Basal adenosine modulates the functional properties of AMPA receptors in mouse hippocampal neurons through the activation of A1R A2AR and A3R

Adenosine is a widespread neuromodulator within the CNS and its extracellular level is increased during hypoxia or intense synaptic activity, modulating pre- and postsynaptic sites. We studied the neuromodulatory action of adenosine on glutamatergic currents in the hippocampus, showing that activation of multiple adenosine receptors (ARs) by basal adenosine impacts postsynaptic site. Specifically, the stimulation of both A1R and A3R reduces AMPA currents, while A2AR has an opposite potentiating effect. The effect of ARs stimulation on glutamatergic currents in hippocampal cultures was investigated using pharmacological and genetic approaches. A3R inhibition by MRS1523 increased GluR1-Ser845 phosphorylation and potentiated AMPA current amplitude, increasing the apparent affinity for the agonist. A similar effect was observed blocking A1R with DPCPX or by genetic deletion of either A3R or A1R. Conversely, impairment of A2AR reduced AMPA currents, and decreased agonist sensitivity. Consistently, in hippocampal slices, ARs activation by AR agonist NECA modulated glutamatergic current amplitude evoked by AMPA application or afferent fiber stimulation. Opposite effects of AR subtypes stimulation are likely associated to changes in GluR1 phosphorylation and represent a novel mechanism of physiological modulation of glutamatergic transmission by adenosine, likely acting in normal conditions in the brain, depending on the level of extracellular adenosine and the distribution of AR subtypes

Dealing with the aftermath of mass disasters. A field study on the application of EMDR integrative group treatment protocol with child survivors of the 2016 Italy earthquakes

This study explored the effects of the EMDR Integrative Group Treatment Protocol (EMDR-IGTP) on child survivors of the earthquakes that struck Umbria, a region of central Italy, on August 24th and on October 26th 2016. Three hundred and thirty-two children from the town of Norcia and nearby severely disrupted villages received 3 cycles of EMDR-IGTP. The Emotion Thermometers (ET-5) and the Children’s Revised Impact of Event Scale (CRIES-13) were administered before (T0) and about 1 week after the conclusion of the third cycle (T3) of EMDR-IGTP. At T3, older children showed a reduction of distress and anger, whereas younger children reported an increase on these domains; moreover, older children reported a greater reduction of anxiety than younger ones. A greater reduction of distress, anxiety, and need for help was evidenced in females, whereas a greater improvement in depressive symptoms was evidenced in males. The effects of the EMDR-IGTP treatment on post-traumatic symptoms were particularly evident in older children, compared to younger ones, and marginally greater in females than in males; moreover, a greater improvement was found in children who had received a timelier intervention, than in those who received delayed treatment. These results provide further evidence for the utility of EMDR-IGTP in dealing with the extensive need for mental health services in mass disaster contexts. Also, these data highlight the importance of providing EMDR-IGTP in the immediate aftermath of a natural disaster, to contribute significantly in restoring adaptive psychological functioning in children, especially in older ones

Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma

BACKGROUND: Growing evidence is showing that metastatic cell populations are able to transfer their characteristics to less malignant cells. Exosomes (EXOs) are membrane vesicles of endocytic origin able to convey their cargo of mRNAs, microRNAs (miRs), proteins and lipids from donors to proximal as well as distant acceptor cells. Our previous results indicated that miR-221&222 are key factors for melanoma development and dissemination. The aim of this study was to verify whether the tumorigenic properties associated with miR-222 overexpression can be also propagated by miR-222-containing EXOs. METHODS: EXOs were isolated by UltraCentrifugation or Exoquick-TC(®) methods. Preparations of melanoma-derived vesicles were characterized by using the Nanosight™ technology and the expression of exosome markers analyzed by western blot. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR. Confocal microscopy was used to evaluate transfer and uptake of microvesicles from donor to recipient cells. The functional significance of exosomal miR-222 was estimated by analyzing the vessel-like process formation, as well as cell cycle rates, invasive and chemotactic capabilities. RESULTS: Besides microvesicle marker characterization, we evidenced that miR-222 exosomal expression mostly reflected its abundance in the cells of origin, correctly paralleled by repression of its target genes, such as p27Kip1, and induction of the PI3K/AKT pathway, thus confirming its functional implication in cancer. The possible differential significance of PI3K/AKT blockade was assessed by using the BKM120 inhibitor in miR-222-transduced cell lines. In addition, in vitro cultures showed that vesicles released by miR-222-overexpressing cells were able to transfer miR-222-dependent malignancy when taken-up by recipient primary melanomas. Results were confirmed by antagomiR-221&222 treatments and by functional observations after internalization of EXOs devoid of these miRs

A Contribuição do serviço social no processo de inclusão da pessoa portadora de deficiência

TCC (graduação) - Universidade Federal de Santa Catarina, Centro Sócio Econômico, Curso de Serviço Social.O presente trabalho consiste em um esforço para a sistematização de um estudo sobre a pessoa portadora de deficiência mental, partindo-se da discussão de como evoluiu a própria concepção da pessoa portadora de deficiência na sociedade e do reconhecimento das políticas de atenção e dos direitos sociais conquistados, com ênfase no direito ao trabalho. Este trabalho também apresenta a história da política estadual, assumida pela Fundação Catarinense de Educação Especial, com base na experiência de estágio no Centro de Educação e Trabalho I e a ação profissional do Serviço Social nesse processo. Os resultados deste estudo apontam para a contribuição do Serviço Social na afirmação da cidadania da pessoa portadora de deficiência, na perspectiva de defesa dos direitos e da promoção de sua inclusão socia

Late diagnosis of celiac disease in an asymptomatic infant with growth failure

The clinical spectrum for celiac disease (CD) is broad and includes cases with either typical (intestinal) or atypical (extraintestinal) features, often making the diagnosis of CD very difficult. We describe the case of a girl presenting with stunted growth and malnourishment. She was evaluated at 14 months for decreased growth rate without any signs of gastrointestinal, renal or endocrine disorders. She was evaluated for CD, but resulted negative for anti-tTG antibodies. At the age of 4.1 years, she exhibited basal dental enamel hypoplasia, iron deficiency anaemia despite repeated iron supplementation, with persistent reduced height (-2.79 SDS), BMI (-0.76 SDS), growth velocity (-1.79 SDS) and delayed bone age (1.5 year). The CD screening was repeated and very high anti-tTG-IgA (128 IU/ml, normal values 40 IELs/100 epithelial cells) confirming the diagnosis of CD. A gluten-free diet was started and after only four months, her growth velocity increased from 4.83 cm/year (-1.79 SDS) to 6.53 cm/year (-0.15 SDS). In conclusion, we report the development of a positive serology for CD in an asymptomatic child with growth retardation, who previously was investigated for CD and resulted negative. Therefore, when faced with retarded growth in young patients, after excluding other malabsorption conditions and even when CD serological markers are negative, the paediatric endocrinologist should request HLA genotyping, before the intestinal biopsy, in order to check for the presence of risk alleles

Patrimonio reciente: arquitectura moderna en La Plata

La arquitectura moderna de la ciudad de La Plata, tiene una trayectoria que se desarrolla,- casi paralelamente a otros centros del país- a partir de la consolidación de las ideas del Movimiento Moderno y la transformación que esta nueva corriente ideológica-arquitectónica difundida en los países centrales establece como paradigmas. Nuevas ideas, necesitan nuevas formas de enseñanza y es así como surge la necesidad de crear un ámbito académico apropiado para lograr profesionales a la altura de esta naciente disciplina en el ámbito local, que se separará definitivamente del academicismo y de la ingeniería, por su condición específica para crear espacios que responden a las nuevas necesidades que la sociedad tiene. A partir de la creación del Departamento de Arquitectura de la UNLP en el año 1952, los primeros arquitectos de la ciudad irrumpirán con propuestas innovadoras para las demandas habitacionales de la época.Área temática 3: Historia de la Arquitectura, la Ciudad y el Territorio - Eje Investigació

Non-adiabatic couplings and dynamics in proton transfer reactions of H n + systems: Application to H 2 + H 2 + → H + H 3 + collisions

Analytical derivatives and non-adiabatic coupling matrix elements are derived for H n + systems (n = 3-5). The method uses a generalized Hellmann-Feynman theorem applied to a multi-state description based on diatomics-in-molecules (for H 3 +) or triatomics-in-molecules (for H 4 + and H 5 +) formalisms, corrected with a permutationally invariant many-body term to get high accuracy. The analytical non-adiabatic coupling matrix elements are compared with ab initio calculations performed at multi-reference configuration interaction level. These magnitudes are used to calculate H 2 (v ′ = 0, j ′ = 0) + H 2 + (v, j = 0) collisions, to determine the effect of electronic transitions using a molecular dynamics method with electronic transitions. Cross sections for several initial vibrational states of H 2 + are calculated and compared with the available experimental data, yielding an excellent agreement. The effect of vibrational excitation of H 2 + reactant and its relation with non-adiabatic processes are discussed. Also, the behavior at low collisional energies, in the 1 meV-0.1 eV interval, of interest in astrophysical environments, is discussed in terms of the long range behaviour of the interaction potential which is properly described within the triatomics-in-molecules formalismWe also thank the support from the European Research Council under the European Union’s Seventh Framework Programme (No. FP/2007-2013)/ERC Grant Agreement No. 610256 (NANOCOSMOS). We also acknowledge the COST Action No. CM1401 “Our Astrochemical History

Heterozygous GHR gene mutation in a child with idiopathic short stature

Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subject

Changes in growth hormone receptor gene expression during therapy in children with juvenile idiopathic arthritis.

Background: High levels of cytokines in juvenile idiopathic arthritis (JIA) can alter target cell sensitivity to growth hormone (GH) leading to short stature in adulthood. We hypothesized that the down-regulation of GH receptor (GHR) gene expression could be involved in growth failure of children with JIA. Methods: In 18 (12 F and 6 M) prepubertal JIA patients and 13 age- and sex-matched healthy children, we evaluated serum growth-promoting factors and inflammatory indexes. We also measured GHR gene expression, by real-time PCR, in lymphocytes of patients and controls. All parameters were evaluated in patients before and after treatment of JIA. Results: The most interesting (p = 0.007) result was the increase in GHR mRNA expression in all JIA patients. Moreover, we observed a significant (p = 0.0156) decrease in IL-6 levels in JIA patients after 2 years of therapy (19.37 +/- 41.01) with respect to basal values (90.84 +/- 124.71). On the contrary, IGF-I significantly (p = 0.0005) increased to a mean SDS value of 0 (range -1.69 to +1.70 SDS) with respect to values at disease onset (-0.64 SDS). Conclusions: Our preliminary data suggest that the restoration of both GHR gene expression and IGF-I secretion correlate with inactive disease in JIA children