2,333 research outputs found

    Overexpression of glucocorticoid-induced leucine zipper (GILZ) increases susceptibility to imiquimod-induced psoriasis and involves cutaneous activation of TGF-β1

    Get PDF
    Psoriasis vulgaris is a chronic inflammatory skin disease affecting millions of people. Its pathophysiology is complex and involves a skin compartment with epidermal and immune cells which produce cytokines, e.g. belonging to the IL-23-Th17-cell axis. Glucocorticoids (GCs) are the most common therapeutics used in cutaneous inflammatory disorders and GC-induced leucine zipper (GILZ) has emerged as a mediator of GCs due to its anti-inflammatory actions, theoretically lacking GC side-effects. We evaluated whether GILZ may provide a better therapeutic index in comparison to GCs during the onset and progression of psoriasis by generating and characterizing a mouse model with generalized overexpression of this protein (GILZ-Tg mice) and the imiquimod (IMQ) psoriasis model. Unexpectedly, in GILZ-Tg mice, the severity of IMQ-induced psoriasis-like skin lesions as well as induction of cytokines commonly up-regulated in human psoriasis (Il-17, Il-22, Il-23, Il-6, S100a8/a9, and Stat3) was significantly more pronounced relative to GILZ-Wt mice. The increased susceptibility to IMQ-induced psoriasis of GILZ-Tg mice was significantly associated with skin-specific over-activation of TGF-beta 1-mediated signaling via SMAD2/3. Our findings demonstrate that GILZ may behave as pro-inflammatory protein in certain tissues and that, similar to prolonged GC therapy, GILZ as an alternative treatment for psoriasis may also have adverse effects

    Geologists of Russian origin in Latin America

    Get PDF
    Se describe la vida y trayectoria de geólogos que más allá de su nacionalidad (rusa, ucraniana, tártara, alemana, etc.), nacieron en territorios que pertenecieron al Imperio Ruso, la Unión Soviética o la Federación Rusa, y de sus descendientes graduados en geología, todos los cuales vivieron y trabajaron en países de Latinoamérica (en los cuales las lenguas que prevalecen son el español y el portugués). También se incluyen geólogos de la URSS que trabajaron temporariamente en algunos países de Latinoamérica y que con sus publicaciones contribuyeron a la Geología.We describe here the life and career of geologists who beyond their nationality(Russian, Ukrainian, Tatar, German, etc.), were born on the territory of the Russian Empire, the SovietUnion or the Russian Federation and their descendants that became geologists, all of whom lived andworked in Latin-American countries (where Spanish and Portuguese languages prevail). We includealso geologists from USSR who worked temporary in some countries of Latin America and leftcontributions to geology in form of publications.Fil: Tchoumatchenco, Platon. Bulgarian Academy Of Sciences; BulgariaFil: Riccardi, Alberto Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Durand Delga, Michel. Centre National de la Recherche Scientifique; FranciaFil: Alonso, Ricardo. Universidad Nacional de Salta; ArgentinaFil: Wiasemsky, Michel. Centre National de la Recherche Scientifique; FranciaFil: Boltovskoy, Demetrio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Charrier González, Reynaldo. Sociedad Geologica de Chile; ChileFil: Minina, Elena. State Geological Museum “V.I.Vernadsky”; Rusi

    Metacognition as a predictor of improvements in personality disorders

    Get PDF
    Personality Disorders (PDs) are particularly hard to treat and treatment drop-out rates are high. Several authors have agreed that psychotherapy is more successful when it focuses on the core of personality pathology. For this reason, therapists dealing with PDs need to understand the psychopathological variables that characterize this pathology and exactly what contributes to maintaining psychopathological processes. Moreover, several authors have noted that one key problem that characterizes all PDs is an impairment in understanding mental states - here termed metacognition - which could also be responsible for therapy failures. Unfortunately, a limited number of studies have investigated the role of mentalization in the process of change during psychotherapy. In this paper, we assume that poor metacognition corresponds to a core element of the general pathology of personality, impacts a series of clinical variables, generates symptoms and interpersonal problems, and causes treatment to be slower and less effective. We explored whether changes in metacognition predicted an improvement among different psychopathological variables characterizing PDs; 193 outpatients were treated at the Third Center of Cognitive Psychotherapy in Rome, Italy, and followed a structured path tailored for the different psychopathological variables that emerged from a comprehensive psychodiagnostic assessment that considered patients' symptoms, metacognitive abilities, interpersonal relationships, personality psychopathology, and global functioning. The measurements were repeated after a year of treatment. The results showed that changes in metacognitive abilities predicted improvements in the analyzed variable

    RNA sequencing and de novo assembly of the digestive gland transcriptome in Mytilus galloprovincialis fed with toxinogenic and non-toxic strains of Alexandrium minutum

    Get PDF
    Background The Mediterranean mussel Mytilus galloprovincialis is marine bivalve with a relevant commercial importance as well as a key sentinel organism for the biomonitoring of environmental pollution. Here we report the RNA sequencing of the mussel digestive gland, performed with the aim: a) to produce a high quality de novo transcriptome assembly, thus improving the genetic and molecular knowledge of this organism b) to provide an initial assessment of the response to paralytic shellfish poisoning (PSP) on a molecular level, in order to identify possible molecular markers of toxin accumulation. Results The comprehensive de novo assembly and annotation of the transcriptome yielded a collection of 12,079 non-redundant consensus sequences with an average length of 958 bp, with a high percentage of full-length transcripts. The whole-transcriptome gene expression study indicated that the accumulation of paralytic toxins produced by the dinoflagellate Alexandrium minutum over a time span of 5 days scarcely affected gene expression, but the results need further validation with a greater number of biological samples and naturally contaminated specimens. Conclusion The digestive gland reference transcriptome we produced significantly improves the data collected from previous sequencing efforts and provides a basic resource for expanding functional genomics investigations in M. galloprovincialis. Although not conclusive, the results of the RNA-seq gene expression analysis support the classification of mussels as bivalves refractory to paralytic shellfish poisoning and point out that the identification molecular biomarkers of PSP in the digestive gland of this organism is problematic

    A cationic tetrapyrrole inhibits toxic activities of the cellular prion protein

    Get PDF
    Prion diseases are rare neurodegenerative conditions associated with the conformational conversion of the cellular prion protein (PrPC) into PrPSc, a self-replicating isoform (prion) that accumulates in the central nervous system of affected individuals. The structure of PrPSc is poorly defined, and likely to be heterogeneous, as suggested by the existence of different prion strains. The latter represents a relevant problem for therapy in prion diseases, as some potent anti-prion compounds have shown strain-specificity. Designing therapeutics that target PrPC may provide an opportunity to overcome these problems. PrPC ligands may theoretically inhibit the replication of multiple prion strains, by acting on the common substrate of any prion replication reaction. Here, we characterized the properties of a cationic tetrapyrrole [Fe(III)-TMPyP], which was previously shown to bind PrPC, and inhibit the replication of a mouse prion strain. We report that the compound is active against multiple prion strains in vitro and in cells. Interestingly, we also find that Fe(III)-TMPyP inhibits several PrPC-related toxic activities, including the channel-forming ability of a PrP mutant, and the PrPC-dependent synaptotoxicity of amyloid-beta (A beta) oligomers, which are associated with Alzheimer's Disease. These results demonstrate that molecules binding to PrPC may produce a dual effect of blocking prion replication and inhibiting PrPC-mediated toxicity

    Exploring the HME and HAE1 efflux systems in the genus Burkholderia

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The genus <it>Burkholderia </it>includes a variety of species with opportunistic human pathogenic strains, whose increasing global resistance to antibiotics has become a public health problem. In this context a major role could be played by multidrug efflux pumps belonging to Resistance Nodulation Cell-Division (RND) family, which allow bacterial cells to extrude a wide range of different substrates, including antibiotics. This study aims to i) identify <it>rnd </it>genes in the 21 available completely sequenced <it>Burkholderia </it>genomes, ii) analyze their phylogenetic distribution, iii) define the putative function(s) that RND proteins perform within the <it>Burkholderia </it>genus and iv) try tracing the evolutionary history of some of these genes in <it>Burkholderia</it>.</p> <p>Results</p> <p>BLAST analysis of the 21 <it>Burkholderia </it>sequenced genomes, using experimentally characterized <it>ceoB </it>sequence (one of the RND family counterpart in the genus <it>Burkholderia</it>) as probe, allowed the assembly of a dataset comprising 254 putative RND proteins. An extensive phylogenetic analysis revealed the occurrence of several independent events of gene loss and duplication across the different lineages of the genus <it>Burkholderia</it>, leading to notable differences in the number of paralogs between different genomes. A putative substrate [antibiotics (HAE1 proteins)/heavy-metal (HME proteins)] was also assigned to the majority of these proteins. No correlation was found between the ecological niche and the lifestyle of <it>Burkholderia </it>strains and the number/type of efflux pumps they possessed, while a relation can be found with genome size and taxonomy. Remarkably, we observed that only HAE1 proteins are mainly responsible for the different number of proteins observed in strains of the same species. Data concerning both the distribution and the phylogenetic analysis of the HAE1 and HME in the <it>Burkholderia </it>genus allowed depicting a likely evolutionary model accounting for the evolution and spreading of HME and HAE1 systems in the <it>Burkholderia </it>genus.</p> <p>Conclusion</p> <p>A complete knowledge of the presence and distribution of RND proteins in <it>Burkholderia </it>species was obtained and an evolutionary model was depicted. Data presented in this work may serve as a basis for future experimental tests, focused especially on HAE1 proteins, aimed at the identification of novel targets in antimicrobial therapy against <it>Burkholderia </it>species.</p

    Geólogos de origem russa na América Latina

    Get PDF
    We describe here the life and career of geologists who beyond their nationality (Russian, Ukrainian, Tatar, German, etc.), were born on the territory of the Russian Empire, the Soviet Union or the Russian Federation and their descendants that became geologists, all of whom lived and worked in Latin-American countries (where Spanish and Portuguese languages prevail). We include also geologists from USSR who worked temporary in some countries of Latin America and left contributions to geology in form of publications.Se describe la vida y trayectoria de geólogos que más allá de su nacionalidad (rusa, ucraniana, tártara, alemana, etc.), nacieron en territorios que pertenecieron al Imperio Ruso, la Unión Soviética o la Federación Rusa, y de sus descendientes graduados en geología, todos los cuales vivieron y trabajaron en países de Latinoamérica (en los cuales las lenguas que prevalecen son el español y el portugués). También se incluyen geólogos de la URSS que trabajaron temporariamente en algunos países de Latinoamérica y que con sus publicaciones contribuyeron a la Geología.Descreve a vida e a trajetória de geólogos que, além de sua nacionalidade (russos, ucranianos, tártaros, alemães, etc.), nasceram em territórios pertencentes ao Império Russo, à União Soviética ou à Federação Russa, e seus descendentes se formaram em geologia, todos os quais viveram e trabalharam em países latinoamericanos (nos quais as línguas dominantes são o espanhol e o português). Também estão incluídos geólogos da URSS que trabalharam temporariamente em alguns países da América Latina e que contribuíram para a Geologia com suas publicações.Facultad de Ciencias Naturales y Muse

    Balance between Regulatory T and Th17 Cells in Systemic Lupus Erythematosus: The Old and the New

    Get PDF
    Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease. Treg cells appear to be impaired and therefore unable to counteract autoreactive T lymphocytes. Conversely, Th17 cells accumulate in target organs contributing to local IL-17 production and eventually tissue damage. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent an intriguing and useful tool for SLE treatment in the next future. In this paper, the current knowledge about Treg and Th17 cells interplay in SLE will be discussed

    Geólogos de origem russa na América Latina

    Get PDF
    We describe here the life and career of geologists who beyond their nationality (Russian, Ukrainian, Tatar, German, etc.), were born on the territory of the Russian Empire, the Soviet Union or the Russian Federation and their descendants that became geologists, all of whom lived and worked in Latin-American countries (where Spanish and Portuguese languages prevail). We include also geologists from USSR who worked temporary in some countries of Latin America and left contributions to geology in form of publications.Se describe la vida y trayectoria de geólogos que más allá de su nacionalidad (rusa, ucraniana, tártara, alemana, etc.), nacieron en territorios que pertenecieron al Imperio Ruso, la Unión Soviética o la Federación Rusa, y de sus descendientes graduados en geología, todos los cuales vivieron y trabajaron en países de Latinoamérica (en los cuales las lenguas que prevalecen son el español y el portugués). También se incluyen geólogos de la URSS que trabajaron temporariamente en algunos países de Latinoamérica y que con sus publicaciones contribuyeron a la Geología.Descreve a vida e a trajetória de geólogos que, além de sua nacionalidade (russos, ucranianos, tártaros, alemães, etc.), nasceram em territórios pertencentes ao Império Russo, à União Soviética ou à Federação Russa, e seus descendentes se formaram em geologia, todos os quais viveram e trabalharam em países latinoamericanos (nos quais as línguas dominantes são o espanhol e o português). Também estão incluídos geólogos da URSS que trabalharam temporariamente em alguns países da América Latina e que contribuíram para a Geologia com suas publicações.Facultad de Ciencias Naturales y Muse

    A particular temper: mineralogical and petrographic characterisation of ceramic fabrics with glauconitic inclusions

    Get PDF
    This paper focuses on the mineralogical and petrographic characterisation of ceramic fabrics rich in glauconitic pellets, found out in a few local productions of European and Mediterranean sites dated from Prehistory to the Middle Ages. The main distinguishing features of glauconitic inclusions are their rounded shape, dark colour and peculiar chemical composition. During the firing – as also evidenced by a few preliminary experimental tests on glauconitic sediments – the pellets change in colour (from green to red or black in thin section) because of the oxidation of divalent iron and their texture becomes more homogeneous, up to the partial or complete vitrification at moderately high temperatures.Dans cet article, on présente la caractérisation minéralogique et pétrographique des pâtes céramiques riches en pellets glauconitiques, trouvées dans quelques productions locales de sites européens et méditerranéens d’age préhistorique à médiéval. Les plus importants éléments discriminants des pellets glauconitiques sont leur forme arrondie, leur couleur rouge ou noire et leur composition chimique particulière. Durant la cuisson, comme quelques tests préliminaires sur sédiments glauconitiques l’ont confirmé, les pellets changent de couleur (de vert à rouge ou noir en lame mince), à cause de l’oxydation du fer bivalent, et leur texture devient plus homogène, jusqu’à la vitrification partielle ou totale à des températures relativement hautes
    corecore