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A common assumption in the study of fixed-interval (FI) timing is that FI performance is largely stable within sessions, once it is stable between sessions. Within-session changes in FI performance were examined in published data (Daniels and Sanabria, 2017), wherein some rats were trained on a FI 30-s schedule of food reinforcement (FI30) and others on a FI 90-s schedule (FI90). Following stability, FI90 rats were pre-fed for five sessions. Response rates declined as a function of trial, due more to latency lengthening than to run-rate reduction. Latencies were best described by a dynamic gamma-exponential mixture distribution, in which latency lengthening was driven by the growth of the criterion pulse count for a response and not by a reduction in the speed of an endogenous clock. The speed of the clock was selectively sensitive to the length of the FI; the prevalence and length of exponentially-distributed latencies were selectively sensitive to pre-feeding. These findings reveal (a) that parameters governing FI latencies are selectively sensitive to a range of manipulations, (b) a potential degradation of the criterion pulse count between consecutive sessions, and (c) a subsequent recovery of the criterion pulse count within sessions.

Sciatic nerve chronic constriction injury (CCI) in rodents produces nerve demyelination via proteolysis of myelin basic protein (MBP), the major component of myelin sheath. Proteolysis releases the cryptic MBP epitope, a demyelination marker, which is hidden in the native MBP fold. It has never been established if the proteolytic release of this cryptic MBP autoantigen stimulates the post-injury increase in the respective circulating autoantibodies. To measure these autoantibodies, we developed the ELISA that employed the cryptic 84-104 MBP sequence (MBP84-104) as bait. This allowed us, for the first time, to quantify the circulating anti-MBP84-104 autoantibodies in rat serum post-CCI. The circulating IgM (but not IgG) autoantibodies were detectable as soon as day 7 post-CCI. The IgM autoantibody level continually increased between days 7 and 28 post-injury. Using the rat serum samples, we established that the ELISA intra-assay (precision) and inter-assay (repeatability) variability parameters were 2.87% and 4.58%, respectively. We also demonstrated the ELISA specificity by recording the autoantibodies to the liberated MBP84-104 epitope alone, but not to intact MBP in which the 84-104 region is hidden. Because the 84-104 sequence is conserved among mammals, we tested if the ELISA was applicable to detect demyelination and quantify the respective autoantibodies in humans. Our limited pilot study that involved 16 female multiple sclerosis and fibromyalgia syndrome patients demonstrated that the ELISA was efficient in measuring both the circulating IgG- and IgM-type autoantibodies in patients exhibiting demyelination. We believe that the ELISA measurements of the circulating autoantibodies against the pathogenic MBP84-104 peptide may facilitate the identification of demyelination in both experimental and clinical settings. In clinic, these measurements may assist neurologists to recognize patients with painful neuropathy and demyelinating diseases, and as a result, to personalize their treatment regimens.

The present study examined how systemic low doses of nicotine affect the microstructure of reinforced food-seeking behavior in rats. Rats were first given an acute saline or nicotine treatment (0.1–0.6 mg/kg, with an inter-injection interval of at least 48 h), and then a chronic saline or nicotine treatment (0.3 mg/kg/day for 10 consecutive days). Immediately after each injection, rats were required to press a lever five times to obtain food that was available at unpredictable times (on average every 80 s) with constant probability. Acute nicotine dose-dependently suppressed behavior prior to the delivery of the first reinforcer, but enhanced food-reinforced behavior afterwards. These effects were primarily observed in the time it took rats to initiate food-seeking behavior. Enhancing effects were also observed in the microstructure of food-seeking behavior, with lower nicotine doses (0.1–0.3 mg/kg) increasing the rate at which response bouts were initiated, and higher doses (0.3–0.6 mg/kg) increasing within-bout response rates. A pre-feeding control suggests that changes in appetite alone cannot explain these effects. Over the course of chronic nicotine exposure, tolerance developed to the suppressive, but not to the enhancing effects of nicotine on food-seeking behavior. These results suggest that (a) lower doses of nicotine enhance the reward value of food and/or food-associated stimuli, (b) higher doses of nicotine enhance motoric activity, and (c) ostensive sensitization effects of nicotine on behavior partially reflect a tolerance to its transient suppressive motoric effects.

Single-atom catalysts (SACs) have shown great potential for achieving superior catalytic activity due to maximizing metal efficiency. The key obstacle in developing SACs lies in the availability of supports that can stabilize SACs. Here we report the first successful development of single gold (Au) atom catalysts supported on high-surface-area hierarchical perovskite oxides. The resulting Au single-atoms are extremely stable at calcination temperatures up to 700 °C in air and under reaction conditions. A high catalytic activity for CO oxidation and distinct self-activating property were also achieved. Furthermore, evidenced by theoretical calculations and experimental studies including X-ray absorption fine structures and in situ Fourier-transform infrared spectra, the surface Au active sites are confirmed to be predominately positively charged. This work provides a generalizable approach to fabricating highly stable Au single-atom catalysts with tunable catalytic performance, and we anticipate that this discovery will facilitate new possibilities for the development of single atom catalysts.

Attention deficit/hyperactivity disorder (ADHD) is a risk factor for tobacco use and dependence. This study examines the responsiveness to nicotine of an adolescent model of ADHD, the spontaneously hypertensive rat (SHR). The conditioned place preference (CPP) procedure was used to assess nicotine-induced locomotion and conditioned reward in SHR and the Wistar Kyoto (WKY) control strain over a range of nicotine doses (0.0, 0.1, 0.3 and 0.6 mg/kg). Prior to conditioning, SHRs were more active and less biased towards one side of the CPP chamber than WKY rats. Following conditioning, SHRs developed CPP to the highest dose of nicotine (0.6 mg/kg), whereas WKYs did not develop CPP to any nicotine dose tested. During conditioning, SHRs displayed greater locomotor activity in the Nicotine-Paired compartment than in the Saline-Paired compartment across conditioning trials. SHRs that received nicotine (0.1, 0.3, 0.6 mg/kg) in the Nicotine-Paired compartment showed an increase in locomotor activity between conditioning trials. Nicotine did not significantly affect WKY locomotor activity. These findings suggest that the SHR strain is a suitable model for studying ADHD-related nicotine use and dependence, but highlights potential limitations of the WKY control strain and the CPP procedure for modeling ADHD-related nicotine reward.

This paper reviews the evidence for nicotine-induced acceleration of the internal clock when timing in the seconds-to-minutes timescale, and proposes an alternative explanation to this evidence: that nicotine reduces the threshold for responses that result in more reinforcement. These two hypotheses were tested in male Wistar rats using a novel timing task. In this task, rats were trained to seek food at one location after 8 s since trial onset and at a different location after 16 s. Some rats received the same reward at both times (group SAME); some received a larger reward at 16 s (group DIFF). Steady baseline performance was followed by 3 days of subcutaneous nicotine administration (0.3 mg/kg), baseline recovery, and an antagonist challenge (mecamylamine, 1.0 mg/kg). Nicotine induced a larger, immediate reduction in latencies to switch (LTS) in group DIFF than in group SAME. This effect was sustained throughout nicotine administration. Mecamylamine pretreatment and nicotine discontinuation rapidly recovered baseline performance. These results support a response-threshold account of nicotinic disruption of timing performance, possibly mediated by nicotinic acetylcholine receptors. A detailed analysis of the distribution of LTSs suggests that anomalous effects of nicotine on LTS dispersion may be due to loss of temporal control of behavior.

A series of new mesoporous silica (MS) sorbents were developed by functionalizing a large-pore 2-D hexagonal MS material, MSU-H, with amidoxime, imide dioxime, phosphonate, and carboxylate functional groups, and characterized by nitrogen adsorption, ζ-potential, infrared spectroscopy, and thermogravimetric analysis. These MS materials have a grafting density of 0.75 to 1.38 mmol/g, and exhibit BET surface areas of 186–526 m 2 /g and average pore sizes of 3.8–7.8 nm. The uranyl sorption by the functionalized MS sorbents was investigated in basic water and artificial seawater at pH = 8.3 ± 0.1. The MS materials exhibited a high U sorption capacity in water (>40 μg U/mg sorbent) with Langmuir isotherms suggesting a saturation U sorption capacity of 185.2 μg U/mg sorbent for the phosphonic acid-modified MS material (MSPh-III). The U sorption capacity in artificial seawater was reduced to 12.1 μg U/mg sorbent for MSPh-III. Langmuir isotherms indicated a saturation sorption capacity of 66.7 μg U/mg sorbent for MSPh-III, which also had the greatest binding affinity for U of all sorbents tested, followed by the imide dioxime-functionalized material MSCA-I. Kinetics studies show rapid uranyl sorption and equilibration in less than 40 min. The U was quantitatively eluted from the MS sorbents by washing with strong acid (>0.1 M HCl). This work represents the first comprehensive study of organo-functionalized MS materials for U extraction, and shows that phosphonic acid- and imide dioxime-functionalized MS materials provide excellent platforms for developing novel sorbents for efficient U extraction from seawater.

Background & Aims: Using a mouse model that reproduces major features of irritable bowel syndrome (long-lasting colon hypersensitivity without inflammation), we examined the contributions of 2 proteins, transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel 3 (ASIC3), on development of behavioral hypersensitivity and assessed the function of colon mechanoreceptors of hypersensitive mice. Methods: Visceral nociceptive behavior was measured as the visceromotor response (VMR) to colorectal distention (CRD) before and after intracolonic treatment with zymosan or saline. Colon pathology was assessed in parallel experiments by quantifying myeloperoxidase activity, intralumenal pH, and tissue histology. Electrophysiologic experiments were performed on naive and zymosan-treated hypersensitive mice using an in vitro colon-pelvic nerve preparation. Results: Zymosan, but not saline, produced significant and persistent increases in the VMRs of control mice; zymosan produced nonsignificant increases in the VMRs in TRPV1 and ASIC3 knockout mice. Colon myeloperoxidase activity and pH were unaffected by either CRD or intracolonic treatments. Pelvic nerve mechanoreceptors recorded from zymosan-treated or naive mice had similar sensitivity to stretch of the colon. When applied acutely, zymosan sensitized muscular/mucosal mechanoreceptors in both naive and hypersensitive mice. Conclusions: Zymosan produced sensitization of colon mechanoreceptors acutely in vitro and chronic (≥7 weeks) behavioral hypersensitivity in the absence of inflammation. The behavioral hypersensitivity was partially dependent on both TRPV1 and ASIC3 because deletions of either of these genes blunted zymosan's effect, suggesting that these proteins may be important peripheral mediators for development of functional (ie, noninflammatory) visceral hypersensitivity.

Mechanosensory information from the colon is conducted via lumbar splanchnic nerves (LSN) and sacral pelvic nerves (PN) to the spinal cord. The precise nature of mechanosensory information encoded by each pathway has remained elusive. Here, we characterize and directly compare the properties of mechanosensitive primary afferents from these 2 pathways.Using a novel in vitro mouse colon preparation, mechanosensitive primary afferents were recorded from the LSN and PN and distinguished based on their response to receptive field stimulation with 3 distinct mechanical stimuli: probing (70 mg-4 g), circular stretch (1-5 g), and mucosal stroking (10-1000 mg).Five different classes of afferent were recorded from the LSN and PN. Three of these classes of afferent (serosal, muscular, and mucosal) were conserved between both pathways; however, their respective proportions, receptive field distributions, and response properties differed greatly. In general, these 3 classes of afferent recorded from the PN responded to lower stimulation intensities, displayed greater response magnitudes, and adapted less completely to mechanical stimulation compared with their LSN counterparts. In addition, the LSN and PN each contain a specialized class of afferent (mesenteric and muscular/mucosal), which is unique to their respective pathway.The splanchnic and pelvic pathways contain distinct populations of mechanosensitive afferents. These afferents are capable of detecting an array of mechanical stimuli and are individually tuned to detect the type, magnitude, and duration of the stimulus. This knowledge contributes to our understanding of the role that these 2 pathways play in conveying mechanical information from the colon.

We model the source of inflation of Long Valley caldera by combining geodetic and micro-gravity data. Uplift from GPS and leveling, two-color EDM measurements, and residual gravity change determinations are used to estimate the intrusion geometry, assuming a vertical prolate ellipsoidal source. The U.S. Geological Survey occupied the Long Valley gravity network six times from 1980 to 1985. We reoccupied this network twice, in the summer of 1998 (33 stations), and the summer of 1999 (37 stations). Before gravity data can be used to estimate the density of the intrusion, they must be corrected for the effect of vertical deformation (the free-air effect) and changes in the water table. We use geostatistical techniques to interpolate uplift and water table changes at the gravity stations. The inflation source (a vertical prolate ellipsoid) is located 5.9 km beneath the resurgent dome with an aspect ratio equal to 0.475, a volume change from 1982 to 1999 of 0.136 km 3 and a density of around 1700 kg/m 3 . A bootstrap method was employed to estimate 95% confidence bounds for the parameters of the inflation model. We obtained a range of 0.105–0.187 km 3 for the volume change, and 1180–2330 kg/m 3 for the density. Our results do not support hydrothermal fluid intrusion as the primary cause of unrest, and confirm the intrusion of silicic magma beneath Long Valley caldera. Failure to account for the ellipsoidal nature of the source biases the estimated source depth by 2.9 km (a 33% increase), the volume change by 0.019 km 3 (a 14% increase) and the density by about 1200 kg/m 3 (a 40% increase).