Using Short Hairpin RNA (shRNA) in Order to Combat the Negative Effects of Autism Spectrum Disorder

By: Ty Krug, Trever Barnes, Chris Spates, and Garrett Briggs

Autism Spectrum Disorder (ASD) is known as a wide-spectrum developmental disorder that causes problems with communication, social, verbal, and motor skills. It is said to be found in 1 in every 68 children, and no two people will have the same effects from autism, as the symptoms vary from person to person (Wright 2015). At this point in time there are no direct causes for autism though many seem to believe it can be caused by genetic, epigenetic, and environmental factors. It is known however, that people with autism have abnormal brain structure and functionality which usually begins before the age of 3. Although it cannot be determined, researchers have narrowed down a possible cause of autism residing in the cortex of the human brain.  ASD is classified as a neurodevelopmental disorder, defined by impairments in social interaction, deficits in verbal and nonverbal communication, and the display of stereotyped and repetitive behaviors (Aigner et al. 2013).  During normal brain development, a burst of synapse formation occurs in infancy. This is particularly pronounced in the cortex, which is central to thought and processing information from the senses.  As an individual gets older, a process in the brain called pruning occurs, where many of the brain synapses are trimmed, leaving only the major synaptic pathways.  Through research, it can be determined that patients with ASD did not go through the pruning process that normal infants did (Wright 2015).

There are many human neurodevelopmental toxicants that have health impacts that are supported through numerous research. These toxins/metals include Mercury, Lead, Arsenic, Fluoride, and Manganese (Kalkbrenner et al. 2014). All of these toxicants can lead to negative effects on the developing nervous system which can result in a loss of IQ points and behavioral problems. Research shows that all of these toxicants can have a negative impact on the human neurological system even at typical exposure levels (Talbott et al. 2015). This can be dangerous for mothers who are pregnant with a baby in the critical developmental stages, and could possibly have a direct affect on the outcome of autism. What is challenging about these toxins is the way people can become exposed to them. Exposure can be from ingestion or even inhalation and overtime can cause effects that last a lifetime. Another form of toxin that has been shown to directly affect autism in the prenatal stages is pesticides(Shelton et al. 2012). Pesticides can lead to neurotoxicity, and unfortunately have been detected in over 97% of biological samples (Kalkbrenner et al. 2014). Pesticides such as organophosphates and pyrethroids have the ability to pass through the placenta and then continue on through the blood-brain barrier which can cause neurodevelopmental problems in a fetus or infant. Infants exposed to these pesticides are 60% more likely to end up with a neurodevelopmental disorder such as ASD. Though these toxins and pesticides discussed above are vastly different they ultimately are shown to have an effect on the prenatal fetus leading to autism (Shelton et al. 2012). It is hard to say specifically how much these factors directly impact the outcome of autism due to the challenge in measuring exposure concentrations and sample sizes, however, it is proven that prenatal exposure to the chemicals thalidomide, folic acid, and valproic acid due lead to an increased risk of autism (Tijdschr 2014).

The cellular phenotype for ASD contains I characteristics which are not severe enough to present definite or readily observable conditions. The combination of this broad variation of phenotypes and a high rate of agreement in identical twins suggests a large number of genetic and environmental biasing factors (Belmonte 2004). According to some estimates, mutations in as many as 1,000 genes could play a role in the development of these disorders (Farley 2013).  

The phenotypes of autism are the primary indicator of the disorder due to the fact that there is not enough known about the genetic factors to diagnose Autism based solely off of DNA.  The “spectrum” of ASD refers to the phenotypic spectrum characterized by behavior studies.  A compilation of data conducted by Biomedical ontologies recognize 283 concepts of autism coming off of the the main three branches (Mccray et al. 2014). The figure to the left illustrates some of the initial branchings that continue to branch until they reach very specific concepts.  Example concepts include “Emotional regulation and control- directing and governing one’s own emotions” and “Self injurious behavior-  behaviors in which a person intentionally hurt or harm themselves.”  (Mccray et al. 2014)  There is a standard test to measure the social and communication deficits in ASD, called the Autism Diagnostic Observation Schedule-Generic (ADOS-G) (Lord et al. 2000).

Many genes can contribute to the phenotypes shown above; for example, in one study, scientists identified 107 genes that show a strong correlation with autism.  Most of the genes encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways.  It is a loss of function in these genes that seems to be related to a person having ASD (De Rubeis et al. 2014).  The chromatin remodelling pathways deal with regulation of gene expression (Allison and Milner 2004).  A malfunction in one of these genes could have an affect on many genes because the protein from this gene is used to regulate the expression of many genes.  According to Dr. Brose,  the synaptic-forming proteins are called neuroligins, and they are responsible for the maturation of the synapses in the brain.   Without neuroligins, the synapses do not have enough receptor proteins, and therefore  have a reduced ability to pass signals (Brose 2006).  The proteins involved with autism are the transcriptional regulation proteins.  A loss of function in these proteins would result in wide-scale mutations in DNA that would not necessarily be related to one gene.

Many genes are linked to ASD, and scientists have yet to discover them all and create a comprehensive list.  It is for this reason that they are often classified into general types by the proteins that they code for, as they are in the previous paragraph.  That being said, this section will explore a few specific genes that have shown to be related to ASD, and their direct effects on the body.  One study shows the relationship between the oxytocin receptor gene (OXTR) and specific phenotypes of ASD: social impairment and repetitive behavior (Yu et al. 2015).  Two single nucleotide polymorphisms (SNP) in the 3’UTR region of the OXTR gene are what causes these two common phenotypes of ASD (Harrison et al. 2015).   Another example of a specific gene  that is strongly related to ASD is the gamma aminobutyric acid receptor (GABA) subunit genes (Ma et al. 2014).  This gene creates the receptor subunit, which controls synaptic inhibition in adults.  A mutated GABA gene does not allow for inhibition of excitement-inducing chemical signals, which contributes to the phenotype of inattention and restlessness in autistic people (Bowery and Smart 2006).

Epigenetics have also been proven to play a large role in autism. However, like other factors, epigenetics can not be summed up in one distinct cause and effect. It can affect the genetic expression in several different ways. Two prevalent ways that epigenetic changes in individuals with autism differ with normal people are through autosomal monoallelic expression and X-inactivation (Ben-David et al. 2014). In an experiment conducted in 2014 by several doctors at the Hebrew University of Jerusalem they explored the role that epigenetic factors played in autism (Ben-David et al. 2014). What they discovered was that individuals with autism rarely express the same genetic mutations (Wong et al. 2013). They also were able to determine that in most cases the regulation of epigenetic factors which restrict genetic expression were not present, in one case allowing up to 10 times more monoallelic expression than in the average human being (Ben-David et al. 2014). This often resulted in a larger brain mass and several different levels of mental retardation ranging from mild to severe (Wong et al. 2013). X-inactivation is also affected in individuals with autism. It has been demonstrated that several epigenetic factors do play some effect on the outcome of an individual’s autistic traits. However with current technology there is no real way to test all the different epigenetic factors that play a role in autism are and how significant they are at this current time (Ben-David et al. 2014).  Because Autism Spectrum Disorder (ASD) has such a vast range of causative factors; with epigenetic, genetic, and environmental influences, it can most clearly be explained by starting with the more clearly defined phenotype, and ending with the almost limitless possible causative factors.  

According to one study, the autism spectrum encompasses 283 distinct phenotypic components, and a person suffering from the disorder will usually display several of them (McCray et al. 2014).  They can be generalized into these categories: impairments in reciprocal social interaction, communication deficits, and restricted patterns of behavior; all of which are neurobiological symptoms that can be related to synaptic issues  (Yu et al. 2015).  

There are many genes which could contribute to the cause of ASD collectively, as they are involved with neurological synapses and leukocyte production.  Genes such as NLGN3 and NLGN4 contribute to the formation of the central nervous system, as well as the surface protein to neural cells (Jamain et. al.).  In regards to leukocyte production with Autism, genes such as HLADR4 and HLADR14, both located on chromosome 6, regulate for a non specific and uncharacterized brain protein which is responsible for the production of autoantibodies (Torres et al. 2012).  Although these specific genes show evidence to being causative to ASD, researchers have narrowed down the underlying cause residing in the synaptic pathways of the brain (Auerbach et al. 2011).

When attempting to narrow down which genes are causative to ASD, we identified one gene in particular, Cx3CR1, which had a significant effect on the brain and their synaptic pathways.  Autism Spectrum Disorder is caused by an excess of brain synapses, most of which are weak and immature (Farley 2013).  In a normal functioning human brain, a child going through infancy expresses this Cx3CR1 gene which is located on chromosome 3, and produces a protein called fractalkine.  Fractalkine, in infants, prunes out the weak and immature brain synapses, leaving strong single firing pathways for brain synapses.  In a child with Autism Spectrum Disorder, a developing child goes through a mutation called a microdeletion, which is an unexpected partial cutting of a chromosome.  In this microdeletion, the Cx3CR1 gene is cut unexpectedly from the child, leading to a microglia deficiency and no production of the fractalkine protein (Bifone et. al 2014).  In absence of the fractalkine receptor protein,  weak and immature synapses are not pruned throughout the autophagic pathways as microglia are not signalled to prune, leading to excess firing of weak synapses and inhibited growth of the more developed and stronger ones (Zhan et al. 2014).  

In a study performed on mice, results showed that autistic-like synaptic deficiencies were directly correlated to levels of mTOR in synaptic pathways, resulting in impaired autophagy.  These results displayed excess mTOR inhibiting synaptic pruning within mice in their first week of development ( Tang et. al. 2014).  Although research was inconclusive in connecting mTOR with the fractalkine protein, their correlation cannot be ignored.  Because excess mTOR results in the blocking of synaptic pruning, a potential treatment would be to inhibit mTOR.  Studies have been done previously to inhibit mTOR production, and mice were injected with the mTOR inhibitor rapamycin.  Following the injection, mice had increased brain function as learning and memory impairments were reversed (Ehninger and Alcino 2011).  This study draws results directed towards the treatment of Autism, as it shows brain deficiencies due to stimulation of weak and immature pathways that were not pruned can be reversed and no irreversible structural damage was caused due to the defect.

In order to correct the symptoms caused by autism it is necessary to combat the loss of fractalkine production which results from the mutation of the Cx3CR1 gene (Bifone et. al, 2014). The loss of the fractalkine protein would result in an excess of synapses because the normal pruning would not occur; meaning that unnecessary synapses would remain, and there would be overstimulation of neuronal signalling. We propose that the solution to the problem is to implant a SRPX2 gene inhibitor as they did in the study conducted by (Sia et al 2013). The inhibitor is a short hair pinned RNA (shRNA).  The SRPX2 gene is responsible for the formation of new synapses.  In their study, they showed that the “SRPX2 blocking compound”, when injected into the mice, resulted in less synaptogenesis.  Humans have the same gene (Sia et al. 2013).  Our treatment would involve injecting the SRPX2 blocking compound into someone with ASD postnatally.  Treatment would occur postnatal because basic synaptic formation would have to take place. However, when symptoms of autism begin to appear, it would be beneficial to reduce the number of synapses being formed to lower it to a normal level. Immediately following birth treatment would begin by way of inserting the blocking compound into the baby in order to regulate the proper amount of synapse activity needed for normal brain function.  Doing so would solve the underlying problem of ASD; too much synaptic activity.  

In order to reduce the phenotypic symptoms of ASD the child would be infected with a virus containing shRNA which would directly limit the amount of synapses. However, the gene could not be fully repressed therefore the shRNA levels inserted into the child would have to be regulated. If the levels are too low then no change will occur yet if the levels are too high it could become toxic within the child. Fortunately, in their study it was proven that you can regulate the proper amount of shRNA depending on what level of expression would result in a more healthy phenotype.

Overall, it is important to point out that Autism is still being researched heavily today. It is unclear what causes each individual mutation that leads to autism, however, genetic research points toward the suppression of brain synapses will minimize the phenotypic problems seen in autism patients. Researchers have displayed positive results from inserting a drug, rapamycin, into the brain of mice which enables a gene to suppress excess mTOR, as it has improved brain function and memory retention, however they have still yet to find a connection to mTOR and excess synapses in autism.  Because there are hundreds of different genes which are causes for ASD, there is no defined pathway which the genetic disorder follows on a case by case basis.  Because of this, not all cases of Autism are directly affected by excess brain synapses.We propose that, in order to show the symptoms of ASD, one must be influenced in each of the following areas: epigenetic, genetic, and environmental.  More specifically we believe that pesticides and pharmaceuticals play the main role in linking the epigenetic, genetic, and environmental factors together that directly relate to prenatal effects causing autism.  However, the proposed treatment plan can improve upon a patient’s symptoms, and could potentially allow them to enjoy a more normal brain function.

WORKS CITED

Aigner, S., Heckel, T., Zhang, J.D., Andreae, L.C., Jagasia, R. 2014. Human pluripotent stemcell models of autism spectrum disorder: emerging frontiers, opportunities, and challenges towards neuronal networks in a dish.  Psychopharmacology (Berl). 2014; 231(6): 1089–1104.

Allison S.J. and Milner J. 2004. Remodelling chromatin on a global scale: A novel protective function of p53. Carcinogenesis 25(9):1551-7.

Auerbach B.D., Osterweil E. K., Bear M. F. (2011). Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480, 63–68 10.1038/nature10658

Belmonte M.K. Autism and abnormal development of brain connectivity. Journal of Neuroscience. 2004 Oct 20;24(42):9228-31

Ben-David E, Shohat S, Shifman S, et al. 2014. Allelic expression analysis in the brain suggests a role for heterogeneous insults affecting epigenetic processes in autism spectrum disorders. Hum. Mol. Genet. 23 (15) Pp. 4111-4124

Bifone A., Paolicelli R.C., Sforazzini F., Weinhard L., Bolasco G., Pagani F,Vyssotski A.L., Gozzi A., Ragozzino D. & Gross C.T. 2014. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nature Neuroscience 400–406

Bowery NG and Smart TG. 2006. GABA and glycine as neurotransmitters: A brief history. Br J Pharmacol 147:S109-19.

Brose N. 2006. Neurology; scientists have decoded the details of a genetic defect that causes autism in humans.  Genomics & Genetics Weekly :203.

De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, et al. 2014. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515(7526):209-15.

Ehninger D., Alcino J.S., “Rapamycin for treating Tuberous Sclerosis and Autism Spectrum Disorders,” Trends Mol Med. 2011 Feb; 17(2): 78–87.

Farley P. 2013.  Scientists Pinpoint Cell Type and Brain Region Affected by Gene Mutations in Autism. Am J Hum Genet 77(3):377-88.

Harrison AJ, Gamsiz ED, Berkowitz IC, Nagpal S, Jerskey BA. 2015. Genetic variation in the oxytocin receptor gene is associated with a social phenotype in autism spectrum disorders. American Journal of Medical Genetics.Part B, Neuropsychiatric Genetics 168(8):720-9.

Jamain S., Quach H., Betancur C., Råstam M., Colineaux C., Gillberg I.C., Soderstrom H., Giros B., Leboyer M., Gillberg C., & Bourgeron T. 2003. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nature Genetics  34, 27 – 29

Kalkbrenner, Amy E., Rebecca J. Schmidt, and Annie C. Penlesky. “Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence.” Current Problems in Pediatric and Adolescent Health Care 44.10 (2014): 277-318.

Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, Pickles A, Rutter M. The Autism Diagnostic Observation Schedule-Generic: a standard measure of social and communication deficits associated with the spectrum of autism.  J Autism Dev Disord. 2000;30(3):205-223.

Ma DQ, Whitehead PL, Menold MM, Martin ER, al e. 2014. Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism. Am J Hum Genet 77(3):377-88.

Mccray AT, Trevvett P, Frost HR. 2014. Modeling the autism spectrum disorder phenotype. Neuroinformatics 12(2):291-305.

Shelton, J.F., Picciotto, I.H., Pessah, I.N. “Tipping the Balance of Autism Risk: Potential Mechanisms Linking Pesticides and Autism.”  Environ Health Perspect 120(7). July 2012

Sia GM, Clem RL, Huganir RL. 2013. The human language-associated gene SRPX2 regulates synapse formation and vocalization in mice. Science 342(6161):987-91.

Talbott, E.O., Marshall, L.P., Rager, J.R., Arena, V.C., Sharma, R.K., Stacy, S.L. 2015. Air toxins and the risk of autism spectrum disorder: the results of a population based case-control study in southwestern Pennsylvania. Environ Health, 14.1:80-85.

Tang G., et. al., “Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits,” Erratum in Neuron. 2014 Sep 17;83(6):1482.

Tijdschr, D. “The Influence of Genes and Environment on the Development of Autism Spectrum Disorders.” Genes, Environment and Autism Spectrum Disorders (2014)

Torres A.R., Westover J.B., Rosenspire A.J., “HLA Immune Function Genes in Autism,”Autism Research and Treatment, vol. 2012, Article ID 959073, 13 pages, 2012.

Wong C.C.Y. ,  Meaburn E.L., Ronald A, Price TS, Jeffries A, Schalkwyk LC, Plomin R and Mill J. et al. 2013. Methylomic analysis of monozygotic twins discordant for autism  spectrum disorder and related behavioural traits. Molecular Psychiatry (2014) 19, 495–503

Wright, Bob. “Autism Speaks.” Autism Speaks, Home Page. N.p., n.d. Web. 9 Dec. 2015.

Yu L, Wu Y, Wu B. 2015. Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of autism. Science China.Life Sciences 58(10):958-67.

Zhan Y. et al., “Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior,” Nature Neuroscience, doi.org:10.1038/nn.3641, 2014.

Photograph:

Mccray AT, Trevvett P, Frost HR. 2014. Modeling the autism spectrum disorder phenotype. Neuroinformatics 12(2):295

Christopher Spates

COL. Ball

ERH 421WX

4/30/15

421WX-Leaves of Grass

            This course Leaves of Grass has been very intriguing. It offered many challenges yet offered me as a student the opportunity to learn about 19^th century American culture. From the very beginning of the class I was clueless about Walt Whitman, and finishing this course I feel I have learned a lot not only about his life but the meaning behind his poetry.  Whitman’s poetry discusses topics such as war, nature, jobs and politics which all tie together to describe America separating from England, the civil war, and even the daily struggles of poverty. Our class discussions, paper’s written and also the virtual scrapbook allowed me to gain insight into the motives for Walt Whitman’s poetry, and how it directly correlates to the true American culture that we still live in today.

One of the things Whitman is known most for is his organic form of poetry. This alone represents the American culture during the 19^th century. Whitman grew up in tough times when America was breaking away from England and was trying to establish itself. With that being something he experienced I believe his free verse of poetry represents freedom. It shows that Whitman was still able to describe his feelings and ideas without typical rhythm and meter. He was able to tell stories about nature, war, jobs, and politics while still focusing it on his idea for everything being unified under equality. More specifically in writing my research paper I learned that Whitman struggled keeping a job. He went through seven different newspaper jobs in four years. Also, throughout Whitman’s life he struggled to have success with his poetry. Having to publish his own Leaves of Grass is an example of the tough times faced by the lower middle class in America during this time.

A big component in Whitman’s poetry that we discussed is nature.  Our assignment in which we had to read Leaves of Grass out in the open air gave me the chance to relate more directly to what he spoke of. Whitman speaks of America and the nature of the 19^th century yet his imagery mirrors the present, and in a sense makes the future seem immediate.  Within my writing of my findings from reading Leaves of Grass outside one thing that stuck out to me is when Whitman says “…and the numberless unknown heroes equal to the greatest heroes known.” This to me represents American culture throughout history and more specifically during the civil war. There are heroes made every day, however, they may not be the famous Robert E. Lee’s or Stonewall Jackson’s of the 19^th century. Whitman made it very clear in “I hear AMERICA singing” that he felt every person had an importance to America regardless of their job. He speaks of the carpenter and the mason and how individually they create a unified country.  Personally, I believe Whitman offered the idea of unity which is one of the strongest characteristics of America even though in the 19^th century he saw the civil war and slavery right in front of his eyes.

The single most important part about this class for me was our in class discussions. It allowed me to broaden my view on what Whitman was saying in his poetry. Being able to hear many other classmates’ ideas of what was said in a specific poem allowed me to put our thoughts together which gave me a better understanding for what Whitman meant. Also, by interacting together and hearing different people read poems would give a different tone depending on the voice. Though reading in class really helped me gain a better understanding one thing I struggled with at times was Whitman’s vocabulary. Vary rarely throughout one of his poems did I not have to look up a word that held a significant meaning behind a sentence or phrase. Though this was a challenge, I believe it has allowed me to broaden my vocabulary and it also gives me more respect toward Whitman’s writing ability.

The main requirement for these civilization and culture courses is the ePortfolio. For me, it was interesting making my virtual scrapbook for the ePortfolio because you are trying to portray information on historical events through a much more advanced piece of technology. This alone shows the advances in the American culture overtime. We are becoming so advanced that we are able to use technology to better understand and describe historical people or events. The ePortfolio is becoming a tool for people to show their work across many different communities whether it be your group of friends, for business, or even for you to get your name out there publicly. I believe it is a great tool that many of people are beginning to take advantage of.

Overall, this class has been interesting, enjoyable, and has allowed me to expand my knowledge about America’s greatest poet Walt Whitman. By doing the papers and virtual scrapbook I was able to further our in class discussions and learn many things about the 19^th century specifically relating to Whitman’s Leaves of Grass. Walt Whitman was so unique in his ability to make his poetry relate to not only the 19^th century, but also to the present. His imagination allowed him to turn so many stories into lessons learned through nature in his poetry.  Finally, throughout the course Leaves of Grass I was able to us my knowledge of the 19^th century to relate it to Walt Whitman’s poetry, and in the process I was able to learn how unique his poetry is and how well he connected with the American culture from the 19^th century and in many cases still today.

Walt Whitman’s Legacy

https://www.youtube.com/watch?v=MWvLspIM_A8

Christopher Spates

COL. BALL

ERH 421WX

April 21^st, 2015

Virtual Scrapbook Narrative

As Walt Whitman once said “Afoot and light-hearted I take to the open road, Healthy, free, the world before me, The long brown path before me leading wherever I choose.” Walt Whitman is known as one of America’s greatest poets. He song of life while also singing of death. For if one is to examine life carefully then death should most certainly be included because to respect life is of the highest ethical order. Walt Whitman died on March 26, 1892 at the age of 72 which is believed to be due to tuberculosis. However, Whitman suffered several strokes and was partially paralyzed, but even though his body was restricted his mind was not.  Right up until his death he continued to work on Leaves of Grass, and had gone through seven editions totaling some 300 poems. He believed that “the proof of a poet is that his country absorbs him as affectionately as he absorbed it.” Though during Whitman’s lifetime he didn’t receive the recognition he strived for he has certainly gained recognition over time.

Due to Whitman’s great work his life has been celebrated with many things named after him. Whitman’s home in Camden, New Jersey is now turned into a museum and is visited from people around the world to experience the last worldly surroundings of America’s great poet of democracy. Also, the Walt Whitman Mall located in Huntington Station, New York which is in close proximity to his birth place, a national historic site on Walt Whitman Road. Another thing named after him is the Walt Whitman bridge. The bridge is a major land mark located along the Delaware River stretching from south Philadelphia to Gloucester City, New Jersey. The bridge was opened in 1957 and is still used heavily today. Also, there is a high school named after Whitman in Montgomery County Maryland right outside of Washington DC.

Walt Whitman is buried in Harleigh Cemetery in Camden, NJ.  Whitman’s tomb cost him around $4,000 and the land was gifted to him by the Harleigh Cemetery Association. Whitman drew up the plans for his tomb before he began the contruction. With it he wanted an iron gate and a large bronze lock, inspired by an etching called “Death’s Door” by William Blake. The tombs ceiling is over a foot deep and was made with extremely heavy blocks. Whitman was so proud of his tomb that he would send pictures to his friends showing them where he would be buried.

“Love the earth and the sun and animals, despise riches, give alms to everyone that ask, stand up for the stupid and crazy, devote your income and labor to others…and your very flesh shall be a great poem.” Walt Whitman’s work has influenced many people like, Puable Neruda a noble prize winning poet who was greatly inspired by Walt Whitman. He states “ I was barely 15 when I discovered Walt Whitman, my primary creditor. I stand among you today still owing this marvelous debt that has helped me live.” Neruda even wrote a poem called the Ode to Walt Whitman. Within it he states “you gathered for me everything; everything that came forth was harvested by you.”

Whitman asks and answers the great question and mystery of death. He says that if you have any doubt of mortality, I say there can be no more doubt of immortality than of mortality. This then calls for an ethical order to recall life as death and death as life and in both of them there is light and there is light in each of us, and there is that great symbol in the sky that gives light and life to everything and inside everyone is a sun. Unfortunately, Walt Whitman wasn’t alive to see all the light that his poetry shined across its readers. Though Whitman passed away a long time ago his light and peace still shines down on us today. As he said “O SUN of real peace! O hastening light! O free and ecstatic! O what I here, preparing, warble for! O the sun of the world will ascend, dazzling, and take his height–and you too, O my Ideal, will surely ascend! O so amazing and broad–up there resplendent, darting and burning!” Walt Whitman’s work will continue to inspire people throughout time as his poetry leaves a lasting impression on everyone it touches.

Works Cited

Leaves of Grass and Other Writings: Walt Whitman

“The Walt Whitman Archive.” Gallery of Images [Page ] 1-10. Web. 21 Apr. 2015.

Velella, Rob. “Whitman’s Funeral and Burial.” The American Literary Blog. 30 Mar. 2010. Web.21 Apr. 2015.

“Walt Whitman Bridge (I-76).” Walt Whitman Bridge (I-76). Web. 21 Apr. 2015.

“Walt Whitman Quotes.” Walt Whitman Quotes (Author of Leaves of Grass). Goodreads. Web.21 Apr. 2015.

“Welcome To Walt Whitman Shops® – A Shopping Center In Huntington Station, NY – A Simon Property.” Welcome To Walt Whitman Shops® – A Shopping Center In Huntington Station, NY – A Simon Property. Simon Property Group. Web. 21 Apr. 2015.

“World Biography.” Walt Whitman Biography. Encyclopedia of World Biography. Web. 21 Apr. 2015.

Reflective Tag

Doing the virtual scrapbook was a very good experience. I was able to learn a lot of interesting facts about Walt Whitman that I wouldn’t have known if I hadn’t chosen the topic that I did. By choosing to look at Walt Whitman’s legacy I was able to look in many different areas like Pablo Neruda who admired Whitman, or even the many things named after Whitman himself.  Also, I was able to take a look into the death of Whitman. This was particularly interesting for me since death is talked about so heavily throughout Whitman’s poetry. It allowed me to gain a better understanding as to how Whitman speaks about death and his true meaning behind it. The topic of death became more evident in more of his poems once I started to look at them from Whitman’s idea of death. However, while working on the virtual scrapbook I was able to see that Whitman’s death has been celebrated just as he would have wanted with so many lively things placed under his name while also Leaves of Grass still being read across the world.

Christopher Spates

Col. Ball

ERH 421WX

April 14^th, 2015

The Critics of Walt Whitman’s Mind

Walt Whitman, one of America’s most famous poet and journalist is known for his controversial topics about the American democracy. Some view negatively of Walt Whitman’s writings and others praise and honor his influence on literature. People often disagree with his writings because it is considered offensive; however, he is not a man to be easily dismissed. Whitman created uproar among society, because of his disputed views and opinions on life. His writings caused people to reflect upon their own views on life and how society can affect an individual’s perception. By reflecting the American way of life, Whitman is able to capture and question the true understanding of human nature and the society around it. Some critics praised his work and believed “his voice will one day be potential or magisterial wherever the English language is spoken” because it is so unique.(Austin) However, other critics completely disagree and find that his writing irrelevant, and claims it barely makes since. Those reviews that critique his writings have helped to popularize his work by making it known to many people. The reviews have also allowed society to consider his beliefs and live a life that reflects Whitman’s views. At the time, his ideas were new and different. Many people had contradicting views on his writing. However, by considering the thoughts within his writing readers are able to apply his thoughts towards modern day society.

Whitman’s poems are not where the controversy started. Whitman’s beliefs have been disputed since he first entered the world of writing. Just like most of society, Whitman’s parents influenced his views and beliefs on America and democracy. When Whitman was seventeen years old he got his first job in a one-room schoolhouse. In 1841 he began his own weekly paper, called the Long-Islander. He moved to New-York city where he became an editor for another newspaper, called the Brooklyn Daily Eagle.(Whitman Bio)  Whitman’s jobs never lasted long. Even then his views and opinions were questionable and not accepted from his co-workers and bosses.  He lost his job from seven different newspapers in only four years.

Whitman’s critics, regardless of whether they offered positive or negative reviews, did not contribute any notable literary works of their own. As I researched works about Walt Whitman it was interesting to see how ready people were to judge the works of Whitman when they couldn’t truly relate to his talent. Without controversial subjects covered, poetry is merely restated material, and without the progression that people like Whitman offered, there can be no change.(WhitmanWiki) This is why to this point today Whitman is known as America’s poet due to his unique thoughts and writing style. More than likely most of his critics had a hard time understanding his writings because there had yet to be anyone else like him. Whitman is known for reshaping poetry, and obviously giving it an entire new identity.  As seen in all of his writings Whitman offered a style that lacked a popular rhyme scheme, typical line breaks, and even rhythm. (Guide to Walt Whitman)  However, many people felt that by doing that he wasn’t writing poetry anymore, rather he was throwing together random thoughts onto paper. Though the critics of Walt Whitman have never grown to be as well-known as his work there are still interesting critical analysis on his work.

Robert Buchanan a Scottish poet, lecturer, and journalist wrote a very strong critical review of Whitman’s writing. Within the review he states that Whitman essentially has poems written about democracy, and general monotonous prophecies throughout Leaves of Grass.(Buchanan)  Buchanan displays Whitman as selfish and unintelligent, and says that all Whitman saw was the “perfect world” where everyone had equals of everything; however Buchanan argues that Whitman’s stance is not realistic.  In his eyes he sees it in a way that Walt Whitman’s writing is for “daintier men” to follow calling Whitman a plain pioneer.(Buchanan) Buchanan believes that young gentlemen followed Whitman’s writing simply because he was loud, massive, gross, and colossal rather than for the truth he was speaking.(Buchanan) Although Whitman is harshly criticized by Buchanan he makes several legitimate points throughout his critical review. At times Whitman’s poetry was inappropriate, however, in order to understand his stories you had to be intelligent and have a sense of how society was changing. Also, Whitman was very unique in ways that many people still to this day will never understand. He carries so many interesting ideals from topics such as death, life, nature, democracy, and love, which to this day can be easily misunderstood.(Guide to Walt Whitman)

Another critic of Walt Whitman is John Trowbridge. He says specifically that Whitman wrote with vigor, graphic force, and also had a strong since of human sympathy.(Trowbridge) Trowbridge sat down and spoke with Whitman in Boston in 1860. In is review he admires Whitman and says that it is amazing how someone can have such love and faith yet have such a large view on life with a strong since of curiosity.(Trowbridge) Whitman told him directly that he couldn’t have created his writings if he hadn’t found himself. He gave direct credit to Emerson for helping him find that and said that Emerson’s letter was seen as blazoned and a chart of an emperor.(Trowbridge) Trowbridge also spoke of Whitman’s physical appearance. Before he saw Whitman for the first time, he expected to see someone who was simple and well looking. When they met Trowbridge was shocked by his grey beard and rough physical appearance. Whitman was very quiet in person, but when reading his poems you would think he was outgoing and grandiose. Overall, Trowbridge saw Whitman as someone who demonstrated everything between nature and man. Many people have miss conceptions simply by reading Whitman’s poems yet never truly look deeply into his personal being to see that his work deserves a form of celebration.

Though Whitman’s work in Leaves of Grass is explained online by many scholarly sources as to what the meaning of his poems are how do we really know that is right? Personally, I see Whitman as someone with a mind of his own that can be easily misinterpreted, but I think that is exactly what he wanted. Though critics have some harsh words against Whitman they still all take his poems and place the circumstances he speaks of into their own lives. This is because Whitman offered up poetry that wasn’t directed particularly toward any one person rather he wanted to reach out to everyone. His poetry gives every reader the opportunity to place themselves into the story that is being told in order to feel the emotion, or even see the picture that he is trying to portray.

Works Cited

Austin, Alfred. “The Poetry of the Period.” The Poetry of the Period: [Review of Poems by Walt Whitman] –. The Walt Whitman Archive, 1 Oct. 1869. Web. 14 Apr. 2015.

Buchanan, Robert. “The Walt Whitman Archive.” Walt Whitman: [Review of Leaves of Grass (1867).and Drum Taps] –. The Broadway, 1 Nov. 1867. Web. 14 Apr. 2015.

“Poets.org Guide to Walt Whitman’s Leaves of Grass.” Poets.org. Academy of American Poets,1 Jan. 2000. Web. 14 Apr. 2015.

Trowbridge, John. “Reminiscences of Walt Whitman.” The Atlantic. Atlantic Media Company, 1 Feb.1902. Web. 14 Apr. 2015.

“Walt Whitman.” Bio. A&E Television Networks, 2015. Web. 13 Apr. 2015.

“Whitman’s Critics.” WhitmanWiki. Wikimedia Foundation. Web. 14 Apr. 2015.

Reflective Tag

While doing research on Walt Whitman’s critics I learned a lot about what people thought of him. It was very interesting to learn about his physical appearance and demeanor. I believe that Whitman was a very interesting person to interact with by reading about his personality.  His work is so unique and offers so many questions to his readers. The imagination he used throughout Leaves of Grass is incredible and makes you truly think. It relates not only to history, but to the present.  Even Whitman’s critics were able to see his ability to relate nature and society into one concept. Also, I was able to see how even back then people believed his work was very explicit and gruesome. However, I think that is what makes him America’s greatest poet. Overall, doing this research paper I was able to gain a better understanding for Whitman’s being and the true concepts of his poetry by learning what other people thought of it.

https://www.youtube.com/watch?v=-kfjYutiuEg

Citations:

Mccauley, Teresa. “VMI Keydets Men’s Soccer.” Shutterfly. Shutterfly. Web. 12 Dec. 2014. <https://vmikeydets.shutterfly.com/>.

Zombie Nation. Sport Chant Stadium Remix. Kernkraft 400-EP, 1999. MP3.

My ePortfolio can now serve many roles in order to cover the material we have discussed over the semester. It can serve as a hub of information about me, my interest, and what my future has in store. It can also serve as an archive to learn more about what I have done in the past. The ePortfolio I have created also gives me credibility as an educated, goal oriented, and driven student who has a professional web presence. My blog can help me currently to receive internships, leadership positions, and potentially allow me to receive acknowledgment for the work I post onto it. Over time my ePortfolio will be transferred to focus more strictly on my career field. Once I am in a career field I will change me ePortfolio in many ways. I will use it in order to help me advertise my practice. Also, I will use it in order to display any findings during research. The most important thing we have learned in my mind over the semester is that your digital identities are being used for many more things than just socializing with family and friends. This is so important with the way technology is advancing today because we must be aware of our web presence in order to appeal as professional as possible. It is important to shape your ePortfolio so that it offers an equal representation of your personality so that you do not create a false identity, however you want to lend yourself to someone who is capable to succeed in a professional atmosphere.

Citations for ePortfolio:

Brown, Colby. “Camera Awesome for Android Released – The Best Camera App on the Market?” Colby Brown Photography. Web. 20 Nov. 2014.

Christopher Spates

Major Garriott

ERH 221

^{November 24th}, 2014

Since 1930 the defibrillator has been evolving into the life saving device that it is today. The defibrillator has had an important role regarding its importance in the medical field. A defibrillator is a device that analyzes the heart’s rhythm and if necessary, uses an electric current toward the chest wall or heart to control heart fibrillation. The defibrillator, like all new technology had imperfections and certain flaws that could be improved. Although the defibrillator has not had a direct impact on my life, it continues to create a safer self-conscious for people with heart conditions whom may need attention at any time.

Over time the defibrillator has changed drastically. When it was first used on a human in 1947 the devices received the electric current from wall sockets; making it very hard to control the amount of volts that would strike a patient at one time. The voltage could vary anywhere between 300 and 1,000 volts. This caused many problems because too much voltage would damage the cells within the patient’s heart muscle. Also the defibrillation devices at this time period were very large which made it very hard for transportation. The method that was used during this time period was considered to be closed-chest because it could only be used when the chest cavity was open during surgery. Even the defibrillator used in the TV show ER was much more technologically advanced than the first set of defibrillators. During  this era of defibrillators doctors had little to no use due to its imperfections and lack of effectivity on patients.

In 1959 the Lown-Berkavits Waveform was created. This allowed for the voltage of energy transferred to the body to be more closely regulated, and also allowed for the voltage to be transferred into the body by paddle electrodes. Finally in the 1980’s the biphasic truncated waveform (BTE) was introduced by the University of Missouri. This new form of defibrillation required lower energy levels, and also lessoned the weight of the machine. From this point on the BTE set the basis for future defibrillators which allowed doctors the ability to more effectively implement this technology on their patients. This set the stage for people beginning to gain common knowledge of this device. After this point in time, people began having more belief in reviving someone whose heart had stopped. While the technology had not yet been perfected it gave physicians yet another tool to improve survival rates, and to offer hope to their patients.

Within the past twenty years the defibrillator has become more technologically advanced. They can be found just about everywhere; including school systems, public areas, and can even be implanted into a person’s chest. In 2010 a computer system was created to coincide with defibrillators in order to give medical personnel knowledge of each specific waveform a person needs in time of an emergency.  Personally, I feel it is vital that people understand that they are able to be prescribed a defibrillator. Regardless of whether or not they ever use the device it gives the person a sense of security. Being that I am interesting in becoming a future physician I find it important that we continue to find ways to improve this device. The defibrillator is capable of saving lives and allowing family members to not live on the edge of their seats wondering what they will do in case of emergency. If it were not for the improvement’s made on the defibrillators the ability to save patient’s life would be hazardous and difficult. It is projected that with current defibrillators being placed in public areas that approximately 100,000 lives can be saved each year. When a patient’s heart stops, there is not a lot of time before severe organ damage or even death can occur. Having a defibrillator in close proximity could make the difference between life and death.

Overall, the defibrillator has become a major aspect of the medical field; with the amount of emergencies that occur today anywhere from heart conditions, car accidents, or even drowning. This technology offers a higher percentage of survival. If someone were to compare the technology in the medical field from twenty years ago to today, you may not notice a huge difference. However, the biggest differences are found in the technologies ability to offer patients more security in knowing medical devices are being placed more broadly in order to cut down on response time. Overtime technology is always changing and affecting the community both in a negative and positive way. However, it is my belief that the defibrillator has always had a positive impact on the community and continues to offer more security to people at risk for heart problems.

Defibrillator timeline

Defibrillator notes

Defibrillator Speech

Project 2: Reflective blog post

While researching information in order to create an archive of the defibrillator I learned a lot of new information. I researched the web in order to gain a better understanding of where the defibrillator originated from.  Also, while collecting information I tried to determine the most important points in the defibrillators lifetime, and learned about the many different models of defibrillators that have been invented. This allowed me to determine which defibrillator models made for the biggest technological improvements over time. By doing this I was able to create my timeline, and make it as accurate as possible toward the defibrillators technological advances. There were many defibrillators created that did not have any major improvements, and that had no historical significance which I did not place on the timeline. The archive that I have created gives incite to the history of the timeline by stating facts that have changed the defibrillator overtime. This is important because it does not just list the names of defibrillators overtime which would be more of a memory; rather I have given brief descriptions of the improvements. If I were to do this project again it would be of significance to have a physical presence with past defibrillators. This would allow me to go into more description of the differences of defibrillators overtime whether it be weight, texture, simplicity, or even how smoothly the device worked. Having this physical collection would give me the ability to visualize the technology in person rather than relying on information gathered online. However, when it comes to determining the dates the devices were created, and the general information of each device I would much rather use the web. It cuts down on the amount of time I would spend researching in books for the information. Essentially, the best way to create your own archive today in my mind is to have a hybrid of information using both digital storage and having a physical collection of information also.