The effects of modifiers on enzyme catalysis: A non-classical nearest neighbor approach

We present a nearest neighbor lattice model of the effects of modifiers on two-state enzyme catalysis of the reaction s ? p-We do not in general make the assumptions of the classical approach to cooperative catalysis that yield (1) adsorption isotherms of the same form as those for the corresponding equilibrium system and (2) a rate of the catalyzed reaction proportional to the number of occupied catalytic sites. Closed form results are obtained for two approximations, the Bragg-Williams and the quasi-chemical. The latter requires (l),but is exact for several simple cases, including the concerted model, under this condition. Under (1) it is found that an interaction between modifier and catalytic sites, whether attractive or repulsive, increases the magnitudes of the slopes of the adsorption isotherms but that interactions between identical sites (catalytic or modifier) increase these magnitudes if attractive and decrease them if repulsive. Thus, the former interaction allows for phase transitions if sufficiently attractive or repulsive, but the latter only if sufficiently attractive. Herein also lies the explanation for why the concerted model displays only “positive cooperativity”. It is further seen that it is not possible to classify a modifier as an activator or inhibitor of the catalyzed reaction solely on the basis of the sign of the interaction energy between catalytic and modifier sites. For agiven energy, the rate of the reaction may increase or decrease in response to the modifier, or it may respond biphasically. Similarly, the rate may respond biphasically to the activities of s or p, lead- ing to instabilities. Thus, possibilities of multiple nonequilibrium stationary states or spatio-temporal patterns are raised-     

Dopamine, affordance and active inference

The role of dopamine in behaviour and decision-making is often cast in terms of reinforcement learning and optimal decision theory. Here, we present an alternative view that frames the physiology of dopamine in terms of Bayes-optimal behaviour. In this account, dopamine controls the precision or salience of (external or internal) cues that engender action. In other words, dopamine balances bottom-up sensory information and top-down prior beliefs when making hierarchical inferences (predictions) about cues that have affordance. In this paper, we focus on the consequences of changing tonic levels of dopamine firing using simulations of cued sequential movements. Crucially, the predictions driving movements are based upon a hierarchical generative model that infers the context in which movements are made. This means that we can confuse agents by changing the context (order) in which cues are presented. These simulations provide a (Bayes-optimal) model of contextual uncertainty and set switching that can be quantified in terms of behavioural and electrophysiological responses. Furthermore, one can simulate dopaminergic lesions (by changing the precision of prediction errors) to produce pathological behaviours that are reminiscent of those seen in neurological disorders such as Parkinson's disease. We use these simulations to demonstrate how a single functional role for dopamine at the synaptic level can manifest in different ways at the behavioural level.     

A giant rhinocerotoid (Mammalia, Perissodactyla) from the Late Oligocene of north-central Anatolia (Turkey)

A giant rhinocerotoid is described for the first time south of the Black Sea, in Turkey. The single specimen, a fragmentary radius referred to Paraceratherium sp., originates from conglomerates nearby at Gözükizilli, in the Çankiri–Çorum Tertiary basin. These layers correspond to the Lower member of the Kizilirmak Formation. The same locality (Gözükizilli-2) yields also the small rhinocerotid Protaceratherium sp., cf. P. albigense (Roman, 1912). Three other mammal localities (Gözükizilli-1, in the Lower Member of the formation, with several rodent species; Tepe 641 and Kizilirmak, in the Upper Member, with a diversified micro- and macro-mammal fauna) allow us to refer the Kizilirmak Formation as a whole to the Late Oligocene. All the observed taxa have strong Asian and/or European affinities, which precludes any geographical insulation for this part of Anatolia during the Late Oligocene.  © 2008 The Linnean Society of London, Zoological Journal of the Linnean Society, 2008, 152 , 581–592.     

Intracellular and extracellular labeling of neurons in fresh slice preparations combined with multiple tract tracing

We describe methods for studying axo-dendritic projections, one of the forms of neural connection involved in the complex circuits of the central nervous system, including brainstem auditory pathways. This form of neural connection is often difficult to visualize by conventional tract tracing techniques. Retrogradely identified cells were filled intracellularly with a mixture of fluorescent Lucifer yellow and nonfluorescent HRP in live slice preparations to reveal the detailed morphological features of these cells with special attention to the distal dendrite that may receive projections from suspected or known input axons. Extracellular or intracellular labeling of cells with axons that project to the distal dendrite of the identified cells was accomplished in the same live slice preparation. Using a live slice rather than a fixed slice allows accurate, visually controlled placement of anterograde tracer, which requires living axons for transport, into the source of input to the identified cells within the slice. Live slices also permit one to characterize the identified cells electrophysiologically. Intracellular labeling of cells in a potential source of local input to the identified cells also provides conclusive information concerning with connections of the cells involved.     

Elevationally biased avian predation as a contributor to the spatial distribution of geometrid moth outbreaks in sub‐arctic mountain birch forest

1. Population dynamics and interactions that vary over a species' range are of particular importance in the context of latitudinal clines in biological diversity. Winter moth (Operophtera brumata) and autumnal moth (Epirrita autumnata) are two species of eruptive geometrids that vary widely in outbreak tendency over their range, which generally increases from south to north and with elevation. 2. The predation pressure on geometrid larvae and pupae over an elevational gradient was tested. The effects of background larval density and bird occupancy of monitoring nest boxes on predation rates were also tested. Predation on larvae was tested through exclusion treatments at 20 replicate stations over four elevations at one site, while pupae were set out to measure predation at two elevations at three sites. 3. Larval densities were reduced by bird predation at three lower elevations, but not at the highest elevation, and predation rates were 1.9 times higher at the lowest elevation than at the highest elevation. The rate of predation on larvae was not related to background larval density or nest box occupancy, although there were more eggs and chicks at the lowest elevation. There were no consistent differences in predation on pupae by elevation. 4. These results suggest that elevational variation in avian predation pressure on larvae may help to drive elevational differences in outbreak tendency, and that birds may play a more important role in geometrid population dynamics than the focus on invertebrate and soil predators of previous work would suggest.