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In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance. Several preclinical studies have also been carried out to determine the long-term mechanism of action of this drug. In this sense, preclinical studies in naïve animals as well as in animal models of disease have shown somewhat discrepant results in conventional tests for assessment of depression- and anxiety-like phenotype in response to psilocybin, but overall suggest positive outcomes. Additionally, several valuable assays in rodent models have been developed over the years to elucidate the neurochemical correlates of serotonin 2A receptor (5HT2AR) activation in the brain, primary molecular target of psilocin. This review aims to provide a general overview of the current and most recent literature in the therapeutic potential of psilocybin through a description of clinical trials of psilocybin-assisted psychotherapy, and to showcase the scene in the up-to-date preclinical research. A detailed description of preclinical rodent models and experimental approaches that have been used to study the neurobiological and behavioural actions of psilocybin is provided, and potential therapeutic mechanisms of action are discussed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jorge Emilio Ortega reports financial support was provided by Government of Spain Ministry of Health. Jorge Emilio Ortega reports financial support was provided by Basque Government. Jose Javier Meana reports financial support was provided by Center for Biomedical Research in Mental Health Network. Jorge Emilio Ortega reports financial support was provided by Vital Foundation. Jose Javier Meana reports a relationship with Janssen-Cilag SAS that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Magnetic anisotropy and magnetic exchange interactions are crucial parameters that characterize the hybrid metal-organic interface, a key component of an organic spintronic device. It is shown that the incorporation of 4f RE atoms to hybrid metal-organic interfaces of CuPc/REAu 2 type (RE = Gd, Ho) constitutes a feasible approach toward on-demand magnetic properties and functionalities. The GdAu 2 and HoAu 2 substrates differ in their magnetic anisotropy behavior. Remarkably, the HoAu 2 surface promotes the inherent out-of-plane anisotropy of CuPc, owing to the match between the anisotropy axis of substrate and molecule. Furthermore, the presence of RE atoms leads to a spontaneous antiferromagnetic exchange coupling at the interface, induced by the 3d-4f superexchange interaction between the unpaired 3d electron of CuPc and the 4f electrons of the RE atoms. It is shown that 4f RE atoms with unquenched quantum orbital momentum ( L $L$ ), as it is the case of Ho, induce an anisotropic interfacial exchange coupling., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 reduction (GLUT1 ΔGFAP mice). These mice also exhibited improved peripheral glucose metabolism especially in obesity, rendering them metabolically healthier. Mechanistically, we observed that GLUT1-deficient astrocytes exhibited increased insulin receptor-dependent ATP release, and that both astrocyte insulin signaling and brain purinergic signaling are essential for improved brain function and systemic glucose metabolism. Collectively, we demonstrate that astrocytic GLUT1 is central to the regulation of brain energetics, yet its depletion triggers a reprogramming of brain metabolism sufficient to sustain energy requirements, peripheral glucose homeostasis, and cognitive function.

The oxidation of Ag crystal surfaces has recently triggered strong controversies around the presence of sulfur impurities that may catalyze reactions, such as the alkene epoxidations, especially the ethylene epoxidation. A fundamental challenge to achieve a clear understanding is the variety of procedures and setups involved as well as the particular history of each sample. Especially, for the often-used X-ray photoemission technique, product detection, or photoemission peak position overlap are problematic. Here we investigate the oxidation of the Ag(111) surface and its vicinal crystal planes simultaneously, using a curved crystal sample and in situ X-ray photoelectron spectroscopy at 1 mbar O 2 near-ambient pressure conditions to further investigate surface species. The curved geometry allows a straightforward comparative analysis of the surface oxidation kinetics at different crystal facets, so as to precisely correlate the evolution of different oxygen species, namely nucleophilic and electrophilic oxygen, and the buildup of sulfur as a function of the crystal orientation. We observed that emission from both surface and bulk oxide contributes to the characteristic nucleophilic oxygen core-level peak, which arises during oxygen dosing and rapidly saturates below temperatures of 180 °C. The electrophilic oxygen peak appears later, growing at a slower but constant rate, at the expenses of the surface oxide. Electrophilic oxygen and sulfur core-levels evolve in parallel in all crystal facets, although faster and stronger at vicinal surfaces featuring B-type steps with {111} microfacets. Our study confirms the intimate connection of the electrophilic species with the formation of adsorbed SO 4 , and points to a higher catalytic activity of B-type stepped silver surfaces for alkene epoxidation or methane to formaldehyde conversion., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

We investigate the chemical interaction of carbon monoxide (CO) and oxygen (O 2 ) with kink atoms on steps of platinum crystal surfaces using a specially designed Pt curved sample. We aim at describing the fundamental stages of the CO oxidation reaction, i.e., CO-covered/poisoned stage and O-covered/active stage, at the poorly known kinked Pt facets by probing CO uptake/saturation and O 2 saturation, respectively. Based on the systematic analysis that the curved surface allows, and using high-resolution X-ray photoemission, a diversity of terrace and step/kink species are straightforwardly identified and accurately quantified, defining a smooth structural and chemical variation across different crystal planes. In the CO-saturated case, we observe a preferential adsorption at step edges, where the CO coverage reaches a CO molecule per step Pt atom, significantly higher than their close-packed analogous steps with straight terrace termination. For the O-saturated surface, a significantly higher O coverage is observed in kinked planes compared to the Pt(111) surface. While the strong adsorption of CO at the kinked edges points toward a higher ignition temperature of the CO oxidation at kinks as compared to terraces, the large O coverage at steps may lead to an increased reactivity of kinked surfaces during the active stage of the CO oxidation., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The ability to confine light down to atomic scales is critical for the development of applications in optoelectronics and optical sensing as well as for the exploration of nanoscale quantum phenomena. Plasmons in metallic nanostructures with just a few atomic layers in thickness can achieve this type of confinement, although fabrication imperfections down to the subnanometer scale hinder actual developments. Here, narrow plasmons are demonstrated in atomically thin crystalline silver nanostructures fabricated by prepatterning silicon substrates and epitaxially depositing silver films of just a few atomic layers in thickness. Specifically, a silicon wafer is lithographically patterned to introduce on-demand lateral shapes, chemically process the sample to obtain an atomically flat silicon surface, and epitaxially deposit silver to obtain ultrathin crystalline metal films with the designated morphologies. Structures fabricated by following this procedure allow for an unprecedented control over optical field confinement in the near-infrared spectral region, which is here illustrated by the observation of fundamental and higher-order plasmons featuring extreme spatial confinement and high-quality factors that reflect the crystallinity of the metal. The present study constitutes a substantial improvement in the degree of spatial confinement and quality factor that should facilitate the design and exploitation of atomic-scale nanoplasmonic devices for optoelectronics, sensing, and quantum-physics applications., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

One of the common tasks in clinical natural language processing is medical entity linking (MEL) which involves mention detection followed by linking the mention to an entity in a knowledge base. One reason that MEL has not been solved is due to a problem that occurs in language where ambiguous texts can be resolved to several named entities. This problem is exacerbated when processing the text found in electronic health records. Recent work has shown that deep learning models based on transformers outperform previous methods on linking at higher rates of performance. We introduce NeighBERT, a custom pre-training technique which extends BERT (Devlin et al [1]) by encoding how entities are related within a knowledge graph. This technique adds relational context that has been traditionally missing in original BERT, helping resolve the ambiguity found in clinical text. In our experiments, NeighBERT improves the precision, recall, and F1-score of the state of the art by 1-3 points for named entity recognition and 10-15 points for MEL on two widely known clinical datasets., Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-023-00136-3., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Using a reactive molecular beam with high kinetic energy ( E kin ), it is possible to speed gas-surface reactions involving high activation barriers ( E act ), which would require elevated pressures ( P 0 ) if a random gas with a Maxwell-Boltzmann distribution is used. By simply computing the number of molecules that overcome the activation barrier in a random gas at P 0 and in a molecular beam at E kin = E act , we establish an E kin - P 0 equivalence curve, through which we postulate that molecular beams are ideal tools to investigate gas-surface reactions that involve high activation energies. In particular, we foresee the use of molecular beams to simulate gas surface reactions within the industrial-range (>10 bar) using surface-sensitive ultra-high vacuum (UHV) techniques, such as X-ray photoemission spectroscopy (XPS). To test this idea, we revisit the oxidation of the Cu(111) surface combining O 2 molecular beams and XPS experiments. By tuning the kinetic energy of the O 2 beam in the range of 0.24-1 eV, we achieve the same sequence of surface oxides obtained in ambient pressure photoemission (AP-XPS) experiments, in which the Cu(111) surface was exposed to a random O 2 gas up to 1 mbar. We observe the same surface oxidation kinetics as in the random gas, but with a much lower dose, close to the expected value derived from the equivalence curve.

Background: Impairment of specific cognitive domains in schizophrenia has been associated with prefrontal cortex (PFC) catecholaminergic deficits. Among other factors, prenatal exposure to infections represents an environmental risk factor for schizophrenia development in adulthood. However, it remains largely unknown whether the prenatal infection-induced changes in the brain may be associated with concrete switches in a particular neurochemical circuit, and therefore, if they could alter behavioral functions., Methods: In vitro and in vivo neurochemical evaluation of the PFC catecholaminergic systems was performed in offspring from mice undergoing maternal immune activation (MIA). The cognitive status was also evaluated. Prenatal viral infection was mimicked by polyriboinosinic-polyribocytidylic acid (poly(I:C)) administration to pregnant dams (7.5 mg/kg i.p., gestational day 9.5) and consequences were evaluated in adult offspring., Results: MIA-treated offspring showed disrupted recognition memory in the novel object recognition task (t = 2.30, p = 0.031). This poly(I:C)-based group displayed decreased extracellular dopamine (DA) concentrations compared to controls (t = 3.17, p = 0.0068). Potassium-evoked release of DA and noradrenaline (NA) were impaired in the poly(I:C) group (DA: F t [10,90] = 43.33, p < 0.0001; F tr [1,90] = 1.224, p = 0.2972; F i [10,90] = 5.916, p < 0.0001; n = 11); (NA: F t [10,90] = 36.27, p < 0.0001; F tr [1,90] = 1.841, p = 0.208; F i [10,90] = 8.686, p < 0.0001; n = 11). In the same way, amphetamine-evoked release of DA and NA were also impaired in the poly(I:C) group (DA: F t [8,328] = 22.01, p < 0.0001; F tr [1,328] = 4.507, p = 0.040; F i [8,328] = 2.319, p = 0.020; n = 43); (NA: F t [8,328] = 52.07; p < 0.0001; F tr [1,328] = 4.322; p = 0.044; F i [8,398] = 5.727; p < 0.0001; n = 43). This catecholamine imbalance was accompanied by increased dopamine D 1 and D 2 receptor expression (t = 2.64, p = 0.011 and t = 3.55, p = 0.0009; respectively), whereas tyrosine hydroxylase, DA and NA tissue content, DA and NA transporter (DAT/NET) expression and function were unaltered., Conclusions: MIA induces in offspring a presynaptic catecholaminergic hypofunction in PFC with cognitive impairment. This poly(I:C)-based model reproduces catecholamine phenotypes reported in schizophrenia and represents an opportunity for the study of cognitive impairment associated to this disorder., (© 2023. The Author(s).)

One of the fundamental applications for monolayer-thick 2D materials is their use as protective layers of metal surfaces and in situ intercalated reactive materials in ambient conditions. Here we investigate the structural, electronic, and magnetic properties, as well as the chemical stability in air of a very reactive metal, Europium, after intercalation between a hexagonal boron nitride (hBN) layer and a Pt substrate. We demonstrate that Eu intercalation leads to a hBN-covered ferromagnetic EuPt 2 surface alloy with divalent Eu 2+ atoms at the interface. We expose the system to ambient conditions and find a partial conservation of the di-valent signal and hence the Eu-Pt interface. The use of a curved Pt substrate allows us to explore the changes in the Eu valence state and the ambient pressure protection at different substrate planes. The interfacial EuPt 2 surface alloy formation remains the same, but the resistance of the protecting hBN layer to ambient conditions is reduced, likely due to a rougher surface and a more discontinuous hBN coating.

Magnetic hybrid metal-organic interfaces possess a great potential in areas such as organic spintronics and quantum information processing. However, tuning their carrier injection barriers on-demand is fundamental for the implementation in technological devices. We have prepared hybrid metal-organic interfaces by the adsorption of copper phthalocyanine CuPc on REAu 2 surfaces (RE = Gd, Ho and Yb) and studied their growth, electrostatics and electronic structure. CuPc exhibits a long-range commensurability and a vacuum level pinning of the molecular energy levels. We observe a significant effect of the RE valence of the substrate on the carrier injection barrier of the hybrid metal-organic interface. CuPc adsorbed on trivalent RE-based surfaces (HoAu 2 and GdAu 2 ) exhibits molecular level energies that may allow injection carriers significantly closer to an ambipolar injection behavior than in the divalent case (YbAu 2 ).

One-dimensional (1D) metal-organic (MO) nanowires are captivating from fundamental and technological perspectives due to their distinctive magnetic and electronic properties. The solvent-free synthesis of such nanomaterials on catalytic surfaces provides a unique approach for fabricating low-dimensional single-layer materials with atomic precision and low amount of defects. A detailed understanding of the electronic structure of MO polymers such as band gap and dispersive bands is critical for their prospective implementation into nanodevices such as spin sensors or field-effect transistors. Here, we have performed the on-surface reaction of quinoidal ligands with single cobalt atoms (Co-QDI) on a vicinal Au(788) surface in ultra-high vacuum. This procedure promotes the growth and uniaxial alignment of Co-QDI MO chains along the surface atomic steps, while permitting the mapping of their electronic properties with space-averaging angle-resolved photoemission spectroscopy. In the direction parallel to the principal chain axis, a well-defined 1D band structure with weakly dispersive and dispersive bands is observed, confirming a pronounced electron delocalization. Low-temperature scanning tunneling microscopy/spectroscopy delves into the atomically precise structure of the nanowires and elucidates their narrow bandgap. These findings are supported with GW 0 band structure calculations showing that the observed electronic bands emanate from the efficient hybridization of Co(3d) and molecular orbitals. Our work paves the way towards a systematic search of similar 1D π-d hybridized MO chains with tunable electronic and magnetic properties defined by the transition or rare earth metal atom of choice.

Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence. Indeed, the peripherally-restricted CB1R specific antagonist AM6545 showed significant mnemonic effects that were occluded in adrenalectomized mice, and after peripheral adrenergic blockade. AM6545 also transiently impaired contextual fear memory extinction. Vagus nerve chemogenetic inhibition reduced AM6545-induced mnemonic effect. Genetic CB1R deletion in dopamine β-hydroxylase-expressing cells enhanced recognition memory persistence. These observations support a role of peripheral CB1R modulating adrenergic tone relevant for cognition. Furthermore, AM6545 acutely improved brain connectivity and enhanced extracellular hippocampal norepinephrine. In agreement, intra-hippocampal β-adrenergic blockade prevented AM6545 mnemonic effects. Altogether, we disclose a novel CB1R-dependent peripheral mechanism with implications relevant for lengthening the duration of non-emotional memory., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Little attention has been paid to the development of human language technology for truly low-resource languages-i.e., languages with limited amounts of digitally available text data, such as Indigenous languages. However, it has been shown that pretrained multilingual models are able to perform crosslingual transfer in a zero-shot setting even for low-resource languages which are unseen during pretraining. Yet, prior work evaluating performance on unseen languages has largely been limited to shallow token-level tasks. It remains unclear if zero-shot learning of deeper semantic tasks is possible for unseen languages. To explore this question, we present AmericasNLI, a natural language inference dataset covering 10 Indigenous languages of the Americas. We conduct experiments with pretrained models, exploring zero-shot learning in combination with model adaptation. Furthermore, as AmericasNLI is a multiway parallel dataset, we use it to benchmark the performance of different machine translation models for those languages. Finally, using a standard transformer model, we explore translation-based approaches for natural language inference. We find that the zero-shot performance of pretrained models without adaptation is poor for all languages in AmericasNLI, but model adaptation via continued pretraining results in improvements. All machine translation models are rather weak, but, surprisingly, translation-based approaches to natural language inference outperform all other models on that task., Competing Interests: AF was employed by Facebook AI Research. VC was employed by Microsoft Turing Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kann, Ebrahimi, Mager, Oncevay, Ortega, Rios, Fan, Gutierrez-Vasques, Chiruzzo, Giménez-Lugo, Ramos, Meza Ruiz, Mager, Chaudhary, Neubig, Palmer, Coto-Solano and Vu.)

A pipeline is proposed here to describe different features to study brain microcircuits on a histological scale using multi-scale analyses, including the uniform manifold approximation and projection (UMAP) dimensional reduction technique and modularity algorithm to identify neuronal ensembles, Runs tests to show significant ensembles activation, graph theory to show trajectories between ensembles, and recurrence analyses to describe how regular or chaotic ensembles dynamics are. The data set includes ex-vivo NMDA-activated striatal tissue in control conditions as well as experimental models of disease states: decorticated, dopamine depleted, and L-DOPA-induced dyskinetic rodent samples. The goal was to separate neuronal ensembles that have correlated activity patterns. The pipeline allows for the demonstration of differences between disease states in a brain slice. First, the ensembles were projected in distinctive locations in the UMAP space. Second, graphs revealed functional connectivity between neurons comprising neuronal ensembles. Third, the Runs test detected significant peaks of coactivity within neuronal ensembles. Fourth, significant peaks of coactivity were used to show activity transitions between ensembles, revealing recurrent temporal sequences between them. Fifth, recurrence analysis shows how deterministic, chaotic, or recurrent these circuits are. We found that all revealed circuits had recurrent activity except for the decorticated circuits, which tended to be divergent and chaotic. The Parkinsonian circuits exhibit fewer transitions, becoming rigid and deterministic, exhibiting a predominant temporal sequence that disrupts transitions found in the controls, thus resembling the clinical signs of rigidity and paucity of movements. Dyskinetic circuits display a higher recurrence rate between neuronal ensembles transitions, paralleling clinical findings: enhancement in involuntary movements. These findings confirm that looking at neuronal circuits at the histological scale, recording dozens of neurons simultaneously, can show clear differences between control and diseased striatal states: "fingerprints" of the disease states. Therefore, the present analysis is coherent with previous ones of striatal disease states, showing that data obtained from the tissue are robust. At the same time, it adds heuristic ways to interpret circuitry activity in different states., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation, though no other collaboration, with one of the author JB at the time of review., (Copyright © 2022 Serrano-Reyes, Pérez-Ortega, García-Vilchis, Laville, Ortega, Galarraga and Bargas.)

The psychedelic 5-HT 2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of psilocin/psilocybin. Competition binding studies with psilocin were performed in brain and cell cultures. The role of 5HT2AR, 5-HT 2C receptors (5HT2CR) and 5-HT 1A receptors (5HT1AR) on the psychosis-like head-twitch response (HTR) and on body temperature in mice after psilocybin administration were evaluated. Psilocin showed similar affinities for 5HT2AR (K i : 120-173 nM), 5HT2CR (K i : 79-311 nM) and 5-HT1AR (K i : 152-146 nM) in human and mice brain. Psilocybin induced a dose-dependent HTR (maximal effect 17.07 ± 1.31 at 1 mg/kg i.p.) that was completely suppressed by the 5HT2AR antagonist MDL11939 (1 mg/kg). Higher doses of psilocybin (3 mg/kg) induced lower HTR (9.00 ± 0.53). The 5HT2CR antagonist SB242084 (0.1 mg/kg) increased HTR exerted by psilocybin (3 mg/kg). Psilocybin significantly raised core body temperature at low dose (0.125 mg/kg) (E max =0.67 ± 0.15 °C), whereas a significant decrease was induced by doses over 1 mg/kg (E max = -1.31 ± 0.16 °C). Pre-treatment with the 5HT1AR antagonist WAY100635 reversed the decrease of body temperature after psilocybin (1 mg/kg), causing hyperthermia (E max = 0.94 ± 0.26 °C). The present work provides key findings on the 5HT2AR, 5-HT2CR and 5HT1AR involvement in the acute central effects of psilocybin. The results may be relevant for understanding the mechanism of action underlying the therapeutic effects and side effects of this psychedelic drug., Competing Interests: Declaration of Competing Interest JJM is supported by an unrestricted grant from Janssen. The rest of the authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Curved crystals are a simple but powerful approach to bridge the gap between single crystal surfaces and nanoparticle catalysts, by allowing a rational assessment of the role of active step sites in gas-surface reactions. Using a curved Rh(111) crystal, here, we investigate the effect of A-type (square geometry) and B-type (triangular geometry) atomic packing of steps on the catalytic CO oxidation on Rh at millibar pressures. Imaging the crystal during reaction ignition with laser-induced CO 2 fluorescence demonstrates a two-step process, where B-steps ignite at lower temperature than A-steps. Such fundamental dissimilarity is explained in ambient pressure X-ray photoemission (AP-XPS) experiments, which reveal partial CO desorption and oxygen buildup only at B-steps. AP-XPS also proves that A-B step asymmetries extend to the active stage: at A-steps, low-active O-Rh-O trilayers buildup immediately after ignition, while highly active chemisorbed O is the dominant species on B-type steps. We conclude that B-steps are more efficient than A-steps for the CO oxidation.

Computer-aided translation tools based on translation memories are widely used to assist professional translators. A translation memory (TM) consists of a set of translation units (TU) made up of source- and target-language segment pairs. For the translation of a new source segment s ' , these tools search the TM and retrieve the TUs (s,t) whose source segments are more similar to s ' . The translator then chooses a TU and edit the target segment t to turn it into an adequate translation of s ' . Fuzzy-match repair (FMR) techniques can be used to automatically modify the parts of t that need to be edited. We describe a language-independent FMR method that first uses machine translation to generate, given s ' and (s,t), a set of candidate fuzzy-match repaired segments, and then chooses the best one by estimating their quality. An evaluation on three different language pairs shows that the selected candidate is a good approximation to the best (oracle) candidate produced and is closer to reference translations than machine-translated segments and unrepaired fuzzy matches ( t). In addition, a single quality estimation model trained on a mix of data from all the languages performs well on any of the languages used.

Chiral graphene nanoribbons are extremely interesting structures due to their narrow band gaps and potential development of spin-polarized edge states. Here, we study their band structure on low work function silver surfaces. The use of a curved Ag single crystal provides, within the same sample, regions of disparate step structure and step density. Whereas the former leads to distinct azimuthal growth orientations of the graphene nanoribbons atop, the latter modulates the substrate's work function and thereby the interface energy level alignment. In turn, we disclose the associated charge transfer from the substrate to the ribbon and assess its effect on the nanoribbon's properties and the edge state magnetization.

Measuring the activity of neuronal populations with calcium imaging can capture emergent functional properties of neuronal circuits with single cell resolution. However, the motion of freely behaving animals, together with the intermittent detectability of calcium sensors, can hinder automatic monitoring of neuronal activity and their subsequent functional characterization. We report the development and open-source implementation of a multi-step cellular tracking algorithm (Elastic Motion Correction and Concatenation or EMC2) that compensates for the intermittent disappearance of moving neurons by integrating local deformation information from detectable neurons. We demonstrate the accuracy and versatility of our algorithm using calcium imaging data from two-photon volumetric microscopy in visual cortex of awake mice, and from confocal microscopy in behaving Hydra, which experiences major body deformation during its contractions. We quantify the performance of our algorithm using ground truth manual tracking of neurons, along with synthetic time-lapse sequences, covering a wide range of particle motions and detectability parameters. As a demonstration of the utility of the algorithm, we monitor for several days calcium activity of the same neurons in layer 2/3 of mouse visual cortex in vivo, finding significant turnover within the active neurons across days, with only few neurons that remained active across days. Also, combining automatic tracking of single neuron activity with statistical clustering, we characterize and map neuronal ensembles in behaving Hydra, finding three major non-overlapping ensembles of neurons (CB, RP1 and RP2) whose activity correlates with contractions and elongations. Our results show that the EMC2 algorithm can be used as a robust and versatile platform for neuronal tracking in behaving animals., Competing Interests: The authors have declared that no competing interests exist.

Steps at metal surfaces may influence energetics and kinetics of catalytic reactions in unexpected ways. Here, we report a significant reduction of the CO saturation coverage in Pd vicinal surfaces, which in turn is relevant for the light-off of the CO oxidation reaction. The study is based on a systematic investigation of CO adsorption on vicinal Pd(111) surfaces making use of a curved Pd crystal. A combined X-ray Photoelectron Spectroscopy and DFT analysis allows us to demonstrate that an entire row of atomic sites under Pd steps remains free of CO upon saturation at 300 K, leading to a step-density-dependent reduction of CO coverage that correlates with the observed decrease of the light-off temperature during CO oxidation in vicinal Pd surfaces.

Monolayer hexagonal boron nitride (hBN) is attracting considerable attention because of its potential applications in areas such as nano- and opto-electronics, quantum optics and nanomagnetism. However, the implementation of such functional hBN demands precise lateral nanostructuration and integration with other two-dimensional materials, and hence, novel routes of synthesis beyond exfoliation. Here, a disruptive approach is demonstrated, namely, imprinting the lateral pattern of an atomically stepped one-dimensional template into a hBN monolayer. Specifically, hBN is epitaxially grown on vicinal Rhodium (Rh) surfaces using a Rh curved crystal for a systematic exploration, which produces a periodically textured, nanostriped hBN carpet that coats Rh(111)-oriented terraces and lattice-matched Rh(337) facets with tunable width. The electronic structure reveals a nanoscale periodic modulation of the hBN atomic potential that leads to an effective lateral semiconductor multi-stripe. The potential of such atomically thin hBN heterostructure for future applications is discussed., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Emerging evidence indicates that early-life exposure to environmental factors may increase the risk for schizophrenia via inflammatory mechanisms. Inflammation can alter the metabolism of tryptophan through the oxidative kynurenine pathway to compounds with neurotoxic and neuroprotective activity and compromise serotonin (5-HT) synthesis. Here we investigate the role of serotonergic and kynurenine pathways in the maternal immune activation (MIA) animal model of schizophrenia. The potential reversion exerted by long-term antipsychotic treatment was also evaluated. MIA was induced by prenatal administration of polyinosinic:polycytidylic acid (poly (I:C)) in mice. Expression of different proteins and the content of different metabolites involved in the function of serotonergic and kynurenine pathways was assessed by RT-PCR, immunoblot and ELISA analyses in frontal cortex of the offspring after puberty. MIA decreased tissue 5-HT content and promoted changes in the expression of serotonin transporter, 5-HT 2A and 5-HT 2C receptors. Expression of indoleamine 2,3-dioxygenase 2 (IDO2) and kynurenine 3-monooxygenase (KMO) was increased by poly (I:C) whereas kynurenine aminotransferase II and its metabolite kynurenic acid were not altered. Long-term paliperidone was able to counteract MIA-induced changes in 5-HT and KMO, and to increase tryptophan availability and tryptophan hydroxylase-2 expression in poly (I:C) mice but not in controls. MIA-induced increase of the cytotoxic risk ratio of kynurenine metabolites (quinolinic/kynurenic acid) was also reversed by paliperidone. MIA induces specific long-term brain effects on serotonergic activity. Such effects seem to be related with alternative activation of the kynurenine metabolic pathway towards a cytotoxic status. Atypical antipsychotic paliperodine partially remediates abnormalities observed after MIA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 MacDowell, Munarriz-Cuezva, Meana, Leza and Ortega.)

Recently, mixed honeycomb-kagome lattices featuring metal-organic networks have been theoretically proposed as topological insulator materials capable of hosting nontrivial edge states. This new family of so-called "organic topological insulators" are purely two-dimensional and combine polyaromatic-flat molecules with metal adatoms. However, their experimental validation is still pending given the generalized absence of edge states. Here, we generate one such proposed network on a Cu(111) substrate and study its morphology and electronic structure with the purpose of confirming its topological properties. The structural techniques reveal a practically flawless network that results in a kagome network multi-band observed by angle-resolved photoemission spectroscopy and scanning tunneling spectroscopy. However, at the network island borders we notice the absence of edge states. Bond-resolved imaging of the network exhibits an unexpected structural symmetry alteration that explains such disappearance. This collective lifting of the network symmetry could be more general than initially expected and provide a simple explanation for the recurrent experimental absence of edge states in predicted organic topological insulators.

One-atom-thick rare-earth/noble metal (RE-NM) compounds are attractive materials to investigate two-dimensional magnetism, since they are easy to synthesize into a common RE-NM2 structure with high crystal perfection. Here we perform a comparative study of the GdAu2, HoAu2, and YbAu2 monolayer compounds grown on Au(111). We find the same atomic lattice quality and moiré superlattice periodicity in the three cases, but different electronic properties and magnetism. The YbAu2 monolayer reveals the characteristic electronic signatures of a mixed-valence configuration in the Yb atom. In contrast, GdAu2 and HoAu2 show the trivalent character of the rare-earth and ferromagnetic transitions below 22 K. Yet, the GdAu2 monolayer has an in-plane magnetic easy-axis, versus the out-of-plane one in HoAu2. The electronic bands of the two trivalent compounds are very similar, while the divalent YbAu2 monolayer exhibits different band features. In the latter, a strong 4f-5d hybridization is manifested in neatly resolved avoided crossings near the Fermi level. First principles theory points to a residual presence of empty 4f states, explaining the fluctuating valence of Yb in the YbAu2 monolayer.

The catalytic oxidation of CO on transition metals, such as Pt, is commonly viewed as a sharp transition from the CO-inhibited surface to the active metal, covered with O. However, we find that minor amounts of O are present in the CO-poisoned layer that explain why, surprisingly, CO desorbs at stepped and flat Pt crystal planes at once, regardless of the reaction conditions. Using near-ambient pressure X-ray photoemission and a curved Pt(111) crystal we probe the chemical composition at surfaces with variable step density during the CO oxidation reaction. Analysis of C and O core levels across the curved crystal reveals that, right before light-off, subsurface O builds up within (111) terraces. This is key to trigger the simultaneous ignition of the catalytic reaction at different Pt surfaces: a CO-Pt-O complex is formed that equals the CO chemisorption energy at terraces and steps, leading to the abrupt desorption of poisoning CO from all crystal facets at the same temperature., (© 2020 Wiley-VCH GmbH.)

We present electronic structure calculations based on a single-parameter plane wave expansion method for basic graphene building blocks, namely n -oligophenylenes and n -oligoacenes, revealing excellent agreement with density-functional theory. When oligophenylene molecules are joined through meta (zigzag) or ortho (chevron) junctions, the resulting molecular dimers and polymers exhibit a semiconducting character. While zigzag dimers of oligoacenes also exhibit gapped electronic structures, their chevron-phase features a sharp metallic band at the Fermi energy. This zero-point-energy state, which transforms into Dirac-like band in chevron polymers, survives at the outer elbows of the dimer irrespective of the molecular length, and has the same origin as reported for the polyacetylene and topologically induced edge states at edge-decorated graphene nanoribbons. These findings assist the engineering of topological electronic states at the molecular level and complement the toolbox of quantum phases in carbon-based nanostructures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

On-surface metal-organic nanoporous networks generally refer to adatom coordinated molecular arrays, which are characterized by the presence of well-defined and regular nanopores. These periodic structures constructed using two types of components confine the surface electrons of the substrate within their nanocavities. However, the confining (or scattering) strength that individual building units exhibit is a priori unknown. Here, we study the modification of the substrate's surface electrons by the interaction with a Cu-coordinated TPyB metal-organic network formed on Cu(111) and disentangle the scattering potentials and confinement properties. By means of STM and angle-resolved photoemission spectroscopy we find almost unperturbed free-electron-like states stemming from the rather weak electron confinement that yields significant coupling between adjacent pores. Electron plane wave expansion simulations match the superlattice induced experimental electronic structure, which features replicating bands and energy renormalization effects. Notably, the electrostatic potential landscape obtained from our ab initio calculations suggests that the molecules are the dominant scattering entities while the coordination metal atoms sandwiched between them act as leaky channels. These metal atom transmission conduits facilitate and enhance the coupling among quantum dots, which are prone to be exploited to engineer the electronic structure of surface electron gases.

Quantum dot arrays in the form of molecular nanoporous networks are renowned for modifying the electronic surface properties through quantum confinement. Here we show that, compared to the pristine surface state, the band bottom of the confined states can exhibit downward shifts accompanied by a lowering of the effective masses simultaneous to the appearance of tiny gaps at the Brillouin zone boundaries. We observed these effects by angle resolved photoemission for two self-assembled homothetic (scalable) Co-coordinated metal-organic networks. Complementary scanning tunneling spectroscopy measurements confirmed these findings. Electron plane wave expansion simulations and density functional theory calculations provide insight into the nature of this phenomenon, which we assign to metal-organic overlayer-substrate interactions in the form of adatom-substrate hybridization. To date, the absence of the experimental band structure resulting from single metal adatom coordinated nanoporous networks has precluded the observation of the significant surface state renormalization reported here, which we infer to be general for low interacting and well-defined adatom arrays.

Disruption of the hypothalamic-pituitary-adrenal axis is an established finding in patients with anxiety and/or depression. Chronic corticosterone administration in animals has been proposed as a model for the study of these stress-related disorders and the antidepressant action. Alterations of the central noradrenergic system and specifically of inhibitory α 2 -adrenoceptors seem to be part of the pathophysiology of depression and contribute to the antidepressant activity. The present study evaluates in male rats the effect of chronic corticosterone treatment during 35 days (16-20 mg kg -1 day -1 ) on the sensitivity of α 2 -adrenoceptors expressed in the somatodendritic and terminal noradrenergic areas locus coeruleus (LC) and prefrontal cortex (PFC), respectively. Further, the effect of chronic fluoxetine treatment (5 mg kg -1 , i.p., since the 15th day) on the sensitivity of α 2 -adrenoceptors was examined under control conditions and in corticosterone-treated rats. The α 2 -adrenoceptor functionality was analysed in vitro by agonist-mediated [ 35 S]GTPγS binding stimulation and in vivo through the modulation of noradrenaline (NA) release evaluated by dual-probe microdialysis. The concentration-effect curves of the [ 35 S]GTPγS binding stimulation by the agonist UK14304 (5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) demonstrated a desensitization of cortical α 2 -adrenoceptors induced by corticosterone (-logEC 50  = 6.7 ± 0.2 vs 8.2 ± 0.3 in controls) that was reverted by fluoxetine treatment (-logEC 50  = 7.5 ± 0.3). Local administration of the α 2 -adrenoceptor antagonist RS79948 ((8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12-(ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine) (0.1-100 μmol L -1 ) into the LC induced a concentration-dependent NA increase in the PFC of the control group (E max  = 191 ± 30%) but non-significant effect was observed in corticosterone-treated rats (E max  = 133 ± 46%), reflecting a desensitization of α 2 -adrenoceptors that control the firing of noradrenergic neurons. Fluoxetine treatment did not alter the corticosterone-induced desensitization in this area (E max  = 136 ± 19%). No effect of fluoxetine on α 2 -adrenoceptor functionality was observed in control animals (E max  = 223 ± 30%). In PFC, the local administration of RS79948 increased NA in controls (E max  = 226 ± 27%) without effect in the corticosterone group (E max  = 115 ± 26%), suggesting a corticosterone-induced desensitization of terminal α 2 -adrenoceptors. Fluoxetine administration prevented the desensitization induced by corticosterone in the PFC (E max  = 233 ± 33%) whereas desensitized α 2 -adrenoceptors in control animals (E max  = -24 ± 10%). These data indicate that chronic corticosterone increases noradrenergic activity by acting at different α 2 -adrenoceptor subpopulations. Treatment with the antidepressant fluoxetine seems to counteract these changes by acting mainly on presynaptic α 2 -adrenoceptors expressed in terminal areas., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pegboard tests are a powerful technique used by health and education professionals to evaluate manual dexterity and fine motor speed, both in children and adults. Using traditional pegboards in tests, the total time that, for example, a 4-year-old child needs for inserting pegs in a pegboard, with the left or right hand, can be measured. However, these measurements only allow for studying the variability among individuals, whereas no data can be obtained on the intraindividual variability in inserting and removing these pegs with one and the other hand., Objective: The aim of this research was to study the intraindividual variabilities in fine manual motor skills of 2- to 3-year-old children during playing activities, using a custom designed electronic pegboard., Methods: We have carried out a pilot study with 39 children, aged between 25 and 41 months. The children were observed while performing a task involving removing 10 pegs from 10 holes on one side and inserting them in 10 holes on the other side of a custom-designed sensor-based electronic pegboard, which has been built to be able to measure the times between peg insertions and removals., Results: A sensor-based electronic pegboard was successfully developed, enabling the collection of single movement time data. In the piloting, a lower intraindividual variability was found in children with lower placement and removal times, confirming Adolph et al's hypothesis., Conclusions: The developed pegboard allows for studying intraindividual variability using automated wirelessly transmitted data provided by its sensors. This novel technique has been useful in studying and validating the hypothesis that children with lower movement times present lower intraindividual variability. New research is necessary to confirm these findings. Research with larger sample sizes and age ranges that include additional testing of children's motor development level is currently in preparation., (©Diego Rivera, Antonio García, Jose Eugenio Ortega, Bernardo Alarcos, Kevin van der Meulen, Juan R Velasco, Cristina del Barrio. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.08.2019.)

Light-matter interaction at the atomic scale rules fundamental phenomena such as photoemission and lasing while enabling basic everyday technologies, including photovoltaics and optical communications. In this context, plasmons, the collective electron oscillations in conducting materials, are important because they allow the manipulation of optical fields at the nanoscale. The advent of graphene and other two-dimensional crystals has pushed plasmons down to genuinely atomic dimensions, displaying appealing properties such as a large electrical tunability. However, plasmons in these materials are either too broad or lying at low frequencies, well below the technologically relevant near-infrared regime. Here, we demonstrate sharp near-infrared plasmons in lithographically patterned wafer-scale atomically thin silver crystalline films. Our measured optical spectra reveal narrow plasmons (quality factor of ∼4), further supported by a low sheet resistance comparable to bulk metal in few-atomic-layer silver films down to seven Ag(111) monolayers. Good crystal quality and plasmon narrowness are obtained despite the addition of a thin passivating dielectric, which renders our samples resilient to ambient conditions. The observation of spectrally sharp and strongly confined plasmons in atomically thin silver holds great potential for electro-optical modulation and optical sensing applications.

Current pharmacological treatments for major depressive disorder (MDD) are severely compromised by both slow action and limited efficacy. RNAi strategies have been used to evoke antidepressant-like effects faster than classical drugs. Using small interfering RNA (siRNA), we herein show that TASK3 potassium channel knockdown in monoamine neurons induces antidepressant-like responses in mice. TASK3-siRNAs were conjugated to cell-specific ligands, sertraline (Ser) or reboxetine (Reb), to promote their selective accumulation in serotonin (5-HT) and norepinephrine (NE) neurons, respectively, after intranasal delivery. Following neuronal internalization of conjugated TASK3-siRNAs, reduced TASK3 mRNA and protein levels were found in the brainstem 5-HT and NE cell groups. Moreover, Ser-TASK3-siRNA induced robust antidepressant-like behaviors, enhanced the hippocampal plasticity, and potentiated the fluoxetine-induced increase on extracellular 5-HT. Similar responses, yet of lower magnitude, were detected for Reb-TASK3-siRNA. These findings provide substantial support for TASK3 as a potential target, and RNAi-based strategies as a novel therapeutic approach to treat MDD.

Understanding nanoparticle catalysis requires novel approaches in which adjoining crystal orientations can be studied under the same reactive conditions. Here we use a curved palladium crystal and near-ambient pressure X-ray photoemission spectroscopy to characterize chemical species during the catalytic oxidation of CO in a whole set of surfaces vicinal to the (111) direction simultaneously. By stabilizing the reaction at fixed temperatures around the ignition point, we observe a strong variation of the catalytic activity across the curved surface. Such spatial modulation of the reaction stage is straightforwardly mapped through the photoemission signal from active oxygen species and poisoning CO, which are shown to coexist in a transient regime that depends on the vicinal angle. Line-shape analysis and direct comparison with ultrahigh vacuum experiments help identifying and quantifying all such surface species, allowing us to reveal the presence of surface oxides during reaction ignition and cooling-off.

Liver cirrhosis (LC) is an inflammatory process associated with impaired functions in adaptive and innate immune responses at both systemic and local levels, also referred as Cirrhosis-Associated Immune Dysfunction. In this study, we evaluated the functionality of neutrophils from ascitic fluid (AF) of patients with hepatic cirrhosis by testing their ability to generate neutrophil extracellular traps (NETs) in vitro. To further determine the activation state of neutrophils, expression of the activation markers CD66b, CD69, and CD80 on these cells was analysed by flow cytometry. The inflammatory environment in AF was assessed by measured concentration of pro- and anti-inflammatory cytokines. Samples were collected from 40 patients with LC, 20 of them with uncomplicated ascites (ASC) and 20 with spontaneous bacterial peritonitis (SBP). Peripheral blood (PB) neutrophils from healthy individuals were used as control (HC). Our results revealed a significant decrease in the release of NETs in neutrophils from the SBP group compared with HC. Low expression of CD69 and CD80 on neutrophils from AF of SBP patients was also observed. Comparisons of inflammatory cytokine levels in AF from the different study groups (SBP and ASC) revealed significant differences. In conclusion, we demonstrate that the development of complications, such as SBP, increases initially the inflammatory status, but chronically results in impaired neutrophil function as demonstrated by the decreased capability of NETs formation. There is also an increase in both pro-inflammatory and anti-inflammatory cytokines, thus predisposing for new episodes of SPB and increasing morbidity and mortality in cirrhotic patients., (© 2018 The Foundation for the Scandinavian Journal of Immunology.)

Designing molecular organic semiconductors with distinct frontier orbitals is key for the development of devices with desirable properties. Generating defined organic nanostructures with atomic precision can be accomplished by on-surface synthesis. We use this "dry" chemistry to introduce topological variations in a conjugated poly( para-phenylene) chain in the form of meta-junctions. As evidenced by STM and LEED, we produce a macroscopically ordered, monolayer thin zigzag chain film on a vicinal silver crystal. These cross-conjugated nanostructures are expected to display altered electronic properties, which are now unraveled by highly complementary experimental techniques (ARPES and STS) and theoretical calculations (DFT and EPWE). We find that meta-junctions dominate the weakly dispersive band structure, while the band gap is tunable by altering the linear segment's length. These periodic topology effects induce significant loss of the electronic coupling between neighboring linear segments leading to partial electron confinement in the form of weakly coupled quantum dots. Such periodic quantum interference effects determine the overall semiconducting character and functionality of the chains.

The challenge of synthesizing graphene nanoribbons (GNRs) with atomic precision is currently being pursued along a one-way road, based on the synthesis of adequate molecular precursors that react in predefined ways through self-assembly processes. The synthetic options for GNR generation would multiply by adding a new direction to this readily successful approach, especially if both of them can be combined. We show here how GNR synthesis can be guided by an adequately nanotemplated substrate instead of by the traditionally designed reactants. The structural atomic precision, unachievable to date through top-down methods, is preserved by the self-assembly process. This new strategy's proof-of-concept compares experiments using 4,4''-dibromo-para-terphenyl as a molecular precursor on flat Au(111) and stepped Au(322) substrates. As opposed to the former, the periodic steps of the latter drive the selective synthesis of 6 atom-wide armchair GNRs, whose electronic properties have been further characterized in detail by scanning tunneling spectroscopy, angle resolved photoemission, and density functional theory calculations.

Activation of serotonin 5-HT 3 receptor (5HT3R) in the locus coeruleus (LC), the principal somatodendritic noradrenergic area, decreases LC firing activity and noradrenaline (NA) release in prefrontal cortex (PFC). Blockade of 5HT3R in coadministration with selective serotonin reuptake inhibitors (SSRIs) has been proposed as a potential strategy to accelerate the onset of action of SSRIs. Dual-probe microdialysis in rats was used to evaluate the involvement of 5HT3R in the in vivo effect exerted by the SSRI citalopram on NA release. Besides, forced swimming test (FST) was carried out in mice to evaluate the antidepressant-like effect of citalopram in combination with a 5HT3R antagonist (Y25130). Systemic administration of the 5HT3R agonist SR57227 (10 mg/kg i.p.) increased NA in LC (Emax = 200 ± 27%) and PFC (Emax = 133 ± 2%). The increase in PFC was enhanced in local presence into LC of Y25130 (50 μM) (Emax = 296 ± 41%) suggesting an inhibitory function on NA release exerted by the activation of 5HT3R located in somatodendritic areas. Citalopram administration (10 mg/kg i.p.) increased NA in LC (Emax = 185 ± 11%) and decreased it in PFC (Emax = -35 ± 7%). Intra-LC (50 μM) or systemic co-administration of Y25130 (10 mg/kg i.p.) with citalopram (10 mg/kg i.p.) switched NA release in the PFC from an inhibition to a stimulatory effect. In mice FST, systemic coadministration of citalopram (2.5 mg/kg i.p.) and Y25130 (10 mg/kg i.p.) potentiated the decrease of immobility time through the increase of both swimming and climbing behaviours. These results suggest that the addition of a 5HT3R antagonist to SSRIs could represent a feasible strategy to improve antidepressant response., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The importance of dopamine (DA) neurotransmission is emphasized by its direct implication in several neurological and psychiatric disorders. The DA transporter (DAT), target of psychostimulant drugs, is the key protein that regulates spatial and temporal activity of DA in the synaptic cleft via the rapid reuptake of DA into the presynaptic terminal. There is strong evidence suggesting that DAT-interacting proteins may have a role in its function and regulation. Performing a two-hybrid screening, we identified snapin, a SNARE-associated protein implicated in synaptic transmission, as a new binding partner of the carboxyl terminal of DAT. Our data show that snapin is a direct partner and regulator of DAT. First, we determined the domains required for this interaction in both proteins and characterized the DAT-snapin interface by generating a 3D model. Using different approaches, we demonstrated that (i) snapin is expressed in vivo in dopaminergic neurons along with DAT; (ii) both proteins colocalize in cultured cells and brain and, (iii) DAT and snapin are present in the same protein complex. Moreover, by functional studies we showed that snapin produces a significant decrease in DAT uptake activity. Finally, snapin downregulation in mice produces an increase in DAT levels and transport activity, hence increasing DA concentration and locomotor response to amphetamine. In conclusion, snapin/DAT interaction represents a direct link between exocytotic and reuptake mechanisms and is a potential target for DA transmission modulation.

Recent advances in graphene-nanoribbon-based research have demonstrated the controlled synthesis of chiral graphene nanoribbons (chGNRs) with atomic precision using strategies of on-surface chemistry. However, their electronic characterization, including typical figures of merit like band gap or frontier band's effective mass, has not yet been reported. We provide a detailed characterization of (3,1)-chGNRs on Au(111). The structure and epitaxy, as well as the electronic band structure of the ribbons, are analyzed by means of scanning tunneling microscopy and spectroscopy, angle-resolved photoemission, and density functional theory.

The high reactivity of magnetic substrates toward molecular overlayers has so far inhibited the realization of more sophisticated on-surface reactions, thereby depriving these interfaces of a significant class of chemically tailored organics such as graphene nanoribbons, oligonuclear spin-chains, and metal-organic networks. Here, we present a multitechnique characterization of the polymerization of 4,4″-dibromo-p-terphenyl precursors into ordered poly(p-phenylene) arrays on top of the bimetallic GdAu 2 surface alloy. The activation temperatures for bromine scission and subsequent homocoupling of molecular precursors were followed by temperature-dependent X-ray photoelectron spectroscopy. The structural characterizations of supramolecular and polymeric phases, performed by low-energy electron diffraction and scanning tunneling microscopy, establish an extraordinary degree of order extending into the mesoscale. Taking advantage of the high homogeneity, the electronic structure of the valence band was determined with angle-resolved photoemission spectroscopy. Importantly, the transition of localized molecular orbitals into a highly dispersive π-band, the fingerprint of successful polymerization, was observed while leaving all surface-related bands intact. Moreover, ferromagnetic ordering in the GdAu 2 alloy was demonstrated for all phases by X-ray absorption spectroscopy. The transfer of well-established in situ methods for growing covalently bonded macromolecules with atomic precision onto magnetic rare-earth alloys is an important step toward toward studying and controlling intrinsic carbon- and rare-earth-based magnetism.

Quantum dots are known to confine electrons within their structure. Whenever they periodically aggregate into arrays and cooperative interactions arise, novel quantum properties suitable for technological applications show up. Control over the potential barriers existing between neighboring quantum dots is therefore essential to alter their mutual crosstalk. Here we show that precise engineering of the barrier width can be experimentally achieved on surfaces by a single atom substitution in a haloaromatic compound, which in turn tunes the confinement properties through the degree of quantum dot intercoupling. We achieved this by generating self-assembled molecular nanoporous networks that confine the two-dimensional electron gas present at the surface. Indeed, these extended arrays form up on bulk surface and thin silver films alike, maintaining their overall interdot coupling. These findings pave the way to reach full control over two-dimensional electron gases by means of self-assembled molecular networks.Arrays of quantum dots can exhibit a variety of quantum properties, being sensitive to their spacing. Here, the authors fine tune interdot coupling using hexagonal molecular networks in which the dots are separated by single or double haloaromatic compounds, structurally identical but for a single atom.

Selective serotonin reuptake inhibitors (SSRIs) regulate brain noradrenergic neurotransmission both at somatodendritic and nerve terminal areas. Previous studies have demonstrated that noradrenaline (NA) reuptake inhibitors are able to desensitize α 2 -adrenoceptor-mediated responses. The present study was undertaken to elucidate the effects of repeated treatment with the SSRI citalopram on the α 2 -adrenoceptor sensitivity in locus coeruleus (LC) and prefrontal cortex (PFC), by using in vivo microdialysis and electrophysiological techniques, and in vitro stimulation of [ 35 S]GTPγS binding autoradiography. Repeated, but not acute, treatment with citalopram (5 mg/kg, i.p., 14 days) increased extracellular NA concentration selectively in PFC. The α 2 -adrenoceptor agonist clonidine (0.3 mg/kg, i.p.), administered to saline-treated animals (1 ml/kg i.p., 14 days) induced NA decrease in LC (E max  = -44 ± 4%; p < 0.001) and in PFC (E max  = -61 ± 5%, p < 0.001). In citalopram chronically-treated rats, clonidine administration exerted a lower decrease of NA (E max  = -25 ± 7%; p < 0.001) in PFC whereas the effect in LC was not different to controls (E max  = -36 ± 4%). Clonidine administration (0.625-20 μg/kg, i.v.) evoked a dose-dependent decrease of the firing activity of LC noradrenergic neurons in both citalopram- (ED 50  = 3.2 ± 0.4 μg/kg) and saline-treated groups (ED 50  = 2.6 ± 0.5 μg/kg). No significant differences between groups were found in ED 50 values. The α 2 -adrenoceptor agonist UK14304 stimulated specific [ 35 S]GTPγS binding in brain sections containing LC (144 ± 14%) and PFC (194 ± 32%) of saline-treated animals. In citalopram-treated animals, this increase did not differ from controls in LC (146 ± 22%) but was lower in PFC (141 ± 8%; p < 0.05). Taken together, long-term citalopram treatment induces a desensitization of α 2 -adrenoceptors acting as axon terminal autoreceptors in PFC without changes in somatodendritic α 2 -adrenoceptor sensitivity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Rationale: Noradrenergic system plays a critical role in the hypothalamic-pituitary-adrenal (HPA) axis regulation and the stress response. A dysregulated HPA axis may be indicative of an increased biological vulnerability for depression. In addition, a variety of studies have focused on specific alterations of α 2 -adrenoceptors as a mechanism involved in the pathogenesis of mood disorders and antidepressant response., Objectives: This study aimed to evaluate the effect of subchronic corticosterone administration on rat brain α 2 -adrenoceptor functionality by in vitro [ 35 S]GTPγS binding stimulation assays and in vivo dual-probe microdialysis determination of extracellular noradrenaline concentrations., Results: Implantation of a time release corticosterone pellet during 14 days induced sustained changes in endocrine function. However, there were no differences in α 2 -adrenoceptor agonist UK14304-induced stimulation of [ 35 S]GTPγS binding in prefrontal cortex (PFC) between corticosterone-treated and control rats. In the same way, the in vivo evaluation of α 2 -adrenoceptor-mediated noradrenaline release responses to the α 2 -adrenoceptor agonist clonidine local administration into the locus coeruleus (LC), and the PFC did not show differences between the groups., Conclusions: The present results show that subchronic corticosterone administration does not induce changes on functionality of α 2 -adrenoceptors neither in the LC nor in noradrenergic cortical terminal areas.