Modeling Calcium Concentration and Biochemical Reactions

Almost all regions of the brain receive one or more neuromodulatory inputs, and disrupting these inputs produces deficits in neuronal function. Neuromodulators act through intracellular second messenger pathways to influence the electrical properties of neurons, integration of synaptic inputs, spatio-temporal firing dynamics of neuronal networks, and, ultimately, systems behavior. Second messengers pathways consist of series of bimolecular reactions, enzymatic reactions, and diffusion. Calcium is the second messenger molecule with the most effectors, and thus is highly regulated by buffers, pumps and intracellular stores. Computational modeling provides an innovative, yet practical method to evaluate the spatial extent, time course and interaction among second messenger pathways, and the interaction of second messengers with neuron electrical properties. These processes occur both in compartments where the number of molecules are large enough to describe reactions deterministically (e.g. cell body), and in compartments where the number of molecules is small enough that reactions occur stochastically (e.g. spines). – In this tutorial, I explain how to develop models of second messenger pathways and calcium dynamics. The first part of the tutorial explains the equations used to model bimolecular reactions, enzyme reactions, calcium release channels, calcium pumps and diffusion. The second part explains some of the GENESIS, Kinetikit and Chemesis objects that implement the appropriate equations. In depth explanation of calcium and second messenger models is provided by reviewing code, both in XPP, Chemesis and Kinetikit, that implements simple models of calcium dynamics and second messenger cascades.

Modernity Strikes Back? A Historical Perspective on the Latest Increase in Interpersonal Violence (1960-1990)

There is a plethora of criminological explanations why criminal violence increased during the three decades between the early 1960s and the early 1990s. This paper argues that most available interpretations are lacking in three respects: they lack a historical perspective that anchors the three critical decades in a wider understanding of long-term trends; they take the nation-state as their unit of analysis and disregard important commonalities across the Western world; and they pay insufficient attention to different trends in broad categories of physical violence.This paper therefore takes a macro-level and long-term perspective on violent crime, focussing on European homicide during the past 160 years. It demonstrates that the period of increase was preceded by a long-term decline and convergence of homicide rates from the 1840s to the 1950s. Also, it shows that both the decline and the increase primarily resulted from temporal variation in the likelihood of physical aggression between men in public space. It argues that explanations of these common trends need to take into account broad long-term cultural change common to Western societies. In particular, the paper suggests that shifts in culturally transmitted and institutionally embedded ideals of the conduct of life may provide an explanation for long-term change in levels of interpersonal violence.