A new high‐resolution structure of a pain‐sensing ion channel, TRPA1, provides a molecular scaffold to understand channel function. Unexpected structural features include a TRP‐domain helix similar to TRPV1, a novel ligand‐binding site, and an unusual C‐terminal coiled coil stabilized by inositol hexakisphosphate (IP6). TRP‐domain helices, which structurally act as a nexus for communication between the channel gates and its other domains, may thus be a feature conserved across the entire TRP family and, possibly, other allosterically‐gated channels. Similarly, the TRPA1 antagonist‐binding (...) site could also represent a druggable location in other ion channels. Combined with known TRPA1 functional properties, the structural role for IP6 leads us to propose that polyphosphate unbinding could act as a molecular kill switch for TRPA1 inactivation. Finally, although packing of the TRPA1 membrane‐proximal region hints at a mechanism for electrophile sensing, the details of how TRPA1 responds to noxious reactive electrophiles and temperature await future studies.Also watch the Video Abstract. (shrink)

In The Philosophy of John Stuart Mill , Alan Ryan suggests there is an underlying unity of conception in Mill's philosophical writing. He identifies this single idea as ‘inductivism’ and, in the first of the two chapters devoted to Mill's ethics, he states that ‘once we understand how this concept of rationality holds together his views on mathematics and justice’, we will find that much ‘light can be shed on the dark places of Mill's philosophy’. No mention will be made (...) in the present essay of Mill's opinions on mathematics, and it is only incidentally concerned with his ideas about justice. However, it shares Ryan's premise that an inductivist interpretation of Mill's moral philosophy is likely to be most enlightening. In particular, our aim is to show how this approach can brighten up two undeniably murky spots in Utilitarianism : the ‘proof passage’ of chapter 4, and the distinction between higher and lower pleasures in chapter 2. (shrink)

Las corrientes filosóficas de inspiración cartesiana tarde o temprano tienen que afrontar el solipsismo como un resultado al menos plausible de su desarrollo. La Fenomenología no podía evitar la misma suerte. Después de un rápido panorama en lo tocante a la fenomenología husserliana y el solipsismo, pasamos a exponer críticamente el texto de las Meditaciones cartesianas de Husserl, específicamente la quinta. Intentaremos señalar la insuficiencia de la exposición husserliana a la hora de superar, desde sus propias bases, la amenaza del (...) solipsismo. (shrink)

Name der Zeitschrift: Das Mittelalter Jahrgang: 20 Heft: 2 Seiten: 266-278.

After a period during which the theological categories of sin and forgiveness were ignored or trivialized, presently these notions are being rediscovered. What could their impact be on bioethics, either in the narrow sense of medical ethics, or in the more encompassing sense of the ethics of the life sciences? This essay begins with describing the processes of transcending and ethitization, which gave rise to the biblical notion of sin. It portrays the theological foundation of sin in terms of a (...) twofold refusal of proper relations to God and other humans. Through the practise of confession in the face of God (coram deo), sin is placed into a horizon of hope for forgiveness and reconciliation. The heuristic and hermeneutical significance of these categories results from their introducing a “surplus value,” which transcends biological and ethical considerations. This additional dimension is illustrated in view of care (cura) for the injured, and in view of individual as well as collective willingness to forgive. (shrink)

The freedom, in Latin libertas, is the object of philosophical reflection since Plato. Yet as the determined philosophical direction it took the form of the „liberalism” on the turning point of the sixteenth and seventeenth century, represented by two philosophers: Thomas Hobbes (1588–1679) and Jean-Jacques Rousseau (1712–1778). Among contemporary scholars Isaiah Berlin is standing out. From his point of view the philosophical problem of the freedom should be examined in two aspects: the negative freedom i.e. the attribute of not hindered (...) freedom in making choices and the positive freedom as opportunity of being the master of one’s own fate. The author of the article, after critical demonstrating the conception of liberalism, sketches the theory of freedom from the position of Christian ethics. As a starting point he takes the conception of man as a person whose rational activities take on the form of twofold freedom of choice. In the psychological aspect, this freedom assumes the ambivalent form of doing good or evil, however in the moral aspect it turns out to be freedom put in order by the hierarchy of objective moral values. In this meaning the freedom also organizes the whole free man's activity and becomes creative strength of his moral personal perfection. It also defines the crucial sense of Christian philosophical science of truth about freedom. (shrink)

Freely falling point-like objects converge toward the center of the Earth. Hence the gravitational field of the Earth is inhomogeneous, and possesses a tidal component. The free fall of an extended quantum mechanical object such as a hydrogen atom prepared in a high principal-quantum-number state, i.e. a circular Rydberg atom, is predicted to fall more slowly than a classical point-like object, when both objects are dropped from the same height above the Earth’s surface. This indicates that, apart from transitions between (...) quantum states, the atom exhibits a kind of quantum mechanical incompressibility during free fall in inhomogeneous, tidal gravitational fields like those of the Earth.A superconducting ring-like system with a persistent current circulating around it behaves like the circular Rydberg atom during free fall. Like the electronic wavefunction of the freely falling atom, the Cooper-pair wavefunction is quantum mechanically incompressible. The ions in the lattice of the superconductor, however, are not incompressible, since they do not possess a globally coherent quantum phase. The resulting difference during free fall in the response of the nonlocalizable Cooper pairs of electrons and the localizable ions to inhomogeneous gravitational fields is predicted to lead to a charge separation effect, which in turn leads to a large Coulomb force that opposes the convergence caused by the tidal gravitational force on the superconducting system.A “Cavendish-like” experiment is proposed for observing the charge separation effect induced by inhomogeneous gravitational fields in a superconducting circuit. The charge separation effect is determined to be limited by a pair-breaking process that occurs when low frequency gravitational perturbations are present. (shrink)

Balancing citizens’ freedom thought, conscience and religion with the authority of the law which applies to all citizens alike presents an especial challenge for the governments of European nations with socially diverse and pluralistic populations. I address this problem from within the republican tradition represented by Machiavelli, Harrington and Madison. Republicans have historically focused on public debate as the means to identify a set of shared interests which the law should uphold in the interests of all. Within pluralistic societies, however, (...) a greater attention must be paid to the background social conditions that may disrupt the deliberative process and lead to factionalism and instability. This includes certain changes in perspectives by both religious and secular citizens. (shrink)

One group of commentators takes book 10 as determinative and thus tortures the text in book 1 to say the same thing. This position is described as intellectualist or exclusivist and produces certain puzzles in reading Aristotle’s ethical theory. These puzzles are not benign since the privileged position given wisdom in book 10 seems at odds with the discussion of virtue in book 1 and its development in the Nicomachean Ethics as a whole. Indeed, Aristotle appears inconsistent or even contradictory, (...) recommending in these two brief chapters of book 10 a life devoted to contemplation that only grudgingly allows for the necessity of the practical life discussed in such detail in the rest of his ethical works. If this is the case, under what conditions are we expected to forgo contemplation to engage in the various activities of the moral virtues? Since no conditions are spelled out in the text, the range of speculation is confused and ways around the apparent inconsistencies complex. (shrink)

Purcell proposes “a small step in the direction of expanding the notion of persons in communion, as a hermeneutic constant for understanding universal humanity in history”. The human-person-as-communional is his heuristic device for exploring both humanity as a communion of persons, and the drama of humanity “as the unfolding and contraction of human persons in social and historical communion and excommunication with one another and their transcendent personal source”.