Serotonin Differentially Regulates Short- and Long-Term Prediction of Rewards in the Ventral and Dorsal Striatum

BACKGROUND: The ability to select an action by considering both delays and amount of reward outcome is critical for maximizing long-term benefits. Although previous animal experiments on impulsivity have suggested a role of serotonin in behaviors requiring prediction of delayed rewards, the underlying neural mechanism is unclear. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the role of serotonin in the evaluation of delayed rewards, we performed a functional brain imaging experiment in which subjects chose small-immediate or large-delayed liquid rewards under dietary regulation of tryptophan, a precursor of serotonin. A model-based analysis revealed that the activity of the ventral part of the striatum was correlated with reward prediction at shorter time scales, and this correlated activity was stronger at low serotonin levels. By contrast, the activity of the dorsal part of the striatum was correlated with reward prediction at longer time scales, and this correlated activity was stronger at high serotonin levels. CONCLUSIONS/SIGNIFICANCE: Our results suggest that serotonin controls the time scale of reward prediction by differentially regulating activities within the striatum

Electrophysiological correlates of associative learning in smokers: a higher-order conditioning experiment

Background: Classical conditioning has been suggested to play an important role in the development, maintenance, and relapse of tobacco smoking. Several studies have shown that initially neutral stimuli that are directly paired with smoking are able to elicit conditioned responses. However, there have been few human studies that demonstrate the contribution of higher-order conditioning to smoking addiction, although it is assumed that higher-order conditioning predominates learning in the outside world. In the present study a higher-order conditioning task was designed in which brain responses of smokers and non-smokers were conditioned by pairing smoking-related and neutral stimuli (CS1smokeand CS1neutral) with two geometrical figures (CS2smokeand CS2neutral). ERPs were recorded to all CSs.Results: Data showed that the geometrical figure that was paired with smoking stimuli elicited significantly larger P2 and P3 waves than the geometrical figure that was paired with neutral stimuli. During the first half of the experiment this effect was only present in smokers whereas non-smokers displayed no significant differences between both stimuli, indicating that neutral cues paired with motivationally relevant smoking-related stimuli gain more motivational significance even though they were never paired directly with smoking. These conclusions are underscored by self-reported evidence of enhanced second-order conditioning in smokers.Conclusions: It can be concluded that smokers show associative learning for higher-order smoking-related stimuli. The present study directly shows the contribution of higher-order conditioning to smoking addiction and is the first to reveal its electrophysiological correlates. Although results are preliminary, they may help in understanding the etiology of smoking addiction and its persistence

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Preparing for an aging Australia: The development of multidisciplinary core competencies for the Australian health and aged care workforce.

Appropriately skilled staff are required to meet the health and care needs of aging populations yet, shared competencies for the workforce are lacking. This study aimed to develop multidisciplinary core competencies for health and aged care workers in Australia through a scoping review and Delphi survey. The scoping review identified 28 records which were synthesized through thematic analysis into draft domains and measurable competencies. Consensus was sought from experts over two Delphi rounds (n = 111 invited; n = 59 round one; n = 42 round two). Ten domains with 66 core competencies, to be interpreted and applied according to the worker's scope of practice were finalized. Consensus on multidisciplinary core competencies which are inclusive of a broad range of registered health professionals and unregistered aged care workers was achieved. Shared knowledge, attitudes, and skills across the workforce may improve the standard and coordination of person-centered, integrated care for older Australians from diverse backgrounds

Conjugates of Heme-Thiolate Enzymes with Photoactive Metal-Diimine Wires

Heme-thiolate enzymes, notably cytochromes P450 and nitric oxide synthases, use dioxygen to oxygenatesubstrates. Photoactive metal-diimine molecular wires that are capable of effecting rapid redox state changesat buried active sites have been developed to generate intermediates in the catalytic cycles of these enzymes.Wires that feature a photoactive head group tethered to an active-site ligand bind P450CAM and induciblenitric oxide synthase (iNOS) primarily by hydrophobic interactions. The wire-binding specificity of eachenzyme is critically dependent on the structural flexibility of the protein. P450CAM:wire conjugates canadopt open or partially open conformations, thereby accommodating a wide range of wires, whereas onlylong wires with smaller [Re(CO)_3(bpy)Im]^+ head groupsare able to bind tightly in the rigid active-site channel of iNOS. Dansyl-terminated molecular wires functionas highly sensitive and isoform specific fluorescent sensors for P450CAM