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)

The book covers scientific and philosophical topics by bringing them closer to literature. Some topics are scientific explanation, the concept of cause, rational argumentation, pseudoscience, language, ethics, philosophy of mind, posthumanism, and democracy. Summary Prefazione di Severino Saccardi. Introduzione. Capitolo 1: Le scrivanie di Eddington. 1.1. Il vecchio Qfwfq (I. Calvino. Le cosmicomiche). 1.2. L’assassino invisibile (L.F. Celine, Il dottor Semmelweis). 1.3. Gli gnommeri di Ingravallo (C.E. Gadda, Quer pasticciaccio brutto de via Merulana). 1.4. I sergenti di Napoleone (L. Tolstoj, (...) Guerra e pace). 1.5. Tex e il Coyote nero (G. Bonelli, Il Coyote nero). 1.6. “Elementare Watson!” (A.C. Doyle, Il segno dei quattro). Capitolo 2. Non saranno mai delusi. 2.1. L’albero di Natale. (V. Perrin, Cambiare l’acqua ai fiori). 2.2. Il dagherrotipo di Buendia. (G.G. Marquez, Cent’anni di solitudine). 2.3. Don Ferrante e la peste. (A. Manzoni, I promessi sposi). Capitolo 3. Capitolo puffo. 3.1. L’Accademia di Lagado. (J. Swift, I viaggi di Gulliver). 3.2. Bruto è uomo d’onore. (W. Shakespeare, Giulio Cesare). 3.3. Le oche mute. (G. Orwell, 1984). Capitolo 4. “Quarantadue!” 4.1. Lo zio N’Ba N’Ga. (I. Calvino, Le cosmicomiche). 4.2. La mosca cocchiera. (J. de La Fontaine, Favole). 4.3. Il fiore del dr. Dek. (E. Salgari, Le meraviglie del Duemila). Capitolo 5. L’ultimo uomo. 5.1. La pernice accusatrice. (Cyrano de Bergerac, Gli stati e gli imperi del Sole). 5.2. Pallino in via Mjasnickaja. (M.A. Bulgakov, Cuore di cane). Capitolo 6. Scenari perturbanti. 6.1. Dissipatio. (G. Morselli, Dissipatio H.G.). 6.2. Un mammifero meccanizzato. (S. Butler, Erewhon). 6.3. Mlle Olimpia. (E.T.A. Hoffmann, Racconti notturni). Capitolo 7. La gente perbene. 7.1. La balena bianca. (H. Melville, Moby Dick). 7.2. Betsabea Everdeene. (T. Hardy, Via dalla pazza folla). 7.3. Un’idea francese. (C. McCarthy, Cavalli selvaggi). 7.4. Le montagne del Montana. (D. Delillo, Rumore bianco). (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)

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)

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, I argue that limitarian policies are a good means to further political equality. Limitarianism, which is a view coined and defended by Robeyns, is a partial view in distributive justice which claims that under non-ideal circumstances it is morally impermissible to be rich. In a recent paper, Volacu and Dumitru level two arguments against Robeyns’ Democratic Argument for limitarianism. The Democratic Argument states that limitarianism is called for given the undermining influence current inequalities in income and wealth (...) have for the value of democracy and political equality. Volacu and Dumitru’s Incentive Objection holds that limitarianism places an excessive and inefficient burden on the rich in ensuring political equality. The Efficacy Objection holds that even if limitarianism limits excessive wealth it still fails to ensure the preservation of political equality. In this paper, I will argue that both of these objections fail, but on separate grounds. I argue that the Incentive objection fails because one could appeal to limitarian policies that are different from the ones discussed by Volacu and Dumitru and which escape the problem of reduced productivity. I argue against the Efficacy Objection that limitarian policies are a partial but highly valuable step towards establishing political equality, and that they can and should complement or be complemented by other strategies. (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)

We examine two competing solutions to Benardete paradoxes: causal finitism, according to which nothing can have infinitely many causes, and the unsatisfiable pair diagnosis (UPD), according to which such paradoxes are logically impossible and no metaphysical thesis need be adopted to avoid them. We argue that the UPD enjoys notable theoretical advantages over causal finitism. Causal finitists, however, have levelled two main objections to the UPD. First, they urge that the UPD requires positing a ‘mysterious force’ that prevents paradoxes from (...) arising. Since such a force is implausible, the UPD is in trouble. Second, they employ recombination or patchwork principles to argue that paradoxical situations would be possible if causal finitism were false. Since such situations are not possible, causal finitism is true, and so a substantive metaphysical thesis is needed to avoid the paradoxes. We argue that the UPD proponent can successfully respond to these objections. (shrink)

The philosophy of biomimicry, I argue, consists of four main areas of inquiry. The first, which has already been explored by Freya Mathews, concerns the “deep” question of what Nature ultimately is. The second, third, and fourth areas correspond to the three basic principles of biomimicry as laid out by Janine Benyus. “Nature as model” is the poetic principle of biomimicry, for it tells us how it is that things are to be “brought forth”. “Nature as measure” is the ethical (...) principle of biomimicry, for it tells us that Nature places ethical limits or standards on what it is possible for us to accomplish. And “Nature as mentor” is the epistemological principle of biomimicry, for it affirms that Nature is the ultimate source of truth, wisdom, and freedom from error. Within this overall framework, I argue that seeing Nature as physis—understood as “self-production” or “self-placing-into-the-open”—constitutes the requisite ground for the poetic, ethical, and epistemological principles of biomimicry, and that biomimicry thus conceived involves a new philosophical paradigm, which I call “enlightened naturalism”. (shrink)

Carl Knight argues that lexical sufficientarianism, which holds that sufficientarian concerns should have lexical priority over other distributive goals, is ‘excessive’ in many distinct ways and that sufficientarians should either defend weighted sufficientarianism or become prioritarians. In this article, I distinguish three types of weighted sufficientarianism and propose a weighted sufficientarian view that meets the excessiveness objection and is preferable to both Knight’s proposal and prioritarianism. More specifically, I defend a multi-threshold view which gives weighted priority to benefits directly above (...) and below its thresholds, but gives benefits below the lowest threshold lexical priority over benefits above the highest threshold. (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)

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.

Despite the prominence of thresholds in theories of distributive justice, there is no general account of what sort of role is played by the idea of a threshold within such theories. This has allowed an ongoing lack of clarity and misunderstanding around views that employ thresholds. In this article, I develop an account of the concept of thresholds in distributive justice. I argue that this concept contains three elements, which threshold views deploy when ranking possible distributions. These elements are (i) (...) the level of the threshold, (ii) what constitutes the value of the threshold, and (iii) how benefits above and below the threshold must be allocated. I highlight three contributions that this particular account of thresholds makes: it clarifies the nature of the shift that occurs at the threshold; it resolves a common misunderstanding about headcount principles; and it shows how the arbitrariness objection can be met. (shrink)

In this article, I propose a novel characterization of sufficientarianism. I argue that sufficientarianism combines three claims: a priority claim that we have non-instrumental reasons to prioritize benefits in certain ranges over benefits in other ranges; a continuum claim that at least two of those ranges are on one continuum; and a deficiency claim that the lower a range on a continuum, the more priority benefits in that range have. This characterization of sufficientarianism sheds new light on two long-standing philosophical (...) debates, namely about the distinctiveness of sufficientarianism as a distributive principle and about the common objections to sufficientarianism. (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)

Limitarianism holds that there is an upper limit to how many resources, such as wealth and income, people can permissibly have. In this article, I examine the conceptual structure of limitarianism. I focus on the upper limit and the idea that resources above the limit are ‘excess resources’. I distinguish two possible limitarian views about such resources: (i) that excess resources have zero moral value for the holder; and (ii) that excess resources do have moral value for the holder but (...) that their claim to such resources is outweighed by other normative concerns. Moreover, I argue that, depending on the values limitarianism seeks to promote, limitarians should care about the number of people with excess resources or the total amount of excess resources (or both), that they can adopt redistributive measures and/or predistributive measures, and that some versions of limitarianism should take into account the distribution of risk among those above the riches line. (shrink)

There is a basic distinction, in the realm of spatial boundaries, between bona fide boundaries on the one hand, and fiat boundaries on the other. The former are just the physical boundaries of old. The latter are exemplified especially by boundaries induced through human demarcation, for example in the geographic domain. The classical problems connected with the notions of adjacency, contact, separation and division can be resolved in an intuitive way by recognizing this two-sorted ontology of boundaries. Bona fide boundaries (...) yield a notion of contact that is effectively modeled by classical topology; the analogue of contact involving fiat boundaries calls, however, for a different account, based on the intuition that fiat boundaries do not support the open/closed distinction on which classical topology is based. In the presence of this two-sorted ontology it then transpires that mereotopology—topology erected on a mereological basis—is more than a trivial formal variant of classical point-set topology. (shrink)

A central question in contemporary ethics and political philosophy concerns which entities have moral status. In this article, I provide a detailed analysis of the view that moral status comes in degrees. I argue that degrees of moral status can be specified along two dimensions: (i) the weight of the reason to protect an entity’s morally significant rights and interests; and/or (ii) the rights and interests that are considered morally significant. And I explore some of the complexities that arise when (...) we link degrees of moral status to the weight of reasons to protect bundles and/or the content and size of these bundles, in particular regarding the attribution of moral status to nonparadigmatic entities (e.g. people with severe cognitive disabilities, children, embryos and foetuses, robots, non-human animals, ecosystems, and rivers). (shrink)

Due to Gӧdel’s incompleteness results, the categoricity of a sufficiently rich mathematical theory and the semantic completeness of its underlying logic are two mutually exclusive ideals. For first- and second-order logics we obtain one of them with the cost of losing the other. In addition, in both these logics the rules of deduction for their quantifiers are non-categorical. In this paper I examine two recent arguments –Warren (2020), Murzi and Topey (2021)– for the idea that the natural deduction rules for (...) the first-order universal quantifier are categorical, i.e., they uniquely determine its semantic intended meaning. Both of them make use of McGee’s open-endedness requirement and the second one uses in addition Garson’s (2013) local models for defining the validity of these rules. I argue that the success of both these arguments is relative to their semantic or infinitary assumptions, which could be easily discharged if the introduction rule for the universal quantifier is taken to be an infinitary rule, i.e. non-compact. Consequently, I reconsider the use of the ω-rule and I show that the addition of the ω-rule to the standard formalizations of first-order logic is categorical. In addition, I argue that the open-endedness requirement does not make the first-order Peano Arithmetic categorical and I advance an argument for its categoricity based on the inferential conservativity requirement. (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)

The modal ontological argument (MOA) proceeds from God’s possible existence to God’s actual existence. A prominent objection to the MOA is that it suffers from a symmetry problem: an exactly parallel modal ontological argument can be given for God's non-existence. Several attempts have been made to break the symmetry between the arguments. This draft is a mostly comprehensive survey of those attempts. -/- The draft was initially written as a supplement to the 2024 Summer edition of the SEP entry on (...) Ontological Arguments. However, the draft is not included in the SEP entry. (shrink)

The New Evil Demon Problem is supposed to show that straightforward versions of reliabilism are false: reliability is not necessary for justification after all. I argue that it does no such thing. The reliabilist can count a number of beliefs as justified even in demon worlds, others as unjustified but having positive epistemic status nonetheless. The remaining beliefs---primarily perceptual beliefs---are not, on further reflection, intuitively justified after all. The reliabilist is right to count these beliefs as unjustified in demon worlds, (...) and it is a challenge for the internalist to be able to do so as well. (shrink)

A discussion of a number of ways that information can be present in a computer program without being explicitly represented.

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)

Benardete paradoxes involve infinite collections of Grim Reapers, assassins, demons, deafening peals, or even sentences. These paradoxes have recently been used in arguments for finitist metaphysical theses such as temporal finitism, causal finitism, and discrete views of time. Here we develop a new finite Benardete-like paradox. We then use this paradox to defend a companions in guilt argument that challenges recent applications of patchwork principles on behalf of the aforementioned finitist arguments. Finally, we develop another problem for those applications by (...) examining the notion of exact duplication. (shrink)

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)

There are conflicting intuitions concerning the status of a boundary separating two adjacent entities (or two parts of the same entity). The boundary cannot belong to both things, for adjacency excludes overlap; and it cannot belong to neither, for nothing lies between two adjacent things. Yet how can the dilemma be avoided without assigning the boundary to one thing or the other at random? Some philosophers regard this as a reductio of the very notion of a boundary, which should accordingly (...) be treated a mere façon de parler. In this paper I resist this temptation and examine some ways of taking the puzzle at face value within a realist perspective—treating boundaries as ontologically on a par with (albeit parasitic upon) extended parts. (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)

In this article I argue that the value of epistemic justification cannot be adequately explained as being instrumental to truth. I intend to show that false belief, which is no means to truth, can nevertheless still be of epistemic value. This in turn will make a good prima facie case that justification is valuable for its own sake. If this is right, we will have also found reason to think that truth value monism is false: assuming that true belief does (...) have value, there is more of final epistemic value than mere true belief. (shrink)

Neutral monism is a position in metaphysics defended by Mach, James, and Russell in the early twentieth century. It holds that minds and physical objects are essentially two different orderings of the same underlying neutral elements of nature. This paper sets out some of the central concepts, theses and the historical background of ideas that inform this doctrine of elements. The discussion begins with the classic neutral monism of Mach, James, and Russell in the first part of the paper, then (...) considers recent neo-Russellian versions in the second half. The chances for a revival of neutral monism are probably slight; its key ideas and starting points lie far from those in contemporary philosophy of mind. A better route might be through the philosophy of science and a deeper understanding of causation. (shrink)

This paper defends the Intention Account of Inquiry. On this account, inquiry is best understood by appeal to a ‘question-directed intention’ (QDI), an intention to answer a question broadly construed. This account’s core commitments help meet recent challenges plaguing extant approaches to characterizing inquiry. First, QDIs are the type of mental state central to inquiry, not attitudes like curiosity or wonder. Second, holding a QDI towards a question and acting in service of it constitutes the start of inquiry. Third, controversial (...) norms which mandate a rational inquirer's ignorance towards the answer to her question can be reformulated and defended by appeal to rational constraints on intention. Fourth, instrumental pressures inquirers face are the standard pressures of plan-rationality. In defending these theses, I show that the Intention Account provides compelling explanations to standing challenges, in ways competitors cannot. It does so by advancing understanding of how our epistemic and practical agency are intertwined. (shrink)

Locke’s property rights are now usually understood to be both fundamental and strictly negative. Fundamental because they are thought to be basic constraints on what we may do, unconstrained by anything deeper. Negative because they are thought to only protect a property holder against the claims of others. Here, I argue that this widespread interpretation is mistaken. For Locke, property rights are constrained by the deeper ‘fundamental law of nature,’ which involves positive obligations to those in need and confines the (...) right to excess property within circumstances where it is not needed to preserve human life. (shrink)

Many believe that the rational evaluation of actions depends on the rational evaluation of even basic desires. Hume, though, viewed desires as "original existences" which cannot be contrary to either truth or reason. Contemporary critics of Hume, including Norman, Brandt and Parfit, have sought a basis for the rational evaluation of desires that would deny some basic desires reason-giving force. I side with Hume against these modern critics. Hume's concept of rational evaluation is admittedly too narrow; even basic desires are, (...) despite their nonrepresentational nature, subject to rational evaluation. But this evaluation is not relevant to their tendency to generate reasons for action, and does not undermine the spirit of the Humean view of rational action. (shrink)

One of the attractions of the Humean instrumentalist theory of practical rationality is that it appears to offer a special connection between an agent's reasons and her motivation. The assumption that Humeanism is able to assert a strong connection between reason and motivation has been challenged, most notably by Christine Korsgaard. She argues that Humeanism is not special in the connection it allows to motivation. On the contrary, Humean theories of practical rationality do connect reasons and motivation in a unique (...) and attractive way, though the nature of this connection has sometimes been misunderstood by both defenders and detractors of the theory. (shrink)

In previous work I have argued that talk about negative events should not be taken at face value: typically, what we are inclined to think of as a negative event (John’s failure to go jogging) is just an ordinary, positive event (his going to the movie instead); it is a positive event under a negative description. Here I consider more closely the difficulties that arise in those cases where no positive event seems available to do the job, as with putative (...) cases of causation by omission. In particular, I elaborate on Helen Beebee’s idea that not all causal explanations are reports of causation. When we mention John’s failure to turn off the gas as an explanans of why there was an explosion, we do not say what caused the explosion. We do not mention any of the relevant causes. We just remark that one sort of event that was supposed to occur, and whose occurrence would have prevented the explosion, did not in fact occur. (shrink)

According to the sufficiency theory of justice in health, justice requires that people have equal access to adequate health. In this article, I lay out the structure of this view and I assess its distributive implications for setting priority (i) between health needs across persons and (ii) between health care spending and other societal goods. I argue, first, that according to the sufficiency theory, deficiency in health cannot be completely offset by providing other societal goods. And, second, that it can (...) prevent the medicalization of societies by stressing that improvements beyond the level of adequate health have relatively little weight, if any, from the standpoint of justice. (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.

In this introduction, before summarizing the contents of the volume, the authors characterize materialism as it is understood within the philosophy of mind, and they identify three respects in which materialism is on the wane.

I argue that the conjunction of perdurantism (the view that objects are temporally extended) and universalism (the thesis that any old class of things has a mereological fusion) gives rise to undesired complications when combined with certain plausible assumptions concerning the semantics of tensed statements.

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.

This paper investigates the prospects of Rodney Brooks’ proposal for AI without representation. It turns out that the supposedly characteristic features of “new AI” (embodiment, situatedness, absence of reasoning, and absence of representation) are all present in conventional systems: “New AI” is just like old AI. Brooks proposal boils down to the architectural rejection of central control in intelligent agents—Which, however, turns out to be crucial. Some of more recent cognitive science suggests that we might do well to dispose of (...) the image of intelligent agents as central representation processors. If this paradigm shift is achieved, Brooks’ proposal for cognition without representation appears promising for full-blown intelligent agents—Though not for conscious agents. (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)

In earlier work on limitarianism, I argued that setting an upper limit to the amount of wealth that people can permissibly have is justified when decision-makers are unaware of or disagree about the appropriate distributive criterion or if they are unaware of people’s relevant features (or both). Robert Huseby has raised several powerful objections to this presumptive argument for limitarianism. Some of these objections call for a revision of my defence of presumptive limitarianism while others call for clarification, both of (...) which I aim to do in this chapter. I will argue that unless decision-makers have substantive reasons to suggest otherwise, they must act as if there is an upper limit to the amount of wealth that people can permissibly have. (shrink)