PDZ (also called DHR or GLGF) domains are found in diverse membraneassociated proteins including members of the MAGUK family of guanylate kinase homologues, several protein phosphatases and kinases, neuronal nitric oxide synthase, and several dystrophin‐associated proteins, collectively known as syntrophins. Many PDZ domain‐containing proteins appear to be localised to highly specialised submembranous sites, suggesting their participation in cellular junction formation, receptor or channel clustering, and intracellular signalling events. PDZ domains of several MAGUKs interact with the C‐terminal polypeptides of a subset (...) of NMDA receptor subunits and/or with Shaker‐type K+ channels. Other PDZ domains have been shown to bind similar ligands of other transmembrane receptors. Recently, the crystal structures of PDZ domains, with and without ligand, have been determined. These demonstrate the mode of ligand‐binding and the structural bases for sequence conservation among diverse PDZ domains. (shrink)

Liquid‐liquid phase separation (LLPS) has recently emerged as a possible mechanism that enables ubiquitin‐binding shuttle proteins to facilitate the degradation of ubiquitinated substrates via distinct protein quality control (PQC) pathways. Shuttle protein LLPS is modulated by multivalent interactions among their various domains as well as heterotypic interactions with polyubiquitin chains. Here, the properties of three different shuttle proteins (hHR23B, p62, and UBQLN2) are closely examined, unifying principles for the molecular determinants of their LLPS are identified, and how LLPS is connected (...) to their functions is discussed. Evidence supporting LLPS of other shuttle proteins is also found. In this review, it is proposed that shuttle protein LLPS leads to spatiotemporal regulation of PQC activities by mediating the recruitment of PQC machinery (including proteasomes or autophagic components) to biomolecular condensates, assembly/disassembly of condensates, selective enrichment of client proteins, and extraction of ubiquitinated proteins from condensates in cells. (shrink)

The landscapes of mammalian genomes are characterized by complex patterns of intersecting and overlapping sense and antisense transcription, giving rise to large numbers of coding and non‐protein‐coding RNAs (ncRNAs). A recent report by Kapranov and colleagues1 describes three potentially novel classes of RNAs located at the very edges of protein‐coding genes. The presence of RNAs from one of these classes appears to be correlated with the expression levels of their associated genes. These results suggest that a proportion of these RNAs (...) might have roles in the cis‐regulation of neighbouring protein‐coding genes' expression. BioEssays 29:1077–1080, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Ao longo da história, as mulheres foram colocadas à margem dos direitos sociais. Apesar disto, foram responsáveis por inúmeras contribuições nos saberes de modo geral. Como afirma Costa e Silva (2000, p. 8): “Não obstante o impacto visível de algumas modificações concretas, a maioria das pessoas, incluindo aí homens e mulheres, mesmo entre setores mais instruídos, continuam a pensar de acordo com esquemas patriarcais antigos”. A partir desta reflexão surge um questionamento: Por que, no ensino médio, se estudam pouquíssimas mulheres (...) filósofas e cientistas? O presente projeto objetiva fomentar a discussão acerca das contribuições de mulheres no âmbito da Filosofia e Ciência, construindo e fortalecendo a autonomia, a emancipação e o empoderamento feminino das alunas do ensino médio. O projeto foi executado na EEEP Guilherme Teles Gouveia em 2022. Estudantes e o professor de filosofia pesquisaram sobre mulheres que contribuíram para a humanidade. A partir das discussões e pesquisas foram elaborados questionários e um evento denominado “Simpósio: mulheres na Ciência e na Filosofia”, que levou alunos e alunas ao conhecimento sobre filósofas e cientistas de todas as épocas. Os resultados foram constatados através dos relatos do público e das participantes, no qual foram avaliados os impactos da ação para a comunidade escolar. (shrink)

People accept conclusions of valid conditional inferences (e.g., if p then q, p therefore q) less, the more disablers (circumstances that prevent q to happen although p is true) exist. We investigated whether rules that through their phrasing exclude disablers evoke higher acceptance ratings than rules that do not exclude disablers. In three experiments we re-phrased content-rich conditionals from the literature as either universal or existential rules and embedded these rules in Modus Ponens and Modus Tollens inferences. In Experiments 2 (...) and 3, we also used abstract rules. The acceptance of conclusions increased when the rule was phrased with “all” instead of “some” and the number of disablers had a higher impact on existential rules than on universal rules. Further, the effect of quantifier was more pronounced for abstract rules and when tested within subjects. We discuss the relevance of phrasing, quantifiers and knowledge on reasoning. (shrink)

Probabilistic theories of reasoning assume that people use their prior knowledge to estimate the conditional probability of q given p and that this probability predicts the acceptance of modus ponens inferences. But how do people reason with unfamiliar conditionals for which they do not have prior knowledge? Reasoning without prior knowledge has been extensively investigated in experiments in which participants were instructed to reason deductively. But it is still not clear how people reason with unfamiliar conditionals when they are instructed (...) to reason as in daily life. Can probabilities also predict reasoning with unfamiliar content? In two experiments we instructed participants to reason as in everyday life and to evaluate conclusions from familiar and unfamiliar conditionals. Results showed that reasoning with familiar conditionals can be predicted by the conditional probability. For unfamiliar conditionals, however, this was not the case. Conclusions from unfamiliar conditionals were accepted more strongly than what could be expected according to their conditional probability. Our findings challenge probabilistic theories of reasoning and suggest that other approaches, such as a dual-strategy model, describe our results more adequately. (shrink)

Les livres deutérocanoniques constituent un «intertestament» entre les écrits de la Bible rabbinique et ceux du Nouveau Testament chrétien. Ils sont sur une frontière, un fossé ou un pont entre le christianisme naissant et le judaïsme renaissant après 135. Ils font aussi le lien entre la Gola araméenne et la Diaspora hellénistique. Les écrits intertestamentaires – et spécifiquement les deutérocanoniques qui sont comme un «intertestament» canonique – sont vraiment nécessaires à la compréhension de la Bible.

Knauff and Gazzo Castañeda (this issue) critique the "new paradigm" – a framework that replaces logic with probabilities – on the grounds that there existed no "old” paradigm for it to supplant. Their position is supported by the large numbers of theories that theorists developed to explain the Wason selection task, syllogisms, and other tasks. We propose some measures to inhibit such facile theorizing, which threatens the viability of cognitive science. We show that robust results exist contrary to the (...) new paradigm, and that it is unable to account for other results. (shrink)

In this paper, we focus on some misconceptions about Critical Pragmatics, what it is, what it assumes and what it proposes. Doubtless, some of these misconceptions are due to clumsy writing on our part; perhaps others are due to inattentive reading. And some may be due to an effort to shield us from the apparent implausibility of what we said—and in fact meant. It does not matter much. We focus on those misunderstandings that most matter to us, either because, by (...) repetition, they have ended up being annoying, even if they are not, perhaps, that important; or because they are substantial enough to represent a distortion of the basic picture of Critical Pragmatics and its theoretical foundations, namely, Critical Referentialism—also known as the Reflexive-referential Theory—and, more generally, Perry’s fundamental views on meaning and content(s). (shrink)

The physician of fifty years ago is barely recognizable today. Rural, autonomous, and isolated, he did everything from mending broken bones to pronouncing people dead. He was responsible for a well-circumscribed community, who came to him for all their medical needs, regardless of the hour.

No es posible una comprensión integral del influyente pensamiento de Anselmo de Canterbury (1033-1109) sin incluir su concepción de la verdad. La articulación entre la famosa demostración de Dios en el "Proslogion" con sus ideas acerca de la libertad en su "Tratado sobre la libertad del albedrío", mediadas por sus planteamientos sobre el origen y el significado del mal en su "Tratado sobre la caída del demonio", requiere centrarse en la presente obra. La presente edición está acompañada de una serie (...) de ensayos sobre el problema de la verdad en la Antigüedad y en la Edad Media que pasa por Aristóteles, Agustín de Hipona, Boecio, Dionisio Areopagita, Tomás de Aquino, Ockham y otros. (shrink)