Positive allosteric modulators of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor

L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a fundamental role in the control of motor function, cognition and mood. The physiological effects of glutamate are mediated through two functionally distinct receptor families. While activation of metabotropic (G-protein coupled) glutamate receptors results in modulation of neuronal excitability and transmission, the ionotropic glutamate receptors (ligand-gated ion channels) are responsible for mediating the fast synaptic response to extracellular glutamate

“Raising the curtain on the equality theatre”: A study of recruitment to first healthcare job post-qualification in the UK National Health Service

Background UK equality law and National Health Service (NHS) policy requires racial equality in job appointments and career opportunities. However, recent national workforce race equality standard (WRES) data show that nearly all NHS organisations in the UK are failing to appoint ethnically diverse candidates with equivalent training and qualifications as their white counterparts. This is problematic because workforce diversity is associated with improved patient outcomes and other benefits for staff and organisations. Aim To better understand the reasons behind underrepresentation of ethnically diverse candidates in first NHS healthcare jobs post-qualification and to identify any structural or systemic barriers to employment for such groups. Methods The study was informed by critical theory and the authors’ interdisciplinary perspectives as educators and researchers in the healthcare professions. Data collected from semi-structured face-to-face interviews with 12 nurse and physiotherapy recruiting managers from two NHS trusts in London were analysed using a healthcare workforce equity and diversity conceptual lens we developed from the literature. Using this lens, we devised questions to examine six dimensions of equity and diversity in the interview data from recruiting managers. Results Recruiting managers said they valued the benefits of an ethnically diverse workforce for patients and their unit/organisation. However, their adherence to organisational policies for recruitment and selection, which emphasise objectivity and standardisation, acted as constraints to recognising ethnicity as an important issue in recruitment and workforce diversity. Some recruiting managers sense that there are barriers for ethnically diverse candidates but lacked information about workforce diversity, systems for monitoring recruitment, or ways to engage with staff or candidates to talk about these issues. Without this information there was no apparent problem or reason to try alternative approaches. Conclusion These accounts from 12 recruiting managers give a ‘backstage’ view into the reasons behind ethnic inequalities in recruitment to first healthcare job in the UK NHS. Adherence to recruitment and selection policies, which aim to support equality through standardisation and anonymisation, appear to be limiting workforce diversity and creating barriers for ethnically diverse candidates to attain the jobs that they are trained and qualified for. The Healthcare Workforce Equity + Diversity Lens we have developed can help to ‘raise the curtain on the equality theatre’ and inform more inclusive approaches to recruitment such as contextualised recruitment or effective allyship between employers and universities

Rapid Maize Leaf and Immature Ear Responses to UV-B Radiation

Because of their sessile lifestyle, plants have evolved adaptations to environmental factors, including UV-B present in solar radiation. To gain a better understanding of the initial events in UV-B acclimation, we have analyzed a 10 min to 1 h time course of transcriptome responses in irradiated and shielded leaves, and immature maize ears to unravel the systemic physiological and developmental responses in exposed and shielded organs. After 10 min of UV-B exposure, 262 transcripts are changed by at least two-fold in irradiated leaves, and this number doubles after 1 h. Indicative of the rapid modulation of transcription, 130 transcripts are only changed after 10 min. This is true not only in irradiated leaves, but also in shielded tissues. After 10 min of exposure, the overlap in transcriptome changes in irradiated and shielded organs is significant; however, after 30 min of UV-B, there are only two transcripts showing similar UV-B regulation between the three organs; 35 are similarly regulated in both IL and SL. Therefore, at longer irradiation times, there is more specificity of responses, and these are organ-specific. We suggest that early signaling in different tissues may be elicited by common signaling pathways, while at longer exposure times responses become more specific. To identify metabolites as possible signaling molecules, we looked for compounds that increased within 5–90 min in both irradiated and shielded leaves, to explain the kinetics of profound transcript changes within 1 h. We found that myoinositol is one such candidate metabolite; and we also demonstrate that if 0.1 mM myoinositol is applied to leaves of greenhouse maize, some metabolites that are changed by UV-B are also changed similarly by the chemical treatment. Therefore, this metabolite can partially mimic UV irradiation

An early evaluation of the 2050 Calculator international outreach programme

This paper presents the findings of an early evaluation of the UK Department of Energy and Climate Change’s 2050 Calculator International Outreach Programme. The programme supported eleven countries to develop their own versions of the 2050 Calculator. Drawing on interviews with stakeholders who were involved directly and indirectly in the development of the 2050 Calculators, this paper evaluates the process of developing these tools in different national contexts and discusses the lessons learnt so far. The findings discussed include the original motivations for involvement and how these evolved through the project, and the process of stakeholder engagement. The latter was expected to be a key benefit of the Calculator, and one which would open up debate about long term energy futures. While the teams developing the Calculators faced challenges, including data availability, political buy-in, and defining scenario trajectories, a flexible approach enabled countries to develop Calculators that were tailored to their national objectives and political environments. Overall, the 2050 Calculators have led to a wide range of benefits and there is ongoing commitment to develop new iterations and applications to use these Calculators to support planning of, and debate on, future energy and emissions trajectories

Lesions of the ventral hippocampus attenuate the acquisition but not expression of sign‐tracking behavior in rats

Individual variation in the attribution of motivational salience to reward‐related cues is believed to underlie addiction vulnerability. Pavlovian conditioned approach measures individual variation in motivational salience by identifying rats that are attracted to and motivated by reward cues (sign‐trackers) or motivationally fixed on the reward itself (goal‐trackers). Previously, it has been demonstrated that sign‐trackers are more vulnerable to addiction‐like behavior. Moreover, sign‐trackers release more dopamine in the nucleus accumbens than goal‐trackers in response to reward‐related cues, and sign‐ but not goal‐tracking behavior is dopamine‐dependent. In the present study, we investigated whether the ventral hippocampus, a potent driver of dopaminergic activity in the nucleus accumbens, modulates the acquisition and expression of Pavlovian conditioned approach behavior. In Experiment 1, lesions of the ventral, but not dorsal or total hippocampus, decreased sign‐tracking behavior. In Experiment 2, lesions of the ventral hippocampus did not affect the expression of sign‐ or goal‐tracking behaviors nor conditioned reinforcement. In addition, temporary inactivation of the ventral subiculum, the main output pathway of the ventral hippocampus, did not affect the expression of sign‐ or goal‐tracking behaviors. High‐pressure liquid chromatography of nucleus accumbens tissue punches revealed that ventral hippocampal lesions decreased levels of homovanillic acid and the homovanillic acid/dopamine ratio (a marker of dopamine release and metabolism) in only sign‐trackers, and decreased accumbal norepinephrine levels in both sign‐ and goal‐trackers. These results suggest that the ventral hippocampus is important for the acquisition but not expression of sign‐tracking behavior, possibly as a result of altered dopamine and norepinephrine in the nucleus accumbens. © 2016 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134415/1/hipo22619.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134415/2/hipo22619_am.pd

Rats that sign-track are resistant to Pavlovian but not instrumental extinction

Individuals vary in the extent to which they attribute incentive salience to a discrete cue (conditioned stimulus; CS) that predicts reward delivery (unconditioned stimulus; US), which results in some individuals approaching and interacting with the CS (sign-trackers; STs) more than others (goal-trackers; GTs). Here we asked how periods of non-reinforcement influence conditioned responding in STs vs. GTs, in both Pavlovian and instrumental tasks. After classifying rats as STs or GTs by pairing a retractable lever (the CS) with the delivery of a food pellet (US), we introduced periods of non-reinforcement, first by simply withholding the US (i.e., extinction training; experiment 1), then by signaling alternating periods of reward (R) and non-reward (NR) within the same session (experiments 2 and 3). We also examined how alternating R and NR periods influenced instrumental responding for food (experiment 4). STs and GTs did not differ in their ability to discriminate between R and NR periods in the instrumental task. However, in Pavlovian settings STs and GTs responded to periods of non-reward very differently. Relative to STs, GTs very rapidly modified their behavior in response to periods of non-reward, showing much faster extinction and better and faster discrimination between R and NR conditions. These results highlight differences between Pavlovian and instrumental extinction learning, and suggest that if a Pavlovian CS is strongly attributed with incentive salience, as in STs, it may continue to bias attention toward it, and to facilitate persistent and relatively inflexible responding, even when it is no longer followed by reward