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)

While C. I. Lewis was traditionally interpreted as an epistemological foundationalist throughout his major works, virtually every recent treatment of Lewis's epistemology dissents. But the traditional interpretation is correct: Lewis believed that apprehensions of "the given" are certain independently of support from, and constitute the ultimate warrant for, objective empirical beliefs. This interpretation proves surprisingly capable of accommodating apparently contrary textual evidence. The non-foundationalist reading, by contrast, simply cannot explain Lewis's explicit opposition to coherentism and his insistence that only apprehensions (...) of the given enable us to answer the regress problem -- and so vindicate the possibility of empirical justification. (shrink)

Many have taken Sellars’s critique of empiricism in “Empiricism and the Philosophy of Mind” (EPM) to be aimed at his teacher C. I. Lewis. But if so, why do the famous arguments of its opening sections carry so little force against Lewis’s views? Understandably, some respond by denying that Lewis’s epistemology is among the positions targeted by Sellars. But this is incorrect. Indeed, Sellars had earlier offered more trenchant (if already familiar) critiques of Lewis’s epistemology. What is original about EPM (...) is that it criticizes empiricist positions like Lewis’s not because of their foundationalism, but because of their psychologism about meaning. Since psychologism turns out to be unacceptable by Lewis’s own lights, EPM has a compelling (if implicit) critique of Lewis to offer after all, one that strikes at the heart of his philosophical system. (shrink)

In this article, I expound and defend an interpretation of Sellars as a metaethical quasi-realist. Sellars analyzes moral discourse in non-cognitivist terms: in particular, he analyzes “ought”-statements as expressions of collective intentions deriving from a collective commitment to provide for the general welfare. But he also endorses a functional-role theory of meaning, on which a statement’s meaning is grounded in its being governed by semantical rules concerning language entry, intra-linguistic, and language departure transitions, and a theory of truth as correct (...) assertibility relative to such semantical rules. On these non-representationalist theories, even though moral statements are expressions of intentions and not fundamentally descriptive, they nevertheless count as assertorically meaningful, and some count as positively true. I further argue that this interpretation is capable not only of explaining Sellars’ explicitly metaethical writings, but also of unifying his scientific realism with his commitment to the ineliminable and indispensable role of the language of intentions: if this linguistic framework does not play an explanatory role, but only an expressive role, this explains both why Sellars’ commitment to it does not contravene his naturalism, as well as why, given the necessity of such language for our practical engagement with the world, the scientific image of humans in the world will only be completed once such language supplements it to enable us to relate practically to it. (shrink)

Charles Sanders Peirce has commonly been interpreted as a proponent of an epistemic theory of truth. Such a theory has the apparent advantage of directly undercutting radical skepticism, but the disadvantage of implausibly entailing that there are no truths concerning irretrievably lost facts. Recently Andrew Howat has defended Peirce’s epistemic constraint on truth by recasting Peirce’s claim that all truths would be believed following sufficient inquiry, not as constitutive of truth, but as a Wittgensteinian hinge proposition. I begin with a (...) twofold historical reply to Howat: first, Peirce can at least plausibly be read as claiming that the claim in question is analytic of the concept <truth>; and second, while Peirce did think we must accept without evidence the further claim that there are any truths (so characterized), he regarded this further claim not as a Wittgensteinian hinge but as a reasonable hope. I then substantively defend the latter Peircean proposal, arguing that hopes, as against beliefs, are chiefly warranted pragmatically, and so can be warranted even to a sufficient level to render them properly action-guiding in cases where belief in the same proposition would remain unjustified. I conclude by suggesting, first, that this proposal is superior to Wittgenstein’s own epistemology in evading psychologism, and second, that it attractively vindicates the reasonableness of inquiry on Peircean grounds that don’t require an appeal to an implausible epistemic theory of truth. (shrink)

This paper explores two related questions in late Athenian and Alexandrian Neoplatonism. First, how can a philosopher contemplate the eternal Forms while engaging in practical agency in the world? Second, do Neoplatonists provide a consistent account of the philosopher’s progress through the ‘stages of virtue’ (βαθμοί τῶν ἀρετῶν), the conceptual structure that underpins late antique philosophical curricula and hagiography? These questions interact, I suggest, because later Platonists appeal to the stages of virtue and divine maniai (βαθμοί τῶν μανίων) to explain (...) the philosopher’s ability to alternate gracefully between contemplation and embodied agency, and even to engage in both activities at the same moment. I argue that apparently contradictory evidence for the highest stages of virtue can be reconciled satisfactorily, shedding light on two models of ethical and perceptual transformation that are consistent throughout later Neoplatonism. In the first, 'painterly' model, we alternate between a vision of the paradigmatic model and its expression in the media of place and time; in the second, 'dancerly' model, we contemplate in action all at once, like a dancer moving to the music. (shrink)

This paper offers a critical interpretation and evaluation of Wilfrid Sellars’s treatment of skepticism about empirical justification. It defends three central claims. First, against the suggestion that Sellars’s work simply bypasses traditional skeptical problems, I make the novel interpretive claim that Sellars not only addresses skepticism about empirical justification, but offers two independent (albeit sketchy) arguments against it: a transcendental argument that the likely truth of our perceptual beliefs is a necessary condition of the possibility of empirical content, and a (...) pragmatic argument that we’re warranted in accepting their likely truth in virtue of our aim of being effective agents. To the extent these have previously been distinctly formulated by commentators, the transcendental argument has been regarded as forceful, while the pragmatic argument has been dismissed as non-responsive. My second and third claims challenge this understanding. I argue, second, that examination of the literature relating to transcendental arguments from semantic externalism like Sellars’s (especially concerning the McKinsey paradox) suggests that such arguments are unpromising, while, third, a modified version of his pragmatic argument represents a powerful skeptical solution to skepticism about empirical justification, one that answers the worry that such skepticism would undermine the rationality of all our practical commitments. (shrink)

Sellars was an inferentialist about meaning. He thus effectively accorded modality a categorial function, maintaining that any meaningful assertion involves implicit commitment to rules of material inference, which modal propositions explicitly endorse. But Sellars was also a modal anti-realist, construing modality as “entirely immanent to thought” (LRB §40), not present in the world an sich. These two commitments, Klemick argues, render it impossible in principle for us to describe the world an sich adequately, undermining Sellars’ scientific realism, on which, at (...) the “ideal outcome of scientific inquiry,” “the gulf between appearances and things-in-themselves [... can] be bridged” (SM II §51). Sellars’ attempt to ground his modal anti-realism in an ideal “pure description of the world” (CDCM §79) cannot succeed, given modality’s categorial function. Further, his subsequent deployment of picturing as a naturalistic criterion of ontological commitment founders on an analogue of the Kantian problem of noumenal affection: the descriptions of picturing relations that render this proposal intelligible are emptied of content by the denial that the in-itself is modally characterized. Sellars’ worthy aim of preserving the world’s independence of our conceptual activity, Klemick concludes, doesn’t require denying that it exhibits modal relations isomorphic to the semantic relations within our conceptual scheme. (shrink)

Since 2023, the UK government's response to the “migrant crisis” has revolved around two controversial flagship policies: the deportation of asylum seekers to Rwanda, and the detention of migrants aboard a giant barge. In this short article, I examine the colonial and gendered dimensions of the two policies, finding them to be examples of the coloniality of gender. What this indicates, I suggest, is that the purpose of these policies is not merely to deter potential migrants—particularly LGBTQIA+ migrants—but also to (...) create a political narrative that allows the Conservative Party to garner right-wing votes by participating in high-profile culture wars; namely, the debate over transgender rights and the debate over how the UK should reckon with its imperial past. (shrink)

Pragmatist responses to skepticism about empirical justification have mostly been underwhelming, either presupposing implausible theses like relativism or anti-realism, or else showing our basic empirical beliefs to be merely psychologically inevitable rather than rationally warranted. In this paper I defend a better one: a modified version of an argument by Wilfrid Sellars that we are pragmatically warranted in accepting that our perceptual beliefs are likely to be true, since their likely truth is necessary for the satisfaction of our goal of (...) effective agency. On the version of the argument I defend, the great good for human life of control over our empirical circumstances renders our goal of effective agency reasonable. But only if our perceptual beliefs are likely to be true—and only if we accept that this is so, assuming it as a premise for inference and a guide for action—will the success of our actions be due to our effective agency, not mere luck. Since we’re warranted in taking the necessary means to our reasonable ends, we’re warranted in accepting that our perceptual beliefs are generally justified, and so that skepticism about empirical justification is false. (shrink)

In “The Fixation of Belief,” Peirce apparently accepts the causal claim that real physical objects cause us to reach an indefeasible “final opinion” concerning them. In “How to Make Our Ideas Clear,” he apparently accepts the constitutive claim that for physical objects to be real just is for them to be represented in that opinion. These claims initially seem inconsistent, since causal claims are explanatory and since equivalent claims cannot explain one another. Contrary to prominent suggestions that Peirce rejected the (...) constitutive claim, however, he actually accepted both, reconciling them via a Humean denial that causal claims are genuinely explanatory. (shrink)

I take up two questions raised by Luz Christopher Seiberth's meticulous reconstruction of Wilfrid Sellars's theory of intentionality. The first is whether we should regard Sellars as a transcendental phenomenalist in the most interesting sense of the term: as denying that even an ideally adequate conceptual structure would enable us to represent worldly objects as they are in themselves. I agree with Seiberth that the answer is probably yes, but I suggest that this is due not to Sellars's rejection of (...) the Myth of the Given or appeal to image-models (as Seiberth maintains), but to his view of modality as categorial but as absent from the world an sich. The second is whether, as Richard Rorty complained, Sellars's appeal to picturing lands his theory of intentionality in intractable skepticism. Pace Seiberth, I argue that the transcendental role of picturing does not mitigate this problem, and I suggest that Sellars's most fruitful resource for doing so is not his semantic externalism, but his purely pragmatic response to skepticism. (shrink)

The proliferation of work by autistic writers continues apace, defying a long and multidisciplinary tradition of constructing autistic people as lacking the capacity for narration. To study neurodivergent literature, then, is to witness the refusal of these exclusionary narrative conventions, and to register the ideological presuppositions that underpin pathologization. In this article, I engage with recent insights from Neurodiversity Studies to explore the connections between narrative neuronormativity and other discourses of oppression, especially those that have generated racialized, gendered, and colonial (...) narratives of desubjectification. Focusing on the neuroqueer movement—an emergent practice of disidentification that refuses the interpellations of neuronormativity, ableism, heteronormativity, and cisnormativity—I discuss the concept of allism, arguing that this satirical critique of pathologization harbors a deconstructive force that denaturalizes the dialectic of recognition. Pursuing the discursive context and theoretical implications of this critique, I provide a short genealogy of narrative neuronormativity, connecting the operation of the dialectic in the early novel to the clinical texts of child psychology. To demonstrate the neuroqueer subversion of this tradition, I then read An Unkindness of Ghosts, by Rivers Solomon, a text that stages a disidentification with storytelling. Protagonist Aster’s neuroqueer refusal indexes the concomitance of the construction of Blackness as an ontological foil for whiteness and the construction of autism as a standard of disordered sociality that neuronorms can be measured against. My reading of Unkindness suggests that the extant techniques of literary narratorship are political instruments that will, unless repurposed, continue to disseminate these dispossessive dialectics. (shrink)

Proclus argues that place (topos) is a body of light, identified as the luminous vehicle of the soul, which mediates between soul and body and facilitates motion. Simplicius (in Phys. 611,10–13) suggests that this theory is original to Proclus, and unique in describing light as a body. This paper focuses on the function of this theory as a bridge between Proclus’ physics and metaphysics, allowing the Aristotelian physical notion of “natural place” to serve as a mechanism for the descent and (...) ascent of the soul. (shrink)

Together we can achieve things that we could never do on our own. In fact, there are sheer endless opportunities for producing morally desirable outcomes together with others. Unsurprisingly, scholars have been finding the idea of collective moral obligations intriguing. Yet, there is little agreement among scholars on the nature of such obligations and on the extent to which their existence might force us to adjust existing theories of moral obligation. What interests me in this paper is the perspective of (...) the moral deliberating agent who faces a collective action problem, i.e. the type of reasoning she employs when deciding how to act. I hope to show that agents have collective obligations precisely when they are required to employ ‘we-reasoning’, a type of reasoning that differs from I-mode, best response reasoning, as I shall explain below. More precisely, two (or more) individual agents have a collective moral obligation to do x if x is an option for action that is only collectively available (more on that later) and each has sufficient reason to rank x highest out of the options available to them. (shrink)

WINNER BEST SOCIAL PHILOSOPHY BOOK IN 2021 / NASSP BOOK AWARD 2022 -/- Together we can often achieve things that are impossible to do on our own. We can prevent something bad from happening or we can produce something good, even if none of us could do it by herself. But when are we morally required to do something of moral importance together with others? This book develops an original theory of collective moral obligations. These are obligations that individual moral (...) agents hold jointly, but not as unified collective agents. To think of some of our obligations as joint or collective is the best way of making sense of our intuitions regarding collective moral action problems. Where we have reason to believe that our efforts are most efficient as part of a collective endeavor we may incur collective obligations together with others who are similarly placed as long as we are able to establish compossible individual contributory strategies towards that goal. The book concludes with a discussion of “massively shared obligations” to large-scale moral problems such as global poverty. (shrink)

We use generic sentences like ‘Blondes are stupid’ to express stereotypes. But why is this? Does the fact that we use generic sentences to express stereotypes mean that stereotypes are themselves, in some sense, generic? I argue that they are. However, stereotypes are mental and generics linguistic, so how can stereotypes be generic? My answer is that stereotypes are generic in virtue of the beliefs they contain. Stereotypes about blondes being stupid contain a belief element, namely a belief that blondes (...) are stupid. This belief is an attitude taken towards the same proposition expressed by the sentence ‘Blondes are stupid’, hence why we use the latter to articulate the former. -/- This generic account of stereotypes can help us better understand their inner workings. I focus on one feature of generics, variability in the types of facts that can make them true, and argue that it can explain how stereotypes shape inferential patterns and thereby guide how we treat members of stereotyped groups. This feature, in turn, illuminates the harms caused by stereotyping and suggests some courses of action. (shrink)

While many scholars join in the call for an experiential shift in thinking and living, it is not always clear how it could be done. Recent environmental philosophy has illuminated the significance of re-animating human–environment relations on an experiential level for endeavouring a new (or renewed) ethical, experiential, and, indeed, existential stance of the human as part of the environed embodiment. In relation to this call, I explore embodied critical thinking (ECT) as a tool for recognising, revitalising, and reflecting embodied, (...) enactive, and embedded thinking that comes from a felt sense. Thus, this chapter employs some of the TAE (Thinking at the Edge) steps for ECT research as a practical approach to facilitating and embracing a new way of thinking that is crucial for reconnecting humans with their lived environments, but also for emancipating research practices to enable research that goes out from such a renewed connectivity. In particular, the chapter traces the application of Eugene Gendlin’s move of instancing to showcase the use of embodied knowing and felt sense in environmental contexts. Thus, it showcases how, in fundamental ways that speak directly to and from our embodied embeddedness, ECT has an emancipatory impact in ways that resonate with lived experiences. (shrink)

Dog whistling—speech that seems ordinary but sends a hidden, often derogatory message to a subset of the audience—is troubling not just for our political ideals, but also for our theories of communication. On the one hand, it seems possible to dog whistle unintentionally, merely by uttering certain expressions. On the other hand, the intention is typically assumed or even inferred from the act, and perhaps for good reason, for dog whistles seem misleading by design, not just by chance. In this (...) paper, I argue that, to understand when and why it’s possible to dog-whistle unintentionally (and indeed, intentionally), we’ll need to recognize the structure of our linguistic practices. For dog whistles and for covertly coded speech more generally, this structure is a pair of practices, one shared by all competent speakers and the other known only to some, but deployable in the same contexts. In trying to identify these enabling conditions, we’ll discover what existing theories of communicated content overlook by focusing on particular utterances in isolation, or on individual speakers’ mental states. The remedy, I argue, lies in attending to the ways in which what is said is shaped by the temporally extended, socio-politically structured linguistic practices that utterances instantiate. (shrink)

It is often argued that our obligations to address structural injustice are collective in character. But what exactly does it mean for ‘ordinary citizens’ to have collective obligations visà- vis large-scale injustice? In this paper, I propose to pay closer attention to the different kinds of collective action needed in addressing some of these structural injustices and the extent to which these are available to large, unorganised groups of people. I argue that large, dispersed and unorganised groups of people are (...) often in a position to perform distributive collective actions. As such, ordinary citizens can have massively shared obligations to address structural injustice through distributive action, but, ultimately, such obligations are ‘collective’ only in a fairly weak sense. (shrink)

The focus of this article is the "good-will theory", which explains the effect humans can have on the safety of AI, along with how it is in the best interest of a superintelligent AI to work alongside humans and not overpower them. Future papers dealing with the good-will theory will be published, but discuss different talking points in regards to possible or real objections to the theory.

Marine ecosystems are under increasing pressure from human activity, yet successful management relies on knowledge. The evidence-based policy (EBP) approach has been promoted on the grounds that it provides greater transparency and consistency by relying on ‘high quality’ information. However, EBP also creates epistemic responsibilities. Decision-making where limited or no empirical evidence exists, such as is often the case in marine systems, creates epistemic obligations for new information acquisition. We argue that philosophical approaches can inform the science-policy interface. Using marine (...) biosecurity examples, we specifically examine the epistemic challenges in the acquisition and acceptance of evidence to inform policy, discussing epistemic due care and biases in consideration of evidence. (shrink)

In Group Duties, Stephanie Collins proposes a ‘tripartite’ social ontology of groups as obligation-bearers. Producing a unified theory of group obligations that reflects our messy social reality is challenging and this ‘three-sizes-fit-all’ approach promises clarity but does not always keep that promise. I suggest considering the epistemic level as primary in determining collective obligations, allowing for more fluidity than the proposed tripartite ontology of collectives, coalitions and combinations.

Moral duties concerning climate change mitigation are – for good reasons – conventionally construed as duties of institutional agents, usually states. Yet, in both scholarly debate and political discourse, it has occasionally been argued that the moral duties lie not only with states and institutional agents, but also with individual citizens. This argument has been made with regard to mitigation efforts, especially those reducing greenhouse gases. This paper focuses on the question of whether individuals in industrialized countries have duties to (...) reduce their individual carbon footprint. To this end it will examine three kinds of arguments that have been brought forward against individuals having such duties: the view that individual emissions cause no harm; the view that individual mitigation efforts would have no morally significant effect; and the view that lifestyle changes would be overly-demanding. The paper shows how all three arguments fail to convince. While collective endeavours may be most efficient and effective in bringing about significant changes, there are still good reasons to contribute individually to reducing emission. After all, for most people the choice is between reducing one’s individual emissions and not doing anything. The author hopes this paper shows that one should not opt for the latter. (shrink)

In the light of Philipp Sarasin's work in Darwin und Foucault: Genealogie und Geschichte im Zeitalter der Biologie, the article delineates a genealogically articulated naturally produced culture and a cultured nature and discusses the genealogical implications of a carnal, becoming self in a world that could rightly be justified "as an aesthetical phenomenon." The article demonstrates the historicity and processual materiality as a conceptual platform for a combination of the notions of experienced carnality and a socially constructed body, demonstrating such (...) a historically embedded carnal body as a binding agent for the "social constructivist" and "biologist" approaches in sciences. Thus, the article builds a framework for the articulation of senseful, processual materiality on the backdrop of a nature-culture continuum via genealogy, suggesting the necessity for change of tone in the communication of human and life sciences via the understanding of a culturally endowed biology. (shrink)

In recent decades, concepts of group agency and the morality of groups have increasingly been discussed by philosophers. Notions of collective or joint duties have been invoked especially in the debates on global justice, world poverty and climate change. This paper enquires into the possibility and potential nature of moral duties individuals in unstructured groups may hold together. It distinguishes between group agents and groups of people which – while not constituting a collective agent – are nonetheless capable of performing (...) a joint action. It attempts to defend a notion of joint duties which are neither duties of a group agent nor duties of individual agents, but duties held jointly by individuals in unstructured groups. Furthermore, it seeks to illuminate the relation between such joint duties on the one hand and individual duties on the other hand. Rebutting an argument brought forward by Wringe, the paper concludes that it is not plausible to assume that all humans on earth can together hold a duty to mitigate climate change or to combat global poverty given that the members of that group are not capable of joint action. (shrink)

This research explores the carnal, experienced self as processual and becoming, situating life as zoe (as per Braidotti) in the context of the Western culture, characterized by alienation (Fromm, Foucault). The study first addresses the ontological disposition of the carnal self and then turns to the concepts of life and death (Freud, Fromm), to explicate the tie between materiality and discourse conditions. Erich Fromm’s classical distinction of having and being is restated as a distinction of having and becoming, which are (...) then explored as complimentary ontological, cultural, and characterological directionalities. A genealogy of their mutual dynamics then allows situating the relations of carnal bodies and inorganic prosthesis (e.g. technologies) in the light of life considered as the necessary synthesis of forces of preservation and perpetual change, beyond subject-object duality. (shrink)

We can often achieve together what we could not have achieved on our own. Many times these outcomes and actions will be morally valuable; sometimes they may be of substantial moral value. However, when can we be under an obligation to perform some morally valuable action together with others, or to jointly produce a morally significant outcome? Can there be collective moral obligations, and if so, under what circumstances do we acquire them? These are questions to which philosophers are increasingly (...) turning their attention. It is fair to say that traditional ethical theories cannot give a satisfying answer to the questions, focusing as they do on the actions and attitudes of discreet individual agents. It should also be noted that the debate surrounding collective moral obligations is ongoing and by no means settled. This chapter discusses and compares the different attempts to date to answer the above questions. It proposes a set of meta-criteria—or desiderata— for arbitrating between the various proposals. (shrink)

Democracy is the central political issue of our age, yet debates over its nature and goals rarely engage with feminist concerns. Now that women have the right to vote, they are thought to present no special problems of their own. But despite the seemingly gender-neutral categories of individual or citizen, democratic theory and practice continues to privilege the male. This book reconsiders dominant strands in democratic thinking - focusing on liberal democracy, participatory democracy, and twentieth century versions of civic republicanism (...) - and approaches these from a feminist perspective. Anne Phillips explores the under-representation of women in politics, the crucial relationship between public and private spheres, and the lessons of the contemporary women's movement as an experience in participatory democracy. (shrink)

This article explores the negative framing of environmental concern in the context of food procurement and consumption, through the lens of the myth of Eden considering the ontological and genealogical aspects of the experienced exile from nature. The article first considers the theoretical context of the negative framing of food ethics. Demonstrating the consequences of the experience of food as abject, the article then goes on to discuss the exile from Eden as an explanatory myth for the perceptual inbetweenness of (...) humankind. The aim of the article is to outline the genealogical markers of the negative framing of food ethics via the discussion of the exile from Eden. In the context of a new materialist understanding of the nature–culture continuum, the article depicts the exile as a perceptual rather than ontological divide that does not reflect a factual human inbetweenness but mirrors the objectification of nature by stripping the flesh of its spirit. Such reenvisioning is thought to be a pivotal aspect for mitigating the affectual abjectivity of food and recapturing the factual entanglement of body–environment to enable affirmative environmental ethics. (shrink)

Fan culture has grown immensely over the past few years. People are constantly looking up to celebrities and personalities as role models for their fashion, identity, and success. During the stage of adolescence, it is normal for teenagers to admire well- known people and form fan attachments as part of their identity formation. However, this admiration of a specific media figure can be associated with one's personality, cognitive processes, and psychological well-being. Thus, the current study aims to investigate the correlation (...) between celebrity admiration and the self-esteem of 238 Filipino male teenagers. The research instruments, namely Celebrity Attitude Scale (CAS) and Rosenberg Self-Esteem Scale (RSES) were both utilized through google forms. Results have shown high scores on celebrity admiration and the normal range of self-esteem of the participants. Using Pearson’s r correlation coefficient, it was found that celebrity admiration and self-esteem of Filipino male teenagers have a significant relationship that exists in a negative direction. (shrink)

COVID-19 vaccine refusal seems like a paradigm case of irrationality. Vaccines are supposed to be the best way to get us out of the COVID-19 pandemic. And yet many people believe that they should not be vaccinated even though they are dissatisfied with the current situation. In this paper, we analyze COVID-19 vaccine refusal with the tools of contemporary philosophical theories of responsibility and rationality. The main outcome of this analysis is that many vaccine-refusers are responsible for the belief that (...) they should not be vaccinated and epistemically rational in holding it. This is an important result because it provides insights into the legitimacy of certain public health policies. In particular, this result shows that a public health policy that would abandon the project of convincing certain vaccine-refusers with reasons – e.g., by simply making vaccination compulsory – is prima facie illegitimate. (shrink)

Our moral obligations can sometimes be collective in nature: They can jointly attach to two or more agents in that neither agent has that obligation on their own, but they – in some sense – share it or have it in common. In order for two or more agents to jointly hold an obligation to address some joint necessity problem they must have joint ability to address that problem. Joint ability is highly context-dependent and particularly sensitive to shared (or even (...) common) beliefs. As such, joint ability can be deliberately generated in a given collection of agents by providing information related to collective goals and contributory actions. As moral agents, we regularly face problems wherein the outcome of our actions depends on how others choose. There are two ways of deliberating about our own choices in such cases. We can either think of our choices as best responses to others’ choices (I-mode reasoning). Or we can think of our own choices as contributions to the collectively best option (even when we do not know how others are (likely) to choose) (we-mode reasoning). In deliberating about the right (individual) course of action vis-à-vis collective action problems, agents regularly we-frame the case at hand, that is, they include options in their deliberation that are only collectively available, and they we-reason with regard to their individual contributory actions. It is a necessary condition for collective obligations that potential collaborators facing a joint necessity case have grounds to privilege we-reasoning over reasoning in I-mode. (shrink)

The mathematician Georg Cantor strongly believed in the existence of actually infinite numbers and sets. Cantor’s “actualism” went against the Aristotelian tradition in metaphysics and mathematics. Under the pressures to defend his theory, his metaphysics changed from Spinozistic monism to Leibnizian voluntarist dualism. The factor motivating this change was two-fold: the desire to avoid antinomies associated with the notion of a universal collection and the desire to avoid the heresy of necessitarian pantheism. We document the changes in Cantor’s thought with (...) reference to his main philosophical-mathematical treatise, the Grundlagen (1883) as well as with reference to his article, “Über die verschiedenen Standpunkte in bezug auf das aktuelle Unendliche” (“Concerning Various Perspectives on the Actual Infinite”) (1885). (shrink)

Is the sense of smell a source of aesthetic perception? Traditional philosophical aesthetics has centered on vision and audition but eliminated smell for its subjective and inherently affective character. This article dismantles the myth that olfaction is an unsophisticated sense. It makes a case for olfactory aesthetics by integrating recent insights in neuroscience with traditional expertise about flavor and fragrance assessment in perfumery and wine tasting. My analysis concerns the importance of observational refinement in aesthetic experience. I argue that the (...) active engagement with stimulus features in perceptual processing shapes the phenomenological content, so much so that the perceptual structure of trained smelling varies significantly from naive smelling. In a second step, I interpret the processes that determine such perceptual refinement in the context of neural decision-making processes, and I end with a positive outlook on how research in neuroscience can be used to benefit philosophical aesthetics. (shrink)

Humans are prone to producing morally suboptimal and even disastrous outcomes out of ignorance. Ignorance is generally thought to excuse agents from wrongdoing, but little attention has been paid to group-based ignorance as the reason for some of our collective failings. I distinguish between different types of first-order and higher order group-based ignorance and examine how these can variously lead to problematic inaction. I will make two suggestions regarding our epistemic obligations vis-a-vis collective (in)action problems: (1) that our epistemic obligations (...) concern not just our own knowledge and beliefs but those of others, too and (2) that our epistemic obligations can be held collectively where the epistemic tasks cannot be performed by individuals acting in isolation, for example, when we are required to produce joint epistemic goods. (shrink)

A fallibilist theory of knowledge is employed to make sense of the idea that agents know what they are doing 'without observation' (as on Anscombe's theory of practical knowledge).

This chapter explores the question of whether or not individual agents are under a moral obligation to reduce their ‘antimicrobial footprint’. An agent’s antimicrobial footprint measures the extent to which her actions are causally linked to the use of antibiotics. As such, it is not necessarily a measure of her contribution to antimicrobial resistance. Talking about people’s antimicrobial footprint in a way we talk about our carbon footprint may be helpful for drawing attention to the global effects of individual behaviour (...) and for highlighting that our choices can collectively make a real difference. But can we be morally obligated to make a contribution to resolving a collective action problem when our individual contributions by themselves make no discernible difference? I will focus on two lines of argument in favour of such obligations: whether a failure to reduce one’s antimicrobial footprint is unfair and whether it constitutes wrongdoing because it is harmful. I conclude by suggesting that the argument from collective harm is ultimately more successful. (shrink)

Most current techniques to deal with invasive species are ineffective or have highly damaging side effects. To this end suppression-drives based on clustered regularly inter-spaced short palindromic repeats (CRISPR/Cas9) have been touted as a potential silver bullet for the problem, allowing for a highly focused, humane and cost-effective means of removing a target species from an environment. Suppression-drives come with serious risks, however, such that the precautionary principle seems to warrant us not deploying this technology. The focus of this paper (...) is on one such risk – the danger of a suppression-drive escaping containment and wiping out the target species globally. Here, I argue that in most cases this risk is significant enough to warrant not using a gene-drive. In some cases, however, we can bypass the precautionary principle by using an approach that hinges on what I term the ‘Worst-Case Clause’. This clause, in turn, provides us with a litmus test that can be fruitfully used to determine what species are viable targets for suppression-drives in the wild. Using this metric in concert with other considerations, I suggest that only three species are currently possible viable targets – the European rabbit, ship rat and Caribbean Tree Frog. (shrink)

The statement that we are currently failing to address some of humanity’s greatest challenges seems uncontroversial—we are not doing enough to limit global warming to a maximum of 2 °C and we are exposing vulnerable people to preventable diseases when failing to produce herd immunity. But what singles out such failings from all the things we did not do when all are unintended? Unlike their individualist counterparts, collective inaction and omission have not yet received much attention in the literature. collective (...) inaction, I argue, can be attributed to a group of agents where a collective action x that the agents did not perform was collectively feasible at time t where each agent in that group had sufficient reason to contribute to performing x or others had a reasonable expectation that they would perform x. I show that, perhaps surprisingly, we can speak of collective inaction even where only one member of the group fails to act. However, where large and dispersed groups of agents are concerned, there is often no meaningful way of attributing collective failings. Still, I contend that the failure to close the global emissions gap and—in some cases—to generate herd immunity are indeed on us. (shrink)

In this article, I will consider whether, and in what way, doxastic states can harm. I’ll first consider whether, and in what way, a person’s doxastic state can harm her, before turning to the question of whether, and in what way, it can harm someone else.

Philosophical discussion about the reality of sensory perceptions has been hijacked by two tendencies. First, talk about perception has been largely centered on vision. Second, the realism question is traditionally approached by attaching objects or material structures to matching contents of sensory perceptions. These tendencies have resulted in an argumentative impasse between realists and anti-realists, discussing the reliability of means by which the supposed causal information transfer from object to perceiver takes place. Concerning the nature of sensory experiences and their (...) capacity to provide access to reality, this article challenges the standard categories through which most arguments in this debate have been framed to date. Drawing on the underexplored case of olfaction, I first show how the details of the perception process determine the modalities of sensory experiences. I specifically examine the role of measurement and analyze its influence on the characterization of perceptions in olfaction. My aim is to argue for an understanding of perception through a process view, rather than one pertaining to objects and properties of objects. (shrink)

Do sensory measurements deserve the label of “measurement”? We argue that they do. They fit with an epistemological view of measurement held in current philosophy of science, and they face the same kinds of epistemological challenges as physical measurements do: the problem of coordination and the problem of standardization. These problems are addressed through the process of “epistemic iteration,” for all measurements. We also argue for distinguishing the problem of standardization from the problem of coordination. To exemplify our claims, we (...) draw on olfactory performance tests, especially studies linking olfactory decline to neurodegenerative disorders. (shrink)

As analysis of Kant’s account of virtue in the Lectures on Ethics shows that Kant thinks of virtue as a form of moral self-mastery or self-command that represents a model of self-governance he compares to an autocracy. In light of the fact that the very concept of virtue presupposes struggle and conflict, Kant insists that virtue is distinct from holiness and that any ideal of moral perfection that overlooks the fact that morality is always difficult for us fails to provide (...) an appropriate model of human virtue. No matter how morally good we are or become, virtue remains a disposition to do one’s duty from duty, out of necessitation by practical reason. Yet, even though finite rational beings require a power of self-constraint in accordance with the commands of duty to comply with the law (which we obey reluctantly), the virtuous agent displays a unified soul that is at peace. This picture of virtue uncovered from the Lectures on Ethics thus reveals the way in which Kant’s conception of virtue accords with his foundational commitments in his moral theory, while at the same time representing a more complex theory of moral character and a life lived in accordance with practical reason. (shrink)

This book engages with the most urgent philosophical questions pertaining to the problem of terrorism. What is terrorism? Could it ever be justified? Assuming that terrorism is just one of many kinds of political violence, the book denies that it is necessarily wrong and worse than war. In fact, it may be justifiable under certain circumstances.

ABSTRACTIn this paper I defend a form of epistocracy I call limited epistocracy – rule by institutions housing expertise in non-political areas that become politically relevant. This kind of limited epistocracy, I argue, isn't a far-off fiction. With increasing frequency, governments are outsourcing political power to expert institutions to solve urgent, multidimensional problems because they outperform ordinary democratic decision-making. I consider the objection that limited epistocracy, while more effective than its competitors, lacks a fundamental intrinsic value that its competitors have; (...) namely, political inclusion. After explaining this challenge, I suggest that limited epistocracies can be made compatible with robust political inclusion if specialized institutions are confined to issuing directives that give citizens multiple actionable options. I explain how this safeguards citizens’ inclusion through rational deliberation, choice, and contestation. (shrink)

This commentary is part of a symposium on my book 'Getting Our Act Together: A Theory of Collective Moral Obligations' (Routledge, 2021). Here, I respond to the members of the North American Society for Social Philosophy’s 2022 Book Award Committee. I discuss whether most moral theory is individualistic, arguing that “traditional ethical theories” - meaning the traditions of Virtue Ethics, Kantian ethics as well as consequentialist ethics - certainly are. All of these focus on what individual agents ought to do (...) or how they ought to be. The commentators wonder whether any substantive moral theory can accommodate the idea of collective obligations? I suggest that one of my conditions for collective moral obligations is incompatible with objectivist versions of act-utilitarianism, which require moral agents to choose the option that actually maximises utility. Having said that, core elements of my account of collective moral obligations can be used with any substantive theory. Further, the theory—in its entirety—can be used with several substantive theories, including versions of all the major types of moral theory. How common are collective obligations? On my understanding, as fundamentally social thinkers, we are fairly flexible at switching between the we-mode and the I-mode, and will regularly respond to contextual cues for framing collective action scenarios. As such, I am not worried that there would be too few circumstances under which we have all-out collective obligations. What is more, we can generate such obligations by providing contextual cues for others that prompt them to frame situations as opportunities for joint action and to perform contributory actions. Another question raised by the commentators was if for having collective obligations it is crucial that we believe others will contribute? My answer is that such obligations do not necessarily depend on having positive evidence that concrete others are or will be contributing. Having said that, where we have positive evidence that others will not contribute and in particular where we know that their failure to contribute will unilaterally undermine the possibility of success of any collective action (as in strict joint necessity cases) this may undermine collective obligations. On my theory, what happens if people disagree on what is morally best? On my view, where such divergence between moral positions comes as a result of disagreement between morally motivated, reasonable, and well-informed people it undermines their collective obligation. Finally, are there “negative” collective duties? Yes, in fact collective harm cases can be conceived of as generating “negative” duties to collectively refrain from generating these kinds of harms, including our obligations to mitigate climate change through reducing greenhouse emissions. (shrink)

There are countless circumstances under which random individuals COULD act together to prevent something morally bad from happening or to remedy a morally bad situation. But when OUGHT individuals to act together in order to bring about a morally important outcome? Building on Philip Pettit’s and David Schweikard’s account of joint action, I will put forward the notion of joint duties: duties to perform an action together that individuals in so-called random or unstructured groups can jointly hold. I will show (...) how this account of joint duties is preferable to one which defends individual duties to cooperate. I then discuss the limits of joint duties and the ways in which one can fail to comply with them. It will become apparent that the circumstances under which individuals in random collectives acquire such joint duties are rare. (shrink)

The article delves into the mystery that underlies the true nature of reality..Do we view reality as it is or is reality an illusion in the sense that it's a product of our senses rather than a fundamental part of the universe? These are some of the questions that have puzzled great thinkers for millennia.. The true nature of reality seems to be utterly elusive just as Brian Greene said "sometimes nature guards her secrets by the unbreakable grip of physical (...) law, sometimes the true nature of reality beckons from just beyond the horizon". (shrink)