The Knower paradox purports to place surprising a priori limitations on what we can know. According to orthodoxy, it shows that we need to abandon one of three plausible and widely-held ideas: that knowledge is factive, that we can know that knowledge is factive, and that we can use logical/mathematical reasoning to extend our knowledge via very weak single-premise closure principles. I argue that classical logic, not any of these epistemic principles, is the culprit. I develop a consistent theory validating (...) all these principles by combining Hartry Field's theory of truth with a modal enrichment developed for a different purpose by Michael Caie. The only casualty is classical logic: the theory avoids paradox by using a weaker-than-classical K3 logic. I then assess the philosophical merits of this approach. I argue that, unlike the traditional semantic paradoxes involving extensional notions like truth, its plausibility depends on the way in which sentences are referred to--whether in natural languages via direct sentential reference, or in mathematical theories via indirect sentential reference by Gödel coding. In particular, I argue that from the perspective of natural language, my non-classical treatment of knowledge as a predicate is plausible, while from the perspective of mathematical theories, its plausibility depends on unresolved questions about the limits of our idealized deductive capacities. (shrink)

Standard semantic theories predict that non-deictic readings for complex demonstratives should be much more widely available than they in fact are. If such readings are the result of a lexical ambiguity, as Kaplan (in: Almog, Perry, Wettstein (eds) Themes from Kaplan, Oxford University Press, Oxford, 1977) and others suggest, we should expect them to be available wherever a definite description can be used. The same prediction follows from ‘hidden argument’ theories like the ones described by King (Complex Demonstratives: a Quantificational (...) Account, MIT Press, Cambridge, 2001) and Elbourne (Situations and Individuals, MIT Press, Cambridge, 2005). Wolter (That’s That; the Semantics and Pragmatics of Demonstrative Noun Phrases. Ph.D. thesis, University of California at Santa Cruz, 2006), however, has shown that complex demonstratives admit non-deictic interpretations only when a precise set of structural constrains are met. In this paper, I argue that Wolter’s results, properly understood, upend the philosophical status quo. They fatally undermine the ambiguity theory and demand a fundamental rethinking of the hidden argument approach. (shrink)

Recently, philosophers have offered compelling reasons to think that demonstratives are best represented as variables, sensitive not to the context of utterance, but to a variable assignment. Variablists typically explain familiar intuitions about demonstratives—intuitions that suggest that what is said by way of a demonstrative sentence varies systematically over contexts—by claiming that contexts initialize a particular assignment of values to variables. I argue that we do not need to link context and the assignment parameter in this way, and that we (...) would do better not to. (shrink)

Most philosophers recognize that applying the standard semantics for complex demonstratives to non-deictic instances results in truth conditions that are anomalous, at best. This fact has generated little concern, however, since most philosophers treat non-deictic demonstratives as marginal cases, and believe that they should be analyzed using a distinct semantic mechanism. In this paper, I argue that non-deictic demonstratives cannot be written off; they are widespread in English and foreign languages, and must be treated using the same semantic machinery that (...) is applied to deictic instances. (shrink)

Stojnić et al. (2013, 2017) argue that the reference of demonstratives is fixed without any contribution from the extra-linguistic context. On their `prominence/coherence' theory, the reference of a demonstrative expression depends only on its context-independent linguistic meaning. Here, we argue that Stojnić et al.’s striking claims can be maintained in only the thinnest technical sense. Instead of eliminating appeals to the extra-linguistic context, we show how the prominence/coherence theory merely suppresses them. Then we ask why one might be tempted to (...) try and offer such a view. Since we are rather sympathetic to the motivations we find, we close by sketching a more plausible alternative. (shrink)

Scholars of ideology in social-scientific disciplines, including psychology, sociology, and political science, stand to benefit from taking seriously the philosophical contributions of Professor Peter Railton. This is because Railton provides much-needed conceptual precision—and a rare sense of epistemological and moral clarity—to a topic that is notoriously slippery and prone to relativistic musing and the drawing of false equivalences. In an essay entitled “Morality, Ideology, and Reflection: Or, the Duck Sits Yet,” Railton (2000/2003) aptly identified the purpose of ideological analysis as (...) the unmasking of “nonepistemic” interests—that is, interests other than truth-seeking, accuracy, or warrant —that contribute to the development, adoption, and dissemination of political and religious belief systems. (shrink)

I present unexplored and unaccounted for uses of 'wants'. I call them advisory uses, on which information inaccessible to the desirer herself helps determine what she wants. I show that extant theories by Stalnaker, Heim, and Levinson fail to predict these uses. They also fail to predict true indicative conditionals with 'wants' in the consequent. These problems are related: intuitively valid reasoning with modus ponens on the basis of the conditionals in question results in unembedded advisory uses. I consider two (...) fixes, and end up endorsing a relativist semantics, according to which desire attributions express information-neutral propositions. On this view, 'wants' functions as a precisification of 'ought', which exhibits similar unembedded and compositional behavior. I conclude by sketching a pragmatic account of the purpose of desire attributions that explains why it made sense for them to evolve in this way. (shrink)

In this paper, I argue that the ‘social meanings’ associated with sociolinguistic variation put pressure on the standard philosophical conception of language, according to which the foremost thing we do with words is exchange information. Drawing on parallels with the explanatory challenge posed by slurs and pejoratives, I argue that the best way to understand social meanings is to think of them in speech act theoretic terms. I develop a distinctive form of pluralism about the performances realized by means of (...) sociolinguistic variants, and I claim that engagement with such performances is an utterly pervasive feature of our linguistic activity. (shrink)

The beginning of the COVID-19 pandemic offers a unique case study for understanding conceptual and linguistic propagation. In early 2020, scientists, politicians, journalists, and other public figures had to, with great urgency, propagate several public health-related concepts and terms to every person they could. This paper examines the propagation of coronavirus and social distancing and develops a framework for understanding how the language used to express a notion can help or hinder propagation. I argue that anyone designing a representational device (...) for propagation needs to appreciate the three-way causal relationship between language, people’s mental representations, and the extramental world. Using this framework, I explore what makes “social distancing” a bad name for social distancing and why it is unproblematic that “coronavirus” is a scientifically loose way of speaking about the virus. Through this and further study of the many historical examples of linguistic and conceptual propagation, conceptual engineers can better understand the complex challenges facing people who want to propagate representational devices. (shrink)

What determines the meaning of a context-sensitive expression in a context? It is standardly assumed that, for a given expression type, there will be a unitary answer to this question; most of the literature on the subject involves arguments designed to show that one particular metasemantic proposal is superior to a specific set of alternatives. The task of the present essay will be to explore whether this is a warranted assumption, or whether the quest for the one true metasemantics might (...) be a Quixotic one. We argue that there are good reasons—much better than are commonly appreciated—for thinking the latter, but that there nevertheless remains significant scope for metasemantic theorizing. We conclude by outlining our preferred option, metasemantic pluralism. (shrink)

This paper aims to clear up the epistemology of learning morality from Artificial Moral Advisors (AMAs). We start with a brief consideration of what counts as moral enhancement and consider the risk of deskilling raised by machines that offer moral advice. We then shift focus to the epistemology of moral advice and show when and under what conditions moral advice can lead to enhancement. We argue that people’s motivational dispositions are enhanced by inspiring people to act morally, instead of merely (...) telling them how to act. Drawing upon these insights, we claim that if AMAs are to genuinely enhance people morally, they should be designed as inspiration and not authority machines. In the final section, we evaluate existing AMA models to shed light on which holds the most promise for helping to make users better moral agents. (shrink)

The twenty-first century will witness an unprecedented decline in the diversity of the world’s languages. While most philosophers will likely agree that this decline is lamentable, the question of what exactly is lost with a language has not been systematically explored in the philosophical literature. In this paper, I address this lacuna by arguing that language loss constitutes a problematic form of illocutionary silencing. When a language disappears, past and present speakers lose the ability to realize a range of speech (...) acts that can only be realized in that language. With that ability, speakers lose something in which they have a fundamental interest: their standing as fully empowered members of a linguistic community. (shrink)

It is increasingly common for philosophers to rely on the notion of an idealised listener when explaining how the semantic values of context-sensitive expressions are determined. Some have identified the semantic values of such expressions, as used on particular occasions, with whatever an appropriately idealised listener would take them to be. Others have argued that, for something to count as the semantic value, an appropriately idealised listener should be able to recover it. Our aim here is to explore the range (...) of ways that such idealisation might be worked out, and then to argue that none of these results in a very plausible theory. We conclude by reflecting on what this negative result reveals about the nature of meaning and responsibility. (shrink)

Gerald Gaus argued in his 1996 book Justificatory Liberalism that proponents of public reason liberalism should attempt to ground their position in a specific epistemology. Critics of public reason liberalism such as David Enoch have also argued that public reason liberals need to elucidate their epistemic claims. Surprisingly, few public reason liberals have taken up Gaus and Enoch on their challenge. This paper will interact with the epistemological position undergirding the public justification principle, access internalism, arguing that it fails. In (...) its place, I put forward and defend proper functionalism as the better grounding epistemology, and then defend the new theory from possible objections. The result will be a synthesis of Nicholas Wolterstorff’s version of liberalism and an externalist version of convergence public reason liberalism. (shrink)

Conceptual engineering is a philosophical method that aims to design and spread conceptual and linguistic devices to cause meaningful changes in the world. So far, however, conceptual engineers have struggled to successfully spread the conceptual and linguistic entities they have designed to their target communities. This paper argues that conceptual engineering is far more likely to succeed if it incorporates empirical data and empirical methods. Because the causal factors influencing successful propagation of linguistic or conceptual devices are as complicated and (...) interwoven as they are, proper empirical research will greatly boost the likelihood that propagation is successful. In arguing for the superiority of empirical conceptual engineering over armchair-based conceptual engineering, this paper proposes a framework for understanding the causal forces at play in propagation. This is a three-part framework between the label of a lexical item, the psychological states associated with the lexical item, and the worldly things associated with the lexical item. By understanding the way causal forces affecting propagation play out at these three levels, conceptual engineers can better conceptualize, study, and harness the different causal forces affecting the success of their conceptual engineering projects. (shrink)

Conceptual engineering is the practice of revising concepts to improve how people talk and think. Its ability to improve talk and thought ultimately hinges on the successful dissemination of desired conceptual changes. Unfortunately, the field has been slow to develop methods to directly test what barriers stand in the way of propagation and what methods will most effectively propagate desired conceptual change. In order to test such questions, this paper introduces the masked time-lagged method. The masked time-lagged method tests people's (...) conceptual understanding at two different points in time without their knowledge of being tested, allowing us to measure conceptual revision in action. Using a masked time-lagged design on a content internalist framework, we attempted to revise PLANET and DINOSAUR in online participants to match experts' concepts. We successfully revised PLANET but not DINOSAUR, demonstrating some of the difficulties conceptual engineers face. Nonetheless, this paper provides conceptual engineers, regardless of framework, with the tools to tackle questions related to implementation empirically and head-on. (shrink)

I have two aims for the present paper, one narrow and one broad. The narrow aim is to show that a class of data originally described by Lynsey Wolter empirically undermine the leading treatments of complex demonstratives that have been described in the literature. The broader aim of the paper is to show that Wolter demonstratives, as I will call the constructions I focus on, are a threat not just to existing treatments, but to any possible theory that retains the (...) uncontroversial assumptions that relative clauses always form a constituent with the nouns they modify, and that semantic composition proceeds sequentially and locally, with the inputs to interpretation having the structure syntax tells us they do. (shrink)

Much has been written on whether practical knowledge (knowledge-how) reduces to propositional knowledge (knowledge-that). Less attention has been paid to what we call deliberative knowledge (knowledge-to), i.e., knowledge ascriptions embedding other infinitival questions, like _where to meet_, _when to leave_, and _what to bring_. We offer an analysis of knowledge-to and argue on its basis that, regardless of whether knowledge-how reduces to knowledge-that, no such reduction of knowledge-to is forthcoming. Knowledge-to, unlike knowledge-that and knowledge-how, requires the agent to have formed (...) certain conditional intentions. We discuss the philosophical implications for knowledge-how, deliberative questions, and virtue. (shrink)

Nelson et al.(2023) argue that the inclusion of personal experience in bioethical debates has significant benefits and liabilities, illustrating their claim with two examples: unproven medical treatments and disability bioethics. We believe that the benefits of including personal experience in disability bioethics far exceed its liabilities. The absence of participants with relevant experience impoverishes and biases bioethical debates, while the biases risked by their inclusion are hardly unique to personal experiences and are readily mitigated.

The last two decades have seen the proliferation of the empirical study of philosophy. This dissertation defends the practice and argues that to understand the way contingent features of the practice of philosophy affect the epistemic standing of philosophers, we need to draw upon a wider and more varied set of empirical data than is sometimes supposed. To explore this, the dissertation focuses on two places where the practices of the discipline of philosophy have an effect on the epistemology of (...) philosophy. -/- First, the dissertation discusses the interaction between notable works of philosophy and their readers. In particular, it critiques the method of defending the epistemic standing of philosophers through careful examination of notable works of philosophy to discern the methods in the text. Ultimately this method is epistemically unmotivated. It is instead far more important to study how people have interacted and reacted to works of philosophy. -/- Second, the dissertation defends the use of lexicography in philosophy. Using "intuition" as a case study, the dissertation argues metasemantically and lexicographically that philosophers often use common words with meanings unique to philosophy. -/- Through both discussions it is argued that experimental philosophers and epistemologists of philosophy need to drastically expand the sorts of data they collect and consider in their theorizing. -/- ​. (shrink)

In this paper, I show how a novel treatment of speech acts can be combined with a well-known liberal argument for multiculturalism in a way that will justify claims about the preservation, protection, or accommodation of minority languages. The key to the paper is the claim that every language makes a distinctive range of speech acts possible, acts that cannot be realized by means of any other language. As a result, when a language disappears, so does a class of speech (...) acts. If we accept that our social identities are in large part constituted by the decisions we make about how to speak, language loss, then, will amount to a substantial infringement on our autonomy in a particularly important domain. (shrink)

I present a paradoxical combination of desires. I show why it's paradoxical, and consider ways of responding. The paradox saddles us with an unappealing trilemma: either we reject the possibility of the case by placing surprising restrictions on what we can desire, or we deny plausibly constitutive principles linking desires to the conditions under which they are satisfied, or we revise some bit of classical logic. I argue that denying the possibility of the case is unmotivated on any reasonable way (...) of thinking about mental content, and rejecting those desire-satisfaction principles leads to revenge paradoxes. So the best response is a non-classical one, according to which certain desires are neither determinately satisfied nor determinately not satisfied. Thus, theorizing about paradoxical propositional attitudes helps constrain the space of possibilities for adequate solutions to semantic paradoxes more generally. (shrink)

The question of Absolute Generality is whether quantifiers are ever as general as can be. Absolutists claim that quantifiers sometimes are absolutely general, while Relativists claim that quantifiers are never absolutely general. Although diverse philosophers have found the Relativist ethos compelling, it has been hard to articulate a consistent thesis which says what the Relativist seems to want to say. In this paper, I offer Relativists a way forward: I argue that what is needed to successfully state Relativism is a (...) way of generalizing that is non-quantificational. After showing how to define such a device of generalization in terms of identity between properties in a higher-order logical language, I use the device to articulate a form of Relativism which I prove to be consistent and which I argue captures the intuitive vision of the Relativist. (shrink)

According to intensional approaches to modeling content (such as "possible worlds semantics"), sentences which are logically equivalent express the same proposition. Partisans of hyperintensionality think this is too coarse-grained. Though there has been substantial interest recently in developing hyperintensional approaches to modeling content, we are still in early days: it is not clear how fine-grained propositions are on the various approaches, and we do not have a systematic map of how the various approaches relate to each other. In this paper, (...) I begin to sketch that map: I show that two prominent hyperintensional approaches can be seen not as rivals but, in large part, as two sides of the same coin. One is the truthmaker semantics, and the other, the "two-component" approach, models propositions as ordered pairs of "truth-conditional content'' and "subject matter''. I show, in particular, that certain versions of the two approaches approaches actually converge when it comes to these questions of fineness of grain. (shrink)

Advocates of the Respect Model of moral status have expressed skepticism about the possibility that radically enhanced persons will have a higher threshold of moral status over non-radically enhanced persons. While several philosophers have already argued that advocates of the Respect Model of moral status should recognize such a possibility in a world with radically enhanced persons, I make room for a stronger claim: advocates of the Respect Model of moral status should not only recognize the possibility of higher thresholds (...) of moral status, but in fact are committed to the normative view that radically enhanced persons should have a higher threshold of moral status over non-radically enhanced persons. This stronger claim induces both rational and self-interested worries about the sacrificeability of non-radically enhanced persons, which takes the form of the inequality of immunity problem. While this problem need not rationally worry the advocate of the Respect Model of moral status, I provide some exploratory solutions that can be implemented now to assuage future self-interested fears so that advocates of the Respect Model may learn to respect the dignity of radically enhanced persons. (shrink)

According to a prevailing view, conceptual engineering introduces a revolutionary philosophical methodology, challenging traditional conceptual analysis. However, in our paper, we argue that closer scrutiny reveals not only the falsity but also the inherent ambiguity of this narrative. We explore four interpretations of the "Anti-Novelty Claim", the claim that conceptual engineering is not a new way of doing philosophy. Discussing the Anti-Novelty Claim from the perspective of a text’s producer, the text’s consumers, and the exegetical potential of the text, we (...) examine each perspective’s metaphilosophical implications and demonstrate that taking each perspective requires different methods. Adopting these different methods, we argue that the different interpretations of the Anti-Novelty Claim range from nearly trivially true to unlikely but untested. Importantly, we emphasize that each interpretation offers unique philosophical insights, yet addressing them requires diverse types of evidence, preventing a singular, straightforward answer to whether conceptual engineering is new. (shrink)

It is hardly a novel claim that the work of Ursula K. Le Guin (1929–2018) contains influences from philosophical Daoism, but I argue that this influence has yet to be fully understood. Several scholars criticize Le Guin for misrepresenting Daoist ideas as they appear in ancient Chinese philosophical texts, particularly the Dao De Jing and the Zhuangzi. While I have sympathy for this charge, especially as it relates to Le Guin’s translation of the Dao De Jing, I argue that it (...) fails to understand the extent to which her fiction contains her own philosophical development of Daoist ideas. Looking at some of her most influential works (e.g., The Left Hand of Darkness, The Dispossessed, The Lathe of Heaven, A Wizard of Earthsea, etc.), I suggest that Le Guin’s fiction is better seen as a refocusing of Daoist concepts such as complementary contrasts and non-action (wu wei) in the contexts of modern feminism, modern anarchism, science fiction, and fantasy. Le Guin was not trying to represent ancient Daoism as a scholar. Rather, she was trying to reimagine Daoism as a creative artist and philosopher in her own right. This way of viewing Le Guin’s work does not fully exorcise the specter of the possibility of Orientalist cultural appropriation, but it does make the issue more complex in a way that can deepen further conversations. To what extent can an artist be guilty of misrepresentation if representation was not, strictly speaking, her goal? I end with a brief reflection on what is perhaps the deepest philosophical lesson of Le Guin’s work: everything is more complicated than it first appears. On that note, the present article is an attempt not just to do philosophy about Le Guin, but to do philosophy in a Le Guinian fashion, which requires rethinking the metaphor of combat that guides much academic philosophy today. (shrink)

We develop and defend a new approach to counterlogicals. Non-vacuous counterlogicals, we argue, fall within a broader class of counterfactuals known as counterconventionals. Existing semantics for counterconventionals, 459–482 ) and, 1–27 ) allow counterfactuals to shift the interpretation of predicates and relations. We extend these theories to counterlogicals by allowing counterfactuals to shift the interpretation of logical vocabulary. This yields an elegant semantics for counterlogicals that avoids problems with the usual impossible worlds semantics. We conclude by showing how this approach (...) can be extended to counterpossibles more generally. (shrink)

Conventional wisdom has it that truth is always evaluated using our actual linguistic conventions, even when considering counterfactual scenarios in which different conventions are adopted. This principle has been invoked in a number of philosophical arguments, including Kripke’s defense of the necessity of identity and Lewy’s objection to modal conventionalism. But it is false. It fails in the presence of what Einheuser (2006) calls c-monsters, or convention-shifting expressions (on analogy with Kaplan’s monsters, or context-shifting expressions). We show that c-monsters naturally (...) arise in contexts, such as metalinguistic negotiations, where speakers entertain alternative conventions. We develop an expressivist theory—inspired by Barker (2002) and MacFarlane (2016) on vague predications and Einheuser (2006) on counterconventionals—to model these shifts in convention. Using this framework, we reassess the philosophical arguments that invoked the conventional wisdom. (shrink)

It is impossible to study philosophical methodology without being struck by the state of absolute chaos of the field’s methodological practices, methodological norms, and metaphilosophical beliefs. Not only are the methods of formal epistemology nothing like the methods of aesthetics, but even within specific debates and subfields, there are often significant disagreements about standards of proof, to say nothing about disagreements about the ultimate nature of the debate. The question facing metaphilosophers is whether this chaos is a feature or a (...) bug. Is the chaos a part of philosophy’s value as an incubator for new ideas or a sign that many philosophers have lost their way and are holding back philosophical progress? (shrink)

This article articulates and assesses an imperatival approach to the foundations of mathematics. The core idea for the program is that mathematical domains of interest can fruitfully be viewed as the outputs of construction procedures. We apply this idea to provide a novel formalisation of arithmetic and set theory in terms of such procedures, and discuss the significance of this perspective for the philosophy of mathematics.

The emphasis in contemporary democratic theory and in the history of political thought on the ‘natural rights’ theory of popular sovereignty of Locke, precursors of which are found in the work of Hugo Grotius and others, obscures an important relationship between constitutional self-government and nationalism. Through an examination of the early political writings of Grotius, especially his Antiquity of the Batavian Republic, this essay shows how a national consciousness forged out of memories of native traditions of self-government, and stories of (...) heroic ancestors who successfully defended those traditions against usurpers and tyrants, gives concrete substance to otherwise inchoate theories of constitutional self-government. (shrink)

The rise of constitutional self-government in early modern Europe, I argue, owes much to a nationalist liberation narrative pioneered by French Huguenot François Hotman in Francogallia (1573). In response to appeals by absolutist thinkers to Ro- man law, which put the power of the king beyond legal or constitutional restraint, Hotman wove together tales of the heroism of ancient Gauls and Franks wresting their native liberties back from the Romans with a theory of constitutionally limited government grounded in the common (...) law of France. This type of narrative was adapted by Dutch and English thinkers who sought to defend constitutionalism in their respective countries. Through this examination of early modern liberation narratives, I argue we can gain insight on the relationship between nationalism and resistance to autocratic governments and the formation of regimes consistent with the principles of constitutional self-government. (shrink)

Counterfactual thinking—the capacity to reflect on what would, could, or should have been if events had transpired differently—is a pervasive, yet seemingly paradoxical human tendency. On the one hand, counterfactual thoughts can be comforting and inspiring (Carroll & Shepperd, Chapter 28), but on the other they can be anxiety provoking and depressing (Zeelenberg & Pieters, Chapter 27). Likewise, such thoughts can illuminate pathways toward better future outcomes (Wong, Galinsky, & Kray, Chapter 11), yet they can also promote confusion and lead (...) us astray (Sanna, Schwarz, & Kennedy, Chapter 13). The first part of this chapter focuses on work that supports the prevailing Zeitgeist in the counterfactual thinking literature: Counterfactual thinking is beneficial. The second part of the chapter, however, strikes a more cautionary tone by reviewing work that describes some deleterious consequences of counterfactual thinking. We conclude by offering a tentative reconciliation of these conflicting perspectives and suggesting directions for future research. (shrink)

What is at stake in determining how to translate the central term of Greek ethical philosophy, that of eudaimonia? The volume Eudaimonia and Well-Being (a collection of ten papers presented at a conference at the University of Cincinnati in 1993) shows that English terms such as happiness, well-being, and flourishing can have significantly different connotations which complicate our understanding of the Greek term. The volume’s contributors work in both ancient Greek ethics and Anglophone contemporary moral philosophy, and although not all (...) the papers bridged the divide between classics and philosophy, on the whole the volume succeeds in elucidating the different meanings “happiness” has for both contemporary and ancient Greek philosophers. The ten papers address five topics, in each case with one author presenting a thesis and another responding as discussant. Most of the papers were revised for publication, and many of the discussants’ papers can stand as independent contributions. Additionally, the editor (who was a participant at the conference) provides a helpful introduction which underscores key themes addressed by many of the papers. The topics examined were whether virtue is sufficient and necessary for happiness (Annas and Sumner); the relationship between fear of death and happiness in Epicurean philosophy (Mitsis and Lesses); the development of the concept of happiness amongst peripatoi in the Hellenistic Lyceum (White and Inwood); the nature of the ethical philosophizing in the sixth book of Polybius’ Histories (Hahm and Jost); and the neo-Aristotelian “capabilities” social philosophy espoused by Martha Nussbaum and Amartya Sen. The volume includes an index locurum, but no comprehensive bibliography. Let me first summarize the debate on the individual topics and then speak to a couple general themes. Given the richness of the papers, space constrains me to restate only the main arguments. (shrink)

In a recent article, Ethan Bradley and Mark Navin (2021) argue that vaccine refusal is not akin to free riding. Here, I defend one connection between vaccine refusal and free riding and suggest that, when viewed in conjunction with their other arguments, this might constitute a reason to mandate Covid-19 vaccination.

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

Richard Linklater’s celebrated Before trilogy chronicles the love of Jesse (Ethan Hawke) and Céline (Julie Delpy) who first meet up in Before Sunrise, later reconnect in Before Sunset and finally experience a fall-out in Before Midnight. Not only do these films present storylines and dilemmas that invite philosophical discussion, but philosophical discussion itself is at the very heart of the trilogy. This book, containing specially commissioned chapters by a roster of international contributors, explores the many philosophical themes that feature (...) so vividly in the interactions between Céline and Jesse, including: the nature of love, romanticism and marriage the passage and experience of time the meaning of life the art of conversation the narrative self gender death Including an interview with Julie Delpy in which she discusses her involvement in the films and the importance of studying philosophy. (shrink)

Three important 20th-century American films prominently feature a hotel as the site for morally ambiguous and sexually charged events depicted in the plot: Orson Welles's Touch of Evil (1958), Alfred Hitchcock's Psycho (1960), and Joel and Ethan Coen's Barton Fink (1991). While all three films have a multiplicity of elements that present how hotel spaces open horizons displaying human behaviors both normal and abnormal, moral and immoral, secret and public, sane and insane, the paper presents an extended argument for (...) seeing these particular cinematic efforts as being built around the same theme: that transgression (of a violent, misogynous nature) is the path to transcendence. (shrink)