DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

The context for biological emergence is modular hierarchical structures; their existence is what enables functional complexity to arise. Because of the openness of organisms to their environment, complete initial data (position, momentum) of all particles making up their structure is insufficient to determine future outcomes, because unpredictable new matter, energy, and information impacts each organism from the exterior. Consequently, through Darwinian evolution, life has developed processes to handle this issue functionally on short time scales as well on longer developmental timescales. (...) Symbolism and technology are the transforming factors handling this issue at the social levels, which is where the most sophisticated outcomes of openness occur. Considering the cosmological context, the issue is, should the universe itself be regarded as an open system over time? I make the case that is indeed so, because radically new outcomes occur such as the existence of aircraft, iPads, and the internet, which could not plausibly have been encoded in some form of data on the Last Scattering Surface in the expanding universe. (shrink)

The topic of a priori knowledge is approached through the theory of evidence. A shortcoming in traditional formulations of moderate rationalism and moderate empiricism is that they fail to explain why rational intuition and phenomenal experience count as basic sources of evidence. This explanatory gap is filled by modal reliabilism -- the theory that there is a qualified modal tie between basic sources of evidence and the truth. This tie to the truth is then explained by the theory of concept (...) possession: this tie is a consequence of what, by definition, it is to possess (i.e., to understand) one’s concepts. A corollary of the overall account is that the a priori disciplines (logic, mathematics, philosophy) can be largely autonomous from the empirical sciences. (shrink)

Nie Bao 聶豹 (1487–1563) was a Neo-Confucian philosopher and scholar-official of sixteenthcentury Ming China. In his Ming ru xue an 明儒學案 (Case studies of Ming Confucians), Huang Zongxi 黃宗羲 placed him in the Jiangxi (Jiangyou 江右) group of Wang Yangming followers. Nie Bao met the influential founder of the Ming School of Mind in 1526 and was inspired by his teaching of the innate knowing (liangzhi 良知). However, he differed from other followers in his quietist approach to realizing and extending (...) this knowledge. While developing his ideas over the course of two decades, as a holder of the highest civil service examination degree, Nie Bao also held a series of impactful official positions, and earned a reputation for effectiveness and integrity. However, he was also the unwitting victim of factionalism at the Ming court, which led to his imprisonment in 1548. The goal of this article is to provide a sketch of Nie Bao’s political trajectory and intellectual development from his early years until his imprisonment, as well as translation of significant passages pertaining to that trajectory and development. By the time of his imprisonment, Nie Bao had articulated the essential elements of his philosophy of returning to the root (by which he meant silence), and attaining centeredness and, with that, his unique interpretation of his teacher’s central tenet. (shrink)

Professor Fletcher challenges the traditional account of the development of tort doctrine as a shift from an unmoral standard of strict liability for directly causing harm to a moral standard based on fault. He then sets out two paradigms of liability to serve as constructs for understanding competing ideological viewpoints about the proper role of tort sanctions. He asserts that the paradigm of reciprocity, which looks only to the degree of risk imposed by the parties to a lawsuit on each (...) other, and to the existence of possible excusing conditions, provides greater protection of individual interests than the paradigm of reasonableness, which assigns liability instrumentally on the basis of a utilitarian calculus. Finally, Professor Fletcher examines stylistic differences between the two paradigms which may explain the modern preference for the paradigm of reasonableness. (shrink)

This paper offers a brand storytelling, that is a narratological account of Covid-19 pandemic’s emergence phase. By adopting a fictional ontological standpoint, the virus’ deploying media story-world is identified with a process of narrative spacing. Subsequently, the brand’s personality is analyzed as a narrative place brand. The narrative model that is put forward aims at outlining the main episodes that make up the virus’ brand personality as process and structural components (actors, settings, actions, relationships). A series of deep or ontological (...) metaphors are singled out as the core DNA of this place brand, by applying metaphorical modeling to the tropical articulation of Covid-19’s narrative. The virus’ kernel is identified with terror, as a menacing force that wipes out existing regimes of signification due to its uncertain motives, origins and operational mode. In this context, familiar urban spaces, cultural practices and intersubjective communications are redefined, repurposed and reprogrammed. This process is called terrorealization, as the desertification and metaphorical sublation of all prior territorial significations. This study contributes to the narrative sub-stream of place branding by approaching a globally relevant sociocultural phenomenon from a brand storytelling perspective. (shrink)

This paper constructs a model of metaphysical indeterminacy that can accommodate a kind of ‘deep’ worldly indeterminacy that arguably arises in quantum mechanics via the Kochen-Specker theorem, and that is incompatible with prominent theories of metaphysical indeterminacy such as that in Barnes and Williams (2011). We construct a variant of Barnes and Williams's theory that avoids this problem. Our version builds on situation semantics and uses incomplete, local situations rather than possible worlds to build a model. We evaluate the resulting (...) theory and contrast it with similar alternatives, concluding that our model successfully captures deep indeterminacy. (shrink)

Social scientists, political scientists and philosophers debate key concepts such as democracy, power and autonomy. Contested concepts like these pose questions: Are terms such as “democracy” hopelessly ambiguous? How can two theorists defend alternative accounts of democracy without talking past each other? How can we understand debates in which theorists disagree about what democracy is? This paper first discusses the popular strategy to answer these questions by appealing to Rawls’s distinction between concepts and conceptions. According to this approach, defenders of (...) rival conceptions of, e.g. justice can disagree without talking past each other because they share the concept of justice. It is argued that this idea is attractive but limited in application and that it fails to do justice to the dynamic and normative aspects of concept formation. Reflective equilibrium is then suggested as an alternative approach. It replaces the static contrast between a conceptual ‘core’ and competing conceptions by a dynamic perspective of concept formation as a partly normative undertaking: pre-theoretic language use and commitments can provide a shared starting point for developing alternative accounts which yield different concepts of, e.g. justice. This perspective provides a new understanding of how it is possible that different theorists defend rival accounts of, e.g. justice, without talking past each other. (shrink)

This paper addresses the scarcely scrutinized topic in the consumer culture literature regarding how a social actor consumes himself through speech acts. More specifically, by introducing a new type of speech act, viz. the taboo speech act, and by effectively differentiating it from expletives, slang, and swearing words and expressions, I outline how subjectivity appropriates and individuates its systemic underpinning as other or linguistic system (Saussure) and wall of language (Lacan) in linguistic acts of transgression. Taboo speech acts do not (...) merely express emotions, such as anger and frustration. They also seek to contain a linguistic system as an ideational totality of acts of parole in a primus affectivus that is incumbent on the inverse sublimation of epithets and cultural symbols standing synecdochically in a pars pro toto relationship for the limits of what is culturally/linguistically sanctioned. The subject consumes/annihilates and institutes itself at the same time in taboo speech acts whose mission may not be fully accounted for through conversational pragmatics, insofar as they perform at a more foundational level a social ontological function. The offered analysis aims at contributing to the extant literature in consumer cultural theory, applied linguistics, and social theory. (shrink)

This paper examines the role of respect (specifically, the interest in having the respect of other people) in enabling blame to be effective: i.e., to achieve the desired effect of changing the blamed’s attitude and behavior. It develops an account of blame’s operations in three different cases: standard, intermediate, and proleptic. It ends by raising the worry that effective blame toward the morally distant approximates manipulation and coercion, leaving a moral residue.

If a political theory of ownership is to be acceptable, it must rationally prescribe one system or model of ownership as opposed to others. Such a prescription would be rational only if strong normative arguments could be mounted to show it more desirable than its competitors. Thus, the prefatory work for such a theory would consist in the construction of viable models of ownership from which a sound choice could be made. This project would, however, be successful only if originating (...) from coherent, evaluatively neutral analyses of the concept of ownership and other related ideas. The point of this essay is to do this prefatory work. (shrink)

Scientific essentialism is the view that some necessities can be known only with the aid of empirical science. The thesis of the paper is that scientific essentialism does not extend to the central questions of philosophy and that these questions can be answered a priori. The argument is that the evidence required for the defense of scientific essentialism is reliable only if the intuitions required by philosophy to answer its central questions is also reliable. Included is an outline of a (...) modal reliabilist theory of basic evidence and a concept-possession account of the reliability of a priori intuition. (shrink)

Usually evolutionary economists equate evolutionary theory with modern Darwinism. However the rise of evolutionary developmental biology (Evo-Devo) puts into question the monopoly of Darwinism in evolutionary biology. The major divergences between the two paradigms in evolutionary biology are drawn in the analysis of three trade-offs: population vs. typological thinking, creative role of natural selection vs. internal (inherent) change, and microevolution vs. macroevolution. It is argued here that the Evo-Devo breakthrough helps to better understand the limits to Darwinism in the social (...) realm and design the contours of an alternative paradigm in evolutionary economics privileging structural macroevolution and what Schumpeter called “change from within”. (shrink)

This study provides a unified theory of properties, relations, and propositions (PRPs). Two conceptions of PRPs have emerged in the history of philosophy. The author explores both of these traditional conceptions and shows how they can be captured by a single theory.

This paper offers a social phenomenological reading of the globally binding practice of 'social distancing' in light of the precautionary measures against the spreading of the Covid-19 virus. Amid speculation about the far-reaching effects of temporarily applicable measures and foresights about the advent of an ethos that has been heralded by the media as the 'new normal', the ubiquitous phenomenon of social distancing calls for a fundamental ontological elucidation. The purported hermeneutic that is situated in the broader place branding and (...) experiential marketing literatures places Covid-19 in the shoes of Being, and, therefore, imagines how Being would behave ontologically if it were a virus. By positing that the virus does operate like Being, five these are formulated as experiential interpretive categories with regard to the ontological status of Covid-19. The adopted approach makes the following contributions to the extant literature: First, it addresses a wholly new phenomenon in place branding, namely a pre-branded place that is non-negotiable, globally applicable and seemingly equivalent to pure void. Second, it advances the application of phenomenological research in experiential consumption by highlighting the aptness of the so far peripheral (in the marketing discipline) strand of Heideggerian fundamental ontology. Third, it expands the notion of place in the place branding literature, by showing how spatialization is the outcome of temporalization, in line with the adopted phenomenological perspective. (shrink)

While it is widely agreed that Hegel’s philosophy is a philosophy of freedom, the significance and scope of Hegel’s theory of freedom is disputed. Most scholarly work on this topic has been devoted to the socio-political philosophy of the Philosophy of Right. But Hegel also speaks of freedom in a way which extends beyond the concerns of his socio-political thought. This dissertation demonstrates how Hegel’s theory of freedom is more fully grasped when it is understood as a comprehensive philosophy which (...) also involves an ontology (a logic of being) and a phenomenology (a direct experience of this logic). The free state which Hegel outlines in the Philosophy of Right is still only a limited manifestation of a freedom which also pervades other aspects of human experience. A way of thinking which is “free” (in the sense that it does not restrict itself by assuming false methodological limitations) is itself essential to our capacity for rational self-determination. Moreover, this “speculative” perspective has only been achieved through the gradual cultivation (Bildung) of the free personality throughout history. -/- This dissertation therefore investigates why Hegel thinks that freedom is at issue in abstract philosophical thought (in his logical works) as well as in concrete historical phenomena (in the Phenomenology of Spirit). This logic and appearance of freedom explicates Hegel’s statement in the Preface of the Phenomenology that the absolute is not only substance, but also subject. Having shown that both the ancient freedom of the “social substance” and the modern freedom of the “pure I” are untenable on their own terms, Hegel advances a logical and phenomenological theory of freedom in which these one-sided truths are reconciled with each other. The “substantial subject” of Hegelian freedom more fully actualizes the purely subjective freedom of the Enlightenment, enabling true individual self-determination. Freedom appears not just as the right to make arbitrary choices, but as substantial thought and conviction. (shrink)

Globalization allegedly constitutes one of the most used and abused concepts in the contemporary academic and lay lexicons alike. This paper pursues a deconstructive avenue for canvassing the semiotic economy of cultural globalization. The variegated ways whereby ideology has been framed in different semiotic perspectives (Peircean, structuralist, post-structuralist, neo-Marxist) are laid out. By engaging with the post-structuralist semiotic terrain, cultural globalization is identified with a transition from Baudrillard’s Political Economy of Signs towards a spectral ideology where signs give way to (...) traces of différance. Subsequently, the process whereby globalization materializes is conceived as a social hauntology. In this context, global citizens engage in a constant retracing of the meaning of signs of globalization that crystallize as translocally flowing ideoscapes and mediascapes. The propounded thesis is exemplified by recourse to cultural consumption phenomena from the domains of cinematic discourse, computer-gaming, food and social gaming. (shrink)

This paper argues that participation in an intimate relationship can generate additional or stronger reasons for one to act paternalistically toward the intimate. Moreover, participation in such a relationship can also weaken or cancel some of the presumptive reasons of respect one would otherwise have not to interfere. The paper also reflects, more generally, on the nature of intimate relationships, the normative significance of paternalism, and the normative differences between paternalism in larger-scale institutional contexts and paternalism in closer, interpersonal ones. (...) -/- . (shrink)

In the Protagoras, Socrates argues that all the virtues are the very same knowledge of human wellbeing so that virtue is all one. But elsewhere Socrates appears to endorse that the virtues-such as courage, temperance, and reverence-are different parts of a single whole. Ambiguity interpretations harmonize the conflicting texts by taking the virtue words to be equivocal, such as between theoretical and applied expertise, or between a power and its deeds. I argue that such interpretations have failed in their specifics (...) and in general, as I defend an alternative that takes into account Socrates' higher purpose in testing others, namely to show them their ignorance of virtue. (shrink)

This paper examines Bernard Williams’ challenge to liberal universalists (liberals “who assume their morality is universally applicable to everyone”) to provide a theory of error: “a story about the subject matter of political morality and about past people’s situation which explains why those people got it wrong about the subject matter.” It develops a theory of error that appeals to socio-historical conditions of the past to explain their role in making (1) liberal values and reasons epistemically inaccessible, and (2) motivations (...) to live up to them unavailable. (shrink)

The paper begins with a clarification of the notions of intuition (and, in particular, modal intuition), modal error, conceivability, metaphysical possibility, and epistemic possibility. It is argued that two-dimensionalism is the wrong framework for modal epistemology and that a certain nonreductionist approach to the theory of concepts and propositions is required instead. Finally, there is an examination of moderate rationalism’s impact on modal arguments in the philosophy of mind -- for example, Yablo’s disembodiment argument and Chalmers’s zombie argument. A less (...) vulnerable style of modal argument is defended, which nevertheless wins the same anti-materialist conclusions sought by these other arguments. (shrink)

Antinatalism, a relatively recent moral philosophical perspective and ideology that avows “it is better not to have ever existed,” has spawned a new social movement with an active presence in social media. This study draws on the discourse historical approach (DHA) to critical discourse analysis for offering a firm understanding as to how the collective identity of the Facebook antinatalist NSM is formed. The findings from the analysis of the situated interaction among the NSM’s members demonstrate that collective identity is (...) far from a knitty-gritty concept, but a dynamic schema that includes a plethora of micro-interactions. Individuals constantly negotiate its meaning in context, as they seek to streamline the antinatalist system of ideas with their lifeworld through a web of interlocking schemata, discursive and rhetorical strategies. (shrink)

In this paper I aim at explaining how analytic philosophical theology developed into a thriving field of research. In doing so, I place analytic philosophical theology into a larger intellectually narrative that is deeply influenced by the philosophy of Enlightenment. This larger framework shows that analytic philosophical theology aims at providing answers to concerns raised by a philosophical tradition that shaped fundamentally the making of our modern Western secular world.

What is it to be a woman? What is it to be a man? We start by laying out desiderata for an analysis of 'woman' and 'man': descriptively, it should link these gender categories to sex biology without reducing them to sex biology, and politically, it should help us explain and combat traditional sexism while also allowing us to make sense of the activist view that gendering should be consensual. Using a Putnam-style 'Twin Earth' example, we argue that none of (...) the existing analyses in the feminist literature succeeds in meeting all of our desiderata. Finally, we propose a positive account that we believe can satisfy all the desiderata outlined. According to our theory, the genders 'woman' and 'man' are individuated not by their contemporary connections to sex biology, but by their historical continuity with classes that were originally closely connected to sex biology. (shrink)

Modal intuitions are not only the primary source of modal knowledge but also the primary source of modal error. An explanation of how modal error arises — and, in particular, how erroneous modal intuitions arise — is an essential part of a comprehensive theory of knowledge and evidence. This chapter begins with a summary of certain preliminaries: the phenomenology of intuitions, their fallibility, the nature of concept-understanding and its relationship to the reliability of intuitions, and so forth. It then identifies (...) two sources of modal error: the first has to do with the failure to distinguish between metaphysical possibility and various kinds of epistemic possibility; the second, with the local misunderstanding of one's concepts. The first source of error is widely misunderstood; the second source has not been discussed in philosophical literature. This source of modal error, and the potential to overcome it, has wide-ranging implications for philosophical method. The failure to understand these sources of modal error has recently led to sceptical accounts of intuition and modal error, which are, ultimately self-defeating. (shrink)

God is dead, but, contrary to Nietzsche’s diagnosis, ‘we’ didn’t kill him; he died of cancer. This perhaps crudely cold and off-putting opening does not refer to a naively metaphorically constituted transcendental abstraction, but to a spatio-temporally situated rock legend, Ronnie James Dio. This study aims at contributing to the burgeoning research field of memory and collective identity by providing a sociosemiotic account of the formation of collective narrative identity. By drawing on the three major categories whereby collective memory is (...) formed, that is artifacts, processes, places, as well as on the three key sociosemiotic metafunctions which are responsible for shaping a cultural event as sign system, the pursued interpretive route seeks to effectively contextualize how collective memory is fleshed out situationally in the context of Dio’s memorial. At the same time, by expanding the interpretive canvass to incorporate phenomenological perspectives on the mode of formation of collective memory, the offered analytic is intent on tracing invisible structures that point to operative mechanisms beyond the formal constraints of a sociosemiotic reading. Both phenomenological and sociosemiotic approaches are reinscribed within an overarching narrativity paradigm, wherein their relative merits in addressing the scrutinized phenomenon are discussed in an attempt to formulate a hybrid sociosemiotic phenomenological perspective of memorial events. (shrink)

Das deutsche Gesundheitswesen steht durch die schnell steigende Anzahl an CO- VID-19-Erkrankten vor erheblichen Herausforderungen. In dieser Krisensituation sind alle Beteiligten mit ethischen Fragen konfrontiert, beispielsweise nach gerech- ten Verteilungskriterien bei begrenzten Ressourcen und dem gesundheitlichen Schutz des Personals angesichts einer bisher nicht therapierbaren Erkrankung. Daher werden schon jetzt klinische und ambulante Ethikberatungsangebote verstärkt mit Anfragen nach Unterstützung konfrontiert. Wie können Ethikberater*innen Entscheidungen in der Krankenversorgung im Rahmen der COVID-19-Pandemie unterstützen? Welche Grenzen von Ethikberatung sind zu beachten? Bislang liegen hierzu (...) noch wenige praktische Erfahrungen vor. Angesichts der dynamischen Entwicklung erscheint es der Akademie für Ethik in der Medizin (AEM) wichtig, einen Diskurs über die angemessene Rolle der Ethikberatung bei der Bewältigung der vielfachen Heraus- forderungen durch die COVID-19-Pandemie zu führen und professionelle Hinweise zu geben. Mit dem vorliegenden Diskussionspapier möchte die AEM einen Beitrag zur Beantwortung wesentlicher Fragen leisten, die sich für die Ethikberatung in den verschiedenen Bereichen des Gesundheitswesens stellen. Sie regt an, diesen Dis- kurs weiter zu führen und hat ein Online-Forum (s. unten) eingerichtet, in dem Ethikberater*innen ihre Erfahrungen teilen und die professionelle Selbstreflexion der Ethikberatung in Pandemiezeiten mit Anregungen fördern können. (shrink)

This paper provides a defense of two traditional theses: the Autonomy of Philosophy and the Authority of Philosophy. The first step is a defense of the evidential status of intuitions (intellectual seemings). Rival views (such as radical empiricism), which reject the evidential status of intuitions, are shown to be epistemically self-defeating. It is then argued that the only way to explain the evidential status of intuitions is to invoke modal reliabilism. This theory requires that intuitions have a certain qualified modal (...) tie to the truth. This result is then used as the basis of the defense of the Autonomy and Authority theses. The paper closes with a defense of the two theses against a potential threat from scientific essentialism. (shrink)

Radical empiricism is the view that a person's experiences (sensory and introspective), or a person's observations, constitute the person's evidence. This view leads to epistemic self-defeat. There are three arguments, concerning respectively: (1) epistemic starting points; (2) epistemic norms; (3) terms of epistemic appraisal. The source of self-defeat is traced to the fact that empiricism does not count a priori intuition as evidence (where a priori intuition is not a form of belief but rather a form of seeming, specifically intellectual (...) as opposed to sensory). Moderate rationalism, by contrast, avoids self-defeat. (shrink)

The various ways whereby spatial conditions afford to monumentalize culture and to appropriate geographically demarcated places in terms of individual and collective meaning structures has been amply documented in urban cultural studies. However, considerably less attention has been paid to how cultural identity is produced against the background of musical temporality. By way of a phenomenological inquiry into the staged spectacle of James Corden’s (the host of CBS Network’s Late Late Show) Carpool Karaoke, this paper addresses the issues of directly (...) lived experience and authenticity as facets of cultural identity. By critically discussing the assumptions of self-presence and auto-affectivity while singing and listening to one’s sung voice against the background of pre-recorded songs, the notion of directly lived musical experience is put to the test. Furthermore, by examining the dramaturgical scaffolding of Carpool Karaoke, the analysis points to wider implications for post-modern cultural studies in terms of an identified ironic reversal of modernist universal criteria of legitimacy in favor of a celebration of postmodern being-with inauthentically. The analysis of the selected Carpool Karaoke corpus utilizes a resourceful blend of phenomenological method, semiotics and interpretive videography while challenging embedded orthodoxies in the extant literature. (shrink)

Logik ist nach dem traditionellen Verständnis eine ars iudicandi, eine Kunst, die Gültigkeit von Schlüssen zu prüfen. Da mit die normalen Mittel der modernen Logik zu diesem Zweck eingesetzt werden können, müssen erst Formeln an die Stelle von Sätzen treten: umgangssprachliche Schlüsse müssen adäquat formalisiert werden. Die richtige Formel entwickelt ein theoretisches Konzept des Formalisierens und praktisch anwendbare Adäquatheitskriterien für Formalisierungen. Dabei werden zentrale Fragen der Philosophie der Logik unter dem Gesichtspunkt des Zusammenspiels von Umgangssprache und Formalismus untersucht. Die ausführliche (...) und systematische Diskussion von Formalisierungstests bietet eine wichtige Ergänzung zu den traditionellen Logiklehrbüchern. (shrink)

The inherently subjective nature of consciousness severely limits our ability to make progress on the problem of consciousness. The inability to acquire objective, publicly available data on the phenomenal aspect of consciousness makes evaluating alternative theories very difficult, if not impossible. However, the anomalous nature of subjective states with respect to our conventional theories of the physical world suggests the possibility of considering other anomalous data around consciousness that happen to be objective. For such purposes, I propose that we examine (...) the psi data gathered under laboratory conditions, which generally receive little attention. I wish to consider whether we have theories or frameworks of consciousness that attempt to account for subjective qualia but also fit the psi data. I argue that Russellian monism can be combined with an argument regarding quantum holism to arrive at a version of cosmopsychism that fits very well with the psi data. While I do not argue that such a framework exhausts the theoretical possibilities, I do suggest we can move forward with a framework that has attractive theoretical features and is also consistent with objective data currently on the table. (shrink)

"Translating Key Terms Terms in Lu Cheng's Records in the Chuan xi lu: Some Preliminary Considerations" Draft paper for the 2024 Conference on [Wang] Yangming's Learning of Mind, Shaoxing, Zhejiang. Updated October 4, 2024. The final version will appear in the conference volume. -/- Criticism and suggestions welcome. Please do email.

Purpose – This paper furnishes an inaugural reading of abjective consumption by drawing on Kristeva’s psychoanalytic theory of abjection within the wider terrain of consumer cultural research. It offers a conceptual framework that rests on three pillars, viz. irrationality, meaninglessness, dissolution of selfhood. Design/methodology/approach – Qualitative research design that adopts a documentary ethnographic approach, by drawing on a corpus of 50 documentary episodes from the TV series “My Strange Addiction” and “Freaky Eaters”. Findings – The findings from this analysis point (...) to different orders of mediatized discourse that are simultaneously operative in different actors’ frames (e.g. moralizing, medical), in Goffman’s terms, yet none of which attains to address the phenomenon of abjective consumption to its fullblown extent. Research limitations/implications – Although some degree of bias is bound to be inherent in the data because of their pre-recorded status, they are particularly useful not in the least because this is a “difficult sample” in qualitative methodological terms. Practical implications – The multi-order dimensionalization of abjective consumption opens up new vistas to marketers in terms of adding novel dimensions to the message structure of their communicative programs, in line with the three Lacanian orders. Social implications – The adoption of a consumer psychoanalytic perspective allows significant others to fully dimensionalize the behavior of abjective consumption subjects, by becoming sensitive to other than symbolic aspects that are endemic in consumer behavior. Originality/value – This paper contributes to the extant consumer cultural research literature by furnishing the novel conceptual framework of abjective consumption, as a further elaboration of my consumer psychoanalytic approach to jouissance consumption, as well as by contrasting this interpretive frame vis-à-vis dominant discursive regimes. (shrink)

A close look at Frege's proof in "Foundations of Arithmetic" that every number has a successor. The examination reveals a surprising gap in the proof, one that Frege would later fill in "Basic Laws of Arithmetic".

Heidegger develops his reading of a-lētheia as privative un-concealment (Unverborgenheit) in tandem with his early phenomenological theory of truth. He is not simply reinterpreting a word, but rather reading Greek philosophy as having a primordial understanding of truth which has itself been concealed in interpretation. After shedding medieval and modern presuppositions of truth as correspondence, the existential truth-experience shows itself, no longer left puzzlingly implicit in unsatisfactory conventional readings of Greek philosophy. In Sein und Zeit §44, Heidegger resolves interpretive difficulties (...) in Parmenides through his interpretation of alētheia and philologically grounds this reading in Heraclitus’s description of the unconcealing logos. Although this primordial sense of the word has already been obscured in Plato and Aristotle, the structural gradation of their theories of truth conserves the primordial pre-Socratic sense of truth as the experience of unconcealment. (shrink)

Zu den weiterreichenden transhumanistischen Zukunftsvisionen gehört Mind-Uploading: Wir werden dank wissenschaftlicher und technologischer Fortschritte in der Lage sein, Bewusstsein auf künstliche Körper oder digitale Strukturen zu transferieren, um sehr viel länger oder gar unendlich lange leben zu können. Im Kern handelt es sich also um die Vision, durch Technik den Tod zu überwinden. In diesem Beitrag gehe ich im Wesentlichen der Frage nach, welche Theorie des Bewusstseins bzw. welches Geist-Körper-Verhältnis im Mind-Uploading vorausgesetzt werden. Ich werde dafür argumentieren, dass das zugrunde (...) gelegte Verständnis des menschlichen Geistes problematisch ist, weil die Rolle des Eingebettet-Seins in einen lebendigen Körper unterschätzt wird. Mind-Uploading arbeitet mit einem stark verkürzten Begriff des Geistes, der den komplexen Bezügen zu den biologischen, psychischen und sozialen Dimensionen unserer Existenz nicht gerecht wird. (shrink)

The role of metaphysics in critique stands as a defining issue for the Frankfurt School theorists. Max Horkheimer himself claims that metaphysics serves as an instrument of domination, leading him to develop an interdisciplinary mate- rialism as a postmetaphysical alternative. Critics such as Georg Lohmann con- tend, however, that Horkheimer’s critique of instrumental reason is aporetic insofar as it undermines all metaphysical claims while implicitly making them. Since Horkheimer narrowly equates metaphysics with identity thinking, this article argues that his appeal (...) to nonidentity thinking as the foundation for critique is better understood as a form of antimetaphysics. This, however, leaves Horkheimer no better situated, since antimetaphysics remains a variant of metaphysics. While Horkheimer reproduces the techniques of domination he sought to avoid, this lapse into metaphysics warns of the difficult path that postmetaphysical thinking must navigate between the antipodes of metaphys- ical and antimetaphysical positions. (shrink)

The paper investigates Ernst Cassirer’s structuralist account of geometrical knowledge developed in his Substanzbegriff und Funktionsbegriff. The aim here is twofold. First, to give a closer study of several developments in projective geometry that form the direct background for Cassirer’s philosophical remarks on geometrical concept formation. Specifically, the paper will survey different attempts to justify the principle of duality in projective geometry as well as Felix Klein’s generalization of the use of geometrical transformations in his Erlangen program. The second aim (...) is to analyze the specific character of Cassirer’s geometrical structuralism formulated in 1910 as well as in subsequent writings. As will be argued, his account of modern geometry is best described as a “methodological structuralism”, that is, as a view mainly concerned with the role of structural methods in modern mathematical practice. (shrink)

Os dois ensaios aqui traduzidos: “Uma visita a uma glândula pineal”, publicado originalmente em 21 de abril de 1713 no número 35 do Guardian e a “A glândula pineal (continuação)”, publicado no dia 25 de abril, no número 39, formam uma unidade não apenas pela referência a ideia de glândula pineal concebida por Descartes como ponto de interação entre a alma e o corpo, mas também pela forma literária e pelo pseudônimo comum. Eles fazem parte de um conjunto de quatorze (...) ensaios atribuídos a George Berkeley, reunidos e publicados pela primeira vez apenas em 1871, no volume III da edição organizada por A. C. Fraser. Os ensaios publicados no Guardian foram escritos durante a permanência de Berkeley em Londres em 1713, quando Jonathan Swift (1667-1745) e Richard Steele (1672-1729), seus conterrâneos, contribuiriam para lhe abrir caminho no ambiente literário inglês. O principal objetivo de Berkeley ao publicar os ensaios foi o de defender o teísmo cristão contra os “livre-pensadores” da época, assumidos como materialistas e ateus. A tradução aqui apresentada foi realizada com base na edição organizada por Luce e Jessop. The Works of George Berkeley Bishop of Cloyne. Luce, A. A. and Jessop, T. E. London and Edimburgh: Nelson, 1948, v. 7, 185-192. (shrink)

In this paper, I explore the link between consciousness and quantum mechanics. Often explanations that invoke consciousness to help explain some of the most perplexing aspects of quantum mechanics are not given serious attention. However, casual dismissal is perhaps unwarranted, given the persistence of the measurement problem, as well as the mysterious nature of consciousness. Using data accumulated from experiments in parapsychology, I examine what anomalous data with respect to consciousness might tell us about various explanations of quantum mechanics. I (...) examine three categories of quantum mechanics interpretations that have some promise of fitting with this anomalous data. I conclude that explanations that posit a substratum of reality containing pure information or potentia, along the lines proposed by Bohm and Stapp, off er the best fit for various categories of this data. (shrink)

My aim in this paper is to show how the functionalist standards assumed in the AI debate are, in fact, the assumptions of a capitalist, ableist society writ large. The already established argument against the proposed humanity of AI systems implies a wider critique of the entire ideology of functionalism under which the notion of intelligent machines has taken root.

Aristotle and William of Ockham both argue that existence or being is a predicate, though not a distinguishing predicate. I place Ockham’s argument in an Aristotelian context and discuss its merits. I then turn to empiricist criticisms of the view that we can coherently predicate being of things. I argue that while Ockham’s argument is cogent, his account of how we come to have the concept of being is inadequate. Ockham’s view needs to be supplemented with Kantian insights.

The cultural consumption research landscape of the 21st century is marked by an increasing cross-disciplinary fermentation. At the same time, cultural theory and analysis have been marked by successive ‘inter-’ turns, most notably with regard to the Big Four: multimodality (or intermodality), interdiscursivity, transmediality (or intermediality), and intertextuality. This book offers an outline of interdiscursivity as an integrative platform for accommodating these notions. To this end, a call for a return to Foucault is issued via a critical engagement with the (...) so-called practice-turn. This re-turn does not seek to reconstitute venerably Foucauldianism, but to theorize ‘inters-’ as vanishing points that challenge the integrity of discrete cultural orders in non-convergent manners. The propounded interdiscursivity approach is offered as a reading strategy that permeates the contemporary cultural consumption phenomena that are scrutinized in this book, against a pan-consumptivist framework. By drawing on qualitative and mixed methods research designs, facilitated by CAQDAS software, the empirical studies that are hosted here span a vivid array of topics that are directly relevant to both traditional and new media researchers, such as the consumption of ideologies in Web 2.0 social movements, the ability of micro-celebrities to act as cultural game-changers, the post-loyalty abjective consumption ethos. The theoretically novel approaches on offer are coupled with methodological innovations in areas such as user-generated content, artists’ branding, and experiential consumption. (shrink)

Past research has identified a number of asymmetries based on moral judgments. Beliefs about what a person values, whether a person is happy, whether a person has shown weakness of will, and whether a person deserves praise or blame seem to depend critically on whether participants themselves find the agent's behavior to be morally good or bad. To date, however, the origins of these asymmetries remain unknown. The present studies examine whether beliefs about an agent's “true self” explain these observed (...) asymmetries based on moral judgment. Using the identical materials from previous studies in this area, a series of five experiments indicate that people show a general tendency to conclude that deep inside every individual there is a “true self” calling him or her to behave in ways that are morally virtuous. In turn, this belief causes people to hold different intuitions about what the agent values, whether the agent is happy, whether he or she has shown weakness of will, and whether he or she deserves praise or blame. These results not only help to answer important questions about how people attribute various mental states to others; they also contribute to important theoretical debates regarding how moral values may shape our beliefs about phenomena that, on the surface, appear to be decidedly non-moral in nature. (shrink)

Criticism and recommendations are very much welcome. Please don't hesitate to contact me with them. -/- .

Why does scholarship on transnational labor regulation (TLR) consistently fails to search for improvements in working conditions, and instead devotes itself to relentless efforts for identifying administrative processes, semantics, and amalgamations of stakeholders? This article critiques TLR from a pro-worker perspective, through the philosophical work of Georg Lukács, and the concepts of reification and commodification. A set of theoretically grounded criteria is developed and these are applied against selected contemporary cases of TLR. In the totality that is capitalism, reification of (...) social relations of production conceals completely the experiences of workers. In TLR, managerialist and process-oriented scholarship is dominant, verifiable outcomes and positive improvements in conditions of employment are not sought, and worse, meaningless procedures are celebrated as positive achievements. (shrink)