COMPARISON OF THE ANALYTIC NETWORK PROCESS AND THE GRAPH MODEL FOR CONFLICT RESOLUTION

1. Introduction A strategic conflict is a situation in which two or more decision-makers are to make a decision that affects issues they have different preferences about (Fang et al. 1993). Conflicts are one of the most characteristic attributes of human societies. Various forms of strategic conflict exist all around us, in areas such as environmental management, international rela-tions, economic competition, and relationships among individuals. Conflicts are studied in a wide range of disci…     

The Siberian Traps and the End-Permian mass extinction: a critical review

The association between the Siberian Traps, the largest continental flood basalt province, and the largest-known mass extinction event at the end of the Permian period, has been strengthened by recently-published high-precision ⁴⁰Ar/³⁹Ar dates from widespread localities across the Siberian province^[1]. We argue that the impact of the volcanism was amplified by the prevailing late Permian environmental conditions―in particular, the hothouse climate, with sluggish oceanic circulation, that was leading to widespread oceanic anoxia. Volcanism released large masses of sulphate aerosols and carbon dioxide, the former triggering short-duration volcanic winters, the latter leading to long-term warming. Whilst the mass of CO₂ released from individual eruptions was small compared with the total mass of carbon in the atmosphere-ocean system, the long ‘mean lifetime’ of atmospheric CO₂, compared with the eruption flux and duration, meant that significant accumulation could occur over periods of 105 years. Compromise of the carbon sequestration systems (by curtailment of photosynthesis, destruction of biomass, and warming and acidification of the oceans) probably led to rapid atmospheric CO₂ build-up, warming, and shallow-water anoxia, leading ultimately to mass extinction.     

Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes

In the fasted state, increases in circulating glucagon promote hepatic glucose production through induction of the gluconeogenic program. Triggering of the cyclic AMP pathway increases gluconeogenic gene expression via the de-phosphorylation of the CREB co-activator CRTC2 (ref. 1). Glucagon promotes CRTC2 dephosphorylation in part through the protein kinase A (PKA)-mediated inhibition of the CRTC2 kinase SIK2. A number of Ser/Thr phosphatases seem to be capable of dephosphorylating CRTC2 (refs 2, 3), but the mechanisms by which hormonal cues regulate these enzymes remain unclear. Here we show in mice that glucagon stimulates CRTC2 dephosphorylation in hepatocytes by mobilizing intracellular calcium stores and activating the calcium/calmodulin-dependent Ser/Thr-phosphatase calcineurin (also known as PP3CA). Glucagon increased cytosolic calcium concentration through the PKA-mediated phosphorylation of inositol-1,4,5-trisphosphate receptors (InsP(3)Rs), which associate with CRTC2. After their activation, InsP(3)Rs enhanced gluconeogenic gene expression by promoting the calcineurin-mediated dephosphorylation of CRTC2. During feeding, increases in insulin signalling reduced CRTC2 activity via the AKT-mediated inactivation of InsP(3)Rs. InsP(3)R activity was increased in diabetes, leading to upregulation of the gluconeogenic program. As hepatic downregulation of InsP(3)Rs and calcineurin improved circulating glucose levels in insulin resistance, these results demonstrate how interactions between cAMP and calcium pathways at the level of the InsP(3)R modulate hepatic glucose production under fasting conditions and in diabetes.     

Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour

Drug-evoked synaptic plasticity is observed at many synapses and may underlie behavioural adaptations in addiction. Mechanistic investigations start with the identification of the molecular drug targets. Cocaine, for example, exerts its reinforcing and early neuroadaptive effects by inhibiting the dopamine transporter, thus causing a strong increase in mesolimbic dopamine. Among the many signalling pathways subsequently engaged, phosphorylation of the extracellular signal-regulated kinase (ERK) in the nucleus accumbens is of particular interest because it has been implicated in NMDA-receptor and type 1 dopamine (D1)-receptor-dependent synaptic potentiation as well as in several behavioural adaptations. A causal link between drug-evoked plasticity at identified synapses and behavioural adaptations, however, is missing, and the benefits of restoring baseline transmission have yet to be demonstrated. Here we find that cocaine potentiates excitatory transmission in D1-receptor-expressing medium-sized spiny neurons (D1R-MSNs) in mice via ERK signalling with a time course that parallels locomotor sensitization. Depotentiation of cortical nucleus accumbens inputs by optogenetic stimulation in vivo efficiently restored normal transmission and abolished cocaine-induced locomotor sensitization. These findings establish synaptic potentiation selectively in D1R-MSNs as a mechanism underlying a core component of addiction, probably by creating an imbalance between distinct populations of MSNs in the nucleus accumbens. Our data also provide proof of principle that reversal of cocaine-evoked synaptic plasticity can treat behavioural alterations caused by addictive drugs and may inspire novel therapeutic approaches involving deep brain stimulation or transcranial magnetic stimulation.     

Light-cone-like spreading of correlations in a quantum many-body system

In relativistic quantum field theory, information propagation is bounded by the speed of light. No such limit exists in the non-relativistic case, although in real physical systems, short-range interactions may be expected to restrict the propagation of information to finite velocities. The question of how fast correlations can spread in quantum many-body systems has been long studied. The existence of a maximal velocity, known as the Lieb-Robinson bound, has been shown theoretically to exist in several interacting many-body systems (for example, spins on a lattice)--such systems can be regarded as exhibiting an effective light cone that bounds the propagation speed of correlations. The existence of such a 'speed of light' has profound implications for condensed matter physics and quantum information, but has not been observed experimentally. Here we report the time-resolved detection of propagating correlations in an interacting quantum many-body system. By quenching a one-dimensional quantum gas in an optical lattice, we reveal how quasiparticle pairs transport correlations with a finite velocity across the system, resulting in an effective light cone for the quantum dynamics. Our results open perspectives for understanding the relaxation of closed quantum systems far from equilibrium, and for engineering the efficient quantum channels necessary for fast quantum computations.     

Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

LGR5+ stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5+ stem cells. Simultaneous deletion of the two genes encoding these proteins in the intestinal epithelium of mice induces rapidly growing adenomas containing high numbers of Paneth and LGR5+ stem cells. In vitro, growth of organoids derived from these adenomas is arrested when Wnt secretion is inhibited, indicating a dependence of the adenoma stem cells on Wnt produced by adenoma Paneth cells. In the HEK293T human cancer cell line, expression of RNF43 blocks Wnt responses and targets surface-expressed frizzled receptors to lysosomes. In the RNF43-mutant colorectal cancer cell line HCT116, reconstitution of RNF43 expression removes its response to exogenous Wnt. We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation.     

Proto-genes and de novo gene birth

Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions. Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes generated by widespread translational activity in non-genic sequences. Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events seem to provide adaptive potential, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.     

On Heidegger’s Actuality

In my reply to the commentaries by Babette Babich and Robert C. Scharff I make a distinction between critical remarks and additions that are relevant for my view on philosophy for substantive reasons and others that relate to a style or way of philosophizing. My reply to Scharff concerns the latter. I continue to defend an updated version of Heidegger’s thinking about technology, which I bring together with elements from the work of Don Ihde and Andrew Feenberg. I read all this from the perspective of a neo-pragmatist way of philosophizing, explicitly inspired by Richard Rorty.     

Diagrams and alien ways of thinking

The recent wave of data on exoplanets lends support to METI ventures (Messaging to Extra-Terrestrial Intelligence), insofar as the more exoplanets we find, the more likely it is that “exominds” await our messages. Yet, despite these astronomical advances, there are presently no well-confirmed tests against which to check the design of interstellar messages. In the meantime, the best we can do is distance ourselves from terracentric assumptions. There is no reason, for example, to assume that all inferential abilities are language-like. With that in mind, I argue that logical reasoning does not have to be couched in symbolic notation. In diagrammatic reasoning, inferences are underwritten, not by rules, but by transformations of self-same qualitative signs. I use the Existential Graphs of C. S. Peirce to show this. Since diagrams are less dependent on convention and might even be generalized to cover non-visual senses, I argue that METI researchers should add some form of diagrammatic representations to their repertoire. Doing so can shed light, not just on alien minds, but on the deepest structures of reasoning itself.