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

In juxtaposition with the myth and tragedy of Ovid’s Medea, this paper investigates the possibility within the Kantian conception of agency of understanding moral evil as acting against one’s better judgment. It defends the thesis that in Kant self-deception, i. e. the intentional untruthfulness to oneself, provides the fundamental structure for choosing against the moral law. I argue that, as Kant’s thought progresses, self-deception slowly proceeds to become the paradigmatic case of moral evil. This is discussed with regard to two (...) important topics in his later moral philosophy: the doctrine of radical evil and the crucial role of the duty of truthfulness in ethics. The inquiry into Kant’s theory of conscience unfolds both against this theoretical background and in light of its historical roots in the polemic against casuistry and probabilism. This contribution closes with a brief look at the tools Kant implements to counter this tendency to self-deception in moral judgment and particularly at the role casuistry plays within his conception of moral education. (shrink)

This work aims to present an overview of the top-level ontology BFO - Basic Formal Ontology - and its applicability for Satellite Systems. As an upper level ontology, the BFO was designed to be extended, providing the basis for the specification of detailed representational artifacts about scientific information domains. These aspects and the challenges of satellite systems complexity and large size compose a suitable scenario for the creation of a specialized dialect to improve efficiency and accuracy when modeling such systems. (...) By analyzing BFO based ontologies in other disciplines and existing satellite models it is possible to describe an application for satellite systems, which can provide a foundation for the creation of a concrete ontology to be applied on satellite modeling. (shrink)

Some of the manuscripts once part of Giovanni Pico della Mirandola’s collection transmit autograph notes, which have been useful to reconstruct his library. A peculiar case is represented by the notes transmitted in a codex containing the Latin translation of Moses Maimonides’ Guide of the Perplexed. These notes are actual corrections to the translation made mostly on the basis of a comparison with the Hebrew text, while in some other cases they derive from a specific interpretation. The aim of this (...) paper is to present some characteristics of the textual revisions, in particular with reference to the Hebrew source. The palaeographic data demonstrate Pico’s direct involvement, which leads to the question of the authorship of these notes, namely if they were the result of an autonomous work or of a collaboration with some other scholar. (shrink)

Can Marxist-Leninist philosophy disregard dialectical materialism, the analysis of material and social contradictions, the need to overcome and resolve them in the service of revolutionary transformation? ‘Does the lecturer acknowledge that the philosophy of Marxism is dialectical materialism’, as Lenin asked Bogdanov one day in May 1908? What had 'official Soviet Marxism' really become, capable of combining ideological dictatorship with militant philosophical ignorance, in turn justified by the achievements of modern science, skilfully used as an instrument of domination and preservation (...) of the established order? How can one conceptually dominate reality and its contradictions, knowing well that knowledge is never neutral but is class-based? These questions are answered by Evald Ilyenkov, one of the greatest Marxist philosophers of the 20th century, re-examining Lenin's Materialism and Empiriocriticism at the end of the 1970s with a text entitled Leninist Dialectics and the Metaphysics of Positivism, still unpublished in Italy, and identifying in the revolutionary leader an exceptional theoretical ally. Just as Lenin had had to fight the attacks promoted by the theories of Bogdanov, who approached the empirio-criticism of Mach, Avenarius and Berman, seeing it as dogmatic and reactionary materialism directed against the natural sciences, so Ilyenkov fought against the penetration of positivism into Soviet politics and philosophy, criticizing the rejection of the dialectic only functional to the technocratic project of building 'socialism' in the Brezhnev era, a disguised heir of the empirio-criticism denounced by Lenin as the natural metaphysical conclusion to the logic of positivism. (shrink)

Preface to the thematic volume Metatheoretical Structuralism: Some Recent Developments and Applications.

In epoca medievale si è molto discusso su alcuni concetti chiave come prova o giustificazione. La teoria della prova contenuta nei trattati di logica medievale prende il nome tecnico di consequentia, che è un tipo di ragionamento fondato sul passaggio dalla concessione (o negazione) di uno o più enunciati denominati antecedenti alla concessione (o negazione) di uno o più enunciati denominati conseguenti. Questo tipo di teoria ha avuto un correlato a livello dei singoli termini che compongono l’enunciato all'interno della teoria (...) nota come suppositio terminorum. Prende, infatti, il nome di descensus, la regola che permette la verifica del passaggio da un termine maggiore (un termine comune) ad un termine minore (che denota individui). La stessa definizione di alcune ramificazioni della teoria della suppositio è col-legata alla possibilità di ammettere o meno il descensus cioè questa "discesa" da un termine comune ad una congiunzione o disgiunzione di termini singolari. Il presente lavoro intende descrivere la teoria del descensus come un tipo particolare di consequentia mostrandone le connessioni con le moderne tecniche logiche. I trattati che si affronteranno appartengono al XIV e al XV secolo, cioè ad un periodo caratterizzato da una sistemazione della materia che li rende confrontabili con un quadro teorico unitario. (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 1931, Evgeny Pashukanis, the distinguished Soviet jurist, author of “The General Theory of Law and Marxism”, following an invitation to celebrate the centenary of Hegel’s death, published an assay entitled “Hegel, the State and Law” (Гегель. Государство и право) aimed to demistify, through a brief retrospective of Hegelian’s philosophy, its specific use, something achieved through the bourgeois ideology which, at some point in history, abandoned Kantism and its followers to embrace Neo-Hegelianism as a philosophy of domination and social control. (...) In this unpublished text, Pashukanis reflects, from a Marxist and Leninist point of view, on the ability to use Hegel as a bourgeois defense tool, when a particular society, specifically the one from the 1920s to the 1930s, began to be affected by the fear of communism and by the crises that endanger its very survival. From this angle, the capitalist interest - following Pashukanisian interpretation of Hegel - will only develop in the terms of a scientific elimination of all those subversive potentials that the economic crisis is destined to produce, thus reformulating the notions of State and Law which, in between obedience, discipline and defense of the homeland, come to assert the official recognition of the inexorably crushed proletariat in a condition in which all relations of production and social reproduction are transferred to the realm of exploitation, as its definitive subsumption to capital. (shrink)

Many philosophers have pointed out that statistical evidence, or at least some forms of it, lack desirable epistemic or non-epistemic properties, and that this should make us wary of litigations in which the case against the defendant rests in whole or in part on statistical evidence. Others have responded that such broad reservations about statistical evidence are overly restrictive since appellate courts have expressed nuanced views about statistical evidence. In an effort to clarify and reconcile, I put forward an interpretive (...) analysis of why statistical evidence should raise concerns in some cases but not others. I argue that when there is a mismatch between the specificity of the evidence and the expected specificity of the accusation, statistical evidence—as any other kind of evidence—should be considered insufficient to sustain a conviction. I rely on different stylized court cases to illustrate the explanatory power of this analysis. (shrink)

Standard interpretations of Descartes' work, especially those inspired by analytic philosophy, assume the syllogism and Principia Mathematica's artificial language are appropriate tools for interpreting Cartesianism, particularly the ontological argument. The dissertation shows technical problems arise when those logics are used for that purpose. An intentianal interpretation along Meinongian lines is proposed, as an alternative to deductive exegeses. This interpretation is developed after arguing that Russell did not identify what I call "the epistemic use" of Meinong's theory of objects. The proposed (...) interpretation is nonlogical in the sense that intentionality alone, not deductive arguments, explains the cogito and res cogitans' belief in god's existence. God is the only one of res cogitan's intentionalia in which existence is analytically included; thus, there is no need for an ontological argument. Such an interpretation is consistent with Descartes' rejection of syllogistics as a truth-discovering tool and provides a framework to evaluate Cartesianism and Kant's criticism of it. Moreover, some problems afflicting logico-deductive readings cannot arise in this interpretation. (shrink)

Il 2021 segna gli ottant’anni dalla nascita di Mario Perniola, uno dei massimi filosofi italiani del secondo dopoguerra. Questo volume raccoglie interventi che esplorano la sua opera mostrandone la fertilità e sottolineando al tempo stesso la prossimità delle sue idee con le principali sfide del nostro tempo. Dall’Italia al Brasile, passando per gli Stati Uniti, l’Irlanda, la Francia, il Belgio, il Messico e la Cina, gli autori si soffermano su temi che comprendono l’estetica, la politica, la teoria della comunicazione, i (...) queer studies, il pensiero rituale e religioso, la sessualità e la letteratura, restituendo la plurivocità e l’originalità di un filosofo di respiro internazionale e più che mai attuale. (shrink)

‘No-fault unbelief’ can be named the view that there are those who do not believe in God through no moral or intellectual fault of their own. This view opposes a more traditional one, which can be named ‘flawed unbelief’ view, according to which religious unbelief signals a cognitive or moral flaw in the non-believer. Since this charge of mental or moral flaw causes a certain uneasiness, I oppose the former view, i.e. ‘no-fault unbelief’, with a strategy that has nothing to (...) do with the latter. I assume that ‘no-fault unbelief’ is correct and show what consequences follow for both unbelievers and believers. I conclude that the assumption in question is superficially beneficial but deeply detrimental to unbelievers, and by contrast, it is superficially detrimental and deeply beneficial to believers. (shrink)

Is the wish to be biologically related to your children legitimate? Here, I respond to an argument in support of a negative answer to this question according to which a preference towards having children one is biologically related to is analogous to a preference towards associating with members of one’s own race. I reject this analogy, mainly on the grounds that only the latter constitutes discrimination; still, I conclude that indeed a preference towards children one is biologically related to is (...) morally illegitimate because, in the context of parental love, biological considerations are normatively irrelevant. (shrink)

In an essay titled Aquinas on the Foundations of Knowledge, Eleonore Stump rejects the idea that Aquinas's epistemology is foundationalist. I agree with Stump, and share in her conviction that the Angelic doctor developed instead what can be seen as a kind of theological reliabilism. In this article, I intend to take her position a step further. First, I would like to show that Thomistic reliabilism falls into a vicious circle if seen as based on a merely rational theism. Second, (...) I am going to argue that for Aquinas such reliabilism depends instead on Christian faith, construed as the act of believing the revealed truth by virtue of the love relationship that God allows human beings to have with him. (shrink)

Smith argues that, unlike other forms of evidence, naked statistical evidence fails to satisfy normic support. This is his solution to the puzzles of statistical evidence in legal proof. This paper focuses on Smith’s claim that DNA evidence in cold-hit cases does not satisfy normic support. I argue that if this claim is correct, virtually no other form of evidence used at trial can satisfy normic support. This is troublesome. I discuss a few ways in which Smith can respond.

Can epistemology be shaped by the Christian faith? Is there anything specific to this faith that can give rise to an equally specific epistemology without compromising the autonomy that the latter requires from faith? In the footsteps of Aquinas's religious epistemology, I first focus on the fact that Christian faith seems to characterize intellectual activity in a way that appears to be irreconcilable with epistemological perspectives that are not shaped by faith. Second, I argue that it is possible to do (...) justice to the irreconcilability in question by making reference to what radically distinguishes the Christian faith from the epistemological reflection. Finally, I focus on two ways in which the specific nature of Christian faith can shape and promote rationality, and give rise to a Christian epistemology. (shrink)

Advances in neuroscience implicate reentrant signaling as the predominant form of communication between brain areas. This principle was used in a series of masking experiments that defy explanation by feed-forward theories. The masking occurs when a brief display of target plus mask is continued with the mask alone. Two masking processes were found: an early process affected by physical factors such as adapting luminance and a later process affected by attentional factors such as set size. This later process is called (...) masking by object substitution, because it occurs whenever there is a mismatch between the reentrant visual representation and the ongoing lower level activity. Iterative reentrant processing was formalized in a computational model that provides an excellent fit to the data. The model provides a more comprehensive account of all forms of visual masking than do the long-held feed-forward views based on inhibitory contour interactions. (shrink)

In this essay, I propose two arguments from Thomas Aquinas’s reflection on theism and faith to rebut Schellenberg’s claim that divine hiddenness justifies atheism. One of those arguments, however, may be employed so as to re-propose Schellenberg’s conviction, which is crucial to his argument, that there are ‘non-resistant’ or ‘inculpable’ unbelievers. I then advance what I call the suffering unbeliever argument. In short, the unbelievers mentioned by Schellenberg are expected to suffer because of their non-belief, which—as Schellenberg says—prevents them from (...) achieving the greatest possible well-being. If they suffer, however, they cannot consider themselves unbelievers, since one cannot suffer from not having been given a certain good if one believes that the good in question has never existed. If they do not suffer, on the other hand, there is simply nothing for which they can consider themselves inculpable. (shrink)

Thinking is overrated: golfers perform best when distracted and under pressure; firefighters make the right calls without a clue as to why; and you are yourself ill advised to look at your steps as you go down the stairs, or to try and remember your pin number before typing it in. Just do it, mindlessly. Both empirical psychologists and the common man have long worked out that thinking is often a bad idea, but philosophers still hang on to an intellectualist (...) picture of human action. This book challenges that picture and calls on philosophers to wake up to the power of mindlessness: it is our habits, skills and conventions that help us cope with a world way too diverse for us to hope to always reinterpret it. The book presents the empirical evidence that has been accumulating over the last few decades and offers a philosophical analysis of mindless phenomena such as habits, skilled activity, automatic actions, emotional and spontaneous reactions and social conventions, arguing that traditional philosophical theories of action should be revised to do justice to this forgotten but important part of our lives: when we act mindlessly, we are free and fully rational even though we neither deliberate nor are aware of what we are doing. (shrink)

This paper approaches Husserl’s analysis of time-consciousness from a mereological perspective. Taking as inspiration Bergson’s idea that pure durée is a multiplicity of interpenetration, I will show, from within Husserlian phenomenology, that the absolute flow can indeed be described as a whole of interpenetrating parts. This mereological perspective will inform my re-consideration of the much-discussed issue of Husserl’s self-criticism concerning the schema of content and apprehension. It will also reveal a fundamental similarity between Husserl’s conception of the absolute flow and (...) Sartre’s conception of lived temporality. This paper consists of four sections. Section 2 presents the basic elements of Husserl’s mereology. Section 3 introduces the difficulty encountered by Husserl’s early account of time that makes use of the schema. I will examine Barry Dainton’s criticism of Husserl’s theory of time-consciousness against the background of the older debate between Meinong and Stern, a debate that has informed Husserl’s own account. Section 4 distinguishes two common criticisms of the schema from Husserl’s own self-criticism, which is in turn divided into two steps. It is shown how the second step of this self-criticism implies the interpenetration of the absolute flow and responds to Dainton’s criticism. Finally, Sect. 5 concludes with some comparative remarks. I will show how Husserl’s notion of absolute flow, as mereologically interpreted, anticipates Sartre’s conception of consciousness as self-transcendence, as well as how it accommodates the apparently conflicting mereological intuitions of Aristotle and Bergson. (shrink)

Kant scholars have rarely addressed the centuries-old tradition of casuistry and the concept of conscience in Kant’s writings. This book offers a detailed exploration of the period from Pascal’s Provincial Letters to Kant’s critique of probabilism and discusses his proposal of a (new) casuistry as part of an moral education. / Trotz der Hinweise an wichtigen Stellen in Kants Schriften richtet die Kantforschung ihre Aufmerksamkeit nur selten auf die Jahrhunderte währende Tradition der Kasuistik und den Begriff des Gewissens, der in (...) ihrem Rahmen ausgearbeitet wird. Eingehend untersucht wird in diesem Buch insbesondere der Zeitabschnitt von Pascals »Briefen in die Provinz« bis zu Kants eigener Kritik des Probabilismus und seinem Entwurf einer (neuen) Kasuistik als Teil der ethischen Methodenlehre. (shrink)

On the verge of the 1917 October revolution, Lenin reads and elaborates on the Hegel's Science of Logic, as if he were attempting to outline, from it, specific effects. Theoretical effects, because human activity is never uncoupled from the logic objective, through which the real matter unfolds and to whom each individual indissolubly belongs. Practical effects, because if Hegelian philosophy is good for the Church, for the bourgeoisie, for the capital, by changing the order of some of its factors it (...) may as well turn out good for guiding the practical-cognitive development of an urgent proletarian revolution. (shrink)

Judith Jarvis Thomson has recently proposed a new argument for the thesis that killing the one in the Trolley Problem is not permissible. Her argument relies on the introduction of a new scenario, in which the bystander may also sacrifice herself to save the five. Thomson argues that those not willing to sacrifice themselves if they could may not kill the one to save the five. Bryce Huebner and Marc Hauser have recently put Thomson's argument to empirical test by asking (...) people what they should do in the new trilemma case, in which they may also sacrifice themselves. They found that the majority judge that they should either kill the one or sacrifice themselves; Huebner and Hauser argue that those numbers speak against Thomson's argument. But Thomson's argument was about the dialectical effect of the new trilemma on the traditional dilemma, rather than about the trilemma itself. Here I present the results of a study in which I asked subjects first what they should do in the trilemma and then what they should do in the traditional Trolley Problem. I found that, if asked first about the trilemma, subjects then have the intuition that killing the one in the traditional Bystander at the Switch is not permissible?exactly what Thomson's argument had predicted. (shrink)

I argue against Appel's recent proposal – in this JOURNAL – that there is a fundamental human right to sexual pleasure, and that therefore the sexual pleasure of severely disabled people should be publicly funded – by thereby partially legalizing prostitution. I propose an alternative that does not need to pose a new positive human right; does not need public funding; does not need the legalization of prostitution; and that would offer a better experience to the severely disabled: charitable non-profit (...) organizations whose members would voluntarily and freely provide sexual pleasure to the severely disabled. (shrink)

In recent decades, Richard Swinburne has offered an influential view of the relationship between faith and reason. In doing so, he focused to a considerable extent on Aquinas’s view of faith. For Swinburne, Aquinas’ view of faith is that to have faith in God is simply to have a belief-that. In contrast, it is another view of faith, which Swinburne calls ‘Lutheran,’ that involves both theoretical beliefs-that and a trust in the Living God. In this article, I argue that Swinburne’s (...) view is not faithful to Aquinas’s doctrine of faith. In the first section, I will explain Swinburne’s view of belief in detail and its application to Aquinas’s doctrine of faith. In the second section, I will bolster my argument by showing that Swinburne’s reading is inconsistent with Aquinas’ statements regarding three relationships, which are essential to Aquinas’s faith. I am referring to the relationships between faith and will, between faith and merit and between faith and doubt. (shrink)

The literature on algorithmic fairness has examined exogenous sources of biases such as shortcomings in the data and structural injustices in society. It has also examined internal sources of bias as evidenced by a number of impossibility theorems showing that no algorithm can concurrently satisfy multiple criteria of fairness. This paper contributes to the literature stemming from the impossibility theorems by examining how informational richness affects the accuracy and fairness of predictive algorithms. With the aid of a computer simulation, we (...) show that informational richness is the engine that drives improvements in the performance of a predictive algorithm, in terms of both accuracy and fairness. The centrality of informational richness suggests that classification parity, a popular criterion of algorithmic fairness, should be given relatively little weight. But we caution that the centrality of informational richness should be taken with a grain of salt in light of practical limitations, in particular, the so-called bias-variance trade off. (shrink)

In this essay, I first show that, from the view that God is the ultimate cause of the human ability to perform ethically laudable acts, does not follow that no continuity between biological and intentional altruism is possible. In line with recent theological research concerning the non-human world, I argue that there is a partial continuity between these two forms of altruism. I also show that, from a naturalistic viewpoint, no continuity at all seems demonstrable between the two forms of (...) altruism at stake. I therefore contribute to strengthen a more general conviction, according to which evolution in itself is more persuasive than its combination with naturalism. (shrink)

Epistemic closure under known implication is the principle that knowledge of "p" and knowledge of "p implies q", together, imply knowledge of "q". This principle is intuitive, yet several putative counterexamples have been formulated against it. This paper addresses the question, why is epistemic closure both intuitive and prone to counterexamples? In particular, the paper examines whether probability theory can offer an answer to this question based on four strategies. The first probability-based strategy rests on the accumulation of risks. The (...) problem with this strategy is that risk accumulation cannot accommodate certain counterexamples to epistemic closure. The second strategy is based on the idea of evidential support, that is, a piece of evidence supports a proposition whenever it increases the probability of the proposition. This strategy makes progress and can accommodate certain putative counterexamples to closure. However, this strategy also gives rise to a number of counterintuitive results. Finally, there are two broadly probabilistic strategies, one based on the idea of resilient probability and the other on the idea of assumptions that are taken for granted. These strategies are promising but are prone to some of the shortcomings of the second strategy. All in all, I conclude that each strategy fails. Probability theory, then, is unlikely to offer the account we need. (shrink)

In this paper I argue that there is an important anomaly to the causalist/compatibilist paradigm in the philosophy of action and free will. This anomaly, which to my knowledge has gone unnoticed so far, can be found in the philosophy of Harry Frankfurt. Two of his most important contributions to the field – his influential counterexample to the Principle of Alternate Possibilities and his ‘guidance’ view of action – are incompatible. The importance of this inconsistency goes far beyond the issue (...) of coherence within Frankfurt’s philosophy. I shall argue that this inconsistency represents an important anomaly within the causalist/compatibilist framework; so that we should start to seriously consider having to move on from the established paradigm. (shrink)

Kant scholars have rarely addressed the centuries-old tradition of casuistry and the concept of conscience in Kant’s writings. This book offers a detailed exploration of the period from Pascal’s Provincial Letters to Kant’s critique of probabilism and discusses his proposal of a (new) casuistry as part of an moral education. *** -/- Die Debatte um Kasuistik und Probabilismus zählt zu den wichtigsten Themen der Moraltheologie und Moralphilosophie der frühen Neuzeit. In der enormen Verbreitung der Literatur über die Gewissensfälle (casus conscientiae) (...) und in der großen Resonanz der Lehre von den wahrscheinlichen Meinungen (opiniones probabiles) in der ersten Hälfte des 17. Jahrhunderts findet sich ein wirkungsmächtiges Modell für die Analyse des moralischen Handelns, in welchem Universalität des Gebots und Kontingenz der Handlung, Notwendigkeit der Norm und individuelle Freiheit miteinander versöhnt werden. Dennoch erregt dieses Modell heftige Kritik, die in Pascals berühmtem Angriff in den Briefen in die Provinz (1656–1657) gipfelt. So beginnt für die Kasuistik und den Probabilismus eine lange Krise, welche die Entstehung der modernen Moralphilosophie und den Siegeszug des kantischen Paradigmas ankündigt. Die Krise von Kasuistik und Probabilismus fällt zusammen mit einer einsetzenden rigoristischen Reaktion der christlichen Moraltheologie sowohl katholischer als auch protestantischer Prägung,welche die moralischen und spekulativen Folgen eines Rückgriffs auf Gewissensfälle und wahrscheinliche Meinungen als inakzeptabel ablehnt. Die Ablehnung geht aber weiter und dringt bis in den Kern der philosophischen Reflexion vor: Die rigoristische Reaktion gegen Kasuistik und Probabilismus entzündet sich im moralphilosophischen Denken Kants als Folge seiner umfassenden kritischen Revision der Grundbegriffe der Moralphilosophie sowie insbesondere seiner Neubestimmung des Verhältnisses von Gewissen und praktischem Urteil. Dem Grundsatz des Probabilismus setzt Kant das Kriterium der moralischen Gewißheit („quod dubitas, ne feceris!“) entgegen, das er als „Postulat des Gewissens“ bezeichnet (RGV 6:185.23–186.9).Und die Kasuistik wird als eine „Critic der Handlungen nach Sophistic“ abgestempelt, als eine „Uebung, um nach der Sophistic das Gewissen zu hintergehen oder es zu chicaniren, insofern man es in Irrthum zu setzen denkt“ (V-MS/Vigil 27:620.2–5). Dennoch weist Kant den kasuistischen Fragen eine herausragende Stellung in der Tugendlehre zu und legt der Kasuistik im Rahmen der ethischen Methodenlehre, also im Hinblick auf pädagogische Anwendungen, letztlich eine positive Funktion bei. Vermutlich ist Kants Angriff auf Kasuistik und Probabilismus durch den Einfluss Pascals philosophisch vermittelt. Kants Verhältnis zu Pascal und, allgemeiner, zu dem historischen Hintergrund, welchem dieser angehört, sind gleichwohl noch erstaunlich wenig erforscht: Trotz der wiederholten (stillschweigenden oder sogar ausdrücklichen) Hinweise an wichtigen Stellen in Kants Schriften richtet die Kant-Forschung ihre Aufmerksamkeit nur selten auf die Jahrhunderte währende Tradition der Kasuistik und den Begriff des Gewissens, der in ihrem Rahmen ausgearbeitet wird. Aus dieser langen Geschichte wird in diesem Band insbesondere der Zeitraum „von Pascal bis Kant“ eingehend untersucht, d.h. der noch wenig erkundete Zeitabschnitt von der beißenden Polemik von Pascals Briefe in die Provinz bis zu Kants eigener Kritik des Probabilismus und seinem Entwurf einer (neuen) Kasuistik als Teil der ethischen Methodenlehre. (shrink)

Philosophical Issues, Volume 31, Issue 1, Page 41-65, October 2021.

I argue that it is possible for prospective mothers to wrong prospective fathers by bearing their child; and that lifting paternal liability for child support does not correct the wrong inflicted to fathers. It is therefore sometimes wrong for prospective mothers to bear a child, or so I argue here. I show that my argument for considering the legitimate interests of prospective fathers is not a unique exception to an obvious right to procreate. It is, rather, part of a growing (...) consensus that procreation can be morally problematic and that generally talking of rights in this context might not be warranted. Finally, I argue that giving up a right to procreate does not imply nor suggest giving up on women’s absolute right to abort, which I defend. (shrink)

I argue that the empirical literature on priming effects does not warrant nor suggest the conclusion, drawn by prominent psychologists such as J. A. Bargh, that we have no free will or less free will than we might think. I focus on a particular experiment by Bargh – the ‘elderly’ stereotype case in which subjects that have been primed with words that remind them of the stereotype of the elderly walk on average slower out of the experiment’s room than control (...) subjects – and I show that we cannot say that subjects cannot help walking slower or that they are not free in doing do. I then illustrate how these cases can be reconciled and normalized within a Davidsonian theory of action to show that, in walking slower, subjects are acting intentionally. My argument applies across various experiments, including those of goal priming. In the final section I argue that the only cases in which priming effects are efficacious are so-called Buridan cases. (shrink)

Both Husserl and Sartre speak of quasi-presence in their descriptions of the lived experience of imagination, and for both philosophers, accounting for quasi-presence means developing an account of the hyle proper to imagination. Guided by the perspective of fulfillment, Husserl’s theory of imaginary quasi-presence goes through three stages. Having experimented first with a depiction-model and then a perception-model, Husserl’s mature theory appeals to his innovative conception of inner consciousness. This elegant account nevertheless fails to do justice to the facticity and (...) bodily involvement of our imaginary experience. Sartre’s theory of analogon, based on his conception of imaginary quasi-presence as ‘magical’ self-affection, embodies important insights on these issues. Kinesthetic sensations and feelings are the modes in which we make use of own body to possess and be possessed by the imaginary object, thus lending it a semblance of bodily presence. (shrink)

This article reconstructs Sartre’s theory of selfhood against the background of the contemporary debate between minimal-self theories and narrative-self theories. I argue that Sartre’s theory incorporates both an emphasis on the singular first-person perspective, which is characteristic of minimal-self theories, and an emphasis on the practical intelligibility of experience, which is characteristic of narrative-self theories. The distinctiveness of the Sartrean combination of these motifs consists in its idea of the necessary ideal-relatedness of consciousness. According to Sartre, the logical structure of (...) the pre-reflective cogito requires the haunting presence of an ideal of self-coincidence, which determines for consciousness the meaning of its lived experiences. Consciousness exists as a question to itself due to this ideal-relatedness, and it answers this question by projecting its possibilities as creative and symbolic realizations of this ideal. Establishing the connection between Sartre’s theory of imagination and his theory of selfhood, I suggest that both the ideal and the possibility of consciousness are lived in the manner of the imaginary. (shrink)

In this article, I focus on the circular relationship that, in his 1998 encyclical, Jean Paul II argued there is between faith and reason. I first note that this image of circularity needs some explaining, because it is not clear where exactly the circular process begins and ends. I then argue that an explanation can be found in Aquinas’s reflection on the gift of understanding. Aquinas referred to the virtue of faith as caused by God, which promotes human reason, and (...) this in turn strengthens the certainty of faith. (shrink)

This article examines Jacobi's two novels, Allwill and Woldemar indirectly showing how much Allwill prefigures Kierkegaard's Seduce in Either/Or and the plot of Woldemar Hegel's final scene of Section VI of his Phenomenology of Spirit.

I argue that we should give up the fight to rescue causal theories of action from fundamental challenges such as the problem of deviant causal chains; and that we should rather pursue an account of action based on the basic intuition that control identifies agency. In Section 1 I introduce causalism about action explanation. In Section 2 I present an alternative, Frankfurt’s idea of guidance. In Section 3 I argue that the problem of deviant causal chains challenges causalism in two (...) important respects: first, it emphasizes that causalism fails to do justice to our basic intuition that control is necessary for agency. Second, it provides countless counterexamples to causalism, which many recent firemen have failed to extinguish – as I argue in some detail. Finally, in Section 4 I argue, contra Al Mele, that control does not require the attribution of psychological states as causes. (shrink)

I defend the argument that if embryo loss in stem cell research is morally problematic, then embryo loss in in vivo conception is similarly morally problematic. According to a recent challenge to this argument, we can distinguish between in vivo embryo loss and the in vitro embryo loss of stem cell research by appealing to the doctrine of double effect. I argue that this challenge fails to show that in vivo embryo loss is a mere unintended side effect while in (...) vitro embryo loss is an intended means and that, even if we refine the challenge by appealing to Michael Bratman's three roles of intention, the distinction is still unwarranted. (shrink)

I comment on two analyses of the Simonshaven case: one by Prakken (2019), based on arguments, and the other by van Koppen and Mackor (2019), based on scenarios (or stories, narratives). I argue that both analyses lack a clear account of proof beyond a reasonable doubt because they lack a clear account of the notion of plausibility. To illustrate this point, I focus on the defense argument during the appeal trial and show that both analyses face difficulties in modeling key (...) features of this argument. (shrink)

I argue against the Doctrine of Double Effect’s explanation of the moral difference between terror bombing and strategic bombing. I show that the standard thought-experiment of Terror Bomber and Strategic Bomber which dominates this debate is underdetermined in three crucial respects: (1) the non-psychological worlds of Terror Bomber and Strategic Bomber; (2) the psychologies of Terror Bomber and Strategic Bomber; and (3) the structure of the thought-experiment, especially in relation to its similarity with the Trolley Problem. (1) If the two (...) worlds are not identical, then it may be these differences between the two worlds and not the Doctrine of Double Effect to explain the moral difference; (2a) if Terror Bomber and Strategic Bomber have the same causal beliefs, then why does Terror Bomber set out to kill the children? It may then be this unwarranted and immoral choice and not the Doctrine of Double Effect that explains the moral difference; (2b) if the two have different causal beliefs, then we can’t rule out the counterfactual that, had Strategic Bomber had the same beliefs as Terror Bomber, she would have also acted as Terror Bomber did. Finally, (3) the Strategic Bomber scenario could also be constructed so as to be structurally equivalent to the Fat Man scenario in the Trolley Problem: but then the Doctrine of Double Effect would give different answers to two symmetrical cases. (shrink)

The concept of agency is of crucial importance in cognitive science and artificial intelligence, and it is often used as an intuitive and rather uncontroversial term, in contrast to more abstract and theoretically heavy-weighted terms like “intentionality”, “rationality” or “mind”. However, most of the available definitions of agency are either too loose or unspecific to allow for a progressive scientific program. They implicitly and unproblematically assume the features that characterize agents, thus obscuring the full potential and challenge of modeling agency. (...) We identify three conditions that a system must meet in order to be considered as a genuine agent: a) a system must define its own individuality, b) it must be the active source of activity in its environment (interactionalasymmetry) and c) it must regulate this activity in relation to certain norms (normativity). We find that even minimal forms of proto-celular systems can already provide a paradigmatic example of genuine agency. By abstracting away some specific details of minimal models of living agency we define the kind of organization that is capable to meet the required conditions for agency (which is not restricted to living organisms). On this basis, we define agency as an autonomous organization that adaptively regulates its coupling with its environment and contributes to sustaining itself as a consequence. We find that spatiality and temporality are the two fundamental domains in which agency spans at different scales. We conclude by giving an outlook to the road that lies ahead in the pursuit to understand, model and synthesis agents. (shrink)

This note discusses three issues that Allen and Pardo believe to be especially problematic for a probabilistic interpretation of standards of proof: (1) the subjectivity of probability assignments; (2) the conjunction paradox; and (3) the non-comparative nature of probabilistic standards. I offer a reading of probabilistic standards that avoids these criticisms.

John Schellenberg’s version of the divine hiddenness argument is based on a concept of God as an omnipotent, morally perfect, and ontologically perfect being. I show that Schellenberg develops his argument in a way that is inconsistent with each of these aspects, from which it follows that the argument in question proves to be unsustainable.

Many believe that a peaceful, tolerant and respectful coexistence among religions is not compatible with the conviction that only one of them is true. I argue that this ‘incompatibility problem’ (IP) is grounded in a ‘naturalistic assumption’ (NA), that is, the assumption that every subject, including religion, should be treated without taking into account that a super‐natural being may exist and reveal to us an unexpected way to deal with our experience. I then argue that in matters of religion, NA (...) is untenable and that its very opposite, which I call ‘super‐naturalistic assumption’ (SA), should be adopted. My thesis is that, once SA is adopted, IP can be dismissed and that it is plausible to maintain that a peaceful, tolerant and respectful coexistence among religions is compatible with the conviction that only one of them is true. (shrink)