Study, measurement and mitigation of radon activity concentration in the School of Computer Science ofA Coruñain the North West of Spain.

A study of the radon activity concentration was carried out at the School of Computer Science of 'Universidade da Coruña' (UDC, Spain). For this purpose, building location, the type of soil and the construction materials were analysed. Subsequently, the radon activity concentration was determined using two different techniques: measurement in situ with an on-site ionization chamber detector (short term) and measurement with trace detectors (long term). Based on the results obtained, and according with the Spanish Law (Spanish Official Bulletin-Boletín Oficial del Estado, of 21 December 2011, IS-33 Instruction), corrective works were performed, consisting on the installation of a forced ventilation system underneath the extent of the suspended floor in order to mitigate the high radon specific activity in the building. Four months and 3 years after the works, new measurements were carried out in order to verify the effectiveness of the new ventilation system, obtaining a decrease of the radon gas values ranging between 87% and 90%, which confirmed long term effectivity.

Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration.

Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, ~80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like responses in mice. After crossing the permeable olfactory epithelium, the sertraline-conjugated-siRNA was internalized and transported to serotonin cell bodies by deep Rab-7-associated endomembrane vesicles. Seven-day C-SERT-siRNA evoked similar or more marked responses than 28-day fluoxetine treatment. Hence, C-SERT-siRNA (i) downregulated 5-HT1A-autoreceptors and facilitated forebrain serotonin neurotransmission, (ii) accelerated the proliferation of neuronal precursors and (iii) increased hippocampal complexity and plasticity. Further, short-term C-SERT-siRNA reversed depressive-like behaviors in corticosterone-treated mice. The present results show the feasibility of evoking antidepressant-like responses by selectively targeting neuronal populations with appropriate siRNA strategies, opening a way for further translational studies.

Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.

OBJECTIVE: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. METHODS: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR. CONCLUSION: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Automated early detection of drops in commercial egg production using neural networks.

1. The purpose of this work was to support decision-making in poultry farms by performing automatic early detection of anomalies in egg production. 2. Unprocessed data were collected from a commercial egg farm on a daily basis over 7 years. Records from a total of 24 flocks, each with approximately 20 000 laying hens, were studied. 3. Other similar works have required a prior feature extraction by a poultry expert, and this method is dependent on time and expert knowledge. 4. The present approach reduces the dependency on time and expert knowledge because of the automatic selection of relevant features and the use of artificial neural networks capable of cost-sensitive learning. 5. The optimum configuration of features and parameters in the proposed model was evaluated on unseen test data obtained by a repeated cross-validation technique. 6. The accuracy, sensitivity, specificity and positive predictive value are presented and discussed at 5 forecasting intervals. The accuracy of the proposed model was 0.9896 for the day before a problem occurs.

Three-year longitudinal population-based volumetric MRI study in first-episode schizophrenia spectrum patients.

BACKGROUND: Schizophrenia is a chronic brain disorder associated with structural brain abnormalities already present at the onset of the illness. Whether these brain abnormalities might progress over time is still under debate. METHOD: The aim of this study was to investigate likely progressive brain volume changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The study included 109 patients with a schizophrenia spectrum disorder and a control group of 76 healthy subjects. Subjects received detailed clinical and cognitive assessment and structural magnetic resonance imaging (MRI) at regular time points during a 3-year follow-up period. The effects of brain changes on cognitive and clinical variables were examined along with the impact of potential confounding factors. RESULTS: Overall, patients and healthy controls exhibited a similar pattern of brain volume changes. However, patients showed a significant lower progressive decrease in the volume of the caudate nucleus than control subjects (F 1,307.2 = 2.12, p = 0.035), with healthy subjects showing a greater reduction than patients during the follow-up period. Clinical and cognitive outcomes were not associated with progressive brain volume changes during the early years of the illness. CONCLUSIONS: Brain volume abnormalities that have been consistently observed at the onset of non-affective psychosis may not inevitably progress, at least over the first years of the illness. Taking together with clinical and cognitive longitudinal data, our findings, showing a lack of brain deterioration in a substantial number of individuals, suggest a less pessimistic and more reassuring perception of the illness.

Hybrid model based on Genetic Algorithms and SVM applied to variable selection within fruit juice classification.

Given the background of the use of Neural Networks in problems of apple juice classification, this paper aim at implementing a newly developed method in the field of machine learning: the Support Vector Machines (SVM). Therefore, a hybrid model that combines genetic algorithms and support vector machines is suggested in such a way that, when using SVM as a fitness function of the Genetic Algorithm (GA), the most representative variables for a specific classification problem can be selected.

Nanoinformatics: developing new computing applications for nanomedicine.

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

3D entropy and moments prediction of enzyme classes and experimental-theoretic study of peptide fingerprints in Leishmania parasites.

The number of protein 3D structures without function annotation in Protein Data Bank (PDB) has been steadily increased. This fact has led in turn to an increment of demand for theoretical models to give a quick characterization of these proteins. In this work, we present a new and fast Markov chain model (MCM) to predict the enzyme classification (EC) number. We used both linear discriminant analysis (LDA) and/or artificial neural networks (ANN) in order to compare linear vs. non-linear classifiers. The LDA model found is very simple (three variables) and at the same time is able to predict the first EC number with an overall accuracy of 79% for a data set of 4755 proteins (859 enzymes and 3896 non-enzymes) divided into both training and external validation series. In addition, the best non-linear ANN model is notably more complex but has an overall accuracy of 98.85%. It is important to emphasize that this method may help us to predict not only new enzyme proteins but also to select peptide candidates found on the peptide mass fingerprints (PMFs) of new proteins that may improve enzyme activity. In order to illustrate the use of the model in this regard, we first report the 2D electrophoresis (2DE) and MADLI-TOF mass spectra characterization of the PMF of a new possible malate dehydrogenase sequence from Leishmania infantum. Next, we used the models to predict the contribution to a specific enzyme action of 30 peptides found in the PMF of the new protein. We implemented the present model in a server at portal Bio-AIMS (http://miaja.tic.udc.es/Bio-AIMS/EnzClassPred.php). This free on-line tool is based on PHP/HTML/Python and MARCH-INSIDE routines. This combined strategy may be used to identify and predict peptides of prokaryote and eukaryote parasites and their hosts as well as other superior organisms, which may be of interest in drug development or target identification.

Effect of salt addition on sous vide cooked whole beef muscles from Argentina.

Sodium chloride (NaCl, 0-1.4%) and sodium tripolyphosphate (STPP, 0-0.5%) were added to Semitendinosus muscles and submitted to sous vide cooking at different temperatures (55-75°C). The effects of these three factors on pH, cooking loss, instrumental colour parameters, protein solubilization and distribution, and micro- and ultra-structure were evaluated. Quadratic surface responses equations were obtained from data (pH, cooking loss and colour parameters) as a function of the salts concentrations and cooking temperature. Both salts - alone or in combination - successfully reduced cooking loss. The best results were obtained for the combinations 0.25%STPP+1.20%NaCl and 0.25%STPP+0.70%NaCl, and temperatures between 60 and 65°C. Under these conditions, cooking loss was reduced close to 0%. pH was only dependent on STPP concentration, with a threshold concentration value of 0.25%. Temperature increment and NaCl addition produced a redness reduction. STPP incorporation recovered partially this parameter in comparison to non-added samples. Microscopy and SDS-PAGE results support the effect of the selected combinations of factors, suggesting that both salts together induced protein solubilization and gelation upon heating.

Parallel Computing for Brain Simulation.

BACKGROUND: The human brain is the most complex system in the known universe, it is therefore one of the greatest mysteries. It provides human beings with extraordinary abilities. However, until now it has not been understood yet how and why most of these abilities are produced. AIMS: For decades, researchers have been trying to make computers reproduce these abilities, focusing on both understanding the nervous system and, on processing data in a more efficient way than before. Their aim is to make computers process information similarly to the brain. Important technological developments and vast multidisciplinary projects have allowed creating the first simulation with a number of neurons similar to that of a human brain. CONCLUSION: This paper presents an up-to-date review about the main research projects that are trying to simulate and/or emulate the human brain. They employ different types of computational models using parallel computing: digital models, analog models and hybrid models. This review includes the current applications of these works, as well as future trends. It is focused on various works that look for advanced progress in Neuroscience and still others which seek new discoveries in Computer Science (neuromorphic hardware, machine learning techniques). Their most outstanding characteristics are summarized and the latest advances and future plans are presented. In addition, this review points out the importance of considering not only neurons: Computational models of the brain should also include glial cells, given the proven importance of astrocytes in information processing.

Cannabinoid system in the budgerigar brain.

Cannabinoid receptor density and cannabinoid receptor-mediated G protein stimulation were studied by autoradiographic techniques throughout the budgerigar (Melopsittacus undulatus) brain. The maximal CB(1) receptor density value (using [(3)H]CP55,940 as radioligand) was found in the molecular layer of the cerebellum (Mol), and high binding values were observed in the nucleus taeniae amygdalae (TnA), nucleus preopticus medialis, and nucleus pretectalis. The highest net-stimulated [(35)S]GTPgammaS binding values induced by the selective CB(1) receptor agonist WIN55,212-2 were observed in the nucleus paramedianus internus thalami, and high values of [(35)S]GTPgammaS binding were observed in the TnA, Mol, arcopallium dorsale and arcopallium intermedium. The distribution data suggest that in the budgerigar, as previously indicated in mammals, cannabinoid receptors may be related to the control of several brain functions in the motor system, memory, visual system, and reproductive behavior. The discrepancies between the cannabinoid receptor densities and the cannabinoid receptor-mediated stimulation found in several budgerigar brain nuclei support the hypothesis, previously described for mammals, of the existence of different G(i/o) protein populations able to associate with the cannabinoid receptors, depending on the brain structure, and could reflect the relative importance that cannabinoid transmission could exerts in each cerebral area.

The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: Adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor.

Preclinical studies support a critical role of 5-HT4 receptors (5-HT4Rs) in depression and anxiety, but their influence in depression- and anxiety-like behaviours and the effects of antidepressants remain partly unknown. We evaluated 5-HT4R knockout (KO) mice in different anxiety and depression paradigms and mRNA expression of some neuroplasticity markers (BDNF, trkB and Arc) and the functionality of 5-HT1AR. Moreover, the implication of 5-HT4Rs in the behavioural and molecular effects of chronically administered fluoxetine was assessed in naïve and olfactory bulbectomized mice (OBX) of both genotypes. 5-HT4R KO mice displayed few specific behavioural impairments including reduced central activity in the open-field (anxiety), and decreased sucrose consumption and nesting behaviour (anhedonia). In these mice, we measured increased levels of BDNF and Arc mRNA and reduced levels of trkB mRNA in the hippocampus, and a desensitization of 5-HT1A autoreceptors. Chronic administration of fluoxetine elicited similar behavioural effects in WT and 5-HT4R KO mice on anxiety-and depression-related tests. Following OBX, locomotor hyperactivity and anxiety were similar in both genotypes. Interestingly, chronic fluoxetine failed to reverse this OBX-induced syndrome in 5-HT4R KO mice, a response associated with differential effects in hippocampal neuroplasticity biomarkers. Fluoxetine reduced hippocampal Arc and BDNF mRNA expressions in WT but not 5-HT4R KO mice subjected to OBX. These results demonstrate that the absence of 5-HT4Rs triggers adaptive changes that could maintain emotional states, and that the behavioural and molecular effects of fluoxetine under pathological depression appear to be critically dependent on 5-HT4Rs.

Flour from Prosopis alba cotyledons: A natural source of nutrient and bioactive phytochemicals.

The Prosopis alba seed is a waste material in the process to produce pod flour. To suggest a potential use of these seeds it is necessary to determine the nutritional, phytochemical and functional quality of cotyledon flour from Prosopis alba. This flour showed high level of proteins (62%), low content of total carbohydrate and fat. Free polyphenol (1150±20mg GAE/100g flour) and carotenoids (10.55±0.05mg ß-CE/100g flour) compounds were the dominant compounds. The main identified constituents in the polyphenolic extracts were C- glycosyl flavones, including schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin. The extract enriched in polyphenolic compounds exhibited ABTS(+) reducing capacity and scavenging activity of H2O2; and was able to inhibit phospholipase, lipoxygenase and cyclooxygenase, three pro-inflammatory enzymes. According to our results, the P. alba cotyledon flour could be considered as a new alternative in the formulation of functional foods or food supplements.

Development and operation of a pixel segmented liquid-filled linear array for radiotherapy quality assurance.

A liquid isooctane (C(8)H(18)) filled ionization linear array for radiotherapy quality assurance has been designed, built and tested. The detector consists of 128 pixels, each of them with an area of 1.7 mm x 1.7 mm and a gap of 0.5 mm. The small pixel size makes the detector ideal for high gradient beam profiles such as those present in intensity modulated radiation therapy (IMRT) and radiosurgery. As the read-out electronics we use the X-ray Data Acquisition System with the Xchip developed by the CCLRC. Studies concerning the collection efficiency dependence on the polarization voltage and on the dose rate have been made in order to optimize the device operation. In the first tests, we have studied dose rate and energy dependences. Dose rate dependence was found to be lower than 2.1% up to 5 Gy min(-1), and energy dependence lower than 2.5% up to 20 cm depth in solid water. Output factors and penumbras for several rectangular fields have been measured with the linear array and were compared with the results obtained with a 0.125 cm(3) air ionization chamber and radiographic film, respectively. Finally, we have acquired profiles for an IMRT field and for a virtual wedge. These profiles have also been compared with radiographic film measurements. All the comparisons show a good correspondence. The device has proved its capability to verify on-line therapy beams with good spatial resolution and signal-to-noise ratio.

Evaluation of different bovine muscles to be applied in freeze-drying for instant meal. Study of physicochemical and senescence parameters.

The aim of the present research was to evaluate bovine muscles to be subjected to freeze-drying for an instant meal. Physicochemical and senescence parameters were evaluated. The experimental part was divided into two steps. In the first step, the Semitendinosus muscle was chosen to establish methodology and experimental conditions. Physicochemical, microstructure and senescence parameters were analysed. In the second step, economic bovine muscles such as Semimembranous and Spinalis dorsi were subjected to the same methodology and conditions as in the first step in order to compare them by analysing the same parameters. L* and a* values were statistically significant (P<0.05) for Semimembranous and Spinalis dorsi muscles, showing differences among condition effects and in muscles. Humidity and water activity showed among the muscles analysed that cooked and rehydrated samples did not exhibit differences. Microstructure of Semitendinosus and Semimembranous were not separated and fragmented as occurred with Spinalis dorsi after freeze-drying. Results allowed us to select among the muscles studied that Semimembranous was suitable and economic to be used in an instant meal.

beta-blocker binding to human 5-HT(1A) receptors in vivo and in vitro: implications for antidepressant therapy.

A novel strategy for improving the treatment of depressive illness is augmentation of antidepressants with a 5-HT1(1A) autoreceptor antagonist. However, trials using the 5-HT1(1A)/beta-blocker pindolol are proving inconsistent. We report how positron emission tomography (PET) and in vitro autoradiography can inform trials of antidepressant augmentation. We show that in healthy volunteers, in vivo, pindolol (n = 10) and penbutolol (n = 4), but not tertatolol (n = 4) occupy the human 5-HT(1A) receptors, at clinical doses. Pindolol, as well as the beta-blockers penbutolol and tertatolol, has high affinity for human 5-HT(1A) receptors in post-mortem brain slices (n = 4). Pindolol shows preference for 5-HT(1A) autoreceptors versus the post-synaptic receptors both in vitro and in vivo. Our data reveal that pindolol doses used in antidepressant trials so far are suboptimal for significant occupancy at the 5-HT(1A) autoreceptor. Penbutolol or higher doses of pindolol are candidates for testing as antidepressant augmenting regimes in future clinical trials.

Influence of age, postmortem delay and freezing storage period on cannabinoid receptor density and functionality in human brain.

It has been suggested that cannabimimetic drugs could be of interest in the treatment of several nervous disorders. Thus, it is important to analyse the distribution and properties of cannabinoid (CB) receptors directly in human brain. As postmortem human tissue is subjected to the effects of several biological variables, we have analyzed by autoradiography the influence of age, postmortem delay and freezing storage period (at -25 degrees C) on two parameters corresponding to cannabinoid CB1 receptors in human frontal cortex: receptor density and degree of activation of G-proteins ([35S]GTPgammaS assays). A significant decrease in the amount of both receptor density and agonist-stimulated G-protein activity was observed with age, revealing a mean reduction of about 10% per decade. In contrast, no significant correlations were found with postmortem delay either for CB1 receptors density or functionality. Finally, both parameters (receptor density and [35S]GTPgammaS response) were significantly reduced with freezing storage period at -25 degrees C in frontal cortical layers. Non-linear analysis of these data yielded values between 12 and 24 months of storage for a 50% reduction. In conclusion, when studying CB1 receptor properties in human brain samples, a careful analysis (and matching) for variables such as age and freezing storage period has to be carried out.

Cardiovascular effects of intracerebroventricular injection of dopamine after selective MAO inhibition in rats.

Intracerebroventricular injection of dopamine (30-300 micrograms) caused a dose-dependent reduction in the blood pressure and cardiac rate of anaesthetized rats. Inhibition of MAO-type A with clorgyline enhanced the vasodepressant effect while it reversed the bradycardiac effect. Deprenyl, a MAO-type B inhibitor, did not modify the cardiovascular effects of dopamine injected into the cerebral ventricles. The persistent hypotensive action of dopamine in clorgyline-pretreated rats was abolished by the central blockade of alpha-adrenoreceptors with intracerebroventricular injection of phentolamine, whereas haloperidol given by the same route did not affect the hypotensive response. The results suggest that dopamine centrally affects cardiovascular regulation, either after conversion into noradrenaline, or through a direct stimulation of central alpha-adrenoceptors.

Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord.

We report on the autoradiographic distribution of 5-HT1B, 5-HT1D and 5-HT1F receptor subtypes in human brain, focusing on the brainstem and cervical spinal cord. We have used [3H]sumatriptan as a radioligand in the presence of suitable concentrations of 5-CT (5-carboxamidotryptamine) to define 5-HT1F receptors, and ketanserin, to discriminate between 5-HT1B and 5-HT1D receptors. In the brainstem the highest concentrations of [3H]sumatriptan binding sites were seen in substantia nigra. The spinal trigeminal nucleus, substantia gelatinosa of the spinal cord, nucleus of the tractus solitarius and periaqueductal grey, also showed significant levels of [3H]sumatriptan binding sites. In the brainstem and spinal cord the total population of 5-CT-insensitive receptors, corresponding to 5-HT1F receptors, ranged from 9.8% in the periaqueductal grey to 53.4% in the substantia gelatinosa. This population represented 67.0% of binding in layer V of the frontal cortex. The decrease in [3H]sumatriptan binding in the presence of 200 nM ketanserin, indicative of the presence of 5-HT1D receptors, was very limited throughout the human brain, only reaching 20% of total specific binding over the periaqueductal grey. The proportion of [3H]sumatriptan binding sites displaced by 5-CT and insensitive to ketanserin, corresponding to 5-HT1B receptors, was, in general, the most abundant, ranging from 43.8% in substantia gelatinosa to 69.9% in the periaqueductal grey. Significant levels of 5-HT1B and 5-HT1D receptors found in migraine control pain areas suggest their involvement in antinociceptive mechanisms.

Serotonin receptors in the human brain--IV. Autoradiographic mapping of serotonin-2 receptors.

The anatomical distribution of serotonin-2 receptors in the human brain was studied by light microscopic autoradiography, using [3H]ketanserin as a ligand. The receptor densities were quantified by microdensitometry with the aid of a computer-assisted image-analysis system. A heterogeneous distribution of serotonin-2 receptor densities was found in the human brain. Very high concentrations were localized over layers III and V of several cortical areas, including the frontal, parietal, temporal and occipital lobes, the anterogenual cortex and the entorhinal area, as well as in the corpus mamillare of the hypothalamus. The claustrum, nucleus lateralis of the amygdala and some cortical layers also presented a high density of serotonin-2 receptors. Intermediate concentrations were found over the hippocampus, the caudatus, putamen and accumbens nuclei, and some nuclei of the amygdala, among other structures. Areas such as the thalamus, brain stem, cerebellum and spinal cord contained, in general, only low to very low densities of serotonin-2 receptors. A very high level of non-specific binding, which was not displaceable by any serotonin-2 compound, was found in some areas of the human brain, including the caudatus and putamen nuclei, the substantia nigra and the raphé nuclei. The distribution of serotonin-2 receptors in the human brain described herein is discussed in relation to the distribution of serotonergic innervation, the central effects which have been proposed to be serotonin-2-mediated, and the neuropathological characteristics of the diseases where a modification in the number of serotonin-2 receptors has been reported.