Wenn Präsident Kennedy nicht erschossen worden wäre, hätte er dann Nordvietnam bombardiert? Das weiß Gott allein. Oder doch nicht? Weiß wenigstens Er, was Kennedy getan hätte? ... Die Jesuiten behaupteten unter anderem, daß viele menschliche Handlungen in dem Sinne frei seien, daß die Ausführenden nicht logisch oder kausal gezwungen seien, sie auszuführen. („Frei“ wird im vorliegenden Aufsatz stets in diesem Sinne verwendet werden.) Wie behält Gott dann die Kontrolle über die menschliche Geschichte? Nicht dadurch, daß Er menschliche Handlungen kausal determiniert, (...) wie die Dominikaner geglaubt zu haben scheinen , sondern indem Er Umstände herbeiführt, von denen Er weiß, daß wir in ihnen freiwillig Seinen Plänen entsprechend handeln werden. (shrink)

ABSTRACT: Discussion (in German) of Robert Muller's "Les Megariques, Fragments et temoignages". Traduit et commentes. Paris, Vrin 1985, with focus on his commentary on ancient paradoxes.

This paper explores a currently popular view in the philosophy of emotion, according to which emotions constitute a specific form of evaluative aspect-perception (cf. esp. Roberts 2003, Döring 2004, Slaby 2008). On this view, adequate or fitting emotions play an important epistemic roe vis à vis evaluative knowledge. The paper specifically asks how to conceive of the adequacy or fittingness conditions of emotion. Considering the specific, relational nature of the evaluative properties disclosed by emotions, it is argued that a suitable (...) standard of fittingness has both a world-involving and person-involving aspect: Fitting emotions require both a fundamentum in re as well as a fundamentum in persona. (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 problem of amodal perception is the problem of how we represent features of perceived objects that are occluded or otherwise hidden from us. Bence Nanay (2010) has recently proposed that we amodally perceive an object's occluded features by imaginatively projecting them into the relevant regions of visual egocentric space. In this paper, I argue that amodal perception is not a single, unitary capacity. Drawing appropriate distinctions reveals amodal perception to be characterized not only by mental imagery, as Nanay suggests, (...) but also by genuinely visual representations as well as beliefs. I conclude with some brief remarks on the role of object-directed bodily action in conferring a sense of unseen presence on an object's occluded features. (shrink)

This chapter critically assesses recent arguments that acquiring the ability to categorize an object as belonging to a certain high-level kind can cause the relevant kind property to be represented in visual phenomenal content. The first two arguments, developed respectively by Susanna Siegel (2010) and Tim Bayne (2009), employ an essentially phenomenological methodology. The third argument, developed by William Fish (2013), by contrast, is supported by an array of psychophysical and neuroscientific findings. I argue that while none of these arguments (...) ultimately proves successful, there is a substantial body of empirical evidence that information originating outside the visual system can nonetheless modulate the way an object’s low-level attributes visually appear. Visual phenomenal content, I show, is not only significantly influenced by crossmodal interactions between vision and other exteroceptive senses such as touch and audition, but also by interactions between vision and non-perceptual systems involved in motor planning and construction of the proprioceptive body-image. (shrink)

Contemporary republicanism is characterized by three main ideas: free persons, who are not subject to the arbitrary power of others; free states, which try to protect their citizens from such power without exercising it themselves; and vigilant citizenship, as a means to limit states to their protective role. This book advances an economic model of such republicanism that is ideologically centre-left. It demands an exit-oriented state interventionism, one that would require an activist government to enhance competition and resource exit from (...) dominating relationships within markets of all types, be they marital, labour, or residential. The substantial intervention and redistribution necessitated by such an approach make it leftist, while its tendency to work with rather than against the grain of markets makes it centrist. It is, in short, a contribution to progressive republican political thought, but one that is less social-democratic than market-democratic in character. (shrink)

Explanatory pluralism holds that the sorts of comprehensive theoretical and ontological economies, which microreductionists and New Wave reductionists envision and which antireductionists fear, offer misleading views of both scientific practice and scientific progress. Both advocates and foes of employing reductionist strategies at the interface of psychology and neuroscience have overplayed the alleged economies that interlevel connections (including identities) justify while overlooking their fundamental role in promoting scientific research. A brief review of research on visual processing provides support for the explanatory (...) pluralist=s general model of cross-scientific relations and discloses the valuable heuristic role hypothetical identities play in cross-scientific research. That model also supplies grounds for hesitation about the correlation objection to the psycho-physical identity theory and complaints about an explanatory gap in physicalist accounts of consciousness. These takes on psycho-neural connections miss both the sorts of considerations that motivate hypothetical identities in science and their fundamental contribution to progressive research. Thus, their focus on the contributions of research at multiple levels of analysis does not bar explanatory pluralists from considering heuristic identity theory (HIT). Arguably, it encourages it. (shrink)

Human beings have the ability to ‘augment’ reality by superimposing mental imagery on the visually perceived scene. For example, when deciding how to arrange furniture in a new home, one might project the image of an armchair into an empty corner or the image of a painting onto a wall. The experience of noticing a constellation in the sky at night is also perceptual-imaginative amalgam: it involves both seeing the stars in the constellation and imagining the lines that connect them (...) at the same time. I here refer to such hybrid experiences – involving both a bottom-up, externally generated component and a top-down, internally generated component – as make-perceive (Briscoe 2008, 2011). My discussion in this paper has two parts. In the first part, I show that make-perceive enables human beings to solve certain problems and pursue certain projects more effectively than bottom-up perceiving or top-down visualization alone. To this end, the skillful use of projected mental imagery is surveyed in a variety of contexts, including action planning, the interpretation of static mechanical diagrams, and non-instrumental navigation. In the second part, I address the question of whether make-perceive may help to account for the “phenomenal presence” of occluded or otherwise hidden features of perceived objects. I argue that phenomenal presence is not well explained by the hypothesis that hidden features are represented using projected mental images. In defending this position, I point to important phenomenological and functional differences between the way hidden object features are represented respectively in mental imagery and amodal completion. (shrink)

Manipulative actions come in a bewildering variety of forms: direct and indirect deception, playing on emotions, tempting, inciting, and so on. It is not obvious what feature all these actions share in virtue of which they are all of the same kind and in virtue of which they are all morally wrong. This article argues that all manipulative actions are cases in which the manipulator attempts to lead the victim astray by trying to get her to have emotions, beliefs, or (...) desires that, as the manipulator sees it, are not ideal for the victim. To attempt to lead a person astray in this way is to fail to respect the moral and rational agency of the victim. This analysis captures the fact that actions of many kinds--and with many different psychological effects--can be manipulative, and it tells us what is wrong with acting manipulatively. It also helps distinguish manipulation from non rational persuasion. (shrink)

This paper evaluates the Natural-Kinds Argument for cognitive extension, which purports to show that the kinds presupposed by our best cognitive science have instances external to human organism. Various interpretations of the argument are articulated and evaluated, using the overarching categories of memory and cognition as test cases. Particular emphasis is placed on criteria for the scientific legitimacy of generic kinds, that is, kinds characterized in very broad terms rather than in terms of their fine-grained causal roles. Given the current (...) state of cognitive science, I conclude that we have no reason to think memory or cognition are generic natural kinds that can ground an argument for cognitive extension. (shrink)

This paper examines two recent contributions to the hate speech literature – by Steven Heyman and Jeremy Waldron – which seek a justification for the legal restriction of hate speech in an account of the way that hate speech infringes against people’s dignity. These analyses look beyond the first-order hurts and disadvantages suffered by the immediate targets of hate speech, and consider the prospect of hate speech sustaining complex social structures whose wide-scale operations lower the social status of members of (...) targeted groups. In Heyman’s and Waldron’s accounts we find plausible insights into the nature of identity-based social hierarchies, and the harms that redound to subordinated people under the operations of such hierarchies. I argue, however, that both analyses are unsuccessful as justifications for the restriction of hate speech, because they do not ultimately provide reason to think that hate speech is responsible for creating or sustaining identity-based social hierarchies. (shrink)

In disagreements about trivial matters, it often seems appropriate for disputing parties to adopt a ‘middle ground’ view about the disputed matter. But in disputes about more substantial controversies (e.g. in ethics, religion, or politics) this sort of doxastic conduct can seem viciously acquiescent. How should we distinguish between the two kinds of cases, and thereby account for our divergent intuitions about how we ought to respond to them? One possibility is to say that ceding ground in a trivial dispute (...) is appropriate because the disputing parties are usually epistemic peers within the relevant domain, whereas in a more substantial disagreement the disputing parties rarely, if ever, qualify as epistemic peers, and so ‘sticking to one’s guns’ is usually the appropriate doxastic response. My aim in this paper is to explain why this way of drawing the desired distinction is ultimately problematic, even if it seems promising at first blush. (shrink)

Numerous research groups are now utilizing Basic Formal Ontology as an upper-level framework to assist in the organization and integration of biomedical information. This paper provides elucidation of the three existing BFO subcategories of realizable entity, namely function, role, and disposition. It proposes one further sub-category of tendency, and considers the merits of recognizing two sub-categories of function for domain ontologies, namely, artifactual and biological function. The motivation is to help advance the coherent ontological treatment of functions, roles, and dispositions, (...) to help provide the potential for more detailed classification, and to shed light on BFO’s general make-up and use. (shrink)

In recent work Mary Kate McGowan presents an account of oppressive speech inspired by David Lewis's analysis of conversational kinematics. Speech can effect identity-based oppression, she argues, by altering 'the conversational score', which is to say, roughly, that it can introduce presuppositions and expectations into a conversation, and thus determine what sort of subsequent conversational 'moves' are apt, correct, felicitous, etc., in a manner that oppresses members of a certain group (e.g. because the suppositions and expectations derogate or demean members (...) of that group). In keeping with the Lewisian picture, McGowan stresses the asymmetric pliability of conversational scores. She argues that it is easier to introduce (for example) sexist presuppositions and expectations into a conversation than it is to remove them. Responding to a sexist remark, she thus suggests, is like trying to "unring a bell". I begin by situating McGowan's work in the wider literature on speech and social hierarchy, and explaining how her account of oppressive speech improves upon the work of others in its explication of the relationship between individuals' verbal conduct and structurally oppressive social arrangements. I then propose an explanation and supportive elaboration of McGowan's claims about the asymmetric pliability of conversations involving identity-oppressive speech. Rather than regarding such asymmetry as a sui generis phenomenon, I show how we can understand it as a consequence of a more general asymmetry between making things salient and un-salient in speech, and I show how this asymmetry also operates in various cases that interested Lewis. (shrink)

With the publication of A Theory of Justice in 1971, John Rawls not only rejuvenated contemporary political philosophy but also defended a Kantian form of Enlightenment liberalism called “justice as fairness.” Enlightenment liberalism stresses the development and exercise of our capacity for autonomy, while Reformation liberalism emphasizes diversity and the toleration that encourages it. These two strands of liberalism are often mutually supporting, but they conflict in a surprising number of cases, whether over the accommodation of group difference, the design (...) of civic education, or the promotion of liberal values internationally. During the 1980’s, however, Rawls began to jettison key Kantian characteristics of his theory, a process culminating in the 1993 release of Political Liberalism and completing the transformation of justice as fairness into a Reformation liberalism. -/- Reconstructing Rawls argues that this transformation was a tragic mistake because it jeopardized the most important features of his theory, viz. the lexical priorities of right, liberty, and fair equality of opportunity as well as the difference principle. Controversially, this book contends that Rawls’s so-called “political turn,” motivated by a newfound interest in diversity and the accommodation of difference, has been unhealthy for autonomy-based liberalism and has pushed liberalism more broadly towards cultural relativism, be it in the guise of liberal multiculturalism or critiques of cosmopolitan distributive-justice theories. The book then demonstrates that the central elements of justice as fairness can only be defended within the context of a Kantian Enlightenment liberalism and that Rawls’s hope for a more pluralistic grounding for his theory, endorsed by a wide variety of belief systems present in modern democratic societies, is illusory. -/- Reconstructing Rawls is the first book to systematically compare Rawls’s and Kant’s theories and the first to offer an internal critique and reconstruction of justice as fairness, reconceiving it as a comprehensive, universalistic Kantian liberalism. By doing so, it gives us both the vision of a liberal world order—“a republicanism of all states, together and separately,” as Kant put it—and a mode of justification addressed to all men and women, not as members of particular nations, races, and faiths, but as human beings, as citizens of the world. In short, it reclaims Rawls for the Enlightenment. (shrink)

Historically, republicans were of different minds about markets: some, such as Rousseau, reviled them, while others, like Adam Smith, praised them. The recent republican resurgence has revived this issue. Classical liberals such as Gerald Gaus contend that neo-republicanism is inherently hostile to markets, while neo-republicans like Richard Dagger and Philip Pettit reject this characterization—though with less enthusiasm than one might expect. I argue here that the right republican attitude toward competitive markets is celebratory rather than acquiescent and that republicanism demands (...) such markets for the same reason it requires the rule of law: because both are essential institutions for protecting individuals from arbitrary interference. I reveal how competition restrains—and in the limit, even eradicates—market power and thereby helps us realize “market freedom,” i.e., freedom as non-domination in the context of economic exchange. Finally, I show that such freedom necessitates “Anglo-Nordic” economic policies. (shrink)

My paper addresses a topic--the implications of Rawls's justice as fairness for affirmative action--that has received remarkably little attention from Rawls's major interpreters. The only extended treatments of it that are in print are over a quarter-century old, and they bear scarcely any relationship to Rawls's own nonideal theorizing. Following Christine Korsgaard's lead, I work through the implications of Rawls's nonideal theory and show what it entails for affirmative action: viz. that under nonideal conditions, aggressive forms of formal equality of (...) opportunity (e.g., sensitivity training, outreach efforts, external monitoring and enforcement) and compensating support (e.g., special fellowship programs, childcare facilities, mentoring, co-op opportunities, etc.) can be justified, but that "hard" and even "soft" quotas are difficult to defend under any conditions. I conclude the paper by exploring the implications of these surprising results for contemporary liberalism more broadly and for constitutional law and public policy. (shrink)

We explore the idea that a group or ‘team’ of individuals can be an agent in its own right and that, when this is the case, individual team members use team reasoning, a distinctive mode of reasoning from that of standard decision theory. Our approach is to represent team reasoning explicitly, by means of schemata of practical reasoning in which conclusions about what actions should be taken are inferred from premises about the decision environment and about what agents are seeking (...) to achieve. We use this theoretical framework to compare team reasoning with the individual reasoning of standard decision theory, and to compare various theories of team agency and collective intentionality. (shrink)

I present a new definition of verisimilitude, framed in terms of causes. Roughly speaking, according to it a scientific model is approximately true if it captures accurately the strengths of the causes present in any given situation. Against much of the literature, I argue that any satisfactory account of verisimilitude must inevitably restrict its judgments to context-specific models rather than general theories. We may still endorse—and only need—a relativized notion of scientific progress, understood now not as global advance but rather (...) as the mastering of particular problems. This also sheds new light on longstanding difficulties surrounding language-dependence and models committed to false ontologies. (shrink)

Vision constitutes an interesting domain, or range of domains, for debate over the extended mind thesis, the idea that minds physically extend beyond the boundaries of the body. In part this is because vision and visual experience more particularly are sometimes presented as a kind of line in the sand for what we might call externalist creep about the mind: once all reasonable concessions have been made to externalists about the mind, visual experience marks a line beyond which lies a (...) safe haven for individualists. Here I want to put a little more pressure on such a view of visual experience, as well as to offer a more constructive, positive argument in defense of the idea of extended vision. (shrink)

Some philosophers take Perky's experiments to show that perceiving can be mistaken for visualizing and so that the two sometimes match in phenomenology. On Segal’s alternative interpretation Perky’s subjects did not consciously perceive the stimuli at all. I argue that even setting this alternative aside, Perky's results do not prove what the philosophers think. She showed her subjects, not the objects they were asked to visualise, but pictures of them. What they mistook for visualizing was not perceptual consciousness of stimuli, (...) but pictorial consciousness. Once clear about the nature of the latter, we can see that Perky's results reveal nothing very surprising. (shrink)

This paper is a critical discussion of John Dupré's recent defence of promiscuous realism in Part 1 of his The Disorder of Things: Metaphysical Foundations of the Disunity of Science. It also discusses some more general issues in the philosophy of biology and science. Dupré's chief strategy of argumentation appeals to debates within the philosophy of biology, all of which concern the nature of species. While the strategy is well motivated, I argue that Dupré's challenge to essentialist and unificationist views (...) about natural kinds is not successful. One conclusion is that an integrative conception of species is a real alternative to Dupré's pluralism. (shrink)

"This volume emerged from workshops held at Pennsylvania State University in 2003 and Stanford University in 2005"--P. vii.

When modern economists use the notions of sympathy or empathy, they often claim that their ideas have their roots in Adam Smith's Theory of Moral Sentiments, while sometimes complaining that Smith fails to distinguish clearly enough between the two concepts. Recently, Philippe Fontaine has described various forms of sympathy and empathy, and has explored their respective roles in Smith's work. My objective in this paper is to argue that Smith's analysis of how people's sentiments impinge on one another involves a (...) concept of fellow-feeling that is distinct from both sympathy and empathy. Unlike sympathy and empathy, fellow-feeling does not fit into the ontological framework of rational choice theory – which may explain why it tends to be overlooked by modern readers of Smith. (shrink)

Desire-based theories of well-being claim that a person's well-being consists of the satisfaction of her desires. Many of these theories say that well-being consists of the satisfaction of desires that she would have if her desires were "corrected" in various ways. Some versions of this theory claim that the corrections involve having "full information" or being an "ideal observer." I argue that well-being does not depend on what one would desire if she were an “ideal observer.” Rather, it depends on (...) what she would desire if she had as much information as she could have and still maintain her identity as the particular person she is. The paper attempts to spell out this suggestion by constructing a notion of integrity. Roughly, integrity is preserved if one’s most central projects, commitments, and character traits are left in tact. I argue that desire-based theories of well-being should define well-being in terms of the satisfaction of those desires that one would have if one’s epistemic situation were idealized as much as would be consistent with maintaining her integrity. (shrink)

Denis Walsh has written a striking new defense in this journal of the statisticalist (i.e., noncausalist) position regarding the forces of evolution. I defend the causalist view against his new objections. I argue that the heart of the issue lies in the nature of nonadditive causation. Detailed consideration of that turns out to defuse Walsh’s ‘description‐dependence’ critique of causalism. Nevertheless, the critique does suggest a basis for reconciliation between the two competing views. *Received December 2009; revised December 2009. †To contact (...) the author, please write to: Department of Philosophy, 599 Lucas Hall, One University Boulevard, University of Missouri, St. Louis, MO 63121; e‐mail: [email protected]. (shrink)

My aim in this article is to contribute to the larger project of assessing the relative merits of different theories of substance. An important preliminary step in this project is assessing the explanatory resources of one main theory of substance, the so-called bundle theory. This article works towards such an assessment. I identify and explain three distinct explanatory challenges an adequate bundle theory must meet. Each points to a putative explanatory gap, so I call them the Gap Challenges. I consider (...) three bundle-theoretic strategies for meeting these challenges. I argue that none of them goes very far. The upshot is that, absent other strategies for meeting the challenges, bundle theory involves a significant amount of stipulation. This black box makes bundle theory relatively weak with respect to its explanatory power—unless, of course, rival theories of substance are unable to do better. (shrink)

I formulate a counterfactual version of the notorious 'Ramsey Test'. Whereas the Ramsey Test for indicative conditionals links credence in indicatives to conditional credences, the counterfactual version links credence in counterfactuals to expected conditional chance. I outline two forms: a Ramsey Identity on which the probability of the conditional should be identical to the corresponding conditional probabihty/expectation of chance; and a Ramsey Bound on which credence in the conditional should never exceed the latter.Even in the weaker, bound, form, the counterfactual (...) Ramsey Test makes counterfactuals subject to the very argument that Lewis used to argue against the indicative version of the Ramsey Test. I compare the assumptions needed to run each, pointing to assumptions about the time-evolution of chances that can replace the appeal to Bayesian assumptions about credence update in motivating the assumptions of the argument.I finish by outlining two reactions to the discussion: to indicativize the debate on counterfactuals; or to counterfactualize the debate on indicatives. (shrink)

This paper argues that scientific studies distinguish themselves from other studies by a combination of their processes, their (knowledge) elements and the roles of these elements. This is supported by constructing a process model. An illustrative example based on Newtonian mechanics shows how scientific knowledge is structured according to the process model. To distinguish scientific studies from research and scientific research, two additional process models are built for such processes. We apply these process models: (1) to argue that scientific progress (...) should emphasize both the process of change and the content of change; (2) to chart the major stages of scientific study development; and (3) to define “science”. (shrink)

In metaphysics, the view that material constitution is transitive is ubiquitous, an assumption expressed by both proponents and critics of constitution views. Likewise, it is typically assumed within the philosophy of mind that physical realization is a transitive relation. In both cases, this assumption of transitivity plays a role in discussion of the broader implications of a metaphysics that invokes either relation. Here I provide reasons for questioning this assumption and the uses to which this appeal to transitivity is put. (...) As my title suggests, I shall focus on the case of material constitution, using a brief discussion of realization at the outset to motivate the discussion of the transitivity of material constitution at the core of the paper. (shrink)

The purpose of this paper is to defend what I call the action-oriented coding theory (ACT) of spatially contentful visual experience. Integral to ACT is the view that conscious visual experience and visually guided action make use of a common subject-relative or 'egocentric' frame of reference. Proponents of the influential two visual systems hypothesis (TVSH), however, have maintained on empirical grounds that this view is false (Milner & Goodale, 1995/2006; Clark, 1999; 2001; Campbell, 2002; Jacob & Jeannerod, 2003; Goodale & (...) Milner, 2004). One main source of evidence for TVSH comes from behavioral studies of the comparative effects of size-contrast illusions on visual awareness and visuo- motor action. This paper shows that not only is the evidence from illusion studies inconclusive, there is a better, ACT-friendly interpretation of the evidence that avoids serious theoretical difficulties faced by TVSH. (shrink)

Conditioning can produce desires that seem to be outside of--or “alien” to--the agent. Desire-based theories of welfare claim that the satisfaction of desires creates prudential value. But the satisfaction of alien desires does not seem to create prudential value. To explain this fact, we need an account of alien desires that explains their moral status. In this paper I suggest that alien desires are desires that would be rational if the person believed something that in fact she believes is false. (...) Such desires could be produced by mental representations--or “quasi-beliefs”--with contents that conflict with the contents of one’s beliefs. The postulation of quasi-beliefs is plausible, for they explain important empirical facts about our behavior--facts that are difficult if not impossible to explain otherwise. Alien desires, I argue, involve quasi-beliefs with contents that conflict with the contents of regular beliefs. This theory provides the distinction between alien and authentic desires that desire-based theories of welfare need. (shrink)

Are materially constituted entities, such as statues and glasses of liquid, something more than their material constituents? The puzzle that frames this paper stems from conflicting answers to this question. At the core of the paper is a distinctive way of thinking about material constitution that posits two concepts of constitution, compositional and ampliative constitution, with the bulk of the discussion devoted to developing distinct analyses for these concepts. Distinguishing these concepts solves our initial puzzle and enriches the space of (...) possibilities for constitution views. (shrink)

A person enters the moral realm when she affirms that other persons matter in the same way that she does. This, of course, is just the beginning, for she must then determine what follows from this affirmation. One way in which we treat other persons as mattering is by respecting them. And one way in which we respect persons is by respecting their wishes, desires, decisions, choices, ends, and goals. I will call all of these things ‘aims.’ Sometimes we respect (...) another person's aims simply byrefrainingfrom doing certain things, such as treating her in ways that thwart her aims, or interfering with her attempt to pursue them. Other times we respect a person's aims by taking positive action to help her pursue them.But how exactly does respect forpersonstranslate into respect for theiraims?And which aims merit respect? One answer comes from Kant. (shrink)

This paper distinguishes and critiques several forms of pluralism about the levels of selection, and introduces a novel way of thinking about the biological properties and processes typically conceptualized in terms of distinct levels. In particular, "levels" should be thought of as being entwined or fused. Since the pluralism discussed is held by divergent theorists, the argument has implications for many positions in the debate over the units of selection. And since the key points on which the paper turns apply (...) beyond this specific issue, the paper may prove of general interest in thinking about the metaphysics of science. (shrink)

Introduction in chapter viii of book ii of An Essay Concerning Human Understanding, John Locke provides various putative lists of primary qualities. Insofar as they have considered the variation across Locke's lists at all, commentators have usually been content simply either to consider a self-consciously abbreviated list (e.g., "Size, Shape, etc.") or a composite list as the list of Lockean primary qualities, truncating such a composite list only by omitting supposedly co-referential terms. Doing the latter with minimal judgment about what (...) terms are co-referential gives us the following list of eleven qualities (in the order in which they appear in this chapter of the Essay): solidity, extension, figure, mobility, motion or rest, number, bulk, texture, motion, size, and situation. Perhaps surprisingly given the attention to the primary/secondary distinction since Locke, Locke's primary qualities themselves have received little more than passing mention in the bulk of the subsequent literature. In particular, no discussion both offers an interpretation of Locke's conception of primary qualities and makes sense of Locke's various lists as lists of primary qualities. A central motivation for this paper is the idea that these two tasks are not independent. (shrink)

According to memory foundationalism, seeming to remember that P is prima facie justification for believing that P. There is a common objection to this theory: If I previously believed that P carelessly (i.e. without justification) and later seem to remember that P, then (according to memory foundationalism) I have somehow acquired justification for a previously unjustified belief. In this paper, I explore this objection. I begin by distinguishing between two versions of it: One where I seem to remember that P (...) while also seeming to remember being careless in my original believing that P and the other where I seem to remember that P while not seeming to remember my past carelessness. I argue that the former case is the real challenge for memory foundationalism. After establishing the case of unforgotten carelessness as objection to memory foundationalism, I recast memory foundationalism in way that allows it to escape this objection. (shrink)

Laws of nature seem to take two forms. Fundamental physics discovers laws that hold without exception, ‘strict laws’, as they are sometimes called; even if some laws of fundamental physics are irreducibly probabilistic, the probabilistic relation is thought not to waver. In the nonfundamental, or special, sciences, matters differ. Laws of such sciences as psychology and economics hold only ceteris paribus – that is, when other things are equal. Sometimes events accord with these ceteris paribus laws (c.p. laws, hereafter), but (...) sometimes the laws are not manifest, as if they have somehow been placed in abeyance: the regular relation indicative of natural law can fail in circumstances where an analogous outcome would effectively refute the assertion of strict law. Many authors have questioned the supposed distinction between strict laws and c.p. laws. The brief against it comprises various considerations: from the complaint that c.p. clauses are void of meaning to the claim that, although understood well enough, they should appear in all law-statements. These two concerns, among others, are addressed in due course, but first, I venture a positive proposal. I contend that there is an important contrast between strict laws and c.p. laws, one that rests on an independent distinction between combinatorial and noncombinatorial nomic principles.2 Instantiations of certain properties, e.g., mass and charge, nomically produce individual forces, or more generally, causal influences,3 in accordance with noncombinatorial.. (shrink)

The first half of this review article on Locke on primary and secondary qualities leads up to a fairly straightforward reading of what Locke says about the distinction in Essay II.viii, one that, in its general outlines, represents a sympathetic understanding of Locke’s discussion. The second half of the paper turns to consider a few of the ways in which interpreting Locke on primary and secondary qualities has proven more complicated. Here we take up what is sometimes called the Berkeleyan (...) interpretation of Locke, the understanding of Locke’s resemblance thesis, and Locke’s views of qualities and their relationship to powers. (shrink)

, whereby some causes are deemed more important than others, are ubiquitous in historical studies. Drawing from influential recent work on causation, I develop a definition of causal-explanatory strength. This makes clear exactly which aspects of explanatory weighting are subjective and which objective. It also sheds new light on several traditional issues, showing for instance that: underlying causes need not be more important than proximate ones; several different causes can each be responsible for most of an effect; small causes need (...) not be less important than big ones; and non-additive interactive effects between causes present no particular difficulty. Key Words: causation • explanation • history • interaction • proximate • underlying. (shrink)

Much has been said about Confucius’ negative formulation of the Golden Rule. Most discussions center on explaining why this formulation, while negative, does not differ at all in intention from the positive formulation. It is my view that such attempts may have the effect of blurring the essential point behind the specifically negative formulation, a point which I hope to elucidate in this essay. It is my first contention that such a negative formulation is consonant with other basic implicit Confucian (...) attitudes such as modesty and the belief in the inherent goodness of human nature. My second contention is that this negative formulation has the intent and/or effect of promoting growth and, more importantly, preventing moral harm. My broader thesis is that the negative version of the Golden Rule does differ significantly from the positive version and that the difference that exists might well have been intended by Confucius to highlight the nature of his most basic moral principle. (shrink)

J. L. Schellenberg claims that the weakness of evidence for God’s existence is not merely a sign that God is hidden, “it is a revelation that God does not exist.” In Divine Hiddenness : New Essays, Michael J. Murray provides a “soul-making” defense of God’s hiddenness, arguing that if God were not hidden, then some of us would lose what many theists deem a good thing: the ability to develop morally significant characters. In this paper, I argue that Murray’s soul-making (...) defense not only fails to defend God’s hiddenness, it produces an argument for the nonexistence of God. (shrink)

The predicates 'is outgrown by Theaetetus,' 'is 300 miles west of a lemur,' and 'is such that 9 is odd' denote properties, but there is a sense in which these properties are not genuine features of the objects that have them. The fact that we find these mere-Cambridge properties odd has something to do with their relational character. But relationality in itself is not an adequate criterion for property-genuineness for there are many relational properties that do not qualify as mere-Cambridge. (...) The goal of this essay is to isolate the special type of relationality needed to explain what makes a property genuine. In the process, the author evaluates causal accounts of property-genuineness, and shows how the analysis presented is superior. (shrink)

Addiction theorists have often utilized the metaphor of the blind men and the elephant to illustrate the complex nature of addiction and the varied methodological approaches to studying it. A common purported upshot is skeptical in nature: due to these complexities, it is not possible to offer a unifying account of addiction. I think that this is a mistake. The elephant is real–there is a _there_ there. Here, I defend a dispositionalist account of addiction as _the systematic disposition to fail (...) to control one’s desires to engage in certain types of behaviors_. I explain this position, defend the inclusion of desires and impaired control, and flesh out the notion of _systematicity_ central to my account. I then illustrate how my dispositionalist framework can unify the disparate and seemingly incompatible accounts of addiction (and their respective methodological approaches). I close with a brief plan to extend and implement my account. (shrink)

Standard statistical measures of strength of association, although pioneered by Pearson deliberately to be acausal, nowadays are routinely used to measure causal efficacy. But their acausal origins have left them ill suited to this latter purpose. I distinguish between two different conceptions of causal efficacy, and argue that: 1) Both conceptions can be useful 2) The statistical measures only attempt to capture the first of them 3) They are not fully successful even at this 4) An alternative definition more squarely (...) based on causal thinking not only captures the second conception, it can also capture the first one better too. (shrink)

This paper responds to Kenneth Waters’s account of actual difference making. Among other things, I argue that although Waters is right that researchers may sometimes be justified in focusing on genes rather than other causes of phenotypic traits, he is wrong that the apparatus of actual difference makers overcomes the traditional causal parity thesis.

In this paper I try to illuminate the Rawlsian architectonic through an interpretation of what Rawls’ Lectures on the History of Political Philosophy say about Rousseau. I argue that Rawls’ emphasis there when discussing Rousseau on interpreting amour-propre so as to make it compatible with a life in at least some societies draws attention to, and helps explicate, an analogous feature of his own work, the strains of commitment broadly conceived. Both are centrally connected with protecting a sense of self (...) which is vital for one’s own agency. This allows us to appreciate better than much of the literature presently does the requirement for Rawls that justice and the good are congruent, that a society of justice does not disfigure citizens’ ability to live out lives relatively unmarked by relations of domination. Some comments on G. A. Cohen’s critiques of Rawls are made. (shrink)