Tuesday, April 29, 2008
Final Unit Count
At the conclusion of our service project, we have completed 7252.94 units for the FightAIDS@Home site. It may seem like a small contribution, but if we can raise the awareness of such a simple method that anyone can do, we could make an even bigger impact together!
Monday, April 21, 2008
The Effects of Heritability and Inbreeding on HIV
1) The estimated value of h^2 for HIV is 0.54 (1). This suggests that the affect of selection on the trait is half and half. Which means that the heritability of HIV is somewhat similar to that of the previous generation. The offspring are similar to their parents. "Most traits and most populations fall somewhere in the middle with offpring showing a moderate resemblence to their parents which is evidence that the variation among individuals is partly due to variation in their environments and partly due to variation in their genes"(2).
2) Inbreeding would reduce the variability of the HIV virus across the entire genome. The parents and offspring would share the same genes which would likely decrease the fitness. Thus inbreeding would affect the evolution of allelic frequencies by increasing the exposure of recessive phenotypes to natural selection. This would likely mean that the types of HIV would become very similar and over time the strands found in one individual will be similar to those in another.
1)http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18288889
2)Freeman, Scott and Jon C. Herron. Evolutionary Analysis. 4th ed. Upper Saddle River, NJ; Prentice Hall, 2007.
2) Inbreeding would reduce the variability of the HIV virus across the entire genome. The parents and offspring would share the same genes which would likely decrease the fitness. Thus inbreeding would affect the evolution of allelic frequencies by increasing the exposure of recessive phenotypes to natural selection. This would likely mean that the types of HIV would become very similar and over time the strands found in one individual will be similar to those in another.
1)http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18288889
2)Freeman, Scott and Jon C. Herron. Evolutionary Analysis. 4th ed. Upper Saddle River, NJ; Prentice Hall, 2007.
Wednesday, April 9, 2008
What we learned
This paper had a lot of information contained in it. It put into context some of the things that I have learned over the semester. Firstly, it made me realize that the quick rate of evolution of the virus, though mainly deterimental to a cure, makes it fairly easy to determine a source if a person is tested soon after contracting it. Also, it was interesting to see how prisoners are not necessarily discouraged from taking intraveneous drugs, just simply given ways of preventing infection.
- Jess
HIV is a difficult disease to combat because of its evolutionary qualities. This paper pointed out that there are different rates of evolution in different areas of the virus, which makes finding a cure difficult. I was also surprised to discover that evolution is a continuing process even within the same viral strain, and the evidence in the paper regarding the different rates brought this idea to light.
-Phil
This paper reinforced what I have been learning about the dynamic nature of the AIDS virus, a feature that allows doctors to establish homologies between several strands of the virus either within several people or one host. That this virus is able to constantly mutate is both an obstacle and an asset to those who study the disease. In the case of the studies undertaken at the Glenochil prison, researchers were able to construct a phylogeny based on the fingerprints left by the changing virus, thus leading to the recognition that transmission had come from a common source. After reading this paper I was left wondering to what degree of impact had the study on the prisoners. Armed with this type of information, one would expect those prisoners not already infected to take precautionary measures, such as not sharing needles, to prevent infection. There seems to have been little done to discourage prisoners from IV drug use, instead the prison took what they felt was a more practical position in distributing fresh needles throughout the inmates to prevent the spread of the virus. I think they would have benefited from more counseling on the dangers of drug abuse to deter those not already abusing and more treatment options to help those prisoners refrain from continued use.
-Aimee
We believe that it is very important for doctors to be aware of evolution because it affects every area of their practice. Viruses continually mutate and become resistant to the antibiotics that have been used previously. Being educated in the processes of evolution allows doctors to be able to control how much and how often they prescribe medication, particularly antibiotics. Also, as in the case of HIV and AIDS, it affects doctors' ability to find cures to diseases. Being aware of evolution will hopefully help them eventually get ahead of the disease and develop a way to kill it.
- Aimee, Phil, and Jess
- Jess
HIV is a difficult disease to combat because of its evolutionary qualities. This paper pointed out that there are different rates of evolution in different areas of the virus, which makes finding a cure difficult. I was also surprised to discover that evolution is a continuing process even within the same viral strain, and the evidence in the paper regarding the different rates brought this idea to light.
-Phil
This paper reinforced what I have been learning about the dynamic nature of the AIDS virus, a feature that allows doctors to establish homologies between several strands of the virus either within several people or one host. That this virus is able to constantly mutate is both an obstacle and an asset to those who study the disease. In the case of the studies undertaken at the Glenochil prison, researchers were able to construct a phylogeny based on the fingerprints left by the changing virus, thus leading to the recognition that transmission had come from a common source. After reading this paper I was left wondering to what degree of impact had the study on the prisoners. Armed with this type of information, one would expect those prisoners not already infected to take precautionary measures, such as not sharing needles, to prevent infection. There seems to have been little done to discourage prisoners from IV drug use, instead the prison took what they felt was a more practical position in distributing fresh needles throughout the inmates to prevent the spread of the virus. I think they would have benefited from more counseling on the dangers of drug abuse to deter those not already abusing and more treatment options to help those prisoners refrain from continued use.
-Aimee
We believe that it is very important for doctors to be aware of evolution because it affects every area of their practice. Viruses continually mutate and become resistant to the antibiotics that have been used previously. Being educated in the processes of evolution allows doctors to be able to control how much and how often they prescribe medication, particularly antibiotics. Also, as in the case of HIV and AIDS, it affects doctors' ability to find cures to diseases. Being aware of evolution will hopefully help them eventually get ahead of the disease and develop a way to kill it.
- Aimee, Phil, and Jess
Monday, March 17, 2008
Service Learning Questions
HIV Questions – Jess, Aimee, and Phil
Questions 1-5 are based on the BMJ paper entitled “Molecular Investigation into Outbreak of HIV in a Scottish Prison” by Yirrell et al.
Note: Maximum likelihood methods reconstruct phylogenies based on the probability that a specific tree best describes the data.
1) Why is the elevated mutation rate in HIV a positive aspect for this phylogenetic study?
The elevated mutation rate in HIV was a positive aspect for this phylogenetic study because it allowed the researchers to determine the relationship between the men infected with HIV and the likely source of the infection. Each mutated strain is genetically different, so the quick rate of mutation allows for a fairly accurate determination of a source. Because 13 out of 14 men had the same evolved strain, it was possible to link these men to a single source.
2) What do env, pol and gag code for in HIV? Why do they differ in their mutation rates? Why, then, did this study choose to sequence gag and env?
The env gene codes for the viral envelope proteins. The pol gene codes for viral enzymes. The gag gene codes for the capsid and the matrix of the virus. They differ in mutation rates because of what they code for. The env gene mutates rapidly because it codes for a susceptible area of the virus that develps first. The pol gene is relatively protected because it codes for the enzymes inside the viral cell. This study chose to sequence the gag and env genes because it is easier to determine similarities between the gag and env gene mutations than in the pol gene mutations. The pol gene is conserved and therefore can be very similar between a wide variety of HIV strains. The env and gag genes will demonstrate more of the differences between strains than the pol genes. The mutation rates of these genes also directly affects the success of treatment. For example, some treatments have targeted the surface proteins of the virus. This treatment is effective in a strain until its gene that codes for the surface protein mutates and then it will not work. In certain cases, this period of time could be as long as many years of effective treatment to only a few weeks.
3) How can you tell, by looking at the phylogenetic trees, that there is a single source of infection for the Glenochil cohort? Could you accurately describe the HIV genes in these prisoners as orthologous? Why or why not?
All of the cohort branches stem from a single node, which suggests that the Glenochil cohort was infected by a single source. No, the HIV genes in the prisoners could not be accurately identified as orthologous because the phylogeny is the best hypothesis of the connection between the prisoners. It is not the definite answer and the genes are always mutating. So the correlation found between the genes in the prisoners is based on close similarities, not exact replications. Also, they are only testing certain sections of the genes, not the entire virus itself. So the different sections can be the same, but the entire chromosomes could have differences.
4) Why was it important to include unrelated HIV strains in this phylogenetic analysis?
It was important to include unrelated HIV strains in the phylogenetic analysis to demonstrate that the results from the prison were not coincidental. It also shows how the unrelated strains are still related in some basic ways to the strain in the prisoners.
5) This paper is over 10 years old. Have there been other measures taken (besides those listed) to reduce the spread of HIV in prisons? At blood centers like the one your interview described?
Resources:
http://www.stanford.edu/group/nolan/tutorials/ret_6_gpedesc.html
Questions 1-5 are based on the BMJ paper entitled “Molecular Investigation into Outbreak of HIV in a Scottish Prison” by Yirrell et al.
Note: Maximum likelihood methods reconstruct phylogenies based on the probability that a specific tree best describes the data.
1) Why is the elevated mutation rate in HIV a positive aspect for this phylogenetic study?
The elevated mutation rate in HIV was a positive aspect for this phylogenetic study because it allowed the researchers to determine the relationship between the men infected with HIV and the likely source of the infection. Each mutated strain is genetically different, so the quick rate of mutation allows for a fairly accurate determination of a source. Because 13 out of 14 men had the same evolved strain, it was possible to link these men to a single source.
2) What do env, pol and gag code for in HIV? Why do they differ in their mutation rates? Why, then, did this study choose to sequence gag and env?
The env gene codes for the viral envelope proteins. The pol gene codes for viral enzymes. The gag gene codes for the capsid and the matrix of the virus. They differ in mutation rates because of what they code for. The env gene mutates rapidly because it codes for a susceptible area of the virus that develps first. The pol gene is relatively protected because it codes for the enzymes inside the viral cell. This study chose to sequence the gag and env genes because it is easier to determine similarities between the gag and env gene mutations than in the pol gene mutations. The pol gene is conserved and therefore can be very similar between a wide variety of HIV strains. The env and gag genes will demonstrate more of the differences between strains than the pol genes. The mutation rates of these genes also directly affects the success of treatment. For example, some treatments have targeted the surface proteins of the virus. This treatment is effective in a strain until its gene that codes for the surface protein mutates and then it will not work. In certain cases, this period of time could be as long as many years of effective treatment to only a few weeks.
3) How can you tell, by looking at the phylogenetic trees, that there is a single source of infection for the Glenochil cohort? Could you accurately describe the HIV genes in these prisoners as orthologous? Why or why not?
All of the cohort branches stem from a single node, which suggests that the Glenochil cohort was infected by a single source. No, the HIV genes in the prisoners could not be accurately identified as orthologous because the phylogeny is the best hypothesis of the connection between the prisoners. It is not the definite answer and the genes are always mutating. So the correlation found between the genes in the prisoners is based on close similarities, not exact replications. Also, they are only testing certain sections of the genes, not the entire virus itself. So the different sections can be the same, but the entire chromosomes could have differences.
4) Why was it important to include unrelated HIV strains in this phylogenetic analysis?
It was important to include unrelated HIV strains in the phylogenetic analysis to demonstrate that the results from the prison were not coincidental. It also shows how the unrelated strains are still related in some basic ways to the strain in the prisoners.
5) This paper is over 10 years old. Have there been other measures taken (besides those listed) to reduce the spread of HIV in prisons? At blood centers like the one your interview described?
Some preventative measures being taken include HIV/AIDS education for the prisoners, providing them with bleach and clean needles and syringes, giving them access to drug treatment programs, and providing them with condoms. Blood banks often ban gay men from donating blood. They thoroughly screen possible donors and they test the blood they receive before it goes to another individual.
6) On the next page you will find a figure from Science entitled “Application and Accuracy of Molecular Phylogenies” (Hillis et al. 1994; Vol. 264: 671-677). In the study referenced, the authors considered the allegations of 7 patients (A-G) that they had contracted HIV from their dentist. Were their allegations correct? Describe how the authors might have generated this tree.
According to the tree, 5 out of seven of the patients contracted HIV from their dentist. Patients D and F did not contract HIV from the dentist. It seems that the authors generated this tree by starting with the dental clade, which they knew was a monophyletic group, and working their way out to the HIVELI strain. They had performed the tests on the areas of the x and y strains to determine whether or not the patients were connected to the dentist's strain, and this provided them with the information necessary to construct the dental clade. From there, they compared the similarities, or lack of, until they ended up with the HIVELI strain.
Resources:
http://www.stanford.edu/group/nolan/tutorials/ret_6_gpedesc.html
Tuesday, February 26, 2008
HIV Interview
Laboratory manager
Community blood center
02/19/2008
-
1.What inspired you to choose this field?
As a young child I was always curious as to how the human body functioned. Why do we sneeze, what makes our heart beat, things of that nature. As I grew older I found myself still asking questions, only then they became more advanced, how does RNA code for proteins, etc. At the same time I knew that I wanted to do something meaningful for my community. That’s why I chose a position in a not for profit agency.
2. Do you personally have experience with someone afflicted by HIV or AIDS?
Fortunately the Aids epidemic has not affected me personally in that none of my loved ones have fell victim to the disease. But you have to realize that this is a non-discriminatory virus, it can affect anyone, no matter their age, race, social or economic status. That is why we must be vigilant in protecting ourselves. This is a totally preventable disease.
3. What do you look for when testing donors for HIV/Aids?
Well, we have several machines that do the testing here at the community blood center. In our viral testing laboratory, the two major testing formats we utilize are the NAT, nucleic acid testing and the EIA. The NAT testing is highly sensitive and rarely exhibits false readings. This machine analyzes PCR, Polyermase chain reaction sequences in a three step process. Our labs also check for HIV antibodies by using the EIA enzyme immunoassay testing. A reactive test result will provoke further confirmation testing.
4. How often do you see positive test results?
In our lab, true positives are rare. I think the last one was about seven months ago. We get several reactive results a day, but further testing usually results in a negative result.
5. Do you have any accounts of positive results that you would like to tell us about?
Well, about a year age we had a blood drive at a nearby high school. We don’t usually get positive results from teen donors, but in this instance we had a unit test positive from a 14 year old boy. Its like I said earlier, HIV does not discriminate in who it targets, we are all at risk. Especially teenagers, who often have the attitude that nothing can hurt them, and who are often exhibiting the types of risky behavior that make them at risk for the diseases.
6. Why should somebody studying HIV be familiar with evolution?
Well, this is a virus that mutates and evolves with a tremendous frequency. It’s good to understand the proponents of evolution to stay ahead of the virus.
7. How does the nature of the gene inhibit scientists from finding a cure or vaccine?
Well, the HIV virus is constantly changing and mutating. Even within its host, there can be all kinds of variant strands within one infected person on any given day. Its fast and we have to be able to keep up with it if we want to be able to one day eradicate the disease.
8. What is your opinion on using grid computing for HIV research?
I’m not that familiar with grid computing. (We explain what it is) Well that sounds like a great idea. It’s really neat that we can help to find a cure at home. I don’t think I had heard of this before, but it makes a lot of sense.
Community blood center
02/19/2008
-
1.What inspired you to choose this field?
As a young child I was always curious as to how the human body functioned. Why do we sneeze, what makes our heart beat, things of that nature. As I grew older I found myself still asking questions, only then they became more advanced, how does RNA code for proteins, etc. At the same time I knew that I wanted to do something meaningful for my community. That’s why I chose a position in a not for profit agency.
2. Do you personally have experience with someone afflicted by HIV or AIDS?
Fortunately the Aids epidemic has not affected me personally in that none of my loved ones have fell victim to the disease. But you have to realize that this is a non-discriminatory virus, it can affect anyone, no matter their age, race, social or economic status. That is why we must be vigilant in protecting ourselves. This is a totally preventable disease.
3. What do you look for when testing donors for HIV/Aids?
Well, we have several machines that do the testing here at the community blood center. In our viral testing laboratory, the two major testing formats we utilize are the NAT, nucleic acid testing and the EIA. The NAT testing is highly sensitive and rarely exhibits false readings. This machine analyzes PCR, Polyermase chain reaction sequences in a three step process. Our labs also check for HIV antibodies by using the EIA enzyme immunoassay testing. A reactive test result will provoke further confirmation testing.
4. How often do you see positive test results?
In our lab, true positives are rare. I think the last one was about seven months ago. We get several reactive results a day, but further testing usually results in a negative result.
5. Do you have any accounts of positive results that you would like to tell us about?
Well, about a year age we had a blood drive at a nearby high school. We don’t usually get positive results from teen donors, but in this instance we had a unit test positive from a 14 year old boy. Its like I said earlier, HIV does not discriminate in who it targets, we are all at risk. Especially teenagers, who often have the attitude that nothing can hurt them, and who are often exhibiting the types of risky behavior that make them at risk for the diseases.
6. Why should somebody studying HIV be familiar with evolution?
Well, this is a virus that mutates and evolves with a tremendous frequency. It’s good to understand the proponents of evolution to stay ahead of the virus.
7. How does the nature of the gene inhibit scientists from finding a cure or vaccine?
Well, the HIV virus is constantly changing and mutating. Even within its host, there can be all kinds of variant strands within one infected person on any given day. Its fast and we have to be able to keep up with it if we want to be able to one day eradicate the disease.
8. What is your opinion on using grid computing for HIV research?
I’m not that familiar with grid computing. (We explain what it is) Well that sounds like a great idea. It’s really neat that we can help to find a cure at home. I don’t think I had heard of this before, but it makes a lot of sense.
Monday, February 4, 2008
FightAIDS@Home
For this project, we have decided to download the FightAIDS@Home program. This site uses Autodock software to run protein simulations to help find new drugs that could potentially be used to treat AIDS. There is no cure for AIDS at this time, and there are very few decent treatments to help those living with the disease. This is such a simple process that could end up finding some solution, even if it's short-term for the time being. Because the HIV virus constantly mutates, it is extremely difficult to combat it. If we can do our part by simply downloading a program and sharing our results, then think of how much we could do with a couple thousand participants.
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