A Relational Moral Theory

A Relational Moral Theory provides a new answer to the long-standing question of what all morally right actions might have in common as distinct from wrong ones, by drawing on neglected resources from the Global South and especially the African philosophical tradition. The book points out that the principles of utility and of respect for autonomy, the two rivals that have dominated Western moral theory for about two centuries, share an individualist premise. Once that common assumption is replaced by a relational perspective that has been salient in African ethical thought, a different comprehensive principle focused on harmony or friendliness emerges, one that is shown to correct the blind spots of the Western principles and to have implications for a wide array of applied controversies that an international audience of moral philosophers, professional ethicists, and similar thinkers will find attractive.

Leveraging Parrondo's paradox for sustainable agriculture

Rotating crops is a sustainable agricultural technique that has been at the disposal of humanity since time immemorial. Switching between cover crops and cash crops allows the fields avoids overexploitation due to intensive farming. How often the respite is to be provided and what is the optimum cash cover rotation in terms of maximising yield schedule is a long-standing question tackled on multiple fronts by agricultural scientists, economists, biologists and computer scientists, to name a few. Dealing with the uncertainty in the field due to diseases, pests, droughts, floods, and impending effects of climate change, is important to consider when designing the cropping strategy. Analysing this time-tested technique of crop rotations with a new lens of Parrondo's paradox allows us to improve upon the technique and use it in synchronisation with the burning questions of contemporary times. By calculating optimum switching probabilities in a randomised cropping sequence, suggesting the optimum deterministic sequences and judicious use of fertilisers, we propose methods for improving crop yield and the eventual profit margins for farmers. Overall we also extend the domain of applicability of the seemingly unintuitive paradox by Parrondo, where two losing situations can be combined eventually into a winning scenario.

PP2A/B55α substrate recruitment as defined by the retinoblastoma-related protein p107

Protein phosphorylation is a reversible post-translation modification essential in cell signaling. This study addresses a long-standing question as to how the most abundant serine/threonine Protein Phosphatase 2 (PP2A) holoenzyme, PP2A/B55α, specifically recognizes substrates and presents them to the enzyme active site. Here, we show how the PP2A regulatory subunit B55α recruits p107, a pRB-related tumor suppressor and B55α substrate. Using molecular and cellular approaches, we identified a conserved region 1 (R1, residues 615-626) encompassing the strongest p107 binding site. This enabled us to identify an 'HxRVxxV619-625' short linear motif (SLiM) in p107 as necessary for B55α binding and dephosphorylation of the proximal pSer-615 in vitro and in cells. Numerous B55α/PP2A substrates, including TAU, contain a related SLiM C-terminal from a proximal phosphosite, 'p[ST]-P-x(4,10)-[RK]-V-x-x-[VI]-R'. Mutation of conserved SLiM residues in TAU dramatically inhibits dephosphorylation by PP2A/B55α, validating its generality. A data-guided computational model details the interaction of residues from the conserved p107 SLiM, the B55α groove, and phosphosite presentation. Altogether these data provide key insights into PP2A/B55α mechanisms of substrate recruitment and active site engagement, and also facilitate identification and validation of new substrates, a key step towards understanding PP2A/B55α role in multiple cellular processes.

Algebraic branch points at all loop orders from positive kinematics and wall crossing

There is a remarkable connection between the boundary structure of the positive kinematic region and branch points of integrated amplitudes in planar $$ \mathcal{N} $$ N = 4 SYM. A long-standing question has been precisely how algebraic branch points emerge from this picture. We use wall crossing and scattering diagrams to systematically study the boundary structure of the positive kinematic regions associated with MHV amplitudes. The notion of asymptotic chambers in the scattering diagram naturally explains the appearance of algebraic branch points. Furthermore, the scattering diagram construction also motivates a new coordinate system for kinematic space that rationalizes the relations between algebraic letters in the symbol alphabet. As a direct application, we conjecture a complete list of all algebraic letters that could appear in the symbol alphabet of the 8-point MHV amplitude.

A Favorable Path to Domain Separation in the Orange Carotenoid Protein

In this work, we have modeled a fundamental part of the defense mechanism of Cyanobacteria against damaging effects of excess light conditions. This mechanism is part of the photoactivation cycle in the Orange Carotenoid Protein (OCP), which involves the separation of protein domains triggered by chromophore translocation. Using carefully designed metadynamics simulations, we have discovered the structural rearrangements along an energetically favorable pathway to the activated state. The structural rearrangement of OCP along its activation path has been a long-standing question, only answered now by our work.<br>

A Favorable Path to Domain Separation in the Orange Carotenoid Protein

In this work, we have modeled a fundamental part of the defense mechanism of Cyanobacteria against damaging effects of excess light conditions. This mechanism is part of the photoactivation cycle in the Orange Carotenoid Protein (OCP), which involves the separation of protein domains triggered by chromophore translocation. Using carefully designed metadynamics simulations, we have discovered the structural rearrangements along an energetically favorable pathway to the activated state. The structural rearrangement of OCP along its activation path has been a long-standing question, only answered now by our work.<br>

West and East in Ashkenaz in the Time of Judah he-Ḥasid

The present study interprets and frames a long-standing question concerning Judah he-Ḥasid’s motivations in migrating to Regensburg against the social and geographical contexts of the Jews of Ashkenaz. By examining the use of Hebrew geographic terminology during the High Middle Ages (Loter, Ashkenaz, Ashkelonia), the article demonstrates that twelfth-century Jews perceived and were engaged in contemporary political and territorial processes of the surrounding kingdom. The Hebrew terms describe the cultural tripartite division of the German kingdom (Regnum Teutonicum) in Lotharingia, the five duchies of the earlier tribes (Saxony, Franconia, Thuringia, Swabia, and Bavaria), and the still Slavic territories of the East. These imperial territories were settled and Christianized by mostly German migrants from the west of the kingdom from the eleventh century onwards. Comparable developments are evident in the movement and expansion of Jewish settlement in the German Kingdom. After many Jewish communities were founded in the Ashkenazic heartlands, beginning in cities on the Rhine, Main, and the Danube, i.e., in the territories of the five duchies (Ashkenaz), Jewish settlers founded new communities and settlements in the still Slavic areas (Ashkelonia), beyond the Elbe and Saale rivers, as part of the German settlement movement. Judah he-Ḥasid’s family’s migration is part of this development. With his relocation to Regensburg, he lived on the border of the Ashkenazic heartland (Old/West Ashkenaz) and the new Ashkenazic settlement areas in Ashkelonia (New/Eastern Ashkenaz). In Regensburg he became one of the central spiritual and halakhic authorities for the communities of the eastern neighboring territories. Through his work Judah he-Ḥasid opened the way to an “Ashkenazation” of the Jewish communities in eastern Central Europe and Eastern Europe.

Constraints and variation in food web link-species space

Predicting food web structure in future climates is a pressing goal of ecology. These predictions may be impossible without a solid understanding of the factors that structure current food webs. The most fundamental aspect of food web structure—the relationship between the number of links and species—is still poorly understood. Some species interactions may be physically or physiologically ‘forbidden'—like consumption by non-consumer species—with possible consequences for food web structure. We show that accounting for these ‘forbidden interactions' constrains the feasible link-species space, in tight agreement with empirical data. Rather than following one particular scaling relationship, food webs are distributed throughout this space according to shared biotic and abiotic features. Our study provides new insights into the long-standing question of which factors determine this fundamental aspect of food web structure.

PP2A/B55α substrate recruitment as defined by the retinoblastoma-related protein p107

Protein phosphorylation is a reversible post-translation modification essential in cell signaling. This study addresses a long-standing question as to how the most abundant serine/threonine Protein Phosphatase 2 (PP2A) holoenzyme, PP2A/B55α, specifically recognizes substrates and presents them to the enzyme active site. Here, we show how the PP2A regulatory subunit B55α recruits p107, a pRB-related tumor suppressor and B55α substrate. Using molecular and cellular approaches, we identified a conserved region 1 (R1, residues 615-626) encompassing the strongest p107 binding site. This enabled us to identify an “HxRVxxV619-625” short linear motif (SLiM) in p107 as necessary for B55α binding and dephosphorylation of the proximal pSer-615 in vitro and in cells. Numerous B55α/PP2A substrates, including TAU, contain a related SLiM C-terminal from a proximal phosphosite, “p[ST]-P-x(5-10)-[RK]-V-x-x-[VI]-R”. Mutation of conserved SLiM residues in TAU dramatically inhibits dephosphorylation by PP2A/B55α, validating its generality. A data-guided computational model details the interaction of residues from the conserved p107 SLiM, the B55α groove, and phosphosite presentation. Altogether these data provide key insights into PP2A/B55α mechanisms of substrate recruitment and active site engagement, and also facilitate identification and validation of new substrates, a key step towards understanding PP2A/B55〈 role in multiple cellular processes.