A pervasive misunderstanding of Confucian philosophy’s concepts considers them to be directives that call for deference and subordination, principally associated with the concept Lǐ 禮 which is understood as rites, rituals, manners, or generally “propriety”. Imposing Lǐ 禮 is considered a path to social and personal harmony. However, an analysis of the conditions and implications of Lǐ 禮 in early Confucian thinking shows that authentic respect, not obedience, is considered the essential condition for good governance and an ordered society. Significantly, authentic respect can only originate from within the self, it cannot be commanded. Based upon self-cultivation, participation in ritual and exemplary conduct establishes a commitment to respect, and the purposeful distinctions expressed through Lǐ 禮 make social order intelligible. Considering the essence of respect in depth, and comparing it to the ethics conceived by Immanuel Kant, neither Confucian nor Kantian ethics are truly deontological in the sense of a “duty that is owed to an external instance”, rather they both rest on the autonomy of the self. A synthesis of both implies that extending authentic respect to an other in an encounter within the context of Lǐ 禮 gives rise to “Existential Reciprocity”: a virtuous cycle which mutually affirms both the self and the other, while rejecting a dichotomous opposition between self-esteem and morality. This is not contingent on external factors, but accessible from a self-determined, autonomous engagement with self-affirming conduct and productive encounters. Benefits are immediate and personal, and this forms the conditions in which harmonious relationships are a natural outcome.

Confucian state doctrines have shaped Asian cultures for millennia as prescriptive codes of conduct with an emphasis on hierarchy and obligation. Yet a premise at the core of li ((sic))- understood as propriety, ritual, or generally a cultural grammar-is authenticity, and authentic respect cannot be commanded. What if the li were to be elegant instead? Hans-Georg Gadamer analyzed play as a fusion of horizons that are absorbed into the same event, co-constituting subject and object in an aesthetic experience, and dissolving their dichotomy. We consider examples from Japanese aesthetics in this framework to give depth to key Confucian concepts: the values that enable a relationality that is not in conflict with autonomy; the points of reference for self--improvement through culture; a social organization that enacts reciprocity; and the essential posture this requires. The radical simplicity of the philosophy of tea, chanoyu, and the aesthetic refinement of the Katsura Rikyu palace illuminate the principle of emotional resonance in encounters, which underlies the fusion of cognitive, ethical, and aesthetic horizons. This view reveals how the relational premise of the Confucian philosophical system entails an ontological commitment to mutuality. This is indeed ethics, but neither particularism nor generalism; in its aesthetic dimension it is the mode of perception of a self fulfilled in play.

Today’s ecological crises are scientifically well understood. Their dire consequences follow predictions with relentless accuracy. What is astounding is how little we can bring ourselves to do about them. Granted, powerful economic interests invest heavily in maintaining the status quo of consumption. But there is another side to this problem, a curious unwillingness, an inability to take personal responsibility. The reasons for this failure to respond are questions for philosophy.

How does the war in Ukraine even make sense?That must be one of the most often asked, and most resoundingly unanswered, questions in March of 2022: How does this make sense?Here we look at the issue from the perspective of game-theory, which analyses how cooperation can establish, thrive -or degrade into confrontation.A simple game in which interacting players can cooperate or choose conflict can be intuitively mapped to recent real world events, and doing so is intriguingly explanatory.We find that a common trope of the apocalypse -the "End" -plays a crucial role.Whenever a relationship is perceived to have an "End" that looms in the future, then cooperation between players must break down.Such an End can take several forms: framing the game as a winner/loser struggle makes an ultimate End inevitable; in a multi-player setting, marginalizing a player and preventing them to "play" results in a perceived End as well; and finally, when ideologies take hold, and a player no longer seeks to maximize their own gains, but to minimize the gains of the other, that too results in an inescapable cycle of confrontation.This simple model is a useful pattern that we can apply to the multiply entangled realities of international politics; not only does it help us to understand some of the motifs that determine such relations, it also highlights how individual events may depart from the premises of this model, and lead to unexpected outcomes.Once this is realized, the contours of a way forward become more clear.A framework is required that is open ended and inclusive, alliances that are committed to a common good and are jointly robust against exploitation, and, perhaps, a framework that is value-based and transcends our current, transactional relations.Let us start with teasing apart a pattern in behaviour that we commonly simply view as "evil": here too, the medium is the message.

Abstract:Confucian state doctrines have shaped Asian cultures for millennia as prescriptive codes of conduct with an emphasis on hierarchy and obligation. Yet a premise at the core of lǐ (禮)—understood as propriety, ritual, or generally a cultural grammar—is authenticity, and authentic respect cannot be commanded. What if the lǐ were to be elegant instead? Hans-Georg Gadamer analyzed play as a fusion of horizons that are absorbed into the same event, co-constituting subject and object in an aesthetic experience, and dissolving their dichotomy. We consider examples from Japanese aesthetics in this framework to give depth to key Confucian concepts: the values that enable a relationality that is not in conflict with autonomy; the points of reference for self-improvement through culture; a social organization that enacts reciprocity; and the essential posture this requires. The radical simplicity of the philosophy of tea, chanoyu, and the aesthetic refinement of the Katsura Rikyū palace illuminate the principle of emotional resonance in encounters, which underlies the fusion of cognitive, ethical, and aesthetic horizons. This view reveals how the relational premise of the Confucian philosophical system entails an ontological commitment to mutuality. This is indeed ethics, but neither particularism nor generalism; in its aesthetic dimension it is the mode of perception of a self fulfilled in play.

"Time-consciousness" (Zeitbewusstsein) constitutes the core of Edmund Husserl's phenomenology. Extending from a project of reviving the comparative method, we develop Husserl's phenomenological analysis of time as a method of literary comparison. Three views of time set the stage: the quatrain "Luan's Fall" by the eighth-century Chinese poet Wang Wei, a stanza from the poem "ETCHED OFF" (WEGGEBEIZT) by Paul Celan, the quintessential post-war poet in German language, and the haiku "Walking, on and on" by the Japanese itinerant monk and free-verse haiku pioneer Santoka Taneda. What makes these poems relevant is not merely their superficially shared theme of time, but an intrinsic affinity, manifested in different poetic "time-objects" (Zeitobjekte), to the very notion of time-consciousness. Through poetic analysis in the context of Husserl's philosophy of time-consciousness, these poetic experiences, embodied in a phenomenological concept of "walking," emphasize time as being.

If a "protein folding code" exists, it ought to give rise to detectable sequence propensities that are associated with low energy conformations, i.e. native structure. To the degree that the frequency of structure patterns in folded proteins has a Boltzmann-like behaviour, such conformations should be detectable by their excess occurrence over random. We have mined a database of non-homologous, well resolved protein structure domains – Nh3D – and have discovered an abundance of such sets of overrepresented structurally similar patterns. We designate the best representatives of a set a motif. Our motif dictionary schematikon shows significant and interesting sequence propensities and is predictive regarding the experimentally determined consequences of sequence change on stability.

Reactive oxygen species (ROS) have been implicated as a signal for general autophagy. Both mitochondrial-produced and exogenous ROS induce autophagosome formation. However, it is unclear whether ROS are required for the selective autophagic degradation of mitochondria, a process called mitophagy. Recent work using carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial-uncoupling reagent, has been shown to induce mitophagy. However, CCCP treatment may not be biologically relevant since it causes the depolarization of the entire mitochondrial network. Since mitochondria are the main ROS production sites in mammalian cells, we propose that short bursts of ROS produced within mitochondria may be involved in the signaling for mitophagy. To test this hypothesis, we induced an acute burst of ROS within mitochondria using a mitochondrial-targeted photosensitizer, mitochondrial KillerRed (mtKR). Using mtKR, we increased ROS levels in the mitochondrial matrix, which resulted in the loss of membrane potential and the subsequent activation of PARK2-dependent mitophagy. Importantly, we showed that overexpression of the mitochondrial antioxidant protein, superoxide dismutase-2, can squelch mtKR-induced mitophagy, demonstrating that mitochondrial ROS are responsible for mitophagy activation. Using this assay, we examined the impact of mitochondrial morphology on mitophagy. It was shown recently that elongated mitochondria are more resistant to mitophagy through unknown mechanisms. Here, we show that elongated mitochondria are more resistant to ROS-induced damage and mitophagy compared with fragmented mitochondria, suggesting that mitochondrial morphology has an important role in regulating ROS and mitophagy. Together, our results suggest that ROS-induced mitochondrial damage may be an important upstream activator of mitophagy.

BACKGROUND:The statistical analysis of protein structures requires datasets in which structural features can be considered independently distributed, i.e. not related through common ancestry, and that fulfil minimal requirements regarding the experimental quality of the structures it contains. However, non-redundant datasets based on sequence similarity invariably contain distantly related homologues. Here we provide a reference dataset of non-homologous protein domains, assuming that structural dissimilarity at the topology level is incompatible with recognizable common ancestry. The dataset is based on domains at the Topology level of the CATH database which hierarchically classifies all protein structures. It contains the best refined representatives of each Topology level, validates structural dissimilarity and removes internally duplicated fragments. The compilation of Nh3D is fully scripted.RESULTS:The current Nh3D list contains 570 domains with a total of 90780 residues. It covers more than 70% of folds at the Topology level of the CATH database and represents more than 90% of the structures in the PDB that have been classified by CATH. We observe that even though all protein pairs are structurally dissimilar, some pairwise sequence identities after global alignment are greater than 30%.CONCLUSION:Nh3D is freely available as a reference dataset for the statistical analysis of sequence and structure features of proteins in the PDB. Regularly updated versions of Nh3D and the corresponding PDB-formatted coordinate sets are accessible from our Web site http://www.schematikon.org.

Publisher Summary This chapter elaborates the consensus-based engineering of protein stability. Protein stability is an experimental metric of the information encoded in a protein sequence. This approach has allowed to engineer hyperstable immunoglobulin domains that can be expressed as intrabodies. Its application by a number of groups to a diverse set of proteins has demonstrated this procedure to be the most reliable strategy for the rational generation of stabilizing mutations. The ability to generate synthetic enzymatically active proteins from consensus sequences emphasizes the statistical nature of natural protein sequences as products of neutral drift and selective pressure. Stabilization is not the only objective for which the approach is useful, and others could include the selection of residues for nondisruptive destabilizing mutations to reduce the lifetime of proteins, or to generate proteins that can be used to screen for second-site revertants in evolutionary engineering strategies. It is found that the final steps of mutagenesis, characterization, and combination of successful residues are specific for each experimental system at hand and should be straightforward.

A major goal of proteomics is the complete description of the protein interaction network underlying cell physiology. A large number of small scale and, more recently, large-scale experiments have contributed to expanding our understanding of the nature of the interaction network. However, the necessary data integration across experiments is currently hampered by the fragmentation of publicly available protein interaction data, which exists in different formats in databases, on authors' websites or sometimes only in print publications. Here, we propose a community standard data model for the representation and exchange of protein interaction data. This data model has been jointly developed by members of the Proteomics Standards Initiative (PSI), a work group of the Human Proteome Organization (HUPO), and is supported by major protein interaction data providers, in particular the Biomolecular Interaction Network Database (BIND), Cellzome (Heidelberg, Germany), the Database of Interacting Proteins (DIP), Dana Farber Cancer Institute (Boston, MA, USA), the Human Protein Reference Database (HPRD), Hybrigenics (Paris, France), the European Bioinformatics Institute's (EMBL-EBI, Hinxton, UK) IntAct, the Molecular Interactions (MINT, Rome, Italy) database, the Protein-Protein Interaction Database (PPID, Edinburgh, UK) and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, EMBL, Heidelberg, Germany).

The optical spectra of the Aequorea victoria green fluorescent protein (GFP) are governed by an equilibrium between three different chromophore states. Mutants that predominantly show either the protonated (A) or the deprotonated (B) form of the chromophore have previously been described. In contrast, the I form, which is formed by rapid excited‐state deprotonation of the A form of the chromophore, has only been described as an obligatory photochemical intermediate. We report the design of a new GFP mutant with a stabilized I form. For this purpose, we introduced two isosteric point mutations, Thr203Val and Glu222Gln, that selectively raise the potential energy of both the A and the B form. Knowledge of the absorption spectrum of the I form at room temperature allows the detailed analysis of concentration dependent changes in bulk wild‐type(wt)‐GFP spectra, as well as the determination of the dimerization constant of GFP. This information expands the use of GFP to that of a spectral probe for protein concentration. We determined energy differences between the chromophore ground states in the monomer and the dimer and reconstructed part of the potential energy surface.

Green fluorescent protein (GFP) and its mutants have become valuable tools in molecular biology. GFP has been regarded as a very stable and rigid protein with the beta-barrel shielding the chromophore from the solvent. Here, we report the 15N nuclear magnetic resonance (NMR) studies on the green fluorescent protein (GFPuv) and its mutant His148Gly. 15N NMR relaxation studies of GFPuv show that most of the beta-barrel of GFP is rigid on the picosecond to nanosecond time scale. For several regions, including the first alpha-helix and beta-sheets 3, 7, 8, and 10, increased hydrogen-deuterium exchange rates suggest a substantial conformational flexibility on the microsecond to millisecond time scales. Mutation of residue 148 located in beta-sheet 7 is known to have a strong impact on the fluorescence properties of GFPs. UV absorption and fluorescence spectra in combination with 1H-15N NMR spectra indicate that the His148Gly mutation not only reduces the absorption of the anionic chromophore state but also affects the conformational stability, leading to the appearance of doubled backbone amide resonances for a number of residues. This suggests the presence of two conformations in slow exchange on the NMR time scale in this mutant.

A revised proof is given that the root-mean-square deviation between more than two vector sets after optimal superposition induces a metric. This corrects an error in a previous manuscript [Kaindl & Steipe (1997). Acta Cryst. A53, 809].

The origin of the low steady‐state fluorescence quantum yield of some blue‐emitting variants of the green fluorescent protein (GFP) is investigated in single‐site mutants in which the tyrosine residue at position 66 has been replaced by phenylalanine or by histidine. Time‐resolved fluorescence measurements reveal excited‐state lifetimes of 74 ps (Y66F) and 0.9 ns (Y66H) at room temperature that increase to values close to the radiative limit as the temperature is lowered. These short lifetimes are explained by temperature‐dependent internal conversion. The pronounced difference between the room‐temperature lifetimes of the two mutants suggests that hydrogen bonding of the distal aromatic ring plays a more important role than tight packing in the fixation of the chromophore.