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)

Recent breakthroughs in stem cell differentiation and reprogramming suggest that functional human gametes could soon be created in vitro. While the ethical debate on the uses of in vitro generated gametes (IVG) was originally constrained by the fact that they could be derived only from embryonic stem cell lines, the advent of somatic cell reprogramming, with the possibility to easily derive human induced pluripotent stem cells from any individual, affords now a major leap in the feasibility of IVG derivation and (...) in the scope of their potential applications. In this paper we develop an ethical framework, rooted in recent scientific evidence, to support a robust experimental pipeline that could enable the first-in-human use of IVG. We then apply this framework to the following objectives: (1) a clarification of the genetic parenting options afforded by IVG, along with their ethical underpinnings; (2) a defence of the use of IVG to remedy infertility, broadening their scope to same-sex couples; (3) an assessment of the most far-reaching implications of IVG for multiplex parenting. These include, first, the liberation of parenting roles from the constraints of biological generations in vivo, allowing multiple individuals to engage in genetic parenting together, thus blurring the distinction between biological and social generations. Second, we discuss the conflation of IVG with sequencing technology and its implications for the possibility that prospective parents may choose among a hitherto unprecedented number of potential children. In view of these perspectives, we argue that, contrary to the exhausted paradigm according to which society lags behind science, IVG may represent instead a salient and most visible instance where biotechnological ingenuity could be used in pursuit of social experimentation. (shrink)

On the ten year anniversary of 2Girls1Cup, this article examines the complex balance of shock, pleasure and disgust elicited by this viral video.

Despite the closure of virtually all original grindhouse cinemas, ‘grindhouse’ lives on as a conceptual term. This article contends that the prevailing conceptualization of ‘grindhouse’ is problematized by a widening gap between the original grindhouse context (‘past’) and the DVD/home-viewing context (present). Despite fans’ and filmmakers’ desire to preserve this part of exploitation cinema history, the world of the grindhouse is now little more than a blurry set of tall-tales and faded phenomenal experiences, which are subject to present-bias. The continuing (...) usefulness of grindhouse-qua-concept requires that one should pay heed to the contemporary contexts in which ‘grindhouse’ is evoked. (shrink)

In a recent publication Tom Douglas and Katrien Devolder have proposed a new account of genetic parenthood, building on the work of Heidi Mertes. Douglas and Devolder’s account aims to solve, among other things, the question of who are the genetic parents of an individual created through somatic cell nuclear transfer (i.e. cloning): (a) the nuclear DNA provider or (b) the progenitors of the nuclear DNA provider. Such a question cannot be answered by simply appealing to the folk account of (...) genetic parenthood, according to which the genetic parents of an individual are those individuals who produced the egg and sperm, respectively, which fused to create the embryo. It cannot be so as in cloning there is no fertilization as such. In this article I critically examine Douglas and Devolder’s new account of genetic parenthood and demonstrate that it is vulnerable to counterexamples that exploit the lack of a condition specifying that genetic parents should cause a child’s coming into existence. (shrink)

Some Comments on de Melo-Martin and Harris.

In the first part of the paper, I present a framework for the description and evaluation of teleosemantic theories of intentionality, and use it to argue that several different objections to these theories (the various indeterminacy and adequacy problems) are, in a certain precise sense, manifestations of the same underlying issue. I then use the framework to show that Millikan's biosemantics, her own recent declarations to the contrary notwithtanding, presents indeterminacy. In the second part, I develop a novel teleosemantic proposal (...) which makes progress in the treatment of this family of problems. I describe a procedure to derive a (unique) homeostatic property cluster [HPC] from facts having to do with the properties that a certain indicator relied on, in the events leading to its fixation in a certain population. This HPC is the one that should figure in the content attribution to the indicator in question. (shrink)

Abstract: Introspection reveals that one is frequently conscious of some form of inner speech, which may appear either in a condensed or expanded form. It has been claimed that this speech reflects the way in which language is involved in conscious thought, fulfilling a number of cognitive functions. We criticize three theories that address this issue: Bermúdez’s view of language as a generator of second-order thoughts, Prinz’s development of Jackendoff’s intermediate-level theory of consciousness, and Carruthers’s theory of inner speech as (...) a rehearsal of action-schemata. We contend they have problems to account for those cases in which inner speech is fragmentary, and for the difference with those instances in which it appears as more sentence-like. In addition, we present verbal overshadowing as a phenomenon that neither of them can easily explain. Finally, we propose an account in which inner speech is fundamentally silent outer speech and argue that it is more explanatory than the alternatives. (shrink)

Philosophical discussions on cognition (ranging from computational and representational approaches to the 4E fra-mework), on the one hand, and those on sound and auditory per-ception, on the other, have hitherto remained apart. In this paper, the author addresses the concept of “auditory cognition”. While committing to the conceptual analysis of the latter, the author in-troduces the discussion of modality-specif ic approaches. Since the contributions made so far in the domain of the philosophy of sound and auditory perception are prone to (...) favor computational-repre-sentational approaches —e.g., the perceptual coherence model (Méndez-Martínez, 2022)—, the exploration of 4E possibilities will lay down a series of questions aimed to encourage future developers from that viewpoint. In that sense, the author explores conceptual entailments and connections between the genealogy of theories within the philosophy of sound and auditory perception, and the hypothesis of the extended cognition (EX). (shrink)

Why do we have social norms—of fairness, cooperation, trust, property, or gender? Modern-day Humeans, as I call them, believe these norms are best accounted for in cultural evolutionary terms, as adaptive solutions to recurrent problems of social interaction. In this paper, I discuss a challenge to this “Humean Program.” Social norms involve widespread behaviors, but also distinctive psychological attitudes and dispositions. According to the challenge, Humean accounts of norms leave their psychological side unexplained. They explain, say, why we share equally, (...) but not why we disapprove of those who don’t. I defend the Humean Program against this challenge. In particular, I suggest an idea for how to extend the Program to account for the psychological side of norms. Socially adaptive behaviors aren’t just likely to emerge in a group; They are also likely to be widely taught within it. The transmission of these behaviors through instruction explains why they are associated with distinctive normative attitudes and dispositions. These attitudes play a pedagogical role in helping transmit these behaviors to children and newcomers. (shrink)

Human eggs for basic, fertility and stem-cell research are in short supply. Many experiments that require their use cannot be carried out at present, and, therefore, the benefits that could emerge from these are either delayed or never materialise. This state of affairs is problematic for scientists and patients worldwide, and it is a matter that needs our attention. Recent advances in chimera research have opened the possibility of creating human/non-human animal chimeras intended for human gamete production (chimeras-IHGP). In this (...) paper, I examine four arguments against the creation of such chimeras and prove that all of them are found wanting. I conclude by showing that there is a strong moral reason for scientists to pursue this research avenue. (shrink)

There has been much discussion of so-called teleosemantic approaches to the naturalization of content. Such discussion, though, has been largely confined to simple, innate mental states with contents such as ?There is a fly here.? Even assuming we can solve the issues that crop up at this stage, an account of the content of human mental states will not get too far without an account of productivity: the ability to entertain indefinitely many thoughts. The best-known teleosemantic theory, Millikan's biosemantics, offers (...) an account of productivity in thought. This paper raises a basic worry about this account: that the use of mapping functions in the theory is unacceptable from a naturalistic point of view. (shrink)

This article develops a diagnostic lens to make sense of the still baffling development of a ‘humanitarian marketplace’. Ambivalently hybrid initiatives such as volunteer tourism, corporate social responsibility or even fair trade do not strictly obey a distributive logic of market exchange, social reciprocity or philanthropic giving. They engender a type of ‘economy’ that must be apprehended in its own terms. The article argues that the large-scale collaborative effects of such a dispersed market can be theorized without resorting to the (...) classical biopolitical move of simplified agency/holistic reification. The argument proceeds counterintuitively, by appropriating the notion of symbiosis as redefined by contemporary biology, contending through historical contextualization and conceptual work that nature itself offers the best example to grasp spontaneous collaboration among unrelated human beings as a non-automatically balanced and intrinsically political affair that calls for critical management through an ex post facto interventionist policy of selective cultivation. (shrink)

Categorization behavior can be fruitfully analyzed in terms of the trade‐off between as high as possible faithfulness in the transmission of information about samples of the classes to be categorized, and as low as possible transmission costs for that same information. The kinds of categorization behaviors we associate with conceptual atoms, prototypes, and exemplars emerge naturally as a result of this trade‐off, in the presence of certain natural constraints on the probabilistic distribution of samples, and the ways in which we (...) measure faithfulness. Beyond the general structure of categorization in these circumstances, the same information‐centered perspective can shed light on other, more concrete properties of human categorization performance, such as the results of certain prominent experiments on supervised categorization. (shrink)

I respond to an objection recently formulated by Barlassina and Hayward against first-order imperativism about pain, according to which it cannot account for the self-directed motivational force of pain. I am going to agree with them: it cannot. This is because pain does not have self-directed motivational force. I will argue that the alternative view—that pain is about dealing with extramental, bodily threats, not about dealing with itself—makes better sense of introspection, and of empirical research on pain avoidance. Also, a (...) naturalistic theory of body-involving commands falls straightforwardly out of our most prominent naturalistic metasemantic accounts, while the token-reflexive contents that would underlie self-directed motivation are more problematic. (shrink)

One prominent argument in international law and religious thought for abolishing capital punishment is that it violates individuals’ right to life. Notably, this _right-to-life argument_ emerged from normative and legal frameworks that recognize deadly force against aggressors as justified when necessary to stop their unjust threat of grave harm. Can capital punishment be necessary in this sense—and thus justified defensive killing? If so, the right-to-life argument would have to admit certain exceptions where executions are justified. Drawing on work by Hugo (...) Bedau, I identify a thought experiment where executions are justified defensive killing but explain why they cannot be in our world. A state’s obligations to its prisoners include the _obligation to use nonlethal incapacitation_ (ONI), which applies as long as prisoners pose no imminent threat. ONI precludes executions for reasons of future dangerousness. By subjecting the right-to-life argument to closer scrutiny, this article ultimately places it on firmer ground. (shrink)

We aim to map out the points of confluence between phronesis and emotion, as well as the nature of this confluence. We do so based on philosophical and psychological explanations of emotions and phronesis. Making sound decisions, which requires phronesis, is an important matter, but its relationship with emotions has only just begun to be studied. We propose that the interplay between phronesis and emotion is possible (rather than inevitable) because both have a cognitive-behavioural structure and because emotions are hierarchical. (...) In the case of emotion, there are no gaps between the cognitive and behavioural dimensions, while phronetic acts can only manifest if cognitive and behavioural aspects are activated simultaneously. The confluence we identify is bidirectional and involves mutual enrichment in this dual dimension. On the one hand, phronesis enriches emotion because it involves extra subjective knowledge and allows emotion to be directed towards higher goals. On the other hand, emotions enrich phronesis because phronesis makes decisions based on sensitive preferences and because emotions confirm correctness in the context of moral decision making. Methodologically, this study is theoretical and interdisciplinary, as our approach is both philosophical and psychological. Philosophy helps us to improve the conceptual foundation of the construct, while psychology provides an analysis of the emotional process, allowing philosophy to understand how emotional evaluation-assessment and motivation lead to decision making. (shrink)

It is widely held that it is unhelpful to model our epistemic access to modal facts on the basis of perception, and postulate the existence of a bodily mechanism attuned to modal features of the world. In this paper I defend modalizing mechanisms. I present and discuss a decision-theoretic model in which agents with severely limited cognitive abilities, at the end of an evolutionary process, have states which encode substantial information about the probabilities with which the outcomes of a certain (...) Bernoulli process occur. Thus, in the model, a process driven by very simple, thoroughly naturalistic mechanisms eventuates in modal sensitivity. (shrink)

Apocalypse, it seems, is everywhere. Preachers with vast followings proclaim the world's end and apocalyptic fears grip even the non-religious amid climate change, pandemics, and threats of nuclear war. But as these ideas pervade popular discourse, grasping their logic remains elusive. Ben Jones argues that we can gain insight into apocalyptic thought through secular thinkers. He starts with a puzzle: Why would secular thinkers draw on Christian apocalyptic beliefs--often dismissed as bizarre--to interpret politics? The apocalyptic tradition proves appealing in part (...) because it theorizes a special relation between crisis and utopia. Apocalyptic thought points to crisis as the vehicle to bring the previously impossible within reach, thus offering apparent resources for navigating challenges in ideal theory, which tries to imagine the best and most just society. By examining apocalyptic thought's appeal and risks, this study arrives at new insights on the limits of ideal theory and utopian hope. (shrink)

I sketch and defend an imperativist treatment of the phenomenology associated with disgusting smells. This treatment, I argue, allows us to make better sense than other intentionalist alter-natives both of the neuroanatomy of olfaction, and of a natural pre-theoretical stance regarding the sense of smell.

This paper addresses the relationship between logic and phenomenology at a historical moment that precedes the big divide between analytic philosophy and phenomenology. In analysing alternative derivations of phenomenological logic, the discussion focuses on the case of two notorious neo-Kantian Mexican philosophers from the first half of the XXth century: Adalberto García de Mendoza and Francisco Larroyo. It is argued that both García de Mendoza and Larroyo made an original contribution to the discussion on the relationship between phenomenology and logic. (...) Further, this paper attempts to present a charitable portrait of both García de Mendoza and Larroyo in contrast to underrating approaches to both Mexican philosophers. In so doing, this paper adopts a historical—though not strictly biographical— perspective. While it is true that neither García de Mendoza nor Larroyo could be considered “phenomenologists” or “Husserl scholars” according to contemporary standards it is worth noticing that they engage in the discussion of phenomenological logic. Both authors had the project of developing a grounding logic for science and, as the article argues, both attempts could be even linked. Their project, however, was unfinished. The plan of this paper is as follows. The first section addresses the problem of the relationship between logic and phenomenology. The second one focuses on García de Mendoza’s contributions. The third one elaborates on Larroyo’s Logic of Sciences. And, finally, the fourth section elaborates on these Mexican philosophers’ contributions to education, making as well further observations concerning the similarities and differences between both authors. (shrink)

Intentionalism is the view that perceptual phenomenology depends on perceptual content. The aim of this paper is to make explicit an ambiguity in usual formulations of intentionalism, and to argue in favor of one way to disambiguate it. It concerns whether perceptual phenomenology depends on the content of one and only one representation (often construed as being identical to a certain perceptual experience), or instead depends on a collection of many different representations throughout the perceptual system. We argue in favor (...) of the latter option. Intentionalism so conceived can make better sense of contemporary neuroscience of perception, and is better equipped to confront several influential objections to traditional intentionalism. (shrink)

There are two broad approaches to theorizing about ontological categories. Quineans use first-order quantifiers to generalize over entities of each category, whereas type theorists use quantification on variables of different semantic types to generalize over different categories. Does anything of import turn on the difference between these approaches? If so, are there good reasons to go type-theoretic? I argue for positive answers to both questions concerning the category of propositions. I also discuss two prominent arguments for a Quinean conception of (...) propositions, concerning their role in natural language semantics and apparent quantification over propositions within natural language. It will emerge that even if these arguments are sound, there need be no deep question about Quinean propositions’ true nature, contrary to much recent work on the metaphysics of propositions. (shrink)

La investigación de la filosofía andina prehispánica, como historia de la filosofía, tiene el propósito descubrir los conceptos de la filosofía en un proceso histórico semejante al de la ciencia presocrática y el idealismo clásico griego, nada distinto de ellas. Esta describe la evolución de las ideas del hombre andino prehispánico, los conceptos que elaboró, manejo y uso en su pensamiento. El concepto de filosofía que asume deviene de Nietzsche, en cuanto pensamiento que se desarrolla con conceptos; la filosofía como (...) el juego de los conceptos, contestando a la pregunta que Engels, planteaba acerca de la relación entre el pensar y el ser, donde nacen los conceptos elementales de la filosofía; ella también sirve para explicar la relación de nuestros pensamientos con el mundo q.ue nos rodea, de si nuestro pensamiento es capaz de conocer el mundo real, de si con nuestras ideas podemos formarnos una imagen refleja exacta del mundo. Es decir, nuestra investigación responde en qué medida el pensamiento andino prehispánico, como indica Hegel, es la teoría del conocimiento de su tiempo, como un pensamiento que se ocupa de sí mismo porque es el objeto de estudio, como pensamiento que “se piensa a sí mismo” respecto sus diferentes determinaciones. (shrink)

En esta investigación se demuestra que no existe oposición antagónica entre la filosofía andina prehispánica y el desarrollo de la filosofía en general, ni con la filosofía occidental griega en particular, salvo en las formas de su temática especial o la profundización del problema filosófico concreto, por cuanto en ningún caso es contraria a la ley del desarrollo filosófico en general, y de ella debemos entender que los nombres, los términos o los vocablos con que designan los conceptos siendo distintos (...) tienen el mismo contenido y sigue igual lógica de desarrollo. Por ejemplo, “Pacha” resulta una formulación más cercana al concepto científico de espacio/tiempo, por cuanto adelanta la imposibilidad de separar el espacio y el tiempo de los objetos o fenómenos de la realidad objetiva, logrado no como un descubrimiento científico sino como una necesidad de formular el pensamiento acerca de dicho fenómeno, tan semejante a la ciencia moderna. O Cay y Camac, los conceptos de “materia” y de “realidad ideal”, perdidos u ocultos en los textos prehispánicos, son categorías que resuelven los problemas fundamentales de la filosofía, como acerca de “¿Cuál es el “verdadero ser”?”, o acerca de la relación ser y pensar. De igual modo consideramos que el idealismo andino prehispánico no difiere antagónicamente del idealismo griego clásico, contrariamente es posible discutir en el mismo nivel con Platón o con cualquier idealista de la filosofía clásica griega. (shrink)

This article aims to theoretically analyse so-called character friendship from the perspective of emotions. From this angle, our research enables us to distinguish different types of emotions, and we propose a conceptual model of the hierarchy of the emotions of character friendship and their influence on social behaviour. With this model in hand, the article discusses whether other-oriented emotions fully explain the emotional underpinnings of character friendship. We find other-oriented emotions to be ambiguous because they may or may not be (...) selfless. Thus we question whether these emotions can adequately explain the bonding content of character friendship. We conclude that there is a higher affective tier related to moral emotions and moral behaviour, which we have labelled the ‘bonding feeling’. This feeling is described with reference to its historical precedents (Rof Carballo’s ‘affective warp’), thus explaining its particularity. (shrink)

This article identifies an argument in Hobbes’s writings often overlooked but relevant to current philosophical debates. Political philosophers tend to categorize his thought as representing consent or rescue theories of political authority. Though these interpretations have textual support and are understandable, they leave out one of his most compelling arguments – what we call the lesser evil argument for political authority, expressed most explicitly in Chapter 20 of Leviathan. Hobbes frankly admits the state’s evils but appeals to the significant disparity (...) between those evils and the greater evils outside the state as a basis for political authority. More than a passing observation, aspects of the lesser evil argument appear in each of his three major political works. In addition to outlining this argument, the article examines its significance both for Hobbes scholarship and recent philosophical debates on political authority. (shrink)

Altruism and solidarity are concepts that are closely related to organ donation for transplantation. On the one hand, they are typically used for encouraging people to donate. On the other hand, they also underpin the regulations in force in each country to different extents. They are often used indistinctly and equivocally, despite the different ethical implications of each concept. This paper aims to clarify to what extent we can speak of altruism and solidarity in the predominant models of organ donation. (...) It also raises the ethical question of whether these categories are adequate as a basis for such models, bearing in mind that organs are a scarce resource and that a shortage of them may mean that fewer lives are saved or improved. (shrink)

An important objection to signaling approaches to representation is that, if signaling behavior is driven by the maximization of usefulness, then signals will typically carry much more information about agent-dependent usefulness than about objective features of the world. This sort of considerations are sometimes taken to provide support for an anti-realist stance on representation itself. The author examines the game-theoretic version of this skeptical line of argument developed by Donald Hoffman and his colleagues. It is shown that their argument only (...) works under an extremely impoverished picture of the informational connections that hold between agent and world. In particular, it only works for cue-driven agents, in Kim Sterelny’s sense. In cases in which the agents’ understanding of what is useful results from combining pieces of information that reach them in different ways, and that complement one another, maximizing usefulness involves construing first a picture of agent-independent, objective matters of fact. (shrink)

In many jurisdictions in the United States and elsewhere, the law governing deadly force by police and civilians contains a notable asymmetry. Often civilians but not police are bound by the imminence requirement—that is, a necessary condition for justifying deadly force is reasonable belief that oneself or another innocent person faces imminent threat of grave harm. In U.S. law enforcement, however, there has been some shift toward the imminence requirement, most evident in the use-of-force policy adopted by the Department of (...) Justice in 2022. This article defends that shift and argues that the ethical case for the imminence requirement in policing is stronger than Shannon Brandt Ford suggests in a recent article. Though the imminence requirement’s impacts on policing and public safety require ongoing study, the principle of equality before the law and the Doctrine of Doing and Allowing both provide moral grounds for this requirement, especially given the lack of evidence that the status quo helps protect life. (shrink)

This article offers a normative analysis of some of the most controversial incidents involving police—what I call police-generated killings. In these cases, bad police tactics create a situation where deadly force becomes necessary, becomes perceived as necessary, or occurs unintentionally. Police deserve blame for such killings because they choose tactics that unnecessarily raise the risk of deadly force, thus violating their obligation to prioritize the protection of life. Since current law in the United States fails to ban many bad tactics, (...) police- generated killings often are treated as “lawful but awful.” To address these killings, some call on changes to departmental policies or voluntary reparations by local governments, yet such measures leave in place a troubling gap between ethics and law. I argue that police-generated killings merit legal sanctions by appealing to a relevant analogy: self-generated self-defense, where the person who engages in self-defense started the trouble. The persistent lack of accountability for police-generated killings threatens life, police legitimacy, and trust in democratic institutions. The article closes by identifying tools in law and policy to address this challenge. (shrink)

Some views articulate reality's hierarchical structure using relations from the fundamental to representations of reality. Other views instead use relations from the fundamental to constituents of non-representational reality. This paper argues against the first kind of view.

Neuroscience investigates how neuronal processing circuits work, but it has problems explaining experiences this way. For example, it hasn’t explained how colour and shape circuits bind together in visual processing, nor why colours and other qualia are experienced so differently yet processed by circuits so similarly, nor how to get from processing circuits to pictorial images spread across inner space. Some theorists turn from these circuits to their electromagnetic fields to deal with such difficulties concerning the mind’s qualia, unity, privacy, (...) and causality. They include Kohler, Libet, Popper, Lindahl, Arhem, Charman, Pockett, John, McFadden, Fingelkurts, Maxwell, and Jones. They’re classifiable as computationalist, reductionist, dualist, realist, interactionist, epiphenomenalist, globalist, and localist. However, they’ve never been analysed together as a whole, which hinders evaluations of them. This article tries to rectify this. It concludes that while field theories face challenges, they aren’t easily dismissed, for they draw on considerable evidence and may avoid serious problems in neuroscience concerning the mind’s qualia, unity, causality, and ontology. (shrink)

Ezra Pound got many things wrong. He was a poor judge of character and a supporter of causes and individuals that have done and continue to do much harm to people around the world. This book addresses the matters (literary and philosophical) that Pound got right, while still pointing out the flaws; it highlights the impact such evidence may yield for the student of art. -/- The result of my research in the pages that follow may be described as a (...) study in aesthetic affinities between Ezra Pound’s thought and the guiding notions found in the Confucian lore. The question it attempts to exemplify is that long-standing one about the nature of knowledge. -/- The analysis that follows seeks to provide a variety of perspectives (both in terms of disciplines and interpretations) about how Pound created with his writings a metaphor of knowledge to understand, assimilate, and put to use his discovery of the East as represented by the Confucian mind. (shrink)

Organiza los relatos, fragmentos y testimonios de la filosofía andinda prehispánica, las mismas que se encuentran en las fuentes documentales registrados durante la colonia, a modo de historia de la filosofía, acompañado de la crítica correspondiente.

Both Franz Brentano and Edmund Husserl addressed sound while trying to explain the inner consciousness of time and gave to it the status of a supporting example. Although their inquiries were not aimed at clarifying in detail the nature of the auditory experience or sounds themselves, they made some interesting observations that can contribute to the current philosophical discussion on sounds. On the other hand, in analytic philosophy, while inquiring the nature of sounds, their location, auditory experience or the audible (...) qualities and so on, the representatives of that trend of thought have remained silent about the depiction of sound and the auditory phenomena in the phenomenological tradition. The paper’s intention is to relate both endeavours, yet the perspective carried out is that of analytic philosophy and, thus, I pay special attention to conceptual analysis as a methodological framework. In this sense, I first explain what sound ontology is in the context of analytic philosophy and the views that it encompasses— namely, the Property View (PV), the Wave View (WV) and the Event View (EV)—. Secondly, I address the problems it entails, emphasising that of sound individuation. In a third section, I propose the possibly controversial conjunction of a “Brentano-Husserl Analysis of the Consciousness of Time” (for short “Brentano-Husserl analysis”) and outline the commonalities of both authors, without ignoring its discrepancies. My main focus is Husserl’s 1905 Vorlesungen zur Phänomenologie des Inneren Zeitbewusstseins. While addressing the Brentano-Husserl analysis, I elaborate on the problem of temporal and spatial extension (Raumlichkeit and Zeitlichkeit, respectively) of both consciousness and sound. Such comparison is a key one, since after these two developments, one can notice some theoretical movements concerning the shift of attention from sounds to the unity of consciousness, and how they mirror each other. After examining the controversial claims concerning the temporal and spatial extension of both consciousness and sound, I argue in the concluding paragraphs that while considering the accounts of sound ontology, the Brentano-Husserl analysis would probably endorse a Property View and that this could have interesting consequences for the issue of Sound Individuation. (shrink)

Using as case studies two early diagrams that represent mechanisms of the cell division cycle, we aim to extend prior philosophical analyses of the roles of diagrams in scientific reasoning, and specifically their role in biological reasoning. The diagrams we discuss are, in practice, integral and indispensible elements of reasoning from experimental data about the cell division cycle to mathematical models of the cycle’s molecular mechanisms. In accordance with prior analyses, the diagrams provide functional explanations of the cell cycle and (...) facilitate the construction of mathematical models of the cell cycle. But, extending beyond those analyses, we show how diagrams facilitate the construction of mathematical models, and we argue that the diagrams permit nomological explanations of the cell cycle. We further argue that what makes diagrams integral and indispensible for explanation and model construction is their nature as locality aids: they group together information that is to be used together in a way that sentential representations do not. (shrink)

The devastating impact of the COVID‐19 (coronavirus disease 2019) pandemic is prompting renewed scrutiny of practices that heighten the risk of infectious disease. One such practice is refusing available vaccines known to be effective at preventing dangerous communicable diseases. For reasons of preventing individual harm, avoiding complicity in collective harm, and fairness, there is a growing consensus among ethicists that individuals have a duty to get vaccinated. I argue that these same grounds establish an analogous duty to avoid buying and (...) eating most meat sold today, based solely on a concern for human welfare. Meat consumption is a leading driver of infectious disease. Wildlife sales at wet markets, bushmeat hunting, and concentrated animal feeding operations (CAFOs) are all exceptionally risky activities that facilitate disease spread and impose immense harms on human populations. If there is a moral duty to vaccinate, we also should recognize a moral duty to avoid most meat. The paper concludes by considering the implications of this duty for policy. (shrink)

Comparing Buddhist and contemporary analytic views about mereological composition reveals significant dissimilarities about the purposes that constrain successful answers to mereological questions, the kinds of considerations taken to be probative in justifying those answers, and the value of mereological inquiry. I develop these dissimilarities by examining three questions relevant to those who deny the existence of composite wholes. The first is a question of justification: What justifies denying the existence of composite wholes as more reasonable than affirming their existence? The (...) second is a question of ontology: Under what conditions are many partless individuals arranged composite-wise? The third is a question of reasonableness: Why, if there are no composites available to experience, do “the folk” find it reasonable to believe there are? I motivate each question, sketch some analytic answers for each, develop in more detail answers from the Theravādin Buddhist scholar Buddhaghosa, and extract comparative lessons. (shrink)

In the realm of the philosophy of sounds and auditory experience there is an ongoing discussion concerned with the nature of sounds. One of the contestant views within this ontology of sound is that of the Property View, which holds that sounds are properties of the sounding objects. A way of developing this view is through the idea of dispositionalism, namely, by sustaining the theory according to which sounds are dispositional properties (Pasnau 1999; Kulvicki 2008; Roberts 2017). That portrayal, however, (...) is not sufficient, as it has not inquired the metaphysical debates about dispositions beyond the conditional analysis. In this paper, I try to advance this view by including recent developments (for instance Bird 2007; Vetter 2015) in the field of dispositionalism and I analyse whether this new version can sort out known and new objections to Property View. (shrink)

How do brains create all our different colors, pains, and other conscious qualities? These various qualia are the most essential aspects of consciousness. Yet standard neuroscience (primarily based on synaptic information processing) has not found the synaptic-firing codes, sometimes described as the “spike code,” to account for how these qualia arise and how they unite to form complex perceptions, emotions, et cetera. Nor is it clear how to get from these abstract codes to the qualia we experience. But electromagnetic field (...) (versus synaptic) approaches to how qualia arise have been offered in recent years by Pockett, McFadden, Jones, Bond, Ward and Guevera, Keppler and Shani, Hunt and Schooler, et cetera. These EM-field approaches show promise in offering more viable accounts of qualia. Yet, until now, they have not been evaluated together. We review various EM field theories of qualia, highlight their strengths and weaknesses, and contrast these theories with standard neuroscience approaches. -/- . (shrink)

Godfrey-Smith advocates for linking deception in sender-receiver games to the existence of undermining signals. I present games in which deceptive signals can be arbitrarily frequent, without this undermining information transfer between sender and receiver.

In the first wave of the COVID-19 pandemic, healthcare workers in some countries were forced to make distressing triaging decisions about which individual patients should receive potentially life-saving treatment. Much of the ethical discussion prompted by the pandemic has concerned which moral principles should ground our response to these individual triage questions. In this paper we aim to broaden the scope of this discussion by considering the ethics of broader structural allocation decisions raised by the COVID-19 pandemic. More specifically, we (...) consider how nations ought to distribute a scarce life-saving resource across healthcare regions in a public health emergency, particularly in view of regional differences in projected need and existing capacity. We call this the regional triage question. Using the case study of ventilators in the COVID-19 pandemic, we show how the moral frameworks that we might adopt in response to individual triage decisions do not translate straightforwardly to this regional-level triage question. Having outlined what we take to be a plausible egalitarian approach to the regional triage question, we go on to propose a novel way of operationalising the ‘save the most lives’ principle in this context. We claim that the latter principle ought to take some precedence in the regional triage question, but also note important limitations to the extent of the influence that it should have in regional allocation decisions. (shrink)

La Educación Sensible es ayuda para que el “yo” habite en su “hogar interior” y crezca hacia su “apoteosis original” en el “nosotros”, donde se hace cocreador de belleza con libertad, sabiduría y amor. La educación sensible es pedagogía no invasiva pero radicalmente exigente para que la persona acepte desplegar su versión original y vivir con gozo en un “nosotros-maduro”. No es una pedagogía que protege a los sensibles; es una educación que atiende a todas las personas, independientemente de su (...) grado de sensibilidad: alta, media o baja (como intervalos comunes que se manejan en las ciencias de la sensibilidad). La sensibilidad personal es capaz de captar la propia originalidad y disponerse para interpretarla en los dos sentidos: comprenderla y actuarla. La sensibilidad humana necesita la educación sensible para que sea punto de partida de un desarrollo personal auténtico y pleno de la propia originalidad que es alterada y altera la de los “yoes” con quien habita la existencia formando “nosotros”, que a su vez, se impactan con interdependencia. Además de al “yo”, la educación sensible se orienta al “nosotros”, que será tanto más “sensible” en la medida que altera la intimidad de la persona con “amor-maduro” que es fuente de gozo, a pesar de los pesares. Sin educación sensible la vida daña y cuanta mayor es la sensibilidad de la persona, mayor es el daño, pero también es mayor la capacidad para detectarlo cicatrizarlo y ayudar a otros con educación sensible. Así, la educación sensible se manifiesta de tres maneras: como acción sanadora de la persona, destrucción creadora para evolucionar en el tiempo, como la crisálida se transforma en mariposa, y acción desarrollante del propio potencial con originalidad. (shrink)

Despite the broad agreement that microaggressions cause harm, there is disagreement on how to capture microaggressor's accountability. Friedlaender (2018) argues that, in many cases, survivors of microaggressions are not justified in holding the microaggressor blameworthy or blaming them (Friedlaender 2018, 14). I argue, in contrast, that we are generally justified in holding most microaggressors blameworthy and blaming them. By adopting a broadly blame-inclusive account of microaggressor accountability, we are in a position to satisfy the desiderata an ideal account should meet: (...) (1) account for cumulative harm; (2) consistently allow for standing to forgive; and (3) be risk sensitive to the microaggressed. By possessing these virtues, I believe my view of microaggressor accountability better equips us to take seriously the harm caused by microaggressions and center the well-being of microaggressees. I respond to Friedlaender's concerns regarding epistemic ignorance and what they call the disaggregation problem. In contrast to Friedlaender's broadly blame-exclusive responsibility model, I motivate a broadly blame-inclusive model for holding microaggressors accountable, explaining how it fulfills the desiderata. I respond to the objection that my account is too blame-inclusive by providing examples of (1) justified microaggressions; (2) excused microaggressions; and (3) blameworthiless microaggressions where blame is justified all the same. (shrink)

The Foucauldian conception of power as ‘productive’ has left us so far with a residual conception of freedom. The article examines a number of historical cases in which ‘relationships of freedom’ have potentially come into existence within Western culture, from ‘revolution’ and ‘political truth-telling’ to ‘cynicism’ and ‘civility’. But the argument is not just about demonstrating that there have in fact been many historical inversions of ‘the conduct of conduct’. It is about theorizing how freedom can be ‘productive’ or give (...) rise to cultural norms if any such inversion can only come into being as an event in itself. (shrink)

I present and defend a novel version of the homeostatic property cluster account of natural kinds. The core of the proposal is a development of the notion of co-occurrence, central to the HPC account, along information-theoretic lines. The resulting theory retains all the appealing features of the original formulation, while increasing its explanatory power, and formal perspicuity. I showcase the theory by applying it to the problem of reconciling the thesis that biological species are natural kinds with the fact that (...) many such species are polymorphic. (shrink)

Our limited a priori-reasoning skills open a gap between our finding a proposition conceivable and its metaphysical possibility. A prominent strategy for closing this gap is the postulation of ideal conceivers, who suffer from no such limitations. In this paper I argue that, under many, maybe all, plausible unpackings of the notion of ideal conceiver, it is false that ideal negative conceivability entails possibility.