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)

Everywhere in the world, and in every period of human history, it has been common for energy decisions to be made in an ethically haphazard manner. With growing population pressure and increasing demand for energy, this approach is no longer viable. We believe that decision makers must include ethical considerations in energy decisions more routinely and systematically. To this end, we propose an applied ethics framework that accommodates principles from three classical ethical theories—virtue ethics, deontology, consequentialism, and two Native American (...) ethics (Lakota and Navajo)—all considered from the perspectives of the impacted communities. We illustrate this framework by evaluating five recent energy decisions: the Dakota Access Pipeline, the Navajo Nation’s possible transition from coal to solar, hydraulic fracturing in Pennsylvania, uranium mining in Virginia, and the construction of the Xiaolangdi Dam in China. An applied ethics framework is preferable to existing ethical analyses because it can serve to sharpen arguments for (un)ethical decisions and action. Rather than treat ethical reasoning as a matter of opinion, we argue that applying ethical principles in a universal and standardized way adds rigor to energy sector decisions by presenting a position available for objective scrutiny. Because our framework identifies which aspects of a targeted action (if any) must adjust to improve ethical merit, it can serve as a practical tool for improving decision-making as we enter a new era of energy transitions. (shrink)

As we look beyond our terrestrial boundary to a multi-planetary future for humankind, it becomes paramount to anticipate the challenges of various human factors on the most likely scenario for this future: permanent human settlement of Mars. Even if technical hurdles are circumvented to provide adequate resources for basic physiological and psychological needs, Homo sapiens will not survive on an alien planet if a dysfunctional psyche prohibits the utilization of these resources. No matter how far we soar into the stars, (...) our psychologies for future generations will be forever tethered to the totality of our surroundings. By shaping our environment toward survival and welfare during the voyage to Mars and in a Martian colony, we indirectly shape our psyches and prepare them for a mission of unprecedented alienation and duration. Once on Mars, human factors such as leadership structure, social organization and code of conduct, group size, gender balance, developmental cycle, mobility, length of stay and the ecological settings and type and manner of subsistence, will create a novel Martian culture. The degree that settlers are severed from the Earth will affect how radically foreign this culture will be when compared with cultures on Earth. (shrink)

An astonishing volume and diversity of evidence is available for many hypotheses in the biomedical and social sciences. Some of this evidence—usually from randomized controlled trials (RCTs)—is amalgamated by meta-analysis. Despite the ongoing debate regarding whether or not RCTs are the ‘gold-standard’ of evidence, it is usually meta-analysis which is considered the best source of evidence: meta-analysis is thought by many to be the platinum standard of evidence. However, I argue that meta-analysis falls far short of that standard. Different meta-analyses (...) of the same evidence can reach contradictory conclusions. Meta-analysis fails to provide objective grounds for intersubjective assessments of hypotheses because numerous decisions must be made when performing a meta-analysis which allow wide latitude for subjective idiosyncrasies to influence its outcome. I end by suggesting that an older tradition of evidence in medicine—the plurality of reasoning strategies appealed to by the epidemiologist Sir Bradford Hill—is a superior strategy for assessing a large volume and diversity of evidence. (shrink)

Measuring the effectiveness of medical interventions faces three epistemological challenges: the choice of good measuring instruments, the use of appropriate analytic measures, and the use of a reliable method of extrapolating measures from an experimental context to a more general context. In practice each of these challenges contributes to overestimating the effectiveness of medical interventions. These challenges suggest the need for corrective normative principles. The instruments employed in clinical research should measure patient-relevant and disease-specific parameters, and should not be sensitive (...) to parameters that are only indirectly relevant. Effectiveness always should be measured and reported in absolute terms (using measures such as 'absolute risk reduction'), and only sometimes should effectiveness also be measured and reported in relative terms (using measures such as 'relative risk reduction')-employment of relative measures promotes an informal fallacy akin to the base-rate fallacy, which can be exploited to exaggerate claims of effectiveness. Finally, extrapolating from research settings to clinical settings should more rigorously take into account possible ways in which the intervention in question can fail to be effective in a target population. (shrink)

This article presents some overlooked evidence on the reception of John Locke’s writings at Christ Church, Oxford. It is intended to supplement a new article in the History of Universities on the surprisingly positive response to Locke’s Essay Concerning Human Understanding (1689) at that bastion of late seventeenth-century high churchmanship. This evidence sheds new light on: the reception of Epicureanism at that college in the 1650s; Locke’s personal connections at Christ Church; book-holdings of Locke’s writings at the early eighteenth-century college; (...) some unnoticed uses of Locke’s writings by members of Christ Church; the European and North American reception of one Christ Church Lockean; and, the changing trajectory of the later eighteenth-century reception of Locke at that college. (shrink)

The world of entrepreneurship has historically been linked with taking risks and the potential for significant rewards. However, there persists a notable gender imbalance in the entrepreneurial landscape, wherein women entrepreneurs remain a minority. Women navigating the entrepreneurial path encounter distinct challenges, setting their experiences apart from their male counterparts. In Balayan, Batangas, despite strides towards gender equality, women entrepreneurs continue to face challenges in the entrepreneurial landscape. This qualitative study delves into the experiences of 10 successful female entrepreneurs who (...) met specific criteria. Accordingly, semi-structured interviews are conducted, exploring various aspects of participants' experiences and revealing their motivations, achievements, challenges, and strategies. Thematic analysis reveals the connection between familial, community-driven, and personal motivations that drive these entrepreneurs forward. Despite facing obstacles such as financial constraints and gender biases, they prioritize financial gains and personal growth. With resilience, innovation, and dedication, these women overcome challenges and achieve success, utilizing support networks and online marketing strategies to their advantage. Recommendations include empowering women in entrepreneurship, strengthening support networks, introducing tailored financial literacy programs, and advocating against gender biases. Implement skill development initiatives and provide specialized education in online marketing. Engage in policy advocacy, celebrate success stories, and continuously research challenges and successes. Foster collaborative partnerships between businesses, educational institutions, and communities, and advocate for increased funding opportunities for sustainable growth. This research emphasizes the strength and capabilities of women entrepreneurs in Balayan, Batangas, affirming that "pink doesn't mean weak.". (shrink)

To be effective, a medical intervention must improve one's health by targeting a disease. The concept of disease, though, is controversial. Among the leading accounts of disease-naturalism, normativism, hybridism, and eliminativism-I defend a version of hybridism. A hybrid account of disease holds that for a state to be a disease that state must both (i) have a constitutive causal basis and (ii) cause harm. The dual requirement of hybridism entails that a medical intervention, to be deemed effective, must target either (...) the constitutive causal basis of a disease or the harms caused by the disease (or ideally both). This provides a theoretical underpinning to the two principle aims of medical treatment: care and cure. (shrink)

Ethical beliefs are not justified by familiar methods. We do not directly sense ethical properties, at least not in the straightforward way we sense colors or shapes. Nor is it plausible to think – despite a tradition claiming otherwise – that there are self-evident ethical truths that we can know in the way we know conceptual or mathematical truths. Yet, if we are justified in believing anything, we are justified in believing various ethical propositions e.g., that slavery is wrong. If (...) ethical beliefs are not justified in these familiar ways, how are they justified? -/- In her widely read, “Modern Moral Philosophy,” and in her short complimentary paper, “On Brute Facts,” G.E.M. Anscombe answers this question with a compelling and unorthodox account of justification in ethics. Because of her polemical tone and because “Modern Moral Philosophy” does so much else besides, this contribution is easy to overlook. But her account is worth taking seriously, since (a) it is an underappreciated yet plausible account that sidesteps traditional controversies, (b) it offers rich conceptual tools for interpreting and critiquing ethical theories, (c) it suggests an appealing account of the place of ethical theory in ethical knowledge and, (d) it provides useful guidance for doing applied ethics. (shrink)

The philosophy of science community mourns the loss of Margaret Catherine Morrison, who passed away on January 9, 2021, after a long battle with cancer. Margie, as she was known to all who knew her, was highly regarded for her influential contributions to the philosophy of science, particularly her studies of the role of models and simulations in the natural and social sciences. These contributions made her a world-leading philosopher of science, instrumental in shifting philosophers' attention from the structure (...) of scientific theories to the practice of science. Her sophisticated studies of the function of models in scientific practice drew on detailed knowledge of the theories and experiments of physics as well as the history of physics. In emphasizing the autonomy of scientific models and their interventional character, her insights had some affinity with Cartwright's and Hacking’s views on phenomenological laws, entity realism, the instrumentalist interpretation of scientific theories, and the disunity of science. But Morrison’s approach was distinguished by the conviction that the existence of unobservable entities cannot be defended independently of the theories that support their evidence, and that scientific practice cannot be adequately understood without examining the reasons for theory unification. (shrink)

I argue that a group can have normative commitments, and that the commitment of a group is not merely a sum or aggregate of the commitments of individual group members. I begin with a set of simple cases which illustrate two structurally different ways that group commitments can go wrong. These two kinds of potential failure correspond to two different levels of commitment: one at the individual level, owed to the other group members, and one at the group level, which (...) the group as a single body owes either to itself or to some third party. I distinguish the content of a commitment (what must be done for the commitment to be fulfilled) from the holder of that commitment: the party to whom the content is owed. I then discuss examples which support the two-level view of group commitment and show that, even when individual-level and group-level commitments have the same content, they are understood to have different holders. Finally I return to my original cases and argue that a two-level structure of group commitment allows us to make sense of the problems that occur in them. (shrink)

Physics presents us with a symphony of natural constants: G, h, c, etc. Up to this point, constants have received comparatively little philosophical attention. In this paper I provide an account of dimensionful constants, in particular the gravitational constant. I propose that they represent inter-quantity structure in the form of relations between quantities with different dimensions. I use this account of G to settle a debate over whether mass scalings are symmetries of Newtonian Gravitation. I argue that they are not, (...) but only if we interpret mass anti-quidditistically. This is analogous to anti-haecceitism in the presence of spacetime symmetries. (shrink)

This is the Guest Editor's Introduction to a volume of Philosophia Reformata that considers Jaap Klapwijk's book in which he seeks to discuss evolutionary biology in relation to Christian philosophy.

Malink’s interpretation is designed to validate Aristotle’s claims of validity and invalidity of syllogistic-style arguments, as well as his conversion claims. The remaining sorts of claims in Aristotle's text are allowed to fall out as they may. Thus, not all of Aristotle’s examples turn out correct: on some occasions, Aristotle claims that a given pair of terms yields a true (false) sentence of a given type although, under Malink’s interpretation, the sentence in question is false (true). Similarly, some of Aristotle’s (...) claims of invalidity of nonsyllogistic-style arguments come out false. For example, under Malink’s interpretation, ‘A applies to all B’ and ‘B necessarily applies to all C’ entail ‘A necessarily applies to some B’, contrary to what Aristotle says. (shrink)

Review of: Margaret A. Boden, Mind as Machine: A History of Cognitive Science, 2 vols, Oxford: Oxford University Press, 2006, xlvii+1631, cloth $225, ISBN 0-19-924144-9. - Mind as Machine is Margaret Boden’s opus magnum. For one thing, it comes in two massive volumes of nearly 1700 pages, ... But it is not just the opus magnum in simple terms of size, but also a truly crowning achievement of half a century’s career in cognitive science.

Norman Levine: Marx’s Discourse with Hegel. Basingstoke: Palgrave Mac- millan 2012. 360 pages. ISBN 978-0230293342. Review by Jacob Blumenfeld -/- “Marx appropriated Hegel’s method, but he rejected Hegel’s system.” This is the core idea that Norman Levine repeatedly asserts throughout his most recent book, Marx’s Discourse with Hegel. Although this is Levine’s main point, it is by far the least interesting and perhaps the least convincing idea to stem from his extensive research. His contribution to the long debate concerning (...) the influence of Hegel on Marx is rather more of a philological nature than anything else. Levine has done the painsta- king and rigorous archival work, with the help of the MEGA , of documenting exactly a) which texts of Hegel’s were available to Marx and when he read them, b) which texts of Hegel’s were available to Marx but were never read, and c) which texts of Hegel’s were never available to Marx (ch. 2). Given this “visible” and “invisible” bibliography of Hegel, Levine then reconstructs, year by year from 1837 to 1848, exactly how Marx’s knowledge of certain texts from Hegel directly influenced Marx’s philosophy, politics, and vocabulary, as can be seen in his dissertation, newspaper articles, manuscripts, and books (ch. 3). With this in view, Levine is able to judge how Marx mis-read Hegel (ch. 4), and how Marx’s method is indebted to Hegel (ch. 5). (shrink)

This essay seeks to see if one side or the other in the hunting debate gets more purchase if we first ask what gives the state the moral right to promote sport hunting when the practice is in deep decline. We look at the dominant economic and political reasons for state support, none of which settle the moral matter. We then look at various state appeals to moral justification (ethical hunting, the right to hunt, the value of heritage, etc.) and (...) determine that they beg the same prior questions that hunters beg--questions about the new scientific understanding of animal cognition and about the ideal individual and society in the 21st C. Neither side in the philosophical debate is helped by state promotion of hunting, given that anti-hunters also often dispense with the deeper questions and the relevant science. Conclusion: the debate should be based on the new scientific understanding of animals' capacities and on current ideals of the individual and society. State policy should reflect that. -/- thehe state should see that it is on slippery ground when it devises programs to gratify hunters and to encourage the innocent, the reluctant, and the lapsed to take up the practice. (shrink)

Why are cities looking more and more alike? Why do hipster coffee shops and clothing boutiques all share that same vibe? One answer is that gentrification represents an invasive force that forcibly re-models cities, from the top-down, to meet the monotone eye of the gentrifier. Gentrification brings in external developers and designers, who create new businesses which all meet that one monotonous aesthetic mold. But I suggest, using work from Quill Kukla and Jane Jacobs, that this top-down model of gentrification (...) is incomplete. Gentrification also incentivizes local residents to remake their own businesses and properties to meet that monotone eye. Gentrification is a pressure which pushes cities to meet a universalized and therefore homogenized taste, rather than letting diverse tastes flourish. (This piece originally published as part of a symposium on Quill Kukla's City Living.). (shrink)

Debates about the genuine disease status of controversial diseases rely on intuitions about a range of factors. Adopting tools from experimental philosophy, this paper explores some of the factors that influence judgments about whether low sexual desire should be considered a disease and whether it should be medically treated. Drawing in part on some assumptions underpinning a divide in the literature between viewing low sexual desire as a genuine disease and seeing it as improperly medicalized, we investigate whether health and (...) disease judgments are affected by factors such as an individual’s gender, the cause of the low desire, whether the desire is high or low, and both personal and societal valuations of the condition. Our main findings indicate that (a) the cause of a condition influences whether it is judged a disorder, (b) how the individual values the condition influences whether the condition is seen as a proper target of medical intervention, and (c) perceived dysfunction influences judgments regarding health, disorder classification, medicalization, and medical intervention. Our findings help further illuminate the intricate interplay of factors that influence judgments about health and disease in controversial conditions. (shrink)

2021 marks Dylan's 80th birthday and his 60th year in the music world. It invites us to look back on his career and the multitudes that it contains. Is he a song and dance man? A political hero? A protest singer? A self-portrait artist who has yet to paint his masterpiece? Is he Shakespeare in the alley? The greatest living exponent of American music? An ironsmith? Internet radio DJ? Poet (who knows it)? Is he a spiritual and religious parking meter? (...) Judas? The voice of a generation or a false prophet, jokerman, and thief? Dylan is all these and none. The essays in this book explore the Nobel laureate’s masks, collectively reflecting upon their meaning through time, change, movement, and age. They are written by wonderful and diverse set of contributors, all here for his 80th birthday bash: celebrated Dylanologists like Michael Gray and Laura Tenschert; recording artists such as Robyn Hitchcock, Barb Jungr, Amy Rigby, and Emma Swift; and 'the professors’ who all like his looks: David Boucher, Anne Margaret Daniel, Ray Monk, Galen Strawson, and more. Read it on your toaster! (shrink)

Jacob Klapwijk’s book Purpose in the Living World? (Cambridge 2998) is examined with special attention given to the scholarly background from out of which it emerges as a significant contribution to reformational philosophical reflection. As an initial step to clarify some important issues raised by Klapwijk’s critical comments about Dooyeweerd’s “essentialist” concept of species, the article probes facets of the way Jan Lever incorporated reformational philosophical concepts into his biological theory and considers the 1959 review written by Herman Dooyeweerd (...) of Lever’s Creation and Evolution. The analysis focuses specifically upon the social responsibilities of these two scholars and the confrontation of their respective views. With the work of Lever and Dooyeweerd we sense something of the ambiguities when reformational philosophy confronts an evangelical scholasticism. This confrontation is an important facet of the context in which Klapwijk has set forth his discussion of creation and emergent evolution. Purpose is also the fruit of scholarly collaboration across disciplines, providing a welcome stimulus for a deepened understanding of the corporate character of the student vocation. (shrink)

This essay is my review of Colleen Dyble’s book, Taming Leviathan: Waging a War of Ideas around the World. Dyble is affiliated with the legendary classical liberal British think tank, the Institute of Economic Affairs. Her anthology is a collection of essays by people around the world who have been involved with similar free-market think tanks in countries with historically statist economic systems. These writers include Greg Lindsay, founder of the Center for Independent Studies in Australia; Margaret Tse, of (...) the Instituto Liberdade in Brazil; Michael Walker, co-founder of the Fraser Institute in Canada; Cristian Larroulet, of Libertad y Desarrollo in Chile; Giancarlo Ibarguen, of the Center for Economic and Social Studies in Guatemala (which actually founded a free-market-oriented university); Parth Shah, founder of the Center for Civil Society in India; Daniel Doron, co-founder of the Israeli Center for Social and Economic Progress; Alberto Mingardi, of the Instituto Bruno Leoni in Italy; Masaru Uchigama, founder of the Japanese for Tax Reform; Elena Leontjeva, co-founder of the Lithuanian Free Market Institute; Alexander Magno, co-founder of the Foundation for Economic Freedom in the Philippines; and last, Leon Louw, of the Free Market Foundation of South Africa. I then discuss seven important reasons why classical liberal think tanks are so important in modern societies. (shrink)

Psychology considered as a natural science began as Aristotelian "physics" or "natural philosophy" of the soul. C. Wolff placed psychology under metaphysics, coordinate with cosmology. Scottish thinkers placed it within moral philosophy, but distinguished its "physical" laws from properly moral laws (for guiding conduct). Several Germans sought to establish an autonomous empirical psychology as a branch of natural science. British and French visual theorists developed mathematically precise theories of size and distance perception; they created instruments to test these theories and (...) to measure visual phenomena such as the duration of visual impressions. These investigators typically were dualists who included mental phenomena within nature. (shrink)

Creativity pervades human life. It is the mark of individuality, the vehicle of self-expression, and the engine of progress in every human endeavor. It also raises a wealth of neglected and yet evocative philosophical questions: What is the role of consciousness in the creative process? How does the audience for a work for art influence its creation? How can creativity emerge through childhood pretending? Do great works of literature give us insight into human nature? Can a computer program really be (...) creative? How do we define creativity in the first place? Is it a virtue? What is the difference between creativity in science and art? Can creativity be taught? The new essays that comprise The Philosophy of Creativity take up these and other key questions and, in doing so, illustrate the value of interdisciplinary exchange. Written by leading philosophers and psychologists involved in studying creativity, the essays integrate philosophical insights with empirical research. CONTENTS I. Introduction Introducing The Philosophy of Creativity Elliot Samuel Paul and Scott Barry Kaufman II. The Concept of Creativity 1. An Experiential Account of Creativity Bence Nanay III. Aesthetics & Philosophy of Art 2. Creativity and Insight Gregory Currie 3. The Creative Audience: Some Ways in which Readers, Viewers and/or Listeners Use their Imaginations to Engage Fictional Artworks Noël Carroll 4. The Products of Musical Creativity Christopher Peacocke IV. Ethics & Value Theory 5. Performing Oneself Owen Flanagan 6. Creativity as a Virtue of Character Matthew Kieran V. Philosophy of Mind & Cognitive Science 7. Creativity and Not So Dumb Luck Simon Blackburn 8. The Role of Imagination in Creativity Dustin Stokes 9. Creativity, Consciousness, and Free Will: Evidence from Psychology Experiments Roy F. Baumeister, Brandon J. Schmeichel, and C. Nathan DeWall 10. The Origins of Creativity Elizabeth Picciuto and Peter Carruthers 11. Creativity and Artificial Intelligence: a Contradiction in Terms? Margaret Boden VI. Philosophy of Science 12. Hierarchies of Creative Domains: Disciplinary Constraints on Blind-Variation and Selective-Retention Dean Keith Simonton VII. Philosophy of Education (& Education of Philosophy) 13. Educating for Creativity Berys Gaut 14. Philosophical Heuristics Alan Hájek. (shrink)

This volume considers challenges to forgiveness in the most difficult circumstances, such as in criminal justice contexts, when the victim is dead or when bystanders disagree, and when anger and resentment seem preferable and important. Contributing philosophers include Myisha Cherry, Jonathan Jacobs, Barrett Emerick, Alice MacLachlan, David McNaughton and Eve Garrard. Contributing psychologists include Pumla Gobodo-Madikizela, Robert D. Enright and Mary Jacqueline Song, C. Ward Struthers, Joshua Guilfoyle, Careen Khoury, Elizabeth van Monsjou, Joni Sasaki, Curtis Phills, Rebecca Young, and Zdravko (...) Marjanovic. (shrink)

Emphasizing the human body in all of its forms, Beauty Unlimited expands the boundaries of what is meant by beauty both geographically and aesthetically. Peg Zeglin Brand and an international group of contributors interrogate the body and the meaning of physical beauty in this multidisciplinary volume. This striking and provocative book explores the history of bodily beautification; the physicality of socially or culturally determined choices of beautification; the interplay of gender, race, class, age, sexuality, and ethnicity within and on the (...) body; and the aesthetic meaning of the concept of beauty in an increasingly globalized world. Foreward by Carolyn Korsmeyer. Authors include Noel Carroll, Gregory Velazco Y Trianosky, Monique Roelofs, Whitney Davis, Eleanor Heartney, Diana Tietjens Meyers, Phoebe M. Farris, Mary Devereaux, Jo Ellen Jacobs, Karina L. Cespedes-Cortes and Paul C. Taylor, Fedwa Malti-Douglas, Stephen Davies, Jane Duran, Valerie Sullivan Fuchs, Keith Lehrer, Allen Douglas, Cynthia Freeland, Eva Kit Wah Man, Mary Bittner Wiseman, and Peg Brand's essay, "ORLAN Revisited: Disembodied Virtual Hybrid Beauty.". (shrink)

DIFERENCIAÇÃO SEXUAL -/- Emanuel Isaque Cordeiro da Silva Instituto Agronômico de Pernambuco Embrapa Semiárido -/- • _____OBJETIVO -/- Os estudantes de Veterinária e de Zootecnia estão ligados à disciplina Reprodução Animal, um pelos mecanismos fisiológicos para evitar e tratar as possíveis patologias do trato reprodutivo dos animais domésticos, e outro para o entendimento dos processos fisiológicos visando o manejo reprodutivo e a procriação para a formação de um plantel geneticamente melhorado. Sendo assim, a finalidade do presente trabalho é apresentar os (...) mecanismos que regulam as diferenças sobre o desenvolvimento embrionário relativos à diferenciação e determinação sexual de machos e fêmeas, que também incluem o desenvolvimento dos órgãos envolvidos na reprodução e a origem das diferenças entre ambos os sexos. -/- •____INTRODUÇÃO -/- Os organismos que se reproduzem sexualmente são descendentes de organismos ao qual não existia a diferenciação sexual. Em algum momento da evolução surgiu a reprodução sexual como um mecanismo para incrementar a diversidade genética e facilitar a troca de informações genéticas mediante o material genético da fêmea com o do macho. Devido sua origem comum, na maioria das espécies, tanto os machos como as fêmeas possuem todos os genes necessários para desenvolverem-se em qualquer dos sexos. O que efetivamente faz diferença entre os sexos é a forma e a ordem ao qual se expressam os genes durante o processo de desenvolvimento. A diferenciação sexual é regulada principalmente por mecanismos epigenéticos, mais do que as diferenças genéticas de grande magnitude entre os sexos. Todo o controle epigenético de qualquer processo de desenvolvimento depende basicamente de uma série de expressões gênicas, através da qual a expressão de certa combinação de genes resulta na presença de determinadas proteínas, conhecidas como os fatores de transcrição, que induzem ou reprimem a expressão de outro(os) gene(es), a partir dos quais se produzem novas proteínas, que em certos casos também atuam como fatores de transcrição para outros genes, e assim sucessivamente. Logo, a expressão ou falta de expressão de um gene ao início da série pode resultar em um ladrão totalmente diferente da expressão de outros genes subsequentes, o que pode ocasionar profundas mudanças no processo de desenvolvimento e até a mutações indesejáveis. O padrão predeterminado de expressões gênica relativo a diferenciação sexual na maioria das espécies tanto domésticas quanto selvagens, leva ao desenvolvimento de um dos sexos (o padrão predeterminado dos mamíferos é o sexo feminino). Em consequência, a diferenciação faz com que um indivíduo do sexo oposto exija a expressão de um gene de determinação sexual que desvie a subsequente série de expressões gênica em direção ao dito sexo. Nos mamíferos, a expressão do gene SRY, localizado no cromossomo Y (e portanto ausente nas fêmeas), redige o padrão de diferenciação sexual de sua via pré-estabelecida feminina em direção ao padrão masculino. A existência de uma única diferença genética (presença do gene SRY nos machos e ausentes nas fêmeas), vai se amplificando e termina resultando no desenvolvimento de indivíduos diferentes entre si. Esse é um mecanismo de diferenciação sexual cromossômica. O primeiro passo de uma série de diferenciação sexual, em sentido estrito, não depende nem requer necessariamente a presença de um gene diferente em algum dos sexos. O gene “disparador” da diferenciação sexual pode estar presente em todos os embriões, porém pode expressar-se somente em algum deles, devido a fatores ambientais que formam parte da sua regulação epigenética, isto é, uma determinação sexual ambiental. Em algumas espécies de tartarugas ou de lagartos a expressão ou falta de expressão do gene “disparador”, por exemplo, depende da temperatura existente durante a incubação dos ovos, pelo qual alguns embriões desenvolvem-se como machos e outros como fêmeas, apesar de não existir diferença genética entre eles, simplesmente como consequência da temperatura: a determinação sexual depende da temperatura a que cada um deles foi submetido durante a incubação. Em certas espécies as temperaturas mais elevadas facilitam o desenvolvimento de fêmeas e outras de machos, enquanto que em outras espécies as temperaturas amenas (intermediárias) resultam em machos, e as inferiores como as superiores induzem o desenvolvimento de fêmeas. A existência dessa diversidade indica que a temperatura por si mesma não é a que induz ou a que provoca o desenvolvimento do macho e da fêmea, senão a que atua somente como um regulador inicial da diferenciação sexual. Em outras espécies o fator ambiental que regula a determinação sexual pode ser distinto. A densidade populacional, por exemplo, pode atuar como um regulador. Podemos concluir que a determinação sexual dependente da temperatura ou de outros fatores ambientais estabelece-se antes da determinação sexual cromossômica, a qual evoluiu depois como um método que oferece maior certeza e resultado, já que a proporção de machos e fêmeas não é afetada por mudanças ambientais ou de hábitat. -/- •___FORMAÇÃO INICIAL DA GÔNADA -/- Basicamente em todos os embriões, inicialmente se formam as chamadas gônadas indiferenciadas (com o potencial de desenvolver-se em ovários ou testículos) a partir da invasão das cristas genitais pelas células germinais primordiais, que migram desde seu local de origem no epiblasto, perto do lugar onde o saco vitelino se une com o intestino primitivo e que chegam até às cristas genitais que são engrossamentos de tecido situados na região mesonéfrica do embrião. A migração das células germinais primordiais ocorre muito cedo sobre o processo de desenvolvimento do embrião (dia 26 nos bovinos). Ao chegas as cristas genitais, as células germinativas proliferam-se e se organizam com as células somáticas já existentes nas cristas para ir formando a gônada (figura 1). Para regular essa remodelação e conformação adequada da gônada vários genes se expressam, como o OCT-4 (que aparentemente mantém a totipotencialidade da gônada), assim como o SF-1 (Fator esteroidogênico 1) e o WT-1 (gene associado ao tumor de Wilms). Esses dois últimos genes estimulam a proliferação celular e estabelecimento dos cordões sexuais. Nessa etapa inicial do desenvolvimento todos esses genes se expressam sem distinção de sexo, pelo que a gônada em formação mantém a capacidade de se diferenciar em testículo ou em ovário. -/- Figura 1: migração das células germinais primordiais em direção a crista gonodal. Diferenciação das gônadas femininas e masculinas. Fonte: ZARCO, 2018. -/- •___SEXO CROMOSSÔMICO -/- Têm-se observado que nos mamíferos a determinação sexual depende diretamente dos cromossomos. As fêmeas possuem dois cromossomos sexuais X (um contribuído do óvulo e o outro por um espermatozoide “X”). Os machos, por sua vez, possuem um cromossomo sexual X(proveniente do óvulo) e um cromossomo sexual Y, que provém de um espermatozoide “Y” (figura 2). A metade dos espermatozoides produzidos por um macho são X e a metade Y, isso porque durante a espermatogênese a divisão meiótica provoca que a partir de cada espermatócito primário, célula diploide que por pertencer a um indivíduo macho tem um cromossomo X e um Y, se originem das espermátides haploides a cada um das que eles tocam cromossomos X, e outras espermátides haploides as que eles tocam os cromossomos Y. Dessa forma, de acordo com o tipo do espermatozoide que fertilize o ovócito, se originará um indivíduo com cariótipo feminino “XX” ou um cariótipo masculino “XY” (figura 2). Esse processo é conhecido como sexo cromossômico, ao qual se determina o momento da fertilização. Figura 2: nos mamíferos todos os óvulos produzidos pelas fêmeas possuem um cromossomo sexual X. A metade dos espermatozoides produzidos pelos machos possuem um cromossomo X e a outra metade possui um cromossomo Y. Dependendo do cromossomo presente no espermatozoide que fertilize o óvulo pode-se gerar um indivíduo XX (fêmea) ou um XY (macho). Fonte: ZARCO, 2018. -/- O cromossomo “Y” é uma “invenção” relativamente recente na história da evolução das espécies e do estudo da genética. Surgiu a partir de uma mutação de um cromossomo “X”, que resultou na perda de um de seus braços, que é por onde se originou a morfologia do cromossomo Y. A maioria dos genes presentes no cromossomo Y também existem no cromossomo X; assim mesmo somente alguns genes do cromossomo Y foram evoluídos até ser diferentes dos genes do cromossomo X. Embora os machos possuam um cromossomo que não está presente nas fêmeas, esse mesmo cromossomo não aporta toda a informação genética original. Todos os genes existentes nas fêmeas estão também presentes nos dos machos, já que eles também possuem um cromossomo X. Uma particularidade do cromossomo Y, ao existir somente uma cópia nos machos, é que ele sofre um entrecruzamento com um cromossomo análogo durante o processo de meiose, pelo que o cromossomo Y de um macho é idêntico ao de seu progenitor e ao de seus descendentes, exceto no caso em que ocorra uma mutação espontânea. Em contraste, os cromossomos X das fêmeas (um proveniente do pai e outro da mãe) se entrecruzam durante a meiose, por onde cada óvulo produzido pela fêmea terá uma combinação de alelos distinta em seu cromossomo X. Ao estudar as diferenças presentes na sequência de DNA do cromossomo Y, é possível identificar a distância filogenética entre os indivíduos (quanto mais diferenças existirem entre os cromossomos significa que seu ancestral comum está mais longe). Algo análogo ocorre com o DNA das mitocôndrias, que sempre são aportados pela mãe e nunca sofrem recombinação genética. Gene SRY -/- Um dos poucos genes do cromossomo Y que não possuem correspondência com o cromossomo X é o gene SRY (Sex-determining Region of the Y chromossome – região do cromossomo Y determinante do sexo). Esse gene se expressa somente na gônada em formação nos embriões machos, em particular em células precursoras das células de Sertoli; ele codifica uma proteína da família SOX (SRY-like Box) que é uma família formada por proteínas que possuem um domínio de união ao DNA e que atuam como fatores de transcrição. Ao produzir-se a proteína SRY nas células precursoras das células de Sertoli estimula-se a expressão (transcrição) de outro gene análogo, denominado SOX-9 que, por sua vez, atua como um fator de transcrição que ativa a expressão de outros genes, como o FGF-9 (Fibroblast Growth Factor-9), ou seja ele é o estimulante de ativação dos demais. Os produtos dos genes SOX-9 e FGF-9 iniciam uma cascata de expressões que provocam a diferenciação das células de suporte da gônada indiferenciada (crista genital) em células de Sertoli. Em seguida, essas células dirigem a diferenciação das células intersticiais da crista genital em células de Leydig, o que finalmente resulta na formação de um testículo. Outro dos efeitos da proteína codificada por SOX-9 é um estímulo maior da expressão de seu próprio gene, pelo qual é produzido um ciclo de retroalimentação positiva que favorece a continuidade do processo de formação testicular. Como nos embriões da fêmea não existe o gene SRY, a gônada indiferenciada não é estimulada para expressar os genes SOX-9 nem o FGF-9 nas células de suporte (que nesse caso serão precursoras de células da granulosa). A gônada, em mudança, expressa em forma constitutiva, isto é, sem a necessidade de estimulação, outra cascata de genes que incluem o WNT4 (Wingless-integration Factor 4) e o RAPO1 (Respondina-1), que por sua vez iniciam uma cascata de expressão gênica, a qual provoca a diferenciação das células somáticas da gônada indiferenciada para formação das células da granulosa e células da teca, esse feito conduz, por sua vez, a formação de um ovário. No embrião macho a proteína SOX-9 inibe a expressão dos genes WNT4 e RSPO-1, pelo que a presença do gene SRY, e portanto de SOX-9, inibem a formação de um ovário ao mesmo tempo que estimulam a formação do testículo (figura 3). Em suma, se o embrião possui genótipo XY (um embrião macho), o gene SRY começa a expressar-se sobre as células precursoras da gônada imediatamente depois da formação da mesma, quando os cordões sexuais primários estão se desenvolvendo na medula. A expressão do gene, assim como a presença subsequente das proteínas SOX-9 e FGF-9 estimula a distinção das células de Sertoli e que se organizem os tubos seminíferos a partir dos cordões sexuais primários. Em contrapartida, em um embrião com genótipo XX (fêmea) não existe o gene SRY, pelo qual é impossível que se elevem os níveis das proteínas SOX-9 e FGF-9 e as células precursoras não se diferenciam em células de Sertoli, e portanto os cordões sexuais primários sofrem regressão. Depois de alguns dias, começam a organizar-se os cordões sexuais secundários e as células precursoras iniciam a expressão do gene WNT4, o que leva as mesmas a diferenciar-se em células da granulosa, que serão a base para a conformação dos folículos ovarianos. Se em um embrião XY, macho, a expressão do gene SRY demora, é formada um ovo-testículo devido a que algumas das células somáticas das cristas gonodais começam a expressar o gene WNT4, e a diferenciar-se em células da granulosa, enquanto que em outras a proteína SRY chega a tempo para dirigir a diferenciação para formação das células de Sertoli. No ovário em formação é expressado um gene denominado DAX-1 (Dosage-sensitive Sex Reversal). Esse gene, localizado no cromossomo X, codifica uma proteína que é um membro da família dos receptores nucleares ao que lhe falta o domínio de união ao DNA, pelo que parece atuar no bloqueio de diversos fatores de transcrição, entre os que se encontra o SRY. Como a proteína DAX-1 impede a ação da proteína SRY, um excesso de expressão do gene DAX-1 pode provocar a feminilização gonodal de indivíduos XY, macho, embora tenham SRY. Em condições normais, a expressão adequada do gene DAX-1 não é capaz de evitar a masculinização gonodal de embriões com o gene SRY, daqui o nome de reversão sexual dependente da dose. Figura 3: série de expressão gênica para a determinação gonodal. SRY (Região do cromossomo Y determinante do sexo), SOX-9 (SRY-like Box-9), FGF-9 (Fator de crescimento de fibroblastos-9), WNT4 (Wingless-integration Factor-4), RSPO-1 (Respondina-1). Uma vez que o SRY induz a expressão de SOX-9 na gônada masculina, inicia-se um processo de feedback positivo mediante o qual os níveis de expressão de SOX-9 e FGF-9 vão aumentando, ao mesmo tempo que inibem a expressão de WNT-4 e RSPO-1. Na gônada feminina não se expressam SRY, SOX-9 e nem FGF-9, o que permite que se expressem os genes WNT-4 e RSPO-1, que iniciam uma cascata de sinalização que dirige a formação de um ovário. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DOS GENITAIS -/- Uma vez que se formam os testículos, todo o desenvolvimento subsequente dos órgãos e as características “masculinas” em lugar das femininas é em consequência dos hormônios produzidos pelos testículos em formação, incluindo os andrógenos e o hormônio inibidor dos ductos de Müller. Mediante a ausência de testículos todo o desenvolvimento dos órgãos genitais internos e externos segue um padrão feminino, sem levar em conta se estão presentes os ovários; o que significa a ausência de hormônios gonodais determina que o embrião se desenvolva como fêmea, uma vez que não requerem hormônios ovarianos para desencadear o padrão feminino. Por sua vez, as gônadas masculinas (os testículos), produzem substâncias que desviam o desenvolvimento em direção ao padrão masculino. Sob etapas relativamente rápidas da diferenciação todos os embriões possuem dois pares de dutos sexuais, os dutos de Wolff ou mesonéfricos e os dutos de Müller ou paramesonéfricos (figura 4). A testosterona secretada pelos testículos do feto macho em desenvolvimento atua sobre os dutos de Wolff, o que induz a formação posterior dos dutos deferentes, do epidídimo e das glândulas seminais (figura 4). Figura 4: formação dos órgãos genitais internos a partir dos dutos de Wolff no macho e dos dutos de Müller na fêmea. Fonte: ZARCO, 2018. -/- Os testículos produzem ao mesmo tempo, uma glicoproteína chamada Hormônio Inibidor dos Dutos de Müller (Müllerian Inhibiting Hormone, MIH, também chamado de Anti-Müllerian Hormone, AMH); como o seu nome indica, inibe o desenvolvimento dos dutos de Müller ou paramesonéfricos, provocando sua regressão, que impede a formação dos órgãos genitais característicos da fêmea como os ovidutos, o útero, a cérvix e a porção cranial da vagina (figura 4). O MIH é uma glicoproteína da família dos fatores de crescimento transformativo β (TGFβ). O gene MIH possui locais de união para os produtos dos genes SOX-9 e SF-1, pelo que a presença simultânea de ambos fatores de transcrição é necessária para a secreção do MIH e leva a cabo sua função de iniciação dos dutos de Müller sobre o embrião macho (vale lembrar que nessa etapa tanto a gônada de embriões machos como de embriões fêmeas expressam o gene SF-1, mas somente o macho expressa o SOX-9, para que unicamente esse último produza MIH). O certo é que na gônada do embrião fêmea não se produzem quantidades importantes da proteína SOX-9, além de que se produz a proteína DAX-1, mesma que antagoniza tanto a SOX-9 como a SF-1, todo o qual impede a produção de MIH e resulta no desenvolvimento dos dutos de Müller até a formação dos ovidutos, útero, cérvix e a porção cranial da vagina (figura 4). Assim, na fêmea, ao não haver testículos não circulam concentrações elevadas de andrógenos, o que impedirá o desenvolvimento dos dutos de Wolff, enquanto que os dutos de Müller se desenvolvem já que não haverá a presença do MIH para impedi-lo. O desenvolvimento dos genitais internos e externos femininos não requerem a presença de nenhum hormônio ovariano o que levará a cabo de maneira predeterminada (ou pré-estabelecida) na ausência de testículos. Outra estrutura interna que também se desenvolve de forma distinta nos machos e nas fêmeas é o seio urogenital, que no embrião macho é estimulado pela testosterona para formação da próstata, das glândulas bulbouretrais e da uretra peniana, enquanto que na fêmea forma a porção caudal da vagina. A respeito dos órgãos genitais externos (figura 5), nos embriões de ambos os sexos existem estruturas precursoras chamadas de tubérculo genital e pregas vestibulares. Na fêmea o tubérculo genital da origem ao clitóris e as pregas vestibulares dão origem aos lábios vulvares sem a necessidade da atuação de hormônios ovarianos, já que o padrão “por via pré-estabelecida” é feminino. Em contrapartida, no macho, tanto o tubérculo genital quanto as pregas vestibulares respondem ao hormônio 5α-dehidro-testosterona (DHT), ao qual se formam as células da pele da zona genital a partir da testosterona que é secretada pelos testículos. Para isso existem nas células a enzima 5α-reductasa, que transforma a testosterona em DHT. Uma vez formada, a DHT atua sobre as pregas vestibulares do embrião macho para que se fusionem e formem o escroto (em lugar dos lábios vulvares), e sobre o tubérculo genital para formar o pênis (em lugar do clitóris). Figura 5: estruturas que se desenvolvem nos embriões de cada sexo a partir do seio urogenital, o tubérculo genital e as pregas vestibulares. A cor do né de cada estrutura final corresponde com a cor do nome da estrutura a partir da qual se originou. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DO SISTEMA NERVOSO -/- Existem inúmeras diferenças funcionais entre o sistema nervoso da fêmeas e o do machos, em humanos podem incluir diferenças tão complexas como a maior capacidade de verbal da mulher ou a maior capacidade de orientação espacial do homem. Nessa parte será abordada aquelas diferenças que influenciam diretamente sobre a função reprodutiva, como as diferenças na regulação da secreção de gonadotropinas ou as diferenças na capacidade de comportamento sexual masculino ou feminino. É necessário lembrar que, apesar de que essas diferenças se originem durante um período crítico da vida fetal ou neonatal (dependendo da espécie), geralmente se fazem presentes até que o animal chegue a vida adulta e demonstre obter ou não a capacidade para se comportar como macho ou como fêmea uma vez que é exposto aos hormônios sexuais que são secretada depois da puberdade. Igualmente aos processos acima citados, podemos afirmar que nos mamíferos o padrão pré-estabelecido de comportamento sexual e de secreção de gonadotropinas é o feminino. Se durante os primeiros dias de vida neonatal uma rata fêmea não é exposta a nenhum hormônio gonodal, ao chegar a vida adulta ela terá a capacidade de se comportar como fêmea na presença de estrógenos, assim como de secretar um pico pré-ovulatório de GnRH/LH em resposta aos mesmos (figura 6). Essa rata, portanto, não poderá se comportar como macho embora que em sua vida adulta seja exposta a testosterona. O sistema nervoso do rato macho recém-nascido que é exposto aos andrógenos produzidos pelos testículos, em detrimento, faz com que adquiram o potencial para se comportar como machos em sua vida adulta e que perdem o potencial para ter conduta de fêmeas na presença e/ou administração de estrógenos (processo conhecido como desfeminização do SNC). Se por meios de experimentos injetamos testosterona em uma rata fêmea recém-nascida, essa rata não poderá se comportar como fêmea em sua vida adulta, e passará a se comportar como macho. A castração neonatal de um rato (visando evitar a exposição de seu SNC a andrógenos testiculares), assim mesmo, resultará em sua vida adulta um padrão feminino (SNC feminizado e não masculinizado). O hipotálamo das ratas adultas possui uma área em que o número, características e densidade dos corpos neurais difere em machos e fêmeas, essa área é denominada como “núcleo sexualmente dimórfico do hipotálamo”, e tem demonstrado que quando as ratas são tratadas com testosterona na vida neonatal, a morfologia de seu núcleo sexualmente dimórfico será masculinizado em sua vida adulta, enquanto que a castração neonatal de ratos resulta em um núcleo sexualmente dimórfico feminizado em sua vida adulta. Isso significa que a exposição ou não a testosterona na vida neonatal é o que determina que tipo de núcleo sexualmente dimórfico se desenvolverá, o que por sua vez está relacionado com o tipo de conduta que o animal poderá expressar em sua vida adulta. Não deixa de ser um paradoxo que ao injetar uma dose elevada de estrógenos nos primeiros dias de vida de uma rata, os núcleos sexualmente dimórficos da mesma se desenvolverão como macho e em sua vida adulta seu potencial de conduta estará masculinizado e desfeminizado. O hormônio “feminino” conhecido como estradiol, masculiniza o hipotálamo e a conduta do animal. Logo, se a rata neonatal for exposta a injeção de andrógeno não-aromatizado (que não pode ser transformado em estrógenos pelas células) ela não se masculiniza. A masculinização e desfeminização dos ratos ou das ratas tratados com testosterona, na realidade, não são provocados pela própria testosterona, senão pelos estrógenos que se formam dentro dos neurônios quando absorvem a testosterona do sangue e a aromatizam para transformá-la em estrógenos (figura 6). Figura 6: desfeminização e masculinização do sistema nervoso central por meio da testosterona, que quando não absorvida pela α-fetoproteína pode entrar nos neurônios, onde se aromatizam para serem transformados em estrógenos, hormônio que é responsável pela desfeminização. Fonte: ZARCO, 2018. Por que as ratas, que possuem ovários funcionalmente produtores de estrógenos, não se masculinizam? A resposta está em uma proteína denominada α-fetoproteína que circula em altas concentrações nos fetos e nos recém-nascidos. Essa proteína possui a capacidade de unir-se aos estrógenos, ao qual impede seu entrada nas células. Os ratos, em desenvolvimento, produzem testosterona, no entanto não possui afinidade pela α-fetoproteína, o que permite com que ela circule livremente. Ao chegar ao SNC, a testosterona (que não foi absorvida) pode entrar nos neurônios e dentro deles se aromatizam e transformam-se em estrógenos, que finalmente masculinizam o SNC. A diferenciação sexual do hipotálamo depende, em síntese, da presença ou ausência dos testículos, o que permite que se produza ou não o hormônio testosterona que pode não ser absorvida por parte da α-fetoproteína, transformar-se em estrógenos e masculinizar o SNC. -/- •___CONCLUSÃO -/- Nos mamíferos todo o processo que se requerem para o desenvolvimento de um macho depende da existência de somente um gene do cromossomo Y, o gene SRY; a ausência desse gene resulta no desenvolvimento de uma fêmea. A presença ou ausência do gene SRY determina, então, a cadeia de eventos morfogênicos que ocorrerá em sua expressão ou não, para desenvolver todos os órgãos e características de um macho ou de uma fêmea. Por essa razão, os indivíduos com uma monossomia XOA (síndrome de Turner) são fêmeas (por não possuir o cromossomo Y nem o gene SRY), enquanto que os indivíduos triploides XXY (síndrome de Kleinefelter) são machos embora possuam dois cromossomos X. Em algumas espécies, no entanto, têm-se identificado machos que são cromossomicamente XX; nesses casos é determinado invariavelmente que por ser um erro durante a meiose a região do cromossomo Y em que reside o gene SRY tem sido transloucada ao cromossomo X. Da mesma forma, em alguns casos tem sido encontrado fêmeas com cariótipo XY; que nelas se identifica uma mutação inabilitante do gene SRY. Isso demonstra experimentalmente que por meio da engenharia genética é possível produzir machos com cariótipo XY mas com o gene SRY eliminado (knockout). Como é de se esperar, esses machos desenvolvem ovários e todos seus órgãos genitais, tanto internos quanto externos, e se desenvolvem como fêmeas. Os machos cromossomicamente XX transgênicos aos que se insertam uma cópia do gene SRY, desenvolvem testículos e um fenótipo masculino, embora sejam estéreis por causa da ausência de alguns genes do cromossomo Y que são necessários para a realização de uma espermatogênese normal. As falhas nos mecanismos de diferenciação sexual podem, diretamente, ocasionar anormalidades como as observadas nas bezerras Freemartin, que são bezerras originadas de uma gestação gemelar em que seu gêmeo era macho. O que sucede é que na espécie bovina, quando há uma gestação gemelar, é produzido um certo grau de anastomose entre as placentas dos fetos, o que permite a troca de sangue e de células entre ambos. Os produtos recebem, então, algumas células de seu gêmeos, que encontram seu lugar no órgão correspondente e se integram a ele. No caso particular das gônadas, quando o ovário primitivo de um embrião fêmea é colonizado por algumas células gonodais de seu gêmeo macho, essas células expressam o gene SRY, o que fará com que essa região da gônada se diferencie como testículo. Como resultado, se desenvolve um ovo-testículo (com maior ou menor proporção de tecido testicular dependendo do grau de colonização da gônada em formação por células provenientes do gêmeo macho). Ademais, ao haver certa quantidade de tecido testicular produtor de MIH, circularão sobre o feto fêmea níveis desse hormônio que, embora baixos, afetarão o desenvolvimento normal dos dutos de Müller, fazendo com que as bezerras Freemartin possuam genitálias internas ausentes ou pouco desenvolvidas. Os andrógenos produzidos pelas zonas de tecido testicular, por fim, são suficientes para causar um certo grau de masculinização, que se manifesta como um clitóris mais grande que o normal ou um desenvolvimento corporal masculinizado. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ARNOLD, Arthur P.; CHEN, Xuqi; ITOH, Yuichiro. What a difference an X or Y makes: sex chromosomes, gene dose, and epigenetics in sexual differentiation. In: Sex and gender differences in pharmacology. Springer, Berlin, Heidelberg, 2013. p. 67-88. CUNNINGHAM, James. Tratado de fisiologia veterinária. Elsevier Health Sciences, 2011. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DA SILVA, Emanuel Isaque Cordeiro. Desenvolvimento Embrionário e Diferenciação Sexual nos Animais Domésticos. Disponível em:. Acesso em: Julho de 2020. HAFEZ, Elsayed Saad Eldin; HAFEZ, Bahaa. Reprodução animal. São Paulo: Manole, 2004. HIDALGO, C. Galina et al. Reproducción de animales domésticos. México: Limusa, 2008. MACLAUGHLIN, David T.; DONAHOE, Patricia K. Sex determination and differentiation. New England Journal of Medicine, v. 350, n. 4, p. 367-378, 2004. MCCARTHY, Margaret M.; ARNOLD, Arthur P. Reframing sexual differentiation of the brain. Nature neuroscience, v. 14, n. 6, p. 677, 2011. PLANT, Tony M.; ZELEZNIK, Anthony J. (Ed.). Knobil and Neill's physiology of reproduction. Academic Press, 2014. REY, Rodolfo. Diferenciación sexual embrio-fetal: De las moléculas a la anatomía. Revista chilena de anatomía, v. 19, n. 1, p. 75-82, 2001. SENGER, P. L. Embryogenesis of the pituitary gland and male or female reproductive system. In. Pathways to Pregnancy and Parturition. Current Conception Inc, v. 1, p. 8-76, 1997. ZARCO, L. Diferenciación sexual. In. PORTA, L. R.; MEDRANO, J. H. H. Fisiología reproductiva de los animales domésticos. Cidade do México: FMVZ-UNAM, 2018. -/- REALIZAÇÃO -/- . (shrink)

At the very beginning of On Interpretation (I, 1, 16a3-14) Aristotle distinguishes four levels and discusses their relationships. From this text, we can infer the following: 1. There are four levels: writing, speaking, mental experience and external world. Since writing and speaking can truly be taken as belonging to the same realm, we can reduce Aristotle’s distinction to three realms: language, thought and external world. 2. The realm of language, in both levels of writing and speaking, is different for different (...) people but both of the other realms of thought and external world are the same for them. By this Aristotle must mean that though people of different languages have different writings and speaking words, the things that are in the world and their affections on people’s thought are the same. 3. The relations both between language and thought and in language itself is symbolization: ‘Spoken words are the symbols of mental experience and written words are the symbols of spoken words.’ 4. The relation between external world and thought is similarity: ‘Those things of which our mental experiences are similarities (παθἠματα τῆς ψυχῆς ... ὁμοιώματα).’ (ΟΙ., 16a7) In de Anima (16a8-9; II, 5, 418a4-5; II, 4, 429a10-11; 429a13-16; 429a23) Aristotle describes thoughts as ‘likenesses of objects.’ Paolo Crivelli says that in these addresses Aristotle believe that ‘a thought is of an object just if it is a likeness of it’ and ‘to be a likeness of an object is to be the result of a process of likening of which that object is a cause.’ This, Crivelli believes, is indeed the basis of the sameness of the objects of thoughts: they are results of the same processes of likening by the same objects. 5. There is a correspondence between nouns and verbs on the one hand and objects of thought without co-positing and positing away on the other hand: ‘Nouns themselves and verbs are like objects of thought (νοἠματι) without co-positing and positing away.’ (OI, I, 1, 16a13-14) A. Relationship between external world and thought The following can be inferred from Aristotle’s works about the relationship between thought and external world: 1. ‘The soul is in a way all existing things; for existing things are either sensible or thinkable, and knowledge is in a way what is knowable, and sensation is in a way what is sensible.’ (So., Γ, 8, 431b21-23) In fact, ‘within the soul the faculties of knowledge and sensation are potentially these objects, the one what is knowable, the other what is sensible.’ (So., Γ, 8, 431b26-27) 2. It is the form of the external objects that are in thought (So., Γ, 8, 431b26-29) and the objects of thought are in the sensible forms, viz. both the abstract objects and all the states and affections of sensible things (ἐν τοῖς εἴδεσι τοῖς αἰσθητοῖς τὰ νοητὰ ἐστι, τά τε ἐν ἀφαιρέσει λεγόμενα, καὶ ὃσα τῶν αἰσθητῶν ἓξις καὶ πάθη). (So., Γ, 8, 432a3-6) 3. While external objects are perishable, objects of thought seem to be eternal. (PrA., A, 33, 47b21-22) B. Relationship between language and the external world 1. There is a correspondence between the external world and the true statements about them: ‘If it is true to say that a thing is white, it must necessarily be white; if the reverse proposition is true, it will of necessity not be white.’ (OI, I, 9, 18a39-b5) 2. While external objects ‘does seem in some way the cause of’ the truth or falsity of lingual statements, ‘the true statement is in no way the cause of the actual thing’s existence.’ (Cat., 12, 14b18-22; cf. OI, I, 9, 18b36-19a6) Thus, the external objects reciprocate as to implication of existence with the corresponding true statement about them and thus are prior to them.’ (Cat., 12, 14b11-23) 3. The opposition between an affirmation and negation corresponds to an opposition in the external world between the objects underlying those statements. (Cat., 10, 12b6-15) 4. The correspondence of the whole structure of the external world and language for Aristotle is so that in analyzing the language he shows himself as analyzing the external world. It is in fact a very crucial and controversial dispute whether Aristotle’s philosophy in its very decisive parts is theorizing about language or about external world. In most of his important theories, he begins with discussing language. In fact, language is where he enters the discussion and, in many cases, where he finishes it. In these cases, he either does not discuss external world at all or only derives some principles or conclusions about it. In some other cases he begins from language but ends in external world. a) Daniel W. Graham thinks that language is Aristotle’s ‘model of the world.’ He refers to ‘subjecthood’ as what formally characterizes primary substance and explains how it bases reality in Aristotle: while to be an absolute subject is equal to be fully real, to be a predicate of a subject is equal to be real. ‘Language is not merely a tool to get around in the world; it reveals the structure of the world … the deep structure of language is isomorphic with the world… In this word, logic can reveal connections between elements because language and the world have a form in common. He lists Trendelenburg (1846, 11-13), Gillespie (1925) and (Ackrill (1963, 78-81) as those who have the same idea. b) Emphasizing on the force of τί in Aristotle’s statement when he says that assertions affirm something (τί) of something (τί) makes Peter Simpson (p. 85) to stress, in his interpretation of Jacob’s theory, on the ontological aspect of Aristotle’s philosophy. Jacob says that in his theory of predication, Aristotle focuses on ‘things’ and not words or concepts and predication is a relationship between extralinguistic entities rather than merely linguistic ones; something extralinguistic and ontological. c) Quoting Ackrill ((1963, 73): ‘the categories classify things, not words’) and Kahn ((1978, 248): ‘Aristotle never regards predication as a grammatical or linguistic relation of word to word, nor does he ever speak of subject and predicate as concepts united in judgment’), Fabio Morales says that Aristotle is not classifying predication in Categories but the attributes or properties these stand for.’ d) Graham thinks that the theory of synonymity-homonimity is not purely linguistic, since it is things rather than words that have these properties. (shrink)

It has been hypothesized that our believing that, or its seeming to us as though, the world is in some way dynamical partially explains (and perhaps rationalizes) future-bias. Recent work has, in turn, found a correlation between future-bias and near-bias, suggesting that there is a common explanation for both. Call the claim that what partially explains our being both future- and near-biased is our believing/it seeming to us as though the world is dynamical, the dynamical explanation. We empirically test two (...) versions of the dynamical explanation. The first is the moving ego explanation—according to which it is our belief that the ego moves, or our phenomenology as of the ego moving, that jointly (partially) explains future- and near-bias. The second is the moving time explanation—according to which it is our belief that time robustly passes, or our phenomenology as of robust passage, which jointly (partially) explain future- and near-bias. We found no evidence in favour of either explanation. (shrink)

Neutral monism is a position in metaphysics defended by Mach, James, and Russell in the early twentieth century. It holds that minds and physical objects are essentially two different orderings of the same underlying neutral elements of nature. This paper sets out some of the central concepts, theses and the historical background of ideas that inform this doctrine of elements. The discussion begins with the classic neutral monism of Mach, James, and Russell in the first part of the paper, then (...) considers recent neo-Russellian versions in the second half. The chances for a revival of neutral monism are probably slight; its key ideas and starting points lie far from those in contemporary philosophy of mind. A better route might be through the philosophy of science and a deeper understanding of causation. (shrink)

Some environmental ethicists and economists argue that attributing infinite value to the environment is a good way to represent an absolute obligation to protect it. Others argue against modelling the value of the environment in this way: the assignment of infinite value leads to immense technical and philosophical difficulties that undermine the environmentalist project. First, there is a problem of discrimination: saving a large region of habitat is better than saving a small region; yet if both outcomes have infinite value, (...) then decision theory prescribes indifference. Second, there is a problem of swamping probabilities: an act with a small but positive probability of saving an endangered species appears to be on par with an act that has a high probability of achieving this outcome, since both have infinite expected value. Our paper shows that a relative concept of infinite value can be meaningfully defined, and provides a good model for securing the priority of the natural environment while avoiding the failures noted by sceptics about infinite value. Our claim is not that the relative infinity utility model gets every detail correct, but rather that it provides a rigorous philosophical framework for thinking about decisions affecting the environment. (shrink)

This article seeks to describe in general terms what has become the standard way of conceptualizing moral injury in the clinical psychological and psychiatric literature, which is the key source for applications of the concept in other domains. What we call “the standard model” draws on certain assumptions about beliefs, mental states, and emotions as well as an implicit theory of causation about how various forms of harm arise from certain experiences or “events” that violate persons’ moral beliefs and systems. (...) Our analysis makes these assumptions more explicit and subjects them to critical scrutiny. In so doing, we survey the current literature and identify basic features of how moral injuries are defined, how they are thought to occur, and the forms of treatment or repair that appear to be indicated. We caution that it matters how moral experience is characterized and argue that an alternative understanding of what is the moral in moral injury is important for overcoming critical challenges to the standard model. Moreover, recently evolving approaches to moral repair could be more consistent with an alternative model. Our concluding suggestion is that a more robust account of the nature of moral experience and its relations to self-identity and social experience more generally could advance understanding of the etiology of moral injury and promote rehabilitation. (shrink)

A look at the dynamical concept of space and space-generating processes to be found in Kant, J.F. Herbart and the mathematician Bernhard Riemann's philosophical writings.

Standpoint theorists have long been clear that marginalization does not make better understanding a given. They have been less clear, though, that social dominance does not make ignorance a given. Indeed, many standpoint theorists have implicitly committed themselves to what I call the strong epistemic disadvantage thesis. According to this thesis, there are strong, substantive limits on what the socially dominant can know about oppression that they do not personally experience. I argue that this thesis is not just implausible but (...) politically pernicious; it is an excuse for ignorance and silence that stifles our ability to address many injustices. Moreover, I argue that if we are to avoid lending support to the SEDT while working within a standpoint theory framework, we must hold that the socially dominant can achieve marginalized standpoints. So, we must hold that men can achieve feminist standpoints, that white women (and men) can achieve black feminist standpoints, and so on. (shrink)

A common view among nontheists combines the de jure objection that theism is epistemically unacceptable with agnosticism about the de facto objection that theism is false. Following Plantinga, we can call this a “proper” de jure objection—a de jure objection that does not depend on any de facto objection. In his Warranted Christian Belief, Plantinga has produced a general argument against all proper de jure objections. Here I first show that this argument is logically fallacious (it makes subtle probabilistic fallacies (...) disguised by scope ambiguities), and proceed to lay the groundwork for the construction of actual proper de jure objections. (shrink)

Grete Hermann’s essay “Die naturphilosophischen Grundlagen der Quantenmechanik” has received much deserved scholarly attention in recent years. In this paper, I follow the lead of Elise Crull who sees in Hermann’s work the general outlines of a neo-Kantian interpretation of quantum theory. In full support of this view, I focus on Hermann’s central claim that limited spatio-temporal, and even analogically causal, representations of events exist within an overall relational structure of entangled quantum mechanical states that defy any unified spatio-temporal description. (...) In my view, Hermann also advances an important transcendental argument that perspectival spatio-temporal representations of nature have their foundations in general relational networks that are not spatio-temporal. The key point is that the adoption of a perspectival system within the general network induces the representation but only for that context. These ideas are consistent with a perspectival subject–object principle in Kant and also with Weyl’s work on Lie groups and their representations. (shrink)

In this paper, multi attribute decision making problem based on grey relational analysis in neutrosophic cubic set environment is investigated. In the decision making situation, the attribute weights are considered as single valued neutrosophic sets. The neutrosophic weights are converted into crisp weights. Both positve and negative GRA coefficients, and weighted GRA coefficients are determined. Hamming distances for weighted GRA coefficients and standard (ideal) GRA coefficients are determined. The relative closeness coefficients are derived in order to rank the alternatives. The (...) relative closeness coefficients are designed in ascending order. Finally, a numerical example is solved to demonstrate the applicability of the proposed approach. (shrink)

Extension is probably the most general natural property. Is it a fundamental property? Leibniz claimed the answer was no, and that the structureless intuition of extension concealed more fundamental properties and relations. This paper follows Leibniz's program through Herbart and Riemann to Grassmann and uses Grassmann's algebra of points to build up levels of extensions algebraically. Finally, the connection between extension and measurement is considered.

The author Jacob Roman (Parr) provides commentary and line by line analysis of 218b10 through 223a23 , which is of Aristotle's Physica . -/- written in 2023 .

What sort of logic do we get if we adopt a supervaluational semantics for vagueness? As it turns out, the answer depends crucially on how the standard notion of validity as truth preservation is recasted. There are several ways of doing that within a supervaluational framework, the main alternative being between “global” construals (e.g., an argument is valid iff it preserves truth-under-all-precisifications) and “local” construals (an argument is valid iff, under all precisifications, it preserves truth). The former alternative is by (...) far more popular, but I argue in favor of the latter, for (i) it does not suffer from a number of serious objections, and (ii) it makes it possible to restore global validity as a defined notion. (shrink)

I focus on three mereological principles: the Extensionality of Parthood (EP), the Uniqueness of Composition (UC), and the Extensionality of Composition (EC). These principles are not equivalent. Nonetheless, they are closely related (and often equated) as they all reflect the basic nominalistic dictum, No difference without a difference maker. And each one of them—individually or collectively—has been challenged on philosophical grounds. In the first part I argue that such challenges do not quite threaten EP insofar as they are either self-defeating (...) or unsupported. In the second part I argue that they hardly undermine the tenability of EC and UC as well. (shrink)

Premier ouvrage de l’histoire de la philosophie à être totalement consacré au concept d’entéléchie, il ne s’agira pas de proposer un essai historique allant de la mise en place de cette notion chez Aristote jusqu’à la conception biologique développée par Hans Driesch. Inscrit dans un projet plus global de compréhension du temps aristotélicien, c’est à une véritable refondation métaphysique du concept que ce travail nous convie. Si Kant, à l’ultime fin de sa première critique, avait admis qu’il n’existait que deux (...) voies possibles de fondation de l’a priori - la voie historique (platonicienne) empruntée par Hegel et la voie physiologique (aristotélicienne) qui sera la nôtre - la première partie de ce second volume prendra pour acquis qu’il n’existe pas de théorie qui puisse unifier ces deux pôles du savoir. Cela impliquera une scission entre deux mouvements irrationnels que sont le mouvement entéléchique aristotélicien et le mouvement dialectique platonicien. A partir du corps a priori du surhomme, le premier mouvement sera à la racine de la théorie de la connaissance (De la science) alors que le second sera au fondement de la théorie des valeurs (De l’Idéologie). En circonscrivant le mouvement dialectique dorien autour du noûs perse (iranien), ce travail offrira une première définition totalement négative du mouvement entéléchique appuyé, lui, sur le noûs ionien (« phénicien ») dont la seconde partie sera l’objet. De l’analyse de la substance première en passant par l’étude phénoménologique des schèmes de la camusité et du membre moteur, cette étude reviendra sur l’élasticité du tendon afin d’approcher non-phénoménalement le concept lui-même et tenter ainsi une première symphyse avec les rythmes circadiens de la biologie contemporaine. (shrink)

There is an undeniable tendency to dismiss women’s sexual assault allegations out of hand. However, this tendency is not monolithic—allegations that black men have raped white women are often met with deadly seriousness. I argue that contemporary rape culture is characterized by the interplay between rape myths that minimize rape, and myths that catastrophize rape. Together, these two sets of rape myths distort the epistemic resources that people use when assessing rape allegations. These distortions result in the unjust exoneration of (...) people we cannot conceive of as monstrous, while making it too easy to believe that some marginalized people could be rapists. I also argue that rape myths enable a novel kind of epistemic injustice. This injustice concerns how our assessments of trustworthiness and our assessments of plausibility interact. I argue that rape myths can result in runaway credibility deflations that can explain both why people fail to believe most women, and also why people may unjustly believe false allegations that white women have been raped by black men. (shrink)

In parts one and two of this three-part series, I developed a framework for ahimsic (nonviolent) communication (AC) as an alternative to the standard communicative norm of civility. The framework presented for AC offers various categories of resistance to violence, including nonviolent forms of negotiation, compromise, protest, verbal force, verbal distraction, argumentation, and communicative satyagraha (Gandhian nonviolence applied to communication). I also provided a range of real-life examples of successful AC resistance, including the stories of Derek Black, Daryl Davis, James (...) Lawson, and Antoinette Tuff. These examples demonstrate that AC “works” even against neo-Nazis, KKK grand wizards, angry punch-throwing bikers, and active school shooters. In this third and final installment, I will explain why AC works—better than any form of violent communication (VC). My main claim is that AC derives strategic power from its moral power. As various components of my argument are drawn from the nonviolence tradition more generally, what follows will double as a primer on the morality of nonviolence. However, we will also see significant differences in how we must adapt nonviolent strategy and morality to the case of communication. (shrink)

This book aims to develop certain aspects of Gottlob Frege’s theory of meaning, especially those relevant to intensional logic. It offers a new interpretation of the nature of senses, and attempts to devise a logical calculus for the theory of sense and reference that captures as closely as possible the views of the historical Frege. (The approach is contrasted with the less historically-minded Logic of Sense and Denotation of Alonzo Church.) Comparisons of Frege’s theory with those of Russell and others (...) are given. It is in the end shown that developing Frege’s theory in these ways reveals serious problems hitherto largely unnoticed, including those possibly rendering a Fregean intensional logic inconsistent even if his naïve class theory is excluded. (shrink)

According to the traditional analysis of propositional knowledge (which derives from Plato's account in the Meno and Theaetetus), knowledge is justified true belief. This chapter develops the traditional analysis, introduces the famous Gettier and lottery problems, and provides an overview of prospective solutions. In closing, I briefly comment on the value of conceptual analysis, note how it has shaped the field, and assess the state of post-Gettier epistemology.

The work argues that engaging Africa's cultural and epistemic resources as social imaginaries, and not as metaphysical or ontological “essences,” could help practitioners of African philosophy overcome the cluster of shortcomings and undesirable features associated with “ethnophilosophy.” A number of points are outlined to buttress this claim. First, the framework of social imaginaries does not operate with the false assumption that Africa's cultural forms and epistemic resources are static and immutable. Second, this framework does not lend itself to sweeping generalizations (...) about Africa or large swathes of it. Third, the framework of social imaginaries remedies ethnophilosophy's problem of collectivism. Fourth, unlike ethnophilosophy, it does not romanticize and canonize a supposedly “idyllic” African past, which militates against a realistic and forward‐looking philosophizing. Finally, with the framework of social imaginaries, Africa's indigenous cultural and epistemic resources become amenable to being engaged with critical philosophical rigor. This not only enhances their potential for cross‐cultural philosophical conversation but also enhances their usefulness for addressing current sociopolitical issues affecting Africa. The discussion in this paper somewhat touches upon the question of method in African philosophy, using the ethnophilosophy problem to navigate the vast gamut of issues involved. (shrink)

Mostly essays on music ontology . Collected but not proofed -- left as-is for each . ToC : September 3, 2013 — “ Frege’s Aesthetics in ‘The Thought‘ “ With humility — “ The Musical Work as Sound and Experience “ September 17, 2014 — “ Argument Critique: Aristotle on Parmenides “ September 21, 2014 — “ Wollheim, Intent, and Correct Perception “ October 29, 2014 — “ When is a Painting a Painting? “ November 19, 2014 — “ Broad (...) and Prior; Time and Change “ December 12, 2014 — “ Beautiful Things: On Kantian Judgment and its Objects “. (shrink)