The Use of Mixl1 in Ex Vivo and Chimeric Organ Regeneration

The Use of Mixl1 in Ex Vivo and Chimeric Organ Regeneration Anokhi Kashiparekh   TA: Goheun Kim Regenerative medicine is a field in biology that uses the underlying cell properties of differentiated growth to create entire tissues and organs from that cell. Regeneration in its true form, applies human pluripotent stem cell (hPSCs) differentiation, to make new organs like the natural regeneration of the human liver or that of the zebrafish heart (Mostoway et al, 2013). A very useful area for such a technique is the organ donation and replacement discipline. One of the greatest challenges for organ replacement is the shortage of organs donated for the cause. This is where the field of regenerative medicine can come in use. If the cells of the person in need of the organs can differentiate in a way that fills up the niche left by the diseased or missing organ, there could be a remarkable decrease in the need for organ transplantation and organ rejection. However, the development of the human organs is a gradual process and may take longer than the time the patient has to survive. A tactic to increase the speediness and the efficiency of organ regeneration is to manipulate certain genes to promote either ex vivo differentiation or differentiation in a chimeric host with a faster developmental time than humans. Specific genes can be engineered to perform specific functions, like prompting apoptosis using the Bcl-2 gene or assessing mesodermal markers using Wnt3 (Wu et al, 2016). Inducing Mixl1, the endoderm and mesoderm formation transcription factor, can play an important role in generating organs from induced pluripotent stem cells (iPSCs). Mixl1 plays an important role in chimeric and ex vivo regeneration models; although further research is required on the viability of these models. The Mixl1 transcription factor binds to the Mix gene and is a part of the hox gene family that codes for homeodomain proteins. The most important function of the Mixl1 is the regulation of cell fate and differentiation during the developmental stages of an organisms life. It regulates the formation of the endodermal and mesodermal layers and consequently can be used to manipulate hPSCs towards a particular lineage of growth. This principal property of the Mixl1 gene, as well its interactions with other genes, has been the focus of genetic regenerative medicine, in order to understand the role and consequent use of said genes. Various experiments have tried to incorporate the Mixl1 system in stem cell growth but two of the most widely known models are the ex vivo regeneration model and the chimeric model. Both of these models rely on the property of Mixl1 to guide iPSCs towards either endodermal or mesodermal fate. The basic difference between these models is the environment in which these cells are allowed to differentiate. The ex vivo model allows cell differentiation and growth outside an organism, generally in a laboratory. It is a widely preferred model due to the fact that cells from an organism can be extracted, cultured in a lab and placed back in the same organism. Each step in the experiment can be tracked and monitored and all the cells are cultured in a sterile environment. Thus, the cells placed back inside the animal are safe from potential bacteria or viruses. However, this also means that the organs generated from this may not be compatible with the surrounding tissue when introduced in an organisms body, due to the lack of interaction with other cells. Ex vivo culture of cells and ultimate organ regeneration is a step towards solving the problem of limited availability of desired cells. This ex vivo model of organ regeneration makes use of different substrates to recreate a natural differentiating environment for the cultured cells. However most times it is hard to push the hPSCs towards a particular lineage of growth, i.e. mesodermal or endodermal. The Mixl1 gene with its property to establish cell fate, is useful in resolving this. The forced expression of Mixl1 in hPSCs, in the right environment, with particular substrates and specific protein mediums, can promote ex vivo cell differentiation. Ex vivo culture, with connection to the Mixl1 gene is efficient due to the control over time of forced expression of the Mixl1 gene as well as external monitoring of the growth. Liu et al (2011)3 established this by using Là °Ã‚ Ã‚ Ã‚ °5ÃŽÂ ²1 and Là °Ã‚ Ã‚ Ã‚ °6ÃŽÂ ²1 protein ligands to promote Mixl1 induced hPSCs, in a BMP4 medium. The procedure included purifying polypeptides, culturing the hPSCs and allowing them to differentiate. The results showed that the differentiation of cells peaked on the third (to) fourth day of culture when both the LÃŽÂ ±5ÃŽÂ ²1 and Là °Ã‚ Ã‚ Ã‚ °6ÃŽÂ ²1 protein ligands were used. This gradual growth was tracked using immunofluorescence and analyzed by flow cytometry. The results of this experiment encompass both the usefulness as well as the disadvantages of an ex vivo regeneration of organs using Mixl1. The biggest challenge encountered in an ex vivo organ regeneration model is the limited number of substrates that the hPSCs can use and differentiate into a mesodermal lineage. In various cases, Mixl1 is induced unsuccessfully. This is due to the high substance substrate specificity of the iPSCs that do not survive long enough for Mixl1 to express and differentiate. Another case seen in Liu et al was the very minute expression of Mixl1 when cultured with various other individual ligands, showing that this procedure also requires the correct combination of substrates. Various agencies have also raised ethical concerns over culturing animal cells in labs. The obtaining of cells, external media and substrates from animal bodies is cited as animal abuse (cruelty). To minimize the use of animal products, a more specific area of the ex vivo model has been developed, called the xeno-free culture. Typically, all components required for a xeno-free culture come from the same organism while taking care that it is completely free of animal or human elements, like bovine blood for culturing media, etc. As a replacement to these essential components, researchers are trying to synthesize new protein ligands that can function in a similar pattern4. To reiterate, genetic manipulation of the ex vivo model has the potential to save lives but requires a deeper study in the areas of limited substrate compatibility and availability. In contrast to the ex vivo model, the chimeric model revolves around cell differentiation inside a living body. Chimeras are organisms made up of a combination of two or more zygotes and thus this model introduces extraction from and cell differentiation in two different individuals. Generation of embryonic chimeras is of both practical and conceptual importance as it provides a method to assess the developmental competence of cells. The cells of the different individuals on the same embryo can be tracked and genes can be manipulated to create a chimeric organism that can act as a vessel for organ generation. Blastocyst complementation and target organ complementation are two important techniques in chimeric organ regeneration. While blastocyst complementation uses iPSCs transferred to an embryo of another species, generally a porcine embryo, target organ complementation is focused on the regeneration of specific organs of the body. Due to the unconventionality, the adherence to soci al and ethical limitations is of great importance and requires more research to be conducted. Experiments combining this regenerative model and the forced expression of the Mixl1 gene have been successful in producing organs in different hosts. By trying to reconcile the idea of targeted generation of organs derived by using the patients own PSCs as seen in the case of the mice, Kobayashi et al (2016) makes use of blastocyst complementation to create pancreatogenesisor nephrogenesis-disabled mice. Blastocyst complementation is a technique that makes use of induced human pluripotent stem cells (iPSCs) transferred to an embryo of another species; thus, following cell growth in another body. This study used Pdx1-LacZ heterozygous mice as the chimeric hosts and injected humanized pancreatic cells in the blastocyst. This complementation was followed by the forced induction and expression of the Mixl1 gene using the pRosa26-tTA-Mixl1 vector. The data was analyzed by Western blotting and flow cytometry. The immediate result showed chimeric cells throughout the bodies of the mice. The mice were then introduced to a cell medium without Doxycycline (Dox). Immunofluorescence confirmed the distribution of cells being confined to just the guts, showing that specific target organ regeneration is possible with suitable environmental conditions and resources for the culturing cells. The forced expression of the MIxl1 gene represses mesodermal fate determination and promotes endodermal fate determination, thus helping to induce the formation of target specific organs, including the pancreas or the liver, in the disabled mice. In order to test for the amount of time Mixl1 takes to express, these mice were injected with Dox at various time intervals and the results were examined using EpCAM, an endodermal genetic marker. The cell growth apex was noted on the 4t h day of Dox administration. This leads to the belief that time is an important factor in understanding cell growth in chimeric organisms. To understand the regulation of Mixl1 based on biological functions, it was allowed to express under the influence of Oct3/4, a genetic marker seen to express in early development. The absence and presence of Dox in the host chimera was compared to establish that its absence would achieve specific target organ regeneration as compared to cell growth throughout the body. The data implied that Mixl1 presence was necessary until the epiblast stage. This gives way to the inference that the time taken for Mixl1 to express can be reduced, thus giving way to a quicker technique of organ regeneration. This model, although promising, is questionable due to the ethical controversies like the formation of human neural cells or germ cells in the host animal. This is a cause for concern due to the fact that the idea of a human brain trapped inside a mute animal is disturbing. Proper manipulation of cell differentiating genes like Mixl1 is essential to keep hPSCs from turning into cells that could humanize the host animal. While understanding and experimenting on techniques that help in human advancement, there has to be a larger focus on the social and ethical concerns of utilizing them. In conclusion, although it is limited by growing ethical concerns, genetic manipulation in chimera may help save lives with the advancement in understanding cell repair and regeneration. Thus, the idea of organ regeneration using chimerism should be looked into by science but in a way that can appeal to social principles. Another problem associated with this model of regeneration is the low success rate of differentiation in non- rodent animals2. Majority chimera experiments include rodent species as the main focus, due to both the size and relatively easy manipulation of the rodents. Although recent experiments have shown (that) porcine hosts act as good carriers for human pancreatic growth6, there is a lot of research to establish pigs as conventional hPSC hosts in order to continue chimeric research to generate bigger organs like the human heart or the human lungs. While comparing the advantages and the disadvantages of both these techniques of organ regeneration, the role and function of Mixl1 itself cannot be overlooked. Mixl1 has been shown to express within 4 days of being induced. More research may lead to a quicker expression time. Mixl1 has also helped to achieve a target specific organ regeneration by promoting mesodermal differentiation as required. The use of Mixl1 is enormous in the field of regenerative biology and can be used in other projects as well as models of regeneration. In conclusion, both ex vivo regeneration and chimeric regeneration have flaws but it is possible to refine them for better and more specific results. While the usefulness of Mixl1 cannot be denied, better models of regeneration must be established to achieve maximum efficiency for its expression. References: Mostowy, S., Boucontet, L., Moya, M. J. M., Sirianni, A., Boudinot, P., Hollinshead, M., Colucci-Guyon, E. (2013). The zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy. PLoS Pathogens, 9(9) Wu, J., Greely, H. T., Jaenisch, R., Nakauchi, H., Rossant, J., Juan Carlos Izpisua Belmonte. (2016). Stem cells and interspecies chimaeras. Nature, 540(7631), 51-59. Yang, L., Wang, X., Kaufman, D., Shen W. (2011) A synthetic substrate to support early mesodermal differentiation of human embryonic stem cells. Biomaterials. 2011 Nov;32(32):8058-66. Karnieli O., Friedner O., Allickson J., Zhang N., Jung S., Fiorentini D., Abraham E., Eaker S., Yong T., Chan A., Griffiths S., When A., Oh S.A consensus introduction to serum replacements and serum-free media for cellular therapies. Cytotherapy , Volume 19 , Issue 2 , 155 169. Kobayashi, T., Kato-Itoh, M., Nakauchi, H. (2015). Targeted organ generation using Mixl1-inducible mouse pluripotent stem cells in blastocyst complementation. Stem Cells and Development, 24(2), 182. Matsunari, H., Nagashima, H., Watanabe, M., Umeyama, K., Nakano, K., Nagaya, M., . . . Nakauchi, H. (2013). Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs. Proceedings of the National Academy of Sciences of the United States of America, 110(12), 4557-4562.

Generally Accepted Accounting Principles Essay

11. a. Year 0 Year 1 Year 2 Year 3 Year 4 Before-tax cash flow $(500,000) $52,500 $47,500 $35,500 $530,500 Tax cost (7,875) (7,125) (5,325) (4,575) After-tax cash flow 44,625 40,375 30,175 525,925 Discount factor (7%) .935 .873 .816 .763 Present value $(500,000) $41,724 $35,247 $24,623 $401,281 NPV $2,875 Investor W should make the investment because NPV is positive. b. Year 0 Year 1 Year 2 Year 3 Year 4 Before-tax cash flow $(500,000) $52,500 $47,500 $35,500 $530,500 Tax cost (10,500) (9,500) (7,100) (6,100) After-tax cash flow 42,000 38,000 28,400 524,400 Discount factor (7%) .935 .873 .816 .763 Present value $(500,000) $39,270 $33,174 $23,174 $400,117 NPV $(4,265) Investor W should not make the investment because NPV is negative. c. Year 0 Year 1 Year 2 Year 3 Year 4 Before-tax cash flow $(500,000) $52,500 $47,500 $35,500 $530,500 Tax cost (5,250) (4,750) (8,875) (7,625) After-tax cash flow 47,250 42,750 26,625 522,875 Discount factor (7%) .935 .873 .816 .763 Present value $(500,000) $44,179 $37,321 $21,726 $398,954 NPV $2,180 Investor W should make the investment because NPV is positive. 16. a. Opportunity 1: Year 0 Year 1 Year 2 Taxable income (loss) $(8,000) $5,000 $20,000 Marginal tax rate .40 .40 .40 Tax $(3,200) $2,000 $8,000 Before-tax cash flow $(8,000) $5,000 $20,000 Tax (cost) or savings 3,200(2,000) (8,000) Net cash flow $(4,800) $3,000 $12,000 Discount factor (12%) .893 .797 Present value $(4,800) $2,679 $9,564 NPV $7,443 Opportunity 2: Year 0 Year 1 Year 2 Taxable income $5,000 $5,000 $5,000 Marginal tax rate .40 .40 .40 Tax $2,000 $2,000 $2,000 Before-tax cash flow $5,000 $5,000 $5,000 Tax (cost) or savings (2,000) (2,000) (2,000) Net cash flow $3,000 $3,000 $3,000 Discount factor (12%) .893 .797 Present value $3,050 $2,679 $2,391 NPV $8,120 Firm E should choose opportunity 2. b. Opportunity 1: Year 0 Year 1 Year 2 Taxable income (loss) $(8,000) $5,000 $20,000 Marginal tax rate .15 .15 .15 Tax $(1,200) $750 $3,000 Before-tax cash flow $(8,000) $5,000 $20,000 Tax (cost) or savings 1,200 (750) (3,000) Net cash flow $(6,800) $4,250 $17,000 Discount factor (12%) .893 .797 Present value $(6,800) $3,795 $13,549 NPV $10,544 Opportunity 2: Year 0 Year 1 Year 2 Taxable income $5,000 $5,000 $5,000 Marginal tax rate .15 .15 .15 Tax $750 $750 $750 Before-tax cash flow $5,000 $5,000 $5,000 Tax (cost) or savings (750) (750) (750) Net cash flow $4,250 $4,250 $4,250 Discount factor (12%) .893 .797 Present value $4,250 $3,795 $3,387 NPV $11,432 Firm E should choose opportunity 2. c. Opportunity 1: Year 0 Year 1 Year 2 Taxable income (loss) $(8,000) $5,000 $20,000 Marginal tax rate .40 .15 .15 Tax $(3,200) $750 $3,000 Before-tax cash flow $(8,000) $5,000 $20,000 Tax (cost) or savings 3,200 (750) (3,000) Net cash flow $(4,800) $4,250 $17,000 Discount factor (12%) .893 .797 Present value $(4,800) $3,795 $13,549 NPV $12,544 Opportunity 2: Year 0 Year 1 Year 2 Taxable income $5,000 $5,000 $5,000 Marginal tax rate .40 .15 .15 Tax $2,000 $750 $750 Before-tax cash flow $5,000 $5,000 $5,000 Tax (cost) or savings (2,000) (750) (750) Net cash flow $3,000 $4,250 $4,250 Discount factor (12%) .893 .797 Present value $3,000 $3,795 $3,387 NPV $10,182 Firm E should choose opportunity 1. 1. a. (1) Year 0 Year 1 Year 2 Before-tax salary/income $80,000 $80,000 $80,000 Marginal tax rate .25 .40 .40 Tax on income $20,000 $32,000 $32,000 After-tax cash flow $60,000 $48,000 $48,000 Discount factor (8%) .926 .857 Present value $60,000 $44,448 $41,136 NPV of salary received by Mrs. X $145,584 (2) Before-tax payment /deduction $80,000 $80,000 $80,000 Marginal tax rate .34 .34 .34 Tax savings from deduction $27,200 $27,200 $27,200 After-tax cost $(52,800) $(52,800) $(52,800) Discount factor (8%) .926 .857 Present value $(52,800) $(48,893) $(45,250) NPV of salary cost to Firm B $(146,943) b. (1) Year 0 Year 1 Year 2 Before-tax salary/income $140,000 $50,000 $50,000 Marginal tax rate .25 .40 .40 Tax on income $35,000 $20,000 $20,000 After-tax cash flow $105,000 $30,000 $30,000 Discount factor (8%) .926 .857 Present value $105,000 $27,780 $25,710 NPV of salary received by Mrs. X $158,490 (2) Before-tax payment /deduction $140,000 $50,000 $50,000 Marginal tax rate .34 .34 .34 Tax savings from deduction $47,600 $17,000 $17,000 After-tax cost $(92,400) $(33,000) $(33,000) Discount factor (8%) .926 .857 Present value $(92,400) $(30,558) $(28,281) NPV of salary cost to Firm B $(151,239) c. Year 0 Year 1 Year 2 Before-tax payment /deduction $140,000 $45,000 $45,000 Marginal tax rate .34 .34 .34 Tax savings from deduction $47,600 $15,300 $15,300 After-tax cost $(92,400) $(29,700) $(29,700) Discount factor (8%) .926 .857 Present value $(92,400) $(27,502) $(25,423) NPV of salary cost to Firm B $(145,325) This proposal is superior (has less cost) to Firm B than its original offer. d. Year 0 Year 1 Year 2 Before-tax salary/income $140,000 $45,000 $45,000 Marginal tax rate .25 .40 .40 Tax on income $35,000 $18,000 $18,000 After-tax cash flow $105,000 $27,000 $27,000 Discount factor (8%) .926 .857 Present value $105,000 $25,002 $23,139 NPV of salary received by Mrs. X $153,141 Mrs. X should accept this counterproposal because it has a greater NPV than Firm B’s original offer.

Sociology Issues in Society for Dummies

Sociology Issues in Society for Dummies Up in Arms About Sociology Issues in Society? Social problems are not easy to fix. Also, sociological problems have a tendency to be terribly unwieldy for everyone unfamiliar with Sociology. In contemporary India, there are a lot of social difficulties. Addressing problems like gang violence aren't effortless, but they're additionally not impossible to cope with. Individuals may also make social problems difficult to fix. Scientists have linked poverty to many crucial issues of child welfare. Individuals must come to be actively involved in discussing the issue. Choosing Sociology Issues in Society Is Simple Generally speaking a perspective usually means a method of looking at things. If only a few individuals are speaking out against it, then it's not a social matter. The social phenomenon is currently understood in the light of scientific wisdom and enquiry. Throughout the life program, there are social problems connected with distinct ages. Things You Won't Like About Sociology Issues in Society and Things You Will 1 group may study the social nature of a particular group of healthcare institutions, while another may concentrate on the social effects of disease. The matter of women in college gives a historical illustration of this latter possibility. Additional lessons cover depression, anxiety and other disorders related to a ging, and several distinct kinds of physical disabilities. Society must handle the underlying issues which make children carry weapons. Civil liberties ought to be protected and respected regardless of whether or not a nation is in war time. Taking away an individual's civil liberties destroys the definition of what living in the USA of America is about. Poverty will help to keep the domination of the bourgeoisie. Rumors, Lies and Sociology Issues in Society Due to Waze and Google Maps, among the most commonly issued traffic violations today is the mobile phone ticket. If there isn't any method of changing what's happening, it isn't a social matter. The victims view point is another component that is normal in all social difficulties. There's no generally accepted way, social issues can be solved. There is a particular fragility of revenue and social position in France. Unequal distribution of wealth ensures the growth of social classes, as in the instance of the United States where there's a vital social difference between both groups. As a consequence, social issues can be raised by the unequal distribution of funding between public schools, like that seen in the United States of america. Look carefully at each detail of the proposal and don't accept it after the 20th. In order to decrease costs and keep product prices down companies are made to outsource manufacturing to other nations. Some solutions can be exceedingly complex, but others appear straight forward. The financial and skilled side is in amazing form. Moreover, you are going to learn about workplace safety, protection of health-related records, ethical considerations, and future trends and advantages in the health care environment. You've got great possibilities for growth and you'll get the job done hard. There are an assortment of methods people use to combat social problems. It's possible to stay as you are, but you'll be invited to new locations. Many sections of the nation experience these problems at any particular time regardless of the reforms. To tackle the problem of juvenile crimes and ethnic groups will call for complex scenarios. Quite a few studies support conclusions on either side of the problem, and, since funding gets scarce, the debate will intensify. Crime remains to be one of the major social problems that challenge the harmony of the American citizens, as it affects them either directly or indirectly based on the prevailing problems. There have to be some public outcry about the matter. Definitions of Sociology Issues in Society Other individuals would like to know what it requires to pursue a career as a medical sociologist and the feasible job opportunities. At UC Davis, not o nly are you going to learn about society, you'll also learn to study society. Majors can take part in internships pertinent to their areas of interest. It aids the individual find his connection to society. It increases the understanding of the society. Sociology due to its bearing upon several of the problems of the present world has assumed such a terrific importance that is regarded as the very best approach to all the social sciences. Sociology due to its bearing upon several of the problems of the present world has assumed such a fantastic importance that it's regarded as the very best approach to all the social sciences.

Article How Can We Train Leaders If We Dont Know What Leadership Is Literature Review - Free Essay Example

Sample details Pages: 9 Words: 2598 Downloads: 5 Date added: 2017/09/11 Category Advertising Essay Did you like this example? Article: How can we train leaders if we dont know what leadership is? Literature Review Critical paper analysis Article: HOW CAN WE TRAIN LEADERS IF WE DO NOT KNOW WHAT LEADERSHIP IS ? By RICHARD A: BARKER 2 CONTENT: 1. summary of the article difference between leader and leadership definitions of leadership different leadership concepts / paradigms difference between leadership and management leadership and leadership training – different ideas 2. Critical discussion Problem of leadership definitions Lack of illustrations Concepts of bureaucracy and adhocracy Problem of ‘leader’ and ‘follower’ Leadership training A manager is not always a leader 3 1. HOW CAN WE TRAIN LEADERS OF WE DO NOT KNOW WHAT LEADERSHIP IS ? BY RICHARD A. BARKER (summary of the article) The article defines leadership and gives examples of many different definitions, past and recent ones, and shows that there is no single generalized leadership concept. Don’t waste time! Our writers will create an original "Article: How Can We Train Leaders If We Dont Know What Leadership Is? Literature Review" essay for you Create order BARKER clearly separates the three terms, leader, leadership and management by explaining and criticizing the old feudal paradigm 1 and the new one which are the basis of conceptualisation of leadership. BARKER points out that there is a difference between being a leader (which is defined by BURNS as leader traits and behaviours ) and the term â€Å"leadership†. According to BURNS, leadership consists of goals that must be related towards an end value and represents a reciprocal process within a context of competition and conflict. Since Burns, the study of leadership has taken many differe nt forms which had a narrower focus on the term, however today there is very little known about leadership. There are very few recent definitions of leadership, although those that exist focus on the leader’s knowledge, traits, skills and abilities and the process of influencing. Contrary to many other authors, BARKER does not make the assumption that people know what leadership is. The responses from various studies which were done with leadership students have shown that there is very little consistency when it comes to the definition of leadership. Often these definitions are contradictory, discrepant and the content and nature of leadership are confused. However, even though there is little tendency in the definition of leadership, scholars have tried to produce a generally accepted perspective of leadership, a paradigm as the base for leadership. 1 Paradigm = a generally accepted perspective of a particular discipline at a given time; he framed the problem within the psychoanalytic paradigm- dictionary 4 This paradigm is a feudal one, where there is a ruler (masculine), within a hierarchical system, who directs and controls the activities of their subjects towards the achievement of the leader’s goals. This is usually in the form of defence and acquisition of land, i. e. war. The feudal system has been adapted slightly to form the Industrial paradigm, with economic warfare. Both paradigms have been used time and time again so that almost all existing theories and concepts of leadership today, rely on this paradigm of ‘one man at the top’. BARKER says that now there has been however a tendency towards circular or horizontal social structures of society so that the old paradigm is no longer very relevant for all organizations. According to ROST and BURNS it focuses on the leader abilities rather than on the process of leadership. Considering the word leadership itself, it can be broken down into 2 different types; abilities and skills or relationships. BARKER detailed that if leadership is focused on behaviours, skills, traits and abilities, the term has two social functions: the hope for salvation and the blame of failure. There is a lot of training for leadership abilities using this old model however it is very difficult for those being trained to put the theory into practice since they are taught simplistic models that must be applied to complex social and organizational processes. Before analysing the leadership training, it is important to ask ROST’S question: ‘how do leaders abilities differ from those of an effective manager? ’ According to BARKER, management is conceptualized as â€Å"a skill or a set of behaviours: the ability to allocate and control resources to achieve specific, planned objectives† wherefore everyone can be or become a manager. Management is the rational process of bringing about and maintaining stability and routine and also to 5 anticipate and adapt to change but not to create it, whereas leadership is all about creating new patterns of behaviour and change. The Industrial paradigm puts the leadership into a dynamic supervisor/subordinate relationship frame which is not clearly defined. The relationship can be political (BURNS) or it can be an interaction with many different people (evolutionary: ROST), but it is not a rational process. ROST’s main idea is â€Å"that leadership is a dynamic social and political relationship that is based on a set of mutual development purposes. † Relations hips are contractual and are a narrower field than the concept of leadership process, which is broader and provides the vehicle for creating leadership relationships. The leadership process is defined as â€Å"a dynamic process of interaction that creates change. † This view of leadership makes a defined leader unimportant and diminishes the relevance of leaders and their characteristics, abilities and behaviours. Leadership can only be defined by the society or culture it is in as it is a democratic and social process, containing complex relationships, which constantly changes its form, speed, direction etc. Ethics also play a major role in the conceptualisation of leadership. The paper describes ethics as end values or outcomes and describes how they are incorporated into the definition of the leadership process. Two constructs of social psychology have been created, that help to explain ethics and their role in leadership. In these constructs the subconscious controls the conscious behaviour. In the two tier framework, ethics are considered as conscious as is leadership, whereas in the three tier model, according to HARRE ET AL. , leadership is seen as more subconscious but profoundly compelling. Leadership is said to be â€Å"a means for individuals to explore, understand, modify and articulate their own and other individuals’ ethics. † Within this paradigm, it is 6 leadership that creates the leader not the other way round. Leadership must necessarily be founded during a crisis2, which acts as a catalyst for the leadership process. This process, occurring in organisations which have serious trouble, is so uncontrollable that it may result in unpredictable outcomes and it can also be very disruptive to the management process. In leadership objectives are mutually created, whereas management has to use an authority relationship with power to manipulate the employees. The new paradigm removes many well-established social institutions: The group becomes responsible for the outcome, not the leader. High executive perks and salaries and the traditional approaches to leadership are not justified anymore. The new concept provides for an examination of the beliefs and assumptions behind the leadership theories. However it remains unaccepted due to being not scientifique enough, contrary to the old paradigm. The old paradigm has four assumptions the new one does not support: Firstly, leadership is often broken down into its basic components to be studied, however leadership has experiential qualities that defy deductive analysis. Secondly, leadership is also broken down into cause-effect relationships; however the new paradigm is about the whole, so it is completely inconsistent with deductive methods. Thirdly, that focus should lead to some sort of predictability and control. But the new paradigm is contrary to this, as there is a strong de -emphasis prediction as a central theme. It focuses on a group process, which is extremely difficult to sort out since it is so complex. This new theory may prove to be too complicated 2 Crisis = a perceived differential between what exists in the social order and what is desired by an individual that is strong enough to be motivating (BARKER), it orients people to think about change. 7 and to unapproachable by the Cartesian theory of explanation. However the current empirical approach is not working so something must be done. Fourthly, the old leadership paradigm was based on the assumption of constancy, but there are problems of inconsistency over time and subjectivity. The main point here is that accepting the new paradigm does not necessarily mean that the old one must be discarded. In some situations, it can still be used to better explain leadership even though there is a trend towards situations where the new paradigm is much better siuted. BARKER points out that there are different ideas about leadership training. ROST and BURNS criticized that management and leadership must be defined in the same way for leadership training to be defended. They said that this ciew is inadequate and over rationalistic. According to KLENKE, training should rather focus on leadership as a process. He avoids a bipolar or dualistic thinking. WREN focuses on citizenship as a function of leadership. Therefore, training should be focused on leadership participants actively shaping their world. BARKER criticises that modern liberal disciplines have 3 problems which has to be solved to make consistency between education and the emerging paradigm in order to make a bette r training : understanding (interpretation) instead of empiricism (rationalism), tendency of relativism in the studies and incorrect bases of academic disciplines. In the final part of the article, BARKER gives some more practical advice on education of leadership, managerial training, executive / managerial 8 development and leadership education3 and he concludes that the experience which is the most important aspect of leadership would be lost if training is only rational and scientific. A new theory is needed to have a better understanding of what leadership is, so as to cope with it. 2. CRITICAL DISCUSSION: BARKER gives a huge variety of different definitions of leadership and analyses them in a very detailed way. He offers the reader different concepts of leadership which use different definitions as their basis. Thus the reader realizes how many points of views about leadership exist and how important it is to know which concept is used if we study leadership. However, BARKERS main weak point is that he gives the reader only an overview and critique of the different definitions and concepts but does not try to find his own definition. He criticizes others for the thing he himself cannot achieve. He makes the reader aware of the lack of a general definition of leadership and underlines this problem but he does not solve it. He puts the reader into a direction, motivates him to reflect and to enlarge his view but leaves the end, the latest version of the definition of leadership which has to be adapted to the actual situation, open. Another critical point of BARKER’S article is the lack of illustrations. He presents to the reader many definitions which have similar tendencies and which are not easily separable. But he does not give the reader any examples. His article remains very theoretical. 3 For further information you can consult the article. 9 When talking about the feudal paradigm and the new one we can use the theory of â€Å"bureaucraty† and â€Å"adhocraty† to further explain the phenomena of the changing leadership concepts. In the bureaucratical organisation there was a high hierarchy and control, many different rules and impersonality which corresponds to the model of the feudal ruler who was at the top of the hierarchy and had the control over his subordinates. In the past few years, the bureaucratical orga nisation has changed towards a more decentralised organisation, where the individualism and responsibility of each person plays an important role, which changes the previous â€Å"agents† into â€Å"actors†. Since leadership is present in organisations, the development of the organisational system should also influence the leadership concept. Here it is evident that BARKER speaks the truth when he says that old leadership ideas cannot be used to answer or explain new phenomena. Therefore leadership training which is based mainly on the old feudal paradigm cannot be used in a new context. The old paradigm makes a difference between the â€Å"leader† and the â€Å"follower†. But in many actual organisations there is no real â€Å"follower† anymore. The members of the organisations are not passive individuals. They have their own values, ideas and objectives which they try to achieve, they have a certain responsibility within the organisations and take decisions. They are â€Å"acteurs†. Thus, it is not only the leader who brings about leadership. The leader needs the collaboration of the others. A person can have the best leadership skills and it might still happen that no leadership occurs if the individuals in the organisation are not willing to achieve the end value or goal and do not want to participate in the leadership. Leadership that includes a certain relationship between the leader and the other individuals has always two sides: the leader’s side and the one of the others who let this person become a leader. 10 In my opinion this is a very important point concerning leadership training. Special institutions offer firms or managers leadership trainings, but they focus on the leader’s skills, abilities and behaviour instead of taking in consideration the persons who have to be led. Often the leadership trainings are held in seminars and take place in courses with many people. Thus the training can not be specific enough. The persons taking part in these courses get general ideas of a good leader, they get to know the most effective skills a leader should have to influence people into his direction. But these courses neither adapt the training to the individual person who has to become a leader nor to the people who has to be led. The training is not put into the actual and specific context in which leadership should arise. Another point that is also very important is the fact that very often firms send managers to these leadership trainings. But I have to mention that managers are not automatically leaders. They say what has to be done , they give certain objectives for the firm and can make the people in the firm work for them in order to achieve the final goal. This is very often realized by the use of power which manifests itself in punishment, violence, seduction and strategy. BARKER is right when he explains, that even if the manager reaches the desired goal, he is not necessarily a leader as this goal is very often not mutual and the origin is not born within the group. In an organisation a leader can be a person which has a lower position than the manager, if he gets the others to work for one common objective . The leader can only become and be a leader if people are willing to legitimate this person as a leader (a manager is not always accepted by the members of an organisation). This person can be for example a powerless worker in a firm who is situated on the lowest hierarchical level. It can be a completely disorganised person who doe not have any managing skills but is accepted as a leader by his collaborators. In my opinion many leadership skills are implicit which means that they are inherited, they are part of the individual’s 11 genes, like for example being charismatic. Charisma cannot be taught or learned as it is a part of your inner self and also a part of your exterior appearance which cannot be changed. I co nclude that even a unique leadership concept and definition of leadership which is based on the new paradigm and adapted to the latest development of organisational and social structures existed, leadership would still not be completely successful. Leadership targets individuals that all differ and some of the most efficient and successful abilities of a leader are not learnable. Leadership training will always fail. 12