concept about why they become one of the either types even though they come from the same neighborhood and attend the same school is that. They are exposed to different �things' in the thymus. The �things' we are talking about are called the ligands. The developing T cells are exposed to several hundred tiny pieces when inside the thymus gland.� Ligands are unique, just like our fingerprints. However, when the researchers limited exposure to only one fingerprint, the T cell mix that emerged was the same.

Ignatowicz said that they focussed on a simple question and that was – if it was going to affect their development and the answer was no. �Ignatowicz opined that since the cells still mature in the thymus, so there must be something else which is determining it. The finding is significant as it can pave way for providing more insight into immunity which could one day enable a new approach to vaccines which makes the thymus gland to produce more of whatever T cell type a particular patient needs. Say, one has a bad infection or cancer more effector cells are needed, in case of autoimmune diseases such as arthritis, multiple sclerosis, etc., more regulatory T cells are needed. It is possible for us to steer the education process in the desired direction.

Learning experience in the thymus is a tough experience. It is observed that the majority of the T cells either learn to be too aggressive or too passive. That is why they never make it out of the thymus. It is also seen that as much as 95% of the T cells that survive eventually becomes effector cells who are someday responsible for driving the response of the immune system to invaders such as bacteria, viruses, and tumors. The effector cells learn to recognize invaders happens when they are out roaming the body.

Dr. Richard A. McIndoe, a bioinformatics expert and Associate Director of the MCG Center of Biotechnology and Genomic Medicine explained that these future aggressors are the ones which bind less strongly to ligands they experience in the thymus. It is not desirable for an effector cell that binds strongly to oneself because that would make it attack the body itself he explained.

In order to conduct this study, the scientists experimented on two mice. Each of them expressed a single ligand in the thymus – the researchers had assumed that it would prompt strong binding. And another one was that would favor a weaker bond and effector cell development.

The mix of resulting T cells was the same � the setting was such both were exposed to the usual thousands of ligands however, there was a difference. Ligands � and eventually bacteria and other such invaders are noticed T cells by activating their receptors. It was seen both CD4T cell types generally have the same receptors, just organized differently. The finding of MCG scientists was that as long as the binding was weak – like it was in the first mouse, there was a lot of overlap in the receptors the ligand bound to in both T cell types. But, in the case of second mouse, which should have favored Treg development because the ligand prompted strong binding, there was significant less overlap.

The task now is to find out what causes that difference remarked Ignatowicz.

References

https://www.eurekalert.org/pub_releases/2014-10/mcog-sqf100814.php

https://www.sciencedaily.com/releases/2014/10/141008131609.htm

Patient’s Dramatic Response and Resistance to Cancer Drug Traced to Unsuspected Mutations

Nov 23, 2014

3894

Researchers from Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard said that the DNA of the woman whose lethal thyroid cancer unexpectedly “melted away” for 18 months has brought to light new mechanisms of cancer response and resistance to the drug everolimus.

The study was published in the October 9 issue of the New England Journal of Medicine. As per the study, it is said that the researchers two mutations in the cancer's DNA that were previous not known. One of the mutations made the woman's cancer quite sensitive to everolimus which explains the remarkably long-lasting response. The second mutation was found in the DNA of her tumor after it had evolved resistance to the drug 18 months after treatment started

This single case study demonstrates how repeatedly sequencing a patient’s cancer DNA can help in finding out unsuspected “response” and “resistance” mutations that may help guide treatment of other patients. The first sequencing is done prior to the treatment and again when the tumor shows signs of resistance. Jochen Lorch, MD, a thyroid cancer specialist at the Head and Neck Treatment Center at Dana-Farber and senior author of the report said that it is like a precise, personalized medicine at its best.

The mutation was identified in the gene called TSC2 � it is what was responsible for the patient's dramatic response to everolimus. In order to research on the same further, Dana-Farber has opened a clinical trial to test the drug’s effectiveness in other patients with TSC2 mutations. Such a type of trial is common because the patients who are “exceptional responders” are revealing previously unknown response mutations to a variety of drugs. Such a trial helps in pooling patients with a particular response mutation, whatever be the type of cancer they suffer from.

First author of the report Nikhil Wagle, MD, oncologist at Dana-Farber and affiliated with Brigham and Women’s Hospital and the Broad Institute of MIT and Harvard said that the study of such patients is important as it gives crucial insights. It can also help in developing methods to make personalized drugs, highlight effective uses for otherwise ‘failed’ therapies, and design new therapeutic strategies that will aid in the fight against cancer.

The study was prompted due to the surprising response to the drug in a 56-year-old woman who was diagnosed with anaplastic thyroid cancer in 2010. �This type of thyroid cancer has always been fatal within a few months. Despite conducting surgery, radiation and chemotherapy, the tumor spread to her lungs. Lorch was at that time leading a clinical trial of everolimus for a more treatable type of thyroid cancer. He decided to include the woman and a handful of other anaplastic patients in the trail.

His trail yielded some unexpected results – he found that after a few months the tumor shrank to a very small size. In fact, it remained that way for a period 18 months which was unheard of before after which until it began to grow again. The investigators used whole-exome DNA sequencing to produce scans of the protein-coding regions of the genome and they discovered a mutation in the TSC2 gene. It is known that the TSC2 protein normally suppresses mTOR activity. In case of its mutation, the mTOR is over activated � making it a prime target for everolimus. Other anaplastic patients didn't show such a condition that is why they didn't benefit from the drug.

When specimens taken from the tumor after it grew again was examined, it showed that there was a mutation in the mTOR protein which was not present in the original biopsy sample. Such type of mutation was not seen in humans earlier and that explained how the cancer acquired resistance to the drug. Further laboratory experiments revealed that even the mutated, resistant cancer cells remained sensitive to a different type of mTOR inhibitor. Now, to take the study further, a new kind of drug is supposed to enter clinical trials. It is going to be tested on the said patient diagnosed with the rare form of cancer and who is still alive four years after her diagnosis. Lorch added that if the study is successful, it can contribute significantly to the fight against cancer.

References

https://www.broadinstitute.org/news/6127

https://www.sciencedaily.com/releases/2014/10/141008203738.htm

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