This paper examines Plato’s conception of shame and the role intoxication plays in cultivating it in the Laws. Ultimately, this paper argues that there are two accounts of shame in the Laws. There is a public sense of shame that is more closely tied to the rational faculties and a private sense of shame that is more closely tied to the non-rational faculties. Understanding this division between public and private shame not only informs our understanding of Plato’s moral psychology, but (...) his political and ethical theory as well. (shrink)

In Republic 1, Thrasymachus makes the radical claim that being just is ‘high-minded simplicity’ and being unjust is ‘good judgment’ (348c–e). Because injustice involves benefiting oneself, while justice involves benefiting others, the unjust are wise and good and the just are foolish and bad (348d–e). The “greedy craftsperson” argument (1.349b–350c) attempts to show that the unjust person's desire to outdo or have more than ( pleon echein) everyone is a symptom of her ignorance. Many commentaries have found the argument problematic (...) and unclear. However, this paper argues that the greedy craftsperson argument defends plausible constraints on the nature of justice and wisdom. (shrink)

In both the Laches (191d-e) and the Laws (1.633c-d, 1.634a-b, and 1. 635d), Plato has his protagonist defend the claim that courage (andreia) is not simply a matter of resisting pain and fear but about overcoming pleasure and desire as well. In this paper, I argue that Plato took the expansive view of courage seriously and that there are several reasons why we should too.

Socrates' attitude towards falsehood is quite puzzling in the Republic. Although Socrates is clearly committed to truth, at several points he discusses the benefits of falsehood. This occurs most notably in Book 3 with the "noble lie" (414d-415c) and most disturbingly in Book 5 with the "rigged sexual lottery" (459d-460c). This raises the question: What kinds of falsehoods does Socrates think are beneficial, and what kinds of falsehoods does he think are harmful? And more broadly: What can this tell us (...) about the relationship between ethics and epistemology? The key to answering these questions lies in an obscure and paradoxical passage in Book II; at 382a-d Socrates distinguishes between "true falsehoods" and "impure lies." True falsehoods are always bad, but impure lies are sometimes beneficial. Despite Socrates' insistence that he is not saying anything deep, his distinction is far from straightforward. Nevertheless, in order to determine why some falsehoods are beneficial and why some are always harmful, we must understand what exactly true falsehoods are and how they differ from impure lies. In this paper, I argue that true falsehoods are a restricted class of false beliefs about ethics; they are false beliefs about how one should live and what one should pursue. I refer to these beliefs as "normative commitments." False normative commitments are always pernicious because they create and sustain psychological disharmony. Unlike true falsehoods, impure lies can be about anything. Nevertheless, they are only beneficial when they help produce and sustain true normative commitments. I argue that the upshot of this is that practical concerns have a kind of primacy over theoretical concerns. (shrink)

In Plato’s Laws, the Athenian Stranger maintains that law should consist of both persuasion (πειθώ) and compulsion (βία) (IV.711c, IV.718b-d, and IV.722b). Persuasion can be achieved by prefacing the laws with preludes (προοίμια), which make the citizens more eager to obey the laws. Although scholars disagree on how to interpret the preludes’ persuasion, they agree that the preludes instill true beliefs and give citizens good reasons for obeying the laws. In this paper I refine this account of the preludes by (...) arguing that the primary purpose of the preludes is to motivate correct action, and that for citizens who lack rational-governance this is achieved via useful false beliefs. That is to say, in many cases, the prelude functions as a “noble lie” (γενναῖον ψεῦδος). (shrink)

The Gorgias ends with Socrates telling an eschatological myth that he insists is a rational account and no mere tale. Using this story, Socrates reasserts the central lessons of the previous discussion. However, it isn’t clear how this story can persuade any of the characters in the dialogue. Those (such as Socrates) who already believe the underlying philosophical lessons don’t appear to require the myth, and those (such as Callicles) who reject these teachings are unlikely to be moved by this (...) far-fetched tale. This raises the question of who the myth is told for and what function it is meant to serve. This chapter argues that the myth is aimed, not at Callicles, but Socrates and those who aspire to follow him. There are uncertainties about the philosophical life that are due to the nature of embodiment, as well as reasons to doubt the connection between happiness and virtue. The myth assists with the former by presenting an image that draws a philosopher away from the goods of the body toward the goods of the soul. The story assists with the latter by presenting an image of cosmic justice, thereby securing happiness in proportion to virtue. (shrink)

A common theological perspective holds that God does not deceive because lying is morally wrong. While Plato denies the possibility of divine deception in the Republic, his explanation does not appeal to the wrongness of lying. Indeed, Plato famously recommends the careful use of lies as a means of promoting justice. Given his endorsement of occasional lying, as well as his claim that humans should strive to emulate the gods, Plato's suggestion that the gods never have reason to lie is (...) puzzling. Our solution to this puzzle centers on the fact that, unlike humans, the gods are self-sufficient. Although lying is good for the souls of neither humans nor gods, human interdependency necessitates lies that will prevent material harms and maintain a just order. In contrast, the self-sufficiency of the gods makes it impossible for them to benefit from deception. (shrink)

Commentators such as Terence Irwin (1999) and Christopher Shields (2006) claim that the Ring of Gyges argument in Republic II cannot demonstrate that justice is chosen only for its consequences. This is because valuing justice for its own sake is compatible with judging its value to be overridable. Through examination of the rational commitments involved in valuing normative ideals such as justice, we aim to show that this analysis is mistaken. If Glaucon is right that everyone would endorse Gyges’ behavior, (...) it follows that nobody values justice intrinsically. Hence, the Gyges story constitutes a more serious challenge than critics maintain. (shrink)

Many transhumanists see their respective movement as being rooted in ancient ethical thought. However, this alleged connection between the contemporary transhumanist doctrine and the ethical theory of antiquity has come under attack. In this paper, we defend this connection by pointing out a key similarity between the two intellectual traditions. Both traditions are committed to the “radical transformation thesis”: ancient ethical theory holds that we should assimilate ourselves to the gods as far as possible, and transhumanists hold that we should (...) enhance ourselves beyond the physical and intellectual parameters of being human so as to become posthuman. By considering the two views in tandem, we develop an account of the assimilation directive that is palatable to contemporary readers and provide a view of posthumanism worth wanting. (shrink)

Russell’s rejection in 1898 of the doctrine of internal relations — the view that all relations are grounded in the intrinsic properties of the terms related — was a decisive part of his break with Hegelianism and opened the way for his turn to analytic philosophy. Before rejecting it, Russell had given the doctrine little thought, though it played an essential role in the most intractable of the problems facing his attempt to construct a Hegelian dialectic of the sciences. I (...) argue that it was Russell’s early reading of Leibniz, in preparation for his lectures on Leibniz given at Cambridge in 1899, that most probably alerted him to the role the doctrine was playing in his own philosophy. Leibniz defended a similar doctrine and extricated it from difficulties like those faced by Russell by means of devices that were not open to Russell. Russell would have come across these views of Leibniz in writings by Leibniz that he read in the summer of 1898, just before he rejected the doctrine of internal relations. (shrink)

Russell is often accused of having a naive ‘Fido’–Fido theory of meaning of the sort Wittgenstein attacked at the beginning of the Philosophical Investigations. In this paper I argue that he never held such a theory though I concede that, prior to 1918, he said various things that might lead a very careless reader to suppose that he had. However, in The Analysis of Mind, a book which we know Wittgenstein studied closely, Russell put forward an account of understanding an (...) utterance which clearly anticipates the use theory of meaning usually attributed to Wittgenstein. The paper concludes with some problems for understanding the use theory of meaning as presented by both Russell and, derivatively, Wittgenstein. (shrink)

In this paper, we highlight some problems for accounts of disability and enhancement that have not been sufficiently addressed in the literature. The reason, we contend, is that contemporary debates that seek to define, characterise or explain the normative valence of disability and enhancement do not pay sufficient attention to a wide range of cases, and the transition between one state and another. In section one, we provide seven cases that might count as disability or enhancement. We explain why each (...) case might count, and on what basis, and why it is been neglected. Each case is explained as a transition in what we call capacity space. We then argue that no definition of disability or enhancement addresses all of these cases, except for strict welfarist accounts of disability that do not rely on a depiction of any particular capacity. We argue further, however, that this is a serious deficiency of welfarist conceptions of disability. We then address objections to our account. (shrink)

This is part 1 of 6 of the dossier What Do We Talk about when We Talk about Queer Death?, edited by M. Petricola. The contributions collected in this article sit at the crossroads between thanatology and queer theory and tackle questions such as: how can we define queer death studies as a research field? How can queer death studies problematize and rethink the life-death binary? Which notions and hermeneutic tools could be borrowed from other disciplines in order to better (...) define queer death studies? The present article includes the following contributions: – MacCormack P., What does queer death studies mean?; – Radomska M., On queering death studies; – Lykke N., Death as vibrancy; – Hillerup Hansen I., What concreteness will do to resolve the uncertain; – Olson P., Queer objectivity as a response to denials of death; – Manganas N., The queer lack of a chthonic instinct. (shrink)

Reflectance physicalists define reflectance as the intrinsic disposition of a surface to reflect finite-duration light pulses at a given efficiency per wavelength. I criticize the received view of dispositional reflectance (David R. Hilbert’s) for failing to account for what I call “harmonic dispersion,” the inverse relationship of a light pulse's duration to its bandwidth. I argue that harmonic dispersion renders reflectance defined in terms of light pulses an extrinsic disposition. Reflectance defined as the per-wavelength efficiency to reflect the superimposed, infinite-duration, (...) Fourier harmonics of pulses can be an intrinsic disposition of surfaces. This conclusion raises questions about mathematical realism, about which I nevertheless remain neutral. (shrink)

Despite the prevalence of human rights discourse, the very idea or concept of a human right remains obscure. In particular, it is unclear what is supposed to be special or distinctive about human rights. In this paper, we consider two recent attempts to answer this challenge, James Griffin’s “personhood account” and Charles Beitz’s “practice-based account”, and argue that neither is entirely satisfactory. We then conclude with a suggestion for what a more adequate account might look like – what we (...) call the “structural pluralist account” of human rights. (shrink)

The urgent importance of dealing with the climate crisis has led some influential theorists to argue that at least some demands for justice must give way to pragmatic and strategic considerations. These theorists (Cass Sunstein, Eric Posner, and David Weisbach, all academic lawyers, and John Broome, an academic philosopher) contend that the failures of international negotiations and other efforts to change economic policies and practices have shown that moral exhortations are worse than ineffective. Although Broome's position is similar in these (...) respects to that of Sunstein, Posner and Weisbach, it differs in other important respects, including his understanding of the idea of justice, his disagreement with the policy approach (which he calls "efficiency with sacrifice") favored by the economists Nicholas Stern and William Nordhaus, and his proposal for establishing a new international financial institution, a World Climate Bank, in addition to putting a price on carbon. Elsewhere I offer a critical analysis of the position taken by Posner and Weisbach in their book, Climate Change Justice. Their arguments against allowing principles of distributive justice (narrowly understood) to constrain treaty negotiations fail to rule out the principles of John Rawls' Law of Peoples (which is a conception of the moral basis of a just international order, including states' obligations to secure basic human rights for all). Therefore their arguments against shaping climate treaties to reflect any principles of justice do not succeed in supporting their position. Here I offer a critical analysis of Broome's position. I raise and discuss objections to Broome's proposal for a WCB, and I argue that the continued relevance of these objections is contingent on how the proposal for a WCB may get developed. (shrink)

In the last decades, several attempts were made to exploit the relatedness between the early analytic philosophers and Hegel. Some 30 years ago, Peter Hylton and Nicholas Griffin investigated the apprenticeship of Bertrand Russell with neo-Hegelians. 25 years later, the direction of interest changed. Paul Redding and Angelica Nuzzo sought a connection between Hegel and analytic philosophy following hints made by Robert Brandom and John McDowell. According to these authors, Hegel can be seen as a theorist of concepts. (...) Moreover, they found that Hegel’s understanding of concepts is close to that of the early analytic philosophy. The approach we are following in this paper is different. We shall concentrate on the relatedness between the method of the early analytic philosophers and aspects of Hegel’s method. This is an unexplored venue and we hope that our study will open a new perspective both in the history of the early analytic philosophy and in Hegel Studies. To be more explicit, we are not going to specifically investigate the genealogical connection between these two methods. We shall be mainly concerned with their kinship. (shrink)

RIGHT TO SILENCE-UK, U.S, FRANCE, and GERMANY SALLY RAMAGE (TRADE MARK REGISTERED) WIPO Orchid ID 0000-0002-8854-4293 Pages 2-30 Current Criminal Law, Volume 1, Issue 2, -/- Sally Ramage, BA (Hons), MBA, LLM, MPhil, MCIJ, MCMI, DA., ASLS, BAWP. Orchid ID 0000-0002-8854-4293 Publisher & Managing Editor Criminal Lawyer series [1980-2022](ISSN 2049-8047) Current Criminal Law series [2008-2022] (ISSN 1758-8405) and Criminal Law News series [2008-2022] (ISSN 1758-8421). Sweet & Maxwell (Thomson Reuters) (Licensed Annotator of UK Statutes) in annual law books Current Law (...) Statutes Annotated, (2006, 2009, 2010 editions) (sole and separate S&M contracts) for 7 UK Criminal Justice Statutes: UK Safeguarding Vulnerable Persons Act 2006; UK International Development Act 2006; UK Fraud Act 2006; UK Policing and Crime Act 2009, UK Local Democracy Act 2009; UK Bribery Act 2010; and UK Crime and Security Act 2010. TradeMark SALLY RAMAGE ® (2005-2025) in the UK, 2401827; WIPO TradeMark SALLY RAMAGE® 900614; USA TradeMark 3,440,910) (2008-2028). WARNING: The doing of an unauthorized act in relation to a copyright work may result in both a civil claim for damages and criminal prosecution. -/- ABSTRACT The privilege of the right to silence can be traced back to the 12th century, becoming more developed in later centuries. -/- Table of cases European Court of Human Rights Deweer v Belgium [1980], Eckle v Germany [1982], DN v The Netherlands [1975], Funke v France [1993] 16 EHRR 297, JP v Austria [1989], Kansal v UK [2003] Application No 21413/02 Khan v UK [2000] 31 EHRR 45, Saunders v UK [1997] 23 EHRR 313, Schenk v Switzerland [1991] 13 EHRR 242, and Tora Tolmos v Spain [1995] Table of Cases United Kingdom Brown v Procurator Fiscal, Dunfermline, [2000] , The Times, Feb 14, High Ct Scot.; HM Advocate v Friel [1978] SLT; Lambe v Munster [1882] 10 QBD 110.; Pearse v Pearse [1846] Eng Rep 950 (on truth); Re Pantmaenog Timber Co Ltd [2003] HL; R v Bryce [1992] 95 Cr App Rep 320; R v Canale [1990] 2 All ER 187; R v Fitzpatrick [1995] 4 SCR 154; R v Herbert [1990] 2 SCR 151; R V Hertfordshire County Council, ex parte Green Environmental Industries and another [2000] 1 All ER 773; R v Keenan [1989] Crim LR 720; R v Maguire [1990] Cr App Rep 115; R v Pound, Green and ors [2004]; R v Sang [1979] Crim LR 655; R v Saunders [1986] unreported; R v Seelig, R v Spens [1991] CA; R v Smith [1992] 95 Cr App. R. 191; R v Steen and ors [2003] unreported; R v Walsh [1981] CrimLR 822; R V Ward 96 Cr App R [1993]; R v Weekes [1993] Crim LR 211; R v White [1999] 2 SCR 417; R v Young [2003] unreported; Thompson Newspaper v Canada [1990] 1 SCR 425; Walsh Automation (Europe) Ltd v Bridgeman and ors [2002] EWHC 1344 QB France-Law France 1789 Declaration des driots de l‟homme et du citoyen 1808 Code d ‟instruction criminelle 1946 Constitution 1958 Code de procedure penale 2000 Penal Code Germany-Law Germany 1871 Criminal Code 1877 Criminal Procedure Code (St PO) 1877 Judicial Organisation Law 1949 Constitution 1975 Criminal Code 1998 Criminal Code Table of Cases Germany Germany BGH Admissibility of secret tape recordings judgement 14 June 1960, in BGHSt 14, 358 BGH Lie detector judgement 16 Feb 1954, in BGHSt 5, 332. BberfG Decision concerning the applicability of ne bis in idem 31 March 1987, in BberfGE 75,1; BGH Sweeping deception of suspect judgement 24 August 1988, in BGHSt 36, 328. BGH Judgement 24 August 1993, in BGHSt 39, 305 Table of Cases United States United States of America California v Byres [1971] 402 U.S. 424; Fisher v United States 475 U.S. 391 [1986]; Griffin v California [1965] 380 US 609 [; Hoffman v United States [1950] 341 U.S. 479; Supreme Court Baldwin v NY, 399 US 143 [1970]; Supreme Court Chavez v Martinez , U.S. 123 [2003]; Supreme Court Doyle v Ohio, 426 U.S. 610 [1976]; Supreme Court Escobedo v Illinois, 378 U.S. 478 [1964]; Supreme Court Giglio v US, 405 U.S. 150 [1972] Supreme Court Harris v NY, 401 U.S. 222 [1971]; Supreme Court Kirby v Illinois, 406 U.S. 682 [1972]; Supreme Court Miranda v Arizona, 384 U.S. 436 [1966]; Supreme Court Moore v Illinois, 408 U.S. 768 [1972]; Supreme Court Moran v Burbine, 475 U.S. [1986]; Supreme Court Orzoco v Texas, 324 U.S.24 [1969]; Supreme Court US v Hale [1975] 422 US 17; Supreme Court US v Leon, 468 U.S. 897 [1984]; Supreme Court US v Salerno, 481 U.S. 739 [1987]; Twining v New Jersey 211 US 78 113 -/- . (shrink)

Çağdaş epistemoloji içerisinde, dışsalcı, güvenilirci ve erdeme dayalı epistemolojik tartışmaların bir benzerini, dini epistemoloji içerisinde etkili bir şekilde yer edinen ve reformcu epistemoloji olarak bilinen yaklaşım üzerinden görebilmek mümkündür. Alvin Plantinga, Nicholas Wolterstorff ve William Alston gibi filozofların öne çıktığı bu yaklaşımın ana iddiası, kanıta ya da argümana dayanmaksızın, Tanrı’nın varlığına inanmanın bütünüyle doğru, rasyonel, makul ve güvenilir olacağı şeklindeki bir tezdir. Kanıtın, gerekçelendirme için zorunlu bir koşul olmadığı fikri, algısal deneyimlerin gerekçelendirilmesine benzer şekilde, dini deneyimlerin de öyle olduğu (...) ve dolayısıyla, aynı epistemik statüye sahip olması gerektiğini öne süren, eşitlik tezine dayanır. İlk ortaya çıktığı günden bugüne, üzerinde çokça konuşulan ve tartışılan bir yaklaşım olan reformcu epistemoloji, özellikle son beş yıl içerisinde, oldukça farklı bir hale gelmiştir. Zira bu yaklaşımı, kanıtsalcılıkla uyumlu, erdem epistemolojisiyle bağlantılı ve diğer teistik dinler üzerinden değerlendiren yeni çalışmalar ortaya çıkmıştır. Bu nedenle, bu makalede, reformcu epistemoloji ana hatlarıyla ele alınmıştır. Beraberinde, ona yöneltilen itirazlara değinilmiş ve sonrasında, bahsi geçen yenilik iddiaları soruşturulmaya çalışılmıştır. Son olarak, teistik inancın rasyonalitesiyle ilgili, farklı bir bakış açısı sunulmuştur. (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. 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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)

Alvin Plantinga, analitik felsefe düşüncesi içerisinde yetişmiş ve bu gelenek içinde teistik din felsefesinin oluşumuna katkıda bulunmuş bir filozoftur. Ayrıca teizmin savunusu için yaptığı çalışmalarla, çeşitli üniversitelerden aldığı onur ödülleri ve 2017 yılında kazandığı Templeton Prize ödülüyle, haklı bir üne kavuşmuş bir şahsiyettir. Bu çalışmayı yapmamızdaki en önemli amaç, Plantinga’nın dini epistemoloji üzerine yaptığı çalışmaları analiz edip bu düşüncelerinin ardalanına dair bir tespitte bulunmaktır. Bu çalışmada yararlandığımız öncelikli kaynaklar, Plantinga’nın Nicholas Wolterstorff ile birlikte kaleme aldığı “Faith and Rationality” adlı (...) eser ile birlikte son dönem epistemik fikirlerinin çerçevesini belirleyen üç ciltlik “Warrant and Proper Function”, “Warrant: The Current Debate”, “Warranted: Christian Belief” isimli eserler olmuştur. Plantinga’nın ilk dönem epistemoloji çalışmalarının gayesini bir tür olumsuzlama diyebileceğimiz klasik temelciliğin ve evidentializmin eleştirisi oluştururken, ikinci döneminde bu eleştirilerden yola çıkarak Tanrı inancının haklı bir temelde ve güvenceye sahip olduğunu gösterme amacına yönelmiştir. Plantinga’nın teolojik fikirlerini oluşturan Kalvinci ekol, onun dini epistemolojisinin de özünü oluşturmaktadır. Plantinga’nın dini epistemolojisini iki boyutlu olarak değerlendirdiğimizde, içe dönük olarak Hristiyan inancıyla ilgilense de çalışmalarının dışsal yönünü daha genel olarak teizmin Tanrı’sı ve onun rasyonelliği oluşturmaktadır. Açıkçası Plantinga’nın epistemolojik külliyatı bir tür kavram zenginliğini de beraberinde getirmektedir. Çalışmamız içerisinde ele aldığımız kadarıyla uygun işlevsellik, tasarım planı, güvence (warrant) gibi kavramlar onun Tanrı inancının epistemik mahiyetini ortaya koymak için ne derece kararlı olduğunu göstermektedir. Netice itibariyle Tanrı inancının ve onun bilgisinin rasyonel olabileceğini ifade eden Plantinga, her ne kadar Hristiyan inancının belli bir koluna mensup olsa da diğer mezhepleri dışlamaz. Ayrıca Plantinga, birçok çalışmasında belirttiği üzere projesinin Yahudilik, İslam gibi diğer teistik dinlere yönelik olduğunu da belirtmektedir. (shrink)

This book is a collection of articles dealing with criticisms of Robert S. Hartman’s theory of formal axiology. During his lifetime, Hartman wrote responses to many of his critics. Some of these were previously published but many are published here for the first time. In particular, published here are Hartman’s replies to such critics as Hector Neri Castañeda, Charles Hartshorne, Rem B. Edwards, Robert E. Carter, G. R. Grice, Nicholas Rescher, Robert W. Mueller, Gordon Welty, Pete Gunter, George Kimball (...) Plochmann, William Eckhardt, and Robert S. Brumbaugh. Crticial essays and responses to them developed by Rem B. Edwards, Frank G. Forrest, and Mark A. Moore after Hartman’s untimely death in 1973 are also included. (shrink)

This paper explores two related questions in late Athenian and Alexandrian Neoplatonism. First, how can a philosopher contemplate the eternal Forms while engaging in practical agency in the world? Second, do Neoplatonists provide a consistent account of the philosopher’s progress through the ‘stages of virtue’ (βαθμοί τῶν ἀρετῶν), the conceptual structure that underpins late antique philosophical curricula and hagiography? These questions interact, I suggest, because later Platonists appeal to the stages of virtue and divine maniai (βαθμοί τῶν μανίων) to explain (...) the philosopher’s ability to alternate gracefully between contemplation and embodied agency, and even to engage in both activities at the same moment. I argue that apparently contradictory evidence for the highest stages of virtue can be reconciled satisfactorily, shedding light on two models of ethical and perceptual transformation that are consistent throughout later Neoplatonism. In the first, 'painterly' model, we alternate between a vision of the paradigmatic model and its expression in the media of place and time; in the second, 'dancerly' model, we contemplate in action all at once, like a dancer moving to the music. (shrink)

This paper offers a critical interpretation and evaluation of Wilfrid Sellars’s treatment of skepticism about empirical justification. It defends three central claims. First, against the suggestion that Sellars’s work simply bypasses traditional skeptical problems, I make the novel interpretive claim that Sellars not only addresses skepticism about empirical justification, but offers two independent (albeit sketchy) arguments against it: a transcendental argument that the likely truth of our perceptual beliefs is a necessary condition of the possibility of empirical content, and a (...) pragmatic argument that we’re warranted in accepting their likely truth in virtue of our aim of being effective agents. To the extent these have previously been distinctly formulated by commentators, the transcendental argument has been regarded as forceful, while the pragmatic argument has been dismissed as non-responsive. My second and third claims challenge this understanding. I argue, second, that examination of the literature relating to transcendental arguments from semantic externalism like Sellars’s (especially concerning the McKinsey paradox) suggests that such arguments are unpromising, while, third, a modified version of his pragmatic argument represents a powerful skeptical solution to skepticism about empirical justification, one that answers the worry that such skepticism would undermine the rationality of all our practical commitments. (shrink)

The Repugnant Conclusion served an important purpose in catalyzing and inspiring the pioneering stage of population ethics research. We believe, however, that the Repugnant Conclusion now receives too much focus. Avoiding the Repugnant Conclusion should no longer be the central goal driving population ethics research, despite its importance to the fundamental accomplishments of the existing literature.

Loneliness in medicine is a serious problem not just for patients, for whom illness is intrinsically isolating, but also for physicians in the contemporary condition of medicine. We explore this problem by investigating the ideal physician-patient relationship, whose analogy with friendship has held enduring normative appeal. Drawing from Talbot Brewer and Nir Ben-Moshe, we argue that this appeal lies in a dynamic form of companionship incompatible with static models of friendship-like physician-patient relationships: a mutual refinement of embodied virtue that draws (...) both persons together. The ideal physician-patient relationship has a dialectical character that fosters each member's improvement of phenomenologically recognizing and embodying moral virtues. A key component of this dynamic is a commitment to the common goal of the patient's health, realized through joint interactivities and conversations over time. The physician's presence to the patient's suffering—understood best as an alienating phenomenological condition for the patient—orients and discloses possibilities for virtuous caregiving by structuring the meanings of the goals, conversations, and joint narrative constitutive of their relationship. Presence to suffering, paradoxically, is perhaps an important prerequisite for this dynamic partnership. These activities dialectically build an interpretive horizon of understanding through which moral goods and character refinement—in and for the other—may become revealed for both persons in their shared being-in-the-world. This analysis of suffering, mood, and revealing of (possible) moral goods has implications for addressing the modern problem of loneliness for patients and physicians, who are increasingly inhibited from building flourishing relationships with each other. (shrink)

Many have taken Sellars’s critique of empiricism in “Empiricism and the Philosophy of Mind” (EPM) to be aimed at his teacher C. I. Lewis. But if so, why do the famous arguments of its opening sections carry so little force against Lewis’s views? Understandably, some respond by denying that Lewis’s epistemology is among the positions targeted by Sellars. But this is incorrect. Indeed, Sellars had earlier offered more trenchant (if already familiar) critiques of Lewis’s epistemology. What is original about EPM (...) is that it criticizes empiricist positions like Lewis’s not because of their foundationalism, but because of their psychologism about meaning. Since psychologism turns out to be unacceptable by Lewis’s own lights, EPM has a compelling (if implicit) critique of Lewis to offer after all, one that strikes at the heart of his philosophical system. (shrink)

Deontological evidentialism is the claim that we ought to form and maintain our beliefs in accordance with our evidence. In this paper, I criticize two arguments in its defense. I begin by discussing Berit Broogard’s use of the distinction between narrow-scope and wide-scope requirements against W.K. Clifford’s moral defense of. I then use this very distinction against a defense of inspired by Stephen Grimm’s more recent claims about the moral source of epistemic normativity. I use this distinction once again to (...) argue that Hilary Kornblith’s criticism of Richard Feldman’s defense of is incomplete. Finally, I argue that Feldman’s defense is insensitive to the relation between normative requirements and privileged values: values that have normative authority over us. (shrink)

Trope theory is a leading metaphysical theory in analytic ontology. One of its classic statements is found in the work of Donald C. Williams who argued that tropes qua abstract particulars are the very alphabet of being. The concept of an abstract particular has been repeatedly attacked in the literature. Opponents and proponents of trope theory alike have levelled their criticisms at the abstractness of tropes and the associated act of abstraction. In this paper I defend the concept of a (...) trope qua abstract particular by rejecting arguments that purport to show that tropes should not be understood as abstract and by arguing that the abstractness of tropes plays an indispensable role in one of our more promising trope-theoretic analyses of universals and of concrete objects. (shrink)

This book is the first comprehensive study of the meaning and measure of enforceability. While we have long debated what restraints should govern the conduct of our social life, we have paid relatively little attention to the question of what it means to make a restraint enforceable. Focusing on the enforceability of legal rights but also addressing the enforceability of moral rights and social conventions, Mark Reiff explains how we use punishment and compensation to make restraints operative in the world. (...) After describing the various means by which restraints may be enforced, Reiff explains how the sufficiency of enforcement can be measured, and he presents a unified theory of deterrence, retribution, and compensation that shows how these aspects of enforceability are interconnected. Reiff then applies his theory of enforceability to illuminate a variety of real-world problem situations. (shrink)

I try to return the focus of the philosophy of history to the nature of understanding, with a particular emphasis on Louis Mink’s project of exploring how historical understanding compares to the understanding we find in the natural sciences. On the whole, I come to a conclusion that Mink almost certainly would not have liked: that the understanding offered by history has a very similar epistemic profile to the understanding offered by the sciences, a similarity that stems from the fact (...) that both are concerned with grasping how the objects of their study are structured, or how the various elements of the things they study depend upon and relate to one another. At the same time, however, I claim that historical inquiry naturally puts us in a position to acquire further epistemic goods, including the old-fashioned epistemic good of wisdom, which is plausibly constituted by knowledge of how to live well. This is something the natural sciences cannot offer, and it is part of the reason why history is such an important form of inquiry. (shrink)

After reviewing Kant’s well-known criticisms of the traditional proofs of God’s existence and his preferred moral argument, this paper presents a detailedanalysis of a densely-packed theistic argument in Religion within the Bounds of Bare Reason. Humanity’s ultimate moral destiny can be fulfilled only through organized religion, for only by participating in a religious community (or “church”) can we overcome the evil in human nature. Yet we cannot conceive how such a community can even be founded without presupposing God’s existence. Viewing (...) God as the internal moral lawgiver, empowering a community of believers, is Kant’s ultimate rationale for theistic belief. (shrink)

Two systems of belief change based on paraconsistent logics are introduced in this article by means of AGM-like postulates. The first one, AGMp, is defined over any paraconsistent logic which extends classical logic such that the law of excluded middle holds w.r.t. the paraconsistent negation. The second one, AGMo , is specifically designed for paraconsistent logics known as Logics of Formal Inconsistency (LFIs), which have a formal consistency operator that allows to recover all the classical inferences. Besides the three usual (...) operations over belief sets, namely expansion, contraction and revision (which is obtained from contraction by the Levi identity), the underlying paraconsistent logic allows us to define additional operations involving (non-explosive) contradictions. Thus, it is defined external revision (which is obtained from contraction by the reverse Levi identity), consolidation and semi-revision, all of them over belief sets. It is worth noting that the latter operations, introduced by S. Hansson, involve the temporary acceptance of contradictory beliefs, and so they were originally defined only for belief bases. Unlike to previous proposals in the literature, only defined for specific paraconsistent logics, the present approach can be applied to a general class of paraconsistent logics which are supraclassical, thus preserving the spirit of AGM. Moreover, representation theorems w.r.t. constructions based on selection functions are obtained for all the operations. (shrink)

An analysis of the recent efforts to define what counts as a "conspiracy theory", in which I argue that the philosophical and non-pejorative definition best captures the phenomenon researchers of conspiracy theory wish to interrogate.

In “The Fixation of Belief,” Peirce apparently accepts the causal claim that real physical objects cause us to reach an indefeasible “final opinion” concerning them. In “How to Make Our Ideas Clear,” he apparently accepts the constitutive claim that for physical objects to be real just is for them to be represented in that opinion. These claims initially seem inconsistent, since causal claims are explanatory and since equivalent claims cannot explain one another. Contrary to prominent suggestions that Peirce rejected the (...) constitutive claim, however, he actually accepted both, reconciling them via a Humean denial that causal claims are genuinely explanatory. (shrink)

There is widespread consensus that present patterns of consumption could lead to the permanent impossibility of maintaining those patterns and, perhaps, the existence of the human race. While many patterns of consumption qualify as ‘sustainable’ there is one in particular that deserves greater attention: virtual consumption. We argue that virtual consumption — the experience of authentic consumptive experiences replicated by alternative means — has the potential to reduce the deleterious consequences of real consumption by redirecting some consumptive behavior from shifting (...) material states to shifting information states. (shrink)

This paper defends a novel account of how to determine the intrinsic value of possible worlds. Section 1 argues that a highly intuitive and widely accepted account leads to undesirable consequences. Section 2 takes the first of two steps towards a novel account by clarifying and defending a view about value-contribution that is based on some of W. D. Ross’ claims about the value of pleasure. Section 3 takes the second step by clarifying and defending a view about value-suppression that (...) is based on Ross’ claims about the interplay between prima-facie duties. Section 4 states and defends the account that I call Rossian Totalism. According to this account, the atoms of intrinsic value within a world only sometimes contribute their intrinsic value to the value of that world. (shrink)

While C. I. Lewis was traditionally interpreted as an epistemological foundationalist throughout his major works, virtually every recent treatment of Lewis's epistemology dissents. But the traditional interpretation is correct: Lewis believed that apprehensions of "the given" are certain independently of support from, and constitute the ultimate warrant for, objective empirical beliefs. This interpretation proves surprisingly capable of accommodating apparently contrary textual evidence. The non-foundationalist reading, by contrast, simply cannot explain Lewis's explicit opposition to coherentism and his insistence that only apprehensions (...) of the given enable us to answer the regress problem -- and so vindicate the possibility of empirical justification. (shrink)

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that (...) has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility. (shrink)

In the Tractatus Theologico-Politicus (TTP), Spinoza argues that an individual’s natural right extends as far as their power. Subsequently, in the Tractatus Politicus (TP), he offers a revised argument for the same conclusion. Here I offer an account of the reasons for the revision. In both arguments, an individual’s natural right derives from God’s natural right. However, the TTP argument hinges on the claim that each individual is part of the whole of nature (totius naturae), and for this reason inherits (...) part of the natural right of that whole. Using several analogous cases from the Ethics, I show that this form of argument from division is not compatible with Spinoza’s considered metaphysical views. The revised argument, by contrast, avoids the pitfalls of his earlier efforts. It also better reveals the deep roots by which the monistic metaphysics of the Ethics feeds into Spinoza’s conception of natural right. (shrink)

Talk of fake news is rife in contemporary politics, but what is fake news, and how, if anything, does it differ from news which is fake? I argue that in order to make sense of the phenomenon of fake news, it is necessary to first define it and then show what does and does not fall under the rubric of ‘fake news’. I then go on to argue that fake news is not a new problem. Rather, if there is problem (...) with fake news it is its centrality in contemporary public debate. (shrink)

The Tree of Life has traditionally been understood to represent the history of species lineages. However, recently researchers have suggested that it might be better interpreted as representing the history of cellular lineages, sometimes called the Tree of Cells. This paper examines and evaluates reasons offered against this cellular interpretation of the Tree of Life. It argues that some such reasons are bad reasons, based either on a false attribution of essentialism, on a misunderstanding of the problem of lineage identity, (...) or on a limited view of scientific representation. I suggest that debate about the Tree of Cells and other successors to the traditional Tree of Life should be formulated in terms of the purposes these representations may serve. In pursuing this strategy, we see that the Tree of Cells cannot serve one purpose suggested for it: as an explanation for the hierarchical nature of taxonomy. We then explore whether, instead, the tree may play an important role in the dynamic modeling of evolution. As highly-integrated complex systems, cells may influence which lineage components can successfully transfer into them and how they change once integrated. Only if they do in fact have a substantial role to play in this process might the Tree of Cells have some claim to be the Tree of Life. (shrink)

What I call the Doxastic Puzzle, is the impression that while each of these claims seems true, at least one of them must be false: (a) Claims of the form ‘S ought to have doxastic attitude D towards p at t’ are sometimes true at t, (b) If Φ-ing at t is not within S’s effective control at t, then it is false, at t, that ‘S ought to Φ at t’, (c) For all S, p, and t, having doxastic (...) attitude D towards p at t is not within S’s effective control at t. All three natural replies to the puzzle have been pursued. Some have claimed that doxastic attitudes like believing that p are, in fact, within our effective control, or sufficiently so. Others have claimed that doxastic ought-claims, strictly speaking, are always false. And some have denied that effective control is required for the adequacy of doxastic ought-claims in general. I here pursue and examine a different strategy. In the first part of this paper, I argue that these claims are not only each true but actually not in tension with each other in the first place. Instead of attempting to dispel the puzzle, this solution proposes to evade it instead: to solve it by properly understanding, and by thereby accepting without contradiction, all of its constitutive claims. In the second part of the paper, I argue that the evasive strategy forces us to re-think our understanding of the place of normative reasons in epistemology. More exactly, it seems to come at the cost of one central way of thinking about our reasons for having doxastic attitudes, one where such reasons are good-standing exemplars of normative reasons in general. The evasive strategy, that is, threatens to lead us very quickly to a deflationary picture of epistemic normativity: it rescues normative talk, but sacrifices normative substance. I conclude by explaining why I think this is more consequential than some have made it out to be, and by suggesting that these consequences are welcome nonetheless. (shrink)

I apply the notion of truthmaking to the topic of fundamentality by articulating a truthmaker theory of fundamentality according to which some truths are truth-grounded in certain entities while the ones that don't stand in a metaphysical-semantic relation to the truths that do. I motivate this view by critically discussing two problems with Ross Cameron's truthmaker theory of fundamentality. I then defend this view against Theodore Sider's objection that the truthmaking approach to fundamentality violates the purity constraint. Truthmaker theorists can (...) have a trouble-free theory of fundamentality. (shrink)

We need urgently to bring about a revolution in universities around the world, wherever possible, so that they take their fundamental task to be, not to acquire and apply knowledge, but rather to help humanity learn how to resolve conflicts and problems of living in increasingly cooperatively rational ways, so that we may make progress towards a good, genuinely civilized, wise world. The pursuit of knowledge would be a vital but subsidiary task. I have argued for the urgent need for (...) such an academic revolution for nearly 50 years, ever since the publication of two books: What’s Wrong With Science? Towards a People’s Rational Science of Delight and Compassion, 1976, and From Knowledge to Wisdom: A Revolution for Science and the Humanities, 1984, both available free online. This article, written in preparation for a talk given to Pittsburgh University on the 15th September 2023, gives an outline of my baffled struggles with problems of philosophy, science, literature and life that led up to the discovery of the urgent need for an intellectual and institutional revolution in universities around the world, needed in order to galvanize the social revolution required to enable us to make progress to a world in which peace, justice, democracy, individual freedom, sustainable prosperity, the possibility of a good life, are available to all, insofar as that is attainable. (shrink)