Oxygen - The New Antibiotic

Along with being antibiotic resistant, bacteria have also adopted sleep as a form of survival. By using toxin antitoxin systems, bacteria can become dormant to resist antibiotic attacks and awaken as soon as their environment permits. These systems, also referred to as biofilm, are responsible for 80% of infections and are often the reason bacteria are referred to as antibiotic resistant.

Earlier this month, Thomas K. Wood and his colleagues analyzed the first known toxin antitoxin system produced by E. coli in a biofilm. It is most unique because it is also the first system found to be dependent upon oxygen. The research conducted revealed that the antitoxin structure produced by the bacteria had passageways big enough to allow oxygen to flow through it. Toxin Hha and antitoxin TomB need oxygen to work. TomB, in conjunction with oxygen, oxidize Hha to wake up dormant bacteria after being stressed.

The research also reveals that only 10% oxygen is enough to awaken the bacteria, and using the oxygen passageways, an entire colony of bacteria can be manipulated into breaking up and dispersing biofilm so an actual antibiotic may be able to attack the active bacteria.

Although interesting, I did not entirely understand how this information can be applied into a human bacterial infection. Normal blood oxygen levels can be anywhere from 95-100%, so how would this knowledge be applied when prescribing an antibiotic treatment? It probably is more useful as prophylactic, to prevent biofilms from forming in the body all together to prevent bacteria from going dormant in order to cure an infection faster.

Image taken from http://news.psu.edu/photo/441070/2016/12/08/toxin-antitoxin-002

Breakthrough in Gene Therapy for Sickle Cell Disease

Breakthrough in Gene Therapy for Sickle Cell Disease

 
                                              

A team of researchers are making breakthroughs when it comes to correcting defective sickle cells with a gene-editing tool called CRISPR. This tool can fix genes that cause sickle cell, and thus can lead to promising gene therapies for this ailment.

The researchers have been able to prove that they can use such mended cells to make a “high functioning hemoglobin molecule” and have it transfer oxygen to cells. When the stem cells were placed in mice they found it successful in treating disorders such as sickle disease and thalassemia.

CRISPR is both an enzyme and “guide RNA” that can cut the part of the gene that causes mutation out and use other tools to make the correct sequence.

Sickle Cell is a disease that make normal cells turn into a sickle shape, which significantly decrease the amount the oxygen being transported around the body. This new breakthrough with CRISPR can be used to help change treatment, and detect and prevent disease in those who fall ill.

Sources:

 1       1. https://www.sciencedaily.com/releases/2016/11/161108112133.htm#

Genes Help Monkeys Stay High

            Rhinopithecus bieti, or colloquially known as the Yunnan snub-nosed monkey to people from Tibet, are a very interesting group of monkeys. Living over 4,000 miles above sea level, it is a wonder as to how they are able to acclimate themselves to not only the weather but also the altitude. So how do these monkeys remain at such high altitudes?

        

            The answer to that question may lie in the snub nosed monkey’s genes. In a genetic study of the monkeys’ DNA, it was determined that there were 19 major gene variations that contribute to the monkey’s ability to thrive at such high altitudes. As the only non human primates to live at such high elevation there must have been many things that contributed to their selection for these genes.

            Through reconstruction of the evolutionary history of these snub nosed monkeys, researchers determined that episodes of climate variation may have shaped these monkeys to what they are today. One of the major genes involved in the monkey’s ability to inhabit such high elevations is the ADAM9 gene (See genome sequenced here). Interestingly enough, there are versions of this same gene located in yaks and chickens found in Tibet. In relation to the selection of genes, the ADAM9 gene was most likely selected for its ability to allow these animals to live in such low oxygenated conditions. Similar to these monkeys, the people of Tibet also have adaptations to the high elevation of Tibet inherited from their extinct relatives known as the Denisovans. The genetic variant that has been examined to be the cause of this adaptation is known as EPAS. Thanks to genes and many years of selection, the snub nosed monkey and many others, including humans, have been able to acclimate themselves to high altitudes where the oxygen levels are scarce.
            As someone who enjoys hiking up large mountains, I think the gene like the ADAM 9 would be something that could help me personally to climb higher mountains without having to waste time acclimating to the altitude. Perhaps in the future, the ADAM 9 gene could be isolated and potentially sequenced to find a similar allele in normal human beings like me. In that way, potentially, regular people could climb higher and higher like these snub nosed monkeys or even Denisovans.  

(https://www.sciencenews.org/blog/science-ticker/genes-help-snub-nosed-monkeys-live-high-life?mode=topic&context=87)            

Evolutionary change in humans?

The Tibetans live at altitudes of about 13,000 feet. The higher the altitude, the harder it is to breathe. This is because at an elevation of 13,000 feet, the air has 40% less oxygen compared to what is available at sea level. However, the Tibetans suffer from very little sickness.




To figure this problem out, researchers compared the genomes of the Tibetans and the Han chinese, which happen to be the two majority ethnic groups in China. The biologist found 40 genes that had undergone mutation or evolutionary change that allowed the Tibetans to adapt to the high altitude. The two groups split apart about 3,000 years ago.

If this holds true, this would be the most recently known example of evolutionary change in humans. When lowlanders try to adjust to the high altitudes, their blood thickens which causes the body to overproduce red blood cells. As a result, this causes mountain sickness which leads to lesser fertility.

I personally find this stuff fascinating. Later in the article it mentions that they think that natural selection played a role as more and more offspring were thrown into the population. However, I am in awe of what the human body is capable of. The way that it can heal itself and change in order to survive is taken for granted, I think.

Elite Athleticism and The deletion of the D allele in Angiotensin-Converting Enzyme(ACE)

        

        There has been research done involving the inheritance of Angiotensin-converting enzyme(ACE). ACE is an enzyme that increases blood pressure and vasoconstriction. In the study shown, they analyze how individuals without the D allele react to physical tasks. Several rats were tested and it showed that exposure to hypoxia increased the expression of ACE, which means that the rat would experience more vasoconstriction, disallowing the oxygen to flow. The study shows that via ACE inhibition, the pulmonary  hypertensive response to hypoxia is reduced, which means that the subject would be able to increase the oxygen in their body. The key to this is the deletion of the D allele. If this condition is in athletes, their body can perform at higher levels when under hypoxia like conditions. When other athletes oxygen levels are low, the athletes without the D allele will have higher levels, and be able to perform better.

Cells compact their DNA when starved of oxygen, nutrients

 
    Many diseases like a heart attack, stroke, and cancer can cause long-term effects to the body. Because there is lack of blood supply to the heart and brain, it causes the cells to be deprived of oxygen and nutrients. This condition is also known as Ischemia and oxygen starvation as hypoxia.

    In a new study, researchers reveal that when cells undergo starvation of oxygen, the DNA in the nucleus becomes compacted. The DNA compresses into tight clumps, which prevents gene-reading molecules from accessing the genetic code. This is a factor to why disease like a heart attack or stroke can occur because the cell eventually stops functioning.

   Scientists are now using new technology to figure out ways to prevent DNA from compressing. The new technology is a development of super-resolution light microscopy. Since the genetic code is tightly packed inside of the chromatin, scientists do not yet have the technology to look at the nanostructures of chromatin. Instead they use a dye that binds to the DNA and the dye allows them to look inside and around the chromatin and define the location of molecules in the DNA.

"What is interesting to me is the cause of the cell to stop functioning. Because the DNA becomes compressed into tight clumps, it is hard for the gene-reading molecules to access the genetic code. If the genetic code is not accessed, then there is no protein built, which could possibly code for a specific function. If there is no cell function, then the cell will die. This makes me think what causes a cell to undergo starvation? If there is treatment to keep the cells from starvation, then the DNA will not compress."

Click HERE for the article!

Synthetic Blood Development Could Be a Breakthrough for Trauma Patients 

Whales and other deep sea diving mammals can hold their breath and keep active for extended amounts of time on just one breath.  This is due to the vast amounts of myoglobin (a protein that helps to hold oxygen in the body) stored in the large mammals’ muscles.

Researchers from Rice University have done studies for quite some time on the myoglobin in the bodies of whales and other marine mammals to hopefully be able to come up with synthetic blood for human trauma patients.  Because the myoglobin in whales can hold so much oxygen, this in turn could be beneficial to humans.  “Whales and other deep-diving marine mammals can pack 10-20 times more myoglobin into their cells than humans can, and that allows them to ‘download’ oxygen directly into their skeletal muscles and stay active even when they are holding their breath” said biochemist, John Olson in a statement.

Whales have a large amount of myoglobin in their muscles which is why they can stay under water for so long.  Humans have less myoglobin in their bodies which is why it is difficult to hold their breath for extended amounts of time.  If synthetic blood were to be developed for trauma patients, it would provide hospitals with a larger blood supply.  This in turn would allow patients to receive blood quicker as well as have that blood “take up” oxygen more efficiently. 

I found this article very interesting.  Although there are many people that donate blood, having synthetic blood on hand could make it easier for patients to be matched for a specific blood type as well as make more blood if needed instead of waiting for a donation. 

To read more, click here and here 

Italian Scientists Link Gene to Longer Life

A team of Italian scientists made an amazing discovery in the genetics of longevity in mice. The discovery's effects is unknown in humans but it could lead to the drugs that postpone the effects of aging.

Oxygen creates many byproducts within the body that can corrode our bodies cells. To battle the corruption of cells and DNA the cells are "programmed" to self destruct before the damage becomes too great and the damaged cells become cancerous cells. The team has studied the gene that makes a protein that triggers the "self-destruct" process in those cells in their response to too much oxygen damage, mice that lacked the trigger protein lived thirty percent longer than normal, with no apparent side effects.

Although the mice were genetically unable to self destruct their damaged cells, they are presumably living longer because they are no longer being zapped by the self destruct mechanism even though they are genetically suffering oxygen damage.

Dr. Pelicci says that the trigger protein belongs to a class of proteins in which many inhibitory drugs are known and it shouldn't be to difficult to create a drug to block the trigger.

Phenotype modification occurs when the expression of one gene alters the expression of another gene. Gene modifiers can cause enhanced phenotypes or reduced phenotypes, and in this case it would be living longer in mice and hopefully drugs that postpone aging in humans.

Caloric restriction is already known to benefit life span in mice and creating a drug that mimics the effects of caloric restriction without the hassle and pain would be extremely valuable.

The downside of caloric restriction in mice however is the reduced fertility, but the fertility of the mice with the blocked trigger protein appears to be normal, but Dr. Pelicci is skeptical that the fertility effect of the blocked trigger protein is too mild to have been detected yet.



Article Link: http://www.nytimes.com/1999/11/18/us/scientists-link-a-single-gene-to-longer-life-in-mice.html
Secondary Link:Modifier Genes in Mice and Humans