Es innegable que desde la publicación de A Theory of Justice en 1971 la filosofía política ha dado un giro en las temáticas que históricamente ha abordado. Pues como afirma Robert Nozick, es imposible realizar cualquier tipo de filosofía práctica, sin considerar el marco teórico ofrecido por la obra de Rawls, dado que lo inédito de su trabajo es ofrecer una teoría sustantiva de justicia que deja atrás la tradición lógica-analítica, así como el mero análisis histórico-sistemático. Las múltiples repercusiones (...) han dado inicio a una vasta cantidad de encuentros y desencuentros en la forma concebir la justicia social. En este debate se enmarca el último libro del profesor Pablo Aguayo Westwood: Justicia social: conceptos, teorías y problemas, donde propone una breve revisión de los principales hitos que han marcado la discusión en torno a la justicia social, así como algunos problemas prácticos que conciernen a esta. (shrink)

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)

If the world itself is metaphysically indeterminate in a specified respect, what follows? In this paper, we develop a theory of metaphysical indeterminacy answering this question.

This paper generalises the classical Condorcet jury theorem from majority voting over two options to plurality voting over multiple options. The paper further discusses the debate between epistemic and procedural democracy and situates its formal results in that debate. The paper finally compares a number of different social choice procedures for many-option choices in terms of their epistemic merits. An appendix explores the implications of some of the present mathematical results for the question of how probable majority cycles (as in (...) Condorcet's paradox) are in large electorates. (shrink)

Recently, a friend of one of these writers told her story of using one of a healthcare product to activate her stem cells as part of regenerative medicine. Regenerative medicine is a field of medicine that seeks to repair or replace damaged or diseased tissues and organs. This can be done through a variety of methods, including stem cell therapy, tissue engineering, and gene therapy. This is a short review article on this rapid field called regenerative medicine, in particular via (...) a new method called photobiomodulation, especially by virtue of low-intensity laser pen treatment. Hopefully it will attract more research in this interesting direction, both for laser/photobiomodulation to boost plant growth as well as in healthcare (see also: Christianto & Smarandache, 2022; Christianto, 2023). (shrink)

Worlds where things divide forever ("gunk" worlds) are apparently conceivable. The conceivability of such scenarios has been used as an argument against "nihilist" or "near-nihilist" answers to the special composition question. I argue that the mereological nihilist has the resources to explain away the illusion that gunk is possible.

Inflicting harm is generally preferable to inflicting death. If you must choose between the two, you should generally choose to harm. But prenatal harm seems different. If a mother must choose between harming her fetus or aborting it, she may choose either, at least in many cases. So it seems that prenatal harm is particularly objectionable, sometimes on a par with death. This paper offers an explanation of why prenatal harm seems particularly objectionable by drawing an analogy to the all-or-nothing (...) problem. It then argues that this analogy offers independent support for the ‘voluntarist’ view that at least some parental role obligations are grounded in the choice to be a parent. (shrink)

I defend the widely-held view that morally worthy action need not be motivated by a desire to promote rightness as such. Some have recently come to reject this view, arguing that desires for rightness as such are necessary for avoiding a certain kind of luck thought incompatible with morally worthy action. I show that those who defend desires for rightness as such on the basis of this argument misunderstand the relationship between moral worth and the kind of luck that their (...) argument employs. Consequently, the argument provides no reason to doubt the popular view that a desire for rightness as such is no part of virtue. I conclude by suggesting that a family of worries about merely accidentally right action presuppose one side of the recent debate about objectivism and perspectivism about moral rightness. (shrink)

We demonstrate how real progress can be made in the debate surrounding the enhanced indispensability argument. Drawing on a counterfactual theory of explanation, well-motivated independently of the debate, we provide a novel analysis of ‘explanatory generality’ and how mathematics is involved in its procurement. On our analysis, mathematics’ sole explanatory contribution to the procurement of explanatory generality is to make counterfactual information about physical dependencies easier to grasp and reason with for creatures like us. This gives precise content to key (...) intuitions traded in the debate, regarding mathematics’ procurement of explanatory generality, and adjudicates unambiguously in favour of the nominalist, at least as far as explanatory generality is concerned. (shrink)

While it is tempting to suppose that an act has moral worth just when and because it is motivated by sufficient moral reasons, philosophers have, largely, come to doubt this analysis. Doubt is rooted in two claims. The first is that some facts can motivate a given act in multiple ways, not all of which are consistent with moral worth. The second is the orthodox view that normative reasons are facts. I defend the tempting analysis by proposing and defending a (...) heterodox account of both normative and motivating reasons that is inspired by Donald Davidson’s primary reasons. We should adopt the heterodox view, I argue, because it addresses an overlooked but fatal defect in the orthodox conception of reasons, of which challenges to the tempting analysis are a special case. (shrink)

Some argue that theories of universals should incorporate structural universals, in order to allow for the metaphysical possibility of worlds of 'infinite descending complexity' ('onion worlds'). I argue that the possibility of such worlds does not establish the need for structural universals. So long as we admit the metaphysical possibility of emergent universals, there is an attractive alternative description of such cases.

Some moral theorists argue that being an innocent beneficiary of significant harms inflicted by others may be sufficient to ground special duties to address the hardships suffered by the victims, at least when it is impossible to extract compensation from those who perpetrated the harm. This idea has been applied to climate change in the form of the beneficiary-pays principle. Other philosophers, however, are quite sceptical about beneficiary pays. Our aim in this article is to examine their critiques. We conclude (...) that, while they have made important points, the principle remains worthy of further development and exploration. Our purpose in engaging with these critiques is constructive — we aim to formulate beneficiary pays in ways that would give it a plausible role in allocating the cost of addressing human-induced climate change, while acknowledging that some understandings of the principle would make it unsuitable for this purpose. (shrink)

Throughout his career, Derek Parfit made the bold suggestion, at various times under the heading of the "Normativity Objection," that anyone in possession of normative concepts is in a position to know, on the basis of their competence with such concepts alone, that reductive realism in ethics is not even possible. Despite the prominent role that the Normativity Objection plays in Parfit's non-reductive account of the nature of normativity, when the objection hasn't been ignored, it's been criticized and even derided. (...) We argue that the exclusively negative attention that the objection has received has been a mistake. On our reading, Parfit's Normativity Objection poses a serious threat to reductivism, as it exposes the uneasy relationship between our a priori knowledge of a range of distinctly normative truths and the typical package of semantic commitments that reductivists have embraced since the Kripkean revolution. (shrink)

This chapter defends the account of metaphysical indeterminacy of Barnes and Williams against Eklund's objections.

I propose and defend a novel view called “de se consequentialism,” which is noteworthy for two reasons. First, it demonstrates—contra Doug Portmore, Mark Schroeder, Campbell Brown, and Michael Smith, among others—that agent-neutral consequentialism is consistent with agent-centered constraints. Second, it clarifies the nature of agent-centered constraints, thereby meriting attention from even dedicated nonconsequentialists. Scrutiny reveals that moral theories in general, whether consequentialist or not, incorporate constraints by assessing states in a first-personal guise. Consequently, de se consequentialism enacts constraints through the (...) very same feature that nonconsequentialist theories do. (shrink)

In large, impersonal moral orders many of us wish to maintain good will toward our fellow citizens only if we are reasonably sure they will maintain good will toward us. The mutual maintaining of good will, then, requires that we somehow communicate our intentions to one another. But how do we actually do this? The current paper argues that when we engage in moral responsibility practices—that is, when we express our reactive attitudes by blaming, praising, and resenting—we communicate a desire (...) to maintain good will to those in the community we are imbedded in. Participating in such practices alone will not get the job done, though, for expressions of our reactive attitudes are often what economists call cheap talk. But when we praise and blame in cases of moral diversity, expressions of our reactive attitudes act as costly signals capable of solving our social dilemma. (shrink)

Philosophical exploration of individualism and externalism in the cognitive sciences most recently has been focused on general evaluations of these two views (Adams & Aizawa 2008, Rupert 2008, Wilson 2004, Clark 2008). Here we return to broaden an earlier phase of the debate between individualists and externalists about cognition, one that considered in detail particular theories, such as those in developmental psychology (Patterson 1991) and the computational theory of vision (Burge 1986, Segal 1989). Music cognition is an area in the (...) cognitive sciences that has received little attention from philosophers, though it has relatively recently been thrown into the externalist spotlight (Cochrane 2008, Kruger 2014, Kersten forthcoming). Given that individualism can be thought of as a kind of paradigm for research on cognition, we provide a brief overview of the field of music cognition and individualistic tendencies within the field (sections 2 and 3) before turning to consider externalist alternatives to individualistic paradigms (section 4-5) and then arguing for a qualified form of externalism about music cognition (section 6). (shrink)

In this paper, we take a meta-theoretical stance and aim to compare and assess two conceptual frameworks that endeavor to explain phenomenal experience. In particular, we compare Feinberg & Mallatt’s Neurobiological Naturalism (NN) and Tononi’s and colleagues' Integrated Information Theory (IIT), given that the former pointed out some similarities between the two theories (Feinberg & Mallatt 2016c-d). To probe their similarity, we first give a general introduction to both frameworks. Next, we expound a ground plan for carrying out our analysis. (...) We move on to articulate a philosophical profile of NN and IIT, addressing their ontological commitments and epistemological foundations. Finally, we compare the two point-by-point, also discussing how they stand on the issue of artificial consciousness. (shrink)

There is an intuitive difference in how we think about pluralism and attitudinal diversity in epistemological contexts versus political contexts. In an epistemological context, it seems problematically arbitrary to hold a particular belief on some issue, while also thinking it perfectly reasonable to hold a totally different belief on the same issue given the same evidence. By contrast, though, it doesn’t seem problematically arbitrary to have a particular set of political commitments, while at the same time thinking it perfectly reasonable (...) for someone in a similar position have a totally different set of political commitments. This chapter examines three explanatory theses that might be used to make sense of this difference: (1) that practical commitments are desire dependent in a way that beliefs are not; (2) that there are reasons to be resolute in practical commitments, but not in beliefs; and (3) that compromise in the face of practical political disagreement doesn’t mitigate controversy, whereas compromise in the face of disagreement about mere beliefs does mitigate controversy. (shrink)

Various exploration in astrophysics has revealed many breakthroughs nowadays, not only with respect to James Webb Telescope, but also recent finding related to water and ice deposits in the Moon surface. Those new findings seem to bring us to new questions related to origin of Earth, Moon and the entire Universe.

Philosophers have recently come to focus on explaining the phenomenon of ​bad beliefs,​ beliefs that are apparently true and well-evidenced but nevertheless objectionable. Despite this recent focus, a consensus is already forming around a particular explanation of these beliefs’ badness called ​moral encroachment​, according to which, roughly, the moral stakes engendered by bad beliefs make them particularly difficult to justify. This paper advances an alternative account not just of bad beliefs but of bad attitudes more generally according to which bad (...) beliefs’ badness originates not in a failure of sufficient evidence but in a failure to respond adequately to reasons. I motivate this alternative account through an analogy to recent discussions of moral worth centered on the well-known grocer case from Kant’s ​Groundwork​, and by showing that this analogy permits the proposed account to generalize to bad attitudes beyond belief. The paper concludes by contrasting the implications of moral encroachment and of the proposed account for bad attitudes’ blameworthiness. (shrink)

How are permutation arguments for the inscrutability of reference to be formulated in the context of a Davidsonian truth-theoretic semantics? Davidson takes these arguments to establish that there are no grounds for favouring a reference scheme that assigns London to “Londres”, rather than one that assigns Sydney to that name. We shall see, however, that it is far from clear whether permutation arguments work when set out in the context of the kind of truth-theoretic semantics which Davidson favours. The principle (...) required to make the argument work allows us to resurrect Foster problems against the Davidsonian position. The Foster problems and the permutation inscrutability problems stand or fall together: they are one puzzle, not two. (shrink)

A common objection to Sosa’s epistemology is that it countenances, in an objectionable way, unsafe knowledge. This objection, under closer inspection, turns out to be in far worse shape than Sosa’s critics have realised. Sosa and his defenders have offered two central response types to the idea that allowing unsafe knowledge is problematic: one response type adverts to the animal/reflective knowledge distinction that is characteristic of bi-level virtue epistemology. The other less-discussed response type appeals to the threat of dream scepticism, (...) and in particular, to the idea that many of our everyday perceptual beliefs are unsafe through the nearness of the dream possibility. The latter dreaming response to the safety objection to Sosa’s virtue epistemology has largely flown under the radar in contemporary discussions of safety and knowledge. We think that, suitably articulated in view of research in the philosophy and science of dreaming, it has much more going for it than has been appreciated. This paper further develops, beyond what Sosa does himself, the dreaming argument in response to those who think safety (as traditionally understood) is a condition on knowledge and who object to Sosa’s account on the grounds that it fails this condition. The payoffs of further developing this argument will be not only a better understanding of the importance of insights about dreaming against safety as a condition on knowledge, but also some reason to think a weaker safety condition, one that is relativised to SSS (i.e., skill/shape/situation) conditions for competence exercise, gets better results all things considered as an anti-luck codicil on knowledge. (shrink)

In the De Anima, Aristotle claims that the five senses are infallible about their proper objects. I contend that this claim means that sight is infallible about its proper object in its most specific form, i. e. sight is infallible about red or green and not merely about color in general. This robust claim is justified by Aristotle’s teleological principle that nature does nothing in vain. Additionally, drawing on Aristotle’s comparison of perception and one’s understanding of the essences, I defend (...) a conception of the senses in which the structure of their contents is simple rather than predicative and show how this coheres better with the rest of my interpretation. (shrink)

Matteo Ricci (1552-1610) was an Italian Jesuit and one of the first Christian missionaries to China in the modern era. He was a genuine polymath—a translator, cartographer, mathematician, astronomer, and musician. Above all, Ricci was a missionary for the gospel. As we briefly examine his 1603 seminal work, The True Meaning of the Lord of Heaven, our hope is that we, as evangelical educators, will perceive some of the deeper principles necessary for our own missionary work among unreached people.

The automation of online social life is an urgent issue for researchers and the public alike. However, one of the most significant uses of such technologies seems to have gone largely unnoticed by the research community: religion. Focusing on Islamic Prayer Apps, which automatically post prayers from its users’ accounts, we show that even one such service is already responsible for millions of tweets daily, constituting a significant portion of Arabic-language Twitter traffic. We argue that the fact that a phenomenon (...) of these proportions has gone unnoticed by researchers reveals an opportunity to broaden the scope of the current research agenda on online automation. (shrink)

Those who endorse the Psychological Continuity Approach (PCA) to analyzing personal identity need to impose a non-branching constraint to get the intuitively correct result that in the case of fission, one person becomes two. With the help of Brueckner's (2005) discussion, it is shown here that the sort of non-branching clause that allows proponents of PCA to provide sufficient conditions for being the same person actually runs contrary to the very spirit of their theory. The problem is first presented in (...) connection with perdurantist versions of PCA. The difficulty is then shown to apply to endurantist versions as well. (shrink)

Suppose that you're certain that a certain sentence, e.g. "Frida is tall", lacks a determinate truth value. What cognitive attitude should you take towards it—reject it, suspend judgment, or what else? We show that, by adopting a seemingly plausible principle connecting credence in A and Determinately A, we can prove a very implausible answer to this question: i.e., all indeterminate claims should be assigned credence zero. The result is striking similar to so-called triviality results in the literature on modals and (...) conditionals. (shrink)

Existing metasemantic projects presuppose that word- (or sentence-) types are part of the non-semantic base. We propose a new strategy: an endogenous account of word types, that is, one where word types are fixed as part of the metasemantics. On this view, it is the conventions of truthfulness and trust that ground not only the meaning of the words (meaning by convention) but also what the word type is of each particular token utterance (words by convention). The same treatment extends (...) to identifying the populations through which the conventions prevail. We consider whether this proposal leads to new underdetermination challenges for metasemantics, and make a case that it does not. (shrink)

The wrong kind of reason (WKR) problem is a problem for attempts to analyze normative properties using only facts about the balance of normative reasons, a style of analysis on which the ‘Reasons First’ programme depends. I argue that this problem cannot be solved if the orthodox view of reasons is true --- that is, if each normative reason is numerically identical with some fact, proposition, or state-of-affairs. That’s because solving the WKR problem requires completely distinguishing between the right- and (...) wrong-kind reasons for an attitude. I argue that some facts give both right- and wrong-kind reasons for an attitude. Consequently, no such distinction between the two types of reasons is complete if reasons are facts or the like. I conclude by suggesting that reasons and facts are related by constitution, not identity. (shrink)

In the same spirit with the theme of last issue of this SGJ journal (“Ongoing creation”), this paper shortly reviews a plausible mechanism from Aether to become ordinary matter from the perspective of Neutrosophic Logic. We also discuss two other possible applications of Neutrosophic Logic, including a resolution of conflicting paradigms in medicine. We hope that some ideas as outlined herein will be proved useful in the near future.

Extending Alvin Plantinga’s model of warranted belief to the beliefs of groups as a whole, I argue that if the dogmatic beliefs of the Catholic Church are true, they are also warranted. Catholic dogmas are warranted because they meet the three conditions of my model: they are formed (1) by ministers functioning properly (2) in accordance with a design plan that is oriented towards truth and reliable (3) in a social environment sufficiently similar to that for which they were designed. (...) I show that according to Catholic doctrine the authoritative spokespersons of the Church—ecumenical councils and popes—meet these conditions when defining dogmas. I also respond to the objection that the warrant of Catholic dogmas is defeated by the plurality of non-Catholic Christian sects that deny Catholic dogmas. (shrink)

This chapter examines two ways in which liberal thinkers have appealed to claims about disagreement in order to defend a principle of free speech. One argument, from Mill, says that free speech is a necessary condition for healthy disagreement, and that healthy disagreement is conducive to human flourishing. The other argument says that in a community of people who disagree about questions of value, free speech is a necessary condition of legitimate democratic government. We argue that both of these arguments, (...) in their standard guises, are premised upon contestable views about the realpolitik of disagreement in a liberal society. (shrink)

In a recent paper, we describe how a model of quantum communication based on combining consciousness experiment and entanglement can serve as impetus to stop 5G-caused diseases. Therefore, in this paper we will discuss how entanglement can be explained in terms of quantum theory. This short review may be considered as an effort to bring QM into real problem solving, i.e. telecommunication.

In this paper, we develop a mathematical model of awareness based on the idea of plurality. Instead of positing a singular principle, telos, or essence as noumenon, we model it as plurality accessible through multiple forms of awareness (“n-awareness”). In contrast to many other approaches, our model is committed to pluralist thinking. The noumenon is plural, and reality is neither reducible nor irreducible. Nothing dies out in meaning making. We begin by mathematizing the concept of awareness by appealing to the (...) mathematical formalism of higher category theory. The beauty of higher category theory lies in its universality. Pluralism is categorical. In particular, we model awareness using the theories of derived categories and (infinity, 1)-topoi which will give rise to our meta-language. We then posit a “grammar” (“n-declension”) which could express n-awareness, accompanied by a new temporal ontology (“n-time”). Our framework allows us to revisit old problems in the philosophy of time: how is change possible and what do we mean by simultaneity and coincidence? Another question which could be re-conceptualized in our model is one of soteriology related to this pluralism: what is a self in this context? A new model of “personal identity over time” is thus introduced. (shrink)

Literature reviews have traditionally been a simple exercise in reporting the current relevant research, both to provide an overview of the current status of the field, and perhaps to draw attention to controversies. From the perspective of positivist research traditions, it was important to neutrally report all the relevant research, which was assumed to be foundational. In this article, written for the Applied Critical Realism special issue of Journal of Critical Realism, I use my own research to illustrate how a (...) literature review might look if it were non-foundational and guided by the principles of immanent critique. Immanent critique is central to Bhaskar’s philosophical methodology but has not been much applied in critical realist empirical research. Following a brief introduction to immanent critique, its history and relation to other ways of grounding knowledge, an excerpt from a literature review is used as backdrop for an extended discussion about various potential applications, and impl... (shrink)

The discussions of conatus – force, tendency, effort, and striving – in early modern metaphysics have roots in Aristotle’s understanding of life as an internal experience of living force. This paper examines the ways that Spinoza’s conatus is consonant with Aristotle on effort. By tracking effort from his psychology and ethics to aesthetics, I show there is a conatus at the heart of the activity of the ψυχή that involves an intensification of power in a way which anticipates many of (...) the central insights of early modern and 20th century European philosophy. The first section outlines how Aristotle’s developmental conception of the soul as geometrically ordered lays the foundation for his understanding of effort. The developmental series of powers of the soul are analogous to the series of shapes in mathematics. The second section links the striving of the soul to the gradual acquisition of virtues as a directed activity unifying multiplicity. The third examines the paradigm of self-awareness that Aristotelian effort involves. In the final section I show how ancient Greek theories of music were founded on the experience of striving. The “nature” of music is defined by Aristoxenus, and Theophrastus, in relation to the passion and intentionality of the soul. The geometrical order, as a synthesis of elements in geometry, music, or ethics, is a generative process in which past elements are retained and reintegrated in later stages of development. It requires effort to think geometrically, and the progress of knowledge itself is an integral aspect of all effort. Effort is the lived and self-aware cause which, moving step by step in an orderly and deliberate way, grows and advances upon itself. For both Spinoza and Aristotle, effort is the immanent intelligence which accomplishes what is in the purview of its understanding. Thus, will, in this conception of effort, is not something we already possess innately, but emerges gradually by an effort aimed at improvement. (shrink)

One critique of experimental philosophy is that the intuitions of the philosophically untutored should be accorded little to no weight; instead, only the intuitions of professional philosophers should matter. In response to this critique, “experimentalists” often claim that the intuitions of professional philosophers are biased. In this paper, we explore this question of whose intuitions should be disqualified and why. Much of the literature on this issue focuses on the question of whether the intuitions of professional philosophers are reliable. In (...) contrast, we instead focus on the idea of “muddled” intuitions—i.e. intuitions that are misdirected and about notions other than the ones under discussion. We argue that the philosophically untutored are likely to have muddled intuitions and that professional philosophers are likely to have unmuddled intuitions. Although being umuddled does not, by itself, establish the reliability of the intuitions of professional philosophers, being muddled is enough to disqualify the intuitions of the philosophically untutored. We then turn to the charge that, despite being unmuddled, professional philosophers still have biased intuitions. To evaluate this charge, we switch focus from the general notion of biased intuition to the more specific notion of theory-laden intuition. We argue that there is prima facie evidence—in the form of the presence of conflicts of intuition—for thinking that at least some of the intuitions of professional philosophers are theory-laden. In summary, we conclude that that there is no clean and easy answer to the question of whose intuitions should matter. (shrink)

For academics and students, Education Management in Managerialist Times offers a critical guide to existing educational management texts and makes a strong case for redefining educational management along more socially and politically informed lines. The book also offers practitioners alternative management strategies intended to contest, rather than support, managerialism, while being realistic about the context within which those who lead and manage schools currently have to work.

This article explores the potential utility of the theory of Holism as developed by South African philosopher, British Commonwealth statesman and military leader, Jan Smuts, for philosophical counselling or practice. Central to the philosophical counseling process is philosophical counsellors or practitioners applying the work of philosophers to inspire, educate and guide their counselees in dealing with life problems. For example, Logic-Based Therapy, a method of philosophical counselling developed by Elliot Cohen, provides a rational framework for confronting problems of living, where (...) the counselor helps the counselee find an uplifting philosophy that promotes a guiding virtue that acts as an antidote to unrealistic and often self-defeating conclusions derived from irrational premises. We present the argument that Holism is one such uplifting philosophy which can be of utility to philosophical counselors or practitioners to help their counselees with confronting problems of living. Furthermore, we argue that Smuts’ articulation of freedom can act as a guiding virtue within this uplifting philosophy of Holism in accordance with the methodology of LBT. Smuts’ contribution to philosophy and psychology is arguably inadequately credited, and for this reason, and to the best of our knowledge, Smuts’ theory of Holism has yet to be discussed in the context of philosophical counseling or practice. Given these omissions, we begin this article with a discussion of his influence on 20th Century Anglo-American psychology. We then provide a brief historical context, and an introduction to the central argument of Smuts’ Holism, as well as a brief overview of the origins of Smut’s Holism and an introduction to his book Holism and Evolution. In the remainder of the article, we discuss several foundational concepts that underlie Smuts’ theory of Holism, as articulated and developed in his book Holism and Evolution, to substantiate our arguments. We conclude by highlighting the limitations of our article, limitations to Smuts’ model, and the challenges inherent in the use of a now largely antiquated theory, even by Smuts’ own admission nineteen years after its publication, for the purposes of contextualizing and substantiating the arguments and recommendations presented herein. (shrink)

If people have stringent moral rights, then the doctrine of double effect is false or unimportant, at least when it comes to making acts permissible or wrong. There are strong and weak versions of the doctrine of double effect. The strong version asserts that an act is morally right if and only if the agent does not intentionally infringe a moral norm and the act brings about a desirable result (perhaps the best state of affairs available to the agent or (...) a promotion of the common good). The weak version asserts that, other things being equal, it is deontically worse to intentionally infringe a norm than to foreseeably do so. A person’s intention or mere foresight might still be relevant to his or her blameworthiness or virtue, but this is a separate issue. (shrink)

Donkey sentences have existential and universal readings, but they are not often perceived as ambiguous. We extend the pragmatic theory of nonmaximality in plural definites by Križ (2016) to explain how context disambiguates donkey sentences. We propose that the denotations of such sentences produce truth-value gaps — in certain scenarios the sentences are neither true nor false — and demonstrate that Križ’s pragmatic theory fills these gaps to generate the standard judgments of the literature. Building on Muskens’s (1996) Compositional Discourse (...) Representation Theory and on ideas from supervaluation semantics, the semantic analysis defines a general schema for quantification that delivers the required truth-value gaps. Given the independently motivated pragmatic theory of Križ 2016, we argue that mixed readings of donkey sentences require neither plural information states, contra Brasoveanu 2008, 2010, nor error states, contra Champollion 2016, nor singular donkey pronouns with plural referents, contra Krifka 1996, Yoon 1996. We also show that the pragmatic account improves over alternatives like Kanazawa 1994 that attribute the readings of donkey sentences to the monotonicity properties of the embedding quantifier. (shrink)

In Humanity’s End: Why We Should Reject Radical Enhancement, Nicholas Agar presents a novel argument against the prospect of radical life-extension. Agar’s argument hinges on the claim that extended lifespans will result in people’s lives being dominated by the fear of death. Here we examine this claim and the surrounding issues in Agar’s discussion. We argue, firstly, that Agar’s view rests on empirically dubious assumptions about human rationality and attitudes to risk, and secondly, that even if those assumptions are granted, (...) the fears that Agar adverts to are unlikely to dominate people’s lives if and when radical life-extension is made possible. Further, we claim that the structure of the decision-making process around life-extension is unlikely to be the way that it would have to be in order for Agar’s claims about fear of death to make sense. Finally, we argue that Agar is implicitly committed to a narrow conception of human value. In response, we suggest that the pursuit of life-extension can itself be seen as an expression of certain important aspects of our distinctively human nature. (shrink)

Saigle, Dubljevic, and Racine (2018) claim that Libet-style experiments are insufficient to challenge that agents have free will. They support this with evidence from experimen- tal psychology that the folk concept of freedom is consis- tent with monism, that our minds are identical to our brains. However, recent literature suggests that evidence from experimental psychology is less than determinate in this regard, and that folk intuitions are too unrefined as to provide guidance on metaphysical issues like monism. In light of (...) this, it is worthwhile to examine the authors’ insuf- ficiency claim under the assumption that monism is false and dualism true (our minds are not identical to our brains). We conclude that, were dualism true, then Libet- style experiments would tell us no more about freedom and moral responsibility than what the authors initially claimed, thus further bolstering their point that Libet-style experiments are ill-suited to speak to the free will of agents. In what follows we first discuss some of the reasons to be skeptical of using folk intuitions to make claims about the nature of freedom and moral responsibility. We then draw from the work of E. J. Lowe to demonstrate that Libet-style experiments would likely give the same results regardless of the truth of monism or dualism. (shrink)

There’s a long but relatively neglected tradition of attempting to explain why many researchers working on the nature of phenomenal consciousness think that it’s hard to explain.1 David Chalmers argues that this “meta-problem of consciousness” merits more attention than it has received. He also argues against several existing explanations of why we find consciousness hard to explain. Like Chalmers, we agree that the meta-problem is worthy of more attention. Contra Chalmers, however, we argue that there’s an existing explanation that is (...) more promising than his objections suggest. We argue that researchers find phenomenal consciousness hard to explain because phenomenal concepts are complex demonstratives that encode the impossibility of explaining consciousness as one of their application conditions. (shrink)

Trivalence is quite natural for deontic action logic, where actions are treated as good, neutral or bad.We present the ideas of trivalent deontic logic after J. Kalinowski and its realisation in a 3-valued logic of M. Fisher and two systems designed by the authors of the paper: a 4-valued logic inspired by N. Belnap’s logic of truth and information and a 3-valued logic based on nondeterministic matrices. Moreover, we combine Kalinowski’s idea of trivalence with deontic action logic based on boolean (...) algebra. (shrink)

This article derives from a paper presented at the Philosophy of Religion and Mysticism Conference hosted by the Russian Academy of Sciences in Moscow, May 22-24, 2014. That paper introduced theories and methods drawn from the ”cognitive science of religion’ and suggested future avenues of research connecting CSR and scholarship on mysticism. Towards these same ends, the present article proceeds in three parts. Part I outlines the origins, aims, and basic tenets of CSR research. Part II discusses one specific causal (...) perspective that informs a wide range of CSR research, Sperber’s ”epidemiological’ approach to cultural expression, and connects this perspective to the example of creator deities. Part III discusses some possible future directions for CSR research concerning mysticism and mystical experience. Finally, a coda addresses two common misunderstandings concerning the ”reductionist’ nature of CSR research. (shrink)

So-called “ugly laws” were mostly municipal statutes in the United States that outlawed the appearance in public of people who were, in the words of one of these laws, “diseased, maimed, mutilated, or in any way deformed, so as to be an unsightly or disgusting object” (Chicago City Code 1881). Although the moniker “ugly laws” was coined to refer collectively to such ordinances only in 1975 (Burgdorf and Burgdorf 1975), it has become the primary way to refer to such laws, (...) which targeted the overlapping categories of the poor, the homeless, vagrants, and those with visible disabilities. Enacted and actively enforced between the American Civil War (1867) and World War I (1918), such laws and their enforcement can tell us much about the very sorts of people who were also, a generation later, subject to explicitly eugenic laws, such as sterilization legislation. And like eugenic laws and policies, such laws continue to affect the lives of people with disabilities to this day (Schweik 2011). (shrink)

As central as the method of forcing is within set theory, it has yet to be incorporated into the philosopher's toolbox. That strikes me as a shame, since it may well have important applications within philosophy. One barrier is that typical presentations of forcing are overly dry and technical and make it seem inherently bound up with its applications within set theory. The purpose of this note is to try to rectify this. In particular, I will explain how the method (...) of forcing can be seen as a way of constructing a certain kind of intensional model that philosophers are already interested in: namely, possibility models. (shrink)

In the paper we provide an overview of issues related to the models used in the research on the logic of norms and actions. We present two models of the variability of the world: temporal (acyclic) and atemporal (cyclic). In the first one the past is always clearly defined, and the future is potentially “branched”. The second type of model allows for a return to the situation that took place. Next we describe different approaches towards agency modeling. We present the (...) most important paradigms, including the logic of actions, where actions are interpreted as transitions between the situations and STIT logic, which states only the responsibility of the agent for particular states of affairs. We discuss questions of determinism and indeterminism of actions, identification of basic actions and operations and the issue of identity. The final part of the paper is devoted to deontic categories. In particular, the applicability of the concepts of strong and weak permission and prohibition in different situational contexts, and their relationship to the two concepts of obligation: abstract and derived. (shrink)