Graded persistent activity in entorhinal cortex neurons

Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time. Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential. Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.     

The deterministic nature of earthquake rupture

Understanding the earthquake rupture process is central to our understanding of fault systems and earthquake hazards. Multiple hypotheses concerning the nature of fault rupture have been proposed but no unifying theory has emerged. The conceptual hypothesis most commonly cited is the cascade model for fault rupture. In the cascade model, slip initiates on a small fault patch and continues to rupture further across a fault plane as long as the conditions are favourable. Two fundamental implications of this domino-like theory are that small earthquakes begin in the same manner as large earthquakes and that the rupture process is not deterministic--that is, the size of the earthquake cannot be determined until the cessation of rupture. Here we show that the frequency content of radiated seismic energy within the first few seconds of rupture scales with the final magnitude of the event. We infer that the magnitude of an earthquake can therefore be estimated before the rupture is complete. This finding implies that the rupture process is to some degree deterministic and has implications for the physics of the rupture process.     

Sarcolemma-localized nNOS is required to maintain activity after mild exercise

Many neuromuscular conditions are characterized by an exaggerated exercise-induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients, and some patients experience severe fatigue without any demonstrable somatic disease. Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown. With no treatment available, this form of inactivity is a major determinant of disability. Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS-null mice do not have muscle pathology and have no loss of muscle-specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction-induced signalling from sarcolemma-localized nNOS, which decreases cGMP-mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling.     

Degenerating Families of Dendrograms

Dendrograms used in data analysis are ultrametric spaces, hence objects of nonarchimedean geometry. It is known that there exist p-adic representations of dendrograms. Completed by a point at infinity, they can be viewed as subtrees of the Bruhat-Tits tree associated to the p-adic projective line. The implications are that certain moduli spaces known in algebraic geometry are in fact p-adic parameter spaces of dendrograms, and stochastic classification can also be handled within this framework. At the end, we calculate the topology of the hidden part of a dendrogram.     

Civic Meaningfulness

This paper starts from qualitative research on volunteering and citizenship, with a special focus on volunteering within a setting of restorative justice and mediation. In a first stage, the author reconstructs two models of meaningfulness as hermeneutical lenses to better understand how volunteers see their engagement and experiences as a source of meaningfulness. The paper argues that a biographical model of meaningfulness (Wolf’s theoretical framework) is in need of a complementary approach to meaningfulness (an existential model of meaningfulness), which focuses on transformational experiences with a strong existential depth. In a second stage, the paper dialogues with the experiences and narratives of the volunteers, and shows how their understanding of citizenship informs, and transforms their ideas of meaningfulness. Both the biographical and the existential approach to meaningfulness appear to be deeply influenced by the volunteers’ civic imaginaries.     

Gene flow maintains a large genetic difference in clutch size at a small spatial scale

Understanding the capacity of natural populations to adapt to their local environment is a central topic in evolutionary biology. Phenotypic differences between populations may have a genetic basis, but showing that they reflect different adaptive optima requires the quantification of both gene flow and selection. Good empirical data are rare. Using data on a spatially structured island population of great tits (Parus major), we show here that a persistent difference in mean clutch size between two subpopulations only a few kilometres apart has a major genetic component. We also show that immigrants from outside the island carry genes for large clutches. But gene flow into one subpopulation is low, as a result of a low immigration rate together with strong selection against immigrant genes. This has allowed for adaptation to the island environment and the maintenance of small clutches. In the other area, however, higher gene flow prevents local adaptation and maintains larger clutches. We show that the observed small-scale genetic difference in clutch size is not due to divergent selection on the island, but to different levels of gene flow from outside the island. Our findings illustrate the large effect of immigration on the evolution of local adaptations and on genetic population structure.