This volume brings together a range of influential essays by distinguished philosophers and political theorists on the issue of global justice. Global justice concerns the search for ethical norms that should govern interactions between people, states, corporations and other agents acting in the global arena, as well as the design of social institutions that link them together. The volume includes articles that engage with major theoretical questions such as the applicability of the ideals of social and economic equality to the (...) global sphere, the degree of justified partiality to compatriots, and the nature and extent of the responsibilities of the affluent to address global poverty and other hardships abroad. It also features articles that bring the theoretical insights of global justice thinkers to bear on matters of practical concern to contemporary societies, such policies associated with immigration, international trade, and climate change. -/- Contents: Introduction; Part I Standards of Global Justice: (i) Assistance-Based Responsibilities to the Global Poor: Famine, affluence and mortality, Peter Singer; We don't owe them a thing! A tough-minded but soft-hearted view of aid to the faraway needy, Jan Narveson; Does distance matter morally to the duty to rescue? Frances Myrna Kamm. (ii) Contribution-Based Responsibilities to the Global Poor: 'Assisting' the global poor, Thomas Pogge; Should we stop thinking about poverty in terms of helping the poor?, Alan Patten; Poverty and the moral significance of contribution, Gerhard Øverland. (iii)Cosmopolitans, Global Egalitarians, and its Critics: The one and the many faces of cosmopolitanism, Catherine Lu; Cosmopolitan justice and equalizing opportunities, Simon Caney; The problem of global justice, Thomas Nagel; Against global egalitarianism, David Miller; Egalitarian challenges to global egalitarianism: a critique, Christian Barry and Laura Valentini. Part II Pressing Global Socioeconomic Issues: (i) Governing the Flow of People: Immigration and freedom of association, Christopher Wellman; Democratic theory and border coercion: no right to unilaterally control your own borders, Arash Abizadeh; Justice in migration: a closed borders utopia?, Lea Ypi. (ii) Climate Change: Global environment and international inequality, Henry Shue; Valuing policies in response to climate change: some ethical issues, John Broome; Saved by disaster? Abrupt climate change, political inertia, and the possibility of an intergenerational arms race, Stephen M. Gardiner; Polycentric systems for coping with collective action and global environmental change, Elinor Ostrom. (iii) International Trade: Responsibility and global labor justice, Iris Marion Young; Property rights and the resource curse, Leif Wenar; Fairness in trade I: obligations arising from trading and the pauper-labor argument, Mathias Risse; Name index. -/- See: www.ashgate.com/default.aspx?page=637&calctitle=1&pageSubject=483&sort=pubdate&forthcoming=1&title_i d=9958&edition_id=13385. (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)

A surprising feature of the White Rose anti-Nazi resistance pamphlets is their appeal to a foundational classical Chinese text, the Laozi (otherwise known as the Daodejing), to buttress their critique of fascism and authoritarianism. I argue that from the perspective of a 1942 educated readership, the act of quoting the Laozi functioned as a subtle and pointed nod to anti-fascist intellectuals in pre-war Germany, many of whom had interpreted the Laozi as an anti-authoritarian and pacifist text. To a sympathetic reader, (...) the Laozi therefore constituted an apt reference point for critiquing National Socialism. I then introduce a complication for this wartime reading of the Laozi from the perspective of its ambiguous reception in ancient Chinese political thought. I more specifically discuss an ancient line of interpretation of the Laozi that points in the direction of authoritarianism — in stark tension with the White Rose message of passive resistance and popular revolt. (shrink)

A well-known debate in normative ethics is that between proponents of Act Consequentialism and Rule Consequentialism. Given the structural similarities between Rule Consequentialism and existing forms of Contractualism, one might expect a similar debate to arise among contractualists. However, this is not the case. Some, following T. M. Scanlon, even argue that this question is “misconceived” – that there is something deeply mistaken about considering the possibility of an act-based form of contractualism. In this paper, I challenge this claim.

Reflection on the historical injustice suffered by many formerly colonized groups has left us with a peculiar account of their claims to material objects. One important upshot of that account, relevant to present day justice, is that many people seem to think that members of indigenous groups have special claims to the use of particular external objects by virtue of their attachment to them. In the first part of this paper I argue against that attachment-based claim. In the second part (...) I suggest that, to provide a normatively defensible account of why sometimes agents who are attached to certain external objects might also have special claims over them, the most important consideration is whether the agents making such claims suffer from structural injustice in the present. In the third part I try to explain why structural injustice matters, in what way attachment-based claims relate to it and when they count. (shrink)

Tracing the leading role of emotions in the evolution of the mind, a philosopher and a psychologist pair up to reveal how thought and culture owe less to our faculty for reason than to our capacity to feel. Many accounts of the human mind concentrate on the brain’s computational power. Yet, in evolutionary terms, rational cognition emerged only the day before yesterday. For nearly 200 million years before humans developed a capacity to reason, the emotional centers of the brain were (...) hard at work. If we want to properly understand the evolution of the mind, we must explore this more primal capability that we share with other animals: the power to feel. Emotions saturate every thought and perception with the weight of feelings. The Emotional Mind reveals that many of the distinctive behaviors and social structures of our species are best discerned through the lens of emotions. Even the roots of so much that makes us uniquely human—art, mythology, religion—can be traced to feelings of caring, longing, fear, loneliness, awe, rage, lust, playfulness, and more. From prehistoric cave art to the songs of Hank Williams, Stephen T. Asma and Rami Gabriel explore how the evolution of the emotional mind stimulated our species’ cultural expression in all its rich variety. Bringing together insights and data from philosophy, biology, anthropology, neuroscience, and psychology, The Emotional Mind offers a new paradigm for understanding what it is that makes us so unique. (shrink)

[Stephen Yablo] The usual charge against Carnap's internal/external distinction is one of 'guilt by association with analytic/synthetic'. But it can be freed of this association, to become the distinction between statements made within make-believe games and those made outside them-or, rather, a special case of it with some claim to be called the metaphorical/literal distinction. Not even Quine considers figurative speech committal, so this turns the tables somewhat. To determine our ontological commitments, we have to ferret out all traces (...) of nonliterality in our assertions; if there is no sensible project of doing that, there is no sensible project of Quinean ontology. /// [Andre Gallois] I discuss Steve Yablo's defence of Carnap's distinction between internal and external questions. In the first section I set out what I take that distinction, as Carnap draws it, to be, and spell out a central motivation Carnap has for invoking it. In the second section I endorse, and augment, Yablo's response to Quine's arguments against Carnap. In the third section I say why Carnap's application of the distinction between internal and external questions runs into trouble. In the fourth section I spell out what I take to be Yablo's version of Carnap. In the last I say why that version is especially vulnerable to the objection raised in the second. (shrink)

How we feel is as vital to our survival as how we think. This claim, based on the premise that emotions are largely adaptive, serves as the organizing theme of Why We Need Religion. This book is a novel pathway in a well-trodden field of religious studies and philosophy of religion. Stephen Asma argues that, like art, religion has direct access to our emotional lives in ways that science does not. Yes, science can give us emotional feelings of wonder (...) and the sublime--we can feel the sacred depths of nature--but there are many forms of human suffering and vulnerability that are beyond the reach of help from science. Different emotional stresses require different kinds of rescue. Unlike secular authors who praise religion's ethical and civilizing function, Asma argues that its core value lies in its emotionally therapeutic power. No theorist of religion has failed to notice the importance of emotions in spiritual and ritual life, but truly systematic research has only recently delivered concrete data on the neurology, psychology, and anthropology of the emotional systems. This very recent "affective turn" has begun to map out a powerful territory of embodied cognition. Why We Need Religion incorporates new data from these affective sciences into the philosophy of religion. It goes on to describe the way in which religion manages those systems--rage, play, lust, care, grief, and so on. Finally, it argues that religion is still the best cultural apparatus for doing this adaptive work. In short, the book is a Darwinian defense of religious emotions and the cultural systems that manage them. (shrink)

This paper focuses on the fact that AI is predominantly portrayed as white—in colour, ethnicity, or both. We first illustrate the prevalent Whiteness of real and imagined intelligent machines in four categories: humanoid robots, chatbots and virtual assistants, stock images of AI, and portrayals of AI in film and television. We then offer three interpretations of the Whiteness of AI, drawing on critical race theory, particularly the idea of the White racial frame. First, we examine the extent to which this (...) Whiteness might simply reflect the predominantly White milieus from which these artefacts arise. Second, we argue that to imagine machines that are intelligent, professional, or powerful is to imagine White machines because the White racial frame ascribes these attributes predominantly to White people. Third, we argue that AI racialised as White allows for a full erasure of people of colour from the White utopian imaginary. Finally, we examine potential consequences of the racialisation of AI, arguing it could exacerbate bias and misdirect concern. (shrink)

In this paper, we argue for a particular informative and unified analysis of normative reasons. According to this analysis, a fact F is a reason to act in a certain way just in case it is evidence that one ought to act in that way. Similarly, F is a reason to believe a certain proposition just in case it is evidence for the truth of this proposition. Putting the relatively uncontroversial claim about reasons for belief to one side, we present (...) several arguments in favor of our analysis of reasons for action. We then turn to consider a series of objections to the analysis. We conclude that there are good reasons to accept the analysis and that the objections do not succeed. (shrink)

This paper investigates whether different philosophers’ claims about “normativity” are about the same subject or (as recently argued by Derek Parfit) theorists who appear to disagree are really using the term with different meanings, in order to cast disambiguating light on the debates over at least the nature, existence, extension, and analyzability of normativity. While I suggest the term may be multiply ambiguous, I also find reasons for optimism about a common subject-matter for metanormative theory. This is supported partly by (...) sketching a special kind of hybrid view of normative judgment, perspectivism, that occupies a position between cognitivism and noncognitivism, naturalism and nonnaturalism, objectivism and subjectivism, making it more plausible that radically different metanormative theories could be about the same thing. I explore three main fissures: between (i) the “normativity” of language/thought versus that of facts and properties, (ii) abstract versus substantive senses, and (iii) formal versus robust senses. (shrink)

Conceptual analysis is undergoing a revival in philosophy, and much of the credit goes to Frank Jackson. Jackson argues that conceptual analysis is needed as an integral component of so-called serious metaphysics and that it also does explanatory work in accounting for such phenomena as categorization, meaning change, communication, and linguistic understanding. He even goes so far as to argue that opponents of conceptual analysis are implicitly committed to it in practice. We show that he is wrong on all of (...) these points and that his case for conceptual analysis doesn't succeed. At the same time, we argue that the sorts of intuitions that figure in conceptual analysis may still have a significant role to play in philosophy. So naturalists needn't disregard intuitions altogether. (shrink)

A mythopoetic paradigm or perspective sees the world primarily as a dramatic story of competing personal intentions, rather than a system of objective impersonal laws. Asma argued that our contemporary imaginative cognition is evolutionarily conserved-it has structural and functional similarities to premodern Homo sapiens’s cognition. This article will outline the essential features of mythopoetic cognition or adaptive imagination, delineate the adaptive sociocultural advantages of mythopoetic cognition, explain the phylogenetic and ontogenetic mechanisms that give rise to human mythopoetic mind, show how (...) mythopoetic cognition challeng­es contemporary trends in cognitive science and philosophy, and recognize and outline empirical approaches for a new cognitive science of the imagination. (shrink)

Hailed as "a feast" (Washington Post) and "a modern-day bestiary" (The New Yorker), Stephen Asma's On Monsters is a wide-ranging cultural and conceptual history of monsters--how they have evolved over time, what functions they have served for us, and what shapes they are likely to take in the future. Beginning at the time of Alexander the Great, the monsters come fast and furious--Behemoth and Leviathan, Gog and Magog, Satan and his demons, Grendel and Frankenstein, circus freaks and headless children, (...) right up to the serial killers and terrorists of today and the post-human cyborgs of tomorrow. Monsters embody our deepest anxieties and vulnerabilities, Asma argues, but they also symbolize the mysterious and incoherent territory beyond the safe enclosures of rational thought. Exploring sources as diverse as philosophical treatises, scientific notebooks, and novels, Asma unravels traditional monster stories for the clues they offer about the inner logic of an era's fears and fascinations. In doing so, he illuminates the many ways monsters have become repositories for those human qualities that must be repudiated, externalized, and defeated. (shrink)

Guided by neuroscience, animal behavior, evolution, philosophy, and psychology, Asma burrows deep into the human psyche to look right at the enigmatic but powerful engine that is our improvisational creativity—the source, he argues, of our remarkable imaginational capacity. How is it, he asks, that a story can evoke a whole world inside of us? How are we able to rehearse a skill, a speech, or even an entire scenario simply by thinking about it? How does creativity go beyond experience and (...) help us make something completely new? And how does our moral imagination help us sculpt a better society? As he shows, we live in a world that is only partly happening in reality. Huge swaths of our cognitive experiences are made up by “what-ifs,” “almosts,” and “maybes,” an imagined terrain that churns out one of the most overlooked but necessary resources for our flourishing: possibilities. Considering everything from how imagination works in our physical bodies to the ways we make images, from the mechanics of language and our ability to tell stories to the creative composition of self-consciousness, Asma expands our personal and day-to-day forms of imagination into a grand scale: as one of the decisive evolutionary forces that has guided human development from the Paleolithic era to today. The result is an inspiring look at the rich relationships among improvisation, imagination, and culture, and a privileged glimpse into the unique nature of our evolved minds. (shrink)

According to content-relativist theories of moral language, different speakers use the same moral sentences to say different things. Content-relativism faces a well-known problem of lost disagreement. Recently, numerous content-relativists (including the author) have proposed to solve this problem by appeal to various kinds of non-content-based, or broadly pragmatic, disagreement. This presents content-relativists with a new problem—of found agreement. Which (if any) of these newly identified kinds of conflict is correctly identified as the lost moral disagreement we were looking for? This (...) paper offers a critical comparison of different content-relativist proposals. It divides them into two broad categories, quasi-expressivist theories (QED) and metalinguistic theories (MLD). Objections to each are considered, and QED is tentatively found to be superior. (shrink)

Most current dental ethics curricula use a deontological approach to biomedical and dental ethics that emphasizes adherence to duties and principles as properties that determine whether an act is ethical. But the actual ethical orientation of students is typically unknown. The purpose of the current study was to determine the ethical orientation of dental students in resolving clinical ethical dilemmas. First-year students from one school were invited to participate in an electronic survey that included eight vignettes featuring ethical conflicts common (...) to the health care setting. The Multidimensional Ethics Scale was used to evaluate the students’ ethical judgments of these conflicts. Students rated each vignette along 13 ethically relevant items using a 7-point scale. Nine of the thirteen items were analyzed because they represent the dominant ethical theories, including deontology. One hundred sixteen dental students successfully completed the survey. Of the analyzed items, those associated with deontology had comparatively weak associations with whether students judged the action to be ethical and whether students judged themselves likely to perform the action. Whether an action was judged to be caring had the strongest association with whether the action was judged to be ethical and whether students judged themselves likely to perform the action. These results suggest that adherence to duties or principles has weaker association with students’ ethical judgments and behavior compared to caring, which was found to be more influential in their ethical judgments and behavior. Current dental school curricula with a primary focus on deontology may no. (shrink)

This paper is a response to two sets of published criticisms of the 'Reasons as Evidence’ thesis concerning normative reasons, proposed and defended in earlier papers. According to this thesis, a fact is a normative reason for an agent to Φ just in case this fact is evidence that this agent ought to Φ. John Broome and John Brunero have presented a number of challenging criticisms of this thesis which focus, for the most part, on problems that it appears to (...) confront when it comes to the topic of the weighing of reasons. Our paper responds to all of the criticisms that these critics have provided, shedding fresh light on this interesting topic in the process. (shrink)

Moral assertions express attitudes, but it is unclear how. This paper examines proposals by David Copp, Stephen Barker, and myself that moral attitudes are expressed as implicature (Grice), and Copp's and Barker's claim that this supports expressivism about moral speech acts. I reject this claim on the ground that implicatures of attitude are more plausibly conversational than conventional. I argue that Copp's and my own relational theory of moral assertions is superior to the indexical theory offered by Barker and (...) Jamie Dreier, and that since the relational theory supports conversational implicatures of attitude, expressive conventions would be redundant. Furthermore, moral expressions of attitude behave like conversational and not conventional implicatures, and there are reasons for doubting that conventions of the suggested kind could exist. (shrink)

Given the fundamental role that concepts play in theories of cognition, philosophers and cognitive scientists have a common interest in concepts. Nonetheless, there is a great deal of controversy regarding what kinds of things concepts are, how they are structured, and how they are acquired. This chapter offers a detailed high-level overview and critical evaluation of the main theories of concepts and their motivations. Taking into account the various challenges that each theory faces, the chapter also presents a novel approach (...) to concepts that is organized around two ideas. The first is a pluralistic view of differing types of conceptual structure. The second is a model that treats concepts as atomic representations that are linked to various types of conceptual structures. (shrink)

After a long hiatus, psychology and philosophy are returning to formal study of imagination. While excellent work is being done in the current environment, this article argues for a stronger thesis than usually adopted. Imagination is not just a peripheral feature of cognition or a domain for aesthetic research. It is instead the core operating system or cognitive capacity for humans and has epistemic and therapeutic functions that ground all our sense-making activities. A sketch of imagination as embodied cognition is (...) offered, followed by suggestions of how to organize imagination studies into a more rigorous science–humanities research area. (shrink)

Music is a universal human activity. Its evolution and its value as a cognitive resource are starting to come into focus. This chapter endeavors to give readers a clearer sense of the adaptive aspects of music, as well as the underlying cognitive and neural structures. Special attention is given to the important emotional dimensions of music, and an evolutionary argument is made for thinking of music as a prelinguistic embodied form of cognition—a form that is still available to us as (...) contemporary music creators and consumers. (shrink)

Many authors have proposed constraining the behaviour of intelligent systems with ‘machine ethics’ to ensure positive social outcomes from the development of such systems. This paper critically analyses the prospects for machine ethics, identifying several inherent limitations. While machine ethics may increase the probability of ethical behaviour in some situations, it cannot guarantee it due to the nature of ethics, the computational limitations of computational agents and the complexity of the world. In addition, machine ethics, even if it were to (...) be ‘solved’ at a technical level, would be insufficient to ensure positive social outcomes from intelligent systems. (shrink)

This paper argues that the new metaphysics of powers, also known as dispositional essentialism or causal structuralism, is an illusory metaphysics. I argue for this in the following way. I begin by distinguishing three fundamental ways of seeing how facts of physical modality — facts about physical necessitation and possibility, causation, disposition, and chance — are grounded in the world. The first way, call it the first degree, is that the actual world or all worlds, in their entirety, are the (...) source of physical modality. Humeanism is the best known such approach, but there are other less well-known approaches. The second way, the second degree, is that the source of physical modality lies in certain second-order facts, involving a relation between universals. Armstrong’s necessitarianism and other views are second-degree views. The third way, the third degree, holds that properties themselves are the source of physical modality. This is the powers view. I examine four ways of developing the third degree: relational constitution, graph-theoretic structuralism, dispositional roles, and powerful qualities. All these ways are either incoherent, or just disguised versions of the first-degree. The new metaphysics of powers is illusory. With the collapse of the third degree, the second degree, the necessitarian view of law, collapses as well. I end the paper with some reflections on the first degree, on the problem of explaining necessary connections between distinct existences, and on the dim prospects of holist ontology. (shrink)

In this paper we present a new metaphysical theory of material objects. On our theory, objects are bundles of property instances, where those properties give the nature or essence of that object. We call the theory essential bundle theory. Property possession is not analysed as bundle-membership, as in traditional bundle theories, since accidental properties are not included in the object’s bundle. We have a different story to tell about accidental property possession. This move reaps many benefits. Essential bundle theory delivers (...) a simple theory of the essential properties of material objects; an explanation of how object coincidence can arise; an actual-world ground for modal differences between coincident objects; a simple story about intrinsic properties; and a plausible account of certain ubiquitous cases of causal overdetermination. (shrink)

What should we make of claims by members of other groups to have moralities different from our own? Human Rights in Chinese Thought gives an extended answer to this question in the first study of its kind. It integrates a full account of the development of Chinese rights discourse - reaching back to important, though neglected, origins of that discourse in 17th and 18th century Confucianism - with philosophical consideration of how various communities should respond to contemporary Chinese claims about (...) the uniqueness of their human rights concepts. The book elaborates a plausible kind of moral pluralism and demonstrates that Chinese ideas of human rights do indeed have distinctive characteristics, but it nonetheless argues for the importance and promise of cross-cultural moral engagement. (shrink)

Over the last fifteen years, an ambitious explanatory framework has been proposed to unify explanations across biology and cognitive science. Active inference, whose most famous tenet is the free energy principle, has inspired excitement and confusion in equal measure. Here, we lay the ground for proper critical analysis of active inference, in three ways. First, we give simplified versions of its core mathematical models. Second, we outline the historical development of active inference and its relationship to other theoretical approaches. Third, (...) we describe three different kinds of claim -- labelled mathematical, empirical and general -- routinely made by proponents of the framework, and suggest dialectical links between them. Overall, we aim to increase philosophical understanding of active inference so that it may be more readily evaluated. -/- This the final submitted version of the Introduction to the Topical Collection "The Free Energy Principle: From Biology to Cognition", forthcoming in Biology & Philosophy. (shrink)

We characterize, more precisely than before, what Rawls calls the “analytical” method of drawing up a list of basic liberties. This method employs one or more general conditions that, under any just social order whatever, putative entitlements must meet for them to be among the basic liberties encompassed, within some just social order, by Rawls’s first principle of justice (i.e., the liberty principle). We argue that the general conditions that feature in Rawls’s own account of the analytical method, which employ (...) the notion of necessity, are too stringent. They ultimately fail to deliver as basic certain particular liberties that should be encompassed within any fully adequate scheme of liberties. To address this under-generation problem, we provide an amended general condition. This replaces Rawls’s necessity condition with a probabilistic condition and it appeals to the standard liberal prohibition on arbitrary coercion by the state. We defend our new approach both as apt to feature in applications of the analytical method and as adequately grounded in justice as fairness as Rawls articulates the theory’s fundamental ideas. (shrink)

I believe that normative force depends on desire. This view faces serious difficulties, however, and has yet to be vindicated. This paper sketches an Argument from Voluntary Response, attempting to establish this dependence of normativity on desire by appeal to the autonomous character of our experience of normative authority, and the voluntary character of our responses to it. I first offer an account of desiring as mentally aiming intrinsically at some end. I then argue that behaviour is only voluntary if (...) it results from such aiming; hence all voluntary behaviour is produced by desire. Full-blooded responses to normativity, I then argue, are voluntary actions: motivation to act arises voluntarily from perception of reasons to act. This fits the desire-based model of normativity but not its rivals. However this argument concludes merely that our responses to normativity are desire-based. I end with some observations about how I think we can bridge the gap from the nature of response to normativity to the nature of normativity itself. (shrink)

What is it that makes someone wise, or one person wiser than another? I argue that wisdom consists in knowledge of how to live well, and that this knowledge of how to live well is constituted by various further kinds of knowledge. One concern for this view is that knowledge is not needed for wisdom but rather some state short of knowledge, such as having rational or justified beliefs about various topics. Another concern is that the emphasis on knowing how (...) to live well fails to do justice to the ancient tradition of ‘theoretical wisdom’. I address both of these concerns in filling out the account. (shrink)

Hutto and Myin claim that teleosemantics cannot account for mental content. In their view, teleosemantics accounts for a poorer kind of relation between cognitive states and the world but lacks the theoretical tools to account for a richer kind. We show that their objection imposes two criteria on theories of content: a truth-evaluable criterion and an intensionality criterion. For the objection to go through, teleosemantics must be subject to both these criteria and must fail to satisfy them. We argue that (...) teleosemantics meets the truth-evaluable criterion and is not required to meet the intensionality criterion. We conclude that Hutto and Myin’s objection fails. (shrink)

Sufferers of eating disorders often hold false beliefs about their own body size. Such beliefs appear to violate norms of rationality, being neither grounded by nor responsive to appropriate forms of evidence. I defend the rationality of these beliefs. I argue that they are in fact supported by appropriate evidence, emanating from proprioceptive misperception of bodily boundaries. This argument has far‐reaching implications for the explanation and treatment of eating disorders, as well as debates over the relationship between rationality and human (...) psychology. (shrink)

Among contemporary epistemologists and scholars of ancient philosophy, one often hears that transmitting propositional knowledge by testimony is usually easy and straightforward, but transmitting understanding and know-how by testimony is usually difficult or simply impossible. Further provocative conclusions are then sometimes drawn from these claims: for instance, that know-how and understanding are not types of propositional knowledge. In contrast, I argue that transmitting propositional knowledge is sometimes easy and sometimes hard, just as transmitting know how and understanding is sometimes easy (...) and sometimes hard. No general lessons can be drawn about the relationships among propositional knowledge, know how, and understanding by considering the case of testimony alone. (shrink)

This paper aims to establish several interconnected points. First, a particular interpretation of the mathematical definition of information, known as the causal interpretation, is supported largely by misunderstandings of the engineering context from which it was taken. A better interpretation, which makes the definition and quantification of information relative to the function of its user, is outlined. The first half of the paper is given over to introducing communication theory and its competing interpretations. The second half explores three consequences of (...) the main thesis. First, a popular claim that the quantification of information in a signal is irrelevant for the meaning of that signal is exposed as fallacious. Second, a popular distinction between causal and semantic information is shown to be misleading, and I argue it should be replaced with a related distinction between natural and intentional signs. Finally, I argue that recent empirical work from microbiology and cognitive science drawing on resources of mathematical communication theory is best interpreted by the functional account. Overall, a functional approach is shown to be both theoretically and empirically well-supported. (shrink)

Bell’s theorem has fascinated physicists and philosophers since his 1964 paper, which was written in response to the 1935 paper of Einstein, Podolsky, and Rosen. Bell’s theorem and its many extensions have led to the claim that quantum mechanics and by inference nature herself are nonlocal in the sense that a measurement on a system by an observer at one location has an immediate effect on a distant entangled system. Einstein was repulsed by such “spooky action at a distance” and (...) was led to question whether quantum mechanics could provide a complete description of physical reality. In this paper I argue that quantum mechanics does not require spooky action at a distance of any kind and yet it is entirely reasonable to question the assumption that quantum mechanics can provide a complete description of physical reality. The magic of entangled quantum states has little to do with entanglement and everything to do with superposition, a property of all quantum systems and a foundational tenet of quantum mechanics. (shrink)

I explore the extent to which the epistemic state of understanding is transparent to the one who understands. Against several contemporary epistemologists, I argue that it is not transparent in the way that many have claimed, drawing on results from developmental psychology, animal cognition, and other fields.

Anti-exceptionalism about logic is the doctrine that logic does not require its own epistemology, for its methods are continuous with those of science. Although most recently urged by Williamson, the idea goes back at least to Lakatos, who wanted to adapt Popper's falsicationism and extend it not only to mathematics but to logic as well. But one needs to be careful here to distinguish the empirical from the a posteriori. Lakatos coined the term 'quasi-empirical' `for the counterinstances to putative mathematical (...) and logical theses. Mathematics and logic may both be a posteriori, but it does not follow that they are empirical. Indeed, as Williamson has demonstrated, what counts as empirical knowledge, and the role of experience in acquiring knowledge, are both unclear. Moreover, knowledge, even of necessary truths, is fallible. Nonetheless, logical consequence holds in virtue of the meaning of the logical terms, just as consequence in general holds in virtue of the meanings of the concepts involved; and so logic is both analytic and necessary. In this respect, it is exceptional. But its methodologyand its epistemology are the same as those of mathematics and science in being fallibilist, and counterexamples to seemingly analytic truths are as likely as those in any scientic endeavour. What is needed is a new account of the evidential basis of knowledge, one which is, perhaps surprisingly, found in Aristotle. (shrink)

….it [is] wholly irrational to regard as doubtful matters that are perceived clearly and distinctly by the understanding in its purity, on account of mere prejudices of the senses and hypotheses in which there is an element of the unknown.Descartes, Geometrical Exposition of the MeditationsSubstance dualism, once a main preoccupation of Western metaphysics, has fallen strangely out of view; today’s mental/physical dualisms are dualisms of fact, property, or event. So if someone claims to find a difference between minds and bodies (...) per se, it is not initially clear what he is maintaining. Maybe this is because one no longer recognizes ‘minds’ as entities in their own right, or ‘substances.’ However, selves - the things we refer to by use of ‘I’ - are surely substances, and it does little violence to the intention behind mind/body dualism to interpret it as a dualism of bodies and selves. If the substance dualist’s meaning remains obscure, that is because it can mean several different things to say that selves are not bodies. (shrink)

Bernard Williams's motivational reasons-internalism fails to capture our first-order reasons judgements, while Derek Parfit's nonnaturalistic reasons-externalism cannot explain the nature or normative authority of reasons. This paper offers an intermediary view, reformulating scepticism about external reasons as the claim not that they don't exist but rather that they don't matter. The end-relational theory of normative reasons is proposed, according to which a reason for an action is a fact that explains why the action would be good relative to some end, (...) where the relevant end for any ascription of reasons is determined by the speaker's conversational context. Because these ends need not be the agent's ends, Williams is wrong to reject the existence of external reasons. But contra Parfit, a reason for action is only important for an agent if it is motivationally internal to that agent. (shrink)

Bird argues that Armstrong’s necessitarian conception of physical modality and laws of nature generates a vicious regress with respect to necessitation. We show that precisely the same regress afflicts Bird’s dispositional-monist theory, and indeed, related views, such as that of Mumford & Anjum. We argue that dispositional monism is basically Armstrongian necessitarianism modified to allow for a thesis about property identity.

Since nothing about God is passive, and the perception of pain is inherently passive, then it seems that God does not know what it is like to experience pain. Nor would he be able to cause us to experience pain, for his experience would then be a sensation (which would require God to have senses, which he does not). My suggestion is that Berkeley avoids this situation by describing how God knows about pain “among other things” (i.e. as something whose (...) identity is intelligible in terms of the integrated network of things). This avoids having to assume that God has ideas (including pain) apart from his willing that there be perceivers who have specific ideas that are in harmony or not in harmony with one another. (shrink)

I argue that no one knows whether there is free will.

The free energy principle is notoriously difficult to understand. In this paper, we relate the principle to a framework that philosophers of biology are familiar with: Ruth Millikan’s teleosemantics. We argue that: systems that minimise free energy are systems with a proper function; and Karl Friston’s notion of implicit modelling can be understood in terms of Millikan’s notion of mapping relations. Our analysis reveals some surprising formal similarities between the two frameworks, and suggests interesting lines of future research. We hope (...) this will aid further philosophical evaluation of the free energy principle. (shrink)

Holmes exists is false. How can this be, when there is no one for the sentence to misdescribe? Part of the answer is that a sentence’s topic depends on context. The king of France is bald, normally unevaluable, is false qua description of the bald people. Likewise Holmes exists is false qua description of the things that exist; it misdescribes those things as having Holmes among them. This does not explain, though, how Holmes does not exist differs in cognitive content (...) from, say, Vulcan does not exist. Our answer builds on an observation of Kripke’s: even if Holmes exists, he is not in this room, for we were all born too late. (shrink)