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)

BAIXE O PDF COMPLETO COM 58 FIGURAS E 50 PÁGINAS!!! -/- INTRODUÇÃO Conhecer a anatomia de um aparelho representa a base para seu estudo amplo e profundo, além de facilitar a compreensão de seu funcionamento. Por isso é importante o conhecimento da anatomia funcional do aparelho reprodutor, já que sua análise permite fixar sólidas bases para o estudo do fenômeno pelo qual se perpetuam as espécies: a reprodução. Nos subtemas compreendidos referentes ao macho e a fêmea, descreve-se cada um dos (...) órgãos que formam o aparelho reprodutor e as suas diferenças entre espécies, assinalando-se em cada um deles a sua função. Obviamente, a parte que trata do funcionamento não é abordada de uma forma muito ampla. Para facilitar o estudo do aparelho reprodutor do macho, seus órgãos podem ser classificados de acordo com sua localização anatômica, em órgãos genitais internos (que compreendem os ductos deferentes, as glândulas acessórias e a uretra pélvica) e órgãos genitais externos (testículos com seu epidídimo). O testículo também foi considerado como órgão sexual primário, enquanto os ductos excretores, glândulas acessórias, pênis e prepúcio são considerados órgãos sexuais secundários. O aparelho reprodutor da fêmea é dividido em ovários e órgãos tubulares (útero, oviduto, cérvix, vagina e vulva). 2.2 APARELHO REPRODUTOR DO MACHO Para avaliar a capacidade reprodutiva dos machos, é primordial conhecer a anatomia e a fisiologia do aparelho reprodutor. Os órgãos genitais incluem testículos, epidídimos, canais deferentes, ampolas deferentes, uretra, glândulas acessórias (próstata, glândulas seminais e glândulas bulbouretrais), pênis e prepúcio, que apresentam diferenças entre as espécies domésticas (tabela 1). Sabe-se que o sistema genital masculino compreende os órgãos envolvidos no desenvolvimento, no amadurecimento, no transporte e no armazenamento dos gametas masculinos (espermatozoides). Ele consiste em um par de testículos, o ducto contorcido do epidídimo, o ducto deferente, a uretra e as glândulas genitais acessórias. Os testículos produzem esperma e hormônios. O epidídimo armazena espermatozoides durante seu amadurecimento antes de passarem para o ducto deferente e pela uretra. As glândulas acessórias também liberam suas secreções na uretra e contribuem para o volume do sêmen. A parte distal da uretra forma o caminho combinado para a passagem tanto da urina como do sêmen. O pênis é o órgão copulador masculino e deposita sêmen no trato reprodutor feminino. As figuras 1-5 apresentam as diferenciações quanto ao sistema genital das espécies domésticas. Conhecer a anatomia dos órgãos reprodutivos é essencial para poder identificar as patologias que possam afetar a capacidade reprodutiva, bem como para entender as diferenças de manejo ao empregar algumas biotecnologias reprodutivas aplicadas aos animais domésticos. Ao longo do texto, a espécie bovina será utilizada como modelo e serão feitas as observações correspondentes às diferenças com as outras espécies. Os órgãos genitais da fêmea incluem os órgãos genitais internos (ovários, ovidutos, útero, cérvix, vestíbulo e vagina) e os órgãos genitais externos (lábios vulvares e clitóris) (tabela 3). Os ovários produzem tanto gametas femininos quanto hormônios. As tubas uterinas pares capturam os oócitos liberados pelos ovários e os transportam para o útero, onde o ovo fertilizado é mantido. A vagina serve como órgão copulatório e, juntamente com sua continuação, o vestíbulo, como canal de parto e passagem para excreção urinária. -/- REFERÊNCIAS BIBLIOGRÁFICAS BOETA, M. et al. Fisiología reproductiva de los animales domésticos. México: FMVZ – UNAM, 2018. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DUKES, Henry Hugh; SWENSON, Melvin J.; REECE, William O. Dukes fisiologia dos animais domésticos. Rio de Janeiro: Editora Guanabara Koogan, 1996. DYCE, Keith M.; WENSING, Cornelius JG; SACK, Wolfganf O. Tratado de anatomia veterinária. Elsevier Brasil, 2004. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. KÖNIG, Horst Erich; LIEBICH, Hans-Georg. Anatomia dos Animais Domésticos-: Texto e Atlas Colorido. Porto Alegre: Artmed Editora, 2016. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. (shrink)

As ever more advanced digital systems are created, it becomes increasingly likely that some of these systems will be digital minds, i.e. digital subjects of experience. With digital minds comes the risk of digital suffering. The problem of digital suffering is that of mitigating this risk. We argue that the problem of digital suffering is a high stakes moral problem and that formidable epistemic obstacles stand in the way of solving it. We then propose a strategy for solving it: Access (...) Monitor Prevent (AMP). AMP uses a ‘dancing qualia’ argument to link the functional states of certain digital systems to their experiences—this yields epistemic access to digital minds. With that access, we can prevent digital suffering by only creating advanced digital systems that we have such access to, monitoring their functional profiles, and preventing them from entering states with functional markers of suffering. After introducing and motivating AMP, we confront limitations it faces and identify some options for overcoming them. We argue that AMP fits especially well with—and so provides a moral reason to prioritize—one approach to creating such systems: whole brain emulation. We also contend that taking other paths to digital minds would be morally risky. (shrink)

The sensorimotor theory of vision and visual consciousness is often described as a radical alternative to the computational and connectionist orthodoxy in the study of visual perception. However, it is far from clear whether the theory represents a significant departure from orthodox approaches or whether it is an enrichment of it. In this study, I tackle this issue by focusing on the explanatory structure of the sensorimotor theory. I argue that the standard formulation of the theory subscribes to the same (...) theses of the dynamical hypothesis and that it affords covering-law explanations. This however exposes the theory to the mere description worry and generates a puzzle about the role of representations. I then argue that the sensorimotor theory is compatible with a mechanistic framework, and show how this can overcome the mere description worry and solve the problem of the explanatory role of representations. By doing so, it will be shown that the theory should be understood as an enrichment of the orthodoxy, rather than an alternative. (shrink)

Abstract: Rice, as a paramount staple crop worldwide, sustains billions of lives. Precise classification of rice types holds immense agricultural, nutritional, and economic significance. Recent advancements in machine learning, particularly Artificial Neural Networks (ANNs), offer promise in enhancing rice type classification accuracy and efficiency. This research explores rice type classification, harnessing neural networks' power. Utilizing a rich dataset from Kaggle, containing 18,188 entries and key rice grain attributes, we develop and evaluate a neural network model. Our neural network, featuring a (...) single hidden layer, achieves remarkable results—a staggering 100% accuracy and a minute average error rate of 0.000001. Beyond performance metrics, we delve into the intricacies of rice type classification through feature importance analysis. The most influential features—'id,' 'Area,' 'MajorAxisLength,' 'MinorAxisLength,' 'Eccentricity,' 'ConvexArea,' 'EquivDiameter,' 'Extent,' 'Perimeter,' 'Roundness,' and 'AspectRatio'—uncover the physiological traits underpinning accurate rice classification. This research contributes to advancing rice classification methods and highlights the potential of ANNs in optimizing agricultural practices, ensuring food safety, and bolstering global trade. (shrink)

Some physical theories predict that almost all brains in the universe are Boltzmann brains, i.e. short-lived disembodied brains that are accidentally assembled as a result of thermodynamic or quantum fluctuations. Physicists and philosophers of physics widely regard this proliferation as unacceptable, and so take its prediction as a basis for rejecting these theories. But the putatively unacceptable consequences of this prediction follow only given certain philosophical assumptions. This paper develops a strategy for shielding physical theorizing from the threat of Boltzmann (...) brains. The strategy appeals to a form of phenomenal externalism about the physical basis of consciousness. Given that form of phenomenal externalism, the proliferation of Boltzmann brains turns out to be benign. While the strategy faces a psychophysical fine-tuning problem, it both alleviates cosmological fine-tuning concerns that attend physics-based solutions to Boltzmann brain problems and pays explanatory dividends in connection with time’s arrow. (shrink)

Philosophers of perception frequently assume that we see actual states of affairs, or facts. Call this claim factualism. In his book, William Fish suggests that factualism is supported by phenomenological observation as well as by experimental studies on multiple object tracking and dynamic feature-object integration. In this paper, I examine the alleged evidence for factualism, focusing mainly on object detection and tracking. I argue that there is no scientific evidence for factualism. This conclusion has implications for studies on the phenomenology (...) and epistemology of visual perception. (shrink)

This article investigates whether the politics of nationalism fosters human development and global peace. Nationalism is a political ideology that primarily gives birth to nation-states based on particular shared identities, such as religion, race, culture, or language. Empirical evidence shows that nationalism causes conflicts, which leads to violence, terrorism or war. On the one hand, nationalism gives birth to nation-states; on the other hand, it creates hostility in the world. However, Lahouari Addi argues that giving birth to nations and their (...) nation-building are two different social phenomena. Addi contends that the public sphere and civil peace are the essential conditions for nation- building. Addi’s argument for nation-building is promising. In line with this argument, this paper asserts that the politics of nationalism should make human development and peace in their respective nation-states. To explain malign and benign aspects, the paper differentiates between two kinds of nationalism: negative and productive. Negative nationalism, based on the politics of exclusion, discriminates, humiliates, exploits, and coerces the people of other nations, which causes conflicts and, eventually violence. This strand of nationalism is inconsistent with human development and global peace. Instead, productive nationalism, based on the politics of inclusion, fosters a sense of reverence for humanity which supports self-respect, dignity, freedom, equality, and fraternity in the world. Productive nationalism helps develop human potential, which leads to positive peace through creative accomplishments, such as performing arts, literature, and sports. Thus, the research implies that the politics of productive nationalism creates positive moral values to promote cooperation among people within and across the nations, which fosters human development and peace in the world. In the domain of qualitative research, this paper adopts the methodology of empirically informed philosophical analysis to evaluate the documentary resources. (shrink)

Metaphysical underdetermination arises when we are not able to decide, through purely theoretical criteria, between competing interpretations of scientific theories with different metaphysical commitments. This is the case in which non-relativistic quantum mechanics (QM) finds itself in. Among several available interpretations, there is the one that states that the interaction with the conscious mind of a human observer causes a change in the dynamics of quantum objects undergoing from indefinite to definite states. In this paper, we argue that there seems (...) to be also a metaphysical underdetermination concerning London and Bauer’s theory of measurement between two methods of phenomenological reduction: the eidetic and the transcendental approaches. Recently, Steven French argued that both methods can be combined in order to interpret London and Bauer’s formalism. However, in this paper we argue that the eidetic one is the only viable phenomenological way to interpret this particular theory of measurement in QM based on the formalism presented by London and Bauer, hence breaking this phenomenological underdetermination. (shrink)

Florence Ashley has argued that requiring patients with gender dysphoria to undergo an assessment and referral from a mental health professional before undergoing hormone replacement therapy (HRT) is unethical and may represent an unconscious hostility towards transgender people. We respond, first, by showing that Ashley has conflated the self-reporting of symptoms with self-diagnosis, and that this is not consistent with the standard model of informed consent to medical treatment. Second, we note that the model of informed consent involved in cosmetic (...) surgery resembles the model Ashley defends, and that psychological assessment and referral is recognised as an important aspect of such a model. Third, we suggest that the increased prevalence of psychiatric morbidity in the transgender population arguably supports the requirement of assessment and referral from a mental health professional prior to undergoing HRT. (shrink)

In this article I argue that we should be prudentially and morally biased toward earlier events: other things equal, we should prefer for good events to occur earlier and disprefer for bad events to occur earlier. The argument contends that we should accord at least some credence—if only a small one—to a theoretical package featuring the growing block theory of time and that this package generates a presumptive bias toward earlier events. Rival theoretical packages are considered. Under reasonable allocations of (...) credence to them, the presumptive bias escapes defeat. The argument has several corollaries: other things equal, we should be biased toward the past over the future, the further past over the nearer past, and the nearer future over the further future. (shrink)

Tyler Burge is famous for defending primitivist naturalism about mental representations, according to which mental representations are primitive natural states. Primitivist naturalism contrasts with semantic reductionism, according to which mental representations are reducible to more fundamental natural states. Burge developed the most compelling and influential attack on semantic reductionism from a primitivist naturalist point of view. My goal in this paper is to defend semantic reduc- tionism from Burge’s attack. I assess and refute his objection to the motivations for semantic (...) reductionism and his objection to the semantic reductionist theory that he takes to be the most promising one, namely, teleosemantics. I argue that in spite of the ingenuity of Burge’s objections, they fail to show that there is no motivation for taking representational states as reducible to more fundamental natural states or that the core thesis of teleosemantics is flawed. (shrink)

Many artists, art critics, and poets suggest that an aesthetic appreciation of artworks may modify our perception of the world, including quotidian things and scenes. I call this Art-to-World, AtW. Focusing on visual artworks, in this paper I articulate an empirically-informed account of AtW that is based on content related views of aesthetic experience, and on Goodman’s and Elgin’s concept of exemplification. An aesthetic encounter with artworks demands paying attention to its aesthetic, expressive, or design properties that realize its purpose. (...) Attention to these properties make percipients better able to spot them in other entities and scenes as well. The upshot is that an aesthetic commerce with artworks enlarges the scope of what we are able to see and has therefore momentous epistemic consequences. (shrink)

Dualism holds that experiences and physical states are distinct in that neither sort of state is identical with or grounded in the other. Cognitive phenomenal realism holds that cognitive experiences are irreducible to sensory experiences. While dualism and cognitive phenomenal realism are logically orthogonal and usually discussed separately, I argue that dualism’s plausibility is sensitive to whether cognitive phenomenal realism is true. In particular, I argue that if cognitive phenomenal realism is true, then it bolsters the case for dualism via (...) a cognitive knowledge argument that has several advantages over the standard sensory knowledge argument. (shrink)

This article defends Ibn Khaldun as a social holist philosopher. Ibn Khaldun is an Arab philosopher regarded as a proto-social holist theorist of modern social thought. The central thesis of social holism asserts that human beings are social creatures because they depend upon one another for their biological existence and the development of human cognitive potential. Many European philosophers since the eighteenth century, including Giambattista Vico, Jean-Jacques Rousseau, Johann Gottfried Herder, Georg Wilhelm Friedrich Hegel, and Ferdinand Tönnies, contributed their roles (...) to the development of social holism in the modern Western tradition. Significantly, after Aristotle and before these European social holist theorists, Ibn Khaldun developed his notion of social holism in the fourteenth century in the Islamic tradition. The key argument of Ibn Khaldun’s social holism holds that cooperation is essential for human existence. He makes a distinction between the sedentary and the nomadic social groups. Ibn Khaldun claims that Asabiyyah is the central value of the nomadic society. ‘Asabiyyah’ refers to ‘social cohesiveness’ which binds people together. Indeed, Ibn Khaldun is an essential philosopher because he is not only a bridge between classical and modern thought in Western tradition but also between Islamic and Western traditions. Thus, I argue that Ibn Khaldun is a significant social holist philosopher. (shrink)

This article explicates the nature of social ontology. There are three social holist theses relevant to the problem: First, the individual and society are not independent of each other. Second, the development of the individual’s human potential depends upon the nature of society. Third, a good society cultivates rather than undermines human potential. To explore the problem, this paper juxtaposes Muhammad Iqbal and Philip Pettit, two social holist philosophers, who belong to the Islamic and Western traditions, respectively. Drawing on the (...) Islamic tradition, Iqbal argues that the individual cannot develop human potential, such as creativity, without a society. Iqbal’s social ontology, based on his theory of egohood, asserts that the individual ego (the individual) develops in relationship to the holistic ego (society). Iqbal repudiates a totalitarian society while supporting an Islamic society based on the principles of freedom, equality, and fraternity. In the Western tradition, Pettit posits an idea of holistic individualism by drawing on four contrasting social theories: atomism, holism, collectivism, and individualism. Pettit envisions a society that is neither totalitarian nor anarchic, but it is a creation of autonomous individuals. Hence, Iqbal’s and Pettit’s social ontological positions are significant to understanding the nature of society and their malign and benign roles in the social world. (shrink)

In this paper, we discuss two recurring themes in Sosa’s work, reexamined in Judgment and Agency (SOSA, 2015) from a new angle, i.e. the place and importance of reflection in the cognitive economy of the epistemic agent, and epistemic value. Regarding the latter, Sosa suggests that knowing full well, which necessarily involves reflection, has value because it contributes to human flourishing. Although Sosa’s “new virtue epistemology” appears very promising in explaining different intuitions regarding epistemology and demonstrating that it is possible (...) to join reliabilist and responsibilist accounts of virtue epistemology, we believe that solving the value problem requires further clarification in order to truly explain the value of knowledge. (shrink)

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

Interpretations are generally regarded as the formal representation of the concept of translation.We do not subscribe to this view. A translation method must indeed establish relative consistency or have some uniformity. These are requirements of a translation. Yet, one can both be more strict or more flexible than interpretations are. In this article, we will define a general scheme translation. It should incorporate interpretations but also be compatible with more flexible methods. By doing so, we want to account for methods (...) that seem to imply a sense of translation but are not reducible to interpretations. The main example will be the relative consistent proof between ZF and NBG given by Novak (1950). Further, we will explore a way of combining interpretations. This should account for truth conditions discarded by interpretations in translated theories. (shrink)

This article fosters the significance of Muhammad Iqbal’s pacifist ethics in the post-9/11 world. In the post-9/11, there emerged a new world order in which violence emerged in many guises, including terrorism and war, which has devastated global peace since the advent of the twenty-first century. Undeniably, the threat of a nuclear war has been constantly harassing the world. Under these atrocious conditions, the question is whether Iqbal’s pacifist ethics could help achieve and sustain global peace. Iqbal was an empirically (...) informed and trained philosopher in the early twentieth century in the Western and Islamic traditions. He witnessed the First World War and identified the factors of the Second World War, which had started just a year after his death. Iqbal identified that materialistic interests and colonial and imperial exploitations cause conflicts, eventually leading to violence and war. The recurrent problem is how we avoid the Third World War to sustain global peace. Iqbal’s ethics offer two ideas for achieving global peace: reverence for humanity and human fraternity. Reverence for humanity helps develop human potential, which promotes creative activities vital for positive peace. Human fraternity is the only dependable unity among human beings, despite their particular races, colours, cultures, or languages, for acquiring global peace. The article thus demonstrates the relevance and significance of Iqbal’s ethics in achieving and sustaining a peaceful co- existence in the world. (shrink)

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

In this article, we analyse the ontological import of adding classes to set theories. We assume that this increment is well represented by going from ZF system to NBG. We thus consider the standard techniques of reducing one system to the other. Novak proved that from a model of ZF we can build a model of NBG (and vice versa), while Shoenfield have shown that from a proof in NBG of a set-sentence we can generate a proof in ZF of (...) the same formula. We argue that the first makes use of a too strong metatheory. Although meaningful, this symmetrical reduction does not equate the ontological content of the theories. The strong metatheory levels the two theories. Moreover, we will modernize Shoenfields proof, emphasizing its relation to Herbrands theorem and that it can only be seen as a partial type of reduction. In contrast with symmetrical reductions, we believe that asymmetrical relations are powerful tools for comparing ontological content. In virtue of this, we prove that there is no interpretation of NBG in ZF, while NBG trivially interprets ZF. This challenges the standard view that the two systems have the same ontological content. (shrink)

In _The Origin of Consciousness in the Breakdown of the Bicameral Mind_, Julian Jaynes presents a philosophy of mind with radical implications for contemporary discussions about artificial intelligence (AI). The ability of AI to replicate the cognitive functions of human consciousness has led to widespread speculation that AI is itself conscious (or will eventually become so). Against this functionalist theory of mind, Jaynes argues that consciousness only arises through the mythopoetic inspiration of metaphorical language. Consciousness develops and enacts new forms (...) of self-understanding, continually evolving new "metaphors of mind," metaphors which must now account for the emergence of AI. (shrink)

Abstract: Research on the nature and varieties of the format of cognitive representations in philosophy and cognitive science have been partly shaped by analogies to external, public representations. In this paper, we argue that relying on such analogies contributes to framing the question of cognitive formats in problematic, potentially counterproductive ways. We show that cognitive and public representations differ in many of their central features, making analogies to public representations ill-suited to improving our understanding of cognitive formats. We illustrate these (...) points by examining two case studies in which analogies to public representations may have had a negative impact on research: the 80’s-90’s debate about compositionality and cognitive architecture between symbolicists and connectionists; and contemporary discussions about the nature of visual demonstratives. Finally, we outline an alternative, computational account of formats that does not share the shortcomings of appeal to public representations. (shrink)

In a recent article in this journal, Abram Brummett argues that new and future assisted reproductive technologies will provide challenging ethical questions relating to lesbian, gay, bisexual and transgender (LGBT) persons. Brummett notes that it is likely that some clinicians may wish to conscientiously object to offering assisted reproductive technologies to LGBT couples on moral or religious grounds, and argues that such appeals to conscience should be constrained. We argue that Brummett's case is unsuccessful because he: does not adequately interact (...) with his opponents’ views; equivocates on the meaning of ‘natural’; fails to show that the practice he opposes is eugenic in any non‐trivial sense; and fails to justify and explicate the relevance of the naturalism he proposes. We do not argue that conscience protections should exist for those objecting to providing LGBT people with artificial reproductive technologies, but only show that Brummett's arguments are insufficient to prove that they should not. (shrink)

At the beginning of the 20th century, Gestalt psychologists put forward the concept of psychoneural isomorphism, which was meant to replace Fechner’s obscure notion of psychophysical parallelism and provide a heuristics that may facilitate the search for the neural correlates of the mind. However, the concept has generated much confusion in the debate, and today its role is still unclear. In this contribution, I will attempt a little conceptual spadework in clarifying the concept of psychoneural isomorphism, focusing exclusively on conscious (...) visual perceptual experience and its neural correlates. Firstly, I will outline the history of our concept, and its alleged metaphysical and epistemic roles. Then, I will clarify the nature of isomorphism and rule out its metaphysical role. Finally, I will review some epistemic roles of our concept, zooming in on the work of Jean Petitot, and suggest that it does not play a relevant heuristic role. I conclude suggesting that psychoneural isomorphism might be an indicator of robustness for certain mathematical descriptions of perceptual content. (shrink)

In this article, instead of taking a particular method as translation, we ask: what does one expect to do with a translation? The answer to this question will reveal, though, that none of the first order methods are capable of fully represent the required transference of ontological commitments. Lastly, we will show that this view on translation enlarge considerably the scope of translatable, and, therefore, ontologically comparable theories.

This paper is a part-review analysis into the modern conception of both the word and Jihād and the violent nature of Islam. In order to develop an overarching modern theory of Jihād, current opinions and general argumtations in the literature are examined. Two theories have emerged in defining Islam and the role of Jihād in Islam. The first is that of the so-called Muslim apologists; scholars who define Jihād as mainly a personal struggle, and whose physical application (warfare) is only (...) in self-defence of the Islamic community. The second sponsors the concept of ‘offensive’ Jihād: that Islam is imperialistic and has a vision of global domination. The stark contrast in the divisions that the scholarship have are indicative of two opposing parties, likely each basing their respective policy positions on beliefs on the nature of Islam as a violent of peaceful ‘religion’. (shrink)

This article intends to show that the defense of “understanding” as one of the major goals of science education can be grounded on an anti-reductionist perspective on testimony as a source of knowledge. To do so, we critically revisit the discussion between Harvey Siegel and Alvin Goldman about the goals of science education, especially where it involves arguments based on the epistemology of testimony. Subsequently, we come back to a discussion between Charbel N. El-Hani and Eduardo Mortimer, on the one (...) hand, and Michael Hoffmann, on the other, striving to strengthen the claim that rather than students’ belief change, understanding should have epistemic priority as a goal of science education. Based on these two lines of discussion, we conclude that the reliance on testimony as a source of knowledge is necessary to the development of a more large and comprehensive scientific understanding by science students. (shrink)

Our universe features a harmonious match between laws and states: applying its laws to its states generates other states. This is a striking fact. Matters might have been otherwise. The universe might have been stillborn in a state unengaged by its laws. The problem of nomological harmony is that of explaining the noted striking fact. After introducing and developing this problem, we canvass candidate solutions and identify some of their virtues and vices. Candidate solutions invoke the likes of a designer, (...) axiarchic meta-laws, multiverses, essential causal powers, and Humean laws. (shrink)

This article discusses the notion of rationality and agency in Fernando Broncano's Racionalidad, Acción y Opacidad (2017). In this book, contradicting the apriorist normative theses or simple naturalistic descriptivism, Broncano argues that rationality is something that is directly associated with our ordinary practices of evaluating the judgments, actions and decisions of others. “Rationality” should be considered as a term we use as an intellectual qualifier or as a virtue we bestow on people who can make theoretical and practical decisions autonomously. (...) Thus, rationality would not be an a priori condition for someone to become a person or a capacity to eliminate the turbulence of human cognitive and moral precariousness, but a form of involvement in the world that positively qualifies the organism that relates thought and action, judgment and choice in the search for lucidity in an uncertain world. With this, rationality and agency would be products of the social interdependence that one has in relation to the other, since we learn it and teach it in the context of natural life. This article is organized in three sections: in the first section I make a very brief presentation of one of the aspects of the problem that has motivated the philosophical discussion on rationality and agency; in the second section, I present my understanding of the themes developed in Racionalidad, Acción y Opacidad, their internal structure and, of course, their central thesis; in the third section, I specifically discuss the theme that the normativity of rationality arises from our dialectical encounter with other people and make personal considerations on the value and scope of the arguments constructed in this book. (shrink)

This paper aims to debunk the spectre of terrorism through social capital. At the advent of the twenty-first century, the menace of terrorism becomes a global phenomenon. Undeniably, terrorism is an evil. The central thesis of social capital theory holds that social relationships matter. There are three central elements of terrorism: politics, terror and ideology. Terrorists plan political strategies using certain kind of ideology to create terror. To deal with all these three elements of terrorism, social capital can be an (...) effective weapon. For explicating the core contours of social capital theory, I draw on Pierre Bourdieu, James Coleman and Robert Putnam. To deal with political, violent and ideological foundations of terrorism, I assert that social capital can be useful for countering all of these foundations. Putnam’s binding and bonding strands of social capital can potentially empower people to develop a social network between people, institutions and states to debunk political, violent and ideological roles of terrorism. Thus, a social capital of intellectuals can repudiate the ideological foundations of terrorism for bringing about global peace. (shrink)

Florence Ashley has responded to our response to ‘Gatekeeping hormone replacement therapy for transgender patients is dehumanising.’ Ashley criticises some of our objections to their view that patients seeking hormone replacement therapy (HRT) for gender dysphoria should not have to undergo a prior psychological assessment. Here we clarify our objections, most importantly that concerning the parity between cosmetic surgery and the sort of intervention Ashley has in mind. Firstly, we show Ashley’s criticism of our comparison is insubstantial. We then examine (...) their comments regarding the analogy between abortion and HRT, and the language of informed consent. We also scrutinize the data upon which Ashley relies to defend the claim that informed consent without assessment always yields positive outcomes, finding this conclusion to be overstated. Finally, even if Ashley’s arguments were vindicated, the claim that the gatekeeping of HRT is motivated by hostility towards transgender people remains unsupported. (shrink)

Abstract: Research on the nature and varieties of the format of cognitive representations in philosophy and cognitive science have been partly shaped by analogies to external, public representations. In this paper, we argue that relying on such analogies contributes to framing the question of cognitive formats in problematic, potentially counterproductive ways. We show that cognitive and public representations differ in many of their central features, making analogies to public representations ill-suited to improving our understanding of cognitive formats. We illustrate these (...) points by examining two case studies in which analogies to public representations may have had a negative impact on research: the 80’s-90’s debate about compositionality and cognitive architecture between symbolicists and connectionists; and contemporary discussions about the nature of visual demonstratives. Finally, we outline an alternative, computational account of formats that does not share the shortcomings of appeal to public representations. (shrink)

This article examines the implications of utilitarianism for social justice, considering different cases of the trolley problems. Utilitarianism comprises a cluster of ethical theses, which have political and legal implications. In general, utilitarianism is assumed to augment the common good, such as pleasure, happiness, satisfaction, and utility, or to reduce pain, suffering, dissatisfaction, and disutility. The article investigates a key problem whether utilitarianism brings about social justice as a moral theory. In recent literature, many moral philosophers have developed several thought (...) experiments, known as trolley problems, that help understand the utilitarian applications to social justice. Philippa Foot and others formulated several thought experiments to help explain the utilitarian difference between the maximum good and the minimum loss. Considering different cases of the trolley problem, I argue that utilitarianism does not do egalitarian justice to all people because it does not eliminate unjust inequalities in society. I hold that utilitarianism is an ethical theory without an egalitarian morality. John Rawls posited a landmark theory of social justice in contrast to the utilitarian notion of social justice. Utilitarianism does not provide social justice to the few, the minority, or the weak in the social world. So, utilitarianism is an inadequate moral theory for acquiring social justice. In qualitative research methodology, I adopt a method of an empirically informed philosophical analysis to examine documentary resources, including journal papers, academic books, and conferences and congresses. (shrink)

Is consistency the sort of thing that could provide a guide to mathematical ontology? If so, which notion of consistency suits this purpose? Mark Balaguer holds such a view in the context of platonism, the view that mathematical objects are non-causal, non-spatiotemporal, and non-mental. For the purposes of this paper, we will examine several notions of consistency with respect to how they can provide a platon-ist epistemology of mathematics. Only a Gödelian notion, we suggest, can provide a satisfactory guide to (...) a platonist ontology. Is consistency the sort of thing that could provide a guide to mathematical ontology? If so, which notion of consistency suits this purpose? Mark Bala-guer holds such a view in the context of platonism, the view that mathematical objects are non-causal, non-spatiotemporal, and non-mental. Balaguer's version of Platonism, Full-Blooded Platonism (FBP), is the view that "there are as many abstract mathematical objects as there could be-i.e., there actually exist abstract mathematical objects of all possible kinds" (Balaguer, 2017, p. 381). He continues: Since FBP says that there are abstract mathematical objects of all possible kinds, it follows that if FBP is true, then every purely mathematical theory that could be true-i.e., that is internally consistent-accurately describes some collection of actually existing abstract objects. Thus it follows from FBP that in order to acquire knowledge of abstract objects, all we have to do is come up with an internally consistent purely mathematical theory (and know that it is internally consistent). (Balaguer, 2017, p. 381) * To be published in 43rd International Wittgenstein Symposium proceedings. (shrink)

O presente artigo relata a estética de classe de um grupo social que foi chamado de pirangueiro. A partir de uma pesquisa observacional, com amparo referencial nas teorias do habitus e do campo, em Bourdieu, baseada na técnica de flanagem, reconstruiu-se a ideia do subcampo da moda de resistência, que se apresenta como contraposição ao campo da moda dominante. Com essa moda de resistência, o jovem pirangueiro traz um elemento de auto-distinção e, ao mesmo tempo, um critério de preconceito.

O artigo trata da ideia de paz política desde a mecânica dos corpos no Leviatã de Thomas Hobbes. Buscou-se compreender como um pressuposto egoísta pode chegar a uma ideia de consenso pela linguagem.

O presente trabalho teórico e bibliográfico se dedica a reconstruir o conceito de declinação espontânea do átomo em Epicuro, tal qual Marx defendeu em sua tese de doutorado. Seu objetivo é descobrir se a clinamen do átomo está presente em Epicuro e, se está, como se pode pensá-la. Percebe-se que a clinamen que aparece nos textos remanescentes de Epicuro não traz a noção de declinação espontânea, como aparece em Lucrécio e Marx, como Quartim de Moraes afirma. Entretanto, tendo como base (...) as premissas fundamentais de Epicuro, conclui-se que é necessário, ao sistematizar o seu pensamento, introduzir a noção de declinação espontânea para não reduzir sua filosofia ao determinismo e ao fatalismo. A clinamen não é um absurdo no pensamento de Epicuro, mas é uma questão fundamental que passa por toda sua filosofia e que poderia estar presente nas obras perdidas deste autor, assim como Marx pensou. Fundamentalmente, como filósofo da felicidade, Epicuro introduz a clinamen como declinação da vida infeliz. (shrink)

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

This essay aims to motivate an epistemic non-individualistic conception of reflection. The proposal is non-individualistic because (a) it addresses more than individual metacognitive performance and (b) it refers to a situation in which two or more people are in dialogical disagreement about the same subject matter or target proposition; (c) their dispute is based on conversational space and they are entitled to expect one another to be engaged in attempts at truth, avoidance of error, and understanding. I call this proposal (...) a Dialectical account of Reflection (DaR). According to (DaR), reflection is a conscious and intentional intellectual operation through which an individual becomes aware of the contents of disputed beliefs in a dialogical or interpersonal exchange, involving both her own beliefs and the beliefs of her interlocutors. In (DaR), reflection produces the epistemic good of avoiding epistemic vices and promoting epistemic moderation. (shrink)

O presente trabalho constrói uma ponte teórica entre Hegel e Marcuse, com intento de demonstrar a possibilidade de transformações históricas concretas, oferecida pela experiência estética. Tendo como paradigma a sociedade administrada, procurou-se estabelecer, a partir de Marcuse e Hegel, um caminho que demonstra como o indivíduo plasma a razão na história, o que pressupõe uma ação libertadora consciente. Todavia, em uma sociedade unidimensional, não há abertura para outras dimensões e, portanto, a razão unidimensional se torna totalitária, paralisando a história. Nesse (...) sentido, buscou-se demonstrar a saída para a dimensão estética, que propicia uma negação da unidimensionalidade da razão moderna. O indivíduo bidimensional, ie, que está aberto para a realidade e para a dimensão estética, pode plasmar a razão na história e, portanto, transformar o mundo. (shrink)

This article intends to show that the defense of ‘‘understanding’’ as one of the major goals of science education can be grounded on an anti-reductionist perspective on testimony as a source of knowledge. To do so, we critically revisit the discussion between Harvey Siegel and Alvin Goldman about the goals of science education, especially where it involves arguments based on the epistemology of testimony. Subsequently, we come back to a discussion between Charbel N. El-Hani and Eduardo Mortimer, on the one (...) hand, and Michael Hoffmann, on the other, striving to strengthen the claim that rather than students’ belief change, understanding should have epistemic priority as a goal of science education. Based on these two lines of discussion, we conclude that the reliance on testimony as a source of knowledge is necessary to the development of a more large and comprehensive scientific understanding by science students. (shrink)

Cicero’s "Academica" offers a particularly rich demonstration of how the unhappy dialectic between stoicism and skepticism engages Roman historical self-consciousness. The Hegelian thesis of philosophy as mediated through historical development is given a clear articulation in the “derivative” Romans, precisely through their reception of a tradition, their experience of philosophy as inseparable from the self-consciousness of historical relation. The dispute happening in the "Academica" between a dogmatic stoicism and academic skepticism thus directly echoes the problems of contemporary 21st century philosophy (...) insofar as the structures of the unhappy consciousness endure in the “academic” give and take between the authority of received doctrine (say, of mainstream post-classical analytic philosophy) and their subversion in skeptical critique. (shrink)

Muhammad Iqbal’s theory of egohood, also known as Khudi, selfhood, I-amness, or individuality, builds the foundation of his entire philosophical oeuvre. Despite a massive hoard of literature produced on the exposition of Iqbal’s theory of egohood, it is still elusive to grasp. Iqbal’s theory of egohood is a metaphysical theory that explains not only the ontology of the universe but also of human beings. An ego is an ontological substance: a unit of metaphysical or mental reality. This substance refers to (...) the unique individuality of the existing beings. Iqbal's metaphysics of egohood contradicts the pantheistic metaphysics developed by Ibn al-Arabi's writings in the Islamic tradition. To make sense of Iqbal's theory of egohood, I investigate three questions: first, why did Iqbal posit his theory of egohood? I argue that Iqbal developed his theory of egohood to reject the pantheistic metaphysics, which undermines the individualities of God and humans as autonomous agencies. According to Iqbal's metaphysics, God and human persons refer to autonomous individualities. Second, what is Iqbal's theory of egohood? Iqbal's theory of egohood explains the ontology of the psychical (mental or immaterial) world, the organic (living physical) world, and the inorganic (non-living physical) world. Iqbal uses the expression Supreme Ego for God, while (finite) egos for humans and other entities of the universe. Third, what does Iqbal want to do with his theory of egohood? Iqbal wants to explain his social, moral, political, and religious philosophies with his theory of egohood. So, the article intends to make sense of Iqbal's metaphysical theory of egohood. (shrink)

Reflections and projections upon the history of ontology and its meaning for the future of philosophy.

The main aim of this paper is to propose that reflection is a performance that has epistemic value. This idea contains two parts: the first asserts that reflection has instrumental value. The second that reflective performance promotes an epistemic virtue that has final value. The first part is not controversial and most epistemologists would accept it. The second, however, asserts that there is a kind of epistemic good which can only be achieved through reflection. There is much controversy in this. (...) Reflection is understood here as a performance, an activity in which the person examines the evidence, content and reliability of their own beliefs. This performance may lead to different results, but if someone is capable of critically reflecting on their own beliefs in skeptical-dialectic contexts, whatever the results, this performance will produce positive epistemic states – contrary to people who, in the face of skeptical challenges, simply decide to remain intellectually immobile, maintaining a cowardly, arrogant or dogmatic position. The critical spirit with which someone discusses opinions in the context of dialectical disagreement, submitting them to the scrutiny of reason (that is, to the arguments for or against), is virtuous and has epistemic value. The consequence of this performance, the epistemic preference, has a final value, since deliberations based on free judgment have final value. (shrink)

Often ZF practice includes the use of the meta-theoretical notion of classes as shorthand expressions or in order to simplify the understanding of conceptual resources. NBG theory expresses formally the internalization of this feature in set theory; in this case, classes, before used metatheoretically, will also be captured by quantifiers of the first order theory. Never- theless there is a widespread opinion that this internalization of classes is harmless. In this context, it is common to refer to the conservativeness of (...) NBG in relation to ZF as a sufficient condition to understand those theories as “equivalent”, attributing a sense of virtuality to the use of classes quantified in NBG. We believe, however, that a technique used to estab- lish relationships between theories is not necessarily neutral in relation to its results - so a conservativeness established through models have different meaning and depth of that rela- tionship established by finitary interpretations. We believe, therefore, that the way in which relationships between theories are established influences the analysis result. In the case of the relationship between NBG and ZF, since NBG is finitely axiomatizible and ZF not, we believe that we have sufficient reasons to assert that the use of different analysis tools may re- veal differences such as expressiveness, ontological commitment and logical conservativeness. Therefore, this project aims to clarify the relationship between these two theories through triangulations between them and the different analysis tools. The use of finitary techniques, in this case, may prove greater expressiveness and ontological commitment of NBG in relation to ZF - relation obscured by an infinitary approach. We believe that, through this research, we can contribute to the debate on the basis of mathematics, denaturalizing the supposedly “equivalent” use of NBG and ZF for this purpose. (shrink)

Introduction to the topical collection "The Structure of Perceptual Objects"—with contributions by Mohan Matthen, EJ Green, Alisa Mandrigin, Blazej Skrzypulec, and Anna Drożdżowicz.