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)

• 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)

Contemporary literature criticises a necessary link between empathy and actions that demonstrate genuine moral worth. If there is such a necessary link, many argue, it must come in the developmental stages of our moral capacities, rather than being found in the mental states that make up our motivating reasons. This paper goes against that trend, arguing that critics have not considered how wide-ranging the mental states are that make up a person’s reasons. In particular, it argues that empathy can play (...) a role in moral motivation when it is to some extent unconscious or it occurs far prior to the moral action itself. (shrink)

An essay on the compatibility of Jewish and Muslim aspirations for the Land that argues that a vision of peaceful coexistence to provide a spur to the settling of grievances, but that this vision must respect the deeply felt aspirations of both communities, including in particular those underpinned by religious lore. Existing formulations of the aims of each community are blatantly inconsistent; it is time to attempt to characterise the just and religiously authentic goals of each community in ways that (...) are compatible. I argue that there religious and personal dimensions of the conflict that have been displaced by less deep-seated political goals, but which can be addressed more readily. I outline a tiered constitutional settlement that could address legitimate aspirations by avoiding the anathema of partition. (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.

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)

As algorithms have become ubiquitous in consequential domains, societal concerns about the potential for discriminatory outcomes have prompted urgent calls to address algorithmic bias. In response, a rich literature across computer science, law, and ethics is rapidly proliferating to advance approaches to designing fair algorithms. Yet computer scientists, legal scholars, and ethicists are often not speaking the same language when using the term ‘bias.’ Debates concerning whether society can or should tackle the problem of algorithmic bias are hampered by conflations (...) of various understandings of bias, ranging from neutral deviations from a standard to morally problematic instances of injustice due to prejudice, discrimination, and disparate treatment. This terminological confusion impedes efforts to address clear cases of discrimination. -/- In this paper, we examine the promises and challenges of different approaches to disambiguating bias and designing for justice. While both approaches aid in understanding and addressing clear algorithmic harms, we argue that they also risk being leveraged in ways that ultimately deflect accountability from those building and deploying these systems. Applying this analysis to recent examples of generative AI, our argument highlights unseen dangers in current methods of evaluating algorithmic bias and points to ways to redirect approaches to addressing bias in generative AI at its early stages in ways that can more robustly meet the demands of justice. (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)

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)

In this position paper, we introduce a new epistemic lens for analyzing algorithmic harm. We argue that the epistemic lens we propose herein has two key contributions to help reframe and address some of the assumptions underlying inquiries into algorithmic fairness. First, we argue that using the framework of epistemic injustice helps to identify the root causes of harms currently framed as instances of representational harm. We suggest that the epistemic lens offers a theoretical foundation for expanding approaches to algorithmic (...) fairness in order to address a wider range of harms not recognized by existing technical or legal definitions. Second, we argue that the epistemic lens helps to identify the epistemic goals of inquiries into algorithmic fairness. There are two distinct contexts within which we examine algorithmic harm: at times, we seek to understand and describe the world as it is, and, at other times, we seek to build a more just future. The epistemic lens can serve to direct our attention to the epistemic frameworks that shape our interpretations of the world as it is and the ways we envision possible futures. Clarity with respect to which epistemic context is relevant in a given inquiry can further help inform choices among the different ways of measuring and addressing algorithmic harms. We introduce this framework with the goal of initiating new research directions bridging philosophical, legal, and technical approaches to understanding and mitigating algorithmic harms. (shrink)

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)

If the world itself is metaphysically indeterminate in a specified respect, what follows? In this paper, we develop a theory of metaphysical indeterminacy answering this question.

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)

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)

A new translation and edition of Aristotle's Protrepticus (with critical comments on the fragments) -/- Welcome -/- The Protrepticus was an early work of Aristotle, written while he was still a member of Plato's Academy, but it soon became one of the most famous works in the whole history of philosophy. Unfortunately it was not directly copied in the middle ages and so did not survive in its own manuscript tradition. But substantial fragments of it have been preserved in several (...) works by Iamblichus of Chalcis, a third century A.D. neo-Pythagorean philosopher and educator. On the basis of a close study of Iamblichus' extensive use and excerption of Aristotle's Protrepticus, it is possible to reconstruct the backbone of the lost work, and then to flesh it out with the other surviving reports about the work from antiquity (for example in Alexander of Aphrodisias and other ancient commentators on Aristotle). It is also possible to identify several papyrus fragments of the work, and many references and literary allusions in later authors, especially Cicero, whose own lost dialogue Hortensius was a defense of philosophy modeleld on Aristotle's. (shrink)

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)

Dispostions, such as solubility, cannot be reduced to categorical properties, such as molecular structure, without some element of dipositionaity remaining. Democritus did not reduce all properties to the geometry of atoms - he had to retain the rigidity of the atoms, that is, their disposition not to change shape when a force is applied. So dispositions-not-to, like rigidity, cannot be eliminated. Neither can dispositions-to, like solubility.

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 winning entry in David Stove's Competition to Find the Worst Argument in the World was: “We can know things only as they are related to us/insofar as they fall under our conceptual schemes, etc., so, we cannot know things as they are in themselves.” That argument underpins many recent relativisms, including postmodernism, post-Kuhnian sociological philosophy of science, cultural relativism, sociobiological versions of ethical relativism, and so on. All such arguments have the same form as ‘We have eyes, therefore we (...) cannot see’, and are equally invalid. (shrink)

Einstein, like most philosophers, thought that there cannot be mathematical truths which are both necessary and about reality. The article argues against this, starting with prima facie examples such as "It is impossible to tile my bathroom floor with regular pentagonal tiles." Replies are given to objections based on the supposedly purely logical or hypothetical nature of mathematics.

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)

The imperviousness of mathematical truth to anti-objectivist attacks has always heartened those who defend objectivism in other areas, such as ethics. It is argued that the parallel between mathematics and ethics is close and does support objectivist theories of ethics. The parallel depends on the foundational role of equality in both disciplines. Despite obvious differences in their subject matter, mathematics and ethics share a status as pure forms of knowledge, distinct from empirical sciences. A pure understanding of principles is possible (...) because of the simplicity of the notion of equality, despite the different origins of our understanding of equality of objects in general and of the equality of the ethical worth of persons. (shrink)

Elizabeth Schechter explores the implications of the experience of people who have had the pathway between the two hemispheres of their brain severed, and argues that there are in fact two minds, subjects of experience, and intentional agents inside each split-brain human being: right and left. But each split-brain subject is still one of us.

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)

Explains Aristotle's views on the possibility of continuous variation between biological species. While the Porphyrean/Linnean classification of species by a tree suggests species are distributed discretely, Aristotle admitted continuous variation between species among lower life forms.

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)

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)

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)

David Lewis is a natural target for those who believe that findings in quantum physics threaten the tenability of traditional metaphysical reductionism. Such philosophers point to allegedly holistic entities they take both to be the subjects of some claims of quantum mechanics and to be incompatible with Lewisian metaphysics. According to one popular argument, the non-separability argument from quantum entanglement, any realist interpretation of quantum theory is straightforwardly inconsistent with the reductive conviction that the complete physical state of the world (...) supervenes on the intrinsic properties of and spatio-temporal relations between its point-sized constituents. Here I defend Lewis's metaphysical doctrine, and traditional reductionism more generally, against this alleged threat from quantum holism. After presenting the non-separability argument from entanglement, I show that Bohmian mechanics, an interpretation of quantum mechanics explicitly recognized as a realist one by proponents of the non-separability argument, plausibly rejects a key premise of that argument. Another holistic worry for Humeanism persists, however, the trouble being the apparently holistic character of the Bohmian pilot wave. I present a Humean strategy for addressing the holistic threat from the pilot wave by drawing on resources from the Humean best system account of laws. (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)

Some courses achieve existence, some have to create Professional Issues and Ethics in existence thrust upon them. It is normally Mathematics; but if you don’t do it, we will a struggle to create a course on the ethical be.” I accepted. or social aspects of science or mathematics. The gift of a greenfield site and a bull- This is the story of one that was forced to dozer is a happy occasion, undoubtedly. But exist by an unusual confluence of outside (...) cirwhat to do next? It seemed to me I should cumstances. ensure the course satisfied these require- In the mid 1990s, the University of New ments: South Wales instituted a policy that all its • It should look good to students, to staff. (shrink)

A semantics is presented for Storrs McCall's separate axiomatizations of Aristotle's accepted and rejected polysyllogisms. The polysyllogisms under discussion are made up of either assertoric or apodeictic propositions. The semantics is given by associating a property with a pair of sets: one set consists of things having the property essentially and the other of things having it accidentally. A completeness proof and a semantic decision procedure are given.

Brains, unlike artificial neural nets, use symbols to summarise and reason about perceptual input. But unlike symbolic AI, they “ground” the symbols in the data: the symbols have meaning in terms of data, not just meaning imposed by the outside user. If neural nets could be made to grow their own symbols in the way that brains do, there would be a good prospect of combining neural networks and symbolic AI, in such a way as to combine the good features (...) of each. The article argues the cluster analysis provides algorithms to perform the task, and that any solution to the task must be a form of cluster analysis. (shrink)

What is it that we are doing when we make ethical claims and judgments, such as the claim that we morally ought to assist refugees? This dissertation introduces and defends a novel theory of ethical thought and discourse. I begin by identifying the surface features of ethical thought and discourse to be explained, including the realist and cognitivist (i.e. belief-like) appearance of ethical judgments, and the apparent close connection between making a sincere ethical judgment and being motivated to act on (...) it. I examine prominent attempts to explain these features, with a focus on recent ‘hybrid’ theories combining elements of expressivism and cognitivism. Despite their initial promise, I argue that extant hybrid theories are nevertheless committed to problematic semantic, metasemantic, or pragmatic assumptions. I then discuss what I take to be the strongest existing option, ethical neo-expressivism (Bar-On and Chrisman, 2009; Bar-On, Chrisman, and Sias, 2014), and develop it into an explicitly hybrid theory proposing that ethical judgments incorporate both motivationally-charged affective states and moral beliefs. I then supplement this account with a theory of the proper function (following Millikan, 1984) of ethical claims and judgments, arguing that they function simultaneously to track the morally salient features of social situations, and to coordinate our behavior around these features. Finally, I defend one of the cognitivist commitments of the theory – namely, that objective moral knowledge is possible – by applying recent work on the epistemology of fundamental or ‘core’ intellectual commitments (Lynch, 2012; Pritchard, 2016) to the moral realm. (shrink)

El objetivo de este artículo es presentar una demostración de un teorema clásico sobre álgebras booleanas y ordenes parciales de relevancia actual en teoría de conjuntos, como por ejemplo, para aplicaciones del método de construcción de modelos llamado “forcing” (con álgebras booleanas completas o con órdenes parciales). El teorema que se prueba es el siguiente: “Todo orden parcial se puede extender a una única álgebra booleana completa (salvo isomorfismo)”. Donde extender significa “sumergir densamente”. Tal demostración se realiza utilizando cortaduras de (...) Dedekind siguiendo el texto “Set Theory” de Jech, y otras ideas propias del autor de este artículo. Adicionalmente, se formulan algunas versiones débiles del axioma de elección relacionadas con las álgebras booleanas, las cuales son también de gran importancia para la investigación en teoría de conjuntos y teoría de modelos, pues estas son poderosas técnicas de construcción de modelos, como por ejemplo, el teorema de compacidad (permite construir modelos no estándar, etc) y el teorema del ultrafiltro, que permite construir ultraproductos (pueden ser usados para investigar problemas de cardinales grandes, etc). Se presentan algunas referencias de problemas abiertos sobre el tema. -/- The objective of this paper is to present a demonstration of a classical theorem on boolean algebras and partial orders of current relevance in set theory, as for example, for applications of model construction method called forcing" (with boolean algebras complete or with partial orders). The theorem to be proved is as follows: Any partial order can be extended to a single complete boolean algebra (up to isomorphism)". Where to extend means embed densely". Such a demonstration is done using Dedekind's cuts following the text Set Theory" of Jech, and other ideas of the author of this article. In addition, some weak versions of the axiom of choice related to boolean algebras are formulated, which are also of great importance for the research in set theory and model theory, since this are powerful model construction techniques, such as the compactness theorem (allows the construction of non-standard models, etc.) and the ultralter theorem, which allows the construction of ultraproducts (can be used to investigate problems of large cardinals, etc). Some references of open problems on the subject are presented. (shrink)

Though there is no international government, there are many international regimes that enact binding regulations on particular matters. They include the Basel II regime in banking, IFRS in accountancy, the FIRST computer incident response system, the WHO’s system for containing global epidemics and many others. They form in effect a very powerful international public sector based on technical expertise. Unlike the public services of nation states, they are almost free of accountability to any democratically elected body or to any legal (...) system. Although by and large they have acted for good, the dangers of long-term unaccountability are illustrated by the travesties of justice perpetrated by the International Labour Organisation Administrative Tribunal. (shrink)

Stove's article, 'So you think you are a Darwinian?'[ 1] was essentially an advertisement for his book, Darwinian Fairytales.[ 2] The central argument of the book is that Darwin's theory, in both Darwin's and recent sociobiological versions, asserts many things about the human and other species that are known to be false, but protects itself from refutation by its logical complexity. A great number of ad hoc devices, he claims, are used to protect the theory. If co operation is observed (...) where the theory predicts competition, then competition is referred to the time of the cavemen, or is reinterpreted as competition between some hidden entities like genes or abstract entities like populations. In a characteristic sally, Stove writes of the sociobiologists' oscillation on the meaning of kin altruism: Any discussion of altruism with an inclusive fitness theorist is, in fact, exactly like dealing with a pair of balloons connected by a tube, one balloon being the belief that kin altruism is an illusion, the other being the belief that kin altruism is caused by shared genes. If a critic puts pressure on the illusion balloon - perhaps by ridiculing the selfish theory of human nature - air is forced into the causal balloon. There is then an increased production of earnest causal explanations of why we love our children, why hymenopteran workers look after their sisters, etc., etc. Then, if the critic puts pressure on the causal balloon - perhaps about the weakness of sibling altruism compared with parental, or the absence of sibling altruism in bacteria - then the illusion balloon is forced to expand. There will now be an increased production of cynical scurrilities about parents manipulating their babies for their own advantage, and vice versa, and in general, about the Hobbesian bad times that are had by all. In this way critical pressure, applied to the theory of inclusive fitness at one point, can always be easily absorbed at another point, and the theory as a whole is never endangered.[ 3] Now, it is uncontroversial to assert that Darwinism is a logically complex theory, and that its relation to empirical evidence is distant and multi faceted. One does not directly observe chance genetic variations leading to the development of new species, or even continuous variations in the fossil record, but must rely on subtle arguments to the best explanation, scaling up from varieties to species, and so on.. (shrink)

Faith is a trusting commitment to someone or something. Faith helps us meet our goals, keeps our relationships secure, and enables us to retain our commitments over time. Faith is thus a central part of a flourishing life. -/- This article is about the philosophy of faith. There are many philosophical questions about faith, such as: What is faith? What are its main components or features? What are the different kinds of faith? What is the relationship between faith and other (...) similar states, such as belief, trust, knowledge, desire, doubt, and hope? Can faith be epistemically rational? Practically rational? Morally permissible? -/- This article addresses these questions. It is divided into three main parts. The first is about the nature of faith. This includes different kinds of faith and various features of faith. The second discusses the way that faith relates to other states. For example, what is the difference between faith and hope? Can someone have faith that something is true even if they do not believe it is true? The third discusses three ways we might evaluate faith: epistemically, practically, and morally. While faith is not always rational or permissible, this section covers when and how it can be. The idea of faith as a virtue is also discussed. (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)

In a recent paper, Barry Loewer attempts to defend Humeanism about laws of nature from a charge that Humean laws are not adequately explanatory. Central to his defense is a distinction between metaphysical and scientific explanations: even if Humeans cannot offer further metaphysical explanations of particular features of their “mosaic,” that does not preclude them from offering scientific explanations of these features. According to Marc Lange, however, Loewer’s distinction is of no avail. Defending a transitivity principle linking scientific explanantia to (...) their metaphysical grounds, Lange argues that a charge of explanatory inadequacy resurfaces once this intuitive principle is in place. This paper surveys, on behalf of the Humean, three strategies for responding to Lange’s criticism. The ready availability of these strategies suggests that Lange’s argument may not bolster anti-Humean convictions, since the argument rests on premises that those not antecedently sharing these convictions may well reject. The three strategies also correspond to three interesting ways of thinking about relations of grounding linking Humean laws and their instances, all of which are consistent with theses of Humean supervenience, and some of which have been heretofore overlooked. (shrink)

I examine three attitudes: belief, faith, and hope. I argue that all three attitudes play the same role in rationalizing action. First, I explain two models of rational action—the decision-theory model and the belief-desire model. Both models entail there are two components of rational action: an epistemic component and a conative component. Then, using this framework, I show how belief, faith, and hope that p can all make it rational to accept, or act as if, p. I conclude by showing (...) how my picture can explain how action-oriented commitments can be rational over time, both in the face of counterevidence and in the face of waning affections. (shrink)

If Tahiti suggested to theorists comfortably at home in Europe thoughts of noble savages without clothes, those who paid for and went on voyages there were in pursuit of a quite opposite human ideal. Cook's voyage to observe the transit of Venus in 1769 symbolises the eighteenth century's commitment to numbers and accuracy, and its willingness to spend a lot of public money on acquiring them. The state supported the organisation of quantitative researches, employing surveyors and collecting statistics to..

Much of the literature on the relationship between belief and credence has focused on the reduction question: that is, whether either belief or credence reduces to the other. This debate, while important, only scratches the surface of the belief-credence connection. Even on the anti-reductive dualist view, belief and credence could still be very tightly connected. Here, I explore questions about the belief-credence connection that go beyond reduction. This paper is dedicated to what I call the independence question: just how independent (...) are belief and credence? I look at this question from two angles: a descriptive one (as a psychological matter, how much can belief and credence come apart?) and a normative one (for a rational person, how closely connected are belief and credence?) Ultimately, I suggest that the two attitudes are more independent than one might think. (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)

El objetivo principal de este artículo es presentar la demostración directa del Teorema de compacidad de la Lógica de primer orden (Gama tiene un modelo si y sólo si cada subconjunto finito de Gama tiene un modelo) que se realiza utilizando el Método de construcción de modelos llamado "Ultraproductos" que, a su vez, usa "Ultrafiltros". Actualmente es más común demostrar el Teorema de compacidad como un corolario del Teorema de completitud de Gödel y usar el método de reducción al absurdo (...) para probarlo. Sin embargo, vale la pena estudiar también esta prueba directa que usa Ultraproductos porque dicha técnica tiene importantes aplicaciones en investigaciones contemporáneas de matemáticas, por ejemplo en la Teoría de conjuntos y en el Análisis. Al final del artículo se realiza un breve comentario sobre Compacidad, Ultraproductos, Cardinales grandes y Modelos no estándar. (shrink)

The late twentieth century saw two long-term trends in popular thinking about ethics. One was an increase in relativist opinions, with the “generation of the Sixties” spearheading a general libertarianism, an insistence on toleration of diverse moral views (for “Who is to say what is right? – it’s only your opinion.”) The other trend was an increasing insistence on rights – the gross violations of rights in the killing fields of the mid-century prompted immense efforts in defence of the “inalienable” (...) rights of the victims of dictators, of oppressed peoples, of refugees. The obvious incompatibility of those ethical stances, one anti-objectivist, the other objectivist in the extreme, proved no obstacle to their both being held passionately, often by the same people. (shrink)

The possibilities of unconscious perception and unconscious bias prompt parallel debates about unconscious mental content. This chapter argues that claims within these debates alleging the existence of unconscious content are made fraught by ambiguity and confusion with respect to the two central concepts they involve: consciousness and content. Borrowing conceptual resources from the debate about unconscious perception, the chapter distills the two conceptual puzzles concerning each of these notions and establishes philosophical strategies for their resolution. It then argues that empirical (...) evidence for unconscious bias falls victim to these same puzzles, but that progress can be made by adopting similar philosophical strategies. Throughout, the chapter highlights paths forward in both debates, illustrates how they serve as fruitful domains in which to study the relationship between philosophy and empirical science, and uses their combined study to further understanding of a general theory of unconscious content. (shrink)