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)

While C. I. Lewis was traditionally interpreted as an epistemological foundationalist throughout his major works, virtually every recent treatment of Lewis's epistemology dissents. But the traditional interpretation is correct: Lewis believed that apprehensions of "the given" are certain independently of support from, and constitute the ultimate warrant for, objective empirical beliefs. This interpretation proves surprisingly capable of accommodating apparently contrary textual evidence. The non-foundationalist reading, by contrast, simply cannot explain Lewis's explicit opposition to coherentism and his insistence that only apprehensions (...) of the given enable us to answer the regress problem -- and so vindicate the possibility of empirical justification. (shrink)

Many have taken Sellars’s critique of empiricism in “Empiricism and the Philosophy of Mind” (EPM) to be aimed at his teacher C. I. Lewis. But if so, why do the famous arguments of its opening sections carry so little force against Lewis’s views? Understandably, some respond by denying that Lewis’s epistemology is among the positions targeted by Sellars. But this is incorrect. Indeed, Sellars had earlier offered more trenchant (if already familiar) critiques of Lewis’s epistemology. What is original about EPM (...) is that it criticizes empiricist positions like Lewis’s not because of their foundationalism, but because of their psychologism about meaning. Since psychologism turns out to be unacceptable by Lewis’s own lights, EPM has a compelling (if implicit) critique of Lewis to offer after all, one that strikes at the heart of his philosophical system. (shrink)

This paper explores two related questions in late Athenian and Alexandrian Neoplatonism. First, how can a philosopher contemplate the eternal Forms while engaging in practical agency in the world? Second, do Neoplatonists provide a consistent account of the philosopher’s progress through the ‘stages of virtue’ (βαθμοί τῶν ἀρετῶν), the conceptual structure that underpins late antique philosophical curricula and hagiography? These questions interact, I suggest, because later Platonists appeal to the stages of virtue and divine maniai (βαθμοί τῶν μανίων) to explain (...) the philosopher’s ability to alternate gracefully between contemplation and embodied agency, and even to engage in both activities at the same moment. I argue that apparently contradictory evidence for the highest stages of virtue can be reconciled satisfactorily, shedding light on two models of ethical and perceptual transformation that are consistent throughout later Neoplatonism. In the first, 'painterly' model, we alternate between a vision of the paradigmatic model and its expression in the media of place and time; in the second, 'dancerly' model, we contemplate in action all at once, like a dancer moving to the music. (shrink)

Charles Sanders Peirce has commonly been interpreted as a proponent of an epistemic theory of truth. Such a theory has the apparent advantage of directly undercutting radical skepticism, but the disadvantage of implausibly entailing that there are no truths concerning irretrievably lost facts. Recently Andrew Howat has defended Peirce’s epistemic constraint on truth by recasting Peirce’s claim that all truths would be believed following sufficient inquiry, not as constitutive of truth, but as a Wittgensteinian hinge proposition. I begin with a (...) twofold historical reply to Howat: first, Peirce can at least plausibly be read as claiming that the claim in question is analytic of the concept <truth>; and second, while Peirce did think we must accept without evidence the further claim that there are any truths (so characterized), he regarded this further claim not as a Wittgensteinian hinge but as a reasonable hope. I then substantively defend the latter Peircean proposal, arguing that hopes, as against beliefs, are chiefly warranted pragmatically, and so can be warranted even to a sufficient level to render them properly action-guiding in cases where belief in the same proposition would remain unjustified. I conclude by suggesting, first, that this proposal is superior to Wittgenstein’s own epistemology in evading psychologism, and second, that it attractively vindicates the reasonableness of inquiry on Peircean grounds that don’t require an appeal to an implausible epistemic theory of truth. (shrink)

Sellars was an inferentialist about meaning. He thus effectively accorded modality a categorial function, maintaining that any meaningful assertion involves implicit commitment to rules of material inference, which modal propositions explicitly endorse. But Sellars was also a modal anti-realist, construing modality as “entirely immanent to thought” (LRB §40), not present in the world an sich. These two commitments, Klemick argues, render it impossible in principle for us to describe the world an sich adequately, undermining Sellars’ scientific realism, on which, at (...) the “ideal outcome of scientific inquiry,” “the gulf between appearances and things-in-themselves [... can] be bridged” (SM II §51). Sellars’ attempt to ground his modal anti-realism in an ideal “pure description of the world” (CDCM §79) cannot succeed, given modality’s categorial function. Further, his subsequent deployment of picturing as a naturalistic criterion of ontological commitment founders on an analogue of the Kantian problem of noumenal affection: the descriptions of picturing relations that render this proposal intelligible are emptied of content by the denial that the in-itself is modally characterized. Sellars’ worthy aim of preserving the world’s independence of our conceptual activity, Klemick concludes, doesn’t require denying that it exhibits modal relations isomorphic to the semantic relations within our conceptual scheme. (shrink)

Since 2023, the UK government's response to the “migrant crisis” has revolved around two controversial flagship policies: the deportation of asylum seekers to Rwanda, and the detention of migrants aboard a giant barge. In this short article, I examine the colonial and gendered dimensions of the two policies, finding them to be examples of the coloniality of gender. What this indicates, I suggest, is that the purpose of these policies is not merely to deter potential migrants—particularly LGBTQIA+ migrants—but also to (...) create a political narrative that allows the Conservative Party to garner right-wing votes by participating in high-profile culture wars; namely, the debate over transgender rights and the debate over how the UK should reckon with its imperial past. (shrink)

In this article, I expound and defend an interpretation of Sellars as a metaethical quasi-realist. Sellars analyzes moral discourse in non-cognitivist terms: in particular, he analyzes “ought”-statements as expressions of collective intentions deriving from a collective commitment to provide for the general welfare. But he also endorses a functional-role theory of meaning, on which a statement’s meaning is grounded in its being governed by semantical rules concerning language entry, intra-linguistic, and language departure transitions, and a theory of truth as correct (...) assertibility relative to such semantical rules. On these non-representationalist theories, even though moral statements are expressions of intentions and not fundamentally descriptive, they nevertheless count as assertorically meaningful, and some count as positively true. I further argue that this interpretation is capable not only of explaining Sellars’ explicitly metaethical writings, but also of unifying his scientific realism with his commitment to the ineliminable and indispensable role of the language of intentions: if this linguistic framework does not play an explanatory role, but only an expressive role, this explains both why Sellars’ commitment to it does not contravene his naturalism, as well as why, given the necessity of such language for our practical engagement with the world, the scientific image of humans in the world will only be completed once such language supplements it to enable us to relate practically to it. (shrink)

This paper offers a critical interpretation and evaluation of Wilfrid Sellars’s treatment of skepticism about empirical justification. It defends three central claims. First, against the suggestion that Sellars’s work simply bypasses traditional skeptical problems, I make the novel interpretive claim that Sellars not only addresses skepticism about empirical justification, but offers two independent (albeit sketchy) arguments against it: a transcendental argument that the likely truth of our perceptual beliefs is a necessary condition of the possibility of empirical content, and a (...) pragmatic argument that we’re warranted in accepting their likely truth in virtue of our aim of being effective agents. To the extent these have previously been distinctly formulated by commentators, the transcendental argument has been regarded as forceful, while the pragmatic argument has been dismissed as non-responsive. My second and third claims challenge this understanding. I argue, second, that examination of the literature relating to transcendental arguments from semantic externalism like Sellars’s (especially concerning the McKinsey paradox) suggests that such arguments are unpromising, while, third, a modified version of his pragmatic argument represents a powerful skeptical solution to skepticism about empirical justification, one that answers the worry that such skepticism would undermine the rationality of all our practical commitments. (shrink)

Pragmatist responses to skepticism about empirical justification have mostly been underwhelming, either presupposing implausible theses like relativism or anti-realism, or else showing our basic empirical beliefs to be merely psychologically inevitable rather than rationally warranted. In this paper I defend a better one: a modified version of an argument by Wilfrid Sellars that we are pragmatically warranted in accepting that our perceptual beliefs are likely to be true, since their likely truth is necessary for the satisfaction of our goal of (...) effective agency. On the version of the argument I defend, the great good for human life of control over our empirical circumstances renders our goal of effective agency reasonable. But only if our perceptual beliefs are likely to be true—and only if we accept that this is so, assuming it as a premise for inference and a guide for action—will the success of our actions be due to our effective agency, not mere luck. Since we’re warranted in taking the necessary means to our reasonable ends, we’re warranted in accepting that our perceptual beliefs are generally justified, and so that skepticism about empirical justification is false. (shrink)

In “The Fixation of Belief,” Peirce apparently accepts the causal claim that real physical objects cause us to reach an indefeasible “final opinion” concerning them. In “How to Make Our Ideas Clear,” he apparently accepts the constitutive claim that for physical objects to be real just is for them to be represented in that opinion. These claims initially seem inconsistent, since causal claims are explanatory and since equivalent claims cannot explain one another. Contrary to prominent suggestions that Peirce rejected the (...) constitutive claim, however, he actually accepted both, reconciling them via a Humean denial that causal claims are genuinely explanatory. (shrink)

The proliferation of work by autistic writers continues apace, defying a long and multidisciplinary tradition of constructing autistic people as lacking the capacity for narration. To study neurodivergent literature, then, is to witness the refusal of these exclusionary narrative conventions, and to register the ideological presuppositions that underpin pathologization. In this article, I engage with recent insights from Neurodiversity Studies to explore the connections between narrative neuronormativity and other discourses of oppression, especially those that have generated racialized, gendered, and colonial (...) narratives of desubjectification. Focusing on the neuroqueer movement—an emergent practice of disidentification that refuses the interpellations of neuronormativity, ableism, heteronormativity, and cisnormativity—I discuss the concept of allism, arguing that this satirical critique of pathologization harbors a deconstructive force that denaturalizes the dialectic of recognition. Pursuing the discursive context and theoretical implications of this critique, I provide a short genealogy of narrative neuronormativity, connecting the operation of the dialectic in the early novel to the clinical texts of child psychology. To demonstrate the neuroqueer subversion of this tradition, I then read An Unkindness of Ghosts, by Rivers Solomon, a text that stages a disidentification with storytelling. Protagonist Aster’s neuroqueer refusal indexes the concomitance of the construction of Blackness as an ontological foil for whiteness and the construction of autism as a standard of disordered sociality that neuronorms can be measured against. My reading of Unkindness suggests that the extant techniques of literary narratorship are political instruments that will, unless repurposed, continue to disseminate these dispossessive dialectics. (shrink)

Russell’s rejection in 1898 of the doctrine of internal relations — the view that all relations are grounded in the intrinsic properties of the terms related — was a decisive part of his break with Hegelianism and opened the way for his turn to analytic philosophy. Before rejecting it, Russell had given the doctrine little thought, though it played an essential role in the most intractable of the problems facing his attempt to construct a Hegelian dialectic of the sciences. I (...) argue that it was Russell’s early reading of Leibniz, in preparation for his lectures on Leibniz given at Cambridge in 1899, that most probably alerted him to the role the doctrine was playing in his own philosophy. Leibniz defended a similar doctrine and extricated it from difficulties like those faced by Russell by means of devices that were not open to Russell. Russell would have come across these views of Leibniz in writings by Leibniz that he read in the summer of 1898, just before he rejected the doctrine of internal relations. (shrink)

I take up two questions raised by Luz Christopher Seiberth's meticulous reconstruction of Wilfrid Sellars's theory of intentionality. The first is whether we should regard Sellars as a transcendental phenomenalist in the most interesting sense of the term: as denying that even an ideally adequate conceptual structure would enable us to represent worldly objects as they are in themselves. I agree with Seiberth that the answer is probably yes, but I suggest that this is due not to Sellars's rejection of (...) the Myth of the Given or appeal to image-models (as Seiberth maintains), but to his view of modality as categorial but as absent from the world an sich. The second is whether, as Richard Rorty complained, Sellars's appeal to picturing lands his theory of intentionality in intractable skepticism. Pace Seiberth, I argue that the transcendental role of picturing does not mitigate this problem, and I suggest that Sellars's most fruitful resource for doing so is not his semantic externalism, but his purely pragmatic response to skepticism. (shrink)

Russell is often accused of having a naive ‘Fido’–Fido theory of meaning of the sort Wittgenstein attacked at the beginning of the Philosophical Investigations. In this paper I argue that he never held such a theory though I concede that, prior to 1918, he said various things that might lead a very careless reader to suppose that he had. However, in The Analysis of Mind, a book which we know Wittgenstein studied closely, Russell put forward an account of understanding an (...) utterance which clearly anticipates the use theory of meaning usually attributed to Wittgenstein. The paper concludes with some problems for understanding the use theory of meaning as presented by both Russell and, derivatively, Wittgenstein. (shrink)

Proclus argues that place (topos) is a body of light, identified as the luminous vehicle of the soul, which mediates between soul and body and facilitates motion. Simplicius (in Phys. 611,10–13) suggests that this theory is original to Proclus, and unique in describing light as a body. This paper focuses on the function of this theory as a bridge between Proclus’ physics and metaphysics, allowing the Aristotelian physical notion of “natural place” to serve as a mechanism for the descent and (...) ascent of the soul. (shrink)

The focus of this article is the "good-will theory", which explains the effect humans can have on the safety of AI, along with how it is in the best interest of a superintelligent AI to work alongside humans and not overpower them. Future papers dealing with the good-will theory will be published, but discuss different talking points in regards to possible or real objections to the theory.

Teaching a compulsory, large-scale Philosophy of Economics (PoE) course to economics students presents distinct challenges. Instructors face a heterogeneous student body with varying levels of interest in the topics, diverse occupational goals and a limited philosophical background. Unlike elective courses, for which students self-select based on interest, a compulsory course entails motivating disengaged students and managing their expectations. We put forward the case for a student-oriented approach to teaching PoE, emphasising four key strategies: recognising students’ limited philosophical knowledge, demonstrating the (...) relevance of PoE to their professional and personal lives, using real-world problems to engage them and avoiding the oversimplification of topics. We argue that PoE instruction should account for the distinct characteristics of economics students, moving beyond a supply-driven approach. Our suggestions aim to enhance student engagement and provide practical guidance for instructors navigating the challenges of teaching PoE at scale. (shrink)

Deleuze’ün Spinozacı yaşam tahayyülünde ‘ne yapmalıyız?’ sorusuna normatif, ahlaki ya da siyasi bir yanıt bulamıyoruz ama varoluşu düşünmenin içkin bir olanağını keşfediyoruz. Düşünmeye 'dışarıdan' yani dünyadan başlamak insani (kurgusal) bir dünyaya değil, içinde yaşadığımız gerçek dünyaya inanmak demektir. İçkinliğin politik anlamı düşünceyi dünyaya getirmektir.

Sometimes constitutions fail. The unprecedented election of Donald Trump, a populist insurgent who lacks the prior political experience or military service of all presidents before him, is such a sharp break in American historical experience that it raises questions as to whether something is deeply amiss with the constitutional order. Constitutional failure is not uncommon. A path-breaking global study of national constitutions shows that on average, they last only nineteen years. The U.S. Constitution is an uncommon outlier and, as such, (...) is accounted by many a long-running success story. But could a bell be tolling for American constitutionalism? In this Essay, I assess the meaning of Trump’s shocking rise for the future of our constitutional order. The shock, of course, was not the election of a Republican president. There have been many Republican presidents since Lincoln, each making their own distinctive contribution to the American tradition. Yet, there are good reasons to think this time around is different. The efficacy and, perhaps, stability of our constitutional order are in question, and we should try to understand why. (shrink)

Skeptical theists are seeking for some reasonable solutions to the evidential problem of evil. One of the most fundamental responses of skeptical theism is that the concept of “gratuitous evil”, which cannot be a proof of the absence of God. Therefore, it is not the existence of God that skeptical theism suspects. Instead, skeptical theism contemplates whether the evil in the world really has a “gratuitous” basis. This paper focuses on Peter van Inwagen's “no-minimum claim”. No-minimum claim” stands in opposition (...) to the views that assume that God minimizes the evils that exist in the world in order to achieve justice. “No-minimum claim” acknowledges that these evils still have enormous amounts to people. Thus “no-minimum claim” suggests that the evils experienced in the world are incompatible with the “best of all possible worlds” views or the other explanations of classical theodicy. According to the “no minimum claim”, the reason why the amount of evil in the world still seems so high may be God’s deliberate calculations in effecting the distribution of these evils. In order to reach these calculations, it is not necessary for the amount of evil that God allowed to reflect on the world to be perfectly manifested at the minimum level. The purpose of this paper is to consider the skeptical theism approach within the framework of Peter van Inwagen's “no-minimum claim” and to limit his arguments to an alternative approach to skeptic theism. Our claim is that such view coincides with skeptical theism, but the “no- minimum claim” still has some ambiguities at the point of the limits of evil. From this, we can conclude that the “no minimum claim” has received many objections in the skeptical theism literature and these objections are justified at certain points. (shrink)

There seems to be confusion and disagreement among scholars about the meaning of interpersonal forgiveness. In this essay we shall venture to clarify the meaning of forgiveness by examining various literary works. In particular, we shall discuss instances of forgiveness from Homer’s The Iliad, Euripides’ Hippolytus, and Aristotle’s Nicomachean Ethics and we shall focus on the changes that the concept of forgiveness has gone through throughout the centuries, in the hope of being able to understand, and therefore, of being able (...) to use more accurately, contemporary notions of forgiveness. We shall also explore the relationship between forgiveness and concepts that are closely associated with it, such as anger/resentment, hurt, clemency, desert/merit, excuse, etc. (shrink)

Are words like ‘woman’ or ‘man’ sex terms that we use to talk about biological features of individuals? Are they gender terms that we use to talk about non-biological features e.g. social roles? Contextualists answer both questions affirmatively, arguing that these terms concern biological or non-biological features depending on context. I argue that a recent version of contextualism from Jennifer Saul that Esa Diaz-Leon develops doesn't exhibit the right kind of flexibility to capture our theoretical intuitions or moral and political (...) practices concerning our uses of these words. I then float the view that terms like 'woman' or 'man' are polysemous, arguing that it makes better sense of the significance of some forms of criticisms of mainstream gender ideology. (shrink)

The article tries to answer the questions ; what is consciousness? Why would a collection of matter be conscious? It attempts to describe a universal consciousness that is a fundamental part of building blocks of nature. It applies a counterintuitive view of consciousness in that consciousness is not a product of a brain but a fundamental part of the universe.. Panpsychism.

The article delves into the mystery that underlies the true nature of reality..Do we view reality as it is or is reality an illusion in the sense that it's a product of our senses rather than a fundamental part of the universe? These are some of the questions that have puzzled great thinkers for millennia.. The true nature of reality seems to be utterly elusive just as Brian Greene said "sometimes nature guards her secrets by the unbreakable grip of physical (...) law, sometimes the true nature of reality beckons from just beyond the horizon". (shrink)

In this аrtiсlе, thе аuthоr fосusеs оn еluсidаting sоmе philоsоphiсаl аspесts оf intеrсulturаl соmmuniсаtiоn in thе соntеxt оf glоbаlizаtiоn оn thе bаsis оf rесоgnizing thе соntributiоns аnd limitаtiоns оf Wittgеnstеin tо thе birth оf philоsоphy. сulturе study. Thоsе philоsоphiсаl issuеs аrе: thе similаrity in thinking аnd асting оf pеоplе асrоss сulturеs; divеrsity оf сulturеs, wоrldviеws аnd wаys оf lifе. Frоm thе Mаrxist pоint оf viеw, thе аuthоr pоintеd оut аnd сritiсizеd thе limitаtiоns оf Wittgеnstеin's philоsоphiсаl соnсеptiоn; аnd аt thе sаmе (...) timе оffеr аnd еxplаin sоlutiоns tо implеmеnt intеrсulturаl соmmuniсаtiоn in thе соntеxt оf сurrеnt glоbаlizаtiоn. (shrink)

Pada musim semi, entah kenapa, tidak banyak ikan. Karena tangkapannya sangat tidak stabil, Pekakak mulai berpikir. Lalu membuat beberapa rencana. Dengan otoritas komandonya, dia memanggil Bangau: – Ini adalah musim penangkapan ikan yang sangat sulit. Jika kita ingin kenyang, kita harus membuat usaha patungan. Bangau mengangguk, menambahkan: - Saya setuju; mari kita beternak ikan kakap putih dan ikan mas krusia. Jenis ini berumur panjang dan sangat produktif. Pekakak dan Bangau sepakat untuk berbagi tugas beternak, dan tidak ada diskriminasi yang diizinkan. (...) Namun imbalannya berbeda: Pekakak bertanggung jawab untuk ikan kakap putih dan, dengan demikian, dapat memiliki lebih banyak ikan kakap putih, sedangkan Bangau mendapat ikan mas krusia. Siapapun yang memelihara ikan mana yang lebih banyak akan menikmati 80% dari panen akhir ikan tersebut. Keduanya akan mengevaluasi dan membagi produk ternak pada akhir musim beternak. Ini berarti mengantongi sendiri ikan hasil usaha patungan untuk diri sendiri itu dilarang. (shrink)

Exclusionary defeat is Joseph Raz’s proposal for understanding the more complex, layered structure of practical reasoning. Exclusionary reasons are widely appealed to in legal theory and consistently arise in many other areas of philosophy. They have also been subject to a variety of challenges. I propose a new account of exclusionary reasons based on their justificatory role, rejecting Raz’s motivational account and especially contrasting exclusion with undercutting defeat. I explain the appeal and coherence of exclusionary reasons by appeal to commonsense (...) value pluralism and the intermediate space of public policies, social roles, and organizations. We often want our choices to have a certain character or instantiate a certain value and in order to do so, that choice can only be based on a restricted set of reasons. Exclusion explains how pro tanto practical reasons can be disqualified from counting towards a choice of a particular kind without being outweighed or undercut. (shrink)

Suatu pagi di musim panas, desa burung diselimuti keheningan. Semua orang sibuk mendengarkan pengembara baru. Burung pengembara ini berasal dari keluarga yang tidak jelas; bulunya berwarna-warni, gerak-geriknya lucu, dan ilmunya baru. Dia bercerita seolah-olah sedang memberi ceramah, tepat sekali, warga desa memanggilnya burung Guru – orang yang menjawab setiap pertanyaan aneh warga desa yang rajin belajar. Burung pelatuk telah belajar menangkap cacing di sore hari, sehingga mereka tidak perlu bangun pagi. Burung pipit sekarang tahu cara mencuri beras dari gudang saat (...) sawah mulai kering. Bulbul, sementara itu, telah mengambil kesempatan berkumpul untuk memamerkan kecantikan dan fashion mereka… . (shrink)

Experimental philosophers have gathered impressive evidence for the surprising conclusion that philosophers' intuitions are out of step with those of the folk. As a result, many argue that philosophers' intuitions are unreliable. Focusing on the Knobe Effect, a leading finding of experimental philosophy, we defend traditional philosophy against this conclusion. Our key premise relies on experiments we conducted which indicate that judgments of the folk elicited under higher quality cognitive or epistemic conditions are more likely to resemble those of the (...) philosopher. We end by showing how our experimental findings can help us better understand the Knobe Effect. (shrink)

Pekakak selama ini tinggal di gua galiannya sendiri di tepi kolam, tapi sekarang dia memutuskan bahwa dia membutuhkan rumah baru. Dia melakukan tur keliling desa untuk melihat bagaimana burung-burung lain membangun rumah mereka. Dia mengunjungi Tuan Pipit, yang tinggal di pohon pinus yang bersiul. Bagian depan bangunannya tampak indah, dan lokasinya yang tinggi memberikan ventilasi yang baik. Tapi, semakin lama dia menginap, dia jadi semakin pusing. Hembusan angin apa pun yang menerpa membuat seluruh struktur bangunan bergetar seolah-olah akan hancur berantakan.

Upon doing something generous for someone with whom you are close, some kind of reciprocity may be appropriate. But it often seems wrong to actually request reciprocity. This chapter explores the wrongness in making these requests, and why they can nevertheless appear appropriate. After considering several explanations for the wrongness at issue (involving, e.g. distinguishing oughts from obligation, the suberogatory, imperfect duties, and gift-giving norms), a novel proposal is advanced. The requests are disrespectful; they express that their agent insufficiently trusts (...) the hearer to recognize their own reasons to reciprocate, and the close relationship between them morally requires this kind of trust. This proposal is articulated and situated in the recent discussion of the normativity of requests. The chapter concludes by explaining how these requests may appear appropriate. Agents in these relationships often have standing to make requests, though the standing is lacking in these particular cases. (shrink)

This study asserts that W.V.O. Quine’s eliminative philosophical gaze into mereological composition affects inevitably his interpretations of composition theories of ontology. To investigate Quine’s property monism from the account of modal eliminativism, I applied to his solution for the paradoxes of de re modalities’ . Because of its vital role to figure out how dispositions are encountered by Quine, it was significantly noted that the realm of de re modalities doesn’t include contingent and impossible inferences about things. Therefore, for him, (...) all the intrinsic forces and elements of entities such as powers and causal or teleological dispositions for ontology demand to be seen necessarily as bound variables from a monist perspective. Although his denial of analyticity and the elimination of dispositional field of ontology, S. Mumford criticizes the monist perspective of Quine’s paradoxical approach to superveniences. Because superveniences create problems while determining type-type identities from a monist mereological perspective. It is observed that Quine faces with a reduction again in terms of his dispositional monism despite his critiques to repulse vagueness from the ontology in his well-known article Two Dogmas of Empiricism. -/- . (shrink)

Political legitimacy is best understood as one type of a broader notion, which I call institutional legitimacy. An institution is legitimate in my sense when it has the right to function. The right to function correlates to a duty of non-interference. Understanding legitimacy in this way favorably contrasts with legitimacy understood in the traditional way, as the right to rule correlating to a duty of obedience. It helps unify our discourses of legitimacy across a wider range of practices, especially including (...) the many evaluations we increasingly make of international institutions of various sorts, but also including domestic institutions. (shrink)

Institutions undertake a huge variety of constitutive purposes. One of the roles of legitimacy is to protect and promote an institution’s pursuit of its purpose; state legitimacy is generally understood as the right to rule, for example. When considering legitimacy beyond the state, we have to take account of how differences in purposes change legitimacy. I focus in particular on how differences in purpose matter for the stringency of the standards that an institution must meet in order to be legitimate. (...) An important characteristic of an institution’s purpose is its deontic status, i.e. whether it is morally impermissible, merely permissible, or mandatory. Although this matters, it does so in some non-obvious ways; the mere fact of a morally impermissible purpose is not necessarily delegitimating, for example. I also consider the problem of conflicting, multiple, and contested institutional purposes, and the different theoretical roles for institutional purpose. Understanding how differences in purpose matter for an institution’s legitimacy is one part of the broader project of theorizing institutional legitimacy in the many contexts beyond the traditional context of the state. (shrink)

The essays collected in this special issue explore what legitimacy means for actors and institutions that do not function like traditional states but nevertheless wield significant power in the global realm. They are connected by the idea that the specific purposes of non-state actors and the contexts in which they operate shape what it means for them to be legitimate and so shape the standards of justification that they have to meet. In this introduction, we develop this guiding methodology further (...) and show how the special issue’s individual contributions apply it to their cases. In the first section, we provide a sketch of our purpose-dependent theory of legitimacy beyond the state. We then highlight two features of the institutional context beyond the state that set it apart from the domestic case: problems of feasibility and the structure of international law. (shrink)

Suppose that we repair a wooden ship by replacing its planks one by one with new ones while at the same time reconstructing it using the discarded planks. Some defenders of vague or indeterminate identity claim that: (1) although the reconstructed ship is distinct from the repaired ship, it is indeterminate whether the original ship is the reconstructed ship and indeterminate whether it is the repaired ship, and (2) the indeterminacy is due to the world and not just an imprecision (...) in the language used to describe the situation. I argue that such a description is incoherent. The argument has two features. First, it differs in spirit from Gareth Evans's more general famous proof against the possibility of indeterminate identity. This is because I rely on facts regarding counting and sets. Second, I focus on Terence Parsons's recent defence of indeterminate identity. I argue that his attempts at making sense of counting objects involving indeterminate identities fail on technical and philosophical grounds. (shrink)

In this article, Deleuze & Guattari (D+G)’s conception of democracy will be approached with regard to art’s envisagement of “becoming-democratic” as a mode of thinking through percepts and affects. For D+G, democracy is, by no means, a desirable political goal or the name of a type of governance appropriate for the world. On the contrary, as long as it is a representation mechanism, democracy has negative connotations since it promotes the dominance of majority. For this reason, the only way of (...) affirming democracy is to cleanse and subtract the governmental layers which fix it as a system of social measurement, and re-associate it with “multiplicity” & “becoming”. In this respect, democracy can only be affirmed if it is paired with the notions of becoming-democratic, becoming-revolutionary and becoming-minor. Nevertheless, it is not the case that mainstream political philosophy or professional politics are the only methods for formulating opinions on democracy. “Politics of art” would provide means of thinking upon becoming democratic since art—being a mode of thinking by itself—may place many issues about which one could talk only theoretically (or which would hardly become a part of daily life) on a living plane, even though that plane would solely exist in the world of the work of art. In brief, on the condition that it is not an apparatus of representation, art may turn into a medium of thinking upon becoming-democratic, in addition to all the other becomings that it is related to. (shrink)

I argue that legitimacy discourses serve a gatekeeping function. They give practitioners telic standards for riding herd on social practices, ensuring that minimally acceptable versions of the practice are implemented. Such a function is a necessary part of implementing formalized social practices, especially including law. This gatekeeping account shows that political philosophers have misunderstood legitimacy; it is not secondary to justice and only necessary because we cannot agree about justice. Instead, it is a necessary feature of actual human social practices, (...) which must be implemented via practitioners' discretion in changing contexts. (shrink)

Standard accounts of civil disobedience include nonviolence as a necessary condition. Here I argue that such accounts are mistaken and that civil disobedience can include violence in many aspects, primarily excepting violence directed at other persons. I base this argument on a novel understanding of civil disobedience: the special character of the practice comes from its combination of condemnation of a political practice with an expressed commitment to the political. The commitment to the political is a commitment to engaging with (...) others as co-members in the on-going political project of living together. I show how such an understanding of civil disobedience is superior to the Rawlsian strain of thought, which focuses on fidelity to law. Rawls was concerned with civil disobedience solely in the context of overriding political obligation. The project of characterizing a contestatory political practice that can be distinguished and used in a wider variety of contexts than Rawls is concerned with, including under illegitimate regimes, beyond the nation-state, or on behalf of anarchism, requires a different understanding of civil disobedience. (shrink)

Ethicists struggle to take reductive views seriously. They also have trouble conceiving of some supervenience failures. Understanding why provides further evidence for a kind of hybrid view of normative concept use.

Eser, yazarın 2008 yılında tamamlamış olduğu “Kur’an’ın Tasdik Ettiği Tevrat’taki Konular” isimli doktora tezinin 2011 yılında “Tevrat’ın Kur’an’a Arzı-Kur’an’ın Tevrat’ta Tasdik Ettiği Konular” ismiyle basılmasıyla yayın hayatına kazandırılmıştır. Kur’an ve Tevrat’taki konular bu çalışmanın öncesinde ve sonrasında genellikle mukayeseli bir biçimde çalışılmıştır. Gerek Kur’an ve Tefsir alanında gerekse Dinler Tarihi alanında kıssalar, tarihi olaylar, hükümler, uygulamalar gibi pek çok açıdan Kur’an ve Tevrat’a dair özellikle mukayese içeren tezler ve eserler bulunmaktadır. Bu çalışmanın alandaki diğer eserlerden farkı Kur’an’ın Tevrat’ı tasdik edici (...) olmasının ne mânaya geldiğini izah etmesi ve Tevrat’ta yer alan hangi konuları doğrulayıcı olduğunu derli toplu bir şekilde ortaya koymasıdır. (shrink)

Amongst invertebrates, molluscs show great variability in their nervous system ranging from primitive arrangement in Chitons to the complex mass of fused ganglia forming the ‘brain’ of cephalopods. Most of the effector organs used for pharmacological or physiological experiments. The neurosecretory cells (NSCs) with their combination of neuronal and glandular capabilities are perfectly suited to translate a neuronal input into the hormonal output best suited to long-term process. In this capacity, the NSCs may produce hormones, which act directly upon the (...) peripheral target or it may exert its effect indirectly by influencing the activity of other non-neural, endocrine organs. Neurosecretory cells have been detected in the cerebral, pedal and visceral ganglia of Lamellidens corrianus. The distribution and biology of freshwater bivalve like Lamellidens corrianus is influenced by local ecological factors (like temperature, pH, inorganic salts, type of soil etc.), water flow system and presence of micro-organisms, teleost fishes and seasonal variations in these parameters. Nitrogenous excretory changes which include ammonia in these molluscs is also influenced by these local ecological factors in which temperature is plays very crucial role. It is well known fact that the high stress conditions during drought or severe winter conditions have been conquered by several lineage of gastropods and sand bivalves and their ability to enter the resistant or dormant stages (low food) protein catabolism increased. Present investigation deals with the oxygen consumption and ammonia excretion ratio of these freshwater pelecypode Lamellidens corrianus. Study on Lemellidens corrianus directed in understanding the different behavioral and physiological aspects after cerebral ganglia removal and injection of their extracts revealed significant changes during summer (April-May). (shrink)

A critical survey of various positions on the nature, use, possession, and analysis of normative concepts. We frame our treatment around G.E. Moore’s Open Question Argument, and the ways metaethicists have responded by departing from a Classical Theory of concepts. In addition to the Classical Theory, we discuss synthetic naturalism, noncognitivism (expressivist and inferentialist), prototype theory, network theory, and empirical linguistic approaches. Although written for a general philosophical audience, we attempt to provide a new perspective and highlight some underappreciated problems (...) about normative concepts. (shrink)

[...] Rousseau bir yandan çağının yükselen değerlerinden yararlanırken diğer yandan bu değerlerin içeriden eleştirisini yapmayı başarabilen düşünürlerden biri olduğu için fikirleri ölümünden asırlar sonra bile önemini yitirmemiştir. Demokratik devletlerin meşruiyet krizinin giderek derinleştiği ve çoğunlukçu, majoritarian, ideolojilerin etraflıca sorgulanmaya başlandığı çağımızda, demokrasiyi çoğunluk kararına ek olarak “rıza”, “Yurttaşlık”, “sivil özgürlük”, “kamusal uzlaşı” ve “Genel İrade” kavramlarıyla birlikte ele alan Rousseau’yu yeniden okumak önemlidir [...] Rousseau-demokrasi ilişkisinin kazılıp ortaya çıkartılacağı bu metinde uğranılacak olan kavramsal duraklar sırasıyla: Eşitsizlik (doğal ve toplumsal), özgürlük (...) (doğal ve sivil), politik bütün (bodypolitic), Genel İrade, ortak iyi (common good) ve Egemen olmalıdır. Söz konusu kavramlar, Rousseau’nun onlara yüklediği özgün anlamları gözden kaçırılmadan sanki ilk defa karşılaşılıyormuşçasına bir zihin açıklığı ile okundukları zaman, onun demokrasi görüşü de gün ışığına çıkartılabilir. (shrink)

The history of western philosophy is split to its core by a long-standing, fundamental dispute. On the one hand there are the so-called empiricists, like Locke, Berkeley, Hume, Mill, Russell, the logical positivists, A. J. Ayer, Karl Popper and most scientists, who hold empirical considerations alone can be appealed to in justifying, or providing a rationale for, claims to factual knowledge, there being no such thing as a priori knowledge – items of factual knowledge that are accepted on grounds other (...) than the empirical. And on the other hand there are the so-called rationalists, like Descartes, Spinoza, Leibniz, Bradley, McTaggart, who hold that a priori knowledge does exist, and even plays a crucial role in science. This long-standing dispute is resolved by the line of thought developed in this essay. The empiricists were right to deny the existence of a priori knowledge where this means factual knowledge of apodictic certainty justified independently of any appeal to experience. They were wrong, however, to deny the existence of a priori knowledge where this means conjectural items of factual knowledge whose acceptance is justified independently of any appeal to experience. Science requires there to be a priori knowledge in this latter sense, and two items of such knowledge will be exhibited. In addition to resolving this empiricist/rationalist dispute, the essay also develops a new conception of science – aim-oriented empiricism – and solves the long-standing problem of what it means to say of a theory that it is unified or explanatory. Furthermore, aim-oriented empiricism does not just change our conception of science; it requires that science itself needs to change. Science needs to become much more like the 17th century conception of natural philosophy, intermingling consideration of testable theories with consideration of untestable metaphysical, epistemological and methodological ideas. The whole relationship between science and the philosophy of science is transformed. The philosophy of science, construed as the exploration and critical assessment of rival ideas about what the aims and methods of science ought to be, ceases to be a meta-discipline, and becomes an integral part of science – or natural philosophy – itself. (shrink)

I develop a cognitive account of how humans make skeptical judgments (of the form “X does not know p”). In my view, these judgments are produced by a special purpose metacognitive "skeptical" mechanism which monitors our reasoning for hasty or overly risky assumptions. I argue that this mechanism is modular and shaped by natural selection. The explanation for why the mechanism is adaptive essentially relies on an internalized principle connecting knowledge and action, a principle central to pragmatic encroachment theories. I (...) end the paper by sketching how we can use the account I develop here to respond to the skeptic. (shrink)

The social group named after the various discourses of individuals who define themselves as the champions of the men's rights movement on social media is called the “Manosphere” in the literature. “Oneitis”, a concept in the jargon of the manosphere, basically refers to a disease state used to represent situations in which a man invests excessive attention in a woman who is not equally interested in him. For the Red Pill movement, the most influential group in the manosphere, oneitis is (...) criticized as a pattern of behavior that should be avoided by men. Red Pill philosophy is also often associated with alt-right ideologies due to its anti-feminist and pragmatic views. Red Pill thought can therefore often be seen as contrasting with Woke Culture, a counter-cultural movement that advocates the constant practice of vigilance against political discourses that oppress certain social groups through structural mechanisms of oppression such as racism, anti-blackness, and anti-feminism. In this paper, I argue that the concept of oneitis, when suspended from its anti-feminist and commodifying contexts, can in fact be read as a critique of a conception of love that is deeply rooted in traditional gender roles that are often criticized from perspectives such as feminism or Woke Culture. When the liberation from oneitis is considered independently of the manosphere framework, it can be read as a critique of coercive social practices in terms of romantic relationships. (shrink)