Reorganization of inhibitory synapses in experimental epilepsy

The integrity and stability of interneurons in a cortical network is essential for proper network function. Loss of interneuron synaptic stability and precise organization can lead to disruptions in the excitation/inhibition balance, a characteristic of epilepsy. This study aimed to identify alterations to the GABAergic interneuron network in the piriform cortex (PC: a cortical area believed to be involved in the development of seizures) after kindling-induced seizures. Immunohistochemistry was used to mark perineuronal nets (PNNs: structures in the extracellular matrix that provide synaptic stability and restrict reorganization of inhibitory interneurons) and interneuron nerve terminals in control and kindled tissue. Results indicated that the expression of fully formed PNNs was significantly decreased in kindled tissue and was correlated with an increased expression of matrix metalloproteinase 9 (MMP9: a protease known to degrade extracellular matrix structures). Inhibition of MMP9 by the anti- inflammatory drug, Doxycycline, provided an antiepileptic effect against amygdala kindling. Additionally, we observed a layer specific increase in interneuron release sites. These data show an important loss of interneuron stability in the PC after seizures. Our data suggests that under pathophysiological conditions interneuron wiring patterns are plastic and their synaptic rearrangement may contribute to the development of epilepsy

Sheep scab spatial distribution: the roles of transmission pathways

Abstract Background Ovine psoroptic mange (sheep scab) is a highly pathogenic contagious infection caused by the mite Psoroptes ovis. Following 21 years in which scab was eradicated in the UK, it was inadvertently reintroduced in 1972 and, despite the implementation of a range of control methods, its prevalence increased steadily thereafter. Recent reports of resistance to macrocyclic lactone treatments may further exacerbate control problems. A better understanding of the factors that facilitate its transmission are required to allow improved management of this disease. Transmission of infection occurs within and between contiguous sheep farms via infected sheep-to-sheep or sheep–environment contact and through long-distance movements of infected sheep, such as through markets. Methods A stochastic metapopulation model was used to investigate the impact of different transmission routes on the spatial pattern of outbreaks. A range of model scenarios were considered following the initial infection of a cluster of highly connected contiguous farms. Results Scab spreads between clusters of neighbouring contiguous farms after introduction but when long-distance movements are excluded, infection then self-limits spatially at boundaries where farm connectivity is low. Inclusion of long-distance movements is required to generate the national patterns of disease spread observed. Conclusions Preventing the movement of scab infested sheep through sales and markets is essential for any national management programme. If effective movement control can be implemented, regional control in geographic areas where farm densities are high would allow more focussed cost-effective scab management. Graphical Abstrac

Assessing the effectiveness of prophylactic treatment strategies for sheep scab

Ovine psoroptic mange (sheep scab) is a condition caused by a hypersensitivity response to the ectoparasitic mite, Psoroptes ovis. It is an animal welfare concern and causes extensive economic losses to the sheep industry worldwide. More effective scab management is required to limit increases in infection prevalence, particularly given growing concerns over acaricide resistance. Here, a stochastic metapopulation model is used to explore the effectiveness of a range of prophylactic acaricide treatment strategies in comparison to no intervention. Over a simulated one-year period, movement control, based on the prophylactic treatment of animals being moved in sales, followed by farm biosecurity of bought in animals, was shown to be the most effective at reducing scab risk and more cost-effective than no intervention. Localised targeting of prophylaxis in areas of high scab prevalence was more effective than using prophylaxis at random, however, this localised effect declined post-treatment because of the import of infected animals. The analysis highlights the role of the movement of infected animals in maintaining high levels of scab infection and the importance of reducing this route of transmission to allow localised management to be effective

Temporal and spatial variability in the composition of lavas exposed along the Western Blanco Transform Fault

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 6 (2005): Q11009, doi:10.1029/2005GC001026.The northern scarp of the western Blanco Transform (BT) fault zone provides a "tectonic window" into crust generated at an intermediate-rate spreading center, exposing a ~2000 m vertical section of lavas and dikes. The lava unit was sampled by submersible during the Blancovin dive program in 1995, recovering a total of 61 samples over vertical distances of ~1000 m and a lateral extent of ~13 km. Major elements analyses of 40 whole rock samples exhibit typical tholeiitic fractionation trends of increasing FeO*, Na2O, and TiO2 and decreasing Al2O3 and CaO with decreasing MgO. The lava suite shows a considerable range in extent of crystallization, including primitive samples (Mg# 64) and evolved FeTi basalts (FeO>12%;TiO2>2%). Based on rare earth element and trace element data, all of the lavas are incompatible-element depleted normal mid-ocean ridge basalts (N-MORB;La/SmN<1). The geochemical systematics suggest that the lavas were derived from a slightly heterogeneous mantle source, and crystallization occurred in a magmatic regime of relatively low magma flux and/or high cooling rate, consistent with magmatic processes occurring along the present-day southern Cleft Segment. The BT scarp reveals the oceanic crust in two-dimensional space, allowing us to explore temporal and spatial relationships in the horizontal and vertical directions. As a whole, the data do not appear to form regular spatial trends; rather, primitive lavas tend to cluster shallower and toward the center of the study area, while more evolved lavas are present deeper and toward the west and east. Considered within a model for construction of the upper crust, these findings suggest that the upper lavas along the BT scarp may have been emplaced off-axis, either by extensive off-axis flow or off-axis eruption, while the lower lavas represent axial flows that have subsided with time. A calculation based on an isochron model for construction of the upper crust suggests that the Cleft Segment requires at least ~50 ka to build the lower extrusive section, consistent to first order with independent estimates for the construction of intermediate-spreading rate crust.This work was supported by the US National Science Foundation (OCE 02- 22154 to E.K. and J.K. and OCE 9400623 to M.T.)

Investigating how to effectively combine static concern location techniques

As software systems continue to grow and evolve, locating code for maintenance tasks becomes increasingly difficult. Studies have shown that combining static global concern lo-cation techniques like search with more structure-based local techniques can improve effectiveness. However, no studies have yet investigated why this occurs. In this paper, we investigate why combining global and local techniques im-proves effectiveness, and under what conditions. We explore such questions as: “What are the limits of lexical informa-tion in locating concerns?”, “How far away does a local tech-nique have to go to locate the remaining relevant elements?”, and “How sensitive are these results to the query or scoring thresholds of the techniques?”. The results of our study can inform design decisions to maximize effective global and lo-cal combinations in future concern location techniques