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)

Using path-breaking discoveries of cognitive science, Mark Johnson argues that humans are fundamentally imaginative moral animals, challenging the view that morality is simply a system of universal laws dictated by reason. According to the Western moral tradition, we make ethical decisions by applying universal laws to concrete situations. But Johnson shows how research in cognitive science undermines this view and reveals that imagination has an essential role in ethical deliberation. Expanding his innovative studies of human reason in Metaphors (...) We Live By and The Body in the Mind, Johnson provides the tools for more practical, realistic, and constructive moral reflection. (shrink)

Aristotle’s dialogue Protrepticus is not only his earliest work of ethics but also the root of all his subsequent investigations into ethics. Here we explore the various ways Aristotle retained in memory the contents of the Protrepticus and redeployed them in the Eudemian Ethics, including the common books. Since Aristotle himself does not explicitly acknowledge the foundational significance of the Protrepticus to his later works, our exploration must proceed on the basis of our knowledge of the earlier work, which can (...) then related to comparable passages in the treatises. But the Protrepticus is a lost work, unlike the EE and the EN, in the sense that no medieval manuscripts of it have survived. And so it first needs to be reconstructed on the basis of the streams of reception that deposited information in surviving works by later ancient authors. We begin in part 1 by reviewing the surviving evidence of the Protrepticus before presenting our wider reconstruction and conception of the work as a dialogue in part 2. In part 3, we discuss ideas and arguments in the reconstructed dialogue that are retained and redeployed in the Eudemian Ethics, focussing on the account of intellectual virtues in EE v and the introduction and methodological framework in EE i-ii.1. (shrink)

In this paper we argue that political envy is central to unraveling the racial dynamics in Spike Lee's Do The Right Thing. Building upon Sara Protasi’s taxonomy of envy and, in particular, from her analysis of some DTRT scenes, we conduct a more thorough interrogation of how political emotions, most notably envy, shape race relations in the film. We start by summarizing Protasi’s account of envy and then review two alternative accounts of political emotions. After elucidating what envy is and (...) how it becomes politically valenced, we analyze three key scenes that are the most emblematic of political envy: 1) a discussion between three Black characters on the street corner, 2) an exchange between the film’s main character, Mookie, and his racist co-worker, Pino; and 3) the film’s climactic riot sequence. Our analysis of these three scenes, in addition to complementing previous readings of Do The Right Thing, highlight envy’s potential to either impede or promote political action. (shrink)

A new translation and edition of Aristotle's Protrepticus (with critical comments on the fragments) -/- Welcome -/- The Protrepticus was an early work of Aristotle, written while he was still a member of Plato's Academy, but it soon became one of the most famous works in the whole history of philosophy. Unfortunately it was not directly copied in the middle ages and so did not survive in its own manuscript tradition. But substantial fragments of it have been preserved in several (...) works by Iamblichus of Chalcis, a third century A.D. neo-Pythagorean philosopher and educator. On the basis of a close study of Iamblichus' extensive use and excerption of Aristotle's Protrepticus, it is possible to reconstruct the backbone of the lost work, and then to flesh it out with the other surviving reports about the work from antiquity (for example in Alexander of Aphrodisias and other ancient commentators on Aristotle). It is also possible to identify several papyrus fragments of the work, and many references and literary allusions in later authors, especially Cicero, whose own lost dialogue Hortensius was a defense of philosophy modeleld on Aristotle's. (shrink)

Anydomainofscientificresearchhasitssustainingorthodoxy. Thatis, research on a problem, whether in astronomy, physics, or biology, is con- ducted against a backdrop of broadly shared assumptions. It is these as- sumptionsthatguideinquiryandprovidethecanonofwhatisreasonable-- of what "makes sense." And it is these shared assumptions that constitute a framework for the interpretation of research results. Research on the problem of how we see is likewise sustained by broadly shared assump- tions, where the current orthodoxy embraces the very general idea that the business of the visual system is to (...) create a detailed replica of the visual world, and that it accomplishes its business via hierarchical organization and by operatingessentiallyindependently of other sensorymodalitiesas well as independently of previous learning, goals, motor planning, and motor execution. (shrink)

Buddhist philosophy asserts that human suffering is caused by ignorance regarding the true nature of reality. According to this, perceptions and thoughts are largely fabrications of our own minds, based on conditioned tendencies which often involve problematic fears, aversions, compulsions, etc. In Buddhist psychology, these tendencies reside in a portion of mind known as Store consciousness. Here, I suggest a correspondence between this Buddhist Store consciousness and the neuroscientific idea of stored synaptic weights. These weights are strong synaptic connections built (...) in through experience. Buddhist philosophy claims that humans can find relief from suffering through a process in which the Store consciousness is transformed. Here, I argue that this Buddhist 'transformation at the base' corresponds to a loosening of the learned synaptic connections. I will argue that Buddhist meditation practices create conditions in the brain which are optimal for diminishing the strength of our conditioned perceptual and behavioural tendencies. (shrink)

Reformation commentators were well aware of the allegorical referents for Leviathan and Behemoth in the book of Job, representing the powerful states of Ancient Egypt and Assyria, but played them down. Hobbes did not.

This paper brings new work to bear on the perennial question about Hobbes's atheism to show that as a debate about scepticism it is falsely framed. Hobbes, like fellow members of the Mersenne circle, Descartes and Gassendi, was no sceptic, but rather concerned to rescue physics and metaphysics from radical scepticism by exploring corporealism. In his early letter of November 1640, Hobbes had issued a provocative challenge to Descartes to abandon metaphysical dualism and subscribe to a ?corporeal God?; a provocation (...) to which the Frenchman angrily responded, but was perhaps importantly influenced. Hobbes's minimal realism was consonant with atheism, to which Descartes felt he was being forced. Moreover, Hobbes was unrelenting in his battle against Cartesian dualism, for which he saw Robert Boyle's experimental science as a surrogate. (shrink)

ABSTRACT: Hobbes belonged to philosophical and scientific circles grappling with the big question at the dawn of modern physics: materialism and its consequences for morality. ‘Matter in motion’ may be a core principle of this materialism but it is certainly inadequate to capture the whole project. In wave after wave of this debate the Epicurean view of a fully determined universe governed by natural laws, that nevertheless allows to humans a sphere of libertas, but does not require a creator god (...) or teleology to explain it, comes up against monotheism and its insistence on the incoherence of an ordered world in the absence of a God and his purposes. The following questions were central to this debate: Can we understand the universe as law-governed in the absence of a god? If so, what room is there in a fully determined mechanical universe for human freedom? If humans do enjoy freedom, does the same hold for other animals? Is this freedom compatible with standard views of morality? (shrink)

This paper focuses on the interpretation of the Italian approximative adverb quasi 'almost' by primarily looking at cases in which it modifies temporal connectives, a domain which, to our knowledge, has been largely unexplored thus far. Consideration of this domain supports the need for a scalar account of the semantics of quasi (close in spirit to Hitzeman's semantic analysis of almost, in: Canakis et al. (eds) Papers from the 28th regional meeting of the Chicago Linguistic Society, 1992). When paired with (...) suitable analyses of temporal connectives, such an account can provide a simple explanation of the patterns of implication that are observed when quasi modifies locational (e. g. quando 'when'), directional (e. g. fino 'until' and da 'since'), and event-sequencing temporal connectives (e. g. prima 'before' and dopo ' after'). A challenging empirical phenomenon that is observed is a contrast between the modification of fino and da by quasi, on the one hand, and the modification of prima and dopo by the same adverb, on the other. While quasi fino and quasi da behave symmetrically, a puzzling asymmetry is observed between quasi prima and quasi dopo. To explain the asymmetry, we propose an analysis of prima and dopo on which the former has the meaning of the temporal comparative più presto 'earlier', while the latter is seen as an atomic predicate denoting temporal succession between events (Del Prete, Nat Lang Semantics 16: 157-203, 2008). We show that the same pattern of implication observed for quasi prima is attested when quasi modifies overt comparatives, and propose a pragmatic analysis of this pattern that uniformly applies to both cases, thus providing new evidence for the claim that prima is underlyingly a comparative. A major point of this paper is a discussion of the notion of scale which is relevant for the semantics of quasi', in particular, we show that the notion of Horn (entailment-based) scale is not well-suited for handling modification of temporal connectives, and that a more general notion of scale is required in order to provide a uniform analysis of quasi as a cross-categorial modifier. (shrink)

Despite considerable growth in understanding of various aspects of sporting and exercise embodiment over the last decade, in-depth investigations of embodied affectual experiences in running remain limited. Furthermore, within the corpus of literature investigating pleasure and the hedonic dimension in running, much of this research has focused on experiences of pleasure in relation to performance and achievement, or on specific affective states, such as enjoyment, derived after completing a run. We directly address this gap in the qualitative literature on sporting (...) and exercise embodiment by contributing novel insights on the mind-body pleasures of running via focusing analytic attention towards the pleasures recalled by runners as experienced during positive, rewarding running experiences. Applying conceptual insights drawn from sociological phenomenology, we analyse data from an in-depth, event-focused interview study with distance runners who reported positive, rewarding experiences in recent recreational runs. Through reflexive thematic analysis, we present findings in relation to three themes: (1) ‘running feels like it should’; (2) sensory engagements; and (3) time out. The study contributes fresh perspectives, both conceptually and in relation to data-collection approach, to a small literature on the lived experience of pleasure in sport, exercise and physical cultures. (shrink)

Quentin Skinner’s dedication to investigating Hobbes’s concept of liberty in a number of essays and books has born some unusual fruit. Not only do we see the enormous problems that Hobbes set himself by proceeding as he did, but Skinner’s careful analysis allows us to chart Hobbes’ ingenuity as he tried to steer a path between the Charybdis of determinism and the Scylla of voluntarism – not very successfully, as we shall see. The upshot is a theory of individual freedom (...) and civil liberty to challenge the classical republican traditionThis Article does not have an abstract. (shrink)

As a representative of the papacy Bellarmine was an extremely moderate one. In fact Sixtus V in 1590 had the first volume of his Disputations placed on the Index because it contained so cautious a theory of papal power, denying the Pope temporal hegemony. Bellarmine did not represent all that Hobbes required of him either. On the contrary, he proved the argument of those who championed the temporal powers of the Pope faulty. As a Jesuit he tended to maintain the (...) relative autonomy of the state, denying the temporal powers ascribed by radical papalists and Augustinians. Their argument was generally framed as a syllogism: Christ, who possessed direct temporal power as both God and man, exercised it on earth; the Pope is the vicar of Christ; therefore the Pope possesses and may exercise direct temporal jurisdiction. Bellarmine simply denied that Christ had exercised the temporal power, which as God, it is true, he possessed. Moreover, he drew up and circulated a list of patristic passages collected under the title De Regno Christi quale sit, to prove to the Pope the orthodoxy of his position. (shrink)

The paper shows that for any invalid polysyllogism there is a procedure for constructing a model with a domain with exactly three members and an interpretation that assigns non-empty, non-universal subsets of the domain to terms such that the model invalidates the polysyllogism.

Hobbes in Leviathan, chapter xv, 4, makes the startling claim: “The fool hath said in his heart, ‘there is no such thing as justice,’” paraphrasing Psalm 52:1: “The fool hath said in his heart there is no God.” These are charges of which Hobbes himself could stand accused. His parable of the fool is about the exchange of obedience for protection, the backslider, regime change, and the tyrant; but given that Hobbes was himself likely an oath-breaker, it is also self-reflexive (...) and self-justificatory. For, Hobbes’s fool is not a windbag, or one of the dumb mob, led astray by priests. He is, in the terminology of Psalm 52, an insipiens, a madman or raving lunatic, whose rebellion against God the King is his own destruction and that of his people. A long iconographic tradition portraying the fool as insipiens, Antichrist, heretical impostor and tyrant king, was at Hobbes’s disposal. (shrink)

"Justice according to Need" is an old socialist slogan and Marxism embraced an ancient theory of true and false needs. But Aristotle also formulated "justice according to need", although in different terms, where "need" is often translated as "demand".

Attention has turned from Hobbes the systematic thinker to his inconsistencies, as the essays in the Hobbes symposium published in the recent volume of Political Theory suggest. Deborah Baumgold, in “The Difficulties of Hobbes Interpretation,” shifted the focus to “the history of the book,” and Hobbes’s method of serial composition and peripatetic insertion, as a major source of his inconsistency. Accepting Baumgold’s method, the author argues that the manner of composition does not necessarily determine content and that fundamental paradoxes in (...) Hobbes’s work have a different provenance, for which there are also contextual answers. Hobbes was a courtier’s client, but one committed early to a materialist ontology and epistemology, and these commitments shackled him in treating the immediate political questions with which he was required to deal, leading to systemic paradoxes in his treatment of natural law, liberty, authorization, and consent. (shrink)

Why would someone concerned with heresy, who defined it as private opinion that flew in the face of doctrine sanctioned by the public person, harbor such a detailed interest in heterodoxy? Hobbes's religious beliefs ultimately remain a mystery, as perhaps they were meant to: the private views of someone concerned to conform outwardly to what his church required of him, and thereby avoid to heresy, while maintaining intellectual autonomy. The hazard of Hobbes's particular catechism is that he and his supporters (...) could never avoid the suspicion of insincerity. His preparedness to believe whatever the prince demanded of him smacked of heresy in the more usual sense, despite elaborate biblical exegesis designed to prove his orthdoxy. Undoubtedly he realized it even as he wrote the last lines of Leviathan, expressing the hope that "I cannot think it will be condemned at this time, either by the Publique Judge of Doctrine, or by any that desires the continuance of Publique Peace/7 Indicating an intention to return to science, he continued, "I hope the Novelty will as much please, as in the Doctrine of this Artificiall Body it useth to offend" (Lev, Rev. and Conclusion, 491). (shrink)

We propose a semantic analysis of the particles afinal (European Portuguese) and alla fine (Italian) in terms of the notion of truth unpersistence, which combines both epistemic modality and constraints on discourse structure. We argue that the felicitous use of these modal particles requires that the truth of a proposition p* fail to persist through a temporal succession of epistemic states, where p* is incompatible with the proposition modified by afinal/alla fine, and that the interlocutors share knowledge of a previous (...) epistemic attitude toward p*. We analyze two main cases, that of plan-related propositions and that of propositions without plans. We also discuss the connections between truth unpersistence and evidentiality. (shrink)

This paper analyzes a non-temporal interpretation of the adverb sempre “always” in European Portuguese and Italian, in which the adverb expresses persistence of the truth of a proposition over time and displays specific contextual constraints (TP-sempre). Despite an overlap in the contexts in which TP-sempre may occur in both languages, we provide data showing that its distribution is not exactly the same in European Portuguese and Italian. In view of these data, we propose that TP-sempre is a modal operator of (...) confirmation in both languages, but that it is more restricted in Italian in that it has a plan presupposition only in this language. (shrink)

Hegel’s interpretation of Sophocles’ play Antigone is central to an understanding of woman’s role in the Hegelian system. Hegel is fascinated by this play and uses it in both the Phenomenology and the Philosophy of Right to demonstrate that familial ethical life is woman’s unique responsibility. Antigone is revealed as the paradigmatic figure of womanhood and family life in both the pagan and modern worlds although there are fundamental differences between these two worlds for Hegel. In order to situate the (...) interpretation of this play within its wider context I shall begin with a brief outline of the pagan world described in the Phenomenology. I will then consider the interpretation of this play within the analysis of the modern world in the Philosophy of Right. Throughout, the focus will be on woman’s role in Hegel’s philosophy. (shrink)

Archytas of Tarentum, a contemporary and associate of Plato, was a famous Pythagorean, mathematician, and statesman of Tarentum. Although his works are lost and most of the fragments attributed to him were composed in later eras, they nevertheless contain valuable information about his thought. In particular, the fragments of On Law and Justice are likely based on a work by the early Peripatetic biographer Aristoxenus of Tarentum. The fragments touch on key themes of early Greek ethics, including: written and unwritten (...) laws; freedom and self-sufficiency; moderation of the emotions and cultivation of virtues; equality and the competence of the majority to participate in government; criticism of “rule by an individual”; a theory of the ideal “mixed constitution”; distributive and corrective justice and punishment, and of the rule of law. The fragments also contain one of the only positive accounts of democracy in ancient Greek philosophy. (shrink)

Thomas Hobbes's 'Historia Ecclesiastica' presents his views on religion and aims to divert the attention of the public from charges against his being a heretic to placing heresy in pagan history, claiming that Greek philosophers were responsible for introducing heresy in the Christian Church. His book reveals his interest in religious history and the growth of hermeticism and Cabalism in England in his age.

This paper provides a semantic analysis of the particles afinal (European Portuguese) and alla fine (Italian) in terms of the notion of truth unpersistence, which can be situated at the intersection of epistemic modality and discourse structure. In the analysis proposed, the particles are propositional operators and require that the truth of a proposition p* fail to persist through a temporal succession of epistemic states, this proposition being incompatible with the prejacent, and that the interlocutors share knowledge of a previous (...) epistemic attitude toward p*. We analyze two main cases (plan-related and non plan-related propositions) and also show that these particles are indexical to one (or more) epistemic agent(s) and allow for shifts in perspective. (shrink)

Since the inception of their discipline, anthropologists have studied virtually every conceivable aspect of other peoples' morality - religion, social control, sin, virtue, evil, duty, purity and pollution. But what of the examination of anthropology itself, and of its agendas, epistemes, theories and praxes? Conceived as a response to Patrick Tierney's hugely inflammatory book Darkness in El Dorado , whose allegations of immoral and negligent anthropological research in South America caused a storm of protest and debate, the book combines theoretical (...) papers and case studies from eminent scholars including Steven Nugent, Marilyn Silverman and Veronica Strang. Showing how the topic of ethics goes to the heart of anthropology, it raises the controversial question of why - and for whom - the anthropological discipline functions. (shrink)

When he gave his first political work the title The Elements of Law Natural and Politic, Hobbes signalled an agenda to revise and incorporate continental Roman and Natural Law traditions for use in Great Britain, and from first to last he remained faithful to this agenda, which it took his entire corpus to complete. The success of his project is registered in the impact Hobbes had upon the continental legal system in turn, specific aspects of his theory, as for instance (...) the right to punish, entering the European civil code through Pufendorf, and remaining to this day. This is a topic of considerable importance at a time at which the UK is considering scrapping the European Union, with all the attendant the legal ramifications. But strangely, despite some acknowledgement of Hobbes’s contribution to European civil law, and specifically the German civil code, the larger legal context for his thought has not thus far been systematically addressed. -/- Key words: Hobbes, civil law, common law, jurisprudence, ‘artificial reason’, natural law, sovereignty,. (shrink)

ABSTRACT: Why would someone concerned with heresy, who defined it as private opinion that flew in the face of doctrine sanctioned by the public person, harbor such a detailed interest in heterodoxy? Hobbes's religious beliefs ultimately remain a mystery, as perhaps they were meant to: the private views of someone concerned to conform outwardly to what his church required of him, and thereby avoid to heresy, while maintaining intellectual autonomy. The hazard of Hobbes's particular catechism is that he and his (...) supporters could never avoid the suspicion of insincerity. His preparedness to believe whatever the prince demanded of him smacked of heresy in the more usual sense, despite elaborate biblical exegesis designed to prove his orthdoxy. Undoubtedly he realized it even as he wrote the last lines of Leviathan, expressing the hope that "I cannot think it will be condemned at this time, either by the Publique Judge of Doctrine, or by any that desires the continuance of Publique Peace/7 Indicating an intention to return to science, he continued, "I hope the Novelty will as much please, as in the Doctrine of this Artificiall Body it useth to Offend" (Lev, Rev. and conclusion, 491). (shrink)

A semantics is presented for Storrs McCall's separate axiomatizations of Aristotle's accepted and rejected polysyllogisms. The polysyllogisms under discussion are made up of either assertoric or apodeictic propositions. The semantics is given by associating a property with a pair of sets: one set consists of things having the property essentially and the other of things having it accidentally. A completeness proof and a semantic decision procedure are given.

Amazon Book Review Series of “Wild Wise Weird”.

Aristotle's syllogistic is extended to include denumerably many quantifiers such as 'more than 2/3' and 'exactly 2/3.' Syntactic and semantic decision procedures determine the validity, or invalidity, of syllogisms with any finite number of premises. One of the syntactic procedures uses a natural deduction account of deducibility, which is sound and complete. The semantics for the system is non-classical since sentences may be assigned a value other than true or false. Results about symmetric systems are given. And reasons are given (...) for claiming that syllogistic validity is relevant validity. (shrink)

This essay, published in Political Theory in 1975, was one of the first to address the subject of the last two long books of Hobbes's Leviathan on religion. It addresses the purpose of these books and the relation between Hobbes's philosophy, ecclesiology and theology and the problems they raise.

Recent archaeological discoveries show ancient, and particularly Near Eastern society to have been supremely contractual, while Mediterranean society was historically characterized by strong family structures, challenging the 19th century evolutionary Status-to-Contract canon.

Hobbes's interest in the power of the Image was programmatic, as suggested by his shifts from optics, to sensationalist psychology, to the strategic use of classical history, exemplified by Thucydides and Homer. It put a great resource at the disposal of the state-propaganda machine, with application to the question of state-management and crowd control.

This essay advances the following set of arguments: First, that we must take seriously Hobbes's claim in Behemoth that "the science of just & unjust" is a demonstrable science, accessible to those of even the meanest capacity. Second, that Leviathan is the work in which this science, intended as a serious project in civic education, is set out. Third, that Hobbes is prepared to accept, like Plato & Aristotle, "giving to each his own," as a preliminary definition of justice, from (...) which however, he draws some very un-Aristotelian conclusions. Fourth, that though in Hobbes's theory "just & unjust" are equivalent of "lawful & unlawful," this is far from being a simple statement of legal positivism, but rather the conclusion of a practical syllogism. Fifth, that the impediments to this demonstrable science of justice being universally accepted, on Hobbes's account, are twofold, explained in terms of religion & the role of preachers & educators produced by the universities, on the one hand, & by the activity of "democratical gentlemen" & classical republicans dominating parliament, on the other. Sixth, that Hobbes's account of the transition from jus to lex, specified in terms of a transition from the state of nature to that of civil society, although Epicurean in origin, is much closer to a conventional civil law position. Adapted from the source document. (shrink)

Malcolm’s English-Latin Leviathan is a marvelous technical accomplishment. My issues are with his contextualization, seeing Leviathan primarily as an advice book for Hobbes’s teenage pupil, the future Charles II. Malcolm’s localization involves minimalizing Leviathan's remoter sources, so the European Republic of Letters, for which Hobbes so painstakingly translated his works into Latin, is almost entirely missing, along with current European traditions of Hobbes scholarship. Is this very British Hobbes truly credible, or do we need a more European Hobbes to account (...) for the complexity of Leviathan? (shrink)

Critics have alleged that Democritus’ ethical prescriptions (“gnomai”) are incompatible with his physics, since his atomism seems committed to necessity or chance (or an awkward combination of both) as a universal cause of everything, leaving no room for personal responsibility. I argue that Democritus’ critics, both ancient and contemporary, have misunderstood a fundamental concept of his causality: a cause called “spontaneity”, which Democritus evidently considered a necessary (not chance) cause, compatible with human freedom, of both atomic motion and human actions. (...) Some influential contemporary compatibilists have argued that freedom and responsibility are compatible with causal determinism, but not intentional constraint where some other agent is intentionally manipulating or coercing one’s actions. In line with this, Democritus holds that humans should not blame their actions on other agents like the gods, or agent-like external forces like fate or chance, but should assume ultimate intentional control over their own choices and actions. The famous remark of his associate Leucippus that “everything happens for a reason and out of necessity” is a fitting slogan of their atomistic philosophy, for Democritus pursued what can without anachronism be recognized as a causal theory of freedom. (shrink)

BioPortal is a Web portal that provides access to a library of biomedical ontologies and terminologies developed in OWL, RDF(S), OBO format, Protégé frames, and Rich Release Format. BioPortal functionality, driven by a service-oriented architecture, includes the ability to browse, search and visualize ontologies (Figure 1). The Web interface also facilitates community-based participation in the evaluation and evolution of ontology content.

This study steps beyond the traditional arguments of feminism and examines homebirth from a libertarian perspective. It addresses the debate over homebirth and midwifery, which includes the use of direct-entry midwives as well as the philosophical implications of individual autonomy expressed through consumer choice. Furthermore, this paper demonstrates that the medical establishment gains economic and political control primarily through medical licensing, and uses the state to undermine personal freedom as it advances a government-enforced monopoly on birth. At the same time, (...) empirical studies have established a substantial record of high safety and low medical complication rates for homebirth as compared to hospital births. Ultimately, the state’s restriction on medical choices is incompatible with the nonaggression principle and voluntarism, and therefore, with libertarianism. (shrink)

As artforms, film and street art seem incompatible. Contra this incompatibility, I investigate their combination: cinematic street art. Two promising cases are the artworks MUTO and Repopulate, but I argue neither is suitable. MUTO only counts if I accept the transparency thesis, the claim that photographs allow us to literally see their depicta. Repopulate only counts if we reject Noel Carroll’s requirement that a cinematic performance token isn’t itself an artwork. However, these imperfect cases demonstrate what is required in order (...) to have cinematic street art: the artwork is a 1) aconsensual artwork that 2) does not merely use street art as imagery or 3) merely use the street as a performance space. I introduce two hypothetical artworks inspired by this approach and discuss their merits, as well as their pitfalls relevant to my own desiderata. As such, this article serves as the foment for broader discussion within the philosophy of street art. (shrink)

Marx in his early Critique of Hegel's Philosophy of Right (1843) declared "Democracy is human existence, while in other political forms man has only legal existence". In the Grundrisse and his late Ethnological Notebooks he studied the emergence of "the political" from primordialism, or the rule of family, tribe and clan .

This is part 1 of 6 of the dossier What Do We Talk about when We Talk about Queer Death?, edited by M. Petricola. The contributions collected in this article sit at the crossroads between thanatology and queer theory and tackle questions such as: how can we define queer death studies as a research field? How can queer death studies problematize and rethink the life-death binary? Which notions and hermeneutic tools could be borrowed from other disciplines in order to better (...) define queer death studies? The present article includes the following contributions: – MacCormack P., What does queer death studies mean?; – Radomska M., On queering death studies; – Lykke N., Death as vibrancy; – Hillerup Hansen I., What concreteness will do to resolve the uncertain; – Olson P., Queer objectivity as a response to denials of death; – Manganas N., The queer lack of a chthonic instinct. (shrink)

Schwarz pursues a primordial theme by Freudian means, extrapolating from the psychogenesis of a person to the psychogenesis of a nation. He thus associates monarchy with culture in its infancy, displaying infantile narcisism and meglomania. But as perhaps the best worst case, Pharaonic Egypt, demonstrates, meglomania and narcissism expresssed in colossi, grandiose claims of the king that would shame even the gods, are more likely a sign of weakness than strength. And classical republicanism continues to maintain a monarchical element, now (...) transferred to presidents. (shrink)

It is my thesis that Renaissance classical translations and imitations were often works of political surrogacy in a literary environment characterized by harsh censorship. So, for instance, the works of Homer, Virgil, and Lucan were read as coded texts, that ranged across the political spectrum.

Social integration was theorized to be a ‘secularizing’ process for immigrants in Western Europe. Assuming that immigrants adapt to new social environments by complying with the mainstream culture of their receiving countries, immigrant religiosity is expected to decline as they assimilate in societies where secular norms prevail. Alternatively, religion could be a coping mechanism for immigrants who struggle to assimilate in their receiving countries. ‘Buffer’ theories of religion suggest that religious identity could be interchangeable with ethnicity and nationality to mitigate (...) the identity conflicts immigrants experience. This paper addresses the following research question: What role does religion play in the identity conflict experienced by immigrants who are both an ethnic minority and a national of a Western European country? Particularly, I explore the pertinence of religious identity for first-generation Sub-Saharan African Christian immigrants (SSACI) in Germany and France, where the models of immigrant assimilation diverge. Statistical tests were conducted on data derived from two surveys to compare religious, national, and ethnic self-identities at the group and individual levels. The group comparisons suggest that Christianity was indeed more salient for SSACI than native-born Christians. SSACIs without citizenship were also more likely to experience identity conflict, to which they may cope by associating less with their ethnicity or more with their religious identity. Perceived discrimination was associated with identity conflict only in Germany where immigrant assimilation is traditionally based on a common ancestry, in contrast to the values-based model in France. These are consistent with the predictions derived from ‘buffer’ theories of immigrant religiosity but longitudinal studies are needed for a more robust understanding of these trends. (shrink)

Authenticates approximately 500 lines of Aristotle's lost work the Protrepticus (Exhortation to Philosophy) contained in the circa third century AD work by Iamblichus of Chalcis entitled Protrepticus epi philosophian. Includes a complete English translation of the authenticated material.

Syllogisms with or without negative terms are studied by using Gergonne's ideas. Soundness, completeness, and decidability results are given.