The anterior insula bidirectionally modulates cost-benefit decision-making on a rodent gambling task.

Deficits in cost-benefit decision-making, as assessed in the Iowa Gambling Task (IGT), are commonly observed in neuropsychiatric disorders such as addiction. There is considerable variation in the maximization of rewards on such tasks, both in the general population and in rodent models, suggesting individual differences in decision-making may represent a key endophenotype for vulnerability to neuropsychiatric disorders. Increasing evidence suggests that the insular cortex, which is involved in interoception and emotional processes in humans, may be a key neural locus in the control of decision-making processes. However, the extent to which the insula contributes to individual differences in cost-benefit decision-making remains unknown. Using male Sprague Dawley rats, we first assessed individual differences in the performance over the course of a single session on a rodent analogue of the IGT (rGT). Rats were matched for their ability to maximize reward and received bilateral excitotoxic or sham lesions of the anterior insula cortex (AIC). Animals were subsequently challenged on a second rGT session with altered contingencies. Finally, animals were also assessed for instrumental conditioning and reversal learning. AIC lesions produced bidirectional alterations on rGT performance; rats that had performed optimally prior to surgery subsequently showed impairments, and animals that had performed poorly showed improvements in comparison with sham-operated controls. These bidirectional effects were not attributable to alterations in behavioural flexibility or in motivation. These data suggest that the recruitment of the AIC during decision-making may be state-dependent and help guide response selection towards subjectively favourable options

Breakdown of Fermi-liquid theory in a cuprate superconductor

The behaviour of electrons in solids is remarkably well described by Landau's Fermi-liquid theory, which says that even though electrons in a metal interact they can still be treated as well-defined fermions, called ``quasiparticles''. At low temperature, the ability of quasiparticles to transport heat is strictly given by their ability to transport charge, via a universal relation known as the Wiedemann-Franz law, which no material in nature has been known to violate. High-temperature superconductors have long been thought to fall outside the realm of Fermi-liquid theory, as suggested by several anomalous properties, but this has yet to be shown conclusively. Here we report on the first experimental test of the Wiedemann-Franz law in a cuprate superconductor, (Pr,Ce)$_2$CuO$_4$. Our study reveals a clear departure from the universal law and provides compelling evidence for the breakdown of Fermi-liquid theory in high-temperature superconductors.Comment: 7 pages, 3 figure

High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction.

Drug addiction is associated with a relative devaluation of natural or socially-valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use.This work was funded by an INSERM AVENIR and Agence Nationale de la Recherche (ANR) ANR12 SAMA00201 grant to DB, the région Poitou-Charentes, an AXA research fund fellowship to ABR, and a Ministère de la Recherche et de la Technologie grant to NV. AM was supported by the Behavioural and Clinical Neuroscience Institute of Cambridge.This is the accepted manuscript of a paper published in Neuropsychopharmacology (2015) 40, 577–589; doi:10.1038/npp.2014.204; published online 17 September 2014

How do you say ‘hello’? Personality impressions from brief novel voices

On hearing a novel voice, listeners readily form personality impressions of that speaker. Accurate or not, these impressions are known to affect subsequent interactions; yet the underlying psychological and acoustical bases remain poorly understood. Furthermore, hitherto studies have focussed on extended speech as opposed to analysing the instantaneous impressions we obtain from first experience. In this paper, through a mass online rating experiment, 320 participants rated 64 sub-second vocal utterances of the word ‘hello’ on one of 10 personality traits. We show that: (1) personality judgements of brief utterances from unfamiliar speakers are consistent across listeners; (2) a two-dimensional ‘social voice space’ with axes mapping Valence (Trust, Likeability) and Dominance, each driven by differing combinations of vocal acoustics, adequately summarises ratings in both male and female voices; and (3) a positive combination of Valence and Dominance results in increased perceived male vocal Attractiveness, whereas perceived female vocal Attractiveness is largely controlled by increasing Valence. Results are discussed in relation to the rapid evaluation of personality and, in turn, the intent of others, as being driven by survival mechanisms via approach or avoidance behaviours. These findings provide empirical bases for predicting personality impressions from acoustical analyses of short utterances and for generating desired personality impressions in artificial voices

Genome-Wide Association Study Identifies Risk Loci for Cluster Headache

OBJECTIVE: To identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways. METHODS: We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model, for each cohort. The two cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed. RESULTS: Initial independent analysis identified two replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 x 10-17 , OR [95%CI] = 1.51 [1.37-1.66]) and rs4519530 (p = 6.98 x 10-17 , OR = 1.47 [1.34-1.61]) on chromosome 2, rs12121134 on chromosome 1 (p = 1.66 x 10-8 , OR = 1.36 [1.22-1.52]) and rs11153082 (p = 1.85 x 10-8 , OR = 1.30 [1.19-1.42]) on chromosome 6. Downstream analyses implicated immunological processes in the pathogenesis of cluster headache. INTERPRETATION: We identified and replicated several genome-wide-significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to e.g. treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache

A dual function of SnRK2 kinases in the regulation of SnRK1 and plant growth

[EN] Adverse environmental conditions trigger responses in plants that promote stress tolerance and survival at the expense of growth(1). However, little is known of how stress signalling pathways interact with each other and with growth regulatory components to balance growth and stress responses. Here, we show that plant growth is largely regulated by the interplay between the evolutionarily conserved energy-sensing SNF1-related protein kinase 1 (SnRK1) protein kinase and the abscisic acid (ABA) phytohormone pathway. While SnRK2 kinases are main drivers of ABA-triggered stress responses, we uncover an unexpected growth-promoting function of these kinases in the absence of ABA as repressors of SnRK1. Sequestration of SnRK1 by SnRK2-containing complexes inhibits SnRK1 signalling, thereby allowing target of rapamycin (TOR) activity and growth under optimal conditions. On the other hand, these complexes are essential for releasing and activating SnRK1 in response to ABA, leading to the inhibition of TOR and growth under stress. This dual regulation of SnRK1 by SnRK2 kinases couples growth control with environmental factors typical for the terrestrial habitat and is likely to have been critical for the water-to-land transition of plants.We thank J.-K. Zhu for the snrk2 mutants, M. Bennett for the SnRK2.2-GFP line, C. Koncz for the SnRK1-GFP line, X. Li for the SnRK2.3-FLAG OE line, J. Schroeder for the GFP-His-FLAG and SnRK2.6-His-FLAG OE lines, C. Mackintosh for the TPS5 antibody and the Nottingham Arabidopsis stock centre for T-DNA mutant seeds. The IGC Plant Facility (Vera Nunes) is thanked for excellent plant care. This work was supported by Fundacao para a Ciencia e a Tecnologia through the R&D Units UIDB/04551/2020 (GREEN-IT-Bioresources for Sustainability) and UID/MAR/04292/2019, FCT project nos. PTDC/BIA-PLA/7143/2014, LISBOA-01-0145-FEDER-028128 and PTDC/BIA-BID/32347/2017, and FCT fellowships/contract nos. SFRH/BD/122736/2016 (M.A.), SFRH/BPD/109336/2015 (A.C.), PD/BD/150239/2019 (D.R.B.), and IF/00804/2013 (E.B.G.). Work in P.L.R.'s laboratory was funded by MCIU grant no. BIO2017-82503-R. C.M. thanks the LabEx Paris Saclay Plant Sciences-SPS (ANR-10-LABX-040-SPS) for support. B.B.P. was funded by Programa VALi+d GVA APOSTD/2017/039. This project has received funding from the European Union Horizon 2020 research and innovation programme (grant agreement no. 867426-ABA-GrowthBalance-H2020-WF-2018-2020/H2020-WF-01-2018, awarded to B.B.P.). This work is dedicated to the memory of our beloved friend and colleague Americo Rodrigues.Belda-Palazón, B.; Adamo, M.; Valerio, C.; Ferreira, LJ.; Confraria, A.; Reis-Barata, D.; Rodrigues, A.... (2020). A dual function of SnRK2 kinases in the regulation of SnRK1 and plant growth. 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Identification of Novel α-Synuclein Isoforms in Human Brain Tissue by using an Online NanoLC-ESI-FTICR-MS Method

Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) are neurodegenerative diseases that are characterized by intra-neuronal inclusions of Lewy bodies in distinct brain regions. These inclusions consist mainly of aggregated α-synuclein (α-syn) protein. The present study used immunoprecipitation combined with nanoflow liquid chromatography (LC) coupled to high resolution electrospray ionization Fourier transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) to determine known and novel isoforms of α-syn in brain tissue homogenates. N-terminally acetylated full-length α-syn (Ac-α-syn1–140) and two N-terminally acetylated C-terminally truncated forms of α-syn (Ac-α-syn1–139 and Ac-α-syn1–103) were found. The different forms of α-syn were further studied by Western blotting in brain tissue homogenates from the temporal cortex Brodmann area 36 (BA36) and the dorsolateral prefrontal cortex BA9 derived from controls, patients with DLB and PD with dementia (PDD). Quantification of α-syn in each brain tissue fraction was performed using a novel enzyme-linked immunosorbent assay (ELISA)

Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli

Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis