CONTENTS: -/- SEZIONE I IL TUTTO E' UNO? IL RISVEGLIO DI UN PROBLEMA TRA SCOLASTICA E RINASCIMENTO Il principio omne causatum est compositum fra Tommaso e Cajetano Igor Agostini, p. 25 Parti e tutto in Montaigne. La natura e l'individuo tra frammentazione e integrazione Raffaele Carbone 45 Le minuzzarie e il tutto. Giordano bruno e la conoscenza universale Maurizio Cambi 75 -/- SEZIONE II A PARTIRE DA CARTESIO. COME PUO' ESSERE UN TUTTO L'UOMO? -/- Mente/Corpo in Cartesio. Spunti per un'interpretazione (...) mereologica Stefano Di Bella 93 Nos sumus ex Deo et pertinemus ad Deum. Appartenenza, dipendenza e relazione nel pensiero e nel lessico di Arnold Guelincx Cristina Santinelli 115 L'integrità di corpo e mente nell'"invenire" terapeutico di E. W. von Tschirnhaus Manuela Sanna 133 L'indivisibilità della natura umana e della società in Francesco Longano. Un episodio della ricezione di Locke in Italia Roberto Evangelista 147 -/- SEZIONE III L'IRROMPERE DELL'ORGANICO. LA BIOLOGIA FILOSOFICA TRA SEI E SETTECENTO -/- Convenienza e discrepanza. Parti e tutto nella Lettera 32 di Baruch Spinoza Francesco Toto 169 Mereologia della sostanza e mereologia del vivente in Leibniz Enrico Pasini 197 Teleologia e mereologia dell’organismo da Leibniz a Bonnet Francesco Piro 209 Il nesso delle parti: mereologia e scienza secondo Christian Wolff Matteo Favaretti Camposampiero 239 Il problema del tutto e delle parti. il caso del vitalismo di Montpellier Charles T. Wolfe 257 -/- SEZIONE 4 TOTALITA' CRITICHE: DALLA CRISI DEL NATURALISMO ILLUMINISTICO ALLA FILOSOFIA DELLE CULTURE -/- La logica del tutto (e delle parti di tutto, vale a dire niente) in Dom Deschamps Jean-Claude Bourdin 273 l’(in)afferabile forma. Totalità e contingenza nel pensiero di Kant tra Critica della ragion pura e Critica del giudizio Luigi Imperato 303 la relazione Parte-Tutto nel primo Schelling Giuseppe D’Anna 327 Hegel o della totalizzazione dello spazio di interiorità Vittorio Morfino 343 A partire da Kant: Begriffsbiìldung teleologica e relazione Parti-Tutto nelle indagini di Rickert sulla logica delle scienze storiche della cultura Edoardo Massimilla 359 . (shrink)

When it originated in the late 19th century, psychometrics was a field with both a scientific and a social mission: psychometrics provided new methods for research into individual differences, and at the same time, these psychometric instruments were considered a means to create a new social order. In contrast, contemporary psychometrics - due to its highly technical nature and its limited involvement in substantive psychological research - has created the impression of being a value-free discipline. In this article, we develop (...) a contrasting characterization of contemporary psychometrics as a value-laden discipline. We expose four such values: that individual differences are quantitative (rather than qualitative), that measurement should be objective in a specific sense, that test items should be fair, and that utility of a model is more important than its truth. Our goal is not to criticize psychometrics for employing these values, but rather to bring them into the open and to show that these values are not inevitable and are in need of systematic evaluation. (shrink)

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a (...) dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

Citizen Satisfaction Index System (CSIS) was used to assess the delivery of support to education initiatives in the municipality of Banga, Aklan, Philippines. The samples were determined using multiple application of stratified random sampling approach. In accordance with the Philippine Statistical Authority's Data on Census Population and Housing for 2015, barangays having a bigger share of the population contributed more respondents to the 150 targeted participants. Following the inclusion criteria, the probability respondents were chosen using the Kish Grid. Pre-numbered questionnaires (...) were distributed, with odd numbers targeting male responders and even numbers targeting females. The following criteria were used to evaluate the respondents' assessments: awareness, availment of the program/service, satisfaction, and need for action. Furthermore, interviews were conducted to better understand and investigate the respondents' thoughts, behavior, and perspectives. The reasons for their reaction were also obtained. The data was provided in percentage as well as frequency distributions. The study inferred that awareness on alternative learning system and/or special education program should be improved since it is the only program that attained low rating for awareness. Most of the residents were not able to avail education programs because they have no household member who attends school. Majority of the respondents who availed the services were satisfied. However, scholarship and other assistance programs to students may be enhanced to improve service delivery. It is highly recommended by the citizens to improve accessibility to scholarship programs and other forms of financial assistance to students. (shrink)

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the (...) development of the community-based Coronavirus Infectious Disease Ontology in early 2020. -/- As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. -/- CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications. (shrink)

Obóz Kultury 2.0 Mirosław Filiciak, Alek Tarkowski, Agata Jałosińska, Andrzej Klimczuk, Maciej Rynarzewski, Jacek Seweryn, Stunża M., D. Grzegorz, Marcin Wilkowski & Anna Orlik .

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set has (...) allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

The article deals with the problem of cognition in the framework of the biogenetic structuralist neurophenomenology of Charles Laughlin. The aim of the article is to study the possibilities of applying the biogenetic structuralist theory as a theoretical and methodological basis for the study of consciousness in Laughlin’s theory. A feature of biogenetic structuralism is the interdisciplinary fusion of anthropology, psychology, and neuroscience. The methodology of biogenetic structuralism allows exploring universal structures of consciousness, which are caused by the genetically predisposed (...) organization of the human nervous system. Universal structures of consciousness include structures that mediate human language, knowledge of time and space. It is shown that the problem of cognition is realized in neurognostic models, which are compared with the operational environment. Neurognostic models include both the real nature of man as an organism and the external environment of the organism. Laughlin introduces the concept of a cognitive environment to designate a set of neurognostic models that can potentially be captured by the area of consciousness. He relies on the idea of a cognitive environment, which is essentially intentional in its organization. The polar interaction between the prefrontal cortex and the sensory cortex of the human brain gives rise to the intentionality of consciousness. Laughlin explains the work of the human cerebral cortex neurognostically as omnipresent for human consciousness, and independent of the cultural background. The cerebral cortex is a field of neural activity that arises and dissolves in temporal sequences and coordinates with cognitive processes that connect meaning and form into a single structure in consciousness. The experience of consciousness suggests a sensitive sphere of the cerebral cortex ascertains the meaningful, phenomenal world. The biogenetic structuralist methodology allows to development of an idea of the intentional structure and uniqueness of consciousness. The biogenetic structuralist approach is heuristic for modern science because, firstly, this approach creates the maximum opportunity to include data obtained from naturalistic, ethnographic, anatomical, clinical, and experimental sources; secondly, biogenetic data have the widest empirical and phenomenological rationale; thirdly, biogenetic concepts are defined in the context of a holistic understanding of the phenomenon through the uniqueness of consciousness. (shrink)

Trope theory is the view that the world consists (wholly or partly) of particular qualities, or tropes. This admittedly thin core assumption leaves plenty of room for variation. Still, most trope theorists agree that their theory is best developed as a one-category theory according to which there is nothing but tropes. Most hold that ‘sameness of property’ should be explained in terms of resembling tropes. And most hold that concrete particulars are made up from tropes in compresence (for an overview, (...) including an introduction to some alternative versions of the view, cf. Maurin, 2014). D. M. Armstrong disagrees. He thinks the world is a world of immanent universals, the thin particulars in which those universals are instantiated, and the states of affairs that—thereby—exist. He holds that ‘sameness of property’ should be explained in terms of numerically identical universals or—if the resembling things are the universals themselves—in terms of partially identical universals. And he believes that concrete particulars are made up from ‘thin particulars’ in which a (sufficient) number of universals are instantiated. In spite of their disagreements, proponents of tropes owe Armstrong a debt of gratitude. First, for being one of the theory’s earliest, most serious, and—not least—most prominent, critics (Armstrong for the first time considers, and rejects, what he then labels ‘particularism’, in his 1978a). But also for being one of the theory’s most ardent champions. Already in his 1989a, Armstrong regrets his 1978-rejection of the view. Equivalence classes of exactly resembling tropes, he now admits, for most purposes “serve as an excellent substitute for universals” (Armstrong 1989a, 122). But then why isn’t Armstrong a trope theorist? In this paper, Armstrong’s main reasons for rejecting the trope view are critically scrutinized. All of them, it is maintained, fail to convince. If this argument is accepted, Armstrong seems to have no—or, at least, no good—reason for not accepting the existence of tropes. But, then, ought Armstrong to have been a trope theorist? If the ‘best’ version of the trope view turns out to be ontologically more parsimonious than Armstrong’s own theory of universals, then, yes. That there is a version of the trope view, a version that is not (or, at least not seriously) considered by Armstrong, that is ontologically more parsimonious than the universals view, is argued in the next section. Why none of Armstrong’s reasons for preferring universals to tropes manage to convince, is explained in the section after that. First, however, and in order to avoid a common misunderstanding of the trope view and, as a consequence, of why one ought to reject it, a few more words about the core-difference between tropes and universals, and about how this difference matters (as well as does not matter) to what—and how well—these theories explain. (shrink)

In this article, I outline a strategy for challenging J.L. Schellenberg’s hiddenness argument, and specifically the premise within the argument that asserts the existence of what Schellenberg calls nonresistant nonbelief. Drawing on some of the philosophical resources of skeptical theism, I show how this premise is based on a particular “noseeum assumption”—what I call Schellenberg’s Noseeum Assumption—that underwrites a particular “noseeum argument.” This assumption is that, regarding putative nonresistant nonbelievers, more likely than not we’d detect these nonbelievers’ resistance toward God (...) if there were any. I give reasons for thinking that it is not more reasonable to affirm than to refrain from affirming Schellenberg’s Noseeum Assumption, and so reason to think that the hiddenness argument is not a good argument for atheism. I also defend the strategy I outline against several objections. (shrink)

The prevailing judgement concerning Merleau-Ponty’s encounter with Saussure’s linguistics is that, although important for the evolution of Merleau-Ponty’s philosophy of language, it was based on a mistaken or at least highly idiosyncratic interpretation of Saussure’s ideas. Significantly, the rendering of Saussure that has been common both in Merleau-Ponty scholarship and in linguistics hinges on the structuralist development of the Genevan linguist’s ideas. This article argues that another reading of Saussure, in the light of certain passages of the Course of General (...) Linguistics forgotten by the structuralists, and of the manuscripts related to the published works, shows to the contrary that Merleau-Ponty’s account was sustainable. An understanding of Saussure’s ideas that does not flinch from their paradoxical features can elucidate the French phenomenologist’s views on language and expression. Moreover, the “linguistic turn” in Merleau-Ponty’s philosophical development, identified by James Edie for example, does not seem to have been so clear-cut as has previously been believed; the influence of Saussure’s thought had certainly begun before Merleau-Ponty wrote Phenomenology of Perception -/- En français: « La rencontre de Merleau-Ponty avec la linguistique saussurienne : lecture fautive, réinterpretation ou prolongement ? » Inspirée de la linguistique Saussurienne, la philosophie du langage de Merleau-Ponty a souvent été considérée comme une interprétation erronée des idées de Ferdinand de Saussure ou tout du moins comme une traduction singulière de son œuvre. On remarque cependant que la relecture critique du linguiste genevois, qu’elle soit effectuée à partir de l’œuvre merleau-pontienne ou, plus généralement, dans le champ de la linguistique, repose en grande partie sur les modes d’analyse structuralistes. À la lumière de certains passages du Cours de linguistique générale négligés par les structuralistes, et des manuscrits qui se rapportent aux œuvres publiées, cet article défendra l’idée que l’interprétation de la pensée saussurienne par Merleau-Ponty reste à bien des égards pertinente, pour autant qu’elle ne recule pas devant les traits paradoxaux résultant de la pensée saussurienne. Un questionnement de la pensée de Saussure ne reculant pas devant ses traits paradoxaux peut contribuer à accroître notre compréhension des notions de langage et d’expression chez le phénoménologue français. Dans ce cadre, le « tournant linguistique » merleau-pontien, décrit par James Edie, ne paraît pas aussi net que l’on l’a soutenu auparavant : l’influence de la pensée de Saussure s’est certainement faite sentir avant l’écriture de Phénoménologie de la perception. (shrink)

In a recent paper, Justin D’Ambrosio (2020) has offered an empirical argument in support of a negative solution to the puzzle of Macbeth’s dagger—namely, the question of whether, in the famous scene from Shakespeare’s play, Macbeth sees a dagger in front of him. D’Ambrosio’s strategy consists in showing that “seeing” is not an existence-neutral verb; that is, that the way it is used in ordinary language is not neutral with respect to whether its complement exists. In this paper, we offer (...) an empirical argument in favor of an existence-neutral reading of “seeing”. In particular, we argue that existence-neutral readings are readily available to language users. We thus call into question D’Ambrosio’s argument for the claim that Macbeth does not see a dagger. According to our positive solution, Macbeth sees a dagger, even though there is not a dagger in front of him. (shrink)

Although it is well known that Gestalt theory had an important impact on Merleau-Ponty’s philosophy throughout his career, there is still no detailed study either of its influence on his ideas or of his own understanding of the notoriously polysemic notion of Gestalt. Yet, this notion is a key to Merleau-Ponty’s fundamental project of overcoming “objective thought” and its inherent dichotomies. By indicating how signification or ideality can be immanent in, rather than opposed to, matter, it compels us to redefine (...) both consciousness and the world it is bound up with. The aim of this article is to clarify Merleau-Ponty’s notion of Gestalt against the historical background that he refers to, including Kurt Goldstein’s theory of the organism that was crucial for his interpretation of it. -/- On sait que la théorie de la Gestalt a eu un impact majeur sur la philosophie merleaupontienne. Il n’existe pourtant pas d’étude extensive de l’influence de cette théorie sur les thèses de Merleau-Ponty ou sur sa compréhension propre de la notion fort polysémique de Gestalt. Or cette notion s’avère être l’une des meilleures clés pour comprendre le projet fondamental du dépassement merleau-pontien de la « pensée objective » et de ses dichotomies. En effet, en montrant comment le sens ou l’idéalité sont immanents, plutôt qu’opposés, à la matière, la Gestalt conduit à définir à nouveaux frais la conscience et le monde auquel elle est liée. L’article vise à clarifier la conception de la Gestalt chez Merleau-Ponty à partir de son fond historique. On étudie en particulier la théorie de l’organisme de Kurt Goldstein, qui a été essentielle pour l’interprétation merleaupontienne de la notion de Gestalt. -/- Benché sia noto che la Gestalttheorie abbia avuto un impatto rilevante sull’intero tragitto della filosofia di Merleau-Ponty, non esiste ancora uno studio dettagliato dell’influenza del gestaltismo sulle sue idee né sulla sua comprensione di un concetto notoriamente sfaccettato come quello di Gestalt. Tuttavia proprio questa nozione costituisce una chiave d’accesso fondamentale al grande progetto merleaupontyano di oltrepassare il “pensiero oggettivo” insieme alle dicotomie che lo accompagnano. Indicando come il significato o l’idealità possano essere immanenti, anziché opposti, alla materia, tale nozione ci obbliga a ridefinire tanto la coscienza quanto il mondo a cui essa è legata. L’obiettivo di questo articolo è quello di chiarire la nozione merleaupontyana di Gestalt nel suo contesto storico, con particolare riferimento alla teoria dell’organismo elaborata da Kurt Goldstein, determinante per l’interpretazione merleaupontyana della nozione di Gestalt. (shrink)

Ziel des Beitrages ist die differenzierende Beschreibung des Projekts Cybersyn sowie die anschließende kritische Perspektivierung ausgewählter neokybernetischer Governance-Konzepte, die in den letzten Jahren verstärkt im Policy-Kontext diskutiert wurden. Die „Entscheidungsmaschine“ Stafford Beers, die der Management-Kybernetiker unter Salvador Allende in den frühen Siebzigern konzipierte, wird zumeist als Projekt eines technisch avancierten, ökonomischen Organisationskonzepts, eines „dritten Wegs“ beschrieben. Der Beitrag diskutiert die Grundkonzeption des „sozialistischen Internets“, seine fortschrittlichen, ökonomischen Ideen und Ästhetiken wie auch die Person Stafford Beer, legt den Fokus aber vor (...) allem auf ein eher selten beschriebenes Teilkonzept, namentlich „Cyberfolk“, eine Art binäres, affektives Echtzeit-Stimmungsbarometer der Bevölkerung zur Live-Bewertung von politischen Reden. In diesem Konnex werden gerade die demokratietheoretischen Implikationen von Cybersyn und seine Vorstellung „totaler Transparenz“ genauer untersucht. Im Anschluss wird expliziert, wie sich in unterschiedlichen gegenwärtigen Konzeptionen fluider Techno- bzw. technoider Expertokratien – von den „smart states“ Beth Novecks bis zur „direct technocracy“ Parag Khannas – die „Kybernetisierung des Politischen“ auch im digitalen Zeitalter – gewissermaßen unter umgekehrtem, d.h. neoliberalen Vorzeichen – revitalisiert und dabei sowohl problematische Partizipations- als auch Emanzipationskonzepte umreisst. Zu untersuchen sind in dieser Hinsicht so auch die reduktiven Aspekte der Beerschen letztlich feedbacklogischen Konzeption des Politischen. (shrink)

This chapter makes the following main claims about Hungarian: A. There is a detailed parallelism between the structures of noun phrases (DPs) and clauses (CPs), involving inflection, possessor extraction, and articles as complementizers. B. "HAVE sentences" are existential sentences involving possessor extraction. C. The argument frame of complex event nominals is identical to that of the underlying verb. D. The deverbal affix in nominals may have either a plain verb or a complex verb in its scope.

This paper seeks to illustrate the advantages of not treating phonological words as distinguished building blocks in compositional semantics. Following Bobaljik 2012, we derive the relative readings of amount superlatives in two steps, [[[d-many] comparative] superlative]. The existence of two comparative constructions is revealed, involving more vs. the more. Each builds a different superlative construction, explaining the conflicting intuitions about superlatives in the literature, as well as puzzles relating to the definite article in superlatives.

Im Beitrag wird die Apple-Watch vor dem Hintergrund ihrer „Ästhetik der Existenz“ als biopolitisches Artefakt und kontrollgesellschaftliches Dispositiv, vor allem aber als kybernetische Black Box aufgefasst und analysiert. Ziel des Aufsatzes ist es, aufzuzeigen, dass sich in dem feedbacklogischen Rückkopplungsapparat nicht nur grundlegende Diskurse des digitalen Zeitalters (Prävention, Gesundheit, bio- und psychopolitische Regulierungsformen etc.) verdichten, sondern dass dieser schon ob seiner inhärenten Logik qua Opazität Transparenz, qua Komplexität Simplizität (d.h. Orientierung) generiert und damit nicht zuletzt ein ganz spezifisches Menschenbild forciert. (...) In methodischer Hinsicht sollen zur Aufschlüsselung der für die digitale Gesellschaft repräsentativen Black Box „Apple-Watch“ wirksame Begriffskonstellationen der Kybernetik – d.h. Feedback, Regulierung, Selbstkontrolle und nicht zuletzt das Prinzip des „schwarzen Kastens“ selbst (Wiener/ Ashby), in dem sich schon die Funktion des Apparats als (Selbst-)Regulierungstool zwischen In- und Outputs reflektiert – in den Blick genommen und mit behavioristischen Konzepten (besonders solche der Gegenwart, d.h. nudging-Konzepte etc.) kontextualisiert werden. Auf dieser Grundlage lässt sich schließlich, so die These, nicht nur ein Subjektivierungsmodell ableiten, sondern auch eine (durchaus realpolitisch wirksame) Regierungskunst („kybernetische Gouvernementalität“) dekodieren. In diesem Zusammenhang ist schließlich die These zu plausibilisieren, dass das zeitgenössische „Sicherheitsregime“ des ‚new dark age‘ (Bridle) respektive der ‚Black-Box-Society‘ (Pasquale) sich nicht auf „die Unterdrückung von Subjektivität [bezieht], sondern vor allem auf ihre ‚(Selbst)-Produktion‘, […] auf die […] Förderung von Selbsttechnologien, die an Regierungsziele gekoppelt werden können.“ (Lemke) Entsprechend fragt der Aufsatz, welche – auch politischen – Auswirkungen die exzessive Verbreitung dieser und ähnlicher „smart devices“ zeitigt: Denn nicht zuletzt lässt sich, mediiert über derartige datengenerierende schwarze Kästen, eine Form der Regierung und des Regierbar-Machens erkennen, die weniger explizit-imperativisch auf Subjekte als vielmehr implizit-suggestiv auf Datenpunkte und -profile einwirkt. (shrink)

With reference to Hungarian, the paper argues that DP is analogous to CP. The D head *a(z)* is an analog of the complementizer C. It enables its complement to act as an argument. Definiteness is anchored in a feature lower in the structure.

We analyse Hutto & Myin's three arguments against computationalism [Hutto, D., E. Myin, A. Peeters, and F. Zahnoun. Forthcoming. “The Cognitive Basis of Computation: Putting Computation In Its Place.” In The Routledge Handbook of the Computational Mind, edited by M. Sprevak, and M. Colombo. London: Routledge.; Hutto, D., and E. Myin. 2012. Radicalizing Enactivism: Basic Minds Without Content. Cambridge, MA: MIT Press; Hutto, D., and E. Myin. 2017. Evolving Enactivism: Basic Minds Meet Content. Cambridge, MA: MIT Press]. The Hard Problem (...) of Content targets computationalism that relies on semantic notion of computation, claiming that it cannot account for the natural origins of content. The Intentionality Problem is targeted against computationalism using non-semantic accounts of computation, arguing that it fails in explaining intentionality. Theion Problem claims that causal interaction between concrete physical processes and abstract computational properties is problematic. We argue that these a... (shrink)

The paper charts both the interpersonal connections between historical anarchist figures and the beat poets as well as the philosophical similarities between them. Almost all the beat poets were anarchists, though their politics was secondary to their attempts to transform consciousness. Among the anarchists, the romantic socialist Gustav Landauer, who was especially popular in post-war American anarchist circles, came closest to the political perspective of the beat poets. Like the beats, Landauer was a poet, a pacifist, an anarchist, a communitarian, (...) a romantic, and a mystic. In northern California, the circle of anarchists surrounding Kenneth Rexroth provided support and inspiration to the early beat movement. In New York, the beats had an affinity with anarchists such as David Thoreau Wieck and the publication "Why?" (later "Resistance"), as well as Dwight Macdonald's "politics" and Holley Cantine's "Retort". (shrink)

Despite increased philosophical and psychological work on practical wisdom, contemporary interdisciplinary wisdom research provides few specifics about how to develop wisdom (Kristjánsson 2022). This lack of practically useful guidance is due in part to the difficulty of determining how to combine the tools of philosophy and psychology to develop a plausible account of wisdom as a prescriptive ideal. Modeling wisdom on more ordinary forms of expertise is promising, but skill models of wisdom (Annas 2011; De Caro et al. 2018; Swartwood (...) 2013b; Tsai 2023) have been challenged on the grounds that there are important differences between wisdom and expert skills (Hacker-Wright 2015, p. 986; Kristjánsson 2015, pp. 98, 101; Stichter 2015, 2016, 2018). I’ll argue that we can both vindicate the promise of skill models of wisdom and begin to specify practically useful strategies for wisdom development by attending to a reflective process that I call Case-Based Critical Reflection. I begin by demonstrating the process as it arose in a notable example from everyday life, illustrating how the process can be usefully applied to a case study of interest to wisdom scientists, and explaining its philosophical pedigree. After isolating the key features that make it relevant to wisdom development, I argue that attending to the importance of Critical Reflection can defuse prominent objections to skill models of wisdom. (shrink)

This paper aims to suggest a new approach to Plato’s theory of being in Republic V and Sophist based on the notion of difference and the being of a copy. To understand Plato’s ontology in these two dialogues we are going to suggest a theory we call Pollachos Esti; a name we took from Aristotle’s pollachos legetai both to remind the similarities of the two structures and to reach a consistent view of Plato’s ontology. Based on this theory, when Plato (...) says that something both is and is not, he is applying difference on being which is interpreted here as saying, borrowing Aristotle’s terminology, 'is is (esti) in different senses'. I hope this paper can show how Pollachos Esti can bring forth not only a new approach to Plato’s ontology in Sophist and Republic but also a different approach to being in general. -/- Keywords Plato; being; difference; image; pollachos esti; pollachos legetai 1. Being, Not-Being and Difference The three dialogues where the notion of "difference" attaches to the notion of being, namely Parmenides II, Sophist and Timaeus,and specifically the first two we try to discuss here. In these dialogues, Plato is going to achieve a new and revolutionary understanding of being which is not anymore based on the notion of "same" as it was before in Greek ontology. It was his discovery, I think, that the notion of being in the Greek ontology is attached to the notion of the "same" and it is because of this attachment that there have always been many problems understanding being especially after Parmenides. That being has always been relying on the "same" can be found out from the way most of the Presocratics understood it. It was based on such a relationship between being and "same" that a later Ionian, Heraclitus of Ephesus, rejected Being by rejecting its sameness: unable to be the same, being cannot be being anymore but becoming. Heraclitus’ criticism of his predecessors’ understanding of being was due to his discovery that what they call being is not the same but different in every moment. The relation of being and sameness reaches to its highest point in Parmenides. What Plato does in using the "difference" is nothing but the establishment of a creative relation between being and "difference". In this new relation, although he is in agreement with Heraclitus that being is not the same but different, he does not do it by use of becoming. He disagrees, on the other hand, with Parmenides that such a relation between being and difference leads to not being. At Parmenides 142b5-6 it is said that if One is, it is not possible for it to be without partaking (μετέχειν) of being (οὐσίας), which leads to the distinction of being and one: -/- So there would be also the being of the one (ἡ οὐσία του̑ ἑνὸς) which is not the same (ταὐτὸν) as the one. Otherwise, it wouldn’t be its being, nor the one would partake of it. (142b7-c1) -/- The fact that what is (ἔστι) signifies (σημαῖνον) is other (ἀλλο) than what One signifies (c4-5), is being taken as a reason for their distinction. The conclusion is that when we say 'one is', we speak of two different things, one partaking of the other (c5-7). Having repeated these arguments of the otherness of being and one at 143a-b, Parmenides says that the cause of this otherness can be neither Being nor One but "difference": -/- So if being is something different (ἕτερον) and one something different (ἕτερον), it is not by being one that the one is different from being nor by its being being that being is other than one, but they are different from each other (ἕτερα ἀλλήλων) by difference (τῷ ἑτερῳ) and otherness (ἄλλῳ). (143b3-6) -/- The fifth hypothesis, 'one is not' (160b5ff.) is also linked with the notion of difference. When we say about two things, largeness and smallness, that they are not, it is clear that we are talking about not being of different (ἕτερον) things (160c2-4). When it is said that something is not, besides the fact that there must be knowledge of that thing, we can say that it entails also its difference: 'difference in kind pertains to it in addition to knowledge' (160d8). Parmenides explains the reason as such: -/- For someone doesn’t speak of the difference in kind of the others when he says that the one is different from the others, but of that thing’s own difference in kind. (160e1-2) -/- Although the theory of being as "difference" is not fulfilled yet, an exact look at what occurs in Sophist can make us sure that this was the launching step for "difference" to get its deserved role in Plato’s ontology. The notion of the "difference" is not yet well-functioned in Parmenides because we can see that being is still attached to the same: -/- For that which is the same is being (ὄν γὰρ ἐστι τὸ ταὐτόν) (162d2-3). -/- The notion of difference in Sophist is the key element based on which a new understanding of being is presented and the problem of not being is somehow resolved. The friends of Forms, the Stranger says, are those who distinguish between being and becoming (248a7-8) and believe that we deal with the latter with our body and through perception while with the former, the real being (ὄντως οὐσίαν) with our soul and through reasoning (a10-11). Being is then bound with the "same" by adding: -/- You say that being always stays the same and in the same state (ἣν ἀεὶ κατὰ ταὐτὰ ὡσαύτως ἔχειν) but becoming varies from one time to another (δὲ ἄλλοτε ἄλλως). (248a12-13) -/- That the theory of the relation of being and capacity (247d8f., 248c4-5) matches more with becoming than with being (248c7-9) must be rejected because being is also the subject of knowledge which is kind of doing something (248d-e). It does, however, confirm that 'both that which changes and also change have to be admitted as existing things (ὄντα) (249b2-3). I believe that this is what Socrates would incline to do at Theaetetus 180e-181a, that is, putting a fight between two parties of Parmenidean being and Heraclitean becoming and then escaping. The solution is that becoming is itself a kind of being and we ought to accept what changes as being. This is what must be done by a philosopher, namely, to refuse both the claim that 'everything is at rest' and that 'being changes in every way' and beg, like a child, for both and say being (τὸὄν) is both the unchanging and that which changes (249c10-d4). This kind of begging for both is obviously under the attack of contradiction (249e-250b). For both and each of rest and change similarly are (250a11-12) but it cannot be said either that both of them change or both of them rest, being must be considered as a third thing both of the rest and change associate with (250b7-10). The conclusion is that 'being is not both change and rest but different (ἕτερον) from them instead' (c3-4). The notion of difference helps Plato to take being departed from both rest and change because it was their sophisticated relation with being that made the opposition of being and becoming. Plato is now trying to separate being from rest and, thus, from "same" by "difference". Such a crucial change is great enough to need a 'fearless' decision (256d5-6). The possibility of being of not being is resulted (d11-12) comes as the answer to the question 'so it’s clear that change is not being and also is being (ἡ κίνησις ὄντως οὐκ ὄν ἐστι καὶ ὄν) since it partakes in being?' (d8-9). It is then by the notion of difference that becoming is considered as that which both is and is not. This coincidence of being and not being about change is apparently similar to Socrates’ paradoxical statement at Republic 477a about what both is and is not. -/- Introduction The Republic 476-477 has always been a matter of controversy mainly about two interwoven points. The first problem is the meaning of being here; that whether what he has in mind is a veridical, existential or propositional sense of being. The second problem is his distinction between the objects of knowledge and opinion which seems to lead, some believe, to the Two Worlds (TW) theory. The crucial point in Republic is that what is considered between knowledge (ἐπιστήμης) and ignorance (α͗γνοιας), namely opinion, must have a different object that leads Socrates to draw the distinction of knowledge and opinion between their objects. The problem of understanding being in the fifth book of the Republic is that when it is said that the Form of F is F but a particular participating in F, both is and is not F, it sounds too bizarre and unacceptable. It cannot be imaginable how a thing can be existent and non-existent at the same time. At the first sight, the only solution seems to be the degrees of existence which is called by Annas (1981, 197) a 'childish fallacy' and a 'silly argument'. Kirwan (1974, 118) thinks that Republic V does not attribute 'any doctrine about existence' to Plato and Kahn (1966, 250) claims that the most fundamental value of einai when used alone (without predicate) is not "to exist" but "to be so", "to be the case" or "to be true". The problems of understanding being in Republic and Sophist besides the difficulties of the existential reading led scholars to the other senses of being, mostly related to the well-known Aristotelian distinctions between different senses of being. In the predicative reading, Annas, for example, refers this difference to the qualified and unqualified application. Whereas the Form of F is unqualifiedly F, a particular instance of F can be F only qualifiedly (1981, 221). Vlastos’ well-known substitution of 'degrees of reality' for 'degrees of being/existence' must be categorized as a predicative reading. Kahn thinks that the basic sense of being for Plato is 'something like propositional structure, involving both predication and truth claims, together with existence for the subject of predication' (2013, 96). Believing that the complete-incomplete distinction terminology is misleading about Plato, he thinks that semantic functions are only second-order uses of the verb and it is the predicative or incomplete function which is fundamental. Suggesting a veridical reading, Fine (2003, 70 ff) thinks that while both existential and predicative readings separate the objects of knowledge and belief, it is only her reading which does not force such separation of the objects and thus does not imply TW. Stokes (1998, 266) thinks that though Fine is right saying that Plato does not endorse TW in book V, she is wrong in rejecting existential in favor of the veridical reading. The reception of existential reading can be seen more obviously in Calvert who thinks, in agreement with Runciman, that 'it would be safer to say that Plato’s gradational ontology is probably not entirely free from degrees of existence' (1970, 46). At Sophist 254d-e Plato singles out five most important kinds (or Forms!?) in which the same (ταὐτὸν) and difference (θάτερον) are regarded besides being, rest and change. They are, therefore, neither the same nor the difference but share in both (b3). Being (τὸ ὄν) cannot be the same also because if they 'do not signify distinct things' both change and rest will have the same label when we say they are (255b11-c1). We have then four distinct kinds, being, change, rest and same, none of them is the other. The case of difference is more complicated. When the stranger wants to assess the relation of being and difference, he can say simply neither that they are distinct nor that they are not. He has to make an important distinction inside being to get able to draw the relation of being and difference: -/- But I think you'll admit that some of the things that are (τῶν ὄντων) are said (λέγεσθαι) by themselves (αὐτὰ καθ’ αὑτά) but some [are said] always referring to (πρὸς) other things (ἄλλα) (255b12-13) -/- The difference is always said referring to other things (τὸδέγ’ ἕτερον ἀεὶ πρὸς ἕτερον) (255d1). It pervades all kinds because each of them should be different from the others and is so due to the difference and not its own nature (253e3f.) After asserting that change is different from being and therefore both is and is not (256d), the difference is described as what makes all the other kinds not be, by making each different from being. Given that all of them are by being, this association of being and difference is the cause of their being and not-being at the same time, the issue that its version at RepublicV made all those controversies we discussed above: -/- So in the case of change and all the kinds, not being necessarily is (Ἔστιν ἄρα ἐξ ἀναγκης τὸ μὴ ὄν). Τhat’s because as applied to all of them, the nature of the difference (ἡ θατέρον φύσις) makes each of them not be by making it different from being. And we’re going to be right if we say that all of them are not in the same way. And conversely [we’re also going to be right if we say] that they are because they partake in being. (Sophist 256d11-e3) -/- Plato’s new construction of five distinct kinds and the role he gives to thedifference among them is aimed to resolve the old problem of understanding being which has always been annoying from the time of Heraclitus and Parmenides. Both the ontological status of becoming and that of not being were, in Plato’s mind, based on the absolute domination of the notion of the Same over being. Now, not only becoming is understandable as being but also not being which is not the contrary of being anymore but only different (ἕτερον) (257b3-4). Though I agree partly with Frede that the account of not being which is needed for false statements is more complicated than just saying, as Cropsey (1995, 101) says, that Plato is substituting 'X is not Y' with 'X is different from Y', I totally disagree with him that when we say X is not beautiful, Plato could not have thought that it is not a matter of its being different from beautiful because 'it would be different from beauty even if it were beautiful by participation in beauty' (1992, 411). Conversely, as we will discuss, it is exactly the relation of the beautiful thing, X, and the beautiful itself, in which X shares that is to be solved by the notion of not being as difference. Though it is beautiful because of sharing in beauty, X is not beautiful because it is different from beautiful itself. What the difference is to do is to show how something can both be and not be the same thing. The difference is what makes one thing both be and not be a certain other thing. This equips the difference with the ability to explain a certain thing’s not-being when it is. Thanks to the notion of difference, it is now possible to explain not only not being but also the simultaneous being and not being of a thing: 'What we call "not-beautiful" is the thing that ἕτερόν ἐστιν from nothing other than του̑ καλου̑ φύσεως' (257d10-11). The result is that not beautiful happens to be (συμβέβηκεν εἶναι) one single thing among kinds of beings (τι τῶν ὄντων τινὸς ἑνὸς γένους) and at the same time set over against one of the beings (πρός τι τῶν ὄντων αὖ πάλιν ἀντιτεθὲν) (257e2-4) and thus be something that happens to be not beautiful (εἶναί τις συμβαίνει τὸ μὴ καλόν); a being set over against being (ὄντος δὴ πρὸς ὄν ἀντίθεσις) (e6-7). Neither the beautiful is more a being (μα̑λλον ... ἐστι τῶν ὄντων) nor not beautiful less (e9-10) and thus both the contraries similarly are (ὁμοίως εἶναι) (258a1). This conclusion, it is emphasized again (a7-9), owes to θατέρου φύσις now turned out as being. Therefore, each of the many things that are of the nature of the difference and set over each other in being (τῆς τοῦ ὄντος πρὸς ἄλληλα ἀντικειμένων ἀντίθεσις) is being as being itself is being (αὐτοῦ τοῦὄν τοςοὐσία ἐστιν) and not less. They are different from, and not the contrary of, each other (a11-b3). This is exactly τὸμὴὄν, the subject of the inquiry (b6-7). Hence, not being has its own nature (b10) and is one εἶδοςamong the many things that are (b9-c3). Such far departing from Parmenides’ ontological principle is done on the basis of the nature of the difference. It was the discovery of such a notion that made the stranger brave enough to say that not being is each part of the nature of the difference that is set over against being (258d7-e3, cf. 260b7-8). That the relation of being and difference is difference is the key element of the new ontology. The difference is, only because of its sharing in being, but it is not that which it shares in but different from it (259a6-8). Not being is exactly based on this difference: ἕτερον δὲ τοῦ ὄντος ὄν ἔστι σαφέστατα ἐξ ἀνάγκης εἶναι μὴ ὄν (a8-b1). 2. Difference and the Being of a Copy We discussed above that the sense of being of particulars in Republic V made so many debates that whether being is there used in an existential sense or not. Particulars in Republic are regarded as images in the allegories of Line and Cave. The being of an image/copy makes, thus, the same problem. Plato’s analogy of original -copy for the relation of Forms and their particulars in Republic has obviously a different attitude to being. The main question is that what is the ontological status of a copy in respect of its original? Are there two kinds of being, 'real being' versus 'being' as Ketchum says (1980, 140) or only one kind? What is the difference of being in an original and its copy? Is it a matter of degrees of being or reality as some commentators have suggested? Is it a matter of being relational? By reducing the ontological issue to an epistemological one, Vlastos’ suggestion of degrees of reality in an article with the same name does neither, I think, pay attention to the problem nor resolve it. He agrees that Plato never speaks of "degrees" or "grades" of reality (1998, 219). What allows him to entitle it as such are some of Plato’s words in Republic as well as Plato’s words in some other dialogues (1998, 219). When Plato states that the Forms only can completely, purely or perfectly be real he means, Vlastos says, they are cognitively reliable (1998, 229); an obvious reduction of the issue to an epistemological one. He thinks that when in Republic we are being said that a particular’s being F is less pure than its Form, it is because it is not exclusively F, but it is and is not F and this being adulterated by contrary characters is the reason of our confused and uncertain understanding of it (1998, 222). Ketchum rightly criticizes Vlastos’ doctrine in its disparting from ontology thinking that 'to understand Plato’s talk of being as talk of reality is to obscure the close relation that exists between "being" and the verb "to be"' (1980, 213). He thinks, therefore, that οὐσία must be understοοd as being rather than reality, τὸὄν as "that which is" and not "that which is real" and … (ibid). His conclusion is that degrees of reality cannot interpret Plato correctly and we must accept degrees of being. Allen believes that a 'purely epistemic' reading of the passage in Republic is patently at odds with Plato’s text (1961, 325). He thinks that not only degrees of reality but also degrees of reality must be maintained (1998, 67). What Cooper suggests gets close to this paper’s solution: -/- Plato does not I think wish to suggest that existence is a matter of degree in the way in which being pleasant or painful is a matter of degree. Rather there are different grades of ontological status. (1986, 241) -/- A more ontological solution for the problem of understanding the being of a copy and its relation with the being of its original is suggested by the theory of copy as a relational entity. Based on this interpretation, 'the very being of a reflection is relational, wholly dependent upon what is other than itself: the original…' (Allen, 1998, 62). As relational entities, particulars have no independent ontological status; they are purely relational entities which derive their whole character and existence from Forms (ibid, 67). Although these relational entities are and have a kind of existence, we must also say that 'they do not have existence in the way that Forms, things which are fully real, do' (ibid). Allen (1961, 331) extends his theory to Phaedo where it is said that particulars are deficient (74d5-7, 75a2-3, 75b4-8), 'wish' to be like (74d10) or desire to be of its nature (75a2); an extension that, like F.C. white (1977, 200), I cannot admit. He correctly states that Plato did not start out with a doctrine of particulars as images and semblances but come to such a view after Phaedo, or perhaps after Republic V (1977, 202). Though we may not agree with him about Republic V, if we have to consider its last pages also, we must agree with him that not only the ontology of Phaedo but also that of Republic II-V (except the last pages of the latter book) are somehow different from (but at the same time appealing to) the ontology of original-copy which should exclusively assign to Sophist, Timaeus and RepublicVI-VII besides the last pages of book V. The answer to the problem of Plato’s sense of being in RepublicV can be reached only if we read Republic V based on and as following Sophist. We can find out his meaning of that which both is and is not only by the ontological status he assigns to a copy in Sophist. The kind of being of a copy in Sophist reveals as Plato’s key for the lock of the problem of not being. Let’s see how the ontological status of a copy is the critical point of Plato’s ontology. In the earlier pages of Sophist, we are still in the same situation about not being. To think that that which is not is is called a rash assumption (237a3-4) and Parmenides’ principle of the impossibility of being of not being is still at work (a8-9). At 237c1-4, the problem of "not being" is noticed in a new way which shows some kinds of a more realistic position to the problem of not being. Nevertheless, not being is still unthinkable, unsayable, unutterable and unformulable in speech (238c10). Soon after mentioning that it is difficult even to refuse not being (238d), the solution to the problem appears: the being of a copy (εἴδωλον) (239d). A copy is, says Theaetetus, something that is made referring to a true thing (πρὸς τἀληθινὸν) but still is 'another such thing (ἕτεροντοιου̑τον)' (240a8). Nevertheless, this 'another such thing' cannot be another such real or true thing. In answer to the question of the Stranger that if this 'another such thing' is the true thing (240a9), Theaetetus answers: οὐδαμῶς ἀληθινόν γε, ἀλλ’ ἐοικὸςμὲν (240b2). A copy’s being 'another such thing' does not mean another true thing but only a resemblance of it. Not only is not a copy another true thing besides the original, but it is the opposite of the true thing (b5) because only its original is the thing genuinely and being a copy is being the thing only untruly. The word ἐοικὸς is opposed to ὄντως ὄν in the next line (240b7): 'So you are saying that that which is like (ἐοικὸς) is not really that which is (οὐκ ὄντως [οὐκ] ὄν)'. But still a copy 'is in a way (ἔστι γε μήν πως)' (b9). While it is not really what it is its resemblance, it has its own being and reality because it really is a likeness (εἰκων ὄντως) (b11). The Stranger asks: -/- So it is not really what is (οὐκ ὄν ἄρα [οὐκ] ὄντως ἐστὶν) but it really is what we call a likeness (ὄντως ἣν λέγομεν εἰκόνα)? (b12-13) -/- This is Plato’s innovative ontological solution to the problem of not being. Theaetetus’ answer confirms this: 'Maybe that which is not is woven together with that which is' (c1-2). Therefore, a copy neither is what really is nor is not-being but only is what in a way is. Thanks to the ontological status of a copy, the third status intermediate between being and not being is brought forth. The essence of an image, in Kohnke’s words, does not consist 'solely in the negation of what is genuine and has real being' because otherwise 'it would be an ὄντως οὐκ ὄν,essentially and really a not being' (1957, 37). The characteristics of a copy can be summed up as folows: i) A copy is a copy by referring to a true thing (πρὸς τἀληθινὸν). ii) A copy is different from that of which it is a copy (ἕτερον). iii) A copy is not itself a true thing (ἀληθινόν) as that of which it is a copy but only that which is like it (ἐοικὸς). iv) It is not really that which really is (ὄντως ὄν) but only really a likeness (εἰκων ὄντως). The conclusion is that: v) A copy in a way (πως) is that means it both is and in not, the product of interweaving being with not being. This leads to the refutation of father Parmenides’ principle, accepting that 'that which is not somehow is (τό τε μὴ ὄν ὡς ἔστι)' and 'that which is, somehow is not (τό ὄν ὡς οὐκ ἔστι) (241d5-7). Besides copies and likenesses (εἰκόνων), we have also imitations (μιμημάτων) and appearances (φαντασμάτων) as the subjects of this new kind of being and thus false belief (241e3). In Timaeus, the world of becoming which cannot correctly be called and thus we have to call it "what is such" (τὸ τοιου̑τον) (49e5) or "what is altogether such" (τὸ διἀ παντὸς τοιου̑τον) (e6-7), consists solely of imitations (μιμημάτα) (50c5) which are identifiable only by the things that they are their imitations. The word τοιου̑τον which had been used to determine the situation of a copy in respect of its original, now becomes the definition of the world of becoming in which everything is an image of another thing, a Being, that stays always the same and is different and separated from its image. Cherniss, in my view rightly, draws attention to the very important point about the ontological status of an image that can at the same time be considered a criticism of the relational theory. What we are being said in Timaeus, he thinks,cannot be explained by saying that an image is not self-related and making its being relational. What is crucial about an image is that it 'stands for something, refers to something, means something and this meaning the image has not independently as its own but only in reference to something else apart from it' (1998, 296). This function finds its best explanation in the theory we are to suggest in the following. 3. πολλαχῶς ἔστι The best way to understand the ontological status of an image in Plato is to see first how his most clever pupil, Aristotle, resolved the same problem that Plato brought his theory of image for its sake. Aristotle’s theory of pollachos legetai is a brilliant and, at the same time, deviated version of Plato’s theory that is able, however, to help us read Plato in a better way. We discuss Aristotle’s theory to reach to a full understanding of Plato’s theory because it is, firstly, constructed in Aristotle in a more clear way and, secondly, it can also be taken as an evidence that our reading of Plato is legitimate. The phrase τὸ ὄν πολλαχῶς λέγεται, a so much repeated phrase in Aristotle’s works, is his resolution for some of the ontological problems of his predecessors all treating being as if it has only one sense. Aristotle is right in his criticism of the philosophical tradition specially Heraclitus, Parmenides and Plato since all did presuppose only one sense for being and his theory is, thus, a creative and revolutionary solution for many problems that all the past philosophers were stuck in. But it is at the same time somehow a borrowed theory. As we will discuss, both the structure of the doctrine and the problems it tries to resolve are the same as Plato’s doctrine (and even is comparable in its phraseology) though it is in Aristotle, as can be expected, a more clear and better structured doctrine. 1) Associated with the theory of pros hen and the theory of substance, the theory of several senses of being provides a structure which, I insist, is the best guide to understand Plato’s theory of Being in Sophist, Timeaus and Republic. a) Although the theory of pollachos legetai is not necessarily based on the theory of pros hen, they become tightly interdependent about being: -/- Being is said in many ways/senses (τὸ δὲ ὄν λέγεται μὲν πολλαχῶς) but by reference to one (πρὸς ἕν) [way/sense] and one kind of nature (μίαν τινὰ φύσιν). (Metaphysics 1003a33-34) -/- The doctrine of pros hen which is Aristotle’s initiative third alternative besides the homonymous and synonymous application of words, is primarily a linguistic theory that tries to provide a new theory to explain the different implementations of the same word. The pros hen implementation of being is to provide an alternative for the theory of the synonymous (in Plato: homonymous) implementation of being which says being is said in one sense (kath hen) (1060b 32-33). That both the pros hen and the kath hen implementation of a word has one thing (hen) as what is common, makes them in opposition to the homonymous implementation which does not consider anything in common. Whereas both pros hen and kath hen assume a common nature, with which all the implementations of the word have some kind of relation, their difference is that while kath hen takes all the implementations of the word as the same with the common nature, pros hen makes them different. Substance is called πρῶτον ὄν because it is said to be primarily: -/- For as is (τὸ ἔστιν) is predicated of all things, not however in the same way (οὐχ ὁμοίως) but of one sort of thing primarily and of others in a secondary way. So too τὸτί ἐστιν belongs simply (ἁπλῶς) to substance but in a limited sense (πῶς) to the others [other categories] (1030a21-23). -/- The word ἁπλῶς standing against κατὰ συμβεβηκός tries to make substance different from the accidents. When we are being said that τὸ ὄν πολλαχῶς λέγεται, it means that only the substance that is simply (ἁπλῶς) the ἕν, the common nature, τὸὄν. When we use the word 'being' about a substance, the being is said differently from when we use 'being' about an accident. The distinction between the substance and the other categories is a distinction between what simply is said to be and what only with reference to (pros) the substance is said to be. The doctrine of pros hen, changing kath hen to pros hen in respect of to on, makes a distinction that wants to show that while there is a kind of implementing the word being that is simply being, there is another kind which is called being only by reference to that which is simply being. In the doctrine of pros hen it is not so that all the things that are said to be are only by reference to a common one thing, but that while one thing is called being because it is that thing itself, the other things are called so without being that thing itself but only by referring to it. At the very beginning of book Γ, it is said that: -/- Being is said in many senses but all refer to one arche. Some things are said to be because they are substances, others because they are affections of substances, others because they are a process towards substances or destructions or privations or qualities of substances … (1003b5-9, cf. 1028a18-20) -/- Substance is what really is said to be and all other things that are said to be are said only in favor of it. This difference of substance from all other senses of being is what is, I believe, primarily aimed in Aristotle’s interrelated theories of pollachos legetai,pros hen and the theory of substance. b) The difference of the implementation of being in the case of substance and the accidents goes so deep that while substance is considered as the real being, the accidents are almost not being. An accident is a mere name (Metaphysics 1026b13-14) and is obviously akin to not being (b21). Aristotle adds that Plato was 'in a sense not wrong' saying that sophists deal with not being (τὸ μὴ ὄν) because the arguments of sophists are, above all, about the accidental (1026b13-16). At the beginning of book , he says about quality and quantity (which look to be more of a being than other accidents) that they are not existent (οὐδ̕ ὄντα ὡς εἰπεῖν) in an unqualified sense (ἁπλῶς) (1069a21-22). The two above-mentioned points, Aristotle’s (a) interwoven theories of pollachos legetai, pros hen and the theory of substance and (b) taking accidents almost as not being, comparedwith substance, brings forth a structure that I shall call Pollachos Legetai (with capital first letters). What is of the highest importance in this structure for me is the difference of substance from accidents and the kind of relation which is settled between them. There is a substance that without any qualification is said to be and the accidents that are said to be only by reference (pros) to it. Adding Aristotle’s point about accidents that they are nearly not being to this relation and difference, we can obviously see how much this structure is close to Plato’s original-copy ontology. We spoke of the relation of being and difference in Plato’s model and the way Plato construes the being of a copy. A copy is a copy only by referring to (pros) a model; it is different from (ἕτερον) that of which it is a copy; it is not itself a true thing as its model and not really that which is (ὄντως ὄν) but only is in a way (πῶς). If we behold the difference of substance and accident in the context of the theory of pollachos legetai and pros hen, we can observe its fundamental similarity with Plato’s original-copy theory in its structure. Allen draws attention to the fact that the relation between Forms and particulars in Plato’s original-copy model is 'something intermediate between univocity and full equivocity' (1998, 70, n. 24) and the same as what Aristotle calls it pros hen (ibid). What made us compare the two structures was not, of course, the complete similarity of two structures (we have to agree with many possible differences of the two theories) but exactly the specific relation between an original and its copy on the one hand, and a substance and its accident on the other hand. As substance and accident do not share a common character and the substance -accident model hints that they stand in a certain relation, there is no common character between the original and copy in Plato’s model as well. Furthermore, their similarity is not confined to their structure only; they are also aimed to solve the same problem. The central point of the theory is that all the predecessors took being in one sense and this was their weakness point. Besides the mentioned above passages about the relation of pollachos legetai and presocratics’, as well as Plato’s, ontology, the relation of the theory with the problem of not being is clear in several passages. In Metaphysics, it is said: 'Being is then said in many senses… It is for this reason that we say even of not being that it is not being' (1003b5-10). Discussing the accidental sense of being, Aristotle points that it is in the accidental way that we say, for example, that not-white is because that of which it is an accident is (1017a18-19, cf. 1069a22-24). We mentioned that he thought Plato was right saying that sophistic deals with not being because sophistic deals with accidental, which is somehow not being (1026b14-16). Plato turned sophistic not-being to what both is and is not and Aristotle to what accidentally is said to be. What helps Aristotle to resolve the problem of not being is his distinction between ἁπλῶς and κατὰ σθμβεβηκός. Aristotle’s "qua" (ᾕ) which is directly linked with his distinction between καθ’ αὑτο λέγεται and κατὰ συμβεβηκός λέγεται, is used to resolve the old problem of coming to be out of not being (Physics 191b4-10). He strictly asserts that his predecessors could not solve the problem because they failed to observe the distinction of "qua itself" from "qua another thing" (b10-13). He then continues: -/- We ourselves are in agreement with them in holding that nothing can be said simply (ἁπλως) to come from not being (μὴὄντος). But nevertheless we maintain that a thing may come to be from not being in an accidental way (κατὰ συμβεβηκός). For from privation which ὅ ἐστι καθ’ αὑτο μὴ ὄν, nothing can become. (Phy. 191b13-16, cf. b19-25) . (shrink)

OBJETIVO A gestação nos mamíferos domésticos é um processo fisiológico que implica mudanças físicas, metabólicas e hormonais na fêmea, que culminam com o nascimento de um novo indivíduo. Desta forma, a compreensão de tais mudanças e como estas favorecem um ambiente ideal de desenvolvimento embrionário inicial, até a placentação e a fisiologia envolvidas durante esses processos é fundamental na tomada de decisões quanto à saúde reprodutiva da fêmea, na seleção de futuras matrizes e até mesmo para a saúde fetal e (...) sanidade do novo animal. Neste capítulo, o estudante compreenderá de forma clara, concisa, didática e objetiva, as adaptações maternas e fetais para o estabelecimento da gestação após a fecundação, o desenvolvimento desta e também identificará as diferenças existentes entre as espécies de interesse zootécnico. INTRODUÇÃO O estabelecimento da gestação nos mamíferos domésticos inclui três etapas fundamentais: o reconhecimento materno da gestação ou prenhez (RMP), a implantação e a placentação. Dentro da fisiologia da reprodução nos mamíferos, a implantação e a placenta- ção constituem processos essenciais na nutrição do embrião e do feto e, portanto, para seu desenvolvimento; devido a isso, são etapas críticas para a produção animal já que possuem um efeito direto sobre a eficiência reprodutiva. Nos bovinos leiteiros, por exemplo, estima-se uma taxa de fertilização perto de 95%, embora apenas 55% desses zigotos se desenvolvam e cheguem ao parto, o qual representa uma perda de gestações perto de 35%. Entre 70% e 80% das mortes embrionárias ocorrem durante as três semanas seguintes à ovulação, o que coincide com o período no qual se estabelecem os processos de implantação e placentação supracitados. O desenvolvimento embrionário precoce depende da sincronia de eventos entre o oviduto-útero e o embrião. Foi determinado que a presença do embrião pode modificar as secreções ovidutais e uterinas durante as fases iniciais de desenvolvimento. O ambiente endócrino materno (predominância de progesterona) também modula as características das secreções ovidutais e uterinas para assegurar a sobrevivência embrionária no caso da fertilização ter sido bem sucedida. Se este último ocorrer, então o embrião deverá indicar à mãe a sua existência para que sejam mantidas as condições adequadas ao seu desenvolvimento. Como supracitado, o embrião em seu curso pelo oviduto requer certas secreções para sobreviver e desenvolver-se, no entanto, graças à fertilização in vitro, têm-se dispensado a importância das secreções ovidutais, já que se observou que um embrião é capaz de se desenvolver em condições laboratoriais fora do aparelho reprodutor materno durante as suas fases iniciais, e consegue estabelecer uma gestação normal que chega a termo após a sua reintrodução no útero. Em estágios mais tardios de desenvolvimento o embrião necessita necessariamente do meio uterino para sobreviver e continuar o seu crescimento. No bovino, por exemplo, o embrião só é capaz de alongar-se estando dentro do útero, indicando a presença de fatores específicos necessários para que o embrião se desenvolva de maneira normal. Um meio endócrino no qual predomina a progesterona materna durante a gestação induz a secreção do histiotrofo (ou leite uterino) que permite a nutrição e a sobrevivência do embrião antes da implantação e da formação da placenta, através do qual obterá a maioria do fornecimento e intercâmbio necessários para continuar o seu desenvolvimento intra-uterino. SEGMENTAÇÃO E DESENVOLVIMENTO EMBRIONÁRIO PRECOCE O desenvolvimento embrionário precoce, conhecido como período de pré- -implantação, é essencial; inclui processos de divisão e diferenciação celular que são realizadas no início com uma elevada sincronização para garantir o desenvolvimento correto do indivíduo dentro do útero. Esta fase envolve a passagem do zigoto (unicelular), a embrião (multicelular) e, por fim, em concepto (quando se distingue o embrião com suas membranas extraembrionárias). O desenvolvimento precoce é o estágio mais dinâmico e vulnerável na formação de um indivíduo. Investigações recentes demonstraram que alterações nesta etapa podem modificar características produtivas ou reprodutivas durante a vida adulta. É por isso que é necessário conhecer as etapas fisiologicamente normais envolvidas neste processo (figura 1). Em fases mais tardias de desenvolvimento, o embrião se converterá em um feto com todos os sistemas e tecidos diferenciados observados num animal adulto. Após a fertilização, o zigoto resultante é capaz de dar origem a um novo organismo completo, de modo que se considera como uma célula totipotencial. O desenvolvimento embrionário começa e se consegue graças a uma série de divisões mitóticas conhecidas como segmentação ou clivagem (cleavage, em inglês). A primeira divisão mitótica dá origem a duas células filhas idênticas (figura 1), e ocorre por volta das 20 às 30 horas depois da fertilização, com divisões subsequentes a cada 12 a 24 h, dependendo da espécie. As células resultantes destas divisões são conhecidas como blastômeros. A orientação da divisão inicial que dá origem aos dois primeiros blastô- meros, parece ser guiada pela posição dos corpos polares. As divisões iniciais das células embrionárias são sincrônicas, no entanto, conforme o desenvolvimento se torna assincrônicas. Assim, a divisão mitótica inicial dá origem a um embrião de duas células (dois blastômeros), a segunda a um embrião de quatro células, a terceira a um de oito células e a quarta a um com 16 células, onde passa a ser chamado de mórula. Estas divisões são realizadas sem o aumento do volume do citoplasma, para que seja restabelecida uma proporção celular mais adequada à das células somáticas, já que o ovócito é a célula mais grande do organismo (um ovócito mede entre 100 e 150 μm do ovócito, enquanto uma célula somática mede de 10 a 20 μm); e porque o embrião ainda está contido dentro da zona pelúcida (figura 1). Um dos pontos críticos durante o desenvolvimento embrionário precoce é a ativação do genoma embrionário. Durante as etapas iniciais após a fertilização, as proteínas e RNAs “herdados” do ovócito são responsáveis pelo metabolismo e desenvolvimento inicial do embrião. É apenas até o estágio de quatro (ratos) ou oito blastômeros (espécies domésticas e humanas) em que o embrião começa a sintetizar o seu próprio RNAm (mensageiro) e as proteínas específicas necessárias para controlar o seu crescimento e metabolismo. A qualidade do ovócito que é fertilizado, consequente- mente, tem um grande impacto sobre a sobrevivência inicial do embrião. Quando o embrião atinge uma média de 16 a 32 células é conhecido como mórula (tabela 1) (do latim morus: mora), e nesta fase o embrião começa a compactar-se, o que ocorre porque começam a estabelecer-se diferentes uniões celulares, de acordo com a relação espacial entre os blastômeros. As células centrais desenvolvem-se incluindo entre elas junções comunicantes, conhecidas também como junções GAP, enquanto as que se encontram na periferia estabelecem uniões estreitas, dando origem a duas subpopulações distintas de blastômeros: periféricos e centrais. Cabe mencionar que os blastômeros que compõem a mórula ainda são células capazes de dar origem a um novo indivíduo completo, ou seja, são totipotenciais. À medida que a mórula continua a dividir-se e a crescer, as células localizadas na periferia começam a liberar sódio para os espaços intercelulares, criando uma diferença na pressão osmótica seguida pela entrada de água ao embrião. O líquido se acumula e provoca a separação das células, distinguindo ainda mais as duas subpopulações de células mencionadas (periféricas e centrais) e forma-se uma cavidade cheia de líquido. Esta cavidade é conhecida como blastocele; com a sua formação o embrião entra em fase de blastocisto (figura 1, tabela 1). Da subpopulação celular da periferia se origina do trofoblasto (trofoectoderma) que formará a maioria das membranas extraembrionárias (placenta), e da subpopulação central é estabelecida a massa celular interna ou embrioblasto, que dará origem ao embrião propriamente dito, ou seja, ao feto. Ao continuar a multiplicação e crescimento do trofoblasto à medida que o blastocisto se desenvolve, as células da massa interna se diferenciam novamente em dois segmentos distintos: a endoderme primitiva ou hipoblasto e o epiblasto (figura 1), em que todos os tecidos do organismo (saco vitelino) são originados e as células germinativas primordiais. Uma vez formado, o epiblasto continua a dividir-se e a diferenciar-se para dar origem às três placas ou camadas germinativas conhecidas como endoderme, mesoderme e ectoderme. Este processo é conhecido como gastrulação, e durante este diferem-se no embrião as porções craniais, caudais, dorsais e ventrais, processo conhecido como polaridade do embrião, que orienta o desenvolvimento dos diversos tecidos e órgãos do indivíduo. À medida que o blastocisto continua crescendo e diferenciando-se, vai-se acumulando mais líquido no blastocele, com o que a pressão interna aumenta e a zona pelúcida começa a ficar mais fina. Este fato, juntamente com a ação de proteases produzidas pelo embrião, leva à ruptura da zona pelúcida e à saída do blastocisto (eclosão), pelo que, uma vez liberado, o embrião é conhecido como blastocisto eclodido. O trofoblasto embrionário entra, então, em contato direto com o endométrio, o que é considerado como o início da implantação. IMPLANTAÇÃO O trofoblasto embrionário, também conhecido como trofoectoderma, dá origem à maioria das membranas fetais ou placenta fetal. O processo no qual o trofoblasto se une ao endométrio materno é conhecido como implantação; para isso ocorre uma série de processos altamente sincronizados envolvendo secreções embrionárias e maternas, e interações físicas, durante um período limitado conhecido como janela de receptividade. A implantação é considerada um processo gradual que genericamente se divide em cinco fases, algumas das quais podem sobrepor-se parcialmente e diferir segundo a espécie: 1. Eclosão do blastocisto da zona pelúcida (figura 2); -/- 2. Pré-contato e orientação do blastocisto. É o contato inicial entre as células do trofoblasto e do epitélio endometrial, bem como a orientação da massa celular interna e do trofoectoderma, que assume especial importância em espécies cuja implantação é invasiva, como em roedores e primatas; 3. Aposição - refere-se ao posicionamento do blastocisto numa determinada área e de uma forma específica no útero. Começa a interdigitação das vilosidades coriônicas com o epitélio luminal do endométrio. 4. Adesão - requer sistemas de sinalização que envolvem glicoproteínas de adesão, como integrinas, selectinas e galectinas, com os seus ligantes, tanto no epitélio luminal como no epitélio trofoectoderma. 5. Invasão endometrial - este termo se relaciona ao tipo de placentação e é pertinente sobretudo para aquelas espécies onde existe uma fusão entre células do trofoblasto e do epitélio do endométrio durante a formação da placenta, ou que as células trofoblásticas penetrem as camadas endometriais e até modifiquem as células do endométrio que as rodeiam. Existem três tipos de implantação ou nidação. Na nidação central ou não invasiva, a vesícula embrionária ocupa uma posição central na luz do útero e, na sua relação com a mucosa uterina, unicamente através das vilosidades coriônicas (projeções das células trofoblásticas dentro das quais crescem capilares do feto), há adesão mas não invasão da mucosa. Este tipo ocorre nos ungulados domésticos, mas não em carnívoros. Na nidação excêntrica a vesícula embrionária está inserida num canal profundo da mucosa, parcialmente isolada da luz principal, e se apresenta na rata, cadela e gata. A nidação intersticial é própria dos primatas, rato e cobaia, e nesta produz-se a destruição do epitélio e do tecido conjuntivo do útero, de modo que a vesícula embrionária se afunda na própria lâmina mucosa e se desenvolve em um espaço intersticial. Até o momento da implantação, a nutrição do embrião é histotrófica, sendo as substâncias necessárias absorvidas através do trofoblasto, como foi mencionado anteriormente. A partir deste momento, o trofoblasto começa o desenvolvimento de uma série de membranas extraembrionárias que permitirão finalmente a troca de nutrientes e metabólitos entre o sangue materno e o do embrião, constituindo a placenta. Um fato necessário na implantação é a perda de receptores para progesterona no epitélio luminal do endométrio, e pré-sensibilização do mesmo pelos estrógenos. Apesar de parecer um efeito contraditório, este requisito permite o desaparecimento de uma camada de mucina e outros compostos proteicos, que revestem o endométrio e que atuam como uma película antiaderente que inicialmente não permite a aposição e adesão do embrião. O desaparecimento desta camada ocorre durante a janela de receptividade, seja em toda a superfície do endométrio (ruminantes, suínos e roedores) ou nas zonas específicas onde o blastocisto será implantado (humano e coelho). Por esta razão, a interação física entre o embrião e o endométrio desempenha um papel importante na implantação. Uma vez que a camada de glicoproteínas desaparecer, é possível a aposição do trofoectoderma embrionário e das células epiteliais do endométrio, iniciando assim a implantação propriamente dita através da intercomunicação entre os dois tecidos. A implantação pode ser considerada como a fixação do embrião ao útero a partir do ponto de vista físico e funcional. No entanto, como se trata de um processo progressivo e gradual, em que algumas das suas fases podem ser parcialmente sobrepostas, não existe consenso sobre o período em que se inicia e termina. Na borrega, por exemplo, estima-se que ocorra entre o dia 10 e o dia 22, enquanto na vaca entre os dias 11 e 40 pós-ovulação. Nas espécies polítocas, isto é, fêmeas que parem várias crias como as porcas, os blastocistos se distribuem ao longo dos cornos uterinos como resultado de movimentos musculares da parede uterina, aparentemente regulados por prostaglandinas e outros fatores secretados pelo útero. Por exemplo, nas porcas, os blastocistos se movem livremente entre os cornos, e a distribuição dos embriões ao implantar-se é mais uniforme do que poderia ser esperado se ocorresse meramente ao acaso. Tem observado que a deficiência na produção de ácido lisofosfatídico 3 (LPA3) e/ou seu receptor, ocasiona uma falha na distribuição dos embriões no útero. Por outro lado, não há evidência de que um blastocisto implantado exerça alguma influência inibitória sobre a implantação de outro blastocisto próximo a ele. Como supracitado, o processo de implantação inclui uma complexa interação entre o embrião e o útero, e cada um deles provê de estímulos essenciais para favorecer a progressão do outro, apresentando-se diferenças em tempos e particularidades dentro das diferentes espécies. -/- Porca O período de adesão situa-se entre os dias 12 e 24 após a fertilização. Ao redor do dia sete, o blastocisto é eclodido, porque o trofoblasto está em contato direto com o epitélio uterino e começa a proliferar com rapidez. O endoderme se forma e o blastocisto muda de uma pequena vesícula esférica para um tubo muito alongado que chega a medir cerca de um metro em poucos dias, ele que lhe proporciona uma superfície muito ampla para a absorção de nutrientes. Cadela Os embriões migram entre os dois cornos uterinos do dia 12 ao 17 após a fertilização, distribuindo-se de maneira uniforme. Estes embriões aderem ao endométrio entre os dias 16 e 18, e alcançam sua implantação final entre o dia 17 e 20 da gestação. Cabe ressaltar que nos caninos o período de pré-implantação é o mais longo das espécies domésticas, o que ocorre porque a cadela ovula ovócitos imaturos (ovócitos primários) que precisam amadurecer por dois a três dias, para formar ovócitos secundários, antes que a fertilização seja possível. Por isso, o zigoto canino chega à junção útero-tubárica entre o sétimo e o décimo dia após o pico pré-ovulatório de LH (a ovulação ocorre, em média, dois dias após o pico de LH), entrando no útero em estágio de mórula ou blastocisto em torno dos dias 10 a 12 depois do referido pico. Ovelha O desenvolvimento precoce do blastocisto é muito semelhante ao da porca. Observa-se certo grau de adesão desde o dia 10 da gestação, mas o alongamento do embrião é menos extenso do que em suínos e tem início entre o dia 11 e 12. Para a terceira semana o embrião ovino chega a medir até 30 cm de comprimento. O processo de implantação é concluído aproximadamente entre a quarta e quinta semana de gestação (figura 3). Vaca O processo de implantação é semelhante ao da borrega, mas tem início mais tarde. A zona pelúcida se perde por volta do dia 9 a 10 (blastocisto eclodido) e o embrião começa a alongar-se ao redor do dia 12 a 14, atingindo um comprimento de cerca de 60 mm para o dia 16, embora possa haver uma grande variação individual. A partir do dia 33, o córion é formado e existe uma adesão inicial que inclui dois ou quatro cotilédones, que se interdigitam rapidamente com o tecido materno de modo que o embrião começa a nutrir-se através deles. Égua O blastocisto atinge um diâmetro de cinco centímetros aos dois meses e pratica- mente não se alonga. Entre os dias seis e sete após a ovulação, o embrião começa a revestir-se de uma camada glicoproteica que se forma entre o trofoectoderma e a zona pelúcida e que contém e mantém o embrião esférico depois de ter eclodido. Esta cápsula é uma estrutura única nos equinos (cápsula embrionária), afina-se no dia 18 e se perde entre os dias 21 e 23 de gestação. Na décima semana as microvilosidades do córion se interdigitam com a mucosa da parede uterina e na semana 14 é completada a implantação. Espécies não domésticas Em algumas espécies como os marsupiais, os ursos, focas, doninhas e alguns tipos de cervídeos, pode interromper-se temporariamente o desenvolvimento do embrião in utero e adiar a sua implantação, como estratégia evolutiva para favorecer o nascimento das crias em condições ambientais favoráveis para a sua sobrevivência. Esta estratégia é conhecida como diapausa e pode ser uma condição obrigatória ou facultativa para cada gestação, dependendo da espécie. Os mecanismos que a desencadeiam e a concluem não estão totalmente explicados e são espécie-específica. RECONHECIMENTO MATERNO DA GESTAÇÃO (RMG/RMP) O estabelecimento da gestação em mamíferos domésticos requer a presença de um corpo lúteo CL funcional que produz progesterona em quantidades adequadas para manter o desenvolvimento embrionário inicial e permitir mudanças necessárias durante o período de peri-implantação. Para que o corpo lúteo seja mantido e a fêmea seja impedida de reiniciar um novo ciclo estral, o embrião deve sinalizar sua presença para a mãe. O sinal para o reconhecimento materno da gestação (RMG) provém então do embrião e podem ser de dois tipos: luteotrópico ou anti-luteolítico. No primeiro, a(s) substância(s) produzida(s) pelo embrião que atua(am) sobre o corpo lúteo para manter sua funcionalidade, por exemplo a gonadotrofina coriônica humana (hCG) e a prolactina em roedores. O segundo tipo de sinal previne ativamente a luteólise, e é o mecanismo presente nas espécies domésticas em que o embrião produz substâncias como o interferon-τ (IFN-τ) em ruminantes ou os estrógenos em suínos. Ruminantes Como supracitado, o IFN-τ é responsável pela sinalização para o reconhecimen- to materno da gestação neste grupo que engloba cabras, ovelhas e vacas (figura 4). É um fator produzido pelas células do trofoblasto do embrião, e pode ser detectado a partir dos dias 11 a 12 em ovinos e de 14 a 15 em bovinos. Uma vez secretado, o IFN-τ impede a lise do corpo lúteo (efeito anti-luteolítico) por meio do bloqueio indireto da síntese de prostaglandina F2 alfa (PGF2α). No trabalho acerca do ciclo estral foi explicado que a luteólise requer a presença de receptores de ocitocina (OTR) no endométrio, que ao unir-se ao seu ligante, a ocitocina (proveniente inicialmente do hipotálamo e posteriormente de origem lútea), estimulam a produção de PGF2α e estabelecem um feedback positivo, que culminará na destruição do CL. Para que os OTRs sejam sintetizados, é necessária uma estimulação prévia do endométrio com estradiol, que ocorre através da ligação com seus receptores (ER-1). O mecanismo pelo qual o IFN-τ impede a lise do corpo lúteo é bloqueando, direta ou indiretamente, a síntese de OTR e, consequentemente, a produção pulsátil de PGF2α. Suínos No caso dos suínos, considera-se que o sinal embrionário para o reconhecimento materno da gestação são os estrógenos, produzidos pelos embriões em torno do dia 11 a 12 pós-ovulação. O endométrio suíno produz PGF2α que, quando não há gestação, é secretado na circulação uterina (secreção endócrina), de onde é transportada em direção ao CL para causar luteólise. Se há embriões no útero produzindo suficiente quantidades de estradiol, isso redireciona a secreção de PGF2α para o lúmen uterino (secreção exócrina), evitando que seja liberado para a circulação e, portanto, é sequestrado impedindo que chegue ao corpo lúteo (figura 5). É importante enfatizar que a produção de PGF2α não é inibida, mas sua secreção é redirecionada. Este mecanismo é conhecido como teoria endócrino-exócrina. Vale ressaltar que para o sinal de reconhecimento materno da gestação na porca ser eficiente, é necessário a presença de pelo menos quatro embriões, dois em cada corno, uma vez que se não houver dois embriões, um em cada corno, ocorre luteólise e reinicia a atividade cíclica. Embora os estrógenos sejam identificados como o sinal de reconhecimento materno nesta espécie, o embrião suíno também produz outros fatores, como a PGE2 e o ácido lisofosfatídico, considerado necessário para o estabelecimento adequado da gestação. A PGE2 ocasiona uma redução na produção de PGF2α em favor da PGE2 no endométrio e favorece a contração do miométrio para permitir a migração de embriões. O ácido lisofosfatídico, juntamente com seu receptor, é um fator crítico que favorece a migração intra-uterina, e permite uma distribuição adequada dos embriões ao longo dos cornos. Outras substâncias produzidas pelo embrião suíno são o IFN-delta (IFN-δ) e IFN-gama (IFN-γ), que não possuem ação anti-luteolítica, mas poderiam intervir no processo de implantação. Equinos Na égua é essencial que o embrião, ainda rodeado pela sua cápsula embrionária, migre de 12 a 14 vezes por dia através do útero, entre os dias 12 e 14 após ovulação, a fim de distribuir o fator de reconhecimento materno (figura 6). Embora seja sabido que existe, este último ainda não foi identificado, mas foi estabelecido que é da natureza proteica e seu principal efeito é a inibição da produção endometrial de PGF₂α, mediante a redução na formação do receptores de ocitocina; desta forma, evita-se o início do sinal luteolítico. É interessante notar que nesta espécie a ocitocina não é de origem lútea e sim endometrial. Primatas Ao contrário das espécies domésticas mencionadas, o mecanismo de ação do sinal de reconhecimento materno em primatas é luteotrópico. No humano, o embrião produz gonadotrofina coriônica humana (hCG) após o início da implantação (dias 6 a 8). A hCG estende a vida funcional do CL por meio de sua ligação a receptores lúteos para LH, estimulando assim a liberação de progesterona. Este efeito permite a “sobrevivência” do CL pelo menos até o momento em que a produção de progesterona é transferida para a placenta para levar a gestação a termo. Carnívoros Na cadela não é necessário o reconhecimento da gestação, já que normalmente o corpo lúteo tem uma vida média maior que a duração da gestação. Como na égua, a migração dos embriões através do útero antes da implantação pode favorecer o reconhecimento materno. Adicionalmente, tem sido descrito que durante o período antes da implantação (< 10 dias depois da ovulação), há um aumento na expressão de genes relacionados com a imunomodulação local (IFN-γ, IL-4 e CD8+), que não estão presentes em cadelas durante o diestro. A produção de IFN-γ por parte do embrião canino, como em outras espécies, pode estar envolvida na implantação ou o reconheci- mento da gestação, mas até o momento não foi demonstrado de forma inequívoca. Na gata doméstica, o fator que favorece o reconhecimento materno da gestação ainda não foi descrito. Temos que lembrar que seja qual for o mecanismo envolvido, a produção do sinal embrionário de reconhecimento materno da gestação é importante, já que a contínua presença de progesterona na circulação materna, faz possível que ocorra o desenvolvimento precoce do embrião e eventualmente a implantação, com a formação do órgão temporal mais importante para o desenvolvimento fetal: a placenta. Resumindo, o sinal enviado pelo embrião deve ser dado antes do útero começar a secretar PGF2a, hormônio que causa a destruição do corpo lúteo produtor da progesterona necessária para a gestação. O embrião deve secretar algumas substâncias (denominadas EPF: Early Pregnant Factors/fatores de gestação precoce) que capte o endométrio materno e sirva para evitar a ação luteolítica da PGF2a. Na porca, em vez de ser evitada a secreção de PGF2a, o referido hormônio é “sequestrado na luz do útero” e, desta forma, passa a secretar-se em forma exócrina, sem ter efeito sobre o corpo lúteo. No bovino, o reconhecimento materno da gestação é o processo fisiológico no qual o embrião, por meio de sinais moleculares como a secreção de interferon-τ (IFN-τ), anuncia sua presença no trato reprodutivo materno a fim de evitar que seja desencadeado o mecanismo luteolítico exercido pela PGF2a sobre o corpo lúteo. PLACENTAÇÃO Nos mamíferos domésticos, o processo de implantação é gradual e prolongado, e ocorre paralelamente a processos como a gastrulação e a formação de membranas extra- embrionárias: saco vitelino, âmnio, alantóides e córion. A formação das membranas extraembrionárias nos mamíferos eutérios, ou seja, aqueles que formam uma placenta completa, é um processo indispensável que permite ao embrião aderir-se ou implantar-se ao endométrio materno. As quatro membranas extraembrionárias mencionadas são formadas a partir do trofoblasto, mesoderme e endoderme embrionários. O saco vitelino fornece nutrientes no desenvolvimento inicial do embrião e se converte em vestigial quando a gestação progride; tem origem no endoderma primitivo, estrutura que junta com o trofoblasto e o mesoderma, formam o córion e âmnions. O âmnion contém o líquido amniótico que está em contato direto com o embrião e é a membrana mais interna; ademais, protege o feto, proporciona lubrificação para o parto e serve como um depósito para urina e resíduos fetais. O córion, por outro lado, é a membrana mais externa do embrião e, portanto, é a que entra em contato direto com o endométrio uterino materno; se fixa ao útero, absorve nutrientes do útero, permite a troca gasosa materno/fetal e produz hormônios. O alantóide se origina de uma evaginação do intestino primitivo e é de onde surge o sistema vascular da placenta fetal; a fusão com o córion (placenta cotiledonária), carrega os vasos sanguíneos do cordão umbilical, que liga o feto com o alantóide e é um reservatório de nutrientes e resíduos. Conforme o embrião se desenvolve, o saco vitelino regride e o alantóide se enche de líquido, pelo que este último se funde com o córion para formar o corioalantóides, que se torna a membrana mais externa e, portanto, a porção fetal do placenta. A placenta é um órgão temporário que representa uma interface através da qual realiza a troca bidirecional de nutrientes, gases, hormônios e outras substâncias entre a mãe e o feto. A unidade funcional da placenta são as vilosidades corioalantóicas, as quais são projeções pequenas dos corioalantóides que se interdigitam com o endométrio uterino, cuja superfície de absorção permite essa troca. A placenta é um órgão endócrino capaz de produzir uma gama de hormônios que ajudam a controlar o ambiente uterino, favorecendo o desenvolvimento do feto, além disso possui um papel importante no momento do parto. Nas diferentes espécies a placenta tem características particulares, pelo qual existem várias classificações, de acordo com a sua posição uterina, a distribuição das vilosidades corioalantóicas e a sua histologia. Posição uterina Refere-se à posição do concepto em relação ao lúmen uterino (figura 7). Central: O concepto ao ser implantado permanece em contato com o lúmen do útero. A maioria das espécies domésticas de importância veterinária estão dentro desta classificação. Excêntrica: O concepto penetra parcialmente o endométrio materno, mas mantém um certo contato com o lúmen uterino. Os roedores (ratos e ratos) e a coelha possuem este tipo de placentação. Intersticial: O embrião invade o endométrio, perde contato com o lúmen uterino, e ao crescer o lúmen uterino se oblitera. Os humanos e a maioria dos primatas mostram este tipo de placenta. Distribuição das vilosidades As vilosidades que formam a interface materno-fetal podem estar distribuídas de maneira diferente ao longo da superfície dos corioalantóides, pelo qual a placenta pode ser classificada como (figura 8): Difusa: Neste tipo de placenta as vilosidades estão distribuídas ao comprimento de toda a superfície do córion (corioalantóides) de maneira uniforme. As placentas de suínos e equinos se enquadram nesta classificação, embora, nesta última espécie, as vilosidades formem estruturas mais ramificadas, que são chamadas microcotilédones (figura 10). Zonal: Esta placenta se apresenta nos carnívoros domésticos, tanto caninos como felinos. As vilosidades que determinam a zona de troca de nutrientes e resíduos, e de ligação com o endométrio são delimitadas de forma a formar uma cintura central em torno do feto (figura 9). Distingue-se também uma segunda região chamada paraplacenta, que se localiza em ambos lados deste “cinto”, e do qual a função não é inteiramente conhecida, embora sabe-se que desempenha um papel importante na troca de ferro da mãe para o feto. As extremidades laterais dos corioalantóides nestas placentas não possuem vilosidades por isso não se ligam ao endométrio. Uma terceira região é a zona transparente nas extremidades distais do córion que tem pouca vascularização. Esta zona pode estar envolvida na absorção de materiais diretamente do lúmen uterino (figura 11). Cotiledonária: É o tipo de placentação que se encontra presente nos ruminantes (ovinos, caprinos e bovinos). As vilosidades coriônicas nestas espécies são agrupadas em pequenas áreas do córion chamadas cotilédones, que se interdigitam e fundem-se parcialmente com locais delimitados no endométrio chamados carúnculas, formando, em conjunto, estruturas conhecidas como placentomas. Cabe destacar que as carúnculas carecem de glândulas endometriais, que só estão presentes nas porções inter-carun- culares do endométrio. Os placentomas, por sua vez, são altamente vascularizados e são remodelados com o progresso da gestação, ramificando-se para aumentar a superfície de troca e o fluxo sanguíneo para aumentar os requisitos do feto em crescimento. Nas zonas inter-carunculares, a placenta é ligada ao endométrio por meio de sistemas de adesão superficial que envolvem glicoproteínas. Acredita-se que a adesão do concepto com o endométrio (carúnculas) é estabelecida em torno de 30 dias em ovinos e 40 dias em bovinos. (figuras 13 a 17). Discoidal: Nestas placentas, as vilosidades agrupam-se numa área circular ou oval, formando uma estrutura discoidal. Este tipo de placenta é encontrada principal- mente em coelhas, roedores e primatas, incluindo os humanos. Histologicamente Esta classificação considera o número de camadas de tecido que compõem a placenta e que separam a circulação materna da circulação fetal (tabela 3). O número máximo é de seis camadas, três do lado fetal (córion, tecido intersticial e endotélio do vaso sanguíneo) e três do lado materno (epitélio endometrial, tecido intersticial e endotélio vascular) (figura 19 e tabela 3). O modo de distinguir e nomear os diferentes tipos de placenta nesta classificação é usando como prefixo a camada materna que está em contato com o córion fetal. As diferentes placentas baseados em sua histologia são as seguintes (figura 19): Epiteliocorial: É o menos íntimo entre os tipos de placentas (figura 20). Estas placentas conservam intactas as seis camadas de tecido, portanto que mantêm as circulações materna e fetal mais separadas, e consideradas como as mais impermeáveis. Este tipo de placenta está presente na porca e égua. Lembre-se de que as placentas da porca e da égua são diferentes e as vilosidades ocupam uma grande proporção da área de superfície do córion (figura 19 A). Também apresenta-se nos ruminantes, no entanto, as placentas dos ruminantes apresentam algumas características particulares que as colocam como um subgrupo e se chamam sinepiteliocorial ou sindesmocorial (figura 19 B). Na vaca, este tipo apresenta-se nos primeiros 2-3 meses de gestação. Além da característica de erosão parcial do epitélio endometrial, um tipo de célula único é encontrado na placenta de ruminantes. Essas células são chamadas células gigantes binucleadas. Como o nome indica, elas são caracterizadas como bastante grandes e com dois núcleos. Na placenta dos ruminantes, algumas células do epitélio coriônico conhecidas como células binucleadas, se fundem com algumas células do epitélio endometrial, criando inicialmente células gigantes trinucleadas e mais tarde placas ou sincícios multinucleados. Estes sincícios têm em consequência uma origem tanto fetal como materna, que criam lugares delimitados nos quais em vez de existir intacta uma camada de epitélio coriônico e outra de epitélio endometrial, encontra-se uma só camada que combina as duas origens. As células gigantes binucleadas migram e mudam seu número ao longo da gestação em forma dinâmica. Este tipo celular é importante porque secretam uma variedade de hormônios. Células gigantes binucleadas aparecem por volta do dia 14 na ovelha e entre os dias 18 e 20 na vaca. Endoteliocorial: 5 camadas. Neste tipo de placentação o córion fetal está em contato direto com o endotélio vascular do endométrio graças à erosão do epitélio e do tecido conectivo endometrial (tecido intersticial) durante a implantação (figura 19 C). De modo que o intercâmbio de substâncias e resíduos só requer atravessar quatro camadas de tecidos. Este tipo de placenta é presente principalmente em cães e felinos. Nota-se nas figuras 19 C e 21 que este tipo de placenta é mais íntimo do que a placenta epiteliocorial porque o epitélio endometrial não existe mais. Hemocorial: 3 camadas (figura 22). Aqui o epitélio coriônico está intacto e entra em contato direto com o sangue materno em regiões onde formam reservatórios de sangue semelhantes a poços (figura 19 D). O intercâmbio de substâncias e resíduos entre a mãe e o feto é mais direto uma vez que é necessário atravessar apenas três camadas para chegar até à circulação fetal. Algumas espécies de primatas, incluindo o ser humano e os roedores possuem este tipo de placentação. MEMBRANAS EXTRAEMBRIONÁRIAS EM AVES Ao mesmo tempo que se estabelece o corpo embrionário e os esboços de cada um dos órgãos começam a gerar-se, torna-se imperioso garantir a sobrevivência do embrião. Tenha-se em conta que nas aves todo o necessário para o desenvolvimento é encontrado no ovo pelo que deve-se reforçar a eficácia das estruturas criadas para garantir o objetivo a que se destina. O exterior é fornecido apenas com o O2; emite CO2 e vapor de água no exterior (perda de 15% da água durante a incubação inicial). Além disso, o neonato não é imaturo, como nos anfíbios, mas está em um estádio maduro juvenil. Como indicado, são quatro as problemáticas a que deve fazer frente o embrião: prover-se de um meio que garanta o desenvolvimento volumétrico, amortecendo os movimentos físicos excessivos que possam traumatizá-lo e evitar a dessecação; assegurar que os nutrientes (vitelo e albúmen) sejam incorporados de forma correta no interior do embrião; assegurar o intercâmbio de gases; e eliminar substâncias tóxicas derivadas do metabolismo proteico. Para atender estas necessidades são desenvolvidas uma série de membranas extrambrionárias que se vão expandindo progressivamente pelo interior do ovo. A dureza da casca e sua relativa impermeabilidade protege-o igualmente da intempérie terrestre. -/- Figura 23: Evolução das membranas extraembrionárias de galinha (3 e 10 dias de incubação). -/- Saco vitelino: o saco vitelino é a primeira membrana extraembrionária em formação. Aparece como consequência direta da gastrulação: as camadas germinativas que se formam ao nível do disco embrionário expandem-se progressivamente contornando o vitelo. Assim, as células provenientes da área opaca (equivalente ao trofoblasto dos mamíferos) migram sobre o vitelo, terminando quase por cobrir, o mesmo ocorre com o endoderma mais internamente, formando-se assim um saco bilaminar. Posteriormente, o mesoderma se interpõe entre ambos, progredindo igualmente no sentido distal, rodeando o endoderma e aderindo-se ao mesmo e ao equivalente de trofoblasto. Ao estabelecer-se o celoma, o saco é constituído pelo endoderma e folha esplâncnica do mesoderma lateral. Este mesoderma vai progredindo no sentido distal e se vasculariza profunda- mente; os vasos distais se anastomosam formando um anel vascular denominado seio terminal, que marca o limite do mesoderma em expansão. Assim, sobre o vitelo é distinguível um área distal não vascularizada (área vitelina) e uma área proximal vascularizada (área vasculosa) que vai ficando progressivamente maior. Ao sexto dia de incubação mais da metade da superfície do vitelo foi envolvido pelo mesoderma. Os nutrientes do vitelo são absorvidos e desdobrados a componentes mais simples por enzimas produzidas pelo endoderma, sendo incorporados aos vasos vitelinos que os veicularão até o coração, que os impulsionará a todo o embrião. Durante a fase embrionária (até ao sexto dia de incubação), o oxigênio do exterior chega até a área vasculosa por difusão, incorporando-se daqui ao embrião; além disso, durante a primeira semana, as alterações na composição e volume do vitelo fazem que se disponha flutuando sobre o albúmen, o que faz com que a área vasculosa fique em contato com a casca, favorecendo-se assim a respiração. O intestino primitivo se instaura a partir das porções mais proximais do saco vitelino à vez que o corpo é fechado (2º-3º dia). O saco vitelino vai regredindo à medida que se vão esgotando os nutrientes do vitelo que aloja. Pouco antes do nascimento é incorporado à cavidade corporal como divertículo vitelino que fica unido ao jejuno; o divertículo vitelino persiste até seis dias após o nascimento, constituindo uma fonte adicional de nutrientes. -/- Figura 24: Feto de galinho ao fim, perto de ser eclodido. -/- mnios: no segundo dia (-30 horas) de incubação se formam as dobras amnióticas na somatopleura extraembrionária, perto do disco embrionário. Progridem dorsalmente, terminando por convergir e fundir-se cerca de 72 horas de incubação, coincidindo com o fechamento corporal, assim sendo constituído o âmnios, que terminará perdendo todo o contato com o córion. A cavidade amniótica que limita está cheia de um líquido seroso que garante que o embrião seja desenvolvido em um meio aquoso; este líquido é secretado pelo âmnios, mas também composto por substâncias formadas pelos rins, cavidade oral e aparelho respiratório. Córion: após a formação do celoma e o estabelecimento e fusão das dobras amnióticas, a parte da somatopleura extraembrionária que fica mais periférica constitui o córion (também denominado serosa nas aves); permanece formada pela área opaca expandida e mesoderma somático. Progressivamente vai aderindo-se à membrana testácea interna deslocando o albúmen; sobre o dia 12 termina por cobrir toda a superfície interna da casca. Intervém na troca gasosa com o meio ambiente através dos poros da casca e na captação do cálcio desta. Alantóides: o alantóide inicia a sua formação no dia 3 de incubação. Cresce rapidamente, ocupando o espaço exocelômico, terminando por cobrir o âmnios e saco vitelino. Progressivamente, entre os dias 4 a 10, sua parte mais externa se funde com o córion, formando-se o alantocórion, membrana trilaminar que cobrirá a superfície interna da casca, aderindo-se à membrana testácea interna, cujo mesoderma (esplâncnico) se vasculariza intensamente. A partir do dia 7 substitui completamente a área vasculosa como órgão respiratório, sendo garantido o aumento gradual das necessidades de troca gasosa na fase fetal do desenvolvimento (desde o dia 8), de rápido crescimento. A capacidade de capilarização desta membrana é muito maior do que a do saco vitelino. Na cavidade alantóica acumula-se a urina produzida pelos rins, afastando os produtos tóxicos do embrião; a membrana também age sobre este fluido intervindo na manutenção do equilíbrio hídrico e mineral do embrião. -/- Figura 25: Formação do saco vitelino. Limite entre a área vascular e avascular. Seio terminal. -/- O albúmen perde água rapidamente e torna-se menos volumoso e mais viscoso, terminando por desaparecer progressivamente. A ligação do alantocórion à membrana testácea interna faz com que seja marginalizado para uma posição periférica, no polo agudo do ovo. Aqui, o alantocórion que o rodeia constitui o saco do albúmen. O albúmen é a principal fonte de água e proteínas. A água é incorporada ao vitelo, o que, ao tornar-se mais volumoso, provoca que, entre os dias 3 e 4, se rompa a membrana vitelina; apenas restos mortais devem permanecer entre o saco vitelino e o albúmen. Dentro do saco vitelino, a água se acumula principalmente sob o embrião -fluido subembrionário-; este fluido atinge o seu volume máximo (15 ml) no dia 6. As proteínas serão incorporadas principalmente a partir de no dia 12, seja através do saco vitelino, do saco do albúmen ou por ingestão de líquido amniótico, dada a comunicação seroamniótica que se estabelece. 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Diferenciação e Determinação Sexual dos Animais. Fisiologia do Ciclo Estral dos Animais Domésticos. Emanuel Isaque Cordeiro da Silva, 2021. Manejo na Avicultura: Postura, Iluminação e Incubação dos Ovos. Transporte de Gametas, Fertilização e Segmentação. FERRER‐VAQUER, Anna; HADJANTONAKIS, Anna‐Katerina. Birth defects associated with perturbations in preimplantation, gastrulation, and axis extension: from conjoined twinning to caudal dysgenesis. Wiley Interdisciplinary Reviews: Developmental Biology, v. 2, n. 4, p. 427-442, 2013. GALINA, Carlos; VALENCIA, Javier. Reproducción de los animales domésticos. 2006. GEISERT, Rodney D.; SPENCER, Thomas E. Placentation in Mammals. Springer, 2021. GINTHER, O. J. Reproductive Biology of The mare: Basic and Applied Aspects. 2. ed. Cross Plains, Wisconsin: Equiservices, 1992. GUILLOMOT, Michel. Cellular interactions during implantation in domestic ruminants. Journal of Reproduction and Fertility-Supplements only, n. 49, p. 39-52, 1995. KLEIN, C.; TROEDSSON, M. H. T. Maternal recognition of pregnancy in the horse: a mystery still to be solved. Reproduction, Fertility and Development, v. 23, n. 8, p. 952-963, 2011. MIGLINO, Maria Angelica et al. The carnivore pregnancy: the development of the embryo and fetal membranes. Theriogenology, v. 66, n. 6-7, p. 1699-1702, 2006. MOFFETT, Ashley; LOKE, Charlie. Immunology of placentation in eutherian mammals. Nature Reviews Immunology, v. 6, n. 8, p. 584-594, 2006. PRETZER, S. D. Canine embryonic and fetal development: A review. Theriogenology, v. 70, n. 3, p. 300-303, 2008. SENGER, Phillip L. et al. Pathways to pregnancy and parturition. Current Conceptions, Inc., 1615 NE Eastgate Blvd., 2012. SOZEN, Berna; CAN, Alp; DEMIR, Necdet. Cell fate regulation during preimplantation development: a view of adhesion-linked molecular interactions. Developmental biology, v. 395, n. 1, p. 73-83, 2014. SPENCER, Thomas E. et al. Pregnancy recognition and conceptus implantation in domestic ruminants: roles of progesterone, interferons and endogenous retroviruses. Reproduction, fertility and development, v. 19, n. 1, p. 65-78, 2006. VERSTEGEN-ONCLIN, K.; VERSTEGEN, J. Endocrinology of pregnancy in the dog: a review. Theriogenology, v. 70, n. 3, p. 291-299, 2008. WOODING, Peter; BURTON, Graham. Comparative placentation: structures, functions and evolution. Springer Science & Business Media, 2008. FIXAÇÃO DO ASSUNTO -/- 1. Defina e diferencie os processos de desenvolvimento embrionário precoce, alonga- mento e gastrulação. -/- 2. O que é implantação? Caracterize as fases do processo de implantação. -/- 3. Qual a importância do acúmulo de líquido no interior do blastocele? Qual a importân- cia da eclosão do blastocisto? -/- 4. Caracterize os três tipos de implantação e, depois, explique e diferencie os meios de implantação nas fêmeas domésticas. -/- 5. Defina e caracterize os meios de reconhecimento materno da gestação (RMG) nos animais domésticos. -/- 6. O que diferencia o RMG em ruminantes e suínos? -/- 7. Qual o papel do estradiol no RMG em porcas? O que ocorre quando a porca não fica gestante? -/- 8. Explique o RMG em cães e gatos. -/- 9. Defina placentação e sua importância para a reprodução dos animais domésticos. -/- 10. Quais são as classificações da placentação? Classifique a placentação das fêmeas domésticas. -/- 11. Caracterize e diferencie o processo de placentação em fêmeas domésticas. -/- 12. Observe a figura e responda o que se pede:. (shrink)

Metaethical expressivism is typically characterised as the view that normative statements express desire-like attitudes instead of beliefs. However, in this paper I argue that expressivists should claim that normative statements express beliefs in normative propositions, and not merely in some deflationary sense but in a theoretically robust sense explicated by a theory of propositional attitudes. I first argue that this can be achieved by combining an interpretationist understanding of belief with a nonfactualist view of normative belief content. This results in (...) a view I call ‘interpretative expressivism’. I then argue that traditional arguments employed by expressivists that normative statements express noncognitive attitudes can just as well support the claim that normative statements express nonfactual or nonrepresentational beliefs. Finally, I argue that this view has a number of advantages to versions of expressivism that deny that normative statements express non-deflationary normative beliefs. (shrink)

The COVID-19 crisis has forced a difficult trade-off between limiting the health impacts of the virus and maintaining economic activity. Welfare economics offers tools to conceptualize this trade-off so that policy-makers and the public can see clearly what is at stake. We review four such tools: the Value of Statistical Life (VSL); the Value of Statistical Life Years (VSLYs); Quality-Adjusted Life-Years (QALYs); and social welfare analysis, and argue that the latter are superior. We also discuss how to choose policies that (...) differentially affect people’s wellbeing. We argue in favor of evaluating policies using a Social Welfare Function (SWF), which evaluates the possible distributions of wellbeing across individuals that may result from a policy. Such a function, we argue, should regard increases in the wellbeing of the less well-off as especially valuable. We then use a model to illustrate how such a framework can help evaluate two broad policy types in response to the pandemic: eradication of the virus, and more lenient control of the spread. Our model reveals how such evaluations depend on many empirical facts but also on key value judgments about the relative importance of health and on the extent of special concern for the worse off. The purpose of this brief is not to make precise recommendations, as conditions vary widely across countries and over time, but to provide a methodology. (shrink)

There is considerable disagreement about the epistemic value of novel predictive success, i.e. when a scientist predicts an unexpected phenomenon, experiments are conducted, and the prediction proves to be accurate. We survey the field on this question, noting both fully articulated views such as weak and strong predictivism, and more nascent views, such as pluralist reasons for the instrumental value of prediction. By examining the various reasons offered for the value of prediction across a range of inferential contexts , we (...) can see that neither weak nor strong predictivism captures all of the reasons for valuing prediction available. A third path is presented, Pluralist Instrumental Predictivism; PIP for short. (shrink)

We investigate claims about the frequency of "know" made by philosophers. Our investigation has several overlapping aims. First, we aim to show what is required to confirm or disconfirm philosophers’ claims about the comparative frequency of different uses of philosophically interesting expressions. Second, we aim to show how using linguistic corpora as tools for investigating meaning is a productive methodology, in the sense that it yields discoveries about the use of language that philosophers would have overlooked if they remained in (...) their "armchairs of an afternoon", to use J.L. Austin’s phrase. Third, we discuss facts about the meaning of "know" that so far have been ignored in philosophy, with the aim of reorienting discussions of the relevance of ordinary language for philosophical theorizing. (shrink)

Traditionally, Aristotle is held to believe that philosophical contemplation is valuable for its own sake, but ultimately useless. In this volume, Matthew D. Walker offers a fresh, systematic account of Aristotle's views on contemplation's place in the human good. The book situates Aristotle's views against the background of his wider philosophy, and examines the complete range of available textual evidence. On this basis, Walker argues that contemplation also benefits humans as perishable living organisms by actively guiding human life activity, including (...) human self-maintenance. Aristotle's views on contemplation's place in the human good thus cohere with his broader thinking about how living organisms live well. A novel exploration of Aristotle's views on theory and practice, this volume will interest scholars and students of both ancient Greek ethics and natural philosophy. It will also appeal to those working in other disciplines including classics, ethics, and political theory. (shrink)

Some philosophers understand natural kinds to be the categories which are constraints on enquiry. In order to elaborate the metaphysics appropriate to such an account, I consider the complicated history of scurvy, citrus, and vitamin C. It may be tempting to understand these categories in a shallow way (as mere property clusters) or in a deep way (as fundamental properties). Neither approach is adequate, and the case instead calls for middle-range ontology: starting from categories which we identify in the world (...) and elaborating their structure, but not pretending to jump ahead to a complete story about fundamental being. (shrink)

This research investigates 3- and 5-year-olds' relative fairness in distributing small collections of even or odd numbers of more or less desirable candies, either with an adult experimenter or between two dolls. The authors compare more than 200 children from around the world, growing up in seven highly contrasted cultural and economic contexts, from rich and poor urban areas, to small-scale traditional and rural communities. Across cultures, young children tend to optimize their own gain, not showing many signs of self-sacrifice (...) or generosity. Already by 3 years of age, self-optimizing in distributive justice is based on perspective taking and rudiments of mind reading. By 5 years, overall, children tend to show more fairness in sharing. What varies across cultures is the magnitude of young children's self-interest. More fairness (less self-interest) in distributive justice is evident by children growing up in small-scale urban and traditional societies thought to promote more collective values. (shrink)

Atomically precise manufacturing (APM) is the assembly of materials with atomic precision. APM does not currently exist, and may not be feasible, but if it is feasible, then the societal impacts could be dramatic. This paper assesses the net societal impacts of APM across the full range of important APM sectors: general material wealth, environmental issues, military affairs, surveillance, artificial intelligence, and space travel. Positive effects were found for material wealth, the environment, military affairs (specifically nuclear disarmament), and space travel. (...) Negative effects were found for military affairs (specifically rogue actor violence and AI. The net effect for surveillance was ambiguous. The effects for the environment, military affairs, and AI appear to be the largest, with the environment perhaps being the largest of these, suggesting that APM would be net beneficial to society. However, these factors are not well quantified and no definitive conclusion can be made. One conclusion that can be reached is that if APM R&D is pursued, it should go hand-in-hand with effective governance strategies to increase the benefits and reduce the harms. (shrink)

Aristotle is essentially human; that is, for all possible worlds metaphysically consistent with our own, if Aristotle exists, then he is human. This is a claim about the essential property of an object. The claim that objects have essential properties has been hotly disputed, but for present purposes, we can bracket that issue. In this essay, we are interested, rather, in the question of whether properties themselves have essential properties (or features) for their existence. We call those who suppose they (...) do “property essentialists”; those who do not, “property anti-essentialists,” or “quidditists.” We offer two complementary arguments. Our total argument is under-girded by two assumptions: transworld identity theory and “received view” counterfactual semantics, a la David Lewis. We then argue that, if one presumes that these are true, then one risks running headlong into paradox if one also accepts property anti-essentialism. That's the first argument. By contrast, if one accepts these same assumptions in conjunction with property essentialism, then the paradox is avoided. This is the second argument. We take it that our arguments work to show that, between property essentialism and quidditism, the property essentialist is on better footing. Plausibly, properties themselves do have essential properties for their existence. (shrink)

Spinoza’s attitude toward nonhuman animals is uncharacteristically cruel. This essay elaborates upon this ostensible idiosyncrasy in reference to Hasana Sharp’s commendable desire to revitalize a basis for animal ethics from within the bounds of his system. Despite our favoring an ethics beginning from animal affect, this essay argues that an animal ethic adequate to the demands of our historical moment cannot be developed from within the confines of strict adherence to Spinoza’s system—and this is not yet to speak of a (...) more robust animal ethics which would advocate actual care and compassion for the animals themselves. We argue that on the assumption of Spinoza’s ontological biocentrism, in the presence of Spinozist determinism and the absence of an axiological biocentrism, an anthropocentric axiology necessarily follows. Any Spinozist animal ethic must fall back, therefore, upon appeals to the maximization of human pleasure and power; hence Spinoza’s ruthless injunction to “use (the animals) at our pleasure.” These are the very ontological and ethical assumptions which have incited human self-exaltation in the modern period, in pursuit of power and pleasure even despite the destructive long-term consequences for all the living. We suggest that an adequate animal ethic would require either an abandonment of Spinoza’s ontological biocentrism or the adoption of an axiological biocentrism. (shrink)

In this paper I propose an interpretation of classical statistical mechanics that centers on taking seriously the idea that probability measures represent complete states of statistical mechanical systems. I show how this leads naturally to the idea that the stochasticity of statistical mechanics is associated directly with the observables of the theory rather than with the microstates (as traditional accounts would have it). The usual assumption that microstates are representationally significant in the theory is therefore dispensable, a consequence which suggests (...) interesting possibilities for developing non-equilibrium statistical mechanics and investigating inter-theoretic answers to the foundational questions of statistical mechanics. (shrink)

In the paper, I defend the skeptical view that no one is ever morally responsible in the basic desert sense since luck universally undermines responsibility-level control. I begin in Section 1 by defining a number of different varieties of luck and examining their relevance to moral responsibility. I then turn, in Section 2, to outlining and defending what I consider to be the best argument for the skeptical view--the luck pincer (Levy 2011). I conclude in Section 3 by addressing Robert (...) Hartman's (2017) numerous objections to the luck pincer. I argue that the luck pincer emerges unscathed and the pervasiveness of luck (still) undermines moral responsibility. (shrink)

This chapter outlines six distinct reasons for rejecting retributivism, not the least of which is that it’s unclear that agents possess the kind of free will and moral responsibility needed to justify it. It then sketches a novel non-retributive alternative called the public health-quarantine model. The core idea of the model is that the right to harm in self-defense and defense of others justifies incapacitating the criminally dangerous with the minimum harm required for adequate protection. The model also draws on (...) the public health framework and prioritizes prevention and social justice. It is argued that not only does the public health-quarantine model offer a stark contrast to retributivism, it also provides a more humane, holistic, and effective approach to dealing with criminal behavior, one that is superior to both retributivism and other leading non-retributive alternatives. (shrink)

Theoretical ethics includes both metaethics (the meaning of moral terms) and normative ethics (ethical theories and principles). Practical ethics involves making decisions about every day real ethical problems, like decisions about euthanasia, what we should eat, climate change, treatment of animals, and how we should live. It utilizes ethical theories, like utilitarianism and Kantianism, and principles, but more broadly a process of reflective equilibrium and consistency to decide how to act and be.

In this paper, I argue that the performance stories in the Zhuangzi, and the Butcher Ding story, emphasize an activity meditation practice that places the performer in a mindfulness flow zone, leading to graceful, efficacious, selfless, spontaneous, and free action. These stories are metaphors showing the reader how to attain a meditative state of focused awareness while acting freely in a flow experience. From my perspective, these metaphors are not about developing practical or technical skills per se. My argument challenges (...) a strict instrumental reading. Although instrumental reasoning can easily lead one to focus on the pragmatic outcomes depicted in these stories (See Eno, “Cook Ding’s Dao;” Callahan, “Cook Ding’s Life;” and Robins, “Beyond Skill”), the proposed pragmatic outcomes are merely a kind of collateral result of effortless, free actions, in the flow experience. The metaphors of Butcher Ding, the Lüliang rapids swimmer, the Wheelwright Bian, the Woodcarver Qing, the cicada catcher, the naked artist and so on are used to show the reader a way to engage in free and graceful action in the flow experience. Zhuangzi is not concerned about developing labour skills. He criticizes such skills; seen below when the Butcher claims to have “… left skill behind …” (進乎技矣) (Graham, Chuang-tzu, 63), and chapter five notes that “… skill is a peddler” (工為商) (Watson, Complete, 75). (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Plato on Knowledge as a Power1Nicholas D. SmithAt 471C4 in Plato’s Republic, the argument takes a sudden turn when Glaucon becomes impatient with all of the specific prescriptions Socrates has been making, and asks to return to the issue Socrates had earlier set aside—whether or not the city he was describing could ever be brought into being. In response to Glaucon’s impatient question, Socrates articulates his “third wave of (...) paradox” (472ag–7), namely, that the ills of the cities will never be ended until either philosophers become rulers or rulers become philosophers (473c11–d6). Glaucon immediately responds that such a view is likely to be greeted with violence and scorn (473e6–474a4), and so Socrates must hasten to explain his odd claim. His explanation, it turns out, is that true philosophers have an enormous cognitive advantage over non-philosophers—philosophers have and use knowledge (ἐπιστήμη), whereas non-philosophers have and use only opinion (δόξα).2 This distinction, between επιστήμη and δόξα, turns out: to be a distinction between two different cognitive powers (δυνάμεις—477d7–e3). And different powers, Plato clearly tells us, apply to or take as their objects (Plato says they are “ἐπί”) different things (477dl).In this paper, I shall argue that the relationship between the cognitive powers and their various objects has been fundamentally misunderstood, which has led scholars into one or more misinterpretations of important and explicit features of the text. At the heart of these misunderstandings, I claim, is [End Page 145] their shared misconception of the relation between the cognitive power and its objects as interpretable in terms of the relationship between a cognitive stale and what the content of that state is of or about.3 One consequence of the view for which I shall argue is that what has come to be known as the “two-worlds theory”4 of Plato’s epistemology is seriously mistaken, but no less mistaken than the alternatives given by its recent critics. Another consequence that I shall draw from my argument is that Plato should be understood neither as a kind of foundationalist with regard to knowledge and warrant, as some have supposed him to be,5 nor as a coherentist, as others have supposed,6 but, rather, as a kind of causal reliabilist. [End Page 146]1. KNOWLEDGE AS A POWERScholarly interpretations of Plato’s epistemology have routinely sought to understand the relationships between each cognitive power of Republic Book V and the objects of the ἐφ’ ᾦ (“what it is related to”) condition by which it is differentiated from other δυνάμεις as Plato’s way of telling us what each sort of cognition is of or aboul. 7 So, for example, we find Gail Fine using the expressions “belief [δόξα] is set over [Fine’s translation of Plato’s ἐπί] …” and “knowledge is set over …” interchangeably with “belief is of …” or “belief is about…” and “knowledge is of …” or “knowledge is about …”8 Against the “two-worlds theory,” Fine argues that, for Plato, there can be knowledge of sensibles and beliefs about Forms. Accordingly, since she assimilates the power-ἐπί-object set of relations to the cognilion-of/about-object relation, she concludes—in order to account for knowledge of sensibles and beliefs about Forms—that the objects of knowledge and opinion must be propositions. Plato’s claims that knowledge is ἐπί what is, whereas opinion is ἐπί what is and is not, Fine understands as, “One can only know true propositions; one can believe both true and false propositions.”9 We shall see later that this “veridical” understanding of what Plato means to identify as “what is,” and “what is and is not” fails to account for important and explicit elements of Plato’s exposition of the epistemological and metaphysical distinctions he is making. For now, it is enough to note that Fine understands the ἐφ’ᾦ) relation in terms of our cognition-of/about-object relation. One finds the same assimilation made by those who advance existential readings of Plato’s “is” and “is not,”10 as [End Page 147] well as those who have urged that we adopt predicative readings of “is” and “is not.”11But I think there are very serious problems with this assimilation. Plato is very... (shrink)

This essay presents the conditional probability of co-contribution account of the individuation of cognitive systems (CPC) and argues that CPC provides an attractive basis for a theory of the cognitive self. The argument proceeds in a largely indirect way, by emphasizing empirical challenges faced by an approach that relies entirely on predictive processing (PP) mechanisms to ground a theory of the cognitive self. Given the challenges faced by PP-based approaches, we should prefer a theory of the cognitive self of the (...) sort CPC offers, one that accommodates variety in the kinds of mechanism that, when integrated, constitute a cognitive system (and thus the cognitive self), to a theory according to which the cognitive self is composed of essentially one kind of thing, for instance, prediction-error minimization mechanisms. The final section focuses on one of the central functions of the cognitive self: to engage in conscious reasoning. It is argued that the phenomenon of conscious, deliberate reasoning poses an apparently insoluble problem for a PP-based view, one that seems to rest on a structural limitation of predictive-processing models. In a nutshell, conscious reasoning is a single-stream phenomenon, but, in order for PP to apply, two streams of activity must be involved, a prediction stream and an input stream. Thus, with regard to the question of the nature of the self, PP-based views must yield to an alternative approach, regardless of whether proponents of the predictive processing, as a comprehensive theory of cognition, can handle the various empirical challenges canvassed in the preceding section. (shrink)

forall x: Calgary is a full-featured textbook on formal logic. It covers key notions of logic such as consequence and validity of arguments, the syntax of truth-functional propositional logic TFL and truth-table semantics, the syntax of first-order (predicate) logic FOL with identity (first-order interpretations), symbolizing English in TFL and FOL, and Fitch-style natural deduction proof systems for both TFL and FOL. It also deals with some advanced topics such as modal logic, soundness, and functional completeness. Exercises with solutions are available. (...) It is provided in PDF (for screen reading, printing, and a special version for dyslexics), HTML, and in LaTeX source code. (shrink)

Critical notice of Guy Fletcher's 'Dear Prudence: The Nature and Normativity of Prudential Discourse' and Dale Dorsey's 'A Theory of Prudence'.

In this essay I explore the resources Thomas Aquinas provides for enquiries concerning the psychological abilities of nonhuman animals. I first look to Aquinas’s account of divine, angelic, human, and nonhuman animal naming, to help us articulate the contours of a ‘critical anthropocentrism’ that aims to steer clear of the mistakes of a na¨ıve anthropocentrism and misconceived avowals to entirely eschew anthropocentrism. I then address the need for our critical anthropocentrism both to reject the mental-physical dichotomy endorsed by ‘folk psychology’ (...) and to articulate a more adequate ‘commonsense psychology’ that acknowledges most embodied animal behavior is observable psychological behavior. Next, I argue that we can develop Aquinas’s doctrine of estimation and conation to formulate an account of nonhuman animal action that more adequately characterizes the purposeful behaviors of nonhuman animals. To do so, we first need to recognize a wider range of nonhuman animal behaviors that are captured by Aquinas’s ‘estimative sense’, and that all of these behaviors are specified by a finite variety of particular goods confined to the animals’ environmental niches. But we also need to supplement Aquinas’s account of human and nonhuman animal agency by exploring the ontogeny and ecology of how humans and other animals become attuned to affordances within these different environmental niches. I argue that we should look to Aquinas’s account of nonhuman animal capacities in ST I-II 6-17 for subtle insights that can expand our understanding of how nonhuman animals engage in purposeful behavior by exercising analogous nonrational and imperfectly voluntary forms of intention, deliberation, choice, execution, and enjoyment. I conclude with an outline for how future enquiry can seek to explain the nonrational purposeful problem-solving competencies of chimps, canines, corvids, cetaceans, cephalopods, and other nonhuman animal species. (shrink)

This essay joins Wilhelm Dilthey’s conception of the metaphysical impulse as a flight from the tragedy of human finitude with Ludwig Wittgenstein’s understanding of how language bewitches intelligence. We contend that there are features of the phenomenology of language that play a constitutive and pervasive role in the formation of metaphysical illusion.

In this paper we investigate composition models of incarnation, according to which Christ is a compound of qualitatively and numerically different constituents. We focus on three-part models, according to which Christ is composed of a divine mind, a human mind, and a human body. We consider four possible relational structures that the three components could form. We argue that a ‘hierarchy of natures’ model, in which the human mind and body are united to each other in the normal way, and (...) in which they are jointly related to the divine mind by the relation of co-action, is the most metaphysically plausible model. Finally, we consider the problem of how Christ can be a single person even when his components may be considered persons. We argue that an Aristotelian metaphysics, according to which identity is a matter of function, offers a plausible solution: Christ's components may acquire a radically new identity through being parts of the whole, which enables them to be reidentified as parts, not persons. (shrink)