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

Since 2023, the UK government's response to the “migrant crisis” has revolved around two controversial flagship policies: the deportation of asylum seekers to Rwanda, and the detention of migrants aboard a giant barge. In this short article, I examine the colonial and gendered dimensions of the two policies, finding them to be examples of the coloniality of gender. What this indicates, I suggest, is that the purpose of these policies is not merely to deter potential migrants—particularly LGBTQIA+ migrants—but also to (...) create a political narrative that allows the Conservative Party to garner right-wing votes by participating in high-profile culture wars; namely, the debate over transgender rights and the debate over how the UK should reckon with its imperial past. (shrink)

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

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

In this article, I expound and defend an interpretation of Sellars as a metaethical quasi-realist. Sellars analyzes moral discourse in non-cognitivist terms: in particular, he analyzes “ought”-statements as expressions of collective intentions deriving from a collective commitment to provide for the general welfare. But he also endorses a functional-role theory of meaning, on which a statement’s meaning is grounded in its being governed by semantical rules concerning language entry, intra-linguistic, and language departure transitions, and a theory of truth as correct (...) assertibility relative to such semantical rules. On these non-representationalist theories, even though moral statements are expressions of intentions and not fundamentally descriptive, they nevertheless count as assertorically meaningful, and some count as positively true. I further argue that this interpretation is capable not only of explaining Sellars’ explicitly metaethical writings, but also of unifying his scientific realism with his commitment to the ineliminable and indispensable role of the language of intentions: if this linguistic framework does not play an explanatory role, but only an expressive role, this explains both why Sellars’ commitment to it does not contravene his naturalism, as well as why, given the necessity of such language for our practical engagement with the world, the scientific image of humans in the world will only be completed once such language supplements it to enable us to relate practically to it. (shrink)

I take up two questions raised by Luz Christopher Seiberth's meticulous reconstruction of Wilfrid Sellars's theory of intentionality. The first is whether we should regard Sellars as a transcendental phenomenalist in the most interesting sense of the term: as denying that even an ideally adequate conceptual structure would enable us to represent worldly objects as they are in themselves. I agree with Seiberth that the answer is probably yes, but I suggest that this is due not to Sellars's rejection of (...) the Myth of the Given or appeal to image-models (as Seiberth maintains), but to his view of modality as categorial but as absent from the world an sich. The second is whether, as Richard Rorty complained, Sellars's appeal to picturing lands his theory of intentionality in intractable skepticism. Pace Seiberth, I argue that the transcendental role of picturing does not mitigate this problem, and I suggest that Sellars's most fruitful resource for doing so is not his semantic externalism, but his purely pragmatic response to skepticism. (shrink)

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

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

The proliferation of work by autistic writers continues apace, defying a long and multidisciplinary tradition of constructing autistic people as lacking the capacity for narration. To study neurodivergent literature, then, is to witness the refusal of these exclusionary narrative conventions, and to register the ideological presuppositions that underpin pathologization. In this article, I engage with recent insights from Neurodiversity Studies to explore the connections between narrative neuronormativity and other discourses of oppression, especially those that have generated racialized, gendered, and colonial (...) narratives of desubjectification. Focusing on the neuroqueer movement—an emergent practice of disidentification that refuses the interpellations of neuronormativity, ableism, heteronormativity, and cisnormativity—I discuss the concept of allism, arguing that this satirical critique of pathologization harbors a deconstructive force that denaturalizes the dialectic of recognition. Pursuing the discursive context and theoretical implications of this critique, I provide a short genealogy of narrative neuronormativity, connecting the operation of the dialectic in the early novel to the clinical texts of child psychology. To demonstrate the neuroqueer subversion of this tradition, I then read An Unkindness of Ghosts, by Rivers Solomon, a text that stages a disidentification with storytelling. Protagonist Aster’s neuroqueer refusal indexes the concomitance of the construction of Blackness as an ontological foil for whiteness and the construction of autism as a standard of disordered sociality that neuronorms can be measured against. My reading of Unkindness suggests that the extant techniques of literary narratorship are political instruments that will, unless repurposed, continue to disseminate these dispossessive dialectics. (shrink)

The article delves into the mystery that underlies the true nature of reality..Do we view reality as it is or is reality an illusion in the sense that it's a product of our senses rather than a fundamental part of the universe? These are some of the questions that have puzzled great thinkers for millennia.. The true nature of reality seems to be utterly elusive just as Brian Greene said "sometimes nature guards her secrets by the unbreakable grip of physical (...) law, sometimes the true nature of reality beckons from just beyond the horizon". (shrink)

Sometimes constitutions fail. The unprecedented election of Donald Trump, a populist insurgent who lacks the prior political experience or military service of all presidents before him, is such a sharp break in American historical experience that it raises questions as to whether something is deeply amiss with the constitutional order. Constitutional failure is not uncommon. A path-breaking global study of national constitutions shows that on average, they last only nineteen years. The U.S. Constitution is an uncommon outlier and, as such, (...) is accounted by many a long-running success story. But could a bell be tolling for American constitutionalism? In this Essay, I assess the meaning of Trump’s shocking rise for the future of our constitutional order. The shock, of course, was not the election of a Republican president. There have been many Republican presidents since Lincoln, each making their own distinctive contribution to the American tradition. Yet, there are good reasons to think this time around is different. The efficacy and, perhaps, stability of our constitutional order are in question, and we should try to understand why. (shrink)

There seems to be confusion and disagreement among scholars about the meaning of interpersonal forgiveness. In this essay we shall venture to clarify the meaning of forgiveness by examining various literary works. In particular, we shall discuss instances of forgiveness from Homer’s The Iliad, Euripides’ Hippolytus, and Aristotle’s Nicomachean Ethics and we shall focus on the changes that the concept of forgiveness has gone through throughout the centuries, in the hope of being able to understand, and therefore, of being able (...) to use more accurately, contemporary notions of forgiveness. We shall also explore the relationship between forgiveness and concepts that are closely associated with it, such as anger/resentment, hurt, clemency, desert/merit, excuse, etc. (shrink)

What grounds human rights? How do we determine that something is a genuine human right? This chapter offers a new answer: human beings have human rights to the fundamental conditions for pursuing a good life. The fundamental conditions for pursuing a good life are certain goods, capacities, and options that human beings qua human beings need whatever else they qua individuals might need in order to pursue a characteristically good human life. This chapter explains how this Fundamental Conditions Approach is (...) better than James Griffin’s Agency Approach as well as Martha Nussbaum’s Central Capabilities Approach. It also shows how it can be compatible with the increasingly popular Political Conceptions of human rights defended by John Rawls, Charles Beitz, and Joseph Raz. (shrink)

Rather than to focus upon a particular ‘right to life’, we should consider what rights there are pertaining to our lives and to our living. There are different sorts. There are, for instance, rights that constitute absences of particular duties and rights that correspond to the duties of other agents or agencies. There are also natural and non-natural rights and duties. Different people in different contexts can have different moral duties and different moral rights including rights to life. The question (...) of the moral rights there are to and pertaining to life is considered with reference to James Griffin’s account of human rights. Also considered is the question of who or what can be a bearer of them. (shrink)

The author seeks to make the fewest changes that would allow Christianity to withstand the challenges of the problem of evil . The project includes a critical review of the theodicies of John Hick and David Griffin, and also draws upon the thought of Sri Aurobindo. ;From Augustinian thought, the author retains the emphasis upon moral evil. He argues that any theodicy resolving moral evil also resolves natural evil, and that natural evil, as such, would not create major barriers (...) to religious faith. ;The author accepts John Hick's ideas of epistemic distance and soul-making, with supplementation. But he rejects Hick's use of the Greater Good Defense, instead positing that evil cannot be justified. The only question is whether it can be healed. ;David Griffin's strategy of adjusting divine traits to solve the POE is rejected. Instead, the author modifies Christian ideas of human identity and human destiny. Griffin's definition of evil is also rejected. Instead, the author defines evil as "a horrendous violation of an important human value." ;The author posits that Aurobindo correctly identified the Christian doctrine of "one lifetime only" as posing major problems for theodicy. The Indian view of multiple lifetimes helps to resolve dysteleological evil. Karma does not solve the POE all by itself, the author holds, but a revised notion of karma as "a law of appropriate experience" can make an essential contribution. The Indian view of human identity in terms of Self and ego personality is also adopted, again with some modification. ;The author uses an analogy of evil with a wound to argue that all evil can be healed, and must be healed in the process of psycho-spiritual growth. The conclusion is that evil may be ultimate to the ego personality, but is not ultimate to the soul, as such. From the perspective of the Soul or Self, suffering can be self-chosen for important and positive reasons. ;In short, a total picture of human identity and destiny gained by borrowing and revising Indian doctrines enables the author to suggest a new format for the interpretation of evil. (shrink)

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

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

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

This article examines the process theodicies of David Ray Griffin and Philip Clayton. It explains their differences on such issues as God’s primordial power and voluntary self-limitation, creativity as an independent metaphysical principle that limits God, creation out of nothing or out of chaos, and God’s voluntary causal naturalism. Difficulties with their positions are discussed. The Clayton-Knapp “no-not-once” principle is explained, and a more comprehensive process theodicy is outlined.

This book attempts to advance Donald Griffin's vision of the "final, crowning chapter of the Darwinian revolution" by developing a philosophy for the science of animal consciousness. It advocates a Darwinian bottom-up approach that treats consciousness as a complex, evolved, and multidimensional phenomenon in nature rather than a mysterious all-or-nothing property immune to the tools of science and restricted to a single species. -/- The so-called emergence of a science of consciousness in the 1990s has at best been a (...) science of human consciousness. This book aims to advance a true Darwinian science of consciousness in which its evolutionary origin, function, and phylogenetic diversity are moved from the field’s periphery to its very centre, thus enabling us to integrate consciousness into an evolutionary view of life. Accordingly, this book has two objectives: (i) to argue for the need and possibility of an evolutionary bottom-up approach that addresses the problem of consciousness in terms of the evolutionary origins of a new ecological lifestyle that made consciousness worth having and (ii) to articulate a thesis and beginnings of a theory of the place of consciousness as a complex evolved phenomenon in nature that can help us to answer the question of what it is like to be a bat, an octopus, or a crow. -/- A Philosophy for the Science of Animal Consciousness will appeal to researchers and advanced students interested in advancing our understanding of animal minds as well as anyone with a keen interest in how we can develop a science of animal consciousness. (shrink)

This chapter focuses on the psychological mechanisms behind the construction of preference, especially the actual processes used by humans when they make decisions in their everyday lives or in business situations. The chapter uses cognitive psychological techniques to break down these processes and set them in their social context. When attributes are compatible with the response scale, they are assigned greater weight because they are most easily mapped onto the response. For instance, when subjects are asked to set a price (...) for a gamble this task is compatible with the information about the gamble payoff, which is also expressed in monetary values (e.g., dollars). Conversely, when the task requires a choice the payoff information is not easily mapped onto the response anymore and loses some of its salience. In fact, Slovic, Griffin, and Tversky (1990) could show that using non-monetary outcomes attenuates preference reversals when no compatibility between the pricing task and the outcome attribute was possible. An assumption of the compatibility effect is that response modes compatible with specific characteristics of the options (e.g., payoffs) draw attention to them. One of the main themes that has emerged from behavioral decision research during the past decades is the view that people's preferences are often constructed—not merely revealed—in the process of elicitation (see e.g. Slovic). This conception is derived in part from studies demonstrating that normatively equivalent methods of elicitation often give rise to systematically different responses. These "preference reversals" violate the principle of procedure invariance fundamental to theories of rational choice and raise difficult questions about the nature of human values. If different elicitation procedures produce different orderings of options, how can preferences be defined and in what sense do they exist? Describing and explaining such failures of invariance will require choice models of far greater complexity than the traditional models -/- . (shrink)

Human rights theory and practice have long been stuck in a rut. Although disagreement is the norm in philosophy and social-political practice, the sheer depth and breadth of disagreement about human rights is truly unusual. Human rights theorists and practitioners disagree – wildly in many cases – over just about every issue: what human rights are, what they are for, how many of them there are, how they are justified, what human interests or capacities they are supposed to protect, what (...) they require of persons and institutions, etc. Disagreement about human rights is so profound, in fact, that several prominent theorists have remarked that the very concept of a “human right” appears nearly criterionless. In my 2012 article, “Reconceptualizing Human Rights”, I diagnosed the root cause of these problems. Theorists and practitioners have falsely supposed that the concept of “human right” picks out a single, unified class of moral entitlements. However, the concept actually refers to two fundamentally different types of moral entitlements: (A) international human rights, which are universal human moral entitlements to coercive international protections, and (B) domestic human rights, which are universal human moral entitlements to coercive domestic protections. Accordingly, I argue, an adequate “theory of human rights” must be a dual theory. The present paper provides the first such theory. First, I show that almost every justificatory ground given for “human rights” in the literature – such as the notion of a “minimally decent human life”, “urgent human interests”, and “human needs” – faces at least one of two fatal problems. Second, I show that after some revisions, James Griffin’s conception of “personhood” provides a compelling justificatory ground for international human rights. Third, I show that the account entails that there are very few international human rights – far fewer than existing human rights theories and practices suggest. Fourth, I show that there are reasons to find my very short list of international human rights compelling: “human rights justifications” for coercive international and foreign policy actions over the past several decades have consistently overstepped what can be morally justified, and my account reveals precisely how existing human rights theories and practices have failed to adequately grapple with these moral hazards. Finally, I outline an account of domestic human rights which fits well with many existing human rights beliefs and practices, vindicating those beliefs and practices, but only at a domestic level. (shrink)

David Ray Griffin does not fully come to terms with the fact that science has already abandoned the narrow materialist view of bits of matter pushing each other around. Even as early as Newton's law of gravitation, and most obviously with quantum physics, science has embraced the view that the world consists of relationships (often described as laws) between different types of processes and states.

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)

In an era of digital revolution, artificial intelligence, big data and augmented reality, technology has shifted from being a tool of communication to a primary medium of experience and sociality. Some of the most basic human capacities are increasingly being outsourced to machines and we increasingly experience and interpret the world through digital interfaces, with machines becoming ever more ‘social’ beings. Social interaction and human perception are being reshaped in unprecedented ways. This book explores this technologisation of the social and (...) the attendant penetration of permanent liminality into those aspects of the lifeworld where individuals had previously sought some kind of stability and meaning. Through a historical and anthropological examination of this phenomenon, it problematises the underlying logic of limitless technological expansion and our increasing inability to imagine either ourselves or our world in other than technological terms. Drawing on a variety of concepts from political anthropology, including liminality, the trickster, imitation, schismogenesis, participation, and the void, it interrogates the contemporary technological revolution in a manner that will be of interest to sociologists, social and anthropological theorists and scholars of science and technology studies with interests in the digital transformation of social life. -/- Table of Contents -/- Introduction: The Technologisation of the Social: A 21st-Century Megamachine? Paul O’Connor -/- 1. Communication as Theatricalisation: Self-Presentation in the Digital Age Arpad Szakolczai -/- 2. Parasites of the Social: Digital Disruptions of the Labour Market Tom Boland -/- 3. Possessed by Technology: The Metastasis of Absence Agnes Horvath -/- 4. Technologisation of the Social: Symbiosis, Parasitism, or Predation? Daniel Gati -/- 5. J'accuse Zéro: The Technology of Zero and the Making of a Personal Void Ray Griffin -/- 6. Digital Affordances and the Liminal Stephen Turner -/- 7. The Smart Womb: Digital Technologies and the Maze of Trickster Politics Marius Ion Benta -/- 8. Brave New Industry? The Dark Side of Dematerialisation and Industry 4.0 Thomas S.J. Smith -/- 9. ‘What Have You Caught?’: Nannycams and Hidden Cameras as Normalised Surveillance of the Intimate Janos Mark Szakolczai -/- 10. Coercive Visibility: Discipline in the Digital Public Arena Paul O’Connor -/- Conclusion: Is There a Way Out of the Technologisation of the Social? Marius Ion Benta. (shrink)

Pragmatist responses to skepticism about empirical justification have mostly been underwhelming, either presupposing implausible theses like relativism or anti-realism, or else showing our basic empirical beliefs to be merely psychologically inevitable rather than rationally warranted. In this paper I defend a better one: a modified version of an argument by Wilfrid Sellars that we are pragmatically warranted in accepting that our perceptual beliefs are likely to be true, since their likely truth is necessary for the satisfaction of our goal of (...) effective agency. On the version of the argument I defend, the great good for human life of control over our empirical circumstances renders our goal of effective agency reasonable. But only if our perceptual beliefs are likely to be true—and only if we accept that this is so, assuming it as a premise for inference and a guide for action—will the success of our actions be due to our effective agency, not mere luck. Since we’re warranted in taking the necessary means to our reasonable ends, we’re warranted in accepting that our perceptual beliefs are generally justified, and so that skepticism about empirical justification is false. (shrink)

The focus of this article is the "good-will theory", which explains the effect humans can have on the safety of AI, along with how it is in the best interest of a superintelligent AI to work alongside humans and not overpower them. Future papers dealing with the good-will theory will be published, but discuss different talking points in regards to possible or real objections to the theory.

In this paper, I argue for a revised account of two organizing principles in late antique Platonism: the scale of virtues (βαθμοί τῶν ἀρετῶν) and of inspired maniai (βαθμοί τῶν μανίων). Both structures are invoked frequently by Athenian and Alexandrian Neoplatonists between the 5th-6th centuries CE, and serve to organize their discussions of ethics and epistemology, metaphysics, hagiography, and philosophical reading curricula. I focus here on apparently contradictory evidence for the highest tiers of these scales, drawing on Hermias (c. 410-450 (...) CE), Damascius (c. 462–after 538 CE), and Olympiodorus (c. 500–after 565 CE). While many interpreters have reasonably found their testimonies irreconcilable, I argue that all three witnesses share a consistent view with one another and with Proclus. Both scales derive from a common model of ethical and perceptual transformation. In the first, 'painterly' model, we alternate between a vision of the paradigmatic model and its expression in the media of place and time; in the second, 'dancerly' model, we contemplate in action all at once, like a dancer moving to the music. (shrink)

Proclus argues that place (topos) is a body of light, identified as the luminous vehicle of the soul, which mediates between soul and body and facilitates motion. Simplicius (in Phys. 611,10–13) suggests that this theory is original to Proclus, and unique in describing light as a body. This paper focuses on the function of this theory as a bridge between Proclus’ physics and metaphysics, allowing the Aristotelian physical notion of “natural place” to serve as a mechanism for the descent and (...) ascent of the soul. (shrink)

The article tries to answer the questions ; what is consciousness? Why would a collection of matter be conscious? It attempts to describe a universal consciousness that is a fundamental part of building blocks of nature. It applies a counterintuitive view of consciousness in that consciousness is not a product of a brain but a fundamental part of the universe.. Panpsychism.

Intelligent tutoring system (ITS) is a computer system which aims to provide immediate and customized or reactions to learners, usually without the intervention of human teacher's instructions. Secretariats professional to have the common goal of learning a meaningful and effective manner through the use of a variety of computing technologies enabled. There are many examples of professional Secretariats used in both formal education and in professional settings that have proven their capabilities. There is a close relationship between private lessons intelligent, (...) cognitive learning and design theories; and there are ongoing to improve the effectiveness of ITS research. And it aims to find a solution to the problem of over-reliance on students' teachers for quality education. The program aims to provide access to high-quality education to every student, and therefore the reform of the education system as a whole. In this paper, we will use Intelligent Tutoring System Builder (ITSB) to build an education system on cloud computing in terms of the concept of cloud computing and components and how to take advantage of cloud computing in the field. (shrink)

Recent thinking within philosophy of mind about the ways cognition can extend has yet to be integrated with philosophical theories of emotion, which give cognition a central role. We carve out new ground at the intersection of these areas and, in doing so, defend what we call the extended emotion thesis: the claim that some emotions can extend beyond skin and skull to parts of the external world.

An Intelligent Tutoring System (ITS) is a computer system that offers an instant, adapted instruction and customized feedback to students without human teacher interference. Reciting "Tajweed" the Holy Quran in the appropriate way is very important for all Muslims and is obligatory in Islamic devotions such as prayers. In this paper, the researchers introduce an intelligent tutoring system for teaching Reciting "Tajweed". Our "Tajweed" tutoring system is limited to "Tafkhim and Tarqiq in TAJWEED" the Holy Quran, Rewaya: Hafs from ‘Aasem. (...) The system was evaluated by reciting teachers and students, and the results were auspicious. (shrink)

This study presented the policy of functional integration of the product planning team as a strategy for the development of the pharmaceutical industry in Palestine. The study population consists of all the workers in companies operating in the field of medicine in Palestine, which are (5) companies producing in the West Bank only for pharmaceuticals used by these companies, which are (296) employees, and was used a simple random sample to choose the sample and size (87) employees of the study (...) population, and to achieve the objectives of the study (87) questionnaires were distributed. The descriptive analytical method was used, and SPSS was used to answer and discuss the study's questions. The results showed that there is a significant relationship between the effectiveness of the policy of product development and the competitiveness of pharmaceutical companies in Palestine (West Bank), where the policy of product development efficiency accounts for 56.6% of the total change in the competitiveness of companies. The product quality component was most influential at all levels of product development effectiveness policy, followed by product identification, product cost reduction, packaging and product deletion. The weakest areas of strategic direction in pharmaceutical companies in Palestine (West Bank) are 67%. The weakest aspects of job integration are: non-regular meetings of representatives of different positions to participate in any project related to product development, to achieve spatial convergence of members of the product planning policy team in offices, laboratories and workplaces. (shrink)

Historically, republicans were of different minds about markets: some, such as Rousseau, reviled them, while others, like Adam Smith, praised them. The recent republican resurgence has revived this issue. Classical liberals such as Gerald Gaus contend that neo-republicanism is inherently hostile to markets, while neo-republicans like Richard Dagger and Philip Pettit reject this characterization—though with less enthusiasm than one might expect. I argue here that the right republican attitude toward competitive markets is celebratory rather than acquiescent and that republicanism demands (...) such markets for the same reason it requires the rule of law: because both are essential institutions for protecting individuals from arbitrary interference. I reveal how competition restrains—and in the limit, even eradicates—market power and thereby helps us realize “market freedom,” i.e., freedom as non-domination in the context of economic exchange. Finally, I show that such freedom necessitates “Anglo-Nordic” economic policies. (shrink)

The study aimed to identify the leadership features and their relationship to increasing achievement motivation among Palestinian police employees in Gaza Strip in light of the Corona pandemic. To achieve the study’s objectives, the researchers used the descriptive method in its analytical method, using a questionnaire applied to the police officers at the Central Governorate Police Station, whose number is (113) individuals. They were chosen in a stratified, random manner, and the study resulted in a set of results, the most (...) important of which is that the effect of leadership characteristics of Palestinian police employees in Gaza Strip, which came with a relative weight (76.20%), which is, to a large extent, the level of increase in achievement motivation among employees in the Palestinian Police in Gaza Strip. Gaza under the outbreak of the Corona epidemic? Which came with a relative weight (82.40%), which is to a large extent. While it resulted in a positive correlation between the impact of leadership characteristics and the increase in achievement motivation, there are no statistically significant differences between the averages of the study sample's estimates about the impact The leadership characteristics of the Palestinian Police in Gaza Strip are attributed to the variable of the age group, academic qualification, scientific specialization, scientific experience. There are no statistically significant differences between the averages of the estimates of the individuals of the study sample about The achievement motivation in the Palestinian Police in Gaza Strip is attributable to a variable, age group, academic qualification, scientific specialization, scientific experience, and in light of these results the researchers suggested a set of recommendations, the most important of which are: The need to tighten penalties for individuals by the Central Governorate Police Station for violating the instructions issued by the Ministry Interior In light of the outbreak of the Corona epidemic, increased interest in preparing and organizing specialized training courses and programs in the field of dealing with all different segments in order to preserve the lives of people from the Corona epidemic. (shrink)

Abstract: This study aims to identify the level of creativity in the University of Palestine from the point of view of the employees, as the researchers used the descriptive and analytical method, through a questionnaire distributed to a sample of employees at the University of Palestine, where the size of the study population is (234) employees, and the size of the sample (117) employees, of which (90) employees responded. The study reached a set of results, the most important of which (...) are: A high degree of creativity from the employees 'point of view, and the study confirmed that there were no differences in the level of creativity at the University of Palestine from the Employees point of view, according to demographic variables. The study presented a set of recommendations, the most important of which are: The need for universities to enhance creativity. (shrink)

Preparing general relativity for quantization in the Hamiltonian approach leads to the `problem of time,' rendering the world fundamentally timeless. One proposed solution is the `thermal time hypothesis,' which defines time in terms of states representing systems in thermal equilibrium. On this view, time is supposed to emerge thermodynamically even in a fundamentally timeless context. Here, I develop the worry that the thermal time hypothesis requires dynamics -- and hence time -- to get off the ground, thereby running into worries (...) of circularity. (shrink)

The pandemic has been the most vivid agent of change that many of us have known. But it has not changed everything: plenty of the institutions, norms, and practices that sustain racial capitalism, settler colonialism, and cisheteropatriarchy have either weathered the storm of the crisis or been nourished by its effects. And yet enough has changed for us to see that the pandemic has profoundly recontextualised those structures and systems of violence, bringing us into a fresh negotiation with, for example, (...) the question of how we discuss and imagine freedom. Responding in part to this unexpected provocation, activist-scholars Robyn Maynard and Leanne Betasamosake Simpson forged a collaboration from the lockdown of 2020, corresponding by letter to create their forthcoming book, Rehearsals for Living, due to be published by Haymarket Books (US) and Knopf (Canada) in 2022. In this interview, we asked them to explain the epistolary form of the book and expand on the concept of “rehearsal”, before inviting them to reflect on a series of issues that animate our current crises: the politics of recognition; the notion of apocalypse; ways to disrupt linear temporalities; practises of reciprocity against proprietary logics; the gendered violence of state apparatuses; and worldbuilding as a method of resistance. In their expansive answers, Robyn and Leanne draw on their experiences as organisers and educators, commenting on anticolonial struggles, the Movement for Black Lives, and the rise of abolition discourse. Stressing the need to build a multiplicity of shared homespaces in the face of racial/colonial capitalism and organized abandonment, they challenge us to rethink the predicaments and possibilities of the present, enabling us to imagine futures liberated of extractivist, carceral governance – “planting more liberatory futures in the present”, as Robyn puts it. The task of sowing those seeds is a collective praxis of rewriting the narratives that constitute us, refusing to hear that nothing can change and insisting that everything must. (shrink)

Clark and Chalmers (1998) defend the hypothesis of an ‘Extended Mind’, maintaining that beliefs and other paradigmatic mental states can be implemented outside the central nervous system or body. Aspects of the problem of ‘language acquisition’ are considered in the light of the extended mind hypothesis. Rather than ‘language’ as typically understood, the object of study is something called ‘utterance-activity’, a term of art intended to refer to the full range of kinetic and prosodic features of the on-line behaviour of (...) interacting humans. It is argued that utterance activity is plausibly regarded as jointly controlled by the embodied activity of interacting people, and that it contributes to the control of their behaviour. By means of specific examples it is suggested that this complex joint control facilitates easier learning of at least some features of language. This in turn suggests a striking form of the extended mind, in which infants’ cognitive powers are augmented by those of the people with whom they interact. (shrink)

We present an axiomatization of non-relativistic Quantum Mechanics for a system with an arbitrary number of components. The interpretation of our system of axioms is realistic and objective. The EPR paradox and its relation with realism is discussed in this framework. It is shown that there is no contradiction between realism and recent experimental results.

The study aimed to identify the level of organizational performance in ceramic companies in the Tenth of Ramadan City, where the researchers used the descriptive analytical method, through a questionnaire distributed. The study reached a set of results, the most important of which are: the presence of a clear consensus of the study sample from the members of the senior management that all dimensions of the balanced scorecard variable are largely present in the ceramic companies under study, and the results (...) showed the approval of the study sample of workers in an average way on the application of the financial dimension and that it is applied Well, the approval of the study sample of the employees in an average way that tends to decline on the degree of application of the customer dimension and that it is applied by the senior management in an inappropriate way, the approval of the study sample of the employees in a large way on the degree of application of the internal operations dimension and that it is applied by the senior management in a large and appropriate way, approval The study sample of workers applying the learning and growth dimension is moderately low and it is applied inappropriately by the senior management. The study presented a set of recommendations, the most important of which are: working on clarifying and translating the vision and strategy of the institution, working on clarifying the strategy and linking it to the goals, planning and setting goals and arranging strategic initiatives, promoting strategic feedback. (shrink)

Half of the drug offenders incarcerated in the United States are black, even though whites and blacks use and sell drugs at the same rate, and blacks make up only 13 percent of the population. Noncomparativists about retributive justice see nothing wrong with this picture; for them, an offender’s desert is insensitive to facts about other offenders. By contrast, comparativists about retributive justice assert that facts about others can partially determine an offender’s desert. Not surprisingly, comparativists, especially comparative egalitarians, contend (...) that differential punishment is retributively unjust. I agree with this assessment, but take issue with the reasons egalitarians cite in its favor. In this paper, I argue that differential punishment violates retributive justice because it contributes to structural racial oppression. Over the course of developing and defending this claim, I identify the shortcomings of both comparative egalitarianism and respectarianism, which is the most popular and plausible brand of noncomparativism. (shrink)

This interview, conducted over the span of several months, tracks the respective journeys of Constantin V. Boundas and Daniel W. Smith with the philosophy of Gilles Deleuze. Rather than “becoming Deleuzian,” which is neither desirable nor possible, these exchanges reflect an array of encounters with Deleuze. These include the initial discoveries of Deleuze’s writings by Boundas and Smith, in-person meetings between Boundas and Deleuze, and the wide-ranging and influential philosophical work on Deleuze’s concepts produced by both Boundas and Smith. At (...) stake in this discussion are key contributions by Deleuze to continental philosophy, including the distinction between the virtual and the actual and the very nature of a “concept.” Also at stake is the formative or pedagogical impact of a philosopher, like Deleuze, on those who find and fully engage with his texts, concepts, and project. Cette interview, menée sur plusieurs mois, suit les parcours respectifs de Constantin V. Boundas et Daniel W. Smith avec la philosophie de Gilles Deleuze. Au lieu de « devenir Deleuzien, » ce qui n’est ni souhaitable ni possible, ces échanges reflètent un éventail de rencontres avec Deleuze. Il s’agit notamment des premières découvertes des écrits de Deleuze par Boundas et Smith, des rencontres en personne entre Boundas et Deleuze, et du travail philosophique vaste et in????luent sur les concepts de Deleuze produit par Boundas et Smith. L’enjeu ici étant les contributions clés de Deleuze à la philosophie continentale, y compris la distinction entre le virtuel et l’actuel, et la nature même d’un « concept. » Mais il y a aussi l’impact formateur ou pédagogique d’un philosophe, comme Deleuze, sur ceux qui trouvent et s’engagent pleinement dans ses textes, ses concepts et ses projets. (shrink)

This essay argues that the exploration of scepticism and its implications in the work of Stanley Cavell and David Hume bears more similarities than is commonly acknowledged, especially along the lines of what I wish to call “sceptical naturalism.” These lines of similarity are described through the way each philosopher relates the “natural” and “nature” to the universal, the necessary, and the conventional.

Most philosophers discuss the Repugnant Conclusion as an objection to total utilitarianism. But this focus on total utilitarianism seems to be one-sided. It conceals the important fact that other competing moral theories are also subject to the Repugnant Conclusion. The primary aim of this paper is to demonstrate that versions of egalitarianism are subject to the Repugnant Conclusion and other repugnant conclusions.

Economic theories of democratic legitimacy have criticized deliberative accounts of democratic legitimacy on the grounds that they do not represent a practical possibility and that they create conditions that make actual democracies worse. It is not simply that they represent the wrong ideal. Rather, they are too idealistic – failing to show proper regard for the cognitive and moral limitations of persons and the depth of disagreement in democratic society. This article aims to show that the minimalist criterion of democratic (...) legitimacy is self-defeating and that even if there are minimal cognitive, moral, and social requirements for the possibility of practicable deliberative democracy, these limitations do not necessarily impose insuperable barriers for democratic deliberation as the normative basis of democratic legitimacy. Thus, the limiting facts do not dictate the structure of appropriate normative models of democracy in the way minimalists have supposed. (shrink)

In the first part of this article we briefly describe the design and development of a Consciousness Studies concentration at Goddard College, a student centered, progressive educational institution in the northeastern United States. We emphasize the tensions we experienced between different orientations in Consciousness Studies and especially the one related to the scientific and transpersonal ends of the spectrum of consciousness. In the second part, we relate the scientific‐transpersonal issue that we experienced at Goddard to the broader theory and practice (...) of Consciousness Studies. We also link the latter to the so‐called explanatory gap between third and first person forms of consciousness and the call for first person methods of exploring consciousness. Our conclusion is that the scientific approach has the edge and is at risk of assimilating other approaches to the detriment of Consciousness Studies. In our view, the future development of Consciousness Studies, both in theory and practice, requires several different approaches from the scientific to the transpersonal and privileging one is to narrow the field of possibilities and to risk falling prey to one‐sidedness. (shrink)