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]

Mass Redistribution Causes the Structural Richness of Ion-Irradiated Surfaces

We show that the “sputter patterning” topographical instability is determined by the effects of ion impact-induced prompt atomic redistribution and that erosion—the consensus predominant cause—is essentially irrelevant. We use grazing incidence small angle x-ray scattering to measure in situ the damping of noise or its amplification into patterns via the linear dispersion relation. A model based on the effects of impact-induced redistribution of those atoms that are not sputtered away explains both the observed ultrasmoothening at low angles from normal incidence and the instability at higher angles.Engineering and Applied Science

Time-resolved measurements of nanoscale surface pattern formation kinetics in two dimensions on ion-irradiated Si

The nanoscale kinetics of surface topography evolution on silicon surfaces irradiated with 1 keV Ar+ ions is examined in both directions perpendicular and parallel to the projection of the ion beam on the surface. We use grazing incidence small angle x-ray scattering to measure in situ the evolution of surface morphology via the linear dispersion relation. We study the transition from surface ultra-smoothening at low angles of deviation from normal ion incidence to a pattern-forming instability at high incidence angles. A model based on the effects of impact-induced redistribution of those atoms that are not sputtered away explains both the observed ultra-smoothening at low angles from normal ion incidence and the instability at higher angles and accounts quantitatively for the measured two-dimensional dispersion relation and its dependence on incidence angle.Physic

Conceptual Profiles: Theoretical-methodological Grounds and Empirical Studies

AbstractIn this paper, we briefly address the theoretical and methodological grounds of the conceptual profile theory and discuss two empirical studies aiming at constructing conceptual profile models and using them to analyze classroom discourse in different sciences, chemistry (entropy and spontaneity) and biology (adaptation). The basic idea is to illustrate how these models were built, considering differences and similarities between the methods used for this purpose. Conceptual profiles are models of different modes of seeing and conceptualizing the world used by individuals to signify their experience. They are built for a given concept and are constituted by several zones, each representing a particular mode of thinking about that concept, related to a particular way of speaking. Each zone is individuated by ontological, epistemological, and axiological commitments underlying discourse. We will show how different concepts, situated in sciences with different levels of conceptual polysemy, demand different methodologies to deal with the variation found in meaning making in the sociocultural, ontogenetic, and microgenetic domains

Submaximal Angioplasty for Symptomatic Intracranial Atherosclerotic Disease: A Meta-Analysis of Peri-Procedural and Long-Term Risk

© 2019 by the Congress of Neurological Surgeons. BACKGROUND: Symptomatic intracranial atherosclerotic disease (ICAD) is an important cause of stroke. Although the high periprocedural risk of intracranial stenting from recent randomized studies has dampened enthusiasm for such interventions, submaximal angioplasty without stenting may represent a safer endovascular treatment option. OBJECTIVE: To examine the periprocedural and long-term risks associated with submaximal angioplasty for ICAD based on the available literature. METHODS: All English language studies of intracranial angioplasty for ICAD were screened. Inclusion criteria were as follows: ≥ 5 patients, intervention with submaximal angioplasty alone, and identifiable periprocedural (30-d) outcomes. Analysis was co-nducted to identify the following: 1) periprocedural risk of any stroke (ischemic or hemorrh-agic) or death, and 2) stroke in the territory of the target vessel and fatal stroke beyond 30 d. Mixed effects logistic regression was used to summarize event rates. Funnel plot and rank correlation tests were employed to detect publication bias. The relative risk of periprocedural events from anterior vs posterior circulation disease intervention was also examined. RESULTS: A total of 9 studies with 408 interventions in 395 patients met inclusion criteria. Six of these studies included 113 posterior circulation interventions. The estimated pooled rate for 30-d stroke or death following submaximal angioplasty was 4.9% (95% CI: 3.2%-7.5%), whereas the estimated pooled rate beyond 30 d was 3.7% (95% CI: 2.2%-6.0%). There was no statistical difference in estimated pooled rate for 30-d stroke or death between patients with anterior (4.8%, 95% CI: 2.8%-7.9%) vs posterior (5.3%, 95% CI: 2.4%-11.3%) circulation disease (P \u3e. 99). CONCLUSION: Submaximal angioplasty represents a potentially promising intervention for symptomatic ICAD

Aprendizagem Baseada em Problemas (ABP) na Educação Científica como Estratégia para Formação do Cidadão Socioambientalmente Responsável

A partir do pressuposto de que o ensino tradicional, na educação científica, é insuficiente para uma aprendizagem integrada de conteúdos relevantes em direção a uma adequada ação social cidadã, defendemos que estratégias pedagógicas com base na Aprendizagem Baseada em Problemas (ABP) podem contribuir para a formação de cidadãos responsáveis no âmbito social e ambiental, ao fornecer um ambiente amplo de aprendizagem e ao promover o desenvolvimento de conteúdos conceituais, procedimentais e atitudinais. Neste artigo, discutimos características de duas estratégias da ABP (resolução de caso e sessões tutoriais) como meio de aproximar a aprendizagem de diferentes conteúdos dos desafios da realidade cotidiana da sociedade contemporânea e favorecer tomadas de decisão que sejam socialmente responsáveis. Apontamos, também, algumas limitações e desafios para o uso dessas estratégias na educação científica

Structure-Function Correlation of the Human Central Retina

The impact of retinal pathology detected by high-resolution imaging on vision remains largely unexplored. Therefore, the aim of the study was to achieve high-resolution structure-function correlation of the human macula in vivo.To obtain high-resolution tomographic and topographic images of the macula spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy (cSLO), respectively, were used. Functional mapping of the macula was obtained by using fundus-controlled microperimetry. Custom software allowed for co-registration of the fundus mapped microperimetry coordinates with both SD-OCT and cSLO datasets. The method was applied in a cross-sectional observational study of retinal diseases and in a clinical trial investigating the effectiveness of intravitreal ranibizumab in macular telangietasia type 2. There was a significant relationship between outer retinal thickness and retinal sensitivity (p<0.001) and neurodegeneration leaving less than about 50 µm of parafoveal outer retinal thickness completely abolished light sensitivity. In contrast, functional preservation was found if neurodegeneration spared the photoreceptors, but caused quite extensive disruption of the inner retina. Longitudinal data revealed that small lesions affecting the photoreceptor layer typically precede functional detection but later cause severe loss of light sensitivity. Ranibizumab was shown to be ineffective to prevent such functional loss in macular telangietasia type 2.Since there is a general need for efficient monitoring of the effectiveness of therapy in neurodegenerative diseases of the retina and since SD-OCT imaging is becoming more widely available, surrogate endpoints derived from such structure-function correlation may become highly relevant in future clinical trials

Establishment of diagnostic reference levels in cardiac computed tomography

The aim of this study was to determine diagnostic reference levels (DRLs) for cardiac computed tomography (CCT) in Jordan. Volume computed tomography dose index (CTDIvol) and dose–length product (DLP) were collected from 228 CCTs performed at seven Jordanian hospitals specialized in cardiac CT. DRLs for cardiac CT were defined at the 75th percentile of CTDIvol and DLP. CTDIvol and DLP were collected from 30 successive cardiac CT in each center except for one center (18 scans). The 75th percentile of the CTDIvol and the DLP of the centers calculated from mixed retrospective and prospective gated modes were 47.74 milligray (mGy) and 1035 mGy/cm, respectively. This study demonstrated wide dose variations among the surveyed hospitals for cardiac CT scans; there was a 5.1-fold difference between the highest and lowest median DLP with a range of 223.2–1146.7 mGy/cm. Differences were associated with variations in the mAs and kVp. This study confirmed large variability in CTDIvol and DLP for cardiac CT scans; variation was associated with acquisition protocols and highlights the need for dose optimization. DRLs are proposed for CCT; there remains substantial potential for optimization of cardiac CT examinations for adults in Jordan

The Effects of Intravitreal Bevacizumab in Infectious and Noninfectious Uveitic Macular Edema

Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI) for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41±16 years with a mean followup of 4±1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet’s disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8±0.8 at baseline to 0.4±0.5 at 1 month and 0.3±0.5 at 3 months (P<0.002, at 3 months). The mean macular thickness was 430±132 μm at baseline. Following IVBI macular thickness improved to 286±93 μm at 1 month and to 265±88 μm at 3 months of followup (P<0.001, at 3 months). Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents