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Rock strength has long been linked to lithospheric deformation and seismicity. However, independent constraints on the related elastic heterogeneity are missing, yet could provide key information for solid Earth dynamics. Using coseismic Global Navigation Satellite Systems (GNSS) data for the 2011 M9 Tohoku-oki earthquake in Japan, we apply an inverse method to infer elastic structure and fault slip simultaneously. We find compliant material beneath the volcanic arc and in the mantle wedge within the partial melt generation zone inferred to lie above ~100 km slab depth. We also identify low-rigidity material closer to the trench matching seismicity patterns, likely associated with accretionary wedge structure. Along with traditional seismic and electromagnetic methods, our approach opens up avenues for multiphysics inversions. Those have the potential to advance earthquake and volcano science, and in particular once expanded to InSAR type constraints, may lead to a better understanding of transient lithospheric deformation across scales.
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Plate reconstruction models are constructed to fit constraints such as magnetic anomalies, fracture zones, paleomagnetic poles, geological observations and seismic tomography. However, these models do not consider the physical equations of plate driving forces when reconstructing plate motion. This can potentially result in geodynamically-implausible plate motions, which has implications for a range of work based on plate reconstruction models. We present a new algorithm that calculates time-dependent slab pull, ridge push (GPE force) and mantle drag resistance for any topologically closed reconstruction, and evaluates the residuals-or missing components-required for torques to balance given our assumed plate driving force relationships. In all analyzed models, residual torques for the present-day are three orders of magnitude smaller than the typical driving torques for oceanic plates, but can be of the same order of magnitude back in time-particularly from 90 to 50 Ma. Using the Pacific plate as an example, we show how our algorithm can be used to identify areas and times with high residual torques, where either plate reconstructions have a high degree of geodynamic implausibility or our understanding of the underlying geodynamic forces is incomplete. We suggest strategies for plate model improvements and also identify times when other forces such as active mantle flow were likely important contributors. Our algorithm is intended as a tool to help assess and improve plate reconstruction models based on a transparent and expandable set of a priori dynamic constraints.
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Placas Óseas , Fracturas Óseas , Humanos , Movimiento (Física) , Geología , TomografíaRESUMEN
RATIONALE: Calcineurin is a protein regulating cytokine expression in T lymphocytes and calcineurin inhibitors such as cyclosporine A (CsA) are widely used for immunosuppressive therapy. It also plays a functional role in distinct neuronal processes in the central nervous system. Disturbed information processing as seen in neuropsychiatric disorders is reflected by deficient sensorimotor gating, assessed as prepulse inhibition (PPI) of the acoustic startle response (ASR). OBJECTIVE: Patients who require treatment with immunosuppressive drugs frequently display neuropsychiatric alterations during treatment with calcineurin inhibitors. Importantly, knockout of calcineurin in the forebrain of mice is associated with cognitive impairments and symptoms of schizophrenia-like psychosis as seen after treatment with stimulants. METHODS: The present study investigated in rats effects of systemic acute and subchronic administration of CsA on sensorimotor gating. Following a single injection with effective doses of CsA, adult healthy male Dark Agouti rats were tested for PPI. For subchronic treatment, rats were injected daily with the same doses of CsA for 1 week before PPI was assessed. Since calcineurin works as a modulator of the dopamine pathway, activity of the enzyme tyrosine hydroxylase was measured in the prefrontal cortex and striatum after accomplishment of the study. RESULTS: Acute and subchronic treatment with the calcineurin inhibitor CsA disrupted PPI at a dose of 20 mg/kg. Concomitantly, following acute CsA treatment, tyrosine hydroxylase activity was reduced in the prefrontal cortex, which suggests that dopamine synthesis was downregulated, potentially reflecting a stimulatory impact of CsA on this neurotransmitter system. CONCLUSIONS: The results support experimental and clinical evidence linking impaired calcineurin signaling in the central nervous system to the pathophysiology of neuropsychiatric symptoms. Moreover, these findings suggest that therapy with calcineurin inhibitors may be a risk factor for developing neurobehavioral alterations as observed after the abuse of psychomotor stimulant drugs.
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Inhibidores de la Calcineurina/farmacología , Ciclosporina/farmacología , Inmunosupresores/farmacología , Filtrado Sensorial/efectos de los fármacos , Animales , Dopamina/biosíntesis , Masculino , Neostriado/enzimología , Corteza Prefrontal/enzimología , Ratas , Ratas Sprague-Dawley , Reflejo de Sobresalto/efectos de los fármacos , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Rare high-3He/4He signatures in ocean island basalts (OIB) erupted at volcanic hotspots derive from deep-seated domains preserved in Earth's interior. Only high-3He/4He OIB exhibit anomalous 182W-an isotopic signature inherited during the earliest history of Earth-supporting an ancient origin of high 3He/4He. However, it is not understood why some OIB host anomalous 182W while others do not. We provide geochemical data for the highest-3He/4He lavas from Iceland (up to 42.9 times atmospheric) with anomalous 182W and examine how Sr-Nd-Hf-Pb isotopic variations-useful for tracing subducted, recycled crust-relate to high 3He/4He and anomalous 182W. These data, together with data on global OIB, show that the highest-3He/4He and the largest-magnitude 182W anomalies are found only in geochemically depleted mantle domains-with high 143Nd/144Nd and low 206Pb/204Pb-lacking strong signatures of recycled materials. In contrast, OIB with the strongest signatures associated with recycled materials have low 3He/4He and lack anomalous 182W. These observations provide important clues regarding the survival of the ancient He and W signatures in Earth's mantle. We show that high-3He/4He mantle domains with anomalous 182W have low W and 4He concentrations compared to recycled materials and are therefore highly susceptible to being overprinted with low 3He/4He and normal (not anomalous) 182W characteristic of subducted crust. Thus, high 3He/4He and anomalous 182W are preserved exclusively in mantle domains least modified by recycled crust. This model places the long-term preservation of ancient high 3He/4He and anomalous 182W in the geodynamic context of crustal subduction and recycling and informs on survival of other early-formed heterogeneities in Earth's interior.
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The lifetime of steam pipelines in long-term operation in coal-fired power plants are limited due to material damage that resulted from creep exposure. In the present study, the authors comparatively assess the damage of ex-service 12% Cr piping steel with varying degrees of exposure while using accelerated creep tests that employ digital image correlation (DIC) as well as microstructural investigation that is based on electron microscopy. The DIC technique, which allows multiple creep curves to be measured at temperatures ranging from 550-600 °C from a single specimen, revealed higher Zener-Hollomon parameters for a high damage material with a high void density when compared to a material with lower damage and lower void density. Both of the material states showed similar hardness values, subgrain sizes, and boundary character, despite the difference in void densities. Slightly higher inter-particle spacing of MX precipitates results in a lower threshold stress of 79 MPa for the high damage steel when compared to 97 MPa for the low damage material. Besides large Laves phase particles (>0.2 µm) that are found in the higher damaged materials that result in solid solution depletion, the most prominent microstructural damage indicator was a lower density of M23C6 precipitates. Therefore, the observations indicate that the Zener-Hollomon parameter and M23C6 particles are good damage assessment indicators between the most extreme damage states and they predict a lower damage level for a medium void density material.
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Skeletal muscle myoblast differentiation involves elaborate signaling networks, including the activity of various ion channels and transporters. Several K+ and Ca2+ channels have been shown to affect myogenesis, but little is known about roles of Cl- channels in the associated processes. Here, we report that the leucine-rich repeat containing family 8 (LRRC8)/volume-regulated anion channel (VRAC) promotes mouse myoblast differentiation. All LRRC8 subunits of heteromeric VRAC were expressed during myotube formation of murine C2C12 myoblasts. Pharmacological VRAC inhibitors, siRNA-mediated knockdown of the essential VRAC subunit LRRC8A, or VRAC activity-suppressing overexpression of LRRC8A effectively reduced the expression of the myogenic transcription factor myogenin and suppressed myoblast fusion while not affecting myoblast proliferation. We found that inhibiting VRAC impairs plasma membrane hyperpolarization early during differentiation. At later times (more than 6 h after inducing differentiation), VRAC inhibition no longer suppressed myoblast differentiation, suggesting that VRAC acts upstream of K+ channel activation. Consequently, VRAC inhibition prevented the increase of intracellular steady-state Ca2+ levels that normally occurs during myogenesis. Our results may explain the mechanism for the thinning of skeletal muscle bundles observed in LRRC8A-deficient mice and highlight the importance of the LRRC8/VRAC anion channel in cell differentiation.
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Diferenciación Celular , Potenciales de la Membrana , Proteínas de la Membrana/metabolismo , Mioblastos/metabolismo , Animales , Línea Celular , Proteínas de la Membrana/genética , Ratones , Mioblastos/citología , Mioblastos/fisiología , Miogenina/genética , Miogenina/metabolismoRESUMEN
Research into the molecular basis of stress resilience is a novel strategy to identify potential therapeutic strategies to treat stress-induced psychopathologies such as anxiety and depression. Stress resilience is a phenomenon which is not solely driven by effects within the central nervous system (CNS) but involves multiple systems, central and peripheral, which interact with and influence each other. Accordingly, we used the chronic social defeat stress paradigm and investigated specific CNS, endocrine and immune responses to identify signatures of stress-resilience and stress susceptibility in mice. Our results showed that mice behaviourally susceptible to stress (indexed by a reduction in social interaction behaviour) had higher plasma corticosterone levels and adrenal hypertrophy. An increase in inflammatory circulating monocytes was another hallmark of stress susceptibility. Furthermore, prefrontal cortex mRNA expression of corticotrophin-releasing factor (Crf) was increased in susceptible mice relative to resilient mice. We also report differences in hippocampal synaptic plasticity between resilient and susceptible mice. Ongoing studies will interpret the functional relevance of these signatures which could potentially inform the development of novel psychotherapeutic strategies.
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Adaptación Psicológica/fisiología , Estrés Psicológico/metabolismo , Animales , Ansiedad/metabolismo , Conducta Animal/fisiología , Corticosterona/análisis , Corticosterona/sangre , Hormona Liberadora de Corticotropina/metabolismo , Depresión/metabolismo , Hipocampo/metabolismo , Relaciones Interpersonales , Masculino , Ratones , Plasticidad Neuronal/fisiología , Sistemas Neurosecretores/metabolismo , Corteza Prefrontal/metabolismo , Resiliencia Psicológica , Conducta SocialRESUMEN
Current post-process heat treatments applied to selective laser melting produced Ti-6Al-4V do not achieve the same microstructure and therefore superior tensile behaviour of thermomechanical processed wrought Ti-6Al-4V. Due to the growing demand for selective laser melting produced parts in industry, research and development towards improved mechanical properties is ongoing. This study is aimed at developing post-process annealing strategies to improve tensile behaviour of selective laser melting produced Ti-6Al-4V parts. Optical and electron microscopy was used to study α grain morphology as a function of annealing temperature, hold time and cooling rate. Quasi-static uniaxial tensile tests were used to measure tensile behaviour of different annealed parts. It was found that elongated α'/α grains can be fragmented into equiaxial grains through applying a high temperature annealing strategy. It is shown that bi-modal microstructures achieve a superior tensile ductility to current heat treated selective laser melting produced Ti-6Al-4V samples.
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The formation of mountain belts or rift zones is commonly attributed to interactions between plates along their boundaries, but the widely distributed deformation of Asia from Himalaya to the Japan Sea and other back-arc basins is difficult to reconcile with this notion. Through comparison of the tectonic and kinematic records of the last 50 Ma with seismic tomography and anisotropy models, we show that the closure of the former Tethys Ocean and the extensional deformation of East Asia can be best explained if the asthenospheric mantle transporting India northward, forming the Himalaya and the Tibetan Plateau, reaches East Asia where it overrides the westward flowing Pacific mantle and contributes to subduction dynamics, distributing extensional deformation over a 3,000-km wide region. This deep asthenospheric flow partly controls the compressional stresses transmitted through the continent-continent collision, driving crustal thickening below the Himalayas and Tibet and the propagation of strike-slip faults across Asian lithosphere further north and east, as well as with the lithospheric and crustal flow powered by slab retreat east of the collision zone below East and SE Asia. The main shortening direction in the deforming continent between the collision zone and the Pacific subduction zones may in this case be a proxy for the direction of flow in the asthenosphere underneath, which may become a useful tool for studying mantle flow in the distant past. Our model of the India-Asia collision emphasizes the role of asthenospheric flow underneath continents and may offer alternative ways of understanding tectonic processes.
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OBJECTIVES: In the ob/ob mouse model of obesity, chronic absence of leptin causes a significant increase of orexin (OX) production by hypothalamic neurons and excessive food intake. The altered OX level is linked to a dramatic increase of the inhibitory innervation of OX producing neurons (OX neurons) and the over expression of the endocannabinoid 2-arachidonoylglycerol (2-AG) by OX neurons of ob/ob mice. Little is known about the function of the excitatory synapses of OX neurons in ob/ob mice, and their modulation by 2-AG. In the present study, we fill this gap and provide the first evidence of the overall level of activation of OX neurons in the ob/ob mice. METHODS: We performed in vitro whole-cell patch-clamp recordings on OX neurons located in the perifornical area of the lateral hypothalamus in acute brain slices of wt and ob/ob mice. We identified OX neurons on the basis of their electrophysiological membrane properties, with 96% of concordance with immunohistochemisty. RESULTS: We found that OX neurons of ob/ob mice are innervated by less efficient and fewer excitatory synapses than wt mice. Consequently, ob/ob OX neurons show more negative resting membrane potential and lower action potential firing frequency than wt. The bath application of the cannabinoid type-1 receptor agonist WIN55,212-2, depresses both the excitatory and the inhibitory synapses in ob/ob animals, but only the excitatory synapses in wt animals. Finally, the physiologic release of 2-AG induces a prevalent depression of inhibition (disinhibition) of OX neurons in ob/ob animals but not in wt. CONCLUSIONS: In ob/ob mice, chronic absence of leptin induces a 2-AG mediated functional disinhibition of OX neurons. This helps explain the increase of OX production and, consequently, the excessive food intake of ob/ob mice.
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Ácidos Araquidónicos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Endocannabinoides/farmacología , Glicéridos/farmacología , Leptina/genética , Neuronas/fisiología , Orexinas/metabolismo , Animales , Ratones , Ratones Obesos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Orexinas/genética , Potenciales SinápticosRESUMEN
Pain perception can become altered in individuals with eating disorders and obesity for reasons that have not been fully elucidated. We show that leptin deficiency in ob/ob mice, or leptin insensitivity in the arcuate nucleus of the hypothalamus in mice with high-fat diet (HFD)-induced obesity, are accompanied by elevated orexin-A (OX-A) levels and orexin receptor-1 (OX1-R)-dependent elevation of the levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), in the ventrolateral periaqueductal gray (vlPAG). In ob/ob mice, these alterations result in the following: (i) increased excitability of OX1-R-expressing vlPAG output neurons and subsequent increased OFF and decreased ON cell activity in the rostral ventromedial medulla, as assessed by patch clamp and in vivo electrophysiology; and (ii) analgesia, in both healthy and neuropathic mice. In HFD mice, instead, analgesia is only unmasked following leptin receptor antagonism. We propose that OX-A/endocannabinoid cross talk in the descending antinociceptive pathway might partly underlie increased pain thresholds in conditions associated with impaired leptin signaling.
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Ácidos Araquidónicos/metabolismo , Endocannabinoides/metabolismo , Glicéridos/metabolismo , Leptina/metabolismo , Neuronas/fisiología , Dolor Nociceptivo/fisiopatología , Orexinas/metabolismo , Percepción del Dolor/fisiología , Animales , Modelos Animales de Enfermedad , Masculino , Potenciales de la Membrana/fisiología , Ratones Obesos , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Neuronas/patología , Dolor Nociceptivo/patología , Receptores de Orexina/metabolismo , Sustancia Gris Periacueductal/patología , Sustancia Gris Periacueductal/fisiopatología , Técnicas de Cultivo de TejidosRESUMEN
Slowly-compressed single crystals, bulk metallic glasses (BMGs), rocks, granular materials, and the earth all deform via intermittent slips or "quakes". We find that although these systems span 12 decades in length scale, they all show the same scaling behavior for their slip size distributions and other statistical properties. Remarkably, the size distributions follow the same power law multiplied with the same exponential cutoff. The cutoff grows with applied force for materials spanning length scales from nanometers to kilometers. The tuneability of the cutoff with stress reflects "tuned critical" behavior, rather than self-organized criticality (SOC), which would imply stress-independence. A simple mean field model for avalanches of slipping weak spots explains the agreement across scales. It predicts the observed slip-size distributions and the observed stress-dependent cutoff function. The results enable extrapolations from one scale to another, and from one force to another, across different materials and structures, from nanocrystals to earthquakes.
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Understanding the causes of intraplate earthquakes is challenging, as it requires extending plate tectonic theory to the dynamics of continental deformation. Seismicity in the western United States away from the plate boundary is clustered along a meandering, north-south trending 'intermountain' belt. This zone coincides with a transition from thin, actively deforming to thicker, less tectonically active crust and lithosphere. Although such structural gradients have been invoked to explain seismicity localization, the underlying cause of seismicity remains unclear. Here we show results from improved mantle flow models that reveal a relationship between seismicity and the rate change of 'dynamic topography' (that is, vertical normal stress from mantle flow). The associated predictive skill is greater than that of any of the other forcings we examined. We suggest that active mantle flow is a major contributor to seismogenic intraplate deformation, while gravitational potential energy variations have a minor role. Seismicity localization should occur where convective changes in vertical normal stress are modulated by lithospheric strength heterogeneities. Our results on deformation processes appear consistent with findings from other mobile belts, and imply that mantle flow plays a significant and quantifiable part in shaping topography, tectonics, and seismic hazard within intraplate settings.
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The high water storage capacity of minerals in Earth's mantle transition zone (410- to 660-kilometer depth) implies the possibility of a deep H2O reservoir, which could cause dehydration melting of vertically flowing mantle. We examined the effects of downwelling from the transition zone into the lower mantle with high-pressure laboratory experiments, numerical modeling, and seismic P-to-S conversions recorded by a dense seismic array in North America. In experiments, the transition of hydrous ringwoodite to perovskite and (Mg,Fe)O produces intergranular melt. Detections of abrupt decreases in seismic velocity where downwelling mantle is inferred are consistent with partial melt below 660 kilometers. These results suggest hydration of a large region of the transition zone and that dehydration melting may act to trap H2O in the transition zone.
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The endocannabinoid system (ECS) is a widespread intercellular signaling system that plays a critical role in energy homeostasis, meant as the precise matching of caloric intake with energy expenditure which normally keeps body weight stable over time. Complex interactions between environmental and neurohormonal systems directly contribute to the balance of energy homeostasis. This review highlights established and more recent data on the brain circuits in which the ECS plays an important regulatory role, with focus on the hypothalamus, a region where numerous interacting systems regulating feeding, satiety, stress, and other motivational states coexist. Although not meant as an exhaustive review of the field, this article will discuss how endocannabinoid tone, in addition to reinforcing reward circuitries and modulating food intake and the salience of food, controls lipid and glucose metabolism in several peripheral organs, particularly the liver and adipose tissue. Direct actions in the skeletal muscle and pancreas are also emerging and are briefly discussed. This review provides new perspectives into endocannabinoid control of the neurochemical causes and consequences of energy homeostasis imbalance, a knowledge that might lead to new potential treatments for obesity and related morbidities.
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Endocannabinoides/fisiología , Metabolismo Energético , Homeostasis , Animales , Regulación del Apetito , Metabolismo de los Hidratos de Carbono , Ingestión de Energía , Humanos , Hipotálamo/fisiología , Metabolismo de los LípidosRESUMEN
Cannabis and 3,4 methylenedioxymetamphetamine (MDMA, "ecstasy") are the most frequently combined illegal drugs among young adults in western societies. This study examined the effects of chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) and MDMA on working memory and effort-based decision making in rats. Treatment consisted of MDMA (7.5 mg/kg), WIN (1.2 mg/kg), a combination of these substances (MDMA+WIN) or vehicle over a period of 25 days during puberty (PD40-65) or adulthood (PD80-105). Ten days after the last treatment, WIN reversed MDMA-induced working memory deficits in the object recognition test in animals treated during adulthood or puberty, but had no influence on impairment of adult rats in the effort-based T-maze task. No differences were observed between groups of pubertally treated rats in the decision making task. During a subsequent acute drug challenge MDMA and MDMA+WIN decreased high reward choices in both age groups, indicating MDMA-induced cost-aversive choice. Differential long-term interactions on the neuronal level in the hippocampus and MDMA-induced disturbances in cortico-limbic connections are suggested.
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Benzoxazinas/administración & dosificación , Toma de Decisiones/efectos de los fármacos , Memoria/efectos de los fármacos , Morfolinas/administración & dosificación , N-Metil-3,4-metilenodioxianfetamina/farmacología , Naftalenos/administración & dosificación , Maduración Sexual , Animales , Benzoxazinas/farmacología , Masculino , Aprendizaje por Laberinto , Morfolinas/farmacología , Naftalenos/farmacología , Ratas , Ratas WistarRESUMEN
The aim of this study was to investigate the involvement of serotonin-1A (5-HT(1A)) receptors in the effects of 3,4-methylenedioxymetamphetamine (MDMA) on prepulse inhibition of acoustic startle (PPI) by comparing male and female wild-type (WT) mice and 5-HT(1A) receptor knockout (1AKO) mice. MDMA dose-dependently decreased PPI in male and female mice although female mice were more sensitive at the 100-ms inter-stimulus interval (ISI). In male mice, 10 mg/kg MDMA disrupted PPI in 1AKO but not in WT controls. There was no genotype difference at higher or lower doses of MDMA. In female mice, there was no difference between genotypes at any dose of MDMA. Average startle was reduced by 10 mg/kg and 20 mg/kg MDMA similarly in male and female mice and all genotypes. These results show an involvement of 5-HT(1A) receptors in the effect of MDMA on PPI in male, but not female mice.
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3,4-Metilenodioxianfetamina/toxicidad , Alucinógenos/toxicidad , Inhibición Neural/efectos de los fármacos , Receptor de Serotonina 5-HT1A/fisiología , 3,4-Metilenodioxianfetamina/administración & dosificación , Estimulación Acústica , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Femenino , Alucinógenos/administración & dosificación , Heterocigoto , Drogas Ilícitas/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor de Serotonina 5-HT1A/genética , Reflejo de Sobresalto/efectos de los fármacos , Caracteres SexualesRESUMEN
Mobile belts are long-lived deformation zones composed of an ensemble of crustal fragments, distributed over hundreds of kilometres inside continental convergent margins. The Mediterranean represents a remarkable example of this tectonic setting: the region hosts a diffuse boundary between the Nubia and Eurasia plates comprised of a mosaic of microplates that move and deform independently from the overall plate convergence. Surface expressions of Mediterranean tectonics include deep, subsiding backarc basins, intraplate plateaux and uplifting orogenic belts. Although the kinematics of the area are now fairly well defined, the dynamical origins of many of these active features are controversial and usually attributed to crustal and lithospheric interactions. However, the effects of mantle convection, well established for continental interiors, should be particularly relevant in a mobile belt, and modelling may constrain important parameters such as slab coherence and lithospheric strength. Here we compute global mantle flow on the basis of recent, high-resolution seismic tomography to investigate the role of buoyancy-driven and plate-motion-induced mantle circulation for the Mediterranean. We show that mantle flow provides an explanation for much of the observed dynamic topography and microplate motion in the region. More generally, vigorous small-scale convection in the uppermost mantle may also underpin other complex mobile belts such as the North American Cordillera or the Himalayan-Tibetan collision zone.
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Serotonin (5-hydoxytryptamine; 5-HT) has been implicated in the regulation of impulsivity, and high levels of impulsive behavior are associated with certain neuropsychiatric disorders. An important aspect of impulsive behavior is the inability to tolerate delays in reward. This study investigated the effects of the 5-HT(2A/C) receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride] and the 5-HT(2A) receptor antagonist ketanserin on impulsive behavior measured in a delay-based decision-making task. Male Wistar rats were trained in a T-maze to choose a large but 10-s delayed food reward instead of a small immediate reward. After stable baseline performance (70% choice of large reward), the effects of acute systemic administration of 5-HT(2A/C) receptor ligands on waiting capacity were tested. Systemic administration of DOI (0.1, 0.3, and 0.5 mg/kg) impaired waiting capacity in a dose-dependent manner, whereas ketanserin had no effect. When combined with ketanserin, DOI did not impair waiting capacity. The data indicate that DOI-induced impairment of the ability to discount a delay in reward in a T-maze is probably regulated by 5-HT(2A) receptors. Furthermore, this study extends the existing findings of 5-HT2 receptor involvement in different tasks of delay aversion in rodents.