The goal of the 2010 Ontology Summit was to address the current shortage of persons with ontology expertise by developing a strategy for the education of ontologists. To achieve this goal we studied how ontologists are currently trained, the requirements identified by organizations that hire ontologists, and developments that might impact the training of ontologists in the future. We developed recommendations for the body of knowledge that should be taught and the skills that should be developed by future ontologists; these (...) recommendations are intended as guidelines for institutions and organizations that may consider establishing a program for training ontologists. Further, we recommend a number of specific actions for the community to pursue. (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 growing proportion of elderly people in society, together with recent advances in robotics, makes the use of robots in elder care increasingly likely. We outline developments in the areas of robot applications for assisting the elderly and their carers, for monitoring their health and safety, and for providing them with companionship. Despite the possible benefits, we raise and discuss six main ethical concerns associated with: (1) the potential reduction in the amount of human contact; (2) an increase in the (...) feelings of objectification and loss of control; (3) a loss of privacy; (4) a loss of personal liberty; (5) deception and infantilisation; (6) the circumstances in which elderly people should be allowed to control robots. We conclude by balancing the care benefits against the ethical costs. If introduced with foresight and careful guidelines, robots and robotic technology could improve the lives of the elderly, reducing their dependence, and creating more opportunities for social interaction. (shrink)

In this paper, we aim to show that the framework of embedded, distributed, or extended cognition offers new perspectives on social cognition by applying it to one specific domain: the psychology of memory. In making our case, first we specify some key social dimensions of cognitive distribution and some basic distinctions between memory cases, and then describe stronger and weaker versions of distributed remembering in the general distributed cognition framework. Next, we examine studies of social influences on memory in cognitive (...) psychology, and identify the valuable concepts and methods to be extended and embedded in our framework; we focus in particular on three related paradigms: transactive memory, collaborative recall, and social contagion. Finally, we sketch our own early studies of individual and group memory developed within our framework of distributed cognition, on social contagion of autobiographical memories, collaborative flashbulb memories, and memories of high school at a high school reunion. We see two reciprocal benefits of this conceptual and empirical framework to social memory phenomena: that ideas about distributed cognition can be honed against and tested with the help of sophisticated methods in the social cognitive psychology of memory; and conversely, that a range of social memory phenomena that are as yet poorly understood can be approached afresh with theoretically motivated extensions of existing empirical paradigms. (shrink)

This paper aims to better motivate the naturalization of metaphysics by identifying and criticizing a class of theories I call ’free range metaphysics’. I argue that free range metaphysics is epistemically inadequate because the constraints on its content—consistency, simplicity, intuitive plausibility, and explanatory power—are insufficiently robust and justificatory. However, since free range metaphysics yields clarity-conducive techniques, incubates science, and produces conceptual and formal tools useful for scientifically engaged philosophy, I do not recommend its discontinuation. I do recommend, however, ending the (...) discipline’s bad faith. That is, I urge that free range metaphysics not be taken to have fully satisfactory epistemic credentials over and above its pragmatic ones. (shrink)

This paper explores the relationship between dignity and robot care for older people. It highlights the disquiet that is often expressed about failures to maintain the dignity of vulnerable older people, but points out some of the contradictory uses of the word ‘dignity’. Certain authors have resolved these contradictions by identifying different senses of dignity; contrasting the inviolable dignity inherent in human life to other forms of dignity which can be present to varying degrees. The Capability Approach (CA) is introduced (...) as a different but tangible account of what it means to live a life worthy of human dignity. It is used here as a framework for the assessment of the possible effects of eldercare robots on human dignity. The CA enables the identification of circumstances in which robots could enhance dignity by expanding the set of capabilities that are accessible to frail older people. At the same time, it is also possible within its framework to identify ways in which robots could have a negative impact, by impeding the access of older people to essential capabilities. It is concluded that the CA has some advantages over other accounts of dignity, but that further work and empirical study is needed in order to adapt it to the particular circumstances and concerns of those in the latter part of their lives. (shrink)

This is a preprint draft. Please cite published version (DOI: 10.1111/mila.12385). The aim of this paper is to provide a novel analysis of anorexia nervosa (AN) in the context of the sense of agency literature. I first show that two accounts of anorexia nervosa that we ought to take seriously— i.e., the first personal reports of those who have experienced it firsthand as well as the research that seeks to explain anorexic behavior from an empirical perspective— appear to be thoroughly (...) in tension with one another in their descriptions of anorexic actions. Rather than proceeding at this point by way of disregarding anorexic testimony as meaningless or insincere, I instead offer a positive account of the sense of agency in anorexia nervosa that renders these two depictions compatible. The resultant picture of anorexic behavior is one that accommodates current empirical findings while also providing valuable insight into how it is that anorexics can sincerely report feeling fully in control over their food restriction. (shrink)

Enactivism and ecological psychology converge on the relevance of the environment in understanding perception and action. On both views, perceiving organisms are not merely passive receivers of environmental stimuli, but rather form a dynamic relationship with their environments in such a way that shapes how they interact with the world. In this paper, I suggest that while enactivism and ecological psychology enjoy a shared specification of the environment as the cognitive domain, on both accounts, the structure of the environment, itself, (...) is unspecified beyond that of contingent relations with the species-typical sensorimotor capacities of perceiving organisms. This lack of specification creates a considerable gap in theory regarding the organization of organisms as coupled with their environments. I argue that this gap can be filled by drawing from resources in developmental systems theory, namely, specifying the environmental state-space as a developmental niche that shapes and is shaped by individual organisms over developmental and, on a population scale, evolutionary time. Defining the environment as an organism’s developmental niche makes it clearer how and why certain contingencies have arisen, in turn, strengthening a joint appeal to both enactivism and ecological psychology as theories asserting complementarity between organisms and their environments. (shrink)

Some contextually sensitive expressions are such that their context independent conventional meanings need to be in some way supplemented in context for the expressions to secure semantic values in those contexts. As we’ll see, it is not clear that there is a paradigm here, but ‘he’ used demonstratively is a clear example of such an expression. Call expressions of this sort supplementives in order to highlight the fact that their context independent meanings need to be supplemented in context for them (...) to have semantic values relative to the context. Many philosophers and linguists think that there is a lot of contextual sensitivity in natural language that goes well beyond the pure indexicals and supplementives like ‘he’. Constructions/expressions that are good candidates for being contextually sensitive include: quantifiers, gradable adjectives including “predicates of personal taste”, modals, conditionals, possessives and relational expressions taking implicit arguments. It would appear that in none of these cases does the expression/construction in question have a context independent meaning that when placed in context suffices to secure a semantic value for the expression/construction in the context. In each case, some sort of supplementation is required to do this. Hence, all these expressions are supplementives in my sense. For a given supplementive, the question arises as to what the mechanism is for supplementing its conventional meanings in context so as to secure a semantic value for it in context. That is, what form does the supplementation take? The question also arises as to whether different supplementives require different kinds of supplementation. Let us call an account of what, in addition to its conventional meaning, secures a semantic value for a supplementive in context a metasemantics for that supplementive. So we can put our two questions thus: what is the proper metasemantics for a given supplementive; and do all supplementives have the same metasemantics? In the present work, I sketch the metasemantics I formulated for demonstratives in earlier work. Next, I briefly consider a number of other supplementives that I think the metasemantics I propose plausibly applies to and explain why I think that. Finally, I consider the prospects for extending the account to all supplementives. In so doing, I take up arguments due to Michael Glanzberg to the effect that supplementives are governed by two different metasemantics and attempt to respond to them. (shrink)

A naturalistic impulse has taken speculative analytic metaphysics in its critical sights. Importantly, the claim that it is desirable or requisite to give metaphysics scientific moorings rests on underlying epistemological assumptions or principles. If the naturalistic impulse toward metaphysics is to be well-founded and its prescriptions to have normative force, those assumptions or principles should be spelled out and justified. In short, advocates of naturalized or scientific metaphysics require epistemic infrastructure. This paper begins to supply it. The author first sketches (...) her conception of suitably naturalized or scientific metaphysics. She then lays out a number of candidate epistemic principles centring around the notion of theoretical constraint. The author offers several arguments for the principles, based on statistical likeliness, agreement, falsity avoidance, and methodological efficiency and inefficiency. Finally, she shows how scientific metaphysics satisfies the epistemic principles and is therefore preferable to its traditional rivals. (shrink)

This paper surveys some of the grounding literature searching for points of contact between theories of ground and science. I find that there are some places where a would-be naturalistic grounding theorist can draw inspiration. I synthesize a list of recommendations for how science may be put to use in theories of ground. I conclude that the prospects for naturalizing the metaphysics of ground are bright.

Philosophers have recently highlighted substantial affinities between causation and grounding, which has inclined some to import the conceptual and formal resources of causal interventionism into the metaphysics of grounding. The prospect of grounding interventionism raises two important questions: exactly what are grounding interventions, and why should we think they enable knowledge of grounding? This paper will approach these questions by examining how causal interventionists have addressed (or might address) analogous questions and then comparing the available options for grounding interventionism. I (...) argue that grounding interventions must be understood in worldly terms, as adding something to or deleting something from the roster of entities, or making some fact obtain or fail to obtain. I consider three bases for counterfactual assessment: imagination, structural equation models, and background theory. I conclude that grounding interventionism requires firmer epistemological foundations, without which the interventionist's epistemology of grounding is incomplete and ineffectually rationalist. (shrink)

In common with traditional forms of epistemic internalism, epistemological disjunctivism attempts to incorporate an awareness condition on justification. Unlike traditional forms of internalism, however, epistemological disjunctivism rejects the so-called New Evil Genius thesis. In so far as epistemological disjunctivism rejects the New Evil Genius thesis, it is revisionary. -/- After explaining what epistemological disjunctivism is, and how it relates to traditional forms of epistemic internalism / externalism, I shall argue that the epistemological disjunctivist’s account of the intuitions underlying the New (...) Evil Genius thought experiment is at best incomplete. As presented, therefore, epistemological disjunctivism is unable to accommodate the core guiding intuitions of epistemic internalism. Given the stated aim of not being revisionary on this score, the view is at a dialectical disadvantage over the traditional forms of epistemic internalism the position is meant to replace. Unfortunately, therefore, at present, the impasse between internalism and externalism remains. (shrink)

This chapter will review selected aspects of the terrain of discussions about probabilities in statistical mechanics (with no pretensions to exhaustiveness, though the major issues will be touched upon), and will argue for a number of claims. None of the claims to be defended is entirely original, but all deserve emphasis. The first, and least controversial, is that probabilistic notions are needed to make sense of statistical mechanics. The reason for this is the same reason that convinced Maxwell, Gibbs, and (...) Boltzmann that probabilities would be needed, namely, that the second law of thermodynamics, which in its original formulation says that certain processes are impossible, must, on the kinetic theory, be replaced by a weaker formulation according to which what the original version deems impossible is merely improbable. Second is that we ought not take the standard measures invoked in equilibrium statistical mechanics as giving, in any sense, the correct probabilities about microstates of the system. We can settle for a much weaker claim: that the probabilities for outcomes of experiments yielded by the standard distributions are effectively the same as those yielded by any distribution that we should take as a representing probabilities over microstates. Lastly, (and most controversially): in asking about the status of probabilities in statistical mechanics, the familiar dichotomy between epistemic probabilities (credences, or degrees of belief) and ontic (physical) probabilities is insufficient; the concept of probability that is best suited to the needs of statistical mechanics is one that combines epistemic and physical considerations. (shrink)

It is possible that the world contains infinitely many agents that have positive and negative levels of well-being. Theories have been developed to ethically rank such worlds based on the well-being levels of the agents in those worlds or other qualitative properties of the worlds in question, such as the distribution of agents across spacetime. In this thesis I argue that such ethical rankings ought to be consistent with the Pareto principle, which says that if two worlds contain the same (...) agents and some agents are better off in the first world than they are in the second and no agents are worse off than they are in the second, then the first world is better than the second. I show that if we accept four axioms – the Pareto principle, transitivity, an axiom stating that populations of worlds can be permuted, and the claim that if the ‘at least as good as’ relation holds between two worlds then it holds between qualitative duplicates of this world pair – then we must conclude that there is ubiquitous incomparability between infinite worlds. I show that this is true even if the populations of infinite worlds are disjoint or overlapping, and that we cannot use any qualitative properties of world pairs to rank these worlds. Finally, I argue that this incomparability result generates puzzles for both consequentialist and non-consequentialist theories of objective and subjective permissibility. (shrink)

This article offers a comprehensive and critical analysis of Eric Heinze’s book Hate Speech and Democratic Citizenship (Oxford University Press, 2016). Heinze’s project is to formulate and defend a more theoretically complex version of the idea (also defended by people like Ronald Dworkin and James Weinstein) that general legal prohibitions on hate speech in public discourse compromises the state’s democratic legitimacy. We offer a detailed synopsis of Heinze’s view, highlighting some of its distinctive qualities and strengths. We then develop a (...) critical response to this view with three main focal points: (1) the characterisation of democratic legitimacy as something distinct from (and whose demands aren’t identical with those of) legitimacy per se; (2) the claim that the requirements of democracy are hypothetical, rather than categorical, imperatives; and relatedly (3) the question of how we should reconcile the requirements of democratic legitimacy with the costs that may follow from prioritising democratic legitimacy. We argue that there are significant difficulties for Heinze’s account on all three fronts. (shrink)

The word ‘naturalism’ has a bewildering array of uses in philosophy. Roughly speaking, it connotes pro-scientific attitudes and approaches. This article introduces the subject of naturalism by sketching a history of pro-scientific attitudes and approaches in philosophy, from their origins in the early modern period through to the present day. It then distinguishes a number of distinct families of naturalism: metaphysical, logico-linguistic, epistemological, and methodological. The resulting taxonomy encompasses a plurality of loosely related views rather than a number of variations (...) on a single clear and unified theme. (shrink)

Intersectionality has become the primary analytic tool that feminist and anti-racist scholars deploy for theorizing identity and oppression. This paper exposes and critically interrogates the assumptions underpinning intersectionality by focusing on four tensions within intersectionality scholarship: the lack of a defined intersectional methodology; the use of black women as quintessential intersectional subjects; the vague definition of intersectionality; and the empirical validity of intersectionality. Ultimately, my project does not seek to undermine intersectionality; instead, I encourage both feminist and anti-racist scholars to (...) grapple with intersectionality's theoretical, political, and methodological murkiness to construct a more complex way of theorizing identity and oppression. (shrink)

This chapter considers potential applications of grounding to the formulation of physicalism. I begin with an overview of competing conceptions of the physical and of physicalism. I then consider whether grounding physicalism overcomes well-known and seemingly fatal problems with supervenience physicalism. I conclude that while grounding physicalism improves upon supervenience physicalism in certain respects, it arguably falls victim to some of the same difficulties.

Insufficient attention has been paid to the use of robots in classrooms. Robot “teachers” are being developed, but because Kline ignores such technological developments, it is not clear how they would fit within her framework. It is argued here that robots are not capable of teaching in any meaningful sense, and should be deployed only as educational tools.

This chapter considers the assumptions required to make scientisms of different forms genuinely threatening to philosophers, where a genuine threat would consist of a concrete risk to their statuses, the value of their teaching and research, their livelihoods, their preferred research methods, or the health of the discipline. I will find that strong and weak forms of scientism alike require substantive assumptions to make them threatening in those regards. In particular, they require sometimes heavy-handed circumscriptions of philosophy and science, as (...) well as their epistemic credentials and achievements, methods, and subject matters. They also require restrictive pronouncements upon the epistemic and non-epistemic goods that are valuable, worth promoting in academic contexts, and relevant to disciplinary health. My aim in this chapter will not to be defeat those assumptions but rather to make them explicit and to emphasize their frequent strength and contentiousness. (shrink)

Many advocate practices of ‘local food’ or ‘locavorism’ as a partial solution to the injustices and unsustainability of contemporary food systems. I think that there is much to be said in favor of local food movements, but these virtues are insufficient to immunize locavorism from criticism. In particular, three duties of international ethics—beneficence, repair and fairness—may provide reasons for constraining the developed world’s permissible pursuit of local food. A complete account of why (and how) the fulfillment of these duties constrains (...) locavorism will require extensive empirical evidence about the relationship between agricultural demand-led industrialization, international trade (rules), and local food practices. In this paper I can only gesture at some of this evidence and, for that reason, my policy prescriptions are merely provisional. Instead, the upshot of this paper is that advocates of locavorism ought to be attentive to the empirical-dependence of the moral permissibility of their projects. As local food ‘scales up’—and comes to be embraced as a goal of political communities—these concerns should receive even greater attention. (shrink)

In two recent papers, Michael Della Rocca accuses Descartes of reasoning circularly in the Fourth Meditation. This alleged new circle is distinct from, and more vicious than, the traditional Cartesian Circle arising in the Third Meditation. We explain Della Rocca’s reasons for this accusation, showing that his argument is invalid.

Francis Bacon’s call for philosophers to investigate nature and ‘‘join in consultation for the common good’’ is one example of a powerful vision that helped to shape modern science. His ideal clearly linked the experimental method with the production of beneficial effects that could be used both as ‘‘pledges of truth’’ and for ‘‘the comforts of life.’’ When Bacon’s program was implemented in the following genera- tion, however, the tensions inherent in his vision became all too real. The history of (...) the Royal Society of London, from its founding in 1660 to the 42-year presidency of Joseph Banks (1778–1820), shows how these tensions led to changes in the way in which both the experimental method and the ideal of the common good were understood. A more nuanced understanding of the problems involved in recent philosophical analyses of science in the public interest can be achieved by appreciating the complexity revealed from this historical perspective. (shrink)

Skeptics of the moral case against industrial farming often assert that harm to animals in industrial systems is limited to isolated instances of abuse that do not reflect standard practice and thus do not merit criticism of the industry at large. I argue that even if skeptics are correct that abuse is the exception rather than the rule, they must still answer for two additional varieties of serious harm to animals that are pervasive in industrial systems: procedural harm and institutional (...) oppression. That procedural and institutional harms create conditions under which abuse is virtually inevitable only increases the skeptic's burden. (shrink)

This paper argues that in Eudemian Ethics 8.3, virtue’s mean between excess and deficiency is defined by the standard of promoting the most contemplation. Promotion is indirect and constrained by virtue’s other essential features. The chapter’s apparent restriction of the standard to actions concerning natural goods actually serves a dialectical, not a restrictive, purpose. This paper proposes to unify the chapter’s argumentative arc.

According to certain kinds of semantic dispositionalism, what an agent means by her words is grounded by her dispositions to complete simple tasks. This sort of position is often thought to avoid the finitude problem raised by Kripke against simpler forms of dispositionalism. The traditional objection is that, since words possess indefinite (or infinite) extensions, and our dispositions to use words are only finite, those dispositions prove inadequate to serve as ground for what we mean by our words. I argue (...) that, even if such positions (emphasizing simple tasks) avoid the traditional form of Kripke's charge, they still succumb to special cases of the finitude problem. Furthermore, I show how such positions can be augmented so as to avoid even these special cases. Doing so requires qualifying the dispositions of interest as those possessed by the abstracted version of an actual agent (in contrast to, say, an idealized version of the agent). In addition to avoiding the finitude problem in its various forms, the position that results provides new materials for appreciating the role that abstracting models can play for a dispositionalist theory of meaning. (shrink)

Russell claims in his autobiography and elsewhere that he discovered his 1905 theory of descriptions while attempting to solve the logical and semantic paradoxes plaguing his work on the foundations of mathematics. In this paper, I hope to make the connection between his work on the paradoxes and the theory of descriptions and his theory of incomplete symbols generally clearer. In particular, I argue that the theory of descriptions arose from the realization that not only can a class not be (...) thought of as a single thing, neither can the meaning/intension of any expression capable of singling out one collection (class) of things as opposed to another. If this is right, it shows that Russell’s method of solving the logical paradoxes is wholly incompatible with anything like a Fregean dualism between sense and reference or meaning and denotation. I also discuss how this realization lead to modifications in his understanding of propositions and propositional functions, and suggest that Russell’s confrontation with these issues may be instructive for ongoing research. (shrink)

This paper discusses certain problems arising within the treatment of the senses of functions in Alonzo Church's Logic of Sense and Denotation. Church understands such senses themselves to be "sense-functions," functions from sense to sense. However, the conditions he lays out under which a sense-function is to be regarded as a sense presenting another function as denotation allow for certain undesirable results given certain unusual or "deviant" sense-functions. Certain absurdities result, e.g., an argument can be found for equating any two (...) senses of the same type. An alternative treatment of the senses of functions is discussed, and is thought to do better justice to Frege's original theory. (shrink)

In he Problems of Philosophy and other works of the same period, Russell claims that every proposition must contain at least one universal. Even fully general propositions of logic are claimed to contain “abstract logical universals”, and our knowledge of logical truths claimed to be a species of a priori knowledge of universals. However, these views are in considerable tension with Russell’s own philosophy of logic and mathematics as presented in Principia Mathematica. Universals generally are qualities and relations, but if, (...) for example, PM’s disjunction (∨) is a relation, what is it a relation between? There is no obvious answer to this given Russell’s other philosophical commitments at this time, although hints are left in some of the pre-PM manuscripts. In this paper, I explore this tension in Russell's philosophy and relate it to developments both before and after Problems. (shrink)

1) Introduction. 2) The key libertarian insight into property and orthodox libertarianism’s philosophical confusion. 3) Clearer distinctions for applying to what follows: abstract liberty; practical liberty; moral defences; and critical rationalism. 4) The two dominant (‘Lockean’ and ‘Hobbesian’) conceptions of interpersonal liberty. 5) A general account of libertarianism as a subset of classical liberalism and defended from a narrower view. 6) Two abstract (non-propertarian, non-normative) theories of interpersonal liberty developed and defended: ‘the absence of interpersonal initiated imposed constraints on want-satisfaction’, (...) abbreviated to ‘no initiated imposed costs’; and ‘no imposed costs’. 7) Practical implications for both main abstract conceptions of liberty derived and compared. 8) How this positive analysis relates to morals. 9) Concluding conjectures: the main abstract theory of liberty captures the relevant interpersonal conception; the new paradigm of libertarianism solves the old one’s problems. (shrink)

ABSTRACT Self-Interest and Public Interest in Western Politics showed that the public, politicians, and bureaucrats are often public spirited. But this does not invalidate public-choice theory. Public-choice theory is an ideal type, not a claim that self-interest explains all political behavior. Instead, public-choice theory is useful in creating rules and institutions that guard against the worst case, which would be universal self-interestedness in politics. In contrast, the public-interest hypothesis is neither a comprehensive explanation of political behavior nor a sound basis (...) for institutional design. (shrink)

Global climate change is one of the most widely discussed problems of our time. However, many libertarian thinkers have not participated in the ethical dimensions of this discussion due to a narrow focus on the scientific basis for concern about climate change. In this paper, I reject this approach and explore the kind of response libertarians should be offering instead. I frame the climate change problem as one which concerns potential rights-infringements and explore different ways in which climate change might (...) be thought to infringe upon rights. I conclude that there are some ways in which climate change might be expected to result in rights-infringements, but that some of the current concern about climate change cannot be reconciled with a rights-oriented paradigm. I close by outlining future directions for research, emphasizing that much remains to be done in order to formulate a complete libertarian perspective on climate change. (shrink)

In this paper I take up (what I call) the pregnancy loss objection to defenses of abortion that deny fetal moral status. Though versions of this objection have been put forth by others—particularly Lindsey Porter’s in a 2015 paper—I argue that the existing versions of the objection are unsuccessful in various ways: failing to explain the ground of moral considerability that would apply to embryos/fetuses in very early pregnancy, lack of clarity about what it means to take grief after miscarriage (...) seriously, and implausible implications regarding pre-embryo and infertility cases. I go on to offer a more plausible version of the objection, which I apply only to mid-pregnancy and fetuses, by drawing on personal narratives of later pregnancy loss and abortion and emphasizing practices that indicate the relevant kind of mourning. I then take up the question of how experience of the sort I have in mind can function as evidence, by situating my version of the objection in a pragmatist ethical view. Finally I consider and respond to some worries about the very idea of taking experience of pregnancy loss to be evidence regarding fetal moral status. (shrink)

From the dictum "ought implies can", it has been argued that no account of belief's normativity can avoid the unpalatable result that, for unbelievable propositions such as "It is raining and nobody believes that it is raining", one ought not to believe them even if true. In this article, I argue that this move only succeeds on a faulty assumption about the conjunction of doxastic "oughts.".

The thesis that rationality consists in the straight-forward maximization of utility has not lacked critics. Typically, however, detractors reject the Humean picture of rationality upon which it seems based; they seek to emancipate reason from the tyranny of the passions. It is, then, noteworthy when an attack on this thesis comes from ‘within the ranks.’David Gauthier's paper ‘Reason and Maximization’ is just such an attack; and for this reason, among others, it is interesting. It is not successful, though. In defense (...) of this conclusion, we shall begin by relating the essentials of Gauthier's argument. Then we shall examine in some detail Gauthier's claim that the principle of straighforward max-imization fails to be self-supporting. We shall argue that Gauthier's defense of this claim is at best incomplete. Finally, we shall show that the fact that a normative principle is self-subverting or non-self-supporting does not entail that the principle is defective. (shrink)

ABSTRACT Objectives There is little research on moral uncertainties and distress of palliative and hospice care providers (PHCPs) working in jurisdictions anticipating legalising voluntary assisted dying (VAD). This study examines the perception and anticipated concerns of PHCPs in providing VAD in the State of Queensland, Australia prior to legalisation of the practice in 2021. The findings help inform strategies to facilitate training and support the health and well-being of healthcare workers involved in VAD. Design The study used a qualitative approach (...) to examine and analyse the perception and anticipated concerns of PHCPs regarding challenges of providing assisted dying in Queensland. Fourteen PHCPs were recruited using a purposive sampling strategy to obtain a broad representation of perspectives including work roles, geographical locations and workplace characteristics. Data were collected via one in-depth interview per participant. The transcripts were coded for patterns and themes using an inductive analysis approach following the tradition of Grounded Theory. Setting The study was conducted in hospital, hospice, community and residential aged care settings in Queensland, Australia. These included public and private facilities, secular and faith-based facilities, and regional/rural and urban facilities. Participants Interviews were conducted with fourteen PHCPs: 10 nurses and 4 physicians; 11 female and 3 male. The median number of years of palliative care practice was 17, ranging from 2 to 36 years. For inclusion, participants had to be practising palliative and hospice care providers. Results PHCPs are divided on whether VAD should be considered part of palliative care. Expectations of moral distress and uncertainty about practising VAD were identified in five areas: handling requests, assessing patient capacity, arranging patient transfers and logistical issues, managing unsuccessful attempts, and dealing with team conflicts and stigma. Conclusions The possibility of having to practise VAD causes moral distress and uncertainty for some PHCPs. Procedural clarity can address some uncertainties; moral and psychological distress, however, remains a source of tension that needs support to ensure ongoing care of both patients and PHCPs. The introduction of VAD post-legalisation may present an occasion for further moral education and development of PHCPs. (shrink)

Jacob Klapwijk’s book Purpose in the Living World? (Cambridge 2998) is examined with special attention given to the scholarly background from out of which it emerges as a significant contribution to reformational philosophical reflection. As an initial step to clarify some important issues raised by Klapwijk’s critical comments about Dooyeweerd’s “essentialist” concept of species, the article probes facets of the way Jan Lever incorporated reformational philosophical concepts into his biological theory and considers the 1959 review written by Herman Dooyeweerd of (...) Lever’s Creation and Evolution. The analysis focuses specifically upon the social responsibilities of these two scholars and the confrontation of their respective views. With the work of Lever and Dooyeweerd we sense something of the ambiguities when reformational philosophy confronts an evangelical scholasticism. This confrontation is an important facet of the context in which Klapwijk has set forth his discussion of creation and emergent evolution. Purpose is also the fruit of scholarly collaboration across disciplines, providing a welcome stimulus for a deepened understanding of the corporate character of the student vocation. (shrink)

Organisms live not as discrete entities on which an independent environment acts, but as members of a reproductive lineage in an ongoing series of interactions between that lineage and a dynamic ecological niche. These interactions continuously shape both systems in a reciprocal manner, resulting in the emergence of reliably co-occurring configurations within and between both systems. The enactive approach to cognition describes this relationship as the structural coupling between an organism and its environment; similarly, Developmental Systems Theory emphasizes the reciprocal (...) nature of structurally coupled systems in its analysis of organisms as developmental processes embedded within a developmental system. Through an enactive-developmental systems framing, this paper identifies the organizational features of cognizing systems in order to motivate a picture of how organism and environment co-determine and co-construct one another. I argue that organisms can be characterized as self-organizing, operationally closed, plastic systems ecologically embedded within a developmental system. In virtue of this organizational makeup, organisms actively engage in the modulation and assessment of their coupling with their environment: cognitive strategies that entail contextualized responses to variations across the web of interactions that comprises the developmental system. (shrink)

It would be an understatement to say that Russell was interested in Cantorian diagonal paradoxes. His discovery of the various versions of Russell’s paradox—the classes version, the predicates version, the propositional functions version—had a lasting effect on his views in philosophical logic. Similar Cantorian paradoxes regarding propositions—such as that discussed in §500 of The Principles of Mathematics—were surely among the reasons Russell eventually abandoned his ontology of propositions.1 However, Russell’s reasons for abandoning what he called “denoting concepts”, and his rejection (...) of similar “semantic dualisms” such as Frege’s theory of sense and reference—at least in “On Denoting”—made no explicit mention of any Cantorian paradox. My aim in this paper is to argue that such paradoxes do pose a problem for certain theories such as Frege’s, and early Russell’s, about how definite descriptions are meaningful. My first aim is simply to lay out the problem I have in mind. Next, I shall turn to arguing that the theories of descriptions endorsed by Frege and by Russell prior to “On Denoting” are susceptible to the problem. Finally, I explore what responses a.. (shrink)

Many have offered moral objections to video games, with various critics contending that they depict and promote morally dubious attitudes and behaviour. However, few have offered moral arguments in favour of video games. In this chapter, we develop one such positive moral argument. Specifically, we argue that video games offer one of the only morally acceptable methods for acquiring some ethical knowledge. Consequently, we have (defeasible) moral reasons for creating, distributing, and playing certain morally educating video games.

For a long time critics of modern and postmodern art have relied on the "Isn't that disgusting" strategy. By that I mean the strategy of pointing out that given works of art are ugly, trivial, or in bad taste, that "a five-year-old could have made them," and so on. And they have mostly left it at that. The points have often been true, but they have also been tiresome and unconvincing—and the art world has been entirely unmoved. -/- Of course, (...) the major works of the twentieth-century art world are ugly. Of course, many are offensive. Of course, a five-year old could in many cases have made an indistinguishable product. Those points are not arguable—and they are entirely beside the main question. The important question is: Why has the art world of the twentieth-century adopted the ugly and the offensive? Why has it poured its creative energies and cleverness into the trivial and the self-proclaimedly meaningless? (shrink)

How does an engagement with religious traditions (broadly construed) illuminate and complicate the task of thinking through the ethics of eating? In this introduction, we survey some of the many food ethical issues that arise within various religious traditions and also consider some ethical positions that such traditions take on food. To say the least, we do not attempt to address all the ethical issues concerning food that arise in religious contexts, nor do we attempt to cover every tradition’s take (...) on food. We look at just a few traditions and a few interesting writings on food ethics and religion: What do they say about the ethics of eating? Why do they say these things? Here we use the terms “food ethics” and “religion” ecumenically as big tents under which many importantly different sorts of things may be grouped. Among the wide range of food ethical issues we consider in this chapter, for example, are religious views about the ethics of keeping, hurting, and killing animals, killing plants, dominion over creation, wastefulness, purity, blessing, atonement, and the connection between food and character. We realize, moreover, that it might be a stretch to label some of the views engaged by selected readings in this chapter as “religious” on a stringent understanding of that term; Lisa Kemmerer’s “Indigenous Traditions,” for instance, addresses some views that are recognizably spiritual but perhaps not religious in a strict sense. We hope that our ecumenical usage of the term can bring these important traditions to bear on the discussion without reducing them to something they are not. (shrink)

From a European perspective the US debate about gun control is puzzling because we have no such debate: It seems obvious to us that dangerous weapons need tight control and that ‘guns’ fall under that category. I suggest that this difference occurs due to different habits that generate different attitudes and support this explanation with an analogy to the habits about knives. I conclude that it is plausible that individual knife-people or gun-people do not want tight regulatory legislation—but tight knife (...) and gun legislation is morally obligatory anyway. We need to give up our habits for the greater good. (shrink)

David Stove reviews Selwyn Grave's History of Philosophy in Australia, and praises philosophers for thinking harder about the bases of science, mathematics and medicine than the practitioners in the field. The review is reprinted as an appendix to James Franklin's Corrupting the Youth: A History of Philosophy in Australia.