PLATAFORMAS INTERATIVAS DIGITAIS PARA PROMOÇÃO DE PRÁTICAS LEITORAS NO ENSINO FUNDAMENTAL: POTENCIALIDADES PARA FORMAÇÃO LEITORA E LETRAMENTO DIGITAL

A formação de leitores é um desafio a professores na educação básica, principalmente na era da cibercultura, que, com ferramentas e recursos interativos, demanda a criação de novas possibilidades para a promoção de leitura no ambiente escolar e também fora dele. Nesse sentido, esse trabalho tem por objetivo apresentar possibilidades de prática de mediação de leitura com exploração de jogos digitais que podem ser construídos com exploração de ferramentas disponíveis em duas plataformas: a ELO e a WORDWALL, selecionadas como objetos de investigação. A pesquisa parte de uma abordagem teórico-crítica sobre jogos digitais e formação leitora, contemplando referência a objetivos da leitura na educação básica – etapa do ensino fundamental, ao letramento digital e a associação entre leitura e tecnologias; em seguida, apresenta uma ilustração de potencialidades dessas plataformas para criação de atividades de promoção de leitura. A partir da análise, observa-se que as plataformas são potenciais recursos que podem ser incorporados às práticas de leitura do ensino fundamental, pois por meio das telas, a interatividade, motivação, ludicidade, concentração e atenção são possíveis e contribuem para a exploração e compreensão do que se lê. Contudo, o bom uso delas depende de criatividade, inovação e abordagem centrada em habilidades de leitura

A Human TREK-1/HEK Cell Line: A Highly Efficient Screening Tool for Drug Development in Neurological Diseases

TREK-1 potassium channels are involved in a number of physiopathological processes such as neuroprotection, pain and depression. Molecules able to open or to block these channels can be clinically important. Having a cell model for screening such molecules is of particular interest. Here, we describe the development of the first available cell line that constituvely expresses the TREK-1 channel. The TREK-1 channel expressed by the h-TREK-1/HEK cell line has conserved all its modulation properties. It is opened by stretch, pH, polyunsaturated fatty acids and by the neuroprotective molecule, riluzole and it is blocked by spadin or fluoxetine. We also demonstrate that the h-TREK-1/HEK cell line is protected against ischemia by using the oxygen-glucose deprivation model

Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design

We found that spadin, a natural peptide derived from sortilin, blocks the mouse TREK-1 channel and might be an efficient and fast-acting antidepressant

APP fragment controls both ionotropic and non-ionotropic signaling of NMDA receptors

NMDA receptors (NMDARs) are ionotropic receptors crucial for brain information processing. Yet, evidence also supports an ion-flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), an amyloid-β precursor protein (APP) cleavage product, as an NMDAR modulator with the unique dual regulatory capacity to impact both signaling modes. AETA inhibits ionotropic NMDAR activity by competing with the co-agonist and induces an intracellular conformational modification of GluN1 subunits. This favors non-ionotropic NMDAR signaling leading to enhanced LTD and favors spine shrinkage. Endogenously, AETA production is increased by in vivo chemogenetically induced neuronal activity. Genetic deletion of AETA production alters NMDAR transmission and prevents LTD, phenotypes rescued by acute exogenous AETA application. This genetic deletion also impairs contextual fear memory. Our findings demonstrate AETA-dependent NMDAR activation (ADNA), characterizing AETA as a unique type of endogenous NMDAR modulator that exerts bidirectional control over NMDAR signaling and associated information processing

Pharmacological inhibition of h-TREK-1 current in whole cell patch clamp configuration by spadin (n = 12 for each dose) and fluoxetine (n = 12 for each dose).

<p>Currents were recorded in the presence of a cocktail of potassium channel inhibitors (K⁺ blockers). The inhibition was obtained after the pre-activation of the current by 10 µM AA. <b>A)</b> Current/potential curves obtained in presence of K⁺ blockers (closed circles), K⁺ blockers + AA (open circles) and K⁺ blockers + AA + spadin 1 µM (closed triangles). The absence of voltage dependence of spadin inhibition (100 nM) was shown in the inset. <b>B)</b> Spadin dose dependent inhibition at 0 mV potential. <b>C)</b> Typical traces of hTREK-1 current pre-activated by 10 µM AA and inhibited by 1 µM spadin. <b>D)</b> Current/potential curves obtained in the presence of K⁺ blockers (closed circles), K⁺ blockers + 10 µM AA (open circles) and K⁺ blockers + 10 µM AA + 30 µM fluoxetine (closed triangles). The absence of voltage dependence of fluoxetine inhibition (10 µM) was shown in the inset. <b>E)</b> Fluoxetine dose-dependent inhibition at 0 mV potential. <b>F)</b> Typical traces of h-TREK-1 current pre-activated by 10 µM AA and inhibited by 30 µM fluoxetine. <b>G, H)</b> Current/potential curves and representative traces of spadin inhibition (1 µM) on 100 µM riluzole activated hTREK-1 current (n = 10). <b>I, J)</b> Current/potential curves and representative traces of fluoxetine inhibition (30 µM) on 100 µM riluzole activated hTREK-1 current (n = 10).</p

GFP expression and functional h-TREK-1 channel activity on h-TREK-1/HEK cells.

<p><b>A</b>) Typical pictures of cells observed in transmission and in fluorescence at round three of cell culture. Functional channel activity was evaluated by current activation with 10 µM AA. <b>B</b>) Typical pictures of cells observed in transmission and in fluorescence at round fourteenth of cell culture. Functional channel activity was evaluated by current activation with 10 µM AA. <b>C</b>) Real time q-PCR. Levels of TREK-1 or sortlin expression were normalized with the cyclophillin D expression.</p

Oxygen deprivation glucose experiments (OGD) on h-TREK-1/HEK cells and on HEK cells (A, B).

<p>After two hours of OGD in control conditions or with different treatments, survival cells were fixed, labeled and counted (n = 8 for each groups). <b>A)</b> Typical pictures of cells from each tested condition. <b>B)</b> Histograms of number of survival cells (Tukey test, F_7,568 = 38.65; *** or ### or $$$ p<0.001) <b>c)</b> The different tested conditions and their corresponding number.</p

Stretch and pH activation of h-TREK-1 current in cell attached (C.A.) and in inside out (I.O.) patch clamp configurations.

<p>Currents were recorded by application of negative pressure and by internal acidification. <b>A, B</b>) Current/pressure relationship and typical current traces obtained on h-TREK-1/HEK cells (closed circle, n = 30) and on HEK cells (closed square, n = 5) in cell-attached patch clamp configuration. <b>C, D</b>) Current/pressure relationship and typical current traces obtained on h-TREK-1/HEK cells (closed circle, n = 30) and on HEK cells (closed square, n = 4) in inside-out patch clamp configuration. Inset: negative pressure step protocol, increase −10 mmHg. <b>E, F</b>) Current/potential curves and corresponding histograms obtained after internal acidification on h-TREK-1/HEK cells (n = 8) and on HEK cells (n = 3).</p

Pharmacological activation of h-TREK-1 current in whole cell patch clamp configuration.

<p>Currents were recorded in the presence of a cocktail of potassium channel inhibitors (K⁺ blockers). <b>A</b>) Current/potential curves and corresponding current traces obtained before (closed circle) and after (open circle) current activation by AA 10 µM (n = 118). <b>B</b>) Current/potential curves and corresponding current traces obtained before (closed circle) and after (open circle) current activation by DHA 10 µM (n = 10). <b>C</b>) Current/potential curves and corresponding current traces obtained before (closed circle) and after (open circle) current activation by ALA 10 µM (n = 10). <b>D</b>) Current/potential curves and corresponding current traces obtained before (closed circle) and after current activation by riluzole 100 µM (n = 12) perfused during 30 s (open circle) or 90 s (closed triangle). Each pharmacological activator was tested on HEK-293 native cells (n = 10) and current/potential curves were shown in the inset of each curve. <b>E</b>) Current density values measured at 0 mV after different times of perfusion of 100 µM riluzole (n = 10 at each time value).</p

The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding

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