GHR Gene Variant Influence on Craniofacial Morphology

GHR Gene Variant Influence on Craniofacial Morphology â€Å"I526L† Growth hormone receptor gene variant and its effect on craniofacial morphology. Abstract OBJECTIVES: To investigate the influence of GHR (Growth Hormone Receptor) gene variant (I526L) on craniofacial morphology. SETTING AND SAMPLE POPULATION: The department of orthodontics, D.A.P.M.R.V.Dental College and Hospital, Bangalore, India. 30 randomly selected subjects, aged 20-30 years who were patients at D.A.P.M.R.V.Dental College Hospital, Bangalore. MATERIALS AND METHODS: DNA was extracted from venous blood samples of all the subjects. The extracted DNA samples were subjected to polymerase chain reaction, where amplification of the selected gene segments was done and later these amplified products were subjected to restriction fragment length polymorphism using HpyCH4V restriction enzyme. Results were documented in specific bands with gel documentation centre. The effects of the gene variant on the 4 craniofacial morphologic parameters of anterior cranial base length, maxillary length, mandibular ramus length/height and mandibular length were obtained from lateral cephalograms and tabulated. Appropriate statistical analysis was carried out. RESULTS: The results indicated that the subjects with I526L variant of GHR gene had a significantly greater mandibular ramus height. GHR gene variant I526L could be a genetic marker for mandibular ramus height. KEY WORDS: Craniofacial morphologic parameters, Growth hormone receptor, Polymerase chain reaction, Restriction fragment length polymorphism. CLINICAL RELEVANCE: The key to the determination of the etiology of malocclusion, and its treatability lies in the ability to differentiate the effect of genes and environment on the craniofacial skeleton in a particular individual. There are numerous ways in which the variant I526L could affect GHR activity. In addition to potentially causing direct changes in protein function, the variants could affect regulation of GHR, and in either case the variant could act singly or in combination with other single nucleotide polymorphisms (SNPs). The effect of these SNPs on GHR function and downstream gene expression should be clarified by further study. A study of gene polymorphisms in GHR would be useful in understanding genetic influences on craniofacial morphological determinants and helps in diagnosis and treatment in orthodontics to be delivered at a molecular level. INTRODUCTION: Growth hormone (GH) is a craniofacial morphologic determinant. Genetic influences are important in the determination of mandibular morphology, and growth hormone receptor (GHR) is believed to have an important influence on the growth of craniofacial bones. Responses to systemic GH therapy are time and site dependent in the craniofacial region, increasing growth, particularly in mandibular ramus. The growth hormone receptor gene is located on chromosome 5p13.1-p12 and is 87 Kb long, with 10 exons encoding 620 amino acids .1 Cartilage-mediated growth in the mandibular condyle is known to play an important role in the determination of growth and morphology of the mandible. GH treatment accelerates craniofacial growth, especially in the mandibular condyle where cartilage-mediated growth occurs. GH receptors have been shown to be present in the mandibular condyle.2 A single-nucleotide polymorphism (SNP) or a gene variant or a missense mutation is a DNA sequence variation occurring when a single nucleotide A, T, C, or G in the genome differs between members of a species or between paired chromosomes in an individual.Sequence analysis showed that 6 SNPs/gene variants were identifiable in the GHR gene in Chinese population, out of which C422F, P477T, I526L, and P561T are SNPs with significant effects.1 The purpose of this study was to investigate the single nucleotide polymorphisms (SNPs) (I526L) in GHR gene and examine the relationship between GHR gene variant I526L and craniofacial morphology. MATERIALS AND METHODS: The sample consisted of 30 randomly selected subjects, aged 20-30 years who were patients at D.A.P.M.R.V.Dental College Hospital, Bangalore. After clearance from ethical committee, venous Blood samples (2ml) were obtained from the subjects with informed consent. Lateral cephalograms of these subjects obtained as a part of routine treatment protocol were used. Method of Polymerase Chain Reaction and Restriction fragment length polymorphism was employed to deduce the genotypes. After collection and storage of blood samples, genomic DNA was isolated and Polymerase Chain Reaction Test was performed using specific primers (rs6180). This was followed by digestion with Restriction Enzymes HpyCH4V.Cephalometric measurements were carried out on standardized lateral cephalograms using Burstone analysis norms3 to measure the craniofacial parameters of anterior cranial base length, maxillary length, mandibular ramus length/height and mandibular length. The results were computed by correlating PCR results with the cephalometric craniofacial measurement values. Statistical analysis using Z test for proportions was carried out to test the level of significance. The Statistical software namely SPSS 11.0 and Systat 8.0 were used for the analysis of the data. RESULTS: The initial PCR product of the GHR gene variant I526L was obtained for the thirty subjects. The size of this PCR product was 602bp. Photograph 1: Initial PCR Product of GHR gene variant I526L (602bp). This was then subjected to digestion with the specific restriction enzyme HpyCH4V for I526L. After digestion, the 602 bp products were completely digested in 16 subjects whereas 14 subjects showed incomplete/no digestion. So the presence of variant I526L was shown in 14 subjects and absence of variant I526L in 16 subjects. Association of the presence or absence of variant I526L with increased, normal and decreased measurements (when compared with norms) of all four craniofacial parameters were tabulated. Table 1: Table comparing the P-values of samples with presence of I526L variant with respect to normal v/s increased, normal v/s decreased and increased v/s decreased mandibular ramus length Graph 1:Presence and absence of variant I526L in samples with normal,increased and decreased ramus height. Out of the four craniofacial parameters investigated association of presence of variant with mandibular ramus height was found to be statistically significant(P=0.002,P DISCUSSION: In the Human Gene Mutation Database, 56 different GHR gene mutations, including 32 missense and nonsense mutations, have been registered.4 In a few reports concerning the effect of GHR gene mutations on craniofacial growth, Chinese Han individuals with a genomic polymorphism at codon 526 of the GHR gene had a greater mandibular ramus length. Presence of variant I526L was seen in 46.67% of the samples. This is in accordance with a study done in Chinese population which showed I526L to have the highest heterozygosity of all the variants i.e 47.6%.1 A significant association was seen with presence of I526L variant and increased ramus height. (P=0.002, 1,5 Evaluation of site specific relationship between various craniofacial morphological determinants and the variant I526L showed significant association of increased ramus height with presence of I526L and this is in accordance with the study done by Zhou et al in Chinese population.1,5 This is also in accordance with a study done on 39 cephalometric variables which are under strong genetic control which showed strong genetic correlation with the vertical parameters.6Since mandibular ramus is the only vertical parameter included in the study it is seen to have a significant correlation with the variants. Further studies with all the four SNPs i.e. C422F, P477T, P561T and I526L can be carried out for a more detailed analysis of their influence on craniofacial morphology . CONCLUSION: This study indicates that subjects with I526L variant of GHR gene had a significantly greater mandibular ramus height. Influence of I526L is site specific as presence of I526L has an influence on increasing ramus height out of the four craniofacial parameters.GHR gene variant I526L could be a genetic marker for mandibular ramus height.

Richard III and Adolf Hitler :: Richard II Richard III Essays

Richard III and Adolf Hitler      Ã‚  Ã‚  Ã‚  Ã‚   In William Shakespeare's Richard III, we see Shakespeare's interpretation of despot rule and the parallels that stem from this interpretation.   The character type of Richard has been examined and marveled for thousands of years.   From Plato's examination of despot rule in the Republic, we see the motives of what drives despot rulers.   A look at the background of Richard and how his upbringing and personal life contributed to his insecurities will help to understand why someone may become a despot.   The comparison of Adolf Hitler to that of Richard, shown by the modern motion picture Richard III, will show the rapid rise and fall of the despot and the reality of totalitarian rule.      Ã‚  Ã‚  Ã‚  Ã‚   Plato's Republic, a fascinating look at the comparison of the just soul and the unjust soul, allows one to see the philosophical motives behind despot rule.   Despot rulers are simply driven by fear.   Their anxieties and insecurities lead to a hatred that has a desire to destroy, deep-rooted in violence.   Despot rulers are also never satisfied with the power they have at any given time, thus exposing their constant fear of retaliation from their subjects.   This examination of the despot ruler by Plato clearly shows the motives by which despot rulers rule, but it fails to explain why and how these motives originate in the human mind.      Ã‚  Ã‚  Ã‚  Ã‚   In order to comprehend why such a high level of fear and insecurity can be brought about, a look at the upbringing and personal life of Richard should be brought into discussion.   One of three brothers, Richard was in constant competition of who would succeed in gaining the throne of England.  Ã‚   Richard, like his other brothers, wanted the title of king quite badly, but as time pressed on it seemed less likely that Richard would succeed in gaining the throne.   His shrewd attitude and a physical deformity, that left him nearly paralyzed, were two of the many reasons why Richard would be kept of the throne.   Richard quickly became aware of this and he therefore began his rampage to insure himself the throne.   After killing off his brothers and many others, who were eligible to succeed, Richard finally became King of England.

The Health Nutritional Education

When parents send their children off to college, they might entertain the notion that their little darlings, having been brought up with the four basic food groups, will continue to practice impeccable dietary habits. Little do they know that their children skip meals, guzzle soda by the case, subsist on a diet that would make a mother cringe (Baker 12). Quick and easy meals are most attractive to students, so the microwave plays a major role in student's living habits. One half of all students say they use a microwave everyday, reports Roper CollegeTrack, an annual survey of student's behavior and attitudes. When college students arrive on campus there are so many changes they must go through. The simple fact of not being home can cause major amounts of stress, therefore changing a young-adult's eating habits. From my personal experiences as a college student, I have seen one of two things happen to students: they either gain weight or lose weight. When I came to college I weighed 150lbs. By the time I went home for my first Christmas break I weighed 173lbs. I got bigger, but not necessarily fatter. I weighed more, but my pants fit more loosely. A steady diet and consistent physical activity are the two keys to keeping the body you want during the most hectic, unstructured time of your life. My roommate played football with me my freshman year and weighed approximately 280lbs. He decided not to play anymore and wanted to lose weight. He began to workout and dieting right. He now weighs approximately 245lbs. This is a prime example of knowing what is right to eat for you. College students who leave home to live on campus or in an apartment face a period of transition during which they must assume greater responsibility for themselves, and this includes responsibility for their nutrition and dietary habits. Differences in dietary habits among college students have been well documented. Several factors have been shown to influence food selection, including gender, the desire to lose weight, age, academic major, and body-image perception. The location of residence has also been shown to influence food selection, but the relation between food selection and nutrient intake has not been documented (Beerman 1). For many students, living on a university campus is a traditional period between living at home with parents and living independently. Food decisions are among the newest responsibility that many students' face. Because new eating habits developed during these years, both negative and positive, are likely to be maintained, nutrient education effects have been targeted towards this group. The amount of information that people know about nutrition does not always affect what they eat. Many college students who do not major in nutrition take a course in basic nutrition, and the changes in student's concerns, habits, and knowledge of nutrition because of taking such a course were studied. Not all college students are required to take a nutrition course as a requirement to complete their degree. I believe that it would make a major difference in eating habits of many college students if they did. I took a â€Å"mini poll† in Whiteford Hall. I asked twenty different girls what their biggest nutritional fear of coming to college was. All twenty girls said that they were scared to get fat or gain weight. I asked them if they were going to take this nutrition course any time during their education here. Only seven said they would consider taking the course. I have not yet completed this course, but I have learned so many new things about my body and the way the works. Now I feel that I can lead a healthy life from the knowledge I have accumulated from this course. Upon completing a basic nutrition course, students felt that they had learned a lot about nutrition, but only 45 percent said that they made changes in their eating habits because of this. The only statistically significant change in food habits was the tendency to drink low-fat milk. Most also decreased their use of vitamins and mineral supplements (Mitchell 7). The Basic Nutrition course for the non-nutrition major may be the most widespread, in-depth means of teaching nutrition to college students. This course provides both academic and practical nutritional education, so the teaching is complicated by the need â€Å"to create informed consumers who value good nutrition and consume nutritious foods throughout their lives. Classroom tests measure textbook nutritional knowledge, but the practical application is not measurable. Several studies have found that nutritional knowledge is not predicting of dietary practices (Mitchell 8). I don't agree with this statement. I believe that the more nutritional knowledge that you have, the better you will eat. If you know something is bad for your body, I'm sure you will refrain from eating it. You might not totally remove it from your diet, but you will probably lower your intake of the specific item. If you have no knowledge of the nutritional value of what you eat, you will have no chance of being a healthy person. College is a very demanding time in your in your life, both physically and mentally. You need all of the help you can get. Having a consistently healthy diet can play a major role in your college existence. You need the right type of energy to complete all of your daily tasks. If you have no knowledge of dietary requirements or the nutritional value of different foods, you can not make the right decisions for food consumption. College students indicated that the greatest value of improved nutrition was better health in the future. This should be considered in motivating students to make dietary changes (Mitchell 8). Vegetarian eating habits are popular among college-aged and teenage people. About 15 percent of the 15 million college students eat vegetarian meals. However, vegetarianism is more popular among women than men. 50 percent of women ages 18-19 believe in vegetarianism. Many young vegetarians choose not to eat meat in order to reduce the intake of fat, but some will occasionally eat meat. However, young vegetarians definitely do not prefer vegetarian-style meat products (Walker 6). To many Americans, the term â€Å"vegetarian† conjures up images of hippies noshing on tofu and brown rice. But a new generation of vegetarians may bring meatless eating out of the extreme and into the mainstream. The new bastions of vegetarianism are college campuses (Walker 7). Young women seem to be driving the trend toward meatless eating. Nearly 50 percent of women college students say vegetarianism is in compared with the 33 percent of men students, according to Roper CollegeTrack. Pamela Limpitt, food service purchasing director for the University of Pennsylvania, agrees: â€Å"I'd say 9 in 10 of our vegetarian students are women (Walker 12). A survey of young female athletes at a midwestern university reveals that nutrition knowledge is positively related to healthy eating practices. Data on these two indicators were collected to compare nutrition between female high school and college athletes in 1992. Analysis shows that the older athletes had more accurate nutrition knowledge and better eating habits than their younger counterparts. Moreover, a significant proportion indicated that they often turn to their coaches and trainers for this type of information, suggesting that physical education teachers can shape nutrition attitudes (Buch 1). Coaches and others who work with athletes must teach young people how to select nutritious foods that will promote a lifetime of good health. Young female athletes' concerns about weight and body image strongly influence their eating practices. Knowledge alone is not enough to ensure good dietary habits. Attitudes also affect behavior (Buch 2). Nutrition knowledge is positively associated with age, education, dietary pattern, sources of nutrition education, and length of time in a sport (Frederick & Hawkins, 1992; Perron & Endres, 1985). Other important factors, such as concern for weight and the dependence on others for food selection, also affect food consumption (Barr, 1987). Athletes are always concerned with their performance and how to improve it. They may work to improve their technique, lift weights, or add the right nutrients in their body to perform at optimum levels. The only problem is that any athletes do not have the proper nutritional knowledge to make the right dietary decisions. For example, to build one pound of lean tissue, an athlete must consume approximately 98 grams of protein and 2,800 calories for extra energy to synthesize muscle (Williams, 1988). If this were the athlete's goal for a week it would mean 14 grams of protein and 400 calories per day in addition to the usual diet. Fourteen grams of protein can be obtained in two glasses of milk or two ounces of lean meat. With a small amount of additional protein and enough fuel from complex carbohydrates, muscle building can occur. This is all very simple if you have the knowledge. Most athletes think that for muscle building you must take supplements or just eat a lot in general. This is why nutritional education is so important for an athlete to succeed in a very competitive age of sports competition. College is a very hard time for a young adult to be worrying about too many things at once. They have been fed all of their lives and been taught what is good and what is bad for them. There are some many outside factors that make your food selections for you. Many of these choices, you have no control over. That is why I believe nutritional knowledge is so very important in a college student's survival. If you eat the right things you will have no weight or health problems. A good diet can ensure a long energetic life. During your college years you need all of the energy you need to pull â€Å"all nighters† during exams and when writing nutrition papers. The more knowledge you have the better your body will feel and the healthier you will be.

The Case For Decentralized Generation Of Electricity

In the article â€Å"The Case for Decentralized Generation of Electricity†, energy policy analyst Thomas R. Casten and project engineer Brennan Downes frame the consequences of meeting up with the demands of power energy with central generation or letting go of decentralized generation that recycles waste energy. They go on to summarize how a new power generation has been built over the past 30 years under given circumstances of technology that was available at the time, the cost of technology and fuel prices, and conclusion of their ideas. From 1910 to 1960, electricity was originally produced by either using hydroelectric dams or burning fossil fuels in order to deliver power to cities and buildings. But those methods proved to be†¦show more content†¦Having these turbines and machines located directly within large populations rather than many miles away was an advantage. Although, they found that using multiple engines and turbines was more cost-effective and less harmful in transmission, electric industries weren’t being fair because they began to charge consumers at very high rates. To regulate the situation in 1978, Congress stepped in and wanted to create competition within the industry in the year. Independent power companies began to advance and develop on-site generation in areas made able to regulate the monopoly. Today, most power companies think that centralized electrical energy gives the most favorable results for all. To support this belief, the International Energy Agency predicted a significant increase in numbers for the next thirty years as our world’s need for electrical power continues to grow every second. According to Figure 1 in the article, the electricity generation capacity for the world will increase by almost 4,500 GW to reach 8,000 GW total. With the demand for burning fossil fuels to increase by 90% and great amount of carbon dioxide emission, we will negatively affect our environments with this hug e contribution to global warming. To meet our increasing reliance and demand for this resource, central generation of electricity will also critically affect the tax market, fossil fuel market, and our world’s environment as a whole. However, with close