Spectral analysis of the Laplacian acting on discrete cusps and funnels

We study perturbations of the discrete Laplacian associated to discrete analogs of cusps and funnels. We perturb the metric and the potential in a long-range way. We establish a propagation estimate and a Limiting Absorption Principle away from the possible embedded eigenvalues. The approach is based on a positive commutator technique

Analytical studies on channel forming proteins

Abstract. Antimicrobial peptides have shown great potential as pharmaceutical agents, they are being considered for their ability to fight bacterial and fungal infections and even to destroy cancerous cells by disrupting the cell membranes of their targets. A clear understanding of the mechanism behind their activity and how this is related to their structure is therefore essential if these peptides are to be considered as precursors for the next generation of a new range of drags. This research project has been involved in the development of a series of analogous model amphiphilic cyclic peptides, which were designed to adopt a ß- sheet conformation on inserting into lipid membranes. The model peptides were examined using a wide range of analytical techniques; these studies have enabled both the propensity of these peptides to adopt transmembrane ß sheet structures to be established and to gain some understanding of their behaviour under different environments. Circular dichroism and its sister technique linear dichroism have shown both the structure and the orientation of the peptide backbone on insertion into lipid membranes. Calorimetrie studies have demonstrated the extent of the cyclic peptide disruption on the phase transition of saturated and unsaturated phospholipid membranes and electron microscopy has revealed the ability of one of the model peptides to form fibrous structures on precipitation from a solution of the fluorinated alcohol, hexafluoroisopropanol (HFIP) in water. A natural ß -sheet forming protein, the C-terminal domain of the autotransporter protein BrKA from Bordetella pertussis was overexpressed to provide a comparison for the model )ff-sheet peptides. Attempts were made to grow highly ordered 2D arrays of the protein in phospholipid membranes for structural analysis by both transmission electron microscopy and atomic force microscopy. The effect of the fluorinated alcohol HFIP, which was used to solubilise the amphiphilic peptides, was examined on phospholipid systems. The study was considered to afford some understanding towards the integration of small molecules into membranes

A 3D SPATIAL NAVIGATION TASK FOR ASSESSING MEMORY IN RODENTS

In the present report we describe a 3-D maze spatial navigation task for rats based on a modification of an eight-arm radial maze. The arms radiating from a central platform can be presented in a horizontal plane either raised 10 cm above the level of a central platform or lowered 10 cm below. Memory of visited and non-visited arms can be guided by distinct internal cues (patterns) that are presented on panels set at the end of each arm. Rats are trained in three different maze configurations (eight session each) with arms set lowered, flattened or raised relative to a central platform. A food pellet is placed at the end of each arm and rats are allowed to make eight arm choices only, in each testing session. In this task rats perform better when moving uphill to raised arms than when moving on flattened arms or when moving downhill to lowered arms. It is likely that spatial navigation on raised arms is based on visual cues that were highly visible from the central platform. This result can be accounted for by the position of the rats' eyes that are placed laterally on the sides of their heads

Effects of methimepip and JNJ-5207852 in Wistar rats exposed to an open-field with and without object and in Balb/c mice exposed to a radial-arm maze

The role of the histamine H3 receptor (H3R) in anxiety is controversial, due to limitations in drug selectivity and limited validity of behavioral tests used in previous studies. In the present report, we describe two experiments. In the first one, Wistar rats were treated with an H3R agonist (methimepip), and exposed to an open-field. In the second one, Balb/c mice were treated with H3R agonist (methimepip) or antagonist (JNJ-5207852), and exposed to an open space 3D maze which is a modified version of the radial-arm maze. C57BL/6J saline treated mice were included for comparisons. When exposed to an empty open field, Wistar rats spent more time in the outer area and made very low number of brief crossings in the central area. However, when an object occupied the central area, rats crossed frequently into and spent a long time in the central area. Administration of a range of different doses of methimepip (selective H3R agonist) reduced the entries into the central area with a novel object, indicating enhanced avoidance response. In the 3D maze, both Balb/c and C57BL/6J saline-treated mice crossed frequently onto the bridges that radiate from the central platform but only C57BL/6J mice crossed onto the arms which extend the bridges. This suggests that Balb/c mice are more anxious than C57BL/6J mice. Neither methimepip nor JNJ-5207852 (selective H3R antagonist/inverse agonist) induced entry into the arms of the maze, indicative of lack of anxiolytic effects

Pre-training in a radial arm maze abolished anxiety and impaired habituation in C57BL6/J mice treated with dizocilpine

Familiarity can imply a reduction of fear and anxiety, which may render learning and memory performance insensitive to NMDA receptor antagonism. Our previous study indicates that MK-801 (dizocilpine), NMDA antagonist, increased anxiety and prevented the acquisition of a spatial memory task. Here, we examined whether MK-801 will produce anxiety in mice that were familiar with the test environment. Male C57BL/6J mice were exposed, one session a day for 7 days, to a 3D maze, which consisted of nine arms attached to upward inclined bridges radiating from a nonagonal platform. In this maze, high anxiety mice avoid the arms in the first sessions. One group of mice received saline (SAL) while a second group received MK-801 (MKD1), both on day one. A third group received saline in the first 3 sessions, and MK 801 in subsequent sessions (MKD4). Saline and MK-801 (0.1 mg/kg) were administered intraperitoneally 30 min before the test. MKD4 mice demonstrated an increase in bridge and arm visits, and reached arm/bridge entries ratio close to 1 in session 5. SAL mice also crossed frequently onto the arms, and reached a comparable ratio, but this was achieved with a lower number of arm visits. MKD1 mice demonstrated a reduced number of arm visits in each session compared to SAL and MKD4 mice. Dizocilpine produced anxiety in mice treated from day 1 of the test, but not in those treated from day 4. It also impaired habituation in animals familiar with the test environment; it produced sustained non-habituating hyperactivity

Pre-training in a radial arm maze abolished anxiety and impaired habituation in C57BL6/J mice treated with dizocilpine

Familiarity can imply a reduction of fear and anxiety, which may render learning and memory performance insensitive to NMDA receptor antagonism. Our previous study indicates that MK-801 (dizocilpine), NMDA antagonist, increased anxiety and prevented the acquisition of a spatial memory task. Here, we examined whether MK-801 will produce anxiety in mice that were familiar with the test environment. Male C57BL/6J mice were exposed, one session a day for 7 days, to a 3D maze, which consisted of nine arms attached to upward inclined bridges radiating from a nonagonal platform. In this maze, high anxiety mice avoid the arms in the first sessions. One group of mice received saline (SAL) while a second group received MK-801 (MKD1), both on day one. A third group received saline in the first 3 sessions, and MK 801 in subsequent sessions (MKD4). Saline and MK-801 (0.1 mg/kg) were administered intraperitoneally 30 min before the test. MKD4 mice demonstrated an increase in bridge and arm visits, and reached arm/bridge entries ratio close to 1 in session 5. SAL mice also crossed frequently onto the arms, and reached a comparable ratio, but this was achieved with a lower number of arm visits. MKD1 mice demonstrated a reduced number of arm visits in each session compared to SAL and MKD4 mice. Dizocilpine produced anxiety in mice treated from day 1 of the test, but not in those treated from day 4. It also impaired habituation in animals familiar with the test environment; it produced sustained non-habituating hyperactivity

Identification of a Novel GABAA Receptor Channel Ligand Derived from Melissa officinalis and Lavandula angustifolia Essential Oils

Aims: Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils and their major constituents ((E) - caryophyllene, caryophyllene oxide, geranyl acetate, linalool, nerol, Oct-1-en-3-ol, 3-Octanone, myrcene, allo-ocimene, p-cymene and α- terpineol) assessed by GC-MS) which are shared by these two essential oils were probed in an attempt to identify the GABAAR ligand(s). Study Design: [35S] t-butylbicyclophosphorothionate (TBPS) radioligand binding assay to GABAA receptors. In vitro neuronal viability assay. Place and Duration of Study: School of Biological and Biomedical Sciences, Durham University, United Kingdom (December 2012 and January 2013). Results: One of the major component (s) of (Mo), trans-ocimene, inhibited [35S] (TBPS) binding to native GABAA receptors in a concentration-dependent manner with an apparent IC50 of 40μM. Concentrations (0.001 mg/ml) of whole (Mo) were shown to display modest beneficial effects upon neuronal viability while at a higher concentration (0.1 mg/ml) of (Mo) and (La) oils induced a neurotoxicity effect. Conclusion: These data provide the first evidence that allo-ocimene is an neuroactive GABAA R inhibitory component found in both (Mo) and (La), and represents a novel GABAA receptor channel chemotype derived from a natural product. - See more at: http://www.sciencedomain.org/abstract.php?iid=474&id=13&aid=4142#.VCFGHBbQpv