283 research outputs found

    Epidemiology of dermatophytoses in 31 municipalities of the province of Buenos Aires, Argentina: A 6-year study

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    Background No reliable data are available in the province of Buenos Aires regarding the frequency of dermatophytoses and other fungal diseases. The distribution of the clinical forms and the species involved are also unknown. Aims To present the data collected by the laboratories participating in the Mycology Network of the province of Buenos Aires (MNPBA) from a retrospective epidemiological survey on dermatophytoses. Methods A descriptive and exploratory analysis was performed on the cases of dermatophytoses gathered between 2002 and 2007 by the Mycology Network of the province of Buenos Aires. Results Of the 3966 dermatophytosis cases reported by 41 laboratories in 31 municipalities, more than a half occurred in three highly populated urban municipalities. The male:female ratio was 1:1.5. The most frequent clinical form was tinea unguium, diagnosed in 904 cases (51.83%), followed by tinea capitis (19.32%), tinea corporis (15.19%), tinea pedis (6.77%), tinea cruris (3.73%), and tinea manuum (2.18%). The species involved was identified in 1368 (33.49%) cases. Trichophyton rubrum was the most common species, with a frequency of 42.03%. An association was found between urban municipalities and T. rubrum or the Trichophyton mentagrophytes complex. Conclusions Results from the MNPBA survey provide valuable information that should enable further interventions to be designed in order to prevent and control the disease.UIQA -Unidade de Investigação Química Ambientalinfo:eu-repo/semantics/publishedVersio

    Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function

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    The P2X7 receptor is a member of the P2X family of ligand-gated ion channels. A single-nucleotide polymorphism leading to a glutamine (Gln) by arginine (Arg) substitution at codon 460 of the purinergic P2X7 receptor (P2X7R) has been associated with mood disorders. No change in function (loss or gain) has been described for this SNP so far. Here we show that although the P2X7R-Gln460Arg variant per se is not compromised in its function, co-expression of wild-type P2X7R with P2X7R-Gln460Arg impairs receptor function with respect to calcium influx, channel currents and intracellular signaling in vitro. Moreover, co-immunoprecipitation and FRET studies show that the P2X7R-Gln460Arg variant physically interacts with P2X7R-WT. Specific silencing of either the normal or polymorphic variant rescues the heterozygous loss of function phenotype and restores normal function. The described loss of function due to co-expression, unique for mutations in the P2RX7 gene so far, explains the mechanism by which the P2X7R-Gln460Arg variant affects the normal function of the channel and may represent a mechanism of action for other mutations.Fil: Aprile García, Fernando. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Metzger, Michael W.. Max Planck Institute of Psychiatry; AlemaniaFil: Paez Pereda, Marcelo. Max Planck Institute of Psychiatry; AlemaniaFil: Stadler, Herbert. Affectis Pharmaceuticals; AlemaniaFil: Acuña, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Senin, Sergio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Hoijman, Esteban. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Microscopías Avanzadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Refojo, Damian. Max Planck Institute of Psychiatry; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mitkovski, Mišo. Max Planck Institute of Experimental Medicine; AlemaniaFil: Panhuysen, Markus. Affectis Pharmaceuticals; AlemaniaFil: Stühmer, Walter. Max Planck Institute of Experimental Medicine; AlemaniaFil: Holsboer, Florian. Max Planck Institute of Psychiatry; Alemania. HMNC Brain Health; AlemaniaFil: Deussing, Jan M.. Max Planck Institute of Psychiatry; AlemaniaFil: Arzt, Eduardo Simon. Max Planck Institute of Psychiatry; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentin

    Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.

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    Stressors motivate an array of adaptive responses ranging from \u27fight or flight\u27 to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF\u27s capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders

    Neddylation regulates excitatory synaptic transmission and plasticity

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    Post-translational modifications, like phosphorylation, ubiquitylation, and sumoylation, have been shown to impact on synaptic neurotransmission by modifying pre- and postsynaptic proteins and therefore alter protein stability, localization, or protein-protein interactions. Previous studies showed that post-translational modifications are essential during the induction of synaptic plasticity, defined by a major reorganization of synaptic proteins. We demonstrated before that neddylation, a post-translational modification that covalently binds Nedd8 to lysine-residues, strongly affects neuronal maturation and spine stability. We now analysed the consequences of inhibiting neddylation on excitatory synaptic transmission and plasticity, which will help to narrow down possible targets, to make educated guesses, and test specific candidates. Here, we show that acute inhibition of neddylation impacts on synaptic neurotransmission before morphological changes occur. Our data indicate that pre- and postsynaptic proteins are neddylated since the inhibition of neddylation impacts on presynaptic release probability and postsynaptic receptor stabilization. In addition, blocking neddylation during the induction of long-term potentiation and long-term inhibition abolished both forms of synaptic plasticity. Therefore, this study shows the importance of identifying synaptic targets of the neddylation pathway to understand the regulation of synaptic transmission and plasticity.Fil: Brockmann, Marisa M.. Universitat Bonn; Alemania. Max Planck Institute Of Psychiatry; AlemaniaFil: Döngi, Michael. Universitat Bonn; AlemaniaFil: Einsfelder, Ulf. Universitat Bonn; AlemaniaFil: Körber, Nils. Universitat Bonn; AlemaniaFil: Refojo, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Stein, Valentin. Universitat Bonn; Alemani

    Neurobiological Mechanisms That Contribute to Stress-related Cocaine Use

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    The ability of stressful life events to trigger drug use is particularly problematic for the management of cocaine addiction due to the unpredictable and often uncontrollable nature of stress. For this reason, understanding the neurobiological processes that contribute to stress-related drug use is important for the development of new and more effective treatment strategies aimed at minimizing the role of stress in the addiction cycle. In this review we discuss the neurocircuitry that has been implicated in stress-induced drug use with an emphasis on corticotropin releasing factor actions in the ventral tegmental area (VTA) and an important pathway from the bed nucleus of the stria terminalis to the VTA that is regulated by norepinephrine via actions at beta adrenergic receptors. In addition to the neurobiological mechanisms that underlie stress-induced cocaine seeking, we review findings suggesting that the ability of stressful stimuli to trigger cocaine use emerges and intensifies in an intake-dependent manner with repeated cocaine self-administration. Further, we discuss evidence that the drug-induced neuroadaptations that are necessary for heightened susceptibility to stress-induced drug use are reliant on elevated levels of glucocorticoid hormones at the time of cocaine use. Finally, the potential ability of stress to function as a “stage setter” for drug use – increasing sensitivity to cocaine and drug-associated cues – under conditions where it does not directly trigger cocaine seeking is discussed. As our understanding of the mechanisms through which stress promotes drug use advances, the hope is that so too will the available tools for effectively managing addiction, particularly in cocaine addicts whose drug use is stress-driven

    Development of a species-specific RNA polymerase I-based shRNA expression vector

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    RNA interference (RNAi) can be induced in vitro either by application of synthetic short interfering RNAs (siRNAs), or by intracellular expression of siRNAs or short hairpin RNAs (shRNAs) from transfected vectors. The most widely used promoters for siRNA/shRNA expression are based on polymerase III (Pol III)-dependent transcription. We developed an alternative vector for siRNA/shRNA expression, using a mouse RNA polymerase I (Pol I) promoter. Pol I-dependent transcription serves in cells for production of ribosomal RNA (rRNA), and as such, is ubiquitously and stably active in different cell types. As Pol I-dependent transcription is highly species-specific, Pol I-based system provides an important biosafety advantage with respect to silencing of genes with unknown functions

    Sustained release of BCNU for the treatment of intraocular malignancies in animal models

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    Sustained release, of 1,3-his(2)chloroethyl)-l-nitrosourea (BCNU) via an episcleral implante

    Quinone oxidoreductase from Staphylococcus aureus

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    Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia ( PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT , Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Fundação para a Ciência e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Fundação para a Ciência e a Tecnologia UI/BD/153052/2022. The work was funded by Fundação para a Ciência e a Tecnologia (PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT, Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Fundação para a Ciência e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Publisher Copyright: © 2022 The Author(s)Staphylococcus aureus is an opportunistic pathogen and one of the most frequent causes for community acquired and nosocomial bacterial infections. Even so, its energy metabolism is still under explored and its respiratory enzymes have been vastly overlooked. In this work, we unveil the dihydroorotate:quinone oxidoreductase (DHOQO) from S. aureus, the first example of a DHOQO from a Gram-positive organism. This protein was shown to be a FMN containing menaquinone reducing enzyme, presenting a Michaelis-Menten behaviour towards the two substrates, which was inhibited by Brequinar, Leflunomide, Lapachol, HQNO, Atovaquone and TFFA with different degrees of effectiveness. Deletion of the DHOQO coding gene (Δdhoqo) led to lower bacterial growth rates, and effected in cell morphology and metabolism, most importantly in the pyrimidine biosynthesis, here systematized for S. aureus MW2 for the first time. This work unveils the existence of a functional DHOQO in the respiratory chain of the pathogenic bacterium S. aureus, enlarging the understanding of its energy metabolism.publishersversionpublishe

    Evaluation of the application of not traumatic linking and learning techniques in two races of horses

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    Existe un conjunto de prácticas que permiten la familiarización del potrillo con el entorno, además de facilitar la detección y el diagnóstico de enfermedades, malformaciones y/o lesiones posparto (Gónzalez del Pino et al, 2009). Se conocen como Técnicas de Vinculación y Aprendizaje no Traumáticas (TVANT) y son realizadas mediante un contacto diario, tanto con el potrillo como con su madre, implicando una revisión habitual a cada individuo desde el día 7 al 14 desde el nacimiento. Nuestra experiencia en raza Criolla ha mostrado que las TVANT producen resultados satisfactorios (Abbiati et al, 2016). El objetivo de este trabajo fue comparar la duración del proceso para las razas Criolla y Silla Argentino en las maniobras de las TVANT.Facultad de Ciencias Veterinaria

    Chronic CRH depletion from GABAergic, long-range projection neurons in the extended amygdala reduces dopamine release and increases anxiety

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    The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release.Fil: Dedic, Nina. Max Planck Institute Of Psychiatry; AlemaniaFil: Kühne, Claudia. Max Planck Institute Of Psychiatry; AlemaniaFil: Jakovcevski, Mira. Max Planck Institute Of Psychiatry; AlemaniaFil: Hartmann, Jakob. Max Planck Institute Of Psychiatry; AlemaniaFil: Genewsky, Andreas J.. Max Planck Institut Of Psychiatry; AlemaniaFil: Gomes, Karina S.. Max Planck Institute Of Psychiatry; AlemaniaFil: Anderzhanova, Elmira. Max Planck Institute Of Psychiatry; AlemaniaFil: Pöhlmann, Max L.. Max Planck Institute Of Psychiatry; AlemaniaFil: Chang, Simon. Max Planck Institute Of Psychiatry; AlemaniaFil: Kolarz, Adam. Max Planck Institute Of Psychiatry; AlemaniaFil: Vogl, Annette M.. Max Planck Institute Of Psychiatry; AlemaniaFil: Dine, Julien. Max Planck Institute Of Psychiatry; AlemaniaFil: Metzger, Michael W.. Max Planck Institute of Psychiatry; ArmeniaFil: Schmid, Bianca. Max Planck Institute Of Psychiatry; AlemaniaFil: Almada, Rafael C.. Max Planck Institute Of Psychiatry; AlemaniaFil: Ressler, Kerry J.. Harvard Medical School; Estados UnidosFil: Wotjak, Carsten T.. Max Planck Institute Of Psychiatry; AlemaniaFil: Grinevich, Valery. University of Heidelberg; AlemaniaFil: Chen, Alon. Max Planck Institute Of Psychiatry; AlemaniaFil: Schmidt, Mathias V.. Institute Of Developmental Genetics, Helmholtz Zentrum; AlemaniaFil: Wurst, Wolfgang. German Center for Neurodegenerative Diseases; AlemaniaFil: Refojo, Damian. Max Planck Institute Of Psychiatry; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Deussing, Jan M.. Max Planck Institute Of Psychiatry; Alemani
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