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Limbs with digits evolved as sarcopterygian fish transitioned to a terrestrial life, giving rise to modern tetrapods. Since the Devonian, most of the sarcopterygian fish diversity became extinct, with the only surviving representatives being two coelacanth and six lungfish species. As the sister group of tetrapods, sarcopterygian fish constitute the ideal models to address questions regarding the transition of vertebrates from water to land. However, distantly related yet experimentally amenable teleost fish species have instead become the organisms of choice for geneticists and developmental biologists. Comparative studies using teleosts, such as zebrafish, have greatly enriched our knowledge on the genetic and regulatory mechanisms underlying fin development. However, their highly derived fin anatomy provides limited insights on the origin of limbs and the teleost-specific whole-genome duplication represents a further complication to comparisons of gene function and regulation. In recent years, refined morphological and behavioral studies and access to lungfish embryos and availability of genetic resources have underscored the value of nontetrapod sarcopterygians as model organisms. Here we review recent studies using lungfishes and coelacanths that shed light on various aspects of the evolution of the tetrapod limb, including the origin of the tetrapod pelvis, limb musculature, digits, locomotion, and regenerative capacity.

Driving pressure (ΔP) is associated with mortality in patients with ARDS and with pulmonary complications in patients undergoing general anesthesia. Whether ΔP is associated with outcomes of patients without ARDS who undergo ventilation in the ICU is unknown. Our objective was to determine the independent association between ΔP and outcomes in mechanically ventilated patients without ARDS on day 1 of mechanical ventilation.This was a retrospective analysis of a cohort of 622 mechanically ventilated adult patients without ARDS on day 1 of mechanical ventilation from five ICUs in a tertiary center in the United States. The primary outcome was hospital mortality. The presence of ARDS was determined using the minimum daily PaoIn patients without ARDS on day 1 of mechanical ventilation, ΔP was not independently associated with hospital mortality (OR, 1.01; 95% CI, 0.97-1.05). The results of the primary analysis were confirmed in a series of preplanned sensitivity analyses.In this cohort of patients without ARDS on day 1 of mechanical ventilation and within the limits of ventilatory settings normally used by clinicians, ΔP was not associated with hospital mortality. This study also confirms the association between ΔP and mortality in patients with ARDS not enrolled in a trial and in hypoxemic patients without ARDS.

Resumen: La pubertad precoz, a pesar de las definiciones clínicas estandarizadas y pruebas de diagnóstico disponibles, requiere, en ciertas situaciones una investigación exhaustiva y estructurada con el fin de conocer la causa.Niña de 4 años de edad, fenotípicamente de sexo femenino, enviada a la consulta de endocrinología pediátrica por pubarquia y telarquia. Se observó aceleración en la tasa de crecimiento con niveles altos de estradiol y testosterona, con determinaciones prepúberes de la hormona luteinizante y foliculoestimulante. El resto del estudio de pubertad precoz periférica mostró la presencia de gonadoblastoma bilateral. El estudio genético reveló cariotipo 46 XY con mutación c.89G> T (p.Arg30Ile) en el exón 1 del gen SRY, confirmando el diagnóstico de disgenesia gonadal completa.Los trastornos de la diferenciación sexual deben ser considerados en el abordaje y la investigación de las causas de la pubertad precoz periférica, especialmente en presencia de tumores de ovario, como gonadoblastoma y disgerminomas. Abstract: Despite standard clinical definitions and availability of diagnostic tests for precocious puberty, an intensive and structured investigation is needed in order to diagnose the aetiology in particular cases.A 4-year-old, phenotypically female child was referred to paediatric endocrinology consultation for premature pubarche and thelarche. There was an acceleration of growth velocity with high levels of estradiol and testosterone, and prepubertal FSH and LH measurements. Investigation showed bilateral gonadoblastoma as the cause of the peripheral precocious puberty.Genetic studies revealed 46 XY karyotype with mutation c.89G> T (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete gonadal dysgenesis. Disorders of sexual differentiation must be considered in the approach and investigation of peripheral precocious puberty, especially in the presence of ovarian tumours, such as gonadoblastoma and dysgerminoma.

Despite standard clinical definitions and availability of diagnostic tests for precocious puberty, an intensive and structured investigation is needed in order to diagnose the aetiology in particular cases.A 4-year-old, phenotypically female child was referred to paediatric endocrinology consultation for premature pubarche and thelarche. There was an acceleration of growth velocity with high levels of oestradiol and testosterone, and prepubertal FSH and LH measurements. Investigation showed bilateral gonadoblastoma as the cause of the peripheral precocious puberty.Genetic studies revealed 46,XY karyotype with mutation c.89G>T (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete gonadal dysgenesis. Disorders of sexual differentiation must be considered in the approach and investigation of peripheral precocious puberty, especially in the presence of ovarian tumours, such as gonadoblastoma and dysgerminoma. Resumen: La pubertad precoz, a pesar de las definiciones clínicas estandarizadas y pruebas de diagnóstico disponibles, requiere, en ciertas situaciones una investigación exhaustiva y estructurada con el fin de conocer la causa.Niña de 4 años de edad, fenotípicamente de sexo femenino, enviada a la consulta de endocrinología pediátrica por pubarquia y telarquia. Se observó aceleración en la tasa de crecimiento con niveles altos de estradiol y testosterona, con determinaciones prepúberes de la hormona luteinizante y foliculoestimulante. El resto del estudio de pubertad precoz periférica mostró la presencia de gonadoblastoma bilateral. El estudio genético reveló cariotipo 46 XY con mutación c.89G> T (p.Arg30Ile) en el exón 1 del gen SRY, confirmando el diagnóstico de disgenesia gonadal completa.Los trastornos de la diferenciación sexual deben ser considerados en el abordaje y la investigación de las causas de la pubertad precoz periférica, especialmente en presencia de tumores de ovario, como gonadoblastoma y disgerminomas.

Este breve ensaio tensiona o conceito de Stimmung (atmosfera) de Hans Ulrich Gumbrecht e as leituras de ambiência na Arte Ambiental de Hélio Oiticica. Parte-se do conceito de Stimmung e suas nuances de significados; em seguida, investiga-se como o conceito de arte ambiental se constitui na perspectiva do artista brasileiro, utilizando como fontes dessa investigação suas obras e textos e também escritos de Mário Pedrosa. Analisa-se o Parangolé e os Bólides indicando como a proposta ambiental de Oiticica constrói uma leitura política do corpo atravessada por seus significados sociais e suas afecções.

The aim of this work was to study the removal of three pesticides using conventional drinking water treatment (DWT) processes. These methods are the most used in Brazil, and include coagulation–flocculation of water. The pesticides/metabolites evaluated were: endosulfan, ethylenethiourea (ETU), and 1,2,4-triazole. The laboratory tests were carried out in triplicate using the jar test. Synthetic water samples prepared with kaolin, simulating the dry and rainy periods, were contaminated with different concentrations of pesticides. Results showed that conventional DWT methods are not suitable for the removal of the pesticides/metabolites evaluated. No significant difference ( p K oc , log K ow and molar mass, in relation to the other two pesticides.

The search for biomarkers has been one of the leading endeavours in biological psychiatry; nevertheless, in spite of hundreds of publications, hardly any marker has proved useful in clinical practice. To study how biomarker research has progressed over the years, we performed a systematic review of the literature to evaluate (a) the most studied peripheral molecular markers in major psychiatric disorders, (b) the main experimental design features of studies in which they are proposed as biomarkers and (c) whether their patterns of variation are similar across disorders. An automated search revealed that, out of the six molecules most commonly present as keywords in articles studying plasmatic markers of schizophrenia, major depressive disorder or bipolar disorder, five (BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same across the three diagnoses. An analysis of the literature on these molecules showed that, whilst 66% of original articles compared their levels between patients and controls, only 35% were longitudinal studies, and only 10% presented an evaluation of diagnostic efficacy, a pattern that has not changed significantly over two decades. Interestingly, these molecules varied similarly across the three disorders, suggesting them to be nonspecific systemic consequences of psychiatric illness rather than diagnostic markers. On the basis of this, we discuss how research fragmentation between diagnoses and publication practices rewarding positive findings may be directing the biomarker literature to nonspecific targets, and what steps could be taken to increase clinical translation in the field.

Schistosomiasis is a neglected tropical disease of a significant public health impact. The water rat Nectomys squamipes is one of the most important non-human hosts in the schistosomiasis mansoni transmission in Brazil, being considered a wild reservoir. Cellular mechanisms that contribute to the physiological adaptation of this rodent to the Schistosoma mansoni parasite are poorly understood. Here we identified, for the first time, that a hepatic steatosis, a condition characterized by excessive lipid accumulation with formation of lipid droplets (LDs) within hepatocytes, occurs in response to the natural S. mansoni infection of N. squamipes, captured in an endemic region. Significant increases of LD area in the hepatic tissue and LD numbers/hepatocyte, detected by quantitative histopathological and ultrastructural analyses, were paralleled by increased serum profile (total cholesterol and triglycerides) in infected compared to uninfected animals. Raman spectroscopy showed high content of polyunsaturated fatty acids (PUFAs) in the liver of both groups. MALDI-TOFF mass spectroscopy revealed an amplified pool of omega-6 PUFA arachidonic acid in the liver of infected animals. Assessment of liver functional activity by the levels of hepatic transaminases (ALT and AST) did not detect any alteration during the natural infection. In summary, this work demonstrates that the natural infection of the wild reservoir N. squamipes with S. mansoni elicits hepatic steatosis in the absence of liver functional harm and that accumulation of lipids, markedly PUFAs, coexists with low occurrence of inflammatory granulomatous processes, suggesting that lipid stores may be acting as a protective mechanism for dealing with the infection.

G protein-coupled receptor oligomerization is a concept which is changing the understanding of classical pharmacology. Both, oligomerization and functional interaction between adenosine A 2A, dopamine D 2 and metabotropic glutamate type 5 receptors have been demonstrated in the striatum. However, the transcriptional consequences of receptors co-activation are still unexplored. We aim here to determine the changes in gene expression of striatal primary cultured neurons upon isolated or simultaneous receptor activation. Interestingly, we found that 95 genes of the total analyzed (15,866 transcripts and variants) changed their expression in response to simultaneous stimulation of all three receptors. Among these genes, we focused on the β-synuclein (β-Syn) gene ( SCNB) . Quantitative PCR verified the magnitude and direction of change in expression of SCNB . Since β-Syn belongs to the homologous synuclein family and may be considered a natural regulator of α-synuclein (α-Syn), it has been proposed that β-Syn might act protectively against α-Syn neuropathology.

The aims of this study were to describe the fresh spermatozoon ultrastructure using scanning and transmission electron microscopy and to improve the sperm cryopreservation methodology for the freshwater ¢sh pirapitinga Brycon nattereri. Extenders (BTS TM and NaCl), straw volumes (0.5 and 4.0 mL), thawing temperatures (30 and 601C) and activating agents (0.29% NaCl and 1% NaHCO3) were tested. Methylglycol was used as a cryoprotectant agent and sperm was frozen in nitrogen vapour (dry-shipper). Post-thawed sperm motility rate, motility quality (score 0 5 no movement; 5 5 rapidly swimming spermatozoa), duration of motility and spermatozoon morphology were evaluated. Fresh spermatozoon was 35.06mm long, the head was ovoid (2.00 � 1.22 mm) with no acrosome, the midpiece was 2.15 mm long and the £agellum was 30.90mm long with the typical 912 axoneme arrangement. Post-thawed sperm motility rate (70^79% motile sperm), motility quality (score 3.1^3.7) and morphology (9.3^11.6% abnormal spermatozoa) were not affected by any of the parameters tested. The duration of sperm motility was longer when triggered in 1% NaHCO 3 (392^1031s) compared with 0.29% NaCl (144^338 s). Brycon nattereri sperm cryopreserved under the conditions described above yields over 70% motility and should last long enough to fertilize oocytes, even after 2 years of freezing.

Xylitol is a natural sugar derived from plants, fruits and vegetables, whose antimicrobial properties are described in the literature. This study aimed to evaluate the antimicrobial effectiveness of C-8 xylitol monoester, for its use as a preservative in cosmetic formulations. The minimum inhibitory concentration (MIC) was determined by the broth macrodilution method, and the antimicrobial effectiveness of C-8 xylitol monoester was determined by using challenge test method. The results obtained in the determination of minimum inhibitory concentration are between 1.0% and 1.25% for Staphylococcus aureus, Escherichia coli and Candida albicans and between 1.0% and 1.5% for Pseudomonas aeruginosa and Aspergillus niger. The amount of 1% of C-8 xylitol monoester was added to the lotion used in the challenge test, observing a rapid decline in the number of CFU g(-1) in stages of evaluation after contamination of the product by all bacteria. The same occurs in relation to C. albicans, which shows a 90% reduction in the number of CFU g(-1). Regarding A. niger, similar reduction is observed when pH value of the lotion is adjusted from 5.5 to 7.0. The results indicate that under the tests conditions, C-8 xylitol monoester has antimicrobial activity and could be considered as an alternative preservative for cosmetic formulations.

Theaimofthisstudywastotesttheeiectsofcryopro-tectants[dimethylsulphoxide(DMSO)andmethylgly-col], extenders (0.9% NaCl, 5% glucose, BeltsvilleThawing Solution TM and Merck III TM ), thawing tem-peratures (30 and 601C) and activating agents(0.29%NaCland1%NaHCO 3 )onthecryopreservationprocessoftietetetraBryconinsignissperm.Spermwasloaded in 0.5mL straws, frozen in nitrogen vapour at 170 1C and stored in liquid nitrogen. Post-thawsperm quality was evaluated in terms of subjectivemotilityrate,qualitymotilityscore(05nomovement;55rapidly swimming spermatozoa), duration of mo-tilityandvitality (eosin^nigrosin staining). Post-thawsperm motility rate was greater in methylglycol (76^88%), compared with DMSO (23^59%). In general,the highest quality motility scores were observedwhenspermwasthawedat 301Candtriggered in1%NaHCO 3 (3.5^4.3). Duration of motility was longerwhen triggered in 1% NaHCO 3 (95^120s) comparedwith0.29%NaCl(69^107s).Spermvitalitywasnotaf-fectedbyanyoftheparameterstestedandvariedfrom51% to 69% intact sperm. Brycon insignis sperm fro-zen in methylglycol combined with any of the exten-ders tested and using the methods described aboveyieldsmotilityabove57%andthatshouldlastlongen-oughtofertilizeoocytes.Keywords: ¢sh, semen, motility, duration of moti-lity, vitalityIntroductionMany South American ¢sh species migrate up-stream to ¢nd clean water and spawn. This processis known as piracema and occurs when the environ-ment is adequate to stimulate the ¢sh reproductivephysiology, such as hormonal stimulus (Godinho GShimo-da 2004), but nowadays this species is threatenedin nature and there is very little information aboutits reproductive behaviour. Knowledge of repro-ductive biology and physiology is critical for con-servation and species management, allowing the

G protein-coupled receptors are known to form homo-and heteromers at the plasma membrane, but the molecular properties of these oligomers are relatively unknown. Here, we show a method that allows the diffusion of G protein-coupled receptors oligomers in the plasma membrane to be monitored in single cells by combining Bimolecular Fluorescence Complementation and Fluorescence Correlation Spectroscopy. With this approach we have measured, for the first time, the membrane diffusional characteristics of adenosine A(1) and A(2A) receptor homo-and heterodimers in Chinese Hamster Ovary cells. Interestingly, both homodimers display similar diffusion co-efficients (D) when expressed in living cells (D=5.0 and 4.8x10(-9) cm(2)/s, respectively) but the heterodimer formed by these receptors exhibit a significantly faster plasma membrane diffusion co-efficent (D=5.6x10(-9) cm(2)/s) when compared to the adenosine A(1) receptor tagged with the full-length yellow fluorescent protein (D=4.0x10(-9) cm(2)/s). Overall, these results demonstrate differences in plasma membrane diffusion between adenosine receptor homo-and heterodimers, providing new insights into the molecular plasticity of G protein-coupled receptor oligomerization.

Despite some caveats, G protein-coupled receptor oligomerization is a phenomenon that is becoming largely accepted. Within these oligomers, however, stoichiometry remains to be elucidated. Here, by using bimolecular fluorescence complementation, we visualized adenosine A2A receptor homodimers in living cells, showing no apparent difference in the subcellular distribution when compared to the YFP-labelled adenosine A2A receptor protomer. Interestingly, the combination of bimolecular fluorescence complementation and bioluminescence resonance energy transfer techniques allowed us to detect the occurrence of adenosine A2A receptors oligomers containing more than two protomers. These results provide new insights into the molecular composition of G protein-coupled receptor oligomers.Structured summaryMINT-6700472:A2A (uniprotkb:P29274), A2A (uniprotkb:P29274) and A2A (uniprotkb:P29274) physically interact (MI:0218) by bioluminescence resonance energy transfer (MI:0012)MINT-6699330:A2A (uniprotkb:P29274) and A2A (uniprotkb:P29274) physically interact (MI:0218) by bimolecular fluorescence complementation (MI:0809)MINT-6699346:A2A (uniprotkb:P29274) and A2A (uniprotkb:P29274) physically interact (MI:0218) by bioluminescence resonance energy transfer (MI:0012)

Molecular accounts of memory consolidation suggest that new learning generates persistent synaptic modifications through activation of an extensive set of neuronal receptors and intracellular signal transduction pathways, accompanied by RNA and protein synthesis. This traditional cellular consolidation theory has been challenged by evidence that reactivation of a previously consolidated memory might render this memory again susceptible to disruption by amnesic treatments, a process generally referred to as reconsolidation. Current evidence indicates that reconsolidation can be disrupted by administration of a variety of pharmacological agents after memory reactivation. Previous studies have indicated that the gastrin-releasing preferring type of bombesin receptor (GRPR) and the N-methyl-D-aspartate glutamate receptor (NMDAR) in the rat hippocampus are involved in consolidation of inhibitory avoidance (IA), a fear-related memory task. We show here that blockade of hippocampal GRPRs or NMDARs after memory reactivation temporarily disrupts memory retention. Post-retrieval intra-hippocampal infusion of the GRPR antagonist RC-3095 or the NMDAR antagonist aminophosphonopentanoic acid (AP5) produced an impairment of IA performance tested 2 days after training in rats. However, this impairment was transient and recovered to levels of control rats in a subsequent test 3 days after training. The drug effects were only present after memory reactivation and not in its absence. These findings provide evidence that GRPR or NMDAR inactivation after retrieval can impair fear memory.

A wide range of data in the literature suggests that environmental enrichment has beneficial effects on various cognitive parameters in rodents. However, the magnitude of these effects and their persistence after the cessation of enrichment vary markedly across studies, with the use of different enrichment protocols probably playing a significant role in this variation. Using an open field habituation task as a paradigm, we investigate whether the duration and starting age of environmental enrichment affect the magnitude and persistence of its behavioral effects on male CF-1 albino mice. Our data shows that, at least in our protocol, (a) environmental enrichment, both after weaning and in early adulthood, decreases locomotion in an open field task, probably by increasing habituation; (b) a minimum enrichment period is necessary to induce this behavioral effect; (c) the effect of enrichment can persist at least partially for many months after its cessation; and (d) the degree of this persistence appears to be somewhat greater in animals exposed to longer durations of enrichment.

In the present work, we report the optical properties of rare-earth doped BaY2F8 and its potential use as a scintillator in radiation detection. The samples were synthesized and grown by the zone melting method under a HF flow. X-ray powder diffraction was performed and quantitative phase analysis was done using the Rietveld method. Emission and excitation spectra of the doped samples were measured at room temperature. The identification of the transitions was done comparing the excitation and emission peaks with the results obtained from computer modelling. The scintillator properties of the pure and doped samples were checked by measuring the radioluminescence of the sample when excited with different types of radiation, revealing that these materials are promising radiation detectors.

The reconsolidation hypothesis, which predicts that consolidated memories become labile and sensitive to amnestic agents upon reactivation, has been one of the most debated topics in memory research over recent years. One of the main criticisms to this hypothesis is the fact that some studies have shown the effects of "reconsolidation blockade" to be transient. Here we show that muscimol inactivation of the dorsal hippocampus following memory reactivation produces a reversible impairment of step-down inhibitory avoidance memory in rats. Moreover, we show that the reversal of this effect is dependent on the passage of time, and not on repeated testing. The implications of the findings to the interpretation of the phenomenon of transient retrieval impairment induced by post-reactivation pharmacological interventions on memory systems are discussed.

A computational approach to calculating the optical properties of doped metal fluoride materials is presented, and applied to rare earth doping in the BaY2F8 and LaF3 systems. Optimal locations for dopant ions are predicted, along with solution energies and charge compensation mechanisms. Energy levels for dopant ions are predicted using adapted crystal field calculations. The results of the predictions are compared with experimental data. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

This paper intends to study presalt region economic viability by choosing the case of Libra field, the only presalt field to be acquired in Production Sharing Contracts bid round until now. Libra is considered one of the most important exploratory areas worldwide and its Brazil´s biggest oil field. For the conclusions of this paper it was necessary to estimate production volumes and costs involved in the development of Libra oil field according to industry parameters and government data. A forecast for oil prices was stipulated according to historical data and future contracts. A cashflow could be determinate by concatenating expected income with production sharing agreement government outcomes, making it possible to define the Payback, Internal Return Rate (IRR), and Net Present Value (NPV) of the investment. Varying the discount rate it was possible to study the NPV sensibility. The Brazilian new exploratory frontier region denominated Presalt is gaining remarkable importance in country´s economic and political scenario. The outlook for the next 10 years is that presalt fields will represent over 50% of Brazilian´s production, calling attention of researchers and experts. To aim high economic benefits, in such alluring area, local Government presented a series of adjustments in its regulations for E&P industry. However, drilling and producing in Presalt presents technology challenges, due to significant distances from shore, extreme water depths, thick and unstable salt layers, and still limited knowledge over reservoir rock. Research and appraisal will consume high investments, since technologies to be used in the region involve high costs. Added to this there are uncertainties concerning the current regulatory changes, which constrain production profits, and rise concerns over projects viability in the region.

The search for biological causes of mental disorders has up to now met with limited success, leading to growing dissatisfaction with diagnostic classifications. However, it is questionable whether most clinical syndromes should be expected to correspond to specific microscale brain alterations, as multiple low-level causes could lead to similar symptoms in different individuals. In order to evaluate the potential multifactoriality of alterations related to psychiatric illness, we performed a parametric exploration of published computational models of schizophrenia. By varying multiple parameters simultaneously, such as receptor conductances, connectivity patterns, and background excitation, we generated 5625 different versions of an attractor-based network model of schizophrenia symptoms. Among networks presenting activity within valid ranges, 154 parameter combinations out of 3002 (5.1%) presented a phenotype reminiscent of schizophrenia symptoms as defined in the original publication. We repeated this analysis in a model of schizophrenia-related deficits in spatial working memory, building 3125 different networks, and found that 41 (4.9%) out of 834 networks with valid activity presented schizophrenia-like alterations. In isolation, none of the parameters in either model showed adequate sensitivity or specificity to identify schizophrenia-like networks. Thus, in computational models of schizophrenia, even simple network phenotypes related to the disorder can be produced by a myriad of causes at the molecular and circuit levels. This suggests that unified explanations for either the full syndrome or its behavioral and network endophenotypes are unlikely to be expected at the genetic and molecular levels.

Esta pesquisa teve por objetivos: estudar as alterações na distribuição de Zn nas diferentes frações químicas de solos tratados com lodo de esgoto, provocadas pela aplicação de carbonatos, óxidos e fosfatos para determinar a eficiência desses produtos na contenção desse elemento, e avaliar a redução de solubilidade através do uso de planta hiperacumuladora. Utilizou-se lodo de esgoto de indústria aplicado em amostras da camada superficial de um Latossolo Vermelho-Amarelo (LVA) e de um Argissolo Vermelho-Amarelo (PVA). A adição de CaCO3 provocou imobilização química do Zn por sua associação às frações químicas mais estáveis. O FeCl3 + EDTA causou dissolução de compostos de Zn e dessorção desses elementos complexados por grupos funcionais de superfície. O KH2PO4 não alterou a distribuição de Zn nas diferentes formas químicas nos solos. O Zn concentrou-se nas raízes, limitando a passagem desses elementos para a parte aérea. Encontrou-se, nos tratamentos com o CaCO3, menor concentração de Zn na raiz e parte aérea. A adição de FeCl3 + EDTA promoveu aumento da concentração de Zn nesses órgãos da planta.This research had as objectives: to study the alterations in the distribution of Zn in different chemical carbonates fractions of soil treated with sewage sludge, caused by the application of carbonates, oxides and phosphates to determine the efficiency of these products in the contention of this element; and to evaluate the solubility reduction through the use of hyper accumulator plant. Industrial sewage sludge was applied in samples of surface layer of a Yellow Red Latossol and Yellow Red Argissol. The addition of CaCO3 caused chemical immobilization of Zn due to association of these elements with more stable chemical fractions. The FeCl3 + EDTA caused dissolution of Zn compounds and dessorption of these elements quelated by surface functional groups. The KH2PO4 did not alter the distribution of Zn in the different chemical forms in the soils. The Zn concentrated, mainly in the roots, which behaved as a natural filter, limiting the flux of these elements to the aerial part. In both soils, CaCO3 caused the smallest concentration of Zn in the root and aerial part. The addition of FeCl3+EDTA promoted the increase of Zn levels in the plant.

Studies have shown that supplementation with berries rich in anthocyanins are effective in reducing oxidative stress associated with aging, and are beneficial in reversing age-related neuronal and behavioral changes. However, there are few reports on other biological activities of these polyphenols, such as genoprotective effects. The present experiments were performed to study the possible effects of 30-day administration of a lyophilized extract of Vaccinium ashei berries on cognitive performance using step-down inhibitory avoidance, open-field habituation and elevated plus-maze tasks, as well as on DNA damage in the hippocampus and cerebral cortex. The present study showed that the extract significantly enhanced long-term memory in the inhibitory avoidance task, induced an increase in the number of crossings during open-field habituation and had an anxiolytic effect in the elevated plus-maze task. Moreover, the extract reduced oxidative DNA damage in brain tissue in vitro. These results suggest that supplementation with V. ashei berries to mice improves performance on memory tasks and has a protective effect on DNA damage, possibly due to the antioxidant activity of polyphenols, including anthocyanins.

Histoplasmosis of the central nervous system occurs in a significant percentage of patients with Histoplasma capsulatum infection, but has usually been described in association with immunosuppression and/or disseminated histoplasmosis. We aim to review the clinical and laboratory features of isolated histoplasmosis of the central nervous system in the immunocompetent host by presenting a series of 11 cases with this condition. Most of these patients presented with headache, meningeal irritation signs and mental status changes, comprising a somewhat different picture from that described in immunosuppressed patients. Moreover, almost all patients had signs of ventricular dilatation in neuroimaging studies, and 8 of the 11 patients had a ventriculoperitoneal shunt at the time of diagnosis, suggesting hydrocephalus to be an important feature of this condition and/or the possibility of shunt infection by the fungus. Immunodiffusion analysis of the cerebrospinal fluid appeared to be the most efficient way to reach the diagnosis and should be considered in immunocompetent patients with chronic lymphocytic meningitis, especially in those who have ventricular shunt or live in endemic areas of Histoplasma capsulatum.

Although many studies have investigated the function of cellular prion protein (PrPc), its physiologic role remains elusive. PrPc null mice have been reported to develop normally and to show normal performance in most behavioural tests. In the present study we investigated whether this also holds true after episodes of acute stress. PrPc gene ablated (Prnp0/0) and wild-type mice were subjected to restraint stress, electric foot shock, or swimming and compared with non-stressed animals. Immediately after the stressful situation, the anxiety levels and locomotion of the animals were measured using plus-maze and open-field tests. Among non-stressed animals, there was no significant difference in performance between Prnp0/0 and wild type animals in either test. However, after acute stress provoked by a foot shock or a swimming trial, Prnp0/0 animals showed a significant decrease in anxiety levels when compared with control animals. Moreover, after the swimming test, knockout mice presented decreased locomotion when compared to wild-type mice. Because of this observation, we also assessed both types of mice in a forced swimming test with the objective of better evaluating muscle function and found that Prnp0/0 animals presented reduced forced swimming capacity when compared to controls. As far as we know, this is the first report suggesting that cellular prion protein is involved in modulation of anxiety or muscular activity after acute psychic or physical stress.

BaY2F8, when doped with rare earth elements is a material of interest in the development of solid-state laser systems, especially for use in the infrared region. This paper presents the application of a new computational technique, which combines atomistic modelling and crystal field calculations in a study of rare earth doping of the material. Atomistic modelling is used to calculate the symmetry and detailed geometry of the dopant ion-host lattice system, and this information is then used to calculate the crystal field parameters, which are an important indicator in assessing the optical behaviour of the dopant-crystal system. Comparisons with the results of recent experimental work on this material are made. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

This paper describes a computational study of the mixed metal fluorides LiCaAlF6 and LiSrAlF6, doped with divalent (Pb2+, Co2+ and Ni2+), trivalent (Cr3+, Fe3+ and Y3+) and tetravalent (Si4+) ions. For each of the frameworks, all three cation sites were considered, as well as a range of charge compensation mechanisms. For the divalent dopants, substitution at the divalent host site is preferred, whilst for the trivalent dopants, Co3+ and Fe3+ prefer the Al3+ site, and Y3+ shows behaviour similar to the rare earths. Finally, it is found that Al3+ is the preferred site for substitution by Si4+ in both host frameworks.

LiCaAlF6 (LiCAF) and LiSrAlF6 (LiSAF) crystal hosts doped with trivalent positive lanthanide ions (Ln3+) were studied via defect simulation techniques and crystal field parameter calculations. Depending on the ratio of ionic radius of the dopant to the host divalent cation, the luminescent ions can occupy the Sr2+ (or Ca2+) site or the Al3+. When the dopant enters at the divalent cation site, charge compensation is needed that changes drastically the starting symmetry of this site. However, when the Al3+ site is preferred, no charge compensation schemes are involved, but nevertheless the lattice is distorted since the sizes of the Ln3+ ions are bigger than the Al3+ ion. The actual positions of the first neighbours of the Ln3+ ion were input in the crystal field parameters equations, through which the conclusions on site symmetry of the optically active ion have been drawn and these results allows the prediction of possible optical activity based on the possibility of the 4f–4f transitions.

Eclampsia is defined as the occurrence of seizures and/or coma resulting from hypertensive encephalopathy on a background of preeclampsia (1). Eclampsia appears to be caused by a failure of the brain’s autoregulatory response to increases in blood pressure, leading to an increase in cerebral perfusion pressure with overperfusion injury similar to that observed in hypertensive encephalopathy (2)(3). Brain edema and hemorrhage ensue, as observed in imaging studies (4)(5), and there is evidence to suggest that these alterations can cause ischemia to brain cells. These events lead to neurologic symptoms (6), including seizures as well as cortical blindness, aphasia, limb weakness, psychosis, coma, and cerebrovascular accidents. Studies have analyzed various diagnostic methods, such as transcranial Doppler measurements, as a way to evaluate neurologic involvement in preeclampsia (3)(7). To date, however, there is no reliable laboratory marker to identify patients at risk for eclampsia or its related complications. S100B is a 21-kDa protein physiologically produced and released primarily by astrocytes in the central nervous system (CNS), where it exerts neurotrophic and gliotrophic actions (8). Because ∼95% of S100B is located in the CNS, the results of several studies have suggested that an increase in S100B in blood and cerebrospinal fluid could be a potential marker of neural injury, indicating reactive gliosis, astrocytic death, and/or blood–brain barrier dysfunction. Accordingly, increased S100B concentrations in cerebrospinal fluid and/or blood have been reported in several pathologic conditions causing acute and chronic brain injury, such as head trauma (9), stroke (10), schizophrenia (11), and human T-lymphotropic virus type 1-associated myelopathy (12). Some studies have also evaluated S100B as a marker of recent seizures. Although S100B has been shown to be increased in both cerebrospinal fluid and brain tissue of patients with temporal lobe epilepsy (13)(14), studies in which …

This paper describes a computational study of the mixed metal fluorides LiCaAlF6 and LiSrAlF6, which have potential technological applications when doped with a range of elements, especially those from the rare earth series. Potentials are derived to represent the structure and properties of the undoped materials, then defect properties are calculated, and finally solution energies for rare earth elements are calculated, enabling preferred dopant sites and charge compensation mechanisms to be predicted.

Com o objetivo de avaliar a concentração de metais pesados no solo e nas plantas de feijão-de-vagem (Phaseolus vulgaris L.) em diferentes sistemas de preparo do solo, foi realizado um experimento em Paty do Alferes (RJ), em um Latossolo Vermelho-Amarelo com 30 % de declividade. Foram instaladas parcelas do tipo Wischmeier com dimensões de 22,0 x 4,0 m; cada parcela era constituída de um sistema de preparo do solo distinto: plantio convencional, aração com trator no sentido morro abaixo e queima dos restos vegetais (PC); plantio em nível com aração tração animal e cordões de vegetação a cada 7,0 m (PN); cultivo mínimo com apenas abertura de covas para plantio e conservação dos restos vegetais (CM). Foram coletadas amostras de solo, de plantas e de agroquímicos, bem como analisados os teores totais de metais pesados. Verificou-se que as maiores adições de Cu no sistema deveram-se ao uso do fungicida Peprosan. Os sistemas de preparo PN e CM favoreceram acúmulo de Zn, Mn, Cd e Pb no solo, quando comparados ao PC, provavelmente, em virtude das menores perdas por erosão. A concentração de Pb na vagem in natura, nos sistemas de preparo PN e CM, esteve acima dos limites permitidos para alimentos in natura, em níveis impróprios para o consumo humano. To evaluate the effect of different soil tillage methods on heavy metal accumulation in soil and edible bean plants (Phaseolus vulgaris L.), a study was carried out in the county of Paty do Alferes, Rio de Janeiro State, Brazil, on a Red-Yellow Latosol with 30 % slope. On 22,0 x 4,0 m Wischmeier plots, the following methods were installed: conventional tillage: downhill furrows and burning of vegetal residues (PC); tillage along contour lines: contour plowing by animal traction with strips of cropping grass every 7,0 m (PN); minimum tillage: opening of ditches for plants only, under preservation of the vegetal residues (CM). Samples of soil, plant and agrochemicals were collected for the determination of heavy metal contents. Peprosan fungicide was responsible for the highest addition of Cu to the soil system. Minimum tillage and tillage along contour lines accounted for a higher accumulation of heavy metals, probably due to smaller erosion losses. Fruits under PN and CM presented Pb concentrations above the levels allowed for fresh food, unfit for human consumption.

In this work, computer modelling of the undoped and Eu3+-doped LiLa(WO4)2 structure was successfully achieved by energy minimization and mean field theory. The results were compared with experimental data previously published and are in good agreement with them. A linear regression of the lattice parameters was also proposed as a function of the dopant concentration. The lattice ordering was evaluated to understand the possibility of structural changes in the crystal. Regarding the optical luminescence, the concentration limit of Eu doping was also determined. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Paty do Alferes (RJ) é um município com tradição agrícola, sendo a olericultura a sua principal atividade econômica. A região apresenta uma topografia e regime de chuvas que favorecem a erosão. A falta de um manejo adequado do solo e o uso excessivo de agroquímicos favorecem os processos de degradação física e química do solo, acarretando sérios impactos ao ambiente. Com o objetivo de avaliar o acúmulo de metais pesados no solo e em plantas de tomate (Lycopersicon esculentum Mill), cultivadas sob diferentes sistemas de preparo do solo, foi realizado um trabalho no município de Paty do Alferes (RJ), entre os meses de agosto e dezembro de 1999. Foram instaladas parcelas do tipo Wischmeier (com coletores de enxurrada e sedimentos), com dimensões de 22,0 x 4,0 m, em um Latossolo Vermelho-Amarelo com 30 % de declividade. Cada tratamento consistiu de um tipo de sistema de preparo do solo: (a) preparo convencional: aração no sentido morro abaixo e queima dos restos vegetais (PC); (b) preparo em curvas de nível: aração com tração animal em nível com faixas de capim-colonião a cada 7,0 m (PN); (c) cultivo mínimo: apenas abertura de covas para plantio e conservação dos restos vegetais (CM). Foram coletadas amostras de solo e plantas de tomate, sendo analisados os teores de metais pesados nas amostras coletadas, a produtividade das plantas e a fertilidade do solo. A produtividade no cultivo mínimo foi significativamente inferior à de outros manejos, apesar de tal sistema favorecer a maior fertilidade do solo. Esse manejo também proporcionou maior acúmulo de metais pesados no solo, principalmente quando comparado ao plantio convencional. Com relação às plantas, a aplicação foliar de defensivos agrícolas favoreceu o maior acúmulo de metais pesados na parte aérea das plantas, e os teores de Cu e Zn estiveram acima dos limites permitidos para metais pesados em plantas. Os frutos produzidos nos três sistemas de preparo do solo apresentaram concentrações de Pb próximas ao limites permitidos para alimentos frescos. Paty do Alferes in the State of Rio de Janeiro, Brazil, is a county with agricultural tradition, whose main economical source is horticulture. Topography and rainfall regime of the region are favorable for erosion. Due to the lack of an appropriate soil management, besides excessive application of agrochemicals, physical and chemical soil degradation processes are favored, causing serious environmental impacts. With the objective to evaluate accumulated heavy metals in soil and in tomato plants (Lycopersicon esculentum Mill), raised in different soil tillage systems, a study was carried out in the county of Paty do Alferes (RJ), in the months from August to December 1999. Wischmeier plots of 22.0 x 4.0 m (with runoff and sediment collectors) were installed on a Red-Yellow Latosol with 30 % incline. Each tillage system represented a treatment: (a) conventional tillage: downhill furrows and burning of vegetal residues (PC); (b) tillage along contour lines: contour plowing by animal traction with strips of cropping grass every 7.0 m (PN); (c) minimum tillage: opening of ditches for plants only, under preservation of the vegetal residues (CM). Soil and tomato plant samples were collected for analyses of heavy metal contents, plant productivity and soil fertility. Productivity in the minimum tillage treatment was significantly lower than in the others, although this system benefited the highest soil fertility. It provided the greatest accumulation of heavy metals in the aerial part of the plants as well, and Cu and Zn contents lay above the permitted heavy metal levels in plants. The fruits of all three soil tillage systems presented Pb concentrations near the limits allowed for fresh food.

This paper describes a computer modelling study of rare earth doping in the mixed metal fluorides LiCaAlF 6 , LiSrAlF 6 and LiYF 4 . All these materials have potential technological applications, p...

Protein disulfide isomerase (PDI) has fundamental roles in the oxidative folding of proteins in the endoplasmic reticulum (ER) of eukaryotic cells. The study of this molecule has been attracting considerable attention due to its association with other cell functions and human diseases. In leukocytes, such as neutrophils, PDI is involved with cell adhesion, signaling and inflammation. However, the expression of PDI in other leukocytes, such as eosinophils, important cells in inflammatory, allergic and immunomodulatory responses, remains to be defined. Here we used different approaches to investigate PDI expression within human eosinophils. Western blotting and flow cytometry demonstrated high PDI expression in both unstimulated and CCL11/eotaxin-1-stimulated eosinophils, with similar levels in both conditions. By using an immunogold electron microscopy technique that combines better epitope preservation and secondary Fab-fragments of antibodies linked to 1.4-nm gold particles for optimal access to microdomains, we identified different intracellular sites for PDI. In addition to predictable strong PDI labeling at the nuclear envelope, other unanticipated sites, such as secretory granules, lipid bodies and vesicles, including large transport vesicles (eosinophil sombrero vesicles), were also labeled. Thus, we provide the first identification of PDI in human eosinophils, suggesting that this molecule may have additional/specific functions in these leukocytes.

Reconsolidation and extinction are two processes occurring upon memory retrieval that have received great attention in memory research over the last decade, partly due to their purported potential in the treatment of anxiety disorders. Due to their opposite behavioral effects, the two phenomena have usually been considered as separate entities, with few attempts to build a unified view of how both could be produced by similar mechanisms. Based on computational modeling, we have previously proposed that reconsolidation and extinction are behavioral outcomes of the same set of plasticity systems, albeit working at different synapses. One of these systems seems to be pharmacologically similar to the one involved in initial memory consolidation, and likely involves traditional Hebbian plasticity, while the second seems to be more involved with the labilization of existing memories and/or synaptic changes. In this article, we review the evidence for the existence of a plasticity system specifically involved in memory labilization, as well as its possible molecular requirements, anatomical substrates, synaptic mechanisms and physiological roles. Based on these data, we propose that the field of memory updating might ultimately benefit from a paradigm shift in which reconsolidation and extinction are viewed not as separate processes but as different instantiations of plasticity systems responsible for reinforcement and labilization of synaptic changes.

When 5-lipoxygenase (5-LO) is inhibited, roughly half of the CNS effect of the prototypic endocannabinoid anandamide (AEA) is lost. Therefore, we decided to investigate whether inhibiting this enzyme would influence physiological functions classically described as being under control of the endocannabinoid system. Although 5-LO inhibition by MK-886 reduced lipoxin A4 levels in the brain, no effect was found in the elevated plus maze (EPM), even at the highest possible doses, via i.p. (10 mg/kg,) or i.c.v. (500 pmol/2 µl) routes. Accordingly, no alterations in anxiety-like behavior in the EPM test were observed in 5-LO KO mice. Interestingly, aged mice, which show reduced circulating lipoxin A4 levels, were sensitive to MK-886, displaying an anxiogenic-like state in response to treatment. Moreover, exogenous lipoxin A4 induced an anxiolytic-like profile in the EPM test. Our findings are in line with other reports showing no difference between FLAP KO or 5-LO KO and their control strains in adult mice, but increased anxiety-like behavior in aged mice. We also show for the first time that lipoxin A4 affects mouse behavior. In conclusion, we propose an age-dependent relevancy of endogenous 5-LO derivatives in the modulation of anxiety-like behavior, in addition to a potential for exogenous lipoxin A4 in producing an anxiolytic-like state.

Benzodiazepines are among the most prescribed and consumed medication groups in the world. Although benzodiazepines are used in the treatment of several psychiatric and non-psychiatric disorders, and are generally safe and well-tolerated, the potential for misuse and abuse is considerable. This makes the study and regulation of benzodiazepine prescription and consumption an item of concern in public health around the world. Most developed countries have consistent data of benzodiazepine sales and consumption; however, data from developing countries is scarce, making health policies on the use of benzodiazepines a much tougher issue in these countries. This article aims to review the epidemiology of benzodiazepine use in Brazil, as well as to analyze how legislation, physician misinformation and economic factors might contribute to making benzodiazepine abuse a problem in the country.

The ectonucleotidase pathway is an important metabolic source of extracellular adenosine. Adenosine has potent anticonvulsant effects on various models of epilepsy. One of these models is pentylenetetrazol (PTZ) kindling, in which repeated administration of subconvulsive doses of this drug induces progressive intensification of seizure activity. In this study, we examine the effect of a single convulsive injection (60 mg/kg, i.p.) or 10 successive (35 mg/kg, i.p.) injections of PTZ on synaptosomal ectonucleotidases. Our results have shown that no changes in ectonucleotidase activities were seen at 0, 1, and 24 h or at 5 days after a single convulsive PTZ injection. However, after PTZ-kindling, rats which were more resistant to seizure development presented an increase in ATP hydrolysis in synaptosomes from hippocampus and cerebral cortex (44% and 28%, respectively). These results suggest that changes in nucleotide hydrolysis may represent an important mechanism in the modulation of chronic epileptic activity in this model.

Com vistas em verificar se a utilização de fertilizantes fosfatados e irrigação com água poluída trazem elevação dos teores de metais pesados no solo, amostras de um Podzólico Amarelo e de dois Latossolos Amarelos, que receberam fertilizante fosfatado, desde 1968, e de um Cambissolo irrigado com água do rio Paraíba do Sul, desde 1978, cultivados com cana-de-açúcar (Saccharum spp.) em Campos dos Goytacazes, RJ, foram analisadas quanto aos teores totais de Cd, Co, Cr, Cu, Mn, Ni, Pb e Zn. Os resultados mostraram que os solos que receberam fertilizantes fosfatados durante 25 anos apresentaram aumento significativo de Cd quando comparados com áreas-controle, sem, contudo, elevá-los a níveis críticos. O Cambissolo irrigado durante 15 anos apresentou aumentos significativos de Cd, Cr, Co, Cu, Ni e Pb, tendo os resultados da extração seqüencial mostrado que a maior percentagem desses elementos encontra-se na fração residual, de baixa biodisponibilidade e mobilidade. To verify if the use of phosphate fertilizer and polluted irrigation water increased the levels of heavy metals in soil, samples of one Yellow Podzolic and two Yellow Latosol soils treated with phosphate fertilizers since 1968, and a Cambisol irrigated with water from the Paraíba do Sul River since 1978, cultivated with sugarcane in Campos dos Goytacazes, RJ, were analysed for total contents of Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn. The results from the soils that received phosphate fertilizers showed a significant increase in Cd concentrations when compared with the control areas. The total concentrations of Cd, Cr, Co, Cu, Ni and Pb were significantly increased in the irrigated Cambisol and the results of the sequential extraction indicated that these elements prevailed in the residual form of low bioavailability and mobility.

A encefalopatia hepática (EH) é uma síndrome multifatorial, na qual a função do sistema nervoso central está alterada devido às conseqüências metabólicas da disfunção hepática. Os dois principais componentes das doenças hepáticas que levam à EH são a diminuição no número de hepatócitos funcionantes e o rearranjo vascular, que leva à diminuição na fração de sangue, efetivamente detoxificado pelo fígado. Os sintomas da EH podem variar de déficits cognitivos leves até o coma profundo. Algum grau de morte neuronal pode ser observado em pacientes com EH, como conseqüência da cirrose hepática, ou, na EH avançada, da presença de edema cerebral. No entanto, a maior parte da síndrome neurológica é reversível com a compensação da doença hepática. A etiologia da EH não é totalmente conhecida e trata-se, provavelmente, de um processo multifatorial. Inicialmente, as teorias apontavam para o acúmulo de neurotoxinas que prejudicariam a função neuronal. Mais recentemente, anormalidades em vários sistemas de neurotransmissão foram propostos como causas potencias da EH como, por exemplo, o aumento observado na neurotransmissão GABAérgica. Existe evidência de que este aumento esteja relacionado com o aumento da potenciação GABAérgica por substâncias de ação similar aos benzodiazepínicos, as quais se encontram aumentadas na EH. Com esta evidência em mente, foi tentada a terapia desta síndrome com flumazenil, um antagonista benzodiazepínico, o qual tem mostrado eficácia clínica em uma porcentagem variável de pacientes em estudos recentes. No entanto, ainda não há evidências conclusivas para sustentar uma relação causal entre o aumento de ligantes ao receptor de benzodiazepínicos e os sintomas da EH. É possível que esta relação exista em alguns, mas não em todos os pacientes com esta síndrome.

Despite standard clinical definitions and availability of diagnostic tests for precocious puberty, an intensive and structured investigation is needed in order to diagnose the aetiology in particular cases. A 4-year-old, phenotypically female child was referred to paediatric endocrinology consultation for premature pubarche and thelarche. There was an acceleration of growth velocity with high levels of estradiol and testosterone, and prepubertal FSH and LH measurements. Investigation showed bilateral gonadoblastoma as the cause of the peripheral precocious puberty. Genetic studies revealed 46 XY karyotype with mutation c.89GT (p.Arg30Ile) in exon 1 of the SRY gene, confirming the diagnosis of complete gonadal dysgenesis. Disorders of sexual differentiation must be considered in the approach and investigation of peripheral precocious puberty, especially in the presence of ovarian tumours, such as gonadoblastoma and dysgerminoma.

Although different hypotheses have been formulated to explain schizophrenia pathogenesis, the links between them are weak. The observation that five psychotic patients on chronic warfarin therapy for deep-vein thrombosis showed long-term remission of psychotic symptoms made us suspect that abnormalities in the coagulation pathway, specifically low tissue plasminogen activator (tPA) activity, could be one of the missing links. Our hypothesis is supported by a high prevalence of conditions affecting tPA activity in drug-naive schizophrenia, such as antiphospholipid antibodies, elevated cytokine levels, hyperinsulinemia and hyperhomocysteinemia. We recently screened a group of schizophrenia patients and controls for conditions affecting tPA activity. Free-protein S deficiency was highly prevalent among patients, but not found in controls. Free-protein S and functional protein C are natural anticoagulants that form complexes that inhibit tPA inhibitors. All participants had normal protein C levels, suggesting that protein S could have a role in schizophrenia, independent of protein C. Chronic patients and those studied during acute episodes had between three and six conditions affecting tPA and/or protein S activity, while patients in remission had up to two, which led us to postulate that multiple conditions affecting tPA and/or protein S activity could contribute to the full expression of schizophrenia phenotype. This paper describes the physiological roles of tPA and protein S, reviewing how their activity influences pathogenesis and comorbidity of schizophrenia. Next, it analyzes how activity of tPA and protein S is influenced by biochemical abnormalities found in schizophrenia. Last, it suggests future directions for research, such as studies on animal models and on therapeutic approaches for schizophrenia aiming at increasing tPA and protein S activity.

Wind power generation plays an important role in most power systems worldwide. Despite that, only in 2009, wind farms appeared as a profitable and competitive investment option in Brazil. The Brazilian power system is mainly hydro based and, due to its many singularities, its coordination is still centralized. A collateral effect of such centralized dispatch coordination is that the system marginal costs, which determine the short-term energy prices, exhibit a highly volatile pattern. In this setting, selling energy through bilateral forward contracts backed up on intermittent generation profiles, such as wind farms and small-run hydros, exposes the generation company (Genco) to the so-called price-quantity risk. In this paper, we explore the well-known complementarity between these two renewable resources (wind and inflows) by proposing a statistical model capable to produce scenarios of renewable resources availability consistently with short-term price scenarios. Hence, we present a novel commercial model for a wind power producer based on a joint-selling strategy with a small-hydro Genco. In this model, the hydro Genco receives a surplus payment in comparison to the amount it would receive in the market and the wind Genco, the rest of the income. We show, by means of realistic data from the Brazilian power system, that such commercial model is able to mitigate the exposure to the short-term price and foster the wind power penetration into the contract market.