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)

The rise of experimental philosophy has placed metaphilosophical questions, particularly those concerning concepts, at the center of philosophical attention. X-phi offers empirically rigorous methods for identifying conceptual content, but what exactly it contributes towards evaluating conceptual content remains unclear. We show how x-phi complements Rudolf Carnap’s underappreciated methodology for concept determination, explication. This clarifies and extends x-phi’s positive philosophical import, and also exhibits explication’s broad appeal. But there is a potential problem: Carnap’s account of explication was limited to empirical and (...) logical concepts, but many concepts of interest to philosophers are essentially normative. With formal epistemology as a case study, we show how x-phi assisted explication can apply to normative domains. (shrink)

NOTE TO THE READER - December, 2021 ●●●●● -/- After a long period of time devoted to research in other areas, the author returned to the subject of this paper in a book-length study, CRITIQUE OF IMPURE REASON: Horizons of Possibility and Meaning. In this book (Chapter 11, “The Metalogic of Meaning”), the position developed in the 1982 paper, "Referential Consistency as a Criterion of Meaning", has been substantively revised and several important corrections made. It is recommended that readers read (...) the revised and corrected version that appears in the book, CRITIQUE OF IMPURE REASON. ●●●●● -/- The book is available in a printed edition, ISBN 978-0-578-88646-6, from online booksellers such as Barnes & Noble, Amazon, and through independent bookstores. The book is also available as a freely downloadable _corrected second edition_ eBook, DOI: 10.5281/zenodo.5458352, through PhilSci, PhilPapers, HAL, and other online archives. ●●●●● -/- In addition to the above-mentioned book, readers may find "A Primer on Bartlett's CRITIQUE OF IMPURE REASON" to be useful as a guide to the nearly 900-page CRITIQUE. The primer is available as a free download through PhilPapers. ●●●●● -/- "Referential Consistency as a Criterion of Meaning" describes a logically compelling criterion of meaning — that is, a necessary condition of meaning, one which is non-arbitrary and compelling. One cannot _not_ accept the proposed criterion without self-referential inconsistency. This “metalogical” variety of self-referential inconsistency is new, opening a third category beyond semantical and pragmatical forms of self-referential inconsistency. ●●●●● -/- It is argued that such a criterion of meaning can serve as an instrument of internal criticism for any theoretical framework that permits reference to a class of objects. The paper combines the concern of the logical empiricists to formulate a rigorous meaning criterion, with the analytical interest in identifying and eliminating self-defeating statements through an analysis of the referential structure of theories. ●●●●● -/- The paper is followed by a list of other publications by the author that further develop and extend the ideas presented here. (shrink)

It is often assumed that neural representation, with content that is in principle detachable from the flow of natural-factive information, is necessary to perceptually experience an object. In this paper we present and discuss two cases challenging this assumption. We take them to show that it is possible to experience an object with which you are interacting through your sensory systems without those systems constructing a representation of the object. The first example is viewing nearby medium-sized groups of objects. The (...) second is hearing objects through misbound sounds. These cases bring out two different ways object representation can fail while object experience persists, suggesting that object experience requires only that the object be revealed through sensory information, not full-blown representation. Constructing object representations is one way sensory systems reveal objects, but it is not the only way. Object representation in neural sensory systems is relatively demanding, rare, and fragile; object experience is relatively easy, pervasive, and robust. We conclude that even minimal forms of neural phenomenal internalism are false. (shrink)

It is well-known that the global structure of every space-time model for relativistic cosmology is observationally underdetermined. In order to alleviate the severity of this underdetermination, it has been proposed that we adopt the Cosmological Principle because the Principle restricts our attention to a distinguished class of space-time models (spatially homogeneous and isotropic models). I argue that, even assuming the Cosmological Principle, the topology of space remains observationally underdetermined. Nonetheless, I argue that we can muster reasons to prefer various topological (...) properties over others. In particular, I favor the adoption of multiply connected universe models on grounds of (i) simplicity, (ii) Machian considerations, and (iii) explanatory power. We are able to appeal to such grounds because multiply connected topologies open up the possibility of finite universe models (consistent with our best data), which in turn avoid thorny issues concerning the postulation of an actually infinite universe. (shrink)

In this paper, we do two things. First, we provide some support for adopting a version of the meaningless strategy with respect to the liar paradox, and, second, we extend that strategy, by providing, albeit tentatively, a solution to that paradox—one that is semantic, rather than logical.

It is our contention that an ontological commitment to propositions faces a number of problems; so many, in fact, that an attitude of realism towards propositions—understood the usual “platonistic” way, as a kind of mind- and language-independent abstract entity—is ultimately untenable. The particular worries about propositions that marshal parallel problems that Paul Benacerraf has raised for mathematical platonists. At the same time, the utility of “proposition-talk”—indeed, the apparent linguistic commitment evident in our use of 'that'-clauses (in offering explanations and making (...) predictions)—is also in need of explanation. We account for this with a fictionalist analysis of our use of 'that'-clauses. Our account avoids certain problems that arise for the usual error-theoretic versions of fictionalism because we apply the notion of semantic pretense to develop an alternative, pretense-involving, non-error-theoretic, fictionalist account of proposition-talk. (shrink)

Social machines are systems formed by technical and human elements interacting in a structured manner. The use of digital platforms as mediators allows large numbers of human participants to join such mechanisms, creating systems where interconnected digital and human components operate as a single machine capable of highly sophisticated behaviour. Under certain conditions, such systems can be described as autonomous and goal-driven agents. Many examples of modern Artificial Intelligence (AI) can be regarded as instances of this class of mechanisms. We (...) argue that this type of autonomous social machines has provided a new paradigm for the design of intelligent systems marking a new phase in the field of AI. The consequences of this observation range from methodological, philosophical to ethical. On the one side, it emphasises the role of Human-Computer Interaction in the design of intelligent systems, while on the other side it draws attention to both the risks for a human being and those for a society relying on mechanisms that are not necessarily controllable. The difficulty by companies in regulating the spread of misinformation, as well as those by authorities to protect task-workers managed by a software infrastructure, could be just some of the effects of this technological paradigm. (shrink)

A large chorus of voices has grown around the claim that theistic belief is epistemically suspect since, as some cognitive scientists have hypothesized, such beliefs are a byproduct of cognitive mechanisms which evolved for rather different adaptive purposes. This paper begins with an overview of the pertinent cognitive science followed by a short discussion of some relevant epistemic concepts. Working from within a largely Williamsonian framework, we then present two different ways in which this research can be formulated into an (...) argument against theistic belief. We argue that neither version works. (shrink)

This paper focuses on the research field of machine ethics and how it relates to a technological singularity—a hypothesized, futuristic event where artificial machines will have greater-than-human-level intelligence. One problem related to the singularity centers on the issue of whether human values and norms would survive such an event. To somehow ensure this, a number of artificial intelligence researchers have opted to focus on the development of artificial moral agents, which refers to machines capable of moral reasoning, judgment, and decision-making. (...) To date, different frameworks on how to arrive at these agents have been put forward. However, there seems to be no hard consensus as to which framework would likely yield a positive result. With the body of work that they have contributed in the study of moral agency, philosophers may contribute to the growing literature on artificial moral agency. While doing so, they could also think about how the said concept could affect other important philosophical concepts. (shrink)

Serious actualists take it that all properties are existence entailing. I present a simple puzzle about sentence tokens which seems to show that serious actualism is false. I then consider the most promising response to the puzzle. This is the idea that the serious actualist should take ordinary property-talk to contain an implicit existential presupposition. I argue that this approach does not work: it fails to generalise appropriately to all sentence types and tokens. In particular, it fails to capture the (...) right distinctions we ought to make between what I call _typographical sentence types_—an interesting and previously undiscussed class of fine-grained sentence types which are partially individuated by their typography, or how they look when written out. (shrink)

Philosophers have not resisted temptation to transgress against the logic of their own conceptual structures. Self-undermining position-taking is an occupational hazard. Philosophy stands in need of conceptual therapy. The author describes three conceptions of philosophy: the narcissistic, disputatious, and therapeutic. (i) Narcissistic philosophy is hermetic, believing itself to contain all evidence that can possibly be relevant to it. Philosophy undertaken in this spirit has led to defensive, monadically isolated positions. (ii) Disputatious philosophies are fundamentally question-begging, animated by assumptions that philosophical (...) adversaries reject. (iii) The intention of therapeutic philosophy is to study philosophical positions from the standpoint of their internal consistency, or lack of it. In particular, its interest is in positions that either compel assent, because they cannot be rejected without self-referential inconsistency, or self-destruct because self-referential inconsistency cannot be avoided. The article's focus is on the latter. Several examples of self-undermining positions are drawn from the history of philosophy, exemplifying two main varieties of self-referential inconsistency: pragmatical and projective. (shrink)

In a series of articles, Dan Lopez De Sa and Elia Zardini argue that several theorists have recently employed instances of paradoxical reasoning, while failing to see its problematic nature because it does not immediately (or obviously) yield inconsistency. In contrast, Lopez De Sa and Zardini claim that resultant inconsistency is not a necessary condition for paradoxicality. It is our contention that, even given their broader understanding of paradox, their arguments fail to undermine the instances of reasoning they attack, either (...) because they fail to see everything that is at work in that reasoning, or because they misunderstand what it is that the reasoning aims to show. (shrink)

From the Editor’s Introduction: "The Internal Limitations of Human Understanding." We carry, unavoidably, the limits of our understanding with us. We are perpetually confined within the horizons of our conceptual structure. When this structure grows or expands, the breadth of our comprehensions enlarges, but we are forever barred from the wished-for glimpse beyond its boundaries, no matter how hard we try, no matter how much credence we invest in the substance of our learning and mist of speculation. -/- The limitations (...) in view here are not due to the mere finitude of our understanding of ourselves and of the world in which we live. They are limitations that come automatically and necessarily with any form of understanding. They are, as we shall see, part and parcel of any organization or ordering of data that we call information. -/- The consequences of these limitations are varied: As a result of them, hermeneutics cannot help but be hermetic; scientific theories of necessity are circumscribed by the boundaries of the ideas that define them; formal systems must choose between consistency and comprehensiveness; philosophical study, because it includes itself within its own proper subject matter, is forced to be reflexive in its self-enclosure. The fundamental dynamic shared by all forms of understanding testifies to an internal limitative keystone. (shrink)

When the third global plague pandemic reached Sydney in 1900, theories regarding the ecology and biology of disease transmission were transforming. Changing understandings led to conflicts over the appropriate response. Medical and government authorities employed symbols like dirt to address gaps in knowledge. They used these symbols strategically to compel emotional responses and to advocate for specific political and social interventions, authorising institutional actions to shape social identity and the city in preparation for Australia's 1901 Federation. Through theoretical and historical (...) analysis, this Element argues that disgust and aversion were effectively mobilised to legitimise these actions. As an intervention in contemporary debates about the impact of knowledge on emotion and affect, it presents a case for the plasticity of emotions like disgust, and for how both emotion and affect can change with new medical information. (shrink)

Central to Sellars’ account of human cognition was a clear distinction, expressed in varying terminology in his different works, “between conceptual and nonconceptual representations.” Those who have come to be known as ‘left-wing Sellarsians’, such as Richard Rorty, Robert Brandom, and John McDowell, have tended to reject Sellars’ appeals to nonconceptual sensory representations. So-called ‘right-wing Sellarsians’ such as Ruth Millikan and Jay Rosenberg, on the other hand, have embraced and developed aspects of Sellars’ account, in particular the central underlying idea (...) that human perceptual cognition involves a certain naturalistic ‘mapping’ correspondence or structural ‘picturing’ isomorphism between internal mental representations and the layout and behavior of objects in the surrounding environment. Sellars, despite his defenses of nonconceptual representational content throughout his career, has with no small irony come to be cited as one of the “founding fathers of conceptualism.” While recognizing the strong conceptualist elements in Sellars’ Kantian account of perceptual cognition, I argue that a central core of Sellars’ account of nonconceptual sensory contents does not by itself fall afoul of the philosophical worries raised by the left-leaning Sellarsians, and that in fact it has significant merits in its own right. (shrink)

Each of the standard outlooks in the philosophy of perception --phenomenalism, direct realism, indirect realism, scepticism -- has thus been viewed as Hume's own considered position in the eyes of informed commentators. I argue that Hume does not ascribe univocally to any one of the traditional stances in the philosophy of perception, nor does he leave us only a schizophrenic or 'mood' scepticism. Hume attempted to resolve the traditional philosophical problem (or perhaps more accurately, to set it aside on principled (...) grounds) by transforming the issue from one of theoretical consistency to one of pragmatic coherence. Hume's moderate scepticism and his systematic naturalism entail a reflective 'return' to the vulgar (cp. T 223), a qualified normative endorsement of the directly realist beliefs of common life. The interpretive challenge is to understand the subtle nature of that endorsement, and to explain how it arises out of genuinely Humean doctrines. The account offered here attempts both to capture Hume's own considered position and to explain the attractions and shortcomings of each of the competing interpretations. After laying out the elements of Hume's account of perceptual belief (section I), I proceed to examine in some detail two recent attempts to interpret Hume as a realist (sections II-III). I contend that these revisionary accounts ascribe unHumean doctrines to Hume. The interpretation of Hume as an irreducible 'mood' sceptic or as a phenomenalist are in that respect both closer to the mark, but Hume's reflective return to the vulgar has recast the nature of the problem and leaves us with a position that is not reflected in the more traditional interpretations (section IV). (shrink)

Ce texte propose une définition de la conscience de soi et explique en quoi cette capacité naît du monde social. Il est postulé que ce dernier permet un mouvement de recul - une «distanciation » - par rapport à soi, et que le cerveau reproduit ce mouvement grâce à certains processus cognitifs qui en ont été imprimés. Parmi ceux-ci, on retrouve le langage intérieur, qui, par analogie, agirait comme un miroir interne capable de confronter l'expérience subjective à elle-même; de cette (...) confrontation naîtrait le soi. Un argument est présenté en faveur de la supériorité du langage intérieur sur d'autres processus cognitifs impliqués dans la conscience de soi. Le problème de la conscience de soi chez les primates est abordé, et l'article conclut sur diverses réflexions ayant trait à la schizophrénie, la prière, la méditation, et les drogues psychodysleptiques.This text proposes a definition of self-awareness and explains its social origin. It is postulated that the social milieu permits a movement to a more objective perspective for self- perception, and that this movement is then reproduced in the brain by specific cognitive processes. It is suggested that inner speech represents one such cognitive processes, which acts like a mirror to reflect subjective experience back upon itself-, the self would be generated by this reflective activity. It is argued that inner speech has a pre-eminent position among the cognitive processes implicated in self-awareness. The problem of self-awareness in primates is discussed, and the article concludes with ideas concerning schizophrenia, prayer, medi- tation, and psychodysleptic drugs. (shrink)

This essay is my review of Erwin Leiser’s excellent documentary film Germany Awake. This classic film first aired in Germany in 1968, and remains to this day one of the best surveys of major Nazi-era movies and exactly what messages they were meant to convey. The film underscores the emphasis the regime put on film as one of the premier mechanisms of propaganda, though Leiser’s film points out that most of the cinema produced by the Nazi regime was not pure (...) propaganda, but mainly entertainment. In the review, I put forward a list of criteria for evaluating the degree of the deceptiveness of propaganda, and why cinema is so apt to exploit those criteria. (shrink)

In this essay, I look at more or less sympathetic portrayals of egoists in film. I start by explaining some basic concepts: psychological egoism; ethical egoism; default egoism; rational egoism; egotism; cynicism; narcissism; and psychopathy. I then review in-depth two excellent WWII films, Stalag 17 and The Bridge on the River Kwai. I note that the key protagonist in both pictures is the same type of character—both played by the same fine actor, William Holden. The main protagonist in both is (...) a soldier in a POW camp, who appears completely egoistic; however, in both cases, the movie shows that he is just a man acting for self-preservation, but within moral limits. The character in both cases is certainly not an egotist, nor a narcissist, much less a psychopath. (shrink)

This essay is my critical review of Al Gini and Alexei Marcoux’s fine text, The Ethics of Business. Unlike most business ethics texts, Gini/Marcoux recognize that most businesses are small, and that business is not inherently immoral and always in need of reform. And they put their focus on using ethical theory to find action-guiding principles to help guide business behavior. Moreover, they adopt the Schumpeterian view that business is an entrepreneurial activity—one that not merely executes transactions, but seeks them (...) out. I critically probe a number of issues with their book such as their reliance upon virtue ethics as their main ethical theory, and their view that trust plays an overwhelming role in business. (shrink)

Dialectic, as commonly approached, is not an analytic study, as the notion is defined in the paper. Where it is analytically approached (as, for example, by Grice and Hamblin), the result is pragmatic in nature, as well as syntactic and semantic. This paper lays the foundations of a purely formal (nonpragmatic) analysis of conversations. This study is accordingly called "Conversation Theory". The key notions of "conversation", "dialogue", "conversation game", "rules of response", "epistemic community" and "channel of informations" are defined precisely, (...) and an analysis of how these notions fit together is given. Particular attention is given to distinguishing conversation theory from standard logic. The paper concludes by analysing a few sample conversation-games, indicating areas needing further research, by pointing out the simplification inherent in the sample games. (shrink)

This essay is my review of Philip Booth’s ...and the Pursuit of Happiness: Wellbeing and the Role of Government. The book is an anthology of original articles by eminent researchers in modern happiness economics, such as: Booth himself; Paul Omerod; David Sacks, Betsey Stephenson, and Justin Wolfers; Christopher Snowden; J. R. Shackleton; Christian Bjornskov; Peter Boettke and Christopher Coyne; and Pedro Schwartz. I conclude by offering several criticisms of the work.

Most explanations are either about events (why things happen), or about properties (why objects have the enduring characteristics that they do). Explanations of events have been studied extensively in philosophy and psychology, whereas the explanations of properties have received little or no attention in the literature. The present study is an exploration of the ways in which we explain various types of properties. Ten participants provided explanations of 45 properties by completing sentences of the form: “Xs have p because…” where (...) p is a property of the concept X. When coded into three traditional kinds of explanation (i.e. causal, purposive, categorical), nearly half of the explanations did not fit into any of these categories and were classified as “other”. Different patterns of preference for explanations emerged across the various property types for each domain. A qualitative analysis of the other kind revealed that the most frequent form of explanation involved another property of the object, as in ‘Xs have property p because they have property q”. Explanations of properties showed a homeostatic character. Simply relating two properties of a concept seems sufficient as an explanation of a property. (shrink)

Psychopaths are the bugbears of moral philosophy. They are often used as examples of perfectly rational people who are nonetheless willing to do great moral wrong without regret; hence the disorder has received the epithet “moral insanity” (Pritchard 1835). But whereas philosophers have had a great deal to say about psychopaths’ glaring and often horrifying lack of moral conscience, their aesthetic capacities have received hardly any attention, and are generally assumed to be intact or even enhanced. Popular culture often portrays (...) psychopaths in ways that suggest a great gap between their amorality and their aesthetic sensitivity. In The Silence of the Lambs (Jonathan Demme, 1991), Hannibal Lecter appreciates fine art, fashion, and wine, while he eats his way through his enemies. His real-life counterparts, however, do not demonstrate the same sensitivities. There is no evidence that psychopaths are capable of real aesthetic appreciation, and some evidence that they are not. In this paper, we set out the limited evidence for the psychopath’s deficient aesthetic sensitivity. The best explanations of what the psychopath lacks turn out to implicate abilities that are also thought to be central to moral thought and action: an impaired capacity for empathizing with others and deficient ability to take a disinterested attitude towards things (socalled distance). We endorse the latter explanation. Thinking about what underlies the psychopath’s deficient aesthetic understanding turns out to throw light on a difficult problem: the connection between ethics and aesthetics. (shrink)

In this essay, I look at two films as possible exemplars of the Nietzschean view of egoism. Compulsion is based on the infamous 1924 Leopold and Loeb murder case. In the movie, two arrogant young men—one of whom admires Nietzsche and preaches the (apparently Nietzschean) view that the strong and superior don’t need to follow conventional morality—kill a boy to prove they can outsmart the unter-menschen police. For a different take on what Nietzsche may have had in mind as “the (...) Overman,” I also look at the film The Moon and Sixpence. Here the protagonist isn’t violent or aggressive, but a completely self-absorbed artist, who paints with genius but uses others without feeling any gratitude or friendship, let alone love. (shrink)

Formal semantic analyses often take words to be minimal building blocks for the purposes of compositionality. But various recent theories of morphology and syntax have converged on the view that there is no demarcation line corresponding to the word level. The same conclusion has emerged from the compositional semantics of superlatives. In the spirit of extending compositionality below the word level, this paper explores how a small set of particles (Japanese KA and MO, Chinese DOU, and Hungarian VALA/VAGY, MIND, and (...) IS) form quantifier words and serve as connectives, additive and scalar particles, question markers, and existential verbs. The main question is whether the meanings of these particles across the varied environments are highly regular, or they are lexicalized with a variety of different meanings that bear a family resemblance. This paper does not reach definitive conclusions, but it raises analytical possibilities using Boolean semantics and the semantics of alternatives. It also draws attention to systematic similarities and some differences between MO and DOU that have not been studied in the literature. (shrink)

From Soul to Self takes us on a fascinating journey through philosophy, theology, religious studies and physiological sciences. The contributors explore the relationship between a variety of ideas that have arisen in philosophy, religion and science, each idea seeking to explain why we think we are somehow unique and distinct.

It is becoming increasingly common for authoritarian regimes to leverage digital technologies to surveil, repress and manipulate their citizens. Experts typically refer to this practice as digital authoritarianism (DA). Existing definitions of DA consistently presuppose a politically repressive agent intentionally exploiting digital technologies to pursue authoritarian ends. I refer to this as the intention-based definition. This paper argues that this definition is untenable as a general description of DA. I begin by illustrating the current predominance of the intention-based definition (Section (...) 2). Section 3 then presents four counterexamples to this definition: benign surveillance; digital sovereignty; attention-harvesting algorithms; and tech-induced loneliness. In each case, we witness authoritarianism being promoted by digital technologies without any evidence of this being intentionally caused by politically repressive agents. Based on these observations, I contend that the intention-based definition is underinclusive and is therefore unsustainable. Section 4 outlines an improved definition of DA – what I call the promotion-based definition. Since this more expansive definition does not posit intentional, politically repressive agency as a precondition of DA, it can accommodate the counterexamples discussed in Section 3. Moreover, it enables us to catch a broader spectrum of cases of DA, such as tech-induced loneliness, which those adhering to the intention-based definition are prone to overlook. After outlining further practical benefits of the promotion-based definition, I argue that we still need to distinguish between intentional and unintentional forms of DA since they call for distinct types of remedial action. -/- . (shrink)

In this paper, I aim to discuss what puns, metaphysically, are. I argue that the type-token view of words leads to an indeterminacy problem when we consider puns. I then outline an alternative account of puns, based on recent nominalist views of words, that does not suffer from this indeterminacy.

Many of us think human extinction would be a very bad thing, and that we have moral reasons to prevent it. But there is disagreement over what would make extinction so bad, and thus over what grounds these moral reasons. Recently, several theorists have argued that our reasons to prevent extinction stem not just from the value of the welfare of future lives, but also from certain additional values relating to the existence of humanity itself (for example, humanity's “final” value, (...) or the value of humanity in itself). In this paper, I argue against these “additional value” views. Despite their initial appeal, these views will inevitably face conflicts between the additional values to which they appeal, and the value of the welfare of future lives. And, I argue, the views cannot plausibly resolve these conflicts. In contrast, these conflicts do not arise for a rival view, on which our reasons to prevent extinction stem just from the value of the welfare of future lives. I conclude that this gives us reason to prefer the latter view, despite the greater initial plausibility of additional value views. (shrink)

One feature of language is that we are able to make mistakes in our use of language. Amongst other sorts of mistakes, we can misspeak, misspell, missign, or misunderstand. Given this, it seems that our metaphysics of words should be flexible enough to accommodate such mistakes. It has been argued that a nominalist account of words cannot accommodate the phenomenon of misspelling. I sketch a nominalist trope-bundle view of words that can.

A belief one has is safe if either (i) it could not easily be false or (ii) in any nearby world in which it is false, it is not formed using the method one uses to form one’s actual belief. It seems our mathematical beliefs are safe if mathematical pluralism is true: if, loosely put, almost any consistent mathematical theory is true. It seems, after all, that in any nearby world where one’s mathematical beliefs differ from one’s actual beliefs, one (...) would believe some other true, consistent theory. Focusing on Justin Clarke-Doane’s recent discussion, I argue the thesis that mathematical beliefs are safe given pluralism faces some obstacles. I argue (i) is true of mathematical belief given pluralism only if we deny plausible claims about the interpretation of non-pluralists who many of us could easily be. Unless strong metasemantic theses are true, it is plausible many of us could easily deny or refuse to believe a consistent and true mathematical theory we actually believe. Since philosophical arguments and controversies permeate the methodology of foundational mathematics, I argue we cannot confidently distinguish the methods we use in mathematics between worlds, thus raising doubts about (ii). (shrink)

This paper examines the integration and unification of the philosophy and psychology of well-being. For the most part, these disciplines investigate well-being without reference to each other. In recent years, however, with the maturing of each discipline, there have been a growing number of calls to integrate the two. While such calls are welcome, what it means to integrate well-being philosophy and psychology can vary greatly depending on one’s theoretical and practical ends. The aim of this paper is to provide (...) a novel conceptual framework for thinking about integrating well-being philosophy and psychology that systematically categorizes different kinds of integration projects. We divide existing attempts in the literature into three broad categories according to the perspective from which the integration takes place: (1) top-down meta-theoretical unification; (2) psychological integration within philosophy; and (3) philosophical integration within psychology. These categories are then broken down into various further subcategories. Our aim in providing this framework is both to facilitate the assessment and comparison of existing integration attempts and to provide a roadmap for future integration attempts. For each category, we discuss one or two representative examples of the approaches. By doing so, we hope to generate interest in the wide variety of existing integration projects, as well as to generate discussion concerning the benefits and pitfalls of different approaches. (shrink)

It is a reasonable worry that God would not truly love us and want our salvation if He fixed a definite point after which He will no longer offer us the graces to repent of our sins. I propose that Thomas Aquinas succeeds in showing us that God would not be cruel or arbitrary in setting up a world where embodied agents end up after death in a state where they will inevitably fail to repent of their sins. Aquinas proposes (...) that being disembodied is to be in a state where a person cannot be mistaken about what they want, given that they know themselves perfectly. If the disembodied state were like this, it would not be surprising that being in that state makes repentance impossible, since a soul would become fully integrated around whatever one desired, without any conflicting desires that could prompt repentance. Thus, humans would persist in whatever desires they had at the moment of death and disembodiment. I conclude by arguing that, while this scenario stands in need of fuller theodicy, Aquinas’ scenario is helpful in defending a view that God is not cruel or arbitrary for creating a world in which post-mortem repentance is impossible. (shrink)

At first glance, Fichte and Nietzsche may strike us as intellectual contraries. For example, Fichte’s belief in historical progress and universal moral law appears to be diametrically opposed to Nietzsche’s searching critique of Enlightenment optimism. This impression is reinforced by Nietzsche’s disparaging remarks about Fichte. What is more, from the dearth of critical literature comparing the two thinkers, one might be tempted to conclude that they are broadly irrelevant to one another. In this paper, however, I argue that their theories (...) of subjectivity are in many respects remarkably similar and worthy of comparison. But I also explain how, despite this convergence, their normative philosophies end up so conspicuously at odds with one another. I begin by examining the resemblance between their denials of the substantial self (Section 1). In Sections 2 and 3, I analyse Fichte’s and Nietzsche’s positive accounts of subjectivity, self-cultivation, and the political preconditions of self-cultivation. In these latter two sections, I focus on pinpointing the conceptual juncture at which their practical outlooks begin to part, which I argue can be located in their drive psychologies and their distinct conceptions of conscience (Gewissen). These theoretical differences then generate a large-scale disagreement regarding the political systems they believe best enable self-cultivation, with Fichte favouring for a democratic regime, and Nietzsche opting for an aristocratic one. I conclude Section 3 by sketching a possible way out of this dilemma. (shrink)

This article criticises David Chalmers’ ‘Reality+’ by interrogating its distinction of virtual reality (VR) from 2D, non-VR video games, a distinction made on the grounds that VR is immersive and these types of video games are not because immersion is a distinct characteristic of 3D perceptually represented VR. Building on the Balcerak Jacksons’ account of ‘representational immersion’, which they acknowledge has ‘perceptual’ and ‘non-perceptual’ elements, I develop an account of ‘non-perceptual representational immersion’ and use it to critique Chalmers’ treatment of (...) VR, immersion, and video games, indirectly problematizing his central ontological claim that ‘virtual reality is genuine reality’ and the reflections he makes about future society which rest upon it. I argue that video games are rich in non-perceptual representational immersion, which includes the representation of non-perceptual information about the structure and behaviour of a virtual world and its systems, the non-perceptual cognitive states that are generated in the player by the virtual world, and the immersion which comes from the constitutively cognitive nature of the player’s engagement with the virtual world, a cognitive engagement construed in an enactive sense. These are just as crucial to the phenomenon of digital immersion as perception. Immersion generally is a much more complicated phenomenon than Chalmers allows for, and it is better conceived as taking place on a spectrum which includes both 3D and 2D experiences of virtual worlds, not as hinging on 3D perceptual representation. I use ‘immersive simulation’ games as a case study. (shrink)

Mathematicians often speak of conjectures as being confirmed by evidence that falls short of proof. For their own conjectures, evidence justifies further work in looking for a proof. Those conjectures of mathematics that have long resisted proof, such as the Riemann hypothesis, have had to be considered in terms of the evidence for and against them. In recent decades, massive increases in computer power have permitted the gathering of huge amounts of numerical evidence, both for conjectures in pure mathematics and (...) for the behavior of complex applied mathematical models and statistical algorithms. Mathematics has therefore become (among other things) an experimental science (though that has not diminished the importance of proof in the traditional style). We examine how the evaluation of evidence for conjectures works in mathematical practice. We explain the (objective) Bayesian view of probability, which gives a theoretical framework for unifying evidence evaluation in science and law as well as in mathematics. Numerical evidence in mathematics is related to the problem of induction; the occurrence of straightforward inductive reasoning in the purely logical material of pure mathematics casts light on the nature of induction as well as of mathematical reasoning. (shrink)

The philosophical interest of mystery is that something may well fall under a distinctive ontological concept of mystery. Such a thing would be explicable with reference to intention, but not uniquely determined by its explicans. This is the "properly mysterious," which is essentially mysterious in virtue of what it is, not just of our epistemic limitations. The richer uses of 'mystery', and defects in recent literature, suggest this line of inquiry. ;Part I rebuts the main arguments against the possibility that (...) something is properly mysterious. First, if something's existence is completely explicable it need not thus be exhaustively explicable . Second, event-determinism is not establishable empirically and nothing establishes general determinism a priori . So there is no reason to think every existent is uniquely determined to exist. But there is good reason to think everything is completely explicable in principle. ;Part II shows there is better reason to think the world's existence properly mysterious than not. The world asked about in the question "Why does the world exist?" should be defined as the totality comprising all that really changes and what is ontologically parasitic thereon . The World's existence is both logically contingent and contingent in one or the other of two de re senses , and thus is either inexplicable for any knower or explicable as intentionally produced. The producer would be extramundane, de re necessary, and could not uniquely determine the existence of The World. Defending classical theism against charges of conceptual incoherence, I conclude that the existence of The World is best thought completely explicable as intentionally created, though not exhaustively explicable by the existence of its creator. ;In conclusion, I expound and adopt Aquinas' account of creation, on which God creates for a reason and freely. Thus there is good reason for the world's existence, but no reason why this world exists rather than some other. (shrink)

J. L. Schellenberg's Philosophy of Religion argues for a specific brand of sceptical religion that takes ‘Ultimism’ – the proposition that there is a metaphysically, axiologically, and soteriologically ultimate reality – to be the object to which the sceptical religionist should assent. In this article I shall argue that Ietsism – the proposition that there is merely something transcendental worth committing ourselves to religiously – is a preferable object of assent. This is for two primary reasons. First, Ietsism is far (...) more modest than Ultimism; Ietsism, in fact, is open to the truth of Ultimism, while the converse does not hold. Second, Ietsism can fulfil the same criteria that compel Schellenberg to argue for Ultimism. (shrink)

ABSTRACT: Central to both James’s earlier psychology and his later philosophical views was a recurring distinction between percepts and concepts. The distinction evolved and remained fundamental to his thinking throughout his career as he sought to come to grips with its fundamental nature and significance. In this chapter, I focus initially on James’s early attempt to articulate the distinction in his 1885 article “The Function of Cognition.” This will highlight a key problem to which James continued to (...) return throughout his later philosophical work on the nature of our cognition, including in his famous “radical empiricist” metaphysics of “pure experience” around the turn of the century. We shall find that James grappled insightfully but ambivalently with the perceptual and conceptual dimensions of the “knowledge relation” or the “cognitive relation,” as he called it—or what, following Franz Brentano, philosophers would later call our object-directed thought or intentionality more generally. Some philosophers have once again returned to James’s work for crucial insights on this pivotal topic, while others continue to find certain aspects of his account to be problematic. What is beyond dispute is that James’s inquiries in this domain were both innovative and of lasting significance. (shrink)

Today, we find ourselves living during the most Religious era in all of human history. If this statement is true, it is also how we can predict the end of the human story.

The Münchhausen trilemma is the following: When trying to prove a fundamental truth, you run into one of, two of, or all three of the following issues: -/- 1: Circular reasoning 2: Infinite regress 3: An arbitrary starting point -/- But what if these are not in fact “problems”, but three different ways to observe the fundamental truth? Reconciling the three and showing how they function together is what I endeavor to articulate here.