The influence of thioether-substituted ligands in dicopper(II) complexes: Enhancing oxidation and biological activities.

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = -2.27 cm-1 and -5.01 cm-1, respectively, H = -2JS1S2) and ferromagnetic coupling for 2 (J = 5.72 cm-1). Broken symmetry DFT calculations attribute this behavior to a major contribution from the dz2 orbitals for 1 and 3, and from the dx2-y2 orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with kcat of (90.79 ± 2.90) × 10-3 for 1, (64.21 ± 0.99) × 10-3 for 2 and (14.20 ± 0.32) × 10-3 s-1 for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

Application of Plant Growth-Promoting Bacteria from Cape Verde to Increase Maize Tolerance to Salinity.

Salinity constitutes a major abiotic factor that negatively affects crop productivity. Inoculation with plant growth-promoting bacteria (PGPB) is proven to increase plant tolerance to abiotic stresses and enhance plant growth, development and productivity. The present study aims to increase the resilience of crops to salinity using bacteria from the microbiome of plants growing in saline environments. For that, the halotolerance of bacteria present in the roots of natural plants growing on Sal Island, which is characterized by its arid environment and maritime influence, was determined, with some strains having extreme halotolerance. Their ability to produce plant growth-promoting traits was evaluated, with most strains increasing indole acetic acid (26-418%), siderophore (>300%) and alginate (2-66%) production and phosphate solubilization (13-100%) under salt stress. The strains evidencing the best performance were inoculated in maize (Zea mays L.) plants and their influence on plant growth and biochemical status was evaluated. Results evidenced bacterial ability to especially increase proline (55-191%), whose osmotic, antioxidant and protein-protecting properties reduced protein damage in salt-stressed maize plants, evidencing the potential of PGPB to reduce the impact of salinity on crops. Enhanced nutrition, phytohormone production and osmolyte synthesis along with antioxidant response all contribute to increasing plant tolerance to salt stress.

A difficult airway approach in a merosin-deficient congenital muscular dystrophy patient: a case report.

Merosin-deficient muscular dystrophy is caused by an autosomal recessive mutation on laminin-..2 gene characterized by severe progressive muscle weakness associated with neuromuscular scoliosis and restrictive lung disease. In this case report, we describe an alternative airway approach performed in a child with anticipated difficult airway and merosin-deficient muscular dystrophy. Significant anesthetic implications may increase the perioperative risk, requiring accurate knowledge to anticipate an adequate management and provide patient-safety strategies.

A difficult airway approach in a merosin-deficient congenital muscular dystrophy patient: a case report

Abstract Merosin-deficient muscular dystrophy is caused by an autosomal recessive mutation on laminin-α2 gene characterized by severe progressive muscle weakness associated with neuromuscular scoliosis and restrictive lung disease. In this case report, we describe an alternative airway approach performed in a child with anticipated difficult airway and merosin-deficient muscular dystrophy. Significant anesthetic implications may increase the perioperative risk, requiring accurate knowledge to anticipate an adequate management and provide patient-safety strategies.

Bioprospecting Soil Bacteria from Arid Zones to Increase Plant Tolerance to Drought: Growth and Biochemical Status of Maize Inoculated with Plant Growth-Promoting Bacteria Isolated from Sal Island, Cape Verde.

Climate change and anthropogenic activities are responsible for extensive crop yield losses, with negative impact on global agricultural production. The occurrence of extreme weather events such as drought is a big challenge for agriculture, negatively impacting crops. Thus, methodologies reducing crop dependence on water will be a great advantage. Plant roots are colonized by soil bacteria, that can establish beneficial associations with plants, increasing crop productivity and plant tolerance to abiotic stresses. The aim of this study was to promote plant growth and to increase crop tolerance to drought by inoculation with osmotolerant bacterial strains. For that, bacteria were isolated from plants growing in Sal Island (Cape Verde) and identified. The osmotolerance and plant-growth promotion (PGP) abilities of the strains were determined. A maize seed cultivar tolerant to drought was inoculated with the strains evidencing best PGP capacity and osmo-tolerance. Results evidenced the ability of some bacterial strains increasing the development and inducing osmotolerance in plants. These results evidence the potential of osmotolerant bacteria to further increase the level of tolerance of maize varieties tolerant to drought, decreasing the dependence of this crop on irrigation, and open new perspectives to growth maize in drought affected areas and to use water more efficiently.

A Multifactorial Approach to Untangle Graphene Oxide (GO) Nanosheets Effects on Plants: Plant Growth-Promoting Bacteria Inoculation, Bacterial Survival, and Drought.

Drought is a limiting factor for agricultural productivity. Climate change threatens to expand the areas of the globe subjected to drought, as well as to increase the severity and duration of water shortage. Plant growth-promoting bacteria (PGPB) are widely studied and applied as biostimulants to increase plant production and to enhance tolerance to abiotic and biotic constraints. Besides PGPB, studies on the potential of nanoparticles to be used as biostimulants are also thriving. However, many studies report toxicity of tested nanoparticles in bacteria and plants in laboratory conditions, but few studies have reported effects of nanoparticles towards bacterial cells and communities in the soil. The combined application of nanoparticles and PGPB as biostimulant formulations are poorly explored and it is important to unravel the potentialities of their combined application as a way to potentiate food production. In this study, Rhizobium sp. E20-8 and graphene oxide (GO) nanosheets were applied on container-grown maize seedlings in watered and drought conditions. Bacterial survival, seedling growth (dry weight), and biochemical endpoints (photosynthetic pigments, soluble and insoluble carbohydrates, proline, lipid peroxidation, protein, electron transport system, and superoxide dismutase) were evaluated. Results showed that the simultaneous exposure to GO and Rhizobium sp. E20-8 was able to alleviate the stress induced by drought on maize seedlings through osmotic and antioxidant protection by GO and mitigation of GO effects on the plant's biochemistry by Rhizobium sp. E20-8. These results constitute a new lead on the development of biostimulant formulations to improve plant performance and increase food production in water-limited conditions.

A influência da inteligência emocional enquanto fator de proteção do stress: Que especificidades nos profissionais de saúde? / The influence of emotional intelligence as a protective factor against stress: What specificities in health professionals?

A globalização da economia, as reduções e os ajustes nas estruturas organizacionais, conduzem a desafios tanto para as empresas como para os seus colaboradores, nomeadamente as que prestam serviços de saúde. Neste contexto, os estudos empíricos assinalam um impacte positivo da inteligência emocional (IE) na gestão de pessoas, com maior expressão nos cuidados de saúde. Assim, pretende-se com esta investigação explorar a relação entre a inteligência emocional e o stress nos trabalhadores, em especial nos profissionais de saúde. Realizou-se um estudo empírico, transversal (cross-sectional) e não-experimental, constituiu-se uma amostra não probabilística por redes de 874 trabalhadores de diferentes grupos de atividade profissional (154 profissionais de saúde). Aplicou-se o questionário que inclui três escalas: Escala de Inteligência Emocional (Rego, Sousa, Pina e Cunha, Correia, & Saur-Amaral, 2007), Escala do Stress Percebido (SP) (Chioda, Dias, Silva, Marôco & Duarte, 2013), Escala do Capital Psicológico (Luthans, Youssef, & Avolio, 2007) e Escala de Espiritualidade Organizacional (Rego, Souto, & Cunha, 2007). A escala de IE globalmente apresenta bons índices de ajustamento [?2/df = 3.965; NFI =.923; RMSEA = .055; ? = .84; ?X=5.11 (?= .63)] e a escala de SP também apresenta globalmente valores toleráveis dos índices de ajustamento [?2/df = 4. 045; NFI = .953; RMSEA= .059; ? = .82; ?X = 1.79 (? = .51)]. Nos profissionais de saúde, considerando as escalas globais de IE e SP obtivemos os valores IE [?X = 5.11 (? = .65)] e SP [?X = 1.81 (? = .46)]. Nas outras categorias profissionais, considerando as escalas globais de IE e SP obtivemos os valores de IE [?X = 5.11 (? = .63)] e SP [?X = 1.77 (? = .51)]. Em ambas categorias profissionais as variáveis sociodemográficas não exercem uma influência que se considere que tenha impacte na IE ou no SP. Os resultados sustentam empiricamente uma relação negativa entre a inteligência emocional e o stress percebido nos trabalhadores. A relação entre a Escala global de IE e a de SP é estatisticamente significativa e negativa tanto na amostra total (r=-.41), como nos profissionais de saúde (r=-.49) e também nas outras categorias profissionais (r=-.40). Verificámos que o teste multivariado indicou a inexistência de diferenças globais ao nível da IE entre profissionais de saúde e outras categorias profissionais [? de Wilks = 0.990, F (6, 867) = 1.43, p = .201]. No teste de diferença de magnitude dos coeficientes de correlação entre a IE e o SP verificámos a existência de correlações negativas significativamente mais elevadas nos profissionais de saúde [r = - .49; R2 = 24%; p < .01] em relação aos outros profissionais saúde [r = - .40; R2 = 16%; p < .01], entre o SP e a escala global da IE, apontando para uma probabilidade de 24% de a inteligência emocional atuar como buffer effect no SP nos profissionais de saúde comparativamente aos 16% em outros profissionais. Concluímos, assim, que a inteligência emocional apresenta uma relação negativa no stress percebido, apresentando maior magnitude nos profissionais de saúde. As implicações deste estudo sugerem que os resultados alcançados poderão concorrer para uma maior sensibilização de gestores e líderes, para a necessidade de implementação de ações organizacionais que promovam o desenvolvimento da IE.

Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol.

El papel del entrenador en la enseñanza de competencias de vida a jóvenes brasileños en riesgo de vulnerabilidad social / The role of the coach in teaching of life competences at risk of social vulnerability to young Brazilians

Este estudio busca investigar y analizar cómo piensan y actúan entrenadores de proyectos sociales brasileños con respecto a la enseñanza de competencias de vida a jóvenes que viven en áreas de riesgo de exclusión social. Entrevistamos a seis entrenadores de fútbol y otros deportes de distintas clases de proyectos de educación por el deporte. Se implementó un análisis cualitativo identificando y organizando meaning units, que resultó en la creación de cuatro grandes dimensiones: Trabajo en Equipo, Disciplina, Actuación y Vínculo, y Educación Integral; formadas por 28 categorías que reflejan las filosofías y prácticas de los educadores. Los resultados indican que todos los entrenadores entrevistados tienen un perfil análogo al modelo de entrenamiento de competencias de vida de Gould, Collins, Lauer y Chung (2007) que utilizan estrategias para la enseñanza de competencias de vida, como por ejemplo fomentar la autonomía, estimular el esfuerzo y dar feedback, aunque carecen de un planteamiento sistemático y tienen recursos precarios para llevar a cabo dicho modelo.

This study aims to investigate and analyze how coaches of Brazilian social projects think and act when teaching life skills to young people who live in areas of social risk. We interviewed six coaches of both football and other sports about different types of educational projects delivered through sport education. A qualitative analysis was developed through the identification of meaning units resulting in the creation of four large dimensions: Teamwork, Discipline, Performance and Bonding, and Integral Education, composing of 28 categories which reflect the philosophies and practices of these educators. The results show that all coaches that participated in this study have a similar profile "coaching life skills model" Gould, Collins, Lauer and Chung (2007) using strategies for teaching life skills, such as fostering autonomy, stimulate the effort and give feedback, but lack a systematic approach and has weak resources to carry out this model.

?Barnabé e sua aventura?: Um projeto de educação para a saúde em disfonia infantil / ?Barnabé and his adventure? A vocal health education project in childhood dysphonia / ?Bernabé y su aventura? Un proyecto de educación para la salud en la disfonía infantil

Os nódulos vocais, associados etiologicamente a um comportamento disfuncional de mau uso e abuso vocal, são os principais responsáveis pela disfonia crônica em crianças de ambos os gêneros. A disfonia infantil pode influenciar a sedimentação das relações sociais da criança disfônica e conduzir a processos de estigmatização e constrangimento por parte de seus pares. O presente instrumento de Educação para a Saúde tem como principal objetivo consciencializar a criança disfônica para o uso corretoda sua voz, diminuindo o impacto biopsicossocial inerente à patologia vocal. Este instrumento, destinado essencialmente a crianças de ambos os sexos entre os sete e os nove anos de idade, e simultaneamenteaos seus pais e professores/educadores de infância, consiste num livro de literatura infantil que aborda a problemática da voz e da patologia nodular infantil, tendo sido concretizado em dois formatos: impressoem formato A5 e em formato digital, com narração áudio incluída. O instrumento elaborado, ideal para a população-alvo pré-definida, consiste num excelente veículo de consciencialização da importância da voz e da promoção de hábitos vocais salutogênicos, podendo ser usado em diversos contextos de vida da criança (terapêutico, familiar e escolar)(AU)

Vocal nodules, etiologically associated to vocal abuse and misuse, are one of the major factors for chronic dysphonia in childhood, in both genders. Childhood dysphonia may influence the effectiveness of dysphonic child?s social relationships, and to lead to stigmatization and embarrassment by their peers. The developed health education instrument principally aims to aware dysphonic children to a correct use of their voice, decreasing biopsychosocial impact of this vocal disturbance. This instrument firstlyaimed to children of both genders, in ages between seven and nine years old, and simultaneously to their parents and educators, consists in a child?s literature book which addresses the problem of voice and child?s nodular pathology, and it was made in two different formats: printed in A5 format and in digital format with audio narration included. This instrument, ideal for the target population, is a great vehicle to raise awareness of the importance of voice and promoting salutogenic vocal habits, so it can be used in various contexts of the child?s life (therapeutical, familiar and educational).(AU)

Los nódulos vocales, etiológicamente asociados a un comportamiento disfuncional de mal uso y abuso vocal, son los principales responsables de la disfonía crónica en niños de ambos los sexos. La disfonía infantil puede influenciar la efectividad de las relaciones sociales del niño disfónico, y conducir a procesos de estigmatización y constreñimiento por sus pares. El presente instrumento de educación para la salud tiene como principal objetivo aumentar la conciencia del niño disfónico para el correctouso de su voz, reduciendo el impacto biopsicosocial inherente a la patología de la voz. Este instrumento, diseñado esencialmente para niños de ambos sexos, entre siete y nueve años de edad, y simultáneamentepara sus padres y profesores, es un libro de literatura infantil que aborda el problema de la voz y de la patología nodular infantil, habiendo sido implementado en dos formatos: impreso en formato A5 y en formato digital con narración de audio incluida. El instrumento elaborado, ideal para la población objetivo previamente definida, es un excelente vehículo para aumentar la conciencia sobre la importancia de la voz y la promoción de hábitos vocales saludables y se puede utilizar en diferentes contextos de la vida del niño (terapéutico, familiar y escolar).(AU)

"Barnabé e sua aventura": Um projeto de educação para a saúde em disfonia infanti / "Barnabé and his adventure" A vocal health education project in childhood dysphonia / "Bernabé y su aventura" Un proyecto de educación para la salud en la disfonía infantil

Os nódulos vocais, associados etiologicamente a um comportamento disfuncional de mau uso e abuso vocal, são os principais responsáveis pela disfonia crônica em crianças de ambos os gêneros. A disfonia infantil pode influenciar a sedimentação das relações sociais da criança disfônica e conduzir a processos de estigmatização e constrangimento por parte de seus pares. O presente instrumento de Educação para a Saúde tem como principal objetivo consciencializar a criança disfônica para o uso corretoda sua voz, diminuindo o impacto biopsicossocial inerente à patologia vocal. Este instrumento, destinado essencialmente a crianças de ambos os sexos entre os sete e os nove anos de idade, e simultaneamenteaos seus pais e professores/educadores de infância, consiste num livro de literatura infantil que aborda a problemática da voz e da patologia nodular infantil, tendo sido concretizado em dois formatos: impressoem formato A5 e em formato digital, com narração áudio incluída. O instrumento elaborado, ideal para a população-alvo pré-definida, consiste num excelente veículo de consciencialização da importância da voz e da promoção de hábitos vocais salutogênicos, podendo ser usado em diversos contextos de vida da criança (terapêutico, familiar e escolar)

Vocal nodules, etiologically associated to vocal abuse and misuse, are one of the major factors for chronic dysphonia in childhood, in both genders. Childhood dysphonia may influence the effectiveness of dysphonic child?s social relationships, and to lead to stigmatization and embarrassment by their peers. The developed health education instrument principally aims to aware dysphonic children to a correct use of their voice, decreasing biopsychosocial impact of this vocal disturbance. This instrument firstlyaimed to children of both genders, in ages between seven and nine years old, and simultaneously to their parents and educators, consists in a child?s literature book which addresses the problem of voice and child?s nodular pathology, and it was made in two different formats: printed in A5 format and in digital format with audio narration included. This instrument, ideal for the target population, is a great vehicle to raise awareness of the importance of voice and promoting salutogenic vocal habits, so it can be used in various contexts of the child?s life (therapeutical, familiar and educational).

Los nódulos vocales, etiológicamente asociados a un comportamiento disfuncional de mal uso y abuso vocal, son los principales responsables de la disfonía crónica en niños de ambos los sexos. La disfonía infantil puede influenciar la efectividad de las relaciones sociales del niño disfónico, y conducir a procesos de estigmatización y constreñimiento por sus pares. El presente instrumento de educación para la salud tiene como principal objetivo aumentar la conciencia del niño disfónico para el correctouso de su voz, reduciendo el impacto biopsicosocial inherente a la patología de la voz. Este instrumento, diseñado esencialmente para niños de ambos sexos, entre siete y nueve años de edad, y simultáneamentepara sus padres y profesores, es un libro de literatura infantil que aborda el problema de la voz y de la patología nodular infantil, habiendo sido implementado en dos formatos: impreso en formato A5 y en formato digital con narración de audio incluida. El instrumento elaborado, ideal para la población objetivo previamente definida, es un excelente vehículo para aumentar la conciencia sobre la importancia de la voz y la promoción de hábitos vocales saludables y se puede utilizar en diferentes contextos de la vida del niño (terapéutico, familiar y escolar).

Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal.

Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence.

Foxj1 regulates floor plate cilia architecture and modifies the response of cells to sonic hedgehog signalling.

Sonic hedgehog signalling is essential for the embryonic development of many tissues including the central nervous system, where it controls the pattern of cellular differentiation. A genome-wide screen of neural progenitor cells to evaluate the Shh signalling-regulated transcriptome identified the forkhead transcription factor Foxj1. In both chick and mouse Foxj1 is expressed in the ventral midline of the neural tube in cells that make up the floor plate. Consistent with the role of Foxj1 in the formation of long motile cilia, floor plate cells produce cilia that are longer than the primary cilia found elsewhere in the neural tube, and forced expression of Foxj1 in neuroepithelial cells is sufficient to increase cilia length. In addition, the expression of Foxj1 in the neural tube and in an Shh-responsive cell line attenuates intracellular signalling by decreasing the activity of Gli proteins, the transcriptional mediators of Shh signalling. We show that this function of Foxj1 depends on cilia. Nevertheless, floor plate identity and ciliogenesis are unaffected in mouse embryos lacking Foxj1 and we provide evidence that additional transcription factors expressed in the floor plate share overlapping functions with Foxj1. Together, these findings identify a novel mechanism that modifies the cellular response to Shh signalling and reveal morphological and functional features of the amniote floor plate that distinguish these cells from the rest of the neuroepithelium.

SOX9 induces and maintains neural stem cells.

Neural stem cells (NSCs) are uncommitted cells of the CNS defined by their multipotentiality and ability to self renew. We found these cells to not be present in substantial numbers in the CNS until after embryonic day (E) 10.5 in mouse and E5 in chick. This coincides with the induction of SOX9 in neural cells. Gain- and loss-of-function studies indicated that SOX9 was essential for multipotent NSC formation. Moreover, Sonic Hedgehog was able to stimulate precocious generation of NSCs by inducing Sox9 expression. SOX9 was also necessary for the maintenance of multipotent NSCs, as shown by in vivo fate mapping experiments in the adult subependymal zone and olfactory bulbs. In addition, loss of SOX9 led ependymal cells to adopt a neuroblast identity. These data identify a functional link between extrinsic and intrinsic mechanisms of NSCs specification and maintenance, and establish a central role for SOX9 in the process.

Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube.

The secreted ligand Sonic Hedgehog (Shh) organizes the pattern of cellular differentiation in the ventral neural tube. For the five neuronal subtypes, increasing levels and durations of Shh signaling direct progenitors to progressively more ventral identities. Here we demonstrate that this mode of action is not applicable to the generation of the most ventral cell type, the nonneuronal floor plate (FP). In chick and mouse embryos, FP specification involves a biphasic response to Shh signaling that controls the dynamic expression of key transcription factors. During gastrulation and early somitogenesis, FP induction depends on high levels of Shh signaling. Subsequently, however, prospective FP cells become refractory to Shh signaling, and this is a prerequisite for the elaboration of their identity. This prompts a revision to the model of graded Shh signaling in the neural tube, and provides insight into how the dynamics of morphogen signaling are deployed to extend the patterning capacity of a single ligand. In addition, we provide evidence supporting a common scheme for FP specification by Shh signaling that reconciles mechanisms of FP development in teleosts and amniotes.

MK-801 alters RGS2 levels and adenylyl cyclase sensitivity in the rat striatum.

The present report examines the effects of acute NMDA antagonism on Regulator of G Protein Signaling 2 (RGS2) expression and adenylyl cyclase sensitivity in the rat striatum. MK-801 and phencyclidine rapidly down-regulate RGS2 mRNA. The down-regulation of RGS2 by MK-801 was dose dependent and transient. Because previous reports showed that RGS2 attenuates activity of adenylyl cyclase, RGS2 protein level and sensitivity of adenylyl cyclase to forskolin was tested 2 h after administration of MK-801 (1 mg/kg). In striatal membranes of these rats, RGS2 protein level was 17% lower and forskolin-stimulated cAMP production 38% higher than in controls. These findings reveal a cross-talk between NMDA receptors and adenylyl cyclase and suggest a general cross-talk mechanism by which RGS proteins transcriptionally regulated by ionotropic receptors can alter signaling properties of metabotropic receptors.

Dopamine receptor-mediated regulation of RGS2 and RGS4 mRNA differentially depends on ascending dopamine projections and time.

RGS2 and RGS4 mRNAs are regulated in the rat striatum by dopaminergic agents. The present study further characterizes this regulation in three experiments. First, dopamine type 1 (receptor) (D1)- and dopamine type 2 (receptor) (D2)-mediated regulator of G-protein signalling (RGS) gene regulation was investigated in animals with deleted ascending dopaminergic pathways. We showed that RGS2 expression is controlled by D1 receptors either by direct action on D1 receptors or indirectly by presynaptic D2 receptors. Conversely, RGS4 gene expression is independent of presynaptic D2 receptors. Second, the study of colocalization between RGS2 or RGS4 and D1 or D2 by double labelling in situ hybridization histochemistry revealed broad expression of RGS2 and RGS4 mRNA in striatal subpopulations with colocalization of RGS2 and RGS4 with both D1 and D2 receptors. Finally, to test how far their gene regulation is temporally concerted, changes in RGS2 and RGS4 mRNA levels were measured in parallel with receptor occupancy by specific dopaminergic drugs at different time-points. RGS2 was rapidly/transiently up-regulated by the D1 agonist SKF82958 and the D2 antagonist haloperidol (peak at 0.5 h) and down-regulated by the D1 antagonist SCH23390 and the D2 agonist quinpirole (trough at 1 and 2 h). RGS4 showed a delayed/transient up-regulation with SCH23390 and quinpirole (peak at 4 and 2 h) and down-regulation with haloperidol (trough at 8 h). Depending on the drug used, the degree of receptor occupancy did (D1 agonist and RGS2) or did not (D2 antagonist and RGS2) run parallel to RGS gene expression changes, indicating that certain drug effects are direct and others indirect. The precise control of RGS2 and RGS4 expression by dopamine receptors pleads in favour of their potential contribution to the fine-tuning of D1 and D2 receptor signalling cascades.