TRANSPORTE DE GAMETAS, FERTILIZAÇÃO E SEGMENTAÇÃO -/- • _____OBJETIVO -/- O entendimento do desenvolvimento embrionário nos estágios iniciais, desde a deposição dos espermatozoides na fêmea, passando pela fertilização deste no ovócito e na formação do zigoto, é de suma importância para diferenciar especialistas em reprodução e manejo reprodutivo no mercado de trabalho e, também, durante a vida acadêmica. Compreender os processos que levam à formação do zigoto na fêmea é essencial para avaliar a capacidade reprodutiva dos animais e, mediante técnicas, (...) avaliar o trato reprodutivo da fêmea e o desenvolvimento do embrião até a formação do feto e, por fim, em um novo animal sadio na propriedade. Com esse trabalho, o estudante de veterinária ou zootecnia, que deseja se aprofundar na fisiologia da reprodução animal, identificará os mecanismos que são envolvidos no transporte dos gametas, bem como os processos que estes últimos devem completar para alcançar a fertilização e para desencadear as divisões iniciais do embrião. -/- • _____INTRODUÇÃO -/- A fertilização ou fecundação é o processo pelo qual os gametas masculino (espermatozoide) e feminino (ovócito) se fundem para gerar um novo indivíduo. Seu êxito depende da culminação adequada dos diferentes processos que devem sofrer os gametas durante sua maduração e percurso; do transporte oportuno destes no trato reprodutivo da fêmea, assim como de uma série de adaptações dos órgãos genitais internos da mãe. A segmentação refere-se às primeiras divisões celulares do embrião. -/- • _____TRANSPORTE DO OVÓCITO -/- O ovócito que é liberado na ovulação, e que se encontra coberto pelas células do cumulus (figura 1), é capturado pela fímbria do infundíbulo ao aderir aos cílios. Esse processo é altamente eficaz, inclusive em espécies onde os ovários possuem várias formações globosas, por exemplo nas porcas, onde os ovidutos capturam entre 95 e 100% dos ovócitos que são ovulados. As contrações das camadas musculares do oviduto e o movimento intenso dos cílios da mucosa faz com que as secreções fluam em direção ao útero, transportando assim o complexo cumulus-ovócito. Esse transporte é relativamente rápido até alcançar a junção da ampola com o istmo (que é considerado o local de fertilização do espermatozoide e ovócito) a partir do qual se torna lento. Devido a fêmea estar em estro, o processo está sob controle endócrino, isto é, controle hormonal através do estradiol. Nas fêmeas domésticas, ao contrário das mulheres, o transporte ao longo do oviduto é extremamente eficiente, pois os embriões passam para o útero sem dificuldade, de modo que gestações ectópicas (tubárias ou em cavidade) são quase inexistentes. A égua, frequentemente, retém por muito tempo os ovócitos não fertilizados no oviduto, provavelmente devido a não secreção de substâncias (como a prostaglandina E) que poderiam favorecer sua passagem, como se propõe que aconteça com os embriões. A figura 2 apresenta um ovócito com suas respectivas estruturas. Figura 1: ovócitos de uma vaca madurados in vitro. Nota-se as células do cumulus que os recobre. -/- Figura 2: estruturas do ovócito de uma ovelha que se encontra na etapa de ovócito secundário, depois da ovulação. Elaborado pelo autor. • _____TRANSPORTE ESPERMÁTICO -/- Para que os espermatozoides sejam capazes de fertilizar o ovócito, deverão sofrer uma série de mudanças bioquímicas e morfológicas ao longo de sua passagem pelo aparelho reprodutor tanto masculino como feminino. Uma vez produzidos na parede do túbulo seminífero, os espermatozoides são liberados em direção ao lúmen tubular e transportados passivamente para uma estrutura ramificada conhecida como rede testicular (rete testis). Dessa rede são conduzidos em direção ao epidídimo passando através de 10 a 20 ductos eferentes localizados no polo superior do testículo. O epidídimo é dividido em três seções denominadas cabeça, corpo e cauda; é constituído por um só ducto longo e tortuoso que continua com o canal deferente. Ao final desemboca nas ampolas seminais, no ducto ejaculatório e na uretra. As funções do epidídimo são as de maduração, transporte e armazenamento dos espermatozoides. O transporte através do epidídimo é lento, aproximadamente de 10 dias em touros, e segue sendo passivo. Os espermatozoides tomados da cabeça do epidídimo são ainda imaturos e incapazes de fertilizar, enquanto os armazenados na cauda são completamente maduros. Durante o trânsito pelo epidídimo os espermatozoides adquirem motilidade e o potencial para fertilizar, o acrossomo é remodelado e a gota citoplasmática migra para o flagelo e é liberada. Quando um macho ejacula com muita frequência, é possível observar espermatozoides com gota citoplasmática no sêmen, já que não há tempo suficiente para que completem sua maduração. Os espermatozoides são expulsados fora do organismo durante a cópula, na masturbação ou em emissões espontâneas. Na ejaculação, os espermatozoides que se encontram suspensos nos fluidos do testículo e do epidídimo, misturam-se ao chegar na uretra com as secreções das glândulas acessórias para formar o sêmen. Essas secreções denominadas plasma seminal, proporcionam substâncias para manter o metabolismo energético das células espermáticas, e integram suas membranas elementos que impedem uma capacitação prematura. Durante a cópula, o sêmen é depositado na vagina ou no útero, variando entre as espécies (tabela 1). Na monta natural, geralmente, o serviço ocorre no momento propício, já que está definido pela fase do ciclo estral em que a fêmea é receptiva ao macho. No entanto, na inseminação artificial, é o macho que deverá determinar o momento ideal, e para isso é importante considerar a vida média dos gametas, ao qual é muito curta no caso dos ovócitos (tabela 1). -/- Tabela 1: local de depósito do sêmen, volume da ejaculação e vida média dos gametas. Espécie Local de deposição Volume (ml) Velocidade de ejaculação Vida média do ovócito Vida média do espermatozoide Bovinos Intravaginal 2 1 – 3 seg 8 h 30 – 48 h Caninos Intravaginal 2 – 30 (10 média) 6 – 45 min 48 – 72 h 9 – 11 d Equinos Intrauterina 50 – 200 20 – 60 seg 6 – 8 h 72 – 120 h Humanos Intravaginal 3 - - 5 – 6 d Ovinos Intravaginal 1 1 – 2 seg 16 – 24 h 30 – 48 h Suínos Intrauterina 200 – 400 5 – 20 min 8 – 10 h 24 – 48 h Onde d = dias; h = horas. A vida fértil do ovócito é muito curta, portanto, o momento do serviço é de grande importância para obter altos índices de fertilização. -/- Independentemente do local em que os espermatozoides sejam depositados no aparelho reprodutor feminino, serão expostos às secreções genitais e sofrem uma série de mudanças em seu trajeto até o local de fertilização antes de penetrar no ovócito. Nas espécies em que o sêmen é depositado na parte cranial da vagina, uma parte do mesmo penetra através da cérvix, enquanto outra parte é eliminada do aparelho genital da fêmea, em pouco tempo, através do fluxo retrógrado. O meio vaginal não é adequado e imobiliza os espermatozoides em pouco tempo, pelo qual deverão entrar no útero onde o ambiente é mais propício. O transporte espermático na fêmea é o resultado da alta contratilidade, do movimento ciliar e o fluido do aparelho genital durante o estro, ao qual está sob controle endócrino e do sistema nervoso. Esse transporte é favorecido pelas características especiais do muco estral, cujas moléculas formam uma espécie de canais que facilitam a passagem dos espermatozoides. Pelo contrário, durante a fase lútea seu transporte é dificultado. Além do meio vaginal, a cérvix também atua como barreira natural para limitar a passagem dos espermatozoides, diminuindo assim a possibilidade de polispermia. Funciona, também, como um filtro que seleciona os espermatozoides aptos dos que não o são, uma vez que somente os primeiros possuem uma motilidade vigorosa que lhes permite passar pelo muco altamente hidratado. Na vaca a cérvix é considerada como um reservatório espermático. Quando atravessam a cérvix, os espermatozoides seguem sua deslocação tanto por movimento próprio como pelas contrações uterinas e tubárias. Nas espécies em que o local de depósito do sêmen do macho na fêmea é intrauterino, como equinos, a principal barreira que os espermatozoides enfrentam é a união ou junção útero-tubárica. A união entre o útero e o oviduto (istmo do oviduto) serve como reservatório funcional dos espermatozoides nas espécies domésticas. Poucos minutos depois da cópula, é possível encontrar alguns espermatozoides no oviduto, que é conhecido como fase de transporte rápido. No entanto, esses espermato-zoides não são os que participam do processo de fertilização e podem apresentar certas anormalidades. Existe um segundo tipo de transporte denominado fase sustentada, a qual consiste na migração prolongada dos espermatozoides em direção as partes mais craniais do aparelho genital feminino, que conduzem à colonização do reservatório funcional e na liberação gradual dos espermatozoides dos reservatórios espermáticos, incluindo este último. O reservatório do istmo fornece aos espermatozoides um ambiente propício, protegendo-os contra a fagocitose, prolongando assim a sua viabilidade. Aqui os esper-matozoides permanecem aderidos a superfície das células ciliadas do epitélio até a finalização de sua capacitação, depois da qual são liberados quando alteram seu padrão de motilidade flagelada, fenômeno conhecido como hipermotilidade, e migram em ondas em direção ao local da fertilização. Dos milhões de espermatozoides ejaculados, somente alguns milhares alcançarão o istmo do oviduto e um número sumamente pequeno será encontrado nas imediações do ovócito no momento da fertilização. -/- • _____CAPACITAÇÃO ESPERMÁTICA E REAÇÃO ACROSSÔMICA -/- A capacitação é um processo gradual e essencial para a fertilização. Os espermato-zoides devem passar por um dado tempo de “incubação” no aparelho genital da fêmea e sofrer uma série de mudanças antes de serem capazes de fecundar o ovócito. A capacita-ção dos espermatozoides começa quando eles entram em contato com as secreções do aparelho genital da fêmea e termina no istmo do oviduto. Durante esse percurso a superfície da cabeça do espermatozoide se modifica já que algumas moléculas como o colesterol são removidas da membrana plasmática, aumentando sua fluidez e alterando suas propriedades bioquímicas. Entre outras coisas, essa reorganização dos lipídios facilita a entrada de cálcio extracelular pelos canais iônicos e ocasiona a desestabilização da membrana, tornando-a mais fusogênica. Também são eliminados outros fatores (conhecidos genericamente como fatores descapacitantes) que expõem receptores membranais indispensáveis para a realização da união entre o espermatozoide e o ovócito durante a fertilização. Os espermatozoides capacitados apresentam um padrão de hipermotilidade e uma maior atividade metabólica, características que devem obter para que sejam capazes de penetrar as camadas do ovócito. A capacitação é necessária para que ocorra a reação acrossômica. A reação acrossomal ou acrossômica (RA) é um fenômeno de exocitose que é desencadeada pela ligação entre as proteínas e receptores localizados na membrana do espermatozoide e a zona pelúcida do ovócito (figura 3). Envolve a fusão da membrana plasmática do espermatozoide com a membrana externa de seu acrossomo; formando, assim, pequenas vesículas, cujo conteúdo de enzimas hidrolíticas, como a hialuronidase e a acrosina, é liberado em direção ao seu exterior, facilitando a penetração da zona pelúcida. A adesão do espermatozoide à zona pelúcida é específica da espécie e depende de glicoproteínas presentes na membrana dos ovócitos maduros; a cabeça do espermatozoide se une com essas glicoproteínas mediante receptores específicos e atravessam em direção oblíqua a zona pelúcida até chegar ao espaço perivitelino. Nos mamíferos, particularmente em roedores e nos humanos, algumas dessas glicoproteínas são conhecidas como ZP1, ZP2 e ZP3. Pensa-se que a união da membrana espermática a esta última é o que desencadeia a reação acrossomal. Posteriormente, as vilosidades do ovócito entram em contato com o espermatozoide e a membrana presente na secreção equatorial da cabeça do espermatozoide, que tem proteínas fusogênicas específicas, une-se a membrana plasmática do ovócito, fusionando-se e permitindo a entrada do núcleo espermático ao citoplasma (figura 4). A capacitação dos espermatozoides é fundamental para o êxito da fertilização, uma vez que apenas os aptos estarão perfeitos e íntegros para que a união e percepção das glicoproteínas presentes nos mesmos possam ocorrer de forma ideal para a penetração deste no ovócito, fertilizá-lo e formar um zigoto. Figura 3: estrutura do espermatozoide. Nota: a membrana é acrossomal e não acrossonal. Elaborado pelo autor. -/- Figura 4: eventos que ocorrem durante a fertilização. A – depois de passar através das células do cumulus, o espermatozoide entra em contato com a zona pelúcida, onde receptores da membrana plasmática reconhecem as proteínas da zona pelúcida; B – é desencadeada, então, a reação acrossomal; C – para que o espermatozoide penetre na zona pelúcida; D – ao atravessar a zona pelúcida e entrar no espaço perivitelino, a cabeça do espermatozoide entra em contato com a membrana vitelina; ambas membranas se fusionam graças ao reconhecimento de proteínas fusogênicas que estão no segmento equatorial. E – ocorre, então, que o núcleo do espermatozoide penetra no citoplasma do ovócito; uma das consequências da fusão da membrana com a cabeça do espermatozoide é a reação cortical, em que os grânulos corticais do ovócito liberam seu conteúdo em direção ao espaço perivitelino, o que resulta na alteração da estrutura da zona pelúcida e da membrana vitelina para bloquear a polispermia. Elaborado pelo autor. • _____CONSEQUÊNCIAS DA PENETRAÇÃO -/- Bloqueio da polispermia -/- A fusão das membranas dos gametas durante a penetração permite a entrada da fosfolipase C zeta (PLCζ) – fator solúvel que provém do espermatozoide – que desencadeia liberação e oscilações de Ca2+ no retículo endoplasmático. Isso, por sua vez, provoca a migração e fusão dos grânulos corticais, com a consequente liberação de enzimas, que mudam tanto a estrutura da zona pelúcida (por exemplo a inativação de ZP3), como a da membrana vitelina. Desse modo, impede-se que outros espermatozoides as penetrem, evitando assim a polispermia (figura 5). -/- Figura 5: os grânulos corticais que encontram-se na periferia do citoplasma, debaixo da superfície da membrana do ovócito, migram e fusionam-se sobre a mesma, liberando seu conteúdo no espaço perivitelino imediatamente depois da penetração do espermatozoide. A – como conse-quência, tanto a membrana vitelina como a zona pelúcida são modificadas, impedindo a entrada de mais espermatozoides, o que evita a polispermia. B – o ovócito retoma, então, sua segunda divisão meiótica, que ocasiona a expulsão do segundo corpúsculo polar, e na formação dos pronúcleos feminino e masculino. C – continuando, os pronúcleos migram, suas membranas se dissolvem e os cromossomos de ambos se condensam e se unem. Completa-se, assim, a singamia e forma-se, então, o zigoto. Elaborado pelo autor baseado nos livros de embriologia e fisiologia da reprodução conforme vida bibliografia. -/- Ativação do ovócito e formação de pronúcleos -/- Na maioria das fêmeas domésticas, com exceção da cadela, o ovócito encontra-se suspenso na metáfase II da segunda meiose no momento da ovulação. A entrada da PLCζ do espermatozoide no citoplasma do ovócito, e a consequente liberação de Ca2+, faz com que o ovócito se ative, terminando a segunda divisão meiótica e expulse o segundo corpo polar. Posteriormente, o material nuclear do ovócito se reorganiza para formar o pronú-cleo feminino. Entretanto, a membrana nuclear do espermatozoide se dissolve, a cromatina descondensa-se, as protaminas são substituídas por histonas, e se forma uma nova membrana nuclear, dando lugar ao pronúcleo masculino. -/- Singamia -/- Uma vez que os pronúcleos feminino e masculino são formados, migram para o centro do ovócito, aproximam-se, suas membranas se dispersam e os cromossomos paternos e maternos se associam, com o qual recupera a condição diploide e dá origem ao zigoto (figura 5). -/- • _____DESENVOLVIMENTO EMBRIONÁRIO -/- Poucas horas após a fertilização ocorre a primeira divisão do zigoto em duas, depois em 4, 8, 16 e 32 células, denominadas blastômeros. Essas divisões mitóticas são conhecidas como divisões de segmentação ou clivagem (figura 6), uma vez que são realizadas sem aumento do citoplasma, de modo que com cada divisão os blastômeros se tornam menores. A partir das 16 células o embrião se chama mórula, e é visto como uma massa celular compacta. A compactação deve-se a informação de proteínas de ligação entre os blastômeros. O embrião acumula líquido em seu interior, formando uma cavidade denominada blastocele. Esse processo é conhecido como blastulação; o embrião, assim, passa a ser chamado de blastocisto. Nessa etapa é possível diferenciar duas populações de células embrionárias: a massa celular interna, embrioblasto ou botão embrionário (que dará origem ao embrião), e a massa celular externa, células superficiais ou trofoblasto, do qual se originam a maioria das membranas fetais. Ao continuar a multiplicação das células e a acumulação de líquido, o blastocisto aumenta de tamanho, convertendo-se em blastocisto expandido. A zona pelúcida torna-se mais fina e, finalmente, o embrião eclode; isto é, o embrião é liberado da zona pelúcida. -/- • _____FERTILIZAÇÕES ATÍPICAS -/- Polispermia -/- É a penetração de dois ou mais espermatozoides no óvulo. Esta condição é letal nos mamíferos, já que o número cromossômico desse zigoto é maior que 2n, o envelheci-mento do ovócito da porca, como consequência do serviço tardio, favorece a apresentação da polispermia, por isso, é comum ver números de nascimentos de média de 10 a 12 leitões por parição nessa espécie. Nas aves, no entanto, a penetração de mais de um espermatozoide é normal, embora apenas um pronúcleo masculino se formará, fundindo-se com o feminino. -/- Figura 6: etapas do processo de segmentação/clivagem. Fonte: aula de reprodução da professora Domenica Palomaris, UFT. -/- Ginogênese -/- É o desenvolvimento de um embrião a partir de um óvulo normal fecundado por um espermatozoide, mas sem a fusão dos cromossomos masculinos com os da fêmea. A função do espermatozoide, nesse caso, é a de ativação do ovócito para que este inicie seu desenvolvimento, mas não há fusão com o núcleo do espermatozoide. Ocorre em plantas, em nematódeos e em algumas espécies de peixes, por exemplo a Poecilia formosa, espécie em que os ovócitos das fêmeas são ativados por machos de outra espécie relacio-nada. -/- Partenogênese -/- Consiste no desenvolvimento do embrião sem a participação do espermatozoide. Ocorre em alguns insetos, o zangão, por exemplo, é partenogenético. Também pode apresentar-se em perus, cujos embriões são machos e, geralmente, morrem antes da eclosão. -/- • _____GÊMEOS -/- Existem dois tipos de gêmeos: idênticos ou monozigóticos e os não idênticos ou dizigóticos. -/- Idênticos ou monozigóticos -/- Originam-se do mesmo zigoto, sendo assim, possuem o mesmo genótipo e um fenótipo similar e, portanto, são do mesmo sexo. Em laboratório é possível gerá-los ao seccionar uma mórula em duas ou mais partes, por meio de um micromanipulador. Uma vez que possuem o mesmo genótipo, os produtos resultantes são clones. -/- Não idênticos ou dizigóticos -/- Provêm da fertilização de dois óvulos distintos por espermatozoides diferentes. Possuem, portanto, genótipos e fenótipos diferentes, e podem ser de sexo diferente. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ALBERTS, Bruce et al. Biologia molecular da célula. Artmed Editora, 2010. AUSTIN, Colin Russell; SHORT, Roger Valentine. Reproduction in Mammals, Book I: Germ Cells and Fertilization. 1982. BEARDEN, Henry Joe et al. Reproducción animal aplicada. México: Manual Moderno, 1982. BOSCH, P.; WRIGHT JR, R. W. The oviductal sperm reservoir in domestic mammals. Archivos de medicina veterinaria, v. 37, n. 2, p. 95-105, 2005. CAPALLEJAS, Roberto Brito; RODRÍGUEZ, Lourdes Tagle. Fisiología de la reproducción animal: con elementos de biotecnología. Editorial Félix Varela, 2010. CROXATTO, Horacio B. Physiology of gamete and embryo transport through the fallopian tube. Reproductive biomedicine online, v. 4, n. 2, p. 160-169, 2002. CUPPS, Perry T. (Ed.). Reproduction in domestic animals. Elsevier, 1991. DIEDRICH, Smidt et al. Endocrinología y Fisiología de la Reproducción de los Animales Zootécnicos. 1972. DUKES, Henry Hugh; SWENSON, Melvin J.; REECE, William O. Dukes fisiologia dos animais domésticos. Editora Guanabara Koogan, 1996. FERREIRA, A. de M. Reprodução da fêmea bovina: fisiologia aplicada e problemas mais comuns (causas e tratamentos). Juiz de Fora: Minas Gerais–Brasil, p. 422, 2010. HAFEZ, Elsayed Saad Eldin; HAFEZ, Bahaa. Reprodução animal. São Paulo: Manole, 2004. HUNTER, Ronald Henry Fraser. The Fallopian tubes in domestic mammals: how vital is their physiological activity?. Reproduction Nutrition Development, v. 45, n. 3, p. 281-290, 2005. HUNTER, R. H. F.; RODRIGUEZ‐MARTINEZ, H. Capacitation of mammalian spermatozoa in vivo, with a specific focus on events in the Fallopian tubes. Molecular Reproduction and Development: Incorporating Gamete Research, v. 67, n. 2, p. 243-250, 2004. GALINA, Carlos; VALENCIA, Javier. Reproducción de los animales domésticos. 2006. HOPPER, Richard M. (Ed.). Bovine reproduction. John Wiley & Sons, 2014. HYTTEL, Poul; SINOWATZ, Fred; VEJLSTED, Morten. Embriologia veterinária. Elsevier Brasil, 2012. KÖLLE, Sabine; REESE, Sven; KUMMER, Wolfgang. New aspects of gamete transport, fertilization, and embryonic development in the oviduct gained by means of live cell imaging. Theriogenology, v. 73, n. 6, p. 786-795, 2010. MCKINNON, Angus O. et al. (Ed.). Equine reproduction. John Wiley & Sons, 2011. OLIVERA, Martha et al. El espermatozoide, desde la eyaculación hasta la fertilización. Revista Colombiana de Ciencias Pecuarias, v. 19, n. 4, p. 426-436, 2006. PLANT, Tony M.; ZELEZNIK, Anthony J. (Ed.). Knobil and Neill's physiology of reproduction. New York: Academic Press, 2014. RODRIGUEZ-MARTINEZ, Heriberto. Role of the oviduct in sperm capacitation. Theriogenology, v. 68, p. S138-S146, 2007. SAAVEDRA LEOS, María Dolores. Estudio de la composición de los gránulos corticales y del oolema de ovocitos porcinos y bovinos madurados y fecundados in vitro. Proyecto de investigación:, 2010. SENGER, Phillip L. et al. Pathways to pregnancy and parturition. Current Conceptions, Inc, 2004. SUAREZ, Susan S. The oviductal sperm reservoir in mammals: mechanisms of formation. Biology of Reproduction, v. 58, n. 5, p. 1105-1107, 1998. VALENCIA MÉNDEZ, Javier de J. Fisiología de la reproducción porcina. 1986. -/- FIXAÇÃO DO ASSUNTO -/- 1. Defina e diferencie fertilização e segmentação. -/- 2. Disserte sobre o transporte do ovócito. Por que no istmo o transporte do ovócito se torna lento? -/- 3. Fale sobre a eficiência do transporte do gameta no trato genital da fêmea e sobre a retenção de ovócitos pela égua. -/- 4. Defina as células do cumulus e explique seu papel sobre o ovócito. -/- 5. Quais as estruturas que compõem o ovócito? Qual a função de cada uma? -/- 6. Todos os ovócitos das fêmeas domésticas são iguais? Justifique. -/- 7. Disserte sobre o papel dos hormônios e das secreções sobre o transporte do ovócito no trato genital da fêmea. -/- 8. Disserte sobre o transporte do espermatozoide. Por que há transporte rápido e lento dos espermatozoides? -/- 9. Fale sobre o local de deposição do sêmen nas espécies domésticas e como esse influen-cia na eficiência da reprodução. -/- 10. Por que a vida média do espermatozoide canino é maior que as outras espécies? -/- 11. Quais as mudanças que os espermatozoides precisam sofrer para conseguir êxito na fertilização e por quê? -/- 12. Defina fase de transporte rápido, fase sustentada e hipermotilidade. Qual a importân-cia de cada um? -/- 13. Como ocorre a reação acrossômica? -/- 14. O que é polispermia e como ocorre seu bloqueio? 15. Como ocorre a ativação do ovócito e como se formam os pronúcleos? -/- 16. O que é e qual a importância da singamia? -/- 17. Disserte sobre as divisões de segmentação e qual a importância destas para o êxito da reprodução. -/- 18. Defina e diferencia mórula e blastocisto. -/- 19. Defina e diferencie ginogênese e partenogênese. -/- 20. Qual o papel endócrino e quais hormônios e enzimas atuam sobre o transporte de gametas, sobre a fertilização e sobre a segmentação? (shrink)

This essay contains an attempt to trace the evolution of the concept of wisdom as found in the thought of Aristotle and Aquinas in terms of how the philosophical concept of wisdom as an intellectual virtue is understood and used to express the theological concept of wisdom as a gift of the Holy Spirit. The main aim is to understand how Aquinas derived the concept of wisdom from Aristotle's metaphysics and developed it in his mysticism. This research is based on (...) a close study of Book Six of Aristotle's Nichomachean Ethics, the corresponding sections of Aquinas' Sententia libri Ethicorum and question forty-five of the second part of the second part of Aquinas' Summa Theologiae. The insights gained from the study are then used to decipher the theoretical meaning of Augustine's famous saying: "love and do what thou wilt" and to expound on the practical value of wisdom for religious leaders. (shrink)

Functionalists about truth employ Ramsification to produce an implicit definition of the theoretical term _true_, but doing so requires determining that the theory introducing that term is itself true. A variety of putative dissolutions to this problem of epistemic circularity are shown to be unsatisfactory. One solution is offered on functionalists' behalf, though it has the upshot that they must tread on their anti-pluralist commitments.

In this paper I address the phenomenon of syncretism with respect to Chinese religions. An analysis of the syncretism that takes place between the three major Chinese religious traditions is first done in its personal and social dimensions. The social structure of Chinese religion is then used as a framework to understand how Buddhism and Daoism were made compatible with Confucianism. All this will serve as a background for the case study of Macau, where Chinese religious syncretism is very much (...) alive. Three popular religious festivals are celebrated annually and simultaneously on the eighth day of the fourth lunar month, namely, zuilongjie (醉龍節) Feast of the Drunken Dragon, tangongdan (譚公誕) Tam Kung Festival and fodanjie (佛誕節) Feast of the Buddha. (shrink)

Confucian education is best captured by the programme described in the Great Learning. Education is presented first as the process of self-cultivation for the sake of developing virtuous character. Self-cultivation then allows for virtue to be cultivated in the familial, social and international dimensions. My central thesis is that Confucianism can serve as a universal framework of educating people for the common good in its promotion of personal cultivation for the sake of human progress. On this account the common good (...) specifically refers to the social order accomplished by the virtuous behaviour found in the members of society. In this paper I argue that the Confucian notion of “lesser learning” sheds light on the concept of general education and the notion of “greater learning” improves our understanding of liberal education. Under this analysis the necessity of general education is assured although its importance should not be overly exaggerated. Furthermore, the objectives of liberal education deserve greater emphasis due to their historical importance and enduring relevance to promoting the common good of universal humanity. (shrink)

In contemporary debates in religious epistemology, theistic philosophers provide differing responses to the evidentialist argument against religious beliefs. Plantinga’s strategy is to argue that evidence is not needed to justify religious beliefs while Swinburne’s strategy is to argue that religious beliefs can be justified by evidence. However, in Aquinas’ account of religious epistemology, he seems to employ both strategies. In his account of religious knowledge by faith, he argues that evidence is unnecessary for religious beliefs. But in his account of (...) religious knowledge by science, he argues that there is evidence for religious beliefs. In this paper, I argue that there is no real dichotomy between Plantinga’s and Swinburne’s responses to the evidentialist argument. From a Thomistic perspective, Reformed Epistemology and Natural Theology are different but compatible responses to Evidentialism. (shrink)

The papers that make up this special issue do not take idealized abstractions of context as their point of departure but rather start with the actual phenomena under study and later generalize. We agree that, more often than not, giving a formal model and providing a theory of a loaded notion – such as context – can lead to important insights. Thus, precise models of context and accompanying theories are useful. However, given the widely different fields, methodologies and worldviews within (...) which people study, an approach that starts with the root phenomena/problems and only attempts normalization and generalization post hoc might be a more productive way to proceed. (shrink)

When talking about truth, we ordinarily take ourselves to be talking about one-and-the-same thing. Alethic monists suggest that theorizing about truth ought to begin with this default or pre-reflective stance, and, subsequently, parlay it into a set of theoretical principles that are aptly summarized by the thesis that truth is one. Foremost among them is the invariance principle.

As much as assumptions about mechanisms and mechanistic explanation have deeply affected psychology, they have received disproportionately little analysis in philosophy. After a historical survey of the influences of mechanistic approaches to explanation of psychological phenomena, we specify the nature of mechanisms and mechanistic explanation. Contrary to some treatments of mechanistic explanation, we maintain that explanation is an epistemic activity that involves representing and reasoning about mechanisms. We discuss the manner in which mechanistic approaches serve to bridge levels rather than (...) reduce them, as well as the different ways in which mechanisms are discovered. Finally, we offer a more detailed example of an important psychological phenomenon for which mechanistic explanation has provided the main source of scientific understanding. (shrink)

One type of argument to sceptical paradox proceeds by making a case that a certain kind of metaphysically “heavyweight or “cornerstone” proposition is beyond all possible evidence and hence may not be known or justifiably believed. Crispin Wright has argued that we can concede that our acceptance of these propositions is evidentially risky and still remain rationally entitled to those of our ordinary knowledge claims that are seemingly threatened by that concession. A problem for Wright’s proposal is the (...) so-called Leaching worry: if we are merely rationally entitled to accept the cornerstones without evidence, how can we achieve evidence-based knowledge of the multitude of quotidian propositions that we think we know, which require the cornerstones to be true? This paper presents a rigorous, novel explication of this worry within a Bayesian framework, and offers the Entitlement theorist two distinct responses. (shrink)

Politics, Philosophy & Economics, Volume 21, Issue 4, Page 347-371, November 2022. We sometimes have to choose between options that are seemingly incomparable insofar as they seem to be neither better than, worse than, nor equal to each other. This often happens when the available options are quite different from one another. For instance, consider a choice between prioritizing either criminal justice reform or healthcare reform as a public policy goal. Even after the relevant details of the goals and possible (...) reforms are filled in, it is plausible that neither goal is better than, worse than, nor equal to the other. Such seemingly incomparable options present a problem for rational choice since it is unclear how an agent might rationally choose between them. What we need are some principles to help govern rational choice when faced with seemingly incomparable options. I here present three such principles. While each principle is individually compelling, I show that they are jointly incompatible. I then argue that the correct response to this inconsistent triad is to reject the principle that rationally censures performing a sequence of choices one knows will result in a suboptimal outcome. The upshot is that when seeming incomparability is involved, an agent can money pump themselves without being less rational for it. (shrink)

In this paper, I explore what gives collective testimony its epistemic credentials, through a critical discussion of three competing accounts of the epistemology of collective testimony. According to the first view, collective testimony inherits its epistemic credentials from the beliefs the testimony expresses— where this can be seen either as the beliefs of all or some of the group’s members, or as the beliefs of group itself. The second view denies any necessary connection to belief, claiming instead that the epistemic (...) credentials of collective testimony derive from the reliability or truth-conduciveness of the statement that expresses the testimony. Finally, the third view claims that the epistemic credentials of collective testimony derive from the fact that it involves undertaking a collective commitment to trustworthiness, which makes the group susceptible to rebuke and blame if its testimony is not trustworthy. I argue that this last account holds the most promise for preserving what is distinctive about testimonial knowledge while still underwriting a robust epistemology of collective testimony. (shrink)

Over the past few decades, Indigenous communities have successfully campaigned for greater inclusion in decision-making processes that directly affect their lands and livelihoods. As a result, two important participatory rights for Indigenous peoples have now been widely recognized: the right to consultation and the right to free, prior and informed consent (FPIC). Although these participatory rights are meant to empower the speech of these communities—to give them a proper say in the decisions that most affect them—we argue that the way (...) these rights have been implemented and interpreted sometimes has the opposite effect, of denying them a say or ‘silencing’ them. In support of this conclusion we draw on feminist speech act theory to identify practices of locutionary, illocutionary, and perlocutionary group silencing that arise in the context of consultation with Indigenous communities. (shrink)

For much of the first fifty years of its existence, analytic philosophy shunned discussions of normativity and ethics. Ethical statements were considered as pseudo-propositions, or as expressions of pro- or con-attitudes of minor theoretical significance. Nowadays, in contrast, prominent analytic philosophers pay close attention to normative problems. Here we focus our attention on the work of Searle, at the same time drawing out an important connection between Searle’s work and that of two other seminal figures in this development: H.L.A. Hart (...) and John Rawls. We show that all three thinkers tend to assume that there is but one type of normativity within the realm of social institutions – roughly, the sort of normativity that is involved in following the results of chess – and that they thereby neglect features that are of crucial significance for an adequate understanding of social reality. (shrink)

Recent feminist philosophy of language has highlighted the ways that the speech of women can be unjustly impeded, because of the way their gender affects the uptake their speech receives. In this chapter, I explore how similar processes can undermine the speech of a different sort of speaker: Indigenous communities. This involves focusing on Indigeneity rather than gender as the salient social identity, and looking at the ways that group speech, rather than only individual speech, can be unjustly impeded. To (...) do this, I make use of the notion of ‘discursive injustice’ that has been developed by Quill Kukla, and, with reference to three case studies, show how discursive injustice can effectively derail the speech of Indigenous communities. (shrink)

Jennifer Lackey (2018) has developed an account of the primary form of group assertion, according to which groups assert when a suitably authorized spokesperson speaks for the group. In this paper I pose a challenge for Lackey's account, arguing that her account obscures the phenomenon of group silencing. This is because, in contrast to alternative approaches that view assertions (and speech acts generally) as social acts, Lackey's account implies that speakers can successfully assert regardless of how their utterances are taken (...) up by their audiences. What reflection on group silencing shows us, I argue, is that an adequate account of group assertion needs to find a place for audience uptake. (shrink)

According Philip Pettit, suitably organised groups not only possess ‘minds of their own’ but can also ‘make up their minds’ and 'speak for themselves'--where these two capacities enable them to perform as conversable subjects or 'persons'. In this paper I critically examine Pettit's case for group personhood. My first step is to reconstruct his account, explaining first how he understands the two capacities he considers central to personhood – the capacity to ‘make up one’s mind’, and the capacity to ‘speak (...) for oneself’ – before showing how he thinks these can be manifested in groups. With Pettit’s account duly reconstructed, I then turn to criticism, arguing that Pettit’s construal of making up one’s mind does not do proper justice to our first-personal self-understanding, nor to our characteristic interpersonal forms of engagement. This leads me, finally, to consider an alternative construal of ‘making up one’s mind’ and ‘speaking for oneself’ that is associated with the work of Richard Moran and whichargue, could usefully be exteextended to groups. (shrink)

Psychoneural reductionists sometimes claim that sufficient amounts of lower-level explanatory achievement preclude further contributions from higher-level psychological research. Ostensibly, with nothing left to do, the effect of such preclusion on psychological explanation is extinction. Reductionist arguments for preclusion have recently involved a reorientation within the philosophical foundations of neuroscience---namely, away from the philosophical foundations and toward the neuroscience. In this chapter, I review a successful reductive explanation of an aspect of reward function in terms of dopaminergic operations of the mesocorticolimbic (...) system in order to demonstrate why preclusion/extinction claims are dubious. (shrink)

The free-energy principle states that all systems that minimize their free energy resist a tendency to physical disintegration. Originally proposed to account for perception, learning, and action, the free-energy principle has been applied to the evolution, development, morphology, anatomy and function of the brain, and has been called a postulate, an unfalsifiable principle, a natural law, and an imperative. While it might afford a theoretical foundation for understanding the relationship between environment, life, and mind, its epistemic status is unclear. Also (...) unclear is how the free-energy principle relates to prominent theoretical approaches to life science phenomena, such as organicism and mechanism. This paper clarifies both issues, and identifies limits and prospects for the free-energy principle as a first principle in the life sciences. (shrink)

On March 14-15, 2006, at the US National Institute of Standards and Technology (NIST) in Gaithersburg, MD there took place the first Upper Ontology Summit (UOS). This was a convening of custodians of several prominent upper ontologies, key technology participants, and interested other parties, with the purpose of finding a means to relate the different ontologies to each other. The result is reflected in a joint communiqué, directed to the larger ontology community and the general public, and expressing a joint (...) intent to build bridges among the existing upper ontologies in ways designed to increase and rationalize their utilization and to enhance their semantic interoperability. (shrink)

Lay persons may have intuitions about morality's objectivity. What do these intuitions look like? And what are their causes and consequences? In recent years, an increasing number of scholars have begun to investigate these questions empirically. This article presents and assesses the resulting area of research as well as its potential philosophical implications. First, we introduce the methods of empirical research on folk moral objectivism. Second, we provide an overview of the findings that have so far been made. Third, we (...) raise a number of methodological worries that cast doubt upon these findings. And fourth, we discuss ways in which lay persons' intuitions aboutmoral objectivity may bear on philosophical claims. (shrink)

The acculturation gap is the changing set of values and culture between a child and parent or guardian. The gap is usually revealed after a family immigrates from one country to another and assimilates into a culture.

Recent years have seen rapid progress in the development of ontologies as semantic models intended to capture and represent aspects of the real world. There is, however, great variation in the quality of ontologies. If ontologies are to become progressively better in the future, more rigorously developed, and more appropriately compared, then a systematic discipline of ontology evaluation must be created to ensure quality of content and methodology. Systematic methods for ontology evaluation will take into account representation of individual ontologies, (...) performance (in terms of accuracy, domain coverage and the efficiency and quality of automated reasoning using the ontologies) on tasks for which the ontology is designed and used, degree of alignment with other ontologies and their compatibility with automated reasoning. A sound and systematic approach to ontology evaluation is required to transform ontology engineering into a true scientific and engineering discipline. This chapter discusses issues and problems in ontology evaluation, describes some current strategies, and suggests some approaches that might be useful in the future. (shrink)

I explore the possibility and rationality of interpersonal mechanisms of doxastic self-control, that is, ways in which individuals can make use of other people in order to get themselves to stick to their beliefs. I look, in particular, at two ways in which people can make interpersonal epistemic commitments, and thereby willingly undertake accountability to others, in order to get themselves to maintain their beliefs in the face of anticipated “epistemic temptations”. The first way is through the avowal of belief, (...) and the second is through the establishment of collective belief. I argue that both of these forms of interpersonal epistemic commitment can function as effective tools for doxastic self-control, and, moreover, that the control they facilitate should not be dismissed as irrational from an epistemic perspective. (shrink)

In this paper I critically discuss Miranda Fricker’s ‘trust-based’ view of collective testimony—that is, testimony that comes from a group speaker. At the heart of Fricker’s account is the idea that testimony involves an ‘interpersonal deal of trust’, to which the speaker contributes a commitment to ‘second-personal epistemic trustworthiness’. Appropriating Margaret Gilbert’s concept of joint commitment, Fricker suggests that groups too can make such commitments, and hence that they, like individuals, can ‘enter into the second-personal relations of trust that characterise (...) testimony’ (Fricker 2012: 272). I argue that this choice to appropriate Gilbert’s concept of joint commitment betrays a deep problem in Fricker’s account—a misconstrual of both the object and the subject(s) of the commitment a speaker makes in testifying. After developing this criticism, I outline an alternative way of construing the speaker’s commitment, which can be applied to both collective and individual testimony. (shrink)

This paper presents an argument against the A-Theory of time. Briefly, I shall contend that the A-Theorist has no explanation for why the present moment in particular has the metaphysical privilege she accords it, and that this puts the theory at a disadvantage. In what follows, I shall begin by presenting this argument. I will follow that with some potential explanations for why the present moment is privileged and reasons militating against them, in addition to some other possible objections to (...) my argument and my responses to them. The conclusion will be that the A-Theorist fails to provide either an obvious or a theoretical explanation of the present time’s privileged status and is thereby at a theoretical disadvantage to theories that do not posit a metaphysically privileged present time. Topics covered include the purported analogy between times and worlds, the possibility that times are individuated by what is true at them, and the semantic status of titles for date-times. (shrink)

Courtesy of its free energy formulation, the hierarchical predictive processing theory of the brain (PTB) is often claimed to be a grand unifying theory. To test this claim, we examine a central case: activity of mesocorticolimbic dopaminergic (DA) systems. After reviewing the three most prominent hypotheses of DA activity—the anhedonia, incentive salience, and reward prediction error hypotheses—we conclude that the evidence currently vindicates explanatory pluralism. This vindication implies that the grand unifying claims of advocates of PTB are unwarranted. More generally, (...) we suggest that the form of scientific progress in the cognitive sciences is unlikely to be a single overarching grand unifying theory. (shrink)

According to Margaret Gilbert, two or more people collectively believe that p if and only if they are jointly committed to believe that p as a body. But the way she construes joint commitment in her account – as a commitment of and by the several parties to “doing something as a body” – encourages the thought that the phenomenon accounted for is not that of genuine belief. I explain why this concern arises and explore a different way of construing (...) joint commitment, in order to avoid the concern. This leads me to propose a revised Gilbertian account of collective belief, according to which two or more people collectively believe that p if and only if they are jointly committed to p as true. (shrink)

In the midst of current social change and public debates regarding provision of reproductive health education and services in the Philippines, the need exists to understand the realities of teenagers and young adults’ lives and the challenges they face in finding the way sexual and reproductive well-being. Although a few studies have focused on quantifying unintended pregnancy and abortion in the Philippines, few investigations using qualitative research methods have been conducted to more fully explore and situate these phenomena. Unsafe abortion (...) through the use of abortifacients has been practiced since time immemorial. An estimated 26 million pregnancies are terminated legally throughout the world, and 20 million are terminated illegally, with more than 78,000 deaths. The Philippines, with a steadily increasing population that is approaching 100 million, faces significant challenges in the area of reproductive health. -/- . (shrink)

This discourse analysis aimed to expose the context of globalization in the face of COVID 19 pandemic. I contend to refute the notion that globalization is the same before and during the pandemic crisis. Moreover, I seek to bring out the contextual landscape of social and cultural changes as influenced by pandemic and how the conduct of globalization in terms of power struggle, digitalization, debt and geographies of blame, care, interdependence, infection, immunization, vulnerability and resilience are being redefined in its (...) optimum level. (shrink)

We distinguish between two different strategies in methodology of economics. The big picture strategy, dominant in the twentieth century, ascribed to economics a unified method and evaluated this m...

According to non-cognitivism, moral sentences and judgements do not aim to represent how things morally are. This paper presents an empirical argument against this view. We begin by showing that non-cognitivism entails the prediction that after some reflection competent ordinary speakers’ semantic intuitions favor that moral sentences and judgements do not aim to represent how things morally are. At first sight, this prediction may seem to have been confirmed by previous research on folk metaethics. However, a number of methodological worries (...) lead us to doubt this interpretation. We, therefore, conducted a psychological study that alleviates these worries as far as possible. It turned out that competent ordinary speakers’ reflective semantic intuitions dominantly fail to favor that moral sentences do not aim to represent how things morally are. This challenge to non-cognitivism is defended and supplemented by considering deflationary theories of moral truth and middle ground theories in the cognitivism/non-cognitivism debate. (shrink)

The cognitive sciences are facing questions of how to select from competing theories or develop those that suit their current needs. However, traditional accounts of theoretical virtues have not yet proven informative to theory development in these fields. We advance a pragmatic account by which theoretical virtues are heuristics we use to estimate a theory’s contribution to a field’s body of knowledge and the degree to which it increases that knowledge’s ability to solve problems in the field’s domain or problem (...) space. From this perspective, properties that are traditionally considered epistemic virtues, such as a theory’s fit to data or internal coherence, can be couched in terms of problem space coverage, and additional virtues come to light that reflect a theory’s alignment with problem-having agents and the context in a societally embedded scientific system. This approach helps us understand why the needs of different fields result in different kinds of theories and allows us to formulate the challenges facing cognitive science in terms that we hope will facilitate their resolution through further theoretical development. (shrink)

This study which utilized the critical analysis, analyzed Wittgenstein’s concept of language-game and its implications in philosophical discipline and contemporary society. To delineate the origin of the problem of language in terms of epistemological dimension, the researcher analyzed the related concepts on classical philosophy. To determine the origin of the concept of language-game, the researcher used the historical method. To constructively criticize the end-goal of language-game, the hermeneutical approach of Hans Georg Gadamer was employed. From the findings and with the (...) aid of the above-mentioned methods, the researcher had come up with these conclusions. Language is inalienable in the sociological nature of man. Man is always related or connected to the other. In this sense, man shares his very subjectivity with the other. Unless he realizes this, he cannot actualize the essential part of his nature. In every aspect of man’s life, it is imperative for him to negotiate, communicate, and collaborate with the members of his household and society. Wittgenstein is the one of the philosophers who gave deeper commitment and emphasis on the concerns of language in man’s life. Mastering our use of language is not just for the sake of conventional understanding, but, more importantly, we use it in its proper context in order to express our thoughts clearly and in the process to understand ourselves. It is because, as we speak or write using language as medium of communication, we are projecting ourselves to the other. If we come up with the c common understanding, then we will be able to create a harmonious society. This study provided the readers with a better understanding of the importance of proper use of words or terminologies in their proper context. It is because this research delved on the conceptual and analytical mechanisms of using language in order to give a systematic pattern of corrective thinking and application for word’s use. Aside from affirming the importance of language in connection with our contemporary activities, this research looked into a deeper realization on the workings of language. This realization originated from Wittgensteinian context of understanding. As affirmation for Wittgenstein, it is appropriate to say that to understand a word in its proper context is to understand the sentence. To understand a sentence is to understand a language. To understand a language means to be master of technique. This signifies that understanding is to know how to do something; in the case of language, understanding language means knowing how to use it. The researcher realized that understanding the meaning of a word is not something private to the mental life of an individual, but something which exist out in the open, in the public domain. This means that understanding the meaning is objectively understandable by people. However, the researcher did not agree with Wittgenstein’s view that philosophy should stop once we clear the way of understanding how our language works. Instead, the researcher adheres to the fact that philosophy as enterprise is an undying process in search for truth. For the researcher, we do not stop philosophizing because our imaginations continue to desire progress in terms of creativity. Thus, he affirmed Gadamer in claiming that we should not hinder our philosophical endeavors by breaking it. Even if we can clear the confusions and misunderstanding of language, still our active minds cling to what is new in the field of learning things. This research led to the formulation of other theories which can be useful tool in understanding the complexities with regards to ourselves and our society as a whole. Henceforth, all the laborious efforts of this research and the regimented time invested in the writing of this work are meaningfully compensated. (shrink)

Many cognitive scientists, having discovered that some computational-level characterization f of a cognitive capacity φ is intractable, invoke heuristics as algorithmic-level explanations of how cognizers compute f. We argue that such explanations are actually dysfunctional, and rebut five possible objections. We then propose computational-level theory revision as a principled and workable alternative.

Concept Progress is a fusion of science fiction and philosophy. It is a thesis on metaphysics that stretches beyond the scope of modern science and scratches many of our curious itches. The thesis is complemented by short and loosely tied sci-fi stories that make its conceptualizations come to life. ​ The central theme throughout is that progress is a driving force in human evolution. This recurring viewpoint has previously stirred much debate. However, as we escalate through the twenty-first century, the (...) evidence is plentiful. Concept Progress offers a fresh perspective into the topic, citing humanity's ongoing accomplishments as a convincing piece of that evidence. In the book, we celebrate ourselves for our achievements, challenge our perceived limits, and conclude that progress will eventually produce the most evolved life form. In so doing, we look back to the beginning of time and circle forward to a time that is farther away than the current age of the universe. ​ While the tone of the book's body resembles that of a philosophical prose, with each chapter, the reader realizes more and more that the narrative is actually one of science fiction. The intent of the book's structure and approach is manifold. ​ First, it is safe to say that any literature that points to the future is already, by definition, a work of fiction—no matter how serious it tries to sound. Imagining future technologies, foreseeing the next stages of human evolution, and exploring the realm of the highest dimension surely makes it a science fiction. ​ Second, the book is a collection of concepts—abstract notions of the mind that reflect our grasp on certain aspects of reality. It is also a play on those concepts, exposing how our progressive understanding of these notions can gradually be transcended. Each chapter starts with a sketch of a particular concept whose humanistic yet quantum mechanical context lets us identify with it and be mystified by it. From the concepts of sound and light to the concepts of consciousness and coexistence, each concept tale depicts a personal expression of our mutual worldview. ​ Third, each one of the ten chapters concludes with a science fiction story. These stories project the theme further and subtly point to each other. As we connect the dots from one story to another, the outline reveals a world that makes us wonder whether we are headed toward its future or whether we will bypass it as an alternate universe. In one story, we meet the inventor of mind-reading technology while in another story, we meet an artificial life form that will be made possible by this technology. Yet another story is about the time-traveling mind of an astrophysicist whose life's work has impacts on whole timelines, as revealed by a different story. In the end, it all comes together with the final piece of the puzzle completing not only the short story series, but also the novel as a whole. ​ Each three-part chapter is a triad with a distinct purpose in mind. We begin the journey with our own curiosity. This basic emotion allows us to open the door to that which we are so curiously seeking. Essentially, that covers everything. In questioning the entirety of existence, we commence with the premise that it is the element of life that sends us on a quest for meaning. So we review the trend of life's evolution on Earth from its roots to the present day and follow this trend into the distant future. The process of evolutionary development leads us to a recipe for one's own personal progress, which is comprised of physical, mental, and spiritual ingredients. It soon becomes clear that a species can change only insofar as its individual members embrace this change. And we realize that our choice in the matter has impacts not only on our own future, but also on the future of everyone who shares our timeline. ​ In some ways, Concept Progress is a modern reflection of Charles Darwin's revolutionary theory of evolution. In other ways, it is an encouraging observation of our humble human existence. As we widen the time scale and follow this evolutionary trend from biological, social, and cosmic angles, the concepts of evolution and progress slowly but surely become synonymous. (shrink)

This paper adds to the philosophical literature on mechanistic explanation by elaborating two related explanatory functions of idealisation in mechanistic models. The first function involves explaining the presence of structural/organizational features of mechanisms by reference to their role as difference-makers for performance requirements. The second involves tracking counterfactual dependency relations between features of mechanisms and features of mechanistic explanandum phenomena. To make these functions salient, we relate our discussion to an exemplar from systems biological research on the mechanism for countering (...) heat shock—the heat shock response system—in Escherichia coli bacteria. This research also reinforces a more general lesson: ontic constraint accounts in the literature on mechanistic explanation provide insufficiently informative normative appraisals of mechanistic models. We close by outlining an alternative view on the explanatory norms governing mechanistic representation. (shrink)

The parceling of land into real estate is more than a simple geometrical affair. Real estate is a historical product of interaction between human beings, political, legal and economic institutions, and the physical environment. And while many authors, from Jeremy Bentham to Hernando de Soto, have drawn attention to the ontological (metaphysical) aspect of property in general, no comprehensive analysis of landed property has been attempted. The paper presents such an analysis and shows how landed property differs from other types (...) of property in a way which implies a special role for political and economic philosophy of property rights in land. This is the Chinese translation of "The Metaphysics of Real Estate", Topoi, 20: 2 (September 2001), 161–172. (shrink)

We focus on Timothy Williamson’s recent attack on the epistemological significance of the a priori–a posteriori distinction, and offer an explanation of why, fundamentally, it does not succeed. We begin by setting out Williamson’s core argument, and some of the background to it and move to consider two lines of conciliatory response to it—conciliatory in that neither questions the central analogy on which Williamson's argument depends. We claim, setting aside a methodological challenge to which Williamson owes an answer, that no (...) satisfactory such reconciliation is in prospect. Rather, as we then argue, —and it is on this that we base our overall negative assessment of his argument—Williamson’s core analogy is flawed by an oversight. We conclude with some brief reflections on Williamson’s ideas about the imagination as a source of knowledge. Our principal conclusion is only that Williamson’s argument fails to perform as advertised. A constructive case for confidence, to the contrary, that the intuitive contrast between a priori and a posteriori reflects something of fundamental epistemological significance is prefigured in our final section, but will not be elaborated here. (shrink)