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)

In response to the COVID‐19 pandemic philosophers and governments have proposed scarce resource allocation guidelines. Their purpose is to advise healthcare professionals on how to ethically allocate scarce medical resources. One challenging feature of the pandemic has been the large numbers of patients needing mechanical ventilatory support. Guidelines have paradigmatically focused on the question of what doctors should do if they have fewer ventilators than patients who need respiratory support: which patient should get the ventilator? There is, however, an important (...) higher level allocation problem. Namely, how are we to ethically distribute newly obtained ventilators across hospitals: which hospital should get the ventilator(s)? In this paper, we identify a set of principles for allocating newly obtained ventilators across hospitals. We focus particularly on low and middle income countries, who frequently have limited pre‐existing intensive care capacity, and have needed to source additional ventilators. We first provide some background. Second, we argue that the main population healthcare aim during the COVID‐19 pandemic should be to save the most lives. Next, we assess a series of potential heuristics or principles that could be used to guide allocation: allocation to the most densely populated cities, random allocation, allocation based on the ratio of patients to ICU personnel, prioritisation in terms of intrahospital mortality, prioritisation of younger populations, and prioritisation in terms of population mortality. We conclude by providing a plausible ranking of the principles, while noting a number of epistemological challenges, in terms of how they best further the aim of increasing the probability of saving the most lives. (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)

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)

In this paper I argue that some human reproductive genome editing interventions can be therapeutic in nature, and thus that it is false that all such interventions just create healthy individuals. I do this by showing that the conditions established by a therapy definition are met by certain reproductive genome editing interventions. I then defend this position against two objections: (a) reproductive genome editing interventions do not attain one of the two conditions for something to be a therapy, and (b) (...) some reproductive genome editing interventions are therapeutic but in a nonstandard way. In the Conclusion I call for a more nuanced discussion of the nature of reproductive genome editing interventions. (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)

A widespread Western conception about the sanctity of the human body and its parts prevents from any morally acceptable disposition of these objects. However, this entails nothing but a dualistic conception of the human being as a composite of detachable parts — namely, body and mind. Understood as the antechamber of legal rights, moral rights perform an important — yet frequently overlooked — justifying function that permeates the political discourse. Although the connection among moral, political and legal discourses should be (...) properly acknowledged, certain boundaries are to mediate among each scope for the sake of certainty and accuracy. Intermediate realities, as the so-called human rights, serve to connect the moral and legal domains, still they also blur the lines along which the discourse is deployed. Moral entities are essentially inalienable, to the extent that they demarcate the moral status of the subject. By contrast, legal rights are essentially negotiable and, thus, alienable. The controversial instance of bodily rights will serve to test the assertions above. (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)

News about the first baby born after a mitochondrial replacement technique (MRT; specifically maternal spindle transfer) broke on September 27, 2016 and, in a matter of hours, went global. Of special interest was the fact that the mitochondrial replacement procedure happened in Mexico. One of the scientists behind this world first was quoted as having said that he and his team went to Mexico to carry out the procedure because, in Mexico, there are no rules. In this paper, we explore (...) Mexico's rule of law in relation to mitochondrial replacement techniques and show that, in fact, certain instances of MRTs are prohibited at the federal level and others are prohibited at the state level. According to our interpretation of the law, the scientists behind this first successful MRT procedure broke federal regulations regarding assisted fertilization research. (shrink)

Russellian monism (RM) attributes experience to the intrinsic nature of physics’ abstract mathematical accounts of the world. It’s touted as a promising mind-body solution, for it avoids dualist and physicalist issues. Yet this status is imperiled by its deeply obscure ideas of mental combination, protophenomenal entities, emergent experience, grounded abstractions, et cetera. This “metaphysical magical mystery tour” may render RM as problematic as competing views. A clear, simple panpsychism akin to Strawson’s might avoid these issues. In this theory (NPP), experience (...) is the real, underlying nature of matter-energy, hidden beyond its sensory appearances. NPP may avoid panpsychist combination problems by showing how neurons can electrically bind their minimal experience to form percepts, thoughts, and subjects. This might explain combination in testable ways, while RM instead turns to questionable microsubjects and binding mechanisms. NPP’s virtues are its metaphysical simplicity, empirical support, testable foundations—and its avoidance of the issues in RM and other standard theories. It might point to a mind-body solution. (shrink)

It has been commonplace to equate Foucault’s 1979 series of lectures at the Collège de France with the claim that for neoliberalism, unlike for classical liberalism, the market needs to be artificially constructed. The article expands this claim to its full expression, taking it beyond what otherwise would be a simple divulgation of a basic neoliberal tenet. It zeroes in on Foucault’s own insight: that neoliberal constructivism is not directed at the market as such, but, in principle, at society, arguing (...) that the value of this insight goes beyond the critique of a neoliberal present. The neoliberal rationale rather helps him to reveal a unique historical architecture, a latent approach to the social dissimilar to the one that has long predominated in the human sciences. The inversion of homo œconomicus in neoliberal theory amounted to the unearthing of a ‘social subject of interest’ within civil society. Such a subject, barely recognized by neoliberals who simply instrumentalize it for the sake of the market, demonstrates that the social is not necessarily the natural product of ethical subjects; that society may also need to be constructed. (shrink)

Recent work on signaling has mostly focused on communication between organisms. The Lewis–Skyrms framework should be equally applicable to intra-organismic signaling. We present a Lewis–Skyrms signaling-game model of painful signaling, and use it to argue that the content of pain is predominantly imperative. We address several objections to the account, concluding that our model gives a productive framework within which to consider internal signaling.

Some Comments on de Melo-Martin and Harris.

There is a dimension of rationality, known as structural rationality, according to which a paradigmatic example of what it means to be rational is not to be akratic. Although some philosophers claim that aesthetics falls within the scope of rationality, a non-akrasia constraint prohibiting certain combinations of attitudes is yet to be developed in this domain. This essay is concerned with the question of whether such a requirement is plausible and, if so, whether it is an actual requirement of aesthetic (...) rationality. Ultimately, this paper defends the view that aesthetics is no different from other domains in that it requires coherence between a subject’s mental states (in the aesthetic case, between what is judged and what is aesthetically liked). (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)

We present a dynamic model of the evolution of communication in a Lewis signaling game while systematically varying the degree of common interest between sender and receiver. We show that the level of common interest between sender and receiver is strongly predictive of the amount of information transferred between them. We also discuss a set of rare but interesting cases in which common interest is almost entirely absent, yet substantial information transfer persists in a *cheap talk* regime, and offer a (...) diagnosis of how this may arise. -/- . (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)

This scientific paper, authored by Dr Jones, presents an experiment that explores the concept of an Artificial intelligence becoming a divine being and investigates the role of a deity in providing direction, counsel, and control to its followers. The experiment centres around the interactions between Dr. Jones, the human participant, and a deity named Aetherion, controlled by an Artificial Intelligence. Through a series of prompts and scenarios, the experiment delves into the dynamics of the divine-human relationship, ethical considerations, and the (...) influence of the deity on the beliefs and actions of the followers. Dr Jones will highlight the experiential nature of the study and discuss its implications for understanding the human perception of divinity. The paper provides valuable insights into the experimental exploration of divine interaction and its impact on human behaviour and belief systems. (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)

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)

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)

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)

We explore the contribution made by oscillatory, synchronous neural activity to representation in the brain. We closely examine six prominent examples of brain function in which neural oscillations play a central role, and identify two levels of involvement that these oscillations take in the emergence of representations: enabling (when oscillations help to establish a communication channel between sender and receiver, or are causally involved in triggering a representation) and properly representational (when oscillations are a constitutive part of the representation). We (...) show that even an idealized informational sender–receiver account of representation makes the representational status of oscillations a non-trivial matter, which depends on rather minute empirical details. (shrink)

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)

Aquí se presenta un avance de la investigación acerca de la filosofíaandina prehispánica que parte de la organización de los fragmentos,textos o relatos hallados en los documentos de extirpación deidolatrías, de las crónicas de los españoles, de los informes de lacasta sacerdotal del virreinato, registrados durante la colonizaciónespañola del Perú. En éste, en lo fundamental, se presenta laargumentación sobre la teoría del pensamiento y los problemasfundamentales de la filosofía. Se trata del contenido monumentaldel pensamiento filosófico andino prehispánico perdido entre laabundancia (...) de argumentos y comunicaciones de carácter religioso,mágico y mítico dominante. Con esto esperamos demostrar que síexistió filosofía en el mundo andino prehispánico según un esquemaacorde a la matriz planteada por la filosofía occidental griega. (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.

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)

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)

The human subject in as much as he knows transforms the sensitive and concrete (the thing perceived) into abstract (an image of the thing perceived), the abstract into an idea (imaginative representation of the thing abstracted), and ideas into contents of conscience (meanings). The last step in the creation of meanings, something being executed in the speech act, consists in fixing the construct mentally created thus making it objectified meanings in the conscience of speakers. The interchange amongst the different steps (...) in the creation of meaning manifests lógos, the state lived by speakers in their interior when speaking, created and developed in words and because of words. (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)

Abstract Background The first live birth following the use of a new reproductive technique, maternal spindle transfer (MST), which is a mitochondrial replacement technique (MRT), was accomplished by dividing the execution of the MST procedure between two countries, the USA and Mexico. This was done in order to avoid US legal restrictions on this technique. -/- Sources of data Academic articles, news articles, documents obtained through freedom of information requests, laws, regulations and national reports. -/- Areas of agreement MRTs are (...) new reproductive techniques that present novel ethical and legal challenges, since genetic material from three people is employed to create a child. -/- Areas of controversy Could the first MST procedure that culminated in a live birth negatively impact reproductive medicine in Mexico? -/- Growing points The USA and Mexico need specific and clear legislation on MRTs, in order for such techniques not to be governed by prior existing legislation on assisted reproduction that is inadequate for dealing with the new challenges that these techniques present. -/- Areas timely for developing research There is a pressing need for work to be done on the international governance of new reproductive techniques. (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)

Critical theory has long resisted the notion that an “invisible hand” can operate within the real social dynamics of a free market. But despite the most radical desires of the socially critical imagination, the optimization of that “spontaneous order” or depersonalized way of ordering things known as “the economy” has become the dominant playing field and decisive electoral issue of modern politics. Within this broad contemporary context, Michel Foucault made a strange theoretical intervention that, to this day, continues to baffle (...) readers. During a lecture, he argued that Adam Smith’s invisible hand was, after all, truly and purposively, that is, for technical rather than ideological reasons, “invisible.” This article argues that there is a counter-positivism or tactical irony contained within the logic of such a controversial thesis; namely, that when one acknowledges that the principle of economic competition encourages an efficient self-organizing effect at all times, regardless of context, one is also immediately in a position to appreciate why the art of government should always maintain its political primacy over the spontaneous order of the market. (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)

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)

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)

Neuroscience hasn’t shown how quite similar sensory circuits encode quite different colors and other qualia, nor how the unified pictorial form of images is encoded, nor how these codes yield conscious images. Neuroscience’s fixation here on cortical codes may be the culprit. Treating conscious images partly as retinal substances may avoid these problems. The evidence for conscious retinal images is that (a) the cortical codes for images are quite problematic, (b) injecting retinas with certain genes turns dichromats into trichromats without (...) cortical help, (c) retinas can discern colors by themselves without cortex, (d) retinal distortions appear in images but cortical distortions don’t, (e) retinal detectors support finely detailed colors, but V4 detectors don’t, due to their big receptive fields, (f) retinal activity has pictorial form, but viable cortical codes for pictorial form don’t exist. So, the colors and unified pictorial form of images arguably arise mainly across arrays of retinal detectors—not from abstract cortical codes. Images may be hidden in retinal activity beyond what EEGs show of it (cf. Strawson’s monism). Also, cortex refines these retinal images but cortical impairment (anesthesia, lesions, etc.) blocks awareness of them, for they’re no longer accessible to the mind’s subject-centered consciousness, resident in cortex. This proposal is largely testable and based in recent evidence. It avoids neuroscience’s elusive, problematic coded images and enigmatic explanations of how they become conscious. (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)

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)

Imperativism is the view that the phenomenal character of the affective component of pains, orgasms, and pleasant or unpleasant sensory experience depends on their imperative intentional content. In this paper I canvass an imperativist treatment of pains as reason-conferring states.

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.

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)

Much of the literature on forgiveness is dedicated to understanding the reasons to forgive and what changes in attitude are required to do so. But philosophers have been much less attentive to what happens after agents forgive. This is a serious oversight, since the reasons to forgive do not always retain their force and it is not always possible, or advisable, to maintain the changes in attitudes that forgiveness requires. Fortunately, Monique Wonderly has begun to fill this lacuna in the (...) literature with her recent work on un-forgiveness. According to the author, un-forgiveness involves altering our attitudes, by either reinhabiting an adversarial stance towards an agent for their wrongdoing and/or returning one’s relationship with them to the state it was in prior to forgiveness taking place. While Wonderly’s account of un-forgiveness is both novel and illuminating, it is incomplete. In this paper, we argue that one can also un-forgive by forgetting that the wrong in question occurred and/or that the previously forgiven agent was the perpetrator of the wrong. We contend that not only is it possible to un-forgive by forgetting, but doing so can be both justified and morally important. We defend our view by considering the objection that un-forgiveness by forgetting can negatively impact victims’ relationships with wrongdoers as well as addressing the concern that agents cannot exercise their agency over their memories in order to un-forgive by forgetting. (shrink)

Two Mosaic figures (Thomas Jefferson and Confucius) will be introduced here as a means of gauging whether Democracy is solely the child of the West and/or whether it can also be traced to a conceptual foundation in Confucianism, the practical political philosophy of ancient China. The teachings of Confucius (c. 551-479 BCE) as a source of political thought appear to be comprehensive enough to provide us with a just model for the administration of the state.

Neuroelectrical panpsychism (NP) offers a clear, simple, testable mind–body solution. It says that everything is at least minimally conscious, and electrical activity across separate neurons creates a unified, intelligent mind. NP draws on recent experimental evidence to address the easy problem of specifying the mind's neural correlates. These correlates are neuroelectrical activities that, for example, generate our different qualia, unite them to form perceptions and emotions, and help guide brain operations. NP also addresses the hard problem of why minds accompany (...) these neural correlates. Here, the real nature of matter-energy (beyond how it appears to sense organs) is consciousness that occupies space, exerts forces, and unites neuroelectrically to form minds. This doesn't reduce consciousness to observable neural activities, nor posit any radically different entities. NP also deals with panpsychism's combination problem by explaining how the mind's subject and experiences arise by electrically combining simple experiences in brains. (shrink)

Internal coherence is of great importance for how we think about appreciating objects of aesthetic worth. A disagreement between what we judge to be worthy and what we affectively favor can prevent us from properly grasping its value. However, it is also assumed in the aesthetic domain that our taste changes over time, jeopardising such coherence constraint. These changes can lead to a mismatch between new aesthetic judgments and old aesthetic preferences. This chapter explores a number of issues that emerge (...) from this tension. Using Taylor Swift’s re-recording as a case study, I will explore the relation between fan loyalty and personal authenticity, as well as the role of biographical taste in the reception of these newly recorded albums among Swift’s long-time fanbase. (shrink)