The bcl‐2 gene product, a 25 kDa membrane protein residing at mitochondrial, microsomal and nuclear membrane sites within many cell types, is a broad and potent inhibitor of cell death by apoptosis. A family of bcl‐2‐related genes with death‐inhibiting or ‐promoting activities has recently been described, indicating a potentially quite complex cell death regulatory network at the level of gene expression and protein‐protein interactions. The function of bcl‐2 may be to regulate a final common pathway in apoptosis. Current hypotheses suggest (...) that oxidative stress, specific proteolytic activity or cell cycle control may be common elements in apoptosis through which bcl‐2 exerts its survival function. Based on the extent to which elements of apoptotic pathways overlap with non‐apoptotic cellular functions, the physiological role of bcl‐2 may also extend to other cellular processes such as differentiation and proliferation. (shrink)

Although the Bcl‐2 family members and p53 are involved in the regulation of apoptosis, the status of apoptotic machinery (eg caspases) plays a major role in determining the mode and timing of cell death. If the apoptotic machinery is lost, inhibited, or intrinsically inactivated, the “death stars”, Bcl‐2 and p53, may become irrelevant to cell death. In this light, high levels of Bcl‐2 may indicate that downstream apoptotic pathways are still functional. This explains why Bcl‐2 overexpression can be a marker (...) of chemosensitivity and favorable prognosis in certain cancers and why retention of wild‐type p53 may manifest inactivation of caspases in aggressive cancers. BioEssays 23:947–953, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The pore‐forming BCL‐2 family proteins are effectors of mitochondrial poration in apoptosis initiation. Two atypical effectors—BOK and truncated BID (tBID)—join the canonical effectors BAK and BAX. Gene knockout revealed developmental phenotypes in the absence the effectors, supporting their roles in vivo. During apoptosis effectors are activated and change shape from dormant monomers to dynamic oligomers that associate with and permeabilize mitochondria. BID is activated by proteolysis, BOK accumulates on inhibition of its degradation by the E3 ligase gp78, while BAK and (...) BAX undergo direct activation by BH3‐only initiators, autoactivation, and crossactivation. Except tBID, effector oligomers on the mitochondria appear as arcs and rings in super‐resolution microscopy images. The BH3‐in‐groove dimers of BAK and BAX, the tBID monomers, and uncharacterized BOK species are the putative building blocks of apoptotic pores. Effectors interact with lipids and bilayers but the mechanism of membrane poration remains elusive. I discuss effector‐mediated mitochondrial poration. (shrink)

Nerve processes elongate, branch and form synaptic contacts in a highly regulated and specific manner. Long‐distance axon elongation is restricted to the main phase of axon formation during development, but can be reinduced upon lesions in the adult (regeneration). It correlates with the expression of defined genes, including proteins involved in signalling (e.g. src, NCAM, integrins), transcription factors (e.g. c‐jun) and structural proteins (e.g. actin and tubulin isoforms). Activation of an axon elongation program may require bcl‐2. The formation and growth (...) of local branches (sprouting) is controlled by mechanisms in the target region. In addition, the expression of growth‐associated proteins such as GAP‐43 and CAP‐23 in neurons lowers the threshold for nerve sprouting and potentiates its vigour. Recent studies suggest that nerve sprouting and long‐distance elongation depend on the expression of different intrinsic components in neurons. One implication of these findings is that the differential expression of genes facilitating local branching may affect structural plasticity in the intact adult nervous system. (shrink)

A marked feature of eukaryotic programmed cell death is an early drop in mitochondrial transmembrane potential. This results from the opening of permeability transition pores, which are composed of adenine nucleotide translocators and mitochondrial porins. The latter share striking similarites with bacterial porins, (including down‐regulation of their pore size by purine nucleotides), suggesting a common origin. The porins of some invasive bacteria play a crucial role during their accommodation inside the host cell and this co‐existence resembles the endosymbiotic origin of (...) mitochondria. The above observations suggest that early in eukaryotic evolution, former invaders may have used porin‐type channels to enter their host and to induce its death when the levels of its cytoplasmic purine nucleotides were dropped. The appearance of adenosine nucleotide translocators in the primitive eukaryotes, which permitted usage of the oxidative metabolism of the invaders, provided the basis for the permeability transition phenomena, now linked to the apoptotic process. Bcl‐2‐type molecules, being able to modulate the permeability transition pores by interaction with adenosine nucleotide translocators, may have played an essential role in conferring a means of controlling apoptosis. (shrink)

Although Caenorhabditis and Drosophila proved invaluable in unraveling the molecular mechanisms of apoptosis, it is now clear that these animals are of limited value for understanding the evolution of apoptotic systems. Whereas data from these invertebrates led to the assumption that the extrinsic apoptotic pathway is restricted to vertebrates, recent data from cnidarians and sponges indicate that this pathway predates bilaterian origins. Here we review the phylogenetic distribution of caspase‐8, the initiator caspase of the extrinsic apoptotic pathway, its paralogs and (...) other components of the network. The ancestral caspase‐8 gave rise to four paralogs early in vertebrate evolution, and these have been maintained in many tetrapods. However, eutherians have lost caspase‐18 and myomorph rodents have lost caspase‐10, these losses suggesting functional redundancy amongst caspase‐8 paralogs. The apoptotic network of the eumetazoan ancestor appears to have been complex and vertebrate like, and is only now being revealed by studying simple animals. (shrink)

(1998). Region, Locality Characteristics, High School Tracking and Equality in Access to Educational Credentials: the case of Palestinian Arab communities in Israel[1] Educational Studies: Vol. 24, No. 2, pp. 233-240.

The recent in vitro derivation of gamete‐like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete‐like (sperm‐like or oocyte‐like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived gamete of the opposite (...) sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells. (shrink)

Por Laura Fraga de Almeida Sampaio, tradutora do livro A aula inaugural, que Foucault pronunciou ao assumir a cátedra vacante no Collège de France pela morte de Hyppolite, pode ser considerada um texto de ligação entre suas obras, datadas dos anos 60, como História da loucura, As palavras e as coisas, A arqueologia do saber, centradas predominantemente na análise das condições de possibilidade das ciências humanas, e as que se seguiram a maio de 68, como Vigiar e punir, voltados ao (...) exame da microfisica do poder. Foucault desvenda a relação entre as práticas discursivas e os poderes que as permeiam. Ao perceber os diversos procedimentos que cerceiam e controlam os discursos da sociedade, o autor comprova que "o discurso não é simplesmente aquilo que traduz as lutas ou os sistemas de dominação, mas aquilo pelo que se luta, o poder de queremos nos apoderar". Na segunda parte do texto, Foucault anuncia a direção em que prosseguirá suas investigações no decorrer dos cursos no Collège de France, apontando para o que denomina o "conjunto crítico" e o "conjunto genealógico" e lança o projeto de estudo das interdições que atingem o discurso da sexualidade. A este trabalho dedicará muitos anos, após a publicação do primeiro volume da História da sexualidade, em 1976: A vontade de saber (uso dos prazeres, vol.2, O cuidado de si, vol, 3, ambos de 1984). (shrink)

COVID-19 poses an exceptional threat to global public health and well-being. Recognition of the need to develop effective vaccines at unprecedented speed has led to calls to accelerate research pathways ethically, including by conducting challenge studies ) with SARS-CoV-2. Such research is controversial, with concerns being raised about the social, legal, ethical and clinical implications of infecting healthy volunteers with SARS-CoV-2 for research purposes. Systematic risk evaluations are critical to inform assessments of the ethics of any proposed SARS-CoV-2 CHIs. Such (...) evaluations will necessarily take place within a rapidly changing and at times contested epidemiological landscape, in which differing criteria for the ethical acceptability of research risks have been proposed. This paper critically reviews two such criteria and evaluates whether the use of effective treatment should be a necessary condition for the ethical acceptability of SARS-CoV-2 CHIs, and whether the choice of study sites should be influenced by COVID-19 incidence levels. The paper concludes that ethical evaluations of proposed SARS-CoV-2 CHIs should be informed by rigorous, consultative and holistic approaches to systematic risk assessment. (shrink)

Accounts of mechanistic explanation, especially as applied to biology and sometimes going under the heading of “new mechanism,” provided an attractive alternative to nomological accounts that preceded them. These accounts were motivated by selected examples, drawn primarily from cell and molecular biology and neuroscience. However, the range of examples that scientists take to be mechanistic explanations is far broader. We focus on examples that differ from those traditionally recruited by Mechanists. Our contention is that attention to additional examples will lead (...) to a richer conception of mechanistic explanation, prompting a shift from what we refer to as Mechanism 1.0 to Mechanism 2.0. (shrink)

The paper examines Martha Nussbaum’s «Aristotelian Social Democracy», and in particular her appropriation of Aristotle’s political philosophy. The paper questions Nussbaum’s claim that Aristotle’s account of human nature and her capabilities approach are not metaphysical. It critically analyses Nussbaum’s egalitarian interpretation of Aristotle’s doctrine of distributive justice, laying out the primary reasons supporting the thesis that Nussbaum’s «Aristotelian Social Democracy» is incompatible with Aristotle’s non-egalitarian political philosophy.

Aristotle’s Eudemian Ethics has always proved to be fertile ground for at times needless textual emendation. I provide a translation and running commentary on Eudemian Ethics II 2 1220a39–b6 in accordance with the MSS text.

Plato's depiction of the world soul's cognitive activity in Timaeus 37 A 2‐C 5 offers a general account of intellectual cognition. He gives this account by describing the activity of an ideal cognitive agent, involving the very same comparative mechanism that governs human intellectual activity, namely, the active production of a propositional grasp of sameness and difference that things have in relation to each other in several respects. Plato depicts the world soul's intellectual activity as entirely devoid of immediate forms (...) of cognition such as perception and/or intellectual intuition: everything the world soul cognizes is the outcome of its active comparison of things with each other. In particular, there is no direct cognitive grasp of the being of things. The paper ends with a suggestion as to how to understand Plato's account of the world soul's activity as an instance of the ‘like is known by like’ principle of cognition. (shrink)

In this article, the concept of system of symbolic 2-plithogenic linear equations and its solutions are introduced and studied. The Cramer's rule was applied to solve the system of symbolic 2-plithogenic linear equations. Also, provided enough examples for each case to enhance understanding.

In the Tractatus Wittgenstein claims that a sentence expresses the same proposition in every possible world and, hence, which proposition is expressed cannot depend on how each world is. In this paper, I shall explore the interpretation of this thesis under the perspective of Stalnaker’s theory of assertions as the reduction of the context set, i.e., the set of possible worlds compatible with the information gathered at a conversation. In Stalnaker’s version, this principle follows from the explication of assertions as (...) having the illocutionary point of excluding some possible worlds from the context set. If there is no unique instruction to exclude some worlds, then it is not clear which reduction is meant by the speaker. This might lead to a better understanding of Wittgenstein’s own version. (shrink)

We have good reason to believe that Nicomachean Ethics VI. 2 is a Nicomachean revision of an originally Eudemian text. Aristotle seems to have inserted lines 1139a31-b11 by means of a marginal note, which the first editor then mistakenly added in the wrong place, and I propose that we move these lines so that they follow the word κοινωνεῖν at 1139a20. The suggested note appears to be Nicomachean for several reasons but most importantly because it contains a desire-based account of (...) the practical intellect as teleologically oriented to action. The NE articulates consequences of this account regarding practical philosophy’s methodology and teleological orientation to action. The EE does not articulate such consequences, and instead seems to assume an object-based account of the practical intellect. Consequently, it would seem that, between the EE and the NE, Aristotle revised his conception of the practical intellect and consequently his conception of practical philosophy. (shrink)

This paper elucidates how the thinking about opposition that we find in the surviving passages of Anaxagoras of Clazomenae and in the fragments of Heraclitus of Ephesus informs discussions of the separability of the body and the soul in the Phaedo. I offer a reconstruction of the way in which these pre-Socratic ideas of opposition are appropriated and refracted in Plato’s Phaedo (especially at 85e–86e, 92a–95a, 102c–e, 102b–107a). I treat Anaxagoras first, in order to explicate how his ideas make up (...) the background of the dialogical study of the separation of the soul from the body (102b–107a). My analysis of Heraclitus comes second and shows how his ideas inform the interlocutors’ assessment of the unity characteristic of the body and the soul (92a–95a). I set the stage for the discussion of Anaxagoras and Heraclitus by relating these thinkers to the broader Pythagorean background that is apparent in the dialogue. (shrink)

El presente trabajo, se avoca a determinar cuál es el status ontológico del principio de no-contradicción -(P -P). Rechazo que la exigencia que dicho principio implica, sea de naturaleza entitativa, es decir, que sea una dimensión constitutiva de los entes exteriores a la función racional de la mente humana. Afirmo que la exigencia que impone dicho principio, se reduce a ser nada más que una exigencia emanada de la humana mente racional, siempre que ésta participe como uno de los miembros (...) de la relación mente-objeto. (shrink)

The modal logic S4.2 is S4 with the additional axiom ◊□A ⊃ □◊A. In this article, the sequent calculus GS4.2 for this logic is presented, and by imposing an appropriate restriction on the application of the cut-rule, it is shown that, every GS4.2-provable sequent S has a GS4.2-proof such that every formula occurring in it is either a subformula of some formula in S, or the formula □¬□B or ¬□B, where □B occurs in the scope of some occurrence of □ (...) in some formula of S. These are just the K5-subformulas of some formula in S which were introduced by us to show the modied subformula property for the modal logics K5 and K5D : 115–122, 2001). Some corollaries including the interpolation property for S4.2 follow from this. By slightly modifying the proof, the finite model property also follows. (shrink)

In times of crisis, one of the areas heavily affected has been food, as a direct consequence of the damage caused to family farming and therefore to Food and Nutrition Security (SAN). Climate change, in turn, causes widespread crises, which, due to their impact on humanity, and above all, on SAN, provide complex humanitarian crises, worsening hunger. The military conflict imposes difficulties in access to food and production. This study aimed to critically describe the panorama of climate change and armed (...) conflicts in Africa, relating them to the pandemic of COVID-19 as a factor of aggravating the situation of food insecurity in African countries. A literature review study was carried out in various databases, journals and portals for this purpose, with emphasis on Google Scholar, CAPES and governmental portals. The results point to climate change, as being multicausal, and constitute a risk factor for agriculture and SAN, in African countries, characterized by the destruction of crops and the reduction of food availability. Armed conflicts makes difficult to produce and distribute food, especially for people who’s affected. (shrink)

After more than a decade teaching ancient Greek history and philosophy at University College, Oxford, British philosopher and political theorist Bernard Bosanquet resigned from his post to spend more time writing. He was particularly interested in contemporary social theory, and was involved with the Charity Organisation Society and the London Ethical Society. Much of his work focused on the place of logic in philosophy, especially its role in metaphysical thought - the area where he is considered to have made his (...) most important intellectual contributions. In 1888 he published this two-volume study of logic, addressing a variety of questions relating to logic, and drawing from the work of Hegel in his examination. In Volume 2, Bosanquet focuses on inference, arguing that it has a similar essence to judgment but is fundamentally different in that it is used to 'mediate' reality. (shrink)

When I first dipped my toe tentatively into the frigid waters of psi research, back in the late 1970s, one of the big issues of the time was whether the ability to replicate experiments distinguishes—or as philosophers often say, demarcates—science from non-science (or pseudoscience). This was a big issue because all too often parapsychological skeptics glibly used that demarcation criterion to bludgeon psi researchers and dismiss them as unscientific. Fortunately, in those days there was some very sensible writing on the (...) subject, particularly from Harry Collins, to whom I was especially indebted when I tackled the topic of replicability myself for the first time.1 The skeptical position on the issue of repeatability struck me as so lame that I even naively expected the debate to be settled rather quickly. However, because psi researchers often enter the field having little acquaintance with the work that preceded them, and because many critics of that research likewise fail to master the relevant issues, I suppose I shouldn’t be surprised that the debate over the nature and importance of replicability still rages. Indeed, little (if any) attention is given to the reasonable points that should have put that issue to rest long ago. Instead, researchers and commentators focus relentlessly—and as usual, inconclusively—on the results of meta-analyses. Some of those meta-analyses are indeed worthy of attention,2 but (I would say) only in light of the overlooked considerations I discuss below. So I’d like to review some problems with the still-widely–held view that the ability to replicate experiments is what demarcates science from non-science or pseudoscience. As I see it, that position is both shallow and confused, and the problems with it don’t even have the virtue of being subtle. First, the skeptical reliance on the demarcation criterion rests on a naïve conception of the actual importance within science of experimental repeatability. Indeed, experimental repeatability plays little if any role in disciplines (including some physical sciences) whose scientific credentials are not in dispute. Second, it seriously misconstrues how the appeal to replicability works even in those physical sciences where it plays a real role. Third, the received view rests on philosophical confusions regarding the nature of similarity—in particular, the flawed idea that there can be formal, context-independent, criteria for the similarity of two things. And fourth, it rests on confusions over the nature of human abilities generally, and in particular, the appropriate methodologies for studying them. One could also argue that a fifth problem for this received view is that psi research can in fact point to replicable results. But that last issue must be reserved for another occasion. (shrink)

This essay constructs a picture of the meaning of life based on De Anima 2. 2-4. It shows that there are organisms that preserve their form through the exercise of identifiable functions. For an individual to be a short, living thing is for it to be one of these naturally species-preserving organisms. For an individual living thing to be actually living is for it to be able to perform one of the psychic or living functions appropriate to its species.

An important question about eye-movement behavior is when the decision is made to terminate a fixation and program the following saccade. Different approaches have found converging evidence in favor of a mixed-control account, in which there is some overlap between processing information at fixation and planning the following saccade. We examined one interesting instance of mixed control in visual search: lag-2 revisits, during which observers fixate a stimulus, move to a different stimulus, and then revisit the first stimulus on the (...) next fixation. Results show that the probability of lag-2 revisits occurring increased with the number of target-similar stimuli, and revisits were preceded by a brief fixation on the intervening distractor stimulus. We developed the Efficient Visual Sampling computational model to simulate our findings and to provide insight into mixed control of fixations and the perceptual, cognitive, and motor processes that produce lag-2 revisits. (shrink)

Over the past thirty years Paul Feyerabend has developed an extremely distinctive and influentical approach to problems in the philosophy of science. The most important and seminal of his published essays are collected here in two volumes, with new introductions to provide an overview and historical perspective on the discussions of each part. Volume 1 presents papers on the interpretation of scientific theories, together with papers applying the views developed to particular problems in philosophy and physics. The essays in volume (...) 2 examine the origin and history of an abstract rationalism, as well as its consequences for the philosophy of science and methods of scientific research. Professor Feyerabend argues with great force and imagination for a comprehensive and opportunistic pluralism. In doing so he draws on extensive knowledge of scientific history and practice, and he is alert always to the wider philosophical, practical and political implications of conflicting views. These two volumes fully display the variety of his ideas, and confirm the originality and significance of his work. (shrink)

El transhumanismo es una moda intelectual que propone la transformación de los seres humanos mediante diversas tecnologías. Expondremos brevemente los rasgos más conspicuos del TH, así como las principales críticas que se le han hecho. Pero la intención de este artículo no es entrar en esta polémica; aportaremos tan solo las claves imprescindibles para poder seguir adelante. Y una de las claves más intrigantes del TH es que, por debajo de su pátina tecno-futurista, remite a ciertas ideas filosóficas tan viejas (...) como, en apariencia, incompatibles entre sí. El TH remite al naturalismo radical, tanto como al nihilismo existencialista. La tesis que aquí se defiende es que tanto el naturalismo radical como el nihilismo existencialista son producto de las diversas oleadas del dualismo: del dualismo platónico antiguo, del dualismo cartesiano moderno. Una vez que separamos, a la manera dualista, la libertad por un lado y la naturaleza por el otro, podemos contar hasta dos, como hacen los dualistas, o quedarnos solo en uno, como hacen los existencialistas, que se paran en la libertad, y los naturalistas, que solo cuentan con la naturaleza. En cualquier caso, la imagen del ser humano, que es libertad y naturaleza, sale dañada. Asoma entonces el animal aporético y enfermizo al cual hay que salvar… de sí mismo. ¿Cómo? Siguiendo el método de Procusto, pero ahora con los prefijos bio e info en lugar de sierra y martillo. Hasta que el pobre ser humano encaje en el lecho de la utopía que algunos visionarios han urdido. ¿Y no hay otra vía, otra forma de mejorar la vida humana que sea más respetuosa para con la humana envergadura? Quizá sí, mas para trazar esa tercera vía, entre el naturalismo radical que mutila y el nihilismo existencialista que descoyunta y estira, habría que negar de antemano el dualismo que a los dos engendra, y atenerse a la sensatez común, en línea con la tradición aristotélica, antes que a las ensoñaciones utópicas. En nuestra opinión, el concepto aristotélico de naturaleza humana nos habilita para juzgar las antropotecnias mejor que la normatividad extraída de las visiones futuristas propias del TH. (shrink)