Successful teamwork doesn't work overnight, what makes teamwork potent is team building. (Plagiarism) According to Abdullah, et. al., (2022) team building training can improve group cohesiveness or the quality of sticking together or unity teamwork more likely to be higher with a significant score difference. This study used mixed methods both qualitative and quantitative data collection, and an analysis method to answer the research method, random sampling is named as such because the data set is chosen via random selection, where (...) every member of the population has an equal probability of being selected (Tao, 2023). The respondents were 100 restaurant employees and 10 managers from the chosen restaurant in Malolos City in Bulacan. The subcategories of team building, including activities, communication, skills, personality, problem-solving, and values, have all received a consensus of strong agreement, with weighted averages falling within the range of 3.26 to 3.44. This level of agreement aligns with the scores for motivation at 3.43 and productivity at 3.38. These values have been calculated by determining the mean, which spans from 3.25 to 4.00. The advantages of team building that is being observed by the managers is to create familiarity and teamwork among the employees, to improve the quality of service and the quality of the food especially the respondents are in the food service sector, development, and training for the employees to achieve the establishments’ goal and lastly rebuilding and build a relationship with one employee to another. However, for the disadvantages, it costs a lot of money to conduct team building in the management. Therefore, the null hypothesis is rejected. Despite the fact that there is a low correlation between teambuilding activities and motivation and employee productivity, there is still a significant relationship between the variables. (shrink)

The National Center for Biomedical Ontology is now in its seventh year. The goals of this National Center for Biomedical Computing are to: create and maintain a repository of biomedical ontologies and terminologies; build tools and web services to enable the use of ontologies and terminologies in clinical and translational research; educate their trainees and the scientific community broadly about biomedical ontology and ontology-based technology and best practices; and collaborate with a variety of groups who develop and use ontologies and (...) terminologies in biomedicine. The centerpiece of the National Center for Biomedical Ontology is a web-based resource known as BioPortal. BioPortal makes available for research in computationally useful forms more than 270 of the world's biomedical ontologies and terminologies, and supports a wide range of web services that enable investigators to use the ontologies to annotate and retrieve data, to generate value sets and special-purpose lexicons, and to perform advanced analytics on a wide range of biomedical data. (shrink)

The capacity to act in accordance with one’s morality (broadly construed) is constitutive of moral agency. This capacity can be undermined—in whole or in part—by for instance, hypnosis, addiction, or obsessive-compulsion. Another way this capacity can be undermined is through poor moral reasoning. Moral irrationality can frustrate one’s capacity to act in accordance with one’s morality and in turn, stunt one’s moral agency. In a similar respect, improving moral rationality can strengthen this capacity and enhance moral agency. The empirical research (...) program on (non-moral) cognitive debiasing inspires developing techniques to improve our moral rational capacities—i.e., moral debiasing. Yet, moral debiasing presupposes moral biases—that is, systematic moral errors. So, what are moral errors exactly? The pertinent kind is subjective moral errors. Ultimately, A’s φ-ing is a subjective moral error insofar as φ-ing deviates from A’s genuine morality per instrumental subjective moral rationality (ISMR)—i.e., insofar as φ-ing frustrates A+’s morally-relevant ends, wherein A+ is a counterfactual idealization of A upon whom is bestowed those endowments that A considers authoritative under ordinary optimal conditions. The provision of an in-principle standard of subjective moral error lays important theoretical groundwork for future empirical inquiry into subjective moral debiasing. (shrink)

In this dissertation, I construct scientifically and practically adequate moral analogs of cognitive heuristics and biases. Cognitive heuristics are reasoning “shortcuts” that are efficient but flawed. Such flaws yield systematic judgment errors—i.e., cognitive biases. For example, the availability heuristic infers an event’s probability by seeing how easy it is to recall similar events. Since dramatic events, such as airplane crashes, are disproportionately easy to recall, this heuristic explains systematic overestimations of their probability (availability bias). The research program on cognitive heuristics (...) and biases (e.g., Daniel Kahneman’s work) has been scientifically successful and has yielded useful error-prevention techniques—i.e., cognitive debiasing. I attempt to apply this framework to moral reasoning to yield moral heuristics and biases. For instance, a moral bias of unjustified differences in the treatment of particular animal species might be partially explained by a moral heuristic that dubiously infers animals’ moral status from their aesthetic features. While the basis for identifying judgments as cognitive errors is often unassailable (e.g., per violating laws of logic), identifying moral errors seemingly requires appealing to moral truth, which, I argue, is problematic within science. Such appeals can be avoided by repackaging moral theories as mere “standards-of-interest” (a la non-normative metrics of purportedly right-making features/properties). However, standards-of-interest do not provide authority, which is needed for effective debiasing. Nevertheless, since each person deems their own subjective morality authoritative, subjective morality (qua standard-of-interest and not moral subjectivism) satisfies both scientific and practical concerns. As such, (idealized) subjective morality grounds a moral analog of cognitive biases—namely, subjective moral biases (e.g., committed anti-racists unconsciously discriminating). I also argue that "cognitive heuristic" is defined by its contrast with rationality. Consequently, heuristics explain biases, which are also so defined. However, such contrasting with rationality is causally irrelevant to cognition. This frustrates the presumed usefulness of the kind, heuristic, in causal explanation. As such, in the moral case, I jettison the role of causal explanation and tailor categories solely for contrastive explanation. As such, “moral heuristic” is replaced with "subjective moral fallacy," which is defined by its contrast with subjective morality and explains subjective moral biases. The resultant subjective moral biases and fallacies framework can undergird future empirical research. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

The Repugnant Conclusion served an important purpose in catalyzing and inspiring the pioneering stage of population ethics research. We believe, however, that the Repugnant Conclusion now receives too much focus. Avoiding the Repugnant Conclusion should no longer be the central goal driving population ethics research, despite its importance to the fundamental accomplishments of the existing literature.

BioPortal is a Web portal that provides access to a library of biomedical ontologies and terminologies developed in OWL, RDF(S), OBO format, Protégé frames, and Rich Release Format. BioPortal functionality, driven by a service-oriented architecture, includes the ability to browse, search and visualize ontologies (Figure 1). The Web interface also facilitates community-based participation in the evaluation and evolution of ontology content.

Due to the emergence of ICT in ELT sector, seasoned English teachers find it resistant to such a shift despite having a positive attitude towards its use. This quasi-experimental study aimed to examine the extent to which seasoned English language teachers developed their ICT skills through a Service-Learning Activity (SLA). Using a one-group pre- and post-test design, this study collected the data through a modified Needs Assessment Survey (NAS) distributed to fourteen purposively selected participants. It was administered to examine what (...) professional ICT development would greatly benefit them. The data were analyzed using descriptive statistics and themes according to the Service-Learning Activity (SLA) topics. A Post Evaluation Survey (PES) was administered, and its result was compared to the initial test. The results showed that the seasoned teachers gained significant learning gains in terms of (1) sharing of knowledge from other teachers; (2) being encouraged to use ICT tools; (3) training opportunities; (4) working with other colleagues; and 5) attending professional workshops which include SLA. However, this study unveiled that the English teachers had no significant difference in perceptions regarding the roles of computers in teaching before and after the intervention. Limitations and recommendations for future studies were discussed. (shrink)

Expressivists traditionally explain normative supervenience by saying it is a conceptual truth. I argue against this tradition in two steps. First, I show the modal claim that stands in need of explanation has been stated imprecisely. Classic arguments in metaethics for normative supervenience and those that rely on it as a premise presuppose a constraint on the supervenience base that is rarely (if ever) made explicit: the repeatability of the non-normative properties on which the normative supervenes. Non-normative properties are repeatable (...) when it is possible for numerically distinct individuals to share them. Second, I show if the modal truth that stands in need of explanation entails that there are individuals exactly alike in repeatable non-normative respects that cannot normatively differ, then standard expressivist accounts of normative supervenience as a conceptual truth are unsuccessful. Expressivist metasemantics for normative terms, together with constitutive facts about the non-cognitive attitudes essentially involved in normative thought, strongly suggest that repeatable supervenience could not be a conceptual truth. I argue, finally, that although repeatable supervenience bears the marks of a conceptual truth, expressivists should be content to treat it as an ordinary normative truth, and to explain it the same way they explain other normative truths. (shrink)

In the history of Chinese philosophy, Mozi calls music a “waste of resources,” considering it an aristocratic extravagance that does not benefit the everyday people. In its defense, Confucians highlight music’s moral and metaphysical qualities, arguing that music aids in moral cultivation and that music’s form mimics the structure of reality. The aim of this paper is to show that Korean philosophers provide yet another reason to think music is important. Music, and art in general, was used to express a (...) national identity at a time Korean philosophers were beginning to develop their own aesthetic consciousness in the seventeenth and eighteenth centuries. A cultural movement called Joseonpoong (조선풍), “Joseon wind”, marked a shift away from Sinocentrism and towards Korea’s own unique value and practices. The new attempt to justify art’s value apart from its relationship to morality or metaphysics set Joseon thinkers apart from their Chinese predecessors. Using art for identity expression allowed the Koreans to reconceive art’s value while Sinocentric cosmological and cultural views were being challenged with the introduction of western knowledge. Art also became a tool for reversing hermeneutic injustice as new artistic practices and standards allowed the Koreans to meaningfully engage with previously neglected aspects of their lived lives. (shrink)

The ninth and tenth chapters of the Origin mark a profound, if perhaps difficult to detect, shift in the book’s argumentative structure. In the previous few chapters and in the ninth, Darwin has been exploring a variety of objections to natural selection, some more obvious (where are all the fossils of transitional forms?) and some showing careful attention to challenging consequences of evolution (could selection really produce instincts?). Starting in the tenth, however, Darwin turns to showing us what kinds (...) of new and unexpected results evolutionary theory might be able to offer us, again in domains both predictable (extinction) and unexpected (biogeography, embryology). It is notable that it is the fossil record that serves as this pivot point, being both a source of potentially powerful objections to evolutionary theory and home to some of its most compelling new explanations. In this chapter, I present both sets of arguments and consider what role Darwin gave to fossil evidence, in the process attempting to discover why it might have played this unique role in two different parts of Darwin’s “long argument” for evolution by natural selection. Geology’s special place, I argue, derives at least in part from its particular importance in Darwin’s social and intellectual context. (shrink)

As State Colleges and Universities (SUCs) grow, they need to offer more services to the community. This is termed as community extension program, and colleges are required by law to have one. The community's needs must be met, and they must also be looked at. This assessment aims to figure out what the communities around J.H. Cerilles State College (JHCSC) need. Through the Peace and Order, Security, and Ability to Serve Enrichment (POSASE) framework, this assessment also set up the framework (...) for extending community services in SUCs. The study's results showed that the communities close to JHCSC needed more governance extension initiatives in the areas of public safety and security, as well as disaster planning and response. (shrink)

State of nature theories have a long history and play a lively role in contemporary work. Theories of this kind share certain nontrivial commitments. Among these are commitments to inclusion of a Lockean proviso among the principles of justice and to an assumption of invariance of political principles across changes of circumstances. In this article I want to look at those two commitments and bring to light what I believe are some important difficulties they engender. For nonpattern state of nature (...) theories, the justness of a society is marked by the conformance of the society to procedural principles. Distributions of resources and the like have no particular import for questions of justice. Whatever may later result, so long as it came about in accordance with the rules determined by the principles of justice, is itself just. The Lockean proviso is one of the principles of justice governing property and other rights of nonpattern theories of justice. The proviso hangs as a "shadow" over the results of the operation of the other (usual) principles of justice. It is intended to remedy a complaint which arises when the positions of those no longer at liberty to use some resource are worsened (1) by no longer being able to use freely what they previously were free to use and (2) in such a way that they fall below a "baseline." Following Locke, a traditional formulation of the proviso is to allow acquisition just so long as there is "enough and as good" left over for others. Section I concerns the relation of the Lockean proviso to pattern and nonpattern principles of justice, demonstrating that a Lockean proviso turns a nonpattern into a pattern theory of justice. Section II is about the relation of the Lockean proviso to the ideas revealed by an examination of a state of nature, suggesting reasons to reject ideal theories of justice. (shrink)

Trademarks are not just property; they are aesthetic creations that pervade everyday experience. As pervasive aesthetic creations having literary, pictorial, graphic, sculptural, and musical content, trademarks deserve aesthetic analysis. So this paper discusses the origins, strength, appeal, and effectiveness of trademarks within the context of aesthetic considerations such as meaning, intention, authorship, and mode of creation. Also reviewed are morphemic and phonemic analysis of trademarks, semantic positioning, the dichotomy between creation and discovery of trademarks, and the differences between trademarks and (...) titles. The discussion is confined to "word marks" consisting of alphanumeric characters because discussing other kinds of marks (such as designs, configurations, sounds, colors, and scents) would raise issues well beyond the scope of a single article. (shrink)

(Original French text followed by English version.) For Berkeley, mathematical and scientific issues and concepts are always conditioned by epistemological, metaphysical, and theological considerations. For Berkeley to think of any thing--whether it be a geometrical figure or a visible or tangible object--is to think of it in terms of how its limits make it intelligible. Especially in De Motu, he highlights the ways in which limit concepts (e.g., cause) mark the boundaries of science, metaphysics, theology, and morality.

The 1830s and 1840s saw the proliferating usage of “the Beyond” (Jenseits) as a choice term for the afterlife in German public discourse. This linguistic innovation coincided with the rise of empiricism in natural science. It also signaled an emerging religious debate in which bald challenges to the very existence of heaven were aired before the wider German public for the first time. Against the belief of many contemporaries that empirical science was chiefly responsible for this attack on one of (...) the central tenets of Christianity, this essay shows instead that the role played by Christian dissenters in the negation of the Beyond. The polemical invocation of an empty Beyond coincided with the separation in the mid 1840s of two dissenting sects – the Deutschkatholiken (“German Catholics”) and the Protestant Free Congregations – from the main Christian Churches. During the Revolution of 1848, these sects, later known as Free Religious Congregations, deepened their critique of the Beyond as they articulated a new creed of radical humanism and natural scientific monism. Yet, despite their secularist agenda the Free Religious failed to fully secularize. The essay concludes by suggesting that the anticlerical activity of the Free Religious and affiliated freethinking organizations, which lasted into the 1930s, marks a century in which movements of radical political and social dissent remained open to and indeed partially dependent on the negation of the Beyond in order to sacralize humanity and nature. (shrink)

Understanding choice of family planning provider is fundamental for policy makers and program managers as they seek ways to both improve the coverage and increase the sustainability and efficiency of family planning services for Egypt to achieve its population objectives. This study focuses first on providing a descriptive profile of the patterns of reliance on sources of family planning services during the early 2000s. Binomial logit models are then estimated to obtain a more in depth understanding of the determinants of (...) the choice of family planning providers in Egypt using the 2000 Egypt Demographic and Health Survey. The study offers insights into a number of aspects of family planning service provision about which there has been less previous investigation. There are marked differences in the extent to which Egyptian women rely on public or private providers for family planning services depending on the type of method they are seeking. Among the more important findings is the consistency women display in the choice of provider among women reporting multiple segments of use. With regard to the determinants of the choice of provider for family planning services, perhaps the most interesting finding is that household wealth was not a significant determinant of the choice of provider. This may reflect that private sources met the demand for family planning services of significant proportions of women in rural areas and among those in the low income groups. (shrink)

En el ámbito de la lógica matemática existe un problema sobre la relación lógica entre dos versiones débiles del Axioma de elección (AE) que no se ha podido resolver desde el año 2000 (aproximadamente). Tales versiones están relacionadas con ultrafiltros no principales y con Propiedades Ramsey (Bernstein, Polarizada, Subretículo, Ramsey, Ordinales flotantes, etc). La primera versión débil del AE es la siguiente (A): “Existen ultrafiltros no principales sobre el conjunto de los números naturales (ℕ)”. Y la segunda versión débil (...) del AE es la siguiente (B): “Existen ultraflitros sobre ℕ”. Se sabe que A implica B, pero se desconoce si B implica A. Di Prisco y Henle conjeturan en los artículos ([1], [2]) que esto no ocurre, es decir, conjeturan que B no implica A, en otras palabras, conjeturan que A es más fuerte estrictamente que B, que A es independiente de B, pero esto no se ha podido demostrar todavía aunque se ha intentado hacer desde hace aproximadamente 21 años. Una descripción detallada de este problema abierto puede encontrarse en esta ponencia (dictada en el marco del Día Mundial de la Lógica 14-01-2022) y en el artículo [3]. [1] C. Di Prisco y H. Henle. “Doughnuts, Floating Ordinals, Square Brackets, and Ultraflitters”. Journal of Symbolic Logic 65 (2000) 462-473. [2] C. Di Prisco y H. Henle. “Partitions of the reals and choice”. En “Models, algebras and proofs”. X. Caicedo y C.M. Montenegro. Eds. Lecture Notes in Pure and Appl. Math, 203, Marcel Dekker, 1999. [3] F. Galindo. “Tópicos de ultrafiltros”. Divulgaciones Matemáticas. Vol. 21, No 1-2, 2020. (shrink)

I argue that the Bradley of the 1883 The Principles of Logic marks and separates contents under tension in judgments. The separation comes in attending to content as a device for recuperation of scale. For Bradley that involves scaling material of immediate presentations under limits. As unrealised commitments of so- called real and ideal are an exclusionary condition of singular comprehension, singularity of judgments is mark of singular reflex with privative force; not some singularity in objects taken in episodic (...) correspondence forming distinctively in singular judgment. The distinguishing input, as it were, to judgment forms is via content in some consequential and fact-like limitive facing of the real. I want to approach Bradley in this slightly negative sense as imposing via inversion some sensible restrictions under some conditions of scaling rather than in direct contact with materials to which one stands in some act of obversion, finally. (shrink)

Some time ago, Joel Katzav and Brian Ellis debated the compatibility of dispositional essentialism with the principle of least action. Surprisingly, very little has been said on the matter since, even by the most naturalistically inclined metaphysicians. Here, we revisit the Katzav–Ellis arguments of 2004–05. We outline the two problems for the dispositionalist identified Katzav in his 2004 , and claim they are not as problematic for the dispositional essentialist at it first seems – but not for the reasons espoused (...) by Ellis. (shrink)

This issue of Technoetic Arts: A Journal of Speculative Research (TA) encompasses eight articles by artists and scholars from around the globe who engage with methodologies of art practice within research that reflects on technological and ecological change, contributing to the discourse on the inclusion of subjective experience in research. The articles by authors Dulmini Perera, Kate Doyle, Nora S. Vaage, Merete Lie, Nikita Peresin Meden, Kristina Pranjić, Peter Purg, Nicolaas H. Jacobs, Marth Munro, Chris Broodryk, Semi Ryu, Rahul Mahata, (...) Doreswamy, Sana Altaf and Aqib Javid Parry form a collection that crosses disciplines and genres to engage in fundamental critique of existing modes of enquiry and conclusion. The texts situate art and design methodologies in particular cultural contexts and in relation to frameworks defined by research methodologies of the sciences and humanities to gain agency for critique and to counter a sense of inevitability that has come to mark the most recent crises. (shrink)

In Nicomachean Ethics 1. 7, Aristotle gives a definition of the human good, and he does so by means of the “ ergon argument.” I clear the way for a new interpretation of this argument by arguing that Aristotle does not think that the ergon of something is always the proper activity of that thing. Though he has a single concept of an ergon, Aristotle identifies the ergon of an X as an activity in some cases but a product in (...) others, depending on the sort of thing the X is—for while the ergon of the eye is seeing, the ergon of a sculptor is a sculpture. This alternative interpretation of Aristotle’s concept of an ergon allows the key explanatory middle term of the ergon argument to be what, I argue, it ought to be: “the best achievement of a human.”. (shrink)

This paper develops and motivates a unification theory of metaphysical explanation, or as I will call it, Metaphysical Unificationism. The theory’s main inspiration is the unification account of scientific explanation, according to which explanatoriness is a holistic feature of theories that derive a large number of explananda from a meager set of explanantia, using a small number of argument patterns. In developing Metaphysical Unificationism, I will point out that it has a number of interesting consequences. The view offers a novel (...) conception of metaphysical explanation that doesn’t rely on the notion of a “determinative” or “explanatory” relation; it allows us to draw a principled distinction between metaphysical and scientific explanations; it implies that naturalness and fundamentality are distinct but intimately related notions; and perhaps most importantly, it re-establishes the unduly neglected link between explanation and understanding in the metaphysical realm. A number of objections can be raised against the view, but I will argue that none of these is conclusive. The upshot is that Metaphysical Unificationism provides a powerful and hitherto overlooked alternative to extant theories of metaphysical explanation. (shrink)

Temporal Changes in Ovarian Gonadotropin-Releasing Hormone mRNA Levels by Gonadotropins in the Rat Sung Ho Lee, Eun-Seob Song, Sun Kyeong Yu, Changmee Kim, Dae Kee Lee, Wan Sung Choi l and Kyungjin Kim* Department of Molecular Biofogy and SRC for Cell Differentiation, Seoul National University, Seoul 150-742, Korea; IDepartment of Anatomy, College of Medicine, Gyeongsanf; National University, Chinju 660-280, Korea (Recei·. cd on December 29, 1993) The present study examines whether gonadotropins are involved in the regulation of ovarian GnRH gene (...) expression and how ovarian GnRH gene expression temporalJy correlates with alterations in hypothalamic GnRH, pituitary LH~ gene expression in respons to gonadotropins. Hypothalamic and ovarian GnRH mRNA and pituitary LH~ mRNA levels were determined by respective RNA-blot hybridizations, and ovarian GnRH and estradiol contents and serum LH levels were measured by respective radioimmunoassays. Three animal models such as 1) PMSG-treated, 2) PMSG and heG-treated immature rats and 3) proestrous stage of adult rats were used. Immature rats (25-days old) were administered with PMSG (10 iu) at 10:00 hand 48 h later with heG (10 iu) to induce ovulation. In the PMSG-injected model, hypothalamic GnRH mRNA levels were markedly augmented about 9-fold at 50 h, and pituitary LH mRNA 3-fold at 52 h after PMSG administration. Serum LH levels were increased to the preovulatory surge levels at 56 h, and ovarian GnRH mRNA levels were augmented 4-fold at 60 h after PMSG injection. Administration of heG also induced a marked enhancement in ovarian GnRH mRNA levels in comparison to the values shown in both intact and PMSGtreated rats at 52 hand 54 h, respectively. In the proestrous stage of normal adult rats, pituitary LH~ mRNA levels were peaked at 16:00 h. The preovulatory LH surge was evident at 4 h before increment in ovarian GnRH mRNA levels as shown in PMSG-treated rats. The present study clearly showed the sequential increase in hypothalamic GnRH mRNA, pituitary LH~ mRNA and ovarian GnRH mRNA levels, indicating that ovarian GnRH may play a possible role in the control of follicular maturation and the ovulation process. (shrink)

The Question of Iterated Grounding (QIG) asks what grounds the grounding facts. Although the question received a lot of attention in the past few years, it is usually discussed independently of another important issue: the connection between metaphysical explanation and the relation or relations that supposedly “back” it. I will show that once we get clear on the distinction between metaphysical explanation and the relation(s) backing it, we can distinguish no fewer than four questions lumped under QIG. I will also (...) argue that given some plausible assumptions about what it would take for a relation to back metaphysical explanation, many salient views about grounding allow us to give “easy” answers to these questions—easy in the sense that we can straightforwardly derive them from the respective conception of grounding without getting into the sorts of complexities that typically inform answers to QIG. The paper's main upshot is that we cannot expect to make much progress on QIG without first addressing the difficult issue of how exactly grounding is related to metaphysical explanation. (shrink)

continent. 1.1 : 3-13. / 0/ – Introduction I want to propose, as a trajectory into the philosophically weird, an absurd theoretical claim and pursue it, or perhaps more accurately, construct it as I point to it, collecting the ground work behind me like the Perpetual Train from China Mieville's Iron Council which puts down track as it moves reclaiming it along the way. The strange trajectory is the following: Kant's critical philosophy and much of continental philosophy which has followed, (...) has been a defense against horror and madness. Kant's prohibition on speculative metaphysics such as dogmatic metaphysics and transcendental realism, on thinking beyond the imposition of transcendental and moral constraints, has been challenged by numerous figures proceeding him. One of the more interesting critiques of Kant comes from the mad black Deleuzianism of Nick Land stating, “Kant’s critical philosophy is the most elaborate fit of panic in the history of the Earth.” And while Alain Badiou would certainly be opposed to the libidinal investments of Land's Deleuzo-Guattarian thought, he is likewise critical of Kant's normative thought-bureaucracies: Kant is the one author for whom I cannot feel any kinship. Everything in him exasperates me, above all his legalism—always asking Quid Juris? Or ‘Haven’t you crossed the limit?’—combined, as in today’s United States, with a religiosity that is all the more dismal in that it is both omnipresent and vague. The critical machinery he set up has enduringly poisoned philosophy, while giving great succour to the academy, which loves nothing more than to rap the knuckles of the overambitious [….] That is how I understand the truth of Monique David-Menard’s reflections on the properly psychotic origins of Kantianism. I am persuaded that the whole of the critical enterprise is set up to to shield against the tempting symptom represented by the seer Swedenborg, or against ‘diseases of the head’, as Kant puts it. An entire nexus of the limits of reason and philosophy are set up here, namely that the critical philosophy not only defends thought from madness, philosophy from madness, and philosophy from itself, but that philosophy following the advent of the critical enterprise philosophy becomes auto-vampiric; feeding on itself to support the academy. Following Francois Laruelle's non-philosophical indictment of philosophy, we could go one step further and say that philosophy operates on the material of what is philosophizable and not the material of the external world. [1] Beyond this, the Kantian scheme of nestling human thinking between our limited empirical powers and transcendental guarantees of categorical coherence, forms of thinking which stretch beyond either appear illegitimate, thereby liquefying both pre-critical metaphysics and the ravings of the mad in the same critical acid. In rejecting the Kantian apparatus we are left with two entities – an unsure relation of thought to reality where thought is susceptible to internal and external breakdown and a reality with an uncertain sense of stability. These two strands will be pursued, against the sane-seal of post-Kantian philosophy by engaging the work of weird fiction authors H.P. Lovecraft and Thomas Ligotti. The absolute inhumanism of the formers universe will be used to describe a Shoggothic Materialism while the dream worlds of the latter will articulate the mad speculation of a Ventriloquil Idealism. But first we must address the relation of philosophy to madness as well as philosophy to weird fiction. /1/ – Philosophy and Madness There is nothing that the madness of men invents which is not either nature made manifest or nature restored. Michel Foucault. Madness and Civilization. The moment I doubt whether an event that I recall actually took place, I bring the suspicion of madness upon myself: unless I am uncertain as to whether it was not a mere dream. Arthur Schopenhauer. The World as Will and Idea, Vol. 3. Madness is commonly thought of as moving through several well known cultural-historical shifts from madness as a demonic or otherwise theological force, to rationalization, to medicalization psychiatric and otherwise. Foucault's Madness and Civilization is well known for orientating madness as a form of exclusionary social control which operated by demarcating madness from reason. Yet Foucault points to the possibility of madness as the necessity of nature at least prior to the crushing weight of the church. Kant’s philosophy as a response to madness is grounded by his humanizing of madness itself. As Adrian Johnston points out in the early pages of Time Driven pre-Kantian madness meant humans were seized by demonic or angelic forces whereas Kantian madness became one of being too human. Madness becomes internalized, the external demonic forces become flaws of the individual mind. Foucault argues that, while madness is de-demonized it is also dehumanized during the Renaissance, as madmen become creatures neither diabolic nor totally human reduced to the zero degree of humanity. It is immediately clear why for Kant, speculative metaphysics must be curbed – with the problem of internal madness and without the external safeguards of transcendental conditions, there is nothing to formally separate the speculative capacities for metaphysical diagnosis from the mad ramblings of the insane mind – both equally fall outside the realm of practicality and quotidian experience. David-Menard's work is particularly useful in diagnosing the relation of thought and madness in Kant's texts. David-Menard argues that in Kant's relatively unknown “An Essay on the Maladies of the Mind” as well as his later discussion of the Seer of Swedenborg, that Kant formulates madness primarily in terms of sensory upheaval or other hallucinatory theaters. She writes: “madness is an organization of thought. It is made possible by the ambiguity of the normal relation between the imaginary and the perceived, whether this pertains to the order of sensation or to the relations between our ideas” Kant's fascination with the Seer forces Kant between the pincers of “aesthetic reconciliation” – namely melancholic withdrawal – and “a philosophical invention” – namely the critical project. Deleuze and Guattari's schizoanalysis is a combination and reversal of Kant's split, where an aesthetic over engagement with the world entails prolific conceptual invention. Their embrace of madness, however, is of course itself conceptual despite all their rhizomatic maneuvers. Though they move with the energy of madness, Deleuze and Guattari save the capacity of thought from the fangs of insanity by imbuing materiality itself with the capacity for thought. Or, as Ray Brassier puts it, “Deleuze insists, it is necessary to absolutize the immanence of this world in such a way as to dissolve the transcendent disjunction between things as we know them and as they are in themselves”. That is, whereas Kant relied on the faculty of judgment to divide representation from objectivity Deleuze attempts to flatten the whole economy beneath the juggernaut of ontological univocity. Speculation, as a particularly useful form of madness, might fall close to Deleuze and Guattari’s shaping of philosophy into a concept producing machine but is different in that it is potentially self destructive – less reliant on the stability of its own concepts and more adherent to exposing a particular horrifying swath of reality. Speculative madness is always a potential disaster in that it acknowledges little more than its own speculative power with the hope that the gibbering of at least a handful of hysterical brains will be useful. Pre-critical metaphysics amounts to madness, though this may be because the world itself is mad while new attempts at speculative metaphysics, at post-Kantian pre-critical metaphysics, are well aware of our own madness. Without the sobriety of the principle of sufficient reason we have a world of neon madness: “we would have to conceive what our life would be if all the movements of the earth, all the noises of the earth, all the smells, the tastes, all the light – of the earth and elsewhere, came to us in a moment, in an instant – like an atrocious screaming tumult of things”. Speculative thought may be participatory in the screaming tumult of the world or, worse yet, may produce its spectral double. Against theology or reason or simply commonsense, the speculative becomes heretical. Speculation, as the cognitive extension of the horrorific sublime should be met with melancholic detachment. Whereas Kant's theoretical invention, or productivity of thought, is self -sabotaging, since the advent of the critical project is a productivity of thought which then delimits the engine of thought at large either in dogmatic gestures or non-systematizable empirical wondrousness. The former is celebrated by the fiction of Thomas Ligotti whereas the latter is espoused by the tales of H.P. Lovecraft. /2/ – Weird Fiction and Philosophy. Supernatural horror, in all its eerie constructions, enables a reader to taste treats inconsistent with his personal welfare. Thomas Ligotti Songs of a Dead Dreamer. I choose weird stories because they suit my inclination best—one of my strongest and most persistent wishes being to achieve,momentarily, the illusion of some strange suspension or violation of the galling limitations of time, space, and natural law which forever imprison us and frustrate our curiosity about the infinite cosmic spaces beyond the radius of our sight and analysis H.P. Lovecraft. “Notes on Writing Weird Fiction” Lovecraft states that his creation of a story is to suspend natural law yet, at the same time, he indexes the tenuousness of such laws, suggesting the vast possibilities of the cosmic. The tension that Lovecraft sets up between his own fictions and the universe or nature is reproduced within his fictions in the common theme of the unreliable narrator; unreliable precisely because they are either mad or what they have witnessed questions the bounds of material reality. In “The Call of Cthulhu” Lovecraft writes: The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents. We live on a placid island of ignorance in the midst of black seas of infinity, and it was not meant that we should voyage far. The sciences, each straining in its own direction, have hitherto harmed us little; but some day the piecing together of dissociated knowledge will open up such terrifying vistas of reality, and of our frightful position therein, that we shall either go mad from the revelation or flee from the deadly light into the peace and safety of a new dark age. Despite Lovecraft's invocations of illusion, he is not claiming that his fantastic creations such as the Old Ones are supernatural but, following Joshi, are only ever supernormal. One can immediately see that instead of nullifying realism Lovecraft in fact opens up the real to an unbearable degree. In various letters and non-fictional statements Lovecraft espoused strictly materialist tenets, ones which he borrowed from Hugh Elliot namely the uniformity of law, the denial of teleology and the denial of non-material existence. Lovecraft seeks to explore the possibilities of such a universe by piling horror upon horror until the fragile brain which attempts to grasp it fractures. This may be why philosophy has largely ignored weird fiction – while Deleuze and Guattari mark the turn towards weird fiction and Lovecraft in particular, with the precursors to speculative realism as well as contemporary related thinkers have begun to view Lovecraft as making philosophical contributions. Lovecraft's own relation to philosophy is largely critical while celebrating Nietzsche and Schopenhauer. This relationship of Lovecraft to philosophy and philosophy to Lovecraft is coupled with Lovecraft's habit of mercilessly destroying the philosopher and the figure of the academic more generally in his work, a destruction which is both an epistemological destruction and an ontological destruction. Thomas Ligotti's weird fiction which he has designated as a kind of “confrontational escapism” might be best described in the following quote from one of his shortstories, “The human phenomenon is but the sum of densely coiled layers of illusion each of which winds itself on the supreme insanity. That there are persons of any kind when all there can be is mindless mirrors laughing and screaming as they parade about in an endless dream”. Whereas Lovecraft's weirdness draws predominantly from the abyssal depths of the uncharted universe, Ligotti's existential horror focuses on the awful proliferation of meaningless surfaces that is, the banal and every day function of representation. In an interview, Ligotti states: We don't even know what the world is like except through our sense organs, which are provably inadequate. It's no less the case with our brains. Our whole lives are motored along by forces we cannot know and perceptions that are faulty. We sometimes hear people say that they're not feeling themselves. Well, who or what do they feel like then? This is not to say that Ligotti sees nothing beneath the surface but that there is only darkness or blackness behind it, whether that surface is on the cosmological level or the personal. By addressing the implicit and explicit philosophical issues in Ligotti's work we will see that his nightmarish take on reality is a form of malevolent idealism, an idealism which is grounded in a real, albeit dark and obscure materiality. If Ligotti's horrors ultimately circle around mad perceptions which degrade the subject, it takes aim at the vast majority of the focus of continental philosophy. While Lovecraft's acidic materialism clearly assaults any romantic concept of being from the outside, Ligotti attacks consciousness from the inside: Just a little doubt slipped into the mind, a little trickle of suspicion in the bloodstream, and all those eyes of ours, one by one, open up to the world and see its horror [...] Not even the solar brilliance of a summer day will harbor you from horror. For horror eats the light and digests it into darkness. Clearly, the weird fiction of Lovecraft and Ligotti amount to a anti-anthrocentric onslaught against the ramparts of correlationist continental philosophy. /3/ – Shoggothic Materialism or the Formless Formless protoplasm able to mock and reflect all forms and organs and processes—viscous agglutinations of bubbling cells—rubbery fifteen-foot spheroids infinitely plastic and ductile—slaves of suggestion, builders of cities—more and more sullen, more and more intelligent, more and more amphibious, more and more imitative—Great God! What madness made even those blasphemous Old Ones willing to use and to carve such things? H.P. Lovecraft. “At the Mountains of Madness” On the other hand, affirming that the universe resembles nothing and is only formless amounts to saying that the universe is something like a spider or spit. Georges Bataille. “Formless”. The Shoggoths feature most prominently in H.P. Lovecraft's shortstory “At the Mountains of Madness” where they are described in the following manner: It was a terrible, indescribable thing vaster than any subway train – a shapeless congeries of protoplasmic bubbles, faintly self -luminous, and with myriads of temporary eyes forming and un-forming as pustules of greenish light all over the tunnel-filling front that bore down upon us, crushing the frantic penguins and slithering over the glistening floor that it and its kind had swept so evilly free of all litter. The term is a litmus test for materialism itself as the Shoggoth is an amorphous creature. The Shoggoths were living digging machines bio engineered by the Elder Things, and their protoplasmic bodies being formed into various tools by their hypnotic powers. The Shoggoths eventually became self aware and rose up against their masters in an ultimately failed rebellion. After the Elder Ones retreated into the oceans leaving the Shoggoths to roam the frozen wastes of the Antarctic. The onto-genesis of the Shoggoths and their gross materiality, index the horrifyingly deep time of the earth a concept near and dear to Lovecraft's formulation of horror as well as the fear of intelligences far beyond, and far before, the ascent of humankind on earth and elsewhere. The sickly amorphous nature of the Shoggoths invade materialism at large, where while materiality is unmistakably real ie not discursive, psychological, or otherwise overly subjectivist, it questions the relation of materialism to life. As Eugene Thacker writes: The Shoggoths or Elder Things do not even share the same reality with the human beings who encounter them—and yet this encounter takes place, though in a strange no-place that is neither quite that of the phenomenal world of the human subject or the noumenal world of an external reality. Amorphous yet definitively material beings are a constant in Lovecraft's tales. In his tale “The Dream-Quest of Unknown Kadatth” Lovecraft describes Azathoth as, “that shocking final peril which gibbers unmentionably outside the ordered universe,” that, “last amorphous blight of nethermost confusion which blashphemes and bubbles at the centre of all infinity,” who, “gnaws hungrily in inconceivable, unlighted chambers beyond time”. Azathoth's name may have multiple origins but the most striking is the alchemy term azoth which is both a cohesive agent and a acidic creation pointing back to the generative and the decayed. The indistinction of generation and degradation materially mirrors the blur between the natural and the unnatural as well as life and non-life. Lovecraft speaks of the tension between the natural and the unnatural is his short story “The Unnameable.” He writes, “if the psychic emanations of human creatures be grotesque distortions, what coherent representation could express or portray so gibbous and infamous a nebulousity as the spectre of a malign, chaotic perversion, itself a morbid blasphemy against Nature?”. Lovecraft explores exactly the tension outlined at the beginning of this chapter, between life and thought. At the end of his short tale Lovecraft compounds the problem as the unnameable is described as “a gelatin—a slime—yet it had shapes, a thousand shapes of horror beyond all memory”. Deleuze suggests that becoming-animal is operative throughout Lovecraft's work, where narrators feel themselves reeling at their becoming non-human or of being the anomalous or of becoming atomized. Following Eugene Thacker however, it may be far more accurate to say that Lovecraft's tales exhibit not a becoming-animal but a becoming-creature. Where the monstrous breaks the purportedly fixed laws of nature, the creature is far more ontologically ambiguous. The nameless thing is an altogether different horizon for thought. The creature is either less than animal or more than animal – its becoming is too strange for animal categories and indexes the slow march of thought towards the bizarre. This strangeness is, as aways, some indefinite swirling in the category of immanence and becoming. Bataille begins “The Labyrinth” with the assertion that being, to continue to be, is becoming. More becoming means more being hence the assertion that Bataille's barking dog is more than the sponge. This would mean that the Shoggotth is altogether too much being, too much material in the materialism. Bataille suggests that there is an immanence between the eater and the eaten, across the species and never within them. That is, despite the chaotic storm of immanence there must remain some capacity to distinguish the gradients of becoming without reliance upon, or at least total dependence upon, the powers of intellection to parse the universe into recognizable bits, properly digestible factoids. That is, if we undo Deleuze's aforementioned valorization of sense which, for his variation of materialism, performed the work of the transcendental, but refuse to reinstate Kant's transcendental disjunction between thing and appearance, then it must be a quality of becoming-as-being itself which can account for the discernible nature of things by sense. In an interview with Peter Gratton, Jane Bennett formulates the problem thusly: What is this strange systematicity proper to a world of Becoming? What, for example, initiates this congealing that will undo itself? Is it possible to identify phases within this formativity, plateaus of differentiation? If so, do the phases/plateaus follow a temporal sequence? Or, does the process of formation inside Becoming require us to theorize a non-chronological kind of time? I think that your student’s question: “How can we account for something like iterable structures in an assemblage theory?” is exactly the right question. Philosophy has erred too far on the side of the subject in the subject-object relation and has furthermore, lost the very weirdness of the non-human. Beyond this, the madness of thought need not override. /4/ - Ventriloquial Idealism or the Externality of Thought My aim is the opposite of Lovecraft's. He had an appreciation for natural scenery on earth and wanted to reach beyond the visible in the universe. I have no appreciation for natural scenery and want the objective universe to be a reflection of a character. Thomas Ligotti. “Devotees of Decay and Desolation.” Unless life is a dream, nothing makes sense. For as a reality, it is a rank failure [….] Horror is more real than we are. Thomas Ligotti. “Professor Nobody's Little Lectures on Supernatural Horror”. Thomas Ligotti's tales are rife with mannequins, puppets, and other brainless entities which of replace the valorized subject of philosophy – that of the free thinking human being. His tales such as “The Dream of the Manikin” aim to destroy the rootedness of consciousness. James Trafford has connected the anti-egoism of Ligotti to Thomas Metzinger – where the self is at best an illusion and we plead desperately for someone else to acknowledge that we are real. Trafford has stated it thus, “Life is played out as an inescapable puppet show, an endless dream in which the puppets are generally unaware that they are trapped within a mesmeric dance of whose mechanisms they know nothing and over which they have no control”. An absolute materialism, for Ligotti, implies an alienation of the idea which leads to a ventriloquil idealism. As Ligotti notes in an interview, “the fiasco and nightmare of existence, the particular fiasco and nightmare of human existence, the sense that people are puppets of powers they cannot comprehend, etc.” And then further elaborates that,“[a]ssuming that anything has to exist, my perfect world would be one in which everyone has experienced the annulment of his or her ego. That is, our consciousness of ourselves as unique individuals would entirely disappear”. The externality of the idea leads to the unfortunate consequence of consciousness eating at itself through horror which, for Ligotti, is more real than reality and goes beyond horror-as-affect. Beyond this, taking together with the unreality of life and the ventriloquizing of subjectivity, Ligotti's thought becomes an idealism in which thought itself is alien and ultimately horrifying. The role of human thought and the relation of non-relation of horror to thought is not completely clear in Ligotti's The Conspiracy Against the Human Race. Ligotti argues in his The Conspiracy Against the Human Race,that the advent of thought is a mistake of nature and that horror is being in the sense that horror results from knowing too much. Yet, at the same time, Ligotti seems to suggest that thought separates us from nature whereas, for Lovecraft, thought is far less privileged – mind is just another manifestation of the vital principal, it is just another materialization of energy. In his brilliant “Prospects for Post-Copernican Dogmatism” Iain Grant rallies against the negative definition of dogmatism and the transcendental, and suggests that negatively defining both over-focuses on conditions of access and subjectivism at the expense of the real or nature. With Schelling, who is Grant's champion against the subjectivist bastions of both Fichte and Kant, Ligotti's idealism could be taken as a transcendental realism following from an ontological realism. Yet the transcendental status of Ligotti's thought move towards a treatment of the transcendental which may threaten to leave beyond its realist ground. Ligotti states: Belief in the supernatural is only superstition. That said, a sense of the supernatural, as Conrad evidenced in Heart of Darkness, must be admitted if one's inclination is to go to the limits of horror. It is the sense of what should not be- the sense of being ravaged by the impossible. Phenomenally speaking, the super-natural may be regarded as the metaphysical counterpart of insanity, a transcendental correlative of a mind that has been driven mad. Again, Ligotti equates madness with thought, qualifying both as supernatural while remaining less emphatic about the metaphysical dimensions of horror. The question becomes one of how exactly the hallucinatory realm of the ideal relates to the black churning matter of Lovecraft's chaos of elementary particles. In his tale “I Have a Special Plan for This World” Ligotti formulates thus: A: There is no grand scheme of things. B: If there were a grand scheme of things, the fact – the fact – that we are not equipped to perceive it, either by natural or supernatural means, is a nightmarish obscenity. C: The very notion of a grand scheme of things is a nightmarish obscenity. Here Ligotti is not discounting metaphysics but implying that if it does exist the fact that we are phenomenologically ill-equipped to perceive that it is nightmarish. For Ligotti, nightmare and horror occur within the circuit of consciousness whereas for Lovecraft the relation between reality and mind is less productive on the side of mind. It is easier to ascertain how the Kantian philosophy is a defense against the diseases of the head as Kant armors his critical enterprise from too much of the world and too much of the mind. The weird fiction of both Lovecraft and Ligotti demonstrates that there is too much of both feeding into one another in a way that corrodes the Kantian schema throughly, breaking it down into a dead but still ontologically potentiated nigredo. The haunting, terrifying fact of Ligotti's idealism is that the transcendental motion which brought thought to matter, while throughly material and naturalized, brings with it the horror that thought cannot be undone without ending the material that bears it either locally or completely. Thought comes from an elsewhere and an elsewhen being-in-thought. The unthinkable outside thought is as maddening as the unthought engine of thought itself within thought which doesn't exist except for the mind, the rotting décor of the brain. /5/ - Hyperstitional Transcendental Paranoia or Self -Expelled Thought Weird fiction has been given some direct treatment in philosophy in the mad black Deleuzianism of Nick Land. Nick Land along with others in the 1990s created the Cyber Culture Research Unit as well as the research group Hyperstition. The now defunct hyperstitional website, an outgrowth of the Cyber Culture Research Unit, defined hyperstition in the following fourfold: 1-Element of effective culture that makes itself real. 2-Fictional quantity functional as a time-traveling device. 3-Coincidence intensifier. 4-Call to the Old Ones. The distinctively Lovecraftian character of hyperstition is hard to miss as is its Deleuzo-Guattarian roots. In the opening pages of A Thousand Plateaus Deleuze and Guattari write, “We have been criticized for over-quoting literary authors. But when one writes, the only question is which other machine the literary machine can be plugged into”. The indisinction of literature and philosophy mirrors the mess of being and knowing as post-correlationist philosophy, where philosophy tries to make itself real where literature, especially the weird, aims itself at the brain-circuit of horror. The texts of both Lovecraft and Ligotti work through horror as epistemological plasticity meeting with proximity as well as the deep time of Lovecraft and the glacially slow time of paranoia in Ligotti. Against Deleuze, and following Brassier, we cannot allow the time of consciousness, the Bergsonian time of the duree, to override natural time, but instead acknowledge that it is an unfortunate fact of existence as a thinking being. Horror-time, the time of consciousness, with all its punctuated moments and drawn out terrors, cannot compare to the deep time of non-existence both in the unreachable past and the unknown future. The crystalline cogs of Kant's account of experience as the leading light for the possibility of metaphysics must be throughly obliterated. His gloss of experience in Prolegomena to any Future Metaphysics could not be more sterile: Experience consists of intuitions, which belong to the sensibility, and of judgments, which are entirely a work of the understanding. But the judgments which the understanding makes entirely out of sensuous intuitions are far from being judgments of experience. For in the one case the judgment connects only the perceptions as they are given in sensuous intuition [....] Experience consists in the synthetic connection of appearances in consciousness, so far as this connection is necessary. Here it is difficult to dismiss the queasiness that Kant's legalism induces upon sight for both Badiou and David-Menard. Kant's thought becomes, as Foucault says when reflecting on Sade's text in relation to nature, “the savage abolition of itself”. For Badiou, Kant's philosophy simply closes off too much of the outside, freezing the world of thought in an all too limited formalism. Critical philosophy is simply the systematized quarantine on future thinking, on thinking which would threaten the formalism which artificially grants thought its own coherency in the face of madness. Even the becoming-mad of Deleuze, while escaping the rumbling ground, makes grounds for itself, mad grounds but grounds which are thinkable in their affect. The field of effects allows for Deleuze's aesthetic and radical empiricism, in which effects and/or occasions make up the material of the world to be thought as a chaosmosis of simulacra. Given a critique of an empiricism of aesthetics, of the image, it may be difficult to justify an attack on Kantian formalism with the madness of literature, which does not aim to make itself real but which we may attempt to make real. That is, how do Lovecraft's and Ligotti's materials, as materials for philosophy to work on, differ from either the operative formalisms of Kant or the implicitly formalized images of Deleuzian empiricism? It is simply that such texts do not aim to make themselves real, and make claims to the real which are more alien to us than familiar, which is why their horror is immediately more trustworthy. This is the madness which Blanchot discusses in The Infinite Conversation through Cervantes and his knight – the madness of book-life, of the perverse unity of literature and life a discussion which culminates in the discussion of one of the weird's masters, that of Kafka. The text is the knowing of madness, since madness, in its moment of becoming-more-mad, cannot be frozen in place but by the solidifications of externalizing production. This is why Foucault ends his famous study with works of art. Furthermore extilligence, the ability to export the products of our maligned brains, is the companion of the attempts to export, or discover the possibility of intelligences outside of our heads, in order for philosophy to survive the solar catastrophe. To borrow again from Deleuze, writing is inseparable from becoming. The mistake is to believe that madness is reabsorbed by extilligence, by great works, or that it could be exorcised by the expelling of thought into the inorganic or differently organic. Going out of our heads does not guarantee we will no longer mean we cannot still go out of our minds. This is simply because of the outside, of matter, or force, or energy, or thing-in-itself, or Schopenhauerian Will. In Lovecraft’s “The Music of Erich Zahn” an “impoverished student of metaphysics” becomes intrigued by strange viol music coming from above his room. After meeting the musician the student discovers that each night he plays frantic music at a window in order to keep some horridness at bay, some “impenetrable darkness with chaos and pandemonium”. The aesthetic defenses provided by the well trained brain can bear the hex of matter for so long, the specter of unalterability within it which too many minds obliterate, collapsing everything before the thought of thought as thinkable or at least noetically mutable on our own terms. Transcendental paranoia is the concurrent nightmare and promise of Paul Humphrey's work, of being literally out of our minds. It is the gothic counterpart of thinking non-conceptually but also of thinking never belonging to any instance of purportedly solid being. As Bataille stated, “At the boundary of that which escapes cohesion, he who reflects within cohesion realizes there is no longer any room for him” Thought is immaterial only to the degree that it is inhuman, it is a power that tries, always with failure, to ascertain its own genesis. Philosophy, if it can truly return to the great outdoors, if it can leave behind the dead loop of the human skull, must recognize not only the non-priority of human thought, but that thought never belongs to the brain that thinks it, thought comes from somewhere else. To return to the train image from the beginning “a locomotive rolling on the surface of the earth is the image of continuous metamorphosis” this is the problem of thought, and of thinking thought, of being no longer able to isolate thought, with only a thought-formed structure. [1] One of the central tenets of Francois Laruelle's non-philosophy is that philosophy has traditionally operated on material already presupposed as thinkable instead of trying to think the real in itself. Philosophy, according to Laruelle, remains fixated on transcendental synthesis which shatters immanence into an empirical datum and an a prori factum which are then fused by a third thing such as the ego. For a critical account of Laruelle's non-philosophy see Ray Brassier's Nihil Unbound. (shrink)

In recent years, metaphysics has undergone what some describe as a revolution: it has become standard to understand a vast array of questions as questions about grounding, a metaphysical notion of determination. Why should we believe in grounding, though? Supporters of the revolution often gesture at what I call the Argument from Explanatoriness: the notion of grounding is somehow indispensable to a metaphysical type of explanation. I challenge this argument and along the way develop a “reactionary” view, according to which (...) there is no interesting sense in which the notion of grounding is explanatorily indispensable. I begin with a distinction between two conceptions of grounding, a distinction which extant critiques of the revolution have usually failed to take into consideration: grounding qua that which underlies metaphysical explanation and grounding qua metaphysical explanation itself. Accordingly, I distinguish between two versions of the Argument from Explanatoriness: the Unexplained Explanations Version for the first conception of grounding, and the Expressive Power Version for the second. The paper’s conclusion is that no version of the Argument from Explanatoriness is successful. (shrink)

Across two studies, one of which was pre-registered, we find that a simple questionnaire that measures intellectual virtue and vice predicts how many fake news articles and conspiracy theories participants accept. This effect holds even when controlling for multiple demographic predictors, including age, household income, sex, education, ethnicity, political affiliation, religion, and news consumption. These results indicate that self-report is an adequate way to measure intellectual virtue and vice, which suggests that they are not fully immune to introspective awareness or (...) “stealthy” in the sense that Cassam (2015) argues. This is an important methodological result and may pave the way for future research on intellectual virtue and vice. (shrink)

This paper develops the Diachronic Self-Making View, the view that we are the non-accidentally best candidate referents of our ‘I’-beliefs. A formulation and defence of DSV is followed by an overview of its treatment of familiar puzzle cases about personal identity. The rest of the paper focuses on a challenge to DSV, the Puzzle of Inconstant ‘I’-beliefs: the view appears to force on us inconsistent verdicts about personal identity in cases that we would naturally describe as changes in one’s de (...) se beliefs. To solve this problem, the paper defends the possibility of overlapping people, and addresses a number of objections to this idea. (shrink)

This paper explains how the practice of ‘no platforming’ can be reconciled with a liberal politics. While opponents say that no platforming flouts ideals of open public discourse, and defenders see it as a justifiable harm-prevention measure, both sides mistakenly treat the debate like a run-of-the-mill free speech conflict, rather than an issue of academic freedom specifically. Content-based restrictions on speech in universities are ubiquitous. And this is no affront to a liberal conception of academic freedom, whose purpose isn’t just (...) to protect the speech of academics, but also to give them the prerogative to determine which views and speakers have sufficient disciplinary credentials to receive a hearing in academic contexts. No platforming should therefore be acceptable to liberals, in principle, in cases where it is used to support a university culture that maintains rigorous disciplinary standards, by denying attention and credibility to speakers without appropriate disciplinary credentials. (shrink)

Permissivism says that for some propositions and bodies of evidence, there is more than one rationally permissible doxastic attitude that can be taken towards that proposition given the evidence. Some critics of this view argue that it condones, as rationally acceptable, sets of attitudes that manifest an untenable kind of arbitrariness. I begin by providing a new and more detailed explication of what this alleged arbitrariness consists in. I then explain why Miriam Schoenfield’s prima facie promising attempt to answer the (...) Arbitrariness Objection, by appealing to the role of epistemic standards in rational belief formation, fails to resolve the problem. Schoenfield’s strategy is, however, a useful one, and I go on to explain how an alternative form of the standards-based approach to Permissivism – one that emphasizes the significance of the relationship between people’s cognitive abilities and the epistemic standards that they employ – can respond to the arbitrariness objection. (shrink)

Nonnaturalist realism is the view that normative properties are unique kind of stance-independent properties. It has been argued that such views fail to explain why two actions that are exactly alike otherwise must also have the same normative properties. Mark Schroeder and Knut Olav Skarsaune have recently suggested that nonnaturalist realists can respond to this supervenience challenge by taking the primary bearers of normative properties to be action kinds. This paper develops their response in two ways. First, it provides (...) additional motivation for the previous claim about the bearers of normative properties by drawing from the work of H. A. Prichard. Second, and more importantly, it formulates a plausible metaphysical framework based on the contemporary trope theory to explain why action kinds would have their second-order properties, including their normative properties, necessarily. (shrink)

Abstract:Skepticism about grounding is the view that ground-theoretic concepts shouldn’t be used in meta­physical theorizing. Possible reasons for adopting this attitude are numerous: perhaps grounding is unintelligible; or perhaps it’s never instantiated; or perhaps it’s just too heterogeneous to be theor­­­­­etically useful. Unfortunately, as currently pursued the debate between grounding enthusiasts and skeptics is insufficiently structured. This paper’s purpose is to impose a measure of conceptual rigor on the debate by offering an opinionated taxonomy of views with a reasonable claim (...) to being “skeptical.” I argue that carving up logical space into pro- and anti-grounding views isn’t especially helpful; rather, we should recognize various degrees of ground-theoretic involvement depending on how inflationary our understanding of the theoretical term ‘ground’ is. (shrink)

In the last decades a growing body of literature in Artificial Intelligence (AI) and Cognitive Science (CS) has approached the problem of narrative understanding by means of computational systems. Narrative, in fact, is an ubiquitous element in our everyday activity and the ability to generate and understand stories, and their structures, is a crucial cue of our intelligence. However, despite the fact that - from an historical standpoint - narrative (and narrative structures) have been an important topic of investigation in (...) both these areas, a more comprehensive approach coupling them with narratology, digital humanities and literary studies was still lacking. With the aim of covering this empty space, in the last years, a multidisciplinary effort has been made in order to create an international meeting open to computer scientist, psychologists, digital humanists, linguists, narratologists etc.. This event has been named CMN (for Computational Models of Narrative) and was launched in the 2009 by the MIT scholars Mark A. Finlayson and Patrick H. Winston1. (shrink)

By focusing on the exchange between Descartes and Hobbes on how the self is related to its activities, Berkeley draws attention to how he and Hobbes explain the forensic constitution of human subjectivity and moral/political responsibility in terms of passive obedience and conscientious submission to the laws of the sovereign. Formulated as the language of nature or as pronouncements of the supreme political power, those laws identify moral obligations by locating political subjects within those networks of sensible signs. When thus (...) juxtaposed with Hobbes, Berkeley can be understood as endorsing a theologically inflected version of deontological ethics in which moral laws are linked directly to the constitution of the self. (shrink)

Supervenience is necessary co-variation between two sets of entities. In the good old days, supervenience was considered a useful philosophical tool with a wide range of applications in the philosophy of mind, metaethics, epistemology, and elsewhere. In recent years, however, supervenience has fallen out of favor, giving place to grounding, realization, and other, more metaphysically “meaty”, notions. The emerging consensus is that there are principled reasons for which explanatory theses cannot be captured in terms of supervenience, or as the slogan (...) goes: “Supervenience Is Nonexplanatory”. While SIN is widely endorsed, it is far from clear what it amounts to and why we should believe it. In this paper, I will distinguish various theses that could be meant by it, and will argue that none of them is both interesting and plausible: on some interpretations of ‘explanatory’, we have no reason to believe that supervenience is unexplanatory, while on other interpretations, supervenience is indeed unexplanatory, but widely accepted textbook cases of explanatory relations come out as unexplanatory, too. This result raises doubts as to whether there is any interesting sense in which SIN is true, and suggests that the contemporary consensus about supervenience is mistaken. (shrink)

In several essays I have argued that Berkeley maintains the same basic notion of spiritual substance throughout his life. Because that notion is not the traditional (Aristotelian, Cartesian, or Lockean) doctrine of substance, critics (e.g., John Roberts, Tom Stoneham, Talia Mae Bettcher, Margaret Atherton, Walter Ott, Marc Hight) claim that on my reading Berkeley either endorses a Humean notion of substance or has no recognizable theory of substance at all. In this essay I point out how my interpretation does not (...) assume that Berkeley adopts a bundle theory of mind, but instead redefines what it means for a simple substance to be the principle by which ideas are perceived. (shrink)

Frege famously claimed that variations in the sense of a proper name can sometimes be ‘tolerated’. In this paper, we offer a novel explanation of this puzzling claim. Frege, we argue, follows Trendelenburg in holding that we think in language—sometimes individually and sometimes together. Variations in sense can be tolerated in just those cases where we are using language to coordinate our actions but are not engaged in thinking together about an issue.

Emotions can be understood generally from two different perspectives: (i) a third-person perspective that specifies their distinctive functional role within our overall cognitive economy and (ii) a first-person perspective that attempts to capture their distinctive phenomenal character, the subjective quality of experiencing them. One emotion that is of central importance in many ethical systems is respect (in the sense of respect for persons or so-called recognition-respect). However, discussions of respect in analytic moral philosophy have tended to focus almost entirely on (...) its functional role, in particular the behaviors that respect disposes us to engage in (or refrain from). Here we wish to investigate the phenomenal character of respect, what it is like to feel respect for persons. Since Kant is the reference point for modern discussions of respect, we try to reconstruct Kant’s account of the phenomenology of respect, but also endeavor to refine his account in light of our own phenomenological observations. (shrink)

Predication is a lingual relation. We have this relation when a term is said (λέγεται) of another term. This simple definition, however, is not Aristotle’s own definition. In fact, he does not define predication but attaches his almost in a new field used word κατηγορεῖσθαι to λέγεται. In a predication, something is said of another thing, or, more simply, we have ‘something of something’ (ἓν καθ᾿ ἑνὸς). (PsA. , A, 22, 83b17-18) Therefore, a relation in which two terms are posited (...) to each other in a way that one is said (predicated) of the other is a predication. The term of which the other term is said is called a subject (ὑποκειμένον) and the other, which is said about the subject, is called the predicate. Thus, in a predication the predicate is predicated of the subject; given that being predicated is almost as the same as being said. The relation between being said and being predicated is so close that ‘if something is said of a subject both its name and its definition are necessarily predicated of the subject.’ (Cat., 5, 2a19-26) This, however, is true only about the second genera and not the accidents. a) Nature of relation in predication What is Aristotle’s theory about the nature of the relation in a predication? How does he fundamentally understand this relation? Phil Corkum distinguishes between predication logic and traditional term logic and argues that the relation between subject and predicate in Aristotle is of the latter kind. While in predicate logic, subjects and predicates have distinct roles, they have the same role in traditional term logic. In predication logic, subjects refer, but predicates characterize. Thereupon, a sentence expresses a truth if the object to which the subject refers is correctly characterized by the predicate. In traditional term logic, both subjects and predicates refer and a sentences expresses a truth if both name one and the same thing. He concludes that Aristotle ‘problematically conflates prediction and identity claims’ because while he thinks both subjects and predicates refer, he would deny that a sentence is true just in case the subject and the predicate name one and the same thing. Based on this, Corkum believes that Aristotle’s core semantic is not identity but the weaker relation of constitution, which is a mereological interpretation: ‘All men are mortal’ is true just in case the mereological sum of humans is part of the mereological sum of mortals. b) Aristotle’s theory of predication: one or two theories? Frank Lewis finds an inconsistent gap between the theory of predication in the Categories and that in the later books of the Metaphysics VII, 6. So too Joan Kung, Terry Irwin, Daniel Graham. c) Distinction of ‘being said of’ and ‘being in’ Owen enumerates the texts in which Aristotle’s distinction between ‘being said of’ and ‘being in’ is asserted: OI. 11b38-12a17; To., 127b1-4; Cat. 1a20-b9; 2a11-14; 2a27-b6; 2b15-17; 3a7-32; 9b22-24 d) Predication in Aristotle and the standard ‘S is P’ Marie De Rijk Lambertus thinks that the ‘S is P’ pattern is misleading when it comes to express predication in Aristotle. In his view, ‘The Aristotelian procedure should be described in terms of appositively assigning an attribute (κατηγορούμενον) to a substrate (ὑποκείμενον), rather than ascribing a predicate to a subject by means of a copula…. The comment should be considered an attribute which is said to fall to a substrate, without understanding this procedure in terms of sentence predication.’ e) Aristotle’s predication: bipartite or tripartite? It is a difficulty to make Aristotle’s theories of name-verb predication and tripartite predication consistent. The reason is that tripartite is not consistant with his name-verb structure based on which he says that the predicate term is the ‘verb.’ (20a31; 20b1-2; 16a13-5) The problem is that in a tripartite form like ‘Socrates is white’ we cannot take ‘is white’ as the verb because, based on Aristotle himself, no part of a verb can be significant itself. (16b6-7) However, his assertions about the equivalences between the two structures (OI. 12, 21b9-10; PrA. 51b13-16; Met., 1017b22-30) must mean that they are not inconsistent in his own view. Thus, as Allen Bāck points, ‘Aristotle seems to think that he has a single, consistent theory.’ The sense of saying or speaking as the root sense of rhema makes the relation between predication (saying something of something) and verb more interesting. The use of rhema in the sense of a long expression approves this. In Plato’s work (399ac) where Socrates claims that the name anthropos derives from anthron ha opopen (‘he who examines what he has seen’) we have an onoma from, or in place of, a rhema. 1) Subject The subject (ὑποκειμένον) is that of which another term is said or predicated. Aristotle’s own definition is of a much more philosophical value: ‘By subject I mean that which is expressed by an affirmative term (λέγω δὲ ὑποκείμενον τὸ κάταφάσει δηλούμενον).’ (Met., K, 1067b18) Throughout Aristotle’s work, three kinds of subjects can be found: possible, prime and absolute subject. a) Possible subject Those things that can take the position of a subject in a predication we call possible subjects, no matter they can or cannot take the position of predicate in any predication. All terms except the ultimate predicates are possible subjects because they can take the position of subject. b) Prime subject Those that in any predication can only take the position of a subject and not the position of a predicate are prime subjects. (Cat., 5, 3a36-b2; Met., Z, 1028b36-1029a1) This is the truest sense of subject and belongs only to substances. (Met., Z, 1029a1-2) In fact, ‘that which is not predicated of a subject, but of which all else is predicated’ is a substance. (Met., Z, 1029a7-9) In Categories, besides primary substances (Cat., 2, 1b3-6), individual qualities are also said not to be able to be said of anything else. (Cat., 2, 1a23-29) Aristotle’s examples are a certain ‘knowledge-of-grammar’ (τὶς γράμματικὴ) and ‘an individual white’ (τὸ τὶ λευκὸν). Thus, although substances are indeed in the truest sense individuals and, thereby, in the truest sense primary subjects, other individuals can take the position of subject as well. c) Absolute subject While substances are prime subjects of all other things, there is still something of which substances can be predicated and this predication is not an accidental predication: matter. (Met., Z, 1029a21-24) This predication is, indeed, the predication of a ‘form or this’ on matter and material substance. (Met., Θ, 1049a34-36) The only thing that is absolutely a subject, therefore, and can be a predicate is prime matter (πρώτη ὓλη). (Met., Θ, 1049a24-27) d) Subject and substance The most important thing in being a substance is being a subject: ‘It is because the primary substances are subjects for all the other things and all the other things are predicated of them or are in them, that they are called substances most of all.’ (Cat., 5, 2b15-17) And what is nearer to this position is more a substance as a species is more a substance than a genus.’ (Cat., 5, 2b7-8) e) Primary versus accidental subject A subject is a primary subject in a predication when the predicate is predicated of it as itself. In such a case, the subject is the subject of the predicate qua itself and not qua something else. A subject, on the one hand, is an accidental subject when it is not the primary subject of the predicate that is predicated on it. It means that a subject is an accidental subject when the predicate is predicated of it not qua itself but qua something else. An accidental subject is, therefore, anything other than a substance. 2) Predicate as universal It is evident from our discussion of kinds of subjects that except matter, primary substances (if we ignore both accidental predication and cases of absolute subjects) and other individuals, everything else can take the position of a predicate. Since primary substances are individuals, it results that everything except matter and individuals are capable to take the position of predicate. The immediate consequence of this is that the predicate must be a universal. When individuals cannot take the position of predicate, this position cannot be taken by any particular. Therefore, only universals can be predicated of others. Moreover, albeit universals can be a simple subject (for another universal), they are not prime subjects. The closeness of universal and predicate is to the extent that Aristotle differentiates universal from subject. (Met., Θ, 1049a27-30) 3) Categories or classes of predicates Aristotle distinguishes ten highest classes into one of which each predicate must necessarily fall: substance (or what a thing is), quality, quantity, relation, place, time, position, state, activity and passivity. (Cat., 4, 1b25-27; To., I, 9, 103b20- ; PsA., A, 22, 83b13-23) The substance counted among predicates must refer to secondary and not primary substances not only because Aristotle insists that primary substances cannot be predicated but also from his own examples of the category of substance: man and animal. (To., I, 9, 103b25) However, if a predicate be asserted of itself or its genus be asserted of it, the predicate signifies substance or what is; but if ‘one kind of predicate is asserted of another kind,’ it signifies one of the other nines. (To., I, 9, 103b30) These categories are so comprehensive that no predicate can remain outside them so that even non-being has as many senses as categories. (Met., M, 1089a26-30) a) That whether Aristotle’s categories are merely linguistic or fundamentally ontological is a so much controversial dispute. Some like G. E. R. Lloyd believe that ‘categories are primarily intended as a classification of reality … rather than of the signifying terms themselves.’ b) Although Aristotle’s categories have been historically regarded as a classification of predications, there are some recent commentators like Jonathan Barnes that think it is classifying predicates and not predications. 4) Kinds of predicates In his introduction of Categories, as J. W. Thorp truly points out , Aristotle distinguishes between the category of substance and the other categories using μὲν ... δὲ construction. This construction illustrates that beside tenfold classification of categories, there is an even more crucial differentiation between two kinds of predicates: substance or what is on the one hand and the other nine ones on the other hand: the distinction between what is predicated of the subject as what it is and what is predicated of it as an accident. Therefore, we have three kinds of classification - a twofold, a fourfold and a tenfold-complicatedly classifying the same thing, viz. the predicate. Predicates can be divided also to four kinds: property, definition, genus and accident. (To., I, 4, 101b11-20) A property is that predicate that is convertible with its subject and does not signify its essence. A definition is that predicate that is convertible with its subject and signifies its essence. It is a genus if it is not predicated convertibly and is contained in the definition of its subject. And it is an accident if it is neither convertible nor contained in the definition of its subject. (To., I, 8, ^103b3) All of these four kinds are among categories. (To., I, 9, 103b20) It seems that there might be some kind of relation between the twofold and the fourfold distinction: whereas genus and definition are predicated as what it is, accidents are not so predicated. There seems to be some rules that determine to each of these four kinds each predicate belongs. At To., IV, 123b30ff. Aristotle asserts: ‘If B has a contrary and A does not, then B does not belong to A as its genus.’ There is a dispute around per se accidents (τὰ καθ’ αὑτὰ συμβεβηκότα) (Topics., 102a18) whether they must be regarded as either of the four kinds or as a fifth kind. Barnes (1970) argued that they ‘do not fit at all neatly into the fourfold classification.’ He argues that based on the definition of accidents at A, 5, 102b4-5, they must be accidents but based on another definition, A, 5, 102b6-7, they cannot be accidents. He also defends the view that they are not properties. Barnes concludes: ‘This shows that the two definitions are not equivalent, and hence that the ‘predicables’ are not well-defined.’ Demetris J. Hadgopoulos defends the view that the two definitions of accidents are equivalent and per se accidents are properties. 5) Five types of predications We have five kinds of predications based on our division of subjects and our discussion of predicates: simple, primary (itself divided to substantial and accident), accidental (itself divided to primary and secondary), aoincidental and absolute predication. a) Simple predication. This is a predication in which a universal is predicated of either a particular or a universal subject. This sense of predication includes all other senses except the first kind of accidental predication. b) Primary predication. This is a predication in which a universal is predicated of a primary subject, namely a substance. A primary predication is of two kinds: i) Substantial predication. A primary predication in which the predicate is part of, or is included in, the definition of the subject. The universal that is the predicate here is the definition or the genus or the species or the diferentia of the subject. It is this predication that Aristotle calls a unity: ‘A statement may be called a unity … because it exhibits a single predicate as inhering not accidentally in a single subject.’ (PsA., B, 10, 93b35-37) It is only substantial predicates that can be predicated of each other: ‘Predicates which are not substantial are not predicated of one another.’ (PsA., A, 22, 83b18-19) Aristotle defines a substantial predication also in another way. A predication in which a higher genus is predicated on a lower genus, species, a substance or an individual, (or a species is predicated on an individual) is a substantial predication. Therefore, a substantial predication is a predication in a series that has individuals on one of its ends and a general category on its other end. In fact, only substantial predicates can be predicated of one another. (PsA., A, 22, 83b17-19) This series cannot be an infinite series because otherwise not only substances would not be definable but also a genus would be equal to one of its own species. (PsA., A, 22, 83b7-10) -/- ii) Accident predication. A primary predication in which the predicate is not part of, or is not included in, the definition of its subject. The universal that is the predicate here is the property or the accident of the subject. c) Accidental predication. This is a predication in which the subject is not a primary subject and its predicate is a substance. This predication is of two kinds: i) Primary accidental predication. This is a predication in which an accident is predicated of substance. Such a predication can go ad infinitum, which is inferable from Aristotle’s assertion that the secondary accidental predication cannot go ad infinitum. ii) Secondary accidental predication. It is a predication in which an accident is predicated of another accident. Such a predication, Aristotle asserts, cannot go ad infinitum because even more than two accidents cannot be combined. Now what is the meaning of Aristotle’s assertion that we cannot continue this ad infinitum? Does it mean that we cannot continue the predication ‘The musician is white’ and say ‘The white is Athenian?’ But why not? Or maybe he means that by adding any predication, we are still in a condition of predicating two accidents of a substance on each other. -/- As primary subjects, substances can also take the position of predicate though not essentially but accidentally. In propositions like ‘the white is a log’ or ‘That big thing is a log’ we observe substance taking the position of predicate but this is only accidentally: ‘When I affirm ‘the white is a log,’ I mean that something which happens to be white is a log- not that white is the subject in which log inheres (οὐχ ὡς τὸ ὑποκείμενον τῷ ξύλῳ τὸ λευκόν ἐστι), for it was not qua white or qua a species of white that the white (thing) came to be a log (οὔτε λευκὸν ὄν οὔθ᾿ ὃπερ λευκόν τι ἐγἐνετο ξύλον), and the white (thing) is consequently not a log except incidentally.’ (PsA., 22, 83a3-9) Aristotle compares this accidental use of substance in the position of predicate with the substantial use of it in the place of a subject: ‘On the other hand, when I affirm ‘the log is white,’ I do not mean that something else, which happens to be a log, is white (οὐχ ὃτι ἓτερόν τί ἐστι λευκόν, ἐκείνῳ δὲ συμβέβηκε ξύλῳ εἶναι), (as I should if I said ‘the musician is white,’ which would mean ‘The man who happens also to be a musician is white’); on the contrary, log is here the subject- the subject which actually came to be white, and did so qua wood or qua a species of wood and qua nothing else.’ (PsA., 22, 83a8-14) Aristotle asks us not to call propositions like ‘The white is a log’ a predication at all or at least call them accidental predication instead of simple (ἁπλως) predication. (PsA., A, 22, 83a14-17) An accidental predication, in which we have a substance in the place of predicate, is different from an essential predication in that while the subject of an accidental predication is said to be the predicate not by itself but as something different with which it coincides, the subject of an essential predicate is said to be the predicate by itself and not because it is something else: ‘Since there are attributes which are predicated of a subject essentially and not accidentally- not, that is, in the sense in which we say ‘That white (thing) is a man,’ which is not the same mode of predication as when we say ‘The man is white’: the man is white not because he is something else but because he is man, but the white is man because ‘being white’ coincides with ‘humanity’ within one subject. Therefore, there are terms such as are essentially subjects of predicates. (PsA., A, 19, 81a24-29) This capability of ‘non-essentially and only accidentally’ being a subject does belong, in fact, to all sensible things. (PsA., A, 27a32-36) d) Coincidental predication. this is a predication in which none of the subject and predicate are a substance or an individual. In this predication, one of the accidents of a substance or individual is predicated of one of the other accidentals of the same substance or individual. For example, when it is said that ‘The white is musical,’ there is an individual, say Socrates, for which both of white and musical are accidents. e) Absolute predication. This is a predication in which a form or a substance is predicated of a matter or a material substance. Some commentators like Loux and Lewis regarded this predication as close to accident predication, both based on inherence. As R.M. Dancy points out, these predications make Aristotle’s theory of predication immanentist: not only accident predications are explained by the immanence of accidents in substances, some of the substantial predications, which were not explained in Categories, are also explained by the immanence of form in matter. It is interesting that in this kind of predication, it is the predicate and not the subject, which is in the strictest sense substance. As the central books of Metaphysics claim, the form is the substance. Thus, in this predication, substance gets away from the sense of ὑποκείμενον. Corkum mentiones 68a19 as the only instance where Aristotle explicitly claims that a term may be predicated of itself, a passage that is, in Corkum’s view, problematic. 6) Demonstrable predicates Those predicates are demonstrable that are so related to their subjects that there are other predicates prior to them predicable of their subjects (ἔτι δ᾿ ἄλλος, εἰ ὧν πρότερα ἄττα κατηγορεῖται). (PsA., A, 22, 83b32-34) 7) Series of predications Since it is possible for a predicate to be itself the subject of another predication, we can have a series of predications in which the predicate of a predication is the subject of the next predication. This series has the following features: a) It has a limit (in number) (PsA., A, 22, 83b14-16) on the side of subjects: there are subjects that cannot themselves be predicated (PsA., A, 27, 43a39-41), which are, as we noted, prime subjects: particulars, i.e. prime substances and other individuals. (PsA., A, 19-22) Aristotle calls them ultimate (ὓστατον). (PsA., 21, 82a36-b1) b) It has a limit (in number of kinds) (PsA., A, 22, 83b14-16) also on the side of predicates: there must be predicates that cannot be subjects. (PsA., A, 19-22; PsA., A, 27, 43a36-39) Aristotle calls them primary (πρῶτον). (PsA., A, 21, 82b1-4) These are the highest categories or the highest genera of categories. (PsA., A, 22, 83b14-16) c) The series has an escalating shape from mere subjects at its downside to mere predicates at its upside. It is Aristotle himself whos uses the words up and down in this sense. (e.g. PsA., A, 22, 83b2-3) d) The predications that lie between lowest and highest ones must be finite in number. (PsA., A, 19-22 especially: 20, 82a21-35) These have subjects and predicates, each capable of both of the roles of being subject and being predicated. A result of this fitness is that neither demonstration can go to infinity nor everything is demonstrable, the two points Aristotle always insist on. e) The upward side includes the more universal ones and the downward the more particular ones. (PsA., 20, 82a21-23) f) It follows from the above features that ‘neither the ascending nor the descending series of predications … are infinite.’ (PsA., A, 22, 83b24-25) g) Reciprocation and convertibility. Except in case of terms (i.e. subjects and predicates) that are at each of the ends of series of predications, namely ultimates and primaries, it is possible to reciprocate (ἀντιστρέφειν) terms and convert the predication. (PsA., A, 19, 82a15-20) h) Antipredication. Antipredication means that in a predication (S is P), the subject becomes the predicate of its predicate (P is S) in the same category its predicate was predicated on it. For example, if P is in the category of quality, antipredication means that S be predicated of P in the category of quality. In other words, P is a quality of S and S is a quality of P. Aristotle rejects this. (PsA., A, 22, 83a36-b3) i) Self-predication versus other-predication. Aristotle distinguishes between a predication in which a term is said of itself and a predication in which a term is said of another. (Phy., Δ, 2, 209a31-33) j) Predicablity (Cat., 5, 3a36-b2): 1) Primary substances and individuals are not predicable. 2) Secondary substances are of two kinds: genus and species i) Genus is predicable able both of the species and of the individuals. ii) Species is predicable of the individual. 3) Differentiae are predicable both of the species and of the individuals. 8) Predication as classification a) Richard Patterson believes that Aristotle’s so repeated construction using hoper (estin A hoper B) in Topics (120a23 sq., 122b19, 26sq., 123a, 124a18, 125a29, 126a21, 128a35. Also in Posterior Analytics (83a24-30) (Brunschwig’s list. ‘expresses the fact that A is a kind of B (esti A B tis), that A is a species of the genus B.’ 9) Universal predication Aristotle defines universal predication (κατὰ παντὸς κατηγορεῖσθαι) as such: ‘wherever no instance of the subject (τῶν τοῦ ὑποκειμέμνου) can be found of which the other term cannot be asserted.’ (PrA., A, 24b27-29) In this predication, the subject is included in another as in a whole (ἐν ὃλῳ εἶναι) and the predicate is predicated of all of the subject (κατὰ παντὸς κατηγορεῖσθαι). (PrA., A, 24b26-27) Attach another discussion we had about ἐν ὃλῳ here. 10) Quantity of predication A predication, truly stated, has a quantity, which is the number of objects under the name of the subject of which the predicate is predicated. The quantity of subject can be stated in four ways: a. Indefinite: when the predicate belongs or does not belong to the subject without any mark to show to haw many of the particulars under the name of the subject it does or does not belong. E.g. ‘Man is white’; ‘Man is not white.’ (PrA., A, 24a20; OI., I, 7, 17b8-12) b. Universal quantity: When the predicate belongs to all or none of the subject. E.g. ‘Every man is animal’; ‘No man is animal.’ (PrA., A, 24a18-19; OI., I, 7, 17b5-6) The contrary of a predication of a universal quality is a predication of a universal quality. E.g. the contrary of ‘Every man is white’ is ‘No man is white.’ (OI., I, 7, 17b20-23) c. Particular quantity: When the predicate belongs (or does not belong) to some of the subject. E.g. ‘Some men are white’; ‘Some men are not white.’ (PrA., A, 24a19-20) d. Single quantity: when the subject is a proper name of only one object. E.g. ‘Socrates is white’; ‘Socrates is not white.’ The contrary of this predication is of a single quantity: ‘Socrates is not white.’ (OI., I, 7, 17b38-18a4) 11) Convertibility of predication. Some predications are convertible, that is, it is possible to change the place of subject and predicate in a true proposition so that the converted proposition remains true. This is supposed to mean that given the truth of a predication, the truth of the converted predication is inferable. The convert form of a predication depends on its quantity. a. Indefinite quantity: This predication has no strictly true convert because its quantity is not stated. b. Universal quantity: It can be converted in two ways: i) A negative universal can be converted to a negative universal in which the terms are changed. E.g. ‘No pleasure is good’ can be converted to ‘No good is pleasure.’ (PrA., A, 2, 25a5-8 and a14-19) ii) An affirmative universal can be converted to an affirmative particular in which the terms are changed. E.g. ‘Every pleasure is good’ can be converted to ‘Some good is pleasure.’ (PrA., A, 2, 25a7-9) c. Particular quantity: If it is negative, it cannot be converted but if it is affirmative, it can be converted to an affirmative predication with particular quantity. E.g. ‘Some pleasure is good’ can be converted to ‘Some good is pleasure.’ (PrA., A, 2, 25a10-13 and a20-24) d. Single quantity: It cannot be converted. 12) Characteristics of relations between subject and predicate 1. A predicate is of a wider range than its subject. It is based on this fact that Aristotle: a) Prevents individuals to be predicate because there is nothing of which an individual be of a wider range. In other words, it is due to the fact that since an individual is only ‘one particular’ thing and, thus, cannot be of a wider extent than anything that Aristotle prevents them of being a predicate. Matthews, however, thinks we cannot use Socrates, a substance and an individual, in the place of predicate and say it of Socrates because ‘Socrates does not classify Socrates: it names him.’ b) Prevents differentia, species and things under species to be predicated of genus. (To., Z, 6, 144a27-) c) Prevents the species and the things under it to be predicated of the differentia. (To., Z, 6, 144b1-4) d) Also about the effect because it is wider than its subject. (PsA., B, 17, 99a) e) Each attribute is wider than every individual it is predicated on, though several attributes, collectively considered, might not be wider but exactly the substance of a thing. (PsA., B, 13, 96a32-b1) 2. The predicate of a predicate of a subject will be predicated of the subject too: ‘whenever one thing is predicated of another as of a subject, all things said of what is predicated will be said of the subject too.’ (Cat., 3, 1b10-15) In fact, it is due to its predication of the subject that it is predicated of its predicate. (Cat., 5, 2a36-b1) Moreover, what is not predicated of the predicate of a subject cannot be predicated of it as well. (PrA., A, 27, 43b22-27) Thus, what, for example, is not predicated of animal, cannot be predicated of man. 3. The predicate of a subject can be predicated of its predicates as well. (Cat., 5, 3a1-6) For example, you call the individual man grammatical and, thence, you call both a man and an animal grammatical. Nonetheless, the predicate of a subject belongs to it more properly than to its higher predicates. (PrA., A, 27, 43a27-32) 4. It is only the subject that can be distributed and not the predicate. (PrA., A, 27, 43b16-22; OI, I, 7, 17b12-16) Therefore, we can say e.g. ‘Every man is animal’ but we cannot say ‘Every man is every animal.’ 5. It is the reason of the relation between subjects and predicates, that is the reason of predication, which is the subject of inquiry. (Met., Z, 1041a20-24) In other words, since it is a meaningless inquiry to ask why a thing is itself (Met., Z, 1041a14-15), the only remaining meaningful inquiry is to ask why something is something else, i.e. to ask about the reason of predication. 6. A subject cannot categorize its predicate in the same category in which it is categorized by it. If e.g. A is a quality of B, B cannot be a quality of A. Therefore, there is no reciprocation in the same category. (PsA., A, 22, 83a36-39) 13) Characteristics of series of predications 1. A series of secondary accidental predication cannot go ad infinitum for not even more than two terms can be comnbined. For an accident is not an accident of an accident, unless it be because both are accidents of the same subject. (Met., Γ, 1007b1-4) 2. Infinite series cannot be traversed in thought. (PsA., A, 22, 83b6-7) 3. The predications of genera on each other must be ended and cannot go to infinity because otherwise not only substances would not be definable but also a genus would be equal to one of its own species. (PsA., A, 22, 83b7-10) Therefore, a series of predication of genera on each other must be limited on both sides. There must be an upward limit in general categories as well as a downward limit in individual because they cannot be predicated of others. Whatever lies between these limits can both be predicated of others and others be predicated of them. (PrA., A, 27, 43a36-43) 4. The order of predicates matters: it makes a difference whether the series be ABC or BAC. (PsA., B, 13, 96b25-32) . (shrink)

Commentators have not said much regarding Berkeley and Stoicism. Even when they do, they generally limit their remarks to Berkeley’s Siris (1744) where he invokes characteristically Stoic themes about the World Soul, “seminal reasons,” and the animating fire of the universe. The Stoic heritage of other Berkeleian doctrines (e.g., about mind or the semiotic character of nature) is seldom recognized, and when it is, little is made of it in explaining his other doctrines (e.g., immaterialism). None of this is surprising, (...) considering how Stoics are considered arch-materialists and determinists. My aim is to suggest that our understanding of Berkeley’s philosophy is improved significantly by acknowledging its underlying Stoic character. I argue that Berkeley proposes not only a semantic ontology based on assumptions of Stoic logic but also a doctrine in which perceptions or ideas are intelligible precisely because they are always embedded in the propositions of a discourse or language. (shrink)

We have a basic definition of genus in Topics (I, 5, 102a31-35): ‘A genus is what is predicated in what a thing is of a number of things exhibiting differences in kind. We should treat as predicate in what a thing is all such things as it would be appropriate to mention in reply to the question “what is the object in question?”; as, for example, in the case of man, if asked that question, it is appropriate to say “He (...) is an animal.”’ He indicates that ‘of the common predicates that which is most definitely predicated in what the thing is, is likely to be the genus.’ (To. , I, 18, ^108b22) From this definition, what is demonstrative in the definition of genus, Aristotle asserts, is ‘what is common to all the cases.’ (To., I, 18, ^108b22) This common thing is ‘one identical thing which is predicated of both and is differentiated in no merely accidental way.’ (Met., I, 1057b37) This means that the things in which the genus is common must be essentially different. In fact, this very common genus must be essentially different in the things it is their genus. Therefore, things that are identical in a genus are at the same time different in that very genus. This means that though the genus is the same in them, it is indeed different in them and they are not the same as each other in that very same genus but specifically different from each other: ‘For not only must the common nature attach to the different things, e.g. not only must both be animals, but this very animal must also be different for each (e.g. in the one case horse, in the other man), and therefore this common nature is specifically different for the two things (διὰ τοῦτο τὸ κοινὸν ἓτερον ἀλλήλων ἐστι τῷ εἴδει). One then will be in virtue of its own nature one sort of animal, and the other another, e.g. one a horse and the other a man. This difference then must be an otherness of the genus. For I give the name of ‘difference in the genus’ to an otherness which makes the genus itself other.’ A. Characteristics of genera The following are the characteristics of genera: 1. Those to which the same figure of predication applies are one in genus. (Met. , Δ, 1016b32-35) 2. Things that are one in genus are all one by analogy while things that are one by analogy are not all one in genus. (Met, Δ, 1016b35-1017a3) 3. A genus includes contraries. (Met., Δ, 1018a25-31) 4. All the intermediates are in the same genus as one another and as the things they stand between. (Met., I, 1057a18-30; 1057b31-34) 5. Not every predicate is a genus of what it is predicated on; for this would equate a genus with one of its own species. (PsA., A, 22, 83b7-10) 6. The opposite of the genus should always be the genus of the opposite. (To., Δ, 4, ^125a27-29) 7. A genus divides the object from other things. (To., Z, 3, 140a^24) 8. None of unity and being is a genus. (Met., B, 998b22-27; Met., K, 1059b31-34; PsA., B, 7, 92b12-14) 9. There is no necessity or even no possibility that things that are the same specifically or generically should be numerically the same. (To., H, I, 152b30-) 10. To be called one due to having one genus is in a way similar to be one due to having the same matter. (Met., Δ, 1016a24-28) 11. The substance of a thing involves its genus, and thereby all the higher genera are predicated of the lower. (To., Z, 5, 143a^20- ) 12. Being falls immediately into genera. (Met., Γ, 1004a4-6) 13. They do not exist apart from the individuals. (Met., B, 999a29-32; Met., I, 1053b21-22) 14. A genus is not a simple qualification but marks off the qualification of substance. (Cat., 5, 3b18-21) 15. Genera are criteria of difference when ‘the things have not their matter in common and are not generated out of each other.’ (Met., I, 1054b27-31) 16. The genus of a thing is its matter (ὓλη). (Met., I, 1058a23-25) 17. A genus is applicable to a wider range than its species. (Cat., 5, 3b21-23) 18. A genus is prior to its species in existence: while a genus reciprocates on the existence of its species, they do not reciprocate on the existence of their genus. (Cat., 13, 15a3- ) Aristotle’s example is this: if there is a fish there is an animal, but if there is an animal, there is not necessarily a fish. 19. The genus of a thing expresses ‘what it is’ and its essence. (To., I, 5, 102a31- ; To., Z, 5, 143a^20- ) 20. A genus is most familiar than its differentia and may be them all. (To., Z, 9, 149a16) 21. The genus is more substantial than its species. (Met., H, 1042a13-16) 22. One, being and substance cannot be classes. (Met., I, 1053b21-24; cf. 1054a8-11) 23. Aristotle draws a distinction between a simple and a composite concept in their falling within a genus. While a simple one can, a composite one cannot. He discusses this between ‘justice’ and ‘just man’: ‘the former falls within the genus, whereas the other does not … for nothing which does not happen to belong to the genus is essentially the genus; e.g. a white man is not essentially a color.’ (To., Γ, 1, ^116a24) 1) Genus and universal ‘Genera are universals’ (Met., Λ, 1069a26-27; Δ, 1014b9-10) and more universal than differentia and species (Met., Δ, 1014b9-12), but it is evident that not all universals are genera. (Met., A, 992b10-13) 2) Co-ordinate species The species resulting from the same division are co-ordinate species. They are the results of the same division in the same genus. Thus, none of them is prior or posterior to others but they are simultaneous by nature. (Cat., 13, 14b33-15a3) 3) Priority of genus to species Aristotle defines prior (λοιπόν) based on reciprocation as to implication of existence: ‘Τhat from which the implication of existence does not hold reciprocally is thought to be prior.’ (Cat., 12, 14a32-34) His examples are genera and species: ‘genera are always prior to species since they do not reciprocate as to implication of existence.’ (Cat., 13, 15a4-6) Τhus, if there is a fish, there is an animal, but if there is an animal, there is not necessarily a fish. 4) Generic versus non-generic attributes As the above discussions illustrates, not all attributes can be genera of their subjects. Thus, we ought to distinguish between generic and non-generic attributes of each subject. K. J. Spalding distinguishes between substantive and classificatory attributes, a distinction that, he believes, is absent from the Aristotelian logic. Classificatory attributes are those that originate and exist in class alone, and are generic like ‘human’ and ‘animal.’ These attributes do not belong to the individual as individual. For example, animal belongs to the Socrates not as Socrates but as man. Substantive attributes, on the other hand, are those that belong to Socrates as Socrates and not as a class. Attributes like sense attributes that originate independently of generic structure and ‘do not involve a necessary relation to or dependence on a class’ are substantive attributes. (shrink)

GAMETOGÊNESE -/- Emanuel Isaque Cordeiro da Silva Instituto Agronômico de Pernambuco Departamento de Zootecnia – UFRPE Embrapa Semiárido -/- • _____OBJETIVO -/- Os estudantes bem informados, estão a buscando conhecimento a todo momento. O estudante de Veterinária e Zootecnia, sabe que a Reprodução é uma área de primordial importância para sua carreira. Logo, o conhecimento da mesma torna-se indispensável. No primeiro trabalho da série fisiologia reprodutiva dos animais domésticos, foi abordado de forma clara, didática e objetiva os mecanismos de diferenciação (...) sexual dos embriões em desenvolvimento, quais os genes envolvidos nesse processo e tudo mais. Nesse segundo trabalho, a abordagem será teórica, mas também clara, sobre a formação primordial dos gametas femininos e masculinos, através da ovogênese nas fêmeas e a espermatogênese nos machos. Esse trabalho visa levar a importância do processo de formação dos gametas e a produção hormonal das gônadas, bem como o entendimento sobre as interações com o eixo hipotálamo-hipofisário. -/- •____INTRODUÇÃO -/- A reprodução sexual é um processo mediante a qual dois organismos da mesma espécie unem seu material genético para dar lugar a um organismo fixo com combinação única de genes; para isso, cada organismo produz células que contém a metade do material genético característico da espécie. Essas células haploides (1n) são denominadas gametas; ao combinar-se um gameta masculino com um feminino produz-se uma célula diploide (2n) (zigoto ou ovo) a partir da qual se forma o embrião. A grande maioria das espécies com reprodução sexual são anisogâmicas, o que significa que produzem dois tipos de gametas diferentes: os gametas masculinos são microscópios, móveis e produzem-se em grande quantidade, enquanto que os femininos são grandes, imóveis e produzem-se em menor quantidade. O tipo de gameta que um indivíduo produz é o que define seu sexo; sobre os animais o macho é o indivíduo que produz grandes quantidades de espermatozoides e a fêmea produz uma menor quantidade de óvulos, enquanto que nas plantas as gônadas masculinas são as produtoras pólen e as femininas produzem oosferas. Os gametas são diferentes do resto das células do organismo, as quais se chamam células somáticas; essas últimas são diploides porque contém dois pares de cromossomos, um par herdado do pai do indivíduo e o outro da mãe. As células somáticas, ademais, se dividem por mitose, ao qual os cromossomos se duplicam antes de cada divisão celular e cada uma das células filhas recebe um complemento diploide idêntico dos cromossomos, logo todas as células somáticas de um indivíduo possuem o mesmo material genético, embora cada tipo celular expresse diferentes combinações de genes. Em contraponto, os gametas são células haploides porque possuem somente um par de cromossomos e a metade do material genético característico da espécie. Cada um dos cromossomos em um gameta é resultado da recombinação dos genes contidos nos cromossomos paterno e materno do indivíduo que originam o gameta, e cada um destes possuem uma combinação única de genes. Os gametas se formam a partir das células germinais, que são células que em sua origem são diploides e elas de “comprometem” a manter-se como uma linha celular especial que em determinado momento sofrerá o processo de meiose para dar origem aos gametas haploides, sejam óvulos ou espermatozoides segundo o sexo do animal. Como descrito no trabalho sobre a diferenciação sexual, as células germinativas primordiais originam-se no epiblasto do embrião, e migram desde o saco vitelino até colonizar as cristas gonodais, onde, por sua vez, proliferam-se e se organizam junto com as células somáticas da gônada primitiva para formar o testículo ou o ovário. As células germinais masculinas e femininas tem a mesma origem embrionária. As gônadas indiferenciadas em um embrião possuem três tipos celulares: as células que dão origem aos gametas (ovogonia ou espermatogonia), as precursoras de células que nutrem os gametas em desenvolvimento (células da granulosa no ovário; células de Sertoli no testículo) e as precursoras de células que secretam hormônios sexuais (células da teca no ovário; células de Leydig no testículo). As células germinais são as únicas estruturas do organismo que têm a capacidade de dividir-se por meiose sofrendo uma redução no número de seus cromossomos, sendo responsável pela transmissão da carga genética aos descendentes. Em contraste, as células somáticas somente se dividem por mitose. A formação dos gametas compreende fases sequenciais de mitose, meiose e pós-meiose. Esses processos são altamente organizados e necessitam de um preciso e bem coordenado programa de expressão genética. Uma das características importantes da gametogênese é a redução cromossômica, que através da meiose, reduz pela metade o número de cromossomos e produz células distintas entre si, devido a trocas de material genético entre os pares de cromossomos provenientes do pai e da mãe, o que ocorre no processo de “crossing over” durante a primeira fase da meiose. A gametogênese é o processo mediante o qual as células germinais de cada sexo se multiplicam, dividem e diferenciam até formar os gametas. No caso da formação dos gametas masculinos o processo recebe o nome específico de espermatogênese, e para os gametas femininos é denominado como ovogênese. Embora os dois processos alcancem o objetivo comum de produção das células haploides, por onde compartilham algumas características, existem diferenças marcadas entre eles devido a necessidade de produzir um número muito distinto de gametas, de tamanho diferente, e com características de motilidade também distintas. -/- •___ESPERMATOGÊNESE -/- A espermatogênese é o processo mediante o qual se produz os gametas masculinos denominados espermatozoides. Durante a vida fetal as células germinais e as células somáticas do testículo em formação organizam-se em túbulos seminíferos que se derivam dos cordões sexuais primários e conformam a maior parte da medula do testículo. Na etapa fetal cada tubo seminífero é delimitado por uma membrana basal, recoberta na parte interior pelas células precursoras das células de Sertoli (um tipo de células somáticas). No exterior do túbulo localizam-se as células precursoras das células de Leydig ou intersticiais (figura 1), que também são células somáticas. Entre a membrana basal e as células de Sertoli encontram-se algumas células germinais denominadas espermatogonias de reserva A0 (denominadas gonócitos) que serão o único tipo de células germinais presentes no testículo enquanto o animal não alcançar a puberdade. As células de Sertoli estabelecem na região basal uniões oclusoras entre si, formando parte da barreira hemato-testicular. As espermatogonias A0 localizam-se por dentro da membrana basal do túbulo seminífero, embora fora da barreira hemato-testicular. Figura 1: fase neonatal. Nota-se a grande infiltração de tecido intersticial em quase 50% da seção originando que os túbulos sejam pequenos e redondos em sua maioria. O citoplasma e núcleo das células pré-Leydig são notadas claramente por essa ser uma espécie suína onde o tecido intersticial está claramente diferenciado. Hematoxilina-eosina (X 220.5). Fonte: Embrapa. -/- O número de células de Sertoli no testículo depende da influência do hormônio folículo estimulante (FSH) presente durante a vida fetal e as primeiras etapas de vida pós-natal. A população de células de Sertoli ao chegar a puberdade se manterá fixa durante o resto da vida do animal; existe uma relação positiva entre o tamanho e a população de células de Sertoli e a capacidade de produção de espermatozoides do testículo. As células de Sertoli são as únicas células somáticas que estão no epitélio seminífero, e sua função é a nutrição, sustentação e controle endócrino das células germinais. As células de Sertoli participam ativamente no processo de liberação dos espermatozoides para a luz do túbulo. Nesse momento, as células de Sertoli realizam a fagocitose de parte do citoplasma do espermatozoide dos chamados corpos residuais. As células de Sertoli também fagocitam as células germinais que se degeneram no curso normal da espermatogênese. Essas células ainda sintetizam grande quantidade de proteínas, como por exemplo as proteínas ABP (androgen hinding protein), que transportam andrógenos para todo o aparelho reprodutivo, transferrinas, que transportam ferro para a respiração celular das células germinais e também às inibinas, que regulam a liberação de FSH pela hipófise, através de um sistema de retroalimentação (feedback) negativa (figura 2). Figura 2: epitélio seminífero, células de Sertoli (flecha) (400 X). Fonte: Embrapa. -/- Antes da puberdade dos túbulos seminíferos observam-se ao corte como estruturas de diâmetro pequeno, sem luz, e conformados unicamente pelas células de Sertoli e espermatogonias de reserva e rodeados por abundante tecido intersticial, ao que estão presentes as células precursoras das células de Leydig. Ainda antes da puberdade, a diferenciação celular manifesta-se primeiro pela presença de espermatócitos primários, os quais se degeneram em geral na fase de paquíteno, por falta de estimulação hormonal. A partir de que o animal chega a puberdade inicia-se o processo de espermatogênese, que se manterá durante toda a vida do animal, exceto em espécies de animais silvestres muito estacionais, ao qual pode se suspender durante a época não reprodutiva para voltar e ser retomada na época ou estação reprodutiva. Depois da puberdade, os túbulos seminíferos possuem um diâmetro muito maior; em seu interior observa-se um grande número de células germinais de todos os tipos, diferentes estádios de divisão, e em seu lúmen contém líquido e espermatozoides. Ainda sobre o alcancei da puberdade, as espermatogonias começam a dividir-se aceleradamente por mitose, enquanto que no espaço intersticial as células mesenquimais também começam a se diferenciar e a dar origem as células de Leydig (figura 3). A partir dessa etapa as células de Leydig (totalmente diferenciadas) são também evidentes no exterior do túbulo, junto com as células mioides ou peritubulares que o rodeiam o que ao contrair-se são responsáveis por controlar o avanço dos fluidos e as células presentes no lúmen do túbulo. As células mioides estão situadas ao redor do túbulo, e é creditado a elas a promoção da contração e da integridade estrutural do túbulo. Esse tipo celular apenas se diferencia na puberdade pela ação dos andrógenos (figura 4). As interações entre as células de Sertoli e as mioides parecem ter um papel importante na manutenção das funções do testículo. Durante o processo de espermatogênese, as espermatogonias de reserva dividem-se periodicamente e enquanto algumas células fixas permanecem como espermatogonias de reserva, outras proliferam e sofrem uma seção de divisões mitóticas durante as quais se vão diferenciando até formarem espermatócitos primários (espermatocitogênese ou fase de mitose), logo sofrem divisões especiais mediante as quais reduzem seu número de cromossomos (fase de meiose), e ao final trocam de forma para converter-se em espermatozoides (espermatocitogênese) (figura 5). Cada uma dessas etapas da espermato- gênese será descrito detalhadamente adiante, antes é necessário a explicação de algumas características das células de Sertoli e de Leydig que ajudarão a entender seu papel durante a espermatogênese. Figura 3: células de Leydig no espaço intersticial do testículo bovino adulto PAS (400 X). Fonte: Embrapa. -/- Figura 4: o estabelecimento da puberdade pela presença de espermatozoides no túbulo. Hematoxilina-eosina (400 X). Fonte: Embrapa. Figura 5: fases mitóticas das espermatogonias (A0 e B) para formação de um espermatócito primário e as duas fases de meiose que se sucedem antes da espermatogênese. Fonte: ZARCO, 2018. -/- Ao início da espermatocitogênese as uniões oclusoras entre as células de Sertoli se abrem por etapas (como as comportas de um submarino) para permitir a passagem das espermatogonias em direção ao centro do túbulo seminífero sem que se estabeleça uma continuidade entre o exterior e o interior da barreira hemato-testicular. Uma vez ultrapassada essa barreira, as sucessivas gerações de espermatogonias, espermatócitos, espermátides e espermatozoides irão se localizar em direção ao interior do túbulo seminífero, em estreita associação com as células de Sertoli. Em consequência, as células de Sertoli dividem o túbulo seminífero em dois compartimentos; o compartimento basal (debaixo das uniões oclusoras das células de Sertoli), ao qual residem as espermatogonias de reserva, e o compartimento adluminal (em direção ao centro do túbulo), cujos espaços entre as células de Sertoli desenvolvem o resto do processo de espermatogênese (meiose e espermatocitogênese). Esse feito é importante porque durante a vida fetal as únicas células germinais existentes eram as espermatogonias de reserva, pelo que os antígenos expressados por gerações mais avançadas (espermatogonias intermediárias, secundárias, espermátides e espermatozoides) não são reconhecidos como próprios do corpo pelo sistema imunológico. Logo, o anterior implica que deve existir uma barreira entre eles e o sangue para evitar um ataque imunológico. Em todas as etapas da espermatogênese, as células de Sertoli atuam como células de suporte para as células germinais, que sempre permanecem recoberta pela membrana das células de Sertoli. Também atuam como células nutricionais já que proporcionam o meio em que as células germinais se desenvolvem e maturam, assim como as substâncias que regulam e sincronizam as sucessivas divisões e transformações das células germinais. As células de Sertoli produzem hormônios, como estrógenos e inibina que atuam sobre a hipófise para regular a secreção das gonadotropinas que controlam a espermatogênese. As células de Leydig que residem no exterior do túbulo seminífero também são importantes para a espermatogênese: produzem a testosterona que estimula e mantém a espermatogênese, bem como serve como substrato sobre o qual atua como aromatizador das células de Sertoli para transformá-las em estrógenos. Como supracitado, para seu estudo podemos dividir a espermatogênese em três fase: espermatocitogênese, meiose e espermiogênese (figura 6). Agora, serão descritas cada uma dessas etapas. Em algumas espécies, incluindo no homem, os macrófagos representam o segundo tipo celular intersticial mais numeroso no testículo, depois das células de Leydig. Os macrófagos e vários subtipos de linfócitos são identificados nós testículos de ovinos e ratos. Eles estão intimamente associados com as células de Leydig e atuam juntamente na regulação da esteroidogênese. Figura 6: fluxograma da espermatogênese. -/- Espermatocitogênese -/- A espermatocitogênese, também chamada de etapa proliferativa ou de mitose, consiste numa série de divisões mitóticas sofridas pelas células descendentes de uma espermatogonia de reserva. Uma vez que a célula se divide, abandona o estado de reserva e começa um processo de diferenciação. As espermatogonias de reserva (denominadas espermatogonias A0 na rata ou As nos humanos) são células que existem desde a vida fetal e que permanecem mitoticamente inativas durante a infância. Uma vez que alcançam a puberdade começam a dividir-se em intervalos regulares, e as células filhas podem permanecer como espermatogonias de reserva ou abandonar a reserva e ingressar na dita espermatocitogênese. Uma vez abandonada a reserva, as células filhas que vão se formando em cada divisão permanecem unidas por pontes citoplasmáticas, constituindo um clone que se divide sincronicamente. As células que se formam depois de cada divisão continuam sendo espermatogonias, porém cada geração é ligeiramente diferente da anterior. Na rata, por exemplo, as espermatogonias tipo A0 ao dividir-se originam espermatogonias do tipo A1, que em sucessivas divisões formam espermatogonias dos tipos A2, A3 e A4, as quais, por sua vez, sofrem outra mitose para formar espermatogonias intermediárias e uma mais para formar espermatogonias do tipo B. Essas últimas se diferenciam (sem se dividir) em espermatócitos primários, processo em que termina a fase de espermatocitogênese, que literalmente significa processo de geração de espermatócitos. As espermatogonias tipo A0 são a fonte para a contínua produção de gametas. A metade delas se dividem e formam células iguais (as chamadas células tronco) e a outra metade forma as espermatogonias A1, que sofre novas divisões mitóticas e formam os tipos 2, 3 e 4. O tipo A4 sofre mitose para formar a intermediária (A In), que por mitose, forma a tipo B (figura 6). Esses tipos de espermatogonias podem ser identificadas em evoluções histológicas de acordo com sua organização topográfica na membrana basal dos túbulos seminíferos ou mediante seu conteúdo de heterocromatina. Outra maneira de diferenciação se baseia em marcadores moleculares específicos que distinguem as espermatogonias tronco (A0) das demais, com os fins de isolamento, desenvolvimento in vitro e transplante. As tipo B passam por mitose para formarem os espermatócitos primários; estes iniciam a primeira etapa da meiose formando os espermatócitos secundários; na segunda etapa da divisão meiótica, cada espermatócito secundário se divide e formam as chamadas espermátides. Quando o testículo alcança seu desenvolvimento total, a meiose completa-se e as espermátides originadas se convertem em espermatozoides. Um dos maiores sinais característicos desse fenômeno é o alargamento das espermátides e sua migração em direção ao lúmen do túbulo seminífero (figuras 4, 7 e 8). Figura 7: espermatogonias marcadas por imuno-histoquímica, anticorpo monoclonal TGFa (400 x). Figura 8: fases de divisões meióticas (M), espermatócitos em paquíteno (PA) e espermatócitos secundários (ES). -/- Figura 9: estádio posterior a liberação dos espermatozoides na luz do túbulo. Hematoxilina-eosina (400 x). Mediante as seis divisões mitóticas que ocorrem durante a espermatocitogênese se forma potencialmente um clone de 64 espermatócitos primários a partir de cada espermatogonia A que ingressa sobre o processo. Não obstante, algumas células sofrem apoptose em cada uma das etapas do processo, ao qual o número real formado é menor. Em outras espécies produzem-se um transcurso similar de divisões mitóticas sucessivas durante a espermatocitogênese, embora a nomenclatura utilizada possa ser distinta, por exemplo nos bovinos as duas últimas divisões mitóticas dão origem as espermatogonias de tipo B1 e B2. -/- Meiose -/- Uma vez que as espermatogonias B se diferenciam em espermatócitos primários, esses iniciam a etapa de meiose, com uma nova divisão; desta vez a divisão é do tipo meiótica. Ao completar-se a primeira divisão meiótica (meiose I) se obtém os espermató-citos secundários, que ao sofrer a segunda divisão meiótica (meiose II) dão origem as espermátides. Vale salientar que a meiose é o processo mediante o qual reduz-se a metade do número de cromossomos, pelo que as espermátides que se obtém são células haploides (1n). Os espermatócitos secundários que se formam depois da primeira divisão meiótica contém a metade do número normal de cromossomos, porém a mesma quantidade de DNA já que cada cromossomo é duplo. As espermátides formadas na conclusão da segunda divisão meiótica (figura 7), por sua vez, contém a metade dos cromossomos, e esse já não são duplos, já que se trata de células 1n. Também deve-se enfatizar que durante a meiose é relevante o entrecruzamento dos cromossomos homólogos, pelo que cada espermátide possui uma combinação única e diferente de genes paternos e maternos. Outro ponto que deve ser levado em consideração é que cada espermátide somente possui um cromossomo sexual; a metade das espermátides contém o cromossomo X herdado da mãe do macho que está levando a cabo a espermatogênese e a outra metade contém o cromossomo Y herdado de seu pai. Para cada espermatócito primário que entra no processo de meiose obtém-se cerca de quatro espermátides, pelo qual ao ser completada a meiose potencialmente se poderiam formar até 256 espermátides por cada espermatogonia que abandona a reserva e ingressa na espermatocitogênese. -/- Espermiogênese -/- Durante a espermiogênese, também chamada de fase de diferenciação, as esper-mátides sofrem, sem se dividir, uma metamorfose que as transforma em espermatozoides, os quais finalmente são liberados das células de Sertoli em direção ao lúmen do túbulo seminífero. A espermiogênese é um processo complicado e longo já que a espermátide deve sofrer complexas trocas nucleares, citoplasmáticas e morfológicas que resultam na forma-ção dos espermatozoides. Algumas dessas mudanças incluem a condensação do material nuclear para formação de um núcleo plano e denso, a eliminação do citoplasma para a constituição de uma célula pequena, a formação de uma estrutura especializada denomi-nada acrossomo ou tampa cefálica, e a formação do pescoço e da cauda (flagelo) do esper-matozoide, do que depende a sua motilidade. Durante a maior parte da espermiogênese, as espermátides se mantém com uma estreita associação com as células de Sertoli; logo, chega-se a observar, então, flagelos que se projetam em direção a luz do túbulo que pare-cem sair das células de Sertoli, sendo na realidade os flagelos dos espermatozoides que ainda não tinham sido liberados pelo lúmen. Ao liberar os espermatozoides em direção a luz do túbulo, as células de Sertoli realizam a fagocitose de parte do citoplasma dos espermatozoides (corpos residuais). Também fagocitam os restos de todas as células germinais que sofrem apoptose ou degeneram-se durante a espermatogênese. Credita-se que ao realizar essas funções as células de Sertoli podem fazer uma monitoração eficiente da espermatogênese, o que lhes permitiria emitir sinais para colaborar na regulação desse processo em nível gonodal e a nível sistêmico através da secreção de hormônios como a inibina e o estradiol. Além da inibina e activina, as células de Sertoli sintetizam outras proteínas, como a ABP (proteína ligadora de andrógenos) que serve como uma molécula de transporte de andrógenos dentro dos túbulos seminíferos, ductos deferentes e epidídimo, ou a transfer-rina, que transporta o ferro necessário para a respiração celular. -/- Resultados da espermatogênese -/- O resultado da espermatogênese não significa apenas uma simples multiplicação das células germinais (até 256 espermatozoides a partir de cada espermatogonia A1), senão que através dela são produzidos gametas haploides pequenos, móveis e com grande diversidade genética entre eles, ao mesmo tempo que se mantêm uma reversa de células mãe (espermatogonias A0) a partir das quais se poderiam originar novos ciclos de esper-matogênese durante o resto da vida do animal. -/- Controle hormonal da espermatogênese -/- Como mencionado, o FSH reproduz um importante papel para o estabelecimento das células de Sertoli durante a vida fetal e início da vida pós-natal. O começo da esper-matogênese também é estimulado pelo FSH, que atua sobre as células de Sertoli para estimular sua função e a ativação de sinais dessas células em direção as células germinais, incluindo-as a abandonar a reserva e ingressar na espermatogênese. O FSH, assim mesmo, estimula a mitose durante o resto da espermatogênese e aumenta a eficiência do processo, já que reduz a apoptose e a degeneração de espermatogonias intermediárias e do tipo B. O FSH também estimula as células de Sertoli para produzirem inibina e ABP. Uma vez iniciada a espermatogênese somente requerem níveis baixos de FSH para se mantê-la. As células de Sertoli também devem ser estimuladas pela testosterona para funcio-nar de maneira adequada; se requer também do LH hipofisário: hormônio que estimula as células de Leydig para produzir testosterona. Por sua vez, a secreção de LH e FSH é regulada pelo GnRH hipotalâmico: esse neurohormônio também faz parte do mecanismo de regulação da espermatogênese. A espermatogênese também é modulada em nível local mediante a produção de determinados fatores e interações entre as células. Dentro dos fatores locais podemos mencionar o fator de crescimento parecido com a insulina 1 (IGF-1), o fator de crescimen-to transformante beta (TGF- β), activina, ocitocina e diversas citocinas. Entre as intera-ções celulares existem tanto uniões de comunicação entre as células de Sertoli e as células germinais, como pontes citoplasmáticas entre todas as células germinais que formam o clone de células descendentes de uma espermatogonia A1. Uma vez que as células de Sertoli iniciam sua função na puberdade é possível manter experimentalmente a espermatogênese somente com testosterona, sem ser requeri-dos nenhum outro hormônio. A quantidade de espermatozoides produzidos, no entanto, é maior quando há presença do FSH. Abaixo do estímulo do FSH as células de Sertoli produzem estradiol e inibina, hormônios que geram uma retroalimentação sobre o eixo hipotálamo-hipofisário para a regulação da secreção de gonadotropinas. Em particular, a inibina reduz a secreção de FSH, pelo qual é factível que sirva como um sinal que evite uma excessiva estimulação as células de Sertoli. -/- Ciclo do epitélio seminífero -/- Em cada espécie as espermatogonias de reserva iniciam um novo processo de divi-sões celulares em intervalos fixos: a casa 14 dias no touro; 12 dias no garanhão e a cada 9 dias no cachaço (reprodutor suíno). A nova geração de células que começam a proliferar sobre a base do tubo deslocam-se em direção ao centro do túbulo a geração anterior, que por sua vez deslocam-se as gerações anteriores. Devido as mudanças que vão sofrendo cada geração celular se ajustam a tempos característicos de cada etapa, já que rodas as células em uma determinada seção do túbulo estão sincronizadas entre si pelas células de Sertoli; em cada espécie somente é possível encontrar um certo número de combinações celulares: 14 diferentes combinações no caso da rata, 8 no touro e 6 no ser humano. A sucessão de possíveis combinações até regressar a primeira combinação se conhece como o ciclo do epitélio seminífero. Na maioria das espécies os espermatozoides que são libera-dos em direção a luz do túbulo provém das células que entraram no processo de esperma-togênese quatro gerações antes que a geração que está ingressando nesse momento, pelo que a espermatogênese no touro dura ao redor de 60 dias e um pouco menos em outras espécies domésticas. Significa que os efeitos negativos das alterações na espermatogêne-se podem estar presentes até dois meses depois de que se produziram essas alterações. Como supracitado, geralmente se observa a mesma combinação celular em toda a área de uma determinada secção transversal do túbulo seminífero. No entanto, se fizermos uma série de secções, observa-se que ao longo do túbulo há uma sucessão ordenada de combinações (a primeira em uma determinada secção; a segunda combinação na seguinte secção, e assim sucessivamente em secções subsequentes até regressar a primeira combi-nação. Teremos, então, que ao início da divisão das espermatogonias A1 se produz de forma sincronizada em uma secção do túbulo, e vai-se transmitindo como uma onda peristáltica as secções adjacentes. Esse processo é denominado como onda do epitélio seminífero e graças à esse túbulo seminífero sempre tem secções em todas as etapas da espermatogênese, com o que se alcança uma produção constante de espermatozoides. -/- Alterações da espermatogênese -/- Nas espécies estacionais a espermatogênese, como já mencionado, pode reduzir-se ou inclusive suspender sua atividade fisiológica durante a época não reprodutiva dessas espécimes, porém esse processo fisiológico não pode ser considerado como uma altera-ção. No entanto, a espermatogênese só pode ser alterada pelas enfermidades ou por fatores externos. A principal causa de alterações na espermatogênese é o aumento da temperatura testicular. Por isso, os testículos são localizados na saco escrotal e são “caídos” para fora do corpo como pode-se observar nos bovinos, caprinos, ovinos, caninos e no próprio homem. A temperatura testicular deve estar cerca de 2 a 6 °C abaixo da temperatura corporal normal. As células germinais masculinas são sensíveis ao calor, pelo qual na maioria dos mamíferos os testículos se encontram fora da cavidade abdominal e existe um sofisticado sistema de termorregulação para mantê-los a uma temperatura menor que a corporal. Se a temperatura corporal for elevada ou se os testículos permanecerem na cavidade abdominal, ou ainda se os sistemas termorreguladores do testículo sejam afetados por fatores inflamatórios como edema ou falta de mobilidade testicular dentro do escroto, a temperatura do tecido testicular aumentará e a espermatogênese sofrerá alterações proporcionais ao excesso de temperatura e a duração da elevação. A espermatogênese também pode ser afetada pela exposição a hormônios ou a outras substâncias. É possível que a causa mais comum (sobretudo no homem) seja o uso de esteroides anabólicos, que elevam a concentração de andrógenos na circulação, provo-cando um feedback negativo sobre a secreção de gonadotropinas. Ao deixar de estimular-se o testículo pelas gonadotropinas, este deixará de produzir testosterona, e as concentra-ções de andrógeno exógeno nunca alcançará as altíssimas concentrações de testosterona que normalmente estão presentes a nível do tecido testicular por ser o local onde se produz o hormônio. Também se supõe que diversas substâncias com propriedades estrogênicas derivadas de processos industriais (indústria dos plásticos, hidrocarbonetos etc.) e presentes no ambiente (fatores xenobióticos) podem ser responsáveis pelas alterações na espermatogênese em diversas espécies, entre as quais se inclui o ser humano. -/- • OVOGÊNESE E FOLICULOGÊNESE -/- A ovogênese é o processo seguido pelas células germinais da fêmea para a forma-ção dos óvulos, que são células haploides. Durante a vida fetal as células germinais proliferam-se no ovário por mitose, formando um grande número de ovogonias, algumas das quais se diferenciam em ovócitos primários que iniciam sua primeira divisão meiótica para deter-se na prófase da divisão. Somente alguns desses ovócitos primários retornarão e concluirão a primeira divisão meiótica em algum momento da vida adulta do animal, dando origem a um ovócito secundário e a um corpo polar. O ovócito secundário inicia a sua segunda divisão meiótica, a qual volta a ficar suspensa até receber um estímulo apropriado, já que somente os ovócitos secundários que são ovulados e penetrados por um espermatozoide retornam e concluem a segunda divisão meiótica, dando origem a um óvulo (figura 10). O processo de ovogênese é realizado dentro dos folículos ovarianos, que também tem que sofrer um longo transcurso de desenvolvimento e diferenciação denominado foliculogênese pelo que a ovogênese como tal realiza-se dentro do marco desse último processo. Por essa razão, na seguinte seção descreverei tanto a ovogênese como a folicu-logênese, e a relação que existe entre ambos. Figura 10: representação da ovogênese. Na etapa de proliferação, as células germinais se diferen-ciam por mitose. A meiose I se caracteriza por uma prófase prolongada, ocorrendo a duplicação do DNA. Nas duas divisões, que ocorrem antes da ovulação e depois da fertilização, a quantidade de DNA é reduzida a 1n, com o fim de que a fusão dos pronúcles (singamia) pós-fertilização, seja gerado um zigoto com um número de cromossomos de 2n (diploide). -/- Geração de ovócitos primários e folículos primordiais Tanto a ovogênese como a foliculogênese iniciam-se durante a vida fetal, quando as células germinais primordiais provenientes do saco vitelino colonizam a gônada primitiva e, junto com as células somáticas z organizam-se para a formação dos cordões sexuais secundários, que se desenvolvem principalmente no córtex do ovário. Nesse período, as células germinais que colonizaram o ovário sofrem até 30 divisões mitóticas, proliferando-se até formar milhares ou milhões de ovogonias, que inicialmente formam “ninhos” constituídos cada um deles por um clone de várias ovogonias que descendem da mesma célula precursora e que se mantêm unidas por pontes citoplasmáticas, sincronizan-do suas divisões mitóticas. Nessa etapa alcança-se a máxima população de células germinais no ovário, que antes de nascer se reduzirá drasticamente por apoptose. No ovário do feto humano chegam a haver até sete milhões de células germinais que ao nascimento se reduzem a dois milhões. Os ovários fetais do bovino, de maneira análoga, chegam a ter até 2.100.000 células germinais, que ao nascimento reduzem para 130.000 aproximadamente. A redução no número de ovogonias produz-se ao mesmo tempo que essas células, que vêm dividindo-se por mitose e estão agrupadas em ninhos, iniciam sua primeira divisão meiótica para se transformarem em ovócitos primários: células germinais que se encontram em uma etapa de suspensão (diplóteno) da prófase da primeira divisão meiótica. Nesse período produz-se uma grande proporção de células germinais; as células somáticas dos cordões sexuais, por sua vez, emitem projeções citoplasmáticas que separam a isolam os ovócitos primários sobreviventes, ficando cada um deles rodeados por uma capa de células aplanadas da (pré) granulosa. Ao mesmo tempo em que se forma uma membrana basal entre as células da granulosa e o tecido intersticial do ovário. Ao ovócito primário rodeado de uma capa de células da (pré) granulosa aplanadas e delimita-das por uma membrana basal denomina-se de folículo primordial (figura 11). Nas vacas os folículos primordiais bem formados já estão presentes nos ovários a partir do dia 90 da gestação. A maioria dos folículos primordiais com os que nasce uma fêmea se manterão inativos durante um longo tempo; muitos deles durante toda a vida do animal. Nos folículos primordiais inativos tanto os ovócitos primários como as células da granulosa conservam sua forma original e mantém um metabolismo reduzido estritamente ao mínimo necessário para manter-se viáveis. Por essa razão, ao realizar um corte histológico de qualquer ovário as estruturas mais numerosas que se observam serão os folículos primordiais. No entanto, cada dia da vida de um animal, inclusive desde a vida fetal, um certo número de folículos primordiais reiniciam seu desenvolvimento, e a partir desse momento um folículo exclusivamente pode ter dois destinos: o primeiro, prosseguir seu desenvolvi-mento até chegar a ovular, e o segundo (que é muito mais frequente) encontrar em algum momento condições inadequadas que fazem fronteira com ele para parar seu desenvolvi-mento, levando-o a sofrer atresia e degenerar até desaparecer do ovário. Figura 11: sequência da foliculogênese apresentando as diferentes estruturas que podemos encontrar em cada fase. Fonte: ZARCO, 2018. Culminação da ovogênese A ovogênese somente se completará quando um ovócito primário reinicia a meio-se; completa sua primeira divisão meiótica para formar um ovócito secundário e um primeiro corpo polar e, quando, finalmente sofrer uma segunda divisão meiótica para formar um óvulo e um segundo corpo polar. Os óvulos são as células 1n que constituem os gametas femininos, pouco numerosos, grandes e imóveis. A grande maioria dos ovóci-tos primários, como veremos mais adiante, nunca retomam a meiose e, em consequência, não chegam a formar ovócitos secundários, e muitos dos ovócitos secundários tampouco sofrem uma segunda divisão meiótica, pelo que não chegam a formar os óvulos. Ao longo da vida de uma fêmea, na maioria das espécies, menos de 0,1% dos ovócitos primários (um a cada mil) chega a terminar a ovogênese, dando origem a um óvulo. O supracitado deve-se a que a ovogênese somente pode retomar-se e ser completa-da em ovócitos primários que se encontram dentro dos folículos primordiais que (uma vez ativados) vão alcançando diversas etapas de seu desenvolvimento em momentos precisos aos que encontram as condições ideais de oxigenação, nutrição, vascularização e exposição a fatores parácrinos e a exposição a concentrações de hormônios que se requerem para que o folículo continue em cada etapa de seu desenvolvimento com o processo de foliculogênese até chegar a ovular. Qualquer folículo que não esteja nessas condições ao longo do desenvolvimento sofrerá degeneração e atresia, pelo que o ovócito primário em seu interior nunca chegará ao ponto em que pode retomar a primeira divisão meiótica. No que resta da presente seção revisaremos o processo de foliculogênese em cujo marco se desenvolve a ovogênese; havemos que tomar de conta que essa última se limita ao que ocorre nas células germinais (ovogonia, ovócito primário, secundário e óvulo), pelo qual depende intimamente do desenvolvimento do folículo de que essas células formam parte. Em um princípio a ativação do folículo primordial e o desenvolvimento folicular são independentes das gonadotropinas: não se conhecem os mecanismos precisos median-te os quais um folículo primordial se ativa e reinicia seu desenvolvimento, nem como se decide quais folículos, dentre as dezenas de milhares de ou centenas de milhares presentes em um ovário se reativarão em um dia em particular. A reativação trata-se de uma liberação de influência de fatores inibidores, já que os folículos primordiais se reativam espontaneamente quando cultivados in vitro, isolados do resto do tecido ovariano. Uma vez que um folículo primordial se ativa, inicia-se um longo processo de desenvolvimento que somente depois de vários meses (ao redor de cinco meses no caso dos bovinos) o levará a um estádio em que seu desenvolvimento posterior requer a presença das gonado-tropinas; daí que se diz que as primeiras etapas do desenvolvimento são independentes das gonadotropinas. Durante a fase independente de gonadotropinas, um folículo primordial que tenha sido ativado e tenha começado a crescer; passará primeiro para a etapa de folículo primá-rio, caracterizada por conter um ovócito primário que está rodeado, por sua vez, por uma capa de células da granulosa, que não são planas, e sim cúbicas. Depois, se o folículo continuar crescendo se transformará em um folículo secundário, ao qual as células da granulosa começam a proliferar (aumentando em número) e se organizam em duas ou mais capas que rodeiam o ovócito primário. Entre o ovócito e as células da granulosa que o rodeiam se forma nesta uma zona pelúcida; ainda assim o ovócito mantém contato direto com essas células, mediante o estabelecimento de pontes citoplasmáticas que atravessam a zona pelúcida. Através dessas pontes citoplasmáticas as células da granulosa podem passar nutrientes e informação ao ovócito primário. O volume e o diâmetro do ovócito primário aumentam ao mesmo tempo que as células da granulosa proliferam-se, para incrementar as capas ao redor do ovócito. De maneira gradual o citoplasma do ovócito primário aumenta até 50 vezes seu volume e a proliferação das células continua. Esses folículos que possuem cada vez mais células e portanto mais capas de células da granulosa se denominam folículos secundários. Para evitar confusões, há a necessidade de nomen-clatura ao qual o folículo vá mudando de nome de primordial a primário e logo, de secun-dário, a terciário, por sua vez, o ovócito que encontra-se em seu interior, a todo momento, segue sendo um ovócito primário. Durante a etapa dependente de gonadotropinas, os folículos secundários começam a formar um espaço cheio de líquido, o antro folicular, desse modo se convertem em folí-culos terciários. Com a utilização de outra nomenclatura, a formação do antro marca a transição entre folículos pré-antrais (sem antro) e folículos antrais (com antro). Em algum momento dessa transição entre folículo secundário e terciário, também aparece a depen-dência de folículos em direção as gonadotropinas, pelo qual somente podem seguir crescendo na presença do hormônio luteinizante (LH) e do hormônio folículo estimulante (FSH). Nos bovinos e em outras espécies (para seu estudo), os folículos antrais são dividi-dos em pequenos, médios e grandes. Embora todos eles possuam um antro folicular, dependendo do seu grau de desenvolvimento requerem diferentes concentrações de gona-dotropinas para continuar o crescimento. Os folículos antrais mais pequenos somente re-querem concentrações baixas de LH e FSH, pelo qual podem continuar crescendo em qualquer momento do ciclo estral inclusive em animais que não estão ciclando (fêmeas em anestro pré-puberal, gestacional, lactacional, estacional). Nas etapas posteriores os folículos antrais requerem primeiro concentrações elevadas de FSH, e nas etapas finais somente podem continuar crescendo na presença de pulsos frequentes de LH, pelo qual somente os folículos que encontram-se sob concentrações apropriadas desses hormônios podem seguir crescendo. Por essa razão, nos animais que se encontram em anestro de qualquer tipo somente é possível encontrar folículos antrais pequenos ou médios, segundo a espécie, e nos animais que se encontram ciclando (estro) o maior tamanho folicular encontrado em um determinado dia do ciclo dependerá das concentrações de FSH e LH presentes nesse momento e nos dias anteriores. Um folículo que chega ao estado máximo de desenvolvimento, conhecido como folículo pré-ovulatório, ao final, somente chegará a ovular se for exposto a um pico pré-ovulatório de LH. Como supracitado, cada dia na vida de uma fêmea inicia seu desenvolvimento um certo número de folículos; a grande maioria sofrem atresia, mas depois da puberdade em cada dia do ciclo estral um ou vários folículos vão encontrando ao longo do seu desenvol-vimento concentrações hormonais que lhes permite chegar na etapa de folículo pré-ovula-tório. Somente nestes folículos, e como consequência de um pico pré-ovulatório de LH, se reinicia e completa-se a primeira divisão meiótica do ovócito primário, produzindo duas células distintas. Uma delas é o ovócito secundário, que retém praticamente todo o citoplasma. Contém, assim mesmo, em seu núcleo um par de cromossomos duplos, a outra é o primeiro corpo polar, que é exclusivamente um núcleo com uma quantidade mínima de citoplasma. Na maioria das espécies ovula-se um ovócito secundário que se encontra, então, suspendido na segunda divisão meiótica. Esta segunda divisão meiótica somente reinicia-rá e completarar-se uma vez que o espermatozoide começa a penetrar sob o ovócito secundário. Ao concluir-se a divisão se forma o segundo corpo polar e completa-se a ovogênese com o qual se obtém o óvulo, célula 1n que constitui o gameta feminino. No entanto, o óvulo existe pouco tempo como tal, já que em poucos minutos/horas (depen-dendo da espécie) se produzirá a fusão do núcleo do mesmo (pró-núcleo feminino) com o do espermatozoide (pró-núcleo masculino), com o qual se completa a fertilização e se forma um novo indivíduo (o ovo ou zigoto). -/- Ondas foliculares -/- Como mencionado supra, todos os dias um determinado número de folículos pri-mordiais se ativam e começam a crescer, os quais crescem em um ritmo característico em cada espécie. Isso provoca que em qualquer momento existam nos ovários folículos pri-mordiais (que começam a crescer em alguns dias ou semanas), assim como folículos secundários em diversas etapas do desenvolvimento, os quais iniciaram seu desenvolvi-mento em semanas ou inclusive meses (segundo o grau de desenvolvimento atual). Também em qualquer momento poderá haver folículos antrais nas etapas iniciais de seu desenvolvimento (com antros que já se podem detectar em cortes histológicos mas não são visíveis macroscopicamente). Todos esses folículos chegaram até seu estado de de-senvolvimento atual (primário, secundário ou antral pequeno), independente da etapa do ciclo estral em que sejam observados ou encontrados. Nos bovinos, os folículos que chegam ao início da etapa antral iniciaram seu desenvolvimento cinco meses antes, e todavia requerem ao redor de 42 dias para chegar ao estado pré-ovulatório. Para continuar seu desenvolvimento, os folículos antrais pequenos devem encon-trar concentrações altas de FSH, que os estimulam para prosseguir o crescimento. Cada vez que se produz uma elevação nas concentrações de FSH, esse hormônio estimula o desenvolvimento de um grupo de folículos antrais pequenos, que começaram a crescer muito tempo antes e que o dia da elevação de FSH tenha alcançado o grau de desenvolvi-mento preciso para responder com eficiência a este hormônio, o qual atuará através de seus receptores nas células da granulosa para estimular a produção de estradiol, a secreção de inibina, a produção de líquido folicular e a proliferação das células da granulosa. Um grupo de folículos antrais pequenos é assim recrutado pelo FSH para acelerar seu cresci-mento e aumentar sua produção de estradiol e inibina (figura 12). Mediante um seguimento ultrassonográfico dos ovários é possível identificar pou-cos dias depois um certo número de folículos, que por haver sido recrutados começam um período de crescimento acelerado. Durante alguns dias vários folículos crescem juntos, porém depois um deles é selecionado para continuar crescendo, enquanto que o restante do grupo deixam de fazê-lo e terminam sofrendo atresia. Através da ultrassom é possível identificar o folículo selecionado, agora chamado folículo domi-nante, já que sua trajetória de crescimento sofre um desvio com respeito a seguida pelo restante do grupo. Os folículos que não foram selecionados deixam de crescer e sofrem atresia já que deixam de possuir o suporte gonadotrópico de FSH, uma vez que as concentrações desse hormônio são suprimidos pela inibina e o estradiol produzidos pelo conjunto de folículos que conformam a onda folicular (figura 12), porém o folículo mais desenvolvido do grupo se converterá em dominante. A inibina atua diretamente a nível hipofisário para reduzir a secreção de FSH. Figura 12: onda folicular e relação dos níveis de FSH, estradiol e LH. Fonte: ZARCO, 2018. -/- Figura 13: Recrutamento, seleção e dominação folicular na espécie ovina e influência do FSH e LH nas fases. Fonte: SILVA, E. I. C. da, 2019. -/- A razão pela qual o folículo dominante é capaz de continuar seu desenvolvimento apesar da baixa nas concentrações de FSH é que o folículo é o único que alcançou o grau de progresso necessário para que apareçam os receptores para LH em suas células da granulosa. Esse processo permite ao folículo dominante ser estimulado pela LH, e que requeira baixas concentrações de FSH para manter seu desenvolvimento. A secreção de LH em forma de pulsos de baixa frequência (um pulso a cada quatro a seis horas), característica da fase lútea do ciclo estral; é suficiente para permitir que um folículo dominante continue crescendo por mais dias depois da sua seleção e que mais tarde mantenha-se viável durante alguns dias embora não aumentem de tamanho. Contu-do, se durante o período viável desse folículo não seja finalizada a fase lútea e não diminuam as concentrações de progesterona, o folículo terminará sofrendo atresia devido a exigência de um padrão de secreção acelerada de LH (aproximadamente um pulso por hora) durante o desenvolvimento pré-ovulatório, que somente pode ser produzido com a ausência da progesterona. Uma vez que um folículo dominante sofre atresia deixa de produzir inibina, pelo qual as concentrações de FSH podem elevar-se novamente para iniciar o recrutamento de outro grupo de folículos a partir da qual se origina uma nova onda folicular. Durante o ciclo estral de uma vaca podem gerar-se dois ou três ondas foliculares; somente em raros casos quatro. A etapa de dominância folicular da primeira onda na grande maioria dos casos não coincide com a regressão do corpo lúteo, pelo qual o primei-ro folículo dominante quase invariavelmente termina em atresia. Em algumas vacas o fo-lículo dominante da segunda onda ainda está viável quando se produz a regressão do corpo lúteo e acelera-se a secreção de LH, pelo qual esse segundo folículo dominante se converte em folículo pré-ovulatório e, ao final ovula. Em outros animais o segundo folícu-lo dominante também perde a sua viabilidade antes da regressão do corpo lúteo, por onde nesses animais se inicia uma terceira onda folicular, da qual surge o folículo que finalmen-te ovulará depois de produzir-se a regressão do corpo lúteo. Sem importar a onda em que se origine, uma vez que um folículo dominante é ex-posto a alta frequência de secreção de LH que se produz depois da regressão do corpo lúteo, aumenta ainda mais sua secreção de estradiol até que as altas concentrações desse hormônio comecem a exercer um feedback positivo para a secreção do LH. Isso provoca-rá a aceleração da frequência de secreção do LH até que os pulsos são tão frequentes que começam a ficar por cima e produzir-se o pico pré-ovulatório de LH, que é responsável pela realização da ovulação e a maturação final do ovócito. -/- •___DIFERENÇAS ENTRE ESPERMATOGÊNESE E OVOGÊNESE -/- Enquanto que na fêmea a ovogênese inicia-se durante a vida fetal, no macho a es-permatogênese começa na puberdade. Na fêmea, a partir de um ovócito primário se origi-na um óvulo; no macho, de um espermatócito primário se produzem, teoricamente, quatro espermatozoides. Outra característica interessante é que enquanto a fêmea já conta desde o nasci-mento com todos os ovócitos que necessitará na vida adulta, o macho necessitará chegar a puberdade para iniciar o desenvolvimento das células sexuais, já que ao nascer somente possui gonócitos precursores das células germinais, células de Sertoli e intersticiais. Na vida adulta de uma fêmea, o número de células germinais desaparece paulati-namente. Uma vez iniciada a espermatogênese no macho, a cada ciclo do epitélio seminí-fero as células germinais são renovadas mantendo a provisão para toda a vida reprodutiva. Na fêmea, a meiose sofre duas interrupções em seu transcurso, e no macho é ininterrupta. Figura 14: representação em diagramação comparativa do desenvolvimento da gametogênese. -/- Principais pontos abordados sobre as diferenças entre a gametogênese masculina e feminina: ❙ Na ovogênese a meiose contêm-se em duas ocasiões esperando acontecimentos externos para prosseguir. Já na espermatogênese não existe a suspensão da meiose. ❙ A espermatogênese é um processo contínuo, enquanto que a ovogênese pode completar exclusivamente um óvulo em cada ciclo estral; já que só pode ser completada por mais de um nas espécies que ovulam vários ovócitos no caso das porcas, cadelas, gatas etc. ❙ Na espermatogênese existem células de reserva que permitem a continuação du-rante toda a vida, enquanto que na ovogênese o número de ovócitos primários é limitado. A fêmea somente conta com os que nasceu, e eles não se dividem. ❙ Na espermatogênese obtém-se até 256 espermatozoides para cada espermatogo-nia que inicia o processo, enquanto que na ovogênese somente se obtém um óvulo a partir de cada ovócito primário. ❙ Durante a espermatogênese se produz uma metamorfose que transforma as es-permátides em espermatozoides. Na ovogênese não ocorre um processo análogo. ❙ Na espermatogênese, durante a meiose produzem-se quatro espermátides a partir de cada espermatócito primário. Na ovogênese se produz somente um óvulo a partir de cada ovócito primário; produz, ademais, dois corpos polares. ❙ Todos os óvulos que se produzem durante a ovogênese contém um cromossomo X, enquanto que a metade dos espermatozoides possuem um cromossomo Y e a outra metade um cromossomo X. ❙ Na espermatogênese produzem-se centenas ou dezenas de milhões de esperma-tozoides por dia, enquanto que na ovogênese se produz um ou alguns óvulos a cada ciclo estral. ❙ A espermatogênese produz gametas macroscópicos e com motilidade própria, enquanto que a ovogênese produz gametas grandes e imóveis. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ABDEL-RAOUF, Mohammed et al. The postnatal development of the reproductive organs in bullswith special reference to puberty.(Including growth of the hypophysis and the adrenals). Acta endocrinologica, n. Suppl No. 49, 1960. ADONA, Paulo Roberto et al. Ovogênese e foliculogênese em mamíferos. Journal of Health Sciences, v. 15, n. 3, 2013. AERTS, J. M. J.; BOLS, P. E. J. Ovarian follicular dynamics: a review with emphasis on the bovine species. Part I: Folliculogenesis and pre‐antral follicle development. Reproduction in domestic animals, v. 45, n. 1, p. 171-179, 2010. AERTS, J. M. J.; BOLS, P. E. J. Ovarian follicular dynamics. A review with emphasis on the bovine species. Part II: Antral development, exogenous influence and future prospects. Reproduction in domestic animals, v. 45, n. 1, p. 180-187, 2010. ALBERTINI, David F.; CARABATSOS, Mary Jo. Comparative aspects of meiotic cell cycle control in mammals. Journal of molecular medicine, v. 76, n. 12, p. 795-799, 1998. AUSTIN, Colin Russell; SHORT, R. Reproduction in mammals. Cambridge, 1972. BAKER, T. G. Oogenesis and ovulation. In. Reproduction in Mammals I Germ Cells and Fertilization, p. 29-30, 1972. BEARDEN, Henry Joe et al. Reproducción animal aplicada. México: Manual Moderno, 1982. BIGGERS, John D.; SCHUETZ, Allen W. Oogenesis. University Park Press, 1972. BINELLI, Mario; MURPHY, Bruce D. Coordinated regulation of follicle development by germ and somatic cells. Reproduction, Fertility and Development, v. 22, n. 1, p. 1-12, 2009. CHIARINI-GARCIA, Helio; RUSSELL, Lonnie D. High-resolution light microscopic characterization of mouse spermatogonia. Biology of reproduction, v. 65, n. 4, p. 1170-1178, 2001. CHOUDARY, J. B.; GIER, H. T.; MARION, G. B. Cyclic changes in bovine vesicular follicles. Journal of animal science, v. 27, n. 2, p. 468-471, 1968. CLERMONT, Yves; PEREY, Bernard. Quantitative study of the cell population of the seminiferous tubules in immature rats. American Journal of Anatomy, v. 100, n. 2, p. 241-267, 1957. COSTA, DEILER SAMPAIO; PAULA, T. A. R. Espermatogênese em mamíferos. Scientia, v. 4, 2003. CUNNINGHAM, James. Tratado de fisiologia veterinária. Elsevier Health Sciences, 2011. CUPPS, Perry T. (Ed.). Reproduction in domestic animals. Elsevier, 1991. DA SILVA, Emanuel Isaque Cordeiro. Fisiologia Clínica do Ciclo Estral de Vacas Leiteiras: Desenvolvimento Folicular, Corpo Lúteo e Etapas do Estro. 2020. Acervo pessoal. DA SILVA, Emanuel Isaque Cordeiro. Fisiologia da Reprodução Animal: Ovulação, Controle e Sincronização do Cio. 2020. Acervo pessoal. DUKES, Henry Hugh; SWENSON, Melvin J.; REECE, William O. Dukes fisiologia dos animais domésticos. Editora Guanabara Koogan, 1996. EPIFANO, Olga; DEAN, Jurrien. Genetic control of early folliculogenesis in mice. Trends in Endocrinology & Metabolism, v. 13, n. 4, p. 169-173, 2002. ERICKSON, B. H. Development and senescence of the postnatal bovine ovary. Journal of animal science, v. 25, n. 3, p. 800-805, 1966. REFERÊNCIAS BIBLIOGRÁFICAS -/- FELDMAN, Edward C. et al. Canine and feline endocrinology-e-book. Elsevier health sciences, 2014. FUSCO, Giuseppe; MINELLI, Alessandro. The Biology of Reproduction. Cambridge University Press, 2019. GALINA-HIDALGO, Carlos Salvador. A study of the development of testicular function and an evaluation of testicular biopsy in farm animals. 1971. Tese de Doutorado. Royal Veterinary College (University of London). GALLICANO, G. Ian. Composition, regulation, and function of the cytoskeleton in mammalian eggs and embryos. Front Biosci, v. 6, p. D1089-1108, 2001. GILBERT, Scott F. Biología del desarrollo. Ed. Médica Panamericana, 2005. GNESSI, Lucio; FABBRI, Andrea; SPERA, Giovanni. Gonadal peptides as mediators of development and functional control of the testis: an integrated system with hormones and local environment. Endocrine reviews, v. 18, n. 4, p. 541-609, 1997. HAFEZ, Elsayed Saad Eldin; HAFEZ, Bahaa. Reprodução animal. São Paulo: Manole, 2004. HEDGER, Mark P. Testicular leukocytes: what are they doing?. Reviews of reproduction, v. 2, n. 1, p. 38-47, 1997. HUTSON, James C. Testicular macrophages. In: International review of cytology. Academic Press, 1994. p. 99-143. HYTTEL, P. Gametogênese. In. HYTTEL, Poul; SINOWATZ, Fred; VEJLSTED, Morten. Embriologia veterinária. São Paulo: Elsevier Brasil, 2012. JOHNSON, Martin H. Essential reproduction. Nova Jersey: John Wiley & Sons, 2018. JONES, Richard E.; LOPEZ, Kristin H. Human reproductive biology. Academic Press, 2013. KIERSZENBAUM, Abraham L.; TRES, Laura L. Primordial germ cell‐somatic cell partnership: A balancing cell signaling act. Molecular Reproduction and Development: Incorporating Gamete Research, v. 60, n. 3, p. 277-280, 2001. MATZUK, Martin M. et al. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science, v. 296, n. 5576, p. 2178-2180, 2002. MCLAREN, Anne. Germ and somatic cell lineages in the developing gonad. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 3-9, 2000. MCKINNON, Angus O. et al. (Ed.). Equine reproduction. John Wiley & Sons, 2011. MERCHANT-LARIOS, Horacio; MORENO-MENDOZA, Norma. Onset of sex differentiation: dialog between genes and cells. Archives of medical research, v. 32, n. 6, p. 553-558, 2001. MINTZ, Beatrice et al. Embryological phases of mammalian gametogenesis. Embryological phases of mammalian gametogenesis., v. 56, n. Suppl. 1, p. 31-43, 1960. MORALES, M. E. et al. Gametogénesis. I. Revisión de la literatura, con enfoque en la ovogénesis. Medicina Universitaria, v. 8, n. 32, p. 183-9, 2006. NAKATSUJI, NORIO; CHUMA, SHINICHIRO. Differentiation of mouse primordial germ cells into female or male germ cells. International Journal of Developmental Biology, v. 45, n. 3, p. 541-548, 2002. NILSSON, Eric; PARROTT, Jeff A.; SKINNER, Michael K. Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Molecular and cellular endocrinology, v. 175, n. 1-2, p. 123-130, 2001. REFERÊNCIAS BIBLIOGRÁFICAS -/- NORRIS, David O.; LOPEZ, Kristin H. The endocrinology of the mammalian ovary. In: Hormones and reproduction of vertebrates. Academic Press, 2011. p. 59-72. PEDERSEN, Torben. Follicle growth in the immature mouse ovary. European Journal of Endocrinology, v. 62, n. 1, p. 117-132, 1969. PINEDA, Mauricio H. et al. McDonald's veterinary endocrinology and reproduction. Iowa state press, 2003. ROSER, J. F. Endocrine and paracrine control of sperm production in stallions. Animal Reproduction Science, v. 68, n. 3-4, p. 139-151, 2001. RUSSELL, Lonnie D. et al. Histological and histopathological evaluation of the testis. International journal of andrology, v. 16, n. 1, p. 83-83, 1993. RÜSSE, I.; SINOWATZ, F. Gametogenese. Lehrbuch der Embryologie der Haustiere, p. 42-92, 1991. SAITOU, Mitinori; BARTON, Sheila C.; SURANI, M. Azim. A molecular programme for the specification of germ cell fate in mice. Nature, v. 418, n. 6895, p. 293-300, 2002. SALISBURY, Glenn Wade et al. Physiology of reproduction and artificial insemination of cattle. WH Freeman and Company., 1978. SAWYER, Heywood R. et al. Formation of ovarian follicles during fetal development in sheep. Biology of reproduction, v. 66, n. 4, p. 1134-1150, 2002. SCARAMUZZI, R. J.; MARTENSZ, N. D.; VAN LOOK, P. F. A. Ovarian morphology and the concentration of steroids, and of gonadotrophins during the breeding season in ewes actively immunized against oestradiol-17β or oestrone. Reproduction, v. 59, n. 2, p. 303-310, 1980. SEIDEL JR, G. E. et al. Control of folliculogenesis and ovulation in domestic animals: puberal and adult function. In: 9th International Congress on Animal Reproduction and Artificial Insemination, 16th-20th June 1980. II. Round tables. Editorial Garsi., 1980. p. 11-16. SKINNER, Michael K. Cell-cell interactions in the testis. Endocrine Reviews, v. 12, n. 1, p. 45-77, 1991. SMITZ, J. E.; CORTVRINDT, Rita G. The earliest stages of folliculogenesis in vitro. Reproduction, v. 123, n. 2, p. 185-202, 2002. SORENSEN, Anton Marinus. Reproducción animal: principios y prácticas. México, 1982. SUTOVSKY, Peter; MANANDHAR, Gaurishankar. Mammalian spermatogenesis and sperm structure: anatomical and compartmental analysis. In. The sperm cell: Production, maturation, fertilization, regeneration, p. 1-30, 2006. TAZUKE, Salli I. et al. A germline-specific gap junction protein required for survival of differentiating early germ cells. Development, v. 129, n. 10, p. 2529-2539, 2002. VAN STRAATEN, H. W. M.; WENSING, C. J. G. Leydig cell development in the testis of the pig. Biology of Reproduction, v. 18, n. 1, p. 86-93, 1978. TURNBULL, K. E.; BRADEN, A. W. H.; MATTNER, P. E. The pattern of follicular growth and atresia in the ovine ovary. Australian Journal of Biological Sciences, v. 30, n. 3, p. 229-242, 1977. WASSARMAN, Paul M. Gametogenesis. Londres: Academic Press, 2012. WROBEL, K.-H.; SÜß, Franz. Identification and temporospatial distribution of bovine primordial germ cells prior to gonadal sexual differentiation. Anatomy and embryology, v. 197, n. 6, p. 451-467, 1998. REFERÊNCIAS BIBLIOGRÁFICAS -/- ZARCO, L. Gametogénese. In. PORTA, L. R.; MEDRANO, J. H. H. Fisiología reproductiva de los animales domésticos. Cidade do México: FMVZ-UNAM, 2018. ZIRKIN, Barry R. et al. Endocrine and Paracrine Regulation of Mammalian Spermatogenesis. In: Hormones and Reproduction of Vertebrates. Academic Press, 2011. p. 45-57. -/- REALIZAÇÃO -/- . (shrink)

Chapter 20 David Kovacs’ “Essence, Grounding, and Explanation” sets out four different ways in which essence might be taken to relate to the notion of grounding or metaphysical explanation, i.e., the type of connection that is often expressed by means of non-causal “in virtue of” or “because”-claims: (i) Unity: essence and grounding belong to a unified set of explanatory concepts; (ii) Supplementation: essence and grounding both contribute in their own way to a distinctive type of explanation; (iii) Independence: essence is (...) a sui generis notion with no straightforward conceptual links to grounding; and (iv) Irrelevance: essence is not an explanatory notion at all and therefore should not be viewed as connected to explanatory notions like grounding. As Kovacs brings out in the chapter, a wide variety of attitudes are represented in the literature even among philosophers who are sympathetic to the recent “hyperintensional” turn in metaphysics when it comes to the question of how the notions of essence and grounding interact with one another. (shrink)

Philosophers have established that certain ethically important val- ues are modally robust in the sense that they systematically deliver correlative benefits across a range of counterfactual scenarios. In this paper, we contend that recourse – the systematic process of reversing unfavorable decisions by algorithms and bureaucracies across a range of counterfactual scenarios – is such a modally ro- bust good. In particular, we argue that two essential components of a good life – temporally extended agency and trust – are under- (...) written by recourse. We critique existing approaches to the conceptualization, op- erationalization and implementation of recourse. Based on these criticisms, we suggest a revised approach to recourse and give ex- amples of how it might be implemented – especially for those who are least well off. (shrink)

This review covers experimental approaches to sound-symbolism—from infants to adults, and from Sapir’s foundational studies to twenty-first century product naming. It synthesizes recent behavioral, developmental, and neuroimaging work into a systematic overview of the cross-modal correspondences that underpin iconic links between form and meaning. It also identifies open questions and opportunities, showing how the future course of experimental iconicity research can benefit from an integrated interdisciplinary perspective. Combining insights from psychology and neuroscience with evidence from natural languages provides us with (...) opportunities for the experimental investigation of the role of sound-symbolism in language learning, language processing, and communication. The review finishes by describing how hypothesis-testing and model-building will help contribute to a cumulative science of sound-symbolism in human language. (shrink)