Serotonin (5-HT) action via the 5-HT 2C receptor (5-HT 2C R) provides an important modulatory influence over neurons of the prefrontal cortex (PFC), which is critically involved in disorders of executive function including substance use disorders. In the present study, we investigated the distribution of the 5-HT 2C R in the rat prelimbic PFC (PrL), a subregion of the medial PFC (mPFC), using a polyclonal antibody raised against the 5-HT 2C R. The expression of 5-HT 2C R immunoreactivity (IR) was highest in the deep layers (layerV/VI) of the mPFC. The 5-HT 2C R-IR was typically most intense at the periphery of cell bodies and the initial segment of cell processes. Approximately 50% of the 5-HT 2C R-IR detected was found in GAD 67-positive neurons. Of the subtypes of γ-aminobutyric acid (GABA) interneurons identified by expression of several calcium-binding proteins, a significantly higher percentage of neurons expressing IR for parvalbumin also expressed 5-HT 2C R-IR than did the percentage of neurons expressing calbindin-IR or calretinin-IR that also expressed 5-HT 2C R-IR. Since parvalbumin is located in basket and chandelier GABA interneurons which project to cell body and initial axon segments of pyramidal cells, respectively, these results raise the possibility that the 5-HT 2C R in the mPFC acts via the parvalbumin-positive GABAergic interneurons to regulate the output of pyramidal cells in the rat mPFC. KeywordsImmunohistochemistry; parvalbumin; calbindin; calretinin; prelimbic prefrontal cortex Recent advances in understanding the neural circuitry and mechanisms underlying the vulnerability to drug abuse, the progression of drug use to addiction, and the triggers for relapse provide hope that new therapeutic approaches are forthcoming for this brain disorder (Kalivas and Volkow, 2005;Koob and Le, 2005;Hyman et al., 2006). A loss of the normal regulatory role for prefrontal cortex (PFC) over the mesoaccumbens dopamine (DA) circuit that is central to drug reward has been identified as a key component in addiction, and pharmacological approaches to reinstate normal PFC function may prove to be Address for Correspondence: Kathryn A. Cunningham, Ph.D., Center for Addiction Research, Department of Pharmacology and Toxicology, University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX 77555-1031, Voice: 409-772-9629, FAX: 409-772-9642, kcunning@utmb.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 August 2. (Kalivas and Volkow, 2005). The PFC i...
Magnetic resonance imaging (MRI) techniques were used to determine the effect of preexisting hyperglycemia on the extent of cerebral ischemia/reperfusion injury and the level of cerebral perfusion. Middle cerebral artery occlusion (MCAO) was induced by a suture insertion technique. Forty one rats were divided into hyperglycemic and normoglycemic groups with either 4 hours of continuous MCAO or 2 hours of MCAO followed by 2 hours of reperfusion. Diffusion-weighted imaging (DWI) was performed at 4 hours after MCAO to quantify the degree of injury in 6 brain regions. Relative cerebral blood flow (CBF) and cerebral blood volume (CBV) were estimated using gradient echo (GE) bolus tracking and steady-state spin echo (SE) imaging techniques, respectively. Brain injury correlated with the perfusion level measured in both SE CBV and dynamic GE CBF images. In the temporary MCAO model, mean lesion size in DWI was 118% larger and hemispheric CBV was reduced by 37% in hyperglycemic compared with normoglycemic rats. Hyperglycemia did not significantly exacerbate brain injury or CBV deficit in permanent MCAO models. We conclude that preexisting hyperglycemia increases acute postischemic MRI-measurable brain cellular injury in proportion to an associated increased microvascular ischemia.
Similarities in the sequence and structure of allergens can explain clinically observed crossreactivities. Distinguishing sequences that bind IgE in patient sera can be used to identify potentially allergenic protein sequences and aid in the design of hypo-allergenic proteins. The property distance index PD, incorporated in our Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/), may identify potentially cross-reactive segments of proteins, based on their similarity to known IgE epitopes. We sought to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to three linear IgE epitopes of Jun a 1, the dominant allergen from mountain cedar pollen. For each of the three epitopes, 60 peptides were designed with increasing PD values (decreasing physicochemical similarity) to the starting sequence. The peptides synthesized on a derivatized cellulose membrane were probed with sera from patients who were allergic to Jun a 1, and the experimental data were interpreted with a PD classification method. Peptides with low PD values relative to a given epitope were more likely to bind IgE from the sera than were those with PD values larger than 6. Control sequences, with PD values between 18 and 20 to all the three epitopes, did not bind patient IgE, thus validating our procedure for identifying negative control peptides. The PD index is a statistically validated method to detect discrete regions of proteins that have a high probability of cross-reacting with IgE from allergic patients.
It is possible for the first time to measure surface area of decubitus ulcers. This may provide a way of determining accurately the dose of newly proposed topical treatments.
This paper presents a syntactic/semantic string representation scheme as well as a string matching method as part of a computer-assisted system to identify dolphins from photographs of their dorsal fins. A low-level string representation is constructed from the curvature function of a dolphin's fin trailing edge, consisting of positive and negative curvature primitives. A high-level string representation is then built over the low-level string via merging appropriate groupings of primitives in order to have a less sensitive representation to curvature fluctuations or noise. A family of syntactic/semantic distance measures between two strings is introduced. A composite distance measure is then defined and used as a dissimilarity measure for database search, highlighting both the syntax (structure or sequence) and semantic (attribute or feature) differences. The syntax consists of an ordered sequence of significant protrusions and intrusions on the edge, while the semantics consist of seven attributes extracted from the edge and its curvature function. The matching results are reported for a database of 624 images corresponding to 164 individual dolphins. The identification results indicate that the developed string matching method performs better than the previous matching methods including dorsal ratio, curvature, and curve matching. The developed computer-assisted system can help marine mammalogists in their identification of dolphins, since it allows them to examine only a handful of candidate images instead of the currently used manual searching of the entire database.
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