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Tuesday, September 2, 2025

Peace and conflict studies

From Wikipedia, the free encyclopedia

Peace and conflict studies is a social science field that identifies and analyzes violent and nonviolent behaviors as well as the structural mechanisms attending conflicts (including social conflicts), to understand those processes which lead to a more desirable human condition. A variation on this, peace studies, is an interdisciplinary effort aiming at the prevention, de-escalation, and solution of conflicts by peaceful means, based on achieving conflict resolution and dispute resolution at the international and domestic levels based on positive sum, rather than negative sum, solutions.

In contrast with strategic studies or war studies, which focus on traditionally realist objectives based on the state or individual unit level of analysis, peace and conflict studies often focuses on the structural violence, social or human levels of analysis.

Disciplines involved may include philosophy, political science, geography, economics, psychology, communication studies, sociology, international relations, history, anthropology, religious studies, gender studies, law, and development studies as well as a variety of others. Relevant sub-disciplines of such fields, such as peace economics, may also be regarded as belonging to peace and conflict studies. The study of peace is also known as irenology.

Historical background

Peace and conflict studies is both a pedagogical activity, in which teachers transmit knowledge to students; and a research activity, in which researchers create new knowledge about the sources of conflict. Peace and conflict studies entails understanding the concept of peace which is defined as political condition that ensures justice and social stability through formal and informal institutions, practices, and norms.

As pedagogical activity

Academics and students in the world's oldest universities have long been motivated by an interest in peace. American student interest in what we today think of as peace studies first appeared in the form of campus clubs at United States colleges in the years immediately following the American Civil War. Similar movements appeared in Sweden in the last years of the 19th century, as elsewhere soon after. These were student-originated discussion groups, not formal courses included in college curricula. The first known peace studies course in higher education was offered in 1888 at Swarthmore College, a Quaker school.

Introduction of peace

The First World War was a turning point in Western attitudes to war. At the 1919 Peace of Paris—where the leaders of France, Britain, and the United States, led by Georges Clemenceau, David Lloyd George, and Woodrow Wilson respectively, met to decide the future of Europe—Wilson proposed his famous Fourteen Points for peacemaking. These included breaking up European empires into nation states and the establishment of the League of Nations. These moves, intended to ensure a peaceful future, were the background to a number of developments in the emergence of Peace and Conflict Studies as an academic discipline. The founding of the first chair in International Relations at Aberystwyth University, Wales, whose remit was partly to further the cause of peace, occurred in 1919.

Indiana's Manchester College was one of the first institutions to offer a major in peace studies.

After World War II, the founding of the UN system provided a further stimulus for more rigorous approaches to peace and conflict studies to emerge. Many university courses in schools of higher learning around the world began to develop which touched upon questions of peace, often in relation to war, during this period. The first undergraduate academic program in peace studies in the United States was developed in 1948 by Gladdys Muir, at Manchester University a liberal arts college associated with the Church of the Brethren. It was not until the late 1960s in the United States that student concerns about the Vietnam War forced ever more universities to offer courses about peace, whether in a designated peace studies course or as a course within a traditional major. Work by academics such as Johan Galtung and John Burton, and debates in fora such as the Journal of Peace Research in the 1960s reflected the growing interest and academic stature of the field. Growth in the number of peace studies programs around the world was to accelerate during the 1980s, as students became more concerned about the prospects of nuclear war. As the Cold War ended, peace and conflict studies courses shifted their focus from international conflict and towards complex issues related to political violence, human security, democratisation, human rights, social justice, welfare, development, and producing sustainable forms of peace. A proliferation of international organisations, agencies and international NGOs, from the UN, Organization for Security and Co-operation in Europe, European Union, and World Bank to International Crisis Group, International Alert, and others, began to draw on such research.

Critical theory agendas relating to positive peace in European academic contexts were already widely debated in the 1960s. By the mid-1990s peace studies curricula in the United States had shifted "...from research and teaching about negative peace, the cessation of violence, to positive peace, the conditions that eliminate the causes of violence." As a result, the topics had broadened enormously. By 1994, a review of course offerings in peace studies included topics such as: "north-south relations"; "development, debt, and global poverty"; "the environment, population growth, and resource scarcity"; and "feminist perspectives on peace, militarism, and political violence".

There is now a general consensus on the importance of peace and conflict studies among scholars from a range of disciplines in and around the social sciences, as well as from many influential policymakers around the world. Peace and conflict studies today is widely researched and taught in a large and growing number of institutions and locations. The number of universities offering peace and conflict studies courses is hard to estimate, mostly because courses may be taught out of different departments and have very different names. The International Peace Research Association website gives one of the most authoritative listings available. A 2008 report in the International Herald Tribune mentions over 400 programs of teaching and research in peace and conflict studies, noting in particular those at the United World Colleges, Peace Research Institute Oslo, Universitat Jaume I in Castellón de la Plana/Spain, the Malmö University of Sweden, the American University, University of Bradford, the UN mandated Peace University UPEACE in Ciudad Colón/Costa Rica, George Mason University, Lund University, University of Michigan, Notre Dame, University of Queensland, Uppsala University, Innsbruck School of Peace Studies/Austria, University of Virginia, and University of Wisconsin. The Rotary Foundation and the UN University supports several international academic teaching and research programs.

A 1995 survey found 136 United States colleges with peace studies programs: "Forty-six percent of these are in church-related schools, another 32% are in large public universities, 21% are in non-church related private colleges, and 1% are in community colleges. Fifty-five percent of the church-related schools that have peace studies programs are Roman Catholic. Other denominations with more than one college or university with a peace studies program are the Quakers, Mennonites, Church of the Brethren, and United Church of Christ. One hundred fifteen of these programs are at the undergraduate level and 21 at the graduate level. Fifteen of these colleges and universities had both undergraduate and graduate programs."

Other notable programs can be found at the University of Toronto, University of Manitoba, Lancaster University, Hiroshima University, University of Innsbruck, Universitat Jaume I, University of Sydney, University of Queensland, King's College (London), Sault College, London Metropolitan, Sabanci, Marburg, Sciences Po, Université Paris Dauphine University of Amsterdam, Otago, St Andrews, Brandeis University's Heller School and York. Perhaps most importantly, such programs and research agendas have now become common in institutions located in conflict, post-conflict, and developing countries and regions such as (e.g., National Peace Council), Centre for Human Rights, University of Sarajevo, Chulalongkorn University, National University of East Timor, University of Kabul, on September 11, 2014 University of peshawar, the provincial capital of Khyber Pakhtunkhwa province in Pakistan established an Institute with prime objective of offering peace education to the youth who suffered it most since 1979 Afghan war. It is called Institute of Peace and Conflict Studies (IPCS).

As research activity

Norwegian academic Johan Galtung is widely regarded as a founder of peace and conflict studies.

Although individual thinkers such as Immanuel Kant had long recognised the centrality of peace (see Perpetual Peace), it was not until the 1950s and 1960s that peace studies began to emerge as an academic discipline with its own research tools, a specialized set of concepts, and forums for discussion such as journals and conferences. Beginning in 1959, with the founding of the Peace Research Institute Oslo (PRIO), associated with Johan Galtung, a number of research institutes began to appear.

In 1963, Walter Isard, the principal founder of regional science, assembled a group of scholars in Malmö, Sweden, for the purpose of establishing the Peace Research Society. The group of initial members included Kenneth Boulding and Anatol Rapoport. In 1973, this group became the Peace Science Society. Peace science was viewed as an interdisciplinary and international effort to develop a special set of concepts, techniques and data to better understand and mitigate conflict. Peace science attempts to use the quantitative techniques developed in economics and political science, especially game theory and econometrics, techniques otherwise seldom used by researchers in peace studies. The Peace Science Society website hosts the second edition of the Correlates of War, one of the most well-known collections of data on international conflict. The society holds an annual conference, attended by scholars from throughout the world, and publishes two scholarly journals: Journal of Conflict Resolution and Conflict Management and Peace Science.

In 1964, the International Peace Research Association was formed at a conference organized by Quakers in Clarens, Switzerland. Among the original executive committee was Johan Galtung. The IPRA holds a biennial conference. Research presented at its conferences and in its publications typically focuses on institutional and historical approaches, seldom employing quantitative techniques. In 2001, the Peace and Justice Studies Association (PJSA) was formed as a result of a merger of two precursor organisations. The PJSA is the North American affiliate of IPRA and includes members from around the world with a predominance from the United States and Canada. The PJSA publishes a regular newsletter (The Peace Chronicle), and holds annual conferences on themes related to the organization's mission "to create a just and peaceful world" through research, scholarship, pedagogy, and activism.

In 2008, Strategic Foresight Group presented its report on an innovative mechanism to find sustainable solution to conflicts in the Middle East. It also developed a new Water Cooperation Quotient, which is a measure of active cooperation by riparian countries in the management of water resources using 10 parameters including legal, political, technical, environmental, economic and institutional aspects.

Institutions like Stockholm International Peace Research Institute (SIPRI) are advancing the understanding of peace and development by analyzing the complex drivers of conflict and insecurity. Their approach acknowledges that conflicts are rarely caused by a single factor. Instead, a constellation of economic, social, political, and environmental factors, often reinforcing and exacerbating each other in ways that can lead to sustained violence or, conversely, pave pathways to peace.

Description

Peace and conflict studies along with its concepts of conflict analysis and conflict resolution can be classified as:

There has been a long-standing debate on disarmament issues, as well as attempts to investigate, catalogue, and analyse issues relating to arms production, trade, and their political impacts. There have also been attempt to map the economic costs of war, or of relapses into violence, as opposed to those of peace.

Peace and conflict studies is now well established within the social sciences: it comprises many scholarly journals, college and university departments, peace research institutes, conferences, as well as outside recognition of the utility of peace and conflict studies as a method.

Peace Studies allows one to examine the causes and prevention of war, as well as the nature of violence, including social oppression, discrimination and marginalization. Through peace studies one can also learn peace-making strategies to overcome persecution and transform society to attain a more just and equitable international community.

Feminist scholars have developed a speciality within conflict studies, specifically examining the role of gender and interlocking systems of inequality in armed and other conflicts. The importance of considering the role of gender in post-conflict work was recognised by the United Nations Security Council resolution 1325. Examples of feminist scholarship include the work of Carol Cohn and Claire Duncanson.

Ideas

Conceptions of peace

Delegates at the 1953 Korean Armistice Agreement achieved negative peace, ending the war but not the wider conflict.

Negative peace refers to the absence of direct violence. Positive peace refers to the critical theory of conflict resolution and the absence of indirect and structural violence, and is the concept that most peace and conflict researchers adopt. This is often credited to Galtung but these terms were previously used by Martin Luther King Jr. in his "Letter from Birmingham Jail" in 1963, in which he wrote about "negative peace which is the absence of tension" and "positive peace which is the presence of justice." These terms were perhaps first used by Jane Addams in a series of lectures about 'positive ideals of peace' begun in 1899 that took form in her book Newer Ideals of Peace where she switched to the term "newer ideals", but continued to contrast them to the term "negative peace"; she described them as we think of them today, as peace with "a sense of justice no longer outraged." The idea was further popularized by then-UN Secretary-General Boutros Boutros-Ghali in his 1992 report An Agenda for Peace, published in the aftermath of the Cold War.

Several conceptions, models, or modes of peace have been suggested in which peace research might prosper.

  • The crux of the matter is that peace is a natural social condition, whereas war is not. The premise is simple for peace researchers: to present enough information so that a rational group of decision makers will seek to avoid war and conflict.
  • Second, the view that violence is sinful or unskillful, and that non-violence is skillful or virtuous and should be cultivated. This view is held by a variety of religious traditions worldwide: Quakers, Mennonites and other Peace churches within Christianity; Baháʼís, Jains, the Satyagraha tradition in Hinduism, Buddhism, and other portions of Indian religion and philosophy; as well as certain schools of Islam.
  • Third is pacifism: the view that peace is a prime force in human behaviour.
  • A further approach is that there are multiple modes of peace.

There have been many offerings on these various forms of peace. These range from the well known works of Kant, Locke, Rousseau, Paine, on various liberal international and constitutional and plans for peace. Variations and additions have been developed more recently by scholars such as Raymond Aron, Edward Azar, John Burton, Martin Ceadal, Wolfgang Dietrich, Kevin Dooley, Johan Galtung, Robert L. Holmes, Michael Howard, Vivienne Jabri, John-Paul Lederach, Roger Mac Ginty, Pamina Firchow, Hugh Miall, David Mitrany, Oliver Ramsbotham, Anatol Rapoport, Mikkel Vedby Rasmussen, Oliver Richmond, S.P. Udayakumar, Tom Woodhouse, others mentioned above and many more. Democratic peace, liberal peace, sustainable peace, civil peace, hybrid peace, post-liberal peace, everyday peace, trans-rational peace(s) and other concepts are regularly used in such work.

Sustainable peace

Under the conceptions of peace, sustainable peace must be regarded as an important factor for the future of prosperity. Sustainable peace must be the priority of global society where state actors and non-state actors do not only seek for the profits in a near future that might violate the stable state of peace. For a sustainable peace, nurturing, empowerment, and communications are considered to be the crucial factors throughout the world. Firstly, nurturing is necessary to encourage psychological stability and emotional maturity. The significance of social value in adequate nurturing is important for sustainable peace. Secondly, in order to achieve real security and sustainable peace, inner security must be secured along with arranged social systems and protection based on firm foundation. Lastly, communications are necessary to overcome ignorance and isolation and establish a community based on reliable and useful information.

Conflict triangle

Johan Galtung's conflict triangle works on the assumption that the best way to define peace is to define violence, its opposite. It reflects the normative aim of preventing, managing, limiting and overcoming violence.

  • Direct (overt) violence: for example, direct attacks and massacres.
  • Structural violence: Structural violence is indirect violence caused by repressive, unequal and unjust social structures, not direct acts of violence or unavoidable causes of harm.
  • Cultural violence: Cultural violence occurs as a result of the cultural assumptions that blind one to direct or structural violence. For example, one may be indifferent toward the homeless, or even consider their expulsion or extermination a good thing.

Each corner of Galtung's triangle can relate to the other two. Ethnic cleansing can be an example of all three.

A simplification of these can be phrased as:

  • Direct violence: harming or hurting the body and mind.
  • Structural violence: economic exploitation and political repression.
  • Cultural violence: underlying values and epistemic models that legitimize direct and structural violence.

Appeasement and deterrence

Appeasement in a strategy of making political, material, or territorial concessions to an aggressive power to avoid conflict. Deterrence is a strategy to use threats or limited force to dissuade an actor from escalating conflict, typically because the prospective attacker believes that the probability of success is low and the costs of attack are high.

Cost of conflict and price of unjust peace

Cost of conflict is an approach which attempts to calculate the price of conflicts. The idea is to examine this cost, not only in terms of the deaths and casualties and the economic costs borne by the people involved, but also the social, developmental, environmental and strategic costs of conflict. The approach considers direct costs of conflict, for instance human deaths, expenditure, destruction of land and physical infrastructure; as well as indirect costs that impact a society, for instance migration, humiliation, growth of extremism and lack of civil society. The price of unjust peace can be higher than the cost of conflict.

Causality

The democratic peace theory claims that democracy causes peace, while the territorial peace theory disagrees and claims that peace causes democracy. The capitalist peace theory claims economic interdependence contributes to peace. Other explanations for peace include institutional liberalism, alliances, Pax Atomica, Pax Americana and political stabilityRealism and liberal internationalism are claimed by some to lead in some cases to more wars and in other cases to fewer wars.

Critical theory

Critical theory argues for a shift from "negative peace" described as absence of violence against individuals to "positive peace" described as the absence of structural violence. This emerged rapidly at the end of the Cold War, and was encapsulated in the report of then-UN Secretary-General Boutros Boutros-Ghali, An Agenda for Peace. Indeed, it might be said that much of the machinery of what has been called "liberal peacebuilding" by a number of scholars and "statebuilding" by another is based largely on the work that has been carried out in this area. Many scholars in the area have advocated a more "emancipatory" form of peacebuilding, however, based upon a "Responsibility to Protect" (R2P), human security, local ownership and participation in such processes, especially after the limited success of liberal peacebuilding/ statebuilding in places as diverse as Cambodia, the Balkans, East Timor, Sierra Leone, Liberia, Nepal, Afghanistan, and Iraq. This approach includes the normatively oriented work that emerged in the peace studies and conflict research schools of the 1960s (e.g. Oslo Peace Research Institute on "Liberal Peace and the Ethics of Peacebuilding") and more critical theory ideas about peacebuilding that have recently developed in many European and non-western academic and policy circles.

Prediction and forecasting

Conflict forecasts and early warnings can be sufficiently precise to be relevant for policy and evaluation of theories. Conflict escalation can be rational for one side of the conflict in some cases of asymmetric conflictsappeasement or for Fait accompli, causing challenges to de-escalation.

Internal conflicts and disaggregated data

Since the beginning of the 2000s, technical advances in geolocation of violent events and spatial analyses have fostered the emergence of a large number of empirical studies carried out at the disaggregated scale of regions, cities or geographical units. A 2019 survey shows that the use of disaggregated data has led to methodological advances that are important in understanding the role played by poverty and natural resources in the emergence of civil conflicts. This evolution of statistical tools also draws promising research perspectives for contemporary and still widely debated issues such as climate change. Nevertheless, this gain in precision must not be at the expense of a better understanding of the regional and global issues that are also involved in the emergence of civil conflicts. Thus, the issues of trade and social cohesion still need to be deepened because they are explained at the level of groups whose dimension is poorly understood.

A subsequent 2024 meta-regression analysis examines the narratives researchers use to describe how various shocks affect internal conflict risk through channels implicitly linked to income. After examining 2,464 subnational estimates from 64 empirical studies, the analysis finds that several publication biases related to scholars' methodological choices influence our understanding of this phenomenon. Importantly, studies that do not uncover empirical effects aligning with researchers' expectations regarding theoretical mechanisms are less likely to be published. After accounting for publication selection bias, the analysis finds that, on average, income-increasing shocks in the agriculture sector are negatively associated with the local risk of conflict. However, the analysis finds no average effect of income-decreasing shocks in the agriculture sector or income-increasing shocks in the extractive sector on the local risk of conflict. This opens avenues for further study on the observed heterogeneity in the literature, particularly focusing on the conditional aspects of how shocks and conflicts are measured, as well as geographical coverage, among other factors.

Complex system approach to peace and armed conflict

In the complex system approach to peace and armed conflict, the social systems of armed conflict are viewed as complex dynamical systems. The study of positive and negative feedback processes, attractors and system dimensionality, phase transitions and emergence is seen as providing improved understanding of the conflicts and of the effectiveness or ineffectiveness of interventions aiming to resolve the conflicts.

Normative aims

Peacekeeping efforts by armed forces can provide one means to limit and ultimately resolve conflict.

The normative aims of peace studies are conflict transformation and conflict resolution through mechanisms such as peacekeeping, peacebuilding (e.g., tackling disparities in rights, institutions and the distribution of world wealth) and peacemaking (e.g., mediation and conflict resolution). Peacekeeping falls under the aegis of negative peace, whereas efforts toward positive peace involve elements of critical theory, peace building and peacemaking.

Peace and conflict studies in military

Peace and conflict are widely studied by militaries. One approach by military to prevent conflict and conflict escalation is deterrenceCritical theory argues that military is overtly committed to combat in the article "Teaching Peace to the Military", published in the journal Peace ReviewJames Page argues for five principles that ought to undergird this undertaking, namely, respect but do not privilege military experience, teach the just war theory, encourage students to be aware of the tradition and techniques of nonviolence, encourage students to deconstruct and demythologize, and recognize the importance of military virtue.

Criticism and controversy

 
Conservative writers Roger Scruton (top) and David Horowitz (bottom) are among the critics of peace and conflict studies.

A number of criticisms have been aimed at critical theory in peace and conflict studies, often but not necessarily from outside the realms of university system, including that peace studies:

  • does not produce practical prescriptions for managing or resolving global conflicts because "ideology always trumps objectivity and pragmatism";
  • are focused on putting a "respectable face on Western self-loathing";
  • are hypocritical because they "tacitly or openly support terrorism as a permissible strategy for the 'disempowered' to redress real or perceived grievances against the powerful" (i.e. ideological anti-Western concepts developed by social scientists such as Johan Galtung which arguably add a sense of unjustified acceptability which is used in support of radicalism);
  • have curricula that are (according to human rights activist Caroline Cox and philosopher Roger Scruton) "intellectually incoherent, riddled with bias and unworthy of academic status...";
  • have policies proposed to "eliminate the causes of violence" that are uniformly leftist policies, and not necessarily policies which would find broad agreement among social scientists;

In 1980, political scientist J. David Singer criticized peace research on three fronts:

  1. Peace research contributed to creating a schism in research into the causes of war, thus making it harder to develop systematic research into war
  2. "many peace researchers had the intellectual innocence of most bright amateurs; they underestimated the rate at which their research findings would become applicable and would be applied to major policy problems of the day."
  3. many peace researchers failed to distinguish between objective research into the conditions of war and peace on one hand, and political action and propaganda in favor of specific policies

Barbara Kay, a columnist for the National Post, specifically criticized the views of Norwegian professor Johan Galtung, who is considered to be a leader in modern peace research. Kay wrote that Galtung has written on the "structural fascism" of "rich, Western, Christian" democracies, admires Fidel Castro, opposed resistance to the Soviet Invasion of Hungary in 1956, and has described Aleksandr Solzhenitsyn and Andrei Sakharov as "persecuted elite personages". Galtung has also praised Mao Zedong for "endlessly liberating" China. Galtung has also stated that the United States is a "killer country" that is guilty of "neo-fascist state terrorism" and has reportedly stated that the destruction of Washington, D.C., could be justified by America's foreign policy. He has also compared the United States to Nazi Germany for bombing Kosovo during the 1999 NATO bombing of Yugoslavia.

In the Summer 2007 edition of City Journal, Bruce Bawer sharply criticized Peace Studies. He noted that many Peace Studies programs in American Universities are run by Marxist or far-left Professors. More broadly, he argued that Peace Studies are dominated by the belief that "America ... is the wellspring of the world's problems" and that while Professors of Peace Studies argue "that terrorist positions deserve respect at the negotiating table," they "seldom tolerate alternative views" and that "(p)eace studies, as a rule, rejects questioning of its own guiding ideology."

Regarding his claim that Peace Studies supports violence in the pursuit of leftist ideology, Bawer cited a quote from Peace and Conflict Studies, a widely used 2002 textbook written by Charles P. Webel and David P. Barash which praised Vladimir Lenin because he "maintained that only revolution—not reform—could undo capitalism's tendency toward imperialism and thence to war."

David Horowitz has argued that Webel and Barash's book implicitly supports violence for socialist causes, noting that the book states "the case of Cuba indicates that violent revolutions can sometimes result in generally improved living conditions for many people." Horowitz also argued that the book "treats the Soviet Union as a sponsor of peace movements, and the United States as the militaristic, imperialist power that peace movements try to keep in check" and that "the authors justify Communist policies and actions while casting those of America and Western democracies in a negative light." Horowitz also claimed that the authors discuss the Cuban Missile Crisis without mentioning its cause (i.e. the placement of the Soviet missiles in Cuba) and blame John F. Kennedy while praising Soviet Premier Nikita Khrushchev for "be[ing] willing to back down". Finally, Horowitz criticized the author's use of Marxist writers, such as Andre Gunder Frank and Frances Moore Lappe, as the sole basis on which to study "poverty and hunger as causes of human conflict."

Kay and Bawer also specifically criticized Professor Gordon Fellman, the Chairman of Brandeis University's Peace, Conflict, and Coexistence Studies Program, who they claimed has justified Palestinian suicide-bombings against Israelis as "ways of inflicting revenge on an enemy that seems unable or unwilling to respond to rational pleas for discussion and justice."

Katherine Kersten, who is a senior fellow at the Minneapolis-based conservative think tank Center of the American Experiment, believes that Peace Studies programs are "dominated by people of a certain ideological bent, and [are] thus hard to take seriously." Robert Kennedy, a professor of Catholic studies and management at the University of St. Thomas, criticized his university's Peace Studies Program in an interview with Minneapolis Star Tribune in 2002, stating that the program employs several adjunct professors "whose academic qualifications are not as strong as we would ordinarily look for" and that "The combination of the ideological bite and the maybe less-than-full academic credentials of the faculty would probably raise some questions about how scholarly the program is."

Responses

Such views have been strongly opposed by scholars who claim that these criticisms underestimate the development of detailed interdisciplinary, theoretical, methodological, and empirical research into the causes of violence and dynamics of peace that has occurred via academic and policy networks around the world.

In reply to Barbara Kay's article, a group of Peace Studies experts in Canada responded that "Kay's...argument that the field of peace studies endorses terrorism is nonsense" and that "(d)edicated peace theorists and researchers are distinguished by their commitment to reduce the use of violence whether committed by enemy nations, friendly governments or warlords of any stripe." They also argued that:

...Ms. Kay attempts to portray advocates for peace as naive and idealistic, but the data shows that the large majority of armed conflicts in recent decades have been ended through negotiations, not military solutions. In the contemporary world, violence is less effective than diplomacy in ending armed conflict. Nothing is 100% effective to reduce tyranny and violence, but domestic and foreign strategy needs to be based on evidence, rather than assumptions and misconceptions from a bygone era.

Most academics in the area argue that the accusations are incorrect that peace studies approaches are not objective, and derived from mainly leftist or inexpert sources, are not practical, support violence rather than reject it, or have not led to policy developments.

The development of UN and major donor policies (including the EU, US, and UK, as well as many others including those of Japan, Canada, Norway, etc.) towards and in conflict and post-conflict countries have been heavily influenced by such debates. A range of key policy documents and responses have been developed by these governments in the last decade and more, and in UN (or related) documentation such as "Agenda for Peace", "Agenda for Development", "Agenda for Democratization", the Millennium Development Goals, Responsibility to Protect, and the "High Level Panel Report". They have also been significant for the work of the World Bank, international development agencies, and a wide range of nongovernmental organisations. It has been influential in the work of, among others, the UN, UNDP, UN Peacebuilding Commission, UNHCR, World Bank, EU, Organization for Security and Co-operation in Europe, for national donors including USAID, DFID, CIDA, NORAD, DANIDA, Japan Aid, GTZ, and international NGOs such as International Alert or International Crisis Group, as well as many local NGOs. Major databases have been generated by the work of scholars in these areas.

Finally, peace and conflict studies debates have generally confirmed, not undermined, a broad consensus (in developed world and the Global South) on the importance of human security, human rights, development, democracy, and a rule of law (though there is a vibrant debate ongoing about the contextual variations and applications of these frameworks). At the same time, the research field is characterized by a number of challenges including the tension between "the objective of doing critical research and being of practical relevance".

Economic discrimination

From Wikipedia, the free encyclopedia

Economic discrimination is discrimination based on economic factors. These factors can include job availability, wages, the prices and/or availability of goods and services, and the amount of capital investment funding available to minorities for business. This can include discrimination against workers, consumers, and minority-owned businesses.

It is not the same as price discrimination, the practice by which monopolists (and to a lesser extent oligopolists and monopolistic competitors) charge different buyers different prices based on their willingness to pay.

History

A recognition of economic discrimination began in the British Railways Clauses Consolidation Act 1845, which prohibited a common carrier from charging one person more for carrying freight than was charged to another customer for the same service. In nineteenth-century English and American common law, discrimination was characterized as improper distinctions in economic transactions; in addition to the above issue in the Railways Clauses Consolidation Act 1845, a hotelier capriciously refusing to give rooms to a particular patron would constitute economic discrimination. These early laws were designed to protect against discrimination from Protestants who might discriminate against Catholics, or Christians who might discriminate against Jews.

By the early twentieth century, economic discrimination was broadened to include biased or unequal terms against other companies or competing companies. In the United States the Robinson-Patman Act (1936), which prevents sellers of commodities in interstate commerce from discriminating in price between purchasers of goods of like grade and quality, was designed to prevent vertically integrated trusts from driving smaller competitors out of the market through economies of scale.

It was not until 1941, when U.S. President Franklin D. Roosevelt issued an executive order forbidding discrimination in employment by a company working under a government defense contract, that economic discrimination took on the overtones it has today, which is discrimination against minorities. By 1960, anti-trust laws and interstate commerce laws had effectively regulated inter-corporate discrimination so problematic in the late nineteenth and early twentieth centuries, but the problem of discrimination on an economic basis against minorities had become widespread.

Causes

There is a wide range of theory concerned with the root causes of economic discrimination. Economic discrimination is unique from most other kinds of discrimination because only a small portion of it is due to racism, but rather is due to what has been called a "cynical realization that minorities are not always your best customers". There are three main causes that most economic theorists agree are likely root causes.

Animosity

Racism, sexism, ageism, and dislike for another's religion, ethnicity or nationality have always been components of economic discrimination, much like all other forms of discrimination.

Most discrimination in the US and Europe is claimed to be in terms of racial and ethnic discrimination—mostly blacks and Hispanics in the US, Muslims in Europe. In most parts of the world, women are held to lower positions, lower pay, and restricted opportunities of land ownership or economic incentive to enter businesses or start them. This case remains the same for racial minorities in certain countries. For example, a study conducted by Nuffield College in the UK found that using identical CVs and cover letters, BAME job applicants had to apply for 60% more jobs to receive the same number of callbacks as white applicants.

This form of economic discrimination is usually performed by whatever groups are held to be "in power" at the time. For example, in America, discrimination is often considered to be the province of Caucasians, while in Saudi Arabia, it's men who are considered discriminatory. One study suggests that the increase in equal opportunity lawsuits has reduced this kind of discrimination in America by a large amount.

Cost and revenue

There is a certain opportunity cost in dealing with some minorities, particularly in highly divided nations or nations where discrimination is tolerated.

A second common reason for this kind of discrimination is when the worker or consumer is not cost-efficient. For example, some stores in the US Northwest do not stock ethnic foods, despite requests for such, since they feel the cost is too high for too low a return.

Additionally, the illegal immigration debate in the US has resulted in some businesses refusing to hire such workers based on the likelihood that they would be fined and litigated against.

Efficiency

In some cases, minorities are discriminated against simply because it is inefficient to make a concerted effort at a fair allocation. For example, in countries where minorities make up a very small part of the population, or are on average less educated than the population average, there is rarely an attempt to focus on employment of minorities.

The Equal Opportunity Employment Act in the US has almost reduced this sort of rationale for discrimination to nothing, according to recent studies.

The relations between economic theory, efficiency and discrimination, or "discriminatory tastes" are much more problematic. Some critics of the concept of a "taste-based" view of discrimination have cited many reasons. One claim against this view is that viewing discrimination as a consumer preference outside of the scope of regulation could make economists indifferent towards its negative effects. Other reasons use the fact that discrimination often exists as a system which feeds on itself as evidence that it can't be viewed in the same way that people could prefer McDonalds over Burger King.

History and tradition

The foundations and roots of economic discrimination lie in history. Discrimination of minorities is a cycle the continues to repeat itself around the world due to historic views and the remnants of generations passed.

Slavery is often referred to as America's 'original sin' as the root of all contemporary racial problems stem from the era. It is racially prejudiced events like this that cause issues like racial residential segregation which persists to cause huge economic problems for African Americans in contemporary US society. In 2020, the funding of schools in white areas was $23 billion higher than the funding of schools in traditionally African American areas.

Wage gaps for minorities are also founded in history. Prejudice against women in high-paid jobs has been carried through generations with women frequently given the domestic worker role that history and tradition have given them. In 2011, a study was conducted by the CMI that predicts that the gender pay gap will not be closed until 2109. Furthermore, the racial pay gap in the US was caused by the prejudice of traditional racist views, in 2020, black families had a median household income of just over $41,000, however, white families have a median household income of more than $70,000. Throughout history the groups that are "in power" have remained the same and it is this power dynamic that continues to cause economic discrimination for minorities.

Forms

There are several forms of economic discrimination. The most common form of discrimination is wage inequality, followed by unequal hiring practices. But there is also discrimination against minority consumers and minority businesses in a number of areas, and religious or ethnic discrimination in countries outside the United States.

Against workers

Most forms of discrimination against minorities involve lower wages and unequal hiring practices.

Wage discrimination

Several studies have shown that, in the United States, several minority groups, including black men and women, Hispanic men and women, white women, gay men of any race and trans people of any race suffer from decreased wage earning for the same job with the same performance levels and responsibilities as heterosexual white and Asian males. Numbers vary from study to study, but most indicate a gap from 5 to 15% lower earnings on average, between an affected minority and other groups.

Studies by experts from Harvard University and the University of Chicago have shown that, at least for some career paths like those of MBA graduates, the pay gap for women is largely due to time taken off to care for children. Their work has shown that the earnings of male and female MBA graduates from top US business schools are nearly identical at the outset of their careers. However, a decade after completing their degree, male graduates begin to earn more than female graduates. Researchers found that three factors account for the gap in earnings: differences in training prior to MBA graduation, differences in career interruptions, and differences in weekly hours. Female graduates had less training outside of their formal MBA, were more likely to take time off to provide full time childcare, and worked fewer hours per week on average. However, these findings appear to be changing as more men are seeking out careers that allow for flexibility in child care and some female dominant fields, like obstetrics, are developing new ways to increase work-life balance.

A recent study indicated that black wages in the US have fluctuated between 70% and 80% of white wages for the entire period from 1954 to 1999, and that wage increases for that period of time for blacks and white women increased at half the rate of that of white males. Other studies show similar patterns for Hispanics. Studies involving women found similar or even worse rates.

Another study indicated that Muslims earned almost 25% less on average than whites in France, Germany, and England, while in South America, mixed-race blacks earned half of what Hispanics did in Brazil.

Most wage discrimination is masked by the fact that it tends to occur in lower-paying positions and involves minorities who may not feel empowered to file a discrimination lawsuit or complain.

UK – On 10 October 2018 the Prime Minister, Theresa May, launched a three-month consultation with businesses on how large businesses would have to report the pay gap between staff of different ethnicities.

Hiring discrimination

Hiring discrimination is similar to wage discrimination in its pattern. It typically consists of employers choosing to hire a certain race candidate over a minority candidate, or a male candidate over a female candidate, to fill a position. A study of employment patterns in the US indicated that the number of hiring discrimination cases has increased fivefold in the past 20 years. However, their percentage as a whole fraction of the workforce hirings has decreased almost as drastically. With the stiff laws against discrimination in hiring, companies are very careful in who they hire and do not hire.

Even so, studies have shown that it is easier for a white male to get a job than it is for an equally qualified man of color or woman of any race. Many positions are cycled, where a company fills a position with a worker and then lays them off and hires a new person, repeating until they find someone they feel is "suitable"—which is often not a minority.

While hiring discrimination is the most highly visible aspect of economic discrimination, it is often the most uncommon. Increasingly strong measures against discrimination have made hiring discrimination much more difficult for employers to engage in. However this is only the case in formal hiring arrangements, with corporations or others subject to public scrutiny and overview. Private hiring, such as apprenticeships of electricians, plumbers, carpenters, and other trades is almost entirely broken down along racial lines, with almost no women in these fields and most minorities training those of their own race.

Against consumers

Most discrimination against consumers has been decreased due to stiffer laws against such practices, but still continues, both in the US and in Europe. The most common forms of such discrimination are price and service discrimination.

Discrimination based on price

Discrimination based on price is charging different prices for goods and services to different people based on their race, ethnicity, religion, or sex. It should not be confused with the separate economic concept of price discrimination. Discrimination based on price includes, but is not limited to:

  • increased costs for basic services (health care, repair, etc.)
  • increased costs for per diem charges (such as charging one person $40 while charging another person $100 for exactly the same service provided)
  • not offering deals, sales, rebates, etc. to minorities
  • higher rates for insurance for minorities

Most charges of discrimination based on price are difficult to verify, without significant documentation. Studies indicate that less than 10% of all discrimination based on price is actually reported to any authority or regulatory body, and much of this is through class-action lawsuits. Furthermore, while a number of monitoring services and consumer interest groups take an interest in this form of discrimination, there is very little they can do to change it. Most discrimination based on price occurs in situations without a standardized price list that can be compared against. In the cases of per diem charges, this is easily concealed as few consumers can exchange estimates and work rates, and even if they do the business in question can claim that the services provided had different baseline costs, conditions, etc.

Discrimination based on price in areas where special sales and deals simply are not offered can be justified by limiting them to those with strong credit ratings or those with past business with the company in question.

Services discrimination

Although price discrimination mentions services, service discrimination is when certain services are not offered at all to minorities, or are offered only inferior versions. According to at least one study, most consumer discrimination falls into this category, since it is more difficult to verify and prove. Some assertions of discrimination have included:

  • offering only high-cost plans for insurance or refusal to cover minorities
  • refusing to offer financing to minorities
  • denial of service

Against businesses

Minority owned businesses can also experience discrimination, both from suppliers and from banks and other sources of capital financing. In the US, there are tax benefits and even public relations benefits from having minority-owned businesses, so most instances of this occur outside of the United States.

Women of color are starting businesses at rates three to five times faster than all other businesses, according to an article from Babson College on "State of Businesses Owned by Women of Color" (Press release). Newswise. May 9, 2008. Retrieved 2008-05-12. However, once in business, their growth lags behind all other firms, according to the results of a multi-year study conducted by the Center for Women's Business Research in partnership with Babson College exploring the impact of race and gender on the growth of businesses owned by women who are African-American, Asian, Latina and other ethnicities.

Discrete usage discrimination

This form of discrimination covers suppliers providing substandard goods to a business, or price gouging the business on purchases and resupply orders.

Capital investment discrimination

A more significant source of perceived discrimination is in capital investment markets. Banks are often accused of not providing loans and other financial instruments for inner-city minority owned businesses. Most research indicates that the banking industry as a whole is systemic in its abuse of the legal system in avoidance of "high risk" loans to minorities, pointing out that banks cannot provide facts backing up their assertions that they deny such loans to a high failure rate.

On the other hand, most financial institutions and some economists feel that all too often, banks are accused unfairly of discrimination against minority owned businesses when said business is simply not worth such a credit risk, and that no one would find such a decision discriminatory if the business were not minority owned. These charges of reverse racism or prejudicial analysis are a longstanding source of controversy in the study of economic discrimination.

Global economic discrimination

An increasing number of economists and international commerce theorists have suggested that economic discrimination goes far beyond the bounds of individuals or businesses. The largest scale forms of economic discrimination, and the widest ranging, affect entire nations or global regions. Many consider that an open world economic system (globalization), which includes world bodies such as the International Monetary Fund (IMF), World Bank, and International Bank for Reconstruction and Development (IBRD), places countries at risk by practicing explicitly discriminatory techniques such as bilateral and regional bargaining, as well as asymmetrical trade balances and the maintaining of cheap force labor. Trade policies like the North American Free Trade Agreement (NAFTA) and General Agreement on Tariffs and Trade (GATT) are often regarded as financial measures serving to economically oppress Third World nations.

This could include:

  • Unfavorable terms for monetary support from world banking institutions
  • Coercive diplomacy to supplant local, regional or national leaders in favor of those who will act as demanded by foreign investors
  • Increased prices for supplying basic medical supplies to nations based on ethnic or religious basis
  • Refusal of trade agreements
  • Restrictive trade agreements

Programmed cell death

From Wikipedia, the free encyclopedia

Programmed cell death (PCD) sometimes referred to as cell, or cellular suicide is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage during an organism's lifecycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development.

Apoptosis and autophagy are both forms of programmed cell death. Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Necrosis was long seen as a non-physiological process that occurs as a result of infection or injury, but in the 2000s, a form of programmed necrosis, called necroptosis, was recognized as an alternative form of programmed cell death. It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is blocked by endogenous or exogenous factors such as viruses or mutations. Most recently, other types of regulated necrosis have been discovered as well, which share several signaling events with necroptosis and apoptosis.

History

The concept of "programmed cell-death" was used by Lockshin & Williams in 1964 in relation to insect tissue development, around eight years before "apoptosis" was coined. The term PCD has, however, been a source of confusion and Durand and Ramsey have developed the concept by providing mechanistic and evolutionary definitions. PCD has become the general terms that refers to all the different types of cell death that have a genetic component.

The first insight into the mechanism came from studying BCL2, the product of a putative oncogene activated by chromosome translocations often found in follicular lymphoma. Unlike other cancer genes, which promote cancer by stimulating cell proliferation, BCL2 promoted cancer by stopping lymphoma cells from being able to kill themselves.

PCD has been the subject of increasing attention and research efforts. This trend has been highlighted with the award of the 2002 Nobel Prize in Physiology or Medicine to Sydney Brenner (United Kingdom), H. Robert Horvitz (US) and John E. Sulston (UK).[12]

Types

Overview of signal transduction pathways involved in apoptosis

Apoptosis

Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organismsBiochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation. It is now thought that- in a developmental context- cells are induced to positively commit suicide whilst in a homeostatic context; the absence of certain survival factors may provide the impetus for suicide. There appears to be some variation in the morphology and indeed the biochemistry of these suicide pathways; some treading the path of "apoptosis", others following a more generalized pathway to deletion, but both usually being genetically and synthetically motivated. There is some evidence that certain symptoms of "apoptosis" such as endonuclease activation can be spuriously induced without engaging a genetic cascade, however, presumably true apoptosis and programmed cell death must be genetically mediated. It is also becoming clear that mitosis and apoptosis are toggled or linked in some way and that the balance achieved depends on signals received from appropriate growth or survival factors.

Extrinsic Vs. Intrinsic Pathways

There are two different potential pathways that may be followed when apoptosis is needed. There is the extrinsic pathway and the intrinsic pathway. Both pathways involve the use of caspases - crucial to cell death.

Extrinsic Pathway

The extrinsic pathway involves specific receptor ligand interaction. Either the FAS ligand binds to the FAS receptor or the TNF-alpha ligand can bind to the TNF receptor. In both situations there is the activation of initiator caspase. The extrinsic pathway can be activated in two ways. The first way is through fast ligan TNF-alpha binding or through a cytotoxic t-cell. The cytotoxic T-cell can attach itself to a membrane, facilitating the release of granzyme B. Granzyme B perforates the target cell membrane and in turn allows the release of perforin. Finally, perforin creates a pore in the membrane, and releases the caspases which leads to the activation of caspase 3. This initiator caspase may cause the cleaving of inactive caspase 3, causing it to become cleaved caspase 3. This is the final molecule needed to trigger cell death.

Intrinsic Pathway

The intrinsic pathway is caused by cell damage such as DNA damage or UV exposure. This pathway takes place in the mitochondria and is mediated by sensors called Bcl sensors, and two proteins called BAX and BAK. These proteins are found in a majority of higher mammals as they are able to pierce the mitochondrial outer membrane - making them an integral part of mediating cell death by apoptosis. They do this by orchestrating the formation of pores within the membrane - essential to the release of cytochrome c. However, cytochrome c is only released if the mitochondrial membrane is compromised. Once cytochrome c is detected, the apoptosome complex is formed. This complex activates the executioner caspase which causes cell death. This killing of the cells may be essential as it prevents cellular overgrowth which can result in disease such as cancer. There are another two proteins worth mentioning that inhibit the release of cytochrome c in the mitochondria. Bcl-2 and Bcl-xl are anti-apoptotic and therefore prevent cell death. There is a potential mutation that can occur in that causes the overactivity of Bcl-2. It is the translocation between chromosomes 14 and 18. This over activity can result in the development of follicular lymphoma.

Autophagy

Macroautophagy, often referred to as autophagy, is a catabolic process that results in the autophagosomic-lysosomal degradation of bulk cytoplasmic contents, abnormal protein aggregates, and excess or damaged organelles.

Autophagy is generally activated by conditions of nutrient deprivation but has also been associated with physiological as well as pathological processes such as development, differentiation, neurodegenerative diseases, stress, infection and cancer.

Mechanism

A critical regulator of autophagy induction is the kinase mTOR, which when activated, suppresses autophagy and when not activated promotes it. Three related serine/threonine kinases, UNC-51-like kinase -1, -2, and -3 (ULK1, ULK2, UKL3), which play a similar role as the yeast Atg1, act downstream of the mTOR complex. ULK1 and ULK2 form a large complex with the mammalian homolog of an autophagy-related (Atg) gene product (mAtg13) and the scaffold protein FIP200. Class III PI3K complex, containing hVps34, Beclin-1, p150 and Atg14-like protein or ultraviolet irradiation resistance-associated gene (UVRAG), is required for the induction of autophagy.

The ATG genes control the autophagosome formation through ATG12-ATG5 and LC3-II (ATG8-II) complexes. ATG12 is conjugated to ATG5 in a ubiquitin-like reaction that requires ATG7 and ATG10. The Atg12–Atg5 conjugate then interacts non-covalently with ATG16 to form a large complex. LC3/ATG8 is cleaved at its C terminus by ATG4 protease to generate the cytosolic LC3-I. LC3-I is conjugated to phosphatidylethanolamine (PE) also in a ubiquitin-like reaction that requires Atg7 and Atg3. The lipidated form of LC3, known as LC3-II, is attached to the autophagosome membrane.

Autophagy and apoptosis are connected both positively and negatively, and extensive crosstalk exists between the two. During nutrient deficiency, autophagy functions as a pro-survival mechanism, however, excessive autophagy may lead to cell death, a process morphologically distinct from apoptosis. Several pro-apoptotic signals, such as TNF, TRAIL, and FADD, also induce autophagy. Additionally, Bcl-2 inhibits Beclin-1-dependent autophagy, thereby functioning both as a pro-survival and as an anti-autophagic regulator.

Other types

Besides the above two types of PCD, other pathways have been discovered. Called "non-apoptotic programmed cell-death" (or "caspase-independent programmed cell-death" or "necroptosis"), these alternative routes to death are as efficient as apoptosis and can function as either backup mechanisms or the main type of PCD.

Other forms of programmed cell death include anoikis, almost identical to apoptosis except in its induction; cornification, a form of cell death exclusive to the epidermis; excitotoxicity; ferroptosis, an iron-dependent form of cell death and Wallerian degeneration.

Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis. Nemosis is another programmed form of necrosis that takes place in fibroblasts.

Eryptosis is a form of suicidal erythrocyte death.

Aponecrosis is a hybrid of apoptosis and necrosis and refers to an incomplete apoptotic process that is completed by necrosis.

NETosis is the process of cell-death generated by neutrophils, resulting in NETs.

Paraptosis is another type of nonapoptotic cell death that is mediated by MAPK through the activation of IGF-1. It's characterized by the intracellular formation of vacuoles and swelling of mitochondria.

Pyroptosis, an inflammatory type of cell death, is uniquely mediated by caspase 1, an enzyme not involved in apoptosis, in response to infection by certain microorganisms.

Plant cells undergo particular processes of PCD similar to autophagic cell death. However, some common features of PCD are highly conserved in both plants and metazoa.

Atrophic factors

An atrophic factor is a force that causes a cell to die. Only natural forces on the cell are considered to be atrophic factors, whereas, for example, agents of mechanical or chemical abuse or lysis of the cell are considered not to be atrophic factors. Common types of atrophic factors are:

  1. Decreased workload
  2. Loss of innervation
  3. Diminished blood supply
  4. Inadequate nutrition
  5. Loss of endocrine stimulation
  6. Senility
  7. Compression

Role in the development of the nervous system

Dying cells in the proliferate zone

The initial expansion of the developing nervous system is counterbalanced by the removal of neurons and their processes. During the development of the nervous system almost 50% of developing neurons are naturally removed by programmed cell death (PCD). PCD in the nervous system was first recognized in 1896 by John Beard. Since then several theories were proposed to understand its biological significance during neural development.

Role in neural development

PCD in the developing nervous system has been observed in proliferating as well as post-mitotic cells. One theory suggests that PCD is an adaptive mechanism to regulate the number of progenitor cells. In humans, PCD in progenitor cells starts at gestational week 7 and remains until the first trimester. This process of cell death has been identified in the germinal areas of the cerebral cortex, cerebellum, thalamus, brainstem, and spinal cord among other regions. At gestational weeks 19–23, PCD is observed in post-mitotic cells. The prevailing theory explaining this observation is the neurotrophic theory which states that PCD is required to optimize the connection between neurons and their afferent inputs and efferent targets. Another theory proposes that developmental PCD in the nervous system occurs in order to correct for errors in neurons that have migrated ectopically, innervated incorrect targets, or have axons that have gone awry during path finding. It is possible that PCD during the development of the nervous system serves different functions determined by the developmental stage, cell type, and even species.

The neurotrophic theory

The neurotrophic theory is the leading hypothesis used to explain the role of programmed cell death in the developing nervous system. It postulates that in order to ensure optimal innervation of targets, a surplus of neurons is first produced which then compete for limited quantities of protective neurotrophic factors and only a fraction survive while others die by programmed cell death. Furthermore, the theory states that predetermined factors regulate the amount of neurons that survive and the size of the innervating neuronal population directly correlates to the influence of their target field.

The underlying idea that target cells secrete attractive or inducing factors and that their growth cones have a chemotactic sensitivity was first put forth by Santiago Ramon y Cajal in 1892. Cajal presented the idea as an explanation for the "intelligent force" axons appear to take when finding their target but admitted that he had no empirical data. The theory gained more attraction when experimental manipulation of axon targets yielded death of all innervating neurons. This developed the concept of target derived regulation which became the main tenet in the neurotrophic theory. Experiments that further supported this theory led to the identification of the first neurotrophic factor, nerve growth factor (NGF).

Peripheral versus central nervous system

Cell death in the peripheral vs central nervous system

Different mechanisms regulate PCD in the peripheral nervous system (PNS) versus the central nervous system (CNS). In the PNS, innervation of the target is proportional to the amount of the target-released neurotrophic factors NGF and NT3. Expression of neurotrophin receptors, TrkA and TrkC, is sufficient to induce apoptosis in the absence of their ligands. Therefore, it is speculated that PCD in the PNS is dependent on the release of neurotrophic factors and thus follows the concept of the neurotrophic theory.

Programmed cell death in the CNS is not dependent on external growth factors but instead relies on intrinsically derived cues. In the neocortex, a 4:1 ratio of excitatory to inhibitory interneurons is maintained by apoptotic machinery that appears to be independent of the environment. Supporting evidence came from an experiment where interneuron progenitors were either transplanted into the mouse neocortex or cultured in vitro. Transplanted cells died at the age of two weeks, the same age at which endogenous interneurons undergo apoptosis. Regardless of the size of the transplant, the fraction of cells undergoing apoptosis remained constant. Furthermore, disruption of TrkB, a receptor for brain derived neurotrophic factor (Bdnf), did not affect cell death. It has also been shown that in mice null for the proapoptotic factor Bax (Bcl-2-associated X protein) a larger percentage of interneurons survived compared to wild type mice. Together these findings indicate that programmed cell death in the CNS partly exploits Bax-mediated signaling and is independent of BDNF and the environment. Apoptotic mechanisms in the CNS are still not well understood, yet it is thought that apoptosis of interneurons is a self-autonomous process.

Nervous system development in its absence

Programmed cell death can be reduced or eliminated in the developing nervous system by the targeted deletion of pro-apoptotic genes or by the overexpression of anti-apoptotic genes. The absence or reduction of PCD can cause serious anatomical malformations but can also result in minimal consequences depending on the gene targeted, neuronal population, and stage of development. Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 knockout mice which develop exencephaly in the forebrain. The brainstem, spinal cord, and peripheral ganglia of these mice develop normally, however, suggesting that the involvement of caspases in PCD during development depends on the brain region and cell type. Knockout or inhibition of apoptotic protease activating factor 1 (APAF1), also results in malformations and increased embryonic lethality. Manipulation of apoptosis regulator proteins Bcl-2 and Bax (overexpression of Bcl-2 or deletion of Bax) produces an increase in the number of neurons in certain regions of the nervous system such as the retina, trigeminal nucleus, cerebellum, and spinal cord. However, PCD of neurons due to Bax deletion or Bcl-2 overexpression does not result in prominent morphological or behavioral abnormalities in mice. For example, mice overexpressing Bcl-2 have generally normal motor skills and vision and only show impairment in complex behaviors such as learning and anxiety. The normal behavioral phenotypes of these mice suggest that an adaptive mechanism may be involved to compensate for the excess neurons.

Invertebrates and vertebrates

A conserved apoptotic pathway in nematodes, mammals and fruitflies

Learning about PCD in various species is essential in understanding the evolutionary basis and reason for apoptosis in development of the nervous system. During the development of the invertebrate nervous system, PCD plays different roles in different species. The similarity of the asymmetric cell death mechanism in the nematode and the leech indicates that PCD may have an evolutionary significance in the development of the nervous system. In the nematode, PCD occurs in the first hour of development leading to the elimination of 12% of non-gonadal cells including neuronal lineages. Cell death in arthropods occurs first in the nervous system when ectoderm cells differentiate and one daughter cell becomes a neuroblast and the other undergoes apoptosis. Furthermore, sex targeted cell death leads to different neuronal innervation of specific organs in males and females. In Drosophila, PCD is essential in segmentation and specification during development.

In contrast to invertebrates, the mechanism of programmed cell death is found to be more conserved in vertebrates. Extensive studies performed on various vertebrates show that PCD of neurons and glia occurs in most parts of the nervous system during development. It has been observed before and during synaptogenesis in the central nervous system as well as the peripheral nervous system. However, there are a few differences between vertebrate species. For example, mammals exhibit extensive arborization followed by PCD in the retina while birds do not. Although synaptic refinement in vertebrate systems is largely dependent on PCD, other evolutionary mechanisms also play a role.

In plant tissue

Programmed cell death in plants has a number of molecular similarities to animal apoptosis, but it also has differences, the most obvious being the presence of a cell wall and the lack of an immune system that removes the pieces of the dead cell. Instead of an immune response, the dying cell synthesizes substances to break itself down and places them in a vacuole that ruptures as the cell dies.

In "APL regulates vascular tissue identity in Arabidopsis", Martin Bonke and his colleagues had stated that one of the two long-distance transport systems in vascular plants, xylem, consists of several cell-types "the differentiation of which involves deposition of elaborate cell-wall thickenings and programmed cell-death." The authors emphasize that the products of plant PCD play an important structural role.

Basic morphological and biochemical features of PCD have been conserved in both plant and animal kingdoms. Specific types of plant cells carry out unique cell-death programs. These have common features with animal apoptosis—for instance, nuclear DNA degradation—but they also have their own peculiarities, such as nuclear degradation triggered by the collapse of the vacuole in tracheary elements of the xylem.

Janneke Balk and Christopher J. Leaver, of the Department of Plant Sciences, University of Oxford, carried out research on mutations in the mitochondrial genome of sun-flower cells. Results of this research suggest that mitochondria play the same key role in vascular plant PCD as in other eukaryotic cells.

PCD in pollen prevents inbreeding

During pollination, plants enforce self-incompatibility (SI) as an important means to prevent self-fertilization. Research on the corn poppy (Papaver rhoeas) has revealed that proteins in the pistil on which the pollen lands, interact with pollen and trigger PCD in incompatible (i.e., self) pollen. The researchers, Steven G. Thomas and Vernonica E. Franklin-Tong, also found that the response involves rapid inhibition of pollen-tube growth, followed by PCD.

In slime molds

The social slime mold Dictyostelium discoideum has the peculiarity of either adopting a predatory amoeba-like behavior in its unicellular form or coalescing into a mobile slug-like form when dispersing the spores that will give birth to the next generation.

The stalk is composed of dead cells that have undergone a type of PCD that shares many features of an autophagic cell-death: massive vacuoles forming inside cells, a degree of chromatin condensation, but no DNA fragmentation. The structural role of the residues left by the dead cells is reminiscent of the products of PCD in plant tissue.

D. discoideum is a slime mold, part of a branch that might have emerged from eukaryotic ancestors about a billion years before the present. It seems that they emerged after the ancestors of green plants and the ancestors of fungi and animals had differentiated. But, in addition to their place in the evolutionary tree, the fact that PCD has been observed in the humble, simple, six-chromosome D. discoideum has additional significance: It permits the study of a developmental PCD path that does not depend on caspases characteristic of apoptosis.

Evolutionary origin of mitochondrial apoptosis

The occurrence of programmed cell death in protists is possible, but it remains controversial. Some categorize death in those organisms as unregulated apoptosis-like cell death.

Biologists had long suspected that mitochondria originated from bacteria that had been incorporated as endosymbionts ("living together inside") of larger eukaryotic cells. It was Lynn Margulis who from 1967 on championed this theory, which has since become widely accepted. The most convincing evidence for this theory is the fact that mitochondria possess their own DNA and are equipped with genes and replication apparatus.

This evolutionary step would have been risky for the primitive eukaryotic cells, which began to engulf the energy-producing bacteria, as well as a perilous step for the ancestors of mitochondria, which began to invade their proto-eukaryotic hosts. This process is still evident today, between human white blood cells and bacteria. Most of the time, invading bacteria are destroyed by the white blood cells; however, it is not uncommon for the chemical warfare waged by prokaryotes to succeed, with the consequence known as infection by its resulting damage.

One of these rare evolutionary events, about two billion years before the present, made it possible for certain eukaryotes and energy-producing prokaryotes to coexist and mutually benefit from their symbiosis.

Mitochondriate eukaryotic cells live poised between life and death, because mitochondria still retain their repertoire of molecules that can trigger cell suicide. It is not clear why apoptotic machinery is maintained in the extant unicellular organisms. This process has now been evolved to happen only when programmed. to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell-death-inducing biochemical cascade. As such, the cell suicide mechanism is now crucial to all of our lives.

DNA damage and apoptosis

Oxidative stress or environmental insults can lead to DNA damage in replicating cells and this can result in apoptosis or cancer.

Repair of DNA damages and apoptosis are two enzymatic processes essential for maintaining genome integrity in humans. Cells that are deficient in DNA repair tend to accumulate DNA damages, and when such cells are also defective in apoptosis they tend to survive even with excess DNA damage. Replication of DNA in such cells leads to mutations and these mutations may cause cancer (see Figure). Several enzymatic pathways have evolved for repairing different kinds of DNA damage, and it has been found that in five well studied DNA repair pathways particular enzymes have a dual role, where one role is to participate in repair of a specific class of damages and the second role is to induce apoptosis if the level of such DNA damage is beyond the cell's repair capability. These dual role proteins tend to protect against development of cancer. Proteins that function in such a dual role for each repair process are: (1) DNA mismatch repair, MSH2, MSH6, MLH1 and PMS2; (2) base excision repair, APEX1 (REF1/APE), poly(ADP-ribose) polymerase (PARP); (3) nucleotide excision repair, XPB, XPD (ERCC2), p53, p33(ING1b); (4) non-homologous end joining, the catalytic subunit of DNA-PK; (5) homologous recombinational repair, BRCA1, ATM, ATR, WRN, BLM, Tip60, p53.

Programmed death of entire organisms

Clinical significance

ABL

The BCR-ABL oncogene has been found to be involved in the development of cancer in humans.

c-Myc

c-Myc is involved in the regulation of apoptosis via its role in downregulating the Bcl-2 gene. Its role the disordered growth of tissue.

Metastasis

A molecular characteristic of metastatic cells is their altered expression of several apoptotic genes.

Rocket propellant

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Rocket_pr...