Indem dieser Band sich auf das Verhältnis von Naturerkennen und Natursein konzentriert, thematisiert er einen wesentlichen Ausschnitt aus dem weiten Spektrum von Böhmes philosophischer Arbeit. Um die Naturthematik möglichst breit zu entfalten und für Querverbindungen offenzuhalten, ist der vorliegende Band in drei Abschnitte gegliedert. Im ersten Abschnitt stehen Charakter und Reichweite der wissenschaftlichen Erkenntnis von Natur im Mittelpunkt. Der zweite Teil des Bandes stellt alternative Perspektiven auf Natur vor. Im dritten Teil schließlich stehen der Mensch und sein Verhältnis zu sich (...) selbst im Mittelpunkt der Untersuchungen. Inhaltsverzeichnis Krohn, Wolfgang: Wissenschaftsentwicklung zwischen Dezentrierung und Dekonstruktion. Stehr, Nico: Von den Grenzen der Macht wissenschaftlicher Erkenntnis. Schäfer, Wolf: Zweifel am Ende des Baconschen Zeitalters. Kamper, Dietmar: Wissen ist Ohnmacht. Macht ist Unwissen. Gamm, der Technik. Janich, Peter: Zeit und Natur. Kimmerle, Heinz: »Es ist Zeit, daß es Zeit wird«. Wie kann Zeit Zeit werden? Schiemann, Gregor: Natur auf dem Rückzug. Zur Relevanz der aristotelischen Unterscheidung von Natur und Technik. Hauskeller, Michael: Ist Schönheit eine Atmosphäre?. Zur Bestimmung des landschaftlich Schönen. Schmitz, Hermann: Situationen und Atmosphären. Zur Ästhetik und Onthologie bei Gernot Böhme. Rehmann-Sutter, Christoph: Über Relationalität. Was ist das »Ökologische« in der Naturästhetik? Meyer-Abich, Klaus Michael: Erinnerung an die natürliche Mitwelt. Andreas-Griesebach, Manon: Idee plus Erfahrung. Goethes Begründung eines neuen Typs von Naturwissenschaft. Engelhardt, Dietrich von: Madame de Stael über Naturphilosophie, Naturwissenschaft und Medizin in De l'Allemagne. Deneke, Michael: Schramm, Engelbert: »Soziale Naturwissenschaft«. Zwischen Sozialwissenschaften und Naturwissenschaften. Böhme, Hartmut: Enthüllen und Verhüllen des Körpers. Biblische, mythische und künstlerische Deutungen des Nackten. Lippe, Rudolf zur: Eine Logik des gestischen Wissens. Müller, Rudolf Wolfgang: Gernot Böhme - Anima naturaliter japonica. Hoffmann, Gisbert: Das menschliche Sein als mediales. Martens, Ekkehard: »Natürlich« denken?. Heideggers Pseudosokratismus als Irrationalismus. Fleischer, Helmut: Naturalität ohne Naturalismus. Zum lebensweltlichen Fundus jeder höheren Erkenntnis-Artistik. Gerhard: Technik als Medium. Grundlinien einer Philosophie. (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

An action-oriented perspective changes the role of an individual from a passive observer to an actively engaged agent interacting in a closed loop with the world as well as with others. Cognition exists to serve action within a landscape that contains both. This chapter surveys this landscape and addresses the status of the pragmatic turn. Its potential influence on science and the study of cognition are considered (including perception, social cognition, social interaction, sensorimotor entrainment, and language acquisition) and its impact (...) on how neuroscience is studied is also investigated (with the notion that brains do not passively build models, but instead support the guidance of action). A review of its implications in robotics and engineering includes a discussion of the application of enactive control principles to couple action and perception in robotics as well as the conceptualization of system design in a more holistic, less modular manner. Practical applications that can impact the human condition are reviewed (e.g., educational applications, treatment possibilities for developmental and psychopathological disorders, the development of neural prostheses). All of this foreshadows the potential societal implications of the pragmatic turn. The chapter concludes that an action-oriented approach emphasizes a continuum of interaction between technical aspects of cognitive systems and robotics, biology, psychology, the social sciences, and the humanities, where the individual is part of a grounded cultural system. (shrink)

In Being Realistic About Reasons,T.M. Scanlon develops a non-naturalistic realist account of normative reasons. A crucial part of that account is Scanlon’s contention that there is no deep epistemological problem for non-naturalistic realists, and that the method of reflective equilibrium suffices to explain the possibility of normative knowledge. In this critical notice we argue that this is not so: on a realist picture, normative knowledge presupposes a significant correlation between distinct entities, namely between normative beliefs and normative facts. This correlation (...) calls for an explanation. We show that Scanlon does not have the resources to offer such an explanation. (shrink)

Andrea Cesalpino is an important figure in the history of science. He demonstrated that blood circulates into heart from veins and from the heart to arteries, paving the way to Harvey’s complete description of blood circulation. Moreover, he was the founder of botany as a systematic discipline, which he based, rather than on the observation of accidental similarities of plants, on the discovery of their vegetative-generative principle. In philosophy, he attempted to conciliate the immortality of the soul (i.e., the form (...) of the body) with the existence of a unique immaterial intellect, which is individuated and multiplied in the singular souls that participate to it. (shrink)

Modern life sciences research is increasingly relying on artificial intelligence (AI) approaches to model biological systems, primarily centered around the use of machine learning (ML) models. Although ML is undeniably useful for identifying patterns in large, complex data sets, its widespread application in biological sciences represents a significant deviation from traditional methods of scientific inquiry. As such, the interplay between these models and scientific understanding in biology is a topic with important implications for the future of scientific research, yet it (...) is a subject that has received little attention. Here, we draw from an epistemological toolkit to contextualize recent applications of ML in biological sciences under modern philosophical theories of understanding, identifying general principles that can guide the design and application of ML systems to model biological phenomena and advance scientific knowledge. We propose that conceptions of scientific understanding as information compression, qualitative intelligibility, and dependency relation modelling provide a useful framework for interpreting ML-mediated understanding of biological systems. Through a detailed analysis of two key application areas of ML in modern biological research – protein structure prediction and single cell RNA-sequencing – we explore how these features have thus far enabled ML systems to advance scientific understanding of their target phenomena, how they may guide the development of future ML models, and the key obstacles that remain in preventing ML from achieving its potential as a tool for biological discovery. Consideration of the epistemological features of ML applications in biology will improve the prospects of these methods to solve important problems and advance scientific understanding of living systems. (shrink)

Teil I: Philosophie und KI Teil II: Ethik, Recht und Ökonomie der KI Teil III: KI zwischen Öffentlichkeit und persönlicher Lebenswelt Teil IV: Letzte Fragen.

The precautionary principle (PP) aims to anticipate and minimize potentially serious or irreversible risks under conditions of scientific uncertainty. Thus it preserves the potential for future developments. It has been incorporated into many international treaties and pieces of national legislation for environmental protection and sustainable development. In this article, we outline an interpretation of the PP as a framework of orientation for a sustainable information society. Since the risks induced by future information and communication technologies (ICT) are social risks for (...) the most part, we propose to extend the PP from mainly environmental to social subjects of protection. From an ethical point of view, the PP and sustainability share the principle of intergenerational justice, which can be used as an argument to preserve free space for the decisions of future generations. Applied to technical innovation and to ICT issues in particular, the extended PP can serve as a framework of orientation to avoid socio-economically irreversible developments. We conclude that the PP is a useful approach for: (i) policy makers to reconcile information society and sustainability policies and (ii) ICT companies to formulate sustainability strategies. (shrink)

There is, in some quarters, concern about high–level machine intelligence and superintelligent AI coming up in a few decades, bringing with it significant risks for humanity. In other quarters, these issues are ignored or considered science fiction. We wanted to clarify what the distribution of opinions actually is, what probability the best experts currently assign to high–level machine intelligence coming up within a particular time–frame, which risks they see with that development, and how fast they see these developing. We thus (...) designed a brief questionnaire and distributed it to four groups of experts in 2012/2013. The median estimate of respondents was for a one in two chance that high-level machine intelligence will be developed around 2040-2050, rising to a nine in ten chance by 2075. Experts expect that systems will move on to superintelligence in less than 30 years thereafter. They estimate the chance is about one in three that this development turns out to be ‘bad’ or ‘extremely bad’ for humanity. (shrink)

A shared narrative in the literature on the evolution of cooperation maintains that social _learning_ evolves early to allow for the transmission of cumulative culture. Social _norms_, whilst present at the outset, only rise to prominence later on, mainly to stabilise cooperation against the threat of defection. In contrast, I argue that once we consider insights from social epistemology, an expansion of this narrative presents itself: An interesting kind of social norm — an epistemic coordination norm — was operative in (...) early and important instances of specialised social learning. I show how there’s a need for such norms in two key social learning strategies and explain how this need is constituted. In assessor-teaching (e.g. Castro et al., 2019b, 2021), epistemic coordination norms allow agents to coordinate around the _content_ of social learning, i.e., what is to be known and how this is to be done. These norms also allow agents to coordinate around the form of cultural learning in what’s sometimes called strategic social learning (Laland, 2004; Hoppitt & Laland, 2013; Heyes, 2018, Chap. 5) and elsewhere. Broadly speaking, this concerns how cultural learning is organised within the social group. The upshot is that the evolution of social learning and social norms are intertwined in important and underappreciated ways from early on. The above matters as it informs our views about the evolution of social norms more generally. Truly _social_ norms emerged to coordinate a plurality of complex behaviours and interactions, amongst them specialised social learning. I substantiate this view by contrasting it with Jonathan Birch’s views on the evolution of norms. What results is a general but cohesive narrative on the early evolution of social norms. (shrink)

The use of computational tools in the humanities for science 2.0 practices is steadily increasing. This paper examines current research practices of a group of philosophers studying the history of philosophical concepts. We explain the methodology and workflow of these philosophers and provide an overview of tools they currently use in their research. The case study highlights a number of fundamental challenges facing these researchers, including: (i) accessing known relevant research content or resources; (ii) discovering new research content or data; (...) (iii) working collaboratively rather than individually. We propose a mash-up of search, visualization, and awareness tools addressing these challenges and discuss the design of the mash-up, its implementation, and evaluation with the target users. Through our case study, we demonstrate the benefits of a user-centered design approach, as well as the benefits of the concrete mash-up for historians of philosophy, and, importantly, the limitations of these tools for conducting historical and philosophical research. (shrink)

La cobertura universal de salud está en el centro de la acción actual para fortalecer los sistemas de salud y mejorar el nivel y la distribución de la salud y los servicios de salud. Este documento es el informe fi nal del Grupo Consultivo de la OMS sobre la Equidad y Cobertura Universal de Salud. Aquí se abordan los temas clave de la justicia (fairness) y la equidad que surgen en el camino hacia la cobertura universal de salud. Por lo (...) tanto, el informe es pertinente para cada agente que infl uye en ese camino y en particular para los gobiernos, ya que se encargan de supervisar y guiar el progreso hacia la cobertura universal de salud. (shrink)

Context: Many recent research areas such as human cognition and quantum physics call the observer-independence of traditional science into question. Also, there is a growing need for self-reflexivity in science, i.e., a science that reflects on its own outcomes and products. Problem: We introduce the concept of second-order science that is based on the operation of re-entry. Our goal is to provide an overview of this largely unexplored science domain and of potential approaches in second-order fields. Method: We provide the (...) necessary conceptual groundwork for explorations in second-order science, in which we discuss the differences between first- and second-order science and where we present a roadmap for second-order science. The article operates mainly with conceptual differentiations such as the separation between three seemingly identical concepts such as Science II, Science 2.0 and second-order science. Results: Compared with first-order science, the potential of second-order science lies in 1. higher levels of novelty and innovations, 2. higher levels of robustness and 3. wider integration as well as higher generality. As first-order science advances, second-order science, with re-entry as its basic operation, provides three vital functions for first-order science, namely a rich source of novelty and innovation, the necessary quality control and greater integration and generality. Implications: Second-order science should be viewed as a major expansion of traditional scientific fields and as a scientific breakthrough towards a new wave of innovative research. Constructivist content: Second-order science has strong ties with radical constructivism, which can be qualified as the most important root/origin of second-order science. Moreover, it will be argued that a new form of cybernetics is needed to cope with the new problems and challenges of second-order science. (shrink)

Was wissen Sie über Kosovo? Nicht genug. Nicht genug jedenfalls über objektive, wertfrei vorgegebene Fakten, mit deren Hilfe man verantwortungsethische Bewertungen des NATO-Angriffs begründen könnte. Trotzdem halte ich drei wertende Aussagen über den Kosovo-Konflikt für vernünftig. Sie lauten (in alphabetischer Reihenfolge): Der bewaffnete Kampf der Albaner im Kosovo war moralisch falsch. Die Militäreinsätze der Serben im Kosovo waren moralisch falsch (schon vor Beginn der NATO-Bombardements und erst recht danach). Und schliesslich: Die Luftschläge des Westens gegen Serbien waren moralisch falsch. Insbesondere (...) diese letzte Behauptung ist der Zielpunkt des Aufsatzes. Mein Plädoyer für diese Behauptung verläuft auf einem dritten Weg zwischen der gesinnungsethischen Position pazifistischer Rigoristen und der verantwortungsethischen Position ihrer Kontrahenten. Die grundlegende Richtlinie für meine Untersuchung besteht darin, keine Behauptungen als objektiv auszugeben, die in Wirklichkeit auf Wertungen beruhen. Schon beim Blick auf die Vorkriegs- und Kriegsgeschehnisse im Kosovo kommen wir nicht ohne die Hilfe von Werten aus; und ich plädiere dafür, diese Geschehnisse im Lichte einer verzweifelten Menschenliebe anzusehen: Daraus ergibt sich eine neue Form von Pazifismus. (shrink)

This paper considers the argument according to which, because we should regard it as a priori very unlikely that we are among the most important people who will ever exist, we should increase our confidence that the human species will not persist beyond the current historical era, which seems to represent a crucial juncture in human history and perhaps even the history of life on earth. The argument is a descendant of the Carter-Leslie Doomsday Argument, but I show that it (...) does not inherit the crucial flaw in its immediate ancestor. Nonetheless, we are not forced to follow the argument where it leads if we instead significantly decrease our confidence that we can affect the long-run future of humanity. GPI Working Paper No. 1-2019. (shrink)

This report from the WHO Consultative Group on Equity and Universal Health Coverage offers advice on how to make progress fairly towards universal health coverage.

In this paper, I argue that the widely held view that Aristotle's vicious agent is a principled follower of a wrong conception of the good whose soul, just like the soul of the virtuous agent, is marked by harmony between his reason and non-rational desires is an exegetical mistake. Rather, Aristotle holds – consistently and throughout the Nicomachean Ethics – that the vicious agent lacks any real principles of action and that his soul lacks unity and harmony even more than (...) the soul of the uncontrolled agent. (shrink)

Will future lethal autonomous weapon systems (LAWS), or ‘killer robots’, be a threat to humanity? The European Parliament has called for a moratorium or ban of LAWS; the ‘Contracting Parties to the Geneva Convention at the United Nations’ are presently discussing such a ban, which is supported by the great majority of writers and campaigners on the issue. However, the main arguments in favour of a ban are unsound. LAWS do not support extrajudicial killings, they do not take responsibility away (...) from humans; in fact they increase the abil-ity to hold humans accountable for war crimes. Using LAWS in war would probably reduce human suffering overall. Finally, the availability of LAWS would probably not increase the probability of war or other lethal conflict—especially as compared to extant remote-controlled weapons. The widespread fear of killer robots is unfounded: They are probably good news. (shrink)

It is popular to hold that our primary epistemic access to specific response-dependent properties like the fearsome or admirable (or so-called ‘affective properties’) is constituted by the corresponding emotion. I argue that this view is incompatible with a widely held meta-ethical view, according to which affective properties have deontic force. More specifically, I argue that this view cannot accommodate for the requirement that deontic entities provide guidance. If affective properties are to guide the formation of the corresponding emotion, our primary (...) access to them cannot be provided by that same emotion. (shrink)

While the consequences of mathematically-based software, algorithms and strategies have become ever wider and better appreciated, ethical reflection on mathematics has remained primitive. We review the somewhat disconnected suggestions of commentators in recent decades with a view to piecing together a coherent approach to ethics in mathematics. Calls for a Hippocratic Oath for mathematicians are examined and it is concluded that while lessons can be learned from the medical profession, the relation of mathematicians to those affected by their work is (...) significantly different. There is something to be learned also from the codes of conduct of cognate but professionalised quantitative disciplines such as engineering and accountancy, as well as from legal principles bearing on professional work. We conclude with recommendations that professional societies in mathematics should sponsor an (international) code of ethics, institutional mission statements for mathematicians and syllabuses of ethics courses for incorporation into mathematics degrees. (shrink)

There is a wide range of things we do out of emotion. For example, we smile with pleasure, our voices drop when we are sad, we recoil in shock or jump for joy, we apologize to others out of remorse. It is uncontroversial that some of these behaviors are actions. Clearly, apologizing is an action if anything is. Things seem less clear in the case of other emotional behaviors. Intuitively, the drop in a sad person’s voice is something that happens (...) to her, rather than something she actively performs. Perhaps more interestingly, even jumping for joy can seem a problematic case: although its execution involves the active performance of certain movements, it has been argued to contrast, e.g., with an act of apology, in that it is not performed in order to achieve some end, such as repairing a relationship. This can make this behavior seem considerably different from paradigm actions. Our central concern in this paper is with which emotional behaviors should be classed as actions and why... (shrink)

There seems to be a minimal core that every theory wishing to accommodate the intuition that the future is open must contain: a denial of physical determinism (i.e. the thesis that what future states the universe will be in is implied by what states it has been in), and a denial of strong fatalism (i.e. the thesis that, at every time, what will subsequently be the case is metaphysically necessary).1 Those two requirements are often associated with the idea of an (...) objective temporal flow and the non-reality of the future. However, at least certain ways to frame the “openness” intuition do not rely on any of these. Branching Time Theory (BTT) is one such: it is compatible with the denial that time flow is objective and it is couched in a language with a (prima facie) commitment to an eternalist ontology. BTT, though, urges us to resist certain intuitions about the determinacy of future claims, which arguably do not lead either to physical determinism or to fatalism. Against BTT, supporters of the Thin Red Line Theory (TRL) argue that their position avoids determinism and fatalism, while also representing the fact that there is a future which is “special” because it is the one that will be the case. But starting with Belnap and Green 1994, some have objected to the tenability of TRL, mainly on metaphysical grounds. In particular, those argue that “positing a thin red line amounts to giving up objective indeterminism,”2 and that “has unacceptable consequences, ranging from a mistreatment of actuality to an inability to talk coherently about what would have happened had what is going to happen not taken place.”3 In this paper, we wish to reframe the.. (shrink)

The paper defends three claims about Aristotle’s theory of uncontrolled actions (akrasia) in NE 7.3. First, I argue that the first part of NE 7.3 contains the description of the overall state of mind of the agent while she acts without control. Aristotle’s solution to the problem of uncontrolled action lies in the analogy between the uncontrolled agent and people who are drunk, mad, or asleep. This analogy is interpreted as meaning that the uncontrolled agent, while acting without control, is (...) still in possession of her knowledge but she is unable to use it as knowledge due to the temporary disablement of her reason by appetite. Due to this disablement, the uncontrolled agent is temporarily unable to be motivated to act by her knowledge and acts merely on her appetite. Second, I argue that the second part of NE 7.3 provides an analysis of the particular mental state from which the uncontrolled action issues. Its central passage is a description of the uncontrolled agent’s state of mind before the uncontrolled action and not, as it has been traditionally understood, a description of her state of mind during the uncontrolled action. Third, I argue that, on Aristotle’s view, the transition from the state before the uncontrolled action to the state in which the agent already acts without control does not involve any psychological state that would constitute the agent’s choice to abandon her decision and give in to her desires but proceeds on a purely physiological level. (shrink)

[This is the short version of: Müller, Vincent C. and Bostrom, Nick (forthcoming 2016), ‘Future progress in artificial intelligence: A survey of expert opinion’, in Vincent C. Müller (ed.), Fundamental Issues of Artificial Intelligence (Synthese Library 377; Berlin: Springer).] - - - In some quarters, there is intense concern about high–level machine intelligence and superintelligent AI coming up in a few dec- ades, bringing with it significant risks for human- ity; in other quarters, these issues are ignored or considered science (...) fiction. We wanted to clarify what the distribution of opinions actually is, what probability the best experts currently assign to high–level machine intelligence coming up within a particular time–frame, which risks they see with that development and how fast they see these developing. We thus designed a brief questionnaire and distributed it to four groups of experts. Overall, the results show an agreement among experts that AI systems will probably reach overall human ability around 2040-2050 and move on to superintelligence in less than 30 years thereafter. The experts say the probability is about one in three that this development turns out to be ‘bad’ or ‘extremely bad’ for humanity. (shrink)

I defend two main theses. First, I argue that Aristotle’s account of voluntary action focuses on the conditions under which one is the cause of one’s actions in virtue of being (qua) the individual one is. Aristotle contrasts voluntary action not only with involuntary action but also with cases in which one acts (or does something) due to one’s nature (for example, in virtue of being a member of a certain species) rather than due to one’s own desires (i.e. qua (...) individual). An action can be attributed to one qua individual in two distinct ways depending on whether one is a rational or a non-rational animal. One is responsible for one’s action in both cases, but only in the former case is one also responsible for being the sort of individual that performs it. Aristotle also distinguishes two ways in which an action can be compelled while still being an action of the agent. In the first case, one is compelled by (physically) external forces or circumstances to act against one’s internal impulse. In the second case, one is compelled to act on (internal) impulses that are fixed by one’s nature against one’s own individual impulse. This latter kind of compelled action is only possible in the case of rational agents. Secondly, I argue that Aristotle’s conception of what it is to be a cause of an action inevitably brings in certain normative features which support evaluative judgments and the practice of praise and blame. On Aristotle’s view, any goal-directed behavior that is properly attributable to an individual is (normally) subject to standards that pertain to behavior of that sort. At the most basic level, these standards establish what counts as a successful realization of the goal that one aims at. Thus even in the case of non-rational animals (or children), one can judge the success of what they are doing and encourage (or discourage) similar behavior by praise or blame. These standards are applicable to one’s conduct simply insofar as one is the controlling origin (or efficient cause) of one’s action qua individual. In the case of rational agents the practice of praise and blame can involve a further normative layer since they can be praised or blamed not only for acting in a certain way so as to encourage or discourage them with a view to the future, but also for being – and having become – individuals of a certain sort. Nevertheless, the applicability of such evaluative judgments and of praise and blame is still warranted by one’s being the controlling origin of one’s actions qua the individual one is (in this case, qua rational individual). (shrink)

El kitsch no es solo una categoría que ha definido una de las posibles gramáticas estéticas de la modernidad, sino también una dimensión antropológica que ha tenido diferentes configuraciones en el curso de los procesos históricos. El ensayo ofrece una mirada histórico-crítica sobre las transformaciones que condujeron desde el kitsch de principios del siglo XX hasta el neokitsch contemporáneo: desde la génesis del kitsch hasta su afirmación como una de las manifestaciones más tangibles de la cultura de masas. Integrándose con (...) la estética posmoderna, el kitsch se transforma en neokitsch, una estética que utiliza el kitsch como su propia sintaxis en el complejo escenario de la estética contemporánea. /// -/- Kitsch is not just a category that has defined one of the possible aesthetic grammars of modernity, but also an anthropological dimension that has had different configurations in the course of historical processes. The essay offers a historical-critical look at the transformations that led from the early twentieth century kitsch to the contemporary neokitsch: from the genesis of kitsch to its affirmation as one of the most tangible manifestations of mass culture. Integrating with postmodern aesthetics, kitsch turns into neokitsch, an aesthetic that deliberately uses kitsch as its own syntax in the complex scenario of contemporary aesthetics. (shrink)

Artificial intelligence (AI) is a digital technology that will be of major importance for the development of humanity in the near future. AI has raised fundamental questions about what we should do with such systems, what the systems themselves should do, what risks they involve and how we can control these. - After the background to the field (1), this article introduces the main debates (2), first on ethical issues that arise with AI systems as objects, i.e. tools made and (...) used by humans; here, the main sections are privacy (2.1), manipulation (2.2), opacity (2.3), bias (2.4), autonomy & responsibility (2.6) and the singularity (2.7). Then we look at AI systems as subjects, i.e. when ethics is for the AI systems themselves in machine ethics (2.8.) and artificial moral agency (2.9). Finally we look at future developments and the concept of AI (3). For each section within these themes, we provide a general explanation of the ethical issues, we outline existing positions and arguments, then we analyse how this plays out with current technologies and finally what policy conse-quences may be drawn. (shrink)

Cumulative cultural knowledge [CCK], the knowledge we acquire via social learning and has been refined by previous generations, is of central importance to our species’ flourishing. Considering its importance, we should expect that our best epistemological theories can account for how this happens. Perhaps surprisingly, CCK and how we acquire it via cultural learning has only received little attention from social epistemologists. Here, I focus on how we should epistemically evaluate how agents acquire CCK. After sampling some reasons why extant (...) theories cannot account for CCK, I suggest that things aren’t as bleak as they might look. I explain how agents deserve epistemic credit for how CCK is transmitted in cultural learning by promoting a central need of their social group: The efficient and safe transmission of CCK. A good initial fit exists between this observation and Greco’s knowledge-economy framework. Ultimately, however, Greco’s account doesn’t straightforwardly account for CCK because of its strict focus on testimony. I point out two issues in the framework due to this focus. The resulting view advocates giving epistemic credit to agents when they act to promote their communities’ epistemic needs in the right way and highlights the various ways in which agents come to do this. (shrink)

Wie sich das Licht blauer und roter Leuchtdioden additiv mischt und Purpur liefert, demonstrierte die Lichtinstallation "Farb-Licht-Nebel" von Bachmann und Pericin auf der Tagung Farbe als Experiment des Deutschen Farbenzentrums (Wuppertal, 25.-26.9.2014). Die Künstler nutzten eine Technik der Farbdarstellung, die Goethe in seiner Farbenlehre (1810) für seinen Angriff auf Newtons Opticks (1704) publik gemacht hatte. Während die Künstler sich mit ihrem Blick auf grünes Licht stark von Goethe absetzten und stattdessen der von Newton geprägten Orthodoxie folgten, passt ihre Purpur-Darstellung gut (...) zu Goethes Farbenlehre. Sie ist bis heute ernstzunehmen. (shrink)

The contribution of the body to cognition and control in natural and artificial agents is increasingly described as “off-loading computation from the brain to the body”, where the body is said to perform “morphological computation”. Our investigation of four characteristic cases of morphological computation in animals and robots shows that the ‘off-loading’ perspective is misleading. Actually, the contribution of body morphology to cognition and control is rarely computational, in any useful sense of the word. We thus distinguish (1) morphology that (...) facilitates control, (2) morphology that facilitates perception and the rare cases of (3) morphological computation proper, such as ‘reservoir computing.’ where the body is actually used for computation. This result contributes to the understanding of the relation between embodiment and computation: The question for robot design and cognitive science is not whether computation is offloaded to the body, but to what extent the body facilitates cognition and control – how it contributes to the overall ‘orchestration’ of intelligent behaviour. (shrink)

It is often assumed that we are only blameworthy for that over which we have control. In recent years, however, several philosophers have argued that we can be blameworthy for occurrences that appear to be outside our control, such as attitudes, beliefs and omissions. This has prompted the question of why control should be a condition on blameworthiness. This paper aims at defending the control condition by developing a new conception of blameworthiness: To be blameworthy, I argue, is most fundamentally (...) to deserve to feel guilty. Being blamed by someone else is not necessarily harmful to the wrongdoer. The blame might not be expressed, or the wrongdoer might not care. But to blame oneself necessarily involves suffering. This conception of blameworthiness explains why the control condition should obtain: We are morally blameworthy for A only if A was under our control because to be blameworthy is to deserve to feel guilty, to feel guilty is to suffer, and one deserves to suffer for A only if A was under one’s control. (shrink)

Reichenbach's 'principle of the common cause' is a foundational assumption of some important recent contributions to quantitative social science methodology but no similar principle appears in econometrics. Reiss (2005) has argued that the principle is necessary for instrumental variables methods in econometrics, and Pearl (2009) builds a framework using it that he proposes as a means of resolving an important methodological dispute among econometricians. We aim to show, through analysis of the main problem instrumental variables methods are used to resolve, (...) that the relationship of the principle to econometric methods is more nuanced than implied by previous work, but nevertheless may make a valuable contribution to the coherence and validity of existing methods. (shrink)

Well-Being in African Philosophy: Insights for a Global Ethics of Development, edited by Bolaji Bateye, Mahmoud Masaeli, Louise Müller, and Angela Roothaan, explores the notion of well-being in African and intercultural philosophy and its insights into global ethics of development. Drawing from longstanding debates on communitarianism in the context of personhood in African philosophy, as well as those in intercultural philosophy, the diverse contributors present manifold ways to philosophize about well-being from African contexts. Hailing from sub-Saharan Africa, Europe, and the (...) Middle East, they address questions of human well-being related to the major global challenges of our time, such as climate change and socio-economic, gender, and racial inequality in society, education, and organization. This collection, building on the work of African independence philosophers as well as oral traditions from a critical development studies perspective, offers fresh views on well-being, development, and morality, thus contributing to global ethics from an African vantage point. (shrink)

Pacifists and their opponents disagree not only about moral questions, but most often about factual questions as well. For example, they came to divergent descriptions of the crisis in Kosovo. According to my reconstruction of pacifism, this is not a surprise because the pacifist, legitimately, looks at the facts in the light of her system of value. Her opponent, in turn, looks at the facts in the light of alternative systems of value, and the quarrel between the two parties about (...) supposedly descriptive matters does not come to an end as there is no objective reality about the war in question that could settle the issue. If I am right, the pacifist's value-laden way of looking at reality can be reconstructed as an obedience to three epistemic imperatives. First, the Epistemic Imperative concerning Human Nature ("Resist against demonizing the other side; always try to understand the case from their point of view"). Second, the Epistemic Imperative concerning Non-Violent Alternatives ("Always search for non-violent alternatives to projected military action"). Third, the Epistemic Imperative concerning Uncontrolled Escalation ("Sharpen your attention for uncontrolled, irreversible side effects of military action, particularly for the danger of escalation to another world war"). Objective reality does not decide how far one should go in following these imperatives. Rather, the decision about this is our's—similarly as in case of the scientist who decides to search for common deep structure behind the chaos of the manifold. So the pacifist's epistemic imperatives can be compared to Kant's regulative principles that are necessary for guiding the scientific scrutiny of reality. (shrink)

People often discriminate based on negative or positive stereotypes about others. Important examples of this are highlighted by the theory of ambivalent sexism. This theory distinguishes sexist stereotypes that are negative (hostile sexism) from those that are positive (benevolent sexism). While both forms of sexism are considered wrong towards women, hostile sexism seems intuitively worse than benevolent sexism. In this article, we ask whether the difference between discriminating based on positive vs. negative stereotypes in itself makes a morally relevant difference. (...) We suggest that it does not. By examining a number of prominent accounts of what makes discrimination wrong, we defend the Moral Irrelevance View according to which stereotype valence is irrelevant to the moral evaluation of discrimination, all else equal. (shrink)

Affirmative action is standardly pursued in relation to admissions to prestigious universities, in hiring for prestigious jobs, and when it comes to being elected to parliament. Central to these forms of affirmative action is that they have to do with competitive goods. A good is competitive when, if we improve A’s chances of getting the good, we reduce B’s chances of obtaining the good. I call this Competitive Affirmative Action. I distinguish this from Non-competitive Affirmative Action. The latter has to (...) do with non-competitive goods, e.g., being granted early parole or freedom from arbitrary arrest. I argue that some of the most prominent objections against affirmative action—in particular, the reverse discrimination objection and the merit objection—speak less against Non-competitive Affirmative Action. And that some of the most prominent arguments in favor of affirmative action, insofar as they justify Competitive Affirmative Action, also justify Non-competitive Affirmative Action. (shrink)

We define a formal semantics of conditionals based on _normatively ideal worlds_. Such worlds are described informally by Armgardt (Gabbay D, Magnani L, Park W, Pietarinen A-V (eds) Natural arguments: a tribute to john woods, College Publications, London, pp 699–708, 2018) to address well-known problems of the counterfactual approach to causation. Drawing on Armgardt’s proposal, we use iterated conditionals in order to analyse causal relations in scenarios of multi-agent interaction. This results in a refined counterfactual approach to causal responsibility in (...) legal contexts, which solves overdetermination problems in an intuitively accessible manner. (shrink)

Ich möchte den Neurowissenschaftlern, die glauben, mit empirischen Mitteln etwas über menschliche Freiheit herausfinden zu können, eine philosophische Herausforderung entgegensetzen. Meine These lautet: Die Frage nach der menschlichen Freiheit ist ein metaphysisches Problem, das sich empirischer Naturforschung entzieht. Um das zu begründen, werde ich ein extremes Gedankenexperiment durchführen. Ich werde zuerst hypothetisch die Situation eines Subjektes beschreiben, dessen Naturwissenschaft berechtigterweise einen durchgängigen kausalen Determinismus im Gehirn postuliert und dessen Libet-Experimente für all seine Handlungen fatal ausgehen (nicht nur für unbedeutende Handbewegungen). (...) Dann werde ich zeigen, dass die deterministische Neurowissenschaft in dieser gedachten Situation gar nichts für oder gegen die Entscheidungsfreiheit des Subjekts austrägt, weil sich die Entscheidungen des hypothetischen Subjekts nicht dort abspielen, wo seine Naturwissenschaft hinzielt. – Wenn es mir gelingt, so eine Situation zu konstruieren, stellt sich die Frage, ob wir nicht in einer ähnlichen Situation stecken könnten. Meiner Ansicht nach lässt sich diese Frage zwar aufwerfen, aber nicht beantworten. Sie gehört ins Reich der metaphysischen Spekulation, genau wie die Frage, ob unser geistiges Leben nach dem biologischen Tod im Jenseits weitergehen könnte. Ziel der Überlegungen ist es, verwirrende Redeweisen wie die von meta-physischer oder transzendentaler Freiheit durch konkrete Modelle verständlicher zu machen. Die Position, die hierbei herauskommen wird, hat einige Gemeinsamkeiten mit Kants Position zur Freiheit. (shrink)

Rollback arguments focus on long sequences of actions with identical initial conditions in order to explicate the luck problem that indeterminism poses for libertarian free will theories (i.e. the problem that indeterministic actions appear arbitrary in a free-will undermining way). In this paper, I propose a rollback argument for probability incompatibilism, i.e. for the thesis that free will is incompatible with all world-states being governed by objective probabilities. Other than the most prominently discussed rollback arguments, this argument explicitly focusses on (...) the ability to act otherwise. It argues that the negligible probability of the relative frequencies in overall rollback patterns being relevantly different indicates that even the ability to act otherwise with regard to individual actions is not free-will enabling. My proposed argument provides probability incompatibilists with a tool to argue against a classical event-causal response to the luck problem, while it can still motivate an agent-causal response to it. (shrink)

The theory that all processes in the universe are computational is attractive in its promise to provide an understandable theory of everything. I want to suggest here that this pancomputationalism is not sufficiently clear on which problem it is trying to solve, and how. I propose two interpretations of pancomputationalism as a theory: I) the world is a computer and II) the world can be described as a computer. The first implies a thesis of supervenience of the physical over computation (...) and is thus reduced ad absurdum. The second is underdetermined by the world, and thus equally unsuccessful as theory. Finally, I suggest that pancomputationalism as metaphor can be useful. – At the Paderborn workshop in 2008, this paper was presented as a commentary to the relevant paper by Gordana Dodig-Crnkovic " Info-Computationalism and Philosophical Aspects of Research in Information Sciences". (shrink)

According to a view called 'nihilism', sentences containing vague expressions cannot strictly speaking be true or false, because they lack definite truth conditions. While most theorists of vagueness tend to regard nihilism as a hopeless view, a few isolated attempts have been made to defend it. This paper aims to develop such attempts in a new direction by showing how nihilism, once properly spelled out, can meet three crucial explanatory challenges that respectively concern truth, assertibility, and communication.