We describe on-going work on IAO-Intel, an information artifact ontology developed as part of a suite of ontologies designed to support the needs of the US Army intelligence community within the framework of the Distributed Common Ground System (DCGS-A). IAO-Intel provides a controlled, structured vocabulary for the consistent formulation of metadata about documents, images, emails and other carriers of information. It will provide a resource for uniform explication of the terms used in multiple existing military dictionaries, thesauri and metadata registries, (...) thereby enhancing the degree to which the content formulated with their aid will be available to computational reasoning. (shrink)

We address the ethics of scenarios in which one party entraps, intentionally tempts or intentionally tests the virtue of another. We classify, in a new manner, three distinct types of acts that are of concern, namely acts of entrapment, of intentional temptation and of virtue testing. Our classification is, for each kind of scenario, of itself neutral concerning the question whether the agent acts permissibly. We explain why acts of entrapment are more ethically objectionable than like acts of intentional temptation (...) and why these, in turn, are more ethically objectionable than like acts of virtue testing. Along the way, we scrutinize, and eventually reject, the view that acts of entrapment are ethically unacceptable because intentional temptation is involved in entrapment. (shrink)

Researchers and practitioners are increasingly using machine‐generated synthetic data as a tool for advancing health science and practice, by expanding access to health data while—potentially—mitigating privacy and related ethical concerns around data sharing. While using synthetic data in this way holds promise, we argue that it also raises significant ethical, legal, and policy concerns, including persistent privacy and security problems, accuracy and reliability issues, worries about fairness and bias, and new regulatory challenges. The virtue of synthetic data is often understood (...) to be its detachment from the data subjects whose measurement data is used to generate it. However, we argue that addressing the ethical issues synthetic data raises might require bringing data subjects back into the picture, finding ways that researchers and data subjects can be more meaningfully engaged in the construction and evaluation of datasets and in the creation of institutional safeguards that promote responsible use. (shrink)

Our question is this: What makes an act one of entrapment? We make a standard distinction between legal entrapment, which is carried out by parties acting in their capacities as (or as deputies of) law- enforcement agents, and civil entrapment, which is not. We aim to provide a definition of entrapment that covers both and which, for reasons we explain, does not settle questions of permissibility and culpability. We explain, compare, and contrast two existing definitions of legal entrapment to commit (...) a crime that possess this neutrality. We point out some problems with the extensional correctness of these definitions and propose a new definition that resolves these problems. We then extend our definition to provide a more general definition of entrapment, encompassing both civil and legal cases. Our definition is, we believe, closer to being extensionally correct and will, we hope, provide a clearer basis for future discussions about the ethics of entrapment than do the definitions upon which it improves. (shrink)

There is a global shortage of organs for transplantation and despite many governments making significant changes to their organ donation systems, there are not enough kidneys available to meet the demand. This has led scientists and clinicians to explore alternative means of meeting this organ shortfall. One of the alternatives to human organ transplantation is xenotransplantation, which is the transplantation of organs, tissues, or cells between different species. The resurgence of interest in xenotransplantation and recent scientific breakthroughs suggest that genetically-engineered (...) pigs may soon present a realistic alternative as sources of kidneys for clinical transplantation. It is therefore important for nurses and allied health professionals to understand what is involved in xenotransplantation and its future implications for their clinical practices. First, we explore the insufficiency of different organ donation systems to meet the kidney shortage. Second, we provide a background and a summary of the progress made so far in xenotransplantation research. Third, we discuss some of the scientific, technological, ethical, and economic issues associated with xenotransplantation. Finally, we summarise the literature on the attitudes of healthcare professionals toward xenotransplantation. (shrink)

Some legal theorists say that legal entrapment to commit a crime is incoherent. So far, there is no satisfactorily precise statement of this objection in the literature: it is obscure even as to the type of incoherence that is purportedly involved. (Perhaps consequently, substantial assessment of the objection is also absent.) We aim to provide a new statement of the objection that is more precise and more rigorous than its predecessors. We argue that the best form of the objection asserts (...) that, in attempting to entrap, law-enforcement agents lapse into a form of practical incoherence that involves the attempt simultaneously to pursue contrary ends. We then argue that the objection, in this form, encompasses all cases of legal entrapment only if it is supplemented by appeal to the premise that law-enforcement agents have an absolute duty never to create crimes. (shrink)

Formal clinical trials of pig-to-human organ transplant—known as xenotransplantation—may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have (...) been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical–ethical account of xenotransplantation and details if or how viewpoints have shifted over time. (shrink)

Under a ‘dirty hands’ model of undercover policing, it inevitably involves situations where whatever the state agent does is morally problematic. Christopher Nathan argues against this model. Nathan’s criticism of the model is predicated on the contention that it entails the view, which he considers objectionable, that morally wrongful acts are central to undercover policing. We address this criticism, and some other aspects of Nathan’s discussion of the ‘dirty hands’ model, specifically in relation to state entrapment to commit a crime. (...) Using János Kis’s work on political morality, we explain three dilemmatic versions of the ‘dirty hands’ model. We show that, while two of these are inapplicable to state entrapment, the third has better prospects. We then pursue our main aim, which is to argue that, since the third model precludes Nathan’s criticism, a viable ‘dirty hands’ model of state entrapment remains an open possibility. Finally, we generalize this result, showing that the case of state entrapment is not special: the result holds good for policing practices more generally, including such routine practices as arrest, detention, and restraint. (shrink)

In August of 2000, Firestone executives initiated the second largest tire recall in U.S. history. Many of the recalled tires had been installed as original factory equipment on the popular Ford Explorer SUVs. At the time of the recall, the tires and vehicles had been linked to numerous accidents and deaths, most of which occurred when tire blowouts resulted in vehicle rollovers. While Firestones role in this case has been widely acknowledged, Ford executives have managed to deflect much of the (...) attention away from themselves, mainly by claiming that the Firestone tires were not its product, and therefore not its responsibility. In this paper, we examine the extent to which Ford can be held morally responsible for the incidents at issue. In so doing, we develop an approach for determining when an item is a product in its own right, as opposed to a component of another product. We argue that such an analysis not only provides a better understanding of this case, but also more properly accounts for the extent to which evolutions in technology and business relationships can affect issues of moral responsibility in business contexts. (shrink)

Benjamin Schnieder has argued that several traditional definitions of truth-functionality fail to capture a central intuition informal characterizations of the notion often capture. The intuition is that the truth-value of a sentence that employs a truth-functional operator depends upon the truth-values of the sentences upon which the operator operates. Schnieder proposes an alternative definition of truth-functionality that is designed to accommodate this intuition. We argue that one traditional definition of ‘truth-functionality’ is immune from the counterexamples that Schnieder proposes and is (...) preferable to Schnieder’s alternative. (shrink)

This review article provides a new perspective on the ethics of green nudging. We advance a new model for assessing the ethical permissibility of green nudges (GNs). On this model, which provides normative guidance for policymakers, a GN is ethically permissible when the intervention is (1) efficacious, (2) cost-effective, and (3) the advantages of the GN (i.e. reducing the environmental harm) are not outweighed by countervailing costs/harms (i.e. for nudgees). While traditional ethical objections to nudges (paternalism, etc.) remain potential normative (...) costs associated with GNs, any such costs must be weighed against the injunction to reduce environmental harm to third parties. (shrink)

Kit Fine has proposed a new solution to what he calls ‘a familiar puzzle’ concerning modality and existence. The puzzle concerns the argument from the alleged truths ‘It is necessary that Socrates is a man’ and ‘It is possible that Socrates does not exist’ to the apparent falsehood ‘It is possible that Socrates is a man and does not exist’. We discuss in detail Fine’s setting up of the ‘puzzle’ and his rejection, with which we concur, of two mooted solutions (...) to it. (One of these uses standard, Kripkean, notions, and the other rests on work done by Arthur Prior.) We set out, and reject, the philosophy of modality underlying Fine’s new solution, and we defend an alternative response to the alleged puzzle. Our solution follows the work of David Wiggins in distinguishing between the sentential operator ‘It is necessary that’ and the predicate modifier ‘necessarily’. We briefly provide this distinction with a possible- world semantics on which it is neither a necessary truth, in some sense, that Socrates exists nor true, in some sense, that Socrates necessarily exists. (shrink)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are (...) extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity. (shrink)

This article explores the law and ethics of lobbying. The legal discussion examines disclosure regulations, employment restrictions,bribery laws, and anti-fraud provisions as each applies to the lobbying context. The analysis demonstrates that given the social value placed on the First Amendment, federal law generally affords lobbyists wide latitude in determining who, what, when, where, and how to lobby.The article then turns to ethics. Lobbying involves deliberate attempts to effect changes in the law. An argument is advanced that because law implicates (...) the use of force and because law ideally reflects the values of a democratic society, seeking to slant the law to serve a client’s narrow interests cannot provide an adequate ethical end for a lobbyist. On the contrary, a lobbyist has an affirmative moral duty to seek reasonably balanced and just laws. The article examines, refines, and defends this proposition in a number of settings. (shrink)

Many commentators lament that American democracy is in crisis. It is becoming a system of minority rule, wherein a party with a minority of the nationwide vote can control the national government. Partisan gerrymandering in the House of Representatives fuels this crisis, as does the equal representation of small and large states in the Senate. But altering these features of the legislature would not end minority rule. Indeed, it has long been held that majority rule cannot be guaranteed within any (...) district system, as a minority of voters nationwide can be efficiently distributed such that a minority party wins a majority of districts by narrow margins. -/- This Article offers a way to save majority rule. Since the way a party can gain control of the legislature with a minority of the vote is to win a majority of districts by narrow margins of victory and lose a minority of districts by large margins of victory, the solution is to make margins matter. Hence, this Article proposes that we preserve electoral districts in which the candidate with the most votes wins, while making the weight of their vote in the legislature (a representative’s “legislative power”) a function of margins of victory. The first goal of this Article is to outline how this proposal, which I call “weighted voting by margin of victory” (WVMV), retains the democratic virtues of district systems while ending minority rule. This is the first basis for the democratic imperative to make margins matter. -/- There is, however, a second basis for that same imperative, which turns on the political equality of voters. The U.S. Supreme Court has long held that the democratic equality should be understood in terms of equal voting power (one person, one vote). But when margins of victory don’t matter, the power of a vote lies exclusively in its potential decisiveness. A vote that changes the margin of victory without changing the victor is “wasted”. But it is an electoral reality that votes in competitive districts are more likely to be decisive, and votes in uncompetitive districts are more likely to be wasted; as a result, candidates and parties are more responsive to some voters than others. So voters are not political equals. They do not have equal voting power, except in an empty formalistic sense. By contrast, WVMV gives votes a second type of power. The power of a vote is to potentially decide who wins and to actually change the legislative power of the victor. Each vote, in effect, transfers a unit of political power to a democratic representative. This “transference” power can be meaningfully equalized between voters. A voter in an uncompetitive district is far less likely to change who wins, but is equally able to change the margin of victory, such that their vote is no longer wasted. This gives candidates and parties a strong reason to be more equally responsive to all voters who can change the margins. Hence, there is a democratic imperative to make margins matter, in order to give voters a meaningfully equal form of voting power. -/- The final goal of this Article is to explain how we can implement WMVM in modern democracies, focusing on three particularly challenging cases: the U.S. Senate, the Parliament of the United Kingdom, and the U.S. House of Representatives. These cases are challenging for several reasons, the most pertinent of which turn on the ways we should understand margins of victory when electorates are of unequal sizes (as in the U.S. Senate) or are contested by more than two parties (as in the U.K.) or are conducted under different voting procedures (as in many districts in the U.S. House). I argue that WVMV should be considered feasible in such contexts, and hence offers a practical, rather than purely theoretical, alternative to the status quo. (shrink)

David Lewis rejected consequentialism in ethics. However, two aspects of his meta-ethical views make it a challenge to see how consequentialism could be resisted. Lewis endorses a maximising conception of rationality, where to be rational is to maximise value of a certain sort; he appears to think it is possible to be both rational and moral; and yet he rejects conceptions of moral action as acting to maximise moral value. The second tension in Lewis's views arises from his meta-ethics. Lewis's (...) naturalisation of morality is in terms of a naturalised account of value, including moral value. Insofar as he offers a motivational story for moral judgements, it is one that goes via a motivational connection to value. Yet his anti-consequentialism seems to commit him to rejecting a story of moral action entirely in terms of pursuit of moral value. In both cases there are things to be said about how to weave these strands of Lewis's thought together. After setting out these two apparent tensions in Lewis's thought about ethics, the paper discusses what a Lewisian could best say about these puzzles. Lewisians do have a number of plausible options for dealing with the first challenge. While there are things a Lewisian could attempt to extend Lewis's moral naturalism in a way that could deal with the second challenge, it is harder to see how to do this in a satisfying way. Attention then turns to what Lewis said in his letters on these topics: on that basis, perhaps Lewis was close to being an agent-relative consequentialist after all. (shrink)

V tomto článku se zamýšlím nad možností „správné“ (objektivní, adekvátní) interpretace Dao De Jingu (DDJ). Zamyšlení nad „komunikační situací“ vede k rozlišení několika základních prvků (autor, text, interpret, adresát). K jednotlivým prvkům stručně shrnuji současný stav interpretačního úsilí odborníků na DDJ (opíraje se především o článek A. Chana). Kontroverzní povaha výsledků současného bádání nás nemá vést ke skepticismu „integrativní hermeneutiky“, která na adekvátní interpretaci rezignuje. Je možné se i nadále držet principů „rekonstruktivní hermeneutiky“, která spatřuje adekvátní interpretaci jakožto svůj cíl.

Causal determinism is the view that all events in the universe are predetermined and that the laws of nature causally necessitate these events. In the debates on free will, there are two different positions called incompatibilism and compatibilism. Accordingly, compatibilist accounts claim that free will and causal determinism can be compatible and coexist. On the contrary, incompatibilist accounts defend that compatibilist accounts are problematic and claim that free will cannot exist in a universe where causal determinism holds. The main approach (...) that we will consider in this work will be the incompatibilist approach of the American philosopher Peter van Inwagen, which he defends in free will debates. The arguments put forward by Peter van Inwagen as the basis of incompatibilism can be summarized as the consequence argument and the Mind argument. The consequence argument, hypothetically takes into account a world in which causally deterministic and claiming that free will doesn't exist in such a world. Peter van Inwagen's Mind argument, on the other hand, claims that agent-causation cannot be sufficient for a definite possession of free will because a person who represents oneself as an agent in every event s/he is involved in, cannot be sure whether the consequences of these events are due to chance. In both arguments, Peter van Inwagen refers to philosophical moves that affirm incompatibilism is consistent for free will debate. Therefore in my dissertation, I argue that incompatibilism is actually a sufficient step towards solving the free will and causal determinism dilemma in a theoretical sense. This work also deals with Peter van Inwagen's views on philosophy of action and philosophy of religion in general. Additionally, in order to draw the relational framework between causal determinism and free will, the concepts of 'event', 'causal powers' and 'states of affairs' are used methodologically. Instead of just having an ethical discussion of free will, I took care to stay within the boundaries of the metaphysics of free will. (shrink)

Everyday media consumption leaves no doubt that the perception of moving images from various media is characterized by experience and understanding. Corresponding research in this field has shown that the stimulus patterns flooding in on us are not only processed mentally, but also bodily. Building on this, the following study argues that incoming stimuli are processed not only visually, but multimodally, with all senses, and moreover affectively. The classical binding of a sensory organ to a medium, on whose delimitation the (...) common understanding of multimodality is based, is thus abolished. Can arguments for this assumption be found? Building on the research of cultural anthropologist Ernst Cassirer and his successors, the two American philosophers Susanne K. Langer and John M. Krois, and supported by research from the life sciences in which, in parallel, the arts also play an important role in understanding image formation, as in the work of Heinz Werner and, following on from this, in the more recent research of the child psychologist Daniel N. Stern in collaboration with mirror neuron research by the group of neuroscientists around Giacomo Rizzolatti in Parma, justifications for this will be provided. What the multimodal processing of film images is concretely based on will finally be made clear by means of an exemplary analysis of a video film by the Swiss artist Pipilotti Rist. It aims to prove, that the prerequisites for the thesis can only lie in the fact, that both the modes of perception (visual, tactile, auditory, olfactory, gustatory) as well as the medially conditioned modes of image formation are based on non-discursive, formal-abstract structures that are also processed affectively. At the same time, the analysis thus shows how the selection and composition of the vital experienced forms can provide information about the socio-culturally shaped self-image of the producer and the viewer. (shrink)

The form of an action has a strong influence on the interaction between humans. According to their mood, people may perform the same gesture in different ways, such as gently or rudely. These aspects of social communication are named vitality forms by Daniel Stern, represent a mean to establish a direct and immediate connection with others. Indeed, the expression of different vitality forms enables us to communicate our affective states and at the same time the perception of these vitality (...) forms enables people around us to understand how we feel in that moment. In the last years of research, different fMRI studies have been carried out to investigate the neural correlates of vitality forms recognition and execution. Moreover, recent psychophysics studies conducted from our research group have demonstrated the presence of an affective contagion effect, during which vitality forms expressed by an agent affect the action perception and the motor response of the receiver. This means that vitality forms expressed by others can influence our mood positively or negatively, modulating as consequence our behavior. Note that vitality forms pervade our lives in a continuous manner and thus they are not expressed and perceived only during social interactions. For example, when we observe an artistic representation at the theatre, the dynamic postures of dancers, together with an alternation of acceleration and deceleration in their movements, communicate to us different affective states. Also when we are in a museum in front of a painting, lines, colors and shapes used by the artist can elicit in us different sensations and modify our attitude. In this view, with the aim to extend the concept of vitality forms from neuroscience and psychology to other disciplines of study, we dedicate part of this review to discuss how art, in all its forms, can be considered a pure expression of vitality forms. (shrink)

Gilles Deleuze was one of the most influential philosophers of the twentieth-century, and Smith is widely recognized to be one of his most penetrating interpreters, as well as an important philosophical voice in his own right. Combining his most important pieces over the last fifteen years along with two new essays, this book is Smith 's definitive treatise on Deleuze. The essays are divided into four sections, which cover Deleuze's use of the history of philosophy, an overview of his philosophical (...) system, an analysis of several Deleuzian concepts, as well as an assessment of his position within contemporary philosophy. (shrink)

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

Cosmopolitanism – the view that moral concern, and consequently moral duties, are not limited by borders – seems to justify colonialism with a ‘civilizing’ mission, because it supports the enforcement of moral norms universally, with no distinctions between territories, and settler colonialism, because it promotes ideas like common ownership of the Earth and open borders. I argue that existing attempts to defend cosmopolitanism from this worry fail, and that instead the cosmopolitan should embrace a cosmopolitan instrumentalist defence. According to cosmopolitan (...) instrumentalism, colonialism is wrong (when it is wrong) for instrumental reasons: it has all sorts of terrible effects. There is nothing per se wrong with colonialism itself, so cosmopolitanism need not worry about licencing it in principle. There is much that is wrong with colonialism in practice, so cosmopolitanism can easily condemn colonialism as egregiously wrong, although it cannot condemn it as per se or necessarily wrong. (shrink)

In this paper, I motivate the view that quantitative parsimony is a theoretical virtue: that is, we should be concerned not only to minimize the number of kinds of entities postulated by our theories (i. e. maximize qualitative parsimony), but we should also minimize the number of entities postulated which fall under those kinds. In order to motivate this view, I consider two cases from the history of science: the postulation of the neutrino and the proposal of Avogadro's hypothesis. I (...) also consider two issues concerning how a principle of quantitative parsimony should be framed. (shrink)

Several democratic theorists have recently sought to vindicate the ideal of equal political power (“political equality”) by tying it to the non-derivative value of egalitarian relationships. This chapter critically discusses such arguments. It clarifies what it takes to vindicate the ideal of political equality, and distinguishes different versions of the relational egalitarian argument for it. Some such arguments appeal to the example of a society without social status inequality (such as caste or class structures); others to personal relationships among equals, (...) like friendship. Each strategy faces problems. After discussing what social status consists in, the chapter argues that social status equality does not require an equal distribution of power, but only that unequal distributions are not justified on grounds incompatible with the citizens’ fundamental equal moral standing. By contrast, personal relationships among equals do require equal power; but establishing that their norms apply to our political community is challenging. (shrink)

What is a normative reason for acting? In this paper, I introduce and defend a novel answer to this question. The starting-point is the view that reasons are right-makers. By exploring difficulties facing it, I arrive at an alternative, according to which reasons are evidence of respects in which it is right to perform an act, for example, that it keeps a promise. This is similar to the proposal that reasons for a person to act are evidence that she ought (...) to do so; however, as I explain, it differs from that proposal in two significant ways. As a result, I argue, the evidence-based account of reasons I advance shares the advantages of its predecessor while avoiding many of the difficulties facing it. (shrink)

What does the aesthetic ask of us? What claims do the aesthetic features of the objects and events in our environment make on us? My answer in this paper is: that depends. Aesthetic reasons can only justify feelings – they cannot demand them. A corollary of this is that there are no aesthetic obligations to feel, only permissions. However, I argue, aesthetic reasons can demand actions – they do not merely justify them. A corollary of this is that there are (...) aesthetic obligations to act, not only permissions. So, I conclude, the aesthetic asks little of us as patients and much of as agents. (shrink)

A critical survey of recent work in epistemology on higher-order evidence. It discusses the nature of higher-order evidence, some puzzles it raises, responses to those puzzles, and problems facing them. It concludes by indicating connections between debates concerning higher-order evidence in epistemology and parallel debates in ethics and aesthetics.

It is commonly said that some standards, such as morality, are ‘normatively authoritative’ in a way that other standards, such as etiquette, are not; standards like etiquette are said to be ‘not really normative’. Skeptics deny the very possibility of normative authority, and take claims like ‘etiquette is not really normative’ to be either empty or confused. I offer a different route to defeat skeptics about authority: instead of focusing on what makes standards like morality special, we should focus on (...) what makes standards like etiquette ‘not really normative’. I defend a fictionalist theory on which etiquette is ‘not really normative’ in roughly the same way that Sherlock is ‘not really a detective’, and show that fictionalism about some normative standards helps us explain the possibility of normative authority. (shrink)

I defend the cosmopolitan instrumentalist theory of secession, according to which a group has a right to secede only if this would promote cosmopolitan justice. I argue that the theory is preferable to other theories of secession because it is an entailment of cosmopolitanism, which is independently attractive, and because, unlike other theories of secession, it allows us to give the answers we want to give in cases like secession of the rich or secession that would make things worse for (...) minorities. I defend the view against the objections that it allows for colonialism and annexation, that it is not a distinct theory, and that it is impractical. (shrink)

In this article we focus on three key precepts shared by Confucianism and the African ethic of Ubuntu: the central value of community, the desirability of ethical partiality, and the idea that we tend to become morally better as we grow older. For each of these broad similarities, there are key differences underlying them, and we discuss those as well as speculate about the reasons for them. Our aim is not to take sides, but we do suggest ways that Ubuntu (...) and Confucianism might have something to learn from each other and perhaps come closer. We hope that our preliminary reflections can inspire further debate and thinking on a theme – dialogues between long-standing and large-scale non-Western traditions – that is bound to increase in importance as non-Western societies play a greater role in the global system and as the search continues for a 'global ethic'. (shrink)

What is aesthetic appreciation? In this paper, I approach this question in an indirection fashion. First, I introduce the Kantian notion of moral worthy action and an influential analysis of it. Next, I generalise that analysis from the moral to the aesthetic domain, and from actions to affects. Aesthetic appreciation, I suggest, consists in an aesthetically worthy affective response. After unpacking the proposal, I show that it has non-trivial implications while cohering with a number of existing insights concerning the nature (...) of appreciation and the constraints to which it is subject. In closing, I note some limitations on the analogy between aesthetic appreciation and morally worthy action. (shrink)

This paper explores various subtleties in our ordinary thought and talk about normative reasons—subtleties which, if taken seriously, have various upshots, both substantive and methodological. I focus on two subtleties in particular. The first concerns the use of reason (in its normative sense) as both a count noun and as a mass noun, and the second concerns the context-sensitivity of normative reasons-claims. The more carefully we look at the language of reasons, I argue, the clearer its limitations and liabilities become. (...) The cumulative upshot is that although talk of reasons is intelligible and useful for the purposes of communication, we should be wary of placing much weight on it when engaging in substantive normative inquiry. By way of illustration, I consider some potential pitfalls of taking our talk of reasons too seriously, explaining how careful attention to the language of reasons undermines the main argument for moral particularism, Mark Schroeder’s recent defense of Humeanism about practical reasons, and the “reasons-first” program in metanormativity. (shrink)

This book contributes to two debates and it does so by bringing them together. The first is a debate in metaethics concerning normative reasons, the considerations that serve to justify a person’s actions and attitudes. The second is a debate in epistemology concerning the norms for belief, the standards that govern a person’s beliefs and by reference to which they are assessed. The book starts by developing and defending a new theory of reasons for action, that is, of practical reasons. (...) The theory belongs to a family that analyses reasons by appeal to the normative notion of rightness (fittingness, correctness); it is distinctive in making central appeal to modal notions, specifically, that of a nearby possible world. The result is a comprehensive framework that captures what is common to and distinctive of reasons of various kinds: justifying and demanding; for and against, possessed and unpossessed; objective and subjective. The framework is then generalized to reasons for belief, that is, to epistemic reasons, and combined with a substantive, first-order commitment, namely, that truth is the sole right-maker for belief. The upshot is an account of the various norms governing belief, including knowledge and rationality, and the relations among them. According to it, the standards to which belief is subject are various, but they are unified by an underlying principle. (shrink)

I make a proposal about what wondering is and how it differs from other mental phenomena like curiosity. I argue that, though it's tempting to analyze wondering as a desire to know the answer to the question one wonders about, that would be wrong, since wondering is an activity rather than a state, i.e., something we do. I also argue that wondering about a question needn't even essentially involve a desire to know the answer to that question, even as a (...) necessary part of what rationalizes the wondering. Instead, on my account, to wonder about a question is to consider various possible answers as possible answers, guided by mechanisms whose function is to make the subject epistemically better off with respect to those answers, and which considering ceases at least when a person is consciously certain of the answer to their question. This allows wondering to not be objectionably metacognitive, and allows us to make sense of cases in which the motivating desire isn't to know an answer but just to wonder itself. (shrink)

An influential proposal is that knowledge involves safe belief. A belief is safe, in the relevant sense, just in case it is true in nearby metaphysically possible worlds. In this paper, I introduce a distinct but complementary notion of safety, understood in terms of epistemically possible worlds. The main aim, in doing so, is to add to the epistemologist’s tool-kit. To demonstrate the usefulness of the tool, I use it to advance and assess substantive proposals concerning knowledge and justification.

I investigate when we can (rationally) have attitudes, and when we cannot. I argue that a comprehensive theory must explain three phenomena. First, being related by descriptions or names to a proposition one has strong reason to believe is true does not guarantee that one can rationally believe that proposition. Second, such descriptions, etc. do enable individuals to rationally have various non-doxastic attitudes, such as hope and admiration. And third, even for non-doxastic attitudes like that, not just any description will (...) allow it. I argue that we should think of attitude formation like we do (practical) choices among options. I motivate this view linguistically, extending "relevant alternatives'' theories of the attitudes to both belief and to the other, non-doxastic attitudes. Given a natural principle governing choice, and some important differences between doxastic and non-doxastic "choices'', we can explain these puzzling phenomena. (shrink)

A central debate in philosophy of race is between eliminativists and conservationists about what we ought do with ‘race’ talk. ‘Eliminativism’ is often defined such that it’s committed to holding that (a) ‘race’ is vacuous and races don’t exist, so (b) we should eliminate the term ‘race’ from our vocabulary. As a stipulative definition, that’s fine. But as an account of one of the main theoretical options in the debate, it’s a serious mistake. I offer three arguments for why eliminativism (...) should not be tethered to vacuity or error theory, and three arguments for why the view shouldn’t be understood in terms of eliminating the term ‘race’ from our vocabulary. Instead, I propose we understand the debate as concerning whether certain uses of ordinary race terms are typically wrong. This proposal is quite simple, and naturally suggested by the common gloss that eliminativism about ‘race’ is akin to a commonsensical view about 'witch' talk. But nonetheless, I argue that it offers a significant recharacterization of this core debate in philosophy of race. (shrink)

“X-Firsters” hold that there is some normative feature that is fundamental to all others (and, often, that there’s some normative feature that is the “mark of the normative”: all other normative properties have it, and are normative in virtue of having it). This view is taken as a starting point in the debate about which X is “on first.” Little has been said about whether or why we should be X-Firsters, or what we should think about normativity if we aren’t (...) X-Firsters. Hence the chapter’s two main goals. First, to provide a simple argument that one shouldn’t be an X-Firster about the normative domain, which starts with the observation that analogous views have dubious merits in analogous domains. Second, to offer an alternative view—taking normativity to be a determinable explained in terms of its determinates—that offers an interesting way to think about the structure and unity of normativity. (shrink)

This article explores the ethical architecture of the ‘beneficiary pays’ principle, which holds that agents can come to possess remedial obligations of corrective justice to others through the involuntary receipt of benefits stemming from injustice. Advocates of the principle face challenges of both persuasion and limitation in seeking to convince those unmoved of its normative force, and to explain in which cases of benefiting from injustice it does and does not give rise to rectificatory obligations. The article considers ways in (...) which advocates of the principle might seek to win over those sceptical of its merits by employing a modified principle which sidesteps the issue of enforceability, before considering the question of whether the argument can be expanded from cases of benefiting from wrongdoing specifically to other sorts of situation where one agent involuntarily benefits from another's loss. (shrink)

In this paper, I show that, in a number of publications in the early 1950s, Margaret Macdonald argues that art does not admit of definition, that art is—in the sense associated with Wittgenstein—a family resemblance concept, and that definitions of art are best understood as confused or poorly expressed contributions to art criticism. This package of views is most typically associated with a famous paper by Morris Weitz from 1956. I demonstrate that Macdonald advanced that package prior to Weitz, indeed, (...) prior to any other philosopher of art of the period. Despite this, Macdonald’s contribution is nowhere to be found in the subsequent literature on the definition of art. In closing, I raise the prospect that Macdonald was in fact the primary influence on the development of Weitz’s critique of the definitional project. (shrink)

Supporters of open borders sometimes argue that the state has no pro tanto right to restrict immigration, because such a right would also entail a right to exclude existing citizens for whatever reasons justify excluding immigrants. These arguments can be defeated by suggesting that people have a right to stay put. I present a new form of the exclusion argument against closed borders which escapes this “right to stay put” reply. I do this by describing a kind of exclusion that (...) has not been discussed in depth, which I call “territorial exclusion.” Territorial exclusion is the process according to which the group that wishes to exclude current citizens secedes from the territory in which those citizens reside. I argue that the wrongness of territorial exclusion explains why there is no pro tanto right for a state to exclude immigrants, because otherwise there would be a pro tanto right for the state to kick people out by seceding from the territory they inhabit. Because kicking people out like this is typically wrong, borders cannot be closed. (shrink)

We should conceive of illegal covert animal rescue as acts of “subrevolution” rather than as civil disobedience. Subrevolutions are revolutions that aim to overthrow some part of the government rather than the entire government. This framework better captures the relevant values than the opposing suggestion that we treat illegal covert animal rescue as civil disobedience. If animals have rights like the right not to be unjustly imprisoned and mistreated, then it does not make sense that an instance of animal rescue (...) will be justifiable only if it meets criteria for justified civil disobedience, e.g., the requirement that the civil disobedient not rescue more animals than would be necessary to communicate their message. Thus, the framework of subrevolution is a more apt way to analyze animal rescue. (shrink)

Well-being measurements are frequently used to support conclusions about a range of philosophically important issues. This is a problem, because we know too little about the intervals of the relevant scales. I argue that it is plausible that well-being measurements are non-linear, and that common beliefs that they are linear are not truth-tracking, so we are not justified in believing that well-being scales are linear. I then argue that this undermines common appeals to both hypothetical and actual well-being measurements; I (...) first focus on the philosophical literature on prioritarianism and then discuss Kahneman’s Peak-End Rule as a systematic bias. Finally, I discuss general implications for research on well-being, and suggest a better way of representing scales. (shrink)

Majority rule is often regarded as an important democratic principle. But modern democracies divide voters into districts. So if the majority should rule, which majority should rule? Should it be the popular majority, or an electoral majority (i.e., either the majority of voters in the majority of districts, or the majority of voters in districts that contain the majority of the population)? I argue that majority rule requires rule by the popular majority. This view is not novel and may seem (...) obvious. But it is rarely defended, and often rejected. I defend it by arguing that this view about which majority should rule is best supported by the arguments for why the majority should rule, and best avoids the arbitrary and perverse verdicts of rule by electoral majorities. I close by considering the significant practical implications of the view. The Electoral College is often criticized on the basis that the winner of the popular vote doesn’t always win the election. But all district-based democracies have this feature, so all district-based democracies must be reformed if they are to satisfy the principle of majority rule. (shrink)

The distinction between objective and subjective reasons plays an important role in both folk normative thought and many research programs in metaethics. But the relation between objective and subjective reasons is unclear. This paper explores problems related to the unity of objective and subjective reasons for actions and attitudes and then offers a novel objectivist account of subjective reasons.