In this paper we analyse the ideas implicit in the style of exhibition favoured by contemporary galleries and museums, and argue that unless the audience is empowered to ascribe meaning and significance to artwork through critical dialogue, the power not only of the audience is undermined but also of art. We argue that galleries and museums preside over an experience economy devoid of art, unless (i) indeterminacy is understood, (ii) the critical rather than coercive nature of art is facilitated, and (...) (iii) the conditions for inter-subjectivity are met. (shrink)

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to (...) UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments. (shrink)

Elite women seized the public health campaign during the 1900 plague outbreak to assert political influence and advocate for sanitation reform grounded in their domestic experiences. These women advocated for their inclusion in the political sphere by valuing their domestic experiences as knowledge relevant for public health initiatives. This reframing of experience positioned them as viable citizens in the imminent Federation. Applying Laura Zanotti's concept of relational ontology, this analysis frames their actions as not simply a battle against institutional authority (...) but as careful and strategic interactions with their era's political context, exploiting aspects of it that were beneficial to them. Their ambivalent involvement in the public health campaign illustrates a complex chapter in Australian medical history. Women used the opportunity of plague to reevaluate their experience of the home as a form of knowledge relevant to public health. At the same time, they leveraged their growing status as political subjects to oppress others. (shrink)

Psychologists and philosophers have not yet resolved what they take implicit attitudes to be; and, some, concerned about limitations in the psychometric evidence, have even challenged the predictive and theoretical value of positing implicit attitudes in explanations for social behavior. In the midst of this debate, prominent stakeholders in science have called for scientific communities to recognize and countenance implicit bias in STEM fields. In this paper, I stake out a stakeholder conception of implicit bias that responds to these challenges (...) in ways that are responsive to the psychometric evidence, while also being resilient to the sorts of disagreements and scientific progress that would not undermine the soundness of this call. Along the way, my account advocates for attributing collective (group-level) implicit attitudes rather than individual-level implicit attitudes. This position raises new puzzles for future research on the relationship (metaphysical, epistemic, and ethical) between collective implicit attitudes and individual-level attitudes. (shrink)

In her 2004 book Carol Gould addresses the fundamental issue of democratizing globalization, that is to say of finding ways to open transnational institutions and communities to democratic participation by those widely affected by their decisions. The book develops a framework for expanding participation in crossborder decisions, arguing for a broader understanding of human rights and introducing a new role for the ideas of care and solidarity at a distance. Reinterpreting the idea of universality to accommodate a multiplicity of (...) cultural perspectives, the author takes up a number of applied issues, including the persistence of racism, cultural rights, women's human rights, the democratic management of firms, the use of the Internet to enhance political participation, and the importance of empathy and genuine democracy in understanding terrorism and responding to it. Accessibly written with a minimum of technical jargon this is a major contribution to political philosophy. (shrink)

I motivate and articulate a dispositional account of aversive racism. By conceptualizing and measuring attitudes in terms of their full distribution, rather than in terms of their mode or mean preference, my account of dispositional attitudes gives ambivalent attitudes (qua attitude) the ability to predict aggregate behavior. This account can be distinguished from other dispositional accounts of attitude by its ability to characterize ambivalent attitudes such as aversive racism at the attitudinal rather than the sub-attitudinal level and its deeper appreciation (...) of the analogy between traits and attitudes. (shrink)

When the third global plague pandemic reached Sydney in 1900, theories regarding the ecology and biology of disease transmission were transforming. Changing understandings led to conflicts over the appropriate response. Medical and government authorities employed symbols like dirt to address gaps in knowledge. They used these symbols strategically to compel emotional responses and to advocate for specific political and social interventions, authorising institutional actions to shape social identity and the city in preparation for Australia's 1901 Federation. Through theoretical and historical (...) analysis, this Element argues that disgust and aversion were effectively mobilised to legitimise these actions. As an intervention in contemporary debates about the impact of knowledge on emotion and affect, it presents a case for the plasticity of emotions like disgust, and for how both emotion and affect can change with new medical information. (shrink)

All the cards seem to be stacked against belief in immortality. Nonetheless, the resources of particular religious traditions may avail where generic philosophical solutions fall short. With attention to the boredom and narcissism critiques, intimations of deathlessness in Śāntideva's radical altruism, and recent Christian debates on the soul and the intermediate state, I propose two criteria for a coherent religion-specific belief in immortality: (1) the belief is supported by a fully realized religious tradition, (2) the belief satisfies the demand for (...) self-transcendence as well as for self-preservation. Where self-transcendence and self-preservation are kept in balance, and where the whole idea rests upon the lattice-work of a fully realized religious tradition, immortality is a fitting object of belief. Moreover, such belief is compatible with considerable speculative freedom concerning matter and spirit, body and soul, and personal identity over time. (shrink)

The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein (...) research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

In this paper I argue that, in addition to having an obligation to resist the oppression of others, people have an obligation to themselves to resist their own oppression. This obligation to oneself, I argue, is grounded in a Kantian duty of self-respect.

On the formation of the School of Interdisciplinary Studies at the University of Glasgow. -/- When the University of Glasgow’s new 'Crichton College' opened its doors in September 1999, its small staff had that rare opportunity in an academic’s career to launch a new curriculum based on clearly enunciated ideals. In the following six years under the direction of Professor Rex C. Taylor, those ideals remained firm even as numbers grew and external circumstances mutated. The theme of this book concerns (...) the ideas, activities and problems – intellectual, curricular and administrative – that shaped the University of Glasgow Crichton Campus during its first six years. Its dozen contributors provide varied perspectives on the problems of creation. (shrink)

Under the traditional system of peer-reviewed publication, the degree of prestige conferred to authors by successful publication is tied to the degree of the intellectual rigor of its peer review process: ambitious scientists do well professionally by doing well epistemically. As a result, we should expect journal editors, in their dual role as epistemic evaluators and prestige-allocators, to have the power to motivate improved author behavior through the tightening of publication requirements. Contrary to this expectation, I will argue that the (...) publication bias literature in academic medicine demonstrates that editor interventions have had limited effectiveness in improving the health of the publication and trial registration record, suggesting that much stronger interventions are needed. (shrink)

In his early experimental work with Suppes, Davidson adopted rationality assumptions, not as necessary constraints on interpretation, but as practical conceits in addressing methodological problems faced by experimenters studying decision making under uncertainty. Although the content of their theory has since been undermined, their methodological approach—a Galilean form of methodological rationalism—lives on in contemporary psychological research. This article draws on Max Weber’s verstehen to articulate an account of Galilean methodological rationalism; explains how anomalies faced by Davidson’s early experimental work gave (...) rise to his later, canonical claims about rationality and interpretation; and reclaims this Galilean framework for use in contemporary psychological research. (shrink)

There has been a growing concern over establishing norms that ensure the ethically acceptable and scientifically sound conduct of clinical trials. Among the leading norms internationally are the World Medical Association's Declaration of Helsinki, guidelines by the Council for International Organizations of Medical Sciences, the International Conference on Harmonization's standards for industry, and the CONSORT group's reporting norms, in addition to the influential U.S. Federal Common Rule, Food and Drug Administration's body of regulations, and information sheets by the Department of (...) Health and Human Services. There are also many norms published at more local levels by official agencies and professional groups.Any account of international standards should cover both scientific and ethical norms at once – the two are conceptually intertwined. Recent sources recognize that “[s]cientifically unsound research on human subjects is unethical in that it exposes research subjects to risks without possible benefit.”. (shrink)

This paper is an attempt to identify certain consonances between contemporary liberalism and classical pragmatism. I identify four of the most trenchant criticisms of classical liberalism presented by pragmatist figures such as James, Peirce, Dewey, Addams, and Hocking: that liberalism overemphasizes negative liberty, that it is overly individualistic, that its pluralism is suspect, that it is overly abstract. I then argue that these deficits of liberalism in its historical incarnations are being addressed by contemporary liberals. Contemporary liberals, I show, have (...) taken on board a surprising number of classical pragmatist insights and have responded to a surprising number of classical pragmatist criticisms. I thus argue that both contemporary pragmatism and contemporary liberalism have much to gain by joining forces. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because (...) proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

In this essay, I consider the question of whether women have an obligation to confront men who sexually harass them. A reluctance to be guilty of blaming the victims of harassment, coupled with other normative considerations that tell in favor of the unfairness of this sort of obligation, might make us think that women never have an obligation to confront their harassers. But 1 argue that women do have this obligation, and it is not overridden by many of the considerations (...) that can override other obligations to confront wrongdoers. (shrink)

The Protein Ontology (PRO) web resource provides an integrative framework for protein-centric exploration and enables specific and precise annotation of proteins and protein complexes based on PRO. Functionalities include: browsing, searching and retrieving, terms, displaying selected terms in OBO or OWL format, and supporting URIs. In addition, the PRO website offers multiple ways for the user to request, submit, or modify terms and/or annotation. We will demonstrate the use of these tools for protein research and annotation.

In this paper I consider the possibility that failing to fulfill the Kantian obligation to protect one’s rational nature might actually vitiate future instances of this obligation. I respond to this dilemma by defending a novel interpretation of Kant’s views on the relation between the value we have and the respect we are owed. I argue, contra the received view among Kant scholars, that the feature in virtue of which someone has unconditional and incomparable value is not the same feature (...) in virtue of which she is owed the respect that constrains how she may be treated. So, even though someone who fails to attempt to protect her rational nature fails to respect herself in the right way, and even though this moral failing does make her lose a certain kind of value, her obligations to respect herself do not go away. (shrink)

The emphasis on evidence based medicine (EBM) has placed increased focus on finding timely answers to clinical questions in presence of patients. Using a combination of natural language processing for the generation of clinical excerpts and information theoretic distance based clustering, we evaluated multiple approaches for the efficient presentation of context-sensitive EBM excerpts.

Ce dossier traite du concept de responsabilité en tant qu‘il constitue l‘une des bases d‘une réflexion éclairée en ce qui concerne les enjeux éthiques engen- drés par les biotechnologies. Qu‘entend-on par le concept de responsabilité ? L‘être humain est-il responsable des artéfacts qu‘il crée ? Si oui, de quel type de responsabilité s‘agit-il ? N‘est-elle que d‘ordre juridique ? Ou également d‘ordre éthique ou morale ? Comment et qui détermine l‘acceptation ou le re- fus des possibilités que nous offrent les (...) biotechnologies ? Qui est respon- sable des innovations produites par les découvertes des scientifiques, et à l‘égard de qui ? (shrink)

Ce dossier traite de l‘influence et de l‘impact de l‘amélioration humaine sur notre société ainsi que sur notre conception de ce que c‘est que d‘être humain. Quels enjeux les technosciences engendrent-elles ? D‘où vient ce besoin de vouloir s‘améliorer ? Quelles libertés a-t-on face à ces nouvelles technologies? Et quelle place tient l‘humain dans ce débat ?

This paper considers why obtaining and sustaining a good sexual life tends to be so challenging and why the temptation to settle for a bad one can be so alluring. We engage these questions by cultivating ideas found in the traditions of feminist philosophy and the philosophy of sex and love in dialogue with the works of two unlikely, canonical bedfellows—Immanuel Kant and Hannah Arendt. We propose that some sources of these challenges and temptations are patterned and manifold in that (...) they involve trying to transform, develop, integrate certain unruly emotional structures in oneself, including together with others. Other equally patterned and unruly sources track inherited oppressive or oppressed behaviors and feelings that make emotionally healthy, morally responsible realizations of sexual ways and being more difficult for all parties involved. In contrast to these patterned challenges, some difficulties that face us stem from the fact that humans are genuinely different from one another and evolving—individually, jointly, and collectively—in their sexual needs and wants. (shrink)

Quels impacts les techniques de procréation médicalement assistée ont-elles sur notre société? En quoi ces techniques nous obligent-elles à remettre en question, voire à repenser certains de nos principes?

Quel rôle la médecine a-t-elle à jouer dans l'accompagnement des personnes en fin de vie? Doit-elle poser certaines limites afin d'éviter un éventuel acharnement thérapeutique? Ou doit-elle laisser une liberté totale au patient concerné ainsi qu'à ses proches? Quels moyens propose-t-elle afin d'aborder la mort le plus sereinement possible?

The purpose of this text is to present a reading of the concept of motherhood that reveals the chains that identify it with a myriad of falsely natural gender roles. Based on the work of other women who compiled testimonies narrating different experiences around motherhood, to show that the understanding of this concept allows for motherhood to be lived within the acknowledgement and acceptance of said gender roles, even if they place mothers in a situation of oppression.

Abstract: This study focused on comparative assessment of the implementation of quality assurance mechanisms in educational management programme of federal and state universities in south-east, Nigeria. Four research questions and four null hypotheses guided the study. The study was carried out in the eight government-owned (3 federal and 5 state) universities in south-east that run educational management programme. The study adopted a survey research design on a population of eight heads of department. A 44-item researcher constructed questionnaire was used to (...) rate the implementation of quality assurance mechanisms as it relates to; moderation of examination, in-service professional development programmes, mock accreditation exercise, and infrastructural facilities. The instrument was validated by three experts, while a grand reliability index of 0.84 was obtained using crombach alpha reliability coefficient. Mean scores were used to answer the four research questions while t-test was used to test the four null hypotheses at 0.05 level of significance. The major findings of the study indicated that both federal and state universities in south-east implement the four mechanisms for quality assurance in educational management programme to a little extent. Though they both have implemented it to a little extent, the federal universities seem to record better implementation of these mechanisms compared to the state universities. This is supported by the outcome of research questions 3 & 4 as well as hypotheses 3 & 4. It was recommended among others that the National Universities Commission (NUC) should lay more emphasis on the state universities during the usual general/main accreditation exercise of institutions. This will reduce the differences that may exist in standard. Conclusions, implications and limitations of the study were made as well as suggestions for further studies. (shrink)

On définit souvent la philosophie comme l’« amour de la sagesse ». En grec, le terme « philosophe » qui signifie « ami de la sa- gesse » (philós= ami, sophía= sagesse) se rapporte à une personne qui aspire à une connaissance globale des choses. (1) Mais que sait-on vraiment de la philosophie? Comment procède-t-elle, à quels thèmes s‘intéresse-t-elle?

Categorization and memory for specific items are fundamental processes that allow us to apply knowledge to novel stimuli. This study directly compares categorization and memory using delay match to category (DMC) and delay match to sample (DMS) tasks. In DMC participants view and categorize a stimulus, maintain the category across a delay, and at the probe phase view another stimulus and indicate whether it is in the same category or not. In DMS, a standard item working memory task, participants encode (...) and maintain a specific individual item, and at probe decide if the stimulus is an exact match or not. Constrained Principal Components Analysis was used to identify and compare activity within neural networks associated with these tasks, and we relate these networks to those that have been identified with resting state-fMRI. We found that two frontoparietal networks of particular interest. The first network included regions associated with the dorsal attention network and frontoparietal salience network; this network showed patterns of activity consistent with a role in rapid orienting to and processing of complex stimuli. The second uniquely involved regions of the frontoparietal central executive network; this network responded more slowly following each stimulus and showed a pattern of activity consistent with a general role in role in decision-making across tasks. Additional components were identified that were associated with visual, somatomotor and default mode networks. (shrink)

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory (...) of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the “bottom up” approach) and (4) how to infer the nature of the last universal common ancestor (the “top down” approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin.We also describe another family of paths motivated by a” circularity” approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question. (shrink)

Three recent research reports by Topping and Trickey, by Fair and colleagues, and by Gorard, Siddiqui and Huat See have produced data that support the conclusion that a Philosophy for Children program of one-hour-per-week structured discussions has a marked positive impact on students. This article presents data from a follow up study done three years after the completion of the study reported in Fair et al.. The data show that the positive gains in scores on the Cognitive Abilities Test were (...) still present and had not faded after three years. Given the strength of these confirmations of the positive durable impact of the P4C program of structured discussions and given the relatively low cost of implementing the P4C program, it is recommended that it become a standard part of the school curriculum. (shrink)

This collection brings together fourteen contributions by authors from around the globe. Each of the contributions engages with questions about how local and global bioethical issues are made to be comparable, in the hope of redressing basic needs and demands for justice. These works demonstrate the significant conceptual contributions that can be made through feminists' attention to debates in a range of interrelated fields, especially as they formulate appropriate responses to developments in medical technology, global economics, population shifts, and poverty.

Eve Sedgwick critiques paranoid methodologies for denying a plurality of affective approaches. Instead, she emphasizes affects such as hope, but her description of hope's openness does not address how hope can avoid discourses that appear to offer amelioration while deceptively masking subjugation. In this context, I will argue that suspicion in feminist political philosophy, as shown in the earlier work of Carole Pateman and Judith Butler, provides a cautious approach toward hope's openness without precluding hope altogether. This analysis will reconsider (...) the domination and empowerment debates in relation to affect, pointing toward compatibilities between the two perspectives. First, I will expand Sedgwick's analysis of hope to explain its potential as a feminist political affect. Second, I will examine the techniques of suspicion employed by Pateman and Butler and how they risk denying possibilities for hope. This will lead to a discussion of how Amy Allen's theory of power indicates that suspicion is compatible with hope. Finally, I will explain how the suspicious approaches of Pateman and Butler illuminate hope as an inherently risky, fragile project. This will show that suspicion does not necessarily take up the totalizing position of paranoia, but rather can productively ensure that hope is not led astray. (shrink)

Effective altruists (EAs) seek to persuade the globally wealthy to donate a proportion of their income to do good, and specifically to donate it to those charit.

This article shows that Paul Ricoeur and Carol Gilligan develop their theories of the self by borrowing critically from Freudian aesthetics, adding an ethical dimension missing in it. Ricoeur critiques, completes and endorses the Freudian interpretation of the Oedipus, while Gilligan rejects it, since she considers it distorted by patriarchal ideology. Both are reclaiming the Freudian theory of culture by focusing on what Freud called the «life drive» as opposed to the «death drive». But Ricoeur does not pay the (...) same attention as Gilligan to patriarchal ideology conveyed by Greek tragedies. Thus, his ethics remains deeply rooted in the language of the tragic conflict (Oedipus, Antigone), while Gilligan’s ethics seeks to renew the language of pleasure (Cupid and Psyche). -/- ----------- Cet article montre que Paul Ricœur et Carol Gilligan développent leurs théories du soi en puisant de manière critique à l’esthétique freudienne, y ajoutant la dimension éthique manquante. Si Ricœur critique, complète et entérine l’interprétation freudienne de l’Œdipe, Gilligan se distingue davantage de Freud, qu’elle juge biaisé par l’idéologie patriarcale. Tous deux se réapproprient la théorie freudienne de la culture en mettant l’accent sur ce que Freud appelait la «pulsion de vie» par opposition à la «pulsion de mort». Mais comme Ricœur n’accorde pas la même attention que Gilligan à l’idéologie patriarcale véhiculée par les tragédies grecques, son éthique reste profondément enracinée dans le langage du conflit tragique (Œdipe, Antigone), alors que celle de Gilligan cherche à renouveler le langage du plaisir (Cupidon et Psyché). (shrink)

Guided by Hegel’s claim that rights are actualized only in the ethical life of the modern state, and that the “abstract spirit of Kant’s cosmopolitanism” is pervasive in Carol Gould’s Globalizing Democracy and Human Rights, Schaff raises a variety of moral, political, and ontological objections to her account of rights. He argues that if we embrace with Gould the idea that people have rights in abstraction, in political communities where they are not practically realized, we unwittingly play into the (...) hands of imperialism cloaked in human rights language—as exemplified by the rhetoric justifying recent U.S. interventions in Afghanistan and Iraq. (shrink)

The paper focuses on the “spillover thesis” which constitutes a pillar of much of contemporary participatory democratic theory; specifically, we assess the claim that workplace democratization leads to a higher degree of political participation amongst labourers. The paper analyses the thesis as formulated by Carole Pateman, including its later revisions triggered by ambiguous results of empirical studies aiming to (dis)prove it. The spillover thesis is then confronted with important methodological and theoretical critiques, the upshot being that in order to be (...) able to arrive at determinate conclusions, more carefully designed empirical studies are needed. Normatively speaking, however, blame can always be laid on the wider environment of market economy and/or representative democracy, to the effect that the spillover thesis is both difficult to disprove and radically subversive. Given the recent dominance of deliberative democratic theory which incorporates a strong participatory element, we finally discuss whether a recent innovation – namely, the concept of deliberative systems – could be fruitfully employed as a flexible umbrella-type framework for the spillover thesis and the participatory ideals related to it. (shrink)

The Biblical story of the Art (a floating, zoo-like device, constructed to survive climate turmoil and mass extinction) can be regarded as an archetypal image (in the terminology of Gaston Bachelard), capturing structural components of the human-animal relationship. Building on the contributions by Larson and Barr, Keulartz, Bovenkerk and Verweij, and Ramp and Bekoff, I will argue that, in the course of history, the Ark has evolved from a fictional (imaginary) icon into something increasingly real. The agricultural village of (...) the Neolithic era already functioned as a sheltered enclave, a survival machine designed to allow a select number of humans and accompanying species to withstand environmental fluctuations and survival pressure. In the current situation, however, the Ark has developed into a Gestell of planetary dimensions. The concept of the anthropocene basically conveys the idea that we have entered a global symbolical Ark, conceptualised by Teilhard de Chardin as the noosphere (the world-wide web of intelligence and policies, technologies and engineering, research and regulations) and emerging against the backdrop of a necro(s)cene: an ambiance of mass extinction. Increasingly, prospects for survival of a disconcertingly large number of species depend on human behaviour and human decision: on our ability or failure to collectively address the daunting challenges of the present. (shrink)

This paper is a response to Val Plumwoods call for writers to engage in ‘the struggle to think differently’. Specifically, she calls writers to engage in the task of opening up an experience of nature as powerful and as possessing agency. I argue that a critical component of opening up who or what can be understood as possessing agency involves challenging the conception of time as linear, externalised and absolute, particularly in as much as it has guided Western conceptions of (...) process, change and invention. I explore this through anthropologist Carol Greenhouse's claim that social conceptions of time can be read as theories of agency. Thus, in seeking to respond to Plumwood’s call to think differently, the question becomes: what kind of writing would enable a fundamental re-thinking of agency without, however, ignoring the way Western notions of agency have been shaped by linear accounts of time? I look to Jacques Derrida's work as one example. I first locate the possibility of re-writing time and agency in the experiential aspects of his writing, which I argue interrupt both the reader’s sense of agency and linear models of reading. But further, I connect Derrida’s work directly with Plumwood’s by examining how his deconstruction of the Western concept of invention may enable another account of creative change that could reshape what counts as ‘agency’ within the Anthropocene. (shrink)

This is a review essay on Carol Rovane's book The Metaphysics and Ethics of Relativism. I outline the main line of argument, clarify the central claim, raise some questions about some of the arguments, and suggest some limits on the extent to which one could see another's views as right but not accept them.

We have a striking ability to alter our psychological access to past experiences. Consider the following case. Andrew “Nicky” Barr, OBE, MC, DFC, (1915 – 2006) was one of Australia’s most decorated World War II fighter pilots. He was the top ace of the Western Desert’s 3 Squadron, the pre-eminent fighter squadron in the Middle East, flying P-40 Kittyhawks over Africa. From October 1941, when Nicky Barr’s war began, he flew 22 missions and shot down eight enemy planes (...) in his first 35 operational hours. He was shot down three times, once 25 miles behind enemy lines while trying to rescue a downed pilot. He escaped from prisoner of war camps four times, once jumping out of a train as it travelled from Italy into Austria. His wife Dot, who he married only weeks before the war, waited for him at home. She was told on at least three occasions that he was missing in action or dead. For 50 years, Nicky Barr never spoke publicly, and rarely privately, of his war-time experiences. He was very much a forgotten and forgetting hero (for further details, see Dornan, 2002). In his first public interview in 2002 on the Australian documentary program “Australian Story”, Nicky explained his 50 year silence by saying. (shrink)

Using the interactionist approach of comparative philosophy, I evaluate the intersecting points made in Animal Liberation by Peter Singer and The Sexual Politics of Meat: A Feminist-Vegetarian Critical Theory by Carol Adams. The purpose of this paper is to examine how a combination of the utilitarian and feminist perspectives helps us adopt a new philosophy accounting for all systems of oppression involved in eating animals. I conclude that by removing unnecessary harm to animals and unlearning phrases with an absent (...) reference to oppressed groups, society can progress toward an anti-oppressive system of liberation. (shrink)

I argue that Carol Gilligan's claims about female moral development reproduce and encourage the oppression of women. A comparison of her descriptions of abortion-decision study cases with those of Mary F. Belenky (whose dissertation recorded more data from the same interviews than did Gilligan's book), show troubling discrepancies. Gilligan's book is more literature than science, retelling women's stories in compelling--but misleading--ways.

In this thesis, I give a metascientific account of causality in medicine. I begin with two historical cases of causal discovery. These are the discovery of the causation of Burkitt’s lymphoma by the Epstein-Barr virus, and of the various viral causes suggested for cervical cancer. These historical cases then support a philosophical discussion of causality in medicine. This begins with an introduction to the Russo- Williamson thesis (RWT), and discussion of a range of counter-arguments against it. Despite these, I (...) argue that the RWT is historically workable, given a small number of modifications. I then expand Russo and Williamson’s account. I first develop their suggestion that causal relationships in medicine require some kind of evidence of mechanism. I begin with a number of accounts of mechanisms and produce a range of consensus features of them. I then develop this consensus position by reference to the two historical case studies with an eye to their operational competence. In particular, I suggest that it is mechanistic models and their representations which we are concerned with in medicine, rather than the mechanism as it exists in the world. -/- I then employ these mechanistic models to give an account of the sorts of evidence used in formulating and evaluating causal claims. Again, I use the two human viral oncogenesis cases to give this account. I characterise and distinguish evidence of mechanism from evidence of difference-making, and relate this to mechanistic models. I then suggest the relationship between types of evidence presents us with a means of tackling the reference-class problem. This sets the scene for the final chapter. Here, I suggest the manner in which these two different classes of evidence become integrated is also reflected in the way that developing research programmes change as their associated causal claims develop. (shrink)

Part of John Andrew Rice’s legacy, besides being a founder of Black Mountain College, is his vision of what a small liberal arts college curriculum should be. This vision helps shed light on some possible avenues by which to answer the following important questions: What implications do John Dewey’s progressive educational ideas have for experimenting with curricular design at small colleges? Does the college teacher’s struggle for improvement or growth depend on her having a belief that there is an ideal (...) liberal arts college curriculum? Probably the best known of such ready-made curricula is the Great Books Program, which employs a list of classic primary-source texts as the entry point into highly engaged dialogue, scholarship and learning guided by a teacher or tutor. In order to answer these questions, the paper turns to the historical debate between John Dewey and Robert Maynard Hutchins over the relative merits of progressive educational ideals and the Great Books approach. Most who have commented on this debate emphasize the differences between Dewey and Hutchins’ views.[ii] While Dewey emphasized learning through practical problem solving, in a dynamic mix of subject matter and method, Hutchins stressed exposure to and discussion of at least one-hundred primary texts in the Western canon, from Plato and Aristotle to Emerson and J.S. Mill. Hutchins resisted what he saw as the progressive educator’s push to transform the proper end of educating the whole person into training her for a particular vocation. In response, Dewey criticized Hutchins’ insistence that there existed a “hierarchy of truths” and that higher learning should remain aloof to the concerns of everyday life. Few commentators, however, mention the significant areas of agreement between the pedagogical approaches of Dewey and Hutchins, as well as other Great Books scholars. Since Rice praised the ideas of at least one Great Books proponent (Stringfellow Barr of St. John’s College), a more positive reconstruction of the Dewey-Hutchins exchange helps us to see how Dewey’s ideas informed Rice’s vision for the experimental college at Black Mountain—or so I argue.[iii]. (shrink)

This study presents a reconsideration of Levinas’s concept of the feminine. This reconsideration facilitated by a philosophically informed analysis of Levinas’s Talmudic readings on that subject. The innovation of this research is based on the methodology which combined the two corpuses of Levinas’ writings as important parts of his thought. Two main phenomena are derived from Levinas’ Talmudic readings and arouse main principles of his ethics. In the hearth of the discussion on Eros stated the differentiation of feminine and masculine (...) in Levinas’ thought, and its implication of gender and Ethics of otherness. In the center of Levinas’ terminology of maternity stated his phenomenology of pregnancy, and its ethical implication on responsibility to the other. The extreme responsibility committed to the subject since there is a immanent conflict between parents and their child. The characters of Leivnas’ discussion which described here are obligating the reconsideration of the philosophical question: are Levinas’ concepts of the feminine exclusive to the women? -/- The subjects of Levinas’s exploration of the feminine, in this view, emerge from his Talmudic readings, but his phenomenological analysis of those very subjects goes beyond what can be found in those readings. Analyzing the meaning of the difference between the sexes—the topic of one of the Talmudic readings—leads Levinas to a wider phenomenological treatment of the status of woman that does not bypass the feminine voice. Delving into the Talmudic concept of rodef (persecutor) as applied to the relationship of fetus and mother leads Levinas to a phenomenological analysis of the concept of maternity and readiness to accept responsibility (even suffering) for the Other. Those two discussions lead us to a rereading of Levinas’s essay “Phenomenology of Eros” and enable us to rebut the charge that in that essay Levinas presents only a masculine voice. Levinas’s concept of “responsibility” will be seen to resemble the feminist psychologist Carol Gilligan’s concept of “care.” We must then reconsider whether Levinas’s concept of the feminine is exclusively the domain of women. -/- . (shrink)

Peer reviewers at many funding agencies and scientific journals are asked to score submissions both on individual criteria and overall. The overall scores should be some kind of aggregate of the criteria scores. Carole Lee identifies this as a potential locus for bias to enter the peer review process, which she calls commensuration bias. Here I view the aggregation of scores through the lens of social choice theory. I argue that, when reviewing grant proposals, it is in many cases impossible (...) to avoid commensuration bias. (shrink)

This article introduces the idea of ‘dependence subtexts’ to explain how the stories that we encounter in property theory and public rhetoric function to make some actors appear ‘independent’, and thus capable of acquiring property in their own right, while making other actors appear ‘dependent’ and thus incapable of acquiring property. The argument develops the idea of ‘dependence subtexts’ out of the work of legal scholar Carol Rose and political theorist Carole Pateman, before using it as a tool for (...) contrasting the canonical property stories of John Locke and Pierre-Joseph Proudhon. We argue that the link between property and dependence provides a useful starting point for understanding issues of economic justice that share a common political problem: how do we choose to govern the relation between dependence and independence through the institution of property? (shrink)

This chapter examines the relation of the Human Development or Capability Approach to liberal political theory. If development is enhancement of capabilities, then this chapter adds that development is human and social: development includes (1) the creation of value as a social process that is (2) a dialectical product of people in their relations. Specifically: (1) The place of the individual within political theory must be revised if the political subject is, as Carol Gould argues, an “individual-in-relations” rather than (...) an autonomous individual agent. (2) New possibilities for valuation are also relational: value is created dialectically along with those possibilities through processes that may be modeled on Denis Goulet’s account of dialectical recognition. These axiological claims hold importance for the place of democratic participation in just politics and development. Building upon David Crocker’s work, this chapter argues that just politics may require a participative approach that is undercut by Martha Nussbaum’s suggestion that a list of central capabilities should guide the drafting of national constitutions. The assimilation of the indigenous concept sumak kawsay to the ideal of buen vivir within Ecuador’s constitution is illustrative, suggesting that prior specification (a list) may limit and distort the dialectical generation of new capabilities. (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. 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