BioQuakes

AP Biology class blog for discussing current research in Biology

Author: leahna

The Brain that Looked like Jello

Scientists at Stanford University made an entire mouse brain and part of a human brain that is the same consistency as Jell-O. The brain model is transparent so that neurons sending and receiving information can be highlighted and in in the same complexity as 3-D, but without having to slice the model. This new process, called Clarity, preserves the biochemistry of the brain so well researchers can reuse the same model over and over again.

Why Now?

The Obama Administration recently announced it’s interest in discovering the secrets of the brain. While this project was not part of the Obama Administration’s new initiative, Dr. Thomas Insel, director of the National Institute of Mental Health said that Clarity will help build the foundation of the Obama administration’s brain initiative.

The Clarity technique also works with brains that have been preserved for years.

One of the challenges of studying a preserved brain is making it clear enough to see into it. Unlike previous methods, Clarity makes the brain clear enough to see its inner workings.

Imagine if you could see through this brain!

 

How it Happened 

There are many was to make a tissue transparent. Clarity uses hydrogel, a substance of water held together by other molecules to give it solidity. The hydrogel forms a mesh that permeates the brain and connects to most molecules other than lipids. The hydrogel brain is then put in a soapy electrical solution, where a current is applied, driving the solution to the brain and getting rid of the lipids. The brain is then transparent with its biochemistry still in tact, so it can be infused with chemicals that will show the details of its structure.

The hardest part of the procedure is obtaining the correct ratio of temperature, electricity and solution. More work is needed to be done before this method can be applied to an entire human brain.

The Benefits 

The Clarity technique gives scientists a more exact image of what’s going on in people’s brains. This process may discover physical reasons for debilitating mental disorders, such as PTDS, schizophrenia, and autism.

Protein Might Help Fight Deadly Diseases

The enzyme “Cholesterol-25-Hydroxylase,” or CH25H, might help fight against human viruses such as Rift Valley Fever, Niphah and HIV. CH25H converts cholesterol to an oxysterol called 25HC, which can permeate a cell’s wall to prevent a virus from getting in. The CH25H enzyme is activated by interferon, an anti-viral cell signaling protein produced in the body.  Researchers have known that interferon has been part of the body’s defense mechanism against viruses, though it does not have any antiviral properties itself.

This discovery is revolutionary because other antiviral genes have not been able to be used for treatment of viruses in humans. According to Yang Lui, a student at the David Geffen School of Medicine at UCLA, most antiviral genes are difficult to use in therapy because the genes are difficult for cells to express. However, CH25H is different because it is naturally synthesized.

HIV Replication within a cell

The discovery of CH25H is relevant to the efforts to develop broad antivirals against an increase of emerging pathogens. In a collaboration with Dr. Lee, another UCLA professor, it was discovered that the 25HC produced from CH25H can inhibit HIV growth in vivo. The researchers initially found that 25HC inhibited HIV growth in cultures. When implanted mice with human tissues, the 25HC reduced the HIV in within 7 days and reversed T-Cell depletion caused by the HIV. It was also discovered that 25HC inhibited the growth of other diseases such as Rift Valley Fever Virus and Ebola.

There are still some weaknesses with the study. It’s difficult to deliver 25HC in the large doses needed to fight viruses. Researchers also need to compare 25HC to other antiviral HIV treatments.

Enzyme Protects Against Dangers of Oxygen

Yes, you read the title correctly: Oxygen can be dangerous.

As you may (or may not) remember, Oxygen is needed for two parts of cellular respiration. 1) For the Pyruvate made in Glycolysis to enter the mitochondria for the Krebs Cycle 2) As the final electron acceptor in the electron transport chain during Chemiosmosis. If there isn’t enough oxygen around (say, you’re running and there’s not enough oxygen to go to your muscle cells), the pyruvate made in glycolysis will not enter the mitochondria, but will instead undergo fermentation, which basically turns the NADH back into NAD+ so cycle of cellular respiration can continue.

Oxygen becomes dangerous when unhealthy cells fail to undergo cellular respiration, despite plentiful oxygen and instead undergo fermentation. This leads to uncontrollable cell growth: cancer. Luckily, scientists just discovered the enzyme superoxide dimutase, or SOD1 for short, regulates cell energy and metabolism by  transmitting signals from oxygen to glucose to repress respiration. This happens through cell signaling, when SOD1 protects the enzyme Kinase-1 gamma, of CK1Y, an important key from switching from respiration to fermentation. The results of this study were published in the Journal “Cell” on January 17th.

 

 

This diagram shows how enzymes, like SOD1, work. The substrate binds to the active site of the enzyme and the enzyme either breaks the substrate in two or puts two substrates together.

 

The interesting thing about this study is that SOD1 is not a new discovery. Scientists have known about SOD1 since 1969, but they thought it only protected against free radicals. Researcher Valeria C. Culotta calls SOD cells “superheroes” because of their many powers: protecting against free radicles and regulating cellular respiration.

According to Vernon Anderson, PhD, the result of this study might find out why cells turn to fermentation, casing cancer and some other diseases.

 

The True Origins of HIV

There’s no doubt you’ve heard of HIV, or Human Immunodeficiency Virus. The HIV virus, if left untreated can lead to AIDS, or Acquired Immunodeficiency Syndrome, which leads to progressive immune system failure (http://en.wikipedia.org/wiki/HIV#Discovery). HIV didn’t become a problem in the United States until the 1980s, but was around long before then. Alfred Roca, an assistant Professor at the University of Illinois believes HIV was around for much longer than we believe.

 

The Origins 

HIV was thought to be originated from SIV, or Simian Immunodeficiency Virus, that infected Chimpanzees in Central Africa. About ninety percent of humans infected with HIV are infected with a strain called HIV-1 Type M, which was believed to have crossed the species barrier anywhere between 1884 and 1924. However, believes that HIV crossed the species barrier many times before 1884, but was most prevalent in rural areas, so it remained undetected.

 

Why it was a mystery

If HIV was around long before we initially thought, why did it remain undetected. According to Roca, “the persistence of HIV in humans requires population densities typically of larger cities that appeared in West Central Africa during the colonial period.” HIV didn’t spread amongst humans pre-1884 because the population was not dense enough. In addition, diseases spread much faster. Many people would have died early from diseases such as smallpox, and those with compromised immune systems would have been hit first, thus the disease couldn’t spread.

Map of the prevalence of HIV in the world, according to the 2008 UNAIDS Preport

Roca also believes that different strains of HIV could affect people with different genes. Using data from The Human Genome Project, Roca was able to analyze the DNA of the Biaka people, who live in the forests where the chimpanzees responsible for our current HIV pandemic reside and 4 other African populations which live outside the chimpanzees’ range. Research done in the 1980s concluded there are 26 genomic locations that help resist HIV.

The results of the research were astounding. Roca and his team identified four genes that code for proteins that affect the ability of the HIV to affect the host or the progression of the disease. Several of these genes were common among the Biaka people. Though the results aren’t definitive, they show that natural selection does play a part in the transfer of HIV to human populations, which is why the disease didn’t thrive earlier.

 

 

Genome Project Helps Connect Ethnicity to Diseases

Though people from all over the globe share over 99% of the same DNA, there are subtle differences that make us all individuals

Scientists at the Washington University School of Medicine in St. Louis have started the “1,000 Genomes Project” in which they will decode the genomes of 1,000 people from all over the world in hopes of finding genetic roots of both rare and common diseases worldwide. On October 31st, the results of DNA variations on people from 14 different ethnic groups were published, but the scientists hope for the project to expand to involve 2,500 people from 26 different world populations. According to Doctor Elaine Mardis, co-director of the Genome Institution at Washington University, “[scientists] estimate that each person carries up to several hundred rare DNA variants that could potentially contribute to disease. Now, scientists can investigate how detrimental particular rare variants are in different ethnic groups.”

 

We are One

Everyone on earth share 99% of the same DNA. That means you, your best friend, your mortal enemy, your boyfriend/girlfriend, next door neighbor, and The President of the United States all share 99% of your DNA. However, there are rare variants that occur with a frequency of less than 1% in a population that are thought to contribute to both rare diseases and common conditions (i.e cancer, diabetes). The rare variants explain why some medications do not effect certain people or cause nasty side effects (i.e insomnia, vomiting, and even death).

 

The goal of the “1,000 Genomes Project” is to identify rare variants across different populations. In the pilot phase of the program, researchers found that most rare variants different from one population to another, and the current study supports this theory.

 

The Study

Researches tested genomes from populations from the Han Chinese in Beijing (and the Southern Han Chinese in China) to Utah Residents with ancestry from Europe to the Toscani people of Italy to the Colombians in Columbia. Participants submitted an anonymous DNA sample and agreed to have their genetic material on an online database. Researchers than sequenced the entire genome of each individual in the study five times. However, decoding the entire genome only detects common DNA changes. In order to find the rare variants, researchers sequences small portions of the genomes about 80 times to look for single letter changes in the DNA called Single Nucleotide Polymorphisms, or SNPs.

 

The Results and Importance

The Study concluded that rare variants vary from one population to another. Researchers found a total of 38 million SNPs, including 99% of the rare variants in the participants’ DNA. In addition, researchers found 1.4 million small sections of insertions or deletions and 14,000 large sections of DNA deletion. The “1,000 Genomes Project” is incredibly important in medical science. It now allows researchers to study diseases, such as cancer, in specific ethnic groups. I personally think this project in incredibly important. As an Ashkenazi Jew from Eastern Europe, my family has a medical history of certain cancers and diseases. With the results of the “1,000 Genome Project,” researches could potentially find out why, and maybe even find a cure for some of these diseases.

Stress is Good for you?

Does this look familiar?

High school is stressful. Students are forced to balance heavy loads of school work on top of family obligations and time-consuming extracurricular activities. We all know a little bit of stress is healthy, providing just enough motivation to give you a kick in the butt, but not enough to make you want to pull your hair out. However, when finals time rolls around and you’re ready to cry because you’re so overburdened, then stress becomes a problem. When you’re stressed, glucocorticoids, or stress hormones increase the level of cortisol in your body, prepping it to take on the physical demands of stress. (In terms of evolution, being under stress is being chased by a lion that thinks you’re dinner, not taking the SAT tomorrow). Science has always told us that stress is bad for us; high levels of cortisol are linked to depression and high levels of cortisol over prolonged periods of time actually impair our ability to cope with stress. Just reading about this is stressful, right? But what if I told you that stress might actually be good for you, at least in one respect. A new study conducted by Ranjish Rao and published in Biological Psychiatry shows that high glucocorticoid levels could potentially help reduce the development of PTSD, or Post-Traumatic Stress Disorder.

 

No, I’m not Crazy. Stress Really Can Be Good for You

PTSD is caused when a person witnesses a traumatic, potentially life-threatening event. For example, combat soldiers and children who were sexually abused often times suffer from PTSD. Recent studies show the “trauma” in PTSD is the impact of stress on the brain structure of the victim, according to Dr. John Krystal, editor of Biological Psychiatry. The study conducted by Rao was inspired by an odd occurrence: clinical reports showed people with low cortisol levels were more likely to develop PTSD, and that cortisol treatment actually reduces the symptoms of PTSD. The study used a model of a rat to study its stress levels in relation to corticoids. Professor Chattarji from the National Center of Biological Sciences in Bangalore, India explains the outcome of the experiment: “ We were able to…. identify a possible cellular mechanism in the amygdala, the emotional hub of the brain [responsible for this odd occurrence.]” It turns out the number of synapses in the amygdala is a fairly accurate predictor of whether or not a person will have high or low anxiety levels. The corticoids given to the rats reset the number of synapses in their amygdalas, and brought down their stress level.

So What Does this Mean for Me?

If you’re a high-stressed, health conscious person like me, after reading this you might feel slightly better about your high stress levels, but don’t celebrate just yet. Even though we all have the potential to develop PTSD, not everyone does, so this study is relevant to only a portion of the population. Even if it were relevant to everyone, the stress hormones in the study were given to the rats under controlled circumstances, and if this were to become an actual therapeutic treatment for PTSD, the patient would most likely ingest corticoids under the close watch of their psychiatrist. In my opinion, the damage caused by high glucocorticoid levels far outweigh the benefits. So, take a deep breath and relax. Maybe go for a run or talk with a friend. Your stress will eventually go away.

 

 

 

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