Preference Reversals and Effects of d-Amphetamine on Within-Session Delay Discounting in Rats

Impulsive choice is correlated with behavioral problems such as attention-deficit/hyperactivity-disorder and can be assessed using delay-discounting procedures in which subjects choose between a smaller, more immediate reinforcer (impulsive choice) and a larger, more delayed reinforcer (self-controlled choice). A within-session delay-discounting procedure in which choice was between one food pellet delivered immediately and three food pellets delivered after increasing delays was used to examine effects of adding or subtracting delays common to both reinforcers on impulsive choice in male Sprague-Dawley rats (N = 8). For all subjects, delay discounting was observed regardless of whether delays common to both reinforcers were added or subtracted. Using area under the curve (AUC) to quantify impulsive choice, adding delays common to both reinforcers decreased impulsive choice whereas subtracting delays common to both reinforcers increased impulsive choice. Prior to d-amphetamine administration, subjects were rank ordered into High-impulsive or Low-impulsive groups using AUC at the final delay condition. Subjects in the High-impulsive group made more impulsive choices than subjects in the Low-impulsive group and effects of d-amphetamine (0.03, 0.1, 0.18, 0.3, 0.56, 1.0, 1.8 mg/kg) generally depended on these differences. Select doses of d-amphetamine decreased impulsive choice for subjects in the High-impulsive group but not for subjects in the Low-impulsive group. These results show that levels of impulsive choice can be altered by changing the delay common to both reinforcers and suggest that effects of d-amphetamine on impulsive choice are determined, in part, by baseline levels of impulsive choice

Effects of Response-Independent Food Pellet Delivery on the Development of Tolerance to the Rate-Decreasing Effect of d-Amphetamine in Rats

The extent to which initial drug administration decreases the ability of an organism to obtain reinforcement can affect the development of behavioral tolerance. Environmental enrichment affects many drug-related phenomena, but its effects on the development of tolerance are not clear. The present study examined how enriching the environment by providing non-contingent food pellets during experimental sessions affects the development of tolerance to a dose of d-amphetamine that produces a loss in reinforcement. Lever pressing for food pellets was maintained under a multiple schedule consisting of two variable-interval (VI) 60-s components. One component was enriched by providing food pellets non-contingently under a variable-time (VT) 120-s schedule for rats in the Less-Enriched Group (n = 6) and a VT 30-s schedule for rats in the More-Enriched Group ( n = 6). Effects of a range of doses of d-amphetamine (0.1 to 3.0 mg/kg) were assessed before (acute) and during (chronic) repeated injections of a dose that reduced the number of food pellets earned by at least 50% from sessions in which saline was tested acutely. There was a dose-dependent decrease in lever pressing, and relatively large doses were required to decrease the number of food pellets earned. Tolerance developed to a similar extent between components with and without non-contingent food pellets for rats in both groups. These results indicate that enriching the environment by providing non-contingent food pellets during experimental sessions does not differentially affect the development of tolerance

The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha

To identify new potential substrates for the MAP kinase signal-integrating kinases (Mnks), we employed a proteomic approach. The Mnks are targeted to the translational machinery through their interaction with the cap-binding initiation factor complex. We tested whether proteins retained on cap resin were substrates for the Mnks in vitro, and identified one such protein as PSF (the PTB (polypyrimidine tract-binding protein)-associated splicing factor). Mnks phosphorylate PSF at two sites in vitro, and our data show that PSF is an Mnk substrate in vivo. We also demonstrate that PSF, together with its partner, p54nrb, binds RNAs that contain AU-rich elements (AREs), such as those for proinflammatory cytokines (e.g. tumor necrosis factor ? (TNF?)). Indeed, PSF associates specifically with the TNF? mRNA in living cells. PSF is phosphorylated at two sites by the Mnks. Our data show that Mnk-mediated phosphorylation increases the binding of PSF to the TNF? mRNA in living cells. These findings identify a novel Mnk substrate. They also suggest that the Mnk-catalyzed phosphorylation of PSF may regulate the fate of specific mRNAs by modulating their binding to PSF·p54nrb

Beauty, Vanity, and Perception in the Sonnets of Shakespeare

https://digitalcommons.usu.edu/english_3315/1005/thumbnail.jp

Modeling and experimental methods to predict oxygen distribution in bone defects following cell transplantation

We have developed a mathematical model that allows simulation of oxygen distribution in a bone defect as a tool to explore the likely effects of local changes in cell concentration, defect size or geometry, local oxygen delivery with oxygen-generating biomaterials (OGBs), and changes in the rate of oxygen consumption by cells within a defect. Experimental data for the oxygen release rate from an OGB and the oxygen consumption rate of a transplanted cell population are incorporated into the model. With these data, model simulations allow prediction of spatiotemporal oxygen concentration within a given defect and the sensitivity of oxygen tension to changes in critical variables. This information may help to minimize the number of experiments in animal models that determine the optimal combinations of cells, scaffolds, and OGBs in the design of current and future bone regeneration strategies. Bone marrow-derived nucleated cell data suggest that oxygen consumption is dependent on oxygen concentration. OGB oxygen release is shown to be a time-dependent function that must be measured for accurate simulation. Simulations quantify the dependency of oxygen gradients in an avascular defect on cell concentration, cell oxygen consumption rate, OGB oxygen generation rate, and OGB geometry

A Clinically Relevant Method of Analyzing Continuous Change in Robotic Upper Extremity Chronic Stroke Rehabilitation

Background. Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over time. Objective. To determine how motor recovery profiles during robotic interventions provide insight into improving clinical gains. Methods. A convenience sample (n = 22), from a larger randomized control trial, was taken of chronic stroke participants completing 12 sessions of arm therapy. One group received 60 minutes of robotic therapy (Robot only) and the other group received 45 minutes on the robot plus 15 minutes of translation-to-task practice (Robot + TTT). Movement time was assessed using the robot without powered assistance. Analyses (ANOVA, random coefficient modeling [RCM] with 2-term exponential function) were completed to investigate changes across the intervention, between sessions, and within a session. Results. Significant improvement (P < .05) in movement time across the intervention (pre vs post) was similar between the groups but there were group differences for changes between and within sessions (P < .05). The 2-term exponential function revealed a fast and slow component of learning that described performance across consecutive blocks. The RCM identified individuals who were above or below the marginal model. Conclusions. The expanded analyses indicated that changes across time can occur in different ways but achieve similar goals and may be influenced by individual factors such as initial movement time. These findings will guide decisions regarding treatment planning based on rates of motor relearning during upper extremity stroke robotic interventions

Analysis of Risk Factors for Fatal Rocky Mountain Spotted Fever: Evidence for Superiority of Tetracyclines for Therapy

Epidemiologic and clinical characteristics of fatal and nonfatal cases of Rocky Mountain spotted fever (RMSF) were compared to identify risk factors for death caused by this disease. Confirmed and probable RMSF cases reported through US national surveillance for 1981- 1998 were analyzed. Among 6388 RMSF patients, 213 died (annual case-fatality rate, 3M; range, 4.9 % in 1982 to 1.1 % in 1996). Use of tetracycline-class antibiotics for treatment of RMSF increased significantly in the 1990s, compared with use in the 1980s. Older patients, patients treated with chloramphenicol only, patients for whom tetracycline antibiotics were not the primary therapy, and patients for whom treatment was delayed ≥5 days after the onset of symptoms were at higher risk for death. Although the case-fatality rate was lower in the 1990s than in the 1980s, risk factors for fatal RMSF were similar. Despite the availability of effective antibiotics, RMSF-related deaths continue to occur because of delayed diagnosis and failure to use appropriate therapy

Analysis of Risk Factors for Fatal Rocky Mountain Spotted Fever: Evidence for Superiority of Tetracyclines for Therapy

Epidemiologic and clinical characteristics of fatal and nonfatal cases of Rocky Mountain spotted fever (RMSF) were compared to identify risk factors for death caused by this disease. Confirmed and probable RMSF cases reported through US national surveillance for 1981- 1998 were analyzed. Among 6388 RMSF patients, 213 died (annual case-fatality rate, 3M; range, 4.9 % in 1982 to 1.1 % in 1996). Use of tetracycline-class antibiotics for treatment of RMSF increased significantly in the 1990s, compared with use in the 1980s. Older patients, patients treated with chloramphenicol only, patients for whom tetracycline antibiotics were not the primary therapy, and patients for whom treatment was delayed ≥5 days after the onset of symptoms were at higher risk for death. Although the case-fatality rate was lower in the 1990s than in the 1980s, risk factors for fatal RMSF were similar. Despite the availability of effective antibiotics, RMSF-related deaths continue to occur because of delayed diagnosis and failure to use appropriate therapy

Regional and cell-type-specific effects of DAMGO on striatal D1 and D2 dopamine receptor-expressing medium-sized spiny neurons

The striatum can be divided into the DLS (dorsolateral striatum) and the VMS (ventromedial striatum), which includes NAcC (nucleus accumbens core) and NAcS (nucleus accumbens shell). Here, we examined differences in electrophysiological properties of MSSNs (medium-sized spiny neurons) based on their location, expression of DA (dopamine) D1/D2 receptors and responses to the μ-opioid receptor agonist, DAMGO {[D-Ala2-MePhe4-Gly(ol)5]enkephalin}. The main differences in morphological and biophysical membrane properties occurred among striatal sub-regions. MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances) compared with cells in the VMS. RMPs (resting membrane potentials) were similar among regions except for D2 cells in the NAcC, which displayed a significantly more depolarized RMP. In contrast, differences in frequency of spontaneous excitatory synaptic inputs were more prominent between cell types, with D2 cells receiving significantly more excitatory inputs than D1 cells, particularly in the VMS. Inhibitory inputs were not different between D1 and D2 cells. However, MSSNs in the VMS received more inhibitory inputs than those in the DLS. Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount. DAMGO also increased cellular excitability in the VMS, as shown by reduced threshold for evoking APs (action potentials). Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects

Long-term biological effects of petroleum residues on fiddler crabs in salt marshes

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Pollution Bulletin 54 (2007): 955-962, doi:10.1016/j.marpolbul.2007.02.015.In September 1969,the Florida barge spilled 700,000 L of No. 2 fuel oil into the salt marsh sediments of Wild Harbor (Buzzards Bay, MA). Today the aboveground environment appears unaffected, but a substantial amount of moderately degraded petroleum still remains 8 to 20 cm below the surface. The salt marsh fiddler crabs, Uca pugnax, which burrow into the sediments at depths of 5 to 25 cm, are chronically exposed to the spilled oil. Behavioral studies conducted with U. pugnax from Wild Harbor and a control site, Great Sippewissett marsh, found that crabs exposed to the oil avoided burrowing into oiled layers, suffered delayed escape responses, lowered feeding rates, and lower densities. The oil residues are therefore biologically active and affect U. pugnax populations. Our results add new knowledge about long-term consequences of spilled oil, a dimension that should be included when assessing oil-impacted areas and developing management plans designed to restore, rehabilitate, or replace impacted areas.This work was funded by a grant from the Woods Hole Oceanographic Institution Sea Grant Program, under grants from the National Oceanic and Atmospheric Administration, U.S. Department of Commerce, under Grant No. NA16RG2273, project no. R/P-73. Additional support was provided by funding from the NSF funded Research Experience for Undergraduates program, award 0453292, an Office of Naval Research Young Investigator Award (N00014-04-01-0029) to C. Reddy, and an USEPA Science to Achieve Results Graduate Fellowship (FP91661801) to E. Peacock