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

In this paper, we aim to show that the framework of embedded, distributed, or extended cognition offers new perspectives on social cognition by applying it to one specific domain: the psychology of memory. In making our case, first we specify some key social dimensions of cognitive distribution and some basic distinctions between memory cases, and then describe stronger and weaker versions of distributed remembering in the general distributed cognition framework. Next, we examine studies of social influences on memory in cognitive (...) psychology, and identify the valuable concepts and methods to be extended and embedded in our framework; we focus in particular on three related paradigms: transactive memory, collaborative recall, and social contagion. Finally, we sketch our own early studies of individual and group memory developed within our framework of distributed cognition, on social contagion of autobiographical memories, collaborative flashbulb memories, and memories of high school at a high school reunion. We see two reciprocal benefits of this conceptual and empirical framework to social memory phenomena: that ideas about distributed cognition can be honed against and tested with the help of sophisticated methods in the social cognitive psychology of memory; and conversely, that a range of social memory phenomena that are as yet poorly understood can be approached afresh with theoretically motivated extensions of existing empirical paradigms. (shrink)

It is possible that the world contains infinitely many agents that have positive and negative levels of well-being. Theories have been developed to ethically rank such worlds based on the well-being levels of the agents in those worlds or other qualitative properties of the worlds in question, such as the distribution of agents across spacetime. In this thesis I argue that such ethical rankings ought to be consistent with the Pareto principle, which says that if two worlds contain the same (...) agents and some agents are better off in the first world than they are in the second and no agents are worse off than they are in the second, then the first world is better than the second. I show that if we accept four axioms – the Pareto principle, transitivity, an axiom stating that populations of worlds can be permuted, and the claim that if the ‘at least as good as’ relation holds between two worlds then it holds between qualitative duplicates of this world pair – then we must conclude that there is ubiquitous incomparability between infinite worlds. I show that this is true even if the populations of infinite worlds are disjoint or overlapping, and that we cannot use any qualitative properties of world pairs to rank these worlds. Finally, I argue that this incomparability result generates puzzles for both consequentialist and non-consequentialist theories of objective and subjective permissibility. (shrink)

The growing proportion of elderly people in society, together with recent advances in robotics, makes the use of robots in elder care increasingly likely. We outline developments in the areas of robot applications for assisting the elderly and their carers, for monitoring their health and safety, and for providing them with companionship. Despite the possible benefits, we raise and discuss six main ethical concerns associated with: (1) the potential reduction in the amount of human contact; (2) an increase in the (...) feelings of objectification and loss of control; (3) a loss of privacy; (4) a loss of personal liberty; (5) deception and infantilisation; (6) the circumstances in which elderly people should be allowed to control robots. We conclude by balancing the care benefits against the ethical costs. If introduced with foresight and careful guidelines, robots and robotic technology could improve the lives of the elderly, reducing their dependence, and creating more opportunities for social interaction. (shrink)

This chapter considers potential applications of grounding to the formulation of physicalism. I begin with an overview of competing conceptions of the physical and of physicalism. I then consider whether grounding physicalism overcomes well-known and seemingly fatal problems with supervenience physicalism. I conclude that while grounding physicalism improves upon supervenience physicalism in certain respects, it arguably falls victim to some of the same difficulties.

This chapter considers the assumptions required to make scientisms of different forms genuinely threatening to philosophers, where a genuine threat would consist of a concrete risk to their statuses, the value of their teaching and research, their livelihoods, their preferred research methods, or the health of the discipline. I will find that strong and weak forms of scientism alike require substantive assumptions to make them threatening in those regards. In particular, they require sometimes heavy-handed circumscriptions of philosophy and science, as (...) well as their epistemic credentials and achievements, methods, and subject matters. They also require restrictive pronouncements upon the epistemic and non-epistemic goods that are valuable, worth promoting in academic contexts, and relevant to disciplinary health. My aim in this chapter will not to be defeat those assumptions but rather to make them explicit and to emphasize their frequent strength and contentiousness. (shrink)

Recalling autobiographical memories with others can influence the quality of recall, but little is known about how features of the group influence memory outcomes. In two studies, we examined how the products and processes of autobiographical recall depend on individual vs. collaborative remembering and the relationship between group members. In both studies, dyads of strangers, friends, and siblings recalled autobiographical events individually (elicitation), then either collaboratively or individually (recall). Study 1 involved typing memory narratives; Study 2 involved recalling aloud. We (...) examined shifts in vividness, emotionality, and pronoun use within memory narratives produced by different relationship types. In Study 2, we also coded collaborative dyads’ “collaborative processes” or communication processes. In Study 1, all relationships showed decreased positive emotion and I-pronouns and increased negative emotion within collaboratively-produced memory narratives. In Study 2, all relationships showed increased vividness, reduced emotionality and positive and negative emotion, and increased I- and we-pronouns within collaborativelyproduced memory narratives. However, strangers used collaborative processes differently from friends and siblings. Some collaborative processes were associated with memory qualities. Across studies, collaboration influenced memory quality more than did relationship type, but relationship type influenced dyads’ recall dynamics. These findings indicate the complexity of social influences on memory. (shrink)

Many have offered moral objections to video games, with various critics contending that they depict and promote morally dubious attitudes and behaviour. However, few have offered moral arguments in favour of video games. In this chapter, we develop one such positive moral argument. Specifically, we argue that video games offer one of the only morally acceptable methods for acquiring some ethical knowledge. Consequently, we have (defeasible) moral reasons for creating, distributing, and playing certain morally educating video games.

This is a preprint draft. Please cite published version (DOI: 10.1111/mila.12385). The aim of this paper is to provide a novel analysis of anorexia nervosa (AN) in the context of the sense of agency literature. I first show that two accounts of anorexia nervosa that we ought to take seriously— i.e., the first personal reports of those who have experienced it firsthand as well as the research that seeks to explain anorexic behavior from an empirical perspective— appear to be thoroughly (...) in tension with one another in their descriptions of anorexic actions. Rather than proceeding at this point by way of disregarding anorexic testimony as meaningless or insincere, I instead offer a positive account of the sense of agency in anorexia nervosa that renders these two depictions compatible. The resultant picture of anorexic behavior is one that accommodates current empirical findings while also providing valuable insight into how it is that anorexics can sincerely report feeling fully in control over their food restriction. (shrink)

This paper aims to better motivate the naturalization of metaphysics by identifying and criticizing a class of theories I call ’free range metaphysics’. I argue that free range metaphysics is epistemically inadequate because the constraints on its content—consistency, simplicity, intuitive plausibility, and explanatory power—are insufficiently robust and justificatory. However, since free range metaphysics yields clarity-conducive techniques, incubates science, and produces conceptual and formal tools useful for scientifically engaged philosophy, I do not recommend its discontinuation. I do recommend, however, ending the (...) discipline’s bad faith. That is, I urge that free range metaphysics not be taken to have fully satisfactory epistemic credentials over and above its pragmatic ones. (shrink)

This paper explores the relationship between dignity and robot care for older people. It highlights the disquiet that is often expressed about failures to maintain the dignity of vulnerable older people, but points out some of the contradictory uses of the word ‘dignity’. Certain authors have resolved these contradictions by identifying different senses of dignity; contrasting the inviolable dignity inherent in human life to other forms of dignity which can be present to varying degrees. The Capability Approach (CA) is introduced (...) as a different but tangible account of what it means to live a life worthy of human dignity. It is used here as a framework for the assessment of the possible effects of eldercare robots on human dignity. The CA enables the identification of circumstances in which robots could enhance dignity by expanding the set of capabilities that are accessible to frail older people. At the same time, it is also possible within its framework to identify ways in which robots could have a negative impact, by impeding the access of older people to essential capabilities. It is concluded that the CA has some advantages over other accounts of dignity, but that further work and empirical study is needed in order to adapt it to the particular circumstances and concerns of those in the latter part of their lives. (shrink)

A naturalistic impulse has taken speculative analytic metaphysics in its critical sights. Importantly, the claim that it is desirable or requisite to give metaphysics scientific moorings rests on underlying epistemological assumptions or principles. If the naturalistic impulse toward metaphysics is to be well-founded and its prescriptions to have normative force, those assumptions or principles should be spelled out and justified. In short, advocates of naturalized or scientific metaphysics require epistemic infrastructure. This paper begins to supply it. The author first sketches (...) her conception of suitably naturalized or scientific metaphysics. She then lays out a number of candidate epistemic principles centring around the notion of theoretical constraint. The author offers several arguments for the principles, based on statistical likeliness, agreement, falsity avoidance, and methodological efficiency and inefficiency. Finally, she shows how scientific metaphysics satisfies the epistemic principles and is therefore preferable to its traditional rivals. (shrink)

Philosophers have recently highlighted substantial affinities between causation and grounding, which has inclined some to import the conceptual and formal resources of causal interventionism into the metaphysics of grounding. The prospect of grounding interventionism raises two important questions: exactly what are grounding interventions, and why should we think they enable knowledge of grounding? This paper will approach these questions by examining how causal interventionists have addressed (or might address) analogous questions and then comparing the available options for grounding interventionism. I (...) argue that grounding interventions must be understood in worldly terms, as adding something to or deleting something from the roster of entities, or making some fact obtain or fail to obtain. I consider three bases for counterfactual assessment: imagination, structural equation models, and background theory. I conclude that grounding interventionism requires firmer epistemological foundations, without which the interventionist's epistemology of grounding is incomplete and ineffectually rationalist. (shrink)

Enactivism and ecological psychology converge on the relevance of the environment in understanding perception and action. On both views, perceiving organisms are not merely passive receivers of environmental stimuli, but rather form a dynamic relationship with their environments in such a way that shapes how they interact with the world. In this paper, I suggest that while enactivism and ecological psychology enjoy a shared specification of the environment as the cognitive domain, on both accounts, the structure of the environment, itself, (...) is unspecified beyond that of contingent relations with the species-typical sensorimotor capacities of perceiving organisms. This lack of specification creates a considerable gap in theory regarding the organization of organisms as coupled with their environments. I argue that this gap can be filled by drawing from resources in developmental systems theory, namely, specifying the environmental state-space as a developmental niche that shapes and is shaped by individual organisms over developmental and, on a population scale, evolutionary time. Defining the environment as an organism’s developmental niche makes it clearer how and why certain contingencies have arisen, in turn, strengthening a joint appeal to both enactivism and ecological psychology as theories asserting complementarity between organisms and their environments. (shrink)

This article argues that postwar Seventeen magazine, a publication deeply invested in enforcing heteronormativity and conventional models of girlhood and womanhood, was in fact a more complex and multivocal serial text whose editors actively sought out, cultivated, and published girls’ creative and intellectual work. Seventeen's teen-authored “Curl Up and Read” book review columns, published from 1958 through 1969, are examples of girls’ creative intellectual labor, introducing Seventeen's readers to fiction and nonfiction which ranged beyond the emerging “young-adult” literature of the (...) period. Written by young people – including thirteen-year-old Eve Kosofsky (later Sedgwick) – who perceived Seventeen to be an important publication venue for critical work, the “Curl Up and Read” columns are literary products in their own right, not simply juvenilia. Seventeen provided these young authors the opportunity to publish their work in a forum which offered girl readers and writers opportunities for intellectual development and community. (shrink)

This paper surveys some of the grounding literature searching for points of contact between theories of ground and science. I find that there are some places where a would-be naturalistic grounding theorist can draw inspiration. I synthesize a list of recommendations for how science may be put to use in theories of ground. I conclude that the prospects for naturalizing the metaphysics of ground are bright.

The word ‘naturalism’ has a bewildering array of uses in philosophy. Roughly speaking, it connotes pro-scientific attitudes and approaches. This article introduces the subject of naturalism by sketching a history of pro-scientific attitudes and approaches in philosophy, from their origins in the early modern period through to the present day. It then distinguishes a number of distinct families of naturalism: metaphysical, logico-linguistic, epistemological, and methodological. The resulting taxonomy encompasses a plurality of loosely related views rather than a number of variations (...) on a single clear and unified theme. (shrink)

This article offers a comprehensive and critical analysis of Eric Heinze’s book Hate Speech and Democratic Citizenship (Oxford University Press, 2016). Heinze’s project is to formulate and defend a more theoretically complex version of the idea (also defended by people like Ronald Dworkin and James Weinstein) that general legal prohibitions on hate speech in public discourse compromises the state’s democratic legitimacy. We offer a detailed synopsis of Heinze’s view, highlighting some of its distinctive qualities and strengths. We then develop a (...) critical response to this view with three main focal points: (1) the characterisation of democratic legitimacy as something distinct from (and whose demands aren’t identical with those of) legitimacy per se; (2) the claim that the requirements of democracy are hypothetical, rather than categorical, imperatives; and relatedly (3) the question of how we should reconcile the requirements of democratic legitimacy with the costs that may follow from prioritising democratic legitimacy. We argue that there are significant difficulties for Heinze’s account on all three fronts. (shrink)

Insufficient attention has been paid to the use of robots in classrooms. Robot “teachers” are being developed, but because Kline ignores such technological developments, it is not clear how they would fit within her framework. It is argued here that robots are not capable of teaching in any meaningful sense, and should be deployed only as educational tools.

Dr Miranda Anderson is an Honorary Fellow in History, Classics and Archaeology at the University of Edinburgh and an Associate Lecturer at the Open University. She has held several prestigious fellowships and was principal investigator of an AHRC-funded project, titled ‘The Art of Distributed Cognition’, which involved collaboration with the Talbot Rice Gallery. Her work has investigated the relations between cognition and culture, particularly literary works, challenging the boundaries between disciplines and engaging with numerous contemporary science, technology and society (...) (STS) questions. In this perspective article, she evokes the ‘fission-fusion’ concept on which she has been working for some years now – a concept that contributes to debates surrounding the issue of identity by drawing on the arts, humanities, social sciences, and natural sciences. (shrink)

What, if anything, is problematic about the involvement of celebrities in democratic politics? While a number of theorists have criticized celebrity involvement in politics (Meyer 2002; Mills 1957; Postman 1987) none so far have examined this issue using the tools of social epistemology, the study of the effects of social interactions, practices and institutions on knowledge and belief acquisition. This paper will draw on these resources to investigate the issue of celebrity involvement in politics, specifically as this involvement relates to (...) democratic theory and its implications for democratic practice. We will argue that an important and underexplored form of power, which we will call epistemic power, can explain one important way in which celebrity involvement in politics is problematic. This is because unchecked uses and unwarranted allocations of epistemic power, which celebrities tend to enjoy, threaten the legitimacy of existing democracies and raise important questions regarding core commitments of deliberative, epistemic, and plebiscitary models of democratic theory. We will finish by suggesting directions that democratic theorists could pursue when attempting to address some of these problems. (shrink)

In 2008 the authors held Involving Interface, a lively interdisciplinary event focusing on issues of biological, sociocultural, and technological interfacing (see Acknowledgments). Inspired by discussions at this event, in this article, we further discuss the value of input from neuroscience for developing robots and machine interfaces, and the value of philosophy, the humanities, and the arts for identifying persistent links between human interfacing and broader ethical concerns. The importance of ongoing interdisciplinary debate and public communication on scientific and technical advances (...) is also highlighted. Throughout, the authors explore the implications of the extended mind hypothesis for notions of moral accountability and robotics. (shrink)

Conversations about the past can involve voicing and silencing; processes of validation and invalidation that shape recall. In this experiment we examined the products and processes of remembering a significant autobiographical event in conversation with others. Following the death of Australian celebrity Steve Irwin, in an adapted version of the collaborative recall paradigm, 69 participants described and rated their memories for hearing of his death. Participants then completed a free recall phase where they either discussed the event in groups of (...) three or wrote about the event on their own. Finally, participants completed the original questionnaire again, both 1 week and 1 month after the free recall phase. Discussion influenced later memories for hearing of Irwin’s death, particularly memories for emotion and shock. Qualitative analysis of the free recall phase suggested that during conversation a shared understanding of the event developed, but that emotional reactions to the event were silenced in ways that minimised the event’s impact. These findings are discussed in terms of the processes and consequences of sharing public and personal memories in conversation. (shrink)

In this paper I take up (what I call) the pregnancy loss objection to defenses of abortion that deny fetal moral status. Though versions of this objection have been put forth by others—particularly Lindsey Porter’s in a 2015 paper—I argue that the existing versions of the objection are unsuccessful in various ways: failing to explain the ground of moral considerability that would apply to embryos/fetuses in very early pregnancy, lack of clarity about what it means to take grief after miscarriage (...) seriously, and implausible implications regarding pre-embryo and infertility cases. I go on to offer a more plausible version of the objection, which I apply only to mid-pregnancy and fetuses, by drawing on personal narratives of later pregnancy loss and abortion and emphasizing practices that indicate the relevant kind of mourning. I then take up the question of how experience of the sort I have in mind can function as evidence, by situating my version of the objection in a pragmatist ethical view. Finally I consider and respond to some worries about the very idea of taking experience of pregnancy loss to be evidence regarding fetal moral status. (shrink)

No capítulo 1 da dissertação “A Colônia de Formigas está Consciente?”, intitulado “O Monismo Nageliano e a Composição Material” examinamos a premissa da Composição Material, a qual estabelece que a consciência depende do modo de disposição material das entidades físicas básicas (átomos, elétrons, etc.), na composição do organismo. Ou seja, a experiência consciente de um sistema vivo se encontra estreitamente conectada com a forma em que seus componentes físicos estão relacionados. Isso significa que cada organismo terá um processo diferente de (...) interação desses componentes formando, então, uma mente subjetiva. As diferenças entre um e outro são em grau. Assim, é possível que haja estruturas com níveis alto, baixo, ausente, e até mesmo intermediários de consciência. E cada nível, por sua vez, corresponde a uma relação específica entre parte e todo, se é um sistema orgânico, ou se está entre o orgânico e o não orgânico. Durante o desenvolvimento embrionário, por exemplo, pode existir um momento fronteiriço entre a individualidade e a não-individualidade (ou ser um agregado celular), um momento em que somos incapazes de determinar quando há um organismo. Nesta linha, a consciência também seria indeterminada. Como desconhecemos a relação exata dos componentes físicos para constituir o todo, temos que considerar a consciência como uma propriedade imprecisa do sistema biológico. O Problema da Composição envolve, portanto, a inconsistência do conceito de organismo. Em linhas gerais, se a noção de indivíduo é vaga, por sua vez, a de consciência também será. Por conseguinte, a correlação entre consciência fenomenológica e organização material torna o próprio conceito de mente em uma propriedade imprecisa da composição. Assim, no presente capítulo, esmiuçamos cada uma das quatro premissas que fundamentam o Pampsiquismo: composição material, antirreducionismo, antiemergentismo e realismo. E, em seguida analisamos cada uma dessa premissas como parâmetros para verificar se uma colônia de formigas pode ser um sujeito experiencial. Supomos que, se a colônia estiver estruturada como um indivíduo genuíno, ela terá alguma fenomenalidade. No entanto, não sabemos de que tipo. Por fim, elucidamos como o chamado Problema da Combinação se aplica à colônia de insetos sociais e quais implicações disso. (shrink)

Cross-cultural comparisons face several methodological challenges. In an attempt at resolving some such challenges, Nathan Sivin has developed the framework of “cultural manifolds.” This framework includes all the pertinent dimensions of a complex phenomenon and the interactions that make all of these aspects into a single whole. In engaging with this framework, Anna Akasoy illustrates that the phenomena used in comparative approaches to cultural and intellectual history need to be subjected to a continuous change of perspectives. Writing about comparative history, (...) Warwick Anderson directs attention to an articulation between synchronic and diachronic modes of inquiry. In addition, he asks: If comparative studies require a number of collaborators, how does one coordinate the various contributors? And how does one ensure that the comparison is between separate entities, without mutual historical entanglement? Finally, how does comparative history stack up against more dynamic approaches, such as connected, transnational, and postcolonial histories? Gérard Colas, for his part, claims that comparisons cannot allow one to move away from the dominant Euroamerican conceptual framework. Should this indeed be the case, we should search for better ways of facilitating a “mutual pollination” between philosophies. Finally, Edmond Eh first asserts that Sivin fails to recognize the difference between comparisons within cultures and comparisons between cultures. He then argues that the application of generalism is limited to comparisons of historical nature. (shrink)

Introduction: Online eye-tracking has been used in this study to assess the impacts of different cultural backgrounds on information discernment. An online platform called RealEye allowed participants to engage in the eye-tracking study from their personal computer webcams, allowing for higher ecological validity and a closer replication of social media interaction. -/- Methods: The study consisted of two parts with a total of five visuals of social media posts mimicking news posts on Twitter, Instagram, and Facebook. Participants were asked to (...) view examples of real and fake news taken from a news fact-checking website, Snopes, and their eye movements were recorded during the process. Participants were recruited through Prolific and SONA; the total sample size for study 1.1 was 29 participants, and the total for study 1.2 was 25 participants, after removing poor eye-tracking data. A total of five visual images comprising true and false news were shown to the participant, study 1.1 had three examples and study 1.2 had two examples. There were two main cultural backgrounds in focus: participants born in China or the United Kingdom. -/- Results: Results suggested that participants follow a similar visual pattern of attention to Areas of Interest (AOIs) on the posts, which leads us to believe that due to the global standardisation of popular social media platforms, a bias might have occurred during information discernment. -/- Discussion: It is suggested that regardless of country background, users may have similar eye-tracking results while viewing a social media post because social media platform formats are standardised globally. Further research would recommend looking at language and linguistic traits when seeking differences between country backgrounds during online information discernment. (shrink)

After stating "I am gay" Navy Lieutenant Paul G. Thomasson was honorably discharged from the military. In Thomasson v. Perry (1996), the United States Court of Appeals for the Fourth District affirmed Thomasson's discharge. Thomasson is now considered the leading case evaluating the U.S. military's "don't ask, don't tell" policy. In this paper, I show that the court's analysis of the Department of Defense policy rests of two unarticulated and undefended assumptions about sexuality. The first is that an act of (...) sex is essentially defined in terms of the sexual orientation of the persons engaging in that act. The second is that whether or not a person is an open homosexual determines the essential nature of the homosexual acts of others. I conclude that both assumptions are untenable, therefore the "don't ask, don't tell" policy is indefensible. (shrink)

In the law of rape, consent has been and remains a gendered concept. Consent presumes female acquiescence to male sexual initiation. It presumes a man desires to penetrate a woman sexually. It presumes the woman willingly yields to the man's desires. It does not presume, and of course does not require, female sexual desire. Consent is what the law calls it when he advances and she does not put up a fight. I have argued elsewhere that the kind of thin (...) consent that the law focuses on is not enough ethically and it should not be enough legally to justify sexual penetration. I advocate sexual negotiation, where individuals discuss sexual desires and boundaries and agree to engage in penetration before it occurs, except under circumstances in which the partners have a reasonable basis to assess one another's nonverbal behavior. I argue that not only is verbal consultation about desire ordinarily ethically necessary before most acts of sexual penetration, it should be legally required. Consultation to ascertain sexual desires and boundaries assures that both parties desire penetration. (shrink)

The field of AI has undergone a series of transformations, each marking a new phase of development. The initial phase emphasized curation of symbolic models which excelled in capturing reasoning but were fragile and not scalable. The next phase was characterized by machine learning models—most recently large language models (LLMs)—which were more robust and easier to scale but struggled with reasoning. Now, we are witnessing a return to symbolic models as complementing machine learning. Successes of LLMs contrast with their inscrutability, (...) inaccuracy, and hallucinations, which underwrite concerns over the reliability and trustworthiness of these systems, motivating investigations into commonsense reasoning, AI explainability, and formal verification techniques. Moreover, proper assessments of hybrid machine learning/symbolic systems require novel strategies to facilitate comparisons of performance and guide future AI progress. The EDGeS AAAI 2023 Spring symposium brought together researchers focusing on novel assessments and benchmarks for evaluating hybrid and artificial general intelligence (AGI) systems. This symposium revealed what was already suspected: research concerning evaluation of machine learning/symbolic hybrids and AGI is, unfortunately, lacking. Even so, the discussion was fruitful. (shrink)

Although typical arguments for knitting are that it is useful, therapeutic or the latest trend, I argue that knitting can play a life-changing part in the creation of a person’s self. Knitting can be a genuinely powerful activity, one worthy of respect and admiration.

Organisms live not as discrete entities on which an independent environment acts, but as members of a reproductive lineage in an ongoing series of interactions between that lineage and a dynamic ecological niche. These interactions continuously shape both systems in a reciprocal manner, resulting in the emergence of reliably co-occurring configurations within and between both systems. The enactive approach to cognition describes this relationship as the structural coupling between an organism and its environment; similarly, Developmental Systems Theory emphasizes the reciprocal (...) nature of structurally coupled systems in its analysis of organisms as developmental processes embedded within a developmental system. Through an enactive-developmental systems framing, this paper identifies the organizational features of cognizing systems in order to motivate a picture of how organism and environment co-determine and co-construct one another. I argue that organisms can be characterized as self-organizing, operationally closed, plastic systems ecologically embedded within a developmental system. In virtue of this organizational makeup, organisms actively engage in the modulation and assessment of their coupling with their environment: cognitive strategies that entail contextualized responses to variations across the web of interactions that comprises the developmental system. (shrink)

In the past decade, experimental philosophy---the attempt at making progress on philosophical problems using empirical methods---has thrived in a wide range of domains. However, only in recent years has aesthetics succeeded in drawing the attention of experimental philosophers. The present paper constitutes the first survey of these works and of the nascent field of 'experimental philosophy of aesthetics'. We present both recent experimental works by philosophers on topics such as the ontology of aesthetics, aesthetic epistemology, aesthetic concepts, and imagination, as (...) well as research from other disciplines that not only are relevant to philosophy of aesthetics but also open new avenues of research for experimental philosophy of aesthetics. Overall, we conclude that the birth of an experimental philosophy of aesthetics is good news not only for aesthetics but also for experimental philosophy itself, as it contributes to broaden the scope of experimental philosophy. (shrink)

We argue that a phenomenological approach to social space, as well as its relation to embodiment and affectivity, is crucial for understanding how the social world shows up as social in the first place—that is, as affording different forms of sharing, connection, and relatedness. We explore this idea by considering two cases where social space is experientially disrupted: Moebius Syndrome and schizophrenia. We show how this altered sense of social space emerges from subtle disruptions of embodiment and affectivity characteristic of (...) these conditions. These disruptions are instructive, we suggest, in that they highlight the foundational role that body and affect play in organizing social space—the lived context in which we first encounter one another as social agents. (shrink)

In the Foundations of Mathematics, Ramsey attempted to amend Principia Mathematica’s logicism to meet serious objections raised against it. While Ramsey’s paper is well known, some questions concerning Ramsey’s motivations to write it and its reception still remain. This paper considers these questions afresh. First, an account is provided for why Ramsey decided to work on his paper instead of simply accepting Wittgenstein’s account of mathematics as presented in the Tractatus. Secondly, evidence is given supporting that Wittgenstein was not moved (...) by Ramsey’s objection against the Tractarian account of arithmetic, and a suggestion is made to explain why Wittgenstein reconsidered Ramsey’s account in the early thirties on several occasions. Finally, a reading is formulated to understand the basis on which Wittgenstein argues against Ramsey’s definition of identity in his 1927 letter to Ramsey. (shrink)

There have been many attempts to retire dualism from active philosophic life, replacing it with something less removed from science, but we are no closer to that goal now than fifty years ago. I propose breaking the stalemate by considering marginal perspectives that may help identify unrecognized assumptions that limit the mainstream debate. Comparison with Whitehead highlights ways that opponents of dualism continue to uphold the Cartesian “real distinction” between mind and body. Whitehead, by contrast, insists on a conceptual distinction: (...) there can no more be body without mind than mind without body (at least at the level of ultimate constituents). Key to this integration is Whitehead’s understanding that mind, at its most rudimentary, is simply the intrinsic temporality of a physical event. Thus, the resulting form of “panpsychism” is more naturalistic than commonly supposed, and it solves both the composition problem (traditionally fatal to panpsychism) and the “hard problem.”. (shrink)

Radical democratic thinking is becoming intrigued by the material situatedness of its political agents and by the role of nonhuman participants in political interaction. At stake here is the displacement of narrow anthropocentrism that currently guides democratic theory and practice, and its repositioning into what we call ‘the nonhuman condition’. This Critical Exchange explores the nonhuman condition. It asks: What are the implications of decentering the human subject via a new materialist reading of radical democracy? Does this reading dilute political (...) agency? Or should this be seen, on the contrary, as an invitation for new voices and demands to enter into democratic assemblages? How might engagement with the more-than-human disrupt or extend theories of radical democracy? Hans Asenbaum and Amanda Machin discuss the human democratic subject both through radical democratic and new materialist lenses. They suggest that a new materialist decentred subject does not lose agency but further gains political responsibility in radical democracy. Jean-Paul Gagnon highlights the possibility of becoming through loss. In losing our anthropocentric arrogance—our understanding of being other and better than animal—we become more connected and discover our place in human-nonhuman assemblages. Melissa Orlie agrees that something can be gained through renouncing dominant human fantasies and presents a ‘radical democratic naturalism’. By renouncing land violence and acknowledging nature’s subjectivity, we can further nonexploitative radical democratic politics. This is where the notion of ‘tidalectic’ processes introduced by James L. Smith is helpful. Focusing on water and the Indigenous knowledges around rivers, he considers how democracy and community can be reimagined as plural, cyclical and attentive to the nonhuman with which the human is inevitably entangled. Diana Leong offers a different approach. Considering the nonhuman from the perspective of Black Studies demands an awareness to how blackness has long been constituted as non- or partially human. (shrink)

Discussions of sexual ethics often focus on the wrong of treating another as a mere object instead of as a person worthy of respect. On this view, the task of sexual ethics becomes putting the other’s subjectivity above their status as erotic object so as to avoid the harms of objectification. Ward and Anderson argue that such a view disregards the crucial, moral role that erotic objecthood plays in sexual encounters. Important moral features of intimacy are disclosed through the (...) experience of being an erotic object for another, as well as in perceiving another as an erotic object. Drawing on phenomenology, especially the insights of Simone de Beauvoir, Ward and Anderson argue that erotic encounters are shaped by the human condition of ambiguity, where being an object for others is intertwined with bodily agency. Because sexual agency is complex in this way, theories of sexual ethics and responsibility must widen their focus beyond transparent communication and authoritative expressions of will. (shrink)

What is so striking about Breaking Bad is how centrally impairment and disability feature in the lives of the characters of this series. It is unusual for a television series to cast characters with visible or invisible impairments. On the rare occasions that television shows do have characters with impairments, these characters serve no purpose other than to contribute to their ‘Otherness.’ Breaking Bad not only centralizes impairment, but impairment drives and sustains the story lines. I use three interrelated themes (...) from Disability Scholarship to analyze Breaking Bad. The first theme, Bodily Control, is that good bodies are controlled bodies and that uncontrolled, messy bodies are frightening, bad bodies. Indeed, the messiness of impairment and disability is so bad, that impaired and disabled individuals are excluded or shut out or excluded from many areas of public life. The second theme, Normalcy, is that the effect of hiding away impairment, of attempting to conceal disability, is that society becomes defined by, and structured around, the concept of normalcy. Normalcy, being normal, attaining and maintaining normalcy, is the preoccupation of most in society. To fail to be normal, or to fall from what is considered to be normal, is a source of tremendous anxiety for most people. These two themes, Bodily Control and Normalcy are conceptually connected: impairment, disease and dying are so feared because they are socially invisible and, therefore unknown and unknowable. They are the undiscussable taboos. The third theme, Bodily Realism, is that having a realistic view of the body, which would at minimum require accepting the fact that human bodies are fragile things, prone to disease and accident and are ultimately destined to die, makes one more at ease in the world, and able to live better lives and live as a better person. Indeed, so the argument goes, our lives would be richer, more rewarding—emotionally and morally—if we cared less about normalcy because of a dread of abnormalcy, but instead learned to accept if not positively value the physical variability of human existence. (shrink)

Nicholas Rescher’s way of understanding process philosophy reflects the ambitions of his own philosophical project and commits him to a conceptually ideal interpretation of process. Process becomes a transcendental idea of reflection that can always be predicated of our knowledge of the world and of the world qua known, but not necessarily of reality an sich. Rescher’s own taxonomy of process thinking implies that it has other variants. While Rescher’s approach to process philosophy makes it intelligible and appealing to mainstream (...) analytic philosophy, it leaves behind the more daring ideas of Bergson, James, and Whitehead, all of whom envisioned the primordial reality of process in a radical ontology of becoming. This variant of process thought can be construed as coherent and self-consistent, but not without relinquishing the correspondence theory of truth and embracing challenging ideas that bring us in close proximity to existentialism, apophatic theology, and Buddhism. (shrink)

Alvin Plantinga has famously argued that the naturalist who accepts evolutionary theory has a defeater for all of her beliefs, including her belief in naturalism and evolution. Hence, he says, naturalism, when conjoined with evolution, is self defeating and cannot be rationally accepted. This is known as the evolutionary argument against naturalism (EAAN). However, Tyler Wunder (Religious Studies 51:391– 399, 2015) has recently shown that if the EAAN is framed in terms of objective probability and theism is assumed to be (...) non-contingent, then either theism is necessarily false or the EAAN is unsound. Neither option is attractive to the proponent of the EAAN. Perry Hendricks (Religious Studies 1–5, 2018) has responded to Wunder’s criticism, showing that the EAAN can be salvaged and, indeed, strengthened, by framing it in terms not of naturalism (N), but of a proposition that is entailed by N that is also consistent with theism. We will show that once Hendricks’ solution to Wunder’s objection is accepted, a puzzle ensues: if the EAAN provides the naturalist with a defeater for all of her beliefs, then an extension of it appears to provide God with a defeater for all of his beliefs. After bringing out this puzzle, we suggest several ways in which the proponent of the EAAN might solve it, but also show some potential weaknesses in these purported solutions. Whether the solutions to the puzzle that we consider ultimately succeed is unclear to us. (Translation: the authors disagree. One author thinks that the solutions (or,at least, some of them) that we consider do solve the puzzle while the other author does not.) However, it is clear to us that this is an issue that proponents of the EAAN need to address. (shrink)

What happens to our minds when we listen to a story or read a book? How about when we watch a play or film? Any story, like a piece of music, plays out across our minds and in the process changes the nature of our notes and expands their range. Stories – whether told orally, read in a book, scrolled through or watched upon screen or stage – enable a metamorphosis of our minds through biological and sociocultural processes operating in (...) concert. (shrink)

Traditional theists are, with few exceptions, global semantic realists about the interpretation of external world statement. Realism of this kind is treated by many as a shibboleth of traditional Christianity, a sine qua non of theological orthodoxy. Yet, this love affair between theists and semantic realism is a poor match. I suggest that everyone (theist or no) has compelling evidence drawn from everyday linguistic practice to reject a realist interpretation of most external world statements. But theists have further reason to (...) forswear this view, because those who insist on global semantic realism open themselves to the charge of hubris of a theologically inappropriate kind. If the arguments in this paper are sound, then neither God nor any of us have reason to apply a realist interpretation to all or even most statements about the external world. (shrink)

I argue that silence is replete with aesthetic character and that it can be a rewarding object of aesthetic appreciation, assessment, and appraisal. The appreciation of silence might initially seem impossible, for, it might seem, there is nothing there to behold. Taking up this challenge, I attempt to dispel the sense of paradox. I contend that, despite our never actually experiencing absolute silence, there is much to enjoy in the silences that we do experience. I go on to argue that (...) proper appreciation of silence is a two-way street, involving quiet on the outside and stillness on the inside. I conclude by offering some suggestions for how to make the aesthetic appreciation of silence part of a flourishing life. (shrink)

This paper looks at the history of the problem of individuation from Plato to Whitehead. Part I takes as its point of departure Reiner Wiehl’s interpretation of the different meanings of “abstract” in the metaphysics of Alfred North Whitehead and arrives at a corresponding taxonomy of different ways things can be called concrete. Part II compares the way philosophers in different periods understand the relation between thought and intuition. The view mostly associated with ancient philosophy is that thought and sense-perception (...) target different kinds of objects. The view mostly associated with modern philosophy (although it was introduced by the Stoics) is that thought and sense-perception are different ways of targeting the same objects. These differences have specific consequences for theories of individuation, which are assessed historically in Part III and then applied to Whitehead’s difficult texts in part IV. (shrink)

Whitehead claims there is only one type of individual in the universe—the actual entity—but there are necessarily multiple tokens of this type. This turns out to be paradoxical. Nevertheless, a type of individuality that is necessarily plural because, for each token, relations to other tokens are constitutive is something familiar from ordinary language, everyday politics, and, not least, 19th century German social thought. Whitehead’s actual entity generalizes the notion of species-being we find in Fichte, Feuerbach, and Marx. The rationale for (...) the concept of species-being brings to light important social and political implications of Whitehead’s cosmology. (shrink)