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)

I argue for an account of grasping, or understanding that, on which we grasp via a higher‐order mental act of Husserlian fulfillment. Fulfillment is the act of matching up the objects of our phenomenally presentational experiences with those of our phenomenally representational thought. Grasping‐by‐fulfilling is importantly different from standard epistemic aims, in part because it is phenomenal rather than inferential. (I endorse Bourget's (2017) arguments to that effect.) I show that grasping‐by‐fulfilling cannot be a species of propositional knowledge or belief, (...) and that it is not essentially connected to justification. I motivate a revisionary epistemology on which achieving propositional knowledge and coming to grasp are dual epistemic aims. My account makes sense of a common occurrence—that we are often unmoved to act on our beliefs until we come to phenomenally experience them in some way. It also explains puzzling features of human inquiry. (shrink)

In August 2021, Froese et al. published survey data collected from 2,543 respondents on their subjective experiences living under imposed social distancing measures during COVID-19 (1). The questionnaire was issued to respondents in the UK, Japan, and Mexico. By combining the authors’ expertise in phenomenological philosophy, phenomenological psychopathology, and enactive cognitive science, the questions were carefully phrased to prompt reports that would be useful to phenomenological investigation and theorizing (2–4). These questions reflected the various author’s research interests (e.g., technology, grief, (...) time). Between April 7th and July 31st, 2021, a second questionnaire with the same question set was issued to respondents of the original who had agreed to do a follow-up. This was intended to capture subjective reports of life under social distancing measures a year after the initial survey. By this time–depending on their country of residence and health status–respondents had potentially lived with repeated and prolonged lockdowns and a variety of other restrictions on their social lives. When taken together, Survey I and Survey II provide a cross-cultural and longitudinal dataset that allows for analysis of longer-term impacts of imposed social distancing measures on people’s experiences. For researchers working in diverse disciplines, this dataset offers a rich resource that reflects people’s reactions to the imposition of different social restrictions in different countries and over different time periods. (shrink)

This project was provoked by the almost nonexistent pushback from the Democratic liberal establishment to the (2020) exoneration of Kyle Rittenhouse, despite his acknowledged killing of two Black Lives Matters protesters against the police murder of George Floyd. It builds on three prior articles arguing for the revival of ancient Dionysian practice, Haitian Vodou, and Indigenous South American shamanism to empower leftist revolution. In essence, I propose an assemblage of spiritual practices that are accessible today for the neo-colonized 99% of (...) the global population, by synthesizing and reconstructing three democratic, lower-SES, Indigenous religions, all of which share a militant defiance of their respective tyrannical plutocracies. To avoid cultural appropriation, I center these reconstructed spiritual practices on the figure of the “mage,” a psychosocial healer loosely analogous to a shaman. And the mage’s signature activity, “magic,” I redefine naturalistically as free interpersonal performative action, practiced using two theoretical disciplines (philosophy and psychology) and two practical disciplines chosen by each mage. More precisely, Spirit/Dance channels the “spirits” of dead ancestors, historical figures, legendary heroes, mythical beings, and fictional characters, into the three ultimate objectives of “mindfulness” for psyches/souls, “liberation” for mindful bodies, and “social justice” for liberated communities, indirectly empowering long-term revolution. (shrink)

Building on my previous exploration of the role of dance in the contemporary French political philosopher Jacques Rancière’s Aisthesis: Scenes from the Aesthetic Regime of Art, first published in French in 2011, the present essay turns to another book originally published in the same year, The Intervals of Cinema. Having previously established that the core of Rancière’s philosophical method is an analysis of philosophical homonyms into figurative dancing conceptual partners, I begin by applying that method to the first chapter of (...) Intervals, “Cinematic Vertigo: Hitchcock to Vertov and Back.” There I identify two series of such dancing partners, as follows: Hitchcock’s image-controlling, capitalist vertiginous fall, and Vertov’s movement-equalizing, communist balanced dance. I then critique the implicit marginalizing of women and female bodies in the films and chapter, including Hitchcock’s protagonist’s best friend and ex-fiancé, and Vertov’s cosmetologists and switchboard operators. Finally, I offer a corrective from the proto-feminist life of my grandmother, a onetime cosmetologist, switchboard operator, and Glamour Shots amateur model, my grandmother, Louise Nunnelley, or “Mamaw.” Such are the unacknowledged material basis of Rancière’s radical democratic philosophy, the specifically-embodied and positioned female dancers who continue to get lost in his figurative dance. (shrink)

The standard view of "believes" and other propositional attitude verbs is that such verbs express relations between agents and propositions. A sentence of the form “S believes that p” is true just in case S stands in the belief-relation to the proposition that p; this proposition is the referent of the complement clause "that p." On this view, we would expect the clausal complements of propositional attitude verbs to be freely intersubstitutable with their corresponding proposition descriptions—e.g., "the proposition that p"—as (...) they are in the case of "believes." In many cases, however, intersubstitution of that-clauses and proposition descriptions fails to preserve truth value or even grammaticality. These substitution failures lead some philosophers to reject the standard view of propositional attitude reports. Others conclude that propositional attitude verbs are systematically ambiguous. I reject both these views. On my view, the that-clause complements of propositional attitude verbs denote propositions, but proposition descriptions do not. (shrink)

Many take Kantian ethics to founder when it comes to our duties to animals. In this paper, I advocate a novel approach to this problem. The paper is divided into three sections. In the first, I canvass various passages from Kant in order to set up the problem. In the second, I introduce a novel approach to this problem. In the third, I defend my approach from various objections. By way of preview: I advocate rejecting the premise that nonhuman animals (...) are nonrational. (shrink)

The introduction to a special issue of Religious Studies on the theme of experimental philosophy of religion.

I defend the view that a reason for someone to do something is just a reason why she ought to do it. This simple view has been thought incompatible with the existence of reasons to do things that we may refrain from doing or even ought not to do. For it is widely assumed that there are reasons why we ought to do something only if we ought to do it. I present several counterexamples to this principle and reject some (...) ways of understanding "ought" so that the principle is compatible with my examples. I conclude with a hypothesis for when and why the principle should be expected to fail. (shrink)

Batı’da teorik felsefe; Analitik Felsefe (AF), Kıta Felsefesi (KF) ve Felsefe Tarihi (FT) olmak üzere üçe ayrılır. Fakat üçünde de işler yolunda değildir. AF, felsefenin bir bilim olabileceği iddiasından kuşku duyduğu için gerçek dünyayla ilgilenmiyorken başından beri uygun bir teorik yöntem izlemeyen Kıta Felsefesinin uygulanışı, belirli politik ve etik yargılara hizmet edecek şekilde özelleştirilmiştir. FT çalışmalarının gidişatı ise eldeki eserin nesnel değerinden daha çok ilgili filozofun ait olduğu ulus veya kültüre göre bölgesel bir temelde gelişmiştir. Felsefede ilerleme sağlanacaksa bu ancak (...) bahsi geçen tuzaklardan kaçınılarak gerçekleşebilir. (shrink)

Disintegration is the most important step for drug bioavailability because after, the disintegration process, the ingredients of solid dosage forms dissolve and become bioavailable. Generally, the tablets and capsules should be taken with a glass of water otherwise the manufacturer gives instructions to use the proper beverage. Several drugs are taken with different forms of beverages to ensure easy swallowing of the tablet, masking the bad taste of the drug and overcoming the drug aftertaste, these beverages can influence the disintegration (...) of the solid dosage form. The most common cold beverages consumed by the Libyan population are juice, milk, and Coca-Cola. These beverages are consumed without awareness of the possible effect of these beverages on drugs, especially over-the-counter drugs such as analgesic, antipyretic, and anti-inflammatory drugs that are taken without a prescription. This study aimed to evaluate the influence of three beverages, namely: orange juice, milk, and Coca-Cola on the disintegration time of four over-the-counter-drugs: Panadol, Congestal, Brufen, and Reality Extra using disintegration test of drugs in 0.1 N HCL and in hybrid medium prepared by combination of 150 ml 0.1 N HCL and 550 ml of beverage to simulate in vivo condition. The findings show that the orange juice significantly increases the disintegration time of all the investigated drugs. Coca-Cola significantly increases the disintegration time of Reality Extra, and slightly increases the disintegration time of Brufen, Congestal, and Panadol and the full-fat milk significantly increases the disintegration time of Reality Extra and Panadol while slightly increasing the disintegration time for Brufen and Congestal. It is concluded that commonly used beverages affect the disintegration time of the examined over-the-counter drugs. Patients should be advised to take these medications without beverages which may delay the disintegration and the onset of action of the drug. (shrink)

Wil Waluchow has advanced perhaps the most convincing argument in favour of what he eloquently termed ‘inclusive legal positivism’, the view that a given legal system could make legal validity depend on moral truths. This chapter refocuses the case for the opposing view of exclusive positivism on the metaphysical tension in seeing law as an institutional social fact and yet for its validity to depend on something that is not a social fact, developing an understanding of official mistake as a (...) way of highlighting that tension. If legal validity itself is understood as a socially constructed status (something with which any legal positivist would agree), key officials (as a group) cannot be wrong about the criteria sufficient for institutional membership having been met. While the officials cannot be wrong about the sufficient conditions, they can be wrong about the necessary (gatekeeping) ones and the moral criteria that inclusive positivists say could be included among the criteria of validity are invariably understood to be necessary conditions. That might look like a point in favour of inclusive positivism, but it is only the sufficient conditions that are constitutive of legal validity. Two facets of legal decisions are then marshalled to buttress the case for exclusive positivism: that almost every legal decision is also a determination of validity, and that all such decisions are systemically treated as correct until reviewed by a court of superior jurisdiction (which is itself a sufficient condition for membership). The implication of this is that moral criteria, understood as gatekeepers for legal validity, cannot be constitutive of legal validity. (shrink)

This work introduces the framework for selecting architecture in 5G networks, considering various technological, performance, economic, and operational factors. With the emergence of 5G technology, the architecture selection process has become pivotal in meeting diverse requirements for ultra-high-speed connectivity, low latency, scalability, and diverse service demands. The evaluation comprehensively analyses different architecture options, including centralized, distributed, cloud-based, and virtualized architectures. Factors such as network performance, scalability, cost-effectiveness, security, and compatibility are considered within a multi-criteria decision-making framework. Findings reveal each architecture (...) option's diverse strengths and limitations, emphasizing the importance of aligning architectural choices with specific use cases, deployment scenarios, and business objectives. We used the concept of multi-criteria decision-making (MCDM) methodology to control the various criteria. We used the single-valued neutrosophic set (SVNS) to deal with vague and inconsistent data. The SVNS is integrated with the hyperSoft set. The proposed methodology uses a single-valued neutrosophic hyperSoft set (SVNHSS) to select the best 5G architecture. We used the VIKOR method as an MCDM method to rank the alternatives. The proposed framework provides stakeholders with a structured methodology to evaluate and prioritize architecture options, facilitating informed decision-making in the complex landscape of 5G network deployments. (shrink)

Abstract: Context: grapevine leaves are an important agricultural product that is used in many Middle Eastern dishes. The species from which the grapevine leaf originates can differ in terms of both taste and price. Method: In this study, we build a deep learning model to tackle the problem of grape leaf classification. 500 images were used (100 for each species) that were then increased to 10,000 using data augmentation methods. Convolutional Neural Network (CNN) algorithms were applied to build this model (...) specifically using the pre-trained model on top of the VGG16 architecture. Then, dense layers were added to classify the output of the Convolutional layers and classify outputs to the five classes (species) the leaf belonged to. Results: It was found that feature extraction without fine-tuning the convolutional layers yielded poor results, about 86% accuracy, while training the whole network along with some data preprocessing gave the best results, about 99.45% accuracy on the testing dataset. Conclusions: The proposed CNN model is an effective one for the problem of classification of grape leaf species. (shrink)

The critique of philosophical foundations of neoclassical economics is significant, because of its hegemony on economic education and research programs in Iran and worldwide academies. Due to an epistemological fallacy, methodological individualism plays a prominent role in the philosophy of economic; since the ontological aspects of economy are reduced to methodological considerations. Accordingly, critique of methodological individualism is regarded as the main entry for philosophical analysis of neoclassical economics. This article aims to analyze and appraise the methodological individualism from critical (...) realism’s point of view. Critical realism is taken as a stand for criticizing methodological individualism, because critical realism and neoclassical economics as a positive approach to economics, both share a realistic worldview. The critical realism’ critique of methodological individualism is bases on analyzing the concepts of formalism, syllogism, social atomism, isolation and reduction. From critical realism’ point of view because of unrealistic postulations of methodological individualism, neoclassical economics is turned to an abstract and deductive science such as mathematics with a low potentiality of explanation. (shrink)

With regards to the inefficiencies and uncompromising situations within the humanities and social sciences field in Iran, the challenge of problematizing these sciences is inevitable. So far, numerous research analyzing humanities and social sciences’ problems in the Iranian academic system have been published. Considering the important role of humanities and social sciences in the modern Iranian society, we attempt to suggest a theoretical framework for the problematization of humanities and social sciences in Iran. The exploration of the main challenges facing (...) humanities and social sciences in Iran from the community, academy and administration point of view, sparks three hypotheses. First, humanities and social sciences’ theories and teachings are not applied accurately. Second, the humanities and social sciences’ schools of thought are not chosen properly according to Iranian circumstances. And third, there are metaphysical differences between axioms and presupposition of humanities and social sciences having western origins and those with Islamic-Iranian culture. (shrink)

Shared conceptualization, in the sense we take it here, is as recent a notion as the Semantic Web, but its relevance for a large variety of fields requires efficient methods of extraction and representation for both quantitative and qualitative data. This notion is particularly relevant for the investigation into, and construction of, semantic structures such as knowledge bases and taxonomies, but given the required large, often inaccurate, corpora available for search we can get only approximations. We see fuzzy description logic (...) as an adequate medium for the representation of human semantic knowledge and propose a means to couple it with fuzzy semantic networks via the propositional Łukasiewicz fuzzy logic such that these suffice for decidability for queries over a semantic-knowledge base such as “to what degree of sharedness does it entail the instantiation C(a) for some concept C” or “what are the roles R that connect the individuals a and b to degree of sharedness ε.” . (shrink)

This paper is a historical, legal and philosophical analysis of the concept of human dignity in German and Kenyan constitutional law. We base our analysis on decisions of the Federal Constitutional Court of Germany, in particular its take on life imprisonment and its 2006 decision concerning the shooting of hijacked airplanes, and on a close reading of the Constitution of Kenya. We also present a dialogue between us in which we offer some critical remarks on the concept of human dignity (...) in the two constitutions, each one of us from his own philosophical perspective. (shrink)

This paper explores the idea of robust discursive equality on which respect-based conceptions of justificatory reciprocity often draw. I distinguish between formal and substantive discursive equality and argue that if justificatory reciprocity requires that people be accorded formally equal discursive standing, robust discursive equality should not be construed as requiring standing that is equal substantively, or in terms of its discursive purchase. Still, robust discursive equality is purchase sensitive: it does not obtain when discursive standing is impermissibly unequal in purchase. (...) I then showcase different candidate conceptions of purchase justice, and draw conclusions about the substantive commitments of justificatory reciprocity. (shrink)

There is a curious phenomenon where people from marginalized populations are taken to be arrogant when they show no signs of superiority. In effect, their actions are misconstrued, and their attitudes are rendered unintelligible. Given that arrogance is standardly taken to be a flaw in one’s moral character, understanding such misattributions should give us insight into the affective marginalization many people face. This talk aims to give a thorough exploration of arrogance under oppression. I argue that arrogance is a kind (...) of self-preoccupation that involves projecting one’s values, goals, and concerns onto others as if they were objective values, goals, and concerns. When the affectively marginalized communicate their self-respect through things like protest, people mistake that self-respect as self-preoccupation given how the affectively marginalized are constructed. Furthermore, given how affective marginalization not only inhibits how the marginalized are understood by others, but inhibits their own affective lives, I argue that taking up an arrogant attitude is not always morally vicious, but can be a beautiful form of political resistance but all things considered good. (shrink)

This paper argues for a conception of the natural rights of non-human animals grounded in Kant’s explanation of the foundation of human rights. The rights in question are rights that are in the first instance held against humanity collectively speaking—against our species conceived as an organized body capable of collective action. The argument proceeds by first developing a similar case for the right of every human individual who is in need of aid to get it, and then showing why the (...) situation of animals is similar. I first review some of the reasons why people are resistant to the idea that animals might have rights. I then explain Kant’s conception of natural rights. I challenge the idea that duties of aid and duties of kindness to animals fit the traditional category of “imperfect duties” and argue that they are instead cases of “imperfect right.” I explain how you can hold a right against a group, and why it is legitimate to conceive of humanity as such a group. I then argue that Kant’s account of the foundation of property rights is grounded in a conception of the common possession of the Earth that grounds a right to aid and the rights of animals to be treated in ways that are consistent with their good. Finally, I return to the objections to the idea that animals have rights and offer some responses to them. (shrink)

This paper discusses ethical issues surrounding Integrated Assessment Models (IAMs) of the economic effects of climate change, and how climate economists acting as policy advisors ought to represent the uncertain possibility of catastrophe. Some climate economists, especially Martin Weitzman, have argued for a precautionary approach where avoiding catastrophe should structure climate economists’ welfare analysis. This paper details ethical arguments that justify this approach, showing how Weitzman’s “fat tail” probabilities of climate catastrophe pose ethical problems for widely used IAMs. The main (...) claim is that economists who ignore or downplay catastrophic risks in their representations of uncertainty likely fall afoul of ethical constraints on scientists acting as policy advisors. Such scientists have duties to honestly articulate uncertainties and manage (some) inductive risks, or the risks of being wrong in different ways. (shrink)

In this article, I apply Australian logician and ecofeminist philosopher Val Plumwood’s Feminism and the Mastery of Nature, specifically its alternative logic of “the dance of interaction,” to a controversial community-engagement program in my home state of Alabama. At Rural Studio, Auburn University students design free housing and public works for one of the poorest regions in the United States, known as the “Black Belt.” Through the lens of Plumwood’s ecofeminist dancing logic, the marginalized source of Rural Studio’s survival is (...) revealed to be the resilience of the disempowered majority-Black community. Inspired thereby, I sketch an ecofeminist choreography with three “dancing” concepts (namely Plumwood’s “the master model,” Vandana Shiva’s “nature’s logic,” and Ariel Salleh’s “holding”), acknowledging the resilience of the disempowered as a necessary step toward an ethically-sustainable aesthetics. (shrink)

We critique two popular philosophical definitions of intellectual humility: the “low concern for status” and the “limitations-owning.” accounts. Based upon our analysis, we offer an alternative working definition of intellectual humility: the virtue of accurately tracking what one could non-culpably take to be the positive epistemic status of one’s own beliefs. We regard this view of intellectual humility both as a virtuous mean between intellectual arrogance and diffidence and as having advantages over other recent conceptions of intellectual humility. After defending (...) this view, we sketch remaining questions and issues that may bear upon the psychological treatment of intellectual humility such as whether evidence will help determine how this construct relates to general social humility on the one hand, and intellectual traits such as open-mindedness, curiosity, and honesty on the other. (shrink)

I propose and articulate a novel theory of desire, called the Revised Reward Theory. As the name suggests, the theory is based—and expands—on Arpaly and Schroeder’s (2014) Reward Theory of Desire. The initial Reward Theory identifies desires with states of the reward learning system such that for an organism to desire some P is for its reward system to treat P as a reward upon receipt. The Revised Reward Theory identifies desires with a different state of the same system, such (...) that for an organism to desire some P is for its reward system to expect or predict that P will be rewarding (roughly) prior to receipt. The difference amounts to equating desires with what we ultimately find rewarding or satisfying versus those that underlie our motivations to obtain that which we take ourselves to desire. I argue that the structure of the reward system is incompatible with the original Reward Theory but compatible with the Revised Reward Theory. I demonstrate that this difference has important philosophical implications. I focus on moral responsibility and demonstrate Arpaly and Schroeder’s argument, that addiction can mitigate moral responsibility, turns on this precise difference. Arpaly, Schroeder, and I all ascribe to a meta-theory called ‘natural kindism’ which identifies mental kinds with neurocognitive kinds. This discussion, in addition to defending a theory of desire, is intended to act as a proof of concept for natural kindism as offering a powerful framework for relating empirical results to philosophical issues. (shrink)

Can the best arguments for a privation theory of evil be parodied, with equal plausibility, as arguments for a privation theory of good? The privation theory of evil claims that evil has no positive existence, and it is but a privation of good. The privation theory of good claims the opposite. I approach this topic as one element in the so-called evil-God Challenge. Stephen Law has argued that the epistemic support for belief in an omniscient, omnipotent, and morally perfect God (...) (theism) is on a par with the epistemic support for belief in an omniscient, omnipotent, but completely evil-God (maltheism). In fact, he concludes, the arguments for an evil God are symmetrical with, and isomorphic to, those for a good God. The privation theory of evil has often been used to defend theism against the argument from evil. Thus, part of the evil-God Challenge is to evaluate arguments for the privation theory of evil for their vulnerability to maltheist parody. I consider a broad range of arguments for the privation theory of evil, and I argue that most of them are vulnerable to parodic neutralization. Furthermore, I argue that although the thesis of the convertibility of being and goodness is often held to entail the privation theory of evil, or to be entailed by it (or to be equivalent to it), it is independent of the privation theory. I do find that David Oderberg’s recent argument for the privation theory of evil resists any easy maltheist parody, but I argue that it has a defect. I sketch an argument according to which his good-as-fulfillment account is compatible with a perfectly evil god. My tentative conclusion is that the privation theory of evil enjoys little more plausibility than does the privation theory of good. (shrink)

The article presents the interdisciplinary approach of Edwin Hutchins, analyzing his conception of distributed cognition as probably the most important and lasting contribution of anthropology to the repertoire of theoretical tools in cognitive science. At the same time, this conception resulted in one of the most interesting relationships between cognitive science and social sciences. These relationships are made possible by the assumptions of Hutchins’ conception, which directly contribute to interdisciplinary collaboration. His account of distributed cognition has enormous potential, allowing the (...) integration of research into cognitive and social processes. This is also because it breaks with methodological individualism. (shrink)

Criminal law practices in the US, including policing and incarceration, have drawn heavy criticism for their disproportionate impact on black people, particularly black men. At the same time, some feminist scholars and activists advocate for increases in criminal law responses to sexual assault, including expanding criminal statutes to cover more instances of sexual assault and increasing sentencing guidelines. These reforms are often justified by claims that criminal law should express more feminist values and reject sexist social schemas. This paper makes (...) the case that criminal legal interventions aimed at changing sexist social schemas, such as ‘rape culture,’ are unlikely to be successful because criminal law is effective at maintaining existing social norms, but bad at introducing novel ones. Similarly, in the US, criminality has been ideologically linked to blackness, so attempts to use the stigma of criminality to combat sexual violence are likely to reinforce anti-black racism. The very meaning of a criminal law depends on related social schemas, and the racist social schemas associated with criminality undermine the ability of criminal legal responses to present anti-sexist values. At best, criminal legal reforms aimed at expressing the equal dignity of women will be ambiguous because their meaning is negotiated by existing sexist and racist social schemas. Thus, penal expressivism cannot offer a justification for using criminal law to combat sexual assault. (shrink)

The puzzle that concerns me is whether it is possible to establish a substantive difference between photographic images and other kinds of visual image, which can explain the special epistemic and aesthetic qualities of photographs, without giving way to scepticism about photographic art. In this essay I offer a philosophical account of the photographic process which is able to resolve this tension. I use this account to argue that, while some photographs are mind independent, mind independence is not a defining (...) feature of all photographs. My account is substantive because it distinctively distinguishes the photographic process from other image-making processes and is able to explain the special qualities of photographs. It is also schematic, because it covers the fullest range of photographic technologies across a comprehensive range of applications. Finally, it is clarificatory because it is able to clear up misunderstandings and resolve philosophical problems. Beyond these theoretical aims, my broader purpose is to provide an account that has applicability for a wide range of art history cases and, furthermore, is acceptable to photographic practitioners. The paper was first presented at the Stockholm Museum of Modern Art, in an interdisciplinary symposium. (shrink)

Puhuttaessa Ukrainan sotaan kärjistyneen Venäjän geopoliittisen ja ideologisen ajattelun filosofis-teoreettisista taustavoimista nousee toistuvasti esiin ”putinismin pääideologiksi” ja ”maailman vaarallisimmaksi filosofiksi” maalaillun Aleksandr Duginin nimi. Kuka Dugin on, millaista on hänen vaarallinen ajattelunsa ja mikä on sen yhteys suurvallan aggressioon ja hyökkäyssotaan? Seuraavassa luodaan tiivis yleiskatsaus Duginin ajattelun kahteen keskeisimpään ideologiseen elementtiin: geopoliittiseen Euraasia-ideologiaan ja Duginin radikaalikonservatiiviseen ”neljänteen poliittiseen teoriaan”. Vaikka Duginin suora vaikutusvalta on rajallinen, hänen ajattelunsa heijastelee Venäjän poliittisen eliitin ajatusmaailmaa laajemminkin.

We can distinguish two concepts of respect for persons: appraisal respect , an attitude based on a positive appraisal of a person's moral character, and recognition respect , the practice of treating persons with consideration based on the belief that they deserve such treatment. After engaging in an extended analysis of these concepts, I examine two "truisms" about them. We justifiably believe of some persons that they have good character and thus deserve our esteem . Frequently it pays to be (...) disrespectful; e.g., insulting those who insult us may put them in their place. By using empirical results from social and personality psychology and techniques from decision theory in addition to conceptual considerations, I argue that, surprisingly, the above two "truisms" are false. Extensive psychological evidence indicates that most persons are indeterminate---overall neither good nor bad nor intermediate---and that our information about specific persons almost never distinguishes those who are indeterminate from those who are not. The strategy of habitually avoiding disrespectful behavior maximizes long-term expected utility. In sum, we have good pragmatic reason to treat persons respectfully, but we have good epistemic reason to avoid esteeming or despising them. (shrink)

Dance is intimately connected to both Kierkegaard’s personal life and his life in writing, as exemplified in his famous nightly attendance at the dance-filled theater, and his invitation to the readers of “A First and Last Explanation” to “dance with” his pseudonyms. The present article’s acceptance of that dance invitation proceeds as follows: the first section surveys the limited secondary literature on dance in Kierkegaard, focusing on the work of M. Ferreira and Edward Mooney. The second section explores the hidden (...) dancing dimensions of Kierkegaard’s “leap” and “shadow-dance”. And the third section reinterprets the pseudonymous works richest in dance, Repetition and Postscript, concluding that the religious for him is the lighthearted dance of a comic actor through the everyday theater of the world. (shrink)

In recent years, educational institutions have started using the tools of commercial data analytics in higher education. By gathering information about students as they navigate campus information systems, learning analytics “uses analytic techniques to help target instructional, curricular, and support resources” to examine student learning behaviors and change students’ learning environments. As a result, the information educators and educational institutions have at their disposal is no longer demarcated by course content and assessments, and old boundaries between information used for assessment (...) and information about how students live and work are blurring. Our goal in this paper is to provide a systematic discussion of the ways in which privacy and learning analytics conflict and to provide a framework for understanding those conflicts. -/- We argue that there are five crucial issues about student privacy that we must address in order to ensure that whatever the laudable goals and gains of learning analytics, they are commensurate with respecting students’ privacy and associated rights, including (but not limited to) autonomy interests. First, we argue that we must distinguish among different entities with respect to whom students have, or lack, privacy. Second, we argue that we need clear criteria for what information may justifiably be collected in the name of learning analytics. Third, we need to address whether purported consequences of learning analytics (e.g., better learning outcomes) are justified and what the distributions of those consequences are. Fourth, we argue that regardless of how robust the benefits of learning analytics turn out to be, students have important autonomy interests in how information about them is collected. Finally, we argue that it is an open question whether the goods that justify higher education are advanced by learning analytics, or whether collection of information actually runs counter to those goods. (shrink)

This study focuses on the step-to-step procedure in creating Facebook Social Learning Group (FBSLG) and the perception of students on using FBSLG as learning management tool. Descriptive method was employed in this study participated by two hundred eighty (280) teacher education students in Nueva Ecija University of Science and Technology – College of Education during the academic year 2020-2021 who were purposively selected based on the criteria set by the researcher. Five simple steps on creating FBSLG were discussed by the (...) researcher. Using the adapted survey questionnaire, the data revealed that the students strongly agreed on the four aspects of perception about FBSLG namely: pedagogical affordance, social affordance, technological affordance, and their overall perception on the platform. Some worries of the students on the platform were addressed like the safety of sharing ideas in the FBSLG and some technical difficulties were encountered. It is concluded that the FBSLG is a good platform of conducting classes during this time of pandemic, so the use of this platform to other subjects is highly recommended. (shrink)

In our dealings with young children, we often get them to do or think things by arranging their environments in certain ways; by dissembling, simplifying, or ambiguating the facts in answer to their queries; by carefully selecting the states of affairs, behavior of others, and utterances to which they shall be privy. We rightly justify these practices by pointing out a child's malleability, and the necessity of paying close attention to formative influences during its years of growth. This filtering of (...) influences is necessary, we point out, if children are ever to reach a degree of maturity and inner stability that will enable them to understand and cope adequately with the complexities, contradictions, and difficulties of the world from which we now seek to shield them. Thus a child's eventual state of competence, maturity, and autonomy adequately justifies our current practices of manipulation and selection of his environment: such practices are rightly held to be ultimately in the child's best interests as an adult. There is no future state of things with reference to which the Utilitarian night justify his policy of secrecy and manipulation, and in light of which this policy night eventually be dispensed with and commonly validated, in retrospect, as a means to the worthwhile goal of moral maturity. That is, there is no point at which the attitude of the Utilitarian to the rest of the community can develop past the analogous attitude of the parent towards the child; no point at which the Utilitarian might eventually bear to others a relationship of mutual acknowledgement and respect as mature, autonomous, moral adults. The consistent Utilitarian, then, largely regards himself as if he were the only adult in a community of children. (shrink)

In this article, I confront Jessica Flanigan’s recent attempt to show not merely that women have a right to commit prenatal injury, but also that women who act on this right are praiseworthy and should not be criticized for this injury. I show that Flanigan’s arguments do not work, and I establish presumptive grounds against any such right—namely, prenatal injury, by definition, involves intentional or negligent harm and, as such, may be subsumed under a wider class of actions that are (...) presumptively wrong. (shrink)

"This self-consistent evolution of the fragments, their causal relationships, and their quantum properties is at the heart of the FCQG-SM framework, providing a unified description of quantum mechanics, general relativity, and the Standard Model.".

The emerging field of the philosophy of dance, as suggested by Aili Bresnahan, increasingly recognizes the problem that (especially pre‐modern) dance has historically focused on bodily perfection, which privileges abled bodies as those that can best make and perform dance as art. One might expect that the philosophy of dance, given the critical and analytical powers of philosophy, might be helpful in illuminating and suggesting ameliorations for this tendency in dance. But this is particularly a difficult task since the analytic (...) philosophy of dance is too young to have achieved a comprehensive treatment of dance per se, let alone to update such a treatment in line with the demands of social justice. As a step in that direction, the present article (a) summarizes dance theorists on disabled dance (as opposed to the dance of the temporarily able‐bodied, or TAB) and then applies (b) the philosophy of art and dance to disability, (c) the philosophy of disability to dance, (d) interdisciplinary disability theory to dance, and (e) my own Figuration philosophy of dance to disability, as inspired in part by John Dewey. (shrink)

This chapter looks closely at the use of resilience as a value in pandemic discourses, and particularly at how it reflects the moral complexity of the situation the pandemic presents: an extended crisis where shocks and stressors interact and have an uncertain end. We review key aspects of how resilience has been conceptualised, generally speaking, focusing on its normative implications. Insofar as resilience is suggested as a goal, or used to evaluate individuals, groups and systems, the rhetorical use of resilience (...) in the pandemic has moral implications that we unpack. Asking questions such as resilience to what, of what, and for whom, drives our analysis of the multiple scales at which morally relevant factors must be considered, in terms of distance and certainty, and across space and over time. Further, we highlight the importance of particularly challenging, intersecting scales both within and beyond the pandemic, such as the interaction between other- and self-regarding concerns and the tension between transformation and conservation, as we consider when to take up opportunities for improving ourselves, our society and our systems, in times of extended crises and radical change. Given that a ‘return to normal’ is neither universally desirable nor likely, we recommend in this chapter ways to address resilience as a value that can shape approaches to policy and behaviour while also being explicit about the normative—evaluative and also prescriptive—implications of its use. (shrink)

Goodman draws together, in this memoir, his explorations of meaning and coincidence, and his lived experiences of chance, and his professional experiences teaching, writing, and consulting about risk. The book opens by describing the author's life-changing encounter with a Zen Buddhist monk in 1977, over a cup of tea. Returning to his beginnings, Goodman recounts his coming-of-age, from participating the 1960’s U.S. protests and Vietnam-War resistance, to finally settling down in Canada. He describes his role in a supporting, silent vigil (...) around Willard Straight Hall at Cornell University, the night after it had been occupied by protestors, and his later application for Conscientious Objector status, following the U.S. draft lottery in 1969. He reflects on the challenges and changes on his road taken, in his career and personal relationships, and in spiritual searches, to share some insights about the seamless nature of chance, and about seeing a Both/And perspective in life that encourages openness to possibilities. -/- . (shrink)

Matters of Certainty and Conviction. In the section on certainty, Shaw puts forth a proof of the external world, and considers topics such as change, difference, time, consciousness, substance and quality.

The present quasi-experimental study was undertaken to study students’ perceptions of the advantages and disadvantages of the LMS and the ‘real’ classroom. The data was collected using the online survey method (Google Form), which included questions related to students' perceptions of the effectiveness of both modes in enhancing knowledge, critical skills, and social competence. The study found that although the ratio of students who preferred ‘real’ classroom learning to learning through the LMS was higher, many students were also comfortable with (...) online learning. The present study concludes that a blended mode of learning, i.e., using digital learning tools with a more traditional classroom, can be a better option to meet the needs of both kinds of learners. (shrink)

Historically, the concept of androgyny has been as problematic as it has been appealing to Western progressives. The appeal clearly includes, inter alia, the opportunity to abandon or ameliorate certain identities. As for the problematic dimension, the central problem seems to be the reduction of otherness to the norms of straight white middle/upper-class Western cismen, particularly because of the consequent worsening of actual others’ marginalization and exclusion from social institutions. Despite these problems, I wish to suggest that androgyny—as evidenced by (...) the enthusiasm felt for it by many Westerners—bespeaks something larger and more important than the concept itself, and that modified conception of it might be helpful in pursuit of social justice. (shrink)

Presentist Fragmentalism is a novel interpretation of quantum mechanics. This paper develops the resulting theory of Quantum Gravity.

Oliver's and Rodriguez-Pereyra's important interpretation of the problem of universals as one concerning truthmakers neglects something crucial: that there is a numerical identity between numerically distinct particulars. The problem of universals is rather how to resolve the apparent contradiction that the same things are both numerically distinct and numerically identical. Baxter's account of instantiation as partial identity resolves the apparent contradiction. A seeming objection to this account is that it appears to make instantiation symmetric, since partial identity is symmetric. Armstrong's (...) standard reply is that the difference between a particular and a universal is what makes instantiation asymmetric. Brown suggests, though, that the instantiation of a universal by a universal is sometimes symmetric. However, the examples on which he relies are not universals. (shrink)

This study's focus was to determine students' English competency level after exposure to video lessons as supplemental materials. The respondents of the study were 139 Grade 9 students of Mahaplag National High School coming from four sections enrolled for School Year 2022-2023. Quasi-experimental method of research particularly the pretest-posttest design was utilized in the study. Frequency counts, mean percentage score, weighted mean, standard deviation, and paired samples T-test were utilized in data analysis. Results of the study revealed that the competency (...) level of the students on all three learning competencies before the exposure to video lessons is in the poor category. On the other hand, it was revealed in the study that after exposure to video lessons and through the administered post-test, students’ competency levels improved, which now belongs to the fair category. As to the student’s acceptance level of video lessons as supplemental materials, it was found that students positively accept video lessons as supplemental materials for selected English 9 competencies. It was also ascertained that there was a statistically significant increase in the scores of the students on all three competencies after exposure to video lessons. Furthermore, there was a significant increase in students' overall scores on the three competencies. From the results of the study, it can be concluded that video lessons can be a great supplemental material in teaching English 9 competencies. (shrink)