The thalamocortical contribution to epilepsy

The experimental literature has dealt intensively with the cortical contribution to epilepsy. Possibly because of the direction of technological advance, much less attention has been paid to the role of other structures. A model which emphasizes the role of some of those non-cortical structures, specifically that of thalamocortical modulation of cortical excitability, is developed. Some aspects of the petit mal seizure, a seizure type considered by some investigators to involve thalamocortical mechanisms, are predicted by the model. Although the thalamocortical mechanisms under study are not the only mechanism underlying seizures, a full understanding of the phenomenology of epilepsy needs to take into account the role of subcortical modification of cortical activities in addition to other mechanisms. Gloor has described two types of epileptogenesis: type I characteristic of non-convulsive seizure and type II characteristic of convulsions. There is disagreement as to whether or not the two mechanisms represent qualitatively different phenomena. Utilizing the thalamocortical model, it can be shown that the two types of epileptogenesis are qualitatively different. Furthermore, the thalamocortical model leads to a possible explanation of clinically different profiles of antipileptic efficacy of medications.     

Native fish entrapment in irrigation systems: A step towards understanding the significance of the problem

Summary   The Australian irrigation industry diverts significant volumes of water from our rivers, and as such, may also divert and entrain riverine fish. Although it is widely acknowledged that our native fish fauna have been greatly affected by a variety of anthropogenic changes, little is known about the extent or significance of fish entrainment in irrigation systems. This paper presents results from a preliminary investigation into the diversion of fish into irrigation channels undertaken in the Goulburn-Murray Irrigation Network, Victoria, Australia. The case study and our knowledge of the life-history strategies of the Basin's fish fauna suggest that the loss of native fish into irrigation networks may be a substantial problem, which, up until recently, has been largely ignored. We strongly suggest that the impact of diversions on native fish populations requires urgent further investigation and quantification, through the cooperation of water management authorities and fish biologists.     

A synergistic approach towards understanding the functional significance of dopamine receptor interactions

The importance of the neurotransmitter dopamine (DA) in the nervous system is underscored by its role in a wide variety of physiological and neural functions in both vertebrates and invertebrates. Binding of dopamine to its membrane receptors initiates precise signaling cascades that result in specific cellular responses. Dopamine receptors belong to a super-family of G-protein coupled receptors (GPCRs) that are characterized by seven trans-membrane domains. In mammals, five dopamine receptors have been identified which are grouped into two different categories D1- and D2-like receptors. The interactions of DA receptors with other proteins including specific Gα subunits are critical in deciding the fate of downstream molecular events carried out by effector proteins. In this mini-review we provide a synopsis of known protein-protein interactions of DA receptors and a perspective on the potential synergistic utility of Caenorhabditis elegans as a model eukaryote with a comparatively simpler nervous system to gain insight on the neuronal and behavioral consequences of the receptor interactions.     

Transfer cell wall architecture: a contribution towards understanding localized wall deposition

Summary. A survey is presented of the architecture of secondary wall ingrowths in transfer cells from various taxa based on scanning electron microscopy. Wall ingrowths are a distinguishing feature of transfer cells and serve to amplify the plasma membrane surface area available for solute transport. Morphologically, two categories of ingrowths are recognized: reticulate and flange. Reticulate-type wall ingrowths are characterized by the deposition of small papillae that emerge from the underlying wall at discrete but apparently random loci, then branch and interconnect to form a complex labyrinth of variable morphology. In comparison, flange-type ingrowths are deposited as curvilinear ribs of wall material that remain in contact with the underlying wall along their length and become variously elaborate in different transfer cell types. This paper discusses the morphology of different types of wall ingrowths in relation to existing models for deposition of other secondary cell walls. Received July 20, 2001 Accepted November 29, 2001     

A first step towards successful conservation: understanding local oviposition site selection of an imperiled butterfly, mardon skipper

Lack of basic biological information is a key limiting factor in conservation of at-risk butterflies. In the Puget prairies of Washington State little is known about the habitat requirements of mardon skipper (Polites mardon, federal candidate, WA endangered). We investigated oviposition site selection and used our results to assess oviposition habitat quality at a restored site with reintroduction potential. During the 2009 flight season we marked eighty-eight eggs and sampled vegetation at oviposition and random locations, measuring habitat variables with respect to the oviposition plant, vegetation structure, and vegetation cover. Eighty-six of the eighty-eight eggs were laid on Festuca roemeri, a native, perennial bunchgrass. Discriminant function analysis revealed selection of oviposition sites based on habitat structure; females laid eggs in small F. roemeri tufts in sparsely vegetated areas of the prairie. These results are contrary to results from a previous study in the Cascade Mountains of WA where females are generalists and selected densely vegetated areas, suggesting that the species has geographically specific habitat requirements. To assess oviposition habitat at a potential reintroduction site we measured the six variables most important for oviposition at the occupied site and a proposed reintroduction site. Results revealed differences in habitat quality between locations and suggest a need for further habitat management at the reintroduction site. Our results highlight the importance of understanding the local habitat use of a rare species where restoration activities occur and increase our ability to target habitat management where it is most needed for the persistence of the species.     

A new approach to understanding the initial step in visual transduction.

Data from picosecond spectroscopic studies of the formation kinetics of bathorhodopsin upon photolysis of rhodopsin and isorhodopsin was analyzed in terms of the Englman-Jortner theory of radiationless transitions. It was found that low frequency vibrations of the protein and/or chromophore are important in coupling bathorhodopsin to its precursor. The results were consistent with a mechanism for bathorhodopsin formation involving only a simple chromophore isomerization. A similar analysis of the formation kinetics of the K state of bacteriorhodopsin showed that different low frequency vibrations than those calculated for rhodopsin couple it to its precursor. The frequency of these vibrations increases upon deuteration for rhodopsin, while it decreases upon deuteration for bacteriorhodopsin. This points out the importance the specific protein matrix has on the primary photolysis reaction.     

Investigations of hippocampal astrocytes in lipopolysaccharide-preconditioned rats in the pilocarpine model of epilepsy

The present paper is the first work to determine the effect of lipopolysaccharide (LPS) in the pilocarpine model of epilepsy on the morphology of rat hippocampal astrocytes in vivo. The study involved adult male Wistar rats, which 72 hours prior to administration of pilocarpine hydrochloride (PILO) were intraperitoneally (ip) preconditioned with LPS at a dose of 0.5 mg/kg b.w. The control animals were administered (ip) saline or LPS alone. The astrocytes in the control animals displayed characteristic stellate morphology. Examinations of the astrocytes were performed on days one, three and 21 of the pilocarpine model of epilepsy (i.e. in the acute, silent and chronic periods). The astrocytes of the CA1 and CA3 pyramidal layers of the hippocampus were observed and analyzed at the structural and ultrastructural levels. It was demonstrated that on days one and three, glial cells from both the nonpreconditioned and the LPS-preconditioned animals displayed similar reactive changes, manifesting themselves as swelling of cell bodies, glial processes, and astrocytosis. Moreover, reduction in cell organelles aggregated at one pole and the presence of vacuoles were observed. The most pronounced astrogliosis and cell swelling occurred on day 21. We conclude that LPS has no effect on the morphology of astrocytes in the pilocarpine model of epilepsy, unlike the results obtained by other authors in vitro.     

Novel semicarbazones based 2,5-disubstituted-1,3,4-oxadiazoles: One more step towards establishing four binding site pharmacophoric model hypothesis for anticonvulsant activity

A series of novel N¹-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N⁴-(4-substitutedbenzaldehyde)-semicarbazone, N¹-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N⁴-[1-(4-substitutedphenyl)ethanone]-semicarbazone and N¹-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N⁴-[1-(4-substitutedphenyl) (phenyl) methanone]-semicarbazone were designed and synthesized on the basis of semicarbazone based pharmacophoric model to meet the structural requirements necessary for anticonvulsant activity. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models. Some of the selected active compounds were subjected to GABA assay to confirm their mode of action. The efforts were also made to establish structure activity relationships among synthesized compounds. The results of the present studying validated that the pharmacophoric model with four binding sites is essential for anticonvulsant activity.     

From information to understanding: the role of model organism databases in comparative and functional genomics

Data integration is key to functional and comparative genomics because integration allows diverse data types to be evaluated in new contexts. To achieve data integration in a scalable and sensible way, semantic standards are needed, both for naming things (standardized nomenclatures, use of key words) and also for knowledge representation. The Mouse Genome Informatics database and other model organism databases help to close the gap between information and understanding of biological processes because these resources enforce well-defined nomenclature and knowledge representation standards. Model organism databases have a critical role to play in ensuring that diverse kinds of data, especially genome-scale data sets and information, remain useful to the biological community in the long-term. The efforts of model organism database groups ensure not only that organism-specific data are integrated, curated and accessible but also that the information is structured in such a way that comparison of biological knowledge across model organisms is facilitated.     

A Comparative View of Alpha Crystallins: The contribution of comparative studies to understanding function

Integration between comparative biology and cellular/molecularbiology has helped advance understanding of the structure, functionand physiology of the vertebrate small heat shock proteins A-and B-crystallin. These proteins are expressed at high concentrationin the eye lens where they contribute to transparency and refractivepower. But they also function similarly to molecular chaperonesby preventing the aggregation of denatured proteins that cancause opacities, or cataracts. -crystallins also serve a numberof other roles in and out of the lens that are still not completelyunderstood. Comparative examination of -crystallins and closelyrelated small heat shock proteins from diverse taxa has helpedprovide insights into the proteins' three-dimensional shapeand structure/function relationships. Until recently, no studieshad examined the tissue specific expression or chaperone-likeactivity of -crystallins from a non-mammalian vertebrate. Ihave been investigating the -crystallins of the zebrafish, Daniorerio, as a first step towards utilizing the bony fishes asa model group for understanding the evolution of -crystallinfunction. Zebrafish A-crystallin displays similar structureand expression and increased chaperone-like activity comparedto its human orthologue. Zebrafish B-crystallin, however, hasa truncated C-terminal extension, more limited expression andlower chaperone-like activity than its human orthologue. Thesedata suggest that A-crystallin physiological function may beconserved between zebrafish and mammals, while B-crystallinphysiological function has diverged. Understanding zebrafish-crystallin physiology is necessary before this species canbe used for developmental and genetic studies, and providesa foundation for further comparative studies.     

Multiple roles of ephrins during the formation of thalamocortical projections: maps and more

The functional architecture of the cerebral cortex is based on intrinsic connections that precisely link neurons from distinct cortical laminae as well as layer-specific afferent and efferent projections. Experimental strategies using in vitro assays originally developed by Friedrich Bonhoeffer have suggested that positional cues confined to individual layers regulate the assembly of local cortical circuits and the formation of thalamocortical projections. One of these wiring molecules is ephrinA5, a ligand for Eph receptor tyrosine kinases. EphrinA5 and Eph receptors exhibit highly dynamic expression patterns in distinct regions of the cortex and thalamus during early and late stages of thalamocortical and cortical circuit formation. In vitro assays suggest that ephrinA5 is a multifunctional wiring molecule for different populations of cortical and thalamic axons. Additionally, the expression patterns of ephrinA5 during cortical development are consistent with this molecule regulating, in alternative ways, specific components of thalamic and cortical connectivity. To test this directly, the organization of thalamocortical projections was examined in mice lacking ephrinA5 gene expression. The anatomical studies in ephrinA5 knockout animals revealed a miswiring of limbic thalamic projections and changes in neocortical circuits that were predicted from the expression pattern and the in vitro analysis of ephrinA5 function.