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)

Para matemáticos interesados en problemas de fundamentos, lógico-matemáticos y filósofos de la matemática, el axioma de elección es centro obligado de reflexión, pues ha sido considerado esencial en el debate dentro de las posiciones consideradas clásicas en filosofía de la matemática (intuicionismo, formalismo, logicismo, platonismo), pero también ha tenido una presencia fundamental para el desarrollo de la matemática y metamatemática contemporánea. Desde una posición que privilegia el quehacer matemático, nos proponemos mostrar los aportes que ha tenido el axioma en varias (...) áreas fundamentales de la matemática, su aplicación en la lógica de primer orden, así como una breve descripción de las pruebas de consistencia relativa debidas a Gödel y Cohen, las cuales establecieron su independencia del sistema axiomático Zermelo-Fraenkel (ZF). Con todo lo anterior mostraremos cómo el quehacer matemático contemporáneo se adscribe al platonismo matemático en los términos de Bernays y Ferreirós. Revisaremos también los argumentos de Zermelo y Cantor para permitir el uso de asunciones en la matemática, los cuales se acercan a los planteamientos de la investigación científica y esbozan relaciones con la filosofía de la práctica matemática. Finalmente, justificamos el uso del axioma de elección en la contemporaneidad, abogando por unas relaciones de equidad entre la matemática y la filosofía, presentando además su plena vigencia, a través de la referencia a algunos problemas abiertos en la actualidad que vinculan el axioma de elección con la teoría de Ramsey. (shrink)

• It would be a moral disgrace for God (if he existed) to allow the many evils in the world, in the same way it would be for a parent to allow a nursery to be infested with criminals who abused the children. • There is a contradiction in asserting all three of the propositions: God is perfectly good; God is perfectly powerful; evil exists (since if God wanted to remove the evils and could, he would). • The religious believer (...) has no hope of getting away with excuses that evil is not as bad as it seems, or that it is all a result of free will, and so on. Piper avoids mentioning the best solution so far put forward to the problem of evil. It is Leibniz’s theory that God does not create a better world because there isn’t one — that is, that (contrary to appearances) if one part of the world were improved, the ramifications would result in it being worse elsewhere, and worse overall. It is a “bump in the carpet” theory: push evil down here, and it pops up over there. Leibniz put it by saying this is the “Best of All Possible Worlds”. That phrase was a public relations disaster for his theory, suggesting as it does that everything is perfectly fine as it is. He does not mean that, but only that designing worlds is a lot harder than it looks, and determining the amount of evil in the best one is no easy matter. Though humour is hardly appropriate to the subject matter, the point of Leibniz’s idea is contained in the old joke, “An optimist is someone who thinks this is the best of all possible worlds, and a pessimist thinks.. (shrink)

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

Using path-breaking discoveries of cognitive science, Mark Johnson argues that humans are fundamentally imaginative moral animals, challenging the view that morality is simply a system of universal laws dictated by reason. According to the Western moral tradition, we make ethical decisions by applying universal laws to concrete situations. But Johnson shows how research in cognitive science undermines this view and reveals that imagination has an essential role in ethical deliberation. Expanding his innovative studies of human reason in Metaphors (...) We Live By and The Body in the Mind, Johnson provides the tools for more practical, realistic, and constructive moral reflection. (shrink)

In a recent book and article, James Sterba has argued that there is no free will defense. It is the purpose of this article to show that, in the most technical sense, he is wrong. There is a version of the free will defense that can solve what Sterba (rightly) takes to be the most interesting and severe version of the logical problem of moral evil. However, I will also argue that, in effect (or, we might say, in practice), Sterba (...) is correct. The only working version of the free will defense requires embracing a view that entails consequences theists traditionally have not and cannot accept. Consequently, the one and only free will solution is not viable. Unless some other solution can be found (Sterba argues there is none), the logical problem of evil, as Sterba understands it, either commits one to atheism, or a version of theism that practically all theists would regard as a heresy. (shrink)

The modern Everett interpretation of quantum mechanics describes an emergent multiverse. The goal of this paper is to provide a perspicuous characterisation of how the multiverse emerges making use of a recent account of (weak) ontological emergence. This will be cashed out with a case study that identifies decoherence as the mechanism for emergence. The greater metaphysical clarity enables the rebuttal of critiques due to Baker (2007) and Dawid and Th\'ebault (2015) that cast the emergent multiverse ontology as incoherent; responses (...) are also offered to challenges to the Everettian approach from Maudlin (2010) and Monton (2013). (shrink)

Whether or not quantum physics can account for molecular structure is a matter of considerable controversy. Three of the problems raised in this regard are the problems of molecular structure. We argue that these problems are just special cases of the measurement problem of quantum mechanics: insofar as the measurement problem is solved, the problems of molecular structure are resolved as well. In addition, we explore one consequence of our argument: that claims about the reduction or emergence of molecular structure (...) cannot be settled independently of the choice of a particular resolution to the measurement problem. Specifically, we consider how three standard putative solutions to the measurement problem inform our under- standing of a molecule in isolation, as well as of chemistry’s relation to quantum physics. (shrink)

Both realist and anti-realist accounts of natural kinds possess prima facie virtues: realists can straightforwardly make sense of the apparent objectivity of the natural kinds, and anti-realists, their knowability. This paper formulates a properly anti-realist account designed to capture both merits. In particular, it recommends understanding natural kinds as ‘categorical bottlenecks,’ those categories that not only best serve us, with our idiosyncratic aims and cognitive capacities, but also those of a wide range of alternative agents. By endorsing an ultimately subjective (...) categorical principle, this view sidesteps epistemological difficulties facing realist views. Yet, it nevertheless identifies natural kinds that are fairly, though not completely, stance-independent or objective. (shrink)

An Aristotelian Philosophy of Mathematics breaks the impasse between Platonist and nominalist views of mathematics. Neither a study of abstract objects nor a mere language or logic, mathematics is a science of real aspects of the world as much as biology is. For the first time, a philosophy of mathematics puts applied mathematics at the centre. Quantitative aspects of the world such as ratios of heights, and structural ones such as symmetry and continuity, are parts of the physical world and (...) are objects of mathematics. Though some mathematical structures such as infinities may be too big to be realized in fact, all of them are capable of being realized. Informed by the author's background in both philosophy and mathematics, but keeping to simple examples, the book shows how infant perception of patterns is extended by visualization and proof to the vast edifice of modern pure and applied mathematical knowledge. (shrink)

The interventionist account of causal explanation, in the version presented by Jim Woodward, has been recently claimed capable of buttressing the widely felt—though poorly understood—hunch that high-level, relatively abstract explanations, of the sort provided by sciences like biology, psychology and economics, are in some cases explanatorily optimal. It is the aim of this paper to show that this is mistaken. Due to a lack of effective constraints on the causal variables at the heart of the interventionist causal-explanatory scheme, as presently (...) formulated it is either unable to prefer high-level explanations to low, or systematically overshoots, recommending explanations at so high of a level as to be virtually vacuous. (shrink)

Scientific realists don’t standardly discriminate between, say, biology and fundamental physics when deciding whether the evidence and explanatory power warrant the inclusion of new entities in our ontology. As such, scientific realists are committed to a lush rainforest of special science kinds (Ross, 2000). Viruses certainly inhabit this rainforest – their explanatory power is overwhelming – but viruses’ properties can be explained from the bottom up: reductive explanations involving amino acids are generally available. However, reduction has often been taken to (...) lead to a metaphysical downgrading, so how can viruses keep their place in the rainforest? In this paper, we show how the inhabitants of the rainforest can be inoculated against the eliminative threat of reduction: by demonstrating that they are emergent. According to our account, emergence involves a screening off condition as well as novelty. We go on to demonstrate that this account of emergence, which is compatible with theoretical reducibility, satisfies common intuitions concerning what should and shouldn’t count as real: viruses are emergent, as are trout and turkeys, but philosophically gerrymandered objects like trout-turkeys do not qualify. (shrink)

Recent discussions of emergence in physics have focussed on the use of limiting relations, and often particularly on singular or asymptotic limits. We discuss a putative example of emergence that does not fit into this narrative: the case of phonons. These quasi-particles have some claim to be emergent, not least because the way in which they relate to the underlying crystal is almost precisely analogous to the way in which quantum particles relate to the underlying quantum field theory. But there (...) is no need to take a limit when moving from a crystal lattice based description to the phonon description. Not only does this demonstrate that we can have emergence without limits, but also provides a way of understanding cases that do involve limits. (shrink)

Comparative valuation of different policy interventions often requires interpersonal comparability of benefit. In the field of health economics, the metric commonly used for such comparison, quality adjusted life years (QALYs) gained, has been criticized for failing to respect the equality of all persons’ intrinsic worth, including particularly those with disabilities. A methodology is proposed that interprets ‘full quality of life’ as the best health prospect that is achievable for the particular individual within the relevant budget constraint. This calibration is challenging (...) both conceptually and operationally as it shifts dramatically when technology or budget developments alter what can be achieved for incapacitated individuals. The proposal nevertheless ensures that the maximal achievable satisfaction of one person’s preferences can carry no more intrinsic value than that of another. This approach, which can be applied to other domains of social valuation, thus prevents implicit discrimination against the elderly and those with irremediable incapacities. (shrink)

It is commonly claimed that the universality of critical phenomena is explained through particular applications of the renormalization group. This article has three aims: to clarify the structure of the explanation of universality, to discuss the physics of such RG explanations, and to examine the extent to which universality is thus explained. The derivation of critical exponents proceeds via a real-space or a field-theoretic approach to the RG. Building on work by Mainwood, this article argues that these approaches ought to (...) be distinguished: while the field-theoretic approach explains universality, the real-space approach fails to provide an adequate explanation. (shrink)

Philosophers of experiment have acknowledged that experiments are often more than mere hypothesis-tests, once thought to be an experiment's exclusive calling. Drawing on examples from contemporary biology, I make an additional amendment to our understanding of experiment by examining the way that `wide' instrumentation can, for reasons of efficiency, lead scientists away from traditional hypothesis-directed methods of experimentation and towards exploratory methods.

I explore how rational belief and rational credence relate to evidence. I begin by looking at three cases where rational belief and credence seem to respond differently to evidence: cases of naked statistical evidence, lotteries, and hedged assertions. I consider an explanation for these cases, namely, that one ought not form beliefs on the basis of statistical evidence alone, and raise worries for this view. Then, I suggest another view that explains how belief and credence relate to evidence. My view (...) focuses on the possibilities that the evidence makes salient. I argue that this makes better sense of the difference between rational credence and rational belief than other accounts. (shrink)

In this paper, I argue that the relationship between belief and credence is a central question in epistemology. This is because the belief-credence relationship has significant implications for a number of current epistemological issues. I focus on five controversies: permissivism, disagreement, pragmatic encroachment, doxastic voluntarism, and the relationship between doxastic attitudes and prudential rationality. I argue that each debate is constrained in particular ways, depending on whether the relevant attitude is belief or credence. This means that epistemologists should pay attention (...) to whether they are framing questions in terms of belief or in terms of credence and the success or failure of a reductionist project in the belief-credence realm has significant implications for epistemology generally. (shrink)

The Tree of Life has traditionally been understood to represent the history of species lineages. However, recently researchers have suggested that it might be better interpreted as representing the history of cellular lineages, sometimes called the Tree of Cells. This paper examines and evaluates reasons offered against this cellular interpretation of the Tree of Life. It argues that some such reasons are bad reasons, based either on a false attribution of essentialism, on a misunderstanding of the problem of lineage identity, (...) or on a limited view of scientific representation. I suggest that debate about the Tree of Cells and other successors to the traditional Tree of Life should be formulated in terms of the purposes these representations may serve. In pursuing this strategy, we see that the Tree of Cells cannot serve one purpose suggested for it: as an explanation for the hierarchical nature of taxonomy. We then explore whether, instead, the tree may play an important role in the dynamic modeling of evolution. As highly-integrated complex systems, cells may influence which lineage components can successfully transfer into them and how they change once integrated. Only if they do in fact have a substantial role to play in this process might the Tree of Cells have some claim to be the Tree of Life. (shrink)

Pascal’s wager and Leibniz’s theory that this is the best of all possible worlds are latecomers in the Faith-and-Reason tradition. They have remained interlopers; they have never been taken as seriously as the older arguments for the existence of God and other themes related to faith and reason.

A polemical account of Australian philosophy up to 2003, emphasising its unique aspects (such as commitment to realism) and the connections between philosophers' views and their lives. Topics include early idealism, the dominance of John Anderson in Sydney, the Orr case, Catholic scholasticism, Melbourne Wittgensteinianism, philosophy of science, the Sydney disturbances of the 1970s, Francofeminism, environmental philosophy, the philosophy of law and Mabo, ethics and Peter Singer. Realist theories especially praised are David Armstrong's on universals, David Stove's on logical probability (...) and the ethical realism of Rai Gaita and Catholic philosophers. In addition to strict philosophy, the book treats non-religious moral traditions to train virtue, such as Freemasonry, civics education and the Greek and Roman classics. (shrink)

Permissivism is the thesis that, for some body of evidence and a proposition p, there is more than one rational doxastic attitude any agent with that evidence can take toward p. Proponents of uniqueness deny permissivism, maintaining that every body of evidence always determines a single rational doxastic attitude. In this paper, we explore the debate between permissivism and uniqueness about evidence, outlining some of the major arguments on each side. We then consider how permissivism can be understood as an (...) underdetermination thesis, and show how this moves the debate forward in fruitful ways: in distinguishing between different types of permissivism, in dispelling classic objections to permissivism, and in shedding light on the relationship between permissivism and evidentialism. (shrink)

In What Science Knows, the Australian philosopher and mathematician James Franklin explains in captivating and straightforward prose how science works its magic. It offers a semipopular introduction to an objective Bayesian/logical probabilist account of scientific reasoning, arguing that inductive reasoning is logically justified (though actually existing science sometimes falls short). Its account of mathematics is Aristotelian realist.

There is a wide range of realist but non-Platonist philosophies of mathematics—naturalist or Aristotelian realisms. Held by Aristotle and Mill, they played little part in twentieth century philosophy of mathematics but have been revived recently. They assimilate mathematics to the rest of science. They hold that mathematics is the science of X, where X is some observable feature of the (physical or other non-abstract) world. Choices for X include quantity, structure, pattern, complexity, relations. The article lays out and compares these (...) options, including their accounts of what X is, the examples supporting each theory, and the reasons for identifying the science of X with (most or all of) mathematics. Some comparison of the options is undertaken, but the main aim is to display the spectrum of viable alternatives to Platonism and nominalism. It is explained how these views answer Frege’s widely accepted argument that arithmetic cannot be about real features of the physical world, and arguments that such mathematical objects as large infinities and perfect geometrical figures cannot be physically realized. (shrink)

How were reliable predictions made before Pascal and Fermat's discovery of the mathematics of probability in 1654? What methods in law, science, commerce, philosophy, and logic helped us to get at the truth in cases where certainty was not attainable? The book examines how judges, witch inquisitors, and juries evaluated evidence; how scientists weighed reasons for and against scientific theories; and how merchants counted shipwrecks to determine insurance rates. Also included are the problem of induction before Hume, design arguments for (...) the existence of God, and theories on how to evaluate scientific and historical hypotheses. It is explained how Pascal and Fermat's work on chance arose out of legal thought on aleatory contracts. The book interprets pre-Pascalian unquantified probability in a generally objective Bayesian or logical probabilist sense. (shrink)

Epistemic permissivism is the thesis that the evidence can rationally permit more than one attitude toward a proposition. Pascal’s wager is the idea that one ought to believe in God for practical reasons, because of what one can gain if theism is true and what one has to lose if theism is false. In this paper, I argue that if epistemic permissivism is true, then the defender of Pascal’s wager has powerful responses to two prominent objections. First, I argue that (...) if permissivism is true, then permissivism is true about theistic belief. Second, I show how epistemic permissivism about theistic belief dispels two objections to Pascal’s wager: the objection that wagering is impossible, and the objection that wagering is epistemically impermissible. (shrink)

Among the factors necessary for the occurrence of some event, which of these are selectively highlighted in its explanation and labeled as causes — and which are explanatorily omitted, or relegated to the status of background conditions? Following J. S. Mill, most have thought that only a pragmatic answer to this question was possible. In this paper I suggest we understand this ‘causal selection problem’ in causal-explanatory terms, and propose that explanatory trade-offs between abstraction and stability can provide a principled (...) solution to it. After sketching that solution, it is applied to a few biological examples, including to a debate concerning the ‘causal democracy’ of organismal development, with an anti-democratic (though not a gene-centric) moral. (shrink)

This paper critiques the new mechanistic explanatory program on grounds that, even when applied to the kinds of examples that it was originally designed to treat, it does not distinguish correct explanations from those that blunder. First, I offer a systematization of the explanatory account, one according to which explanations are mechanistic models that satisfy three desiderata: they must 1) represent causal relations, 2) describe the proper parts, and 3) depict the system at the right ‘level.’ Second, I argue that (...) even the most developed attempts to fulfill these desiderata fall short by failing to appropriately constrain explanatorily apt mechanistic models. -/- *This paper used to be called "The Emperor's New Mechanisms". (shrink)

Philosophical discussions of species have focused on multicellular, sexual animals and have often neglected to consider unicellular organisms like bacteria. This article begins to fill this gap by considering what species concepts, if any, apply neatly to the bacterial world. First, I argue that the biological species concept cannot be applied to bacteria because of the variable rates of genetic transfer between populations, depending in part on which gene type is prioritized. Second, I present a critique of phylogenetic bacterial species, (...) arguing that phylogenetic bacterial classification requires a questionable metaphysical commitment to the existence of essential genes. I conclude by considering how microbiologists have dealt with these biological complexities by using more pragmatic and not exclusively evolutionary accounts of species. I argue that this pragmatism is not borne of laziness but rather of the substantial conceptual problems in classifying bacteria based on any evolutionary standard. (shrink)

Sometimes epistemologists theorize about belief, a tripartite attitude on which one can believe, withhold belief, or disbelieve a proposition. In other cases, epistemologists theorize about credence, a fine-grained attitude that represents one’s subjective probability or confidence level toward a proposition. How do these two attitudes relate to each other? This article explores the relationship between belief and credence in two categories: descriptive and normative. It then explains the broader significance of the belief-credence connection and concludes with general lessons from the (...) debate thus far. (shrink)

Belief-credence dualism is the view that we have both beliefs and credences and neither attitude is reducible to the other. Pragmatic encroachment is the view that practical stakes can affect the epistemic rationality of states like knowledge or justified belief. In this paper, I argue that dualism offers a unique explanation of pragmatic encroachment cases. First, I explain pragmatic encroachment and what motivates it. Then, I explain dualism and outline a particular argument for dualism. Finally, I show how dualism can (...) explain the intuitions that underlie pragmatic encroachment. My basic proposal is that in high-stakes cases, it is not that one cannot rationally believe that p; instead, one ought not to rely on one's belief that p. One should rather rely on one's credence in p. I conclude that we need not commit ourselves to pragmatic encroachment in order to explain the intuitiveness of the cases that motivate it. (shrink)

Nearly all defences of the agent-causal theory of free will portray the theory as a distinctively libertarian one — a theory that only libertarians have reason to accept. According to what I call ‘the standard argument for the agent-causal theory of free will’, the reason to embrace agent-causal libertarianism is that libertarians can solve the problem of enhanced control only if they furnish agents with the agent-causal power. In this way it is assumed that there is only reason to accept (...) the agent-causal theory if there is reason to accept libertarianism. I aim to refute this claim. I will argue that the reasons we have for endorsing the agent-causal theory of free will are nonpartisan. The real reason for going agent-causal has nothing to do with determinism or indeterminism, but rather with avoiding reductionism about agency and the self. As we will see, if there is reason for libertarians to accept the agent-causal theory, there is just as much reason for compatibilists to accept it. It is in this sense that I contend that if anyone should be an agent-causalist, then everyone should be an agent-causalist. (shrink)

Blaming (construed broadly to include both blaming-attitudes and blaming-actions) is a puzzling phenomenon. Even when we grant that someone is blameworthy, we can still sensibly wonder whether we ought to blame him. We sometimes choose to forgive and show mercy, even when it is not asked for. We are naturally led to wonder why we shouldn’t always do this. Wouldn’t it be a better to wholly reject the punitive practices of blame, especially in light of their often undesirable effects, and (...) embrace an ethic of unrelenting forgiveness and mercy? In this paper I seek to address these questions by offering an account of blame that provides a rationale for thinking that to wholly forswear blaming blameworthy agents would be deeply mistaken. This is because, as I will argue, blaming is a way of valuing, it is “a mode of valuation.” I will argue that among the minimal standards of respect generated by valuable objects, notably persons, is the requirement to redress disvalue with blame. It is not just that blame is something additional we are required to do in properly valuing, but rather blame is part of what that it is to properly value. Blaming, given the existence of blameworthy agents, is mode of valuation required by the standards of minimal respect. To forswear blame would be to fail value what we ought to value. (shrink)

The universality of critical phenomena is best explained by appeal to the Renormalisation Group (RG). Batterman and Morrison, among others, have claimed that this explanation is irreducible. I argue that the RG account is reducible, but that the higher-level explanation ought not to be eliminated. I demonstrate that the key assumption on which the explanation relies – the scale invariance of critical systems – can be explained in lower-level terms; however, we should not replace the RG explanation with a bottom-up (...) account, rather we should acknowledge that the explanation appeals to dependencies which may be traced down to lower levels. (shrink)

Journal of Applied Philosophy, EarlyView.

Throughout history, almost all mathematicians, physicists and philosophers have been of the opinion that space and time are infinitely divisible. That is, it is usually believed that space and time do not consist of atoms, but that any piece of space and time of non-zero size, however small, can itself be divided into still smaller parts. This assumption is included in geometry, as in Euclid, and also in the Euclidean and non- Euclidean geometries used in modern physics. Of the few (...) who have denied that space and time are infinitely divisible, the most notable are the ancient atomists, and Berkeley and Hume. All of these assert not only that space and time might be atomic, but that they must be. Infinite divisibility is, they say, impossible on purely conceptual grounds. (shrink)

What is it about a person's becoming an adult that makes it generally inappropriate to treat that person paternalistically any longer? The Standard View holds that a mere difference in age or stage of life cannot in itself be morally relevant, but only matters insofar as it is correlated with the development of capacities for mature practical reasoning. This paper defends the contrary view: two people can have all the same general psychological attributes and yet the mere fact that one (...) person is at the beginning of a life and another in the middle of one can justify treating the younger person more paternalistically than the older one. Recognising the moral relevance of age, moreover, is crucial if one is to accommodate both the liberal moral ideal of respect for autonomy and our demanding educational aims, given that these otherwise come into conflict with one another. (shrink)

Multiple realisation prompts the question: how is it that multiple systems all exhibit the same phenomena despite their different underlying properties? In this paper I develop a framework for addressing that question and argue that multiple realisation can be reductively explained. I illustrate this position by applying the framework to a simple example – the multiple realisation of electrical conductivity. I defend my account by addressing potential objections:contra Polger and Shapiro, Batterman, and Sober, I claim that multiple realisation is commonplace, (...) that it can be reductively explained, but that it requires asui generisreductive explanatory strategy. (shrink)

The logical interpretation of probability, or "objective Bayesianism'' – the theory that (some) probabilities are strictly logical degrees of partial implication – is defended. The main argument against it is that it requires the assignment of prior probabilities, and that any attempt to determine them by symmetry via a "principle of insufficient reason" inevitably leads to paradox. Three replies are advanced: that priors are imprecise or of little weight, so that disagreement about them does not matter, within limits; that it (...) is possible to distinguish reasonable from unreasonable priors on logical grounds; and that in real cases disagreement about priors can usually be explained by differences in the background information. It is argued also that proponents of alternative conceptions of probability, such as frequentists, Bayesians and Popperians, are unable to avoid committing themselves to the basic principles of logical probability. (shrink)

Philosophical theories of gender are typically understood as theories of what it is to be a woman, a man, a nonbinary person, and so on. In this paper, I argue that this is a mistake. There’s good reason to suppose that our best philosophical theory of gender might not directly match up to or give the extensions of ordinary gender categories like ‘woman’.

Why is it that some instances of disagreement appear to be so intractable? And what is the appropriate way to handle such disagreements, especially concerning matters about which there are important practical and political needs for us to come to a consensus? In this paper, I consider an explanation of the apparent intractability of deep disagreement offered by hinge epistemology. According to this explanation, at least some deep disagreements are rationally unresolvable because they concern ‘hinge’ commitments that are unresponsive to (...) rational considerations. This explanation, if correct, seems to have troubling implications for how we should respond to deep disagreement. If my position on a topic is not responsive to rational considerations, then what choice have I but to dogmatically hold to that position, and simply dismiss the views of those with whom I disagree? I address this problem by identifying an attitude of intellectual humility that is appropriate to have towards one's hinge commitments, and suggest that this attitude provides the basis for a non-rational, constructive way to resolve deep disagreement. (shrink)

A question of recent interest in epistemology and philosophy of mind is how belief and credence relate to each other. A number of philosophers argue for a belief-first view of the relationship between belief and credence. On the belief-first view, what it is to have a credence just is to have a particular kind of belief, that is, a belief whose content involves probabilities or epistemic modals. Here, I argue against the belief-first view: specifically, I argue that it cannot account (...) for agents who have credences in propositions they barely comprehend. I conclude that, however credences differ from beliefs, they do not differ in virtue of adding additional content to the believed proposition. (shrink)

Metaphysical orthodoxy maintains that the relation of ontological dependence is irreflexive, asymmetric, and transitive. The goal of this paper is to challenge that orthodoxy by arguing that ontological dependence should be understood as non- symmetric, rather than asymmetric. If we give up the asymmetry of dependence, interesting things follow for what we can say about metaphysical explanation— particularly for the prospects of explanatory holism.

In this article, I argue that mass incarceration belongs to a category of social status interventions by which the modern state either withholds the ordinary protections and benefits of the law from outlawed groups or subjects them to private punishment based on their mere membership in those groups. In the US these groups include immigrants and resident Latinos, the homeless, the poor and poor blacks, sex workers, and ex-convicts. Outlawry is a fundamentally anti-democratic practice that cannot be justified in terms (...) of deterrence and is incompatible with public safety. (shrink)

The genetic modification of pigs as a source of transplantable organs is one of several possible solutions to the chronic organ shortage. This paper describes existing ethical tensions in xenotransplantation (XTx) that argue against pursuing it. Recommendations for lifelong infectious disease surveillance and notification of close contacts of recipients are in tension with the rights of human research subjects. Parental/guardian consent for pediatric xenograft recipients is in tension with a child’s right to an open future. Individual consent to transplant is (...) in tension with public health threats that include zoonotic diseases. XTx amplifies concerns about justice in organ transplantation and could exacerbate existing inequities. The prevention of infectious disease in source animals is in tension with the best practices of animal care and animal welfare, requiring isolation, ethologically inappropriate housing, and invasive reproductive procedures that would severely impact the well-being of intelligent social creatures like pigs. (shrink)

Permissivism is the view that there are evidential situations that rationally permit more than one attitude toward a proposition. In this paper, I argue for Intrapersonal Belief Permissivism (IaBP): that there are evidential situations in which a single agent can rationally adopt more than one belief-attitude toward a proposition. I give two positive arguments for IaBP; the first involves epistemic supererogation and the second involves doubt. Then, I should how these arguments give intrapersonal permissivists a distinct response to the toggling (...) objection. I conclude that IaBP is a view that philosophers should take seriously. (shrink)

As inductive decision-making procedures, the inferences made by machine learning programs are subject to underdetermination by evidence and bear inductive risk. One strategy for overcoming these challenges is guided by a presumption in philosophy of science that inductive inferences can and should be value-free. Applied to machine learning programs, the strategy assumes that the influence of values is restricted to data and decision outcomes, thereby omitting internal value-laden design choice points. In this paper, I apply arguments from feminist philosophy of (...) science to machine learning programs to make the case that the resources required to respond to these inductive challenges render critical aspects of their design constitutively value-laden. I demonstrate these points specifically in the case of recidivism algorithms, arguing that contemporary debates concerning fairness in criminal justice risk-assessment programs are best understood as iterations of traditional arguments from inductive risk and demarcation, and thereby establish the value-laden nature of automated decision-making programs. Finally, in light of these points, I address opportunities for relocating the value-free ideal in machine learning and the limitations that accompany them. (shrink)

Just before the Scientific Revolution, there was a "Mathematical Revolution", heavily based on geometrical and machine diagrams. The "faculty of imagination" (now called scientific visualization) was developed to allow 3D understanding of planetary motion, human anatomy and the workings of machines. 1543 saw the publication of the heavily geometrical work of Copernicus and Vesalius, as well as the first Italian translation of Euclid.

Collection of articles on themes of Australian Catholic philosophy and history. Articles of philosophical interest include 'Catholic thought and Catholic Action: Dr Paddy Ryan MSC' (on the scholastic philosopher and anti-Communist), 'Catholic schooldays with philosophy', 'Traditional Catholic philosophy: baby and bathwater', 'Secular versus Catholic conceptions of values in Australian education', 'Accountancy as computational casuistics', 'The Mabo High Court and natural law values', and 'Stove, Hume and Enlightenment'.

What gender are you? And in virtue of what? These are questions of gender categorization. Such questions are increasingly at the core of many contemporary debat.