I reconcile the spatiotemporal location of repeatable artworks and impure sets with the non-location of natural numbers despite all three being varieties of abstract objects. This is possible because, while the identity conditions for all three can be given by abstraction principles, in the former two cases spatiotemporal location is a congruence for the equivalence relation featuring in the relevant principle, whereas in the latter it is not. I then generalize this to other ‘physical’ properties like shape, mass, and causal (...) powers. (shrink)

In this article, I argue that there is no discrepancy between Kant's Doctrine of Right (The Metaphysics of Morals) (1797), which legally permits lies that do not deprive someone of their rights or property, and his On a Supposed Right to Lie from Love of Humanity (1797), which argues that it would be a crime to lie to a murderer about the whereabouts of the innocent person he is pursuing.

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)

For many years there has been a debate about the role of the parietal lobe in the generation of behavior. Does it generate movement plans (intention) or choose objects in the environment for further processing? To answer this, we focus on the lateral intraparietal area (LIP), an area that has been shown to play independent roles in target selection for saccades and the generation of visual attention. Based on results from a variety of tasks, we propose that LIP acts as (...) a priority map in which objects are represented by activity proportional to their behavioral priority. We present evidence to show that the priority map combines bottom-up inputs like a rapid visual response with an array of top-down signals like a saccade plan. The spatial location representing the peak of the map is used by the oculomotor system to target saccades and by the visual system to guide visual attention. (shrink)

In this paper, I explore two differing conceptions of J.G. Fichte’s Anstoß and how it relates to his Transcendental ‘I’, the ground of his Wissenschaftslehre. I argue that one should not attempt to read later interpretations of the Anstoß back into his earlier definition, but find that attempts to tread a middle way between the original and later interpretations have thus far been equally unsuccessful. Instead, I suggest a new way of interpreting the Anstoß as a constituent component of the (...) absolute I, built into his first principle of self-consciousness, and argue that this way allows the I to turn back upon itself without being externally determined. I argue that this way also avoids solipsistic and nihilistic objections by actually supporting the arguments of the proponents of earlier interpretations. I then advance to advocate the Anstoß’s importance in the wider sphere of understanding how Fichte’s theory of transzendentallogisch enables his first and rudimentary derivation of consciousness, prior to the finitely derived practical I of his later Jena writings. (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

In August 2021, Froese et al. published survey data collected from 2,543 respondents on their subjective experiences living under imposed social distancing measures during COVID-19 (1). The questionnaire was issued to respondents in the UK, Japan, and Mexico. By combining the authors’ expertise in phenomenological philosophy, phenomenological psychopathology, and enactive cognitive science, the questions were carefully phrased to prompt reports that would be useful to phenomenological investigation and theorizing (2–4). These questions reflected the various author’s research interests (e.g., technology, grief, (...) time). Between April 7th and July 31st, 2021, a second questionnaire with the same question set was issued to respondents of the original who had agreed to do a follow-up. This was intended to capture subjective reports of life under social distancing measures a year after the initial survey. By this time–depending on their country of residence and health status–respondents had potentially lived with repeated and prolonged lockdowns and a variety of other restrictions on their social lives. When taken together, Survey I and Survey II provide a cross-cultural and longitudinal dataset that allows for analysis of longer-term impacts of imposed social distancing measures on people’s experiences. For researchers working in diverse disciplines, this dataset offers a rich resource that reflects people’s reactions to the imposition of different social restrictions in different countries and over different time periods. (shrink)

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (shrink)

Context — Children and adults with psychopathic traits and conduct or oppositional defiant disorder demonstrate poor decision making and are impaired in reversal learning. However, the neural basis of this impairment has not previously been investigated. Furthermore, despite high comorbidity of psychopathic traits and attention deficit/hyperactivity disorder, to our knowledge, no research has attempted to distinguish neural correlates of childhood psychopathic traits and attention-deficit/hyperactivity disorder. Objective—To determine the neural regions that underlie the reversal learning impairments in children with psychopathic traits (...) plus conduct or oppositional defiant disorder. Design — Case-control study. Setting — Government clinical research institute. Participants — Forty-two adolescents aged 10 to 17 years: 14 with psychopathic traits and oppositional defiant disorder or conduct disorder, 14 with attention-deficit/hyperactivity disorder only, and 14 healthy controls. Main Outcome Measure — Blood oxygenation level–dependent signal as measured via functional magnetic resonance imaging during a probabilistic reversal task. Results — Children with psychopathic traits showed abnormal responses within the ventromedial prefrontal cortex (Brodmann area 10) during punished reversal errors compared with children wit hattention deficit/hyperactivity disorder and healthy children (P < .05 corrected for multiple comparisons). Conclusions — To our knowledge, this study provides the first evidence of abnormal ventromedial prefrontal cortex responsiveness in children with psychopathic traits and demonstrates this dysfunction was not attributable to comorbid attention-deficit/hyperactivity disorder. These findings suggest that reversal learning impairments in patients with developmental psychopathic traits relate to abnormal processing of reinforcement information. (shrink)

According to the dogmatism puzzle, for any S and any p, if S knows that p, then she’s entitled to be dogmatic about p, and so disregard any evidence against p, for she knows that (or is in a position to know that) that evidence is misleading. But this seems clearly problematically dogmatic. The standard solution to the dogmatism puzzle involves appealing to the view that acquiring new evidence (even misleading evidence) can undermine one’s knowledge that p. That’s why one (...) can’t rightly disregard any future evidence against p. This solution to the dogmatism puzzle has come to be called ‘the defeat solution’. Maria Lasonen-Aarnio has recently argued, however, that the defeat solution leaves unsolved a partial defeat version of the dogmatism puzzle, where some subject acquires weak misleading evidence against p, but, since it is weak, it doesn’t rob her of knowledge that p. Lasonen-Aarnio argues that solving this partial defeat version of the dogmatism puzzle requires those who endorse the defeasibility of knowledge to either go dogmatist or reject an extremely plausible principle that she calls ‘Entitlement’ (roughly, for any S and any e, if S knows that evidence e is misleading, then S can rightly disregard e). In this paper, however, I argue that defeasibilists face no such challenge from any version of the dogmatism puzzle, since the dogmatism puzzle, in both its original and partial defeat form, rests on an assumption that we have very good reason to think is mistaken. Specifically, the assumption that, for any S and any p, if S knows that p, then S knows (or is in a position to know) that any evidence against p is misleading. I further argue that rejecting this assumption also yields a neat solution to the dogmatism puzzle involving intention originally proposed by Saul Kripke and recently adapted by R.E. Fraser. (shrink)

Conscious recollection, of the kind characterised by sensory mental imagery, is often thought to involve ‘episodically’ recalling experienced events in one’s personal past. One might wonder whether this overlooks distinctive ways in which we sometimes recall ordinary, persisting objects. Of course, one can recall an object by remembering an event in which one encountered it. But are there acts of recall which are distinctively objectual in that they are not about objects in this mediated way (i.e., by way of being (...) about events in which they featured)? This question has broad implications, not least for understanding the nature and role of imagery in remembering, the requirements of memory-based singular thought about objects, and the sense in which remembering involves ‘mental time travel’ through which one ‘relives’ past events. In this paper, I argue that we sometimes do recall objects from our past without remembering events in which they featured. The positive view of such cases I go on to propose draws on a wide body of empirical work in its support and accommodates a more nuanced picture of the role of imagery in remembering. In a slogan: remembering might essentially involve a kind of ‘re-experiencing’, but it need not involve ‘reliving’. (shrink)

Th e present article reports a series of experiments designed to extend the empirical investigation of folk metaethical intuitions by examining how different kinds of ethical disagreement can impact attributions of objectivity to ethical claims.

Recently several authors have argued that accuracy-first epistemology ends up licensing problematic epistemic bribes. They charge that it is better, given the accuracy-first approach, to deliberately form one false belief if this will lead to forming many other true beliefs. We argue that this is not a consequence of the accuracy-first view. If one forms one false belief and a number of other true beliefs, then one is committed to many other false propositions, e.g., the conjunction of that false belief (...) with any of the true beliefs. Once we properly account for all the falsehoods that are adopted by the person who takes the bribe, it turns out that the bribe does not increase accuracy. (shrink)

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory (...) of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the “bottom up” approach) and (4) how to infer the nature of the last universal common ancestor (the “top down” approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin.We also describe another family of paths motivated by a” circularity” approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question. (shrink)

The alienation constraint on theories of well-being has been influentially expressed thus: 'what is intrinsically valuable for a person must have a connection with what he would find in some degree compelling or attractive …. It would be an intolerably alienated conception of someone’s good to imagine that it might fail in any such way to engage him' (Railton 1986: 9). Many agree this claim expresses something true, but there is little consensus on how exactly the constraint is to be (...) understood. Here, I clarify the sense in which the quote offers a basic constraint on theories of well-being—a constraint that should be adopted by (e.g.) hedonists, desire satisfactionists, and objective list theorists alike. This constraint focuses on affective engagement, or positive affective stances in connection with a proposed good. I show that the constraint explains a near-universal intuition, and rules out a number of well-known theories of well-being. (shrink)

A review of David E. Cooper's book, "Animals and Misanthropy", which argues that reflection on awful treatment of animals justifies a negative critical judgment on human life and culture.

One objection to conventional AI ethics is that it slows innovation. This presentation responds by reconfiguring ethics as an innovation accelerator. The critical elements develop from a contrast between Stability AI’s Diffusion and OpenAI’s Dall-E. By analyzing the divergent values underlying their opposed strategies for development and deployment, five conceptions are identified as common to acceleration ethics. Uncertainty is understood as positive and encouraging, rather than discouraging. Innovation is conceived as intrinsically valuable, instead of worthwhile only as mediated by social (...) effects. AI problems are solved by more AI, not less. Permissions and restrictions governing AI emerge from a decentralized process, instead of a unified authority. The work of ethics is embedded in AI development and application, instead of functioning from outside. Together, these attitudes and practices remake ethics as provoking rather than restraining artificial intelligence. (shrink)

Ontology is one strategy for promoting interoperability of heterogeneous data through consistent tagging. An ontology is a controlled structured vocabulary consisting of general terms (such as “cell” or “image” or “tissue” or “microscope”) that form the basis for such tagging. These terms are designed to represent the types of entities in the domain of reality that the ontology has been devised to capture; the terms are provided with logical defi nitions thereby also supporting reasoning over the tagged data. Aim: This (...) paper provides a survey of the biomedical imaging ontologies that have been developed thus far. It outlines the challenges, particularly faced by ontologies in the fields of histopathological imaging and image analysis, and suggests a strategy for addressing these challenges in the example domain of quantitative histopathology imaging. The ultimate goal is to support the multiscale understanding of disease that comes from using interoperable ontologies to integrate imaging data with clinical and genomics data. (shrink)

Background: The attitudes of many undergraduates towards practicum exercise is declining in each passing year, affecting the quality of educational leaders produced from higher education. Studies in the past, have documented that there is no significant difference in the attitudes of students with or without practicum experience towards academic activities in higher education. Little or nothing seems to be known at the moment regarding the reasons why there is an indifference in the attitudes of students after completing a practicum course. (...) In response to this gap, we designed this study to assess principals' leadership variables as the presumed cause of undergraduates' declining attitudes towards practicum exercise in secondary schools. -/- Methods: A census study was carried out in Cross River State, where the entire 667 secondary school administrators (271 principals and 396 vice principals) were studied. “Principals’ Leadership Variables and Undergraduates’ Attitudes Towards Practicum Exercise Questionnaire” (PLVUATPEQ), designed by the researchers, was used in data collection. Data collected were analysed using simple linear regression analysis. Results: We find amongst others, that principals’ leadership styles, communication patterns, decision-making and supervisory approaches significantly predict undergraduates' attitudes towards practicum exercise relatively. Each of these independent variables accounts differently for the variance in the dependent variable based on their unique coefficient of determination. -/- Conclusion: It was concluded generally, that principals’ leadership variables significantly predict undergraduates’ attitudes towards practicum exercise. The attitudes of undergraduates towards practicum exercise increases as the leadership styles, communication patterns, decision-making skills, and supervisory approaches of principals improve. The implications of this study are discussed for policy and educational reforms. (shrink)

While many philosophers of religion are familiar with the reconciliation of grace and freedom known as Molinism, fewer by far are familiar with that position initially developed by Molina’s erstwhile rival, Domingo Banez (i.e., Banezianism). My aim is to clarify a serious problem for the Banezian: how the Banezian can avoid the apparent conflict between a strong notion of freedom and apparently compatibilist conclusions. The most prominent attempt to defend Banezianism against compatibilism was (in)famously endorsed by Reginald Garrigou-Lagrange. Even if (...) it were true that freedom does not require alternative possibilities, Banezians have a grounding problem. (shrink)

Recent theorizing argues that online communication technologies provide powerful, although precarious, means of emotional regulation. We develop this understanding further. Drawing on subjective reports collected during periods of imposed social restrictions under COVID-19, we focus on how this precarity is a source of emo-tional dysregulation. We make our case by organizing responses into five distinct but intersecting dimensions wherein the precarity of this regulation is most relevant: infrastructure, functional use, mindful design (individual and social), and digital tact. Analyzing these reports, (...) along with examples of mediating technologies (i.e., self-view) and common interactive dynamics (e.g., gaze coordination), we tease out how breakdowns along these dimensions are sources of affective dysregulation. We argue that the adequacy of available technological resources and competencies of various kinds matter greatly to the types of emotional experiences one is likely to have online. Further research into online communication technologies as modula-tors of both our individual and collective well-being is urgently needed, especially as the echoes of the digital push that COVID-19 initiated are set to continue rever-berating into the future. (shrink)

The second half of the 20th century may fairly be considered a golden age for the study of ancient philosophy. This period witnessed the creation of four English-language journals for specialists and two professional societies. Throughout this period there were numerous regional and national conferences, reading groups, NEH-sponsored summer seminars and institutes on various aspects of ancient thought, successful graduate programs in ancient philosophy at a sizable number of American universities, and a steady supply of jobs for specialists in the (...) field. Seminal studies by Gregory Vlastos and G.E.L. Owen stimulated broad interest in ancient Greek philosophy by showing how the methods and issues explored by ancient thinkers were relevant to contemporary philosophical debates. On a less happy note, in recent years some influential analytic philosophers have discounted the value of work in the history of philosophy, and public funding for philosophy, along with other humanities fields, has declined sharply. -/- . (shrink)

Research has probed the consequences of providing people with different types of information regarding why a person possesses a certain characteristic. However, this work has largely examined the consequences of different information subsets (e.g., information focusing on internal versus societal causes). Less work has compared several types of information within the same paradigm. Using the legal system as an example domain, we provided children (N=198 6- to 8-year-olds) with several types of information—including information highlighting internal moral character, internal biological factors, (...) behavioral factors, and societal factors—about why a specific outcome (incarceration) might occur. We examined how such language shaped children’s attitudes. In Study 1, children reported the most positivity toward people who were incarcerated for societal reasons and the least positivity toward people who were incarcerated for their internal moral character; attitudes linked with behavioral information fell between these extremes. Studies 2a-2b suggested that Study 1’s effects could not be fully explained by participants drawing different about individuals in Study 1. Study 3 replicated Study 1’s results and showed that information linking incarceration with internal biological factors led to more positivity than information linking incarceration with internal moral character. Finally, Study 4 suggested that the patterns found in Studies 1 and 3 generalize to non-punitive contexts. Moreover, Study 4 found that the effects in Studies 1 and 3 emerged regardless of whether information was communicated via explanations or descriptions. These results demonstrate that how we express our beliefs about social phenomena shape the realities in which others live. (shrink)

This paper challenges the standard a priori/a posteriori distinction by looking at statements in which comprehension requires more that merely passive awareness of objects and their properties. A proposal is made to add to the traditional categories of knowledge, the “a positio,” characterized by active, intentional, and collective involvement of language users in the existence and nature of objects of reference needed for the truth of statements about various kinds of artifacts, broadly construed. The conditions of understanding statements about institutions, (...) institutional activity and standards of measurement are considered in some detail. (shrink)

The COVID-19 pandemic led to social restrictions that often prevented us from hugging the ones we love. This absence helped some realize just how important these interactions are to our sense of care and connection. Many turned to digitally mediated social interactions to address these absences, but often unsatisfactorily. Some theorists might blame this on the disembodied character of our digital spaces, e.g., that interpersonal touch is excluded from our lives online. However, others continued to find care and connection in (...) their digitally mediated interactions despite not being able to touch. Inspired by such contrasting cases, we ask if ‘digital hugs’ can work? We use the Mixed Reality Interaction Matrix to examine hugging as a social practice. This leads us to several claims about the nature of our embodied social interactions and their digital mediation: (1) all social interaction is mediated; (2) all virtual experiences are embodied; (3) technology has become richer and more supportive of embodiment; and (4) expertise plays a role. These claims help make the case that quality social connections online are substantially dependent upon the dynamic skilful resourcing of multiple mediating components, what we term digital tact. By introducing and developing this concept, we hope to contribute to a better understanding of our digital embodied sociality and the possibilities for caring connections online. (shrink)

A common response to radical skeptical challenges to our knowledge of the external world has been that there are explanatory reasons (e.g., simplicity, coherence, explanatory power, conservatism) for favoring commonsense explanations of our sensory experiences over skeptical explanations. Despite the degree of visibility this class of response has enjoyed, it has often been viewed with skepticism [sic] by the epistemological community because of concerns about the epistemic merits of explanatory reasoning. I argue that skeptical challenges that employ skeptical hypotheses presuppose (...) central explanationist tenets and that this fact should raise one’s estimation of the strength of explanationist responses to skepticism. (shrink)

Amie Thomasson’s work provides numerous ways to rethink and improve our approach to metaphysics. This chapter is my attempt to begin to sketch why I still think the easy approach leaves room for substantive metaphysical work, and why I do not think that metaphysics need rely on any ‘epistemically metaphysical’ knowledge. After distinguishing two possible forms of deflationism, I argue that the easy ontologist needs to accept (implicitly or explicitly) that there are worldly constraints on what sorts of entities could (...) exist, and could co-exist. I argue this leaves room for a substantive role for metaphysics if (following the work of E.J. Lowe) we take metaphysics to be concerned with the possible ways that reality could be. I explain how this conception does not need to appeal to any ‘epistemically metaphysical’ knowledge, and need only make use of conceptual and/or empirical means to arrive at views on what could exist (and co-exist). Thus, the answer I propose to the question posed in the title, at least in my view, is no-one. Or, at least, no-one should be afraid of conceptual analysis. Not even metaphysicians. (shrink)

Arthur Danto claims that knowing that S is not a property of some individual knower M but a relation between M and some object O in the world, where O is what makes S true. For if knowledge were a property of M it would be possible to determine whether M knew simply by examining M, which is typically not the case (i.e. unless S happens to be about M). I argue that Danto errs in: (1) claiming that we can (...) determine whether or not some assertion S is true only by observing the truth conditions for S; (2) claiming that we cannot determine whether s is true by examining M; and (3) claiming that since the statement that M knows that S ‘says something about both M and the world’ it must assert a relation between M and the world. (shrink)

This chapter examines the views of Socrates, Plato, and Aristotle on lying. It it outlines the differences between different kinds of falsehoods in Plato (real falsehoods and falsehoods in words), the difference between myths and lies, the 'noble' (i.e., pedigree) lie in The Republic, and how Plato defended rulers lying to non-rulers about, for example, eugenics. It considers whether Socrates's opposition to lying is consistent with Socratic irony, and especially with his praise of his interlocutors as wise. Finally, it looks (...) at Aristotle's condemnation of lies, and asks whether lies to enemies, and self-deprecating lies by the magnanimous person, are not base. (shrink)

Let me say something, to begin with, about wanting weird stuff. Stuff like saucers of mud. The example, famously, is from Anscombe’s Intention (Anscombe Anscombe 957)) where she is, in effect, defending a version of the old scholastic maxim, Omne appetitum appetitur sub specie boni. If your Latin is rusty like mine, what that says is just that every appetite – for better congruence with modern discussions, let’s say every desire – desires under the aspect of the good, or in (...) the wording made current by Velleman, under the guise of the good (Velleman 992). To desire something is to regard it as good in some way, as having some desirability characteristic. And not just any old thing can be regarded as good in some way, as having some desirability characteristic. Obviously if this is correct, it rules against our giving desires any sort of ground-floor role in our understand-. (shrink)

Gender, race, and sexuality are not just identities; they are also systems of social organization – i.e., systems of privilege and oppression. This article addresses two main ways privilege and oppression (e.g., racism, misogyny, heteronormativity) are relevant topics in and for philosophical aesthetics: (i) the role of the aesthetic in privilege and oppression, and (ii) the role of philosophical aesthetics, as a discipline and a body of texts, in constructing and naturalizing relations of privilege and oppression (i.e., white heteropatriarchy). The (...) first part addresses how systems of privilege and oppression use the aesthetic. I will discuss various ways race, gender, and sexuality, as both embodied identities and broader social institutions, work with and through “the aesthetic”. The second part addresses racism and (hetero) sexism in the discipline of aesthetics. Both in its history and its present practice aesthetics’apparent neutrality on questions of privilege and oppression is actually evidence of its investment in systems of privilege and oppression. (shrink)

Public reason liberalism is the political theory which holds that coercive laws and policies are justified when and only when they are grounded in reasons of the public. The standard interpretation of public reason liberalism, consensus accounts, claim that the reasons persons share or that persons can derive from shared values determine which policies can be justified. In this paper, I argue that consensus approaches cannot justify fair educational policies and preserving cultural goods. Consensus approaches can resolve some controversies about (...) teaching values in the educational system, such as curriculum choice. But they cannot determine which culture goods, e.g., architecture, artwork, or language ought to be preserved in the education system. Consensus approaches cannot fairly resolve competing claims about these kinds of disputes. -/- I propose that convergence accounts of public reason, which allow individuals to draw on their own comprehensive doctrines in limited ways, can remedy these weaknesses in the mainline public reason tradition. The convergence approach can justify a pluralist state that can advance valuable community goods. John Henry Newman’s advocacy of liberal arts education finds resonance in other cultures, notably among Confucians, illustrating that there can be a shared moral vision and inquiry into the good life across deep substantive disagreements about educational values and policies, once we expand our notion of justification to be more inclusive. (shrink)

I am interested in the use Kant makes of the pure intuition of space, and of properties and principles of space and spaces (i.e. figures, like spheres and lines), in the special metaphysical project of MAN. This is a large topic, so I will focus here on an aspect of it: the role of these things in his treatment of some of the laws of matter treated in the Dynamics and Mechanics Chapters. In MAN and other texts, Kant speaks of (...) space as the “ground,” “condition,” and “basis” of various laws, including the inverse-square and inverse-cube laws of attractive and repulsive force, and the Third Law of Mechanics. Moreover, in his proofs of all the laws just mentioned, the language of “construction” figures prominently, which suggests that Kant’s proofs (somehow) rest on or involve mathematical construction in his technical sense. Such claims give rise to a number of questions. How do properties and principles of space and spaces serve to ground this particular set of laws? Which spatial properties and principles is Kant appealing to? What, if anything, does the spatial grounding of the inverse-square and inverse-cube laws of diffusion (treated in the Dynamics Chapter) have in common with that of the Third treated in the Mechanics Chapter)? What role—if any—does mathematical construction play in Kant’s proofs of these laws? Finally, how if at all, are Kant’s grounding claims consistent with his other commitments—for example, how are they consistent with his notorious denial in Prolegomena §38 that there are any laws that “lie in space” (Prol 4:321)? I offer answers to these questions. (shrink)

In the last decade, there has been a notable upsurge in property (PD) and generic substance dualism (SD). By SD I mean the view that there is a spiritual substantial soul that is different from but variously related to its body. SD includes Cartesian, certain forms of late Medieval hylomorphic (e.g., Aquinas'), and Haskerian emergent SD. Nevertheless, some form of physicalism remains the majority view in philosophy of mind. Several fairly standard objections have been raised against SD, and SDists have (...) been preoccupied with these objections. As a result, a potent objection has not been given the attention it deserves. The purpose of this article is to fill that lacuna by raising the visibility of this objection and providing plausible responses to it. First, I shall clarify the explanatory–impotence challenge and, second, provide defeaters against it. Note that several of the issues to follow apply both to PD and SD. I will focus mostly on SD, but sometimes PD is a part of the discussion in that certain arguments for and against PD indirectly affect SD. When it is important for me to note that either SD or PD is specifically being addressed, I will notify the reader. (shrink)

A ‘duality’ is a formal mapping between the spaces of solutions of two empirically equivalent theories. In recent times, dualities have been found to be pervasive in string theory and quantum field theory. Naïvely interpreted, duality-related theories appear to make very different ontological claims about the world—differing in e.g. space-time structure, fundamental ontology, and mereological structure. In light of this, duality-related theories raise questions familiar from discussions of underdetermination in the philosophy of science: in the presence of dual theories, what (...) is one to say about the ontology of the world? In this paper, we undertake a comprehensive and non-technical survey of the landscape of possible ontological interpretations of duality-related theories. We provide a significantly enriched and clarified taxonomy of options—several of which are novel to the literature. (shrink)

It is well known that the following features hold of AR + T under the strong Kleene scheme, regardless of the way the language is Gödel numbered: 1. There exist sentences that are neither paradoxical nor grounded. 2. There are 2ℵ0 fixed points. 3. In the minimal fixed point the weakly definable sets (i.e., sets definable as {n∣ A(n) is true in the minimal fixed point where A(x) is a formula of AR + T) are precisely the Π1 1 sets. (...) 4. In the minimal fixed point the totally defined sets (sets weakly defined by formulae all of whose instances are true or false) are precisely the ▵1 1 sets. 5. The closure ordinal for Kripke's construction of the minimal fixed point is ωCK 1. In contrast, we show that under the weak Kleene scheme, depending on the way the Gödel numbering is chosen: 1. There may or may not exist nonparadoxical, ungrounded sentences. 2. The number of fixed points may be any positive finite number, ℵ0, or 2ℵ0 . 3. In the minimal fixed point, the sets that are weakly definable may range from a subclass of the sets 1-1 reducible to the truth set of AR to the Π1 1 sets, including intermediate cases. 4. Similarly, the totally definable sets in the minimal fixed point range from precisely the arithmetical sets up to precisely the ▵1 1 sets. 5. The closure ordinal for the construction of the minimal fixed point may be ω, ωCK 1, or any successor limit ordinal in between. In addition we suggest how one may supplement AR + T with a function symbol interpreted by a certain primitive recursive function so that, irrespective of the choice of the Godel numbering, the resulting language based on the weak Kleene scheme has the five features noted above for the strong Kleene language. (shrink)

This (1982) essay sets out the claim that psychoanalysis is a cogent extension of the intuitive common sense psychology by which we naturally understand human action. In this psychology explanation proceeds by relating actions to the logically and causally cohering desires and beliefs of agents. As Freud showed, this kind of explanation is systematically deepened and extended by the explanation of dreams, the symptoms of mental disorder, and other related phenomena via the Freudian concept of wish fulfilment, which was later (...) extended to the more inclusive post-Freudian concept of phantasy. In this extension everyday actions, such as Freud's writing up his patient Irma's case history on the day before his dream of Irma's injection, are seen to be rooted in the same unconscious motives as are represented as fulfilled in dreams and symptoms -- e.g., in this case, by unconscious stirrings of deep guilt on the topic of injection, of which Freud was unaware until he analysed the dream. As this illustrates, the understanding of wishfulfilments and other formations of phantasy enables us fill out our account of agents and their actions by adding a stock of previously unacknowledged desires and modes of expression of desire. These are seen to cohere with, and also to deepen, our previous understanding: after understanding Freud's dream, we also have a deeper and firmer (and so more cogent) understanding of his behaviour on the previous day. In this way Freud effected an extension of our everyday mode of understanding that was cogent, cumulative, and radical, as illustrated further by examination of Freud's case history of the patient described as the Rat Man. (shrink)

This is a book review of Becoming Bamboo....

Much work has highlighted the degree to which children and adults view human characteristics as immutable. Less work has elucidated how people may conceptualize such immutability. Using immigration as an example domain, we examined the extent to which children’s (N=112 5- to 10-year-olds) immutability concepts reflected beliefs about others lacking the ability and/or the desire to change. Children readily agreed that immigrants could—and wanted to—change certain aspects of their identities (i.e., by adopting the norms of their new country). We also (...) investigated the social ramifications of messages focusing on different aspects of immutability. Children felt and behaved more positively toward people who had the ability and desire to change than toward those who did not. Moreover, information about desires played a greater role in shaping children’s attitudes and behaviors than did information about abilities. This work extends scholarship on psychological essentialism by highlighting the need to study sub-components of a specific pillar of essentialist thought (i.e., separating the immutability component of essentialism into perceptions regarding people's perceived desire and, separately, perceived ability to change), partially because essentialism impacts social cognition and behavior differently across sub- components. (shrink)

Feminist, critical race, and postcolonial theories have established that social identities such as race and gender are mutually constitutive—i.e., that they “intersect.” I argue that “cultural appropriation” is never merely the appropriation of culture, but also of gender, sexuality, class, etc. For example, “white hipness” is the appropriation of stereotypical black masculinity by white males. Looking at recent videos from black male hip-hop artists, I develop an account of “postmillennial black hipness.” The inverse of white hipness, this practice involves the (...) appropriation, by black men, of stereotypical white gay masculinity and/or non-American, non-white femininity. I also argue that Shephard Fairey’s recent images of (mainly militant) non-Western women of color can be read as a new form of white hipness that revises the traditional logic in two ways: (1) by appropriating non-white femininity rather than masculinity, and (2) by adopting the practice of postmillennial black hipness itself. (shrink)

I will argue that the Kane-Widerker objection to Frankfurt examples is much weaker than is generally recognized. The Kane-Widerker objection holds that proponents of Frankfurt examples beg the question against incompatibilist accounts of free and responsible action by constructing examples that tacitly assume a compatibilist account of moral responsibility; that is, they assume that one can have non-derivative responsibility for choices that were not undetermined prior to their occurrence. The notion of an event, E, being ‘undetermined prior to its occurrence’ (...) is ambiguous. It can mean either (1) with respect to each time t prior to E’s occurrence, it is not the case that at t E’s occurrence is determined to take place, or it can mean (2) with respect to the whole collection of times prior to E’s occurrence, E’s occurrence is not determined to take place. Kane’s argument shows that (under certain constraints) if a choice is to be undetermined (in the second sense) prior to its occurrence, then a prior-sign Frankfurt example cannot be successful. But he fails to show that prior-sign Frankfurt examples cannot be constructed in which the choice is undetermined (in the first sense) prior to its occurrence, and he would need to do so in order to sustain his charge that those using Frankfurt examples beg the question against traditional incompatibilist accounts of responsibility. Widerker’s argument avoids the above problem, but at the cost of only applying to a rather restricted set of Frankfurt examples. (shrink)

The philosophical study of irrationality can yield interesting insights into the human mind. One provocative issue is self-defeating behaviours, i.e. behaviours that result in failure to achieve one’s apparent goals and ambitions. In this paper I consider a self-defeating behaviour called choking under pressure, explain why it should be considered irrational, and how it is best understood with reference to skills. Then I describe how choking can be explained without appeal to a purely Freudian subconscious or ‘sub-agents’ view of mind. (...) Finally, I will recommend an alternative way to understand self-defeating behaviour which comes from a synthesis of Peter Strawson’'s explanation of ‘self-reactive attitudes’, Mark Johnston’'s notion of ‘mental tropisms’, and revised Freudian descriptions of the causes of self-defeating behaviour. (shrink)

A. E. Taylor states the widely held view that Plato’s Euthyphro posed a question which figured prominently in later ethical controversies: “It amounts to asking whether acts of piety, or more generally virtuous acts, derive their character of being right from the mere fact of being commanded or are commanded because they are antecedently intrinsically right.” I argue against this characterization of the Euthyphro. The argument Socrates deploys against Euthyphro’s third and most serious definition of holiness or piety (to hosion) (...) is not the opening round in the debate over divine command theory nor is a discussion of the nature of holiness ipso facto an exercise in ethical theory. (shrink)

In this chapter, the frameworks of enactive cognitive science (e.g., Baran- diaran 2008, 2017; Di Paolo et al. 2018) and ontological design, particu- larly the work of Tony Fry (e.g., 2009), are synthesized to give a general account of how humans act toward change at multiple scales. According to this synthesis, design is understood as a spatiotemporally extended form of adaptive self-regulation, or adaptivity in the enactive vocabulary (Di Paolo 2005). When we design, we regulate ourselves in the local-present to (...) resource our future selves in ways that make certain regulations either possible or easier, and thus, desired outcomes more probable. Adaptivity, here, entails an ongoing redirection of the individuating tendencies of person-world systems either for maintaining some existing trajectories or for stabilizing new ones. This happens predominantly through modify- ing constraints at what Secchi and Cowley (2018, 2021) term the meso- scale of social organizing. This chapter considers diferent types of design (maintenance, habit, identity) operative across scales, from organisms to organizations. It concludes with some indications for how this perspective might be valuable in facing current ecological and environmental chal- lenges and the obvious demands they put on the need for change across all scales of human living. (shrink)

I argue that, although education should have positive effects on students’ epistemic character, it is often actually damaging, having bad effects. Rather than cultivating virtues of the mind, certain forms of education lead to the development of the vices of the mind - it is therefore epistemically corrupting. After sketching an account of that concept, I offer three illustrative case studies.

The teachings and actions of Jesus Christ (Yeshua Ha'Mashiach) and the apostles recorded in the New Testament are analyzed in regard to their ethical and political philosophy, with analysis of context vis-à-vis the Old Testament (Tanakh, or Hebrew Bible) being given. From this analysis, it is shown that Jesus is a libertarian anarchist, i.e., a consistent voluntaryist. The implications this has for the world are profound, and the ramifications of Jesus's anarchism to Christians' attitudes toward government (the state) and its (...) actions are explicated. (shrink)

The purpose of this paper is to analyze the theoretical commitments of autopoietic enactivism in relation to Errol E Harris’s dialectical holism in the interest of establishing a common metaphysical ground. This will be undertaken in three stages. First, it is argued that Harris’s reasoning provides a means of developing enactivist ontology beyond discussions limited to cognitive science and into domains of metaphysics that have traditionally been avoided by phenomenologists. Here, I maintain enactivist commitments are consistent with Harris’s reasoning from (...) certain synthetic a priori first principles, to his derivation of a teleological anthropic principle, which asserts the necessity of consciousness within the cosmos. Second, it is proposed that Steven Rosen’s long-standing proposal for a topology of phenomenology may provide a common logical foundation for both Harris and enactivists regarding anthropic reasoning. Third, it is argued that a pragmatic approach to process ontology is the most rigorous way of responding to the realism/anti-realism concerns that inevitably follow. If successful, this work will update Harris’s arguments with contemporary scientific and philosophical terminology and extend enactivism from philosophy of mind, into a general phenomenological ontology. (shrink)