Es innegable que desde la publicación de A Theory of Justice en 1971 la filosofía política ha dado un giro en las temáticas que históricamente ha abordado. Pues como afirma Robert Nozick, es imposible realizar cualquier tipo de filosofía práctica, sin considerar el marco teórico ofrecido por la obra de Rawls, dado que lo inédito de su trabajo es ofrecer una teoría sustantiva de justicia que deja atrás la tradición lógica-analítica, así como el mero análisis histórico-sistemático. Las múltiples repercusiones (...) han dado inicio a una vasta cantidad de encuentros y desencuentros en la forma concebir la justicia social. En este debate se enmarca el último libro del profesor Pablo Aguayo Westwood: Justicia social: conceptos, teorías y problemas, donde propone una breve revisión de los principales hitos que han marcado la discusión en torno a la justicia social, así como algunos problemas prácticos que conciernen a esta. (shrink)

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

The idea that qualities can be had partly or to an intermediate degree is controversial among contemporary metaphysicians, but also has a considerable pedigree among philosophers and scientists. In this paper, we first aim to show that metaphysical sense can be made of this idea by proposing a partial taxonomy of metaphysical accounts of graded qualities, focusing on three particular approaches: one which explicates having a quality to a degree in terms of having a property with an in-built degree, another (...) based on the idea that instantiation admits of degrees, and a third which derives the degree to which a quality is had from the aspects of multi-dimensional properties. Our second aim is to demonstrate that the choice between these accounts can make a substantial metaphysical difference. To make this point, we rely on two case studies (involving quantum observables and values) in which we apply the accounts in order to model apparent cases of metaphysical gradedness. (shrink)

This paper generalises the classical Condorcet jury theorem from majority voting over two options to plurality voting over multiple options. The paper further discusses the debate between epistemic and procedural democracy and situates its formal results in that debate. The paper finally compares a number of different social choice procedures for many-option choices in terms of their epistemic merits. An appendix explores the implications of some of the present mathematical results for the question of how probable majority cycles (as in (...) Condorcet's paradox) are in large electorates. (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.

Decisions are made under uncertainty when there are distinct outcomes of a given action, and one is uncertain to which the act will lead. Decisions are made under indeterminacy when there are distinct outcomes of a given action, and it is indeterminate to which the act will lead. This paper develops a theory of (synchronic and diachronic) decision-making under indeterminacy that portrays the rational response to such situations as inconstant. Rational agents have to capriciously and randomly choose how to resolve (...) the indeterminacy relevant to a given choice-situation, but such capricious choices once made constrain how they will choose in the future. The account is illustrated by the case of self-interested action in situations where it is indeterminate whether you yourself will survive to benefit or suffer the consequences. The conclusion emphasizes some distinctive anti-hedging predictions of the account. (shrink)

Might it be that world itself, independently of what we know about it or how we represent it, is metaphysically indeterminate? This article tackles in turn a series of questions: In what sorts of cases might we posit metaphysical indeterminacy? What is it for a given case of indefiniteness to be 'metaphysical'? How does the phenomenon relate to 'ontic vagueness', the existence of 'vague objects', 'de re indeterminacy' and the like? How might the logic work? Are there reasons for postulating (...) this distinctive sort of indefiniteness? Conversely, are there reasons for denying that there is indefiniteness of this sort? (shrink)

Inscrutability arguments threaten to reduce interpretationist metasemantic theories to absurdity. Can we find some way to block the arguments? A highly influential proposal in this regard is David Lewis’ ‘ eligibility ’ response: some theories are better than others, not because they fit the data better, but because they are framed in terms of more natural properties. The purposes of this paper are to outline the nature of the eligibility proposal, making the case that it is not ad hoc, but (...) instead flows naturally from three independently motivated elements; and to show that severe limitations afflict the proposal. In conclusion, I pick out the element of the eligibility response that is responsible for the limitations: future work in this area should therefore concentrate on amending this aspect of the overall theory. (shrink)

While it is tempting to suppose that an act has moral worth just when and because it is motivated by sufficient moral reasons, philosophers have, largely, come to doubt this analysis. Doubt is rooted in two claims. The first is that some facts can motivate a given act in multiple ways, not all of which are consistent with moral worth. The second is the orthodox view that normative reasons are facts. I defend the tempting analysis by proposing and defending a (...) heterodox account of both normative and motivating reasons that is inspired by Donald Davidson’s primary reasons. We should adopt the heterodox view, I argue, because it addresses an overlooked but fatal defect in the orthodox conception of reasons, of which challenges to the tempting analysis are a special case. (shrink)

Alongside existing research into the social, political and economic impacts of the Web, there is a need to study the Web from a cognitive and epistemic perspective. This is particularly so as new and emerging technologies alter the nature of our interactive engagements with the Web, transforming the extent to which our thoughts and actions are shaped by the online environment. Situated and ecological approaches to cognition are relevant to understanding the cognitive significance of the Web because of the emphasis (...) they place on forces and factors that reside at the level of agent–world interactions. In particular, by adopting a situated or ecological approach to cognition, we are able to assess the significance of the Web from the perspective of research into embodied, extended, embedded, social and collective cognition. The results of this analysis help to reshape the interdisciplinary configuration of Web Science, expanding its theoretical and empirical remit to include the disciplines of both cognitive science and the philosophy of mind. (shrink)

In this Introduction we introduce the central themes of the Evaluative Perception volume. After identifying historical and recent contemporary work on this topic, we discuss some central questions under three headings: (1) Questions about the Existence and Nature of Evaluative Perception: Are there perceptual experiences of values? If so, what is their nature? Are experiences of values sui generis? Are values necessary for certain kinds of experience? (2) Questions about the Epistemology of Evaluative Perception: Can evaluative experiences ever justify evaluative (...) judgments? Are experiences of values necessary for certain kinds of justified evaluative judgments? (3) Questions about Value Theory and Evaluative Perception: Is the existence of evaluative experience supported or undermined by particular views in value theory? Are particular views in value theory supported or undermined by the existence of value experience? (shrink)

The concept of moral wrongness, many think, has a distinctive kind of referential stability, brought out by moral twin earth cases. This article offers a new account of the source of this stability, deriving it from a metaphysics of content: “substantive” radical interpretation, and first-order normative assumptions. This story is distinguished from extant “reference magnetic” explanations of the phenomenon, and objections and replies are considered.

Lewis (1973) gave a short argument against conditional excluded middle, based on his treatment of ‘might’ counterfactuals. Bennett (2003), with much of the recent literature, gives an alternative take on ‘might’ counterfactuals. But Bennett claims the might-argument against CEM still goes through. This turns on a specific claim I call Bennett’s Hypothesis. I argue that independently of issues to do with the proper analysis of might-counterfactuals, Bennett’s Hypothesis is inconsistent with CEM. But Bennett’s Hypothesis is independently objectionable, so we should (...) resolve this tension by dropping the Hypothesis, not by dropping CEM. (shrink)

Worlds where things divide forever ("gunk" worlds) are apparently conceivable. The conceivability of such scenarios has been used as an argument against "nihilist" or "near-nihilist" answers to the special composition question. I argue that the mereological nihilist has the resources to explain away the illusion that gunk is possible.

Artificial intelligence (AI) systems have demonstrated impressive performance across a variety of clinical tasks. However, notoriously, sometimes these systems are “black boxes.” The initial response in the literature was a demand for “explainable AI.” However, recently, several authors have suggested that making AI more explainable or “interpretable” is likely to be at the cost of the accuracy of these systems and that prioritizing interpretability in medical AI may constitute a “lethal prejudice.” In this paper, we defend the value of interpretability (...) in the context of the use of AI in medicine. Clinicians may prefer interpretable systems over more accurate black boxes, which in turn is sufficient to give designers of AI reason to prefer more interpretable systems in order to ensure that AI is adopted and its benefits realized. Moreover, clinicians may be justified in this preference. Achieving the downstream benefits from AI is critically dependent on how the outputs of these systems are interpreted by physicians and patients. A preference for the use of highly accurate black box AI systems, over less accurate but more interpretable systems, may itself constitute a form of lethal prejudice that may diminish the benefits of AI to—and perhaps even harm—patients. (shrink)

The view that it is better for life to be created free of disability is pervasive in both common sense and philosophy. We cast doubt on this view by focusing on an influential line of thinking that manifests it. That thinking begins with a widely-discussed principle, Procreative Beneficence, and draws conclusions about parental choice and disability. After reconstructing two versions of this argument, we critique the first by exploring the relationship between different understandings of well-being and disability, and the second (...) by more briefly focusing on the idea of a significant reason. By placing these results against the broader historical and ongoing contexts in which the lives of those with disabilities have been deemed of inferior quality, we conclude with a call for greater humility about disability and well-being in thought and practice. (shrink)

Majority cycling and related social choice paradoxes are often thought to threaten the meaningfulness of democracy. But deliberation can prevent majority cycles – not by inducing unanimity, which is unrealistic, but by bringing preferences closer to single-peakedness. We present the first empirical test of this hypothesis, using data from Deliberative Polls. Comparing preferences before and after deliberation, we find increases in proximity to single-peakedness. The increases are greater for lower versus higher salience issues and for individuals who seem to have (...) deliberated more versus less effectively. They are not merely a byproduct of increased substantive agreement. Our results both refine and support the idea that deliberation, by increasing proximity to single-peakedness, provides an escape from the problem of majority cycling. (shrink)

Joyce (1998) gives an argument for probabilism: the doctrine that rational credences should conform to the axioms of probability. In doing so, he provides a distinctive take on how the normative force of probabilism relates to the injunction to believe what is true. But Joyce presupposes that the truth values of the propositions over which credences are defined are classical. I generalize the core of Joyce’s argument to remove this presupposition. On the same assumptions as Joyce uses, the credences of (...) a rational agent should always be weighted averages of truth value assignments. In the special case where the truth values are classical, the weighted averages of truth value assignments are exactly the probability functions. But in the more general case, probabilistic axioms formulated in terms of classical logic are violated—but we will show that generalized versions of the axioms formulated in terms of non-classical logics are satisfied. (shrink)

Competitive negotiators frequently use tactics which others view as "unethical", in that these tactics either violate standards of truth telling or violate the perceived rules of negotiation. This paper sought to determine how business students viewed a number of marginally ethical negotiating tactics, and to determine the underlying factor structure of these tactics. The factor analysis of these tactics revealed five clear factors which were highly similar across the two samples, and which parallel (to a moderate degree) categories of tactics (...) proposed by earlier theory. Data from one sample also permitted comparisons of the appropriateness of certain tactics across gender, nationality, ethnic origin and perception of one's negotiating style. (shrink)

Sometimes it is indeterminate what an agent morally ought do. This generates a Decision Ought Challenge—to give moral guidance to agents in such a scenario. This article is a field guide to the options for a theory of the decision ought for cases of indeterminacy. Three categories of view are evaluated, and the best representative for each is identified.

Jeff Paris proves a generalized Dutch Book theorem. If a belief state is not a generalized probability then one faces ‘sure loss’ books of bets. In Williams I showed that Joyce’s accuracy-domination theorem applies to the same set of generalized probabilities. What is the relationship between these two results? This note shows that both results are easy corollaries of the core result that Paris appeals to in proving his dutch book theorem. We see that every point of accuracy-domination defines a (...) dutch book, but we only have a partial converse. (shrink)

Revisionary theories of logic or truth require revisionary theories of mind. This essay outlines nonclassically based theories of rational belief, desire, and decision making, singling out the supervaluational family for special attention. To see these nonclassical theories of mind in action, this essay examines a debate between David Lewis and Derek Parfit over what matters in survival. Lewis argued that indeterminacy in personal identity allows caring about psychological connectedness and caring about personal identity to amount to the same thing. The (...) essay argues that Lewis's treatment of two of Parfit's puzzle cases—degreed survival and fission—presuppose different nonclassical treatments of belief and desire. (shrink)

Many accounts of structural rationality give a special role to logic. This paper reviews the problem case of clear-eyed logical uncertainty. An account of rational norms on belief that does not give a special role to logic is developed: doxastic probabilism.

Are counterfactuals with true antecedents and consequents automatically true? That is, is Conjunction Conditionalization: if (X & Y), then (X > Y) valid? Stalnaker and Lewis think so, but many others disagree. We note here that the extant arguments for Conjunction Conditionalization are unpersuasive, before presenting a family of more compelling arguments. These arguments rely on some standard theorems of the logic of counterfactuals as well as a plausible and popular semantic claim about certain semifactuals. Denying Conjunction Conditionalization, then, requires (...) rejecting other aspects of the standard logic of counterfactuals, or else our intuitive picture of semifactuals. (shrink)

It is widely thought that functionalism and the qualia theory are better positioned to accommodate the ‘affective’ aspect of pain phenomenology than representationalism. In this paper, we attempt to overturn this opinion by raising problems for both functionalism and the qualia theory on this score. With regard to functionalism, we argue that it gets the order of explanation wrong: pain experience gives rise to the effects it does because it hurts, and not the other way around. With regard to the (...) qualia theory, we argue that it fails to capture the sense in which pain 's affective phenomenology rationalises various bodily-directed beliefs, desires, and behaviours. Representationalism, in contrast, escapes both of these problems: it gets the order of explanation right and it explains how pain 's affective phenomenology can rationalise bodily-directed beliefs, desires, and behaviours. For this reason, we argue that representationalism has a significant advantage in the debates about pain 's affective phenomenology. We end the paper by examining objections, including the question of what representationalists should say about so-called ‘disassociation cases’, such as pain asymbolia. (shrink)

Objectives: Machine learning (ML) has the potential to facilitate “continual learning” in medicine, in which an ML system continues to evolve in response to exposure to new data over time, even after being deployed in a clinical setting. In this article, we provide a tutorial on the range of ethical issues raised by the use of such “adaptive” ML systems in medicine that have, thus far, been neglected in the literature. -/- Target audience: The target audiences for this tutorial are (...) the developers of ML AI systems, healthcare regulators, the broader medical informatics community, and practicing clinicians. -/- Scope: Discussions of adaptive ML systems to date have overlooked the distinction between 2 sorts of variance that such systems may exhibit—diachronic evolution (change over time) and synchronic variation (difference between cotemporaneous instantiations of the algorithm at different sites)—and underestimated the significance of the latter. We highlight the challenges that diachronic evolution and synchronic variation present for the quality of patient care, informed consent, and equity, and discuss the complex ethical trade-offs involved in the design of such systems. (shrink)

There is an intuitive difference in how we think about pluralism and attitudinal diversity in epistemological contexts versus political contexts. In an epistemological context, it seems problematically arbitrary to hold a particular belief on some issue, while also thinking it perfectly reasonable to hold a totally different belief on the same issue given the same evidence. By contrast, though, it doesn’t seem problematically arbitrary to have a particular set of political commitments, while at the same time thinking it perfectly reasonable (...) for someone in a similar position have a totally different set of political commitments. This chapter examines three explanatory theses that might be used to make sense of this difference: (1) that practical commitments are desire dependent in a way that beliefs are not; (2) that there are reasons to be resolute in practical commitments, but not in beliefs; and (3) that compromise in the face of practical political disagreement doesn’t mitigate controversy, whereas compromise in the face of disagreement about mere beliefs does mitigate controversy. (shrink)

People sometimes try to call others’ beliefs into question by pointing out the contingent causal origins of those beliefs. The significance of such ‘Etiological Challenges’ is a topic that has started attracting attention in epistemology. Current work on this topic aims to show that Etiological Challenges are, at most, only indirectly epistemically significant, insofar as they bring other generic epistemic considerations to the agent’s attention. Against this approach, we argue that Etiological Challenges are epistemically significant in a more direct and (...) more distinctive way. An Etiological Challenge prompts the agent to assess whether her beliefs result from practices of indoctrination, and whether she should reduce confidence in those beliefs, given the anti-reliability of indoctrination as a method of belief-acquisition. Our analysis also draws attention to some of the ways in which epistemic concerns interact with political issues—e.g. relating to epistemic injustice, identity-based discrimination, and segregation—when we’re thinking about the contingent causal origins of our beliefs. (shrink)

I outline and motivate a way of implementing a closest world theory of indicatives, appealing to Stalnaker's framework of open conversational possibilities. Stalnakerian conversational dynamics helps us resolve two outstanding puzzles for a such a theory of indicative conditionals. The first puzzle -- concerning so-called 'reverse Sobel sequences' -- can be resolved by conversation dynamics in a theoryneutral way: the explanation works as much for Lewisian counterfactuals as for the account of indicatives developed here. Resolving the second puzzle, by contrast, (...) relies on the interplay between the particular theory of indicative conditionals developed here and Stalnakerian dynamics. The upshot is an attractive resolution of the so-called "Gibbard phenomenon" for indicative conditionals. (shrink)

A popular “Reductionist” account of personal identity unifies person stages into persons in virtue of their psychological continuity with one another. One objection to psychological continuity accounts is that there is more to our personal identity than just mere psychological continuity: there is also an active process of self-interpretation and self-creation. This criticism can be used to motivate a rival account of personal identity that appeals to the notion of a narrative. To the extent that they comment upon the issue, (...) proponents of narrative accounts typically reject Reductionist metaphysics that (ontologically) reduce persons to aggregates of person stages. In contrast to this trend, we seek to develop a narrative account of personal identity from within Reductionist metaphysics: we think person stages are unified into persons in virtue of their narrative continuity with one another. We argue that this Reductionist version of the narrative account avoids some serious problems facing non-Reductionist versions of the narrative account. (shrink)

A general survey of Frege's views on truth, the paper explores the problems in response to which Frege's distinctive view that sentences refer to truth-values develops. It also discusses his view that truth-values are objects and the so-called regress argument for the indefinability of truth. Finally, we consider, very briefly, the question whether Frege was a deflationist.

We distinguish between two different strategies in methodology of economics. The big picture strategy, dominant in the twentieth century, ascribed to economics a unified method and evaluated this m...

Supervaluationism is often described as the most popular semantic treatment of indeterminacy. There’s little consensus, however, about how to fill out the bare-bones idea to include a characterization of logical consequence. The paper explores one methodology for choosing between the logics: pick a logic thatnorms beliefas classical consequence is standardly thought to do. The main focus of the paper considers a variant of standard supervaluational, on which we can characterizedegrees of determinacy. It applies the methodology above to focus ondegree logic. (...) This is developed first in a basic, single-premise case; and then extended to the multipremise case, and to allowdegreesof consequence. The metatheoretic properties of degree logic are set out. On the positive side, the logic is supraclassical—all classical valid sequents are degree logic valid. Strikingly, metarules such as cut and conjunction introduction fail. (shrink)

Some argue that theories of universals should incorporate structural universals, in order to allow for the metaphysical possibility of worlds of 'infinite descending complexity' ('onion worlds'). I argue that the possibility of such worlds does not establish the need for structural universals. So long as we admit the metaphysical possibility of emergent universals, there is an attractive alternative description of such cases.

There are advantages to thrift over honest toil. If we can make do without numbers we avoid challenging questions over the metaphysics and epistemology of such entities; and we have a good idea, I think, of what a nominalistic metaphysics should look like. But minimizing ontology brings its own problems; for it seems to lead to error theory— saying that large swathes of common-sense and best science are false. Should recherche philosophical arguments really convince us to give all this up? (...) Such Moorean considerations are explicitly part of the motivation for the recent resurgence of structured metaphysics, which allow a minimal (perhaps nominalistic) fundamental ontology, while avoiding error-theory by adopting a permissive stance towards ontology that can be argued to be grounded in the fundamental. This paper evaluates the Moorean arguments, identifying key epistemological assumptions. On the assumption that Moorean arguments can be used to rule out error-theory, I examine deflationary ‘representationalist’ rivals to the structured metaphysics reaction. Quinean paraphrase, fictionalist claims about syntax and semantics are considered and criticized. In the final section, a ‘direct’ deflationary strategy is outlined and the theoretical obligations that it faces are articulated. The position advocated may have us talking a lot like a friend of structured metaphysics—but with a very different conception of what we’re up to. (shrink)

A growing body of work in free speech theory is interested in the nature of counterspeech, i.e. speech that aims to counteract the effects of harmful speech. Counterspeech is usually defined in opposition to legal responses to harmful speech, which try to prevent such speech from occurring in the first place. In this paper we challenge this way of carving up the conceptual terrain. Instead, we argue that our main classificatory division, in theorising responses to harmful speech, should be between (...) pro-discursive and anti-discursive responses. Some legal responses to harmful speech, so we argue, make a positive discursive contribution in their own right. That is, legal restrictions on harmful speech can have a function that is importantly similar to speech that aims at countering the effects of harmful speech. (shrink)

In his absorbing book Art as Performance, David Davies argues that artworks should be identified, not with artistic products such as paintings or novels, but instead with the artistic actions or processes that produced such items. Such a view had an earlier incarnation in Currie’s widely criticized “action type hypothesis”, but Davies argues that it is instead action tokens rather than types with which artworks should be identified. This rich and complex work repays the closest study in spite of some (...) basic objections to be raised concerning Davies’s central concept of an action token. (shrink)

MMA fighting in a competition is not necessarily wrong and is often, as far as we can tell, permissible. Our argument has two premises. First, if an act does not infringe on anyone’s moral right or violate another side-constraint, then it is morally permissible. Second, MMA-violence does not infringe on anyone’s moral right or violate another side-constraint. The first premise rested on two assumptions. First, if a person does a wrong act, then he wrongs someone. Second, if one person wrongs (...) a second, then the first infringes on the second’s right. We then looked at Nicholas Dixon’s powerful Kantian argument that MMA fighting is wrong. (shrink)

Existing metasemantic projects presuppose that word- (or sentence-) types are part of the non-semantic base. We propose a new strategy: an endogenous account of word types, that is, one where word types are fixed as part of the metasemantics. On this view, it is the conventions of truthfulness and trust that ground not only the meaning of the words (meaning by convention) but also what the word type is of each particular token utterance (words by convention). The same treatment extends (...) to identifying the populations through which the conventions prevail. We consider whether this proposal leads to new underdetermination challenges for metasemantics, and make a case that it does not. (shrink)

In some sense, survival seems to be an intrinsic matter. Whether or not you survive some event seems to depend on what goes on with you yourself —what happens in the environment shouldn’t make a difference. Likewise, being a person at a time seems intrinsic. The principle that survival seems intrinsic is one factor which makes personal fission puzzles so awkward. Fission scenarios present cases where if survival is an intrinsic matter, it appears that an individual could survive twice over. (...) But it’s well known that standard notions of “intrinsicality” won’t do to articulate the sense in which survival is intrinsic, since ‘personhood’ appears to be a maximal property. We formulate a sense in which survival and personhood (and perhaps other maximal properties) may be almost intrinsic—a sense that would suffice, for example, to ground fission arguments. It turns out that this notion of almost-intrinsicality allows us to formulate a new version of the problem of the many. (shrink)

Why should musical compositions and artistic images be included among the types of expression covered by free speech principles? One way to answer this question is to show how expression in nonverbal media can be functionally similar to other types of verbal expression. But this leaves us with an intuitively unsatisfying explanation of why free speech principles cover nonverbal creative expression that does not functionally emulate literal speech. In this article, as an alternative justification, we develop and defend the idea (...) that musical and pictorial expression‚ much like literal speech, can be media through which people think aloud, as opposed to mere tools for the transmission of thought. We use this proposal to provide a more robust justification for including nonverbal creative expression in the scope of free speech coverage, and we outline some of the practical policy implications that come with adopting this justificatory strategy. (shrink)

This essay explores the thesis that for vague predicates, uncertainty over whether a borderline instance x of red/large/tall/good is to be understood as practical uncertainty over whether to treat x as red/large/tall/good. Expressivist and quasi-realist treatments of vague predicates due to John MacFarlane and Daniel Elstein provide the stalking-horse. It examines the notion of treating/counting a thing as F , and links a central question about our attitudes to vague predications to normative evaluation of plans to treat a thing as (...) F . The essay examines how the account applies to normatively defective or contested terms. The final section raises a puzzle about the mechanics of MacFarlane’s detailed implementation for the case of gradable adjectives. (shrink)

Claims about what justice “requires” and the “requirements” of justice are pervasive in political philosophy. However, there is a highly significant ambiguity in such claims that appears to have gone unnoticed. Such claims may pick out either one of two categorically distinct and noncoextensive kinds of requirement that we call 1) requirements-as-necessary-conditions for justice and 2) requirements-as-demands of justice. This is an especially compelling instance of an ambiguity that John Broome has famously observed in the context of claims about other (...) requirements (notably the requirements of rationality and morality). But it appears to have been overlooked by political philosophers in the case of claims about the requirements of justice. The ambiguity is highly significant inasmuch as failing to notice it is liable to distort our normative thinking about politics and make us vulnerable to certain kinds of normatively consequential errors: both mistakenly drawing inferences about what justice demands of us from claims that certain states or societies are not just; and mistakenly drawing inferences about what states or societies are or would be just from claims that justice does not demand of states or societies that they do certain things. Paying greater attention to the distinction between these two different kinds of requirements and the ways in which they come apart is helpful, not merely in avoiding these distortions and errors, but also in resolving, or at least clarifying, a number of other notoriously murky meta-normative debates, especially various important debates about realism and idealism in political philosophy. (shrink)

How are permutation arguments for the inscrutability of reference to be formulated in the context of a Davidsonian truth-theoretic semantics? Davidson takes these arguments to establish that there are no grounds for favouring a reference scheme that assigns London to “Londres”, rather than one that assigns Sydney to that name. We shall see, however, that it is far from clear whether permutation arguments work when set out in the context of the kind of truth-theoretic semantics which Davidson favours. The principle (...) required to make the argument work allows us to resurrect Foster problems against the Davidsonian position. The Foster problems and the permutation inscrutability problems stand or fall together: they are one puzzle, not two. (shrink)

In her latest book, The End of Progress, Amy Allen embarks on an ambitious and much-needed project: to decolonize contemporary Frankfurt School Critical Theory. As with all of her books, this is an exceptionally well-written and well-argued book. Allen strives to avoid making assertions without backing them up via close and careful textual reading of the thinkers she engages in her book. In this article, I will state why this book makes a central contribution to contemporary critical theory (in the (...) broader sense), after which I pose a few questions. These questions are not meant to prove that there are any serious problems with her argumentation. Instead, they are meant in the spirit of dialogue and allow her to elaborate her work for her audience. (shrink)

This paper investigates whether search engines and other new modes of online communication should be covered by free speech principles. It criticizes the analogical reason-ing that contemporary American courts and scholars have used to liken search engines to newspapers, and to extend free speech coverage to them based on that likeness. There are dissimilarities between search engines and newspapers that undermine the key analogy, and also rival analogies that can be drawn which don’t recommend free speech protection for search engines. (...) Partly on these bases, we argue that an analogical approach to questions of free speech coverage is of limited use in this context. Credible verdicts about how free speech principles should apply to new modes of online com-munication require us to re-excavate the normative foundations of free speech. This method for deciding free speech coverage suggests that only a subset of search engine outputs and similar online communication should receive special protection against government regulation. (shrink)

How do archaeologists make effective use of physical traces and material culture as repositories of evidence? Material Evidence is a collection of 19 essays that take a resolutely case-based approach to this question, exploring key instances of exemplary practice, instructive failures, and innovative developments in the use of archaeological data as evidence. The goal is to bring to the surface the wisdom of practice, teasing out norms of archaeological reasoning from evidence. -/- Archaeologists make compelling use of an enormously diverse (...) range of material evidence, from garbage dumps to monuments, from finely crafted artifacts rich with cultural significance to the inadvertent transformation of landscapes over the long term. Each contributor to Material Evidence identifies a particular type of evidence with which they grapple and considers, with reference to concrete examples, how archaeologists construct evidential claims, critically assess them, and bring them to bear on pivotal questions about the cultural past. -/- Historians, cultural anthropologists, philosophers, and science studies scholars are increasingly interested in working with material "things" as objects of inquiry and as evidence – and they acknowledge on all sides just how challenging this is. One of the central messages of the book is that close analysis of archaeological best practice can yield constructive guidelines for practice that have much to offer practitioners within archaeology and well beyond. (shrink)

Saigle, Dubljevic, and Racine (2018) claim that Libet-style experiments are insufficient to challenge that agents have free will. They support this with evidence from experimen- tal psychology that the folk concept of freedom is consis- tent with monism, that our minds are identical to our brains. However, recent literature suggests that evidence from experimental psychology is less than determinate in this regard, and that folk intuitions are too unrefined as to provide guidance on metaphysical issues like monism. In light of (...) this, it is worthwhile to examine the authors’ insuf- ficiency claim under the assumption that monism is false and dualism true (our minds are not identical to our brains). We conclude that, were dualism true, then Libet- style experiments would tell us no more about freedom and moral responsibility than what the authors initially claimed, thus further bolstering their point that Libet-style experiments are ill-suited to speak to the free will of agents. In what follows we first discuss some of the reasons to be skeptical of using folk intuitions to make claims about the nature of freedom and moral responsibility. We then draw from the work of E. J. Lowe to demonstrate that Libet-style experiments would likely give the same results regardless of the truth of monism or dualism. (shrink)