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)

Many oppose the use of profile evidence against defendants at trial, even when the statistical correlations are reliable and the jury is free from prejudice. The literature has struggled to justify this opposition. We argue that admitting profile evidence is objectionable because it violates what we call “equal protection”—that is, a right of innocent defendants not to be exposed to higher ex ante risks of mistaken conviction compared to other innocent defendants facing similar charges. We also show why admitting other (...) forms of evidence, such as eyewitness, trace, and motive evidence, does not violate equal protection. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy and Literature 26.1 (2002) 207-215 [Access article in PDF] Notes and Fragments Poetics of Sentimentality Rick Anthony Furtak IN HIS MAJOR WORK, The Passions, Robert Solomon argues that emotions are judgments. 1 Through a series of persuasive examples, he shows that emotions are best understood as mental states which involve certain beliefs about the world. This means that every emotion has an object: if I am angry (...) at John for stealing my car, the object of my anger is the fact (or what I take to be a fact) that my car has been stolen by John. If I find out that this is not the case, that my car has not even left the garage, then my anger should vanish along with its justification. 2 The key point here is that anger, like any other emotion, may be reasonable or inappropriate depending on the situation. If there is nothing to be angry about, then it would be irrational for me to cultivate anger simply because I enjoy having this particular emotion. In general, emotional responses are cognitively flawed whenever they are at odds with the properties of their objects. If we want our judgments to be realistic and not delusional, then we must avoid this kind of error.It is curious, then, that Solomon has written an essay in which he categorically declares that "there is nothing wrong with sentimentality." 3 For it would appear that his theory of emotion provides precisely the terms needed in order to specify what is wrong with it. If emotions are judgments, then "sentimentality" ought to be an important critical term to designate the habit of having emotions that involve either impaired or mistaken judgment. Nevertheless, Solomon is willing to defend any and every episode of tender emotion, of the kind associated with the [End Page 207] death of Little Nell in The Old Curiosity Shop (S, p. 240). He suggests that the more we can muster up this sort of response to literature or life, the better. What he seeks to encourage, in other words, is what Hume would call "delicacy" of (aesthetic) taste and of (ethical) passion. 4 But while Hume acknowledges that sensitivity to beauty and to ugliness are two sides of the same coin, such that anyone who is susceptible to lively enjoyments is also liable to undergo pungent sorrows, Solomon wants to promote only the tender aspect of emotion.On the principle of passionate maximization, it is good if I can be tenderly affected by a poem—any poem! The problem with such crass emotion-stoking is that it precludes the possibility of distinguishing between, for instance, the two stanzas below. Both are by Wilfred Owen: the first was written in 1914 and the second in 1918. 5 I O meet it is and passing sweet To live in peace with others, But sweeter still and far more meet To die in war for brothers. II Bent double, like old beggars under sacks, Knock-kneed, coughing like hags, we cursed through sludge, Till on the haunting flares we turned our backs And towards our distant rest began to trudge. Men marched asleep. Many had lost their boots But limped on, blood-shod. All went lame; all blind; Drunk with fatigue; deaf even to the hoots Of tired, outstripped Five-Nines that dropped behind. Only if emotions did not involve rational judgment could a person's passionate response to these two stanzas be a matter of indifference. But it seems that, on the contrary, an essential component of understanding them is recognizing that they express irreconcilable cognitive attitudes. The tone of the 1918 stanza is strikingly different from that of the earlier one, even though they share roughly the same topic. The latter stanza is stark and ominous, and filled with vivid detail; the one from 1914 is sweet and vague. Clearly, we might describe the earlier of the two as "sentimental"—the question is, what kind of judgment does [End Page 208] it involve? I suggest that its insipid jingles endorse the view that war is a delightful opportunity to nurture brotherhood and gain... (shrink)

Parents play a critical role in their child’s personal development and day-to-day experiences. However, as digital technologies are increasingly embedded in most New Zealand children’s everyday life activities parents face the task of ensuring their child’s online safety. To do so, they need to understand the way their child engages with and through these tools and make sense of the rapidly changing, and more technically complex, nature of digital devices. This presents a digital parenting dilemma: maximising children’s online opportunities while (...) minimising online risks and potential harm. This factsheet presents evidence about digital parenting in New Zealand based on nationally representative data collected from parents, caregivers and whānau and their children aged 9-17. It uses measures from the Global Kids Online project to explore the prevalence of different practices used by New Zealand parents to influence or mediate children’s internet use. (shrink)

While children’s experiences of online risks and harm is a growing area of research in New Zealand, public discussion on the matter has largely been informed by mainstream media’s fixation on the dangers of technology. At best, debate on risks online has relied on overseas evidence. However, insights reflecting the New Zealand context and based on representative data are still needed to guide policy discussion, create awareness, and inform the implementation of prevention and support programmes for children. This research report (...) presents findings from a quantitative study regarding different aspects related to risks and online safety. It looks at the online experiences that children find bothersome and upsetting and explores the hurtful behaviours they encounter or engage in, both online and in person. Evidence regarding exposure to different types of potentially harmful online content is also presented. Another relevant contribution is the insights related to excessive internet use.The findings presented in this report are based on data from 2,061 New Zealand children aged 9-17. We hope the findings will contribute to the development of policies, practices and services designed to support New Zealand children to safely take advantage of the opportunities available to them online. (shrink)

While children’s interaction with digital technologies is a matter of interest around the world, evidence based on nationally representative data about how integrated these tools are in children’s everyday life is still limited in New Zealand. This research report presents findings from a study that explores children’s internet access, online skills, practices, and opportunities. This report is part of Netsafe’s research project Ngā taiohi matihiko o Aotearoa - New Zealand Kids Online, and our first publication as a member of Global (...) Kids Online. Generating insightful, reliable evidence about New Zealand children’s online experiences is vital to develop adequate support that reflects children’s experiences and needs. This, in turn, will help them to manage online risks and potential harm from behaviours such as cyberbullying, harassment, and other forms of abuse and intimidation. (shrink)

Research suggests that parents tend to largely underestimate their child’s engagement in risky and/or hurtful behaviours as well as their experiences of harm online. While helpful, the available international evidence is not only limited but also does not reflect the New Zealand context. In addition, understanding parental knowledge of the online experiences of children is important as parents play a critical role in helping their child to prevent or deal with bothering experiences and risky behaviours as well as providing children (...) with emotional support when things go wrong online. To help close the gap of New Zealand-based evidence on the topic, this factsheet presents findings from a quantitative study conducted with New Zealand parents and their children. The objectives of the study are to measure parental knowledge of children’s experiences of risks and harm online, and to compare parents’ level of awareness with their child’s self-reported experiences. The study found a mismatch between parents’, caregivers’ and whānau awareness and their children’s reports of bothering or upsetting experiences online. (shrink)

This study aims to generate thorough and comprehensive review of the teacher’s perspective and hands-on experience in mainstreaming LSENs in a regular classroom, including teachers’ attitudes and perceptions, challenges encountered, and teaching approach in handling mainstreamed classrooms. A scoping review framework by Arksey and O’Malley’s (2005) systematically analyzed the data of the different articles conducted by various scholars. Through scrupulous and through selection of related studies, 10 articles were included in the review from 6 different countries across the globe. The (...) articles included were conducted from 6 countries and various databases. The study highlighted that: 1) teachers have positive and negative attitudes towards mainstreaming, 2) teachers experienced various challenges in handling a mainstream classroom, and 3) learner-centered approach to learning is used in the classroom. Mainstreaming LSENs in a regular classroom has pros and cons among teachers, regular students, and the LSENs themselves. Hence, a daunting responsibility for the teachers. Nevertheless, it is imperative to support teachers by giving seminars and training, especially to those non-special education majors, to be fully equipped to handle mainstreamed classrooms. (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)

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)

Tato studie recenzuje knihu: Charles CAMIC - Neil GROSS - Michèle LAMONT, Social Knowledge in the Making. Chicago: University of Chicago Press, 2011, a zasazuje ji do kontextu současných úvah o proměnách výzkumné praxe sociálních věd, akademické kultury, stylů myšlení a psaní. Pokouší se analyzovat v knize ohlašovaný „obrat k praxi" a ukazuje, nakolik samotné výzkumné praktiky v sociálních vědách ovlivňuje neexistence „standardních" forem, způsobů či stylů bádání. Detailně jsou představeny rovněž výchozí myšlenky takzvané „nové" sociologie idejí, jež stojí v (...) pozadí celého projektu analýzy sociálních praktik projevujících se v procesech „produkce, evaluace a aplikace" sociálního vědění. Jako klíčová se ukazuje potřeba nově promyslet samotnou koncepci „profesionalizované" sociální vědy, jež byla v dřívějším vývoji odmítnuta jako morálně i prakticky neudržitelná, neboť s demokratizací výzkumného procesu a proměnou vztahu mezi sociálními vědami a jejich publikem se stále zřetelněji projevuje, že s odklo- nem od konceptu profesionální sociální vědy se veřejná irelevance sociálního vědění spíše stále více prohlubuje. (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)

This brief commentary has three goals. The first is to argue that ‘‘framework debate’’ in cognitive science is unresolvable. The idea that one theory or framework can singly account for the vast complexity and variety of cognitive processes seems unlikely if not impossible. The second goal is a consequence of this: We should consider how the various theories on offer work together in diverse contexts of investigation. A final goal is to supply a brief review for readers who are compelled (...) by these points to explore existing literature on the topic. Despite this literature, pluralism has garnered very little attention from broader cognitive science. We end by briefly considering what it might mean for theoretical cognitive science. (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.

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)

The nature of temporal experience is typically explained in one of a small number of ways, most are versions of either retentionalism or extensionalism. After describing these, I make a distinction between two kinds of temporal character that could structure temporal experience: A-ish contents are those that present events as structured in past/present/future terms, and B-ish contents are those that present events as structured in earlier-than/later-than/simultaneous-with relations. There are a few exceptions, but most of the literature ignores this distinction, and (...) silently assumes temporal experience is A-ish. I then argue that temporal character is not scale invariant, but rather that temporal experience is A-ish at larger scales, and B-ish at smaller scales. I then point out that this scale non-invariance opens the possibility of hybrid views. I clarify my own view as a hybrid view, according to which temporal experience is B-ish at small scales – and at this scale my trajectory estimation model applies – but A-ish at larger scales, and at the larger scale my TEM does not apply. I then motivate this hybrid position by first defending it against arguments that have tried to show that the TEM is untenable. Since the hybrid view has TEM as its small-scale component, it must address this objection. I then put pressure on the main alternative account, extentionalism, by showing that its proponents have not adequately dealt with the problem of temporal illusions. The result is a new theory motivated by i) explaining its virtues, ii) showing that objections to it can be met, and iii) showing that objections to its main competitors have not been met. (shrink)

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)

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)

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)

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)

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 both psychology and philosophy, cognitive theories of emotion have met with increasing opposition in recent years. However, this apparent controversy is not so much a gridlock between antithetical stances as a critical debate in which each side is being forced to qualify its position in order to accommodate the other side of the story. Here, I attempt to sort out some of the disagreements between cognitivism and its rivals, adjudicating some disputes while showing that others are merely superficial. Looking (...) at evidence from neuroscience and social psychology, as well as thought experiments and theoretical arguments, I conclude that it is necessary to acknowledge both that emotions have intentional content and that they involve somatic agitation. I also point out some of the more promising directions for future research in this area. (shrink)

This paper is largely exegetical/interpretive. My goal is to demonstrate that some criticisms that have been leveled against the program Gareth Evans constructs in The Varieties of Reference (Evans 1980, henceforth VR) misfire because they are based on misunderstandings of Evans’ position. First I will be discussing three criticisms raised by Tyler Burge (Burge, 2010). The first has to do with Evans’ arguments to the effect that a causal connection between a belief and an object is insufficient for that belief (...) to be about that object. A key part of Evans’ argument is to carefully distinguish considerations relevant to the semantics of language from considerations relevant to the semantics (so to speak) of thought or belief (to make the subsequent discussion easier, I will henceforth use ‘thought’ as a blanket term for the relevant mental states, including belief). I will argue that Burge’s criticisms depend on largely not taking account of Evans’ distinctions. Second, Burge criticizes Evans’ account of ‘informational content’ taking it to be inconsistent. I will show that the inconsistency Burge finds depends entirely on a misreading of the doctrine. Finally, Burge takes Evans to task for a perceived over-intellectualization in a key aspect of his doctrine. Burge incorrectly reads Evans as requiring that the subject holding a belief be engaged in certain overly intellectual endeavors, when in fact Evans is only attributing these endeavors to theorists of such a subject. Next, I turn to two criticisms leveled by John Campbell (Campbell, 1999). I will argue that Campbell’s criticisms are based on misunderstandings – though they do hit at deeper elements of Evans’ doctrine. First, Campbell reads Evans’ account of demonstrative thought as requiring that the subject’s information link to an object allows her to directly locate that object in space. Campbell constructs a case in which one tomato (a) is, because of an angled mirror, incorrectly seen as being at a location that happens to be occupied by an identical tomato (b). Campbell claims that Evans’ doctrines require us to conclude that the subject cannot have a demonstrative thought about the seen tomato (a), though it seems intuitively that such a subject would be able to have a demonstrative thought about that tomato, despite its location is inaccurately seen. I show that Evans’ position in fact allows that the subject can have a demonstrative thought about the causal-source tomato in this case because his account does not require that the location of demonstratively identified objects be immediately accurately assessed. What is crucial is that the subject have the ability to accurately discover the location. Second, Campbell criticizes Evans’ notion of a fundamental level of thought. I show that this criticism hinges on view of the nature and role of the fundamental level of thought that mischaracterizes Evans’ treatment of the notion. (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.

This essay explains why partisanship is justified in contemporary America and environments with similar voting systems and coalition structures. It explains how political parties operate, how helping a party succeed can be a goal of genuine ethical significance, and how trusting one party while mistrusting another can be a reliable route to true belief about important political issues.

It is standard in set theory to assume that Cantor's Theorem establishes that the continuum is an uncountable set. A challenge for this position comes from the observation that through forcing one can collapse any cardinal to the countable and that the continuum can be made arbitrarily large. In this paper, we present a different take on the relationship between Cantor's Theorem and extensions of universes, arguing that they can be seen as showing that every set is countable and that (...) the continuum is a proper class. We examine several principles based on maximality considerations in this framework, and show how some (namely Ordinal Inner Model Hypotheses) enable us to incorporate standard set theories (including ZFC with large cardinals added). We conclude that the systems considered raise questions concerning the foundational purposes of set theory. (shrink)

A pervasive thought in contemporary philosophy of mathematics is that in order to justify reflection principles, one must hold universism: the view that there is a single universe of pure sets. I challenge this kind of reasoning by contrasting universism with a Zermelian form of multiversism. I argue that if extant justifications of reflection principles using notions of richness are acceptable for the universist, then the Zermelian can use similar justifications. However, I note that for some forms of richness argument, (...) the status of reflection principles as axioms is left open for the Zermelian. (shrink)

According to Bernard Williams, if it is true that A has a normative reason to Φ then it must be possible that A should Φ for that reason. This claim is important both because it restricts the range of reasons which agents can have and because it has been used as a premise in an argument for so-called ‘internalist’ theories of reasons. In this paper I rebut an apparent counterexamples to Williams’ claim: Schroeder’s example of Nate. I argue that this (...) counterexample fails since it underestimates the range of cases where agents can act for their normative reasons. Moreover, I argue that a key motivation behind Williams’ claim is compatible with this ‘expansive’ account of what it is to act for a normative reason. (Published with Open Access.). (shrink)

It is commonly assumed that causation is transitive and in this paper I aim to reconcile this widely-held assumption with apparent evidence to the contrary. I will discuss a familiar approach to certain well-known counterexamples, before introducing a more resistant sort of case of my own. I will then offer a novel solution, based on Yablo’s proportionality principle, that succeeds in even these more resistant cases. There is a catch, however. Either proportionality is a constraint on which causal claims are (...) true, and the solution works, or it is not and causation is not transitive after all. I will argue that the first horn has unacceptable consequences and should be rejected, but that the second horn is less costly than it might initially appear. (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.

Nietzsche holds that one should believe what best promotes life, and he also accepts the correspondence theory of truth. I’ll call this conjunction of views Nietzschean pragmatism. This article provides textual evidence for attributing this pragmatist position to Nietzsche and explains how his broader metaethical views led him to it.The following section introduces Nietzschean pragmatism, discussing how Nietzsche expresses it in BGE, and distinguishing it from William James’s pragmatism about truth. The second section explains how Nietzsche’s skepticism about values that (...) can’t be grounded in individual passion attracted him to this kind of pragmatism. The third section explores an early application of Nietzschean... (shrink)

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 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)

I provide an examination and comparison of modal theories for underwriting different non-modal theories of sets. I argue that there is a respect in which the `standard' modal theory for set construction---on which sets are formed via the successive individuation of powersets---raises a significant challenge for some recently proposed `countabilist' modal theories (i.e. ones that imply that every set is countable). I examine how the countabilist can respond to this issue via the use of regularity axioms and raise some questions (...) about this approach. I argue that by comparing them with the `standard' uncountabilist theory, a new approach that brings in arbitrariness rather than the strict controls of forcing is desirable. (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)

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.

Set-theoretic and category-theoretic foundations represent different perspectives on mathematical subject matter. In particular, category-theoretic language focusses on properties that can be determined up to isomorphism within a category, whereas set theory admits of properties determined by the internal structure of the membership relation. Various objections have been raised against this aspect of set theory in the category-theoretic literature. In this article, we advocate a methodological pluralism concerning the two foundational languages, and provide a theory that fruitfully interrelates a `structural' perspective (...) to a set-theoretic one. We present a set-theoretic system that is able to talk about structures more naturally, and argue that it provides an important perspective on plausibly structural properties such as cardinality. We conclude the language of set theory can provide useful information about the notion of mathematical structure. (shrink)

A collection of essays, mostly original, on the actual and possible positions on free will available to Buddhist philosophers, by Christopher Gowans, Rick Repetti, Jay Garfield, Owen Flanagan, Charles Goodman, Galen Strawson, Susan Blackmore, Martin T. Adam, Christian Coseru, Marie Friquegnon, Mark Siderits, Ben Abelson, B. Alan Wallace, Peter Harvey, Emily McRae, and Karin Meyers, and a Foreword by Daniel Cozort.

Response to commentary. We are grateful to Crockett and Craigie for their interesting remarks on our paper. We accept Crockett’s claim that there is a need for caution in drawing inferences about patient groups from work on healthy volunteers in the laboratory. However, we believe that the evidence we cited established a strong presumption that many of the patients who are routinely taking a medication, including many people properly prescribed the medication for a medical condition, have morally significant aspects of (...) their cognition and behavior modified in a way that is unintended and may sometimes be unwelcome. Crockett notes that in some cases the effects of long-term drug use may differ, sometimes markedly, from the effects of short-term use. However, if acute use of a drug affects a neural system involved in mediating moral cognition or behavior, this nevertheless provides some evidence that chronic use of the drug may affect that same system and thus have morally significant effects. It is also plausible, in some cases, that an acute moral effect would give rise to a chronic moral effect via cognitive mechanisms. ... (shrink)

Critical review of Buddhist theories of free will published between 2000 and 2014.

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.

Recent work in neuroimaging suggests that some patients diagnosed as being in the persistent vegetative state are actually conscious. In this paper, we critically examine this new evidence. We argue that though it remains open to alternative interpretations, it strongly suggests the presence of consciousness in some patients. However, we argue that its ethical significance is less than many people seem to think. There are several different kinds of consciousness, and though all kinds of consciousness have some ethical significance, different (...) kinds underwrite different kinds of moral value. Demonstrating that patients have phenomenal consciousness — conscious states with some kind of qualitative feel to them — shows that they are moral patients, whose welfare must be taken into consideration. But only if they are subjects of a sophisticated kind of access consciousness — where access consciousness entails global availability of information to cognitive systems — are they persons, in the technical sense of the word employed by philosophers. In this sense, being a person is having the full moral status of ordinary human beings. We call for further research which might settle whether patients who manifest signs of consciousness possess the sophisticated kind of access consciousness required for personhood. (shrink)

We can infer moral conclusions from nonmoral evidence using a three-step procedure. First, we distinguish the processes generating belief so that their reliability in generating true belief is statistically predictable. Second, we assess the processes’ reliability, perhaps by observing how frequently they generate true nonmoral belief or logically inconsistent beliefs. Third, we adjust our credence in moral propositions in light of the truth ratios of the processes generating beliefs in them. This inferential route involves empirically discovering truths of the form (...) “Process P, which generates belief in moral proposition M, has truth ratio T", and using them to discover probabilities for moral propositions. The inferential route is noncircular, and progress along it is driven fundamentally by induction. (shrink)

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.

In this article I explore a number of questions that have not been adequately investigated in philosophy of mind circles: are minds located in the same place as the brains (or other computing machinery) supporting them? Must they exist at the same location as the body? Must they exist at the same time? Could a single mind be implemented in multiple brains, or multiple minds in a single brain? Under what conditions might a single mind persist despite being implemented successively (...) in different brains? What contributions do features of the computing machinery make to these questions, compared to the contribution made by the body and embedded point of view? Some of these questions have been touched on previously, but there hasn’t been any attempt at a systematic analysis of the various consequences that different approaches in the philosophy of mind have for how the spatiotemporal location, synchronic individuation and diachronic identity of minds relates to the spatiotemporal location, synchronic individuation, and diachronic identity of both the implementing computational machinery and the embodied embedded point of view. I make a first stab at such an analysis by discussing a variety of thought experiments in which such questions of location, individuation, and identity arise, and I explore how various approaches to understanding the mind – identity theoretic, functionalist, contentualist, embodied/embedded/extended, and so forth – would respond to such situations. A number of novel issues emerge, and some surprising affinities are revealed. (shrink)

A critical review of Charles Goodman's view about Buddhism and free will to the effect that Buddhism is hard determinist, basically because he thinks Buddhist causation is definitively deterministic, and he thinks determinism is definitively incompatible with free will, but especially because he thinks Buddhism is equally definitively clear on the non-existence of a self, from which he concludes there cannot be an autonomous self.