This paper takes up the question of knowing one's general mental traits, including one's goals, beliefs, and motives. One conclusion is that this is a difficult project. The issue of attributing to oneself ulterior or hidden motives is considered.

This essay critiques the return to objects posited by certain new materialisms, most specifically the speculative realism of Harman, Meillassoux and Brassier. It argues that their “non-relational” and “autonomous” ontology represents a neo-positivist conception of reality. In place of such an atomistic ontology, I will suggest that the new materialisms develop a more productive, “non-reductive materialism”—a term drawn from analytic philosophy of mind. I will interpret Merleau-Ponty and Jean-Luc Nancy as crucial examples of such a materialism on the continental (...) side. Rather than being based on the non-relational innerness of an object, this position instead takes into account matter’s fundamentally extended nature. Confirmed by examples such as the growing evidence for neuroplasticity, the externalist, non-reductive view advances the new materialist argument that matter is “agentive” and “active” rather than “mechanic” and “passive,” without slipping into an anti-social-constructionist biologism or behaviorism. (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 advent of contemporary evolutionary theory ushered in the eventual decline of Aristotelian Essentialism (Æ) – for it is widely assumed that essence does not, and cannot have any proper place in the age of evolution. This paper argues that this assumption is a mistake: if Æ can be suitably evolved, it need not face extinction. In it, I claim that if that theory’s fundamental ontology consists of dispositional properties, and if its characteristic metaphysical machinery is interpreted within the framework (...) of contemporary evolutionary developmental biology, an evolved essentialism is available. The reformulated theory of Æ offered in this paper not only fails to fall prey to the typical collection of criticisms, but is also independently both theoretically and empirically plausible. The paper contends that, properly understood, essence belongs in the age of evolution. (shrink)

Post-market pharmaceutical surveillance or ‘pharmacovigilance’ relies on the reporting of suspected adverse drug reactions to regulatory databases. Recently, more ‘active’ methods that directly involve patients in identifying and reporting suspected adverse drug reactions have been suggested. This is different than traditional ‘passive’ methods, e.g., using databases without contacting patients directly. Though there are benefits to active pharmacovigilance, it is not without its potential risks. Here I highlight one of those risks – the nocebo effect. Nocebo effects are harms that are (...) thought to arise by conditioning or negative expectation. If a patient engaged in active pharmacovigilance is improperly motivated to seek out and report suspected adverse drug reactions, nocebo harms can occur. Not only is this a bioethical concern about harm, but it is also an epistemic or data-quality problem. Since nocebo effects are not due to the pharmacological properties of the drugs under investigation, nocebo effects reported as suspected adverse drug reactions constitute false positives in these databases. (shrink)

Side effects are ubiquitous in medicine and they often play a role in treatment decisions for patients and clinicians alike. Philosophers and health researchers often use side effects to illustrate issues with contemporary medical research and practice. However, technical definitions of ‘side effect’ differ among health authorities. Thus, determining the side effects of an intervention can differ depending on whose definition we assume. Here I review some of the common definitions of side effect and highlight their issues. In response, I (...) offer an account of side effects as jointly (i) unintended and (ii) effects due to the causal capacities or invariances of an intervention. I discuss (i) by examining the intentions or reasons behind therapeutic interventions, and I discuss (ii) by appealing to a manipulationist model of causation. The analysis here highlights that side effects are conceptually distinct from related outcomes like adverse events, adverse drug reactions, and placebo effects. The analysis also allows for reflection on the utility of ‘side effect’ as a technical term in medical research and practice. (shrink)

Although they are continually compositionally reconstituted and reconfigured, organisms nonetheless persist as ontologically unified beings over time – but in virtue of what? A common answer is: in virtue of their continued possession of the capacity for morphological invariance which persists through, and in spite of, their mereological alteration. While we acknowledge that organisms‟ capacity for the “stability of form” – homeostasis - is an important aspect of their diachronic unity, we argue that this capacity is derived from, and grounded (...) in a more primitive one – namely, the homeodynamic capacity for the “specified variation of form”. In introducing a novel type of causal power – a „structural power‟ – we claim that it is the persistence of their dynamic potential to produce a specified series of structurally adaptive morphologies which grounds organisms‟ privileged status as metaphysically “one over many” over time. (shrink)

Though the realm of biology has long been under the philosophical rule of the mechanistic magisterium, recent years have seen a surprisingly steady rise in the usurping prowess of process ontology. According to its proponents, theoretical advances in the contemporary science of evo-devo have afforded that ontology a particularly powerful claim to the throne: in that increasingly empirically confirmed discipline, emergently autonomous, higher-order entities are the reigning explanantia. If we are to accept the election of evo-devo as our best conceptualisation (...) of the biological realm with metaphysical rigour, must we depose our mechanistic ontology for failing to properly “carve at the joints” of organisms? In this paper, I challenge the legitimacy of that claim: not only can the theoretical benefits offered by a process ontology be had without it, they cannot be sufficiently grounded without the metaphysical underpinning of the very mechanisms which processes purport to replace. The biological realm, I argue, remains one best understood as under the governance of mechanistic principles. (shrink)

Although contemporary metaphysics has recently undergone a neo-Aristotelian revival wherein dispositions, or capacities are now commonplace in empirically grounded ontologies, being routinely utilised in theories of causality and modality, a central Aristotelian concept has yet to be given serious attention – the doctrine of hylomorphism. The reason for this is clear: while the Aristotelian ontological distinction between actuality and potentiality has proven to be a fruitful conceptual framework with which to model the operation of the natural world, the distinction between (...) form and matter has yet to similarly earn its keep. In this chapter, I offer a first step toward showing that the hylomorphic framework is up to that task. To do so, I return to the birthplace of that doctrine - the biological realm. Utilising recent advances in developmental biology, I argue that the hylomorphic framework is an empirically adequate and conceptually rich explanatory schema with which to model the nature of organisms. (shrink)

As there is currently a neo-Aristotelian revival currently taking place within contemporary metaphysics and dispositions, or causal powers are now being routinely utilised in theories of causality and modality, more attention is beginning to be paid to a central Aristotelian concern: the metaphysics of substantial unity, and the doctrine of hylomorphism. In this paper, I distinguish two strands of hylomorphism present in the contemporary literature and argue that not only does each engender unique conceptual difficulties, but neither adequately captures the (...) metaphysics of Aristotelian hylomorphism. Thus both strands of contemporary hylomorphism, I argue, fundamentally misunderstand what substantial unity amounts to in the hylomorphic framework – namely, the metaphysical inseparability of matter and form. (shrink)

The underreporting of suspected adverse drug reactions hinders pharmacovigilance. Solutions to underreporting are oftentimes directed at clinicians and health care professionals. However, given the recent rise of public inclusion in medical science, solutions may soon begin more actively involving patients. I aim to offer an evaluative framework for future possible proposals that would engage patients with the aim of mitigating underreporting. The framework may also have value in evaluating current reporting practices. The offered framework is composed of three criteria that (...) are bioethical, social-epistemic, and pragmatic: (i) patients should not be exposed to undue harms, e.g., nocebo effects; (ii) data should be collected, analyzed, and communicated prioritizing pharmacovigilance’s aims, i.e., free from industry bias; and (iii) proposals should account for existing and foreseeable pragmatic constraints like clinician ‘buy in’ and existing reporting infrastructure. Proposals to engage patients in pharmacovigilance that fulfil or address these criteria are preferable to those that do not. (shrink)

Dispositional properties are often referred to as ‘causal powers’, but what does dispositional causation amount to? Any viable theory must account for two fundamental aspects of the metaphysics of causation – the causal complexity and context sensitivity of causal interactions. The theory of mutual manifestations attempts to do so by locating the complexity and context sensitivity within the nature of dispositions themselves. But is this theory an acceptable first step towards a viable theory of dispositional causation? This paper argues that (...) the reconceptualization that the theory entails comes at too high a price, and is an unnecessary step in the wrong direction: these two central aspects concerning the metaphysics of causation can and should be accounted for in a dispositional account of causation without it. (shrink)

According to contemporary ‘process ontology’, organisms are best conceptualised as spatio-temporally extended entities whose mereological composition is fundamentally contingent and whose essence consists in changeability. In contrast to the Aristotelian precepts of classical ‘substance ontology’, from the four-dimensional perspective of this framework, the identity of an organism is grounded not in certain collections of privileged properties, or features which it could not fail to possess, but in the succession of diachronic relations by which it persists, or ‘perdures’ as one entity (...) over time. In this paper, I offer a novel defence of substance ontology by arguing that the coherency and plausibility of the radical reconceptualisation of organisms proffered by process ontology ultimately depends upon its making use of the ‘substantial’ principles it purports to replace. (shrink)

Exploratory experiments are widely characterized as experiments that do not test hypotheses. Experiments that do test hypotheses are characterized as confirmatory experiments. Philosophers have pointed out that research programmes can be both confirmatory and exploratory. However, these definitions preclude single experiments being characterized as both exploratory and confirmatory; how can an experiment test and not test a hypothesis? Given the intuition that some experiments are exploratory, some are confirmatory, and some are both, a recharacterization of the relationship between exploratory and (...) confirmatory experimentation is needed. I discuss ‘phase IV’ trials to show what this recharacterization could look like. Phase IV trials can be exploratory and confirmatory insofar as they concurrently test hypotheses and explore for unforeseen phenomena. Even if it is uncontroversial that a single experiment can have multiple aims, the recharacterization of the relationship between exploratory and confirmatory experimentation is still required for these aims to be held together coherently. I offer an alternative characterization of the relationship between exploratory and confirmatory experimentation where the former remains a distinct kind of experimentation but is not characterized as non-hypothesis-testing. (shrink)

Precision medicine functions by grouping patients along genetic, molecular, and related ‘-omics’ factors. This stratification relies on large, growing databases of patient-volunteered information. Both private companies and government bodies incentivize patients to volunteer this genetic information appealing to the creation of collaborative patient partnerships and the concept of empowerment. This paper aims to address two related questions: (1) what is the actual nature of patient participation in precision medicine research? And (2) is this participation in precision medicine research really that (...) empowering for the average patient? I contend that firstly, the nature of this participation is best conceived of as merely contributory. Contributory participation, as it will be shown, falls short of collaboration. The partnership created by participation in precision medicine research is not one of sharing values, equal say in decisions, or shared benefit. Secondly, I contend that there are important caveats to claims that patient participation in precision medicine is empowering. Empowerment is hindered by the type of participation, the practical use or actionability of genetic data, genetic literacy, the cost of precision drugs for patients that qualify for them, and bioethical considerations of informed consent. (shrink)

In identifying intrinsic molecular chance and extrinsic adaptive pressures as the only causally relevant factors in the process of evolution, the theoretical perspective of the Modern Synthesis had a major impact on the perceived tenability of an ontology of dispositional properties. However, since the late 1970s, an increasing number of evolutionary biologists have challenged the descriptive and explanatory adequacy of this “chance alone, extrinsic only” understanding of evolutionary change. Because morphological studies of homology, convergence, and teratology have revealed a space (...) of possible forms and phylogenetic trajectories that is considerably more restricted than expected, evo-devo has focused on the causal contribution of intrinsic developmental processes to the course of evolution. Evo-devo’s investigation into the developmental structure of the modality of morphology – including both the possibility and impossibility of organismal form – has led to the utilisation of a number of dispositional concepts that emphasise the tendency of the evolutionary process to change along certain routes. In this sense, and in contrast to the perspective of the Modern Synthesis, evo-devo can be described as a “science of dispositions.” This chapter discusses the recent philosophical literature on dispositional properties in evo-devo, exploring debates about both the metaphysical and epistemological aspects of the central dispositional concepts utilised in contemporary evo-devo and addressing the epistemological question of how dispositional properties challenge existing explanatory models in evolutionary biology. (shrink)

According to the proponents of Developmental Systems Theory and the Causal Parity Thesis, the privileging of the genome as “first among equals” with respect to the development of phenotypic traits is more a reflection of our own heuristic prejudice than of ontology - the underlying causal structures responsible for that specified development no more single out the genome as primary than they do other broadly “environmental” factors. Parting with the methodology of the popular responses to the Thesis, this paper offers (...) a novel criterion for ‘causal primacy’, one that is grounded in the ontology of the unique causal role of dispositional properties. This paper argues that, if the genome is conceptualised as realising dispositional properties that are “directed toward” phenotypic traits, the parity of ‘causal roles’ between genetic and extra-genetic factors is no longer apparent, and further, that the causal primacy of the genome is both plausible and defensible. (shrink)

Evolutionary developmental biology represents a paradigm shift in the understanding of the ontogenesis and evolutionary progression of the denizens of the natural world. Given the empirical successes of the evo-devo framework, and its now widespread acceptance, a timely and important task for the philosophy of biology is to critically discern the ontological commitments of that framework and assess whether and to what extent our current metaphysical models are able to accommodate them. In this paper, I argue that one particular model (...) is a natural fit: an ontology of dispositional properties coherently and adequately captures the crucial casual-cum-explanatory role that the fundamental elements of evo-devo play within that framework. (shrink)

The biological sciences have always proven a fertile ground for philosophical analysis, one from which has grown a rich tradition stemming from Aristotle and flowering with Darwin. And although contemporary philosophy is increasingly becoming conceptually entwined with the study of the empirical sciences with the data of the latter now being regularly utilised in the establishment and defence of the frameworks of the former, a practice especially prominent in the philosophy of physics, the development of that tradition hasn’t received the (...) wider attention it so thoroughly deserves. This review will briefly introduce some recent significant topics of debate within the philosophy of biology, focusing on those whose metaphysical themes (in everything from composition to causation) are likely to be of wide-reaching, cross-disciplinary interest. (shrink)

According to dispositionalism, de re modality is grounded in the intrinsic natures of dispositional properties. Those properties are able to serve as the ground of de re modal truths, it is said, because they bear a special relation to counterfactual conditionals, one of truthmaking. However, because dispositionalism purports to ground de re modality only on the intrinsic natures of dispositional properties, it had better be the case that they do not play that truthmaking role merely in virtue of their being (...) embedded in some particular, extrinsic causal context. This paper examines a recent argument against dispositionalism that purports to show that the intrinsicality of that relation cannot be maintained, due to the ceteris paribus nature of the counterfactuals that dispositions make-true. When two prominent responses are examined, both are found wanting: at best, they require unjustified special pleading, and at worst, they amount to little more than ad hoc conceptual trickery. (shrink)

Supra-Bayesianism is the Bayesian response to learning the opinions of others. Probability pooling constitutes an alternative response. One natural question is whether there are cases where probability pooling gives the supra-Bayesian result. This has been called the problem of Bayes-compatibility for pooling functions. It is known that in a common prior setting, under standard assumptions, linear pooling cannot be nontrivially Bayes-compatible. We show by contrast that geometric pooling can be nontrivially Bayes-compatible. Indeed, we show that, under certain assumptions, geometric and (...) Bayes-compatible pooling are equivalent. Granting supra-Bayesianism its usual normative status, one upshot of our study is thus that, in a certain class of epistemic contexts, geometric pooling enjoys a normative advantage over linear pooling as a social learning mechanism. We discuss the philosophical ramifications of this advantage, which we show to be robust to variations in our statement of the Bayes-compatibility problem. (shrink)

_Colonialism and Neo-Colonialism_ is a classic critique of France's policies in Algeria in the 1950s and 1960s and inspired much subsequent writing on colonialism, post-colonialism, politics, and literature. It includes Sartre's celebrated preface to Fanon's classic _Wretched_ _of the Earth. Colonialism and Neo-Colonialism _ had a profound impact on French intellectual life, inspiring many other influential French thinkers and critics of colonialism such as Jean-Francois Lyotard, Frantz Fanon, Pierre Bourdieu and Jacques Derrida.

The underreporting of suspected adverse drug reactions remains a primary issue for contemporary post-market drug surveillance or ‘pharmacovigilance.’ Pharmacovigilance pioneer W.H.W. Inman argued that ‘deadly sins’ committed by clinicians are to blame for underreporting. Of these ‘sins,’ ignorance and lethargy are the most obvious and impactful in causing underreporting. However, recent analyses show that diffidence, insecurity, and indifference additionally play a major role. I aim to augment our understanding of diffidence, insecurity, and indifference by arguing these sins are underwritten by (...) value judgments arising via epistemic risk. I contend that ‘evidence-based’ medicine codifies these sins. (shrink)

A study is reported testing two hypotheses about a close parallel relation between indicative conditionals, if A then B , and conditional bets, I bet you that if A then B . The first is that both the indicative conditional and the conditional bet are related to the conditional probability, P(B|A). The second is that de Finetti's three-valued truth table has psychological reality for both types of conditional— true , false , or void for indicative conditionals and win , lose (...) , or void for conditional bets. The participants were presented with an array of chips in two different colours and two different shapes, and an indicative conditional or a conditional bet about a random chip. They had to make judgements in two conditions: either about the chances of making the indicative conditional true or false or about the chances of winning or losing the conditional bet. The observed distributions of responses in the two conditions were generally related to the conditional probability, supporting the first hypothesis. In addition, a majority of participants in further conditions chose the third option, “void”, when the antecedent of the conditional was false, supporting the second hypothesis. (shrink)

The aim of this paper is to clarify the role of category theory in the foundations of mathematics. There is a good deal of confusion surrounding this issue. A standard philosophical strategy in the face of a situation of this kind is to draw various distinctions and in this way show that the confusion rests on divergent conceptions of what the foundations of mathematics ought to be. This is the strategy adopted in the present paper. It is divided into 5 (...) sections. We first show that already in the set theoretical framework, there are different dimensions to the expression foundations of. We then explore these dimensions more thoroughly. After a very short discussion of the links between these dimensions, we move to some of the arguments presented for and against category theory in the foundational landscape. We end up on a more speculative note by examining the relationships between category theory and set theory. (shrink)

It is widely held that under ordinal utility, utility differences are ill-defined. Allegedly, for these to be well-defined (without turning to choice under risk or the like), one should adopt as a new kind of primitive quaternary relations, instead of the traditional binary relations underlying ordinal utility functions. Correlatively, it is also widely held that the key structural properties of quaternary relations are entirely arbitrary from an ordinal point of view. These properties would be, in a nutshell, the hallmark of (...) cardinal utility. While much is obviously true in these two tenets, this note explains why, as stated, they should be abandoned. Any ordinal utility function induces a rich quaternary relation. There is such a thing as ordinal utility differences. Furthermore, this induced quaternary relation respects, apart from completeness, the most standard structural properties of quaternary relations. These properties are, from an ordinal point of view, anything but arbitrary; from a quaternary perspective only completeness should be considered the hallmark—if any—of cardinal utility. These facts are explained to be especially relevant to the critical appreciation of the ordinalist methodology. (shrink)

It is popular to hold that emotions are evaluative. On the standard account, the evaluative character of emotion is understood in epistemic terms: emotions apprehend or make us aware of value properties. As this account is commonly elaborated, emotions are experiences with evaluative intentional content. In this paper, I am concerned with a recent alternative proposal on how emotions afford awareness of value. This proposal does not ascribe evaluative content to emotions, but instead conceives of them as evaluative at the (...) level of intentional mode or attitude. I first argue that this proposal fails to make emotions intelligible as value apprehensions. There are reasons to suppose that emotions do not apprehend value to begin with, but are related to values in a different, non-epistemic sense. I then go on to show that the notion of an evaluative intentional mode can still help elucidate the evaluative character of emotion. I argue that there is a plausible non-epistemic understanding of the view that emotions are evaluative modes. On this account, emotions are not ways of apprehending values, but ways of acknowledging values. (shrink)

The Sure-Thing Principle famously appears in Savage’s axiomatization of Subjective Expected Utility. Yet Savage introduces it only as an informal, overarching dominance condition motivating his separability postulate P2 and his state-independence postulate P3. Once these axioms are introduced, by and large, he does not discuss the principle any more. In this note, we pick up the analysis of the Sure-Thing Principle where Savage left it. In particular, we show that each of P2 and P3 is equivalent to a dominance condition; (...) that they strengthen in different directions a common, basic dominance axiom; and that they can be explicitly combined in a unified dominance condition that is a candidate formal statement for the Sure-Thing Principle. Based on elementary proofs, our results shed light on some of the most fundamental properties of rational choice under uncertainty. In particular they imply, as corollaries, potential simplifications for Savage’s and the Anscombe- Aumann axiomatizations of Subjective Expected Utility. Most surprisingly perhaps, they reveal that in Savage’s axiomatization, P3 can be weakened to a natural strengthening of so-called Obvious Dominance. (shrink)

Est-il possible de parler de ce qui n’est pas ou d’y penser sans présupposer une forme d’être pour cela même que nous pensons ne pas exister? La vieille énigme parménidienne, qui hante toujours la philosophie contemporaine, est au cœur non seulement de la philosophie médiévale mais aussi des études médiévales, comme en témoigne le récent ouvrage d’Alain de Libera sur la référence vide. L’objet de cette étude est en comparaison beaucoup plus...

It is widely assumed that emotions are evaluative. Moreover, many authors suppose that emotions are important or valuable as evaluations. According to the currently dominant version of cognitivism, emotions are evaluative insofar as they make us aware of value properties of their intentional objects. In attributing to emotions an epistemic role, this view conceives of them as epistemically valuable. In this paper, I argue that proponents of this account mischaracterize the evaluative character of emotions and, a fortiori, their value. Moreover, (...) I propose an alternative view of emotional evaluation, according to which emotions are practically rather than epistemically important. As I argue, emotions are ways of acknowledging their intentional objects as (dis)valuable. As such, they do not apprehend values but make them count. I elaborate this idea by drawing an analogy with legal and political sanctions. The resulting view has it that emotions are practically important in that they affirm the cares and concerns which serve as standards of emotional evaluation. (shrink)

I examine the once popular claim according to which interpersonal comparisons of welfare are necessary for social choice. I side with current social choice theorists in emphasizing that, on a narrow construal, this necessity claim is refuted beyond appeal. However, I depart from the opinion presently prevailing in social choice theory in highlighting that on a broader construal, this claim proves not only compatible with, but even comforted by, the current state of the field. I submit that all in all, (...) the most accurate philosophical assessment consists not in flatly rejecting this necessity claim, but in accepting it in a suitably revised form. (shrink)

The basic axioms or formal conditions of decision theory, especially the ordering condition put on preferences and the axioms underlying the expected utility formula, are subject to a number of counter-examples, some of which can be endowed with normative value and thus fall within the ambit of a philosophical reflection on practical rationality. Against such counter-examples, a defensive strategy has been developed which consists in redescribing the outcomes of the available options in such a way that the threatened axioms or (...) conditions continue to hold. We examine how this strategy performs in three major cases: Sen's counterexamples to the binariness property of preferences, the Allais paradox of EU theory under risk, and the Ellsberg paradox of EU theory under uncertainty. We find that the strategy typically proves to be lacking in several major respects, suffering from logical triviality, incompleteness, and theoretical insularity. To give the strategy more structure, philosophers have developed “principles of individuation”; but we observe that these do not address the aforementioned defects. Instead, we propose the method of checking whether the strategy can overcome its typical defects once it is given a proper theoretical expansion. We find that the strategy passes the test imperfectly in Sen's case and not at all in Allais's. In Ellsberg's case, however, it comes close to meeting our requirement. But even the analysis of this more promising application suggests that the strategy ought to address the decision problem as a whole, rather than just the outcomes, and that it should extend its revision process to the very statements it is meant to protect. Thus, by and large, the same cautionary tale against redescription practices runs through the analysis of all three cases. A more general lesson, simply put, is that there is no easy way out from the paradoxes of decision theory. (shrink)

The Planteome project provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology, and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides (...) access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. (shrink)

It is popular to hold that our primary epistemic access to specific response-dependent properties like the fearsome or admirable (or so-called ‘affective properties’) is constituted by the corresponding emotion. I argue that this view is incompatible with a widely held meta-ethical view, according to which affective properties have deontic force. More specifically, I argue that this view cannot accommodate for the requirement that deontic entities provide guidance. If affective properties are to guide the formation of the corresponding emotion, our primary (...) access to them cannot be provided by that same emotion. (shrink)

A prominent version of emotional cognitivism is the view that emotions are preceded by awareness of value. In a recent paper, Jonathan Mitchell (2019) has attacked this view (which he calls the content-priority view). According to him, extant suggestions for the relevant type of pre-emotional evaluative awareness are all problematic. Unless these problems can be overcome, he argues, the view does not represent a plausible competitor to rivaling cognitivist views. As Mitchell supposes, the view is not mandatory since its core (...) motivations can be accommodated by competing views, too. I argue that Mitchell's case against the content-priority view is unconvincing as it misconceives the principal motivation for the view. As I show, properly reconstructed, this motivation provides a strong case for the indispensability of the view to any adequate cognitivist treatment of emotion. Moreover, Mitchell's survey of candidates for pre-emotional value awareness can be seen to rest on problematic phenomenological assumptions. (shrink)

According to a well-known view in the philosophy of mind, intentional attitudes by their very nature satisfy requirements of rationality (e.g. Davidson 1980; Dennett 1987; Millar 2004). This view (which I shall call Constitutivism) features prominently as the ‘principle of minimal rationality’ in de Sousa’s monograph The Rationality of Emotion (1987). By explicating this principle in terms of the notion of the formal object of an attitude, de Sousa articulates an interesting and original version of Constitutivism, which differs in important (...) respects from other extant versions. In this paper, I explore this version of Constitutivism against the background of recent developments in the theory of rationality and make explicit its ramifications for the long-standing dispute over whether the mind is essentially normative. My focus will be on how to conceive of the form of the rationality requirements that attitudes as such must satisfy according to this principle. I argue that, although de Sousa seems officially to endorse a structuralist conception of rationality, according to which these requirements are requirements of coherence, his considerations on formal objects suggest that they are more aptly conceived in terms of a reasons-responsive conception of rationality. I further argue that which of these two readings we choose makes a significant difference to the prospect of vindicating the essential normativity of mind by invoking the principle of minimal rationality. (shrink)

I examine Bayle's infamous statement that Christian mysteries are not only "above" human reason, but are "against" it. I put it back in the context of 16th-17th century Reformed thought. I then discuss the relation between reason and faith according to Bayle.

It is a popular thought that emotions play an important epistemic role. Thus, a considerable number of philosophers find it compelling to suppose that emotions apprehend the value of objects and events in our surroundings. I refer to this view as the Epistemic View of emotion. In this paper, my concern is with a rivaling picture of emotion, which has so far received much less attention. On this account, emotions do not constitute a form of epistemic access to specific axiological (...) aspects of their objects. Instead it proposes that they are ways of taking a stand or position on the world. I refer to this as the Position-Taking View of emotion. Whilst some authors seem sympathetic to this view, this it has so far not been systematically motivated and elaborated. In this paper, I fill this gap and propose a more adequate account of our emotional engagement with the world than the predominant epistemic paradigm. I start by highlighting the specific way in which emotions are directed at something, which I contrast with the intentionality of perception and other forms of apprehension. I then go on to offer a specific account of the valence of emotion and show how this account and the directedness of emotions makes them intelligible as a way of taking a position on something. (shrink)

State-dependent utility is a problem for the behavioural branch of decision theory under uncertainty. It questions the very possibility that beliefs be revealed by choice data. According to the current literature, all models of beliefs are equally exposed to the problem. Moreover, the problem is solvable only when the decision-maker can influence the resolution of uncertainty. This article gives grounds to reject these two views. The various models of beliefs can be shown to be unequally exposed to the problem of (...) state-dependent utility. The problem can be argued to be solved even when the decision-maker has no influence over the resolution of uncertainty. The implications of such reappraisal for a philosophical appreciation of the revealed preference methodology are discussed. (shrink)

Le réalisme scientifique occupe une place centrale dans le système philosophique de Mario Bunge. Au cœur de cette thèse, on trouve l’affirmation selon laquelle nous pouvons connaître le monde partiellement. Il s’ensuit que les théories scientifiques ne sont pas totalement vraies ou totalement fausses, mais plutôt partiellement vraies et partiellement fausses. Ces énoncés sur la connaissance scientifique, à première vue plausible pour quiconque est familier avec la pratique scientifique, demandent néanmoins à être clarifiés, précisés et, ultimement, à être inclus dans (...) un cadre théorique plus large et rigoureux. Depuis ses toutes premières publications sur ces questions et jusqu’à récemment, Mario Bunge n’a cessé d’interpeller les philosophes afin qu’ils développent une théorie, au sens propre du terme, de la vérité partielle afin de clarifier les enjeux épistémologiques liés au réalisme scientifique. Bunge a lui-même proposé plusieurs parties de cette théorie au fil des années, mais aucune de ces propositions ne l’a satisfait pleinement et la construction de cette théorie demeure un problème entier. Dans ce texte, nous passerons rapidement en revue certaines des approches proposées par Bunge dans ses publications et nous esquisserons certaines pistes qui devraient servir à tout le moins de desiderata pour la construction d’une théorie de la vérité partielle. (shrink)

While there is considerable disagreement on the precise nature of material objecthood, it is standardly assumed that material objects must be spatial. In this paper, I provide two arguments against this assumption. The first argument is made from largely a priori considerations about modal plenitude. The possibility of non-spatial material objects follows from commitment to certain plausible principles governing material objecthood and plausible principles regarding modal plenitude. The second argument draws from current philosophical discussions regarding theories of quantum gravity and (...) the emergence of spacetime. When it is appreciated what possible worlds these current theories commit us to, the possibility of non-spatial material objects will follow. Thus, either route will lead us to the possibility of non-spatial material objects. The significance of this result is that we need to revise our accounts of material objecthood to both accommodate these possibilities and the theories that lead to them. (shrink)

This paper explores the origins of the term "causa sine qua non" used by Durand de Saint-Pourçain to describe the role of material things in knowledge. I show that its technical meaning comes from the Stoics and was transmitted to the Middle Ages by Boethius' commentary on Cicero's Topics. The expression "sine qua non" here does not have the ordinary and restricted meaning of "indispensable", "necessary condition", which can also apply to direct, per se causes of an effect. In the (...) present context, sine qua non causes do not act on the effect in question, either as concomitant, secondary, or instrumental causes, or as remote causes. They act only on that which hinders the actualization of a potentiality, in order to remove that obstacle. For example, the removal of a support that prevented something from falling does not act on that thing, nor does it add anything to its tendency to fall; it simply enables that thing to exercise its own actualization. Similarly, in cognitive processes, external things do not impose anything on the soul, but simply give it the opportunity to actualize its faculties of its own accord. I situate Durand's use of this form of causality in the context of late 13th/early 14th century theories of cognition, among several other attempts to find an alternative theory to the standard Aristotelian model and to maintain the pure activity of the soul with respect to the body. (shrink)

The representational theory of measurement has long been the central paradigm in the philosophy of measurement. Such is not the case anymore, partly under the influence of the critique according to which RTM offers too poor descriptions of the measurement procedures actually followed in science. This can be called the metrological critique of RTM. I claim that the critique is partly irrelevant. This is because, in general, RTM is not in the business of describing measurement procedures, be it in idealized (...) form. To support this claim, I present various cases where RTM can be said to investigate measurement without providing any measurement procedure. Such limit cases lead to a better understanding of the RTM project. They also illustrate some of the questions which the philosophy of measurement can explore, when it is ready to go beyond the metrological viewpoint. (shrink)

Structuralism has recently moved center stage in philosophy of mathematics. One of the issues discussed is the underlying logic of mathematical structuralism. In this paper, I want to look at the dual question, namely the underlying structures of logic. Indeed, from a mathematical structuralist standpoint, it makes perfect sense to try to identify the abstract structures underlying logic. We claim that one answer to this question is provided by categorical logic. In fact, we claim that the latter can be seen—and (...) probably should be seen—as being a structuralist approach to logic and it is from this angle that categorical logic is best understood. (shrink)