Wednesday, November 30, 2011

Organ Circadian Clock?





New research shows that each of our organs contains cells with their own circadian-clock genes that help bodily processes operate with maximum efficiency at certain times of day. Each organ operates on its own internal clock, producing enzymes and molecules at different levels depending on the time of day; the brain works to make sure all the clocks are synchronized. Dyssynchrony between the brain and the rest of the organs, or between individual organs, can lead to problems. For example, if the pancreas is out of sync with the liver, insulin production may be too low or too high

In 2005, a team demonstrated that mice with a mutation to a clock gene in the brain's "suprachiasmatic nucleus," the region thought responsible for synchronizing circadian rhythm across the body, had a disrupted feeding pattern.

The mice ate more at all hours of the day, rather than primarily in the evening, when they are typically awake. These mutant mice were obese and had a number of metabolic problems. The researchers found that their behavior influenced the clock genes. Eating a high-fat diet appeared to change the circadian-clock genes in a part of the brain, the liver, and in fat tissue.

Other researchers have looked at the effect of clock genes on the liver. Steve Kay, dean of the biological-sciences division at the University of California, and his colleagues showed that a particular clock gene shuts down excess glucose production in the liver.

A team from the University of Pennsylvania, led by medicine and genetics professor Mitch Lazar, recently found a clock-gene mechanism that reduces the production of fat in the liver at certain times of the day. Such findings suggest manipulating these clock genes could have implications for diabetes or fatty liver disease.

In a case where the rhythm of a particular organ is out of sync with other organs, realignment is more difficult. It may not possible for an individual to control by changing their behaviors, but opens up the possibility of novel ways of treating disease.

I thought this was interesting because it never occurred to me before that individual organs had their own cycles of sleep-wake. This could be used advantageously in many fields if more was known about how each organ functioned at certain times.


http://online.wsj.com/article/SB10001424052748704471904576228532850374342.html

Researchers have made two big discoveries involving embryonic stem cells. For one, they discovered that certain tissue contains the information necessary for it to form complex structures like an organ. In this case, they found that ectoderm when exposed to hypothalamic neuroepithelia in the presence of Sonic Hedgehog Protein, would form invaginated and hollow vesicles. These vesicles are similar to pituitary precursor organ called Rathke’s pouch. This tissue even exhibited the characteristic chemical markers associated with this tissue.

Second, they found that interfering with the Notch signaling pathway could induce coricotrophs differentiation. These cells, found in the anterior pituitary, are responsible for releasing the adrenocorticotropic hormone. This tissue was highly functional, even after implantation, and highlights how manipulation of signaling pathways such as Notch can induce differentiation.

As a student heavily interested in tissue engineering, I picked this article because I find stem cells fascinating because they offer an alternative solution to the traditional methods of cell-scaffold based artificial tissue. With stem cells, one could repair or fix an organ without having to replace it. This however, is far in the future as currently we are having difficult turning embryonic stem cells into any adult cell line in tissue (which is only the first step). What is relevant, however, is that the mechanisms behind stem cell differentiation can allow for the development of better in-vitro tissue, which I plan to get involved in an undergraduate lab working in.

Source: http://www.nature.com/nature/journal/v480/n7375/full/480044a.html


Picture 1: Development of Pituitary and Hypothalamus. While this picture is only somewhat related to the article, it shows how complex the tissue system is. If we can get tissues to perform some of these functions in vitro, it would be a big leap in tissue engineering.

In the Absence of Pain


When I was little I remember wishing that I could not feel pain. This sensation normally came after stubbing my toe, or a shot, or some other quick stinging pain. It would have made life so much easier to not have to be held back by pain. However, I now understand how useful pain is to the body. House did an episode of a girl who could not feel pain, and in typical House fashion there was of course something more life threateningly wrong with her. This episode got me thinking about the causes of not feeling pain, and this article is what resulted.
Congenital Analgesia, or indifference to pain is a rare condition causing lack of pain sensation, but not other sensations. There have only been 100 cases in the US since 1932, and unfortunately the exact cause of the condition is unknown. However, due to frequencies of occurrences it is believed that the gene is autosomal recessive, but it may be caused by more than one allele.
I was surprised to find that there are other conditions with similar effects and one of them is congenital insensitivity to pain with anhidrosis (CIPA). This condition is caused by a mutation of the NRTK1 gene and results in a decreased number of small myelinated and unmediated nerve fibers. People with this condition also lack sensitivity to temperature change and cannot regulate body temperature by sweating. A third condition is hereditary sensory and autonomic neuropathy type 5 (HSAN5). This is different from CIPA in that individuals with HSAN5 do not have anhidrosis. It also appears to be caused by an autosomal allele.
After reading the article I was very surprised to find that the exact causes are unknown, especially considering the potential of self mutilation from an unknown injury. Any further research in this matter may even be used to develop new ways to block pain.

Scientists use brain imaging to reveal the movies in our mind



This is seriously the coolest article I've ever read. Imagine if we could hook our brains up to a machine and watch on a screen what we are imagining in our heads. I've always thought about this as a child and had no idea that it was possible.

What if we could hook are brains up before we go to bed and record our dreams so we can watch them later? Researchers at UC Berkeley are bringing this idea one step closer to reality. Using MRIs and computational models, the researchers are able to reconstruct peoples visual experiences. As of yet, this only works on movie people have already viewed.

Just imagine the implications of such a reality as dream watching. Doctors would finally be able to understand what is going on in coma patients minds. Stroke patients and neurodegenerative patients who can not communicate verbally could possibly be able to communicate with this device.

It's articles like this that keep me motivated to achieve a degree in biomedical engineering.



http://newscenter.berkeley.edu/2011/09/22/brain-movies/

Nanomedicine: Using Nanostructures to Combat Drug-Resistant Bacteria



The incredible drug resistance exhibited by some bacteria has been a source of concern for medical authorities for years. Most threatening is the seeming cyclical effect of it all-- strain becomes resistant to antibiotic, strain treated with stronger dose, strain acclimates to dose... and so on. However, recent developments have been made in the field of nanomedicine that offer respite from such a troubling pattern. Antimicrobial agents have been created that mimic the amphiphathic characteristic of peptides in a way that allows them to associate with the microbial membranes of certain bacteria. Once there, they can recruit additonal polymer molecules which result in the actual physical destruction of the membrane. As opposed to many traditional antibiotics (which inhibit certain functional pathways of the pathogen), these nanostructures alter the morphology of the bacteria and eliminate the risk of the development of a drug resistance.
Success has been found with many Gram-positive bacteria, including MRSA, whose drug resistance to methicillin is a huge problem in hospitals. The implications of studies such as this one are incredible- the quick destruction of bacteria eliminates the threat of breeding a "super-bug" that may one day be completely untreatable by modern medicine. Most exciting to me in my interest to pursue a medical career, is that this study casts hope in the direction of a multitude of other diseases--including viruses such as HIV--through the successful creation of a nanostructure that can interact with a pathogenic membrane. If other materials can be synthesized to interact with and compromise the ever-changing membranes of life-threatening viruses, we may move one step closer to finding an effective treatment for diseases that seem unstoppable today.

Drug Shows Promise For Ebola Virus Treatment In Primates


In a recent study, scientists for the first time have successfully treated monkeys with the Ebola virus. The ebola virus is a severe and often lethal (if left untreated) disease that causes a hemorrhagic fever. Vomiting and bloody diarrhea are also symptoms of the virus. Although it is not very contagious, outbreaks of Ebola do occur in poor areas without modern hospitals and can have fatality rates as high as 68%.
Thomas W. Geisbert and colleagues from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) injected 12 rhesus monkeys with Ebola virus in this study. Nine of the twelve specimens were treated with a drug (recombinant nematode anticoagulant protein c2), while the other three were left untreated. The treatments were administered daily. This drug took a unique approach to combatting the virus; rather than combat the virus itself, the goal was to combat the symptoms of the virus. Ebola causes coagulation and abnormal blood clotting. Studies show that macrophages play an important role in this process. They express a clotting protein on their surface during this process. The administered drug blocks the effects of the clotting proteins.
Of the nine treated monkeys, three survived and six died. All three of the untreated monkeys died much sooner than the six that were treated. These results are promising, and the drug is already being used to treat certain coronary diseases and will hopefully be used one day to treat viral hemorrhagic fevers in humans.
I am interested in pathology, so this article interested me. It is interesting to read about the current research on some of the world's deadliest diseases and how treatment can be applied to not only treat the disease, but also treat other diseases.

There's an app for that.

If its as simple as spitting on a smartphone screen to see if someone has the flu, this is the most affordable doctor out there. Visionaries at KAIST (Korean Advanced Institution for Science and Technology) think that a smartphone screen might be capable enough to diagnose different types of disease from fluid body samples. This was inspired by the lab-on-a-chip design, which is a small device the size of a USB chip that is disposable and will be used for the detection of the disease.  A study was done to see if a smartphone screen was sensitive enough to detect different concentrations of certain liquid droplets at a small capacitance.  They took different concentrations of DNA from a bacteria that is known to cause chlamydia and used a smartphone sized multi-touch screen for a proof-of-concept test. Each droplet was only a microlitre and the screen's electrodes were able to detect the difference in concentration of the droplets.
This technology has not been created yet but is in the process of being created and this is why I was initially so interested in this article. After doing the nano-machine project I could see that so many potential things already around now could be used for biotechnology in the future. In our nano-machine the parts are around today but we predict that they will be smaller in the future so that they can be on the nano-scale these researchers are taking the multi-touch displays and predicting that they will be able to make an app that diagnoses diseases in the future. Their prediction might not be so far away in the future seeing from the studies they are already doing and hopefully this can be true for nano-machines ideas that we created.

http://www.newscientist.com/article/mg21228405.800-to-selfdiagnose-spit-on-an-iphone.html?DCMP=OTC-rss&nsref=online-news

Bear serum prevents osteoporosis?




Over 40 million americans are at risk for developing Osteoporosis. It is an unfortunate disease doing highly destructive and degrading damage to your bones due to disuse. Currently, it accounts for $20 billion in health care funds, but imagine if we could find a way to slow the effects or completely forget about it. Bears spend six to eight months in hibernation, not using any of their bones or muscles, but this does not affect their structures. The serum element creatinine, which has linked with hibernation in bears and its apoptosis-inhibiting qualities might be able to prevent or limit the apoptosis of bone-constructing cells, osteoblasts. What if this was the solution to osteoporosis!

Gene therapy used to protect against HIV transmission

Doctors have started to use gene therapy as a way to protect from HIV transmission. They decided to use this form of therapy since vaccines don’t work against it. The disease has managed to mutate so many times and those mutations effectively protect themselves against attack from antibodies. This method of gene therapy was based off the successful experiments on monkeys who have the simian version of HIV.
The doctors started of experimenting on mice using 5 different antibodies. Out of the five, two of the antibodies completely protected the mice against HIV transmission, and continued to do so after even after a year. Despite success in monkeys and mice, doctors are wary about how successful this form of treatment would be in humans.
This is interesting because after all this time a possible form of treatment for HIV has been found after many failed attempts. Although this treatment can negatively affect some who may have adverse reactions to the antibodies, there will be many more who will benefit from this treatment.

http://www.nature.com/news/gene-therapy-can-protect-against-hiv-1.9516

Interfacing with Neurons to Control Prostheses



Liang Guo et al. are experimenting with the idea of controlling prostheses using the neurons that were damaged in an amputation. They hope to do this by directly interfacing the damaged nerve with the prosthetic device. Using natural or induced regeneration of axons, they believe they can make re-grown axons integrate with a microelectrode array. The ultimate goal for this interface is to establish bi-directional communications between the nerve and the prosthetic, which has been an elusive problem to solve.

They have created a nanofiber-based regenerative scaffold with tunnels through which the proximal stump of a cut axon should grow. Incorporated within the scaffold is a polydimethylsiloxane-based (PDMS-based) conformable microelectrode array. This array is connected to the positive input terminals of an amplifier, and the negative input terminals are connected to the reference electrode. The purpose of the amplifier, which is also incorporated into the scaffold, is to reduce the signal-to-noise ratio in order to facilitate neuron interfacing. The implanted electronics and arrays within the scaffold are connected by PDMS cables, and the I/Os of the electronics are wired to a headstage via subcutaneous wires. Testing has already shown the effectiveness of the electrode channels as well as the biocompatibility of the system, but more tests are necessary to determine the overall effectiveness.

I believe this article was worth sharing in light of the Oscar Pistorius SNBAL. This shows there are people working on controlling prostheses like a normal body part, thus increasing ease of use. Coupled with the growing efficiency of prosthetic devices, the time when artificial body parts perform better than natural ones may be approaching faster than one might imagine.


http://ieeexplore.ieee.org/xpls/abs_all.jsp?arnumber=5709604&tag=1

Frogs for your health

So as I am sure most if not all of you are aware we are kind of running out of effective antibiotics as microorganisms develop resistances to drugs like penicillin as we continue to use them frequently. Because of this scientists are always on the hunt for new sources of antibiotics and they seem to have found an abundant new source, though in a rather unconventional place. It would seem that so called "odorous frogs", which live in more bactericidal active environments than most frogs are covered in antibiotic substances called AMP's or antimicrobial peptides. Through taking samples of these substances from just nine species of these odorous frogs an incredible 728 AMP's were found with 662 of those being previously undiscovered. All of these AMP's showed strong results when purified and used against microbes. One particularly interesting property of these antimicrobial peptides is not only that they acted as antibiotics but that when activated they also increased the response of the frogs immune system. These AMP's could possibly be used as antibiotics alone or to influence research with the goal of creating AMP's that influence the human immune system.

Violent Video Games Cause Changes in the Brain

Think playing video games won't affect brain performance? Think again. Protective mothers across the country relieve a sigh of "I told you so." Playing violent video games, a recent study of young men shows, decreased the players' brain activity in their left inferior frontal lobe while performing emotional tasks and counting tasks. A dearth of activity in this area of the brain is thought to cause violent behavior. The study involved making some men play violent video games for one week, testing their brain activity, restricting them from video games for a week, and then testing their brain activity during different tasks again. The researchers found that while playing violent video games reduces activity in the frontal lobe, the effect is diminished after a week of not playing video games. So the effects of violent video games, while they make a significant short term difference, can be counteracted by refraining from playing them. Them study team now hopes to see if pro-societal video games will stimulate brain activity in the left inferior frontal lobe.
This article was particularly relevant to me, not because I play a lot of violent video games, but because my roommates do, and I like to watch them. It's interesting to see how environmental factors, like playing violent video games, change how we act. Maybe one day, we will better understand the effects of these factors and be able to predict people's actions or tendencies.

http://www.sciencedaily.com/releases/2011/11/111130095251.htm
Radiological Society of North America. "Violent video games alter brain function in young men."ScienceDaily, 30 Nov. 2011. Web. 30 Nov. 2011.

Researchers Examine Role of Inflammatory Mechanisms in a Healing Heart


Researchers at Virginia Commonwealth University are investigating the role of a certain inflammatory mechanism called an inflammasome. While they do not have complete knowledge of inflammasomes' full roles in a healing heart, it is theorized that blocking the mechanisms will allow the heart to heal more quickly due to the lowered risk of inflammation. Inflammasomes help generate Interleukin-1Beta, which is a key inflammatory mediator. Blocking the interleukin will hopefully reduce further damage to the heart during the healing process. This research will aid tremendously in future heart operations. This allows a much easier recovery from people getting heart transplants or any mechanical implant. As biomedical technology gets more and more advanced, this will allow for a less stressful healing process.
Photo: A detailed picture of an inflammasome and the process it uses to create Interleukin-1Beta.

Eating baked fish helps protect the heart?




Since we were kids, we have been hearing from doctors and parents that eating fish helps to keep your heart healthy. Dr Donald Lloyd-Jones of Northwestern school of medicine in Illinois confirms the fact that "How you prepare fish is just as important as the type of fish in terms of seeing benefits
A test conducted on about 85,000 women has determined that just eating any kind fish does not help boost the heart health, but only baked and/or broiled fish help to keep the heart healthy. It is important to know this fact because keeping a healthy diet helps keep the body healthy and disease free.
A fatty acid (omega-3) found in the fishes was significant in lowering inflammation and blood pressure. The Omega-3 did not cause any changes on its own but was only effective when it was included with other chemicals from the fish (the whole fish had to be eaten to gain these results).
This area of physiology is very interesting as it brings to light how a single substance in the food we eat can cause some changes in our body, but it also needs many more substances with it to help the body stay healthy.


Reference
http://www.cnn.com/2011/HEALTH/05/24/baked.broiled.fish.heart/index.html

Fish and Alzheimer's





A new study has shown that eating fish once a week can lead to a healthier brain and a decrease in Alzheimer's disease. In this study, people who ate baked or broiled fish at least once a week showed increased gray matter in the brain. The areas that showed increased brain matter were shown to have been involved the part of the brain associated with memory and learning. It has been shown that people with larger volumes of gray matter in the areas of memory and learning has been shown to have a reduced risk of developing Alzheimer's disease. Although the baked or broiled fish showed an increase in the gray matter people who ate fried fish had no increase in the gray matter; therefore not decreasing the risk of developing Alzheimer's. The study used magnetic resource imaging, or MRI, to scan the brains ten years after a group of people were surveyed about their weekly fish consumption. In the results, people with greater volumes of gray matter in the hippocampus, posterior cingulated, and orbital frontal cortex were less likely to have Alzheimer's disease. Fish contains omega-3 fatty acids, which improve blood flow to the brain, and delivers more oxygen and nutrients to brain cells. Omega-3s can also reduce inflammation in the brain caused by amyloid plaque buildup, a possible cause of Alzheimer's disease. Although more research is needed to validate the results, it is a good start to something that can influence the development of Alzheimer's disease.

I find this topic very interesting and important for future research in brain diseases. If diet could be found to play a role in the decrease of the development of Alzheimer's disease, it could be a simple fix to a very common disease. Although the research has yet to be validated this is a start in the right direction to finding new breakthroughs.