Methods in molecular biology
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For decades, researchers have used animal self-administration models to examine the effects drugs of abuse have on physiology and behavior. Sophisticated self-administration procedures have been developed to model many different aspects of drug addiction. ⋯ In this way, animals can hold the lever down for any duration of time thereby self-administering any dose on a continuous spectrum. This procedure eliminates some of the ambiguity in translating results from effects only observed at one unit dose and allows examination of which dose the animal "prefers" at different times.
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Central neuropathic pain is associated with many disease states including multiple sclerosis, stroke, and spinal cord injury, and is poorly managed. One type of central neuropathic pain that is particularly debilitating and challenging to treat is pain that occurs below the level of injury (below-level pain). The study of central neuropathic pain is commonly performed using animal models of stroke and spinal cord injury. ⋯ The second was developed to accommodate intrathecal application of pharmacological manipulations. This model provides an additional means by which to investigate central pain states associated with spinal cord injury, including below-level pain. Finally, a brief discussion of at-level pain measurement is described as it has been suggested in the literature that the mechanisms underlying below- and at-level pain are different.
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All investigators face the same challenge - the highly competitive nature of the grant review process. Innovation alone is not enough to ensure grant supported funding. ⋯ Therefore, specific granting mechanisms and program initiatives target translational research studies. This chapter provides grant writing tips and lists resources that may prove helpful for new investigators seeking research funding in support of translational research, biobanking, and research utilizing molecular biomarkers.
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Translational bioinformatics plays an indispensable role in transforming psychoneuroimmunology (PNI) into personalized medicine. It provides a powerful method to bridge the gaps between various knowledge domains in PNI and systems biology. Translational bioinformatics methods at various systems levels can facilitate pattern recognition, and expedite and validate the discovery of systemic biomarkers to allow their incorporation into clinical trials and outcome assessments. ⋯ Methods based on data integration, data mining, and knowledge representation are essential elements in building health information systems such as electronic health records and computerized decision support systems. Data integration of genes, pathophysiology, and behaviors are needed for a broad range of PNI studies. Knowledge discovery approaches such as network-based systems biology methods are valuable in studying the cross-talks among pathways in various brain regions involved in disorders such as Alzheimer's disease.
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The role of membrane proteins is critical for regulation of physiologic and pathologic cellular processes. Hence it is not surpassing that membrane proteins make ∼70% of contemporary drug targets. Quantitative profiling of membrane proteins using mass spectrometry (MS)-based proteomics is critical in a quest for disease biomarkers and novel cancer drugs. ⋯ After mixing, the differentially labeled peptides are fractionated using off-line strong cation exchange (SCX) followed by on-line reversed phase nanoflow reversed-phase liquid chromatography (nanoRPLC)-MS identification/quantiation of peptides/proteins. The use of methanol-based buffers in the context of the post-digestion (18)O exchange/labeling eliminates the need for detergents or chaotropes that interfere with LC separations and peptide ionization. Sample losses are minimized because solubilization, digestion, and stable isotope labeling are carried out in a single tube, avoiding any sample transfer or buffer exchange between these steps.