World Community Grid-Our Contribution and Reflection

Our Contribution

The Grid computing was done via the WorldCommunityGrid and it was run using the BOINC agent on the Macbook Pro of one of the group members.

Results since January 21, 2015 when the project began running

Table 1 shows the totals for our service project. The total time run was a little more than 16 days. The points generated were 53,239 which is based on the computer's computing power (fast or slow) and the specific research project such as "Outsmart Ebola Together" listed in the second table. The computing power is important because it takes into account the fact that the same work unit is compared no matter what the computing power is of the computer so the statistics can be universally use. There is also a safeguard for people trying to tamper with the statistics to make it look like their computer did more work than it actually did.

Table 2 shows the project name and the break down of points generated for that project, the results returned, and the time run. The results returned by our group are determined after the points have been validated. The formula can be found here: http://en.wikipedia.org/wiki/BOINC_Credit_System. The results help in cancer treatment and solar energy research.

Reflection

Our particular topic was on Neurological disorders, but the medical cause is the same: to better people's health!

This service project put in perspective the technological advances that can potentially change the future of disease. With these programs running in the background of more and more computers the possibilities are endless. Grid computing is still rather innovative, but spreading the word starting with Dr. Walker telling us, and our class spreading the word to more and more students, grid computing can take the research world by storm.

This project was one of the most fascinating forms of service that anyone in our group had ever done. To be honest, none of us even knew that the ability to do this existed until we got to this class. The idea that we are able to assist in ongoing research simply by downloading and running a program is incredible. The topic that our group chose to do our project on also turned out to be very fascinating, because not only did it deal with evolutionary biology and psychology, but it also had a strong connection to the medical field which is what many of the people in our group are pursuing.

Schizophrenia Research Article & Questions

This is a link to the research article used in the discussion questions below: http://schizophreniabulletin.oxfordjournals.org/content/34/4/722.full

Questions and Answers:

1. Is schizophrenia a qualitative or quantitative trait?  What is the estimated heritability of this phenotype? (You may have to use other sources to determine this).               Schizophrenia is a quantitative trait meaning that there is a range of differences that exist for the disease among different individuals. Schizophrenia is polygenic or coded for by more than one gene and there is a genetic and environmental factor for the disease. This is why there can sometimes be incomplete penetrance of the disease and why some people have worse schizophrenia than others. One percent of people worldwide are affected by schizophrenia. The heritability of this disorder is around 83% for genetic factors and 17% due to environmental factors found in a research article on Pub Med (http://www.ncbi.nlm.nih.gov/pubmed/9435762). Lastly, men have higher lifetime prevalence than women do for the disorder, which was found in the same article listed in the previous sentence.

2. For the next few questions, I will pose some of the same ones asked and addressed in the paper.  Please provide a summary to answer each:
1. What kind of inheritance explains the observed patterns seen in schizophrenia?   
   There is not one particular gene that is considered to cause schizophrenia itself, but instead many different aspects within genes that contribute to it. Certain neurodevelopmental errors or normal single nucleotide polymorphisms (SNPs), copy number variants (CNVs), or insertions/deletions all aid in morphing certain genes. When expressed separately, many of these changes are not considered bad, some are even beneficial. However, when many of these changed genes are expressed together, that is what greatly increases the cause of disease such as schizophrenia.
               Due to these genes being considered “normal” when expressed separately, they tend to be “below the radar” of selection and are not able to be selected against. It is thought that in certain circumstances or environments, changes in genes like this can be utilized in beneficial ways, adding another reason to why they are not selected against.
2. Why do schizophrenia risk genes persist in evolution?                             Schizophrenia is a quantitative trait, meaning it is polygenic. Each gene by itself has a small effect on the individual, but with the wrong combination of the multiple genes, schizophrenia can manifest. The genes could each have variations within their normal range. These genes still persist in evolution because some of them are either neutral or advantageous to the population. In other words, there is a selection for the advantageous alleles, and there is not selection against the neutral alleles. Chance, assortive mating, and other mechanisms can cause the wrong combination of genes that result in schizophrenia.
3. What are the possible heterozygote advantages associated with schizophrenia?  Do you agree?                                                                                                              Balancing selection could be a possible advantage meaning that the alleles sometimes increase fitness. The idea of increased fitness for schizophrenia is not plausible because in most cultures today it is seen as a dysfunction. The heterozygote advantage tends to favor environmental adaptations (no heritability) or high-frequency alleles (which have been found through psychiatric genetics). The susceptible alleles can give hidden benefits to patients with schizophrenia or to their first-degree relatives that might explain its persistent existence. These benefits include increased intelligence or creativity in relatives and shamanism in patients with schizophrenia. Shamanism is the most ancient form of healing. It involves a change of consciousness to request healing and advice from the spiritual world. Some say that behavioral traits such as paranoia could have been beneficial in environments that were under attack by nonhuman predators, but overall the heterozygote advantage is not very beneficial. Today, schizophrenia is associated with decreased fertility, reduced survival, and reduced attractiveness for mating, lower marriage rates and even reduced fertility once married.

3. If heterosis is acting on the schizophrenia alleles, what might you expect will happen to these alleles over the long term? (Think fitness tables...)                                                    Over the long term if heterosis were to occur, the highest frequency would be the heterozygote, Aa for example. There would be equilibrium of alleles and neither fixation or extinction would occur for either allele. Variation would be maintained at the locus.

4. This paper, and much of evolutionary psychology, is panselectionist or ultradarwinist.  What does that mean?  What other mechanisms of evolution might be at play here? 
   Panselectionism (or ultradarwinism) is the idea that all changes in genes are either beneficial or detrimental to an organism, meaning that there are no neutral changes. Therefore, every trait with a genetic origin must have some adaptive value and has evolved solely through natural selection. This thinking tends to rule out other evolutionary processes such as genetic drift, which is simply the chance changes in the genetic structure of a population, and gene flow, which is the exchange of alleles between or among conspecific populations. In all likelihood, gene flow probably played a major role in this disorder because it is prevalent in many areas of the world. A mechanism that also plays a role is mutation. When coupled with natural selection, mutation can be a potent force of evolution, and may play a role in schizophrenia. Because it is believed that there is an environmental component of the onset of schizophrenia, it can be assumed that there is some sort of epigenetic component of this disorder as well.

Q & A with an expert

An interview was conducted on an expert, Dr. Nicolai Ph.D., in the field of Psychology and neural disorders. She is a Psychology professor at Rockhurst University in Kansas City. Below is the interview with Questions and answers with her permission:

Why did you choose this field?

She found that questions that psychologists asked were the most interesting ones. She enjoys investigating how and why humans think and feel the way they do. This is also one of the most fascinating parts of the field for her. She loves teaching at the college level and talking with intelligent students about psychological topics.

Do you have any accounts of patients with neurological disorders?  Which ones? What can you tell me about these disorders?

She has not been in the clinical world for 20 years now, but she did spend 2.5 years as a clinician while pursuing her doctorate. She worked with patients with psychiatric disorders such as schizophrenia and autism. A question lies in what a neurological disorders actually is. She believes all psychiatric disturbances can be considered a neurological disorder such as Schizophrenia and tic disorders. She is most interested in neurological disorders because they have been maintained in the population, haven’t been selected against, and don’t seem to confer a reproductive advantage. Some disorders are later onset, after child-bearing years, so they don’t detract from reproductive fitness.

Why do you think a psychologist studying neurological disorders should know about evolution?

She believes that evolution is important to find out why these disorders have been maintained in the population. She stated that, “Evolutionary history is the story of the ways in which our genetic makeup as a species has responded to and changed by the environments. Psychologists are interested in environments in which humans live and interact and how those environments have an impact on thoughts and behavior. Our genetic makeup influences how we interact with environment. For human, social interaction is key to the environment. It is most important to survival. Social milieu is unique to humans. Evolution of the human brain both influences and is influenced by the fact that humans are a social species.”

How important is the search for a cure or medications to help cope with the disorders?

Dr. Nicolai finds it very important that mental disorders are number 3 or 4 on the list of disabilities that are costly in building economies in terms of health care and inability to work. In terms of human misery and suffering, it is extremely important to try to help prevent and treat these disorders. Dr. Nicolai believes that if a person is more productive and has more energy, he or she can do positive things for the social world.

Have you heard of grid computing? What do you think about using grid computing in the search for a cure?

Dr. Nicolai knows that grid computing is a relatively new method that allows researchers to compile genetic DNA such as brain imaging data to look at huge samples of people with different stages of disorders to try and identify areas of the brain affected earliest. The goal is to identify markers to help find a cure. MRI and fMRI data analysis takes time and needs a lot of space. When processing large amounts of data, it is not always representative based on available resources.

Where does the root of the problem for most neurological disorders exist? 

She believes the problem is in epigenetic regulation in a combination of genes that predispose individuals in combination with environmental interaction. This combination could manifest a phenotypic disorder (diagnosable condition). This is true for not just neurological disorders. Our genes direct how our hardware is built.

Are there any new means for neurological disorder prevention? 

She believes there is and that it lies in epigenetics, which is the way in which the environment across generations can have impact on genetic transmission. If you change the environment and change people’s behavior, one might be able to prevent the disorder. Good access to healthcare, prenatal especially, educating people early on to take care of their nervous systems by reducing stress, naps/rest and strengthening social networks can help their brain’s thrive in social environments. Throughout evolutionary history the focus has been on building the social brain. Good nutrition, exercise, sleep and peace are highly recommended. If a child grows up and sees carnage every day, it affects the way he or she processes information. It can trigger aggression in the presence of bombs going off outside their home. This can spike adulthood violence.

What misconceptions exist about neurological disorders? Can these patients be treated/live healthy normal lives?

She believes that a misconception is that our genetic make up is static and unchanging. It is alive throughout our life and nervous systems change as time goes on. Critical periods exist between prenatal/infancy, and rewiring and trimming occurs during adolescence. Schizophrenia is genetically predisposed, but the wiring that occurs prenatally is affected by genetic and environmental factors. Prenatal exposure to viruses in the 2^nd trimester can be linked to schizophrenia. Symptoms don’t emerge until late adolescence or early adulthood. This is because the functionality doesn’t manifest until adolescence. Schizophrenia is a spectrum disorder, which means on a continuum (Asperger’s to debilitating autism). Schizophrenia is a group of disorders that shares features but also share differences. Hallucinating can begin at age 6, but for others it does not emerge until the early thirties. Some people recover completely, but others need institutionalization for rest of their lives. Schizophrenia has a relatively stable prevalence around the world (about 1-1.5% around the world regardless of the culture). This suggests that when the split happened, if schizophrenia was not part of our species specific genetic makeup then we would see differences before people left the land to migrate. There is a relationship between evolution and characteristics that make up a species and that relationship is in genes that predispose. There is some reproductive advantage because those genes with the disorder actually do something else positive for the human.

What is there still to be discovered about neurological disorders?

“Schizophrenia patients don’t have that many kids because they are not reproductively fit. Why has this been maintained in the species? Because human brain development in evolutionary history, development of language and specialization of left hemisphere for language function. When schizophrenia starts to emerge as a dysfunctional disorder is important. Language function is disrupted in schizophrenia patients. There is a disruption in the connections pointing to when the manifestation became a problem. Relatives of people with schizophrenia have fewer children, but if there is positive reproductive success, why does this happen? This is not the case for mood disorders because relatives have more children.”

Side notes for Dr. Nicolai

“Seventy percent of Asians have genes that predispose them to anxiety. Their social structure was probably built to eliminate anxiousness of the culture. An example would be not looking people in eye and talking farther away from each other in public settings. This is why people act differently in China. They are less likely to push the prevalent predisposition to anxiety present in that culture.”

“In the past, when schizophrenia patients heard voices they were thought to have a connection to the spirit world…we don’t see that today. Technology has put behaviors in a different light. Back then, cultures understood schizophrenia as something way different than today. Schizophrenia patients were deemed reproductively fit because the spouse wanted the children to have a connection to the spiritual world.”

Group Reflection

1. Describe your feelings about or response to the interview.

We thought that Dr. Nicolai gave very informative and relative answers to our questions. It was interesting to hear a professional’s remarks, knowledge, and opinions on the matter. Dr. Nicolai put into perspective how the knowledge we are gaining in class applies to the world outside of college. Learning specifically about schizophrenia and how it relates to evolution was a great way to gain a better understanding of not only the disease, but also how the amount of knowledge a society has about a condition can affect its prevalence in their culture.

2. What changes occurred for you as a result of your interview?

The changes that occurred for us as a result of the interview included a different outlook on how evolution can affect the social atmosphere of society. It opened our minds to how important it actually can be to have a solid understanding of evolution. It also showed us that just because something is heritable does not mean that environmental factors cannot also be affecting it. Epigenetics is also important to understand to know whether the factors of a disease is actually evolving or not.

3. Did anything about the interview disturb you?

Nothing was really that disturbing in regards to the interview. However, we found it really interesting how neural disorders can influence whole cultures. When Dr. Nicolai informed us about the genetic predisposition to anxiety in Asians, it gave us a whole new perspective on neural disorders and how it can evolve in a way that impacts social behaviors. We never had thought about it in this way before.

4. Describe the connections you found between the interview and your research & classwork.

Dr. Nicolai’s answers had many connections to our research and in class. For example, Dr. Nicolai shared that prenatal exposure to viruses in the 2^nd trimester can be linked to schizophrenia, and in our research, we found that influenza during pregnancy may be associated with the development of schizophrenia. This was very closely related. Additionally, Dr Nicolai discussed evolution, which is related to our classwork. She gave the example of how schizophrenia was selected for in the past but selected against as we gained a better understanding of the disorder. Using schizophrenia as an example, the postulates of natural selection can be applied directly to this neurological disorder: There is variation in humans for schizophrenia, both in the disease and having the disease. At least some of these variations are heritable. Not everyone in each generation can survive. Finally, natural selection operates on the population. The survival and reproduction are not random; as we gained more knowledge of schizophrenia, the reproduction rate decreased. The individuals with the more favorable adaption of not having schizophrenia tend to out reproduce the individuals with schizophrenia. Overall, the connections in the interview helped us have a better understanding of our classwork and our research.

Grid Computing and Neural Disorders

Grid-Computing Project
Within our evolution class, we are doing a service learning project through the use of grid-computing. We are making an effort to understand neural disorders through research, through insightful questions, and by conducting an interview of an expert in the neurological field.

About Grid Computing 
Grid computing is a cheap and simple way to use thousands of computers to work together to produce molecular simulations for biomedical research in the areas of HIV or cancer, to name a few (1). Data and resources from each computer are combined to produce a supercomputer. If the resources are shared across many computers, the job can be done more efficiently (2).

Normally a computer has a maximum limit for how much of its resources it can use, but within grid computing, it can share resources from other participating computers (2).  To achieve this sharing, there needs to be one computer (often a server) that handles all the administrative duties, a network of computers running the grid computing software, and software called middleware—which allows for communication among the computers that are part of the grid computing system.  Computers within the supercomputer have to have interoperability as well. This allows for computers with different networks, such as PCs and Macs, to continue to operate successfully together even though different operating systems are being used (2). Even if interoperability exists, without a service, computers cannot interact with each other over a shared network (2).

               

1. http://searchdatacenter.techtarget.com/definition/grid-computing

2. http://computer.howstuffworks.com/grid-computing1.htm

Grid Computing Diagram

Our actual grid computing screen when mapping cancer marker work is being run

About Neural Disorders

Neural disorders (also called neurological disorders) are classified as any disorder of the nervous system. This can include abnormalities in the brain, spinal cord, or other nerves in the body.

Examples of Neural Disorders

Alzheimer’s Disease: 

            Alzheimer’s disease is a form of dementia that involves memory loss, thinking skills, and behavior. It progressively worsens over time and currently has no cure. “Scientists believe Alzheimer's disease prevents parts of a cell's factory from running well. They are not sure where the trouble starts. But just like a real factory, backups and breakdowns in one system cause problems in other areas. As damage spreads, cells lose their ability to do their jobs and, eventually die, causing irreversible changes in the brain.” (3) This disease can be devastating to those diagnosed with it, as well as close friends and family. Those affected are generally older people, aged 65 and up. However, early onset Alzheimer’s can be diagnosed as early as 40s or 50s. 

3. http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp

Huntington’s Disease:

            Huntington’s Disease is a hereditary disease that causes the progressive degeneration of nerve cells in the brain. This can interfere with a person’s ability to walk, talk, or think. Such symptoms as involuntary movements of the head, trunk, and limbs occur, as well as loss of concentration and memory. One’s capability of walking, talking, or even swallowing will diminish over time and eventually the person will lose total ability to care for his or her own self. Fatalities from the disease usually occur from complications like choking, infection, or heart failure. It’s devastating to those diagnosed, as well as those close to them because there is currently no cure and only one treatment for a symptom of the disease. 

 4. http://www.hdsa.org/about/our-mission/what-is-hd.html

Schizencephaly:

            Schizencephaly is an extremely rare birth defect that involves slits or clefts in the hemispheres of the brain. The slits can be on one (unilateral) or both (bilateral) sides. Unilateral clefts often result in one side of the body being paralyzed but the individual will still have average intelligence, while bilateral individuals often have difficulty with delays in speech and language skills, as well as with brain to spinal cord communication. Most experience seizures, as well as abnormally small heads, mental retardation, paralysis, or poor muscle tone. There is currently no cure for this disease but treatment includes physical therapy and drugs to help prevent seizures.

5. http://www.ninds.nih.gov/disorders/schizencephaly/schizencephaly.htm

Interesting Facts

Some interesting facts about the brain, including facts about neurological disorders can be found at http://facts.randomhistory.com/human-brain-Facts.html. Several are listed below:

1. "A mother’s illness may severely affect fetal brain cells; studies suggest that influenza or malnutrition during pregnancy may be associated with the development of schizophrenia. Damage to developing cells may also occur from maternal smoking and drinking, prenatal exposure to chemicals, or excess heat.

1. Scientists claim that the most complicated and mysterious thing in the universe is the human brain. Scientists know more about stars exploding billions of light years away than they know about the brain.
2. Researchers at Baylor University have found that children deprived of touch, play, and interaction with others have brains 20-30% smaller than normal for their age. Child abuse can inhibit brain development in a child and permanently negatively affect brain development.
3. While general vocabulary and knowledge about the world often stays sharp through one’s 70s, memory for names begins to decline as early as age 35. The ability to recognize faces and find one’s car has already begun to wane by the 20s. However, research shows that brain stimulation not only stops cells from shrinking, but it can also increase brain cell and dendrite branching.
4. ^{Neurological complications occur in at least 70% of patients who are diagnosed with AIDS. At autopsy, 80-90% have neurological abnormalities.}
5. Humans have more brain cells at the age of two than at any other time of their lives.
6. Swiss researchers have discovered that certain types of brain lesions lead average eaters to become addicted to thinking about and eating gourmet foods.
7. Research shows that those who are clinically depressed or suicidal have abnormal levels of the brain chemicals serotonin and norepinephrine. Flaws in the brain’s serotonin levels have been linked to violent suicide attempts and aggression.
8. When a person diets or deprives himself of food, the neurons in the brain that induce hunger start eating themselves. This “cannibalism” sparks a hunger signal to prompt eating.
9. Scientists note that children with autism have normal-sized brains at birth, but at some point—usually at the end of the first year of life—a part of the brain called the amygdala grows on average 13% larger than in non-autistic children."

Another interesting fact is that dogs can have neural disorders as well. For example, the King Charles Cavalier Spaniel can develop syringomyelia. More information about this disorder can be found in a video at: https://www.youtube.com/watch?v=tp_XFlNdHzY