The immediate early gene Egr3 Is required for hippocampal induction of Bdnf by electroconvulsive stimulation

Early growth response 3 (Egr3) is an immediate early gene (IEG) that is regulated downstream of a cascade of genes associated with risk for psychiatric disorders, and dysfunction of Egr3 itself has been implicated in schizophrenia, bipolar disorder, and depression. As an activity-dependent transcription factor, EGR3 is poised to regulate the neuronal expression of target genes in response to environmental events. In the current study, we sought to identify a downstream target of EGR3 with the goal of further elucidating genes in this biological pathway relevant for psychiatric illness risk. We used electroconvulsive stimulation (ECS) to induce high-level expression of IEGs in the brain, and conducted expression microarray to identify genes differentially regulated in the hippocampus of Egr3-deficient (-/-) mice compared to their wildtype (WT) littermates. Our results replicated previous work showing that ECS induces high-level expression of the brain-derived neurotrophic factor (Bdnf) in the hippocampus of WT mice. However, we found that this induction is absent in Egr3-/- mice. Quantitative real-time PCR (qRT-PCR) validated the microarray results (performed in males) and replicated the findings in two separate cohorts of female mice. Follow-up studies of activity-dependent Bdnf exons demonstrated that ECS-induced expression of both exons IV and VI requires Egr3. In situ hybridization demonstrated high-level cellular expression of Bdnf in the hippocampal dentate gyrus following ECS in WT, but not Egr3-/-, mice. Bdnf promoter analysis revealed eight putative EGR3 binding sites in the Bdnf promoter, suggesting a mechanism through which EGR3 may directly regulate Bdnf gene expression. These findings do not appear to result from a defect in the development of hippocampal neurons in Egr3-/- mice, as cell counts in tissue sections stained with anti-NeuN antibodies, a neuron-specific marker, did not differ between Egr3-/- and WT mice. In addition, Sholl analysis and counts of dendritic spines in golgi-stained hippocampal sections revealed no difference in dendritic morphology or synaptic spine density in Egr3-/-, compared to WT, mice. These findings indicate that Egr3 is required for ECS-induced expression of Bdnf in the hippocampus and suggest that Bdnf may be a downstream gene in our previously identified biologically pathway for psychiatric illness susceptibility.US National Institute of Mental Health [R01MH097803, R21MH113154]; Natural Sciences and Engineering Research Council of CanadaOpen access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Long-Term Oxygen Therapy in COPD: evidences and open questions of current indications

Long term oxygen therapy (LTOT) has been shown to improve the survival rate in Chronic Obstructive Pulmonary Disease (COPD) patients with severe resting hypoxemia by NOTT and MRC studies, published more than 25 years ago. The improved survival was found in patients who received oxygen for more than 15 hours/day. The effectiveness of LTOT has been documented only in stable COPD patients with severe chronic hypoxemia at rest (PaO255%. In fact no evidence supports the use of LTOT in COPD patients with moderate hypoxemia (55<PaO2<65 mmHg), and in those with decreased oxygen saturation (SO2<90%) during exercise or sleep. Furthermore, it is generally accepted without evidence that LTOT in clinical practice is warranted in other forms of chronic respiratory failure not due to COPD when arterial blood gas criteria match those established for COPD patients. The prescription of oxygen in these circumstances, as for unstable patients, increases the number of patients receiving supplemental oxygen and the related costs. Comorbidities are likely to affect both prognosis and health outcomes in COPD patients, but at the moment we do not know if LTOT in these patients with complex chronic diseases and mild-moderate hypoxemia could be of any use. For these reasons a critical revision of the actual guide lines indications for LTOT in order to optimise effectiveness and costs, and future research in the areas that have not previously been addressed by NOTT and MRC studies, are mandatory

Two Disk Components from a Gas Rich Disk-Disk Merger

We employ N-body, smoothed particle hydrodynamical simulations, including detailed treatment of chemical enrichment, to follow a gas-rich merger which results in a galaxy with disk morphology. We trace the kinematic, structural and chemical properties of stars formed before, during, and after the merger. We show that such a merger produces two exponential disk components, with the older, hotter component having a scale-length 20% larger than the later-forming, cold disk. Rapid star formation during the merger quickly enriches the protogalactic gas reservoir, resulting in high metallicities of the forming stars. These stars form from gas largely polluted by Type II supernovae, which form rapidly in the merger-induced starburst. After the merger, a thin disk forms from gas which has had time to be polluted by Type Ia supernovae. Abundance trends are plotted, and we examine the proposal that increased star formation during gas-rich mergers may explain the high alpha-to-iron abundance ratios which exist in the relatively high-metallicity thick disk component of the Milky Way.Comment: 10 pages, 1 color figure. Accepted for publication in Ap

Effects of endurance, resistance and neuro-muscular electrical stimulation trainings to the anthropometric and functional mobility domains in elderly

Background and aims There\u2019s the need to increase physical activity engagement to promote healthy ageing. Different training protocols elicit different morpho-functional effects: the comprehension of the related assessment tests is a key to improve the specific proposals and to monitor adequately the adaptations. We aimed to identify the functional adaptation processes basing on different training protocols. Methods 40 healthy elderly (28 males and 12 females, 70.7 \ub1 4.39 y) were randomly divided into 4 groups: endurance, resistance, Neuro-Muscular Electrical Stimulation and control, trained for 12 weeks andex-post evaluated on anthropometric and functional domains. Results We found: significant effect for gender, time and time 7 protocols for Five Times Sit-to-Stand Test and Timed Up-and-Go test. Post-hoc analyses revealed effect for resistance and Neuro-Muscular Electrical Stimulation on Five Times Sit-to-Stand Test, and for endurance and Neuro-Muscular Electrical Stimulation on Timed Up-and-Go test. Correlations and factorial analysis linked Five Times Sit-to-Stand Test and Timed Up-and-Go test on the functional domain. Conclusions Medium-term physical interventions significantly modified functional characteristics of elderly. We found no ex-post effect on anthropometric parameters. The two functional tests are based on different underlying domains, our data therefore suggest to use both of them to specifically evaluate the training-induced functional adaptations in elderly. Our results promote the usefulness of evidence-based trainin

The Red Halo Phenomenon

Optical and near-IR observations of the halos of disk galaxies and blue compact galaxies have revealed a very red spectral energy distribution, which cannot easily be reconciled with a normal, metal-poor stellar population like that in the stellar halo of the Milky Way. Here, spectral evolutionary models are used to explore the consequences of these observations. We demonstrate that a stellar population of low to intermediate metallicity, but with an extremely bottom-heavy initial mass function, can explain the red halos around both types of objects. Other previously suggested explanations, like nebular emission or very metal-rich stars, are shown to fail in this respect. This indicates that, if the reported halo colours are correct, halo populations dominated by low-mass stars may be a phenomenon common to galaxies of very different Hubble types. Potential tests of this hypothesis are discussed, along with its implications for the baryonic dark matter content of galaxies.Comment: 6 pages, 3 figures, Accepted for publication in Ap

The digital whomanities project. Best practices for digital pedagogy in the pandemic era

This paper aims to enter the ongoing debate about the critical issues of digital pedagogy through the presentation of Digital WHOmanities, a series of online conferences and workshops held at the University of Bologna. Distance learning has become one of the most discussed topics in educational institutions during the spread of Covid-19, revealing a discrepancy between the rapid development of technology and the ability of learning environments to adapt to this turn. In view of this ongoing debate, Digital WHOmanities tried to define the complex and multifaceted figure of the digital humanist and to provide a methodological framework that could foster further online academic initiatives. Specifically, the accurate organization of timing and contents and the adoption of synchronous and asynchronous approaches have highlighted the effectiveness of flexible digital didactics

Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma.

Omalizumab is a humanized monoclonal anti-IgE antibody approved in 2005 by the European Medicine Agency (EMA) for the treatment of severe persistent allergic asthma, which remains inadequately controlled despite optimal therapy with high doses of inhaled corticosteroids and long-acting β2-adrenergic agonists. Within this context, the present observational study refers to 16 patients currently treated with omalizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy, whose anti- IgE therapy was started in the period included between March 2007 and February 2010, thus lasting at least 10 months. After 40 weeks of add-on treatment with omalizumab, very relevant decreases were detected, in comparison with pre-treatment mean (± standard deviation) values, in monthly exacerbation numbers (from 1.1 ± 0.6 to 0.2 ± 0.4; p < 0.01) and oral corticosteroid consumption (from 22.6 ± 5.0 to 1.2 ± 2.9 mg/day of prednisone; p < 0.01). These changes were associated with stable improvements in lung function, expressed as increases of both FEV1 (from 53.6 ± 14.6% to 77.0 ± 14.9% of predicted values; p < 0.01) and FEV1/FVC ratio (from 56.3 ± 9.5% to 65.8 ± 9.2%; p < 0.01). Moreover, in 5 patients who persistently had increased numbers of eosinophils (mean ± SD: 15.9 ± 8.0% of total WBC count; absolute number: 1,588.0 ± 956.9/μl) despite a long-lasting therapy with inhaled and systemic corticosteroids, the peripheral counts of these cells decreased down to near normal levels (mean ± SD: 6.3 ± 2.3% of total WBC count; absolute number: 462.0 ± 262.3/μl) after 16 weeks of treatment with omalizumab. Therefore, this descriptive evaluation confirms the efficacy of add-on omalizumab therapy in selected patients with exacerbation-prone, chronic allergic uncontrolled asthma, requiring a continuous intake of oral corticosteroids

The Milky Way: An Exceptionally Quiet Galaxy; Implications for the formation of spiral galaxies

[Abridged]We compare both the Milky Way and M31 galaxies to local external disk galaxies within the same mass range, using their relative locations in the planes formed by V_flat versus M_K, j_disk, and the average Fe abundance of stars in the galaxy outskirts. We find, for all relationships, that the MW is systematically offset by ~ 1 sigma, showing a significant deficiency in stellar mass, in angular momentum, in disk radius and [Fe/H] in the stars in its outskirts at a given V_flat. On the basis of their location in the M_K, V_flat, and R_d volume, the fraction of spirals like the MW is 7+/-1%, while M31 appears to be a "typical'' spiral. Our Galaxy appears to have escaped any significant merger over the last ~10 Gyrs which may explain why it is deficient by a factor 2 to 3 in stellar mass, angular momentum and outskirts metallicity and then, unrepresentative of the typical spiral. As with M31, most local spirals show evidence for a history shaped mainly by relatively recent merging. We conclude that the standard scenario of secular evolution is generally unable to reproduce the properties of most (if not all) spiral galaxies. However, the so-called "spiral rebuilding'' scenario proposed by Hammer et al. 2005 is consistent with the properties of both distant galaxies and of their descendants - the local spirals.Comment: 14 pages, 6 figures, to appear in Ap