The transactivation response‐DNA binding protein of 43 kDa (TDP‐43) is an aggregation‐prone nucleic acid‐binding protein linked to the etiology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). These conditions feature the accumulation of insoluble TDP‐43 aggregates in the neuronal cytoplasm that lead to cell death. The dynamics between cytoplasmic and nuclear TDP‐43 are altered in the disease state where TDP‐43 mislocalizes to the cytoplasm, disrupting Nuclear Pore Complexes (NPCs), and ultimately forming large fibrils stabilized by the C‐terminal prion‐like (...) domain. Here, we review three emerging and poorly understood aspects of TDP‐43 biology linked to its aggregation. First, how post‐translational modifications in the proximity of TDP‐43 N‐terminal domain (NTD) promote aggregation. Second, how TDP‐43 engages FG‐nucleoporins in the NPC, disrupting the pore permeability and function. Third, how the importin α/β heterodimer prevents TDP‐43 aggregation, serving both as a nuclear import transporter and a cytoplasmic chaperone. (shrink)

In The Cultural Roots of Strategic Intelligence, Gino LaPaglia argues that Strategic Intelligence is a core dynamic of human rationality and that it has always been foundational for creating meaning in society. For thousands of years the identity of the heroic strategist has provided hope for human life lived in extremis.

In _The Enigma of Art. On the provenance of Artistic Creation_ Gino Zaccaria offers a meditation on art in light of its ancient Greek sense and of its task inaugurated by “artist-thinkers” like Cézanne, Boccioni and van Gogh.

It is now generally accepted that the motor system is not purely dedicated to the control of behavior, but also has cognitive functions. Mirror neurons have provided a new perspective on how sensory information regarding others’ actions and gestures is coupled with the internal cortical motor representation of them. This coupling allows an individual to enrich his interpretation of the social world through the activation of his own motor representations. Such mechanisms have been highly preserved in evolution as they are (...) present in humans, apes and monkeys. Recent neuroanatomical data showed that there are two different connectivity patterns in mirror neuron networks in the macaque: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and the new data show that it is connected with limbic structures. The mouth mirror sector seems to be wired not only for ingestive behaviors but also for orofacial communicative gestures and vocalizations. Notably, the hand and mouth mirror networks partially overlap, suggesting the importance of hand-mouth synergies not only for sensorimotor transformation, but also for communicative purposes in order to better convey and control social signals. (shrink)

A comprehensive interpretation of the "Scienza Nuova" and of the ways in which Vico managed to present his essentially naturalistic philosophy in a form acceptable within the ecclesiastical climate of 18th century Italy.

Archibald Pitcairne’s medical writings are inspired by Newton’s Principia mathematica, as the Scottish physician assumed Newtonian physics as a model for scientific inquiry that should be applied to other branches of natural philosophy, including physiology and pathology. The ideal of a comprehensive mathematical science was very appealing to late seventeenth-century intellectuals, including physicians. This essay focuses on how Pitcairne tried to implement these ideas. In particular, I argue that Pitcairne’s medical thinking is based on three philosophical assumptions: first, a methodological (...) assumption, for which medical knowledge should be sought in the form of a deductive system; second, an epistemological assumption, that is, that our knowledge of physiological processes is sound only when we reduce them to a set of mathematical laws; and, third, an ontological assumption that identifies blood as the substance on which animal life most directly depends. I also suggest that such ideas should be studied against the backdrop of Pitcairne’s general mindset, including his personal sympathy for political conservativism. I further argue that his insistence on the reduction of natural processes to mathematical relations and his search for the universal order of nature also connect to his religious and political ideals. (shrink)

Loyalty is considered central to people’s moral life, yet little is known about how people think about what it means to be loyal. We used a prototype approach to understand how loyalty is represented in Colombia and the United States and how these representations mediate attributions of loyalty and moral judgments of loyalty violations. Across 7 studies (N = 1,984), we found cross-cultural similarities in the associative meaning of loyalty (Study 1) but found differences in the centrality of features associated (...) with loyalty (Study 2) and the latent structure of loyalty representations (Study 3). Colombians represent loyalty in terms of more general moral characteristics, while US participants represent loyalty in terms of interpersonal commitment, both in contrast with current approaches to loyalty. By comparing representations of loyalty and honesty, we establish that difference in loyalty conceptualizations reflect a different way of thinking about loyalty rather than morality more generally (Study 4). Further, Colombians attributed greater loyalty to individuals with general moral characteristics compared to participants from the United States sample (Study 5) and were more likely to classify non-loyal values as loyalty-related (Study 6). While the centrality of prototypical features predicts categorizing norm violations as loyalty-related, differences in prototypical structure account for differences in the severity of moral judgment for such violations (Study 7), which suggests that loyalty representations have similar functions even though these representations differ in structural characteristics. (shrink)

It has been shown that quantum mechanics in its orthodox interpretation violates four different formulations of causality principle endowed with empirical meaning. The present work aims to highlight how even a realistic non-standard interpretation of the theory conflicts with causality in its Cartesian formulation of the principle of the non-inferiority of causes over effects. Such an interpretation, which attributes some form of weak physical reality to the wave function (called empty wave, regarded as a zero-energy wave-like phenomenon), is a sort (...) of precursor of the more recent so-called wavefunction realism. We also discuss a more radical realistic interpretation according to which physical properties can also be assigned to non-metaphysical relative nothing, seen as the simple absence of a particle such as a photon, but not of its corresponding state (no-photon), which is considered real. By interpreting the wave function collapse as a consequence of an interaction with empty waves or of a detection of the no-photon, we will highlight how more real physical effects can derive from lower causes, including relative nothing. Finally, we will show how these interpretations, while violating Cartesian causality in its two variants, do not seem to affect the validity of the principle of a rational explanation that nothing can derive from (absolute) nothing, which does not seem satisfied by the orthodox interpretation. (shrink)

Dieser Aufsatz zeigt die Möglichkeiten auf, aus den von Leibniz im April 1679 geschriebenen logischen Abhandlungen ein numerisches Modell für die durch Widerspruchsfreiheit bestimmten Modalbegriffe zu lesen. Dazu wird als erstes die Definition der Modalisatoren durch die Widerspruchsfreiheit betrachtet und die Probleme‚ die das Leibniz'sche ‘continere’ oder ‘implicare contradictionem’ auslöst. Danach werden die in den Schriften von 1679 entwickelten numerischen Modelle untersucht‚ besonders dasjenige‚ das sich auf den Mechanismus des charakteristischen Zahlenpaares stützt. Dieses Modell wird für den Aufbau formaler Definitionen (...) von Möglichkeit‚ Unmöglichkeit‚ Kompatibilität und Inkompatibilität benutzt. Schließlich werden kurz einige spezifische Probleme angeführt‚ die die vorgeschlagene Interpretation offenläßt: die Darstellung der einfachen Begriffe innerhalb des numerischen Kalküls und die Beziehung zwischen den Wortpaaren Kompatibilität-Inkompatibilität und Kompossibilität-Inkompossibilität. Was diese letzteren betrifft‚ wird die Bedeutung betont‚ die eine diachronische Betrachtung der Leibnizschen Lehre für ein besseres Verständnis der theoretischen Zusammenhänge hat‚ in denen diese Bezeichnungen auftreten. (shrink)

The paper offers a survey of different kinds of electronic textuality (e-mail, blog, sms, tweets, social networks, e-book), considered from the point of view of their ability to convey complex textual structures and arguments. While e-mail and sms are characterized by a low level of complexity, twitter hashtags allow for relatively complex threads to be built upon extremely short and simple messages. New web tools such as Storify.com represent a further step in the direction of building complexity out of simple (...) and molecular content, mainly drawn from social networks. Augmented e-books allow for still higher levels of complexity, adding to the traditional ability of books to convey structured and highly sophisticated reasoning, the ability of providing both content and service layers (including social reading tools) and of visually representing complex datasets. (shrink)

El vínculo entre músicos/as de rock y agencias estatales ha sido en nuestro país históricamente dinámico, intermitente, cambiante. Un clima de época iniciado en los años 2000, tanto en Argentina como en Latinoamérica, caracterizado por demandas de políticas culturales democrático-participativas, se tradujo en una modificación en el vínculo entre hacedores culturales y agentes estatales. Buscando contribuir al debate en torno al diseño e implementación de estas políticas, este artículo tiene como objetivo analizar las lógicas, las legitimidades y las disputas existentes (...) en el vínculo entre músicos/as de rock de la ciudad de La Plata y agencias estatales locales. Para ello, partiremos de un conjunto de políticas culturales que tuvo lugar durante 2016 y 2017 que permitió ver procesos de articulación entre ambos actores, así como instancias de tensión, consenso y reposicionamiento. La investigación se desarrolló en base a una estrategia metodológica de tipo cualitativa, aplicando distintas técnicas de recolección y producción de datos, como entrevistas en profundidad, observación participante, cartografía, sombreo (Jirón, 2012) y relevamiento y análisis de fuentes primarias y secundarias. (shrink)

Describing the will and the extent of its causal power over human actions, Joseph Priestley famously compared the mind to a stone, as both are subject to deterministic laws: “Though an inclination...

Unethical and dishonest behavior has increasingly attracted the attention of scholars from various disciplines. Recent work has begun to focus on a previous overlooked factor predicting dishonest behavior: the beneficiary or victim of dishonest acts. In two laboratory experiments, we manipulate the level of resources allocated to our participants (their "wealth") and investigate whether perceived inequity from wealth that is randomly or subjectively assigned leads individuals to cross ethical boundaries through helping or hurting others. The results show that dishonest behavior (...) is influenced by positive and negative inequity that motivates helping and hurting acts. Furthermore, a third experiment shows that people tend to discount the wrongness of crossing ethical boundaries to hurt or help others when the action restores equity. (shrink)

The author Gino Capozzi, founder of the institutionalist napolitan phenomenological school, includes an original and promising exposition based on the contributions of praxeology and praxeologism, in relation to being and what should be the reality of human rights, their genesis, the development of..