Effects of chronic cannabinoid exposure during adolescence on reward preference and mPFC activation in adulthood.

Cannabis is one of the most commonly used drugs among adolescents, with initial use beginning between the ages of 12 to 17. Although often perceived as a 'soft drug', both short- and long-term use have been associated with numerous adverse outcomes, including cognitive impairment, increased risk of substance abuse, and heightened risk of psychosis or schizophrenia in individuals with a predisposition. Further, the severity of these impairments is closely linked to initiation of use, i.e. earlier use increases risk. It has been suggested that adolescent vulnerability to the adverse consequences of cannabis use is due to ongoing brain development occurring during this time. Indeed, the adolescent brain continues to be remodeled well into adolescence and early adulthood, particularly in the prefrontal cortex (PFC). The medial prefrontal cortex (mPFC) has been implicated in reward processing and decision-making and alterations in mPFC development due to adolescent cannabis exposure could impair these functions. To model the effects of cannabis on mPFC function, we administered the synthetic cannabinoid WIN 55, 212-2 (WIN) to male and female rats from postnatal day 30-60. Once animals reached adulthood, we used a Probabilistic Reward (PR) choice task to elicit PFC activity and measure how patterns of activity to task-related events were modulated by adolescent WIN-treatment. Adult animals showed subtle effects of WIN-treatment on choice patterns. During task performance, mPFC activity elicited by lever press at the time of choices and reward delivery following choices were reduced in WIN-treated animals. This lasting effect of WIN suggests an impairment of the maturation of excitatory-inhibitory balance of signals in mPFC during adolescence, which may alter executive function into adulthood.

Why self-controlled feedback enhances motor learning: Answers from electroencephalography and indices of motivation.

It was tested whether learners who choose when to receive augmented feedback while practicing a motor skill exhibit enhanced augmented feedback processing and intrinsic motivation, along with superior learning, relative to learners who do not control their feedback. Accordingly, participants were assigned to either self-control (Self) or yoked groups and asked to practice a non-dominant arm beanbag toss. Self participants received augmented feedback at their discretion, whereas Yoked participants were given feedback schedules matched to Self counterparts. Participants' visual feedback was occluded, and when they received augmented feedback, their processing of it was indexed with the electroencephalography-derived feedback-related negativity (FRN). Participants self-reported intrinsic motivation via the Intrinsic Motivation Inventory (IMI) after practice, and completed a retention and transfer test the next day to index learning. Results partially support the hypothesis. Specifically, Self participants reported higher IMI scores, exhibited larger FRNs, and demonstrated better accuracy on the transfer test, but not on the retention test, nor did they exhibit greater consistency on the retention or transfer tests. Additionally, post-hoc multiple regression analysis indicated FRN amplitude predicted transfer test accuracy (accounting for IMI score). Results suggest self-controlled feedback schedules enhance feedback processing, which enhances the transfer of a newly acquired motor skill.

"Selling" value: the influence of language on willingness-to-accept.

In behavioral economics, the "endowment effect" describes the robust finding that prices people are willing to accept (WTA) for a good exceed prices people are willing to pay (WTP) for the same good. The increase in WTA values is often explained by the sellers' negative hedonic response to losing their item. Recent studies, however, show that subtle cues may change participants' perspective, influencing their valuations. We hypothesized that implicit connotations of instructional language may be one of those cues. To test this hypothesis we manipulated the wording of instructions in two conditions: in the Sell condition, subjects were endowed with a set of pens and asked to select an amount of money for which they would sell the pens back and in the Take condition, subjects were endowed with the pens and asked to select an amount of money they would take for the pens. Participants in each condition also estimated the market value of the pens. Consistent with our hypothesis, WTA in the Sell condition was higher than in the Take condition, though there were no differences in market values between conditions. These findings show that instructional language does influence participant valuations. Furthermore, we suggest that those being asked to "sell" use their market estimations as the salient reference point in the transaction.

Dissociating Value Representation and Inhibition of Inappropriate Affective Response during Reversal Learning in the Ventromedial Prefrontal Cortex.

Decision-making studies have implicated the ventromedial prefrontal cortex (vmPFC) in tracking the value of rewards and punishments. At the same time, fear-learning studies have pointed to a role of the same area in updating previously learned cue-outcome associations. To disentangle these accounts, we used a reward reversal-learning paradigm in a functional magnetic resonance imaging study in 18 human participants. Participants first learned that one of two colored squares (color A) was associated with monetary reward, whereas the other (color B) was not, and then had to learn that these contingencies reversed. Consistent with value representation, activity of a dorsal region of vmPFC was positively correlated with reward magnitude. Conversely, a more ventral region of vmPFC responded more to color A than to color B after contingency reversal, compatible with a role of inhibiting the previously learned response that was no longer appropriate. Moreover, the response strength was correlated with subjects' behavioral learning strength. Our findings provide direct evidence for the spatial dissociation of value representation and affective response inhibition in the vmPFC.

The efficacy of auditory probes in indexing cognitive workload is dependent on stimulus complexity.

We examined whether the utility of a recently developed auditory probe technique for indexing cognitive workload was dependent on the stimulus properties of the probes. EEG was recorded while participants played a videogame under various levels of cognitive workload. At each level of workload, participants were probed with one of four different types of auditory stimuli: novel complex, repeated complex, novel simple, or repeated simple sounds. Probe efficacy at indexing cognitive workload was assessed by determining which probes elicited ERP components that decreased monotonically as a function of workload. Results suggest that complex auditory stimuli were significantly more effective in indexing cognitive workload than simple stimuli. The efficacy of complex stimuli was due to their ability to elicit a robust orienting response, indexed by the early P3a component of the ERP, which decreased monotonically as a function of cognitive workload.

Impaired associative learning with food rewards in obese women.

Obesity is a major epidemic in many parts of the world. One of the main factors contributing to obesity is overconsumption of high-fat and high-calorie food, which is driven by the rewarding properties of these types of food. Previous studies have suggested that dysfunction in reward circuits may be associated with overeating and obesity. The nature of this dysfunction, however, is still unknown. Here, we demonstrate impairment in reward-based associative learning specific to food in obese women. Normal-weight and obese participants performed an appetitive reversal learning task in which they had to learn and modify cue-reward associations. To test whether any learning deficits were specific to food reward or were more general, we used a between-subject design in which half of the participants received food reward and the other half received money reward. Our results reveal a marked difference in associative learning between normal-weight and obese women when food was used as reward. Importantly, no learning deficits were observed with money reward. Multiple regression analyses also established a robust negative association between body mass index and learning performance in the food domain in female participants. Interestingly, such impairment was not observed in obese men. These findings suggest that obesity may be linked to impaired reward-based associative learning and that this impairment may be specific to the food domain.

Identification and synthesis of new volatile molecules found in extracts obtained from distinct parts of cooked chicken.

Several chicken parts (skin, fat, juice) were cooked in different ways (roasting, simmering) and investigated separately for their volatile composition. In-depth GC/MS analysis of the separate fractions revealed several unknown molecules. Mass spectra interpretation allowed us to identify nine molecules for the first time in chicken, including cyclic aldehydes, cyclic ketones, and new δ-lactones containing an unsaturated linear chain. Identification was confirmed by chemical synthesis followed by comparison of the mass spectra and linear retention indices. The natural occurrence of five of these molecules is reported here for the first time in a natural product.

Oligomeric aggregates of amyloid beta peptide 1-42 activate ERK/MAPK in SH-SY5Y cells via the alpha7 nicotinic receptor.

The production and aggregation of amyloid beta peptides (Abeta) has been linked to the development and progression of Alzheimer's disease. It is apparent that the various structural forms of Abeta can affect cell signalling pathways and the activity of neurons differently. In this study, we investigated the effects of oligomeric and fibrillar aggregates of Abeta 1-42 (Abeta42) and non-aggregated peptide upon activation of the ERK/MAPK signalling pathway. In SH-SY5Y cells, acute exposure to oligomeric Abeta42 led to phosphorylation of ERK1/2 at concentrations as low as 1 nM and up to 100 nM. These changes were detected as early as 5 min following exposure to 100 nM oligomeric Abeta42, reaching a maximum level after 10 min. Phosphorylation of ERK1/2 subsequently declined to and remained at basal levels after 30 min to 2h of exposure. Fibrillar aggregates of Abeta42 did not significantly induce phosphorylation of ERK1/2 and non-aggregated Abeta42 did not activate the pathway. The effects of oligomeric Abeta42 to increase ERK phosphorylation above basal levels were inhibited by MLA, a specific antagonist of the alpha7 nAChR. U0126, an inhibitor of MEK, the upstream activator of ERK1/2, completely blocked induction of ERK1/2 phosphorylation. Oligomeric aggregates of Abeta42 are the principal structural form of the peptide that activates ERK/MAPK in SH-SY5Y cells and these effects are mediated by the alpha7 nAChR.

Synthesis of loliolide, actinidiolide, dihydroactinidiolide, and aeginetolide via cerium enolate chemistry.

Loliolide, aeginetolide, actinidiolide, and dihydroactinidiolide were synthesized in racemic form from a single common intermediate, prepared through the 1,2 addition of the cerium enolate of ethyl acetate to 2,6,6-trimethylcylohexenone.

Differential expression of surfactant protein A in the nasal mucosa of patients with allergy symptoms.

OBJECTIVE: To characterize surfactant protein A (SP-A) expression in human nasal tissue and correlate differential expression of SP-A with symptoms suggestive of allergic rhinitis. DESIGN: Allergic rhinitis symptom data were prospectively collected in the form of the Rhinitis Symptom Utility Index, the Rhinoconjunctivitis Quality of Life Questionnaire, and a Visual Analog Scale. Immunohistochemical staining for SP-A was performed on resected nasal tissue. Quantitative polymerase chain reaction amplification of the SP-A gene referenced to beta-actin was performed on complementary DNA samples synthesized from total RNA isolates. SETTING: Academic tertiary referral center, department of otolaryngology laboratories. PATIENTS: Twenty-five consecutive patients undergoing nasal surgery. MAIN OUTCOME MEASURES: Immunohistochemical staining of SP-A in human nasal mucosa and submucosa, polymerase chain reaction amplification of SP-A messenger RNA, and rhinitis symptom scores. RESULTS: Immunostaining localized SP-A to the mucosa and submucosal glands in specimens. Quantitative polymerase chain reaction demonstrated correlation between SP-A messenger RNA concentration and the total Rhinitis Symptom Utility Index score (0.51, P = .009) as well as "sneezing over the previous week" (0.40, P = .049), "runny nose over the previous week" (0.55, P = .005), and "sneezing today" (0.47, P = .02). CONCLUSIONS: To our knowledge, this is the first report of SP-A expression in human nasal tissue. Furthermore, the degree of expression correlated with severity of disease as measured by the Rhinitis Symptom Utility Index in patients with allergic rhinitis symptoms.

A direct route toward assembly of nanoparticle-carbon nanotube composite materials.

The preparation of nanocomposite materials from carbon nanotubes (CNTs) and metal or metal oxide nanoparticles has important implications to the development of advanced catalytic and sensory materials. This paper reports findings of an investigation of the preparation of nanoparticle-coated carbon nanotube composite materials. Our approach involves molecularly mediated assembly of monolayer-capped nanoparticles on multiwalled CNTs via a combination of hydrophobic and hydrogen-bonding interactions between the capping/mediating shell and the CNT surface. The advantage of this route is that it does not require tedious surface modification of CNTs. We have demonstrated its simplicity and effectiveness for assembling alkanethiolate-capped gold nanoparticles of 2-5 nm core sizes onto CNTs with controllable coverage and spatially isolated character. The loading and distribution of the nanoparticles on CNTs depend on the relative concentrations of gold nanoparticles, CNTs, and mediating or linking agents. The composite nanomaterials can be dispersed in organic solvent, and the capping/linking shells can be removed by thermal treatment to produce controllable nanocrystals on the CNT surfaces. The nanocomposite materials are characterized using transmission electron microscopy and Fourier transform infrared spectroscopy techniques. The results will be discussed in terms of developing advanced catalytic and sensory nanomaterials.

Measurement of colony-stimulating factors in synovial fluid: potential clinical value.

In this study, 100 synovial fluid (SF) samples from patients with a variety of arthritides were assayed for levels of colony-stimulating factors (CSFs) using a human bone-marrow bioassay and enzyme immunoassays for granulocyte (G-) and granulocyte-macrophage (GM-) CSFs. GM-CSF was found more frequently in samples from rheumatoid arthritis (RA) subjects (49%) than in non-RA samples (29%). Absence of GM- but not G- or bioassay CSFs characterised samples from subjects with psoriatic arthritis and ankylosing spondylitis (n = 14). There was strong evidence of an antagonistic relationship between levels of G- and GM-CSFs in samples from RA patients, an effect independent of drug treatment. However, treatment with non-steroidal anti-inflammatory agents (NSAIDs) may affect reported CSF concentrations: G-CSF levels were significantly lower in samples from subjects not taking NSAIDs. These results suggest that SF-CSF estimations using commercially available assays could provide useful diagnostic clues for clinicians, but careful interpretation is warranted particularly in patients on long-term NSAID treatment.

Diclofenac inhibits monocyte superoxide production ex vivo in rheumatoid arthritis.

Effects of the nonsteroidal anti-inflammatory drug, diclofenac, on stimulated monocyte superoxide production were assessed directly in vitro and following treatment of patients with rheumatoid arthritis ex vivo. Diclofenac inhibited superoxide generation provoked by serum treated zymosan (STZ) and fluoride anion (F) but not by phorbol myristate acetate (PMA) in vitro. Following patient therapy, inhibition of superoxide production occurred when STZ and PMA, but not F were used as stimuli. No changes were seen in control subjects. The contrasting profiles of inhibition seen in vitro and ex vivo suggest an indirect effect on superoxide production during clinical use of the agent. These data are consistent with the hypothesis that anti-inflammatory drugs may act in rheumatoid arthritis by inhibiting phagocyte superoxide anion production.

Detection and partial characterization of human B cell colony stimulating activity in synovial fluids of patients with rheumatoid arthritis.

The joint fluids of 37 patients with rheumatoid arthritis, eight patients with traumatic injuries to their joints, two patients with Reiter's syndrome and three patients with psoriatic arthritis were tested for the presence of B cell colony stimulating activity (B cell CSA). B cell CSA was found in all of the joint fluids from the patients with rheumatoid arthritis but in none of the joint fluids from patients with traumatic injuries to their joints or in the joint fluids from the patients with Reiter's syndrome. A trace of B cell CSA was found in the joint fluid of one of the three patients with psoriatic arthritis. There was a positive correlation (r = 0.796) between the amount of rheumatoid factor present in the joint fluids and the titre of B cell CSA. This correlation was highly significant (P less than 0.001). The B cell CSA was localized to component(s) with molecular weight ranges 115-129 kD and 64-72 kD and an isoelectric point of 6.8. Its activity was sensitive to reduction with 2-mercaptoethanol and to the oxidising action of potassium periodate.