A review of A. Hisch and N. de Marchi's thorough historical study on Milton Friedman's life-long work as an economist (and more specifically as a monetary economist) and as an economic methodologist (in his famous essay "The Methodology of Positive Economics".

The starting point of our study is the awareness that currently we are in a phase of epochal change of the epistemological paradigm. As for the passage from oral to writing culture, now we can see, with the technological diffusion, a further transition to digital culture. Our aim is to make psychotherapists, researchers, and educators aware that the new phenomena emerging in relation to this technological diffusion bring on a necessary change. Such a change is needed in the way these (...) phenomena are appraised and treated at the psychological and sociological level. (shrink)

MARGARET LYNN SCHABAS (Toronto, 1954) is professor of philosophy at the University of British Columbia in Vancouver and served as the head of the Philosophy Department from 2004-2009. She has held professoriate positions at the University of Wisconsin-Madison and at York University, and has also taught as a visiting professor at Michigan State University, University of Colorado-Boulder, Harvard, CalTech, the Sorbonne, and the École Normale de Cachan. As the recipient of several fellowships, she has enjoyed visiting terms at Stanford, Duke, (...) MIT, Cambridge, the LSE, and the MPI-Berlin. In addition to her doctorate in the history and philosophy of science and technology (Toronto 1983), she holds a bachelor of science in music (oboe) and the philosophy of science (Indiana 1976), a master’s degree in the history and philosophy of science (Indiana 1977), and a master’s degree in economics (Michigan1985). -/- She has published four books and over forty articles or book chapters in science studies. Some of the journals in which her articles can be found are Isis, Monist, History of Political Economy, Public Affairs Quarterly, Daedaelus, Journal of Economic Perspectives, and Studies in the History and Philosophy of Science. Her first book, A world ruled by number (1990) examines the emergence of mathematical economics in the second half of the nineteenth century. Her second book, The natural origins of economics (2005), traces the transformation of economics from a natural to a social science. She also has two co-edited collections, Oeconomies in the age of Newton (2003), with Neil De Marchi, and David Hume’s political economy (2008), with Carl Wennerlind. She is currently writing a monograph on Hume’s economics, as well as articles on the history and philosophy of bioeconomics. She is currently president of the History of Economics Society. -/- EJPE interviewed Margaret Schabas at the University of British Columbia in March 2013. In this interview, she recounts her earliest foray into the history and philosophy of economics, the conceptual trade between economics and natural science, and her most recent undertaking: the history and philosophy of bioeconomics. (shrink)

De Cruz and Levy, in their commentaries on Religion as make‐believe, present distinct questions that can be addressed by clarifying one core idea. De Cruz asks whether one can rationally assess the mental state of religious credence that I theorize. Levy asks why we should not explain the data on religious “belief” merely by positing factual beliefs with religious contents, which happen to be rationally acquired through testimony. To both, I say that having religious credences is p‐irrational: a purposeful departure (...) from rational thought and behavior, where the purpose in question is maintaining a group identity. (shrink)

Pietro Gori dedicates Nietzsche’s Pragmatism “To the wanderers and Good Europeans,” and Anglophone wanderers into Sarah de Sanctis’s translation will indeed find good European Nietzsche scholarship. The table of contents is a helpful map of the book, with five chapters consisting of twenty-eight sections on a sequence of philosophical and interpretive topics. Perspectival thought, addressed in the subtitle, is the explicit topic of the third chapter. Pragmatism, mentioned in the title, is the explicit topic of the fifth and final chapter. (...) While both topics also are discussed in many other places, the overall focus is on Nietzsche’s views of epistemology and truth.The first chapter discusses Nietzsche’s views of... (shrink)

XENOLOGY AND XENOTOPOGRAPHY OF BERNHARD WALDENFELS The paper strives to adapt Bernhard Waldenfels’ xenology and so called ‘xenotopography’ for the philosophico-literary studies in fantastic world-building with a special concern of the ‘portal-quest’ model of fantasy and SF. Following Waldenfel’s remarks on the nature of post- Husserlian diastasis of our world [Heimwelt] and otherworld [Fremdwelt] and acknowledging the consequences of allocating one’s attitude towards the otherness in the symbolical borderland [‘sphere of intermonde’] in between, it is examined whether such a model (...) can occur in the fantastic literature and what may be the consequence of xenotopographic reconsideration of its basic ontological premises. Additionally, the article offers an original xenotopograpfic model of worldbuilding which addresses three carefully chosen case studies of fantastic worlds from Orson Scott Card’s Ender’s Game tetralogy, Neil Gaiman’s Stardust and George R. R. Martin’s The Song of Ice and Fire. In the end, it is suggested that hitherto presented xenotopography gravely inspired a postmodern shift in the genres of fantasy and SF which results in more ethically conscious representations of the otherness and even more concise and alien comprehensive world-building. (shrink)

The paper discusses Beauvoir's interpretation of the Marxist and Freudian contributions to our understanding of the feminine condition. Several epistemological assumptions derived from Sartre's philosophy are pointed out. Beauvoir's reading of Marx, Engels, and Freud is discussed, claiming that her reading is biased by humanistic and historicist assumptions. This is an unpublished English version of Sergio Cremaschi, “Marxismo e psicanalisi in Il secondo sesso di Simone de Beauvoir”, Vita e Pensiero, 67 (1975), 3-4, pp. 510-525; reprint in E. De (...) class='Hi'>Marchi (ed.), In nome della donna, Editrice Vita e Pensiero, Milano, 1976, pp. 510-525. (shrink)

Introduction / St.L. JAKI (pp. 9-19). Présentation / J.-Fr. STOFFEL (p. 21). – L'œuvre de Pierre Duhem (pp. 25-113). Publications post­humes (pp. 115-129). – IIe partie : Les travaux de ses doc­torands. Fernand Caubet (pp. 133-135). Henry Chevallier (pp. 137-141). Émile Lenoble (pp. 143-144). Lucien Marchis (pp. 145-154). Eugène Monnet (pp. 155-156). Henri Pélabon (pp. 157-168). Paul Saurel (pp. 169-172). Albert Turpain (pp. 173-197). – IIIe partie : La litté­rature secondaire. Thèses et mé­moires (pp. 201-202). Livres (pp. 203-205). Biographies et (...) étu­des générales (pp. 207-209). Duhem en perspective (pp. 211-212). Le philosophe de la physique (pp. 213-234). L'histo­rien des théories physiques (pp. 235-243). Le physicien (pp. 245-251). Le croyant (pp. 253-256). Notices nécrologiques (pp. 257-258). Notices de dictionnaires et d'encyclopédies (pp. 259-260). – IVe partie : Index. (shrink)

In this public debate with Philippe Deterre (research director in immunology at the CNRS) – held at l'Enclos Rey in Paris' 15th district during the biennial Conference of the Réseau Blaise Pascal in March 2017 –, I defended the usefulness of natural theology. I first clarify theology's nature and understanding, then I speak about a tradition that upheld the public and exterior knowledge of God, and make an effort to show the presence of a theme reminiscent of natural theology behind (...) attempts at the good life. I then ask whether natural theology would only exist for the Christian. In the reply to my opponent's own reaction, I insist on the incongruity of separating our knowledge of God from our knowledge of science's wonderful discoveries, I ask whether nature could be said to be crafty and "ingenious," and I conclude by building a case for the return of God in public conversation, as part of an effort that our world needs in terms of finding back its compass, and restoring an ideal of living rationally. (shrink)

Citation:Christodoulou, Marina. “Technopolis as the Technologised Kingdom of God. Fun as Technology, Technology as Religion in the 21st Century. God sive Fun.” Cahiers d'études germaniques N° 74, 2018. La religion au XXIe siècle - Perpectives et enjeux de la discussion autour d'une société post-séculière. Études reunites par Sébastian Hüsch et Max Marcuzzi, 119-132. -/- -------- -/- Neil Postman starts his book Technopoly: The Surrender of Culture to Technology (1993)1 with a quote from Paul Goodman’s New Reformation: “Whether or not (...) it draws on new scientific research, technology is a branch of moral philosophy, not of science.” (Postman 1993: motto; Goodman 2010: 40). I would extend Postman’s Technopoly to Technopolis, to give it more of a presence in time and space. Hence, I will use the term Technopoly when I am referring to Postman; the term Technopolis is my own. -/- In his book From Faith to Fun: The Secularisation of Humour, Russel Heddendorf argues that humour is a technology (Heddendorf 2009: 32-34), as it is understood and theorized by Neil Postman in Technopoly. Russel Heddendorf also argues that “Technopoly” is a term correlated with Wittgenstein’s use of the term “worldview” (Weltanschauung) (Heddendorf 2009: 11). -/- I would like to draw on these thoughts to propose that Technopoly (or Technopolis) could be the secularized Kingdom of God, namely that Technology is the Religion of the 21st century, and that Fun is a paradigm of such a Technology / Technique. God is yet another technique or Technology of and in Technopoly. -/- The godless individual in the 21st century, I will argue, is as much a believer as the faithful in the Sacred Religion (term used in opposition to Secular or rather Technological or Technologized Religion, which is Fun). He believes in Fun (as a post-modern form of pleasure), as much as the believer believes, or more accurately, believed in God. In the 21st century, the faithful in Sacred Religion believes in a fun God, as opposed to the serious God of the past. Fun is turning into the Technologized Religion for all; for the faithful in Godly / Sacred Religion, as well for as the unfaithful. Fun (pleasure, humour) is the definitive qualia of 21st century pleasure. The mechanics of Fun make it absolutely functional for controlling people; as Aldous Huxley wrote in Brave New World, people “are controlled by inflicting pleasure” (cited in Heddendorf 2009: 158). Now, indulging in pleasure is having Fun. In the 21st century, nobody is unfaithful, nobody disputes God, because God has been manufactured into Fun. We are living in the most religious century of all. -/- The commodity of God, now inextricably blended into work and leisure ethics and culture, is as unavoidable as survival. You don’t work, you don’t survive, you don’t exist. You work, you are entitled to leisure, or free time – the time (“busy-time”) when you are busy is work. The free time of leisure (“fun-time”) is a time for fun (pleasure). The time dedicated to Fun is culturally (capitalistically) pre-defined; no moment is actually free, each moment that is sold as free is to be bought with Work Time tokens –which is money. Believe is Enjoy. Happiness, achieved through pleasure, and pleasure through Fun, and Life as Play, is the recipe for Teleology in the 21st century. -/- The Technological God (Fun), as the Sacred God before him, is sovereignty’s technique or a social “mode of release”: demonstrations, marches, petitions, freedom of speech, citizen and human rights vindications, are “modes of release”, so that the next day, feeling relieved and released that you are working for a better life and a better world, you can wake up cheerfully to walk to your workplace, feeling it will change because of your marching, or your petition, or your speech, or the mass you attended, or the prayer you said yesterday. Thus life continues unchanging, through postponing hope; the tension of the tragedy is always released (lysis) in catharsis: refreshment for the next day of work. Art, especially cinema, (namely, simulated life) follows the same cathartic principles as real life. Thus, you can keep coping, and hoping in the meantime is of much help. Religion, Art, Science, Therapy, and Technology are all technologies used to market life, sell it or lend it, and humans are buying it back. Fun is free to produce, and expensive to buy. (shrink)

Neil Gorsuch lauds judges who purport to “apply the law as it is, focusing backward, not forward, and looking to text, structure, and history to decide what a reasonable reader at the time of the events in question would have understood the law to be . . . .” It’s hard to see how such a form of Originalism withstands scrutiny. -/- First, using “reasonable reader” understandings rather than speaker meaning turns language and law on their heads. Audiences effectively (...) become the speakers in ordinary speech (since reader or audience meaning prevails), and audiences (and thus the ruled) effectively become the rulers when interpreting law (since audiences’ meaning prevails). -/- Second, since laws look forward to govern conduct, how can best legal practices keep such a backward focus? -/- Third, words (however understood by others at the time “originally” uttered) may or may not (depending on speaker and not reader meaning) signify concepts whose meanings embrace change over time. For example, the word “planet” used by a speaker before the discovery of Uranus and Neptune may or may not include further planets depending upon what the speaker meant by “planet.” (The same applies to the inclusion or exclusion of Pluto had the speaker used the word “planet” after the discovery of Pluto but before its exclusion by current science.) Unlike the “reasonable” reader of Gorsuch’s Originalism as phrased above, speakers run the gamut from reasonable to unreasonable, from informed to uninformed, and from thoughtful to thoughtless. -/- Fourth, to the extent a judge is principally “constrained” by a text or texts (as he may determine), by dictionaries that he chooses, and by “history” as the judge understands it, isn’t judicial activism encouraged rather than restrained? Talk of a “reasonable” reader masks the fact that there can be multiple “reasonable” conclusions of what a reasonable or unreasonable speaker meant. Is a judge not therefore left to pick definitions and applications of terms that accord with the judge’s understandings of history, understandings that may well be colored by the judge’s politics and judicial philosophy? This applies to principles as well as labels for things. Principles are also subject to multiple frames, and their terms are subject to multiple definitions therefore raising the very same questions just raised above. -/- Finally, such Originalism doesn’t merely fail with legal texts. It also fails when applied to other texts (including sacred texts such as the Ten Commandments) and when used to interpret art (such as “Landscape with the Fall of Icarus” often attributed to Bruegel and which inspired such great ekphrasis as Auden’s “Musée Des Beaux Arts”). These further failures underscore the dysfunction of Originalism in Gorsuch's form noted above. -/- Keywords: Originalism, Neil Gorsuch, Text, Textualism, Scalia, Interpretation, Pragmatics, Speaker Meaning, Art, Painting, Bruegel, Auden, Ekphrasis, Icarus, Bible, Ten Commandments, Herod, Declaration of Independence, Abraham Lincoln. (shrink)

ABSTRACT The individual-community relationship has always been one of the most fundamental topics of social sciences. In sociology, this is known as the micro-macro relationship while in economics it refers to the processes, through which, individual actions lead to macroeconomic phenomena. Based on philosophical discourse and systems theory, many sociologists even use the term "emergence" in their understanding of micro-macro relationship, which refers to collective phenomena that are created by the cooperation of individuals, but cannot be reduced to individual actions. (...) "Emergence" theories attempt to explain the nature of society as a complex system by examining how individuals and their relationships lead to the creation of integrated and macro-social phenomena such as markets, educational systems, cultural beliefs, and shared social practices. As a prelude to activity, every researcher has to answer the question from the methodological point of view, how is it possible to study the behavior of social groups and how can we gain knowledge about the laws related to social groups? Anyone who deals with humanities and social sciences or any reality and phenomenon that affects human beings, inevitably deals with the reality that is emerging. In fact, emergence occurs when one level of reality emerges radically from another level. Examples of emergent levels of reality include how the mind emerges from the body; or the way society emerges from human beings. Therefore, when there is an emerging factor, different scientific disciplines should be used, because it is inevitable to talk about social affairs, psychology and neurobiology, as well as physical and even chemical. -/- INTRODUCTION Since its beginning in the 19th century, sociology has faced the fundamental question of what a social phenomena stands for? At a glance, sociologists deal with the study of social groups, collective behavior, institutions, social structures, social networks, and social dynamics, and ultimately all such phenomena are composed of individuals. Therefore, social phenomena seem to have no independent ontological status, and in this case, sociology is ultimately about reducible individuals. Different approaches about the micro-macro relationship, using the concept of "emergence", argue that although collective phenomena are created by individuals, they cannot be reduced to individual action. The term "emergence" is used to distinguish "emergent results" from " Procedural results". Results are called Procedural that can only be calculated by adding or subtracting the causes that act together. On the contrary, they are emergent outcomes that are qualitatively novel compared to the causes from which they originate. An example of such emergent results is mental characteristics that emerge from neural processes, but are not considered among the characteristics of neural processes of components - which are their origin. Philosophical debates about emergentism and reductionism focus on the mind-brain relationship, but as many philosophers have noted, they can be generalized to apply to any hierarchical set of features. The cognitive revolution reactivated a 19th century controversy between theorists of Identity and dualism. The theorists of Identity believe in reductionist materialism and elimination of metaphysics, according to which the mind is nothing more than the biological, while the dualists believe that the mind and the brain are distinct from each other. Emergence has been considered as a third way between the theories of Identity and dualism. -/- METHODOLOGY Interdisciplinarity Is fundamentally indicated by the dominance of open systems as well as social and emerging systems at different levels. Therefore, as long as we are facing a new emergentism, there will necessarily be different fields and an interdisciplinary method. The commonality of social sciences and cognitive sciences on the issue of emergence provides the possibility of interaction and exchange of concepts between these two for deeper research. Therefore, in this research, apart from the concepts of Subvenience and downward causation, we have used multiple realization and wildly disjunctive, which are used to explain the emerging concept in cognitive sciences, including neurobiology, psychology, and philosophy. For analytical and interdisciplinary approaches, after examining the concepts of subvenience, and wildly disjunctive, Individualistic and collectivist emergentism have been reviewed. And then their adequacy is criticized and evaluated in meeting strong emergence conditions. -/- FINDINGS Philosophers of the mind have been able to define the conditions of irreducibility and downward causation, which are essential for strong emergence, by using the principle of subvenience with the help of multiple realization and wildly disjunctive principles. Therefore, by definition, emergentist individualism suffers from the problem of how to explain downward causality and irreducibility, and emergentist collectivism faces the challenge of reification. The analysis of the challenges facing the two methodological approaches of individualism and collectivism leads us to three unresolved issues about the emerging phenomenon, which are realism, downward causality, and mechanism. Despite the differences in the stances of these two approaches regarding the aforementioned triple problems, individualists and collectivists both agree that some social characteristics are reducible; and some others are irreducible due to their complexity, the determination of which, depends on the case study of the mechanism of emergence of each social characteristic. -/- CONCLUSION An emergence that is consistent with reductionism is called a weak emergence. And strong emergence includes the principle of irreducibility and downward causality. According to strong emergence, the characteristics of social phenomena have downward causal power, which cannot be reduced to the causal forces. The principle of subvenience, together with multiple realization and wildly disjunctive, can provide the conditions of irreducibility and downward causality, which are essential conditions of strong emergence. Based on the philosophical analysis of two methodological approaches, individualist and collectivist, it can be concluded that emergentist individualism suffers from the problem of how to explain downward causality and irreducibility, and reification collectivism faces the challenge of reification. The analysis of the problems faced by these two approaches leads us to three unresolved issues, which are realism, downward causality, and mechanism. individualist emergentists acknowledge the existence of emergent social characteristics, but despite this, they believe that these characteristics are not real but merely analytical constructs that require explanation based on individuals and their mutual actions. But collectivists argue that emergentism yields a categorical ontology and supports social realism. They accept the dependence of social characteristics on individuals, but claim that social entities and structures are ontologically independent. Individualists and collectivists both agree that some social characteristics are reducible; and others are irreducible due to their complexity; and the only way to recognize this is to engage in empirical studies of the mechanisms and temporal processes of "emergence" that create social characteristics. -/- NOVELTY The newness of this compact article is as follows: a) Presenting an interdisciplinary approach using the analysis of philosophy of cognitive sciences, including the philosophy of mind, neurobiology and psychology to formulate the issue of social emergence; b) Criticizing individualist and collectivist methodological approaches to the issue of social emergence and explaining the sufficiency and shortcomings of both in providing weak and strong emerging conditions; c) Explaining and categorizing the challenges facing methodological approaches in explaining the phenomenon of social emergence, in three categories: realism, downward causality, and mechanism. BIBLIOGRAPHY Beckermann, A., Flohr, H., & Kim, J. (eds.) (1992). Emergence or reduction? Essays on the prospects of nonreductive physicalism. Berlin: Walter de Gruyter. Bhaskar, R. (1979). The possibility of Naturalism. New York: Routledge. Bhaskar, R., Danermark, B. & Price, L. (2018). Interdisciplinarity and wellbeing: A critical realist general theory of interdisciplinarity. London and New York: Routledge. Blau, P.M. (1981). Introduction: diverse views of social structure and their common denominator. In Blau, P.M. & Merton, R.K. (eds.), Continuity in Structural Inquiry (pp. 1–23). Beverly Hills: Sage. Blau, P.M. (1987). Microprocess and macrostructure. In K.S. Cook (ed.), Social Exchange Theory (pp. 83–100). Newbury Park, CA: Sage. Brooks, R.A., & Maes, P. (eds). (1994). Artificial life IV; proceedings of the Fourth International Workshop on the Synthesis and Simulation of Living Systems. Cambridge, Mass: MIT Press. Clark, A. (1997). Being there: Putting brain, body, and world together again. Cambridge, Mass.: MIT Press. Coleman, J. S. (1987). Microfoundations and macrosocial behavior. In: J. C. Alexander, B. Giesen, R. Munch, & Neil J. Smelser (Eds.). The Micro-Macro Link (pp. 153–73). Berkeley: University of California. Coleman, J. S. (1990). Foundations of social theory. Cambridge, MA: Harvard University Press. Elster, J. (1985). Making sense of Marx. New York: Cambridge University Press. Fodor, J.A. (1974). Special sciences (Or: The disunity of science as a working hypothesis). Synthese, 28(2), 97–115. Fodor, J.A. (1989). Making mind matter more. Philosophical Topics, 17, 59-79. Giddens, A. (1984). The constitution of society: Outline of the theory of structuration. Berkeley: University of California Press. Hempel, C.G. (1965). Aspects of scientific explanation and other essays in the philosophy of science. New York: The Free Press. Horgan, T. (1993). From supervenience to superdupervenience: meeting the demands of a material world. Mind, 102, 555-586. Humphreys, P. (1997). How properties emerge”. Philosophy of Science, 64, 1-17. Kim, J. (1999). Making sense of emergence. Philosophical Studies, 95, 3–36. Kincaid, H. (1997). Individualism and the unity of science. New York: Rowman & Littlefield. Lewis, D.K. (1986). The plurality of worlds. Oxford: Oxford University Press. Nigel, G., & Conte, R. (eds.) (1995). Artificial societies; The computer simulation of social life. London: UCL Press. O’Connor, T. (1994). Emergent properties. American Philosophical Quarterly, 31, 91-104. Popper, K.R. (1968). Conjectures and refutations: The Growth of Scientific Knowledge. New York: Harper & Row. Sawyer, R. K. (2001). Emergence in sociology: contemporary philosophy of mind and some implications for sociological theory. American Journal of Sociology, 107, 551-585. Sawyer, R. K. (2004). The mechanisms of emergence. Philosophy of the Social Sciences, 34, 260–282. Sawyer, R. K. (2005). Social emergence: societies as complex systems. Cambridge: Cambridge University Press. Sawyer, R.K. (2003). Nonreductive individualism: Part 2, Social causation. Philosophy of the Social Sciences, 33, 203–224. Winch, P. (1993). The idea of a social science and its relation to philosophy‭ (SAMT, Trans.). Tehran, Iran: SAMT. (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

In this eleventh book of scilogs – called in-turns and out-turns –, one may find new and old questions and solutions, referring mostly to topics on Neutrosophy, but also Multispace, with miscellaneous addition of topics on Physics, Mathematics, or Sociology – email messages to research colleagues, or replies, notes about authors, articles, or books, spontaneous ideas, and so on. -/- Exchanging ideas with Prem Kumar Singh, Feng Liu, Nicolae Bălașa, Jimmy Quellet, Minodora Rușchița, Frank Gelli, A. R. Vătuiu, Victor Christianto, (...) Vladimir I. Rogozhin, Robert Neil Boyd, Akira Kanda, Stefan Spaarmann, Oliver Consa, Yabin Shao, Junle Zhuo, Nivetha Martin, Said Broumi, Jean Dezert, Erick González, Tomasz Witczak, B. De Baets, I. Couso, D. Dubois, L. Good, Mihaela Colhon, Atiqe Ur Rahman, Muhammad Saeed, Muhammad Ihsan, Edeline Nancy, Shawkat Alkhazaleh, Shazia Rana, Vasantha Kandasamy, Santanu Acharjee, Mohamed Al-Shmrani, Parimala Manie, Mehmet Unver, Murat Olgun, Adel Aleidhri, Akira Kanda, Ilanthenral Kandasamy, Mircea Zărnescu, R. Tayebi Khorami, Arsham Borumand Saeid, Maisam Jdid, M. Abobala, Riad Hamido, Rafael Rojas, Esmaeil Zarei, Faisal Khan, Rouzbeh Abbassi, Adel Al-Odhari, Henry Garrett, Ackbar Rezaei, Saeid Jafari, Karthika Muthusamy, Harish Garg, Huda E. Khalid, Gonca D. Güngör, Muslim A. Noah Zainal, Fakhry Asad Agusfrianto, Madeleine Al-Tahan, Mariam Hariri, Yudi Mahatma, Masoud Ghods, Marco Brigliadori, Luis Enrique Aponte Pérez, Amr Mohammed, M. Aslam (in order of reference in the book). (shrink)

Revista Cunoașterea Științifică este o publicație trimestrială din domeniile științei și filosofiei, și domenii conexe de studiu și practică. -/- Cuprins: -/- EDITORIALE Cunoașterea, de Nicolae Sfetcu Cuvânt introductiv pentru (și despre) „Cunoașterea Științifică”, de Adrian Klein Viitorul științei – Știința științelor, de Nicolae Sfetcu -/- ȘTIINȚE NATURALE Teste gravitaționale, de Nicolae Sfetcu Inside, and Beyond „Nothingness”, de Adrian Klein și Robert Neil Boyd Anomalii ale relativității generale, de Nicolae Sfetcu -/- ȘTIINȚE SOCIALE Fondarea Uniunii Europene și evoluția tratatelor (...) comunității europene, de Alexandru Cristian Istoria eugeniei, de Nicolae Sfetcu Contextul intrării României în al Doilea Război Mondial, de Nicolae Sfetcu Dezvoltarea capabilităților europene în domeniul managementului crizelor, de Alexandru Cristian The Security Management System from the Perspective of the Global Energy Crisis and the Extended Black Sea Region Escalating Conflict, de Daniela Georgiana Golea, Andreea Florina Radu, și Tiberiu Tănase Closed Economies, Autarchy – Failure and Economic Disaster, de Darius-Antoniu Ferenț -/- ȘTIINȚE FORMALE Ontologii de intreprindere în tehnologia blockchain, de Nicolae Sfetcu Învățarea automată a regulilor de asociere în mineritul datelor (data mining), de Drew Bentley -/- FILOSOFIE Platon: Biografia, de Nicolae Sfetcu Karl Popper și problema demarcației între știință și ne-știință, de Nicolae Sfetcu A Scientifically Acceptable Mechanism for the Reincarnation Process of the Self, de Adrian Klein -/- RECENZII CĂRȚI Lebăda Neagră, un risc asumat – Merită?, de Nicolae Sfetcu Republica lui Platon, de Nicolae Sfetcu -/- ISSN 2971 – 9070 ISSN-L 2821 – 8086, DOI: 10.58679/CS83230. (shrink)

Revista Cunoașterea Științifică este o publicație trimestrială din domeniile științei și filosofiei, și domenii conexe de studiu și practică. -/- Cuprins: -/- EDITORIAL Cunoașterea, de Nicolae Sfetcu Cuvânt introductiv pentru (și despre) „Cunoașterea Științifică”, de Adrian Klein -/- ȘTIINȚE NATURALE Teste gravitaționale, de Nicolae Sfetcu Inside, and Beyond „Nothingness”, de Adrian Klein și Robert Neil Boyd -/- ȘTIINȚE SOCIALE Fondarea Uniunii Europene și evoluția tratatelor comunității europene, de Alexandru Cristian Istoria eugeniei, de Nicolae Sfetcu Contextul intrării României în al (...) Doilea Război Mondial, de Nicolae Sfetcu -/- ȘTIINȚE FORMALE Ontologii de intreprindere în tehnologia blockchain, de Nicolae Sfetcu -/- FILOSOFIE Platon: Biografia, de Nicolae Sfetcu -/- RECENZII CĂRȚI Lebăda Neagră, un risc asumat – Merită?, de Nicolae Sfetcu -/- ISSN 2821– 8086 ISSN – L 2821 – 8086, DOI: 10.58679/CS18266 -/- EAN 743837007520 , Cod CS11P , ID 11130 . (shrink)

This study investigates strategies for hotels situated near Taal Volcano to lessen the impact of natural disasters, specifically volcanic eruptions. The hospitality industry in this region faces a unique threat due to the volcano's activity. This research addressed a critical gap by implementing effective preparedness and response plans. A qualitative multiple case study design was employed by the researchers. Seven (7) hotel executives from different hotels situated in Batangas who had directly encountered and navigated the impacts of natural disasters were (...) selected through the purposive sampling technique. The findings revealed several common natural hazards faced by hotels include Taal volcano eruptions, typhoons, earthquakes, ashfall, and sulfur dioxide emissions. Despite of this natural hazards, hotel executives were still capable of safeguarding their guests by implementing strategies including evacuation procedures, staff training, communication and coordination and preventive measures. In conclusion, to overcome the challenges identified in disaster preparedness, hotels in Batangas should consider several strategic actions. Hotels are recommended to take several crucial actions to enhance their preparedness and response capabilities to natural hazards. Adhering to safety regulations will help hotels maintain a high level of preparedness and minimize risks associated with natural hazards, ultimately safeguarding the well-being of guests and staff alike. (shrink)

The following is a transcript of the interview I (Yasuko Kitano) conducted with Neil Levy (The Centre for Applied Philosophy and Public Ethics, CAPPE) on the 23rd in July 2009, while he was in Tokyo to give a series of lectures on neuroethics at The University of Tokyo Center for Philosophy. I edited his words for publication with his approval.

The rightness and wrongness of actions fits on a continuous scale. This fits the way we evaluate actions chosen among a diverse range of options, even though English speakers don’t use the words “righter” and “wronger”. I outline and defend a version of scalar consequentialism, according to which rightness is a matter of degree, determined by how good the consequences are. Linguistic resources are available to let us truly describe actions simply as right. Some deontological theories face problems in accounting (...) for degrees of rightness, as they don't invoke continuous parameters among the right-making features of action. (shrink)

This essay makes a number of distinctions between the motives of love and of duty, and argues that ideally they act in concert so as to generate constancy in loving relations. The essay revolves around a case in which a husband or wife is tempted to infidelity. It is argued that resistance to the temptation is optimally grounded in love for the spouse rather than simply in a duty to resist initiated perhaps through promise or vow. This is not, however, (...) to undermine altogether the significance of promises of this sort; it is rather to put a proper emphasis on the sentiment of love as an effective spring to action and to suggest that the sentiment itself ideally brings a past promise or vow of fidelity into present relief in a choice situation. (shrink)

This essay defends a strong version of the Humean theory of motivation on which desire is necessary both for motivation and for reasoning that changes our desires. Those who hold that moral judgments are beliefs with intrinsic motivational force need to oppose this view, and many of them have proposed counterexamples to it. Using a novel account of desire, this essay handles the proposed counterexamples in a way that shows the superiority of the Humean theory. The essay addresses the classic (...) objection that the Humean theory cannot explain the feeling of obligation, Stephen Darwall's example of motivationally potent reasoning that is not based on preexisting desires, Thomas Scanlon's criticism that the Humean theory fails to account for the structure and phenomenology of deliberation, and the phenomenon of akrasia as discussed by John Searle. In each case a Humean account explains the data at least as thoroughly as opposing views can, while fitting within a simpler total account of how we deliberate and act. (shrink)

What is posthumanism and why does it matter? This book offers an introduction to the ways in which humanism's belief in the natural supremacy of the Family of Man has been called into question at different moments and from different theoretical positions. What is the relationship between posthumanism and technology? Can posthumanism have a politics—postcolonial or feminist? Are postmodernism and poststructuralism posthumanist? What happens when critical theory meets Hollywood cinema? What links posthumanism to science fiction. Posthumanism addresses these and other (...) questions in an attempt to come to terms with one of the most pressing issues facing contemporary society. (shrink)

This paper explores connections between theories of morality and theories of properties. It argues that (1) moral realism is in tension with predicate, class and mereological nominalism; (2) moral non-naturalism is incompatible with standard versions of resemblance nominalism, immanent realism and trope theory; and (3) the standard semantic arguments for property realism do not support moral realism. I also raise doubts about trope-theoretic explanations of moral supervenience and argue against one version of the principle that we should accept theories that (...) maintain neutrality. (shrink)

A number of concerns have been raised about the possible future use of pharmaceuticals designed to enhance cognitive, affective, and motivational processes, particularly where the aim is to produce morally better decisions or behavior. In this article, we draw attention to what is arguably a more worrying possibility: that pharmaceuticals currently in widespread therapeutic use are already having unintended effects on these processes, and thus on moral decision making and morally significant behavior. We review current evidence on the moral effects (...) of three widely used drugs or drug types: propranolol, selective serotonin reuptake inhibitors, and drugs that effect oxytocin physiology. This evidence suggests that the alterations to moral decision making and behavior caused by these agents may have important and difficult-to-evaluate consequences, at least at the population level. We argue that the moral effects of these and other widely used pharmaceuticals warrant further empirical research and ethical analysis. (shrink)

This essay presents an ideal for modern Western romantic love.The basic ideas are the following: people want to form a distinctive sort of plural subject with another, what Nozick has called a "We", they want to be loved for properties of certain kinds, and they want this love to establish and sustain a special sort of commitment to them over time.

I argue that one intends that ϕ if one has a desire that ϕ and an appropriately related means-end belief. Opponents, including Setiya and Bratman, charge that this view can't explain three things. First, intentional action is accompanied by knowledge of what we are doing. Second, we can choose our reasons for action. Third, forming an intention settles a deliberative question about what to do, disposing us to cease deliberating about it. I show how the desire- belief view can explain (...) why these phenomena occur when they occur, and why they don't when they don't. (shrink)

This paper argues that qualia share their physical correlates' locations. The first premise comes from the theory of relativity: If something shares a time with a physical event in all reference frames, it shares that physical event’s location. The second premise is that qualia share times with their correlates in all reference frames. Having qualia and correlates share locations makes relations between them easier to explain, improving both physicalist and dualist theories.

Propositionalism is the view that the contents of intentional attitudes have a propositional structure. Objectualism opposes propositionalism in allowing the contents of these attitudes to be ordinary objects or properties. Philosophers including Talbot Brewer, Paul Thagard, Michelle Montague, and Alex Grzankowski attack propositionalism about such attitudes as desire, liking, and fearing. This article defends propositionalism, mainly on grounds that it better supports psychological explanations.

This chapter considers the nature of imagination and belief, exploring how deeply these two states of mind differ. It first addresses a range of cognitive and motivational differences between imagination and belief which suggest that they're fundamentally different states of mind. Then it addresses imaginative immersion, delusions, and the different norms we apply to the two mental states, which some theorists regard as providing support for a more unified picture of imagination and belief.

Causal exclusion arguments are taken to threaten the autonomy of the special sciences, and the causal efficacy of mental properties. A recent line of response to these arguments has appealed to “independently plausible” and “well grounded” theories of causation to rebut key premises. In this paper I consider two papers which proceed in this vein and show that they share a common feature: they both require causes to be proportional to their effects. I argue that this feature is a bug, (...) and one that generalises: any attempt to rescue the autonomy of the special sciences, or the efficacy of the mental, from exclusion worries had better not look to proportionality for help. (shrink)

Ethical reductionism is the best version of naturalistic moral realism. Reductionists regard moral properties as identical to properties appearing in successful scientific theories. Nonreductionists, including many of the Cornell Realists, argue that moral properties instead supervene on scientific properties without identity. I respond to two arguments for nonreductionism. First, nonreductionists argue that the multiple realizability of moral properties defeats reductionism. Multiple realizability can be addressed in ethics by identifying moral properties uniquely or disjunctively with properties of the special sciences. Second, (...) nonreductionists argue that irreducible moral properties explain empirical phenomena, just as irreducible special-science properties do. But since irreducible moral properties don't successfully explain additional regularities, they run the risk of being pseudoscientific properties. Reductionism has all the benefits of nonreductionism, while also being more secure against anti-realist objections because of its ontological simplicity. (shrink)

Let's suppose you think that there are no uncountable sets. Have you adopted a restrictive position? It is certainly tempting to say yes---you've prohibited the existence of certain kinds of large set. This paper argues that this intuition can be challenged. Instead, I argue that there are some considerations based on a formal notion of restrictiveness which suggest that it is restrictive to hold that there are uncountable sets.

Actions performed in a state of automatism are not subject to moral evaluation, while automatic actions often are. Is the asymmetry between automatistic and automatic agency justified? In order to answer this question we need a model or moral accountability that does justice to our intuitions about a range of modes of agency, both pathological and non-pathological. Our aim in this paper is to lay the foundations for such an account.

Heidegger’s ontological views, his observations about liberalism and fascism, and his evaluative commitments are three premises of an argument for fascism. The ontological premise is that integrated wholes and objects of a creator or user’s will are ontologically superior, as Being and Time suggests in discussing Being-a-whole, creating art, and using equipment. The social premise is that fascist societies are wholes integrated by dictatorial will, while liberal societies are looser aggregates of free individuals, as Heidegger describes in his 1930s seminars. (...) The evaluative premise, shared with the medieval tradition and expressed in his notebook remarks about war, is that ontological superiority makes things better. The conclusion that fascism is better than liberalism should be rejected along with the evaluative premise. (shrink)

Bayesian models of legal arguments generally aim to produce a single integrated model, combining each of the legal arguments under consideration. This combined approach implicitly assumes that variables and their relationships can be represented without any contradiction or misalignment, and in a way that makes sense with respect to the competing argument narratives. This paper describes a novel approach to compare and ‘average’ Bayesian models of legal arguments that have been built independently and with no attempt to make them consistent (...) in terms of variables, causal assumptions or parameterization. The approach involves assessing whether competing models of legal arguments are explained or predict facts uncovered before or during the trial process. Those models that are more heavily disconfirmed by the facts are given lower weight, as model plausibility measures, in the Bayesian model comparison and averaging framework adopted. In this way a plurality of arguments is allowed yet a single judgement based on all arguments is possible and rational. (shrink)

Some philosophers (including Urmson, Humberstone, Shah, and Velleman) hold that believing that p distinctively involves applying a norm according to which the truth of p is a criterion for the success or correctness of the attitude. On this view, imagining and assuming differ from believing in that no such norm is applied. I argue against this view with counterexamples showing that applying the norm of truth is neither necessary nor sufficient for distinguishing believing from imagining and assuming. Then I argue (...) that the different functional properties of these mental states are enough to distinguish them, and that norm-application doesn't help us draw the functional distinctions. (shrink)

This paper outlines a new metasemantic theory of moral reason statements, focused on explaining how the reasons thus stated can be inescapable. The motivation for the theory is in part that it can explain this and other phenomena concerning moral reasons. The account also suggests a general recipe for explanations of conceptual features of moral reason statements. (Published with Open Access.).

In this paper we sketch a new version of aesthetic expressivism. We argue that one advantage of this view is that it explains various putative norms on the formation and revision of aesthetic judgement. We begin by setting out our proposed explananda and a sense in which they can be understood as governing the correct response to putative higher-order evidence in aesthetics. We then summarise some existing discussions of expressivist attempts to explain these norms, and objections raised to them. This (...) will allow us to identify the pitfalls that a good expressivist explanation needs to avoid. Finally, we sketch our preferred version of aesthetic expressivism which includes as a crucial part a hypothesis concerning the distinctive expressive function of aesthetic practice. We then consider how this theory can explain the putative aesthetic norms whilst avoiding the previous objections. (shrink)

The ‘doctrine of double effect’ claims that it is in some sense morally less problematic to bring about a negatively evaluated state of affairs as a ‘side effect’ of one’s pursuit of another, morally unobjectionable aim than it is to bring it about in order to achieve that aim. In a first step, this chapter discusses the descriptive difference on which the claim is built. That difference is shown to derive from the attitudinal distinction between intention and ‘acceptance’, a distinction (...) that is in turn claimed to ground in a feature of the decisions that generate the attitudes in question. The resulting analysis is then plugged into two different normative principles that may each be thought to specify the intuitions behind the doctrine of double effect, but which have frequently been conflated. The first concerns the permissibility of bringing about the merely accepted state of affairs, the second its reduced attributability. It is argued that examination of the intuitions behind the two principles supports neither version of the doctrine. Rather, the intuitions are best captured in an attribution principle based on subjective probabilities and a principle of attitude evaluation, neither of which make explicit reference to the attitude of intending. (shrink)

This paper examines the prospects for a conceptual or functional role theory of moral concepts. It is argued that such an account is well-placed to explain both the irreducibility and practicality of moral concepts. Several versions of conceptual role semantics for moral concepts are distinguished, depending on whether the concept-constitutive conceptual roles are wide or narrow normative or non-normative and purely doxastic or conative. It is argued that the most plausible version of conceptual role semantics for moral concepts involves only (...) ‘narrow’ conceptual roles, where these include connections to motivational, desire-like, states. In the penultimate section it is argued, contrary to what Wedgwood, Enoch and others have claimed, that such an account of moral concepts cannot plausibly be combined with the claim that moral concepts refer to robust properties. (Published with Open Access.). (shrink)

Awarding rights to rivers, forests, and other environmental entities (EEs) is a new and increasingly popular approach to environmental protection. The distinctive feature of such rights of nature (RoN) legislation is that direct duties are owed to the EEs. This paper presents a novel rebuttal of the strongest argument against RoN: the no interest argument. The crux of this argument is that because EEs are not sentient, they cannot possess the kinds of interests necessary to ground direct duties. Therefore, they (...) cannot be legitimate rights-bearers. After considering and rejecting standard responses to this argument, the paper challenges its fundamental assumption: that rights-correlative duties must be grounded in the interests of the rights-bearer. The paper then presents the RoN critic with a dilemma. The critic must either accept that EEs are legitimate rights-bearers, or delegitimise many well-established rights-bearers along with EEs. Either way, the no interest argument loses its force. (shrink)

In this chapter, we argue for three theses: (1) we lack the power to form beliefs at will (i.e., directly); at very least, we lack the power to form at will beliefs of the kind that proponents of doxastic voluntarism have in mind; but (2) we possess a propensity to form beliefs for non-epistemic reasons; and (3) these propensities—once we come to know we have them—entail that we have obligations similar to those we would have were doxastic voluntarism true. Specifically, (...) we will argue that we have obligations to avoid triggering these propensities to form beliefs that are unwarranted or even immoral. (shrink)

The moral belief problem is that of reconciling expressivism in ethics with both minimalism in the philosophy of language and the syntactic discipline of moral sentences. It is argued that the problem can be solved by distinguishing minimal and robust senses of belief, where a minimal belief is any state of mind expressed by sincere assertoric use of a syntactically disciplined sentence and a robust belief is a minimal belief with some additional property R. Two attempts to specify R are (...) discussed, both based on the thought that beliefs are states that aim at truth. According to the first, robust beliefs are criticisable to the extent that their content fails to match the state of the world. This sense fails to distinguish robust beliefs from minimal beliefs. According to the second, robust beliefs function to have their content match the state of the world. This sense succeeds in distinguishing robust beliefs from minimal beliefs. The conclusion is that the debate concerning the cognitive status of moral convictions needs to address the issue of the function of moral convictions. Evolutionary theorising may be relevant, but will not be decisive, in answering this question. (shrink)

This paper applies the theory of teleosemantics to the issue of moral content. Two versions of teleosemantics are distinguished: input-based and output-based. It is argued that applying either to the case of moral judgements generates the conclusion that such judgements have both descriptive (belief-like) and directive (desire-like) content, intimately entwined. This conclusion directly validates neither descriptivism nor expressivism, but the application of teleosemantics to moral content does leave the descriptivist with explanatory challenges which the expressivist does not face. Since teleosemantics (...) ties content to function, the paper also offers an account of the evolutionary function of moral judgements. (shrink)

This paper presents the Universality Argument that pleasure is goodness. The first premise defines goodness as what should please all. The second premise reduces 'should' to perceptual accuracy. The third premise invokes a universal standard of accuracy: qualitative identity. Since the pleasure of all is accurate solely about pleasure, pleasure is goodness, or universal moral value. The argument proceeds from a moral sense theory that analyzes moral concepts as concerned with what all should hope for, feel guilty about, and admire. (...) This requires rejecting practical anti-empiricism, the view that moral judgment concerns empirically inaccessible norms governing action. (shrink)

In the contemporary philosophy of set theory, discussion of new axioms that purport to resolve independence necessitates an explanation of how they come to be justified. Ordinarily, justification is divided into two broad kinds: intrinsic justification relates to how `intuitively plausible' an axiom is, whereas extrinsic justification supports an axiom by identifying certain `desirable' consequences. This paper puts pressure on how this distinction is formulated and construed. In particular, we argue that the distinction as often presented is neither well-demarcated nor (...) sufficiently precise. Instead, we suggest that the process of justification in set theory should not be thought of as neatly divisible in this way, but should rather be understood as a conceptually indivisible notion linked to the goal of explanation. (shrink)

A central area of current philosophical debate in the foundations of mathematics concerns whether or not there is a single, maximal, universe of set theory. Universists maintain that there is such a universe, while Multiversists argue that there are many universes, no one of which is ontologically privileged. Often forcing constructions that add subsets to models are cited as evidence in favour of the latter. This paper informs this debate by analysing ways the Universist might interpret this discourse that seems (...) to necessitate the addition of subsets to V. We argue that despite the prima facie incoherence of such talk for the Universist, she nonetheless has reason to try and provide interpretation of this discourse. We analyse extant interpretations of such talk, and analyse various tradeoffs in naturality that might be made. We conclude that the Universist has promising options for interpreting different forcing constructions. (shrink)

Trust not only disposes us to feel betrayed, trust can be betrayed. Understanding what a betrayal of trust is requires understanding how trust can ground an obligation on the part of the trusted person to act specifically as trusted. This essay argues that, since trust cannot ground an appropriate obligation where there is no prior obligation, a betrayal of trust should instead be conceived as the violation of a trust-based obligation to respect an already existing obligation. Two forms of trust (...) are evaluated for their potential to ground such a second-order obligation. One form counts as a gift to the trusted person only because it does not involve an expectation of trustworthiness; the other form cannot count as a gift but confers an honor because it does include an expectation of trustworthiness. Only trust that confers an honor generates a second-order obligation whose violation would be a betrayal of trust. -/- . (shrink)