This well chosen collection of essays written by recognized scholars addresses many of the intriguing aspects concerning the controversy over meat consumption. These aspects include not only eating meat, but also hunting animals, breeding, feeding, killing, and shredding them for our use, buying meat, the economics of the meat industry, the understanding of predation and food webs in ecology, and the significance of animals for issues about nutrition, gender, wealth, and cultural autonomy. Dombrowski rightly notes that the contemporary debate regarding (...) philosophical vegetarianism has been profoundly shaped by the historical figures who have rejected or embraced the anthropocentrism entrenched in Western thought. Three anthropological-medical essays compare meat with vegetarian diets. Eight essays treat the recent philosophical debate over the moral status of animals and whether vegetarianism is obligatory. Several essays discuss religious views on meat-eating and vegetarianism. Three essays explore meat, patriarchy, and the exploitation of nature and animals with respect to race, gender, sexual orientation, and socioeconomic class. The last four essays debate how to understand predation, environmental ethics, and animal protection. This collection is a fine entrée for all readers of this journal, since the debate over meat must by now figure into every thinking person’s diet. (shrink)

Are animals our domestic companions, fellow citizens of the ecosystems we inhabit, mobile meals and resources for us, or some combination thereof? This well chosen collection of essays written by recognized scholars addresses many of the intriguing aspects concerning the controversy over meat consumption. These aspects include not only eating meat, but also hunting animals, breeding, feeding, killing, and shredding them for our use, buying meat, the economics of the meat industry, the understanding of predation and food webs in ecology, (...) and the significance of animals for issues about nutrition, gender, wealth, and cultural autonomy. (shrink)

This chapter examines the possibility of using AI technologies to improve human moral reasoning and decision-making, especially in the context of purchasing and consumer decisions. We characterize such AI technologies as artificial ethics assistants (AEAs). We focus on just one part of the AI-aided moral improvement question: the case of the individual who wants to improve their morality, where what constitutes an improvement is evaluated by the individual’s own values. We distinguish three broad areas in which an individual might think (...) their own moral reasoning and decision-making could be improved: one’s actions, character, or other evaluable attributes fall short of one’s values and moral beliefs; one sometimes misjudges or is uncertain about what the right thing to do is in particular situations, given one’s values; one is uncertain about some fundamental moral questions or recognizes a possibility that some of one’s core moral beliefs and values are mistaken. We sketch why one might think that AI tools could be used to support moral improvement in those areas, and describe two types of assistance: preparatory assistance, including advice and training supplied in advance of moral deliberation; and on-the-spot assistance, including on-the-spot advice and facilitation of moral functioning over the course of moral deliberation. Then, we turn to some of the ethical issues that AEAs might raise, looking in particular at three under-appreciated problems posed by the use of AI for moral self-improvement: namely, reliance on sensitive moral data; the inescapability of outside influences on AEAs; and AEA usage prompting the user to adopt beliefs and make decisions without adequate reasons. (shrink)

To hold an environmental ethic is to hold that non-human beings and states of affairs in the natural world have intrinsic value. This seemingly straightforward claim has been the focus of much recent philosophical discussion of environmental issues. Its clarity is, however, illusory. The term ‘intrinsic value’ has a variety of senses and many arguments on environmental ethics suffer from a conflation of these different senses: specimen hunters for the fallacy of equivocation will find rich pickings in the area. This (...) paper is largely the work of the underlabourer. I distinguish different senses of the concept of intrinsic value, and, relatedly, of the claim that non-human beings in the natural world have intrinsic value; I exhibit the logical relations between these claims and examine the distinct motivations for holding them. The paper is not however merely an exercise in conceptual underlabouring. It also defends one substantive thesis: that while it is the case that natural entities have intrinsic value in the strongest sense of the term, i.e., in the sense of value that exists independently of human valuations, such value does not as such entail any obligations on the part of human beings. The defender of nature’s intrinsic value still needs to show that such value contributes to the well-being of human agents. (shrink)

Several philosophers have recently advanced wager-based arguments for the existence of irreducibly normative truths or against normative nihilism. Here I consider whether these wager-based arguments would cause a normative Pyrrhonian skeptic to lose her skepticism. I conclude they would not do so directly. However, if prompted to consider a different decision problem, which I call the normativity wager for skeptics, the normative Pyrrhonian skeptic would be motivated to attempt to act in accordance with any normative reasons to which she might (...) be subject. Consideration of the normativity wager will not inevitably cause the normative Pyrrhonian skeptic to lose her skepticism, but there are at least three routes by which it might: first, in considering the wager the agent may spontaneously (non-rationally) acquire a normative belief; second, considering the wager can motivate the agent to cause herself to (non-rationally) acquire a normative belief. Via either of these indirect, non-rational routes, she would cease to be a normative Pyrrhonian skeptic. Thus, consideration of the normativity wager may have value, even if it does not supply a rational argument that will dissuade skeptics. In addition, I consider the possibility of a third (rational) route by which the agent might lose her skepticism. (shrink)

This paper addresses ways of arguing fors ome form of economic democracy from within a broadly Rawlsian framework. Firstly, one can argue that a right to participate in economic decision-making should be added to the Rawlsian list of basic liberties, protected by the first principle of justice. Secondly,I argue that a society which institutes forms of economic democracy will be more likely to preserve a stable and just basic structure over time, by virtue of the effects of economic democratization on (...) the development of an active, democratic character among citizens. Thirdly, I argue that a proper understanding of the demands of the difference principle shows that justice demands more than ex post redistribution, but also requires the ex ante redistribution of power and authority in economic life. This connects to Rawls’s discussion of the badness of inequality, and to his endorsement of a “property-owning democracy”. -/- My conclusion is that, even if we may doubt the success of this first Rawlsian argument,the second and third arguments are both successful, and together establish a strong Rawlsian case forseeing economic democratization as a requirement of justice. (shrink)

Cameras, microphones, and other sensors continue to proliferate in the world around us. I offer a new metaphor for conceptualizing these technologies: they are _digital wormholes_, transmitting representations of human persons between disparate points in space–time. We frequently cannot tell when they are operational, what kinds of data they are collecting, where the data may reappear in the future, and how the data can be used against us. The wormhole metaphor makes the mysteriousness of digital sensors salient: digital sensors have (...) brought us to a strange place. If humans are to be capable of making sensible decisions while under observation by digital sensors, we must improve the epistemic position of potential sensor subjects. (shrink)

The focus of this article is on the place of the limited-liability joint stock corporation in a satisfactory account of social justice and, more specifically, the question of how such corporations should be regulated and taxed in order to secure social justice. -/- Most discussion in liberal political philosophy looks at state institutions, on the one hand, and individuals, on the other hand, without giving much attention to intermediate institutions such as corporations. This is in part a consequence of a (...) certain degree of idealization in terms of the background model of society with which such theories operate. Intermediate institutions are in an important sense optional or discretionary, and one would be hampering an account of justice if it built-in from the start particular kinds of institutions which we could imagine doing without. The only non-state institution that has received adequate attention in political philosophy is the nuclear family, in part because of its pervasiveness and resilience. But the corporation is probably second only to the family in its significance, in terms of its effects on the lives of individuals, and yet has been left without adequate attention. (shrink)

If solutions to the problem of inequality are to be as radical as reality now demands, what is instead required is a reimagining of what would be involved comprehensively to tame capitalism through democratic means. This will involve much further development of the kind of plurality of institutional and policy proposals sketched by Meade, and will involve both the private and public – individual and collective – forms of capital predistribution that Meade advocated. Piketty, like Meade, sees the need for (...) both redistribution and predistribution, and both see that the institutional means necessary to create a more equal society will involve pursuing a plurality of parallel paths. It is closely in keeping with the spirit of Piketty’s Capital that the political and intellectual agenda ahead will be one that economics on its own cannot hope to encompass. It’s a vital agenda, with high stakes, and presents challenges to both academic researchers and political activists. On the success of this endeavour depends nothing less than the prospects for legitimate continuation of our economic system. (shrink)

If pursued with serious intent, Pre-distribution has the capacity to create an exciting and radical new agenda for social democracy. But the politics of Pre-distribution cannot be innocuous or uncontroversial. -/- In its more radical forms, predistribution is a potentially radical and inspiring project for social democrats who have come to see the limitations of the old ways of doing things. It’s a project that promises a strategy to deliver abundantly on values of social justice, economic freedom, and equality of (...) opportunity. But it’s a project that involves going head-to-head with entrenched interests, breaking up existing concentrations of wealth and economic power. The politics of Pre-distribution, if taken seriously, simply cannot be a politics without enemies. Labour must decide whether its engagement with pre-distribution is to be limited to tinkering at the edges of neoliberalism, or whether it will instead fully embrace the opportunities of the present moment, decide to be radical, and realise the full promise of the politics of predistribution. -/- . (shrink)

This paper examines demonic agency and epistemology in the thought of Augustine. When Augustine claims that demons can “work miracles,” he means this in a specific sense: the actions and intelligence of demons are only miraculous from the standpoint of humans, whose powers of perception and action are limited in relation to those of demons. The character of demons’ bodies and the length of their lives provide abilities beyond what humans possess, but, as natural, created beings, demons adhere to the (...) physical rules of nature. Demons possess neither supernatural powers, nor perfect knowledge. Just as our wonder ceases when we are shown how a magic trick is executed, human astonishment makes way for rational understanding once we comprehend demonic nature. (shrink)

This paper, as a response to Mark K. Spencer’s, “Perceiving the Image of God in the Whole Human Person” in the present volume, argues in defence of Aquinas’s position that the Imago Dei is limited in the human being to the rational, intellective soul alone. While the author agrees with Spencer that the hierarchical relation between body and soul in the human composite must be maintained while avoiding the various permeations of dualism, nevertheless, the Imago Dei cannot be located in (...) the human body or the principle of the body considered within the body/soul composite without betraying a number of fundamental Thomistic metaphysical principles. Essential to these includes Aquinas’s position that an image of God should image not only the Divine Nature, but also the Trinitarian relations between the Divine Persons. Further, the paper also argues that a phenomenology of sense experience could not, on principle, attain to an image of God in the whole human person within a Thomistic framework generally. (shrink)

The necessity for a government “lender of last resort” has been advanced as a justification for central banking. In this paper, I compare lending practices under central banking with those that would be likely to exist under a system of fractional-reserve free banking (FRFB). To do this I examine the underlying nature of banks as warehousing and credit-granting institutions and consider how redemption runs can arise as a consequence of fractional reserves in this system. Following the work of Thornton and (...) Bagehot, I describe principles of prudent lending that can be used to stem a redemption run when it arises. I examine the market incentives that apply under FRFB and how these incentives are perverted under a system of central banking. I find that a government central bank is not well-placed to lend according to prudent standards, and in fact is likely to use its power to pursue political goals that are at odds with prudent lending. I examine the US financial crisis and the actions of the Federal Reserve System to illustrate this view. (shrink)

John Rawls is arguably the most important political philosopher of the past century. His theory of justice has set the agenda for debate in mainstream political philosophy for the past forty years, and has had an important influence in economics, law, sociology, and other disciplines. However, despite the importance and popularity of Rawls's work, there is no clear picture of what a society that met Rawls's principles of justice would actually look like. This article sets out to explore that question.

In this paper, I first discuss Augustine’s description of time and relate this to Boethius’ explanation of the distinction between time and eternity. I then connect this distinction to Augustine’s understanding of memory as an image of eternity, showing that the analogy between God and the human with reference to time involves a comparison not between eternity and time, but rather, between eternity and a limited experience of eternity within the mind and its distension: time is not the image of (...) eternity, the human mind is, particularly its power of memory (memoria). The accounts of time and eternity of both thinkers provide further evidence for Augustine’s influence on and importance for the thought of Boethius. Both figures describe the past and future as united in the present under the divine purview of God. (shrink)

The future state of the redeemed human being in heaven is difficult, if not impossible, to pin down in this life. Nevertheless, Augustine and Anselm speculate on the heavenly life of the human being, proceeding from certain theological premises gathered from Scripture, and their arguments often both mirror and complement one another. Because Anselm and Augustine hold the premise that human beings in heaven are “equal to the angels” (Luke 20:36), our understanding of the heavenly condition of the human can (...) be illuminated by angelology, and vice-versa; each reveals the nature of the other. The paper examines aspects of the positions of Augustine and Anselm on the original state of the angels, their fall, and their confirmation, and then explores the condition of prelapsarian Adam and the transformation of the elect in order to illuminate how these figures conceive the afterlife. The angelologies (and demonologies) of Augustine and Anselm help one to understand the heavenly goal of human life, how the redeemed state of human beings differs from their original condition in Eden, and why there is no redemption for the fallen angels. (shrink)

An overview of the ancient philosophers and their philosophical system (divided into the fields of logic, physics, and ethics) comprising the living, organic, enduring, and evolving body of interrelated ideas identifiable as the Stoic perspective.

Augustin est bien connu comme défenseur d’une « théorie privative » du mal. On peut lire, par exemple, dans les Confessions que « le mal n’est que la privation du bien, à la limite du pur néant ». Le problème, cependant, avec les théories privatives du mal est qu’elles ne nous offrent pas, généralement, une explication robuste ni de l’activité du mal, ni de son pouvoir à causer des effets bien réels ; effets desquels l’expérience demande, malgré tout, une explication (...) rationnelle. Or, selon Augustin, la privation seule ne permet pas de rendre compte de toutes les manifestations du mal. L’explication privative du mal est, certes, la plus étudiée par la littérature ; mais elle ne constitue qu’une partie du tableau. Cet article veut souligner quatre moments de l’explication du mal qu’Augustin propose : le mal comme privation ; le mal comme parasite par rapport à l’être ; le mal comme perversion de la volonté ; et finalement, le mal comme conflit d’intérêts. Chacun de ces moments éclaire un type de mal, mais aucun ne permet à lui seul de rendre compte du problème. Pris ensemble, cependant, et gardant leurs différences respectives à l’esprit, la réponse d’Augustin à la question du mal se révèle beaucoup plus sophistiquée et exhaustive qu’on ne voudrait souvent l’admettre lorsqu’on se limite uniquement à la théorie de la privation. | : Augustine is well-known for advocating a ‘privation theory’ of evil. In Confessions, he writes that “evil has no existence except as a privation of good, down to that level which is altogether without being.” The problem with privation theories of evil generally is that they do not provide a robust enough account of the activity and power of evil to cause the very real effects for which experience demands a rational explanation. For Augustine, however, privation alone does not fully account for evil in all of its manifestations. The privation account of evil receives much scholarly treatment, but it is only part of the complete Augustinian picture. This paper outlines four accounts of evil in Augustine : evil as privation, as parasitic on being, as perversion of the will, and as conflict of interest. Each deals with a kind of evil, but none alone provides a complete account. Taken together, however, with their differences in mind, Augustine’s explanation of evil is shown to be much more sophisticated and comprehensive than is often recognised when one limits one’s understanding of Augustine’s conception of evil to the privation theory alone. (shrink)

I show that in Epictetus’ view (1) the wise man genuinely loves (στέργειv) and is affectionate (φιλόστoργoς) to his family and friends; (2) only the Stoic wise man is, properly speaking, capable of loving—that is, he alone actually has the power to love; and (3) the Stoic wise man loves in a robustly rational way which excludes passionate, sexual, ‘erotic’ love (’έρως). In condemning all ’έρως as objectionable πάθoς Epictetus stands with Cicero and with the other Roman Stoics, Seneca and (...) Musonius Rufus, and against the Greeks of the early Stoa. Epictetus’ conception of love excludes erotic passion because of its intrinsic excessiveness and uncontrollableness, which inevitably endanger mental serenity, but includes and emphasizes the soberly rational, purely positive joy of interpersonal affiliation. Epictetus’ account of how the Stoic Sage loves is, I think, more consistent and less problematic than that of the Greek Stoics. (shrink)

People more frequently select norm-violating factors, relative to norm- conforming ones, as the cause of some outcome. Until recently, this abnormal-selection effect has been studied using retrospective vignette-based paradigms. We use a novel set of video stimuli to investigate this effect for prospective causal judgments—i.e., judgments about the cause of some future outcome. Four experiments show that people more frequently select norm- violating factors, relative to norm-conforming ones, as the cause of some future outcome. We show that the abnormal-selection effects (...) are not primarily explained by the perception of agency (Experiment 4). We discuss these results in relation to recent efforts to model causal judgment. (shrink)

Inchoate crime consists of acts that are regarded as crimes despite the fact that they are only partial or incomplete in some respect. This includes acts that do not succeed in physically harming the victim or are only indirectly related to such a result. Examples include attempts (as in attempted murder that does not eventuate in the killing of anyone), conspiracy (in which case the crime has only been planned, not yet acted out) and incitement (where the inciter does not (...) himself commit the crime he is urging others to undertake). The present paper attempts to analyze these inchoate crimes from a libertarian perspective, based on the non-aggression principle. (shrink)

Although recent scholarship has begun to clarify Porphyry’s position on the first principle in its distinction from that of Plotinus we must be careful not to gloss over the crucial ramifications of Porphyry’s developments. The Plotinian One is beyond Being, and thus beyond all relation and difference. In his attempt to understand how such a principle can be productive of all else that follows from it, Porphyry considers the Plotinian One in both its transcendent and creative aspects, introducing the notions (...) of difference and self-relation within the One itself. Porphyry’s modifications of Plotinus’s doctrine, however, result in a first principle having a character utterly distinct from what Plotinus envisioned, and from what I believe Plotinus would have accepted. Because Porphyry’s first principle is relational, it loses its decisive Plotinian character as absolutely transcendent. This distinction between the first principles of Porphyry and Plotinus has important ramifications for each of their philosophical itineraria, and further strengthens the status of Plotinus within the Neoplatonic tradition. Plotinus is a unique thinker within the Neoplatonic tradition, and we must be careful not to equate Neoplatonism with Plotinus, when in fact, it is Plotinus who against both his own predecessors and successors often stands alone. (shrink)

Bryant’s paper, "A Logic of Multiplicities: Deleuze, Immanence, and Onticology," is useful for showing how the historical legacy of hierarchy in its many philosophical forms is still present, important, and, in fact, required even by those such as Bryant who would seek to deconstruct or ignore it. The following response will discuss Bryant’s presentation of his alternative position and throughout point out: a) the straw-man versions of hierarchy that Bryant employs; b) why what Bryant claims to be inherent negatively in (...) hierarchy is not the case; c) how Bryant’s position actually relies upon hierarchy for its own explication, and finally; d) the various principles of hierarchical metaphysics that are required in order to make sense of experience and reality. These latter include the notions that i) there are many kinds of hierarchy; ii) Being and Unity are prior to Multiplicity; iii) relation without substance is incoherent; iv) hierarchy is not inherently tyrannical; v) the distinction between essentially and accidentally ordered causal series is a real and useful one; and vi) the existence of hierarchy is more self evident than is flat ontology. (shrink)

The norms of simplicity, convenience, unfussiness, and self-control guide Diogenes the Cynic, Zeno of Citium, Chrysippus, Seneca, Musonius Rufus, Epictetus, and Marcus Aurelius in approaching food. These norms generate the precept that meat and dainties are luxuries, so Stoics should eschew them. Considerations of justice, environmental harm, anthropogenic global climate change, sustainability, food security, feminism, harm to animals, personal health, and public health lead contemporary Stoics to condemn the meat industrial complex, debunk carnism, and select low input, plant-based foods.

First, the thorny problem of locating the Midwest is treated. Second, the ancient Stoics’ understanding of nature is proposed as a fertile field of ecological wisdom. The significance of nature in Stoicism is explained. Stoic philosophers (big-S Stoics) are distinguished from stoical non-philosophers (small-s stoics). Nature’s lessons for living a good Stoic life are drawn. Are such lessons too theoretical to provide practical guidance? This worry is addressed by examining the examples of Cincinnatus and Cato the Elder—ancient Romans lauded for (...) their virtues who worked the land. They exhibited the virtues of civic responsibility, justice, self-sufficiency, parsimony, perseverance, equanimity, modesty, and respect for limits—an agrarian virtue dear to Wendell Berry. Agrarianism views rural society as superior to urban society and the independent farmer as superior to the paid worker. Reflection on the virtues of stoical Roman agrarians suggests that features of Roman Stoic agrarianism resonate with a contemporary instantiation of Stoicism in the Midwest. The main thesis is that Midwest Stoic agrarianism (MSA), guided by an array of earthy virtues, promotes agricultural practices that harmonize with nature and support living in agreement with nature, while rejecting agricultural practices contrary to nature and propelled by vice. MSA endorses, e.g., locally sourced, sustainably grown crops instead of CAFOs. MSA tackles the ecological and sociopolitical pressures confronting Midwest farmers in the Anthropocene and can fortify environmental virtue ethics beyond this region. (shrink)

What would be a fair model for flood insurance? Catastrophic flooding has become increasingly frequent in the UK and, with climate change, is likely to become even more frequent in the future. With the UK's current flood insurance regime ending in 2013, we argues that: -/- - there is an overwhelming case for rejecting a free market in flood insurance after 2013; - this market-based approach threatens to leave many thousands of properties uninsurable, leading to extensive social blight; - there (...) are a number of possible flood insurance models that would be fairer and more sustainable. -/- We outline three approaches to 'fairness' in flood insurance, and argues that the second and third of these would be the most 'solidaristic' – i.e. those at lower risk of flooding would contribute to the support of people at higher risk: -/- 'pure actuarial fairness' – insurance costs directly reflect the level of risk faced by individuals; 'choice-sensitive fairness' – insurance costs should reflect only those risks that result from each individual's choices; 'fairness as social justice' – insurance should be provided independently of individuals' risks and choices when covering basic requirements of social justice. (shrink)

The ancient Stoics believed that virtue is the only true good and as such both necessary and sufficient for happiness. Accordingly, they classified food as among the things that are neither good nor bad but "indifferent." These "indifferents" included health, illness, wealth, poverty, good and bad reputation, life, death, pleasure, and pain. How one deals with having or lacking these things reflects one’s virtue or vice and thus determines one’s happiness or misery. So, while the Stoics held that food in (...) itself contributes nothing to a person’s happiness, how one obtains, prepares, and serves it, and both what and how one eats, all reveal a person’s character as good or bad. Thus, understanding the purpose of food, the necessity of frugality, and the virtue of temperance are all important in Stoicism. This paper traces the ethical views on food from Zeno of Citium and Chrysippus to Seneca, Musonius Rufus, Epictetus, and Marcus Aurelius. They agree that the wise and temperate know that simple, inexpensive foods in moderate amounts produced locally are easy to get and prepare, healthy for the body, and good for the mind. Thus, Stoicism dictates frugality of diet and the rejection of ambitious eating, gluttony, luxuries, delicacies, and gustatory extravagance. Some Stoics favor vegetarianism. All Stoics think it wise to limit eating and drinking to strict bodily need and to eradicate all food anxieties. (shrink)

How does character information inform judgments of blame? Some argue that character information is indirectly relevant to blame because it enriches judgments about the mental states of a wrongdoer. Others argue that character information is directly relevant to blame, even when character traits are causally irrelevant to the wrongdoing. We propose an empirical synthesis of these views: a Two Channel Model of blame. The model predicts that character information directly affects blame when this information is relevant to the wrongdoing that (...) elicits blame. Further, the effect of character information on blame depends on judgments about the true self that are independent of judgments of intentionality. Across three pre-registered studies (N = 662), we found support for all three predictions of the Two Channel Model. We propose that this reflects two distinct functions of blame: a social regulatory function that encourages norm compliance and a pedagogical function that encourages personal improvement. (shrink)

In this paper, we engage in dialogue with Jonathan Pugh, Hannah Maslen, and Julian Savulescu about how to best interpret the potential impacts of deep brain stimulation on the self. We consider whether ordinary people’s convictions about the true self should be interpreted in essentialist or existentialist ways. Like Pugh et al., we argue that it is useful to understand the notion of the true self as having both essentialist and existentialist components. We also consider two ideas from existentialist philosophy (...) – Jean-Paul Sartre and Simone de Beauvoir’s ideas about “bad faith” and “ambiguity” – to argue that there can be value to patients in regarding themselves as having a certain amount of freedom to choose what aspects of themselves should be considered representative of their true selves. Lastly, we consider the case of an anorexia nervosa-patient who shifts between conflicting mind-sets. We argue that mind-sets in which it is easier for the patient and his or her family to share values can plausibly be considered to be more representative of the patient’s true self, if this promotes a well-functioning relationship between the patient and the family. However, we also argue that families are well-advised to give patients room to figure out what such shared values mean to them, since it can be alienating for patients if they feel that others try to impose values on them from the outside. (shrink)

The Roman imperial Stoics were familiar with exile. This paper argues that the Stoics’ view of being a refugee differed sharply from their view of what is owed to refugees. A Stoic adopts the perspective of a cosmopolitēs, a “citizen of the world,” a rational being everywhere at home in the universe. Virtue can be cultivated and practiced in any locale, so being a refugee is an “indifferent” that poses no obstacle to happiness. Other people are our fellow cosmic citizens, (...) however, regardless of their language, race, ethnicity, customs, or country of origin. Our natural affinity and shared sociability with all people require us to help refugees and embrace them as welcome neighbors. Failure to do so violates our common reason, justice, and the gods’ cosmic law. (shrink)

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

Cheney’s claim that there is a subtextual affinity between ancient Stoicism and deep ecology is historically unfounded, conceptually unsupported, and misguided from a scholarly viewpoint. His criticisms of Stoic thought are thus merely ad hominem diatribe. A proper examination of the central ideas of Stoic ethics reveals the coherence and insightfulness of Stoic naturalism and rationalism. These Stoic concepts fit well with a rational social ecology (like Murray Bookchin's) which is sensitive to the unique capacities and unique responsibilities of human (...) beings. (shrink)

The Roman imperial Stoics were familiar with exile. I argue that the Stoics’ view of being a refugee differed sharply from their view of what is owed to refugees. A Stoic adopts the perspective of a cosmopolitēs, a ‘citizen of the world’, a rational being everywhere at home in the universe. Virtue can be cultivated and practiced in any locale, so being a refugee is an ‘indifferent’ that poses no obstacle to happiness. But other people are our fellow cosmic citizens (...) regardless of their language, race, ethnicity, customs, or country of origin. Our natural affinity and shared sociability with all people require us to help refugees and embrace them as welcome neighbors. Failure to do so violates our common reason, justice, and the gods’ cosmic law. (shrink)

Two principal questions are addressed: In De Finibus 3.54 what position does Cicero imagine the talus to fall and lie? How does this talus simile shed light on the problematic relationship between the Stoics’ doctrine of ‘preferred indifferents’ and their definition of the Good as virtue?

Schmidt's main thesis is that Lucretius did not exclusively use the writings of Epicurus in composing De rerurn natura, and that it is emphatically doubtful that Epicurus was even his principal source. Rather, Schmidt argues that it is virtually certain that early Epicurean writings are used in several passages, and that they are the most probable sources for the whole poem. Schmidt sees Lucretius as closely caught up with the current polemics between the Stoic and Epicurean schools of his time. (...) Schmidt is broadly successful in making his case that Lucretius did not exclusively follow Epicurus, but also had early Epicurean sources. The indices are helpful and the survey of competing views is scrupulously inclusive. This book deserves to be seriously considered by future researchers into the sources of De rerum natura inasmuch as it has certainly advanced the discussion. (shrink)

What is the fundamental purpose that justifies the existence of the modern university? The answer proposed in this essay is the promotion of social freedom. The essay begins by distinguishing social freedom from negative freedom and reflective freedom along the lines proposed by other theorists of social freedom, such as Frederick Neuhouser and Axel Honneth. After noting the need for a more developed account of the university than has so far been provided by these other theorists, the essay analyses the (...) various dimensions in which universities have, at their best, promoted social freedom. The essay then explains why it is through the promotion of social, as distinct from negative or reflective freedom, that universities fulfil their purpose. It concludes with some reflections on how this understanding of the purpose of the university fits an “immanent” model of social criticism. (shrink)

This paper argues that Plato recognized that Socrates’ rational, reflective love, learned from the wise Diotima, is the only means of achieving secure, self-sufficient happiness and so the only way to avoid tragedy in human life.

The New Labour we got was different from the New Labour that might have been, had the reform agenda associated with stakeholding and pluralism in the early-1990s been fully realised. We investigate the road not taken and what it means for ‘one nation’ Labour.

These comments on Sabine Grebe, "The Transformation of the Husband/Wife Relationship during Exile: Letters from Cicero and Ovid" raise questions about the similarities and dissimilarities of marriage and friendship examined in the marriages of Cicero and Ovid.

At Temple College, a community college in Texas, the administration forced Kerry Laird, a literature and composition professor, to remove from his office door the quote from Friedrich Nietzsche "Gott ist tot." The college says that to leave the phrase up would offend others and constitute an endorsement of the phrase. Laird, Cary Nelson, the national president of the American Association of University Professors, and William O. Stephens, chair of the American Philosophical Association Committee for the Defense of the Professional (...) Rights of Philosophers, see the ban as a violation of academic freedom and a double standard, since many other faculty members are permitted to display pro-religion statements and images on their doors. Stephens said that ever the ancient Athenians put Socrates to death for expressing non-traditional views, great philosophers have often caused offense. (shrink)

Charlie Croker, a self-made real estate tycoon, ex-Georgia Tech football star, horseback rider, quail-hunter, snakecatcher, and good old boy from Baker county Georgia, is the protagonist in Tom Wolfe’s latest novel, the deliciously provocative A Man in Full (New York: Farrar Straus Giroux, 1998).  In this article I examine the evolving conception of manhood in Wolfe’s novel.  Two different models of manliness will be delineated and compared. The first model—represented by Charlie Croker—gradually weakens and is replaced by the (...) second model—represented by Conrad Hensley. My aim is to show how Stoicism serves to critique the first model and articulate the second.  Stoicism, I argue, provides the deliverance of both Hensley and his convert Croker, while at the same time transforming the conception of manliness explored in A Man in Full. (shrink)