text:
The American School/The Role of Education in a Democratic Society

Purpose of a Civic Education
When asked [in 1787] by a certain Mrs. Powell of Philadelphia what kind of government had been bestowed on the country as a result of the [Constitutional] Convention's four-month effort, Benjamin Franklin was reported to have said: “A republic, madam, if you can keep it” (Morrow, 1999, pp. 1–2) Franklin's response to Mrs. Powell demonstrates the necessity for citizens to engage in the functioning of their democratic government if it is to prosper. Society struggles with how to impart its knowledge to the next generation in a manner that integrates social learning, civic learning, and moral learning into academic learning. These necessities led Jefferson to pursue the development of a system of public education: “Preach, my dear Sir, a crusade against ignorance; establish and improve the law for educating the common people. Let our countrymen know that the people alone can protect us against these evils” (as cited in Ravitch & Thernstrom, 1992, p. xi). Dewey (1916, 1938) was resolute in defining the overarching goal of education to be no less than fostering and maintaining a democracy. Applying a strict definition of civic education, political scholars would define citizenship as voting (Walker, 2000). Scholars would note that youth's knowledge of the particulars of government are on the decline (Niemi & Junn, 1998) as the focus for a clear definition of civic education center on the knowledge required of the citizenry to participate in a democracy as evidenced through the explicit act of voting. Flanagan and Faison (2001) utilize an action definition pertaining to civic participation, the civitas, where individuals freely associate in self-selected groups to meet their needs and promote and define their beliefs. When asked to describe a “good citizen” students responded that “the task of being a good citizen carries no additional meaning or special responsibilities beyond simply being a ‘good person’” (p. 6). The basic civic duty to vote was mentioned by only 12 percent of the respondents as a component of citizenship (People for the American Way, 1989, pp. 12-15). The State of Michigan mandates the teaching of civics as detailed in the Michigan Curriculum Framework. The State of Michigan’s Department of Education (MDE) defines its purpose for the social studies in the realm of civic education as follows: “The purpose of social studies is to develop social understanding and civic efficacy; the readiness and willingness to assume citizenship responsibilities and to make informed and reasoned decisions for the public good as citizens of a democratic society” (MDE, 2006, 8). Ultimately, to assume the responsibilities of a citizen would mean that one is actively involved in the governance of their own being; the self. Aristotle's Politics (c 340 BC) reflects on the notion that the ideals of a democracy are sufficiently achieved when all persons share in government to the best of their abilities: “If liberty and equality, as is thought by some, are chiefly to be found in democracy, they will be attained when all persons alike share in the government to the utmost.” The rights and responsibilities of citizen from our beginnings to modern times have deep roots and shared meaning when set side by side; the ancient philosopher with the current goals of the state. In summary, there is little confusion on the need for the public schools to teach the civic skills and knowledge necessary for an informed citizenry to complete measurable acts of citizenship such as voting, service, and volunteerism. The determination of how to best instill those skills and knowledge to best allow for their articulation as demonstrated in increased civic participation remains to be seen.

Essential Components of a Civic Education
An effective democracy requires a citizenry with a civic education. The public schools were founded in part to create an informed citizenry through a curriculum that formally promotes common knowledge, skills and dispositions allowing for authentic engagement in the business of a democracy. The civic knowledge and participation necessary for a democracy are not inherently passed down from generation to generation – “they require that each generation of students learn civic facts, explore democratic ideals and connect such concepts to the responsibility of citizenship” (NACE, 2006, 1). There is widespread agreement in the United States of America that “good citizenship” contributes to a better democracy which, in turn, contributes to a stable society of opportunity and justice (Isaac, 1992). Practicing civics, becoming a skilled citizen, using one's skills to overcome apathy, ignorance, greed or abuses of power in society at all levels requires knowledge of civic history, understanding of civic rights and strategies and sharing in a growing civic culture of regular participation. The next three subsections define what is meant by civic knowledge, civic skills, and civic dispositions as they pertained to this study.

Civic knowledge
The irony of defining a body of finite knowledge in a democratic system is that it cannot be done without limiting the deliberative discourse necessary for a democracy to exist. Both the National Standards and the Civics Framework for the 1998 National Assessment of Educational Progress (NAEP) have developed five essential questions to promote the discussion towards a shared understanding of what citizens ought to know:

 * What are civic life, politics, and government?
 * What are the foundations of the American political system?
 * How does the government established by the Constitution embody the purposes, values, and principles of American democracy?
 * What is the relationship of the United States to other nations and to world affairs?
 * What are the roles of citizens in American democracy?

The civic knowledge defined by the five questions requires the citizenry to put into context those systems, historical documents, cultural pieces, values, law, international government and non-governmental organizations, and individual rights and responsibilities. To gain an understanding of this civic knowledge would require the social studies educator to address these questions in an authentic manner in the civics classroom as supported by NCSS (1992, 2001) and their definition of what a civic educator is as well as through their definition of an effective citizen.

Civic skills
A civic base of knowledge in a democracy would hold no value if citizens were unable to critically think about and act upon that knowledge (NCSS, 2001). In a democracy, citizens are decision-makers and are expected to continually develop and improve their abilities to evaluate, take and defend a position (Branson, 1998), to articulate the meaning of the tangible and intangible symbols of a democracy, to explain how a function of government should operate and the consequences of that operation, as well as to be able to interact, monitor and influence the political process of a democracy (Branson, 1998). Critical thinking in the social studies has been seen as a necessary goal to effective civic education. According to Ennis (1985), "Critical thinking is reflective and reasonable thinking that is focused on deciding what to believe or do" (p. 45). Limited definitions focus on evaluation or appraisal; critical thinking is formulation and use of criteria to make warranted judgments about knowledge claims, normative statements, methods of inquiry, policy decisions, alternative positions on public issues, or any other object of concern. Critical thinking, defined narrowly, is an essential element of general cognitive processes, such as problem solving or decision making, but is not synonymous with them. Critical thinking, whether conceived broadly or narrowly, implies curiosity, skepticism, reflection, and rationality. Critical thinkers have a propensity to raise and explore questions about beliefs, claims, evidence, definitions, conclusions, and actions. (Patrick, 1986, pp. 2–3) Despite the identified importance of critical thinking in civic education along with increased research and discourse on the topic it has not been found to be taught satisfactorily in most social studies classrooms. This has been noted by the governing body for social studies education, NCSS, as they continue to reinforce the need for the connection between critical thinking and civic efficacy: Powerful social studies teaching begins with a clear understanding of the subject's unique purposes and goals. NCSS's statement “Essentials of the Social Studies” identifies citizenship education as the primary purpose of K-12 social studies. Noting that concern for the common good and citizen participation in public life are essential to the health of our democratic system, it states that effective social studies programs prepare young people to identify, understand, and work to solve the problems facing our diverse nation in an increasingly interdependent world. (NCSS, 1999) Goodlad's nationwide study of schooling demonstrated little evidence of the critical thinking supported by NCSS and concluded that "preoccupation with the lower intellectual processes pervades social studies and science as well" (1984, p. 236).

Civic dispositions
The “habits of the heart” (de Toqueville as cited in Mayer, 1969), or civic dispositions, are those pieces of private and public character that weave a democracy together allowing for it to be celebrated and critiqued in the public square. The purpose and necessity of these civic dispositions are perhaps articulated best by Judge Learned Hand (1944): “Liberty lies in the hearts of men and women; when it dies there, no constitution, no law, no court can save it; no constitution, no law, no court can even do much to help it. While it lies there, it needs no constitution, no law, no court to save it (1).” To have civic knowledge and skill without the capacity to implement and assess them makes them valueless. The National Standards for Civics and Government have identified those dispositions “that contribute to the political efficacy of the individual, the healthy functioning of the political system, a sense of dignity and worth, and the common good” (Branson, 1998, p. 8):

 * Becoming an independent member of society
 * Assuming the personal, political, and economic responsibilities of a citizen
 * Respecting individual worth and human dignity
 * Participating in civic affairs in a thoughtful and effective manner
 * Promoting the healthy functioning of constitutional democracy

All of these dispositions require the citizenry to accept responsibility for one's self and their actions, to listen and read for information, to lead, to accept majority decisions while recognizing minority opinions, to act and to invoke change through legal means.

Key to the implementation of civic knowledge, skills, and dispositions is how the curriculum in public schools is supported to foster these civic attributes. The following section in this chapter discusses the literature as it pertains to the formal and informal delivery of civic instruction.

How Civic Education Takes Place
Civics education occurs in theory at both a formal and informal level. The more formal instruction reflects those curricular pieces utilized as the means by which to teach civics while the informal instruction is demonstrated through the manner in which those curricular pieces are taught in the classroom setting.

Formal Instruction
The formal instruction in a civics curriculum is one of emphasis on the documents and systems of American democracy (Barr, Barth & Shermis, 1977; Jenness, 1990; National Commission in Education, 1983; Task Force of the National Council for the Social Studies, 1994; Saxe, 1998). The study of these documents and systems should be used to gain an understanding of the rights and responsibilities of the citizenry in the realm of personal rights and responsibilities, political rights and responsibilities, and economic rights and responsibilities as supported by the standards and benchmarks of states across America. The formal instruction of these rights should be used to generate a personal understanding that none of these rights are absolute and they all come attached with certain reasonable limits (Scheurman & Newman, 1998; Sunal, Sunal, & Haas, 1996). The rights discussed and emphasized must be accompanied with clear instruction on the personal and civic responsibilities attached to these rights. Since 1955, an expanding environments approach (Superka, Hawke, & Morrisett, 1980) for teaching the social studies has been the most frequently used format for civic education. This approach uses a focus on the self and family in the kindergarten years and moves the student into a wider range of cultures through grade seven and then moves into a U.S. history focus in Grade 8. Social studies educators during the 1970s supported and promoted a curriculum based on essential concepts from history and the social sciences (Taba, Durkin, Fraenkel, & McNaughton, 1971) believing social problems would provide a solid foundation for a solid social studies curriculum (Engle & Ochoa, 1988). In spite of these efforts, evidence has shown students in eighth grade and seventh grade currently studying essentially the same topics their counterparts have since 1916 (Morrissett, 1981; Superka, Hawke, & Morrissett, 1980).

Informal Instruction
The informal instruction that occurs in civics education is exemplified in the manner in which an educator manages teaching and learning. It is also exemplified in how they foster positive relationships in the schools. Holding students accountable in an equitable manner models the rights and responsibilities of the formal curriculum in civics and students who have a positive relationship with adults in this venue are more motivated to learn and more apt to lead (Apple, 1979, 1982, 1988; Banks, 1991; Bissex, 1980; Bowles & Gintis, 1976; Bruner, 1959; Freire, 1970, 1973, 1978, 1990; Giroux, 1988; Goodlad, 1984; Kohn, 2004; Marshall, 2004; McGregor, 1960; Meier, 1990; Piaget, 1979; Sapon-Shevin & Schniedwind, 1991; Schniedewind & Davidson, 1987; Shor, 1992; Silberman, 1970; Smith, 1983; Wertsch, 1985). The National Longitudinal Study on Adolescent Health (Resnick, et al., 1997) found that “connectedness with school” is a determining and critical factor in the lives of young people and that “School engagement is a critical and protective factor against a variety of risky behaviors, influenced in good measure by perceived caring from teachers and high expectations for student performance” (p. 827). Students will most likely duplicate the adult behaviors they observe in the school setting. It is for this reason that the informal processes we utilize in the school setting should most reflect those civic virtues and formal pieces of the curriculum we are teaching and assessing. The learning of civics should be one supported by a true sense of purpose supported through a modeled social experience (Dewey, 1938; Freire1970, 1973, 1978, 1990; Marshall, 2004). In a civics classroom the opportunity for the civic educator, in their role of expert citizen due to their assumed experience in authentic civic engagement as well as their role as civic expert due to the nature of their position, working in collaboration with the civic student, who by their very nature are novices in matters of civic engagement, are afforded the opportunity to create a shared culture and understanding of what civic efficacy is through the informal social experience of the classroom setting (Schein, 1992).

Culture of Civic Education
Galston (1991) acknowledges the constant reemphasis special interest groups have placed upon the necessity to revamp civic education citing that our survival as Americans in a viable democracy depends upon our transmission of liberty and equality to each new generation of Americans. Although this urgency has existed and continues to exist as acknowledged by several social educators true inquiry into social issues pertaining to developing civic efficacy are not commonplace in classrooms. Saye and Brush (2006) have identified research highlighting obstacles to inquiry-based teaching that are related to teachers and learners (Newmann, 1991; Parker, Mueller, & Wendling, 1989) as well as to the culture of schools and society at large (Onosko, 1991). Identified barriers limiting a culture of authentic inquiry in the social studies classroom exist. Class size, preparation time, isolation from supportive peers, and accountability for high-stakes testing are powerful disincentives to complex instruction (Konopak, Wilson, & Readence, 1994; Grant et al., 2002; Onosko, 1991; Saye, 1998; Schlechty, 1993). Sternberg (1985) notes the difference in the problems students are asked to solve in school and those they are asked to solve in real life. The authenticities of the problems students are asked to solve at school do not necessarily follow the same ill-structured patterns real life problems follow. In addition to these barriers, studies suggest that teachers’ understanding of the concepts and methodology of the social studies discipline affects their willingness to engage students in authentic critical thinking in this subject area (Bain, 1995; Windeburg & Wilson, 1991). Adding to the complexity of the teaching in this area are suggestions by Shaver (1996) that authentic critical thinking in the social studies centered on real-world issues requires a teacher who is able to cope with the uncertainty such instruction brings. Scant research exists on the effectiveness of teachers who are able to utilize more of an inquiry approach to the teaching of social issues. Rossi and Pace (1995, 1998) caution that even those teachers who have the capacity to employ an inquiry approach to their teaching face the obstacle of deciding what is desirable to pursue as it conflicts with supporting meaningful student inquiry processes in the classroom. Another identified barrier to authentic civics instruction may come from the field of social studies itself as advocates for history, a social studies discipline, have been prone to attack other social studies disciplines “which they believe have supplanted history as the core of the social studies curriculum” (Brophy & Alleman, 2007, p. 7). History advocates argue that curriculum and instruction centered on history and supported by all the other components of the social studies allows for a greater and more thorough coverage of any individual topic. History-centered reform proposals have not been received warmly by social studies leaders and professional organizations. Part of the conflict involves disciplinary turf protection: The social sciences do not want to cede curricular airtime to history. In addition, social scientists argue that their disciplines offer important insights about how the social world functions that all citizens ought to understand and be able to bring to bear in their civic decision making. Some of them also disparage the value of history as a basis for citizen education, arguing that knowledge about the past has limited application to the complexities of the contemporary world. (Engle & Ochoa as cited in Evans, 2004, p. 124) Reform ideas to the social studies curriculum are not new. During the 1960s and 1970s proponents of a history and literature perspective to social studies thought it wise to abandon social studies as a subject designed to pursue civic efficacy goals. “Instead, they would offer separate courses in the academic disciplines, simplified as needed but designed to pursue the goals of history and the social sciences rather than the goals of citizenship education” (Brophy & Alleman, 2007, p. 12). These programs were called the “new social studies” but never really caught on because of their narrow focus on specific subjects and their lack of acknowledgement for the importance of citizenship education. The 1980s witnessed a variation of this approach with Egan (1988) and Ravitch (1987) leading the call for a curriculum heavy on history and literature, particularly the myth and folklore of the American experience. Lack of value on the reality of social studies as it would be substituted with myth and folklore pushed this type of curriculum to the area of language arts instruction where it was thought to be better suited. Hirsch (1987) proposed a cultural literacy common to all Americans as the basis for reform in social studies education. The late 1980s saw Hirsch's list of 5,000 items “of knowledge that he believed should be acquired in elementary school as a way to equip students with a common base of prior knowledge to inform their social and civic decision making” (Brophy & Alleman, 2007, p. 11) emerge on the scene. Hirsch's list of 5,000 unorganized facts was deemed by social educators to be too specific and too broad discounting the development of connected knowledge around meaningful themes and ideas. Hirsch's list did give way to the CORE curriculum which attempted to integrate science, social studies, and the arts but even this modification on the Hirsch list was seen as too focused on the distant past ignoring the value of personal experience with students as a viable tool for engaging with the curriculum. Perhaps the greatest cultural piece influencing civic education has been the lack of political support at the national and state levels to create a unified message in regards to civic education. While 31 states currently test civics topics, only 29 states require high school students to take a course in government or civics (NACE, 2006). Additionally, 23 of the 50 states present their civic standards as explicit standards within their social studies standards and three states have separate civic standards. Another 18 states weave civics into their social studies standards (Policy Research Project on Civic Education Policies and Practices, 1999). The American Federation of Teachers [AFT] has reported on the difficulty related to setting clear and specific objectives in the area of civic education and recommends that a more unified approach, as has been done in math and science, would move teaching and learning in the social studies out of the lower thinking categories it is currently resigned to (1999). Civic educators see the concern extending to the No Child Left Behind Act [NCLB] as it does not emphasize testing of civics as it does for math and reading thus pulling the focus away from potential reform in civics education. Since the late 1960s, civic education at the secondary level has declined substantially. High school students now enroll typically in only one year of government and civics classes instead of three. NCLB does not emphasize civics proficiency, which further erodes the value of civics education at the high school level. To rectify this situation, national assessments in civics should be administered more frequently, and state officials should incorporate civics into their standards. (American Youth Policy Forum, 2006, ¶ 1). Many states fear the policies of NCLB marginalize civic education even further as other core subject areas are supported through legislation and testing. These fears reinforce the need for a connection between content and authentic opportunities for the application of that content in the lives’ of students.

Need to Improve Civic Education
When Americans were asked which qualities or aptitudes schools consider “essential” or “very important,” 86 percent replied “being a good citizen” (U.S. Department of Education, 1997). In the same U.S. Department of Education survey (1997) only 59 percent or respondents stated they believed schools had a major impact on the development of “being a good citizen” (¶ 4). There is ample research to show the American citizenry's interest in government is disappointing (Delli, Michael & Keeter, 1996; Erskine, 1963; Hyman & Sheatsley, 1947) as fewer and fewer Americans are showing up to vote (Abramson & Aldrich, 1982; Miller, 1992; Teixeira, 1987, 1992). The 1960 presidential election had a participation rate of 63 percent. The voting rate declined to about 50 percent in the 1996 presidential election with the 2000 presidential election showing a participation rate of 51 percent of eligible voters. While Americans between ages 18 and 30 make up the largest bloc of eligible voters in the country (at about 25 percent), abysmally low (and increasingly declining) numbers in this age group actually vote. According to a recently published Carnegie Corporation of New York report, youth voter turnout has dropped by at least 13 percent since 1972 and the occurrence of such social and political flashpoints such as Watergate; this equates to less than a 13 percent voter turnout among eligible young voters. Among the youngest voters, those between the ages of 18 and 24, the voting rate has dropped by a third over the same three decades. (Fields, 2003, p. 1) Putnam (2000) believes voter apathy as evidenced through statistics reflecting the downward trend is indicative of a more cynical view of civic participation: During the last third of the twentieth century formal membership in organizations in general has edged downward by perhaps 10-20 percent. More important, active involvement in clubs and other voluntary associations has collapsed at an astonishing rate, more than halving most indexes of participation within barely a few decades most Americans no longer spend much time in community organizations, we’ve stopped doing committee work, stopped serving as officers and stopped going to meetings. (p. 63) The 1998 National Assessment of Educational Progress (NAEP) survey found that only 6 percent of eighth-grade students could explain how countries benefit from a written constitution and only 30 percent of high school seniors understood the use of judicial review by the United States Supreme Court to protect minority rights (Hoff, 1999). The 1997 American Freshman: National Norms for Fall 1997 report (Sax & Astin et al., 1997) shows college freshman at a record low 26.7 percent when asked if it was essential for them to stay “up to date with political affairs.” This was a 2.7 percent drop from the previous year and a 31.1 percent drop from the 1966 reported high. The same National Norms report (1997) documented another all-time low 13.7 percent of freshmen reporting they frequently discuss politics. The all-time high for this category was in 1968 with 29.9 percent of college freshmen reporting they frequently discuss politics. Similarly, the ultimate act of citizen participation as defined by the political scientists (Walker, 2000), the act of voting, is also at an all-time low according to the 1997 National Norms report. Student election turnout plummeted from 76.9 percent in 1968 to 21.3 percent in 1997. The 1990 NAEP Report Card in Civics (as cited in Branson, 1998) results revealed that students have only a superficial knowledge of civics and lack depth of understanding. For example, only 38 percent of 8th graders knew that Congress makes laws; and nearly half of high school seniors did not recognize typical examples of the federal system of checks and balances. Although half of the high school seniors tested displayed a detailed knowledge of major government structures and their functions, only six percent demonstrated a more developed understanding of a wide range of political institutions and processes. (p. 16) “National, state, and local standards all indicate that the task in social studies classrooms is to support learning that really does increase a student’s competence and confidence in using important social studies knowledge and skills to have a better life and to contribute more as a citizen” (Sunal & Haas, 2002, p. 4). As evidenced by data in the previous section, increases in standardized test results and survey results have not been evident supporting the need for more overt connections between teaching of civic knowledge and skills to authentic assessments measuring student efficacy in civics.

Current Instructional Models for Teaching Civic Education
The challenges of deciding what content and purpose should be taught in civic education are exacerbated by the various approaches to teaching civic education and the defined goal of each approach. Civic educators have traditionally utilized one of the following approaches to teach civics: citizenship transmission, social science/history, reflective inquiry, personal development, or informed social criticism/reform (Barr, Barth, & Shermis, 1977). A brief review of the traditional approaches to civic education follows.

Citizenship Transmission
Citizenship transmission insists schools instill the “American creed” in children with the defined purpose of binding the nation together (Shaver, 1985). This creed would include those core democratic values centered on due process, freedom of choice, respect for others, multiculturalism, free access to information, and respect and value for rational thought (Shaver as cited in Chapin & Messick, 2002). According to Shaver (1985) the student must accept the basic values in the creed as fundamental beliefs. The assumption with the citizenship transmission model is that it is the teacher's job to assure students arrive at the correct answer for any civic concept. The student is strictly the receiver of any piece of civic information. The fear of opponents to the citizenship transmission approach within the context of developing a citizenry that is adept at critiquing the world around them to authentically engage in the democratic process is that students are being trained to accept a solution to a problem rather than exploring the solution to the problem on their own or with guidance. Citizenship transmission stresses the knowing of civic values as most important. Therefore, the understanding of the civic values is not a priority thus limiting discourse and leading to a form of indoctrination (Chapin & Messick, 2002).

Social Science/History
The social/science history model is one predicated on a knowledge-centered approach (Chapin & Messick, 2002). The intent of this model is to inform students of the major social studies concepts in each of the social studies disciplines. Applied to civics education, the social science/history model would have students reviewing primary and secondary source documents and comparing the documents to formulate a hypothesis. The purpose is to show students how our assumptions lead us to jump to conclusions. The model often utilizes an interdisciplinary approach where students might study a topic such as the Civil Rights Movement where each student is required to provide hard data on a given topic and to write deeply about the facts and opinions related to the topic. This would require students to engage in those areas of the social studies necessary to successfully demonstrate their understanding such as, in this case, sociology and history. More specifically, students would use primary and secondary source documents to study specific pieces of legislation connected to the Civil Rights Movement. The model comes under much criticism due to the ill-defined parameters of the hypothesis formulation, and the primary and secondary source documents are often too difficult for the students to read and comprehend.

Reflective Inquiry
Reflective inquiry, also labeled public issues-centered approach or real-world problems approach, emphasizes the importance of motivating students to think critically (Chapin & Messick, 2002). Typically students would be responsible for identifying an issue to explore, to find evidence for or research the issue, to analyze the evidence or research and to interpret or act upon their discoveries. The fault of this model lies in the lack of a clear and concise definition of reflective inquiry.

Informed Social Criticism/Reform
Informed social criticism/reform is used to guide students to change an existing institution in our world through an understanding of the necessary knowledge and skills. Students are challenged to use the ideas of justice, democracy and human rights as the means by which to critique social institutions (Chapin & Messick, 2002). The informed social criticism/reform model requires teachers and students alike to be willing to discuss the potentially highly controversial issues associated with the social institutions under critique. In addition, students involved in this type of model need to believe or trust that their actions will be accepted by governmental actors and lead to change.

Democratic Schools
There is much talk these days about the importance of teaching democratic values in our public schools. It appears that newspaper columnists, teachers' unions, public organizations and other civic minded people have suddenly come to realize that our youth is growing up ignorant of, and uncommitted to, the great principles upon which our nation is based.

Although there may be full agreement that the problem exists, it seems that the proposed cure – more classes on democracy – is no better than the disease. It can be asked why is it that people persist in thinking that the solution to real-life problems is talking about them, or if anyone really believe that subjecting children to yet another course will achieve really meaningful goals. Schools can't even get kids to read or write or do arithmetic properly, despite endless hours of classroom effort. And the question is if we are going to make them into the defenders of freedom by adjusting the curriculum once more.

The simple fact is that children are not committed to democratic principles, or political freedom, or the bill of rights, or behaving as responsible people because they themselves do not experience any of these lofty matters in their everyday lives, and in particular in their schools. Children do not have rights in school, they do not participate in meaningful decision-making at school (even where the decisions directly affect their own lives) nor do they have the freedom of self determination in school. In fact, the schools are models of autocracy - sometimes benevolent, sometimes cruel, but always in direct conflict with the principles on which our country is based.

The way to ensure that people of any age will be deeply committed to the American Way is to make them full participants in it: making schools democratic, giving children freedom of choice and the basic rights of citizenship in schools, and they will have no problem understanding what this country is about (Greenberg, 1992).

Summary
Certainly any one of the aforementioned instructional social studies models or any combination of those models would be sufficient to successfully instill the knowledge, skills, and dispositions for an adequate civic education. Throughout the review of the instructional models used to teach civics, little has been explored as to how to transfer the strengths or intentions of these models into adulthood and civic action through authentic classroom practice. Nor have we seen how these models are used differently or why their use is altered as students move through the public school system. What is clear is the importance of teacher expertise in increasing civic engagement and results and that placing non-experts, or out-of-field teachers, assume the responsibility for increasing student achievement in the area of civics will only exasperate the problem (Ingersoll, 1998). The consequences of not realizing expert guidance and leadership in civic education will have a direct negative impact on our democratic process and the effectiveness of that process. To limit civic education to a prescribed model does not allow students or teachers to authentically engage in the identified characteristics of an effective citizen (NCSS Task Force, 2001). The instructional model developed in this research does not assume every student will obtain the characteristics of an effective citizen, but that most students must if we are to continue with an active and engaged citizenry necessary for an effective democracy. What the model did assume is the need for “…attending more carefully to the moral requirements of liberal public life and by doing what is possible and proper to reinforce them” (Galston, 1991). Public schools, as an agent of the government, are poised to allow students to each identify, explore, and articulate these moral requirements. To do this free of prescribed means and outcomes while at the same time working within those civic virtues (characteristics) would allow for students to rehearse what it means to be a citizen. ...we need a group differentiated citizenship and a heterogeneous public. In a heterogeneous public, differences are publicly recognized and acknowledged as irreducible, by which I mean that a person from one perspective or history can never completely understand and adopt the point of view of those with other group-based perspectives and histories” (Young, 1989). Young (1989) goes on to argue for a classroom where students are given defined spaces to reflect upon and to have discourse on issues of importance; a classroom where the virtues of civics can be explored, understood, and questioned. Galston's work (1991) identified those liberal virtues in their broadest sense: Some of the virtues needed to sustain the liberal state are requisites of every political community. From time to time, each community must call upon its members to risk their lives in its defense. Courage – the willingness to fight and even die on behalf of one's country – is thus very widely honored, even though there may be occasions on which the refusal to fight is fully justified. In addition, every community creates a complex structure of law and regulations in the expectation that they will be legitimate, hence binding, without recourse to direct threats or sanctions. The net social value of law is equal to the social benefits it engenders minus the social costs of enforcing it. As the individual propensity to obey the law diminishes, so does a society's ability to pursue collective goals through the law. Law-abidingness is therefore a core social virtue... Finally, every society is constituted by certain core principles and sustained by its members’ active belief in them. Conversely, every society is weakened by the diminution of its members’ belief in legitimacy. Loyalty – the developed capacity to understand, to accept, and to act on the core principles of one's society – is thus a fundamental virtue. (p. 221) While the need for a civic education to sustain an effective democracy has been agreed upon by many groups, the participation in that democracy “does not occur instinctively nor does it develop organically. Educators have a role to play – helping students in thinking carefully…” (Kahne & Middaugh, 2006, p. 607).

Questions

 * 1) Which approach to civic education is the best for creating the informed citizenry the Founders felt necessary to a robust democracy?
 * 2) Why does “good citizenship” lead to good democracy; or does it?
 * 3) Why do students view voting as a unnecessary part of being a citizen?
 * 4) Should all public high schools facilitate registration and voting for their students?
 * 5) If civics was a component of high-stakes testing, how would it be taught?
 * 6) In what ways might the decrease in recess in the early grades effect outcomes for civic efficacy in the public schools?
 * 7) Shouldn't civics fall into the hands of parents to teach?
 * 8) Do you believe history should be at the center of a solid civic education?
 * 9) If we are to model civic efficacy for students, should we involve them in the design and assessment of their curriculum?


text: Bicycles/Maintenance and Repair/Bottom Brackets

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Bicycles/Maintenance and Repair/Freewheels and Cassettes

General The freewheel is the ratchet device on the rear wheel that makes it possible to roll without pedaling, for example, when free-wheeling down a hill. It operates whenever the wheels are going faster than the drive-force, in this case the pedals and chain. The term is also used to describe a bicycle component that combines both a ratchet and a cog-set in one single screw-on assembly, and this is the most commonly used meaning. The alternative way of installing a cog-set is to use a cassette, a stack of cogs that slides onto a splined hub. Whether a freewheel or a cassette is used on the rear hub of the bike, there is always a ratchet; in the case of a freewheel assembly the ratchet is unscrewed with the cogs, whereas a cassette is merely a stack of cogs, and the ratchet is within the freehub of the wheel. Cog pitch (here is means inter- cog center-to-center spacing) is the main consideration for shifting and apart from the restricted choice of freewheels, it is unimportant to the derailleur whether a freewheel or a cassette is installed, provided that the spacing between the cogs is right.

Bikes without gear-changing exist, so-called fixed-gear bikes or fixies. They have one chain-ring and one rear cog. Although such bikes are not technically prevented from having a ratchet device, they usually have none, so that the rider's legs will be forced to rotate whenever the bike is moving. Some new riders of such bikes can find the experience disturbing.

The threaded hub of the freewheel installation is clearly different from the splined freehub of the cassette installation and the cog-set of one type cannot be installed onto the other. When an upgrade from freewheels to cassettes is to be made, it is most convenient to do so by changing the rear wheel for one with a freehub and cassette already installed. Examples of a freehub and of a threaded hub can be seen clearly in the adjacent photographs.

Both freewheels and cassettes exist in a variety of cog combinations, and because chains are all half-inch spaced, cogs can be defined entirely by their numbers of teeth. For example, an 11T cog has eleven teeth, and a cog-set with a range of 11T-30T might have say, seven cogs, the smallest having eleven teeth and the largest thirty. Because cog-sets have been in use for a long time, the most useful sets have been identified by code letters, for example, the above set is designated  'am' .

For those who need more than seven rear cogs, a bike with a cassette becomes the choice. This is because bikes are rarely made with freewheels of more than seven cogs. Larger numbers of gears can be obtained even with a seven speed freewheel or cassette by simply having more front chainrings. For example, the combination of three front chainrings and seven rear sprockets provides 21 gear combinations (3 X 7), and enjoys the wider working tolerances of seven speed shifting at the rear.

This page explains how to remove and fit cassettes and freewheels and provides links for further information on that subject. An introduction to the principles of indexed shifting is given, and notes on the complexity of gear-shifting standards is provided with the help of tables.

Complexity
The hub of a rear wheel has an extension on it, and this is threaded or splined to fit either a freewheel or a cassette respectively. Extensions differ in length, according to the number of cogs to be installed, but to maintain reasonable chain alignment and reduce the stresses on the hub, there is a limit to the extension that can be considered. So, when a number of cogs greater than say, seven, is crammed into a set, the teeth and spacers need to be made thinner. In this way the space or pitch between the cogs can be reduced. (See the table in the drop box below for a summary on cog-pitch.)  A narrower chain is also needed for a narrower cog-pitch.

Although cassette cogs and most freewheel cogs can be replaced individually, doing so favors cassettes. Freewheel cogs need two chain-whips to remove them from the cluster after the freewheel itself if free of its hub, one to unscrew the cog and another to prevent the freewheel from rotating; anyway, individual replacement cogs for freewheels are now hard to find. Freewheels rarely exist beyond 7-speeds, while cassettes exist in up to 11-speeds. Cassette cogs are easier to remove, are abundant in supply, and offer the greatest scope for modification.

Cog pitch (here means inter-cog spacing), cog thickness, and spacer thickness differ greatly for the various bike types, (see Sheldon Brown's Cribsheet on Spacing for detailed lists), not only for different sizes of cog-sets, but between different manufacturers for the same size of cog-set. As a result, the derailleurs and shifters used differ greatly as well. When the different shift ratios of derailleurs, cable-pull-lengths of shifters, and the pitch (inter-cog spacing) of cog-sets  are considered together, it becomes clear that arbitrarily selected drive components will hardly ever work well together.

Examples of the various manufacturers' cog-pitches and the expected results of mixing drive gear can be found in the drop-box below. For the full description upon which these notes were based, see CTC on Rear Shifting. In the way of relief, some notes on the more common ground are given in the next section.

Consistencies
Although complexity is the rule as opposed to the exception, there are some consistencies in manufactured goods. Examples include manufacturers who produce components that suit the drive-trains of others, a tendency to standardize spline patterns for cassettes on the most popular brand name, and the standardized pitch (inter-cog spacing) for 7-speed cog-sets.

Some SRAM shifters, for example, GripShift types marked as MRX, are suitable for Shimano systems, since these shifters suit the so-called 2 : 1 family of Shimano derailleurs; in fact their shift ratios are not exactly 2 but 1.7. (Shift ratio is the reciprocal of actuation ratio which is itself the ratio of input change to output change, so here, one length of cable pull causes a transverse movement that exceeds it by 1.7 times). Other shifters by the same SRAM manufacturer, are suited to the 1:1 family of derailleurs; (with exact 1.1 shift ratios), and so these do not match the Shimano derailleurs. The subject of compatibility in drive-train gear has received much attention over the years and despite the complexities involved, it has been found that some mixed systems can work well enough provided that there is careful selection. (See the examples in the drop-box of the above section).

Cassette spline patterns for Shimano freehubs fit a number of other makes of cassette, and within its own products is the same for virtually every type of cassette. With minor exceptions, the SRAM manufacturer has used the same sprocket pitch (inter-sprocket spacing) and spline pattern as Shimano, so that their products are used interchangeably, (with the possible exception of cog ramping functions). The tool used to remove Shimano cassette locking-rings will unlock them for all of their modern cassettes, and in addition, the cassette locking-rings of SRAM, SunRace, SunTour, Chris King and various others. A similar situation exists for freewheel removals, with the Shimano freewheel tool unlocking all of its own and Sachs, Aris, and Sun Race freewheels besides. As far as is known, the Campagnolo cassette removal tool is intended only for its own locking rings, though some report that a Shimano tool is a (risky?) 'near fit'. The Shimano standards for spline-fittings come closest to an informal industry standard.

Seven-speed sprocket pitch is almost always 5mm , so shifter/derailleur combinations that are designed for seven-speed use can be made to work on all seven-speed sprocket sets, (subject to any frame fitting constraints). Consideration of the mixed shifts and pitches given elsewhere on this page will emphasize how unusual this fortunate situation is. The main consideration is that the shifter's cable-pull suits the derailleur's shift ratio so that between them they make the necessary 5mm gear shifts. How the necessary shift is accomplished is of no concern. For example, a Shimano 7-speed shifter pulls the cable by 2.9 mm while the derailleur has a shift ratio of 1.7. The resulting product, (2.9 mm x 1.7 = 4.93 mm), is about 5mm so the combination works well. Another shifter and derailleur combination, say SRAM, also produces the necessary 5mm derailleur shift using 4.5 mm of cable pull and a derailleur shift ratio of 1.1. (4.5mm x 1.1 = 4.95mm = approx 5mm). There is little cross-manufacturer consistency for the pitch of the larger sprocket-sets, so the mixing of components for these larger cog-sets needs more care. See CTC on Rear Shifting for more on mixing components of the drive system.

Freewheel threads on modern bikes are the same.  Regardless of where in the world the bike is made, the standard (ISO) for freewheel mounting threads is  1.375 inches in diameter and 24 threads per inch. This means that any modern freewheel is likely to fit a standard threaded hub. This is not necessarily the case for older bikes, and the details for these can be found at Sheldon Brown's Freewheels. There are a number of other ISO standards in use for bikes; see Sheldon Brown's ISO Standards for Bikes.

Removal and Replacement
The tools needed to remove and replace cassettes differ according to the manufacturer. The most commonly used tools include a locking ring remover (see the image), shaped for the lock ring in use, and a chain-whip (see the image), a tool that engages with the cogs to prevent turning while the locking ring is being unscrewed. (A chain-whip is needed only for cassette removal). Because the locking ring remover is merely a tool-end, an extension arm or a long adjustable spanner is needed to provide the necessary torque. An external page that describes the different removal tools of various manufacturers is provided at Park Tool's Cassette and Freewheel Removal, along with other practical advice.

The tools needed for the removal of freewheels have similar appearance to those for cassettes, though the removal tools might not always be interchangeable. The effort in removing a freewheel is likely to be greater than that for a cassette's locking ring owing to the freewheel's self-tightening during normal cycling.

The removal of cassettes and freewheels that have been in use require considerable force, and under force the tool might tend to slip, possibly damaging the tool or its receptacle. For this reason some mechanics modify the simple procedures below by fastening the tool in position with the reassembled quick-release wheel skewer. When this is done the skewer springs are omitted and the skewer cap is tightened against the removal tool to take up the slack. The tool must not exceed one turn with the skewer still in place, and must be removed before completing the removal of the cassette or freewhweel.

Tools required

 * Cassette locking ring or freewheel removal tool for the product in use.
 * Adjustable wrench, about one foot long, or specific tools with similar leverage.
 * A chain whip, for cassette removal only.
 * Torque wrench, in a range that includes 30 ft.lbs:  Mainly for cassette locking ring replacement, (optional).
 * Bench with a secure vice, (optional).

Cassette Removal
Howsoever the effort is eventually applied or from what angle, these directions are made assuming that the cogs of the wheel are facing you.
 * Remove the rear wheel from the bike.
 * Unscrew and remove the skewer assembly from the wheel.
 * Fit the correct locking ring removal tool against the locking ring. Some removal tools have their own guide rods that feed through the middle of the hub.
 * Apply a chain whip to the cogs to pull them clockwise, to prevent them from turning anti-clockwise during removal.
 * While holding the cogs firmly with the chain whip, turn the removal tool with the wrench or lever-arm anti-clockwise to release it.  Slackening requires considerable force, so a longer lever arm or pipe extension might help.   It is usual to hear a clicking  noise as the ring is initially released.   Note that the torque wrench should never be used for heavy work of this kind.
 * The cluster of cogs can then be removed.  Note the alignment and sequence of the parts for reassembly before splitting up the cog-set. Consider stringing them together, since the spacer thicknesses might differ within the cluster.   The smallest cogs will be noted to have built-in spacers, and perhaps shims.

For those who have a bench fitted with a suitable vice, fit the tool into the cassette in the usual way and if possible use the skewer and its cap (no springs) to set it in position. Having done so, and with the wheel flat and the cog-set on the underside, grip the flats of the removal tool in the vice. Hold the cogs in the chain-whip and with it, turn the cogs anti- clockwise, (looking down on top of the wheel), to release the ring. Do not turn the wheel to make this release, but use only the chain-whip, letting the wheel turn with the cogs.

Further details on the subject of cassette removal can be found at Park Tool's Cassette and Freewheel Removal. A video that clearly shows the unlocking of a typical cassette is available at FR-5 Lock-ring video.

Cassette Replacement
The replacement of a cassette does not require the use of a chain whip, and the process is otherwise just a reverse of the removal. The procedure is as follows:

Howsoever the effort is eventually applied or from what angle, these directions are made assuming that the cogs of the wheel are facing you.
 * Clean the cassette and oil-wipe the cogs of the cluster.  Grease the threads of the locking-ring and its receptacle.
 * Fit the cassette cogs onto the freehub splines with the correct orientation. While manufacturers attempt to ensure that only one working alignment can exist, there will no doubt be exceptions. In addition, take care that the cassette spacers are in the correct sequence, since they are not always identical.
 * Screw on the locking ring loosely into position.
 * Turn the tool on the locking ring clockwise with a wrench, (no chain whip needed), to establish the manufacturer's recommended torque.  In the absence of data, aim for about  of 360in.lbs,  (40N.m),  (30 ft.lbs).

Freewheel Removal
Howsoever the effort is eventually applied or from what angle, these directions are made assuming that the cogs of the wheel are facing you. If a bench-vice is to be used, then first set the removal tool in the wheel and if possible use the skewer and its cap (no springs) to set it in position. Place the wheel, cogs down with the flats of the tool in the vice. Turn the wheel anti-clockwise, (looking down on top of the wheel), to unscrew the freewheel. An inflated tire gives the best grip.
 * Remove the rear wheel from the bike.
 * Unscrew and remove the skewer assembly from the wheel.
 * Fit the correct removal tool into the recess in the hub. Some removal tools have their own guide rods that feed through the middle of the hub.
 * Turn the removal tool with the wrench or lever-arm anti-clockwise to slacken the freewheel.  Slackening requires considerable force, so a longer lever arm or pipe extension might help.   Consider the use of a bench and vice if it is available.   Note that the torque wrench should never be used  for heavy work of this kind.
 * The freewheel cluster can then be removed as a complete unit.

Freewheel Replacement
Howsoever the effort is eventually applied or from what angle, these directions are made assuming that the cogs of the wheel are facing you.
 * Unscrew the skewer assembly from the wheel.
 * Clean the freewheel, oil-wipe the cogs, and grease both its threads and the threads on the hub.
 * Fit the freewheel onto the hub threads until it is hand tight. Tighten the freewheel further using the wrench and tool in a clock-wise direction, to obtain the torque recommended by the manufacturer.  In the absence of data, aim for about  of 240 in.lbs,  (27 N.m),  (20 ft.lbs).  The freewheel will tighten in use in any case;  the above figure is given to avoid uncertainty at the point of delivery.

There is little advantage in making use of a vice for the freewheel fitting, but for those who intend to do so, they can find a method at Park Tool's Cassette and Freewheel Removal.

Gearing Calculations
This section provides the rudimentary calculations associated with bicycle gearing.

Distance Shifted
In all indexed shifting, (as opposed to friction shifting), there is a fundamental relation to describe the transverse distance that a derailleur cage shifts across the cog-set or chainrings. The transverse distance shifted is equal to the product of the shifter's cable pull and the derailleur's shift ratio. In practice, the distance shifted must equal the center to center spacing of the cogs, (or chainrings). Most modern rear-shifting is indexed, and some front-shifting is indexed (for example, Shimano). See Gear Changing Dimensions for a selection of such data. Transverse Distance of Derailleur Cage = Shifter Cable Pull  x   Derailleur Shift Ratio

For example:  For a seven-speed rear cogset, a Shimano rear derailleur, and a SRAM MRX twist 7-speed shifter; we have; Transverse Distance of Derailleur Cage = 1.7 ratio x   2.9mm cable pull    =    4.93mm    Approximately 5mm This suits all seven speed center to center spacings since they are all set at 5mm centers.

Derailleur Capacity
When a rear-derailleur is planned or when an existing chain ring or cogset is changed, the required total capacity of the derailleur needs to be checked. The total capacity refers to the ability of the derailleur to take up slack across the entire range of gear combinations. Since the gear combinations are affected by the range of both the chain rings and the rear cogset, these are both represented in the calculation. The required capacity of the rear derailleur becomes:

Minimum Required Capacity = (Largest cog - Smallest cog) + (Largest chainring - Smallest chainring)

For example:  For a cogset 11T - 30T with only one chainring of 38T; we have; Minimum Required Capacity = (30T - 11T) + (38T - 38T) = 19T   The 'total capacity' spec for the derailleur must be at least 19T.

Another example: For a cogset 11T - 28T and chain rings 20, 30, and 42; we have; Minimum Required Capacity = (28T - 11T) + (42T - 20T) = 39T   The 'total capacity' spec for the derailleur must be at least 39T.

Other consideraions within a derailleur's specification sheet include front chain ring tooth difference and smallest and largest rear cog sizes. This latter requirement ensures that as the derailleur traverses the cogs on its in-built gradient, the clearance of the cage, as set by the 'b-height' adjustment, is reasonably consistent. Attention should also be paid to the number of gears for which the derailleur is intended, and whether or not the shifter is compatible with its shift ratio.

Gear-Inches and Ground Covered
Gear inch calculations are used by those who plan the design of cycle gearing, and are useful when a new bike is being considered. They allow a tabular layout where the gears associated with adjacent chain rings can be studied for their overlap and convenience, and allow a purchaser to predict whether or not an intended ride will have a similar sweet spot, or feel, like their existing bike. Multiplying the gear-inch figure by the constant pi (approximately 3) gives the distance covered by one complete turn of the pedals. Calculations are made for each gear combination of front chain ring and rear sprocket. The formula for any one combination is just: Gear Inches = Outside Inch-Diameter of driven Bicycle Wheel  X  (Size front chain ring / Size rear sprocket)

For example:  For an 11T rear sprocket and a 38T chain ring, with a 26 inch rear wheel diameter, we have: Gear Inches  =   26   X   (38T / 11T)   =  89.8

and the distance covered in one turn of pedals is: Distance (inches)  =   gear-inches  X  pi   =   89.8   x   3.142   =   282.2 inches   =   23.5 feet for one turn of the pedals.

It is usual to make a table of the gear inches and then possibly another table showing the change in gear inches between adjacent gears. This permits an understanding of the relative effort required in the use of adjacent gears. An on-line calculator that saves some work can be found at Gears'' by Sheldon Brown. A typical gear-inch table is shown below, and although it is not entirely obvious in this example, for convenient arrangements, the top figure of each column is most usually found in the middle of the next column to its right.


text: Bicycles/Maintenance and Repair/Shifters


text: Bicycles/Maintenance and Repair/Headsets


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Talk:The American School/The Role of Education in a Democratic Society

"On April 20, 1999, two seniors killed 12 students and one teacher at Columbine High School in Littleton, Colorado. This marked the first school shooting ever and America’s citizens were stunned."

The first school shooting ever? The authors need to check their facts. Cilantrohead (talk) 15:41, 4 February 2008 (UTC)


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User talk:Parallelized

Welcome!
Come introduce yourself at the new users page. If you have any questions, you can ask there or contact me personally.--Whiteknight (Page) (Talk) 16:17, 4 February 2008 (UTC)

title: User talk:Parallelized


text:
User talk:Swarhan

Welcome!
Come introduce yourself at the new users page. If you have any questions, you can ask there or contact me personally.--Whiteknight (Page) (Talk) 16:17, 4 February 2008 (UTC)

title: User talk:Swarhan


text:
Metabolomics/Analytical Methods/NMR

Back to Previous Chapter: Hormones Next chapter: Computational Modeling of Metabolic Control Go to: Mass Spectrometry
 * 1) 1H NMR
 * 2) 13C NMR
 * 3) 31P NMR
 * 4) Other nuclei

Articles and Web Pages for Review and Inclusion
Peer-Reviewed Article #1:

Metabolic changes of salicylic acid-elicited Catharanthus roseus cell suspension cultures monitored by NMR-based metabolomics

Biotechnology Letters, Volume 31, Number 12 / December, 2009, 1967-1974

Main Focus

 * Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.

New Terms

 * New Term 1: Definition. (source: http://)
 * New Term 2: Definition. (source: http://)
 * New Term 3: Definition. (source: http://)
 * New Term 4: Definition. (source: http://)
 * New Term 5: Definition. (source: http://)
 * New Term 6: Definition. (source: http://)
 * New Term 7: Definition. (source: http://)
 * New Term 8: Definition. (source: http://)
 * New Term 9: Definition. (source: http://)
 * New Term 10: Definition. (source: http://)

Summary

 * Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

Relevance to a Traditional Metabolism Course

 * Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?

title: Metabolomics/Analytical Methods/NMR


text:
Metabolomics/Metabolites/Carbohydrates

Back to Previous Chapter: Introduction to Metabolomics Next chapter: Hormones Go to: Lipids

 * 1) Glucose
 * 2) Sucrose and Other Dissacharides
 * 3) Polysaccharides

=Carbohydrates=

KEGG MAPS
Examples of Carbohydrate Metabolites

Lactose: http://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&cid=6134 (PubChem)

Glycogen: http://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&cid=439177 (PubChem)

Ribose http://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&cid=5779 (PubChem)

Glyceraldehyde http://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&cid=751 (PubChem)

Starch: http://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?t=l&cid=439341 (PubChem)

Websites

'''[http://www.whatislife.com/reader2/Metabolism/pathway/glycogen.html What is Life? Pentose Phosphate Pathway and Glycogen Metabolism] and [http://www.whatislife.com/reader2/Metabolism/pathway/glycolysis.html What is Life? Glycolysis and Gluconeogenesis]'''

 Summary:  This website gives a basic overview of carbohydrates and the role they play in the human body. It also covers metabolism of carbohydrates. Glucose oxidation can be seen in Glycolysis as well as the pentose-phosphate pathway while the regeneration of glucose is seen in gluconeogenesis. This website shows, step by step, the reactions of these pathways and the energy yield from each step. The second link for this website goes to a page covering glycogen metabolism, showing the net reactions for the synthesis and degradation of glycogen. Both links have sections on major control mechanisms for glucose and glycogen metabolism.

 Terms:  Glucosidases – enzymes involved in breaking down complex carbohydrates such as starch and glycogen

ascorbic acid – a sugar acid with antioxidant properties. Scurvy is the disease caused by a deficiency of vitamin C.

glucostat – removing glucose when offered in excess via glycogen synthesis and glycolysis and providing glucose when needed by gluconeogenesis

concomitant – accompanying in a passive way

hepatic lipase – lipolytic enzyme, synthesized by hepatocytes and found localized at the surface of liver sinusoid capillaries

phosphoglucomutase – an enzyme that transfers a phosphoryl group on a glucose monomer from the 1' to the 6' position in the forward direction or the 6' to the 1' position in the reverse

UTP – (Uridine triphosphate) - a pyrimidine nucleotide, consisting of the organic base uracil

Relation: This website clearly explains what is meant by carbohydrate metabolism. It shows the relationship between glycolysis and gluconeogenesis and the three enzymes that are different between the two pathways. It also shows major control methods for the metabolism of carbohydrates, specifically glucose and glycogen in this case. This site is a great resource to use for a more in depth coverage of glucose and glycogen metabolism.

The Human Metabolome Database

Summary: The Human Metabolome Database is a database that contains information about small metabolites. This information includes chemical composition, taxonomy, location in the body, normal levels of the metabolite, genomic sequence, pathways it is involved in, and other molecules it interacts with. This site has links to KEGG, PubChem, MetaCyc, ChEBI, PDB, Siss-Prot, and GenBank (see terms below). This website is particularly easy to use and has enormous amounts of information on each molecule. Just go to the main page and type in the name of the molecule you are looking for.

Terms: KEGG – Kyoto Encyclopedia of Genes and Genomes - bioinformatics resource for linking genomes to life and the environment

PubChem – Free database of chemical structures of small organic molecules and information on their biological activities

MetaCyc – Encyclopedia of Metabolic Pathways - contains over 900 pathways from more than 900 different organisms

ChEBI – Chemical Entities of Biological Interest (ChEBI) is a freely available dictionary of molecular entities focused on 'small' chemical compounds

PDB – Protein Data Bank - Archive of experimentally-determined, biological macromolecule 3-D structures from the Brookhaven National Laboratory

Swiss-Prot – manually curated biological database of protein sequences

GenBank – NIH genetic sequence database, an annotated collection of all publicly available DNA sequences

Relation: This website provides easy access to information on small molecules, such as carbohydrates, that would be useful in the study of metabolomics. You are able to determine what the normal levels of a metabolite is in the body and the pathways involved that could increase or decrease those levels. This would be helpful in screening for particular metabolic diseases.

University of Akron: Carbohydrate Metabolism

Summary: This is a very basic website outlying the principles of carbohydrate metabolism. It touches on the metabolite glucose including its synthesis and degradation pathways. It also touches upon other carbohydrates such as starch, glycogen, and maltose. This site describes what these metabolites are used for in the body and how they are a part of several different pathways. Biosynthesis and regulation of carbohydrate metabolites are also a part of this website.

Terms: Fructose – is a simple reducing sugar (monosaccharide) found in many foods

Aldolase – an enzyme that helps convert glucose into energy

Fermentation – the process of energy production in a cell under anaerobic conditions (without oxygen)

Propionate – is a naturally-occurring carboxylic acid

Biotin – vitamin H or B7, water-soluble B-complex vitamin, used in carboxylation reactions

NDP-Glucose – Nucleoside diphosphate-Glucose – activated intermediate

Glycosidic bond – certain type of functional group that joins a carbohydrate (sugar) molecule to another

Relation: This site shows the different ways that carbohydrate metabolites interact in our body and how they can by synthesized and broken down. This site is a great tool to visualize where certain metabolites are found and the pathways they are involved in. With many diagrams, this site is ideal for piecing together where carbohydrate metabolites fit in the grand scheme of things in the human body.

Peer-review Articles

A Model for Carbohydrate Metabolism in the Diatom Phaeodactylum tricornutum Deduced from Comparative Whole Genome Analysis

Summary: Diatoms are responsible for 20% of the earth’s carbon fixation. However, this mechanism is not well understood. This paper attempt to clarify this process by proposing a model for carbon fixation by diatoms. Little is also known about the synthesis and storage of Chrysolaminaran, the main carbohydrate in diatoms. This carbohydrate is secreted and is a major component of biofilms. In this paper, a model for the carbon concentrating mechanism, photorespiration, the oxidative and reductive pentose phosphate pathways and a model of the glycolytic reactions were generated. The model for the glycolytic reaction is shown below.

Link to glycolytic reaction proposed by this paper

Terms: Diatoms – major group of eukaryotic algae, and are one of the most common types of phytoplankton, most are unicellular

Rubisco – Ribulose-1,5-bisphosphate carboxylase/oxygenases - catalyzes the incorporation of CO2

Chrysolaminaran – the principle storage carbohydrate in diatoms

Chimeras – two or more different populations of genetically distinct cells

Endosymbiont – any organism that lives within the body or cells of another organism

Plastids – organelles that only exist in plant cells and photosynthetic protists, responsible for photosynthesis

in silico analysis – analysis performed using computers in conjunction with informatics capabilities

chlorenchyma cells – parenchyma cells that contain chlorophyll

periplasmic space – space seen between the plasma membrane and the outer membrane

Relation: Much is known about carbohydrate metabolism and the many different carbohydrate metabolites in the human body. However, it is surprising that little is known about how diatoms fix carbon dioxide since it is so important to our survival. This paper takes the first step in proposing a mechanism by which this takes place. Someday, we may find this very diagram in our textbooks.

Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress

Summary: In order to access this article, you must first complete a free registration with the journal of biology. This study is one of the first to develop a mathematical model that describes the observed experimental changes in metabolic flux. In response to reactive oxygen species, yeast will shift from glycolysis to the pentose-phosphate pathway as an immediate and protective response to ROS. This shift is made in order to maintain redox balance in the cell.

Terms: Deleterious – harmful, injurious

Triose-phosphate isomerase – TPI - catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate

metabolic flux – the rate of flow of metabolites

Reactive oxygen species – ROS - oxygen ions, free radicals, and peroxides, both inorganic and organic

Perturbations – disturbance of motion, course, arrangement, or state of equilibrium

de novo – afresh, anew, beginning again

diamide – Any compound containing two amido groups united with one or more acid or negative radicals

Relation: It is well known that the human body will alter which pathway it uses (glycolysis or gluconeogenesis) depending on the carbohydrate status of the blood. This study has now shown that yeast will change from using glycolysis to the pentose phosphate pathway in response to reactive oxygen species. It is interesting to see how many different organisms have the ability to switch between pathways in order to counteract detrimental affects or to save energy.

Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism

Summary: This paper demonstrates the importance of the ATP-sensitive potassium channel in controlling the amount of insulin secreted by pancreatic cells. It is shown that having a mutation in the genes encoding for this potassium channel can depolarize the membrane leading to an increase in the basal level of insulin secretion. This can lead to the disease, hyperinsulinism.

Terms: Hyperinsulinism – refers to an above normal level of insulin in the blood of a person or animal

Sulfonylurea – A class of oral hypoglycemic agents (pills and capsules taken to lower the level of blood glucose) by people with type 2 diabetes

Phosphoinositides – serve as direct local modulators or recruiters of the protein machineries that control membrane trafficking

Hypoglycemia – is the medical term for a pathologic state produced by a lower than normal level of glucose in the blood

Somatostatin – growth hormone inhibiting hormone

octreotide.- potent inhibitor of growth hormone, glucagon, and insulin

Chemiluminescence – the emission of light (luminescence) with limited emission of heat as the result of a chemical reaction

Exogenous – caused by factors from outside the organism or system

Relation: Throughout the study of metabolism, we learn that a pH and charge gradient is necessary to have across a membrane. In this case, the charge gradient is essential for proper signaling in the cell. With a lower depolarization, insulin is secreted at a higher basal level, leading to the disease of hyperinsulinism.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1694820.com

Summary: The main point of this peer review article is to discuss the glycolysis process, which results in the formation of ATP as the main fuel in the anaerobic eukaryote, Monocercomonoides. Both ATP and Glucose are metabolites that relate directly to glycolysis and would be included in the organism's metabalome. Since anaerobic eukaryotes lack a complete tricarboxylic acid cycle, they can only extract few molecule of ATP per molecule of glucose. This is opposite of human cells, which makes this article important as it discusses alternate versions of enzymes in glycolysis. In anaerobic eukaryotes, enzymes such as pyruvate orthophosphate dikinase and pyrophosphate-fructose 6-phosphate phosphotransferase were examined through horizontal gene transfers from the bacteria in question to other eukaryotes. Horizontal gene transfers are processes in which an organism transfers genetic material to another cell that is not its offspring. Analysis of the glycolytic pathway of Monocercomonoides resulted in identification of both single-gene trees and conserved HGT events that provide evidence for the monophyly of protists known as Ecavata. Shared horizontal gene transfer events between oxymonads and both Giardia and Trichomonas further supported this relationship. This relationship becomes an important resource as it focuses on using glucose metabolites of Monocercomonoides to determine its lineage.

Terms: Horizontal Gene Transfer- process in which an organism transfers genetic material to another cell that is not its offspring

Monophyly- a group of organisms that includes an ancestral species and all of its descendants.

Oxymonad- a group of flagellated protozoa found exclusively in the intestines of termites and other wood-eating insects.

Diplomonads- a group of flagellates, most of which are parasitic. Also classified as Protists.

Walking primers-is a sequencing method for sequencing large DNA fragments (between 1,3 and 7 kilobases) that works by dividing long sequences into several consecutive short ones.

Phylogenetic analysis- Analysis of the evolutionary connections between traits (for example, sequences)

Taxa- Any organism or group of organisms of the same taxonomic rank; for example, members of an order, family, genus, or species.

Relation: This resource is very closely related to our current coursework. As one would recall we had to memorize the complete glycolysis pathway, which is exactly what this article covered. It focused on the enzymes involved in the pathway, which are some that I have memorized. It also reviewed the process through an anaerobic prospective, which sheds light on how glycolysis can be altered but still produce ATP. This is very interesting as we mainly focused on just the one type of glycolysis.

Flux control and excess capacity in the enzymes of glycolysis and their relationship to flight metabolism in Drosophila melanogaster

Summary: The focus of this research article is to study the degree of flux control of several enzymes involved in the glycolytic pathway on flight performance of the fruit fly. The author’s were able to research this by “knocking out” the enzymes phosphoglucose isomerase, phosphoglucomutase, triosephosphate isomerase, hexokinase, pyruvate kinase, and glycogen phosphorylase and studying the effect each knockout had on wing beat frequency of Drosophila. Wing-beat frequency is an accurate measure of flux control because it is closely correlated with oxygen consumption and directly reflects the rate of the hydrolysis of ATP.

Terms: Dipteran - A member of the insect order Diptera (the two-winged, or "true," flies), characterized by the use of only one pair of wings for flight and the reduction of the second pair of wings to knobs used for balance. P-element - a transposon that is present in the fruit fly Drosophila melanogaster, and is used widely for mutagenesis and the creation of genetically modified flies used for genetic research. Hemolymph – insect “blood” Polymorphism - The occurrence of different forms, stages, or types in individual organisms or in organisms of the same species, independent of sexual variations. Dysgenic - Relating to or causing the deterioration of hereditary qualities in offspring. Introgression - Infiltration of the genes of one species into the gene pool of another through repeated backcrossing of an interspecific hybrid with one of its parents.

Relevance: The research carried out in this article involves the glycolytic pathway, which we have covered in class. The authors researched the control of several of the enzymes involved in glycolysis on the regulation of flight in Drosophila. The authors tested the enzymes’ regulatory effectiveness by reducing each enzyme’s activity and calculating their flux controls on flight performance.

Dynamic profiling of the glucose metabolic network in fasted rat hepatocytes using (1,2-13C2) glucose

Summary: This paper focused on measuring the rate at which metabolites flow through the pathway (i.e. the flux) of the rat hepatic glucose metabolic network in both forward and reverse directions.

Terms: Ion exchange chromatography – A process that allows the separation of ions and polar molecules based on the charge properties of the molecules. Electron impact ionization – Method of mass spectrometry ionisation. The sample of interest is vaporized into the mass spectrometer ion source, where it is impacted by the a beam of electrons with sufficient energy to ionise the molecule. Isotopomer – (isotopic isomer) Isomer having the same number of each isotopic atom but differing in their positions. Outflux – Movement of metabolites out of the pathway. Influx – Movement of metabolites into the pathway. Anaplerosis - An intermediate enzyme reaction that replaces the concentration of vital reacting compound that has been depleted in an organism.

Relevance: The paper involves two major concepts that have been discussed in class. First, it uses a measurement of flux as a means to analyze the metabolic control of a pathway. Secondly, it mentions that, rather than existing in isolation, many pathways are in fact linked and integrated into each other through the sharing of substrates, activators, inhibitors etc, so that changes in one have an effect on the others.

Metabolic-flux profiling of yeasts S.cerevisiae and P.stipitis

Summary: This research explores the differences in metabolic regulation between 2 strains of yeast, S.cerevisiae and P.stipitis, when grown in media containing different concentrations of glucose. The central carbon metabolism of P.stipitis is largely unidentified, while that of S.cerevisiae is well documented. Metabolic-flux ratio analysis was used to identify active pathways in the central carbon metabolism of P.stipitis. Differences in flux ratios were indicative of differences in activity in pathways between the strains of yeast.

Terms: METAFoR (Metabolic-flux ratio) Analysis – a method to determine the rate at which a metabolite is produced NMR (nuclear magnetic resonance) spectroscopy – a technique used to identify molecules Chemostat Cultures – cultures grown in a static chemical environment anaplerosis – process of restoring depleted sources of metabolic intermediates respiro-fermentative metabolism – simultaneous execution of fermentation and respiration

Relevance: This research can be directly tied to the content of this course. It focuses on 3 metabolic pathways: glycolysis, pentose phosphate, and the citric acid cycle. The analysis of these pathways and subsequent comparison between 2 organisms is an investigation of metabolic regulation.

Articles and Web Pages for Review and Inclusion
Peer-Reviewed Article #1:

Transcriptomic and metabolomic profiling of Zymomonas Mobilis during aerobic and anaerobic fermentations
[http://www.biomedcentral.com/1471-2164/10/34 Yang S, Tschaplinski TJ, Engle NL, Carroll SL, Martin SL, Davison BH, Palumbo AV, Rodriguez M and Brown SD. BMC Genomics (2009) 10:34]

Reviewer: Shannon B

Main Focus: The main focus of the article was to understand how the aerobic and anerobic Z.mobilis fermentations mixture with ZM4s would affect their growth with and without oxygen.

Summary: Zhomana mobilis (ZM4) produces very closely to the theoretical yields of ethanol with high productivity that is specific. The recombinant strains are able to ferment both C-5 and C-6 sugars. ZM4 is achieved best under anaerobic conditions but is an aerotolerant organism. This particular DNA molecule is not well understood under the genetic and physiological responses to stresses. For Zhomana mobilis (ZM4), a type of bacteria, transcriptomic and metabolomic aerobic and anaerobic fermentations were demonstrated by microarray analysis. High-performance liquid chromatography (HPLC), gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) were also demonstrated to the experiment. When oxygen was not present, ZM4 absorbed glucose more rapidly, higher growth rate, and the major end product was ethanol. There were other end products that produced a great amount such as acetate, lactate, and acetoin. There was only 1.7% of ethanol shown aerobically as there was anaerobically. Certain gene expressions were not examined during the early exponential growth phase between aerobic and anaerobic conditions via microarray analysis. As fermentations continued there were greater differences in extracellular metabolite profiles. Under anaerobic conditions ZM4 contained lower levels of amino acids such as alanine, valine and lysine relating to aerobic conditions. In the stationary phase, the microarray analysis showed that 166 genes were differently expressed by more than a two-fold. ZM4 ferments glucose, fructose, and sucrose producing ethanol and carbon dioxide via the Enterner-Doudoroff (ED) pathway. A key enzyme was encoded by transcripts of the ED pathway genes. During the ZM4 fermentations the high oxygen concentration negatively influenced the fermentation performance and the maximum specific growth rates were not very different between the aerobic and anaerobic conditions. Although, oxygen did affect the physiology of the cells which lead to the buildup of metabolic byproducts which after awhile led to high differences in transcriptomic profiles in stationary phase.

Helpful links: http://www1.eere.energy.gov/vehiclesandfuels/pdfs/success/zmobilis_mar_2001.pdf

http://www.uniprot.org/taxonomy/542

New Terms
High-performance liquid chromatography (HPLC): is a form of column chromatography that separates, identifies, and quantifies compounds based on their idiosyncratic polarities and interactions with the column's stationary phase. (http://en.wikipedia.org/wiki/High_performance_liquid_chromatography)

Gas chromatography (GC): A chromatography that is used for separating and analyzing compounds that can be vaporized without decomposition. (http://en.wikipedia.org/wiki/Gas-liquid_chromatography)

Gas chromatography-mass spectrometry (GC-MS): identifies different substances within a test sample that combines gas-liquid chromatography and mass spectrometry. (http://en.wikipedia.org/wiki/GC-MS)

Microarray analysis: determines which genes in a cell are switched on at a certain point in time. Thousands of samples are measured in a single assay of many different types of assays that are used. (http://www.wisegeek.com/what-is-microarray-analysis.htm)

Lignocellulosic: "A compound of lignin and cellulose that occurs in the walls of xylem cells in woody tissue." (http://www.thefreedictionary.com/lignocellulose)

Entner-Doudoroff (ED) pathway: uses a set of enzyme that is different than what is used in glycolysis or the pentose phosphate pathway that catabolizes glucose to pyruvate. (http://en.wikipedia.org/wiki/Entner%E2%80%93Doudoroff_pathway)

Aerotolerant organism: An organism that is anaerobic and is capable of surviving or growing regardless of the presence of oxygen. (http://www.biology-online.org/dictionary/Aerotolerant)

Zymomonas mobilis: a bacterium that belongs to the genus Zymomonas.It's known for it's bioethanol-producing capabilities. "It was originally isolated from alcoholic beverages like the African palm wine, the Mexican pulque, and also as a contaminant of cider and beer in European countries." (http://en.wikipedia.org/wiki/Zymomonas_mobilis)

Relevance Statement: There are quite a lot of techniques used in this article which will be useful in the study of metabolism and different metabolites. For example, gas chromatography (GC), High-performance liquid chromatography, gas chromatography-mass spectrometry. As our course concentrates on different metabolic pathways these techniques are pretty helpful on understanding the metabolic measurements and results of these metabolic pathways. This article concentrates more on the aerobic and anaerobic fermentation. This gives us a better idea of where this metabolic pathway is applied in different organisms like the Zymomonas mobilis. Different bacteria have been studied such as Escherichia coli, Zymomonas mobilis, and Klebsiella oxytoca. Gram positive bacteria have also been studied such as Bacillus subtilis and corynebacterium glutamicum.

title: Metabolomics/Metabolites/Carbohydrates


text:
Metabolomics/Metabolites/Lipids

Back to Previous Chapter: Introduction to Metabolomics Next chapter: Hormones Go to: Amino Acids Go back to: Carbohydrates

=Lipids=

 * 1) Energy Storage
 * 2) Membrane Lipids
 * 3) Steroids

Peer-Reviewed Article #1:
Lipid metabolome-wide effects of the PPAR{gamma} agonist rosiglitazone

Journal of Lipid Research, Vol. 43, 1809-1817, November 2002

Reviewer: Monique Harris

Related Image(s)

 * The image above is one of the Type 2 diabetes drug rosiglitazone shown in both orientations.

Main Focus

 * The main focus of this paper was to observe the effect of Type 2 diabetes drug, rosiglitazone has on the liver and its’ structural lipid metabolome. The experimental phase was done using male mice that had Type 2 diabetes and were obese. The peroxisome proliferator-activated receptor γ or PPARγ was specifically observed for changes in process.

New Terms

 * Hyperlipidemia: a disorder of high cholesterol and high blood triglycerides that is passed down through families. (source: http://www.nlm.nih.gov/medlineplus/ency/article/000396.htm)
 * Adipogenesis: the production of fat, either fatty degeneration or fatty infiltration; also applied to the normal deposition of fat or to the conversion of carbohydrate or protein to fat. (source: http://www.mondofacto.com/facts/dictionary?adipogenesis)
 * Hepatotoxicity: liver damage that is done by chemicals either by medication or laboratory testing. (source: http://en.wikipedia.org/wiki/Hepatotoxicity)
 * Steatosis: a fatty liver. (source: http://emedicine.medscape.com/article/175472-overview)
 * Hyperinsulinemia: the presence of excess insulin in the blood. (source: http://dictionary.reference.com/browse/hyperinsulinemia)
 * Inguinal: relating to, or situated in the region of the groin or in either of the lowest lateral regions of the abdomen. (source: http://www.merriam-webster.com/dictionary/inguinal)
 * Hyperglycemia: an abnormally increased content of glucose in the blood. (source: http://medical-dictionary.thefreedictionary.com/hyperglycemia)
 * Lipogenesis: is the process by which simple sugars such as glucose are converted to fatty acids. (source: http://en.wikipedia.org/wiki/Lipogenesis)
 * Modulate: to adjust or adapt to a certain proportion; regulate or temper. (source: http://www.thefreedictionary.com/modulate)
 * Plasmalogen: a group of glycerol-based phospholipids in which a fatty acid group is replaced by a fatty aldehyde. (source: http://www.answers.com/topic/plasmalogen)

Summary

 * The quantitative and comprehensive analysis of the structural lipid metabolome was applied to gain an understanding of the effect that the Type 2 diabetes drug rosiglitazone has on the liver metabolism. Thiazolidinediones (TZDs) are potent therapeutic agents that have proven successful in the treatment of Type 2 diabetes in rodent models and in humans. TZDs include troglitazone, pioglitazone, and rosiglitazone. The peroxisome proliferator-activated receptor γ or PPARγ is supposed to have a high sensitivity to TZDs and after activation, is supposed to improve insulin sensitivity.
 * However, TZD usage is accompanied by increased adipogenesis and lipid accumulation in tissues. There is question if the benefits to circulating lipid concentration can be disassociated from metabolic side effects including hepatic lipid accumulation. For the mice that were used, some had diabesity genes that led to early onset obesity leading to a progressively more sever hyperinsulinemia. TZD treatment was done one the liver metabolism and rosiglitazone was more potent antidiabetic TZD than troglitazone in early studies.
 * It was revealed that actions of rosiglitazone and putatively PPARγ had key targets on lipid metabolism. Two groups of mice, one control and one experimental were used in the experiment. The mice were a cross of Nonobese Nondiabetic Zealand Obese (NZO/HILt) and Nonobese Nondiabetic (NON/LT) strains. They were feed for 4 weeks and then euthanized at which point blood, heart tissue, liver tissue and inguinal adipose were collected, weighed and frozen for analysis.
 * Gene expression data was obtained by measuring the fluorescence intensity for each PCR reaction using the system software and was analyzed in EXCEL®. Lipids from plasma and tissues were extracted and prepared thin-layer chromatography to analysis. Also fatty acid methyl esters were collected and ran by capillary gas chromatography using a gas chromatograph. Quantitative data was visualized suing the Lipomic Surveyor™ software system which made a heat-map graph of the difference between control and treated mice. The heat map displayed the increase in each metabolite in rosiglitazone-treated mice relative to control mice by the intensity of the brightness.
 * After 4 weeks of rosiglitazone treatment, diabetic hyperglycemia was completely reversed. That reversal also was accompanied by decline in plasma concentrations of insulin, leptin, triacylglyerides and cholesterol. The rosiglitazone treated mice had gained more body weight that the control mice, especially in the inguinal fat, heart and liver areas. Liver lipid metabolism results included a substantial accumulation of triacylglyerides and the inhibition of normal liver-plasma lipid exchange. Heart lipid metabolism results included the increased biosynthesis of n-7 fatty acids and increased concentration of triacylglyerides and free fatty acids of plasma. The hearts of the rosiglitazone treated mice were significantly enriched with cardiolipin however concentrations of plasmalogens were lower. This was consistent with a decrease peroxisome synthesis of lipids within hearts of treated mice. Adipose lipid metabolism results included a decrease in triacylglyerides content but an increase in fatty acids. The treated mice had an n-7 and n-3 fatty acid accumulation while have a depletion of n-9 fatty acids. The plasmalogen lipids in inguinal fat phospholipids were depleted by the treatment.
 * Overall the rosiglitazone treatment is often accompanied by weight gain. Increased synthesis of fatty acids occurred as well as an upregualtion of expression of genes associated with adipogenesis and fatty acid synthesis was found. Palmitoleic acid was an excellent indicator of the increased synthesis of fatty acids in both the live and adipose tissue. Rosiglitazone, a PPARγ agonist has an inhibitory effect on lipid biosynthesis in the peroxisome. It induced hyperlipidemia by disruption the mobilization of liver lipids into plasma and induced de novo fatty acid synthesis. Diminished the biosynthesis of lipids synthesized within the peroxisome and had substantial effect on the heart cardiolipin and free fatty acid metabolism. Lastly, it exerted tissue specific effects on lipid metabolism.
 * It is hypothesized that the mice used in the experiment might have had underlying defects that rendered them sensitive to steatosis inducing effect to TZDs. Over all it should be noted that mice metabolism is very distinctly different than human lipid metabolism and directly application needs to be tested.

Relevance to a Traditional Metabolism Course

 * The topic of metabolome wide effects is a topic that could be easily related to a metabolism course. The paper mentions some pathways that are affected and could be further studied to see the complete involvement of the Type 2 diabetes drug rosiglitazone. One pathway is the electron transport chain. It is known that cardiolipin composition and content is important to the efficiency of electron transport. An increase in cardiolipin increased electron transport efficiency as well as decreased electron leakage. Also, there were two major lipid structures studied that are produce with in the peroxisome and these fatty acids as well as plasmalogen lipids are involved with the dihydroxyacetone phosphate biosynthetic pathway. Lastly, the study looked at the conversation of polyunsaturated rich phospholipids to triacylglyerides via a phospholipase C pathway.

title: Metabolomics/Metabolites/Lipids