Krabbe's disease is an inherited neurological disease caused by galactosylceramidase deficiency in children. Castelvetri et al. focused on psychosine in this study as a potential causative agent in Krabbe disease because psychosine (galactosylsphingosine) has shown to be a causative agent of the pathological condition found in the nervous system of patients with Krabbe’s disease. They supported the role of psychosine as a potential causative agent in Krabee disorder by discussing the important role, which psychosine play in this disease. Castelvetri et al. stated that the accumulation of psychosine is recognized to be a causative lipid for the loss of oligodendrocytes and myelin sheath in Krabbe's disease. Thus, psychosine is highly cytotoxic and responsible for the extensive pathology of the disease. Moreover, it has been shown that psychosine is responsible for loss in function in galactosylceramidase lysosomal activity that results in demyelination and vulnerability of different neurons. Additionally, by examining the in vitro myelin free, it showed that psychosine was able to inhibit fast axonal transport (FAT) via activating axonal PP1 and GSK3β in the axon. Defects in FAT are indicated by the formation of localized swelling of the axon. Castelvetri et al. showed that FAT defects present in cellular and animal models of Krabbe disease and sphingolipid psychosine has been demonstarated as FAT inhibitor. Thus, psychosine is highly cytotoxic and responsible for the extensive pathology of the disease that is able to block fast axonal transport. Additionally, this is the first study to show the molecular mechanism of dying back degeneration in this inherited genetic disease.
To examine whether sphingolipid psychosine is able to i...
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...n et al. 2012).
Castelvetri et al. indicated that due to the interference of different pathogenic mechanisms with each other, it affect the efficiency of hematogenous replacement therapy. Additionally, their results showed that use of psychosine as a FAT inhibitor was able to activate the PP1-GSK3β pathway, which could be used as a potential therapy for Krabbe disease neurodegeneration by reversing FAT defects. Interestingly, they declared that the pharmacological treatment that they used in their study was not associated with any metabolic correction. Therefore, the treated mutants in their research were able to demonstrate neurological symptoms of the disease. For all these reasons, they concluded that neuroprotective treatments could be used with the traditional hematogenous replacement as a potential therapy for Krabbe disease as well as other leukodystrophies.
Tay-Sachs disease is a form of these lysosomal storage diseases. It is scientifically known as GM2 gangliosidosis: Hexosaminidase alpha-subunit deficiency. Three polypeptides encoded by three separate locations on the chromosome are needed for the catabolism of GM2 gangliosides. When these genes are mutated, the result is a buildup of the glycosphingolipid GM2 gangliosides. Over 50 mutations have been identified. Tay-Sachs disease is the most common form of gangliosidosis and results from a mutation of the alpha-subunit location on chromosome 15. This causes a severe dysfunction in the enzyme hexosaminidase A.
Korsakoff’s syndrome is a brain disorder that is related to heavy alcohol use over a long period of time. This disorder is caused by a lack of Thiamine, or vitamin B1. Excessive amounts of alcohol use lead to Thiamine deficiency, which affects the brain and nervous system. Thiamine deficiency can be caused by poor eating habits, as heavy drinkers typically do not have nutritional diets that fulfill their vitamin needs. Alcohol can also disrupt the process in which Thiamine is changed into the active form, Thiamine Pyrophosphate. Alcohol also inflames the stomach lining, causing vomiting; again, this affects the body’s absorption of key vitamins. The effect alcohol has on the liver also affects the storage of these vitamins. Korsakoff’s syndrome is also related to another brain disorder, Wernicke-Korsakoff syndrome. This syndrome involves the Korsakoff syndrome and also Wernicke. Wernicke’s syndrome involves undernutrition, jerky eye movements, poor balance, and memory loss, which is caused by heavy alcohol consumption. If this condition is...
...s Elevated in Brain of Patients with Dominantly Inherited Olivopontocerebellar Atrophy. Neuroscience Letters (submitted publication).
While the Type I Gaucher Disease is non-neuronopathic (not affecting the nervous system) the second two types are neuronopathic. Yet even though the three types of Gaucher produce different symptoms, all three types result from the same cause: a lack of glucocerebrosidase enzyme. The glucocerebrosidase enzyme functions to break down the compound glucocerebroside, a fatty compound which usually is stored in all cells of the body in very small amounts. In Gaucher patients, an excess of glucocerebroside builds up in the body, and is stored abnormally in lysosome, or storage cells (3) . Typically, macrophages are able to aid in the degradation process of glucocerebroside. However, due to the lack of glucocerebrosidase in Gaucher patients, glucocerebroside stays in the lysosome, preventing macrophages from acting upon them. Macrophages which are enlarged and contain an abnormal buildup of...
Americans have embraced debate since before we were a country. The idea that we would provide reasoned support for any position that we took is what made us different from the English king. Our love of debate came from the old country, and embedded itself in our culture as a defining value. Thus, it should not come as a surprise that the affinity for debate is still strong, and finds itself as a regular feature of the mainstream media. However, if Deborah Tannen of the New York Times is correct, our understanding of what it means to argue may be very different from what it once was; a “culture of critique” has developed within our media, and it relies on the exclusive opposition of two conflicting positions (Tannen). In her 1994 editorial, titled “The Triumph of the Yell”, Tannen claims that journalists, politicians and academics treat public discourse as an argument. Furthermore, she attempts to persuade her readers that this posturing of argument as a conflict leads to a battle, not a debate, and that we would be able to communicate the truth if this culture were not interfering. This paper will discuss the rhetorical strategies that Tannen utilizes, outline the support given in her editorial, and why her argument is less convincing than it should be.
Neurodegeneration is used mainly for diseases that are characterised by progressive loss of structure and function of neurons. There are many neurodegenerative diseases including amyotrophic lateral sclerosis that...
It is not surprised that one of the common progressive motor neuronal disease, ALS, is also genetically connected to the mutations of degradation machineries with varied etiology. Even the majority of ALS is sporadic, two of familial ALS is mainly associated with simple monogenic factors, the mutation of SOD (D90A) and a large hexanucleotide (GGGGCC) repeat expansion in chromosome 9 open reading frame 72 (C9ORF72). However, growing evidence of genetic mutations in proteostasis factors discovered in familial ALS such as, UBQLN2, VCP/CDC48 in the UPS and SQSTM1/p62, VAPB and some of the vesicular traffic proteins in autophagy have been suggesting a fragile capacity of proteostasis in vulnerable neurons (Bedford et al., 2008; Deng et al., 2011; Paine et al., 2013; Johnson et al., 2010).
Tay-Sachs disease is a genetic disorder, which destroys nerve cells in the brain and spinal cord (See picture B). It is a mutation to the Hex-A gene. The enzyme created by the Hex-A gene, beta-hexosaminidase A, breaks down fatty substances called GM2 ganglioside. Because the gene is mutated and can no longer break down the substance, it eventually builds up and becomes toxic to the body. This substance destroys neurons in the brain and spinal cord leading to various symptoms many dealing with the break down of muscles and nerves (ghr.nlm.nih.gov).
(Marieb, 2016). Myelin is the protective coat surrounding and insulating the nerve fibers of CNS. Myelin is fatty tissue substance that if attacked by immune cells causing a short-circuits in the current so that the successive gaps are excited more and more slowly, and eventually impulse conduction ceases which resulted in various forms of symptoms (Marieb, 2016). The degradation could either be “by inflammation, stroke, immune disorder, metabolic disorders, or nutritional deficiencies” (Slomski, 2005). The target that immune cells are sensitized to attack remains
In Chapter One of Emerging Systems for Managing Workplace Cnflict: Lessons from American Corporations for Managers and Dispute Resolution Professionals, authors, David Lipsky, Ronald Seeber, and Richard Fincher (2003) lay the foundation for the rest of the book. They provide historical background on why corporations have shifted from dispute resolution to conflict management and stress the fact the “substantial dissatisfaction” that must drive companies to change how they handle dispute resolution (Lipsky, Seeber, & Fincher, 2003, Chapter 1, Inclination to Change). In addition, the authors articulated the differences between dispute management and conflict management (Chapter 1, Litigation, Dispute, and Conflict Management), detailed the five characteristics of an integrated conflict management system, listed the eight essential elements of a fair conflict management system, and pointed out other characteristics that effective conflict management systems share (Chapter 1, The Concept of a Conflict Management System).
The crime drama, “Beyond a Reasonable Doubt”, was produced in 2009 by Faisal Al-Saud, Mark Brooke, and Stephanie Caleb and directed by Peter Hyams. The two lead male actors were C.J. Nicholas as Jesse Metcalfe and Michael Douglas as District Attorney Mark Hunter. The lead female actor was Amber Tamblyn as Assistant District Attorney Ella Crystal.
...t one has it. Many scientists hypothesize that there is an inflammatory response in the brain when there is an extensive B-42 amassing. To slow or stop this, scientists theorize that the use of anti-inflammatory drugs, such as aspirin, could delay the swelling in the brain. Also, as scientists have known that taking a multi-vitamin tablet each day is good for you, there has been recent research demonstrating that the use of antioxidants may protect neurons, not just the immune system and keeping the body healthy by providing vitamins and minerals. These special supplements protect the neurons from the effects of the accruing B-Amyloid that would likely cause the plaque that causes AD.
I believe it is important for any student who wants to do their best in a class to take a moment to evaluate their own work to determine the rate their writing is progressing and how they can continue to advance their writing. When I looked through my own work I asked myself “what have I learned this semester?” and “what do I still need to learn in order to improve my writing?”. Answering both these questions will help me with my last step of my self-evaluation, developing a plan to learn new skills.
The book I'm a Stranger Here Myself, written by Bill Bryson, is based on a collection of written articles. Bryson writes about everyday events and shows their negative qualities through whining or creative criticism. He attracts the readers' attention by writing ideas that relate to a normal persons life. His methods are very powerful because it attracts his main audience of common people through his simple vocabulary use and everyday middleclass situations. Also between his "complaining" he throws in little jokes that make his stories entertaining. This makes the reader continue reading because it constantly grabs their attention. Another reason of why Bryson's style of writing is very effective is because all of his stories have a main theme that gives a strong and important message to the reader. Some of these messages may be a little controversial to some readers but are very thought out and well explained.
The movie that I have chosen to review is called the League of their own, which was based on a true story took place in during World War 2. The main focus of this film is fore the view to see that although baseball was a sport that was designed for man, women would be able to be just as good at it, if not better than man. Although it was the women who were going to be playing a man's sport, they would still have to act and be a lady and fallow certain rules.