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)

Unfortunately, many people today see the regulation of lies, disinformation, hate speech, and fake news as an infringement of free speech, at least when such speech is ‘political,’ despite the damage that such speech can do. But this very protective attitude toward speech rests on a mistaken understanding of the role of free speech in a liberal society. The right to free speech is based on the liberal value of freedom, and as such can be no broader than freedom itself. (...) And freedom has always been subject to reasonable limits in a liberal society. Indeed, while the principles of toleration and neutrality are often cited as supporting a broad interpretation of the right to free speech, they also tell us that certain limits apply to that right. We need not tolerate speech that encourages intolerance, and while government should be neutral between reasonable conceptions of the good, it need not be neutral between reasonable and unreasonable conceptions. These ideas form the framework of liberal society, and as I shall show, also provide a guide for understanding what kind of speech is protected in a liberal society and what it is not. (shrink)

Because corporate social responsibility can be beneficial to both companies and its stakeholders, interest in factors that support CSR performance has grown in recent years. A thorough integration of CSR in core business processes is particularly important for achieving effective long-term CSR practices. Here, we explored the individual CSR-related competencies that support CSR implementation in a corporate context. First, a systematic literature review was performed in which relevant scientific articles were identified and analyzed. Next, 28 CSR directors and managers were (...) interviewed. The literature review complemented with interview data resulted in the following eight distinct CSR-related competencies: Anticipating CSR challenges; Understanding CSR-relevant systems and subsystems; Understanding CSR-relevant standards; CSR management competencies, including Leading CSR programs, Managing CSR programs, and Identifying and realizing CSR-related business opportunities; Realizing CSR-supportive interpersonal processes; Employing CSR-supportive personal characteristics and attitudes; Personal value-driven competencies, including Ethical normative competencies, Balancing personal ethical values and business objectives, and Realizing self-regulated CSR-related behaviors and active involvement; and Reflecting on personal CSR views and experiences. Based on these results, implications for further research on this topic, as well as implications for practitioners, are discussed. (shrink)

Thomas Reid (1710–96) is increasingly being seen as a highly significant philosopher and a central figure in the Scottish Enlightenment. This new edition of Reid's classic philosophical text in the philosophy of mind at long last gives scholars a complete, critically edited text of the Inquiry. The critical text is based on the fourth life-time edition (1785). A selection of related documents showing the development of Reid's thought, textual notes, bibliographical details of previous editions and a full introduction by the (...) editor makes this an important contribution to the study of this increasingly respected philosopher. Key Features: Complete, critically edited text of the Inquiry accompanied by a judicious selection of manuscript evidence relating to its composition. Comprehensive Introduction providing an historical and philosophical account of the formation of the Inquiry. Detailed textual notes which include bibliographical details and allusions, translations, references to secondary literature and selected passages from Reid's manuscripts. (shrink)

It is unknown to what extent medical researchers generalize study findings beyond their samples when their sample size, sample diversity, or knowledge of conditions that support external validity do not warrant it. It is also unknown to what extent medical researchers describe their results with precise quantifications or unquantified generalizations, i.e., generics, that can obscure variations between individuals. We therefore systematically reviewed all prospective studies (n = 533) published in the top four highest ranking medical journals, Lancet, New England Journal (...) of Medicine (NEJM), Journal of the American Medical Association (JAMA), and the British Medical Journal (BMJ), from January 2022 to May 2023. We additionally reviewed all NEJM Journal Watch clinical research summaries (n = 143) published during the same time. Of all research articles reporting prospective studies, 52.5% included generalizations beyond specific national study populations, with the numbers of articles with generics varying significantly between journals (JAMA = 12%; Lancet = 77%) (p < 0.001, V = 0.48). There was no evidence that articles containing broader generalizations or generics were correlated with larger or more nationally diverse samples. Moreover, only 10.2% of articles with generalizations beyond specific national populations reported external validity strengthening factors that could potentially support such extrapolations. There was no evidence that original research articles and NEJM Journal Watch summaries intended for practitioners differed in their use of broad generalizations, including generics. Finally, from the journal with the highest citation impact, articles containing broader conclusions were correlated with more citations. Since there was no evidence that studies with generalizations beyond specific national study populations or with generics were associated with larger, more nationally diverse samples, or with reports of population similarity that may permit extensions of conclusions, our findings suggest that the generalizations in many articles were insufficiently supported. Caution against overly broad generalizations in medical research is warranted. (shrink)

I claim that Berkeley's main argument against abstraction comes into focus only when we see Descartes as one of its targets. Berkeley does not deploy Winkler's impossibility argument but instead argues that what is impossible is inconceivable. Since Descartes conceives of extension as a determinable, and since determinables cannot exist as such, he falls within the scope of Berkeley's argument.

Resumo A criação de bezerras está entre as atividades mais importantes da pecuária leiteira, pois reflete a genética e a produção do rebanho. Um bom manejo nutricional de novilhas durante a fase recria é essencial para o desenvolvimento ponderal adequado, pois melhora da função imunológica e precocidade reprodutiva. Este estudo teve como objetivo avaliar a relação do peso de novilhas holandesas com a idade na primeira inseminação artificial, primeiro parto e volume de leite produzido na primeira lactação. Foram utilizados os (...) registros de 200 novilhas holandesas submetidas a inseminação artificial em tempo fixo (IATF) em uma fazenda leiteira na região de Lagoa Formosa, MG, no período de janeiro a dezembro de 2020 a 2023, considerando informações sobre de ganho de peso no período de recria até o primeiro serviço idade na IATF e idade ao primeiro parto, produção de leite (em litros) e tempo de lactação. Os registros com as informações foram tabelados no software Exel® e avaliados. As novilhas foram divididas em três (3) grupos de acordo com o ganho de peso alcançado até a primeira inseminação, sendo: grupo A (GA) acima de 390 kg, grupo B (GB) de 360 a 389 kg e grupo C (GC) abaixo de 359 kg. O GA apresentou menor idade na primeira inseminação e no primeiro parto e maior produção de leite, porém a duração da lactação foi menor em relação aos demais grupos. O escore corporal se mostrou determinante para o bom desempenho na reprodução, na produção e na geração de renda ao produtor. -/- Abstract Raising calves is among the most important activities in dairy farming, as it reflects the genetics and production of the herd. Good nutritional management of heifers during the rearing phase is essential for adequate weight development, as it improves immune function and reproductive precocity. This study aimed to evaluate the relationship between the weight of Holstein heifers and age at first artificial insemination, first calving and volume of milk produced in the first lactation. We used the records of 200 Holstein heifers submitted to fixed-time artificial insemination (FTAI) on a dairy farm in the region of Lagoa Formosa, MG, from January to December 2020 to 2023, considering information on weight gain in the period from rearing to first service age at TAI and age at first calving, milk production (in liters) and lactation time. The records with the information were tabulated in the Exel® software and evaluated. The heifers were divided into three (3) groups according to the weight gain achieved until the first insemination, being: group A (GA) above 390 kg, group B (GB) from 360 to 389 kg and group C (GC) below 359 kg. The GA showed a younger age at first insemination and first birth and higher milk production, but the duration of lactation was shorter compared to the other groups. Body score proved to be decisive for good performance in reproduction, production and income generation for the producer. -/- Resumen La cría de terneros es una de las actividades más importantes en la ganadería lechera, ya que refleja la genética y la producción del rebaño. Un buen manejo nutricional de las novillas durante la fase de cría es esencial para un adecuado desarrollo del peso, ya que mejora la función inmune y la precocidad reproductiva. Este estudio tuvo como objetivo evaluar la relación entre el peso de las vaquillonas Holstein y la edad a la primera inseminación artificial, primer parto y el volumen de leche producida en la primera lactancia. Se utilizaron los registros de 200 novillas Holstein sometidas a inseminación artificial en tiempo fijo (FTAI) en una granja lechera de la región de Lagoa Formosa, MG, de enero a diciembre de 2020 a 2023, considerando información sobre ganancia de peso en el período de recría a primera edad de servicio en TAI y edad al primer parto, producción de leche (en litros) y tiempo de lactancia. Los registros con la información fueron tabulados en el software Exel® y evaluados. Las vaquillonas se dividieron en tres (3) grupos de acuerdo a la ganancia de peso lograda hasta la primera inseminación, siendo: grupo A (GA) por encima de 390 kg, grupo B (GB) de 360 a 389 kg y grupo C (GC) por debajo de 359 kg. El AG mostró una menor edad a la primera inseminación y al primer parto y mayor producción de leche, pero la duración de la lactancia fue menor en comparación con los otros grupos. La puntuación corporal resultó ser determinante para un buen desempeño en la reproducción, la producción y la generación de ingresos para el productor. (shrink)

The case for reparations for grievous acts of historical injustice has been getting a lot of attention lately. But I aim to broaden the discussion in two ways. First, I am not only going to talk about reparations as a means of rectifying the injuries inflicted by slavery and the genocide of indigenous peoples, the theft of their land, and the ongoing ripple effects of these historic wrongs. I am also going to talk about reparations for a wider variety of (...) historical injustices, including, most importantly, the long-term economic oppression of women, and the historical exploitation of labor. Second, I am not going to base my argument on the principle of equality, as most people currently do, but on the principle of liberty, as it is understood by libertarians on both the right and the left, at least as long as they believe what they say they believe. Not because I think that egalitarian demands for reparations are wrong. Rather, my point is that the principle of liberty, which is often raised as a defense to claims based on the principle of equality, actually leads to exactly the same place. Finally, I will discuss one possible form of reparations that has largely been ignored, but which has a special connection to libertarian principles, and I will show how it can provide some real relief without provoking the opposition that society-wide redistributive remedies usually face. (shrink)

In this article, I show the role that the philosopher of cognitive science can cur-rently play in cognitive science research. I argue for the important, and not yet considered, role of the philosophy of cognitive science in cognitive science, that is, the importance of cooperation between philosophers of science with cogni-tive scientists in investigating the research methods and theoretical assump-tions of cognitive science. At the beginning of the paper I point out, how the philosopher of science, here, the philosopher of (...) cognitive science, can participate in interdisciplinary research. I am opting of the cooperation in investigating the so-called reflective problems. Then, I discuss four examples of issues important for the cognitive science, in which the competences possessed by the philosopher are useful. At the ending I point out wider landscape of possible cooperation of philosophers with cognitive scientists. (shrink)

Central to Sellars’ account of human cognition was a clear distinction, expressed in varying terminology in his different works, “between conceptual and nonconceptual representations.” Those who have come to be known as ‘left-wing Sellarsians’, such as Richard Rorty, Robert Brandom, and John McDowell, have tended to reject Sellars’ appeals to nonconceptual sensory representations. So-called ‘right-wing Sellarsians’ such as Ruth Millikan and Jay Rosenberg, on the other hand, have embraced and developed aspects of Sellars’ account, in particular the central underlying idea (...) that human perceptual cognition involves a certain naturalistic ‘mapping’ correspondence or structural ‘picturing’ isomorphism between internal mental representations and the layout and behavior of objects in the surrounding environment. Sellars, despite his defenses of nonconceptual representational content throughout his career, has with no small irony come to be cited as one of the “founding fathers of conceptualism.” While recognizing the strong conceptualist elements in Sellars’ Kantian account of perceptual cognition, I argue that a central core of Sellars’ account of nonconceptual sensory contents does not by itself fall afoul of the philosophical worries raised by the left-leaning Sellarsians, and that in fact it has significant merits in its own right. (shrink)

Despite the enormity of the financial losses flowing from the 2008 financial crisis and the outrageousness of the conduct that led up to it, almost no individual involved has been prosecuted for criminal conduct, much less actually gone to prison. What this chapter argues is that the failure to punish those in management for their role in this misconduct stems from a misunderstanding of the need to prove that they personally knew of this wrongdoing and harbored an intent to defraud. (...) But not only would negligence be a sufficient legal and moral basis for imposing terms of imprisonment in these cases, mere causal responsibility would also be enough, for causal responsibility has embed in it all we need to find those causally responsible morally responsible too, and once some basis for moral responsibility is established, the imposition of terms of imprisonment is both legally permitted and morally just. (shrink)

Demonstrating that a developing norm is not yet well established in international law is frequently thought to show that states are not bound by the norm as law. More precisely, showing that a purported international legal norm has only limited support from well-established international legal sources is normally seen as sufficient to rebut an obligation on the part of subjects to comply with the norm in virtue of its legal status. I contend that this view is mistaken. Nascent norms of (...) international law (e.g., crystallizing norms of customary law) can be binding in much the same way as better-established doctrine. This point becomes perspicuous, I argue, once we get a clear sense of the plausible options for grounding the moral authority of international law generally. -/- This result is interesting in its own right, but it also reveals two other features of the character of state responsibility under international law. First, the distinction between legislation and compliance is less pronounced compared to domestic law. Consequently, the virtues of good governance will frequently be pertinent to determining the content of states’ obligations under international law. Second, normally more powerful and influential agents will be more strongly bound by international law than other subjects. This is an attractive result, addressing a concern that motivates many international lawyers to view international law as absolutely binding. An absolutist view international legal authority is unnecessary for showing that the most powerful and dangerous states are strongly bound by the terms of much existing law. (shrink)

Classically, Christians have professed the saving efficacy of the cross. Does Karl Rahner? Recent commentary on Foundations of Christian Faith has described Rahner as conflating “atonement” generally with penal substitutionary theories of a changing God, as ruling out the redemptive significance of Christ’s death, and as denigrating the normativity of Scripture in order to do so. This article responds to these claims, unfolding Rahner’s soteriology and arguing that he advances a theology of the cross which affirms its saving efficacy, including (...) in the last decade of his work. (shrink)

While the volume of material inspired by Rawls’s reinvigoration of the discipline back in 1971 has still not begun to subside, its significance has been in serious decline for quite some time. New and important work is appearing less and less frequently, while the scope of the work that is appearing is getting smaller and more internal and its practical applications more difficult to discern. The discipline has reached a point of intellectual stagnation, even as real-world events suggest that the (...) need for what political philosophy can provide could not be more critical. What follows then is a set of statements about how I believe that we, as political philosophers, should approach what we do. It contains my view as to what political philosophy should be about, how political philosophy should be done, and how courses in political philosophy should be taught, interlaced with commentary on the current state of the profession. (shrink)

Pace much of the literature, I argue that Aristotle endorses what I call the ‘strong link thesis’: the claim that virtuous and vicious acts are voluntary just in case the character states from which they flow are voluntary. I trace the strong link thesis to Plato’s Laws, among other texts, and show how it functions in key arguments of both philosophers.

The author reviews the planned withdrawal of healthcare from the primary public hospital, Grady Memorial Hospital, of Atlanta, Georgia. Prior to passage of the Affordable Care Act of 2010, at least half of the patients had no public or private health insurance and their care was financially supported by State and County funding as well as supplementation from Emory University. New administration in the elected positions of the State and County and at the University reached agreement to decrease care. The (...) University President stated that the Hippocratic Oath was no longer valid for salaried physicians who must follow the direction of their business manager. The author, a tenured Professor, was forcibly transferred to the Veterans Hospital, which also was withholding standard medical care, including life-saving medications. Organizing multiple concerned organizations including members of the King Center, the Carter Center, the Open Door Community Center, Gay Rights, etc., (Grady Coalition) multiple public protests were successful in raising the necessary funds to continue adequate care at Grady and begin an investigation of the Veterans Affairs Hospital. (shrink)

This paper explores the usefulness of the 'ethical matrix', proposed by Ben Mepham, as a tool in technology assessment, specifically in food ethics. We consider what the matrix is, how it might be useful as a tool in ethical decision-making, and what drawbacks might be associated with it. We suggest that it is helpful for fact-finding in ethical debates relating to food ethics; but that it is much less helpful in terms of weighing the different ethical problems that it uncovers. (...) Despite this drawback, we maintain that, with some modifications, the ethical matrix can be a useful tool in debates in food ethics. We argue that useful modifications might be to include future generations amongst the stakeholders in the matrix, and to substitute the principle of solidarity for the principle of justice. (shrink)

I reply to criticisms of the divine command theory with an eye to noting the relation of ethics to an ontological ground. The criticisms include: the theory makes the standard of right and wrong arbitrary, it traps the defender of the theory in a vicious circle, it violates moral autonomy, it is a relic of our early deontological state of moral development. I then suggest how Henry Veatch's view of good as an ontological feature of the world provides a context (...) in which the divine command theory can be reasonably justified. (shrink)

This chapter explores the idea that the need to establish common knowledge is one feature that makes social cognition stand apart in important ways from cognition in general. We develop this idea on the background of the claim that social cognition is nothing but a type of causal inference. We focus on autism as our test-case, and propose that a specific type of problem with common knowledge processing is implicated in challenges to social cognition in autism spectrum disorder (ASD). This (...) problem has to do with the individual’s assessment of the reliability of messages that are passed between people as common knowledge emerges. The proposal is developed on the background of our own empirical studies and outlines different ways common knowledge might be comprised. We discuss what these issues may tell us about ASD, about the relation between social and non-social cognition, about social objects, and about the dynamics of social networks. (shrink)

While it is clear what those attracted to fascism today are against, it is less clear what they are for. Not in the sense of how they want to remake society—this is usually clear enough. What is less clear is the fundamental values that are driving their desire to create a different kind of order. Compounding this difficulty, too many liberals are stubbornly sticking to some conventional beliefs: that human nature is as liberals think it is, not something that is (...) fundamentally disputed; that facts are what liberals think they are, even if some people choose to ignore them; and that everybody is pursuing basically the same conception of the good, even if some of them are deluded as to where we are now and how to get where we want to go. -/- But this move to the right is not being driven simply by mistakes; it is a principled move, backed by a coherent, consistent, and historically well-sourced value system, even if this value system is perverse. Fascism has its own conception of the moral subject; of the need for a rigid social hierarchy of men; of the nature of individual rights; and of the importance of purity in blood, soil, and ideology. It believes in the unity of the people, the leader, and the state; it embraces very different and (to liberals) often disturbing moral ends; and it employs starkly different rules of social interaction. And it believes, in the end, that this all leads to the greatest expression of democracy ever invented. (shrink)

ChatGPT – a large language model – recently passed the U.S. bar exam. The startling rise and power of generative artificial intelligence (AI) systems such as ChatGPT lead us to consider whether and how more specialized systems could be used to overcome existing barriers to the legal system. Such systems could be employed in either of the two major stages of the pursuit of justice: preliminary information gathering and formal engagement with the state’s legal institutions and professionals. We focus on (...) the former and argue that developing and deploying publicly funded AI legal advisors can reduce economic and shame-based cultural barriers to the information-gathering stage of pursuing justice. (shrink)

This quantitative study utilized the descriptive method of research that aimed to assess the implementation of environmental conservation practices in Baybay City Leyte with 92 officials and 115 zone residents of the 23 barangays in the city. Data were gathered through online and pen-paper surveys using frequency mean and Chi-square test. Barangay officials & Zone residents showed the same level of awareness of the environmental conservation practices implemented in Baybay City. Based on the results, the highest average weighted mean environmental (...) conservation practices were the Ordinance on Solid Waste Management. Whereas, the Ordinance on the Use of Plastics Bags has the lowest average weighted mean. There is no significant difference in the level of awareness of the environmental conservation practices between the barangay officials and zone residents. The findings on the level of implementation of the environmental conservation practices, barangay officials asserted a high level of implementation while zone residents claim to have implemented of all the (3) ordinances. For barangay officials, the Ordinance on Solid Waste Management had the highest weighted mean. While the Ordinance on the Use of Plastics Bags had the lowest weighted mean. Whereas, for the zone residents the Ordinance on Regulating the Use of Plastics Bags had the highest weighted mean. While the Ordinance on Anti-Littering and Prohibiting Persons from Throwing any Refuse or Garbage, Spitting, or Improper Urinating into Streets and Canals had the lowest weighted mean. There is a significant difference in the level of implementation of the environmental conservation practices between the barangay officials and zone residents on the Ordinance on Anti-Littering and Prohibiting Persons from Throwing any Refuse or Garbage, Spitting, Improper Urinating into Streets and Canal and Ordinance on Solid Waste Management. However, there is no significant difference in the level of implementation of environmental conservation practices in the Ordinance of the Use of Plastics Bags. (shrink)

An orthodox view in marketing ethics is that it is morally impermissible to market goods to specially vulnerable populations in ways that take advantage of their vulnerabilities. In his signature article “Marketing and the Vulnerable,” Brenkert (Bus Ethics Q Ruffin Ser 1:7–20, 1998) provided the first substantive defense of this position, one which has become a well-established view in marketing ethics. In what follows, we throw new light on marketing to the vulnerable by critically evaluating key components of Brenkert’s general (...) arguments. Specifically, we contend that Brenkert has failed to offer us any persuasive reasons to think that it is immoral to market to the vulnerable in ways that take advantage of their vulnerability. Although Brenkert does highlight the fact that the specially vulnerable are at greater risk of being harmed by already immoral marketing practices (e.g., deception, manipulation), he fails to establish that the specially vulnerable are a unique moral category of market clients or that there are special moral standards that apply to them. Moreover, even if Brenkert’s position were theoretically defensible, the practical implications of his position are far less tenable than he suggests. If our criticisms are sound, then Brenkert and others who endorse his position are seriously mistaken regarding how one can permissibly market products to vulnerable populations, and, in addition, they have improperly categorized certain morally permissible marketing practices as being immoral. (shrink)

Recent research has begun to investigate sensory processing in relation to nonclinical variation in traits associated with the autism spectrum disorders (ASD). We propose that existing accounts of autistic perception can be augmented by considering a role for individual differences in top-down expectations for the precision of sensory input, related to the processing of state-dependent levels of uncertainty. We therefore examined ASD-like traits in relation to the rubber-hand illusion: an experimental paradigm that typically elicits crossmodal integration of visual, tactile, and (...) proprioceptive information in an unusual illusory context. Individuals with higher ASD-like traits showed reduced effects of the rubber-hand illusion on perceived arm position and reach-to-grasp movements, compared to individuals with lower ASD-like traits. These differences occurred despite both groups reporting the typical subjective experience of the illusion concerning visuotactile integration and ownership for the rubber hand. Together these results suggest that the integration of proprioceptive information with cues for arm position derived from the illusory context differs between individuals partly in relation to traits associated with ASD. We suggest that the observed differences in sensory integration can be best explained in terms of differing expectations regarding the precision of sensory estimates in contexts that suggest uncertainty. (shrink)

Ethics, Policy & Environment, Volume 14, Issue 3, Page 345-359, October 2011.

Imre Lakatos' conception of the history of science is explicated with the purpose of replying to criticism leveled against it by Thomas Kuhn, Ian Hacking, and others. Kuhn's primary argument is that the historian's internal—external distinction is methodologically superior to Lakatos' because it is "independent" of an analysis of rationality. That distinction, however, appears to be a normative one, harboring an implicit and unarticulated appeal to rationality, despite Kuhn's claims to the contrary. Lakatos' history, by contrast, is clearly the history (...) of a normatively defined discipline; of science and not scientists and their activities. How such history can be written, the historiographic and critical tools available for its construction, and its importance as history, are considered in detail. In an afterword, the prevalence of Lakatos' treatment of history in philosophical discussion is indicated: A related approach is shown to arise in social contract theory. (shrink)

Investigation of neural and cognitive processes underlying individual variation in moral preferences is underway, with notable similarities emerging between moral- and risk-based decision-making. Here we specifically assessed moral distributive justice preferences and non-moral financial gambling preferences in the same individuals, and report an association between these seemingly disparate forms of decision-making. Moreover, we find this association between distributive justice and risky decision-making exists primarily when the latter is assessed with the Iowa Gambling Task. These findings are consistent with neuroimaging studies (...) of brain function during moral and risky decision-making. This research also constitutes the first replication of a novel experimental measure of distributive justice decision-making, for which individual variation in performance was found. Further examination of decision-making processes across different contexts may lead to an improved understanding of the factors affecting moral behaviour. (shrink)

It is frequently claimed that breeding animals that we know will have unavoidable health problems is at least prima facie wrong, because it harms the animals concerned. However, if we take ‘harm’ to mean ‘makes worse off’, this claim appears false. Breeding an animal that will have unavoidable health problems does not make any particular individual animal worse off, since an animal bred without such problems would be a different individual animal. Yet, the intuition that there is something ethically wrong (...) about breeding animals—such as purebred pedigree dogs—in ways that seem negatively to affect welfare remains powerful. In this paper, an animal version of what is sometimes called the non-identity problem is explored, along with a number of possible ways of understanding what might be wrong with such breeding practices, if it is not that they harm the animal itself. These possibilities include harms to others, placeholder arguments, non-comparative ideas of harm, an ‘impersonal’ approach, and concerns about human attitudes and dispositions. (shrink)

Amazon Book Review Series of “Wild Wise Weird”.

How coherent is Descartes' conception of vacuum in the Principles? Descartes' arguments attacking the possibility of vacuum are difficult to read and to understand because they reply to several distinct threads of discussion. I separate two strands that have received little careful attention: the scholastic topic of annihilation of space, particularly represented in Albert of Saxony, and the physical arguments concerning vacuum in Galileo that are also continued after the publication of the Principles in Pascal. The distinctness of the two (...) sorts of opponent accounts for Descartes' odd habit of summarily declaring vacuum "contradictory" in some contexts, while providing extended conceptual and physical arguments meant to establish its "impossibility" in others. In several passages late in the Principles, Descartes also considers the physical ramifications of "empty space," including a discussion of the appearance of a star, were an empty space situated at the center of the celestial vortex. I argue that the discussion allows for a sensible conception of space with extension, but without matter, quite adequate to the physical discussions of vacuum among Descartes' contemporaries. (shrink)

(Article part 1 of 2) This introduction notes the contributions of various authors to the first issue of the Journal of Global Ethics 2015 Forum and briefly explains the United Nations process through which the sustainable development goals have been formulated up to the receipt by the General Assembly, in August 2014, of the Report of the Open Working Group of the General Assembly on Sustainable Development Goals. The goals are identified as a confluence of distinct streams of UN work (...) attended to variously by policy experts and political figures in the past several decades. Sources include, most obviously, the Millennium Declaration of 2000 and the Millennium Development Goals, but also the 1992 United Nations Conference on Environment and Development, the Human Development Reports of 1990 forward, and the 1987 Brundtland Report. (shrink)

A longish (12 page) discussion of Richard Sorabji's excellent book, with a further discussion of what it means for a theory of emotions to be a cognitive theory.

The constitutions of many nations have been explicitly or implicitly founded upon principles of the social contract derived from Thomas Hobbes. The Hobbesian egoism at the base of the contract fairly accurately represents the structure of market enterprise. A contractarian analysis may, then, allow for justified or rationally acceptable universal standards to which businesses should conform. This paper proposes general rational restrictions upon multi-national enterprises, and includes a critique of unjustified restrictions recently proposed by the Organization for Economic Cooperation and (...) Development (OECD). I propose restrictions that may be tighter than the OECD and international law currently demand, because reason requires that the activities of enterprises accord with standards of environmental and governmental sustainability in addition to consortium, national law and international law agreements. I argue that it is justifiable that indictments may be presented by a citizen or a government against the local arm of a multinational enterprise in response to violations committed by an arm within a different country. (shrink)

(Article part 2 of 2) This introduction notes the contributions of authors to the second issue of the Journal of Global Ethics 2015 Sustainable Development Goals Forum. It briefly explains the process through which the Sustainable Development Goals have developed from their receipt in 2014 to their passage in September 2015 by the UN General Assembly, and it considers their development in prospect. The Millennium Development Goals, which spanned 1990–2015, present a case study that reveals the changeability of such long-term (...) multilateral commitments. They were enmeshed in overlapping and inconsistent national and intergovernmental commitments reaching from 1995 to 2005, and the text of those goals also evolved, stabilizing for the last time in 2007. The SDGs and attendant commitments should be expected to evolve similarly over their 15-year run. This presents a concern, for among the three committees established by the UN to create the goals, the two committees charged with public consultation were retired as pl.. (shrink)

Individual attributes, such as educational background, may influence the degree of health consideration in food consumption. The local social norms may affect the same consideration in the collective level. Represented by education level and the custom rules adherence in food choosing behavior, this study aimed to examine how knowledge influences health consideration in food consumption and how the local social norms moderate this association in a multicultural enriched society. By utilizing the Bayesian Mindsponge Framework (BMF) as a conceptual framework, this (...) study analyzed a dataset of 710 urban residents in Indonesia. There was a negative association between education level and health consideration in food consumption in which the custom rules adherence in food choosing behavior moderated against this negative association. For those with a low level of custom-based food consumption, their health consideration is lower as they have higher education level. However, the opposite trend which is a more intuitive positive association was found in those who consume more custom-based food. Socio-cultural factors have a complex impact on food choosing behavior among Indonesian urban residents. Therefore, governmental policies in the health promotion campaign of healthy-nutritious food should incorporate socio-cultural aspects with a deeper understanding of the human mind’s information processing. (shrink)

Case study for Business Ethics, 5000 words. Considers the state of the payday lending market in USA and Canada as of March 2018. Suitable for undergraduate or business school use. Includes the discussion of: Storefront and online payday lending in state/province and national contexts. Applicability of the concept of exploitation to payday lending. Alternatives to payday lending ("Payday Alternative Loans" provided through credit unions, and savings incentive programs that reduce demand for payday lending). U.S. government regulation of 2017 that was (...) rescinded shortly before it was to have effects on business, specifically due to change of Presidential administration (January 2018). Class discussion questions. References. (shrink)

Scholars have associated the character of Pangloss in Voltaire’s Candide variously with the ideas of Gottfried Leibniz, Alexander Pope, and Christian Wolff. With them he is associated, but on whom is he modeled? Pangloss is the image of a French popularizer of science celebrated in his day but little noticed in ours: Noël Antoine Pluche (1688-1761), the author of a highly popular work, Le Spectacle de la Nature.

Distributive justice decision making tends to require a trade off between different valued outcomes. The present study tracked computer mouse cursor movements in a forced-choice paradigm to examine for tension between different parameters of distributive justice during the decision-making process. Participants chose between set meal distributions, to third parties, that maximised either equality (the evenness of the distribution) or efficiency (the total number of meals distributed). Across different formulations of these dilemmas, responding was consistent with the notion that individuals tend (...) to base decisions in part on the magnitude of these parameters. In addition, dilemmas associated with inconsistent responding across the sample tended to elicit the greatest spatial deviation of the cursor, potentially reflecting dilemma difficulty. One interpretation of these results is that individuals value equality and efficiency in such a way that moral dilemmas are resolved by comparing the perceived value of these qualitatively different parameters, consistent with a value pluralistic framework of decision making. A post-hoc analysis indicated that individuals also incorporated sufficiency concerns during distributive justice decision making. The results are discussed in relation to political philosophy. (shrink)

Exploration of a hypothetical model of the structure of the Emergent Event. -/- Key Words: Emergent Event, Foundational Mathematical Categories, Emergent Meta-system, Orthogonal Centering Dialectic, Hegel, Sartre, Badiou, Derrida, Deleuze, Philosophy of Science.

This chapter examines the relation of the Human Development or Capability Approach to liberal political theory. If development is enhancement of capabilities, then this chapter adds that development is human and social: development includes (1) the creation of value as a social process that is (2) a dialectical product of people in their relations. Specifically: (1) The place of the individual within political theory must be revised if the political subject is, as Carol Gould argues, an “individual-in-relations” rather than an (...) autonomous individual agent. (2) New possibilities for valuation are also relational: value is created dialectically along with those possibilities through processes that may be modeled on Denis Goulet’s account of dialectical recognition. These axiological claims hold importance for the place of democratic participation in just politics and development. Building upon David Crocker’s work, this chapter argues that just politics may require a participative approach that is undercut by Martha Nussbaum’s suggestion that a list of central capabilities should guide the drafting of national constitutions. The assimilation of the indigenous concept sumak kawsay to the ideal of buen vivir within Ecuador’s constitution is illustrative, suggesting that prior specification (a list) may limit and distort the dialectical generation of new capabilities. (shrink)

Constructions of the animal and animality are often pivotal to religious discourses. Such constructions create the possibility of identifying and valuing what is "human" as opposed to the "animal" and also of distinguishing human beliefs and behaviors that can be characterized as being animal from those that are "truly human." Some discourses also employ the concept of savagery as a bridge between the human and the animal, where the form of humanity but not its ideal beliefs and practices can be (...) displayed. This paper explores the work of the influential scientist, philosopher, and theologian A. N. Whitehead in this context. His ideas of what constitutes "the animal," the "primitive" and the "civilized" are laid out explicitly in his now little-used history of religions text, Religion in the Making. This paper explores these ideas in this history and then considers how the same ideas permeate his currently more popular philosophical and theological writing Process and Reality. Drawing on some work in post-colonial theory, the paper offers a critique of this understanding of animality, savagery, and civilization and suggests that using Whitehead to underpin modern theological work requires considerable caution. (shrink)

(Pre-publication draft November 2015: Partial content of "Introduction: The 2030 Agenda," Journal of Global Ethics 11:3 [December 2015], 262-270) This introduction briefly explains the process through which the Sustainable Development Goals have developed from their receipt in 2014 to their passage in September 2015 by the UN General Assembly, and it considers their development in prospect. The Millennium Development Goals, which spanned 1990-2015, present a case study that reveals the changeability of such long-term multilateral commitments. They were enmeshed in overlapping (...) and inconsistent national and intergovernmental commitments reaching from 1995 to 2005, and the text of those goals also evolved, stabilizing for the last time in 2007. The Sustainable Development Goals and attendant commitments should be expected to evolve similarly over their fifteen year run. This presents a concern, for among the three committees established by the UN to create the goals, the two committees charged with public consultation were retired as planned in 2014. The process evident thereafter has displayed a shift towards a strategy of enrolling broad public endorsement that leaves such consultation and specific responsibility to those consulted in doubt. This bodes ill for public deliberation on the goals and for public accountability as the agenda proceeds towards 2030. (shrink)

I briefly consider why Descartes stopped work on the _Rules_ towards the end of my paper. My main concern is to accurately characterize the project represented in the _Rules_, especially in its relation to early-modern logic.